Genetic variation of 20 autosomal STRs in Jats belonging to Delhi, India.
The present study based on 20 autosomal STR polymorphism reveals the genetic diversity of the Jat population of Delhi, India (n = 120). A total of 240 alleles were observed for this study. The allele frequency ranged from 0.004 to 0.508. The studied loci followed the Hardy-Weinberg equilibrium (HWE), and the heterozygosity ranged from 0.658 to 0.908. The locus Penta-E was found the most polymorphic and discriminating in the studied population with the value 0.910 and 0.981, respectively, whereas the locus TPOX was found least polymorphic and discriminating with the value 0.612 and 0.833, respectively. The combined paternity index (CPI) was 1.46 × 109, and the probability of match (CPm) was 2.68 × 10-25 for all 20 autosomal STR loci. The generated data adds to the Indian population database. It will be used for forensic purposes and in other population-based genetic studies.


Dynamics of in vitro intermediate filament length distributions.
An aggregation model with explicit expression of association rate constants is considered to study in vitro type III intermediate filament length distribution dynamics. Different assumptions on the properties of filaments and probability of aggregation are considered, leading to four models. Fitting of model responses to experimental data leads to the identification of the most appropriate model to represent each time point of the assembly. A combination of models allows the construction of a mixed model that represents well the complete assembly dynamics: it is found that the rate constants decrease with respect to filament size when the aggregation involves at least one short filament, whereas for longer filaments they are almost independent of size. The flexible nature of filaments is thus important in the assembly of intermediate filaments.


Pulmonary valve reconstruction for acquired pulmonary regurgitation in patients with treated congenital heart disease.
Pulmonary valve regurgitation is a common problem after relief of right ventricular outflow tract (RVOT) obstruction with a transannular patch. Pulmonary valve replacement with a homograft or xenograft is the routine treatment. Longevity of biological valves and the availability of homografts are limited. Alternatives to restore RVOT competence are evaluated. The goal of this study was to present intermediate-term results for pulmonary valve reconstruction (PVr) in patients with severe regurgitation. PVr was performed in 24 patients (August 2006‒July 2018). We analysed perioperative data, pre- and postoperative cardiac magnetic resonance (CMR) imaging studies, freedom from valve replacement and risk factors for pulmonary valve dysfunction. The underlying diagnoses were tetralogy of Fallot (n = 18, 75%), pulmonary stenosis (n = 5, 20.8%) and the double outlet right ventricle post banding procedure (n = 1, 4.2%). The median age was 21.5 (14.8-23.7) years. Main (n = 9, 37.5%) and branch pulmonary artery procedures (n = 6, 25%) and surgery of the RVOT (n = 16, 30.2%) were often part of the reconstruction. The median follow-up after the operation was 8.0 (4.7-9.7) years. Freedom from valve failure was 96% at 2 and 90% at 5 years. The mean longevity of the reconstructive surgery was 9.9 years (95% confidence interval: 8.8-11.1 years). CMR before and 6 months after surgery showed a reduction in the regurgitation fraction [41% (33-55) vs 20% (18-27) P = 0.00] and of the indexed right ventricular end-diastolic volume [156 ml/m2 (149-175) vs 116 ml/m2 (100-143), P = 0.004]. Peak velocity across the pulmonary valve (determined by CMR) half a year after surgery was 2.0, unchanged. PVr can be achieved with acceptable intermediate-term results and may delay pulmonary valve replacement.


Minimally invasive plate osteosynthesis in distal radius fractures with metaphyseal extension: A series of 13 cases.
To evaluate objective and subjective outcomes after minimally invasive volar locked plate fixation of distal radius fractures with metaphyseal extension, we retrospectively evaluated 13 patients with unstable distal radius fractures with metaphyseal extension, treated by minimally invasive volar locked plating. Patients' average age was 41 years. Two volar incisions, 2 to 3cm long, were made; indirect reduction was performed and a volar locked T-plate was placed submuscularly under fluoroscopy guidance. Twelve fractures healed after an average of 2.46 months; one patient needed revision due to a new injury. The plate had to be removed in one patient. On X-rays, radial height averaged 12.78mm, radial inclination averaged 21.34° and volar tilt averaged 8.22°. Flexion averaged 75°, extension 71.5°, pronation 82.08° and supination 83.08°. Grip strength averaged 83.75% of the contralateral wrist. The DASH score averaged 13.91 points and pain assessed on VAS averaged 0.92 points. In unstable distal radius fractures with metaphyseal extension, minimally invasive plate osteosynthesis using volar locked plates led to good reduction and stable fixation, with low pain levels, and good functional and esthetic results. Indirect reduction techniques, fluoroscopy, and restoration of radial length, rotation and alignment, are necessary to achieve these outcomes. IV.


Congenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5.
The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two protein isoforms, Stx5 Long (Stx5L) from the first starting methionine and Stx5 Short (Stx5S) from an alternative starting methionine at position 55. In this study, we identify a human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform. Patients suffer from an early fatal multisystem disease, including severe liver disease, skeletal abnormalities and abnormal glycosylation. Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking. Measurements of cognate binding SNAREs, based on biotin-synchronizable forms of Stx5 (the RUSH system) and Förster resonance energy transfer (FRET), revealed that the short isoform of Stx5 is essential for intra-Golgi transport. Alternative starting codons of Stx5 are thus linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking.


Delayed posthypoxic leukoencephalopathy: a case series and review of the literature.
Delayed posthypoxic leukoencephalopathy (DPHL) is a rare and underrecognized entity where patients manifest a neurological relapse after initial recovery from an acute hypoxic episode. We sought to describe the magnetic resonance imaging (MRI) findings in a group of patients with DPHL and review the available literature. Retrospective case series including patients who presented with neurological and/or psychiatric symptoms after recovery from an acute hypoxic episode. The history and clinical presentation were reviewed from the electronic medical records. MRI scans were evaluated from the picture archiving and communication system. We performed a comprehensive review of the English medical literature for prior published cases of DPHL and describe the key imaging findings that have been reported related to this condition. A total of five patients were identified, including four patients with respiratory failure due to drug overdoses from benzodiazepines, opioids, and/or barbiturates, and one patient who presented after cardiopulmonary arrest due to pulmonary embolism. All patients showed diffuse, extensive, and confluent white matter signal abnormalities including prominent restricted diffusion, extending to the subcortical white matter and respecting the U-fibers. There was no gyral edema or contrast enhancement. In one case histopathology was available, which highlighted patchy subcortical myelin loss with sparing of U-fibers and demonstrated prominent macrophage/microglial inflammation with extensive axonal damage. Of the other four patients, two were at their neurological baselines and two had persistent neurological deficits at the time of discharge. The described constellation of MRI findings is highly suggestive of DPHL in the appropriate clinical setting.


Expression of genes encoding for enzymes associated with O-GlcNAcylation in endometrial carcinomas: clinicopathologic correlations.
O-GlcNAcylation is an abundant modification of cellular proteins which consist of single N-acetylglucosamine residues attached by O-linkage to serine or threonine residues. Abnormal O-GlcNAcylation seems to be a feature of malignant cancer cells. The aim of the present study was to determine the relationship between the expression of genes encoding O-GlcNAc cycling enzymes (OGT and MGEAS) and clinicopathological parameters of endometrial carcinomas. The mRNA expression levels of O-GlcNAc cycling enzymes in series of 76 samples of endometrial carcinoma were studied by real time RT-PCR method. The OGT and MGEA5 mRNA expression was significantly higher in tumors of higher histological grade than in well-differentiated tumors. Statistically significant association was found between OGT and MGEA5 mRNA expression and depth of myometrial invasion. Both OGT and MGEA5 expression profiles showed no significant association with the clinical stage of endometrial cancer. O-GlcNAcylation may be an important regulatory modification involved in endometrial cancer pathogenesis but the actual significance of this modification for endometrial cancer progression needs to be investigated further.


Increased expression of FOXD1 is associated with cervical node metastasis and unfavorable prognosis in oral squamous cell carcinoma.
Previous studies suggest that FOXD1 is involved in tumorigenesis and closely related to the patients' poor outcome in human cancer. However, its expression pattern in primary oral squamous cell carcinoma (OSCC) remains uncovered. In this study, we tried to explore the expression pattern of FOXD1 and its clinicopathological significance in primary OSCC. Data mining and analysis on FOXD1 mRNA expression in OSCC samples were performed using publicly available databases. Its protein expression was supervised by immunohistochemistry in a retrospective cohort containing 58 primary OSCC samples. Furthermore, the potential associations between FOXD1 expression and various clinicopathological characteristics and patients' survival were further investigated. Bioinformatic analysis indicated that FOXD1 mRNA abundance was obviously up-regulated in OSCC cohorts. Immunohistochemical staining results showed that FOXD1 protein was significantly up-regulated in OSCC specimens as compared to normal counterparts and its aberrant up-regulation was remarkably related to cervical lymph node metastasis (P = .0198) and decreased overall survival (P = .0281) and disease-free survival (P = .0312). Both univariate and multivariate Cox regression analysis further revealed the expression pattern of FOXD1 as an independent prognostic factor for overall survival of patients. Taken together, these findings indicate that the aberrant up-regulation of FOXD1 is related to cervical node metastasis and unfavorable prognosis in OSCC and it also may play a key role during OSCC tumorigenesis and regard as a novel diagnostic and prognostic biomarker for OSCC.


Review of the application of pulsed electric fields (PEF) technology for food processing in China.
With the improvement of living standards, growing consumer demand for high-quality and natural foods has led to the development of new mild processes to enhance or replace conventional thermal and chemical methods for food processing. Pulsed electric fields (PEF) is an emerging and promising non-thermal food processing technology, which is ongoing from laboratory and pilot plant level to the industrial level. Chinese researchers have made tremendous advances in the potential applications of PEF for processing a wide range of food commodities over the last few years, which contributes to the current understanding and development of PEF technology. The objective of this paper is to conduct a systematic review on the achievements of PEF technology used for food processing in China and the corresponding processing principles. Research on the applicability of PEF in food processing suggests that PEF can be used alone or in combination with other methods, not only to inactivate microorganisms and extract active constituents, but also to modify biomacromolecules, enhance chemical reactions and accelerate the aging of fermented foods, which are mainly related to permeabilization of biomembranes, occurrence of electrochemical and electrolytic reactions, polarization and realignment of molecules, and reduction of activation energy of chemical reactions induced by PEF treatments. In addition, some of the most important challenges for the successful implementation of large-scale industrial applications of PEF technology in the food industry are discussed. The results bring out the benefits of both researchers and the industry.


