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Title:
Effects of chronic administration of caffeine and stress on feeding behavior of rats
Abstract:
Abstract Anorectic effects of caffeine are controversial in the literature, while stress and obesity are growing problems in our society.
Since many stressed people are coffee drinkers, the objective of the present study was to evaluate the effect of stress and chronic administration of caffeine on feeding behavior and body weight in male and female rats.
Wistar rats (both males and females) were divided into 3 groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water).
These groups were subdivided into non-stressed and stressed (repeated-restraint stress for 40 days).
During the entire treatment, chow consumption was monitored and rats were weighed monthly.
Afterwards, feeding behavior was evaluated during 3-min trials in food-deprived and ad libitum fed animals and also in repeated exposures, using palatable food (Froot Loops® and Cheetos®).
Chronic administration of caffeine did not affect rat chow consumption or body weight gain, but diminished the consumption of both salty (Cheetos®) and sweet (Froot Loops®) palatable food.
In the repeated trial tests, stress diminished savory snack consumption in the later exposures [I.S. Racotta, J. Leblanc, D. Richard The effect of caffeine on food intake in rats: involvement of corticotropin-releasing factor and the sympatho-adrenal system.
Pharmacol Biochem Behav.
1994, 48:887–892; S.D. Comer, M. Haney, R.W. Foltin, M.W. Fischman Effects of caffeine withdrawal on humans living in a residential laboratory.
Exp Clin Psychopharmacol.
1997, 5:399–403; A. Jessen, B. Buemann, S. Toubro, I.M. Skovgaard, A. Astrup The appetite-suppressant effect of nicotine is enhanced by caffeine.
Diab Ob Metab.
2005, 7:327–333; J.M. Carney Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats.
Br J Pharmacol.
1982, 75:451–454] and caffeine diminished consumption of both palatable foods (savory and sweet) during the early and later exposures.
Most responses to caffeine were stronger in females, and stress exposure influenced the effect.
Neither chronic caffeine nor stress affected adrenal weight and plasma corticosterone levels of the rats.
These observations suggest that chronic caffeine consumption may have sex-specific effects on palatable food ingestion. | 151 |
Title:
Threshold values, stability analysis and high-q asymptotics for the coloring problem on random graphs
Abstract:
We consider the problem of coloring Erdös-Rényi and regular random graphs of finite connectivity using q colors.
It has been studied so far using the cavity approach within the so-called one-step replica symmetry breaking (1RSB) ansatz.
We derive a general criterion for the validity of this ansatz and, applying it to the ground state, we provide evidence that the 1RSB solution gives exact threshold values c(q) for the transition from the colorable to the uncolorable phase with q colors.
We also study the asymptotic thresholds for q>>1 finding c(q) =2q ln q-ln q-1+o (1) in perfect agreement with rigorous mathematical bounds, as well as the nature of excited states, and give a global phase diagram of the problem. | 170 |
Title:
Synthesis of macromolecules by Escherichia coli near the minimal temperature for growth.
Abstract:
When a culture of Escherichia coli ML30 growing exponentially at 37 C in a glucose minimal medium was shifted abruptly to 10 C, growth decreased for about 4.5 hr.
There was no net synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein.
The cells, however, respired at a rate characteristic of cells growing in the steady state at 10 C and were able to accumulate alpha-methyl-d-glucoside.
When growth recommenced at 10 C, protein synthesis started at 4 hr, RNA synthesis, with a burst at 6 hr, and DNA synthesis, with a burst at 7 hr.
One synchronous division occurred at about 11 hr after shifting to 10 C. There was no alteration in the steady-state RNA to protein ratio.
The results are discussed in relation to other reported effects of shifts in environmental conditions.
The lag at 10 C was dependent on prior conditions of growth at 37 C. Growth at 37 C under conditions giving catabolite repression were necessary for the lag to be established on shifting to 10 C. | 414 |
Title:
Correlations in interacting systems with a network topology
Abstract:
We study pair correlations in interacting systems placed on complex networks.
We show that usually in these systems, pair correlations between interacting objects (e.g., spins), separated by a distance $\ensuremath{\ell}$, decay, on average, faster than $1∕(\ensuremath{\ell}{z}_{\ensuremath{\ell}})$. Here ${z}_{\ensuremath{\ell}}$ is the mean number of the $\ensuremath{\ell}$th nearest neighbors of a vertex in a network.
This behavior, in particular, leads to a dramatic weakening of correlations between second and more distant neighbors on networks with fat-tailed degree distributions, which have a divergent number ${z}_{2}$ in the infinite network limit.
In large networks of this kind, only pair correlations between the nearest neighbors are actually observable.
We find the pair correlation function of the Ising model on a complex network.
This exact result is confirmed by a phenomenological approach. | 1,313 |
Title:
Urothelial carcinoma in a pyelocaliceal diverticulum discovered by magnetic resonance urography
Abstract:
Neither computed tomography (CT) nor intravenous pyelography (IVP) alone can diagnose tumors of renal pelvic diverticula, but magnetic resonance urography (MRU) can obtain accurate preoperative information.
caSe | 1,712 |
Title:
Evolution of cis-regulatory elements in yeast de novo and duplicated new genes
Abstract:
BackgroundNew genes that originate from non-coding DNA rather than being duplicated from parent genes are called de novo genes.
Their short evolution time and lack of parent genes provide a chance to study the evolution of cis-regulatory elements in the initial stage of gene emergence.
Although a few reports have discussed cis-regulatory elements in new genes, knowledge of the characteristics of these elements in de novo genes is lacking.
Here, we conducted a comprehensive investigation to depict the emergence and establishment of cis-regulatory elements in de novo yeast genes.
ResultsIn a genome-wide investigation, we found that the number of transcription factor binding sites (TFBSs) in de novo genes of S. cerevisiae increased rapidly and quickly became comparable to the number of TFBSs in established genes.
This phenomenon might have resulted from certain characteristics of de novo genes; namely, a relatively frequent gain of TFBSs, an unexpectedly high number of preexisting TFBSs, or lower selection pressure in the promoter regions of the de novo genes.
Furthermore, we identified differences in the promoter architecture between de novo genes and duplicated new genes, suggesting that distinct regulatory strategies might be employed by genes of different origin.
Finally, our functional analyses of the yeast de novo genes revealed that they might be related to reproduction.
ConclusionsOur observations showed that de novo genes and duplicated new genes possess mutually distinct regulatory characteristics, implying that these two types of genes might have different roles in evolution. | 1,819 |
Title:
Next-generation sequencing for virus detection: covering all the bases
Abstract:
Background ::: The use of next-generation sequencing has become an established method for virus detection.
Efficient study design for accurate detection relies on the optimal amount of data representing a significant portion of a virus genome. | 1,821 |
Title:
Interlaboratory Surveys of the Determination of Tumour Markers Scatter and Repeatability of the Results
Abstract:
Data collected between 1983 and 1991 in interlaboratory surveys of the determination of tumour markers are used to show the magnitude of the scatter of results from different laboratories for the analysis of a single quantity in a given matrix.
These data also show that the varying specificity of different reagent combinations appears to make a considerable contribution to this scatter, and that the used reagent combinations were not of uniform quality over a relatively extended period.
The results for the following tumour markers were studied: alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), human chorionic gonadotropin (hCG), human chorionic gonadotropin+beta-subunit (hCG+beta-hCG), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA 125), prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA). | 1,939 |
Title:
Double coronary artery stent fracture with coronary artery microaneurysms.
Abstract:
Even though drug-eluting stent (DES) implantation is an effective treatment for coronary artery stenosis, there are growing concerns related to the real usefulness of DESs due to their increased incidence of thrombosis, stent fracture, and late stent malapposition in comparison to bare metal stents.
We have previously reported a case of stent fractures and multiple microaneurysms in both the left anterior descending and left circumflex coronary arteries.
In the present case, we demonstrate the ability of dual-source spiral computed tomography to evaluate the various complications of DESs. | 1,958 |
Title:
IL-12 could induce monocytic tumor cells directional differentiation
Abstract:
Interleukin-12 (IL-12), a member of interleukin family, plays a critical role in immune responses and anti-tumor activity.
In this study, the effects of IL-12 on monocytic tumor cell lines differentiation to macrophagocyte and its likely mechanism was investigated.
We examined the differentiation markers, morphological and functional changes, and possible mechanism in IL-12-treated THP-1 and U937 cells.
It was found that IL-12 could up-regulated macrophage surface marker CD68 and CD11b expression in a time-dependent manner.
Morphologically, after IL-12 treatment, THP-1 and U937 cells became round or irregular shape, even stretched many cell membrane protuberances; some cell nuclei became fuzzy or completely disappeared, and the chromatin appeared dense and cordlike.
Furthermore, IL-12-induced monocytic tumor cell differentiation was accompanied by the growth arrest with G1-phase accumulation and S-phase reduction; apoptosis increased with anti-apoptosis protein Bcl-2 down-expression and pro-apoptosis protein Fas up-regulation, and enhanced phagocytosis function.
The IL-12-induced macrophage differentiation of THP-1 and U937 cells was associated with the up-regulation of c-fms expression and the CSF-1R Tyr 809 site phosphorylation.
These findings have revealed that IL-12 could induce monocytic tumor cells directional differentiation into macrophage-like cells, and its mechanism is possible connected with the up-regulation of c-fms expression and the phosphorylation of CSF-1R Tyr-809 site. | 1,976 |
Title:
The feasibility study and characterization of a two-dimensional diode array in “magic phantom” for high dose rate brachytherapy quality assurance
Abstract:
PURPOSE ::: High dose rate (HDR) brachytherapy is a radiation treatment technique capable of delivering large dose rates to the tumor.
Radiation is delivered using remote afterloaders to drive highly active sources (commonly (192)Ir with an air KERMA strength range between 20,000 and 40,000 U, where 1 U = 1 μGy m(2)/h in air) through applicators directly into the patient's prescribed region of treatment.
Due to the obvious ramifications of incorrect treatment while using such an active source, it is essential that there are methods for quality assurance (QA) that can directly and accurately verify the treatment plan and the functionality of the remote afterloader.
This paper describes the feasibility study of a QA system for HDR brachytherapy using a phantom based two-dimensional 11 × 11 epitaxial diode array, named "magic phantom." ::: ::: ::: METHODS ::: The HDR brachytherapy treatment plan is translated to the phantom with two rows of 10 (20 in total) HDR source flexible catheters, arranged above and below the diode array "magic plate" (MP).
Four-dimensional source tracking in each catheter is based upon a developed fast iterative algorithm, utilizing the response of the diodes in close proximity to the (192)Ir source, sampled at 100 ms intervals by a fast data acquisition (DAQ) system.
Using a (192)Ir source in a solid water phantom, the angular response of the developed epitaxial diodes utilized in the MP and also the variation of the MP response as a function of the source-to-detector distance (SDD) were investigated.
These response data are then used by an iterative algorithm for source dwelling position determination.
A measurement of the average transit speed between dwell positions was performed using the diodes and a fast DAQ. ::: ::: ::: RESULTS ::: The angular response of the epitaxial diode showed a variation of 15% within 360°, with two flat regions above and below the detector face with less than 5% variation.
For SDD distances of between 5 and 30 mm the relative response of the epitaxial diodes used in the MP is in good agreement (within 8%) with radial dose function measurements found within the TG-43 protocol, with SDD of up to 70 mm showing a 40% over response.
A method for four-dimensional localization of the HDR source was developed, allowing the source dwell position to be derived within 0.50 mm of the expected position.
An estimation of the average transit speed for varying step sizes was determined and was found to increase from (12.8 ± 0.3) up to (38.6 ± 0.4) cm/s for a step size of 2.5 and 50 mm, respectively. ::: ::: ::: CONCLUSIONS ::: Our characterization of the designed QA "magic phantom" with MP in realistic HDR photon fields demonstrates the promising performance for real-time source position tracking in four dimensions and measurements of transit times.
Further development of this system will allow a full suite for QA in HDR brachytherapy and analysis, and for future in vivo tracking. | 1,999 |
Title:
Influence of serum adiponectin level and SNP +45 polymorphism of adiponectin gene on myocardial fibrosis
Abstract:
Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardiomyocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene polymorphism on myocardial fibrosis.
Our study investigates the influence of the SNP +45 polymorphism of the adiponectin gene and serum levels of adiponectin on myocardial fibrosis in patients with essential hypertension.
A case-control study was conducted on 165 hypertensive patients and 126 normotensive healthy controls.
The genotypes of adiponectin gene polymorphisms were detected by the polymerase chain reaction (PCR) method.
Serum concentrations of procollagen were measured by a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects.
The integrated backscatter score (IBS) was measured in the left ventricular myocardium using echocardiography.
The serum levels of adiponectin in hypertensive patients were significantly lower than those in the normal control group ((2.69±1.0) μg/ml vs. (4.21±2.89) μg/ml, respectively, P<0.001).
The serum levels of type-I procollagen carboxyl end peptide (PICP) and type-III procollagen ammonia cardinal extremity peptide (PIIINP) in the hypertension group were significantly higher than those in the control group.
In the hypertension group, serum levels of adiponectin were significantly and negatively related to the average acoustic intensity and corrected acoustic intensity of the myocardium (r=0.46 and 0.61, respectively, P<0.05 for both).
The serum levels of PICP and PIIINP were significantly different among the three genotypes of SNP +45 (P<0.01).
Logistic regression analyses showed that sex and genotype (GG+GT) were the major risk factors of myocardial fibrosis in hypertensive patients (OR=5.343 and 3.278, respectively, P<0.05).
These data suggest that lower levels of adiponectin and SNP +45 polymorphism of the adiponectin gene are likely to play an important role in myocardial fibrosis in hypertensive patients. | 2,049 |
Title:
Outer membrane protein sequence variation in lambs experimentally infected with Anaplasma phagocytophilum.
Abstract:
Anaplasma phagocytophilum has long been known to cause tick-borne fever in ruminants and has been identified more recently as the causative agent of the emerging disease human granulocytic anaplasmosis.
The related organism Anaplasma marginale uses gene conversion of the expression site for two major outer membrane proteins (OMPs) to generate extensive sequence and antigenic variation in these OMPs.
This is thought to present a continuously varying repertoire of epitopes to the mammalian host and allow disease persistence.
Recent genomic and structural data on human strains of A. phagocytophilum, together with animal studies in model systems, have implicated an orthologous OMP of A. phagocytophilum in a similar mechanism of variation.
However, to date there has been little investigation of the mechanisms of antigenic variation or disease persistence in hosts naturally infected with field strains of A. phagocytophilum.
