Urinary excretion of arginine-vasopressin and prostaglandin E2 in essential fatty acid-deficient rats after oral supplementation with unsaturated fatty acid esters.
Essential fatty acid-deficient rats were supplemented with 300 mg/d of pure fatty acid esters: oleate (O), linoleate (L), arachidonate (A), and columbinate (C) for 10 d. The 24-h urine collections from each animal, collected 3 d before supplementations and again the last 3 d of the 10-d supplementation period, were analyzed for volume, and by radioimmunoassay for arginine-vasopressin (AVP) and prostaglandin E2 (PGE2). Linoleate and arachidonate supplements both decreased the initial high urinary AVP excretion, whereas it was further increased by the oleate supplement. There was no effect of columbinate supplementation on urinary AVP excretion. Urinary PGE2 excretion was increased ca. twofold by both linoleate and oleate supplements, increased ca. fivefold by arachidonate supplementation but was unaffected by columbinate supplementation. There was no effect of any of the supplemented fatty acids on urine output. Fatty acid analysis of total kidney lipids revealed a low percentage of 20:3(n-9) in the rats supplemented with (n-6) fatty acid (L, A and C). The triene-tetraene ratio was 1.8 +/- 0.6 (n = 6) in the kidneys of the oleate-supplemented rats. No relationship was found between urinary PGE2 excretion and the percentage of arachidonate or the ratio of 20:3 (n-9)/20:4(n-6) in total kidney lipids. It is suggested that increased urinary AVP excretion in EFA-deficient rats is mainly caused by a change in the renal excretatory mechanism of AVP rather than reflecting an increased plasma AVP concentration. Furthermore it is suggested that renal PGE2 synthesis in vivo is unaffected by high levels of 20:3(n-9) in kidney lipids.


Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9.
Many host-factors are inducibly expressed during the development of inflammatory bowel disease (IBD), each having their unique properties, such as immune activation, bacterial clearance, and tissue repair/remodeling. Dysregulation/imbalance of these factors may have pathogenic effects that can contribute to colitis-associated cancer (CAC). Previous reports showed that IBD patients inducibly express colonic chitinase 3-like 1 (CHI3L1) that is further upregulated during CAC development. However, little is known about the direct pathogenic involvement of CHI3L1 in vivo. Here we demonstrate that CHI3L1 (aka Brp39) knockout (KO) mice treated with azoxymethane (AOM)/dextran sulphate sodium (DSS) developed severe colitis but lesser incidence of CAC as compared to that in wild-type (WT) mice. Highest CHI3L1 expression was found during the chronic phase of colitis, rather than the acute phase, and is essential to promote intestinal epithelial cell (IEC) proliferation in vivo. This CHI3L1-mediated cell proliferation/survival involves partial downregulation of the pro-apoptotic S100A9 protein that is highly expressed during the acute phase of colitis, by binding to the S100A9 receptor, RAGE (Receptor for Advanced Glycation End products). This interaction disrupts the S100A9-associated expression positive feedback loop during early immune activation, creating a CHI3L1hi S100A9low colonic environment, especially in the later phase of colitis, which promotes cell proliferation/survival of both normal IECs and tumor cells.


Re-engineering of CYP2C9 to probe acid-base substrate selectivity.
A common feature of many CYP2C9 ligands is their weak acidity. As revealed by crystallography, the structural basis for this behavior involves a charge-pairing interaction between an anionic moiety on the substrate and an active site R108 residue. In the present study we attempted to re-engineer CYP2C9 to better accept basic ligands by charge reversal at this key residue. We expressed and purified the R108E and R108E/D293N mutants and compared their ability with that of native CYP2C9 to interact with (S)-warfarin, diclofenac, pyrene, propranolol, and ibuprofen amine. As expected, the R108E mutant maintained all the native enzyme's pyrene 1-hydroxylation activity, but catalytic activity toward diclofenac and (S)-warfarin was abrogated. In contrast, the double mutant displayed much less selectivity in its behavior toward these control ligands. Neither of the mutants displayed significant enhancement of propranolol metabolism, and all three preparations exhibited a type II (inhibitor) rather than type I (substrate) spectrum with ibuprofen amine, although binding became progressively weaker with the single and double mutants. Collectively, these data underscore the importance of the amino acid at position 108 in the acid substrate selectivity of CYP2C9, highlight the accommodating nature of the CYP2C9 active site, and provide a cautionary note regarding facile re-engineering of these complex cytochrome P450 active sites.