Effects of ATRA, acitretin and tazarotene on growth and apoptosis of Tca8113 cells.
To investigate the effects of ATRA, acitretin and tazarotene on the growth and apoptosis of human tongue squamous cell carcinoma cell line Tca8113. The effect of retinoids on growth of Tca8113 cells in vitro was examined by MTT assay and Trypan blue exclusion assay. Cell cycle analysis, early apoptosis analysis with double staining with Annexin V-FITC and PI, and active caspase-3 analysis with the staining of FITC-conjugated monoclonal rabbit anti-active caspase-3 antibody were made by flow cytometer. Streptavidin-biotin complex (SABC) immunocytochemical assays were employed for the detections of Bax/Bcl-2 proteins expressions. Our results showed that the retinoids inhibited growth of Tca8113 cells in a dose- and time-dependent manner with maximal inhibition 24 h after treatment of 10(-5) mol/L. 10(-5) mol/L retinoids altered cell cycle distribution of Tca8113 cells, revealing an increase in G0/G1-phase population, a decrease in S-phase population and the inhibition of G1/S switching. 10(-5) mol/L retinoids significantly induced apoptosis of Tca8113 cells (all P < 0.05), elevated the cells population with detectable active caspase-3 (P < 0.05 for all), increased the number of cells forming Bax and decreased the number of cells forming Bcl-2 significantly (all P < 0.05). Acitretin played a most prominent role among the retinoids. It is concluded that the inhibition of cell cycle progress of Tca8113 cells by ATRA, acitretin and tazarotene is one of the possible mechanisms for proliferation arrest of Tca8113 cells elicited by the retinoids. The retinoids mediate apoptosis in Tca8113 cells that may be caspase-dependent through mitochondria pathway. High concentration retinoids inhibit growth of Tca8113 cells in vitro by interfering with proliferation and inducing apoptosis of cells. Acitretin may be an alternative medicine for the prevention and treatment of tongue squamous cell carcinoma.


Correction: Decoding Sensorimotor Rhythms during Robotic-Assisted Treadmill Walking for Brain Computer Interface (BCI) Applications.
[This corrects the article DOI: 10.1371/journal.pone.0137910.].


Piperine suppresses inflammatory fibroblast-like synoviocytes derived from rheumatoid arthritis patients Via NF-κB inhibition.
Rheumatoid Arthritis (RA) is a common autoimmune disease recognized by hyperplasia of synoviocytes and chronic joint inflammation. Activation of fibroblast-like synoviocytes (FLSs) is one of the main features of RA which can trigger inflammation leading to articular cartilage and joint destruction. Aberrant activation of NF-κB signaling cascade was found to be responsible for the high proliferation and defective apoptosis of FLSs and subsequent inflammation in RA. Piperine is a principal constituent of piper species frequently used as antitumor and anti-inflammatory natural compound. In this study we aimed to assess the anti-inflammatory effect of piperine on RA-FLS through NF-κB inhibition. FLSs were isolated from 68 RA patients and 30 healthy controls and were exposed to piperine. The main assays were MTT assay, flow cytometric analysis, PI staining, reverse transcription-PCR (RT-PCR), and ELISA. Results showed that piperine can induce the apoptosis and reduce the proliferation of RA-FLSs in vitro. Moreover, piperine directly reduced the phosphorylation of NF-kB and the expression of NF-κB target genes related to RA-FLSs proliferation (c-Myc and Cycline D1), apoptosis inhibition (Bcl2 and Bcl-xl) and inflammation (COX2, IL-1β, TNF-α,IL-6, CCL5 and CXCL10) while increasing the expression of apoptosis related ones (Bax) in vitro. Piperine also reduced the protein levels of cytokines and chemokines secreted by FLSs as a result of NF-κB inhibition. In conclusion, our results provide evidence for the anti-inflammatory capacity of piperine through inhibition of NF-κB pathway in FLSs proposing this compound as a suitable alternative for chemical treatment of RA.


Case with Brunsting-Perry-like localized subepidermal blister formations and immunoglobulin G antibodies against unidentified basement membrane zone antigen.
Brunsting-Perry type bullous pemphigoid is defined by the blister formation limited to the head and neck, and autoantibodies to type VII collagen are detected in several cases. However, the pathomechanisms and autoantigens in this condition remain unknown. We report a 20-year-old female patient with a more than 2-year history of recurrent tense blisters localized on the face with no distinct atrophic scar formation. The patient had neither extensive sun exposure nor a history suggestive of contact dermatitis. Oral betamethasone was effective on the skin lesions. Histopathology revealed subepidermal blister formation with dermal infiltrates of neutrophils. Although direct and indirect immunofluorescence tests detected immunoglobulin G antibodies to the basement membrane zone (BMZ), no known dermal or epidermal autoantigens were detected in immunoblot analyses. Therefore, this case may be a rare variant of Brunsting-Perry type localized bullous pemphigoid with autoantibodies to an undetermined BMZ antigen.


Comparison between a commercial ELISA, Rubazyme, and hemolysis-in-gel test for determination of rubella antibodies.
A commercial enzyme-linked immunosorbent assay, Rubazyme, was compared with the hemolysis-in-gel (HIG) test for antibodies to rubella in 826 sera. The results were in agreement for 99.4% of the 725 sera tested for immunity. However, the Rubazyme assay was no more efficient that either the hemagglutination-inhibition or HIG test in discriminating between sera with low levels of antibody and negative sera. Thus, it was concluded that the HIG test is the method of choice for immunity testing because of the low cost and simplicity. Rubazyme may be of value to confirm equivocal HIG results.


Neurogenic mechanisms in control of the rabbit iris sphincter muscle.
The iris sphincter muscle is supplied with cholinergic, adrenergic and substance P-containing nerve fibers, all with a possible role in the control of pupil size. The functional significance of the various nervous components in the rabbit iris sphincter muscle was examined in vitro and in vivo. The contractile response to electrical stimulation is composed of several contractions, occurring along different time scales. Single pulse stimulation produced an atropine-sensitive twitch. Pulse train stimulation revealed two successive atropine-sensitive twitches followed by a slow, long-lasting contraction, sensitive to Spantide, an antagonist of tachykinins such as substance P. A guanethidine- and phentolamine-sensitive contractile response to pulse train stimulation could be demonstrated in the presence of both atropine and Spantide. Only the Spantide-sensitive response could be completely exhausted by prolonged electrical stimulation. In vivo, neither the adrenergic nor the substance P-containing nerve fibres appeared to contribute to the miotic response to light since Spantide and guanethidine were without effect. This response was inhibited by atropine only.


Synthesis and antidiabetic evaluation of benzimidazole-tethered 1,2,3-triazoles.
Some novel benzimidazole-tethered 1,2,3-triazole derivatives (4a-r) were synthesized by a click reaction between 2-substituted 1-(prop-2-yn-1-yl)-1H-benzo[d]imidazole and in situ azide. The structures of the synthesized compounds were confirmed by spectroscopic studies (one- and two-dimensional nuclear magnetic resonance, Fourier transform infrared, and high-resolution mass spectra). The synthesized compounds were evaluated for their antidiabetic activity. Compounds 4a-r exhibited a good-to-moderate α-amylase and α-glucosidase inhibitory activity, with IC50 values ranging from 0.0410 to 0.0916 µmol/ml and 0.0146 to 0.0732 µmol/ml, respectively. Compounds 4e, 4g, and 4n were found to be most active. Furthermore, the binding conformation of the most active compounds was ascertained by docking studies.


Survival and outcome of infants 501 to 750 gm: a six-year experience.
We investigated the outcome of 60 infants with birth weight 501 to 750 gm, admitted to our neonatal intensive care unit over six years. Twenty-five infants were inborn and 35 outborn. Twenty-eight survived 28 days or longer (47%), and 24 were discharged (40%). The infants who died had a significantly increased incidence of intracranial hemorrhage, and their mothers had a significantly decreased use of tocolytic drugs and betamethasone. Of the 24 survivors, two died after discharge, leaving 22 long-term survivors. Of these, 18 (82%) were observed until 20 months to 7 years of age. Mean height and weight were near the fifth percentile until 3 years of age, then increased to the tenth to fiftieth percentiles between 4 and 6 years. Mean head circumferences always remained between the tenth and fiftieth percentiles. Mean IQ was 100.0 +/- 17.9 for the inborn and 87.2 +/- 15.1 for the outborn infants (excluding two whose IQ was less than 50). Two infants (11%) had neurologic sequelae, 12 (67%) were completely normal, and four (22%) were functional and of borderline or below average intelligence. No statistical differences were found between the inborn and outborn children. This study indicates that, with aggressive therapy, outcome of the infant with birth weight 501 to 750 gm is much improved.


Bcl-2 clearance: optimising outcomes in follicular non-Hodgkin's lymphoma.
The long median survival time of patients with follicular non-Hodgkin's lymphoma (NHL), means that the efficacy of new treatments are difficult to assess in the short term. Bcl-2 is an inhibitor of apoptosis and overexpression of the bcl-2 gene in the blood or bone marrow is a feature in up to 85% of patients with follicular NHL. Levels of bcl-2(+) cells in the peripheral blood or bone marrow therefore are a useful measure of disease status in such patients and can be detected by polymerase chain reaction (PCR). Complete bcl-2 clearance from the bone marrow (molecular remission) following autologous stem cell transplant (ASCT) for follicular NHL is considered to be an important prognostic factor for disease-free survival. Tumour cell contamination of the stem cell grafts used in ASCT is commonly associated with relapse. This can be addressed by purging the stem cell harvest prior to transplantation. Various methods of in vitro purging after stem cell collection have been shown to reduce the level of contamination but yield is invariably reduced and grafts remain bcl-2 positive. However, in vivo purging with rituximab during the process of collection has been used to obtain bcl-2-negative stem cell harvests without compromising the yield. Rituximab is a monoclonal antibody licensed for treatment of relapsed and refractory low-grade or follicular NHL. Rituximab targets the CD20 antigen, which is found on cells of the B cell lineage. When used for in vivo purging it depletes the peripheral blood of CD20-positive cells and prevents contamination by lymphoma cells. Molecular remission, as measured by bone-marrow bcl-2 clearance, has been achieved in 7/7 patients with follicular NHL at 1 year after treatment with ASCT using rituximab as an 'in vivopurse', followed by rituximab maintenance. Early clinical outcomes are also encouraging.