Approximately 300,000 lambs in Norway suffer severe disease caused by A. phagocytophilum annually.
We show here the persistent and cyclic nature of infection in these animals that is accompanied by loosely programmed sequence variation of the major OMP expression site in each rickettsemic peak.
These data will allow analysis of interactions between A. phagocytophilum and the host immune system in naturally occurring persistent infections and provide an important comparison with enduring infections of cattle caused by A. marginale. | 2,056 |
Title:
Hitting the Bull’s-Eye in Metastatic Cancers—NSAIDs Elevate ROS in Mitochondria, Inducing Malignant Cell Death
Abstract:
Tumor metastases that impede the function of vital organs are a major cause of cancer related mortality.
Mitochondrial oxidative stress induced by hypoxia, low nutrient levels, or other stresses, such as genotoxic events, act as key drivers of the malignant changes in primary tumors to enhance their progression to metastasis.
Emerging evidence now indicates that mitochondrial modifications and mutations resulting from oxidative stress, and leading to OxPhos stimulation and/or enhanced reactive oxygen species (ROS) production, are essential for promoting and sustaining the highly metastatic phenotype.
Moreover, the modified mitochondria in emerging or existing metastatic cancer cells, by their irreversible differences, provide opportunities for selectively targeting their mitochondrial functions with a one-two punch.
The first blow would block their anti-oxidative defense, followed by the knockout blow—promoting production of excess ROS, capitulating the terminal stage—activation of the mitochondrial permeability transition pore (mPTP), specifically killing metastatic cancer cells or their precursors.
This review links a wide area of research relevant to cellular mechanisms that affect mitochondria activity as a major source of ROS production driving the pro-oxidative state in metastatic cancer cells.
Each of the important aspects affecting mitochondrial function are discussed including: hypoxia, HIFs and PGC1 induced metabolic changes, increased ROS production to induce a more pro-oxidative state with reduced antioxidant defenses.
It then focuses on how the mitochondria, as a major source of ROS in metastatic cancer cells driving the pro-oxidative state of malignancy enables targeting drugs affecting many of these altered processes and why the NSAIDs are an excellent example of mitochondria-targeted agents that provide a one-two knockout activating the mPTP and their efficacy as selective anticancer metastasis drugs. | 2,069 |
Title:
The Xenopus homologue of Down syndrome critical region protein 6 drives dorsoanterior gene expression and embryonic axis formation by antagonising polycomb group proteins
Abstract:
Mesoderm and embryonic axis formation in vertebrates is mediated by maternal and zygotic factors that activate the expression of target genes.
Transcriptional derepression plays an important role in the regulation of expression in different contexts; however, its involvement and possible mechanism in mesoderm and embryonic axis formation are largely unknown.
Here we demonstrate that XDSCR6, a Xenopus homologue of human Down syndrome critical region protein 6 (DSCR6, or RIPPLY3), regulates mesoderm and embryonic axis formation through derepression of polycomb group (PcG) proteins.
Xdscr6 maternal mRNA is enriched in the endoderm of the early gastrula and potently triggers the formation of dorsal mesoderm and neural tissues in ectoderm explants; it also dorsalises ventral mesoderm during gastrulation and induces a secondary embryonic axis.
A WRPW motif, which is present in all DSCR6 homologues, is necessary and sufficient for the dorsal mesoderm- and axis-inducing activity.
Knockdown of Xdscr6 inhibits dorsal mesoderm gene expression and results in head deficiency.
We further show that XDSCR6 physically interacts with PcG proteins through the WRPW motif, preventing the formation of PcG bodies and antagonising their repressor activity in embryonic axis formation.
By chromatin immunoprecipitation, we demonstrate that XDSCR6 releases PcG proteins from chromatin and allows dorsal mesoderm gene transcription.
Our studies suggest that XDSCR6 might function to sequester PcG proteins and identify a novel derepression mechanism implicated in embryonic induction and axis formation. | 2,092 |
Title:
Synthetic 2,3-Butanediol Pathway Integrated Using Tn7-tool and Powered Via Elimination of Sporulation and Acetate Production in Acetogen Biocatalyst
Abstract:
Acetogen Clostridium sp. MT1802 originally producing 336-mM acetate from inorganic carbon of CO2/CO was engineered to eliminate acetate production and sporulation using Cre-lox66/lox71-approach.
The recombinant started producing 105-mM formate expressing synthetic formate dehydrogenase integrated in two copies.
Formate-producing recombinant was further engineered to express synthetic formate acetyltransferase, acetolactate synthase, acetolactate decarboxylase, and alcohol dehydrogenase integrated in two copies each using Tn7 tool.
The resulted recombinant started producing 102-mM 2,3-butanediol (23BD).
23BD production was confirmed in five independent single step fermentation runs 25 days long each in five repeats using syngas blend 60 % CO and 40 % H2 (v/v) (p <0.005).
23BD production was 78 % if only CO2/H2 blend was fed instead of syngas (p <0.005).
23BD from CO2/H2 blend might serve as a commercial route to mitigate global warming in proportion to CO2 fermentation scale worldwide. | 2,181 |
Title:
Building blocks for automated elucidation of metabolites: Machine learning methods for NMR prediction
Abstract:
Background ::: Current efforts in Metabolomics, such as the Human Metabolome Project, collect structures of biological metabolites as well as data for their characterisation, such as spectra for identification of substances and measurements of their concentration.
Still, only a fraction of existing metabolites and their spectral fingerprints are known.
Computer-Assisted Structure Elucidation (CASE) of biological metabolites will be an important tool to leverage this lack of knowledge.
Indispensable for CASE are modules to predict spectra for hypothetical structures.
This paper evaluates different statistical and machine learning methods to perform predictions of proton NMR spectra based on data from our open database NMRShiftDB. | 2,217 |
Title:
Characteristics of cerebrospinal fluid (CSF) among children with ventriculoperitoneal shunt infections
Abstract:
A common (5%) complication of cerebrospinal fluid (CSF) shunt systems is infection.
CSF cytochemical findings have been used to choose the initial empirical antimicrobial treatment.
The objective was to evaluate the results of cytochemical and microbiological analyses of CSF samples obtained from children with pyogenic ventriculitis associated to ventriculoperitoneal shunt systems.
This was a retrospective, descriptive and analytical study.
Thirty-two cases of pyogenic ventriculitis were included; Gram-positive bacteria were predominant in 26 cases (81.25%); the rest corresponded to Gram-negative bacteria.
There were no statistically significant differences for the studied outcome variables (CSF cellularity, glucose and protein levels).
Conclusion: Gram-positive bacteria were widely predominant as a cause of pyogenic ventriculitis associated to the surgical procedure.
CSF characteristics show a high heterogeneity and were not associated to the type of microorganism in this | 2,252 |
Title:
Measurement of Corneal Thickness by Laser Doppler Interferometry
Abstract:
The laser Doppler interferometry (LDI) technique, which was recently developed for axial eye length measurement, has been modified to measure the corneal thickness of the human eye in vivo.
High accuracy is achieved.
The standard deviation of the technique is about 7 μm, and improvement by a factor of 5 is possible.
First comparisons with a usual slit lamp pachometer show a general agreement but a systematic difference of about 20 μm.
Possible reasons for this discrepancy are discussed.
Finally, the new method is compared to standard optical and ultrasound pachometry from a theoretical point of view, and advantages and drawbacks of the various techniques are discussed. | 2,284 |
Title:
Apical deficiency triggers JNK-dependent apoptosis in the embryonic epidermis of Drosophila
Abstract:
Epithelial homeostasis and the avoidance of diseases such as cancer require the elimination of defective cells by apoptosis.
Here, we investigate how loss of apical determinants triggers apoptosis in the embryonic epidermis of Drosophila.
Transcriptional profiling and in situ hybridisation show that JNK signalling is upregulated in mutants lacking Crumbs or other apical determinants.
This leads to transcriptional activation of the pro-apoptotic gene reaper and to apoptosis.
Suppression of JNK signalling by overexpression of Puckered, a feedback inhibitor of the pathway, prevents reaper upregulation and apoptosis.
Moreover, removal of endogenous Puckered leads to ectopic reaper expression.
Importantly, disruption of the basolateral domain in the embryonic epidermis does not trigger JNK signalling or apoptosis.
We suggest that apical, not basolateral, integrity could be intrinsically required for the survival of epithelial cells.
In apically deficient embryos, JNK signalling is activated throughout the epidermis.
Yet, in the dorsal region, reaper expression is not activated and cells survive.
One characteristic of these surviving cells is that they retain discernible adherens junctions despite the apical deficit.
We suggest that junctional integrity could restrain the pro-apoptotic influence of JNK signalling. | 2,294 |
Title:
A formative study to inform mHealth based randomized controlled trial intervention to promote exclusive breastfeeding practices in Myanmar: incorporating qualitative study findings
Abstract:
Undernutrition is a major concern for Myanmar children with low exclusive breastfeeding rate (24%).
A formative study was conducted to explore the perceptions and practices relating to exclusive breastfeeding, and barriers and facilitators to using mobile communications for exclusive breastfeeding counselling.
The results inform the design of a randomized control trial to promote exclusive breastfeeding practices among Myanmar mothers.
We conducted twenty in-depth interviews with pregnant women and accompanying family members attending an antenatal clinic at the Central Women’s Hospital, Yangon, seven key-informant interviews and one focus group discussion with fifteen service providers such as nurses, doctors, managers and staff from the National Nutrition Centre, Department of Health, United Nations Children’s Fund International and National Non-Government Organizations and Ooredoo, a private mobile company.
Widespread practices of feeding water, honey, infant formula and semi-solid food were reported to be existed in the community before the child reaches four months, mostly influenced by grandmothers from both sides.
All couples knew breast milk was good for baby and intended to breastfeed, though limited understanding of the term exclusive breastfeeding was reported.
Perception that breast milk alone was not sufficient to provide all nutrients needed for the first six months of baby’s life, mother had insufficient milk supply or breast problems, mother’s back to work and grandmothers’ influence emerged as barriers to breastfeed exclusively for six months.
All women knew how to make basic phone calls, majority could read mobile text message in Burmese and possess mobile phones while a few of them shared phones with their husbands.
All couples preferred to receive text messages 2–3 times per week in the evening.
Institutional staff suggested messages to be simple, easily understandable and culturally appropriate.
Perceived barriers included limited mobile network coverage, affordability of mobile handset and phone bills, literacy and community familiarity with text messages.
All respondents welcomed the idea of planned intervention.
We incorporated findings to develop messages and determine the modality, inclusion criteria and tailored with gestation and child age, to be delivered in the randomized controlled trial intervention. | 2,327 |
Title:
Identifying Molecular Effects of Diet through Systems Biology: Influence of Herring Diet on Sterol Metabolism and Protein Turnover in Mice
Abstract:
BACKGROUND ::: Changes in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide.
To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD).
This will require methods for linking nutrient intake with specific metabolic processes in different tissues. ::: ::: ::: METHODOLOGY/PRINCIPAL FINDING ::: Low-density lipoprotein receptor-deficient (Ldlr -/-) mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis.
The diets were supplemented with either beef or herring, and matched in macronutrient contents.
Body composition, plasma lipids and aortic lesion areas were measured.
Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues.
Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice.
::: ::: ::: CONCLUSION ::: This study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways.
This could not have been achieved using standard clustering methods.
In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression.
This could be applied to improve diets for subjects exposed to health risks associated with obesity. | 2,381 |
Title:
First report of prevalence of non-syndromic hereditary prosopagnosia (HPA)
Abstract:
Acquired prosopagnosia (PA) is a rare condition after, for example, a stroke or brain injury.
The congenital form of PA is generally considered to be even less common.
Beside a few single case reports and anecdotal mentioning of familial cases no data on the epidemiology exists.
Following a questionnaire-based screening in local secondary schools and at our medical faculty, candidates suspicious for PA underwent a semi-structured interview followed by examinations of first degree relatives.
Among 689 local pupils and medical students of our university we found 17 with congenital PA.
This corresponds to a prevalence rate of 2.47% (95% CI 1.31-3.63).
The frequency is among the highest known for a monogenic disorder.
All those index subjects (n = 14) of the target group who agreed to further examinations of their family members had other first degree relatives with the same cognitive disorder.
This study provides epidemiological evidence that congenital PA is a very common cognitive disorder which almost always runs in families.
The segregation pattern of this hereditary prosopagnosia (HPA) is fully compatible with autosomal dominant inheritance. | 2,401 |
Title:
P2X7 Receptor Stimulation of Membrane Internalization in a Thyrocyte Cell Line
Abstract:
Using fluorescent membrane markers, we have previously shown that extracellular ATP stimulates both exocytosis and membrane internalization in the Fisher rat thyroid cell line FRTL.
In this study, we examine the actions of ATP using whole-cell recording conditions that favor stimulation of membrane internalization.
ATP stimulation of the P2X(7) receptor activated a reversible, Ca(2+)-permeable, cation conductance that slowly increased in size without changes in ion selectivity.
ATP also induced a delayed irreversible decrease in cell capacitance (C(m)) that was equivalent to an 8% decrease in membrane surface area.
Addition of guanosine 5'-0-2-thiodiphosphate to the pipette solution inhibited the ATP-induced decrease in C(m) without affecting channel activation.
The effects of ATP on membrane conductance were mimicked by 2',3'-O-(4-benzoylbenzoyl)-ATP, but not by UTP, adenosine, or 2-methylthio-ATP, and were inhibited by pyridoxal phosphate-6-azophenyl-2'4'-disulfonic acid, adenosine 5'-triphosphate-2'3'-dialdehyde, and Cu(2+).
The capacitance decrease persisted in Na(+)-, Ca(2+)- and Cl(-)-free external saline or with Ca(2+)-free pipette solution.
It is concluded that ATP activation of the inotropic P2X(7) receptor stimulates membrane internalization by a mechanism that involves intracellular GTP, but does not require internal Ca(2+) or influx of Na(+) or Ca(2+) through the receptor-gated channel. | 2,490 |
Title:
Amyloid Precursor Protein (APP)/APP-like Protein 2 (APLP2) Expression Is Required to Initiate Endosome-Nucleus-Autophagosome Trafficking of Glypican-1-derived Heparan Sulfate*
Abstract:
Anhydromannose (anMan)-containing heparan sulfate (HS) derived from the proteoglycan glypican-1 is generated in endosomes by an endogenously or ascorbate-induced S-nitrosothiol-catalyzed reaction.
Processing of the amyloid precursor protein (APP) and APP-like protein 2 (APLP2) by β- and γ-secretases into amyloid β (Aβ) and Aβ-like peptides also takes place in these compartments.
