N-heterocyclic carbene catalyzed oxidative coupling of aldehydes with carbodiimides under aerobic conditions: efficient synthesis of N-acylureas.
The oxidative coupling reaction of aldehydes with N,N'-disubstituted carbodiimides catalyzed by N-heterocyclic carbenes under aerobic conditions has been achieved. This reaction gives the corresponding N-acylurea derivatives in good to high yields. Various kinds of aldehydes including aliphatic ones and carbodiimides are applicable to this reaction.


Novel bis[5-(fluoren-2-yl)thiophen-2-yl]benzothiadiazole end-capped with carbazole dendrons as highly efficient solution-processed nondoped red emitters for organic light-emitting diodes.
A series of novel red-emitting bis[5-(fluoren-2-yl)thiophen-2-yl]benzothiadiazole-cored dendrimers containing carbazole dendrons up to the third generation are synthesized. Their photophysical, thermal, electrochemical, and electroluminescent properties as nondoped solution-processed red light-emitters for OLEDs are investigated. By using carbazole dendrons as the end caps, we are able to reduce the crystallization and retain the high emissive ability of a planar fluorescent core in the solid state as well as improve the thermal stability of the material. These dendrimers show a bright-red fluorescence and can form morphologically stable amorphous thin films with glass-transition temperatures as high as 283 °C. Simple structured solution-processed OLEDs using these materials as hole-transporting nondoped emitters and BCP as the hole-blocking layer emit a stable red color around 622-645 nm, with high luminance efficiencies (up to 4.80 cd A(-1) at 1.2 mA cm(-2)) and CIE coordinates of (0.65, 0.33), which are close to the pure red color.


Cardiac myxoma the great imitators: comprehensive histopathological and molecular approach.
Cardiac myxomas are rare benign and slowly proliferating neoplasms of uncertain histogenesis with heterogeneous histomorphology and variable and sometimes clinically quite malignant pathological manifestations. Majority of cardiac myxoma occur sporadically while a relatively small proportion of diagnosed cases develop as a part of Carney complex syndrome with established familial pattern of inheritance. Although histologically indistinguishable these two forms of cardiac myxoma exhibit distinct cytogenetic make-up and apparent pathological differences important for their clinical presentation and prognosis. Additional problem is presented with secondary lesions with more aggressive histology and significantly faster cell proliferation suggesting their successive malignant alteration. Surgical resection of cardiac myxoma is currently the only treatment of choice. However, to avoid potentially hazardous operating procedures and possible postoperative complications and to prevent recurrence of the neoplastic lesions it is necessary to develop alternative approaches and identify a possible drug targets for their successful pharmacological treatment. Due to the rarity of the disease, a small number of cases in one institution and lack of comprehensive experimental data particularly concerning the cases of metastatic dissemination and secondary lesions with malignant nature, a comprehensive multi-institutional approach is required for better understanding of their molecular pathology and illumination of key molecular, genetic as well as epigenetic markers and regulatory pathways responsible for their development. In this article we provide comprehensive pathohistological, molecular and cytogenetic overview of sporadic cardiac myxoma cases restating the major hypothesis concerning their histogenesis and emphasizing potential approaches for their further reexamination.


Evidence of an adenosine-dependent mechanism in the hypotensive effect of L-arginine in man.
1. The hypothesis that endogenous adenosine could play a role in the haemodynamic response to L-arginine is investigated. 2. The study has been divided into two parts. The first part was a single blind, randomized, placebo-controlled study in which L-arginine i.v. infusion (0.07 mmol/kg per min) in five healthy volunteers caused a significant fall in systolic (-14.2%, from 129.0 +/- 8.2 to 110.6 +/- 8.5 mmHg; F = 62.89, P < 0.01), diastolic (-16%, from 80.0 +/- 7.9 to 67.2 +/- 7.0 mmHg; F = 18.97, P < 0.01) and mean (-15.5%, from 96.4 +/- 6.7 to 81.4 +/- 6.5 mmHg; F = 28.78, P < 0.01) arterial blood pressure, with a concomitant increase of plasma adenosine concentration (from 244.0 +/- 32.2 to 637.0 +/- 43.4 nmol/L; F = 79.3 P < 0.01). Maximal effects were obtained at the end of L-arginine infusion: haemodynamic parameters returned to basal values in about 30 min while adenosine concentrations normalized in about 15 min. Saline infusion had no effect on these parameters. 3. In the second study the effect of L-arginine i.v. infusion on arterial blood pressure, lower limb blood flow and plasma adenosine, before and after theophylline treatment (1000 mg/day for 3 days, p.o.) was examined.(ABSTRACT TRUNCATED AT 250 WORDS)


The mumps virus nucleocapsid mRNA sequence and homology among the Paramyxoviridae proteins.
The nucleotide sequence of mumps virus nucleocapsid protein (NP) mRNA has been determined from two overlapping cDNA clones and confirmed by partial sequencing of the mRNA and the genome. The mRNA contains 1844 nucleotides excluding poly(A) and encodes a protein of 553 amino acids with a calculated molecular weight of 61,792. A comparison of the mumps virus nucleocapsid protein sequence with that of other paramyxoviruses revealed a moderate degree of homology (33.1%) with the Newcastle disease virus (NDV) only. The nucleocapsid proteins of all paramyxoviruses studied to date, excluding that of the genus pneumovirus, have a conserved sequence of six amino acids (Ser-Tyr-Ala-Met-Gly-Val) except that of NDV which has a mismatch of two amino acids (Ser-Phe-Ala-Met-Gly-Met) in that sequence. In addition, there is another conserved region of seven amino acids (Phe-Ala-Pro-Gly-X-Tyr-Pro) in the nucleocapsid proteins of mumps virus, Sendai virus and parainfluenza virus type 3. The nucleocapsid proteins of measles virus and canine distemper virus (CDV) also have this conserved region but with three conservative amino acid changes.


Gelatin molecular structures affect behaviors of fish oil-loaded traditional and Pickering emulsions.
As the differences of traditional and Pickering emulsions might have resulted from stabilizer structures, this study analyzes the effects of gelatin molecular structures (uncrosslinked molecules vs. crosslinked molecules) on the preparation, long-term storage, and dilution of fish oil-loaded traditional and Pickering emulsions. Both traditional and Pickering emulsions have three types of droplets with different sizes, and all the droplet sizes were exponentially decreased with the increase of stabilizer concentration. Pickering emulsions have slightly lower droplet sizes compared with traditional emulsions. Traditional emulsions have three different emulsion forms (liquid, redispersible emulsion gel, and unredispersible emulsion gel), whereas Pickering emulsions only have the liquid form. Emulsion creaming stability was dependent on stabilizer molecular structures and stabilizer concentrations. The two emulsions have similar and good dilution stability. This work demonstrates that gelatin molecular structures affect droplet size, emulsion forms, and creaming stability, but not droplet size types and emulsion dilution stability.


A practical guide for investigating cardiac physiology using living myocardial slices.
Ex vivo multicellular preparations are essential tools to study tissue physiology. Among them, the recent methodological and technological developments in living myocardial slices (LMS) are attracting increasing interest by the cardiac research field. Despite this, this research model remains poorly perceived and utilized by most research laboratories. Here, we provide a practical guide on how to use LMS to interrogate multiple aspects of cardiac function, structure and biochemistry. We discuss issues that should be considered to conduct successful experiments, including experimental design, sample preparation, data collection and analysis. We describe how laboratory setups can be adapted to accommodate and interrogate this multicellular research model. These adaptations can often be achieved at a reasonable cost with off-the-shelf components and operated reliably using well-established protocols and freely available software, which is essential to broaden the utilization of this method. We will also highlight how current measurements can be improved to further enhance data quality and reliability to ensure inter-laboratory reproducibility. Finally, we summarize the most promising biomedical applications and envision how living myocardial slices can lead to further breakthroughs.


Sustainable approaches on industrial food wastes to value-added products - A review on extraction methods, characterizations, and its biomedical applications.
The concept of zero waste discharge has been gaining importance in recent years towards attaining a sustainable environment. Fruit processing industries generate millions of tons of byproducts like fruit peels and seeds, and their disposal poses an environmental threat. The concept of extracting value-added bioactive compounds from bio-waste is an excellent opportunity to mitigate environmental issues. To date, significant research has been carried out on the extraction of essential biomolecules, particularly polysaccharides from waste generated by fruit processing industries. In this review article, we aim to summarize the different extraction methodologies, characterization methods, and biomedical applications of polysaccharides extracted from seeds and peels of different fruit sources. The review also focuses on the general scheme of extraction of polysaccharides from fruit waste with special emphasis on various methods used in extraction. Also, the various types of polysaccharides obtained from fruit processing industrial wastes are explained in consonance with the important techniques related to the structural elucidation of polysaccharides obtained from seed and peel waste. The use of seed polysaccharides as pharmaceutical excipients and the application of peel polysaccharides possessing biological activities are also elaborated.


Automatic detection of COVID-19 from chest radiographs using deep learning.
The breakdown of a deadly infectious disease caused by a newly discovered coronavirus (named SARS n-CoV2) back in December 2019 has shown no respite to slow or stop in general. This contagious disease has spread across different lengths and breadths of the globe, taking a death toll to nearly 700 k by the start of August 2020. The number is well expected to rise even more significantly. In the absence of a thoroughly tested and approved vaccine, the onus primarily lies on obliging to standard operating procedures and timely detection and isolation of the infected persons. The detection of SARS n-CoV2 has been one of the core concerns during the fight against this pandemic. To keep up with the scale of the outbreak, testing needs to be scaled at par with it. With the conventional PCR testing, most of the countries have struggled to minimize the gap between the scale of outbreak and scale of testing. One way of expediting the scale of testing is to shift to a rigorous computational model driven by deep neural networks, as proposed here in this paper. The proposed model is a non-contact process of determining whether a subject is infected or not and is achieved by using chest radiographs; one of the most widely used imaging technique for clinical diagnosis due to fast imaging and low cost. The dataset used in this work contains 1428 chest radiographs with confirmed COVID-19 positive, common bacterial pneumonia, and healthy cases (no infection). We explored the pre-trained VGG-16 model for classification tasks in this. Transfer learning with fine-tuning was used in this study to train the network on relatively small chest radiographs effectively. Initial experiments showed that the model achieved promising results and can be significantly used to expedite COVID-19 detection. The experimentation showed an accuracy of 96% and 92.5% in two and three output class cases, respectively. We believe that this study could be used as an initial screening, which can help healthcare professionals to treat the COVID patients by timely detecting better and screening the presence of disease. Its simplicity drives the proposed deep neural network model, the capability to work on small image dataset, the non-contact method with acceptable accuracy is a potential alternative for rapid COVID-19 testing that can be adapted by the medical fraternity considering the criticality of the time along with the magnitudes of the outbreak.