Evaluation of classification approaches for distinguishing brain states predictive of episodic memory performance from electroencephalography: Abbreviated Title: Evaluating methods of classifying memory states from EEG.
Previous studies have attempted to separate single trial neural responses for events a person is likely to remember from those they are likely to forget using machine learning classification methods. Successful single trial classification holds potential for translation into the clinical realm for real-time detection of memory and other cognitive states to provide real-time interventions (i.e., brain-computer interfaces). However, most of these studies-and classification analyses in general- do not make clear if the chosen methodology is optimally suited for the classification of memory-related brain states. To address this problem, we systematically compared different methods for every step of classification (i.e., feature extraction, feature selection, classifier selection) to investigate which methods work best for decoding episodic memory brain states-the first analysis of its kind. Using an adult lifespan sample EEG dataset collected during performance of an episodic context encoding and retrieval task, we found that no specific feature type (including Common Spatial Pattern (CSP)-based features, mean, variance, correlation, features based on AR model, entropy, phase, and phase synchronization) outperformed others consistently in distinguishing different memory classes. However, extracting all of these feature types consistently outperformed extracting only one type of feature. Additionally, the combination of filtering and sequential forward selection was the optimal method to select the effective features compared to filtering alone or performing no feature selection at all. Moreover, although all classifiers performed at a fairly similar level, LASSO was consistently the highest performing classifier compared to other commonly used options (i.e., naïve Bayes, SVM, and logistic regression) while naïve Bayes was the fastest classifier. Lastly, for multiclass classification (i.e., levels of context memory confidence and context feature perception), generalizing the binary classification using the binary decision tree performed better than the voting or one versus rest method. These methods were shown to outperform alternative approaches for three orthogonal datasets (i.e., EEG working memory, EEG motor imagery, and MEG working memory), supporting their generalizability. Our results provide an optimized methodological process for classifying single-trial neural data and provide important insight and recommendations for a cognitive neuroscientist's ability to make informed choices at all stages of the classification process for predicting memory and other cognitive states.


Expression, purification and guanine nucleotide binding characterization of Arabidopsis RabE1d13-185 GTPase.
Arabidopsis RabE1d subclass plays important plant-specific functions in plant growth and development, response to ethylene and defence to plant pathogen, besides their basic cellular role in membrane trafficking. In this study, we present the expression, purification, and characterization of the recombinant core domain of AtRabE1d13-185. AtRabE1d13-185 was successfully expressed in Escherichia coli and purified via two-step nickel affinity chromatography followed by gel filtration, and identified single band in SDS-PAGE. The resultant protein was functionally active, as determined by interaction with guanine nucleotide by a fluorescence-based assay. The intrinsic tryptophan of AtRabE1d13-185 showed fluorescence resonance energy transfer (FRET) effect upon forming complex with fluorescent methylanthraniloyl (mant)-GDP, but quenched when binding with non-labelled guanine nucleotide. The association rate of mantGDP with AtRabE1d13-185 was determined to be 3.48 × 10(7) s(-1) M(-1). The dissociation rates of GDP and mantGDP from the complex with AtRabE1d13-185 were similar. The koff values were determined to be 4.02 × 10(-4) s(-1) based on the FRET effect for the AtRabE1d13-185:GDP and 5.41 × 10(-4) s(-1) for mantGDP excited directly.


Expression patterns of microRNAs 155 and 451 during normal human erythropoiesis.
To clarify the roles of microRNAs (miRNAs) in erythropoiesis, the expression of miR-155, miR-221, miR-223, and miR-451 were analyzed during the differentiation of purified normal human erythroid progenitors in a liquid culture system. Cells increased almost 500-fold in a number, and differentiated to benzidine-positive mature erythroblasts. Analyses of miRNA expression using the quantitative real-time polymerase chain reaction showed that the expression level of miR-155 decreased about 200-fold, and that the expression of miR-451 increased about 270-fold during 12 days of cultures. A moderate down-regulation of miR-221 and miR-223 was observed. MiR-451 was expressed in red blood cells about 10(4)-fold more than in granulocytes, obtained from normal human peripheral blood. These observations suggest that miR-155 and miR-451 are key molecules for normal erythroid differentiation, and that quantitative assays of the two miRNAs may be a relevant method for analyzing pathological erythropoiesis.


Aspects of the reproductive ecology of four australian Hakea species (Proteaceae) in South Africa.
Four shrub species of the Australian Proteaceae (Hakea sericea, H. gibbosa, H. suaveolens and H. salicifolia) were introduced to South African fynbos shrublands between 1840 and 1860. H. sericea is highly invasive, H. gibbosa and H. suaveolens are moderately invasive and H. salicifolia is not invasive. The allocation of reproductive energy, germinability, the ability to survive fires and to germinate in burnt and unburnt areas, and the nutrient content of seeds were assessed for the four species. The information was used to investigate whether the success of H. sericea relative to the other three species could be explained by the superior expression of any trait. The most important trait which separates H. sericea from the other species is its ability to produce a large seed bank in its adopted environment in the absence of seed predators. Seed production in H. sericea shrubs with an above-ground dry mass of 8 kg is four times greater than H. gibbosa and more than 16 times that of H. suaveolens. Although H. salicifolia also produces a large seed bank, its seeds are unable to survive fires due to inadequate insulation by the small follicles. The results are compared to dispersal and seed bank data for indigenous South African Proteaceae, which have low dispersal and suffer high pre-dispersal seed predation. We suggest that potential invasives in the fynbos can be identified as species that have: (i) a potentially high seed production that is limited by specialized predators; (ii) an ability to disperse over long distances; and (iii) are pre-adapted to frequent fires and low soil nutrients. The data also support the current strategy of combatting H. sericea using specialized insect seed predators.


ER chaperone-metal interactions: links to protein folding disorders.
Chaperones in the endoplasmic reticulum play vital roles in the folding, assembly, and post-translational modification of secretory proteins and also recycle, refold, or initiate degradation of misfolded proteins. Chaperone deficiencies in either amount or function are implicated in the etiology or pathogenesis of Alzheimer's disease and other protein folding disorders of the central nervous system. In this review, we discuss evidence that chaperones become pathologic through deleterious interactions with metals and then promote protein folding disorders. The "master regulator" chaperone GRP78 in the endoplasmic reticulum is a compelling subject for investigation in this context because it is located at the hub of signaling pathways in a complex chaperone network. It has therefore been studied by several laboratories in conjunction with exposure to toxic metals. The key points of this review are that metals are implicated in the etiology or pathogenesis of Alzheimer's disease and other protein folding disorders, metals induce the expression GRP78, often associated with oxidative stress, some metals bind to GRP78, and lead (Pb) impairs GRP78 function when it binds to GRP78. If certain metals do indeed cause or promote the aggregation of toxic proteins in the central nervous system, as the available evidence indicates, the identification of the mechanisms by which they act would provide valuable leads for the development of therapies to prevent or reverse toxic protein aggregation.


Dual mechanism of the stimulant action of N,N-dimethyl-5-hydroxy-tryptamine (bufotenine) on cardiac sympathetic nerves.
The indirect sympathomimetic effects of N,N-dimethyl-5-hydroxytryptamine (bufotenine) have been analysed on the rabbit heart perfused in vitro by the Langendorff technique. Comparisons have been made with the effects of 5-hydroxytryptamine (5-HT), which activates tryptamine receptors, and dimethylphenylpiperazinium (DMPP), which stimulates nicotine receptors. Bufotenine, 5-HT and DMPP stimulated the rate and force of cardiac contraction but whereas all were powerful stimulants of cardiac rate, bufotenine and DMPP were much stronger stimulants of atrial and particularly ventricular tension than 5-HT. Responses to 5-HT were markedly reduced by perfusion of hearts with an excess of 5-HT, and those to DMPP, during perfusion with hexamethonium. A combination of 5-HT with hexamethonium was necessary to abolish the effects of bufotenine. The data suggest a dual mechanism of stimulant action of bufotenine on the cardiac sympathetic nerves of the rabbit heart involving activation of receptors sensitive to 5-HT and nicotine receptors.


Triterpenoid saponin from the bark of Guaiacum officinale L.
A new triterpenoid saponin, guaianin R (1) was isolated from the n-BuOH extract of bark of Guaiacum officinale L. It was characterized as akebonic acid-3-O-[alpha-L-rhamnopyranosyl-(1 --> 3)-beta-D-glucopyranosyl-(1 --> 3)-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranoside]-28-O-[beta-D-glucopyranosyl]-ester. The structure was established with the help of a comparative study of 1D and 2D 1H- 13C NMR methods. A number of other saponins were isolated and reported from the same species.


Foetal monitoring: a woman-centred decision-making pathway.
Many midwives continue to use continuous foetal monitoring on low risk women in labour, despite evidence based clinical guidelines to the contrary. Continuous foetal monitoring has been linked to increased rates of medical intervention during labour and birth with no improvement in long term neonatal outcomes. Midwives who used continuous foetal monitoring on low risk women in labour at two regional Queensland hospitals. This Grounded Theory study explored midwives' decision-making processes related to the use of continuous electronic foetal monitoring on low risk labouring women. Primary data were gathered in semi-structured interviews with five purposively selected midwives and concurrently analysed using Grounded Theory techniques of theoretical sampling and constant comparison. The midwives made the decision that led to continuous electronic foetal monitoring on low risk women at two key decision points during labour care; the first during the midwives' initial assessment of the woman and foetus, and the second when the midwives categorised the women as high or low risk. However, various factors impacted on these decisions including trust and staff workloads within a context of risk management and medical dominance. There was limited opportunity for women to be involved in the decision-making process about foetal monitoring and only partial information was provided prior to cardiotocography. Consistent with current clinical guidelines which recommend open, consultative discussion with the woman about foetal monitoring and a partnership approach towards decision-making following informed choice, a woman-centred foetal monitoring decision-making pathway is proposed. This pathway is applicable in midwifery education, research and clinical practice to promote both evidence based practice and woman-centred decision-making.


Doppler guided extrathoracic introducer insertion.
Recent reports have raised concern over the use of standard subclavian puncture for placement of permanent pacing leads. This study reports the initial experience of one implanter in 59 consecutive, unselected patients undergoing implantation of a variety of pacing leads in whom a simple Doppler flow detector was used to guide extrathoracic venipuncture of the lateral subclavian/axillary vein. A total of 100 leads were placed for 48 right- and 11 left-sided systems. Lead insertion by this technique was successful in all patients. One small pneumothorax and two uncomplicated arterial punctures occurred. One patient's leads were revised electively because of unacceptable loss of redundancy when standing. There have been no infections or other late complications. A simple Doppler flow detector appears to be useful in identifying the lateral subclavian/axillary vein for extrathoracic pacemaker lead placement.