Moreover, anMan-containing HS suppresses the formation of toxic Aβ assemblies in vitro.
We showed by using deconvolution immunofluorescence microscopy with an anMan-specific monoclonal antibody as well as 35S labeling experiments that expression of APP/APLP2 is required for ascorbate-induced transport of HS from endosomes to the nucleus.
Nuclear translocation was observed in wild-type mouse embryonic fibroblasts (WT MEFs), Tg2576 MEFs, and N2a neuroblastoma cells but not in APP−/− and APLP2−/− MEFs.
Transfection of APP−/− cells with a vector encoding APP restored nuclear import of anMan-containing HS.
In WT MEFs and N2a neuroblastoma cells exposed to β- or γ-secretase inhibitors, nuclear translocation was greatly impeded, suggesting involvement of APP/APLP2 degradation products.
In Tg2576 MEFs, the β-inhibitor blocked transport, but the γ-inhibitor did not.
During chase in ascorbate-free medium, anMan-containing HS disappeared from the nuclei of WT MEFs.
Confocal immunofluorescence microscopy showed that they appeared in acidic, LC3-positive vesicles in keeping with an autophagosomal location.
There was increased accumulation of anMan-containing HS in nuclei and cytosolic vesicles upon treatment with chloroquine, indicating that HS was degraded in lysosomes.
Manipulations of APP expression and processing may have deleterious effects upon HS function in the nucleus. | 2,493 |
Title:
Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance
Abstract:
Purpose ::: Growth factor receptor-bound 2 (Grb2)-mediated HER2 signaling is thought to play a critical role in gastric cancer development, progression and metastasis.
However, little is known about their expression in gastric cancer.
In this study, we try to explore their relationship with clinicopathological parameters and prognostic significance in gastric cancer patients. | 2,580 |
Title:
User-Friendly Interactive Image Segmentation Through Unified Combinatorial User Inputs
Abstract:
One weakness in the existing interactive image segmentation algorithms is the lack of more intelligent ways to understand the intention of user inputs.
In this paper, we advocate the use of multiple intuitive user inputs to better reflect a user's intention.
In particular, we propose a constrained random walks algorithm that facilitates the use of three types of user inputs: 1) foreground and background seed input, 2) soft constraint input, and 3) hard constraint input, as well as their combinations.
The foreground and background seed input allows a user to draw strokes to specify foreground and background seeds.
The soft constraint input allows a user to draw strokes to indicate the region that the boundary should pass through.
The hard constraint input allows a user to specify the pixels that the boundary must align with.
Our proposed method supports all three types of user inputs in one coherent computational framework consisting of a constrained random walks and a local editing algorithm, which allows more precise contour refinement.
Experimental results on two benchmark data sets show that the proposed framework is highly effective and can quickly and accurately segment a wide variety of natural images with ease. | 2,621 |
Title:
Sudden unilateral blindness after intracranial aneurysm surgery
Abstract:
The incidence of unilateral blindness and ophthalmoplegia after aneurysm surgery is very rare, but if it occurs, it is mainly caused by intra-operative nerve injury.
We experienced 6 cases of unilateral blindness immediately after surgery for 3 recent years.
These patients were classified into Hunt-Hess grade I to II except for one patient with III.
All patients complained of visual loss with varying degree of lid oedema and ophthalmoplegia ipsilateral to the site of surgery.
Angiographic examination of these patients revealed that the aneurysm was located at the internal carotid artery bifurcation in one case and the middle cerebral artery bifurcation in five cases.
All of them were relatively far from the optic nerve.
The aneurysm was clipped easily with minimal brain retraction via standard pterional craniotomy since the brain was slack in all cases.
In all cases, injuring the optic nerve during surgery was remote.
All patients showed evidence of retinal ischaemia on fundoscopy with or without fluorescein angiography.
The pathophysiology of this ischaemic event is unknown.
In our patients, we could exclude possible aetiological factors such as abnormal systemic and ocular conditions, causing ischaemia in intra-orbital structures, increased intracranial pressure, intra-operative hypotension, carotid atherosclerosis, and ocular vasospasm etc.
Accordingly we speculate that the complications seen in our cases were most likely related to intra-orbital ischaemia initiated by a collapse of the arterial and venous channels in the orbit and/or to direct or indirect contusion on the intra-orbital structures.
These situations could be produced by inadvertent pressure placed on the eyeball with a bulky retracted frontal skin flap.
Visual acuity in these patients ranged from no light perception to the ability to see objects and detect colour.
Their conditions were irreversible.
The degree of visual recovery seems to be dependent on the duration and severity of retinal ischaemia by orbital compression.
Unfortunately there is no satisfactory treatment.
We recommend the use of an eye shield to protect ipsilateral eyeball just before aneurysm surgery. | 2,635 |
Title:
Renal Venous Renin Determinations in the Diagnosis of Surgically Correctable Hypertension
Abstract:
Renin activity in renal vein plasma was measured in six normal subjects and 59 hypertensive patients.
The average renin value in renal venous plasma in normal subjects was the same as that found in patients with essential hypertension and renal parenchymal hypertension.
Renal venous renin levels were markedly elevated in patients with significant renal lesions who were improved by surgery but were normal in patients with insignificant renal artery stenosis.
We defined an abnormal renal vein renin level as one which is higher than 4.1 ng/ml of plasma, the highest normal, and which is also more than twice as great as the level obtained from the opposite kidney.
On 19 patients who were operated upon for renal hypertension, there were no "false positive tests," and two "false negative tests.
" One patient with essential hypertension had abnormal values by these standards.
Since occasional "false positive" and "false negative" results occur, we presently recommend that this test be used with, but not to the exclusion of, other tests of renal function in preoperative evaluations.
As experience with the test increases, and as more prospective studies are done, it may prove to be the single most useful device to predict surgical success in patients with renal artery and renal parenchymal hypertension. | 2,647 |
Title:
Apical membrane Cl-butyrate exchange: Mechanism of short chain fatty acid stimulation of active chloride absorption in rat distal colon
Abstract:
The cellular model of short chain fatty acid stimulation of electroneutral Na-Cl absorption in large intestine proposes that SCFA, following its uptake across the apical membrane, recycles and is coupled to functional Na-H and Cl-short chain fatty acid exchanges.
To establish the presence of a Cl-butyrate exchange (used as a model short chain fatty acid), studies of 36Cl and 14C-butyrate uptake across apical membrane vesicles of rat distal colon were performed.
An outward butyrate-gradient stimulated transient accumulation of 36Cl uptake that was not inhibited by pH clamping with valinomycin (a K ionophore) and FCCP (a proton ionophore).
Outward butyrate-gradient-stimulated 36Cl uptake was inhibited by 4,4′-diisothiocyanatostilbene2,2′-disulfonic acid (DIDS) with a half-maximal inhibitory concentration (IC50) of 68.4 μm, and was saturated by both increasing extravesicular Cl concentration (K m for Cl of 26.8 ±3.4 mm and a Vmax of 12.4±0.6 nmol/mg protein·9 sec) and increasing intravesicular butyrate concentration (K m for butyrate of 5.9 mm and a Vmax for Cl of 5.9 nmol/mg protein · 9 sec).
36Cl uptake was also stimulated by outward gradients of other short chain fatty acids (e.g., propionate, acetate and formate).
In contrast, an outward Cl gradient failed to enhance 14C-butyrate uptake.
Extravesicular Cl more than extravesicular butyrate enhanced 36Cl efflux from apical membrane vesicles.
These studies provide compelling evidence for the presence of an electroneutral, pH-activated, Cl-butyrate exchange which in concert with Na-H exchange is the mechanism by which butyrate stimulates electroneutral Na-Cl absorption. | 2,777 |
Title:
Distribution and sources of organochlorine pesticides in sediments of the coastal East China Sea
Abstract:
Abstract Forty-two surface sediment samples collected from the southern coastal East China Sea (ECS) were analyzed for organochlorine pesticides (OCPs).
The results showed high concentrations of DDTs and parent DDT fractions in the nearshore area, suggesting that there is still a fresh input of these species from non-point sources, probably due to the recent usage of relevant products.
However, for HCHs, the high concentrations with elevated β-HCH fraction were focused at the local major river estuaries, indicating that soils-released HCH input was mainly from the major river runoffs.
The distribution and composition of OCPs in the coastal ECS could be more prominently controlled by the direct regional inputs rather than the general natural sorption process on particulate organic carbon.
DDTs and chlordane are more important for their potential ecotoxicological risk on neighboring benthic community in the nearshore region and the local major river estuaries. | 2,782 |
Title:
Growth Performance of West African Dwarf (WAD) Sheep Fed Biodegraded <i>Enterolobium cyclocarpum</i> Based Diets
Abstract:
The performance and economics of ::: production of West African Dwarf (WAD) sheep was investigated in an experiment that ::: lasted for 70 days.
Twelve ::: male sheep averaging 9.9 kg in liveweight ::: and aged 7 - 9 months were randomly assigned to four ::: treatment groups in a completely randomized design with three animals per ::: treatment.
Chemical composition of diets, intake, liveweight gain and cost implication ::: of feeding WAD sheep with grass, a conventional concentrate, an autoclaved and ::: biodegraded Enterolobium cyclocarpum based diet were determined.
The crude protein content of Guinea grass (4.43%) ::: was relatively low compared to that of biodegraded Enterolobium cyclocarpum (14.13%). ::: Total consumption and liveweight change were not significantly different (P 0.05).
The ::: growth rate of animals fed concentrates were significantly (P 0.05) higher ::: than those on the grass diet.
Cost per Kg of feed was the highest for control and least for guinea ::: grass diet.
However, cost per unit gain was the highest for Guinea grass diet (N176.73) and least for biodegraded Enterolobium cyclocarpum diet (N72.62).
It was cheaper to produce 1 kg mutton using biodegraded EC diets than ::: control, autoclaved and guinea grass diets ::: respectively.
The results suggest that biodegrading of Enterolobium ::: cyclocarpum improved its nutrient quality, utilization and the performance ::: and economy of production of West African Dwarf sheep. | 2,808 |
Title:
Insights into lysosomal cobalamin trafficking: lessons learned from cblF disease
Abstract:
Vitamin B(12) (cobalamin) is essential in animals and humans for metabolism of methylmalonic acid, for the remethylation of homocysteine to methionine and, consequently, for all S-adenosylmethionine-dependent methylation reactions, including DNA synthesis.
In man, cobalamin deficiency leads to anemia and neurologic and cognitive impairment.
In the cblF inborn error of vitamin B(12) metabolism, free vitamin accumulates in lysosomes and cannot be converted to cofactors for mitochondrial methylmalonyl-CoA mutase and cytosolic methionine synthase.
Recent work has shown that this defect is caused by mutations in the lysosomal membrane protein LMBD1, which shows significant homology to lipocalin membrane receptors, thereby indicating that LMBD1 is a lysosomal membrane exporter for cobalamin. | 2,809 |
Title:
Don't Wait for a Sensory Level–Listen to the Symptoms: a Prospective Audit of the Delays in Diagnosis of Malignant Cord Compression
Abstract:
AIM ::: To report details concerning symptoms (especially pain) preceding the development of malignant cord compression (MCC); delays between onset/reporting of symptoms and confirmed diagnosis of MCC; accuracy of investigations carried out. ::: ::: ::: METHODS ::: A prospective observational study examined the diagnosis, management and outcome of 319 patients diagnosed with MCC at three Scottish cancer centres between January 1998-April 1999.
The process was considered from the perspectives of the patient, the GP and the hospital doctor. ::: ::: ::: RESULTS ::: At diagnosis, most patients (82%) were either unable to walk or only able to do so with help.
Pain was reported by nearly all patients interviewed (94%) and had been present for approximately 3 months (median=90 days).
It was severe in 84% of cases, with the distribution and characteristics of nerve root pain in 79%.
The site of pain did not correspond to the site of compression.
Where reported, weakness and/or sensory problems had been noticed by the patient for some time before diagnosis (median intervals 20 and 12 days, respectively).
Most patients reported early symptoms to their General Practitioner (GP) and diagnosis was established, following referral and investigation, approximately 2 months (median=66 days) later. ::: ::: ::: CONCLUSION ::: Patients who develop spinal metastases are at risk of irreversible spinal cord damage.
Weakness and sensory abnormalities are reported late and identified even later, despite patients having reported pain for a considerable time.
Patients with cancer who describe severe back or spinal nerve root pain need urgent assessment on the basis of their symptoms, as signs may occur too late.
Plain films and bone scans requested for patients in this audit predicted accurately the level of compression in only 21% and 19% of cases, respectively.
The only accurate investigation to establish the presence and site of a compressive lesion is magnetic resonance imaging (MRI).
A referral guideline based on suspicious symptoms in addition to suspicious signs is suggested. | 2,813 |
Title:
Gender and cognitive–emotional factors as predictors of pre-sleep arousal and trait hyperarousal in insomnia
Abstract:
Abstract Objective Elevated pre-sleep arousal has been consistently associated with insomnia, yet the cognitive–emotional mechanisms involved in sleep-related arousal remain unclear.
The purpose of this study was to identify predictors of pre-sleep arousal and trait hyperarousal from a set of variables that included self-reported affect, sleep-related cognitions, locus of control, and gender.
Methods Cross-sectional data were analyzed for 128 participants (89 females) who met criteria for psychophysiological insomnia and completed a set of questionnaires that included the Beliefs and Attitudes about Sleep (BAS), Positive and Negative Affect Schedule (Negative Subscale (nPANAS) and Positive Subscale (pPANAS)), Sleep Locus of Control (SLOC), Pre-Sleep Arousal Scale (PSAS), Hyperarousal Scale (HAS) and demographic information.
Step-wise regression was conducted with a set of independent variables, with PSAS and HAS serving as separate dependent variables.
Results Trait hyperarousal was associated with higher levels of both negative and positive emotionality, as well as negative beliefs about sleep, in both genders.
Pre-sleep arousal was associated with greater negative emotionality and internal sleep locus of control, varying by gender.
Among women, high pre-sleep arousal was associated with negative emotionality, while in men greater pre-sleep arousal was associated with an internal sleep locus of control.
Conclusion These findings have clinical implications, suggesting that men and women may require different cognitive targets when addressing pre-sleep arousal. | 2,850 |
Title:
The Climate and the Occurrence of Carbon Monoxide Poisoning in Taiwan
Abstract:
Taiwan is an island situated in the subtropics.
The lowest average temperature is around 15 degrees C (59 degrees F) during winter).