Is Karl Landsteiner the Einstein of the biomedical sciences?
If Albert Einstein is the acclaimed peerless genius among the physical scientists of this century, who can claim the equivalent title among the biomedical scientists? The research contributions of 24 Nobelists in medicine (contemporaries of Einstein) who received the Nobel prize between 1912 and 1966 were analyzed. When assessed on three criteria, (a) influence in multiple disciplines, (b) revolutionary in opening new vistas of knowledge, and (c) significant impact to human life, Karl Landsteiner's discoveries of the human blood groups stand out prominently. Thus, Landsteiner seems an appropriate choice to use as a 'control' to analyze Einstein's productivity.


[Electroanalytical characteristics of ofloxacin in micellar solution].
In a pH 6.30 buffer solution containing 0.001% Tween-80, ofloxacin (OFX) gives a sensitive polarographic wave at -1.46 V (vs SCE), which can be used for the determination of OFX down to 10(-8) mol.L-1. The linear range is from 1.39 x 10(-7) to 1.39 x 10(-5) mol.L-1. The proposed method was applied to determination of OFX in urine and serum samples with relative standard deviation less than 7.0%.


Protein kinase C in primary astrocyte cultures: cytoplasmic localization and translocation by a phorbol ester.
The distribution of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) in supernatant and particulate fractions of primary cultures of rat astrocytes and its translocation by a phorbol ester were studied. We observed that 91% of protein kinase C activity in astrocytes was in the supernatant fraction, as measured by lysine-rich histone phosphorylation assay. Attempts to uncover latent activity in the particulate fraction were unsuccessful. Approximately 75% of the supernatant protein kinase C activity could be translocated to the particulate fraction by prior treatment (30-60 min) of the cultures with 100 nM 12-O-tetradecanoyl-phorbol 13-acetate (TPA), but not with 4 alpha-phorbol, an inactive phorbol ester. Investigation of endogenous substrates for protein kinase C showed that TPA treatment brought about an increase in phosphorylation in membrane proteins and a decrease in phosphorylation of supernatant proteins. These findings indicate that the distribution of protein kinase C in astrocytes differs substantially from that in whole brain tissue, where approximately two-thirds of the protein kinase C activity is associated with the particulate fraction. Because protein kinase C is concentrated in the cytosol of astrocytes and most of this activity can be translocated to membranes, astrocytes may be particularly well-suited to respond to signals that activate phosphoinositide-linked receptors in brain.


Use of doxapram to increase respirations without a concomitant increase in intracranial pressure.
We treated a brain-damaged 8-month-old male with iv doxapram in order to discontinue mechanical ventilation. We were able to monitor intracranial pressure (ICP) throughout the course of doxapram via an ICP monitor. Despite normal and then excessive PaCO2, the patient's spontaneous respiratory rate remained nil before doxapram treatment. However, after an iv bolus dose followed by a maintenance drip, the patient's spontaneous respiratory rate increased while his ICP remained at baseline or slightly less than baseline, thereby allowing mechanical ventilation to be discontinued.


Observation of kinetic and structural scalings during slow coalescence of nanobubbles in an aqueous solution.
The addition of salt can induce the slow coalescence of nanobubbles (approximately 100 nm) in an aqueous solution of alpha-cyclodextrin (alpha-CD). A combination of static and dynamic laser light scattering was used to follow the coalescence. Our results reveal that its kinetic and structural properties follow some scaling laws; namely, the average size (<zeta>) of the nanobubbles is related to their average mass (<M>) and the coalescence time (t) as <M> approximately <zeta>(d(f)) and <zeta> approximately t(gamma) with two salt-concentration-dependent scaling exponents (d(f) and gamma). For a lower sodium chloride concentration (C(NaCl) = 40 mM), gamma = 0.13 +/- 0.01 and d(f) = 1.71 +/- 0.02. The increase of C(NaCl) to 80 mM results in gamma = 0.32 +/- 0.01 and d(f) = 1.99 +/- 0.01. The whole process has two main stages: the aggregation and the coalescence. At the lower C(NaCl), the process essentially stops in the aggregation stage with some limited coalescence. At higher C(NaCl), coalescence occurs after the aggregation and results in large bubbles.


BRCA1-like profile predicts benefit of tandem high dose epirubicin-cyclophospamide-thiotepa in high risk breast cancer patients randomized in the WSG-AM01 trial.
BRCA1 is an important protein in the repair of DNA double strand breaks (DSBs), which are induced by alkylating chemotherapy. A BRCA1-like DNA copy number signature derived from tumors with a BRCA1 mutation is indicative for impaired BRCA1 function and associated with good outcome after high dose (HD) and tandem HD DSB inducing chemotherapy. We investigated whether BRCA1-like status was a predictive biomarker in the WSG AM 01 trial. WSG AM 01 randomized high-risk breast cancer patients to induction (2× epirubicin-cyclophosphamide) followed by tandem HD chemotherapy with epirubicin, cyclophosphamide and thiotepa versus dose dense chemotherapy (4× epirubicin-cyclophospamide followed by 3× cyclophosphamide-methotrexate-5-fluorouracil). We generated copy number profiles for 143 tumors and classified them as being BRCA1-like or non-BRCA1-like. Twenty-six out of 143 patients were BRCA1-like. BRCA1-like status was associated with high grade and triple negative tumors. With regard to event-free-survival, the primary endpoint of the trial, patients with a BRCA1-like tumor had a hazard rate of 0.2, 95% confidence interval (CI): 0.07-0.63, p = 0.006. In the interaction analysis, the combination of BRCA1-like status and HD chemotherapy had a hazard rate of 0.19, 95% CI: 0.067-0.54, p = 0.003. Similar results were observed for overall survival. These findings suggest that BRCA1-like status is a predictor for benefit of tandem HD chemotherapy with epirubicin-thiotepa-cyclophosphamide.


Hydroxyindole-O-methyltransferase (HIOMT) activity in the retina of melatonin-proficient mice.
Numerous pieces of evidence support the expression by the mammalian retina of Hydroxyindole-O-methyltransferase (HIOMT, EC 184.108.40.206), the enzyme directly responsible for the biosynthesis of the pineal chronobiotic hormone melatonin (MLT). However, conflicting results obtained so far by enzyme-kinetic and immune-detection techniques still make HIOMT presence and relevance in the eye a matter of debate. This work aimed at evaluating unambiguously HIOMT activity in the mouse retina, a valuable model for studying the effects of MLT variations on ocular pathophysiology. Since laboratory mouse strains can bear genetic polymorphisms yielding defective enzymes of MLT biosynthesis, retinas and control pineal glands used in this study were obtained in a MLT-proficient crossing of A/J mice, the A/J/C57BL/10 strain. To improve the radiochemical reference assay, we tested different homogenization procedures coupled with HPLC detection. Concomitantly, we quantified MLT, and its precursor N-acetyl-serotonin (NAS) by HPLC coupled to electrochemical detection in retinas isolated from either light- or dark-adapted mice. Results showed that the standard radio-chemical assay was successful for pineal HIOMT only, whereas specific homogenization buffers and HPLC were required to detect retinal activity, presumably due to interfering methyl-transferases inhibited by NAS. Under present conditions, retinal HIOMT Vmax accounted for by ≈ 40 fmol/h/mg protein, 2.6-hundreds-fold lower than the pineal counterpart, displaying equivalent KMs (≈10 μM). Moreover, NAS and MLT rapidly decreased in light-exposed isolated retinas, corroborating light-sensitive in-situ MLT formation. Conclusively, we measured mouse retinal HIOMT kinetics under basal conditions, a useful result to elucidate the regulatory patterns, the possible impact on eye health, and therapeutic approaches related to this enzyme.


Enriched topological learning for cluster detection and visualization.
The exponential growth of data generates terabytes of very large databases. The growing number of data dimensions and data objects presents tremendous challenges for effective data analysis and data exploration methods and tools. Thus, it becomes crucial to have methods able to construct a condensed description of the properties and structure of data, as well as visualization tools capable of representing the data structure from these condensed descriptions. The purpose of our work described in this paper is to develop a method of describing data from enriched and segmented prototypes using a topological clustering algorithm. We then introduce a visualization tool that can enhance the structure within and between groups in data. We show, using some artificial and real databases, the relevance of the proposed approach.


Evolutionary Learning-Derived Clinical-Radiomic Models for Predicting Early Recurrence of Hepatocellular Carcinoma after Resection.
Current prediction models for early recurrence of hepatocellular carcinoma (HCC) after surgical resection remain unsatisfactory. The aim of this study was to develop evolutionary learning-derived prediction models with interpretability using both clinical and radiomic features to predict early recurrence of HCC after surgical resection. Consecutive 517 HCC patients receiving surgical resection with available contrast-enhanced computed tomography (CECT) images before resection were retrospectively enrolled. Patients were randomly assigned to a training set (n = 362) and a test set (n = 155) in a ratio of 7:3. Tumor segmentation of all CECT images including noncontrast phase, arterial phase, and portal venous phase was manually performed for radiomic feature extraction. A novel evolutionary learning-derived method called genetic algorithm for predicting recurrence after surgery of liver cancer (GARSL) was proposed to design prediction models for early recurrence of HCC within 2 years after surgery. A total of 143 features, including 26 preoperative clinical features, 5 postoperative pathological features, and 112 radiomic features were used to develop GARSL preoperative and postoperative models. The area under the receiver operating characteristic curves (AUCs) for early recurrence of HCC within 2 years were 0.781 and 0.767, respectively, in the training set, and 0.739 and 0.741, respectively, in the test set. The accuracy of GARSL models derived from the evolutionary learning method was significantly better than models derived from other well-known machine learning methods or the early recurrence after surgery for liver tumor (ERASL) preoperative (AUC = 0.687, p < 0.001 vs. GARSL preoperative) and ERASL postoperative (AUC = 0.688, p < 0.001 vs. GARSL postoperative) models using clinical features only. The GARSL models using both clinical and radiomic features significantly improved the accuracy to predict early recurrence of HCC after surgical resection, which was significantly better than other well-known machine learning-derived models and currently available clinical models.