Update in the Management of Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome.
Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are the most common disorders of neuromuscular transmission in clinical practice. Disorders of the neuromuscular junction (NMJ) are characterized by fluctuating and fatigable weakness and include autoimmune, toxic, and genetic conditions. Adults with NMJ disorders are most often antibody mediated, with MG being the most common, having a prevalence of approximately 1 in 10,000, and with women being affected about twice as often as men. This article focuses on advances in management of autoimmune MG and LEMS.


Analyzing the effect of pH on microalgae adhesion by identifying the dominant interaction between cell and surface.
Microalgae adhesion plays a critical role in developing effective photobioreactors for large-scale production of microalgae biofuel. This study focused on elucidating the influencing mechanism of liquid medium pH on microalgae adhesion by identifying the dominant interactions between cell and substratum using a criterion. Herein, the adhesion of three microalgae onto two substrata at a series of pH was observed using a flow chamber. The results indicated that the adhesion of freshwater Chlorella sp. onto PVC and glass and marine Chlorella sp. and N. oculata onto glass decreased with increasing pH, because these adhesions were dominated by the EL interaction, and the pH would influence the adhesion primarily by affecting the ζ potential of the cell and substratum. Whereas, the adhesion of marine Chlorella sp. and N. oculata onto PVC increased with increasing pH, because these adhesions were dominated by Lewis acid-base (AB) interaction, and the pH would influence the adhesion primarily by affecting the components of surface free energy of cell. The study demonstrated that the influencing mechanism of pH on adhesion can be conclusively elucidated by identifying the dominant interaction between the cell and the surface, and may have significant implications for predicting cell adhesion in various applications.


[Unexpected anti-inflammatory activity of rigid structure derivatives of 6-arylpyridazinone antihypertensives. I. Synthesis and activity of 4,4a-dihydro-5H-indeno[1,2c]pyridazin-3-ones].
The antihypertensive 5-methyl-6-p.cyanophenyl-4,5-dihydro-3(2H)-pyridazinone has been embodied in a rigid framework corresponding to a 4,4a-dihydro-5H-indeno[1,2-c]-3-pyridazinonic structure (II). The resulting 7-cyano derivative (IIc) was found to be devoid of antihypertensive activity. However this compound, as well as other members having structure (II), exhibited antiinflammatory properties.


Surgery with complete resection improves survival in radiooncologically treated patients with cervical lymph node metastases from cancer of unknown primary.
To assess long-term toxicity, outcome and prognostic factors after multimodal treatment of cervical lymph node metastases from cancer of unknown primary (CUP). In a retrospective study, the treatment results of 84 patients with CUP (median age 63 years, N1 n = 0, N2 n = 44, N3 n = 39, Nx n = 1), treated between 1971 and 2002 with radiotherapy (n = 84, median dose 60 Gy), platinum-based chemotherapy (n = 23) and surgery (n = 69, tonsillectomy [n = 40], neck dissection [n = 52], suprahyoid dissection [n = 18], lymph node excision [n = 14]), were analyzed. After a mean follow-up time of 25 months (ranging from 0.1 to 260 months), the 3- and 5-year overall (disease-free) survival rates were 30% (39%) and 27% (34%), respectively. 75% of individuals achieved remission, whereas 23% showed no change or progression after treatment. The 3-, 5- and 10-year local control rates were 58%, 58% and 46%, respectively. 40% of patients suffered grade 3/4 late toxicity: severe skin contracture/induration (n = 2) and severe xerostomia (n = 32). Tonsillectomy (p = 0.003) and neck dissection (p = 0.037) performed before radiotherapy significantly improved outcome. Other prognostic factors were age (p = 0.0235), extracapsular spread (n = 63; p = 0.0045), incomplete resection (n = 24; p = 0.0026), nodal disease (p = 0.0034), and distant metastases (n = 17; p = 0.0002). After multivariate analysis only extracapsular spread (p = 0.004) and tonsillectomy (p = 0.01) showed impact on survival. Irradiation of cervical lymph node metastases from CUP is an effective treatment option with acceptable late toxicity. Complete tonsillectomy and neck dissection significantly improved survival in N2/N3 disease. Extracapsular spread was the best predictor for survival and local control. Prospective studies defining a standard treatment are needed.


Physical and social characteristics and support needs of adult female childhood cancer survivors who underwent hormone replacement therapy.
Female childhood cancer survivors who develop gonadal dysfunction require female hormone replacement therapy (HRT) from puberty until menopause. However, the support provided in such cases has not been studied. We investigated the physical and social characteristics and support needs of adult female childhood cancer survivors who underwent HRT. Forty-nine adult female childhood cancer survivors completed self-administered questionnaires. We compared the clinical characteristics, health status, and social conditions between a group that underwent HRT and a group that did not, and we surveyed support needs of the group that underwent HRT. The median age of the subjects was 25.0 years (range 20-41). Twenty subjects (40.8%) underwent HRT. A significantly high number of those who underwent HRT also underwent radiation therapy (p < 0.01) and hematopoietic stem cell transplantation (p < 0.001), and none of them had a history of pregnancy or childbirth (p < 0.05). There were no significant differences in physical symptoms and social characteristics between the groups. Those who experienced anxiety regarding fertility required information about HRT, a platform to share their concerns, and psychological support and cooperation among healthcare providers. Although the subjects of this survey exhibited good social adjustment regardless of whether or not they underwent HRT, they were anxious about fertility. It is important to understand the concerns and anxieties unique to female childhood cancer survivors and to enhance psychological support in addition to providing educational support so that HRT can be administered.


Conjugation between 3D and 2D aromaticity: does it really exist? The case of carborane-fused heterocycles.
Although several synthesized icosahedral carborane fused 2D π-ring systems are known, and even considerable conjugation has been noted between them in some cases, the phenomenon itself is not fully understood. Based on the results of our computational study, it can be concluded that the 2D aromatic character of the fused (exo) five-membered ring is low, even in cases where significant conjugation was proposed in previous studies. Moreover, the carborane moiety constricts the bonding properties of the exo ring, thus prohibiting or promoting different Lewis resonance structures. These results will shed further light on the design and electronic modulation of new carborane-based materials.


Pharmacological modulation of GABA(A) receptor-mediated postsynaptic potentials in the CA1 region of the rat hippocampus.
It is unclear whether GABA(A) receptor-mediated hyperpolarizing and depolarizing synaptic potentials (IPSP(A)s and DPSP(A)s, respectively) are evoked by (a) the same populations of GABAergic interneurones and (b) exhibit similar regulation by allosteric modulators of GABA(A) receptor function. We have attempted to address these questions by investigating the effects of (a) known agonists for presynaptic receptors on GABAergic terminals, and (b) a range of GABA(A) receptor ligands, on each response. The GABA uptake inhibitor NNC 05-711 (10 microM) enhanced whereas bicuculline (10 microM) inhibited both IPSP(A)s and DPSP(A)s. (-)-Baclofen (5 microM), [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAGO; 0.5 microM), and carbachol (10 microM) caused substantial depressions (up to 99%) of DPSP(A)s that were reversed by CGP 55845A (1 microM), naloxone (10 microM) and atropine (5 microM), respectively. In contrast, 2-chloroadenosine (CADO; 10 microM) only slightly depressed DPSP(A)s. Quantitatively, the effect of each agonist was similar to that reported for IPSP(A)s. The neurosteroid ORG 21465 (1 - 10 microM), the anaesthetic propofol (50-500 microM), the barbiturate pentobarbitone (100-300 microM) and zinc (50 microM) all enhanced DPSP(A)s and IPSP(A)s. The benzodiazepine (BZ) agonist flunitrazepam (10-50 microM) and inverse agonist DMCM (1 microM) caused a respective enhancement and inhibition of both IPSP(A)s and DPSP(A)s. The BZomega1 site agonist zolpidem (10-30 microM) produced similar effects to flunitrazepam. The anticonvulsant loreclezole (1-100 microM) did not affect either response. These data demonstrate that similar populations of inhibitory interneurones can generate both IPSP(A)s and DPSP(A)s by activating GABA(A) receptors that are subject to similar allosteric modulation.


Characterization of a mutant of serotype g Streptococcus mutans strain 6715 lacking dextran-induced agglutination.
A spontaneous mutant of Streptococcus mutans 6715 (serotype g) defective in dextran-induced agglutination ability was isolated. The wild type strain and its mutant were termed as 6715-DP and 6715-DN, respectively. Both strains possessed serotype g antigen, and exerted similar sugar fermentation patterns. Strain 6715-DP was rapidly and strongly agglutinated upon addition of high molecular weight dextran, whereas the mutant strain 6715-DN was not. [14C]Dextran prepared from Leuconostoc mesenteroides dextransucrase and [14C]sucrose bound to fresh or lyophilized 6715-DP cells, but not to the mutant 6715-DN cells. However, both strains adhered to a glass surface in the presence of sucrose. Furthermore, heat-treated (100 degrees C, 10 min) cells of both strains bound cell-free glucosyltransferase, although dextran agglutination ability of strain 6715-DP was destroyed by this treatment, indicating that receptors for dextran and glucosyltransferase were different entities. Furthermore, serotype c, e, and f strains S. mutans did not agglutinate upon addition of dextran, nor did they bind [14C]dextran. However, all these strains and both 6715-DP and 6715-DN strains induced marked dental caries in SPF rats. It is concluded that dextran-induced agglutination ability is not a necessary condition for S. mutans to induce dental caries.


Respiratory syncytial virus (RSV) RNA loads in peripheral blood correlates with disease severity in mice.
Respiratory Syncytial Virus (RSV) infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.