Metastases of a spinal glioblastoma multiforme into an intracranial arachnoid cyst.
Spread of spinal cord glioblastoma multiforme to the intracranial compartment is uncommon. This report documents a case of metastatic spread of glioblastoma multiforme from the spinal cord to an intracranial arachnoid cyst. Seeding of the cyst cavity could have occurred by direct permeation of the cyst wall by the neoplastic glial cells spreading via the cerebrospinal fluid or by direct access of the cells through a defect in the arachnoid cyst wall and their subsequent entrapment by a ball valve type mechanism, leading to multiple implants.


Protein-calorie malnutrition, macronutrient supplements, and tuberculosis.
Protein-calorie malnutrition (PCM) is a risk factor for tuberculosis (TB) disease and may affect treatment outcomes. There is currently no recommended macronutrient intervention for improving the outcome of anti-tuberculosis treatment. We reviewed current literature on PCM and low body mass index (BMI) as risk factors for tuberculous infection and TB disease, and their effects on anti-tuberculosis treatment. We summarize clinical trials of macronutrient supplementation in the treatment of TB. PCM is a well-established risk factor for TB disease; however, data on malnutrition and the risk of tuberculous infection are limited. Malnutrition is associated with an increased risk of mortality and relapse of active TB. Clinical trials of macronutrient supplementation during treatment confirm a 2-3 kg improvement in weight gain at 2 months, and may result in improvement in physical function, sputum conversion and treatment completion, but they have not been powered to assess effects on mortality or relapse. Assessment of dietary intake, food security, and baseline BMI should be standard practice in anti-tuberculosis treatment, along with dietary counselling. As macronutrient supplementation may have modest benefits and is not associated with adverse events, patients with BMI values <18.5 kg/m(2) should be provided with balanced macronutrient supplementation whenever possible.


[Pharmacological aspects of the problem of leukotrienes].
Possible sites of action of various drugs are discussed in the light of the existing conceptions of the ways of formation of leukotrienes and realisation of their effects. The expediency and possibility of the rational solving of the problem by using the drugs which selectively act on a link in the process remain to be doubtful. The system under study requires the complex pharmacological correction. One should first of all aim at the desirable final result of therapy.


Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus.
Reovirus is under development as a therapeutic for numerous types of cancer. In contrast to other oncolytic viruses, the safety and efficacy of reovirus have not been improved through genetic manipulation. Here, we tested the oncolytic capacity of recombinant strains (rs) of prototype reovirus laboratory strains T1L and T3D (rsT1L and rsT3D, respectively) in a panel of non-small cell lung cancer (NSCLC) cell lines. We found that rsT1L was markedly more cytolytic than rsT3D in the large cell carcinoma cell lines tested, whereas killing of adenocarcinoma cell lines was comparable between rsT1L and rsT3D. Importantly, non-recombinant T1L and T3D phenocopied the kinetics and magnitude of cell death induced by recombinant strains. We identified gene segments L2, L3, and M1 as viral determinants of strain-specific differences cell killing of the large cell carcinoma cell lines. Together, these results indicate that recombinant reoviruses recapitulate the cell killing properties of non-recombinant, tissue culture-passaged strains. These studies provide a baseline for the use of reverse genetics with the specific objective of engineering more effective reovirus oncolytics. This work raises the possibility that type 1 reoviruses may have the capacity to serve as more effective oncolytics than type 3 reoviruses in some tumor types.


Different functions of DEPTOR in modulating sensitivity to chemotherapy for esophageal squamous cell carcinoma.
There have been paradoxical findings regarding the expression of DEP domain-containing mTOR-interacting protein (DEPTOR) and its role in predicting prognosis in esophageal squamous cell carcinoma (ESCC). Here we show that DEPTOR expression was significantly increased in tumor tissues and predicted good survival in early stage ESCC patients but not in advanced stage patients. In vitro,our studies showed that ESCC cell lines could be classified into relatively high and low DEPTOR-expressing subgroups according to esophageal squamous epithelial cell line Het-1A.In our study, different levels of DEPTOR expression absolutely determined the response to chemotherapy. In relatively low-expressing cell lines, DEPTOR increased chemotherapy sensitivity via deactivation of the AKT pathway. In relatively high-expressing cell lines, DEPTOR increased cell survival and chemoresistance by strong feedback activation of the IRS1-PI3K-AKT-survivin pathway that occurred after downregulation of ribosomal protein S6 kinase (S6K). Collectively, our findings highlight the dichotomous nature of DEPTOR functions in modulating chemotherapy sensitivity in different ESCC cells.


Acute urinary retention.
Urinary retention is most commonly caused by obstruction in men and neuromuscular dysfunction in women. A careful history, physical examination, and urethral catheterization will lead to the correct diagnosis in the majority of cases. For nonobstructive causes, a careful survey of the patient's other illnesses and medications will often lead to diagnosis. Successful treatment of nonobstructing causes can be effectively managed by the primary care physician.