Despite the mild climate, carbon monoxide intoxication still occurs frequently, especially during the winter.
We studied which meteorological factor(s) affected the occurrence of carbon monoxide poisoning in Taiwan.
Retrospective data over a period from December 1, 1986, to December 31, 1991, from patients who reported with carbon monoxide poisoning to the Poison Control Center, together with meteorological data were analysed.
We found that a lower daily average temperature, especially while a special regional circulation pattern, called a 'cold front' or 'cold surge' (during winter) covers the Taiwan area, is strongly related to the occurrence of CO poisoning. | 2,981 |
Title:
How do we evaluate the economics of health care?
Abstract:
Economic evaluation has become an integral component of health service research in recent years and will no doubt become more influential.
As resources are reduced in health services, more questions are likely to be asked on the costs and benefits of new treatments.
Questions are also likely to be aimed at treatments that are currently provided.
Economics related to health care is complex and numerous methods of economic evaluation exist.
Full economic evaluation involves the assessment of both costs and outcomes and is ideal for comparing the efficiency of treatments.
Partial evaluations can also provide useful information on the contribution of component costs to treatment costs as a whole.
The aim of this review is to assess the various methods available to evaluate the economics of health care and to place in context how these methods may be used within dentistry. | 3,003 |
Title:
Effect of the accommodation-vergence conflict on vergence eye movements
Abstract:
Abstract With the broader use of stereoscopic displays, a flurry of research activity about the accommodation-vergence conflict has emerged to highlight the implications for the human visual system.
In stereoscopic displays, the introduction of binocular disparities requires the eyes to make vergence movements.
In this study, we examined vergence dynamics with regard to the conflict between the stimulus-to-accommodation and the stimulus-to-vergence.
In a first experiment, we evaluated the immediate effect of the conflict on vergence responses by presenting stimuli with conflicting disparity and focus on a stereoscopic display (i.e. increasing the stereoscopic demand) or by presenting stimuli with matched disparity and focus using an arrangement of displays and a beam splitter (i.e. focus and disparity specifying the same locations).
We found that the dynamics of vergence responses were slower overall in the first case due to the conflict between accommodation and vergence.
In a second experiment, we examined the effect of a prolonged exposure to the accommodation-vergence conflict on vergence responses, in which participants judged whether an oscillating depth pattern was in front or behind the fixation plane.
An increase in peak velocity was observed, thereby suggesting that the vergence system has adapted to the stereoscopic demand.
A slight increase in vergence latency was also observed, thus indicating a small decline of vergence performance.
These findings offer a better understanding and document how the vergence system behaves in stereoscopic displays.
We describe what stimuli in stereo-movies might produce these oculomotor effects, and discuss potential applications perspectives. | 3,027 |
Title:
Evaluation of Resistance to Ralstonia solanacearum in Tomato Genetic Resources at Seedling Stage
Abstract:
Bacterial wilt of tomatoes caused by Ralstonia solanacearum is a devastating disease that limits the production of tomato in Korea.
The best way to control this disease is using genetically resistant tomato plant.
The resistance degree to R. solanacearum was evaluated for 285 tomato accessions conserved in the National Agrobiodiversity Center of Rural Development Administration.
These accessions of tomato were originated from 23 countries.
Disease severity of tomato accessions was investigated from 7 days to 14 days at an interval of 7 days after inoculation of R. solanacearum under greenhouse conditions.
A total of 279 accessions of tomato germplasm were susceptible to R. solanacearum, resulting in wilt and death in 70 to 90% of these plants.
Two tomato accessions were moderately resistant to R. solanacearum.
Only four accessions showed high resistance against R. solanacearum.
No distinct symptom of bacterial wilt appeared on the resistant tomato germplasms for up to 14 days after inoculation of R. solanacearum.
Microscopy of resistant tomato stems infected with R. solanacearum revealed limited bacterial spread with thickening of pit membrane and gum production.
Therefore, these four resistant tomato germplasms could be used in tomato breeding program against bacterial wilt. | 3,034 |
Title:
Chinese Herbal Medicine for Dysfunctional Uterine Bleeding: a Meta-analysis
Abstract:
We conducted a systematic review to evaluate the efficacy and safety of Chinese herbal medicine (CHM) for dysfunctional uterine bleeding (DUB) by performing a meta-analysis.
Randomized controlled trials (RCTs) or quasi-RCTs comparing CHM vs no treatment, placebo, conventional western medicine (CWM), or general non-specific surgical treatment for DUB were identified by electronic and manual searches.
Trials of CHM treatments with CWM treatments were compared with CWM treatments alone.
Jadad scale and allocation concealment were used to assess the quality of included studies.
Four RCTs or quasi-RCTs involving 525 patients were included.
The methodological quality was poor in all trials except one trial.
No serious adverse events were reported in the included studies.
With the lack of trials comparing CHM with no treatment or placebo, it is impossible to accurately evaluate the efficacy of CHM.
However, CHM in these studies seem to show an encouraging comparative effectiveness with CWM.
More RCTs with a higher quality are required. | 3,363 |
Title:
Efficacy of adjuvant Immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials
Abstract:
The benefits of immunochemotherapy employing the biological response modifier polysaccharide K (PSK) for patients with curatively resected colorectal cancer was reassessed by means of a meta-analysis of data with center randomization from 1,094 patients enrolled in three clinical trials.
In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK.
The endpoints were overall survival and disease-free survival; and intent-to-treat analysis was performed without patient exclusion.
Data were analyzed using the weighted average of the individual log hazard ratios.
The overall survival risk ratio for all eligible patients was 0.71 (95% confidence interval (CI) : 0.55–0.90; P=0.006), and the disease-free survival risk ratio was 0.72 (95% CI: 0.58–0.90; P=0.003).
The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with curatively resected colorectal cancer. | 3,482 |
Title:
The Evaluation for Alterations of DOM Components from Upstream to Downstream Flow of Rivers in Toyama (Japan) Using Three-Dimensional Excitation-Emission Matrix Fluorescence Spectroscopy
Abstract:
The dissolved organic matter (DOM) is one of the important factors for controlling water quality.
The behavior and constitutions of DOM is related to the risk of human health because it is able to directly or indirectly affect the behavior, speciation and toxicity of various environmental pollutants.
However, it is not easy to know the contents of DOM components without using various complicated and time consuming analytical methods because DOM is a complex mixture and usually exists at low concentration.
Here, we describe the fluorescence properties of DOM components in water samples collected from four rivers in Toyama, Japan by means of the three-dimensional excitation-emission matrix (3DEEM) fluorescence spectroscopy.
In order to evaluate the alterations of DOM components in each of the river during the flow from upstream to downstream, the patterns of relative fluorescence intensity (RFI) at six peaks which are originated from fluorophores including humic-like and protein-like components were investigated.
The changes in the patterns of RFI values at each of the peak and the concentration of dissolved organic carbon (DOC) for each river water sample were discussed in connection with the differences of land use managements and basic water quality parameters, such as pH, EC, turbidity, Fe3+, T-N, NO3-N, T-P, PO4-P, chlorophyll a, DOC and N/P ratio.
The DOC concentrations in the water samples collected from these rivers were relatively low (0.63–1.16 mg/L).
Two main peaks which have a strong RFI value expressed a positive correlation with the DOC concentration (r = 0.557, 0.535).
However, the correlations between the RFI values for other four peaks and the DOC concentration were below 0.287.
The alterations of DOM components during the flow of a river from upstream to downstream were investigated from the changes in the patterns of RFI values for six fluorescent peaks.
It was clarified that the great increase of RFI values in peak A and peak T from river water located in urban area showed high concentration of PO4-P and Fe3+, and low N/P ratio due to the high biological activities.
The values of fluorescence index (FIX) and biological index (BIX) were as high as 1.60 and 0.72, respectively. | 3,668 |
Title:
Quality of life in higher resolution: the next generation of comparative effectiveness research in malignant hematology
Abstract:
Quality of Life (QOL) is among the most important considerations for patients facing a cancer diagnosis.[1][1] Given the high response rates and even curability of many hematologic cancers, however, QOL considerations often take a back seat to active disease treatment, particularly in the curative- | 3,758 |
Title:
NKX2.2 Suppresses Self-Renewal of Glioma-Initiating Cells
Abstract:
Glioblastoma (GBM) is the most aggressive and destructive form of brain cancer.
Animal models that can unravel the mechanisms underlying its progression are needed to develop rational and effective molecular therapeutic approaches.
In this study, we report the development of mouse models for spontaneous gliomas representing distinct progressive stages of disease that are governed by defined genetic alterations.
Neural stem/progenitor cell (NPC)-specific constitutive Ras activation in vivo plus p53 deficiency led to development of primarily anaplastic astrocytoma (grade III), whereas combined loss of p53 plus p16(Ink4a)/p19(Arf) led to development of GBM (grade IV) at 100% penetrance within 6 weeks.
These glioma models showed enhanced stem cell properties (stemness) accompanied by malignant progression.
Notably, we determined that, in our models and in human specimens, downregulation of the homeodomain transcription factor NKX2.2, which is essential for oligodendroglial differentiation, was correlated with increased tumor malignancy.
NKX2.2 overexpression by GBM-derived glioma-initiating cells (GIC) induced oligodendroglial differentiation and suppressed self-renewal capacity.
By contrast, Nkx2.2 downregulation in mouse NPCs accelerated GBM formation.
Importantly, the inhibitory effects of NXK2.2 on GIC self-renewal were conserved in human cells.
Thus, our mouse models offer pathobiologically significant advantages to investigate the nature of brain tumors, with improved opportunities to develop novel mechanism-based therapeutic approaches. | 3,782 |
Title:
Genome-scale engineering for systems and synthetic biology
Abstract:
Genome-modification technologies enable the rational engineering and perturbation of biological systems.
Historically, these methods have been limited to gene insertions or mutations at random or at a few pre-defined locations across the genome.
The handful of methods capable of targeted gene editing suffered from low efficiencies, significant labor costs, or both.
Recent advances have dramatically expanded our ability to engineer cells in a directed and combinatorial manner.
Here, we review current technologies and methodologies for genome-scale engineering, discuss the prospects for extending efficient genome modification to new hosts, and explore the implications of continued advances toward the development of flexibly programmable chasses, novel biochemistries, and safer organismal and ecological engineering. | 3,833 |
Title:
Psychotherapy as a treatment modality for psychiatric disorders: Perceptions of general public of Karachi, Pakistan
Abstract:
BackgroundPsychiatric disorders affect about 450 million individuals worldwide.
A number of treatment modalities such as psychotropic medications, psychotherapy and electroconvulsive therapy can be used to treat these disorders.
Attitudes of general public play a pivotal role in effective utilization of mental health services.
We explored the perceptions of general public of Karachi, Pakistan regarding psychotherapy.
MethodsA cross-sectional study was conducted in Karachi, Pakistan during July-August, 2008.
A three-step sampling strategy and a structured questionnaire were employed to survey knowledge and perceptions of adult general public about psychotherapy.
Descriptive statistics were used for baseline characteristics.
Logistic regression models were used to investigate any significant associations between baseline characteristics of the participants and their perceptions.
ResultsThe study sample comprised of 985 individuals (536 males; 531 financially independent) with an average age of 36.7 years (SD 13.54 years) and 12.5 years (SD 3.09 years) of education were included.
Majority (59.4%; n = 585) claimed to be aware of psychotherapy as a treatment option for psychiatric disorders but 47.5% of these (n = 278/585) failed to identify its correct definition.
Concerns voiced by the participants about psychotherapy included stigma (48.7%) and breech in confidentiality (39.5%); 60.7% opined it cost effective and 86.5% favored its use as an adjuvant modality.
A preference for psychotherapy as the treatment strategy for psychiatric disorders was demonstrated by 46.6% (n = 459/985).
Younger, more educated, financially independent and female participants were more likely to prefer psychotherapy as were those who deemed it cost effective.
ConclusionPositive attitudes regarding the acceptability, clinical utility and cost-effectiveness of psychotherapy were observed in a sample representative of general public of Karachi, Pakistan.
These findings highlight its potential utility for devising pragmatic mental health strategies in the face of limited resources. | 3,949 |
Title:
Outcome following Total Knee Arthroplasty in Obese versus Non-Obese Asian Patients
Abstract:
PURPOSE.
To compare the outcome following total knee arthroplasty (TKA) in obese and non-obese Asian patients.
METHODS.
27 obese patients were compared with 27 non-obese controls matched for age, gender, diagnosis (osteoarthritis), prosthesis, preoperative Knee Society knee and function scores, preoperative Oxford Knee Score, and follow-up duration.
All TKAs were performed by a single surgeon.
Patients were assessed at 6 months and 2 years for the range of motion, Knee Society knee and function scores, Oxford Knee Score, and Short Form-36 Health Survey (SF-36).
RESULTS.
The obese and non-obese groups did not differ significantly in pre- and post-operative variables: range of motion, Knee Society knee and function scores, Oxford Knee Score, and SF-36 score.
Using revision as an end-point, implant survival was 100%.
There were no intra- or post-operative complications in either group.
CONCLUSION.
Obese and non-obese Asian patients achieved a comparable outcome following TKA. | 4,064 |
Title:
Process of Coping with Mastectomy: a Qualitative Study in Iran
Abstract:
BACKGROUND ::: Breast cancer is the most prevalent cancer among Iranian women and mastectomy comprises 81% of surgeries for treatment of breast cancer.
Mastectomy may create feelings such as deformation or impairment in patients, cause body-image disorder, and reduce sexuality and sexual activity which in turn may entail mental disorders.
The study aimed to elaborate coping processes.
::: ::: ::: MATERIALS AND METHODS ::: A grounded theory method was used in conducting this study.
Twenty Iranian participants undergoing mastectomy were recruited with purposive sampling.
An open, semi-structured questionnaire were developed.
Obtaining consent, conversations were recorded and immediately transcribed after each session.
Data analysis was carried out with the constant comparative method using the Strauss Corbin approach. ::: ::: ::: RESULTS ::: Analyzing the collected data, the study came up with seven main categories which affected the coping process in patients with breast cancer, namely: reactions to mastectomy; loss and death contest; reconstruction of evaluation system; consent for undergoing mastectomy; reactions and troubles after loss; confrontation of loss and health; and reorganization and compatibility with changes. ::: ::: ::: CONCLUSIONS ::: The results of the study indicated: when patients become informed of their breast cancer and the necessity of undergoing mastectomy as the treatment, they probably pass through seven categories to adapt after mastectomy.