[Bibliometric map of research carried out in Primary Care in Spain during the period 2013-2017].
To describe the Spanish scientific production of primary care during 2013-2017 and analyze their geographical distribution, impact factor, areas of research and involvement of different institutional sectors. Observational study bibliometric. The study focused on publications indexed in Medline. Journal and year of publication, first/last author, workplace and autonomous community. Later, articles were classified according to their content. The impact factor was obtained from the basis of bibliometric analysis Journal Citation Reports. Using search criteria, were selected 980 documents. The transiency rate was 78,8%. The highest proportion of articles (43.2%) came from health centers, but we observed an increase of the articles from units or research institutes (14.9% in 2013, 19.1% in 2017). Of the total, 63.3% were classified as "clinical aspects", 19.3% were published in the journal Atención Primaria, 40.6% in foreign journals and 72.4% in journals with impact factor, being this proportion significantly lower (p <0.001) in those coming from health centers (59.6%) or teaching units/management/health services (70.0%) with respect to those originated in research units/institutes (93.1%) or in universities (89.0%). In relation to population (articles/100.000 inhab.), the most productive communities were Cataluña (4.2), Aragón (3.9), e Islas Baleares (3.3). In primary care publications there is great diversity in both research areas such as in journals where published. Most are from health centers, treat clinical aspects and published in Spanish journals. Differences in the volume of scientific production between regions are observed.


Prevalence of dysphagia and risk of pneumonia and mortality in acute stroke patients: a meta-analysis.
Post-stroke dysphagia (PSD) has been associated with high risk of aspiration pneumonia and mortality. However, limited evidence on pooled prevalence of post-stroke dysphagia and influence of individual, disease and methodological factors reveals knowledge gap. Therefore, to extend previous evidence from systematic reviews, we performed the first meta-analysis to examine the pooled prevalence, risk of pneumonia and mortality and influence of prognostic factors for PSD in acute stroke. Our search was conducted in CINAHL, Cochrane Library, EMBASE, Ovid-Medline, PubMed, and Web of Science an initial search in October 2020 and a follow-up search in May 2021. Data synthesis was conducted using the Freeman-Tukey double-arcsine transformation model for the pooled prevalence rate and the DerSimonian-Lard random-effects model for prognostic factors and outcomes of PSD. The pooled prevalence of PSD was 42% in 42 studies with 26,366 participants. PSD was associated with higher pooled odds ratio (OR) for risk of pneumonia 4.08 (95% CI, 2.13-7.79) and mortality 4.07 (95% CI, 2.17-7.63). Haemorrhagic stroke 1.52 (95% CI, 1.13-2.07), previous stroke 1.40 (95% CI, 1.18-1.67), severe stroke 1.38 (95% CI, 1.17-1.61), females 1.25 (95% CI, 1.09-1.43), and diabetes mellitus 1.24 (95% CI, 1.02-1.51) were associated with higher risk of PSD. Males 0.82 (95% CI, 0.70-0.95) and ischaemic stroke 0.54 (95% CI, 0.46-0.65) were associated with lower risk of PSD. Haemorrhagic stroke, use of instrumental assessment method, and high quality studies demonstrated to have higher prevalence of PSD in the moderator analysis. Assessment of PSD in acute stroke with standardized valid and reliable instruments should take into account stroke type, previous stroke, severe stroke, diabetes mellitus and gender to aid in prevention and management of pneumonia and thereby, reduce the mortality rate. https://osf.io/58bjk/?view_only=26c7c8df8b55418d9a414f6d6df68bdb .


Greenhouse and field evaluation of isoxaflutole for weed control in maize in China.
Greenhouse and field studies were conducted to provide a reference for pre-emergence (PRE) application of isoxaflutole on maize in China. In greenhouse study, the isoxaflutole PRE application at 30 g active ingredient (a.i.) ha-1 could effectively control large numbers of weeds, especially some large-seeded broadleaves, tested in this study. The tolerance results indicated 21 maize hybrids showed different responses to isoxaflutole under greenhouse conditions. In 2015 and 2016, field experiments were conducted to determine and compare the weed control efficacy and safety to Zhengdan 958 maize with 6 herbicide treatments. In both years, isoxaflutole PRE at 100 to 250 g a.i. ha-1 was sufficient to provide satisfactory full-season control of the dominant common broadleaf and grass weeds in the field. Temporary injury to maize was observed with isoxaflutole treatments of 125, 150, and 250 g a.i. ha-1 in both years, but plants recovered within 4 to 6 wk. To maximize maize yield and provide satisfactory weed control, a range of 100 to 150 g a.i. ha-1 of isoxaflutole is recommended, depending on the soil characteristics, weather, and weed species present at the experimental site. Based on the results, isoxaflutole PRE has good potential for weed control in maize in China.


Cognitive and neurological sequelae after stereoendoscopic disconnection of a hypothalamic hamartoma. A case study.
Hypothalamic hamartomas (HH) are congenital malformations of the hypothalamus, often generating medically refractory gelastic seizures. There is great risk of progression to various complex partial and generalized seizures and of cognitive and behavioral deterioration. Hence, various surgical approaches have been introduced to resect or disconnect the HH from surrounding tissue, and stereoendoscopic disconnection has been advocated as one of the most lenient approaches to sessile HH embedded in the third ventricle. In fact, no long-term neurological or cognitive impairments have hitherto been reported after this procedure. Yet, unforeseen complications may arise in any surgical intervention on this region. We found serious deterioration of memory and reading skills by comprehensive neuropsychological assessments pre- and postoperatively in a child who, before surgery, was age-appropriate with respect to cognitive, emotional, and behavioral development. The child also contracted a permanent oculomotor paresis. Our results are discussed in light of previous relevant findings.


Influence of isotypes of disease-associated autoantibodies on the expression of natural autoantibody repertoires in humans.
Current understanding of immune network interactions mediated by immunoglobulins focuses on the role of idiotypes expressed on antibody variable regions. Idiotype interactions account significantly for the functional integrity of natural self-reactive antibody repertoires, whereas immunoglobulin isotypes are not considered to direct natural autoimmunity. Autoimmune thrombocytopenic purpura (AITP), a bleeding disorder caused by clonally restricted platelet-specific autoantibodies of the IgM or IgG isotype, is an excellent model to investigate the impact of isotype differences of immunoglobulins on the selection of natural self-reactive antibody repertoires in humans. Using specific analytical techniques to characterize the natural self-reactive antibody repertoire (i.e. quantitative immunoblotting, affinity biosensor technology), we here demonstrate that isotype differences of disease-associated autoantibodies are associated with altered natural self-reactive antibody repertoires in humans. Our data suggest that regulation of natural autoreactivity by antibody isotype might occur under certain conditions. The control of natural self-reactive antibody repertoires by immunoglobulin isotypes at a supraclonal level may provide a structural basis for non-organ-specific broad alterations of natural self-reactive antibody repertoires in organ-specific autoimmune diseases.


Effect of glycation degree on the structure and digestion properties of ovalbumin: A study of amino acids and peptides release after in vitro gastrointestinal simulated digestion.
Glycation can improve the functional properties of protein. However, in vitro and animal studies have shown that glycation induced lysine blockage and impaired protein digestibility. This study aimed to explore the effects of different glycation degree on the structure and digestive characteristics of ovalbumin. The results showed that glycation decreased the turbidity and hydrophobicity of the protein and changed the protein structure. Moreover, the results of in vitro simulated digestion revealed that glycation reduced the contents of essential amino acids and total amino acids after digestion. Glycation changed the amino acids and peptides release from the protein by resisting the digestion of digestive enzymes, especially trypsin. In conclusion, this work links glycation, protein digestibility, and the release of amino acids and peptides. This emphasizes the importance of the balance between improving properties and ensuring the digestibility of proteins during food processing.


Posterior shoulder dislocation with associated reverse Hill-Sachs lesion: clinical outcome 10 years after joint-preserving surgery.
Posterior shoulder dislocation in association with reverse Hill-Sachs lesion is a rather rare injury. Few studies reporting results after joint-preserving surgery in these cases are available. This current study presents the clinical outcomes 10 years postoperatively. In a prospective case series, we operatively treated 12 consecutive patients (all males) after posterior shoulder dislocation with associated reverse Hill-Sachs lesion using joint-preserving techniques. Patients received surgery in a single center between January 2008 and December 2011. The joint-preserving surgical procedure was chosen depending on the defect size and bone quality. The following outcome-measures were analyzed: Constant-Score, DASH-Score, ROWE-Score, and SF-12. Results 1, 5, and 10 years postoperatively were compared. Out of 12 patients, ten patients (83.3%) were followed-up with a mean follow-up interval of 10.7 years (range 9.3-12.8). The mean patient age at the time of the last follow-up was 51 years (32-66). The outcome scores at the final follow-up were: Constant 92.5 (range 70.0-100), DASH 3.2 (0.0-10.8), ROWE 91.0 (85.0-100), and SF-12 87.8 (77.5-98.3). Clinical results had improved from 1 to 5 years postoperatively and showed a tendency for even further improvement after 10 years. Joint-preserving surgical therapy of posterior shoulder dislocation provides excellent results when the morphology of the reverse Hill-Sachs lesion is respected in surgical decision-making. 223/2012BO2, 02 August 2010.


Rate of nuisance bleedings and impact on compliance to prasugrel in acute coronary syndromes.
Antiplatelet agents are critical to prevent thrombotic events in patients with acute coronary syndromes, particularly those who undergo percutaneous coronary intervention. Prasugrel is a potent P2Y(12)-adenosine diphosphate receptor antagonist that is superior to clopidogrel in such patients. Previous studies have observed that nuisance and internal bleedings were relatively frequent in patients under clopidogrel therapy and were associated with noncompliance. Furthermore, premature drug discontinuation is associated with thrombotic recurrences. The aim of the present study was to investigate the rate of nuisance or internal bleedings in patients receiving prasugrel and its relation with compliance. This prospective multicenter study included 396 patients. Bleeding events were recorded and classified as alarming, nuisance, or internal according. Compliance with prasugrel therapy was assessed. Almost half of the patients (48.5%) were included for ST-segment elevation acute coronary syndromes. During the 1-month follow-up period, 54 patients (13.6%) had bleeding events. Most bleeding events were classified as internal or nuisance (96%). Internal and nuisance bleedings were associated with high rates of prasugrel discontinuation (16.6% and 14.7%, respectively). Nuisance and internal bleedings were significantly associated with prasugrel discontinuation in multivariate analysis (odds ratio 3.1, 95% confidence interval 1.01 to 9.2, p = 0.04). The rate of major adverse cardiovascular events was 2.3%. No relation was observed between minor bleeds, compliance, and major adverse cardiovascular events. In conclusion, in the present study, minor bleedings were common during the first month after percutaneous coronary intervention and were significantly associated with prasugrel withdrawal.