Physical Rehabilitation for Small Animals.
Physical rehabilitation incorporates several elements, including but not limited to therapeutic exercises, manual therapy, and physical modalities. Understanding of the effects, indications, contraindications, and precautions is essential for proper use, while understanding of the diagnosis, assessment of the stage of tissue healing and repair, and accurate clinical assessment of the functional limitations are essential when establishing a physical rehabilitation plan.


Mechanical properties of interphase nuclei probed by cellular strain application.
The mechanical properties of the interphase nucleus have important implications for cellular function and can reflect changes in nuclear envelope structure and/or chromatin organization. Mutations in the nuclear envelope proteins lamin A and C cause several human diseases, such as Emery-Dreifuss muscular dystrophy, and dramatic changes in nuclear stiffness have been reported in cells from lamin A/C-deficient mice. We have developed a cellular strain technique to measure nuclear stiffness in intact, adherent cells and have applied this experimental method to fibroblasts from mouse models of Emery-Dreifuss muscular dystrophy and to skin fibroblasts from laminopathy patients and healthy control subjects. The experimental protocol is based on measuring induced nuclear deformations in cells plated on a flexible silicone substrate; the nuclear stiffness can subsequently be inferred from the ratio of induced nuclear strain to the applied membrane strain. These experiments reveal that lamins A and C are important determinants of nuclear stiffness and that lamin mutations associated with muscular dystrophies and other laminopathies often result in disturbed nuclear stiffness that could contribute to the tissue-specific disease phenotypes.


High-performance liquid chromatographic assay of rat-brain dopamine and norepinephrine.
A high-performance liquid chromatographic method for the assay of dopamine (DM) and norepinephrine (NE) in rat brain has been developed. 3,4-Dihydroxybenzylamine was added to the sample as an internal standard. The isolated amines and the internal standard were subjected to reaction with fluorescamine, separated liquid chromatographically on a glycol-type gel and determined fluorimetrically. The standard deviation of the method was +/-2.7% for DM and +/-5.3% for NE. The contents of DM and NE in rat brain, with or without administration of a tyrosine hydroxylase inhibitor, as measured by the proposed method were always lower than those obtained by the trihydroxyindole method.


Mitoxantrone therapy in rapidly worsening multiple sclerosis.
This study evaluates mitoxantrone (MX) therapy in patients with relapsing remitting and secondary progressive multiple sclerosis (MS). Evaluation of the disability progression and side effects of MX. There were studied 33 patients (10 males, 23 females), average age 48.5+/-9.9 SD) with relapsing remitting and secondary progressive MS. The disability was evaluated using Expanded Disability Status Scale (EDSS). Time period from the onset to secondary progressive course of the disease was 9.3 years. Patients, whose disability progression increased by one or more EDSS point per one year, and not responding to other therapy, were treated with mitoxantrone. Patients were treated once monthly with intravenous administration of mitoxantrone 12 mg/m2, not exceeding the maximum cumulative dose of 14 mg/m2 and Solu-Medrol 1000 mg. Six pulses were done in each patient. EDSS score was measured at the beginning of the treatment and after twelwe month. Disability progression was evaluated. Nonparametric Wilcoxon matched pair test was used for statistical analysis. (Tab. 1, Fig. 3, Ref: 5.)


SRC tyrosine kinase inhibitor, m475271, suppresses subcutaneous growth and production of lung metastasis via inhibition of proliferation, invasion, and vascularization of human lung adenocarcinoma cells.
Src, a proto-oncogene, has been strongly implicated in the growth, progression and metastasis of a number of human cancers. Its role in lung cancer is, however, still unknown. In the present study, we assessed the expression of Src in three different human lung adenocarcinoma cell lines (PC-9, PC14PE6, A549), and explored the effect of a novel Src kinase inhibitor, M475271, on the behavior of the cell lines. The three cell lines expressed various levels of auto-phosphorylated Src. While M475271 reduced Src-phosphorylation and invasiveness of all three cell lines, it inhibited the proliferation of PC-9 and A549 cells with highly phosphorylated Src, but not PC14PE6 cells. We further examined the effect of M475271 on subcutaneous tumors and lung metastasis caused by PC-9 and/or A549 cells in NK-cell depleted SCID mice. Daily oral treatment with M475271 inhibited the growth of subcutaneous tumors with PC-9 and A549 cells via inhibition of tumor cells proliferation, VEGF production and/or vascularization in the mice in a dose-dependent manner. In the metastasis model with A549 cells, the lung weight in the M475271 (50 mg/kg)-treated group was less than that of the control group, despite no difference in the number of metastatic nodules. Our results suggest that inhibition of tyrosine kinase Src by M475271 could reduce the growth, invasion and VEGF-mediated neovascularization of lung adenocarcinoma cells, resulting in inhibition of growth of subcutaneous tumors and lung metastasis. Therefore, a novel Src tyrosine kinase inhibitor, M475271, might be helpful for controlling the progression of human lung adenocarcinoma.


Effect of a Garcinia gardneriana (Planchon and Triana) Zappi hydroalcoholic extract on melanogenesis in B16F10 melanoma cells.
Garcinia gardneriana (Planchon and Triana) Zappi (Clusiaceae) is popularly called "bacopari" in southern Brazil. The leaves of this plant are traditionally used to treat skin disorders. This study evaluated the effects of a hydroalcoholic extract of Garcinia gardneriana leaves (HEGG) on B16F10 murine melanoma cells in order to search for new depigmenting agents. The effects of HEGG were assessed in melanin content assays in B16F10 melanoma cells compared with the reference drug kojic acid (500mM). Melanin content was measured after spontaneous melanogenesis, UVB-induced melanogenesis and melanogenesis induced by α-MSH. At the same time, cell viability assays were conducted. Intracellular and mushroom tyrosinase activity assays were employed to evaluate the effect of HEGG on tyrosinase activity. HEGG decreased the level of melanin under all three experimental conditions of melanin content evaluation without reducing cell viability. In intracellular tyrosinase assays, the enzyme's activity was reduced about 19% with extract concentrations ranging 0.1-10µg/mL. In the mushroom tyrosinase activity assay a maximal inhibition of 35% (1000µg/mL) was observed. These results suggest that HEGG inhibition relates to its tyrosinase activity. Therefore, the hydroalcoholic extract of Garcinia gardneriana shows great potential for use as a depigmenting agent in hyperpigmentation disorders.


From global bioethics to ethical governance of biomedical research collaborations.
One of the features of advanced life sciences research in recent years has been its internationalisation, with countries such as China and South Korea considered 'emerging biotech' locations. As a result, cross-continental collaborations are becoming common generating moves towards ethical and legal standardisation under the rubric of 'global bioethics'. Such a 'global', 'Western' or 'universal' bioethics has in turn been critiqued as an imposition upon resource-poor, non-Western or local medical settings. In this article, we propose that a different tack is necessary if we are to come to grips with the ethical challenges that inter-continental biomedical research collaborations generate. In particular we ask how national systems of ethical governance of life science research might cope with increasingly global research collaborations with a focus on Sino-European collaboration. We propose four 'spheres' - deliberation, regulation, oversight and interaction - as a helpful way to conceptualise national systems of ethical governance. Using a workshop-based mapping methodology (workshops held in Beijing, Shanghai, Changsha, Xian, Shenzen and London) we identified three specific ethical challenges arising from cross-continental research collaborations: (1) ambiguity as to which regulations are applicable; (2) lack of ethical review capacity not only among ethical review board members but also collaborating scientists; (3) already complex, researcher-research subject interaction is further complicated when many nationalities are involved.


Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events.
To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999-2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as >or=one vessel with >or=50% stenosis. Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.


Endoscopic Screening for Barrett's Esophagus and Esophageal Adenocarcinoma: Rationale, Candidates, and Challenges.
Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), a cancer with increasing incidence and poor survival. Risk of EAC in patients with BE is higher compared with the general population. Endoscopic screening for BE is performed to identify patients earlier in the metaplasia-dysplasia-carcinoma sequence from BE to EAC to enable eradication therapy. BE screening should be considered in individuals with multiple risk factors for BE and EAC. Challenges to BE screening include the absence of a cost-effective, widely applicable minimally invasive screening tool, gastroesophageal reflux disease centric screening recommendations, and limitations of current endoscopic surveillance practice.


Luting of ceramic crowns with a self-adhesive cement: effect of contamination on marginal adaptation and fracture strength.
This study evaluated the percentages of continuous margins (%CM) and fracture strength (FS) of crowns made out from blocs of leucite-reinforced ceramic (IPS Empress CAD) and luted with a representative self-adhesive cement (RelyX Unicem) under four contaminating agents: saliva, water, blood, a haemostatic solution containing aluminium chloride (pH= 0.8) and a control group with no contamination. %CM at both tooth-cement (TC) and cement-crown (CC) interfaces were determined before and after a fatigue test consisting of 600'000 chewing loads and 1'500 temperature cycles changing from 5⁰ C to 50⁰ C. Load to fracture was recorded on fatigued specimens. Kruskal-Wallis test was used to compare %CM and FS between the five groups with a level of confidence of 95%. At the TC interface, no significant differences in marginal adaptation before loading could be detected between groups. After loading, a significant marginal degradation was observed in the group contaminated with aluminium chloride (52 ± 22 %CM) in respect to the other groups. No significant differences in %CM could be detected between the groups contaminated with saliva, water, blood and the control. At the CC interface, no significant differences in marginal adaptation were observed between the groups. The FS on loaded specimens was around 1637N, with no significant differences between groups as well. An adverse interaction of the highly acidic haemostatic agent with either dentin or the self-adhesive cement could explain the specimens' marginal degradation. The self-adhesive cement tested in this study was no sensitive to moisture contamination either with saliva, water or blood.