The Influence of Perceptual-Motor Variability on the Perception of Action Boundaries for Reaching in a Real-World Setting.
The ability to accurately perceive the extent over which one can act is requisite for the successful execution of visually guided actions. Yet, like other outcomes of perceptual-motor experience, our perceived action boundaries are not stagnant, but in constant flux. Hence, the perceptual systems must account for variability in one's action capabilities in order for the perceiver to determine when they are capable of successfully performing an action. Recent work has found that, after reaching with a virtual arm that varied between short and long each time they reach, individuals determined their perceived action boundaries using the most liberal reaching experience. However, these studies were conducted in virtual reality, and the perceptual systems may handle variability differently in a real-world setting. To test this hypothesis, we created a modified orthopedic elbow brace that mimics injury in the upper limb by restricting elbow extension via remote control. Participants were asked to make reachability judgments after training in which the maximum extent of their reaching ability was either unconstricted, constricted or variable over several calibration trials. Findings from the current study did not conform to those in virtual reality; participants were more conservative with their reachability estimates after experiencing variability in a real-world setting.


The angiotensin AT2 receptor in inflammation.
Chronic inflammation is increasingly regarded not just as a consequence of a continuous infectious hazard, but also as an integral part of many noninfectious diseases such as autoimmune disorders, diabetes or cardiovascular disease. Thus, it is not surprising that some hormonal systems, like the renin-angiotensin system (RAS), which were originally described in the context of cardiovascular disease have also turned out to be major regulators of the inflammatory response. This review focuses on the role of the RAS in inflammation, with particular emphasis on the role of the angiotensin AT(2) receptor. While the proinflammatory features of the angiotensin AT(1) receptor are well established, most current evidence supports an anti-inflammatory role for AT(2) receptor. However, data on this receptor in inflammation are still rather sparse and are somewhat controversial. This article will discuss the principal mechanisms of AT(2) receptor-coupled interference with proinflammatory pathways as well as data derived from animal models of specific diseases. Finally, it will give a brief outlook into new possibilities in AT(2) receptor research and in the potential utilization of AT(2) receptor stimulation as a novel pharmacological concept in anti-inflammation.


Low cost and compact analytical microsystem for carbon dioxide determination in production processes of wine and beer.
The design, construction and evaluation of a low cost, cyclic olefin copolymer (COC)-based continuous flow microanalyzer, with optical detection, to monitor carbon dioxide in bottled wines and beers as well as in fermentation processes, is presented. The microsystem, constructed by computer numerically controlled (CNC) micromilling and using a multilayer approach, integrates microfluidics, gas-diffusion module and an optical flow-cell in a single polymeric substrate. Its size is slightly bigger than a credit card, exactly 45 × 60 × 4 mm in the microfluidic and diffusion module zone and 22.5 × 40 × 3 mm in the flow-cell zone. The gas-diffusion module is based on a hydrophobic polyvinylidene fluoride (PVDF) membrane, which allows the transfer of the carbon dioxide present in the sample to a bromothymol blue (BTB) pH-sensitive acceptor solution, where the color change is measured optically. The detection system consisted of a LED with an emission peak at 607 nm and a photodiode integrated in a printed circuit board (PCB). The obtained analytical features after the optimization of the microfluidic platform and hydrodynamic variables are a linear range from 255 to 10000 mg L(-1) of CO2 and a detection limit of 83 mg L(-1) with a sampling rate of 30 samples h(-1).


Evolutionary transience of hypervariable minisatellites in man and the primates.
Using PCR, two minisatellite loci showing extreme repeat-unit copy-number variation in humans have been characterized in great apes and monkeys. In contrast to humans, minisatellite locus MS32 is monomorphic with only 3-4 diverged repeat units in great apes, Old World and New World monkeys, this organization presumably representing the relatively stable ancestral precursor state of the human hypervariable locus. Similarly, minisatellite MS1 shows extreme repeat-copy-number variability in man compared with low copy number and minimal variability in great apes. Analysis of variant repeat units shows that the 5' and 3' regions of MS1 are relatively stable in great apes and man, and that variability in man is confined to the central region of the minisatellite. In contrast to the great apes, MS1 is highly variable in Old World monkeys. These results, as well as computer simulations of minisatellite evolution based on known mutation rates, show that short minisatellites are stable within the genome, and that the degree of polymorphism at a given locus can change dramatically over a short period of evolutionary time. The ability of hypervariable minisatellites to detect highly informative loci by cross-species hybridization is therefore largely unpredictable.