Effects of age and environmental factors on semen production and semen quality of Austrian Simmental bulls.
More than 90% of the breeding stock of Austrian dual purpose Simmental cows is artificially inseminated. Knowledge of factors affecting sperm production and semen quality is of importance with regard to reproductive efficiency and thus genetic improvement as well as for the productivity and profitability of AI centers. Hence, semen data from two Austrian AI centres collected in the years 2000 and 2001 were evaluated. In total, 3625 and 3654 ejaculates from 147 and 127 AI bulls, respectively, were analysed regarding ejaculate volume, sperm concentration, percentage of viable spermatozoa in the ejaculate, total spermatozoa per ejaculate and motility. Effects accounted for were the bull (random), age of bull, collection interval, number of collection on collection day, bull handler, semen collector, temperature on day of semen collection, in the course of epididymal maturation (average temperature of days 1-11 before collection) and during spermatogenesis (average temperature of days 12-65 before collection). Age of bull significantly affected all traits (P<0.01 to P<0.001) except motility score in center 2. Ejaculate volume and total number of spermatozoa increased with age of bull while sperm concentration was lower in higher age classes (center 1). The collection team was also found to significantly influence semen quality traits. With increasing collection interval ejaculate volume and total number of spermatozoa increased significantly (P<0.05 to P<0.001) while collection intervals between 4-9 days and 1-6 days were superior with regard to sperm concentration and percentage of viable spermatozoa, respectively (P<0.10 to P<0.001). First ejaculates were superior with respect to ejaculate volumes, sperm concentrations and total number of spermatozoa per ejaculate (P<0.001). Temperature, either on day of semen collection or during epididymal maturation or spermatogenesis, had important but inconsistent effects on semen production and sperm quality. Overall, however, ambient temperatures in the range of 5-15 degrees C were found to be optimal for semen production.


Quercetin-mediated alteration in photosynthetic efficiency, sugar metabolism, elemental status, yield, and redox potential in two varieties of okra.
Quercetin is a bioactive natural compound with an antioxidative property that can potentially modify plant physiology. The current investigation aimed to gauge the effect of different concentrations of foliar spray of quercetin (0, 0.5, 1, 1.5, 2.0 mM) on several morphological and physio-biochemical performances of Abelmoschus esculentus L. (Moench.) plants under normal environmental conditions. The foliar spray on the plant leaves was applied 25 days after sowing (DAS) and continued up to 30 DAS once each day. The plants were sampled at 30 and 45 DAS to monitor several parameters. The foliar treatments of quercetin significantly upgraded all the studied parameters. The results direct that most of the traits such as growth, nutrient uptake, photosynthetic, and enzyme activities were promoted in a dose-dependent way. Quercetin application lowered the reactive oxygen species (ROS) buildup by increasing the antioxidant enzyme activities. Microscopic investigations further revealed a significant enhancement in the stomatal aperture under quercetin application. Out of several doses tested, 1 mM of quercetin proved best and can be used for further investigations.


Surgical treatment of recurrent primary malignant tumor of the left atrium.
A young woman presented with a tumor in the left atrium resembling a left atrial myxoma. After simple excision of the tumor the diagnosis of primary malignant fibrous histiocytoma of the heart was made. A course of radiation therapy was given. Four subsequent recurrences were treated by cardiotomy and resection of the left atrial wall. At the third, fourth, and fifth operations fulguration of the left atrial wall was performed. Subsequent chemotherapy failed to control the tumor. The patient was admitted 6 weeks after the last resection and died. Postmortem examination revealed a large recurrent tumor obstructing the left atrium with no metastases. The clinical course, cardiac catherization data, and postmortem examination are presented. Palliation was achieved by repeated resection of a radiation-resistent primary sarcoma of the heart.


Reappraisal of tubulopapillary hidradenoma-like tumor of the mandible: Suggested change in nomenclature to reflect tumor origin.
Several cases of intraosseous mandibular tumors have been reported under the name "tubulopapillary hidradenoma-like tumor of the mandible (TPHLTM)." However, the intraosseous occurrence of sweat gland tumors needs to be reappraised. The aim of this review was to propose a new name for these tumors to reflect the possible tumor origin. In view of the incidence and the tissue of origin, TPHLTM is more likely to be a salivary gland tumor than a sweat gland tumor. Among salivary gland tumors, a recently described salivary neoplasm called "sialadenoma papilliferum-like intraductal papillary tumor (SP-IPT)" seems to be histologically and genetically identical to tubulopapillary hidradenoma. Therefore, we proposed that the term TPHLTM be replaced by "SP-IPT of the mandible," which better explains its origin and could help in clarifying the nature of SP-IPT.


Localization of activin subunits in early murine development determined by subunit-specific antibodies.
Activins are thought to be involved in early differentiation processes during amphibian and avian development. Little is known, however, about the role of activins in early developmental stages of higher vertebrates. In order to study activin protein expression in early murine development we have prepared polyclonal antibodies against synthetic peptides corresponding to C-terminal sequences of the murine beta A and beta B activin subunits. Both antibodies recognized specifically activin A and activin B in different immunological assays including ELISA and immunoblotting. Using these antibodies in immunofluorescence experiments a good correlation between mRNA and protein expression of the beta subunits was observed in different in vitro model systems for early murine development. In addition, beta A and beta B subunit protein localization appeared to be different in 3.5- and 4.5-day mouse blastocysts. The results presented here are consistent with a role for different activin forms in the regulation of distinct processes in early murine development.


Evaluation of the Fight Asthma Now (FAN) program to improve asthma knowledge in urban youth and teenagers.
School-based asthma education programs targeting disadvantaged youth and teens with asthma are lacking. To assess the impact of the Fight Asthma Now (FAN) educational program among 2 populations of predominantly low-income minority students: youth (3(rd)-6(th) graders) and teens (7(th)-8(th) graders). Chicago-area elementary schools were invited to participate in this stratified 2-arm study. Eligible schools were assigned to participate either in the intervention or in the control arm. Within each participating school, eligible students were recruited and grouped (stratified by grade and age) to form teen or youth classes. Participants completed a pre- and post-intervention asthma knowledge questionnaire and observation for spacer technique competency. The treatment group received the FAN curriculum between the evaluations. A sample of 26 low-income, predominantly minority-serving schools was recruited. Most participating schools were randomized in a 3:1 ratio to form 25 youth classes (19 intervention and 6 control group) and 16 teen classes (11 intervention and 5 control group), resulting in 275 vs 69 youth and 141 vs 51 teens in the intervention and control groups, respectively. Stratified analyses were performed, and clustering within the school and class was taken into consideration in analyses. Multilevel models adjusting for school, class, ethnicity, sex, and pretest score indicate that the FAN intervention significantly increased both knowledge and spacer competency test scores, among both the youth and teen participants (P = .011 with respect to knowledge score among teen students, P < .0001 for all other cases). This study suggests that FAN significantly increases asthma knowledge and spacer technique competency within this high-risk population.


Nonerythropoietic Erythropoietin-Derived Peptide Suppresses Adipogenesis, Inflammation, Obesity and Insulin Resistance.
Erythropoietin (EPO) has been identified as being crucial for obesity modulation; however, its erythropoietic activity may limit its clinical application. EPO-derived Helix B-surface peptide (pHBSP) is nonerythrogenic but has been reported to retain other functions of EPO. The current study aimed to evaluate the effects and potential mechanisms of pHBSP in obesity modulation. We found that pHBSP suppressed adipogenesis, adipokine expression and peroxisome proliferator-activated receptor γ (PPARγ) levels during 3T3-L1 preadipocyte maturation through the EPO receptor (EPOR). In addition, also through EPOR, pHBSP attenuated macrophage inflammatory activation and promoted PPARγ expression. Furthermore, PPARγ deficiency partly ablated the anti-inflammatory activity of pHBSP in macrophages. Correspondingly, pHBSP administration to high-fat diet (HFD)-fed mice significantly improved obesity, insulin resistance (IR) and adipose tissue inflammation without stimulating hematopoiesis. Therefore, pHBSP can significantly protect against obesity and IR partly by inhibiting adipogenesis and inflammation. These findings have therapeutic implications for metabolic disorders, such as obesity and diabetes.


Extracellular superoxide dismutase, a potential extracellular biomarker candidate for prolactinoma.
To investigate whether the extracellular superoxide dismutase (EC-SOD) and manganese superoxide dismutase (Mn-SOD) level changes during prolactinoma (PRL) development. Surgical tissues from 37 female patients with PRL were tested for Mn-SOD and serum samples from such PRL patients were tested for EC-SOD level changes with Western Blot. The MnSOD level from blood cells was also investigated to show whether the Mn-SOD variation could locate tumorigenesis tissues. According to the patients' age analysis, age 20-40 years is high risk for getting PRL. There is a positive relationship between the PRL severity and EC-SOD. The Mn-SOD level from surgical tissues, but not blood cells, also shows a corresponding positive relationship to PRL severity, which indicates that elevated Mn-SOD might only happen in PRL tumorigenesis tissues. Extracellular superoxide dismutase is an extracellular protein and the serum EC-SOD could be a good candidate for the diagnoses of prolactinoma.


Effects of cinnarizine on calcium and pressure-dependent potassium currents in guinea pig vestibular hair cells.
In vestibular hair cells, K+ currents induced by rises in hydrostatic pressure have recently been demonstrated. These currents are inhibited by charybdotoxin, a blocker of Ca2+-dependent K+ channels. On the other hand, cinnarizine is a blocker of voltage-gated Ca2+ currents in hair cells and is used as a drug in conditions with vestibular vertigo. Our aim was to test in patch-clamp experiments (conventional whole-cell mode) whether cinnarizine, by reducing Ca2+ influx, inhibited Ca2+ and pressure-sensitive K+ currents in vestibular type-II hair cells of guinea pigs. A quantitatively similar inhibition of K+ currents was evoked by extracellular Ca2+ removal, cinnarizine (0.5 microM), and the L-type Ca2+ channel blocker nifedipine (3 microM). Cinnarizine abrogated increases of K+ currents induced by increases in the hydrostatic pressure (from 0.2 to 0.5 cm H2O). At a higher concentration (1 microM), cinnarizine elicited K+ current inhibitions larger than those elicited by Ca2+ removal. Moreover, it reduced K+ currents in the absence of Ca2+, in contrast to nifedipine. However, charybdotoxin abolished these effects of cinnarizine. We thus conclude that cinnarizine inhibits, by two mechanisms, pressure-induced currents that are sensitive to charybdotoxin and Ca2+. It reduces Ca2+ influx and exerts a Ca2+-independent inhibition, with a lower IC50 than that required for Ca2+ channel blockade. These two actions may importantly contribute to its therapeutic effects.