Early proctoscopy is a surrogate endpoint of late rectal toxicity in prostate cancer treated with radiotherapy.
To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade ≥ 2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade ≥ 2 clinical rectal late toxicity was higher in patients with grade ≥ 2 (32% vs. 15 %, p = 0.02) or grade ≥ 3 VRS telangiectasia (47% vs. 17%, p ≤ 0.01) and an overall VRS score of ≥ 2 (31% vs. 16 %, p = 0.04) or ≥ 3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.


Role of TRPV1 receptors in descending modulation of pain.
Transient receptor potential vanilloid type 1 (TRPV1) receptor is a ligand-gated non-selective cation channel activated by heat (>43 degrees C), low pH and endogenous lipid molecules such as anandamide, N-arachidonoyl-dopamine, N-acyl-dopamines and products of lipoxygenases (12- and 15-(S)-HPETE) termed endovanilloids. Apart from peripheral primary afferent neurons and dorsal root ganglia, TRPV1 receptor is expressed throughout the brain. Recent evidence shows that TRPV1 receptor stimulation by endocannabinoids or by capsaicin within the periaqueductal grey (PAG) leads to analgesia and this effect is associated with glutamate increase and the activation of OFF cell population in the rostral ventromedial medulla (RVM). Activation of the antinociceptive descending pathway via TPRV1 receptor stimulation in the PAG may be a novel strategy for producing analgesia. This review will summarize the more recent insights into the role of TRPV1 receptor within the antinociceptive descending pathway and its possible exploitation as a target for novel pain-killer agents.


Optimizing modulation transfer spectroscopy signals for frequency locking in the presence of depleted saturating fields.
A theoretical model of modulation transfer spectroscopy (MTS) that includes pump beam depletion is presented and experimentally verified with data covering visible iodine transitions at 532, 543, and 612 nm. This model is used to determine the values for pressure, interaction length, and saturation intensity that yield maximum MTS signals for frequency locking to iodine transitions. The approach is demonstrated for iodine transitions at 532, 633, and 778 nm, with the results showing that theoretically the frequency instability scales inversely to the absorption coefficient.


Psychological and clinical correlates of posttraumatic growth in cancer: A systematic and critical review.
The objective of this study is to describe major findings on posttraumatic growth (PTG) in cancer, by analyzing its various definitions, assessment tools, and examining its main psychological and clinical correlates. A search in relevant databases (PsycINFO, Pubmed, ProQuest, Scopus, and Web of Science) was performed using descriptors related to the positive reactions in cancer. Articles were screened by title, abstract, and full text. Seventy-two met the inclusion criteria. Most articles (46%) focused on breast cancer, used the PTG inventory (76%), and had a cross-sectional design (68%). The PTG resulted inversely associated with depressive and anxious symptoms and directly related to hope, optimism, spirituality, and meaning. Illness-related variables have been poorly investigated compared to psychological ones. Articles found no relationship between cancer site, cancer surgery, cancer recurrence, and PTG. Some correlations emerged with the elapsed time since diagnosis, type of oncological treatment received, and cancer stage. Only few studies differentiated illness-related-life-threatening stressors from other forms of trauma, and the potentially different mechanisms connected with PTG outcome in cancer patients. The evaluation of PTG in cancer patients is worthy, because it may promote a better adaption to the illness. However, many investigations do not explicitly refer to the medical nature of the trauma, and they may have not completely captured the full spectrum of positive reactions in cancer patients. Future research should better investigate issues such as health attitudes; the risks of future recurrences; and the type, quality, and efficacy of medical treatments received and their influence on PTG in cancer patients.


Incidence, treatment, and survival trends in older versus younger women with epithelial ovarian cancer from 2005 to 2018: A nationwide Danish study.
To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (<70 and ≥ 70 years), stage, and period (2005-09, 2010-13, 2014-18). We included 7522 patients. The incidence decreased from 16.3 (2005) to 11.4 (2018) per 100,000 woman-years, driven by the younger cohort. While the proportion of patients with stage IIIC-IV disease undergoing primary debulking surgery (PDS) decreased, the proportion of patients having interval debulking surgery (IDS) and no debulking surgery increased significantly. In 2014-18, 36% and 24% had PDS for younger and older patients, respectively, compared to 72% and 62% in 2005-09. In both age cohorts, the proportion of patients debulked to no residual disease increased significantly among patients with stage IIIC-IV and in the total cohort. Two-year cancer-specific survival increased from 75% (2005-09) to 84% (2014-18) for younger patients and from 53% to 66% for older patients. After adjusting for potential confounders, age ≥ 70 was associated with a 1.4-fold increased risk of cancer-specific death (95% confidence interval: 1.2,1.5). The proportion of patients with advanced EOC not undergoing PDS or IDS increased significantly. During the same period, patients debulked to no residual disease, and cancer-specific survival increased. However, a survival gap in favor of the younger patients remains after adjusting for potential confounders.


Identification and determination of four metabolites of mangiferin in rat urine.
Four metabolites of mangiferin were firstly isolated and identified from rat urine. The structures of the four metabolites were determined to be 1,3,7-trihydroxyxanthone (M-1), 1,3,6,7-tetrahydroxyxanthone (M-2), 1,3,6-trihydroxy-7-methoxyxanthone (M-3) and 1,7-dihydroxyxanthone (M-4), respectively. A simple and specific analytical method for determination of the four metabolites in rat urine was developed by high performance liquid chromatography (HPLC). Quercetin was employed as an internal standard. The correlation coefficients of the calibration curves were higher than 0.997, both intra- and inter-day precision of four metabolites were determined and their R.S.D. did not exceed 10%. The accuracy and linear range had been investigated in detail. The cumulative urinary excretions of the four metabolites were measured and the possible metabolic pathway of the metabolites was discussed.


A possible model for the structure of the Neurospora carbamoyl phosphate synthase-aspartate carbamoyl transferase complex enzyme.
The pyrimidine-3 locus of Neurospora crassa specifies a multienzyme complex comprising pyrimidine-specific carbamoyl phosphate synthase (CPSpyr) and aspartate carbamoyl transferase (ACT). It appears to be divided into a translationally proximal CPS-specific region and a distal ACT-specific region. Levels of complementation for ACT activity between pairs of four pyr-3 CPS+ ACT- mutants showed a range from 12% to 68% of the wild-type level of the enzyme. This is interpreted as interallelic complementation, contradicting certain earlier suggestion of two dissimilar ACT subunits. Proteolysis of an extract from a heterokaryon formed from two of the above CPS+ ACT- alleles (alpha and beta) did not lead to loss of ACT activity, but led to the formation of a fragment with ACT activity with a similar molecular weight (92,000 daltons) to that produced in extracts of wild type strain. The pyr-3 polar mutant 43-174 which is enzymatically CPS+ ACT- and which fails to complement with any other CPS+ ACT- alleles, thus suggesting its location towards the proximal end of the ACT region, has CPS activity associated with a form of 180,000 daltons molecular weight. These findings are used to contruct a model for structure of the native enzyme complex.


Erratum.
Erratum to"The Incidence of Desaturation during Anesthesia in Adult and Pediatric Patients: A Retrospective Study", which appeared in the October 2018 issue, Vol.72,No.5, pp467-478.


The internet as a source of information used by women after childbirth to meet their need for information: A web-based survey.
the aims of this survey were: (a) to evaluate the need of information after childbirth and what questions do 'new' mothers ask themselves; (b) to assess why and how women use the Internet to meet their need of information; (c) to describe how the respondents evaluate the reliability of the information found; (d) to understand how the information found on the Internet affects women's decision-making; and (e) to appreciate how health professionals react to the information found by the women. this study used a large web-based survey that was widely broadcasted on various websites and social networks. belgian women who had a child under 2 years old and who agreed to participate were included in the study. 349 questionnaires were valid for analyses. After childbirth, 90.5% of women admitted to using the Internet to seek information about themselves or about their baby, regardless of socioeconomic status or age. There were various reasons for seeking information on the Internet, but the most frequent reason the women expressed was to find information 'on their own' (88.1%). The most searched for topic was breastfeeding. The women believed that the information was quite useful (82.7%) but they assigned an average score of 5.3 out of 10 for the quality of the information they found on the Internet. Approximately 80% of the women felt that the Internet helped them control a decision that they made 'a little', 'often' or 'very often'. Professionals are not always willing to talk about information found on the Internet with mothers. Therefore, many women believed that health professionals should suggest reliable Internet websites for new mothers. the integration of the Internet and new technologies could be a useful tool during postpartum management.


Bone tunnel enlargement after anterior cruciate ligament reconstruction with semitendinosus tendon using Endobutton fixation on the femoral side.
We evaluated 29 knees with a minimum follow-up of 2 years after anterior cruciate ligament (ACL) reconstruction using doubled autogenous semitendinosus tendons. On the femoral side, a 5-mm Mersilene tape (Ethicon, Norderstedt, Germany) with an Endobutton (Acufex Microsurgical, Mansfield, MA) was used. The tendon was fixed on the tibial side with two staples. Regarding the IKDC score, 66% of the patients were graded as normal or nearly normal. The anterior laxity side-to-side difference (KT 1000, man-max-drawer) was under 3 mm in 55% and under 5 mm in 90%. Radiographs taken in the lateral and anteroposterior projections of the knee showed sclerotic bone tunnel margins. The diameter of the bone tunnels were measured, corrected for magnification, then compared with the original reamed diameter to determine any change in size. Enlargement of at least 2 mm was identified in 72% of the femoral tunnels and 38% of the tibial tunnels. No correlation was found concerning the enlargement of the tunnel and the IKDC score or the residual joint laxity. We conclude that using an Endobutton-Mersilene construct in ACL reconstruction leads to femoral and tibial bone tunnel enlargement at follow-up of 2 years.