Having insight about them is likely to contribute medical personnel in leading patients to the highest degree of feeling healthy. | 4,282 |
Title:
Mass visual field investigation in 1834 persons with supposedly normal eyes
Abstract:
The visual fields of 1834 subjects with supposedly normal eyes were examined during a mass screening program with the Visual Field Analyser.
All defects were checked by means of static and kinetic perimetry.
Visual field defects were encountered in almost 2% of the subjects.
It was shown that reliable mass visual field examinations can very well be carried out in a relatively short time (6 min per two eyes).
The expenses are low and there are few false positive results (about 1‰). | 4,311 |
Title:
Dysfunctional and compensatory duality in mild cognitive impairment during a continuous recognition memory task.
Abstract:
Abstract One of the current issues of debate in the study of mild cognitive impairment (MCI) is deviations of oscillatory brain responses from normal brain states and its dynamics.
This work aims to characterize the differences of power in brain oscillations during the execution of a recognition memory task in MCI subjects in comparison with elderly controls.
Magnetoencephalographic (MEG) signals were recorded during a continuous recognition memory task performance.
Oscillatory brain activity during the recognition phase of the task was analyzed by wavelet transform in the source space by means of minimum norm algorithm.
Both groups obtained a 77% hit ratio.
In comparison with healthy controls, MCI subjects showed increased theta (p | 4,357 |
Title:
DIDS (4,4-Diisothiocyanatostilbenedisulphonic Acid) Induces Apoptotic Cell Death in a Hippocampal Neuronal Cell Line and Is Not Neuroprotective against Ischemic Stress
Abstract:
DIDS is a commonly used anion channel antagonist that is putatively cytoprotective against ischemic insult.
However, recent reports indicate potentially deleterious secondary effects of DIDS.
To assess the impact of DIDS on cellular viability comprehensively we examined neuronal morphology and function through 24 hours treatment with ACSF ± DIDS (40 or 400 µM).
Control cells were unchanged, whereas DIDS induced an apoptotic phenotype (chromatin condensation, nuclear fragmentation and cleavage of the nuclear membrane protein lamin A, expression of pro-apoptotic proteins c-Jun N-terminal kinase 3, caspase 3, and cytochrome C, Annexin V staining, RNA degradation, and oligonucleosomal DNA cleavage).
These deleterious effects were mediated by DIDS in a dose- and time-dependant manner, such that higher [DIDS] induced apoptosis more rapidly while apoptosis was observed at lower [DIDS] with prolonged exposure.
In an apparent paradox, despite a clear overall apoptotic phenotype, certain hallmarks of apoptosis were not present in DIDS treated cells, including mitochondrial fission and loss of plasma membrane integrity.
We conclude that DIDS induces apoptosis in cultured hippocampal neurons, in spite of the fact that some common hallmarks of cell death pathways are prevented.
These contradictory effects may cause false-positive results in certain assays and future evaluations of DIDS as a neuroprotective agent should incorporate multiple viability assays. | 4,573 |
Title:
Inverse problem in optical diffusion tomography . III . Inversion formulas and singular-value decomposition
Abstract:
We continue our study of the inverse scattering problem for diffuse light.
In particular, we derive inversion formulas for this problem that are based on the functional singular-value decomposition of the linearized forward-scattering operator in the slab, cylindrical, and spherical geometries.
Computer simulations are used to illustrate our results in model systems. | 4,583 |
Title:
Detection of partial deletion and partial duplication of dystrophin gene in Japanese patients with Duchenne or Becker muscular dystrophy
Abstract:
The dystrophin gene was analyzed in 59 Japanese patients with Duchenne muscular dystrophy (DMD) from 48 unrelated families, including 11 pairs of siblings, and three patients with Becker muscular dystrophy (BMD) from two unrelated families, including one pair of siblings.
The relationship between the type of gene abnormality and clinical symptoms was examined.
Twenty-seven of 50 (54.0%) unrelated DMD or BMD patients were found to have partial deletions, and five (10%) appeared to have partial duplications in the dystrophin gene.
Nine DMD patients, including three pairs of siblings, showed mental retardation, the existence of which was coincident in each pair of siblings, but deletion of an identical exon was not always related to mental retardation in unrelated patients. | 4,584 |
Title:
Reduced Abuse, Therapeutic Errors, and Diversion Following Reformulation of Extended-Release Oxycodone in 2010
Abstract:
Abstract This study evaluated changes in abuse exposures, therapeutic error exposures, and diversion into illegal markets associated with brand extended-release oxycodone (ERO) following introduction of reformulated ERO.
Original ERO and reformulated ERO street prices also were compared.
Data from the Poison Center and Drug Diversion programs of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System were used.
Quarterly rates 2 years prior to introduction of reformulated ERO (October 2008 through September 2010) were compared to quarterly rates after introduction (October 2010 through March 2012) using negative binomial regression.
Street prices were compared using a mixed effects linear regression model.
Following reformulated ERO introduction, poison center ERO abuse exposures declined 38% (95% confidence interval [CI]: 31–45) per population and 32% (95% CI: 24–39) per unique recipients of dispensed drug.
Therapeutic error exposures declined 24% (95% CI: 15–31) per population and 15% (95% CI: 6–24) per unique recipients of dispensed drug.
Diversion reports declined 53% (95% CI: 41–63) per population and 50% (95% CI: 39–59) per unique recipients of dispensed drug.
Declines exceeded those observed for other prescription opioids in aggregate.
After its introduction, the street price of reformulated ERO was significantly lower than original ERO.
Perspective This article indicates that the abuse, therapeutic errors, and diversion of ERO declined following the introduction of a tamper-resistant reformulation of the product.
Reformulating abused prescription opioids to include tamper-resistant properties may be an effective approach to reduce abuse of such products. | 4,595 |
Title:
Evidence of one-step replica symmetry breaking in a three-dimensional Potts glass model
Abstract:
We study a 7-state Potts glass model in three dimensions with first, second, and third neighbor interactions with a bimodal distribution of couplings by Monte Carlo simulations.
Our results show the existence of a spin-glass transition at a finite temperature T_c, a discontinuous jump of an order parameter at T_c without latent heat, and a non-trivial structure of the order-parameter distribution below T_c.
They are compatible with a one-step replica symmetry breaking. | 4,846 |
Title:
Cognitive Inhibition and Thought Disorder in Schizophrenia
Abstract:
In schizophrenia, inhibitory control is reported to be disturbed and has been associated with formal thought disorder (TD).
The negative priming task (NP) is used as a measure for inhibition; however, | 4,873 |
Title:
Dynamics of Protein Hydration Water
Abstract:
We present the frequency- and temperature-dependent dielectric properties of lysozyme solutions in a broad concentration regime, measured at subzero temperatures and compare the results with measurements above the freezing point of water and on hydrated lysozyme powder.
Our experiments allow examining the dynamics of unfreezable hydration water in a broad temperature range including the so-called No Man's Land (160 - 235 K).
The obtained results prove the bimodality of the hydration shell dynamics and are discussed in the context of the highly-debated fragile-to-strong transition of water. | 4,914 |
Title:
Outcomes after accelerated partial breast irradiation in patients with ASTRO consensus statement cautionary features.
Abstract:
PURPOSE ::: To evaluate outcomes among women with American Society for Radiation Oncology (ASTRO) consensus statement cautionary features treated with brachytherapy-based accelerated partial breast irradiation (APBI). ::: ::: ::: METHODS AND MATERIALS ::: Between March 2001 and June 2006, 322 consecutive patients were treated with high-dose-rate (HDR) APBI at the University of Wisconsin.
A total of 136 patients were identified who met the ASTRO cautionary criteria.
Thirty-eight (27.9%) patients possessed multiple cautionary factors.
All patients received 32 to 34 Gy in 8 to 10 twice-daily fractions using multicatheter (93.4%) or Mammosite balloon (6.6%) brachytherapy. ::: ::: ::: RESULTS ::: With a median follow-up of 60 months, there were 5 ipsilateral breast tumor recurrences (IBTR), three local, and two loco-regional.
The 5-year actuarial rate of IBTR was 4.8%±4.1%.
The 5-year disease-free survival was 89.6%, with a cause-specific survival and overall survival of 97.6% and 95.3%, respectively.
There were no IBTRs among 32 patients with ductal carcinoma in situ (DCIS) vs. 6.1% for patients with invasive carcinoma (p=0.24).
Among 104 patients with Stage I or II invasive carcinoma, the IBTR rate for patients considered cautionary because of age alone was 0% vs. 12.7% in those deemed cautionary due to histopathologic factors (p=0.018). ::: ::: ::: CONCLUSIONS ::: Overall, we observed few local recurrences among patients with cautionary features.
Women with DCIS and patients 50 to 59 years of age with Stage I/II disease who otherwise meet the criteria for suitability appear to be at a low risk of IBTR.
Patients with tumor-related cautionary features will benefit from careful patient selection. | 4,938 |
Title:
Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging.
Abstract:
Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities.
A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7).
To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term.
In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms.
In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 microm2/ms).
Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter.
Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 +/-
0.24 versus 1.15 +/-
0.09 microm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus 22.9 +/-
3.0%, p = 0.001; internal capsule, 24.0 +/-
4.44 versus 33.1 +/-
0.6% p = 0.006).
Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization.
The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants. | 4,983 |
Title:
MCRS1 overexpression, which is specifically inhibited by miR-129*, promotes the epithelial-mesenchymal transition and metastasis in non-small cell lung cancer
Abstract:
BackgroundAlthough tumor invasion and metastasis are both classical hallmarks of cancer malignancy and the major causes of poor clinical outcomes among cancer patients, the underlying master regulators of invasion and metastasis remain largely unknown.
In this study, we observed that an overexpression of microspherule protein 1 (MCRS1) promotes the invasion and metastasis of non-small cell lung cancer (NSCLC) cells.
Furthermore, we sought to systematically investigate the pathophysiological functions and related mechanisms of MCRS1.MethodsRetrovirus-mediated RNA interference was employed to knockdown MCRS1 expression in NSCLC cell lines.
Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot respectively were used to measure levels of mRNA and protein.
Further cell permeability assessment, invasion and proliferation assays were conducted to evaluate MCRS1 functions in vitro while nude mice experiments were performed to examine metastatic capability in vivo.
Microarray analysis and microRNA (miRNA) sequencing were respectively carried out for mRNA and miRNA expression profiling, while chromatin immunoprecipitation (ChIP), luciferase reporter assay, and miRNA transfection were used to investigate the interaction between MCRS1 and miRNAs.
ResultsMCRS1 knockdown induced morphological alterations, increased monolayer integrity, decreased cellular invasion and metastasis, and attenuated stemness and drug resistance among tested NSCLC cells.
The levels of MCRS1 expression were likewise correlated with tumor metastasis among NSCLC patients.
We identified differentially expressed genes after MCRS1 silencing, which included cell junction molecules, such as ZO-1, Occludin, E-cadherin, and DSG2.
However, these differentially expressed genes were not directly recognized by a transcriptional complex containing MCRS1.
Furthermore, we found that MCRS1 binds to the miR-155 promoter and regulates its expression, as well as MCRS1 promotes epithelial-mesenchymal transition (EMT), invasion, and metastasis through the up-regulation of miR-155.
Systematic investigations ultimately showed that MCRS1 was directly and negatively regulated by the binding of miR-129* to its 3’-UTR, with miR-129* overexpression suppressing the growth and invasion of NSCLC cells.
ConclusionsMiR-129* down-regulation induced MCRS1 overexpression, which promotes EMT and invasion/metastasis of NSCLC cells through both the up-regulation of miR-155 and down-regulation of cell junction molecules.
This miR-129*/MCRS1/miR-155 axis provides a new angle in understanding the basis for the invasion and metastasis of lung cancer. | 4,994 |
Title:
Evaluation of a Rapid Diagnostic Test for Yaws Infection in a Community Surveillance Setting
Abstract:
Yaws is a non-venereal treponemal infection caused by Treponema pallidum ssp.
pertenue.
The WHO has launched a worldwide control programme, which aims to eradicate yaws by 2020.
The development of a rapid diagnostic test (RDT) for serological diagnosis in the isolated communities affected by yaws is a key requirement for the successful implementation of the WHO strategy.
We conducted a study to evaluate the utility of the DPP test in screening for yaws, utilizing samples collected as part of a community prevalence survey conducted in the Solomon Islands.
415 serum samples were tested using both traditional syphilis serology (TPPA and quantitative RPR) and the Chembio DPP Syphilis Screen and Confirm RDT.
We calculated the sensitivity and specificity of the RDT as compared to gold standard serology.
The sensitivity of the RDT against TPPA was 58.5% and the specificity was 97.6%.
The sensitivity of the RDT against RPR was 41.7% and the specificity was 95.2%.
The sensitivity of the DPP was strongly related to the RPR titre with a sensitivity of 92.0% for an RPR titre of >1/16.
Wider access to DPP testing would improve our understanding of worldwide yaws case reporting and the test may play a key role in assessing patients presenting with yaws like lesions in a post-mass drug administration (MDA) setting. | 5,096 |
Title:
Histopathological Changes by the Use of Soft Reline Materials: A Rat Model Study
Abstract:
Aim ::: To assess the histopathological changes of rat palatal mucosa exposed to soft reline materials. | 5,131 |
Title:
Evaluation of carotid arteries in stroke patients using color Doppler sonography: A prospective study conducted in a tertiary care hospital in South India
Abstract:
Aims and Objectives: Cerebral ischemic stroke is life-threatening and debilitating neurological disease, it is the third leading cause of death in the world.
Studies have shown that there is a close relationship between carotid artery stenosis and ischemic cerebral vascular disease.
This study is done to assess the carotid arteries with the help of color Doppler sonography and to correlate cerebrovascular accidents.
Materials and Methods: The prospective study was carried out on 50 patients using purposive sampling technique.
Risk factors such as hypertension, diabetes mellitus, smoking, and family history were documented.
The data gathered from color Doppler examination consisted of peak systolic velocity of common carotid artery (CCA) and internal carotid artery (ICA), velocity ratios between CCA and ICA and plaque characteristics as seen on real-time image.
Statistical Analysis Used: The collected data were analyzed and presented in the form of tables, figures, graphs, and diagrams wherever necessary.
As this study deals with the only frequency distribution of various factors, so no tests of significance were applied.
Results: The highest incidence of stroke was found in the male population in the age group of 60-69 years.
Various risk factors included hypertension, diabetes mellitus, smoking, and family history.
Of 50 patients, 12 patients showed significant stenosis (>60%).
Atherosclerotic plaques were seen in 39 patients (78%).