Prognostic value of end-tidal carbon dioxide during exercise testing in heart failure.
The partial pressure of end-tidal carbon dioxide production (P(ET)CO2) at ventilatory threshold (VT) has been shown to be strongly correlated with cardiac output during exercise in patients with heart failure (HF), but few data are available regarding its prognostic utility. The purpose of this study was to assess the ability of P(ET)CO2 to predict cardiac-related events in a group of subjects with HF. One hundred and thirty subjects diagnosed with compensated HF underwent cardiopulmonary exercise testing (CPX). Peak oxygen consumption (VO2), the minute ventilation-carbon dioxide production (VE/VCO2) slope and P(ET)CO2 were determined. Receiver operating characteristic (ROC) curve analysis revealed that P(ET)CO2 at the ventilatory threshold (VT) was a significant predictor of cardiac-related events (ROC area=0.82, p<0.001). The optimal P(ET)CO2 at a VT threshold value for separating high (< or =) and low (>) risk groups was 36.1 mm Hg (77% sensitivity, 69% specificity). In a multivariate Cox regression analysis, P(ET)CO2 at VT added significant predictive value to the VE/VCO2 slope and peak VO2. These results indicate that P(ET)CO2 during CPX is a significant predictor of cardiac-related events in patients with HF. Clinical assessment of this variable in patients with HF undergoing CPX may therefore be warranted.


[Characteristics of reversible and irreversible Ca2+-induced efflux of Ca2+ from mitochondria in permeabilized Ehrlich ascites carcinoma cells].
The Cyclosporin A-sensitive mitochondrial permeability transition in Ehrlich ascites tumour cells has been investigated. It was shown that Ca2+ ions induce both the self-reversible and irreversible mitochondrial permeability transition. ADP effectively inhibits the reversible but has no effect on the irreversible permeability transition. Bromophenacyl bromide, a potent inhibitor of phospholipase A2, effectively inhibits both the reversible and irreversible permeability transition. Accumulation of phosphatidylcholine and phosphatidylethanolamine lysoforms in mitochondria during Ca(2+)-induced Ca2+ release from mitochondria was found. The role of lysophospholipids in the formation of the non-selective pore in inner mitochondrial membranes during the mitochondrial permeability transition was postulated.


Unsatisfactory nutritional parameters in non-insulin-dependent diabetes mellitus.
Four-day food records, body mass index and glycosylated hemoglobin levels were measured in 212 subjects with established non-insulin-dependent diabetes, who volunteered for a trial of educational programmes. Of these subjects, 79% were above their ideal body weights and 75% of subjects had a glycosylated haemoglobin level that was above the normal range. Ninety-five per cent of subjects reported a total fat intake greater than 30% of their total energy intake, and 80% of subjects reported total carbohydrate intake of less than 50% of their total energy intake. These results suggest that the current methods for the management of non-insulin-dependent diabetes do not achieve optimal long-term dietary results.


Effects of 3-dimensional conformal or intensity-modulated radiotherapy on dental pulp sensitivity during and after the treatment of oral or oropharyngeal malignancies.
Radiation therapy (RT) of malignant tumors in the head and neck area may have damaging effects on surrounding tissues. The aim of this investigation was to evaluate the effects of RT delivered by 3-dimensional conformal radiotherapy (3D-RT) or intensity-modulated radiotherapy (IMRT) on dental pulp sensitivity. Twenty patients with oral or oropharyngeal cancer receiving RT with 3D-RT or IMRT underwent cold thermal pulp sensitivity testing (PST) of 2 teeth each at 4 time points: before RT (TP1), the beginning of RT with doses between 30 and 35 Gy (TP2), the end of RT with doses between 60 and 70 Gy (TP3), and 4 to 5 months after the start of RT (TP4). All 40 teeth showed positive responses to PST at TP1 (100%) and 9 at TP2 (22.5%; 3/16 [18.8%] for 3D-RT and 6/24 [25.0%] for IMRT). No tooth responded to PST at TP3 and TP4 (0%). A statistically significant difference existed in the number of positive pulp responses between different time points (TP1 through TP4) for all patients receiving RT (P ≤ .05), IMRT (P ≤ .05), and 3D-RT (P ≤ .05). No statistically significant differences in positive sensitivity responses were found between 3D-RT and IMRT at any time point (TP1, TP3, TP4, P = 1.0; TP2, P = .74). A statistically significant correlation existed between the location of the tumor and PST at TP2 for IMRT (P ≤ .05) but not for 3D-RT (P = .14). RT decreased the number of teeth responding to PST after doses greater than 30 to 35 Gy. The type of RT (3D-RT or IMRT) had no influence on the pulp responses to PST after the conclusion of RT.


Predictors of acute carpal tunnel syndrome associated with fracture of the distal radius.
A better understanding of the risk factors for acute carpal tunnel syndrome (CTS) associated with fracture of the distal radius might influence recommendations for prophylactic carpal tunnel release. Fifty patients who had release of an acute CTS in association with open reduction and internal fixation (ORIF) of a fracture of the distal radius were identified from orthopedic trauma databases at 2 institutions. Each patient was matched with a control patient (ORIF, but no acute CTS) of the same gender, similar age (+/-4 years), and similar injury mechanism. The prevalence of acute CTS among patients with a surgically treated fracture of the distal radius was 5.4%. In univariate analysis, only fracture translation was a significant predictor of acute CTS, but ipsilateral upper extremity trauma and status as a multitrauma patient were nearly significant. The best multivariate model included fracture translation alone and accounted for 60% of the observed increase in risk. A subgroup analysis using receiver operating characteristics (ROC) identified a threshold of approximately 35% fracture translation associated with a significantly increased risk of acute CTS in women less than 48 years of age. No threshold was identified in the other 3 subgroups. Fracture translation is the most important risk factor for acute CTS in patients who subsequently had ORIF of a fracture of the distal radius. On the basis of these data, prophylactic carpal tunnel release might be appropriate in women less than 48 years of age with greater than 35% fracture translation, but further investigation is needed to confirm that a true threshold exists.


Life history implications of allocation to growth versus reproduction in dynamic energy budgets.
We compare the implications of determinate vs. indeterminate growth of a parthenogenetic iteroparous ectotherm at constant food density in the context of the dynamic energy budget theory, which specifies the tight links between life history traits, such as feeding, aging, growth and reproduction. We do a comparative analysis using, as measure of fitness, the life span reproduction, the population growth rate, and the conversion efficiency of food to biomass. When extrinsic mortality is constant, indeterminate growth cannot maximize fitness if measured by the population growth rate or the conversion efficiency, except when mortality is low, in which case both types of animals are similar. If the fitness measure is life span reproduction, indeterminate growth maximizes fitness even with constant mortality, provided it is not very high. When mortality decreases with size, indeterminate growth maximizes fitness for almost all measures of fitness. Finally, we suggest an evolutionary link between allocation strategies and expected life span. In populations of long living species, each type of animal can establish in the population of the other. In populations of short living species, determinate growers can invade, and displace, a population of indeterminate ones. However, when the mortality risk of organisms with small size is much higher than those of large size, indeterminate growers can be superior.


C1-C2 pedicle screw fixation with rigid cantilever beam construct: case report and technical note.
Transarticular screw fixation of the C1-C2 complex provides immediate rigid fixation of the unstable spine. The technique is not feasible in a certain proportion of patients because of the position of the vertebral artery or the patient's body habitus. The authors describe a rigid screw technique for the surgical treatment of a woman who was excluded as a candidate for C1-C2 transarticular screw fixation. C1-C2 pedicle screw fixation was achieved using a fixed moment arm cantilever beam system. This system provided immediate rigid fixation of the C1-C2 complex in a patient who was not a candidate for transarticular screw fixation. This technique is technically more forgiving than posterior transarticular screw fixation and may be applied to a broader spectrum of patients.


Effect of GnRHa, pimozide and Ovaprim on ovulation and plasma sex steroid hormones in African catfish Clarias gariepinus.
Nine groups each of four fish were injected with a single intramuscular dose of the following preparations: Physiological saline (0.9% NaCl) as a control group, 0.5 ml kg(-1) Ovaprim, 20 and 40 μg kg(-1) BW of GnRHa, 8 and 16 mL kg(-1) pimozide tablets and the following combination of GnRHa with pimozide (GP): 20 μg + 4 mg, 30 μg + 8 mg and 40 μg + 16 mg kg(-1) BW. The primary oocyte diameter (POD) before hormone administration ranged from 943.3 to 1071.0 μm. The latency periods (LP) were in the range of 9.0 to 12.0 h after injection. The highest ovulation ratio (OR) was observed in groups Ovaprim, GP(30 + 8) and GP(40 + 16). Other treatments were effective for ovulation, the ovulation ratio in Groups G(40) and GP(20 + 4) were significantly higher than G(20) treatment. The ovulation index (OI) was in the range 62 to 77% and showed significant differences among groups. There was no significant difference in fertilization ratio (FR) among Ovaprim, GP(30 + 8) and GP(40 + 16) groups, while there were significant difference between the previous group and G(20) and G(40) groups. Control, P8, P16 showed negative results in all the parameters LP, OED, OR, OI and FR. Levels of sex steroids were analyzed on 6 and 12 h after initiation of treatments. A significant increase in plasma E(2) with GP(30 + 8) injection was observed 6 and 12 h after injection, while there were no significant increase between all the other groups 6 h after injection. Treatments with GP(20 + 4) resulted in a significant increase in plasma T concentration in females compared with control after 6 h. In contrast, plasma T and E(2) concentrations were lower during the combined GP(20 + 4), GP(30 + 8) and GP(40 + 16) after 12 h than after 16 h of injection. The combined treatments (GnRHa + PIM) are better compared with Ovaprim which gave the same results, they have some advantages, such as reliable response and low cost. Ovaprim is more than 3 to 5-fold of the cost of (GnRH + PIM). Therefore, this method could be useful tool for commercial catfish breeders to ensure spawning success.