Heterozygous inactivation of plasma membrane Ca(2+)-ATPase in mice increases glucose-induced insulin release and beta cell proliferation, mass and viability.
Calcium plays an important role in the process of glucose-induced insulin release in pancreatic beta cells. These cells are equipped with a double system responsible for Ca(2+) extrusion--the Na/Ca exchanger (NCX) and the plasma membrane Ca(2+)-ATPase (PMCA). We have shown that heterozygous inactivation of NCX1 in mice increased glucose-induced insulin release and stimulated beta cell proliferation and mass. In the present study, we examined the effects of heterozygous inactivation of the PMCA on beta cell function. Biological and morphological methods (Ca(2+) imaging, Ca(2+) uptake, glucose metabolism, insulin release and immunohistochemistry) were used to assess beta cell function and proliferation in Pmca2 (also known as Atp2b2) heterozygous mice and control littermates ex vivo. Blood glucose and insulin levels were also measured to assess glucose metabolism in vivo. Pmca (isoform 2) heterozygous inactivation increased intracellular Ca(2+) stores and glucose-induced insulin release. Moreover, increased beta cell proliferation, mass, viability and islet size were observed in Pmca2 heterozygous mice. However, no differences in beta cell glucose metabolism, proinsulin immunostaining and insulin content were observed. The present data indicates that inhibition of Ca(2+) extrusion from the beta cell and its subsequent intracellular accumulation stimulates beta cell function, proliferation and mass. This is in agreement with our previous results observed in mice displaying heterozygous inactivation of NCX, and indicates that inhibition of Ca(2+) extrusion mechanisms by small molecules in beta cells may represent a new approach in the treatment of type 1 and type 2 diabetes.


What is the proper experimental unit for long-term rodent studies? An examination of the NTP benzyl acetate study.
The National Toxicology Program (NTP) rat bioassay on benzyl acetate shows an apparent increase in acinar-cell adenomas of the pancreas in male rats [1]. The statistical significance of the apparent trend is examined using the animal, cage, or rack/shelf location as the statistical independent experimental (sampling) unit. Experimental, statistical, and empirical considerations indicate that, in this experiment, if there is a proper experimental unit, it is the shelf of animals on a rack rather than the individual animal or cage of animals. Using the shelf as the experimental unit, the apparent increase in acinar-cell adenomas is not statistically significant. There is strong evidence for pancreatic tumor rates to differ among shelves which implies that toxicologists should consider cage randomization.


An investigation on 3-hydroxybenzaldehyde for exploring terahertz low-frequency vibration modes with quasi-harmonic approximation method.
3-Hydroxybenzaldehyde (3-HBA) was investigated in the range of 0.6-2.8 THz by terahertz time-domain spectroscopy (THz-TDS) and solid-state density functional theory (ss-DFT) with first-principles calculation. Four distinct peaks were found respectively, and among them, the intensity disparity between experiment and simulation spectra at 2.04 THz was recognized as the biggest inconsistency. Considering thermal behavior can be responsible for this, quasi-harmonic approximation (QHA) method was introduced to mimic the unit cell volume expansion. According to vibrational modes analysis, it was ascertained that the biggest vibrational modes discrepancy was also located at 2.04 THz. Molecules in 0% and 4% unit cell expansion exhibit an opposite rotational direction in a-b plane compared with 2% unit cell expansion. Noncovalent intermolecular interactions were investigated with independent gradient model (IGM), and the result indicates that hydrogen bonding is the dominating noncovalent interaction of 3-HBA. While calculating systematic potential energy to the displaced bonds stretching involving hydrogen atoms, it was found the anomalous potential energy variation to the bond stretching provides a possible explanation for the rotation direction divergence, that is, the rotation direction divergence can be related to some hydrogen atoms seeking lower overall potential energy around their equilibrium positions during bond stretching in response to the variational intermolecular van der Waals force. This research combined THz-TDS with the quasi-harmonic approximation method, elucidating the principle of vibrational characteristics in different volumes, which is beneficial to the investigation of the terahertz low-frequency vibration to thermal behavior as a reference in biochemistry and other fields.


Amino acid metabolism, lipid metabolism, and oxidative stress are associated with post-stroke depression: a metabonomics study.
Post-stroke depression (PSD) is a mood disorder characterized by depression and anhedonia caused by stroke. Metabolomics identified metabolites associated with PSD, but previous studies are based on gas chromatography (GC)/mass spectrometry (MS). This study aimed to perform a liquid chromatography (LC)-MS-based metabolomics study of the plasma metabolite profiles between patients with PSD and controls. This was a prospective study of patients with stroke enrolled between July and December 2017 at the Second Affiliated Hospital of Nanchang University. Patients were grouped as Hamilton Depression Rating Scale > 7 (PSD) or < 7 (controls). Metabonomics profiling of plasma sampled was conducted by LC-MS. By combining multivariable and univariable statistical analyses, significant differential metabolites between the two groups were screened. The threshold for significant differences was VIP ≥1 and P < 0.05. Log2FC is the logarithm of the mean ratio between the two groups. There were no significant difference with respect to age, NIHSS score, and MMSE between the two groups (all P > 0.05). There were six differential metabolites between the PSD and stroke groups, of which three metabolites were increased and three were decreased. Compared with the control group, p-chlorophenylalanine (Log2FC = 1.37, P = 0.03), phenylacetyl glutamine (Log2FC = 0.21, P = 0.048), and DHA (Log2FC = 0.77, P = 0.01) levels were higher in the PSD group, while betaine (trimethylglycine) (Log2FC = - 0.79, P = 0.04), palmitic acid (Log2FC = - 0.51, P = 0.001), and MHPG-SO4 (Log2FC = - 2.37, P = 0.045) were decreased. Plasma metabolomics showed that amino acid metabolism (phenylacetyl glutamine, p-chlorophenylalanine, trimethylglycine), lipid metabolism (DHA, palmitic acid, trimethylglycine), and oxidative stress (DHA, palmitic acid, trimethylglycine) were associated with PSD. These results could help to reveal the pathophysiological mechanism of PSD and eventually identify treatment targets.


Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients. Peripheral blood of 34 SLE patients and 18 healthy controls (HC) was stimulated with phorbol myristate acetate (PMA) and calcium ionophore (Ca-Io). Percentages of IL-21- and IL-17A expressing T-cells were analysed by flow cytometry. The expression levels of the transcription factors B-cell lymphoma-6 (BCL-6) and factors retinoid-related orphan receptor (ROR-γt) were assessed in T-cells by real-time RT-PCR and flow cytometry. Additionally, IL-21 receptor (IL-21R) expression on B- and T-cells of patients and HC was analyzed. Significantly increased percentages of IL-21 expressing CD4+ T-cells and CD8+ T-cells were found in SLE patients as compared to HC. The percentages of IL-21+ CD4+ T-cells and CD8+ T-cells correlated significantly with the percentages of IL-17A+ CD4+ T-cells and CD8+ T-cells, respectively. The relative expression of BCL-6 and ROR-γt did not differ between SLE patients and HC. IL-21R expression occurred mainly on B-cells and was not different comparing SLE patients and HC. This study demonstrates an increased proportion of IL-21+ T-cells in SLE patients correlating with the proportion of IL-17+ T-cells. This suggests a pivotal role of IL-21 in the pathogenesis of SLE.


Triggers of migraine in children at a public hospital in India.
We conducted a descriptive study of children presenting with recurrent headaches to the general pediatric services of a tertiary-care, public hospital in northern India. This paper reports on the triggering factors of migraine in this population. 43 children, 3-18 year old (23 females, median age 10 years), presenting with recurrent headache from April, 2011 to January, 2012, were enrolled. History, clinical examination and follow-up were done using a structured proforma. Headache diagnosis was made on the basis of International Classification of Headache Disorders, 2nd edition (ICHD-II). 26 patients (60.5%) had headache with migraine features (11 had Tension type headache and 4 had non-specific headaches). Stress (both physical and emotional) was identified by the majority of children (46.1%) as the trigger for the headache. The triggers reported were different from those reported from other settings in India. We wish to highlight that the relative contribution of triggers in pediatric migraine may not be similar across regions/populations.


Similar somatotopy for active and passive digit representation in primary somatosensory cortex.
Scientists traditionally use passive stimulation to examine the organisation of primary somatosensory cortex (SI). However, given the close, bidirectional relationship between the somatosensory and motor systems, active paradigms involving free movement may uncover alternative SI representational motifs. Here, we used 7 Tesla functional magnetic resonance imaging to compare hallmark features of SI digit representation between active and passive tasks which were unmatched on task or stimulus properties. The spatial location of digit maps, somatotopic organisation, and inter-digit representational structure were largely consistent between tasks, indicating representational consistency. We also observed some task differences. The active task produced higher univariate activity and multivariate representational information content (inter-digit distances). The passive task showed a trend towards greater selectivity for digits versus their neighbours. Our findings highlight that, while the gross features of SI functional organisation are task invariant, it is important to also consider motor contributions to digit representation.


The application of chitosan as a carrier for fertilizer: A review.
The smart combination of agriculture and other sciences can greatly reduce the limits of fertilizer use. Chitosan is a linear amino polysaccharide with a rigid structure which has hydrophilic and crystal properties. The formation of intermolecular hydrogen bonds the presence of reactive groups and cross-linking, the formation of salts with organic and inorganic acids with complexing and chelating properties ionic conductivity, film formation are the characteristics of chitosan. With the presence of amino groups, chitosan can form a complex with other compounds and also enter the vascular system of plants and lead to the activation of metabolic-physiological pathways of plants. This polymeric compound can bond with other natural polymers and in combination with fertilizers and nutritional elements, on the one hand, it can provide the nutritional needs of the plant and on the other hand, it also helps to improve the soil texture. Chitosan nanomaterials as a Next-generation fertilizers act as plant immune system enhancers through slow, controlled, and targeted delivery of nutrients to plants. Chitosan can assist agricultural researchers and has become an ideal and effective option with its many applications in various fields.