Conclusion: Color Doppler examination is an economic, safe, reproducible, and less time-consuming method of demonstrating the cause of cerebrovascular insufficiency in extracranial carotid artery system and will guide in instituting treatment modalities. | 5,141 |
Title:
Dissociation of retinal and headcentric disparity signals in dorsal human cortex
Abstract:
Recent fMRI studies have shown fusion of visual motion and disparity signals for shape perception (Ban et al., 2012), and unmasking camouflaged surfaces (Rokers et al., 2009), but no such interaction is known for typical dorsal motion pathway tasks, like grasping and navigation.
Here, we investigate human speed perception of forward motion and its representation in the human motion network.
We observe strong interaction in medial (V3ab, V6) and lateral motion areas (MT+), which differ significantly.
Whereas the retinal disparity dominates the binocular contribution to the BOLD activity in the anterior part of area MT+, headcentric disparity modulation of the BOLD response dominates in area V3ab and V6.
This suggests that medial motion areas not only represent rotational speed of the head (Arnoldussen et al., 2011), but also translational speed of the head relative to the scene.
Interestingly, a strong response to vergence eye movements was found in area V1, which showed a dependency on visual direction, just like vertical-size disparity.
This is the first report of a vertical-size disparity correlate in human striate cortex. | 5,175 |
Title:
Specific protein dynamics near the solvent glass transition assayed by radiation-induced structural changes
Abstract:
The nature of the dynamical coupling between a protein and its surrounding solvent is an important, yet open issue.
Here we used temperature-dependent protein crystallography to study structural alterations that arise in the enzyme acetylcholinesterase upon X-ray irradiation at two temperatures: below and above the glass transition of the crystal solvent.
A buried disulfide bond, a buried cysteine, and solvent exposed methionine residues show drastically increased radiation damage at 155 K, in comparison to 100 K. Additionally, the irradiation-induced unit cell volume increase is linear at 100 K, but not at 155 K, which is attributed to the increased solvent mobility at 155 K. Most importantly, we observed conformational changes in the catalytic triad at the active site at 155 K but not at 100 K. These changes lead to an inactive catalytic triad conformation and represent, therefore, the observation of radiation-inactivation of an enzyme at the atomic level.
Our results show that at 155 K, the protein has acquired—at least locally—sufficient conformational flexibility to adapt to irradiation-induced alterations in the conformational energy landscape.
The increased protein flexibility may be a direct consequence of the solvent glass transition, which expresses as dynamical changes in the enzyme's environment.
Our results reveal the importance of protein and solvent dynamics in specific radiation damage to biological macromolecules, which in turn can serve as a tool to study protein flexibility and its relation to changes in a protein's environment. | 5,179 |
Title:
The anatomic variations of the posterior talofibular ligament associated with os trigonum and pathologies of related structures
Abstract:
PURPOSE ::: The aim of this study is to investigate the detailed anatomy of the posterior talofibular ligament (PTFL) on MR images in patients with os trigonum.
We also evaluated the pathological conditions of the PTFL, anterior talofibular ligament (ATFL), flexor hallucis longus (FHL) tendon, talus and os trigonum. ::: ::: ::: METHODS ::: Ankle MRIs of 70 patients with os trigonum (study group) and 70 patients without it (control group) were reviewed for the anatomy of the anterior and posterior fibers of PTFL.
The prevalence of PTFL and ATFL pathologies was also compared between two groups.
Additionally FHL tenosynovitis and osseous pathologies were evaluated.
::: ::: ::: RESULTS ::: The posterior fibers inserted into the lateral tubercule of the posterior process of the talus in the control group whereas if an os trigonum was present, the posterior fibers of PTFL were inserted only into the os trigonum.
The origins of anterior and posterior fibers were the medial surface of the lateral malleolus and the insertion of the anterior fibers was lateral surface of the talus posterior to the lateral malleolar facet in both groups.
There was a significant association between an abnormal PTFL, ATFL and the presence of os trigonum.
FHL tenosynovitis was higher in the study group but it did not meet the statistical significance.
The most common pathology of the talus and os trigonum was subchondral edema along the synchondrosis. ::: ::: ::: CONCLUSIONS ::: In patients with os trigonum, the posterior fibers of the PTFL were inserted herein.
In the case of an os trigonum signal alterations of ligaments were more common, which may reflect chronic instability. | 5,253 |
Title:
A case presentation of a large rhinolith.
Abstract:
Rhinolith is like a stone formation within the nasal cavity.
Although stones rarely form in the nasal cavity, the findings of calcified objects or stones anywhere within the body has long been a subject of interest.
Though infrequently observed, nasal concretions can be the source of bad smell from the nose and therefore a social concern for the patient.
The salient features of such Rhinoliths and their relevance to clinical practice are discussed and a case of a large Rhinolith is presented in this article.
So as to enable the attending clinician to be aware of this forgotten entity, which requires a high index of suspicion. | 5,355 |
Title:
Interpretation Bias in Social Anxiety as Detected by Event-Related Brain Potentials
Abstract:
Little is known about psychophysiological correlates of interpretation bias in social anxiety.
To address this issue, the authors measured event-related brain potentials (ERPs) in high and low socially anxious individuals during a task wherein ambiguous scenarios were resolved with either a positive or negative ending.
Specifically, the authors examined modulations of the P600, an ERP that peaks approximately 600 ms following stimulus onset and indexes violations of expectancy.
Low-anxious individuals were characterized by an increased P600 to negative in comparison with positive sentence endings, suggesting a positive interpretation bias.
In contrast, the high-anxious group evidenced equivalent P600 magnitude for negative and positive sentence endings, suggesting a lack of positive interpretation bias.
Similar, but less reliable results emerged in earlier time windows, that is, 200-500 ms poststimulus.
Reaction time, occurring around 900 ms poststimulus, failed to show a reliable interpretation bias.
Results suggest that ERPs can detect interpretation biases in social anxiety before the emission of behavioral responses. | 5,367 |
Title:
Gas-Phase Acidities of Nitrated Azoles as Determined by the Extended Kinetic Method and Computations
Abstract:
Making use of the extended kinetic method and the alternative method for data analysis, we have experimentally determined ΔH°acid (kcal/mol) for six mononitrated azole species (2-nitropyrrole = 337.0, 3-nitropyrrole = 335.8, 3-nitropyrazole = 330.5, 4-nitropyrazole = 329.5, 2-nitroimidazole = 327.4, and 4-nitroimidazole = 325.0).
We report an absolute uncertainty of ±2.2 kcal/mol that arises from the uncertainties of the reference acids; the relative values are known within 0.4 kcal/mol.
Combining these experimental ΔH°acid values with ΔS°acid values calculated at the B3LYP/aug-cc-pVTZ level of theory, we report ΔG°acid (kcal/mol) for the nitroazoles (2-nitropyrrole = 329.4, 3-nitropyrrole = 328.4, 3-nitropyrazole = 323.1, 4-nitropyrazole = 322.0, 2-nitroimidazole = 319.7, and 4-nitroimidazole = 317.6); the absolute uncertainties are ±2.4 kcal/mol.
In addition to the experimental studies, we have computationally investigated the gas-phase acidities and electron affinities of the azoles in this work, as well as higher-order aza- and dinitro-substituted azoles.
We discuss trends in the stabilities of the deprotonated azoles based on aza substitution and nitro group placement.
4-Nitroimidazole has already found use as the anionic component in ionic liquids, and we propose that the additional nitrated azolate ions are potential candidates for the anionic component of ionic liquids. | 5,466 |
Title:
Handling missing rows in multi-omics data integration: multiple imputation in multiple factor analysis framework
Abstract:
Background ::: In omics data integration studies, it is common, for a variety of reasons, for some individuals to not be present in all data tables.
Missing row values are challenging to deal with because most statistical methods cannot be directly applied to incomplete datasets.
To overcome this issue, we propose a multiple imputation (MI) approach in a multivariate framework.
In this study, we focus on multiple factor analysis (MFA) as a tool to compare and integrate multiple layers of information.
MI involves filling the missing rows with plausible values, resulting in M completed datasets.
MFA is then applied to each completed dataset to produce M different configurations (the matrices of coordinates of individuals).
Finally, the M configurations are combined to yield a single consensus solution. | 5,497 |
Title:
Seizures as the presenting symptom of brain tumours in children
Abstract:
Seizures were the presenting clinical symptom in 10 (12%) of 81 consecutive children with a primary brain tumour treated in a tertiary paediatric oncology unit over 5 years.
Nine patients experienced partial seizures, and in seven a waking electroencephalogram showed focal or lateralising abnormalities.
Astrocytoma was the most common tumour histology.
The delay in tumour diagnosis from the onset of seizures ranged from 2 weeks to 2 years with a mean of 6 months.
Complete resection of the tumour was the only treatment in three patients and four underwent resection followed by radiotherapy and/or chemotherapy.
Two patients died.
Three patients became seizure free receiving no antiepileptic medication and the remaining five showed a 50-80% reduction in seizures between 2 and almost 5 years following treatment. | 5,508 |
Title:
Chronic Inflammation and Cytokines in the Tumor Microenvironment
Abstract:
Acute inflammation is a response to an alteration induced by a pathogen or a physical or chemical insult, which functions to eliminate the source of the damage and restore homeostasis to the affected tissue.
However, chronic inflammation triggers cellular events that can promote malignant transformation of cells and carcinogenesis.
Several inflammatory mediators, such as TNF-α, IL-6, TGF-β, and IL-10, have been shown to participate in both the initiation and progression of cancer.
In this review, we explore the role of these cytokines in important events of carcinogenesis, such as their capacity to generate reactive oxygen and nitrogen species, their potential mutagenic effect, and their involvement in mechanisms for epithelial mesenchymal transition, angiogenesis, and metastasis.
Finally, we will provide an in-depth analysis of the participation of these cytokines in two types of cancer attributable to chronic inflammatory disease: colitis-associated colorectal cancer and cholangiocarcinoma. | 5,510 |
Title:
Preoperative Upper Endoscopy is Useful Before Revisional Bariatric Surgery
Abstract:
Background and Objectives: We hypothesized that patients who have previously had bariatric surgery and are undergoing revision to laparoscopic Roux-en-Y gastric bypass would have abnormal findings detected by upper endoscopy that could potentially influence patient management.
The procedures that are being revised include vertical banded gastroplasty, laparoscopic adjustable gastric bands, nonadjustable gastric bands and previous Roux-en-Y gastric bypass (open and laparoscopic).
Methods: We conducted a retrospective chart review of patients who previously had undergone vertical banded gastroplasty or nonadjustable gastric banding.
We preoperatively performed an upper endoscopy on all patients.
The endoscopy reports were reviewed and the findings entered into a database.
Results: Eighty-five percent of 46 patients undergoing revisional bariatric surgery had an abnormal upper endoscopy.
Eleven percent had a gastrogastric fistula.
Gastritis and esophagitis were noted in 65% and 37%, respectively.
Eleven percent of patients had band erosion, 2 from a nonadjustable band, and 5 from vertical banded gastroplasties.
Based on our findings, 65% of our patients required medical treatment.
Conclusions: Preoperative upper endoscopy provides valuable information before revisional laparoscopic bariatric surgery.
In addition to identifying patients who need preoperative medications, the preoperative upper endoscopy also provided valuable information regarding pouch size and anatomy.
Preoperative upper endoscopy should be performed by the operating surgeon on every patient undergoing revisional bariatric surgery. | 5,614 |
Title:
The association between HIV, antiretroviral therapy, and gestational diabetes mellitus
Abstract:
OBJECTIVES ::: The widespread, chronic use of antiretroviral therapy raises questions concerning the metabolic consequences of HIV infection and treatment.
Antiretroviral therapy, and specifically protease inhibitors, has been associated with hyperglycemia.
As pregnant women are vulnerable to development of hyperglycemia, the objective of this study was to explore existing literature on the relationship between HIV infection, HIV treatment, and gestational diabetes mellitus (GDM). ::: ::: ::: METHODS ::: A systematic search was conducted in six databases for articles providing data on HIV-positivity, protease inhibitor exposure, and GDM or glucose intolerance development in pregnancy.
The quality of articles was evaluated using an adapted Cochrane Collaboration bias assessment tool.
Risk ratios were generated from pooled data using meta-analysis by the Mantel-Haenszel method.
::: ::: ::: RESULTS ::: Of 891 references screened, six studies on the role of HIV-positivity, 10 on protease inhibitor use, and two on both were included.
Meta-analysis showed no significant relationship between HIV infection and the development of GDM [risk ratio 0.80, 95% confidence interval (CI): 0.47-1.37, I = 0%].
Meta-analysis of protease inhibitor exposure showed increased GDM in studies using first-generation protease inhibitors (risk ratio 2.29, 95% CI: 1.46-3.58) and studies using the strictest diagnosis criteria, the National Diabetes Data Group criteria for 3-h oral glucose tolerance test (risk ratio 3.81, 95% CI: 2.18-6.67). ::: ::: ::: CONCLUSION ::: Meta-analysis showed no significant association between HIV-positivity and GDM.
Significance of protease inhibitor use was limited to studies using the strictest diagnostic criteria for GDM.
Results are limited by high risk of bias.
Well designed prospective studies are needed to further clarify this relationship and its consequences for clinical practice. | 5,622 |
Title:
Determinants of attending antenatal care at least four times in rural Ghana: analysis of a cross-sectional survey
Abstract:
ABSTRACTBackground: Improving maternal health is a global challenge.
In Ghana, maternal morbidity and mortality rates remain high, particularly in rural areas.
Antenatal care (ANC) attendance is known to improve maternal health.
However, few studies have updated current knowledge regarding determinants of ANC attendance.
Objective: This study examined factors associated with ANC attendance in predominantly rural Ghana.
Methods: We conducted a cross-sectional study at three sites (i.e. Navrongo, Kintampo, and Dodowa) in Ghana between August and September 2013.
We selected 1500 women who had delivered within the two years preceding the survey (500 from each site) using two-stage random sampling.
Data concerning 1497 women’s sociodemographic characteristics and antenatal care attendance were collected and analyzed, and factors associated with attending ANC at least four times were identified using logistic regression analysis.
Results: Of the 1497 participants, 86% reported attending ANC at least four times, wh... | 5,682 |
Title:
High fat diet intake during pre and periadolescence impairs learning of a conditioned place preference in adulthood
Abstract:
BackgroundBrain regions that mediate learning of a conditioned place preference (CPP) undergo significant development in pre and periadolescence.
Consuming a high fat (HF) diet during this developmental period and into adulthood can lead to learning impairments in rodents.
The present study tested whether HF diet intake, consumed only in pre and periadolescence, would be sufficient to cause impairments using a CPP procedure.