Interaction between roxarsone, an organic arsenic compound, with humic substances in the soil simulating environmental conditions.
In environmental systems, the soil is a principal route of contamination by various potentially toxic species. Roxarsone (RX) is an arsenic (V) organic compound used to treat parasitic diseases and as an additive for animal fattening. When the animal excretes RX, the residues may lead to environmental contamination. Due to their physicochemical properties, the soil's humic substances (HS) are important in species distribution in the environment and are involved in various specific interaction/adsorption processes. Since RX, an arsenic (V) compound, is considered an emerging contaminant, its interaction with HS was evaluated in simulated environmental conditions. The HS-RX interaction was analyzed by monitoring intrinsic HS fluorescence intensity variations caused by complexation with RX, forming non-fluorescent supramolecular complexes that yielded a binding constant Kb (on the order of 103). The HS-RX interaction occurred through static quenching due to complex formation in the ground state, which was confirmed by spectrophotometry. The process was spontaneous (ΔG < 0), and the predominant interaction forces were van der Waals and hydrogen bonding (ΔH < 0 and ΔS < 0), with an electrostatic component evidenced by the influence of ionic strength in the interaction process. Structural changes in the HS were verified by synchronized and 3D fluorescence, with higher variation in the region referring to the protein-like fraction. In addition, metal ions (except ions Cu(II)) favored HS-RX interaction. When interacting with HS, the RX epitope was suggested by 1H NMR, which indicated that the entire molecule interacts with the superstructure. An enzyme inhibition assay verified the ability to reduce the alkaline phosphatase activity of free and complexed RX (RX-HS). Finally, this work revealed the main parameters associated with HS and RX interaction in simulated environmental conditions, thus, providing data that may help our understanding of the dynamics of organic arsenic-influenced soils.


Evolution, expression, and developmental function of Hox-embedded miRNAs.
Exquisite regulation of Hox protein activity is fundamental to the regionalization of the early embryo across diverse taxa. Highlighting the critical importance of these transcription factors, an astonishing number of different mechanisms have evolved to tightly coordinate their activity both in time and in space. The recent identification of numerous microRNAs that are not only embedded within Hox clusters but also target numerous Hox genes suggests an important role for these regulatory molecules in shaping Hox protein output. Here, we discuss the positioning of these miRNAs within clusters over evolutionary time, the unexpected complexity in miRNA processing and target interactions, and the current understanding of Hox-embedded miRNA function during development.


Influence of different application protocols of universal adhesive system on the clinical behavior of Class I and II restorations of composite resin - a randomized and double-blind controlled clinical trial.
Multimode adhesives incorporate the versatility of adapting to various clinical situations by its capacity to be used in different protocols. This study aimed to evaluate the clinical behavior of composite resin direct restorations (Class I and II) performed with different universal dentin adhesive application protocols comparing adapted FDI and adapted USPHS criteria. The current study is a randomized, double-blind, split-mouth, and convenience sample controlled clinical trial. The participants (age ≥ 18 years) had restorative need of Class I and/or II due to the presence of carious lesions and/or unsatisfactory restorations in at least three dental elements. Each participant received three application protocols for Scotchbond Universal adhesive (3M ESPE), one in each tooth to be restored: ER = etch-and-rinse + adhesive (n = 50); SEE = selective enamel etch + adhesive (n = 50) and SE = self-etch adhesive (n = 50). All teeth were restored in a similar way using Filtek™ Supreme composite resin (3M ESPE). Restorations were evaluated using the adapted FDI and adapted USPHS criteria, at baseline after 7 to 21 (12.02 ± 5.68) days (T1; n = 50 per group) and after 12 to 20 (15.8 ± 2.7) months (T2; n = 46 per group) by two previously calibrated evaluators (Kappa > 0.80). The statistical tests were performed between groups (Friedman), intragroup (Wilcoxon), and between the criteria considering acceptable and not acceptable restorations (McNemar), α = 0.05. A statistically significant difference was observed only for the property "superficial staining", between groups at T2 (p = 0.01) for ER (n = 13 with score 2 or more) and SEE (n = 3 with score 2 or more) and intragroup for ER (T1, n = 1 with score 2 or more; T2, n = 13 with score 2 or more, p = 0.001) and SE (T1, n = 0 with score 2 or more; T2, n = 8 with score 2 or more p = 0.007). For the other comparisons between groups, intragroup, and between the adapted FDI and adapted USPHS criteria, there were no statistically significant differences (p ≥ 0.05). It can be concluded that the different application protocols of the universal adhesive resulted in clinically "acceptable" restorations after 15.8 ± 2.7 months of follow-up. Adapted FDI and adapted USPHS criteria provided similar results to each other. Number in Brazilian Registry of Clinical Trials (ReBEC): RBR-9p3hdp. Registered 24 May 2015.


Strengthening Community: Older Asian Immigrants' Contributions to New Zealand Society.
This study sought to uncover the process through which older Chinese, Indian and Korean immigrants residing in Auckland, New Zealand contribute to, and participate in, local community. There is a paucity of literature addressing the everyday activities of older Asian immigrants living in New Zealand. The few studies that do exist focus solely on one ethnic group with little discussion of how community participation occurs. Grounded theory methodology was employed. Focus groups and individual interviews with 76 Chinese, Indian or Korean older immigrants were recorded, transcribed, translated, and analysed using grounded theory methods of dimensional analysis to develop a theory of participation. Older Asian immigrants contribute to society through a process of Strengthening Community; comprising three perspectives: Advancing Cultural Connectedness, Giving Service and Caring for Family. Each perspective is mediated by conditions and strategies that facilitate when and how participants engage in their chosen activities. Older Asian immigrants are active social contributors to New Zealand communities. Although they encounter barriers to participation, they constantly seek ways to work individually and in community groups to effectively contribute to civic society. In doing so, they take pride in giving back to their host country.


Tissue engineering of the stomach.
Tissue engineering combines engineering principles with the biological sciences to create functional replacement tissues. The underlying principle of tissue engineering is that isolated cells combined with biomaterials can form new tissues and organs in vitro and in vivo. This review focuses on stomach tissue engineering, which is a promising approach to the treatment of gastric cancer, the fourth most common malignancy in the world and the second-leading cause of cancer mortality worldwide. Although gastrectomy is a reliable intervention to achieve complete removal of cancer lesions, the limited capacity for food intake after resection results in lower quality of life for patients. To address this issue, we have developed a tissue-engineered stomach to increase the capacity for food intake by creating a new food reservoir. We have transplanted this neo-stomach as a substitute for the original native stomach in a rat model and confirmed functional adaptation. Furthermore, we have demonstrated the feasibility of transplanting a tissue-engineered gastric wall patch in a rat model to alleviate the complications after resection of a large area of the gastric wall. Although progress has been achieved, significant challenges remain to bring this approach to clinical practice. Here, we summarize our work and present the state of the art in stomach tissue engineering.


Frequent miRNA-convergent fusion gene events in breast cancer.
Studies of fusion genes have mainly focused on the formation of fusions that result in the production of hybrid proteins or, alternatively, on promoter-switching events that put a gene under the control of aberrant signals. However, gene fusions may also disrupt the transcriptional control of genes that are encoded in introns downstream of the breakpoint. By ignoring structural constraints of the transcribed fusions, we highlight the importance of a largely unexplored function of fusion genes. Here, we show, using breast cancer as an example, that miRNA host genes are specifically enriched in fusion genes and that many different, low-frequency, 5' partners may deregulate the same miRNA irrespective of the coding potential of the fusion transcript. These results indicate that the concept of recurrence, defined by the rate of functionally important aberrations, needs to be revised to encompass convergent fusions that affect a miRNA independently of transcript structure and protein-coding potential.Fusion gene research traditionally focuses on fusions that result in hybrid proteins or promoter switching events. Here, the authors demonstrate enrichment of fusions in miRNA host genes in breast cancer, highlighting that disparate fusions could have convergent impact on miRNA.


Infratentorial neurilemmoma of the trigeminal nerve in a child. Report of a case.
A case of trigeminal nerve infratentorial neurilemmoma in a 11-year-old girl is reported. The author remarks on this tumor's low incidence in this age group. A correlative analysis between the clinical and radiological findings in this case and those reported on the literature is made.


Co-delivery of GOLPH3 siRNA and gefitinib by cationic lipid-PLGA nanoparticles improves EGFR-targeted therapy for glioma.
Glioblastoma is one of the most aggressive types of brain tumor. Epidermal growth factor receptors (EGFRs) are overexpressed in glioma, and EGFR amplifications and mutations lead to rapid proliferation and invasion. EGFR-targeted therapy might be an effective treatment for glioma. Gefitinib (Ge) is an EGFR tyrosine kinase inhibitor (TKI), and Golgi phosphoprotein 3 (GOLPH3) expression is associated with worse glioma prognosis. Downregulation of GOLPH3 could promote EGFR degradation. Here, an angiopep-2 (A2)-modified cationic lipid-poly (lactic-co-glycolic acid) (PLGA) nanoparticle (A2-N) was developed that can release Ge and GOLPH3 siRNA (siGOLPH3) upon entering glioma cells and therefore acts as a combinatorial anti-tumor therapy. The in vitro and in vivo studies proved that A2-N/Ge/siGOLPH3 successfully crossed the blood-brain barrier (BBB) and targeted glioma. Released siGOLPH3 effectively silenced GOLPH3 mRNA expression and further promoted EGFR and p-EGFR degradation. Released Ge also markedly inhibited EGFR signaling. This combined EGFR-targeted action achieved remarkable anti-glioma effects and could be a safe and effective treatment for glioma. KEY MESSAGES: Angiopep-2-modified cationic lipid polymer can penetrate the BBB. Gefitinib can inhibit EGFR signaling and block the autophosphorylation of critical tyrosine residues on EGFR. GOLPH3 siRNA can be transfected into glioma and downregulate GLOPH3 expression. A2-N/Ge/siGOLPH3 can inhibit glioma growth.


The effects of H1- and H2-receptor agonists and antagonists on total lung resistance, dynamic lung compliance and irritant receptor discharge in the anaesthetized dog.
1 The effects of histamine and 4 methylhistamine (i.v.) alone, and in the presence of chlorpheniramine or cimetidine, on total lung resistance (RL), dynamic lung compliance (Cdyn) and irritant receptor activity have been studied in dogs anaesthetized with chloralose. 2 Histamine produced dose-related increases in RL and irritant receptor activity with associated falls in Cdyn which were blocked by chlorpheniramine but unaffected by cimetidine. 3 4 Methylhistamine produced small insignificant changes in RL and Cdyn and small significant increases in irritant receptor activity which were reduced with chlorpheniramine but unaffected by cimetidine. 4 The results suggest that histamine increases irritant receptor activity, either directly or indirectly, via H1-receptors.