Hybridization between alien species Rumex obtusifolius and closely related native vulnerable species R. longifolius in a mountain tourist destination.
Alien species expand their distribution by transportation network development. Hybridization between alien species Rumex obtusifolius and closely related native vulnerable species R. longifolius was examined in a mountain tourist destination in central Japan. The three taxa were morphologically identified in the field. Stem height and leaf area were greater in R. longifolius than R. obtusifolius; hybrids were intermediate between the two Rumex species. R. longifolius and the hybrids grew mainly in wet land and the river tributary; R. obtusifolius grew mainly at the roadside and in meadows. Hybrid germination rates of pollen and seeds were much lower than for the two Rumex species. Clustering analysis showed the three taxa each formed a cluster. Most hybrids were F1 generation; the possibility was low of introgression into the two Rumex species by backcross. This study clarified that (1) hybridization occurred between R. obtusifolius and R. longifolius because they occurred together in a small area, but grew in different water habitat conditions, and (2) hybridization was mostly F1 generation because hybrid pollen and seed fertility was low. However, we need caution about introgression into R. longifolius by R. obtusifolius in this area because of the slight possibility of F2 generation and backcrosses.


Characteristics of a ferritin-binding protein present in human serum.
The ferritin present in human serum differs from the ferritins found in tissues and other body fluids in having negligible proportions of H subunits. This has been related to the possible presence of binding factors which would form complexes with H-subunit containing ferritins and thereby determine their rapid clearance and/or interference with immunoassays ('serum inhibition'). In this work we have tried to identify and characterize these binding factors. Dotting and blotting experiments demonstrated an interaction between tissue ferritins and human serum. This was stronger with human heart and recombinant H-type ferritin obtained from E. coli than with human liver ferritin. The serum binder appeared to be a glycoprotein migrating in the beta-2 region and with a molecular weight of about 200,000 and pI between 4 and 5. Two different approaches to purification of the ferritin-binding protein yielded enriched fractions containing also the complement proteins C3 and C4, the plasma protease inhibitor alpha-2-macroglobulin, and immunoglobulins. These in vitro findings may have physiological relevance.


Comparison of Hydralazine/Nitrate and Angiotensin Receptor Neprilysin Inhibitor Use Among Black Versus Nonblack Americans With Heart Failure and Reduced Ejection Fraction (from CHAMP-HF).
Underuse of hydralazine/nitrate (HYD/NIT) in black patients with heart failure and reduced ejection fraction (HFrEF) has been previously described, but whether this important treatment gap persists in contemporary practice is unknown. Sacubitril/valsartan has become a part of guideline-directed medical therapy for HFrEF but data on utilization of this therapy in black patients is lacking. This study addressed these issues by assessing the frequency of HYD/NIT and sacubitril/valsartan use in black patients with HFrEF in the Change the Management of Patients with Heart Failure Registry, a multicenter cohort study. The association of race with utilization rates of these agents was also evaluated. Clinical and medication data at baseline and during 12 months of follow-up from black and nonblack registry patients without documented contraindications or intolerance to the medications of interest were analyzed. Data were available from December 2015 to October 2017, in 4,848 HFrEF patients, of whom 853 were black (18%) and 3995 were nonblack. Black patients were younger, more likely to be female, and had lower ejection fractions compared with nonblacks. Only 11% of black patients were receiving HYD/NIT therapy at baseline and 13% at 1 year. The percentage of black patients treated at baseline with sacubitril/valsartan was also low at 18% and remained unchanged at 1 year. After adjustment for covariates, race was independently associated with HYD/NIT use (odds ratio 8.32; 95% confidence interval 6.12 to 11.3; p < 0.0001), but not for sacubitril/valsartan. In conclusion, study findings demonstrate a marked persistent treatment gap for HYD/NIT and similar poor utilization of sacubitril/valsartan in black patients with HFrEF despite current guideline recommendations.


An approach to automated measuring morphological parameters of proximal femora on three-dimensional models.
Analyses of the morphology of proximal femora are essential for preoperative planning and designing customized femoral stems in total hip arthroplasty as well as intramedullary nailing fixation. Various studies reported measurements and analyses on the general geometry of proximal femora three-dimensionally. However, the modeling and measurements are time-consuming and unfriendly to surgeons. Thus, automated measurement and modeling of the femoral medullary canal are critical to promote the clinical application. An approach to automated measuring morphological parameters of proximal femur was proposed, and a software allowing importing femur models and manually locating the related anatomic landmarks was developed in the current study. 3D modeling of the femoral medullary canal was created by the semispherical iterative searching algorithm, and 16 key anatomic parameters of the proximal femur were automatically calculated by the least-squares fitting algorithm. By experimenting on 196 femur STL models, the average execution time of single measurement was 0.88 (SD = 0.13) s, and the intra-class correlation coefficient of 10 anatomic parameters was between 0.880 and 0.996, showing high intra-rater and inter-rater reliability. The parameters of proximal femur can be easily measured, and the 3D modeling of the femoral medullary canal can be rapidly achieved. The approach will be easily applicable to clinical practice and has the potential to be applied in the design of customized femoral stems.


[Seasonal variations in nutrition behavior: results of the dietary survey of 1984/85 of the MONICA project in Augsburg].
Seven-day food records of the MONICA project Augsburg dietary survey, which were collected between October 1984 and May 1985 in 899 men aged 45-64 years, were used to analyse seasonal variations. Variations could be found in several food groups, but nutrient intake was nearly the same in autumn, winter and spring--with the exceptions of total fibre and alcohol.


Structure trees and species trees: what they say about morphological development and evolution.
The evolutionary history of morphological structures generally is equated with that of the taxa that carry them. It is argued here that, analogous to genes, developmental genetic pathways underlying morphological structures may be subject to developmental evolutionary changes that result, for instance, in duplication (serial homology analogous to gene duplication and paralogy). Entities that undergo evolution are expected to be related to each other as a tree. Just as with molecular evolution, "structure trees" and species trees sometimes may be incongruent, with implications for morphological homology concepts. Detection of structure trees through morphological evolutionary analyses may point to an entity that is maintained through evolution, possibly in part because it is a developmentally integrated structure ("individualized"). This idea is illustrated in a morphological evolutionary analysis of leaf primordia. These analyses suggest that leaf primordia in monocots and close relatives are related to each other as a tree and, therefore, are developmentally integrated, evolving entities. Among monocot primordia this tree structure breaks down, and it is concluded that there is no entity, the "monocot leaf primordium." However, one group of primordia is identified within monocots that have uniform characteristics and that are well represented by model species maize and rice. Such analyses of structure trees can facilitate the extrapolation and interpretation of results from molecular developmental and other comparative studies.


Microelements in seminal plasma of infertile men infected with Ureaplasma urealyticum.
The purpose of this study was to assess the association among male infertility, infection of Ureaplasma urealyticum (Uu), and microelements in seminal fluid. Semen analysis and cultivation of Uu were carried out on 160 samples of seminal fluid. The concentrations of microelements, such as arsenic (As), molybdenum (Mo), magnesium (Mg), lead (Pb), copper (Cu), cadmium (Cd), and zinc (Zn) in the samples were measured by an inductively coupled plasma quantometer (ICP). The ratios Cu/Zn and Cd/Zn in the poor spermatic quality group were obviously higher than those in seminal plasma of the group with normal spermatic quality (p<0.01 and p<0.05, respectively), whereas the concentrations of As, Mg, Mo, and Pb showed no difference in the two groups. The ratios Cu/Zn and Cd/Zn and the concentrations of As and Mg in seminal plasma infected with Uu were markedly higher than those not infected with Uu (p<0.05, p<0.01, p<0.05, and p<0.05, respectively), whereas the concentrations of Mo and Pb showed no statistical difference. The ratios Cu/Zn and Cd/Zn and the concentrations of As and Mg in seminal plasma of the semen with poor spermatic quality and Uu infection were obviously higher than those not infected with Uu (p<0.05), whereas the concentrations of Mo and Pb showed no statistical difference. Abnormally high ratios Cu/Zn and Cd/Zn as well as an overdose of As were found to be predisposed to Uu infection. Uu infection resulted in an increase of the ratios Cu/Zn and Cd/Zn and the concentrations of As and Mg in seminal fluid, which therefore caused spermatic quality decline.


A mu-opioid feedback model of human social behavior.
Since the discovery of pain relieving and rewarding properties of opiates such as morphine or heroin, the human mu-opioid system has been a target for medical research on pain processing and addiction. Indeed, pain and pleasure act mutually inhibitory on each other and the mu-opioid system has been suggested as an underlying common neurobiological mechanism. Recently, research interest extended the role of the endogenous mu-opioid system beyond the hedonic value of pain and pleasure towards human social-emotional behavior. Here we propose a mu-opioid feedback model of social behavior. This model is based upon recent findings of opioid modulation of human social learning, bonding and empathy in relation to affiliative and protective tendencies. Fundamental to the model is that the mu-opioid system reinforces socially affiliative or protective behavior in response to positive and negative social experiences with long-term consequences for social behavior and health. The functional implications for stress, anxiety, depression and attachment behaviors are discussed.


Examining the association between pediatric bipolar disorder and anxiety disorders in psychiatrically referred children and adolescents.
To examine the association between anxiety (ANX) and bipolar disorders (BPD) in a clinically referred pediatric sample. Subjects were consecutively referred youth aged <18 years, with a DSM-III-R/DSM-IV diagnosis of BPD (n=297) or a disruptive behavior disorder (DBD) (n=1100) on structured interview. Bipolar disorder in youth was associated with a significantly increased risk for most of the DSM-IV anxiety disorders and was not specifically linked to any one disorder in particular. Bipolar disorder in youth is a significant risk factor for anxiety comorbidity. Considering the morbidity and dysfunction as well as the differing therapeutic needs associated with bipolar and anxiety symptomatology, appropriate therapeutic approaches will be needed for the management of youth with this comorbidity.