MethodsRats were randomly assigned to consume a HF or a low fat (LF) diet during postnatal days (PD) 21-40 and were then placed back on a standard lab chow diet.
A 20-day CPP procedure, using HF Cheetos® as the unconditioned stimulus (US), began either the next day (PD 41) or 40 days later (PD 81).
A separate group of adult rats were given the HF diet for 20 days beginning on PD 61, and then immediately underwent the 20-day CPP procedure beginning on PD 81.ResultsPre and periadolescent exposure to a LF diet or adult exposure to a HF diet did not interfere with the development of a HF food-induced CPP, as these groups exhibited robust preferences for the HF Cheetos® food-paired compartment.
However, pre and periadolescent exposure to the HF diet impaired the development of a HF food-induced CPP regardless of whether it was assessed immediately or 40 days after the exposure to the HF diet, and despite showing increased consumption of the HF Cheetos® in conditioning.
ConclusionsIntake of a HF diet, consumed only in pre and periadolescence, has long-lasting effects on learning that persist into adulthood. | 5,684 |
Title:
The Anti-Inflammatory Drug, Nimesulide (4-Nitro-2-phenoxymethane-sulfoanilide), Uncouples Mitochondria and Induces Mitochondrial Permeability Transition in Human Hepatoma Cells: Protection by Albumin
Abstract:
Like other nonsteroidal anti-inflammatory drugs, nimesulide (4-nitro-2-phenoxymethane-sulfoanilide) triggers hepatitis in a few recipients.
Although nimesulide has been shown to uncouple mitochondrial respiration and cause hepatocyte necrosis in the absence of albumin, mechanisms for cell death are incompletely understood, and comparisons with human concentrations are difficult because 99% of nimesulide is albumin-bound.
We studied the effects of nimesulide, with or without a physiological concentration of albumin, in isolated rat liver mitochondria or microsomes and in human hepatoma cells.
Nimesulide did not undergo monoelectronic nitro reduction in microsomes.
In mitochondria incubated without albumin, nimesulide (50 μM) decreased the mitochondrial membrane potential (ΔΨ m ), increased basal respiration, and potentiated the mitochondrial permeability transition (MPT) triggered by calcium preloading.
In HUH-7 cells incubated for 24 h without albumin, nimesulide (1 mM) decreased the ΔΨ m and cell NAD(P)H and increased the glutathione disulfide/reduced glutathione ratio and cell peroxides; nimesulide triggered MPT, ATP depletion, high cell calcium, and caused mostly necrosis, with rare apoptotic cells.
Coincubation with either cyclosporin A (an MPT inhibitor) or the combination of fructose-1,6-diphosphate (a glycolysis substrate) and oligomycin (an ATPase inhibitor) prevented the decrease in ΔΨ m , ATP depletion, and cell death.
A physiological concentration of albumin abolished the effects of nimesulide on isolated mitochondria or HUH-7 cells.
In conclusion, the weak acid, nimesulide, uncouples mitochondria and triggers MPT and ATP depletion in isolated mitochondria or hepatoma cells incubated without albumin.
However, in the presence of albumin, only a fraction of the drug enters cells or organelles, and uncoupling and toxicity are not observed. | 5,694 |
Title:
Potency of Myopic Defocus in Spectacle Lens Compensation
Abstract:
PURPOSE ::: Previous studies have shown that chick eyes compensate for positive or negative lenses worn for brief periods if the chicks are in darkness the remainder of the time.
This study was undertaken to determine whether chicks can compensate for brief periods of lens wear if given unrestricted vision the remainder of the time.
Previous studies have also shown that chick eyes alternately wearing positive and negative lenses for brief periods compensate for the positive lenses.
The current study sought to determine whether brief periods of positive lens wear can outweigh daylong wearing of negative lenses. ::: ::: ::: METHODS ::: Chicks wore +6 D or +10 D lenses for between 8 and 60 min/d, in two to six periods and wore either no lenses or negative lenses for the remainder of the 12-hour daylight period.
Refraction and ultrasound biometry were performed before and after the 3-day-long experiments. ::: ::: ::: RESULTS ::: Wearing positive lenses for as little as 12 min/d (six periods of 2 minutes) with unrestricted vision the remainder of the time caused eyes to become hyperopic and reduced the rate of ocular elongation.
These effects also occurred when the scene viewed was beyond the far point of the lens-wearing eye and thus was myopically blurred.
Even when chicks wore negative lenses for the entire day except for 8 minutes of wearing positive lenses, the eyes compensated for the positive lenses, as though the negative lenses had not been worn.
When chicks wore binocular negative lenses for the entire day except for 8 minutes of wearing a positive lens on one eye and a plano lens on the other, the eye wearing the positive lens became less myopic than the eye wearing the plano lens. ::: ::: ::: CONCLUSIONS ::: Brief periods of myopic defocus imposed by positive lenses prevent myopia caused by daylong wearing of negative lenses.
This implies that periods of myopic and hyperopic defocus do not add linearly.
If children are like chicks and if the hyperopic defocus of long daily periods of reading predisposes a child to myopia, regular, brief interruptions of reading might have use as a prophylaxis against progression of myopia. | 5,707 |
Title:
Individual Mycobacterium tuberculosis Resuscitation-Promoting Factor Homologues Are Dispensable for Growth In Vitro and In Vivo
Abstract:
Mycobacterium tuberculosis possesses five genes with significant homology to the resuscitation-promoting factor (Rpf) of Micrococcus luteus.
The M. luteus Rpf is a secreted ∼16-kDa protein which restores active growth to cultures of M. luteus rendered dormant by prolonged incubation in stationary phase.
More recently, the Rpf-like proteins of M. tuberculosis have been shown to stimulate the growth of extended-stationary-phase cultures of Mycobacterium bovis BCG.
These data suggest that the Rpf proteins can influence the growth of mycobacteria; however, the studies do not demonstrate specific functions for the various members of this protein family, nor do they assess the function of M. tuberculosis Rpf homologues in vivo.
To address these questions, we have disrupted each of the five rpf-like genes in M. tuberculosis Erdman, and analyzed the mutants for their growth in vitro and in vivo.
In contrast to M. luteus, for which rpf is an essential gene, we find that all of the M. tuberculosis rpf deletion mutant strains are viable; in addition, all show growth kinetics similar to Erdman wild type both in vitro and in mouse organs following aerosol infection.
Analysis of rpf expression in M. tuberculosis cultures from early log phase through late stationary phase indicates that expression of the rpf-like genes is growth phase-dependent, and that the expression patterns of the five M. tuberculosis rpf genes, while overlapping to various degrees, are not uniform.
We also provide evidence that mycobacterial rpf genes are expressed in vivo in the lungs of mice acutely infected with virulent M. tuberculosis. | 5,733 |
Title:
Impact of Nursing Educational Program on Reducing or Preventing Postoperative Complications for Patients after Intracranial Surgery
Abstract:
Intracranial surgery means any surgery performed inside the skull to treat problems in thebrain and surrounding structures.
Aim: Evaluate the impact of nursing educational program on reducing or preventing postoperative complications for patients after intracranial surgery.
Subjects and methods: Sixty adult patients had intracranial surgery (burr hole, craniotomy and craniectomy) were included in this study.
Their age ranged from18-65 years old, fully conscious after operation.
Patients divided into two groups; control group (30 patients who received routine care) and study group (30 patients who received nursing educational program).
Three tools were used for data collection; tool I patient assessment sheet, tool II nursing educational program after intracranial surgery and tool III patient evaluation sheet.
Results: A good improvement in total knowledge scores of study group patients after application of nursing educational program.
Significant reduction and/or prevention of systemic and neurosurgical postoperative complications for study group patients after application of nursing educational | 5,788 |
Title:
Pregnancy and chiropractic: a narrative review of the literature.
Abstract:
OBJECTIVE ::: The purpose of this article is to review the literature on the topic of chiropractic care during pregnancy. ::: ::: ::: METHODS ::: A PubMed search was performed using the terms pregnancy and chiropractic.
Sources were cross-referenced to obtain further articles and research information after reviewing the articles obtained through the search. ::: ::: ::: RESULTS ::: Thirty-three references were used for this review.
The current literature reports favorable results on the use of chiropractic care throughout pregnancy. ::: ::: ::: CONCLUSIONS ::: Chiropractic evaluation and treatment during pregnancy may be considered a safe and effective means of treating common musculoskeletal symptoms that affect pregnant patients.
The scarcity of published literature warrants further research. | 5,812 |
Title:
Induction of myelodysplasia by myeloid-derived suppressor cells.
Abstract:
Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis.
Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis.
These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors.
Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33.
These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33’s immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells.
S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia.
Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif–bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype.
These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS. | 5,836 |
Title:
Iron Status and Inflammation in Early Stages of Chronic Kidney Disease
Abstract:
BACKGROUND/AIMS ::: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease.
The main pathomechanism responsible for ACD is subclinical inflammation.
The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.
The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism.
::: ::: ::: METHODS ::: The study included 69 patients.
Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid.
Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. ::: ::: ::: RESULTS ::: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients.
Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency.
In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR.
Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6.
::: ::: ::: CONCLUSION ::: Inflammation is correlated with iron status.
Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency. | 5,945 |
Title:
Impairment of insulin signalling in peripheral tissue fails to extend murine lifespan
Abstract:
Summary ::: Impaired insulin/IGF1 signalling has been shown to extend lifespan in model organisms ranging from yeast to mammals.
Here we sought to determine the effect of targeted disruption of the insulin receptor (IR) in non-neuronal tissues of adult mice on the lifespan.
We induced hemizygous (PerIRKO+/−) or homozygous (PerIRKO−/−) disruption of the IR in peripheral tissue of 15-weeks-old mice using a tamoxifen-inducible Cre transgenic mouse with only peripheral tissue expression, and subsequently monitored glucose metabolism, insulin signalling and spontaneous death rates over 4 years.
Complete peripheral IR disruption resulted in a diabetic phenotype with increased blood glucose and plasma insulin levels in young mice.
Although blood glucose levels returned to normal, and fat mass was reduced in aged PerIRKO−/− mice, their lifespan was reduced.
By contrast, heterozygous disruption had no effect on lifespan.
This was despite young male PerIRKO+/− mice showing reduced fat mass and mild increase in hepatic insulin sensitivity.
In conflict with findings in metazoans like Caenorhabditis elegans and Drosophila melanogaster, our results suggest that heterozygous impairment of the insulin signalling limited to peripheral tissues of adult mice fails to extend lifespan despite increased systemic insulin sensitivity, while homozygous impairment shortens lifespan. | 6,001 |
Title:
Mismatch Negativity Results from Bilateral Asymmetric Dipole Sources in the Frontal and Temporal Lobes
Abstract:
The event-related potential (ERP) reflecting auditory change detection (mismatch negativity, MMN) registers automatic selective processing of a deviant sound with respect to a working memory template resulting from a series of standard sounds.
Controversy remains whether MMN can be generated in the frontal as well as the temporal cortex.
Our aim was to see if frontal as well as temporal lobe dipoles could explain MMN recorded after pitch-deviants (Pd-MMN) and duration deviants (Dd-MMN).
EEG recordings were taken from 32 sites in 14 healthy subjects during a passive 3-tone oddball presented during a simple visual discrimination and an active auditory discrimination condition.
Both conditions were repeated after one month.
The Pd-MMN was larger, peaked earlier and correlated better between sessions than the Dd-MMN.
Two dipoles in the auditory cortex and two in the frontal lobe (left cingulate and right inferior frontal cortex) were found to be similarly placed for Pd- and Dd-MMN, and were well replicated on retest.
This study confirms interactions between activity generated in the frontal and auditory temporal cortices in automatic attention-like processes that resemble initial brain imaging reports of unconscious visual change detection.. The lack of interference between sessions shows that the situation is likely to be sensitive to treatment or illness effects on fronto-temporal interactions involving repeated measures. | 6,094 |
Title:
Changes in mitochondrial density and succinic dehydrogenase activity in Euglena gracilis as a function of the dependency on light for growth
Abstract:
Mitochondria from Euglena gracilis strain z grown under strictly heterotrophic conditions have higher equilibrium densities and higher succinate dehydrogenase activities than those grown in the presence of light.
There is a consistent trend toward lower mitochondrial density with increasing time of exposure to light.
Experiments reported here indicate that the development of dependency upon light for the provision of energy results in the repression of mitochondrial development with respect to both density and enzymatic activity. | 6,098 |
Title:
FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53
Abstract:
The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2), but maintains MDM2 expression as part of a negative feedback loop.
We have identified the immunophilin, 25 kDa FK506-binding protein (FKBP25), previously shown to be regulated by p53-mediated repression, as an MDM2-interacting partner.
We show that FKBP25 stimulates auto-ubiquitylation and proteasomal degradation of MDM2, leading to the induction of p53.
Depletion of FKBP25 by siRNA leads to increased levels of MDM2 and a corresponding reduction in p53 and p21 levels.
These data are consistent with the idea that FKBP25 contributes to regulation of the p53-MDM2 negative feedback loop. | 6,110 |
Title:
The antineoplastic bryostatins affect human basophils and mast cells differently
Abstract:
Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multi-potential stimulators of immune cells.
We have examined the effects of bryostatins on mediator release from human basophilic leukocytes and human tissue mast cells.
Bryostatins 1, 2, and 5 (10 to 3,000 nmol/L) induced histamine secretion from purified and unpurified peripheral blood basophils, whereas they caused no release of peptide-leukotriene C4 from these cells.
The rate of histamine release caused by bryostatin 1 was slower than that caused by anti-IgE (t1/2 +/- SEM = 38.2 +/- 4.7 minutes v 8.9 +/- 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37 degrees C, approximately 30% less at 30 degrees C, and no release at 22 degrees C or 4 degrees C).
The addition of increasing concentrations of extracellular Ca2+ to the medium caused histamine release in the presence of bryostatins.
Subeffective concentrations of bryostatins and anti-IgE produced a synergistic effect on histamine release from basophils.
Staurosporine, chelerythrine, and calphostin C (0.1 to 10 nmol/L), which are protein kinase C inhibitors, inhibited the histamine secretion activated by bryostatin 1 and tetradecanoylphorbol-acetate (TPA).
Preincubation with granulocyte-monocyte colony-stimulating factor (GM-CSF; 1 and 5 nmol/L) and interleukin-3 (IL-3; 10 ng/mL) potentiated the activation of human basophils induced by bryostatin 1.
Neither bryostatin 1 nor bryostatin 2 induced the release of histamine from mast cells isolated from human lung or skin tissues.