Validation of radiation dose received by frozen unprocessed and processed bone during terminal sterilisation.
Fresh frozen femoral heads (FH) and frozen processed bone (FP) are widely used as a source of allograft bone. The FP bone and some of the FH are terminally sterilised by the National Blood Service Tissue Services (NSBTS), via application of a minimum 25 kGy gamma radiation dose. To comply with the Guidelines for the Blood Transfusion Services in the United Kingdom (2002), frozen musculoskeletal tissue must be maintained below -40 degrees C during storage and transit. In practice, NBSTS stores bone long-term in -80 degrees C freezers. During transport for irradiation, a temperature of circa -79 degrees C is maintained by packing the bone in dry ice. An evaluation of the radiation dose received by bone has previously been made via dosimeters located within the tissue and dry ice, however, some evidence suggests that low temperature can influence the accuracy of the dosimeter readings. The aim of this study was to determine the actual radiation dose received by FH and FP bone during the irradiation process. This was accomplished by comparing radiation dose readings from dosimeters placed in dry ice with dosimeters placed in a dry ice substitute of similar dimensions and density i.e., polytetrafluoroethylene (PTFE) at ambient temperature. New packing formats were developed for both FH and FP bone such that 15 FH or 3 kg of FP bone could be irradiated in one transport box at any given time in a standardised fashion. The data show that low temperature consistently increased dosimeter readings 10--27%, and that radiation dose always fell within the range of 25--40 kGy (FH=25.1--35.7 kGy; FP bone=25.2--32.4 kGy).


Multiple daily fractions of radiation in the palliation of pain from bone metastases.
Twenty consecutive patients have been treated for palliation of pain from bony metastases with radiotherapy using a regime of multiple daily fractions. Patients received up to three treatments daily with 3-4 hour intervals between fractions. Pain was relieved in all cases and pain relief took place earlier in the treatment than with conventional daily regimes. Nausea was mild in most cases. Some factors in its aetiology are discussed. Acute skin reactions were minimal. The total dosage required and the advantages and disadvantages of the method are discussed.


Oxidation of alkyl nitronates catalyzed by 2-nitropropane dioxygenase from Hansenula mrakii.
2-Nitropropane dioxygenase from Hansenula mrakii was expressed in Escherichia coli cells and purified in active and stable form using 60% saturation of ammonium sulfate and a single chromatographic step onto a DEAE column. MALDI-TOF mass spectrometric and spectrophotometric analyses of the flavin extracted by heat or acid denaturation of the enzyme indicated that FMN, and not FAD as erroneously reported previously, is present in a 1:1 stoichiometry with the protein. Inductively coupled plasma mass spectrometric analysis of the enzyme established that H. mrakii 2-nitropropane dioxygenase contains negligible amounts of iron, manganese, zinc, and copper ions, which are not catalytically relevant. Anaerobic substrate reduction and kinetic data using a Clark oxygen electrode to measure rates of oxygen consumption indicated that the enzyme is active on a broad range of alkyl nitronates, with a marked preference for unbranched substrates over propyl-2-nitronate. Interestingly, the enzyme reacts poorly, if at all, with nitroalkanes, as suggested by lack of both anaerobic reduction of the enzyme-bound flavin and consumption of oxygen with nitroethane, nitrobutane, and 2-nitropropane. Finally, both the tight binding of sulfite (K(d)=90 microM, at pH 8 and 15 degrees C) to the enzyme and the formation of the anionic flavosemiquinone upon anaerobic incubation with alkyl nitronates are consistent with the presence of a positively charged group in proximity of the N1-C2=O atoms of the FMN cofactor.


Interaction of spectrin with phospholipids. Quenching of spectrin intrinsic fluorescence by phospholipid suspensions.
Phospholipid suspensions prepared of phosphatidylethanolamine, phosphatidylserine and their mixtures are able to influence the intrinsic protein fluorescence of spectrin. In the case of phosphatidylethanolamine suspension up to 75% of protein fluorescence can be quenched. The interaction of phospholipid aggregates with spectrin is modulated by pH and ionic strength. Phospholipids, particularly phosphatidylethanolamine display a 'stabilizing' effect against the changes of protein fluorescence induced by increasing ionic strength and by thermal denaturation.


Global, region and national trends and age-period-cohort effects in colorectal cancer burden from 1990 to 2019, with predictions to 2039.
Nowadays, colorectal cancer (CRC) is the second leading cause of cancer deaths and contributes to a gradually increasing disease burden. We aimed to estimate the secular trends of global CRC burden, the effect of age, period, and birth cohort, and project the global burden over time. Based on the epidemiological CRC data from 1990 to 2019 in 204 countries and territories from GBD 2019, the estimated annual percentage change (EAPC), was calculated from a linear model and joinpoint regression model. We utilized an age-period-cohort model to reckon age, period, and birth cohort effects on CRC age-standardized rate. The burden of CRC was projected by conducting the BAPC model. Globally, there was a slight decline in the age-standardized DALY rate, which was more apparent in females, with high SDI regions and in Australia and Western Europe areas. Meanwhile, our model predicts a weaker increase in morbidity (EAPC of 0.37) and a speedier reduction in mortality (EAPC of -0.66) by the next 20 years. The relative risk of period for high SDI regions decreased from 1.08 (95%UI: 1.06-1.1) in 1990-1994 to 0.85 (95%UI:0.83-0.88) in 2015-2019, but worsens in low and middle SDI regions. The local drifts were more than 1 in the 30-34 and 35-39 age groups, indicating the rising tide of early-onset CRC. Given the gender and region-specific CRC, targeted efforts to reduce the prevalence of risk factors, improve screening coverage rates, and strengthen foundational medical facilities are necessary.


Frequency Tuning of Hearing in the Beluga Whale.
Data on frequency tuning in odontocetes are contradictory: different authors have reported filter qualities from 2 to almost 50. In this study, frequency tuning was measured in a beluga whale (Delphinapterus leucas) using a rippled-noise test stimulus in conjunction with the auditory evoked potential (AEP) technique. The response to ripple reversions was considered to indicate resolvability of the ripple pattern. The limit of ripple-pattern resolution ranged from 20 to 32 ripples per octave (rpo). A model of interaction of the ripple spectrum with frequency-tuned filters suggests that this resolution limit requires a filter quality of 29-46.


Tumor localization by Prostate Imaging and Reporting and Data System (PI-RADS) version 2.1 predicts prognosis of prostate cancer after radical prostatectomy.
An improved reading agreement rate has been reported in version 2.1 (v2.1) of the Prostate Imaging and Reporting and Data System (PI-RADS) compared with earlier versions. To determine the predictive efficacy of bi-parametric MRI (bp-MRI) for biochemical recurrence (BCR), our study assessed PI-RADS v2.1 score and tumor location in Japanese prostate cancer patients who underwent radical prostatectomy. Retrospective analysis was performed on the clinical data of 299 patients who underwent radical prostatectomy at Chiba University Hospital between 2006 and 2018. The median prostate-specific antigen (PSA) level before surgery was 7.6 ng/mL. Preoperative PI-RADS v2.1 categories were 1-2, 3, 4, and 5 in 35, 56, 138, and 70 patients, respectively. Tumor location on preoperative MRI was 107 in the transition zone (TZ) and 192 in the peripheral zone (PZ). BCR-free survival was significantly shorter in the PZ group (p = 0.001). In the total prostatectomy specimens, preoperative PI-RADS category 5, radiological tumor location, pathological seminal vesicle invasion, and Grade Group ≥ 3 were independent prognostic factors of BCR. These four risk factors have significant potential to stratify patients and predict prognosis. Radiological tumor location and PI-RADS v2.1 category using bp-MRI may enable prediction of BCR following radical prostatectomy.


Complementary and Integrative Treatments of Aggressiveness/Emotion Dysregulation: Associated with Disruptive Disorders and Disruptive Mood Dysregulation Disorder.
Youth with emotional dysregulation (ED) and irritability/aggression, common in disruptive disorders (frequently comorbid with attention-deficit/hyperactivity disorder), are underserved by conventional treatments. Anger dysregulation is usually the core feature of ED. Complementary and integrative Medicine (CIM) treatments for youth with disruptive disorders and ED are reviewed. Broad-spectrum micronutrient supplementation has a medium effect and is supported by two double-blind randomized controlled trials using similar formulations. Other CIM treatments supported by controlled data but needing further research, include omega-3 fatty acid supplementation, music therapy, martial arts, restricting exposure to media violence, decreasing sleep deprivation, and increased exposure to green-blue spaces.


Added value of pharmacogenetic testing in predicting statin response: results from the REGRESS trial.
It was investigated whether pharmacogenetic factors, both as single polymorphism and as gene-gene interactions, have an added value over non-genetic factors in predicting statin response. Five common polymorphisms were selected in apolipoprotein E, angiotensin-converting enzyme, hepatic lipase and toll-like receptor 4. Linear regression models were built and compared on R(2) to estimate the added value of single polymorphisms and gene-gene interactions. The selected polymorphisms and the gene-gene interactions had a small added value in predicting change in low-density lipoprotein cholesterol levels (LDL-c) as response to statins over the non-genetic predictors (P=0.104), and also in predicting LDL-c in non-treated patients (P=0.016). Moreover, four gene-gene interactions with statin therapy were identified. The added value of genetic factors over non-genetic variables is for the greater part produced by gene-gene interactions. This underlines the importance to examine gene-gene interactions in future (pharmaco)genetic research.


Psychiatry in the Deep South: a pilot study of integrated training for psychiatry residents and seminary students.
The authors describe an interdisciplinary training experience developed for psychiatry residents and seminary students that assessed each group's beliefs and attitudes toward the other's profession. The training was designed to enhance awareness, positive attitudes, and interaction between the disciplines. From 2005 to 2008, PGY-2 general-psychiatry residents and PGY-5 child-psychiatry residents (N=30) participated alongside psychology interns (N=13) and seminary students (N=41). The intervention consisted of two 3-hour sessions. Measurements addressed demographics, participants' spirituality, and attitudes toward mental illness, mental-health practitioners, and clergy. The psychiatry residents' knowledge regarding the training of clergy was significantly increased by the training sessions. The seminary students' attitudes and knowledge of psychiatry/psychology changed significantly in a positive direction. This pilot course had a positive impact on both groups of participants. This model could be modified for other psychiatry programs, to include clergy students of different religious faiths as relevant to the demographics of the training location.


A New Formulation of Oral Viscous Budesonide in Treating Paediatric Eosinophilic Oesophagitis: A Pilot Study.
Oral viscous budesonide is a recent therapeutic option for eosinophilic oesophagitis (EoE) compared with dietary restriction and inhaled steroids. This single-centre, open-label, not blinded study aims to evaluate the efficacy and safety of a new, preprepared oral viscous budesonide suspension (PVB) in children and adolescents with EoE. We treated 36 children with PVB (29 boys; median age 12 years) with EoE diagnosed according to European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines. Patients <150 and >150 cm height received 2 and 4 mg PVB daily, respectively, for 12 weeks. Upper gastrointestinal endoscopy was performed at baseline, after 12 weeks of therapy and 24 weeks after the end of therapy. Baseline and post-treatment scores were calculated for symptoms, endoscopy, and histology. Serum cortisol was performed at baseline, 12, and 36 weeks. At the end of PVB trial, endoscopy showed macroscopic remission in 32 patients (88.9%), whereas at histology median pre- and post-treatment peak eosinophil count/high power field (HPF) markedly decreased from 42.2 (range: 15-100) to 2.9 (range: 0-30); moreover, mean symptom and histology scores impressively improved compared with baseline (P < 0.01). At 24 weeks after the end of PVB therapy, endoscopy showed oesophageal relapse in 21 patients (58.3%), whereas 15 (41.7%) were still in remission. Seven children (19.4%) with positive multichannel intraluminal impedance-pH were treated also with proton pump inhibitors. No significant difference between pre-/post-treatment morning cortisol levels occurred. The new PVB suspension presented in the present study is effective and safe for treating children with proven EoE. Larger placebo-controlled clinical trials would provide more information about dosing, efficacy, and long-term safety of this formulation, specifically designed for the oesophagus.


[Global ablation of endometrium as a new uterus sparing operative method in uterine dysfunctional bleeding].
A new method of endometrial ablation has been presented. This is the method of bipolar tridimensional device "NOVA SURE". This innovative method enables to destruct the basal and functional layer of the uterus and thus leads to amenorrhea and hypomenorrhea.


Deficits in coordinated motor behavior and in nigrostriatal dopaminergic system ameliorated and VMAT2 expression up-regulated in aged male rats by administration of testosterone propionate.
The effects of testosterone propionate (TP) supplements on the coordinated motor behavior and nigrostriatal dopaminergic (NSDA) system were analyzed in aged male rats. The present study showed the coordinated motor behavioral deficits, the reduced activity of NSDA system and the decreased expression of vesicular monoamine transporter 2 (VMAT2) in 24 month-old male rats. Long term TP treatment improved the motor coordination dysfunction with aging. Increased tyrosine hydroxylase and dopamine transporter, as well as dopamine and its metabolites were found in the NSDA system of TP-treated 24 month-old male rats, indicative of the amelioratory effects of TP supplements on NSDA system of aged male rats. The enhancement of dopaminergic (DAergic) activity of NSDA system by TP supplements might underlie the amelioration of the coordinated motor dysfunction in aged male rats. TP supplements up-regulated VMAT2 expression in NSDA system of aged male rats. Up-regulation of VMAT2 expression in aged male rats following chronic TP treatment might be involved in the maintenance of DAergic function of NSDA system in aged male rats.


[Skeletal findings in historical beheadings in the Bern canton].
The skeleton of a decapitated buried in historical times (before 1798) is compared with the anatomical findings on cervical vertebrae from the last seven decapitated individuals on Bernese territory (19th century).


The locus ceruleus: a possible neural focus for genetic differences in emotionality.
The Maudsley Reactive and Non-Reactive strains have been developed as a model for the study of individual variations in stress-reactivity, and many differences in biobehavioral systems have been found between them. This review discusses limitations of the 'emotionality' construct in accounting for differences between the Maudsley strains and offers an alternative, theoretical approach. Amaral and Sinnamon have proposed that the locus ceruleus (LC) plays a stress-attenuating role in mediating behavioral, physiological and neuroendocrine response to prepotent, emergency-provoking stimuli and, building upon this formulation, it is proposed that the LC has been an important focus for gene action in the Maudsley model. It is suggested that the LC of the Non-Reactive strain is more strongly activated by stressful stimuli than the LC of Reactive rats, and is the basis of many of the behavioral and physiological differences between them. Behavioral and biochemical evidence consistent with this proposition is reviewed. Identification of the LC as a target for gene-action in the Maudsley model has an important advantage. It substitutes variations at a specific anatomic location in the brain for a loosely defined construct like emotionality, and the hypothesis is amenable to empirical tests by a variety of experimental approaches.


Errors in MDCT diagnosis of acute mesenteric ischemia.
The causes of diagnostic errors during daily medical practice can be several, mainly attributable to perceptual, interpretive and communication factors. The eventuality of radiological error is much more amplified in the emergency setting where a high number of complex multidetector-row computed tomography (MDCT) images must be evaluated quickly and critical time decisions need to be taken. In particular, in this context, the diagnosis of vascular intestinal diseases represents a crucial and difficult challenge in case of acute abdominal pain given the importance of being able to identify patient with high suspicious for intestinal ischemia and for a specific patient to judge if his ischemia is reversible or irreversible. Awareness of potential biases which can lead to diagnostic errors together with an extensive knowledge of the imaging features of these pathologies can lead to promptly recognize them with fewer mistakes, improving patients' outcome. This article reviews the MDCT findings of acute intestinal ischemia and acute colonic ischemia and analyzes the main types of diagnostic errors, underlining the importance of being familiarized with them to avoid misdiagnosis.


Enhancing acetabular reaming accuracy: optimal techniques and a novel reamer design.
Successful press-fit implantation relies on an accurately reamed bone cavity. Inaccurate reaming can lead to a suboptimal press-fit risking fracture and cup deformation or excessive micromotion and loosening. Several factors may impact reaming accuracy including the reamer design, the surgeon's technique and the bone quality. The aim of this study is to investigate the accuracy of reaming techniques and the accuracy of a novel reamer design. Eighty composite bone models, half high density and half low density, were reamed with either a conventional or an additively manufactured reamer with a novel design employing either a straight or 'whirlwind' reaming technique. Reamed cavities were scanned using a 3D laser scanner and the median difference between achieved and expected diameters compared. The novel reamer design was more accurate than the unused conventional reamer, using both whirlwind (0.1 mm (IQR 0-0.2) vs. 0.3 mm (IQR 0.3-0.4); p < 0.001) and straight techniques (0.3 mm (IQR 0.1-1.0) vs. 1.2 mm (IQR 1-1.6); p = 0.001). Whirlwind reaming was more accurate than straight reaming using both conventional (0.3 mm (IQR 0.3-0.4) vs. 1.2 mm (IQR 1-1.6); p < 0.0001) and single use reamers (0.1 mm (IQR 0-0.2) vs. 0.3 mm (IQR 0.1-1.0); p = 0.007). Reaming errors were higher in low-density bone compared to high-density bone, for both reamer types and reaming techniques tested (0.6 mm (IQR 0.3-1.5) vs. 0.3 mm (IQR 0.1-0.8); p = 0.005). We present a novel reamer design that demonstrates superior accuracy to conventional reamers in achieving the desired reaming diameter. Improved reaming accuracy was also demonstrated using both devices and in both bone models, using a 'whirlwind' technique. We recommend the use of this novel reamer design employing a 'whirlwind' technique to optimize reaming accuracy. Particular attention should be paid toward patients with lower bone quality which may be more susceptible to higher inaccuracies.


Forssman antigenicity of chemically synthesized globopentaose.
The Forssman antigenicity of a chemically synthesized globopentaose was studied. Globopentaose at 40 ng showed strong inhibitory activity for the formation of a precipitin line between globopentaosylceramide (Forssman glycolipid) and anti-Forssman rabbit antiserum, while much more pentasaccharide (7 and 100 micrograms, respectively) was required to inhibit a 50% quantitative precipitin reaction and a hemolysis reaction. An immune complex of the 3H-labeled globopentaose with anti-Forssman antibody was hardly formed. Thus, the chemically synthesized globopentaose possesses the same antigenic specificity as globopentaosylceramide but it is difficult to achieve a stable complex with Forssman antibody.


"Do-It-Yourself" Ear Canal Care.
There are a large variety of over-the-counter home remedies and devices for cerumen impaction available in the United States. It is a challenge for clinicians to maintain awareness of the safety and efficacy of these tools, as they are not considered "medical devices" and frequently have no requirement for demonstrating safety or efficacy. This article provides a broad overview of the products being advertised to patients and discusses considerations when recommending home cerumen maintenance.


Adsorption and adhesion processes in microbial growth at interfaces.
By considering bacteria as living colloidal particles it is possible to define, at least in part, the physicochemical and biological factors involved in the adhesion of bacteria to apparently inert surfaces. Adhesion is considered in terms of the attraction and repulsion forces operative as the organism approaches a substratum surface, as well as in terms of the surface free energies of the bacterium, the substratum and the liquid phase. Bacterial adhesion at a surface is preceded by molecular adsorption, a process that may alter the substratum surface properties and may provide a concentrated source of nutrients allowing limited growth of the bacteria at the surface.


52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis.
To compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA. In a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score (mTSS). Safety and immunogenicity were also evaluated. A total of 596 patients were randomized to receive either SB4 (n = 299) or ETN (n = 297) and 505 (84.7%) patients completed 52 weeks of the study. At week 52, the ACR20 response rates in the per-protocol set were comparable between SB4 (80.8%) and ETN (81.5%). All efficacy results were comparable between the two groups and they were maintained up to week 52. Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN. The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2% in the SB4 and ETN groups, respectively. Efficacy including radiographic progression was comparable between SB4 and ETN up to week 52. SB4 was well tolerated and had a similar safety profile to that of ETN. ClinicalTrials.gov NCT01895309, EudraCT 2012-005026-30.