However, brief (10 minutes) preincubation with bryostatin 1 (3 to 300 nmol/L) potently inhibited the histamine secretion induced by anti-IgE from skin or lung mast cells.
Bryostatin 1 was a more potent (by approximately 30 times) inhibitor of IgE- mediated histamine release than was TPA.
The heterogeneous effects exerted by bryostatins on human basophils and mast cells can be of interest for those designing therapeutic trials using these agents. | 6,141 |
Title:
Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines.
Abstract:
Because regional spread to lymph nodes without systemic spread is a relatively common event in squamous cell cancer of the head and neck (SCCHN), it is possible that lymphoid-related receptors or cytokines might directly impact the growth of these tumors.
In the present study, we have shown by flow cytometry and Western blotting that the central lymphoid regulatory molecule, CD40, is expressed on the surface of all seven SCCHN tumor cell lines studied.
Tumor cell lines also expressed epidermal growth factor (EGF) receptor, MHC class I, and CD95 (Fas) but did not uniformly express other important lymphoid regulatory molecules such as CD80, CD86, or interleukin (IL) 2 receptor components.
CD40 ligation by trimeric CD40 ligand (CD40L) resulted in a 20-45% inhibition of tumor cell growth in three of seven cell lines tested.
The cytokines IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-11, and IL-15 neither inhibited nor stimulated growth in any of the cell lines tested.
EGF had pleiotropic effects on cell growth; it inhibited growth in two cell lines, stimulated growth in one cell line, and had no effect in four cell lines.
When coligation by EGF and CD40L was studied, additive or supra-additive growth inhibition was seen in four cell lines.
Three cell lines were unaffected by EGF, CD40, or coligation with both reagents.
Examination of tumor tissues from 12 previously untreated patients representing a broad spectrum of patients presenting with SCCHN demonstrated CD40 expression in all 12 tumor specimens.
This study supports the notion that CD40 is a regulatory molecule for the growth of SCCHN.
The important role of CD40-CD40L interactions in the regulation of immune cells in the lymph node and the unique high-level expression of CD40L by these immune cells lend support to the hypothesis that this ligand/receptor pair is an important mediator of cell growth in SCCHN. | 6,176 |
Title:
Effects of water temperature on the swimming and climbing behaviour of glass eels, Anguilla spp.
Abstract:
We used controlled laboratory experiments to test the hypothesis that glass eels, Anguilla spp., display distinct locomotion behaviour patterns at different water temperatures.
The threshold and peak temperatures for active swimming were lower than those for vertical climbing.
These differences in threshold and peak temperatures for swimming and climbing behaviour correspond to field observations on these eels entering freshwater rivers in Iceland.
The differences in threshold and peak temperatures account for the observations that glass eels first swim into freshwater and then later begin upstream movement over waterfalls or other barriers. | 6,341 |
Title:
A Brief Prehospital Stroke Severity Scale Identifies Ischemic Stroke Patients Harboring Persisting Large Arterial Occlusions
Abstract:
Background and Purpose— The Los Angeles Motor Scale (LAMS) is a brief 3-item stroke severity assessment measure designed for prehospital and Emergency Department use.
Methods— The LAMS and NIHSS were scored in under-12-hour acute anterior circulation ischemic stroke patients.
Stroke severity ratings were correlated with cervicocerebral vascular occlusion on CTA, MRA, and catheter angiography.
Receiver operating curves, c statistics, and likelihood ratios were used to evaluate the predictive value for vascular occlusion of stroke severity ratings.
Results— Among 119 patients, mean age was 67 (±18), 45% were male.
Time from onset to ED arrival was mean 190 minutes (range 10 to 660).
Persisting large vessel occlusions (PLVOs) were present in 62% of patients.
LAMS stroke severity scores were higher in patients harboring a vascular occlusion, median 5 (IQR 4 to 5) versus 2 (IQR 1 to 3).
Similarly, NIHSS stroke severity scores were higher in PLVO patients, 19 (14 to 24) versus 5 (3 to 7).
ROC curves demonstrate... | 6,489 |
Title:
Genetic Taste Responses to 6-n-Propylthiouracil Among Adults: a Screening Tool for Epidemiological Studies
Abstract:
Genetically mediated taste responsiveness to 6-n-propylthiouracil (PROP) has been linked to reduced acceptance of some bitter foods.
In this community-based study male (n =364) and female (n =378) adults enrolled in a self-help dietary intervention trial were screened for PROP taster status.
Respondents, aged 18–70 years, were mailed filter papers impregnated with PROP or with aspartame solutions.
They received instructions to rate taste intensity and hedonic preference using nine point category scales.
Women rated PROP as more bitter than did men.
Both sweetness and bitterness ratings were lower for older adults.
Taste responsiveness to PROP was unrelated to body mass index in women or men.
Higher bitterness ratings for PROP were weakly associated with higher sweetness ratings for aspartame, but were unrelated to sweet taste preferences.
Successful administration of PROP filter papers by mail suggests new avenues for the screening of taste phenotypes in epidemiological studies. | 6,625 |
Title:
Multiple gene genealogies and AFLPs suggest cryptic speciation and long-distance dispersal in the basidiomycete Serpula himantioides (Boletales)
Abstract:
Serpula himantioides (Boletales, Basidiomycota) produces thin resupinate basidiocarps on dead coniferous wood worldwide and causes damage in buildings as well.
In this study, we present evidence for the existence of at least three phylogenetically defined cryptic species (referred to as Sib I-III) within the morphospecies S. himantioides, a conclusion based on analyses of sequence data from four DNA regions and amplified fragment length polymorphisms (AFLPS).
A low degree of shared sequence polymorphisms was observed among the three lineages indicating a long-lasting separation.
The AFLPs revealed two additional subgroups within Sib III.
Results from mating studies were consistent with the molecular data.
In Sib III, no correspondence between genetic and geographical distance was observed among isolates worldwide, presumably reflecting recent dispersal events.
Our results indicate that at least two of the lineages (Sib II and Sib III) have wide sympatric distributions.
A population genetic analysis of Sib III isolates, scoring sequence polymorphisms as codominant SNP markers, indicates that panmictic conditions exist in the Sib III group.
This study supports the view that cryptic speciation is a common phenomenon in basidiomycete fungi and that phylogenetic species recognition can be a powerful inference to detect cryptic species.
Furthermore, this study shows that AFLP data are a valuable supplement to DNA sequence data in that they may detect a finer level of genetic variation. | 6,631 |
Title:
Dopamine Modulates Delta-Gamma Phase-Amplitude Coupling in the Prefrontal Cortex of Behaving Rats
Abstract:
Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex functioning.
To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial prefrontal cortex (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light.
LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations.
Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection.
The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma.
The results, albeit preliminary due to the low number of animals studied (N=3), suggest that the dopamine-mediated modification of the frequencies involved in the comodulation may be a mechanism by which this neurotransmitter regulates mPFC functioning. | 6,639 |
Title:
The Hellenic type of nondeletional hereditary persistence of fetal hemoglobin results from a novel mutation (g.-109G>T) in the HBG2 gene promoter
Abstract:
Nondeletional hereditary persistence of fetal hemoglobin (nd-HPFH), a rare hereditary condition resulting in elevated levels of fetal hemoglobin (Hb F) in adults, is associated with promoter mutations in the human fetal globin (HBG1 and HBG2) genes.
In this paper, we report a novel type of nd-HPFH due to a HBG2 gene promoter mutation (HBG2:g.-109G>T).
This mutation, located at the 3′ end of the HBG2 distal CCAAT box, was initially identified in an adult female subject of Central Greek origin and results in elevated Hb F levels (4.1%) and significantly increased Gγ-globin chain production (79.2%).
Family studies and DNA analysis revealed that the HBG2:g.-109G>T mutation is also found in the family members in compound heterozygosity with the HBG2:g.-158C>T single nucleotide polymorphism or the silent HBB:g.-101C>T β-thalassemia mutation, resulting in the latter case in significantly elevated Hb F levels (14.3%).
Electrophoretic mobility shift analysis revealed that the HBG2:g.-109G>T mutation abolishes a transcription factor binding site, consistent with previous observations using DNA footprinting analysis, suggesting that guanine at position HBG2/1:g.-109 is critical for NF-E3 binding.
These data suggest that the HBG2:g-109G>T mutation has a functional role in increasing HBG2 transcription and is responsible for the HPFH phenotype observed in our index cases. | 6,736 |
Title:
Factors influencing the adoption of a healthy eating campaign by federal cross-sector partners: a qualitative study
Abstract:
The Eat Well Campaign (EWC) was a social marketing campaign developed by Health Canada and disseminated to the public with the help of cross-sector partners.
The purpose of this study was to describe factors that influenced cross-sector partners’ decision to adopt the EWC.
Thematic content analysis, based primarily on an a priori codebook of constructs from Roger’s diffusion of innovations decision process model, was conducted on hour-long semi-structured telephone interviews with Health Canada’s cross-sector partners (n = 18).
Dominant themes influencing cross-sector partners’ decision to adopt the EWC were: high compatibility with the organization’s values; being associated with Health Canada; and low perceived complexity of activities.
Several adopters indicated that social norms (e.g., knowing that other organizations in their network were involved in the collaboration) played a strong role in their decision to participate, particularly for food retailers and small organizations.
The opportunity itself to work in partnership with Health Canada and other organizations was seen as a prominent relative advantage by many organizations.
Adopters were characterized as having high social participation and positive attitudes towards health, new ideas and Health Canada.
The lack of exposure to the mass media channels used to diffuse the campaign and reserved attitudes towards Health Canada were prominent obstacles identified by a minority of health organizations, which challenged the decision to adopt the EWC.
Most other barriers were considered as minor challenges and did not appear to impede the adoption process.
Understanding factors that influence cross-sector adoption of nutrition initiatives can help decision makers target the most appropriate partners to advance public health objectives.
Government health agencies are likely to find strong partners in organizations that share the same values as the initiative, have positive attitudes towards health, are extremely implicated in social causes and value the notion of partnership. | 6,755 |
Title:
Immunohistochemical and clinicopathological correlation of the metastasis-associated gene 1 (MTA1) expression in benign and malignant pancreatic endocrine tumors
Abstract:
Pancreatic endocrine tumors are rare tumors with unpredictable clinical behavior.
No histological features or immunohistochemical markers reliably predict malignant progression and the molecular basis of progression of pancreatic endocrine tumors remains unknown.
The metastasis-associated gene 1 is thought to play a role in transcription repression and estrogen receptor interaction and is overexpressed in several human cancers, including endocrine neoplasms.
The purpose of this study was to analyze the expression of metastasis-associated gene 1 in pancreatic endocrine tumors for its possible role in malignant progression.
Twenty-seven pancreatic endocrine tumors were identified from our archive.
The mean age at presentation was 57 years (range 28-86); the male/female ratio was 1.25 to 1, and the mean size was 4.5 cm (0.1-18 cm).
The clinical follow-up data were examined and tumors were classified according to the 2004 World Health Organization criteria as benign behavior (WHO 1.1), uncertain behavior (WHO 1.2), well-differentiated endocrine carcinoma (WHO 2), and poorly differentiated endocrine carcinoma (WHO 3).
Histopathological and immunohistochemical stains were evaluated and metastasis-associated gene 1 expression scored semiquantitatively as absent (1+), weak (2+), moderate (3+), or strong (4+).
Statistical analysis was performed using Kruskal-Wallis nonparametric analysis of variance with a significance level of 0.05.
Metastasis-associated gene 1 expression was significantly higher in malignant tumors (n=17) with a mean staining intensity of 3.8 compared with 2.9 in benign tumors (n=10, P=0.046).
The expression levels were significantly associated with WHO class (P=0.028), as well as size of tumor (P=0.029), and mitotic rate (P=0.035).
Metastasis-associated gene 1 expression was associated with local invasion with borderline significance (0.062).
We show that metastasis-associated gene 1 expression is significantly associated with malignant behavior in pancreatic endocrine tumors.
This may suggest a potential role for metastasis-associated gene 1 in the malignant progression and metastasis and its use as biomarker for malignant pancreatic endocrine tumors. | 6,776 |
Title:
Sterol synthesis. A simplified method for the synthesis of 32-oxygenated derivatives of 24,25-dihydrolanosterol.
Abstract:
A simplified method is described for the preparation of 14 alpha-hydroxymethyl-4,4-dimethyl-5 alpha-cholest-8-en-e beta-ol, 14 alpha-hydroxymethyl-4,4-dimethyl-5 alpha-cholest-7-en-3 beta-ol, and 14 alpha-hydroxymethyl-4,4-dimethyl-5-alpha-cholest-6-en-3 beta-ol from commercial lanosterol.
This method represents a modification of the approach introduced by Fried and co-workers (Fried, J., J. W. Brown, and L. Borkenhagen.
1965.
Tetrahedron Lett. 2499-2504). | 6,789 |
Title:
M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice
Abstract:
Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity.
We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656).
In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation.
Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment.
The number of CD11b+ F4/80+ CD11c− CD206+ (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice.
These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α.
rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue.
These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice.
Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages.
::: ::: IMPORTANCE HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research.
Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus.
We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism observed following rVV-N25 treatment. | 6,887 |
Title:
A comparative study on the effect of rosemary extract and sodium ascorbate on lipid and pigment oxidative stability of liver pate
Abstract:
A comparative study on the antioxidant effect of rosemary extract (RE) and sodium ascorbate (SA) on lipid and colour oxidation of liver pâté made of lard and pork liver was done.
During the 48 hour experimental time all the pâtés were wrapped in a foil and stored in cold room of 3.5°C under light of 1000 lux.
Colour stability was monitored by instrumental colour measurement (CIE L*a*b* colour space) whereas lipid stability was measured by the determination of the 2-thiobarbituric acid reactive substances (TBARS).
In the present study RE doses range (0,125, 250, 375 and 500 ppm) showed no significant (p>0.05) and linear effect on colour stability.
However thez RE revealed a significant effect (p<0.05) against lipid oxidation and linearly reduces the TBARS number.
The added SA doses (0, 250, 500, 750 and 1000 ppm) revealed significant (p<0.05) and linear effect in reducing discoloration.
However the studied SA dose ranges showed no significant (p>0.05) effect on TBARS number.
In this study RE was showed better performance against lipid oxidation and SA was potent against discoloration.
The effect of the added spices used in manufacturing of the studied product showed no significant (p>0.05) effect against lipid and color oxidation.
However the added spices revealed possible antagonistic and synergetic relationship with the studied the antioxidant systems (RE & SA). | 6,902 |
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