The continuous performance test aids the diagnosis of post-stroke cognitive impairment in patients with right hemisphere damage.
The purpose of the study was to investigate the time course difference of relative changes in oxygenated hemoglobin (Oxy-Hb) concentration in the prefrontal cortex (PFC) between controls and patients with post-stroke cognitive impairment (PSCI) who had right hemisphere damage (RHD) using the continuous performance test (CPT) and functional near-infrared spectroscopy (fNIRS) technology. The study aimed to evaluate the feasibility of CPT in the diagnosis and evaluation of PSCI with RHD. A total of 16 patients with RHD (RHD group) and 32 normal subjects (control group) were recruited. The Montreal Cognitive Assessment Scale was used to assess post-stroke cognitive impairment. The CPT and fNIRS were employed to investigate task-related changes in Oxy-Hb levels. The RHD group showed significantly lower accuracy and hit rates than the control group; however, the average reaction time was significantly longer in the former. Although the two groups showed no statistically significant difference in terms of left and right PFC integral values, the mean values were greater in the RHD group. The centroid value of the right PFC was significantly higher in the RHD group than in the control group. The time course of Oxy-Hb concentrations in the PFC differed between the two groups. In the RHD group, neural compensation was observed in both prefrontal lobes; however, the rate of compensation was slower on the affected side. The CPT may be helpful in the clinical diagnosis of PSCI with RHD. It may therefore be used to evaluate the effectiveness of cognitive interventions.


Novel algorithm for transcriptome analysis.
A growing body of evidence implicates the oocyte as a key regulator of ovarian folliculogenesis and early embryonic development. We have screened bovine cDNA microarrays (containing expressed sequence tags representing >15,000 unique genes) with Cy3- and Cy5-labeled cDNA derived from bovine oocyte samples collected at two different stages of meiotic maturation (germinal vesicle vs. metaphase II; n = 3 samples per group). Here, we present a novel data analysis approach that uses all available information from above experiments to obtain and index the transcriptome of bovine oocytes and changes in transcriptome composition in response to meiotic maturation. Signal intensities (Fg) for all housekeeping genes were omitted prior to analysis. A local threshold for gene expression was computed as background intensity (Bg) plus 2 times the standard deviation of background and foreground signals. Within each array, data were normalized by the LOWESS procedure. Subsequently, a two-stage mixed model was fitted to remove systematic variations. In the first stage, the response was the LOWESS normalized Fg with treatment as a fixed effect. In stage 2, the residuals from stage 1 were analyzed in a gene-specific model that included treatment group and spots nested within patch and array. A test for the difference between least squares means for the treatment effect was performed. A false discovery rate (FDR) adjustment on the p values for the difference was carried out. This novel algorithm was compared with approaches that ignore the FDR and the threshold described herein and stark differences obtained.


Correlation Between C-MYC, BCL-2, and BCL-6 Protein Expression and Gene Translocation as Biomarkers in Diagnosis and Prognosis of Diffuse Large B-cell Lymphoma.
This study investigates the protein expression of C-MYC, BCL-2, and BCL-6 in diffuse large B-cell lymphoma (DLBCL) and their relationship with genetic abnormalities. A retrospective study of 42 cases on paraffin-embedded tissue specimens diagnosed with DLBCL was performed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The expression of C-MYC, BCL-2, BCL-6 protein, and gene abnormalities in these tissue samples was analyzed. The relationship in genetic abnormalities and Ki-67, Hans classification, gender, and age was also evaluated. It was found that the positive rate of C-MYC expression was 47.6% (20/42), the rate of C-MYC gene abnormality was 26.2% (11/42), in which gene translocation accounted for 23.8% (10/42) and gene amplification 2.4% (1/42); C-MYC protein expression was positively correlated with C-MYC gene translocation (χ2 = 11.813; P = 0.001); C-MYC gene translocation was mainly found in germinal center B cell type (χ2 = 4.029; P = 0.045). The positive rate of BCL-2 protein expression was 85.71% (36/42), the positive rate of translocation was 42.86% (18/42) and the amplification rate was 26.19% (11/42); the overexpression of BCL-2 protein was correlated with the BCL-2 translocation (χ2 = 3.407; P = 0.029). The positive rate of BCL-6 protein expression was 45.24% (19/42), the positive rate of BCL-6 translocation was 14.29% (6/42) and the positive rate of BCL-6 amplification was 7.14% (3/42); the overexpression of BCL-6 protein was significantly correlated with BCL-6 translocation (χ2 = 6.091; P = 0.014). The Ki-67 index was significantly higher in C-MYC translocation cases than in non-C-MYC translocation cases (χ2 = 4.492; P = 0.034). Taken together, our results suggest that the protein expression of C-MYC, BCL-2, and BCL-6 are positively correlated with their gene translocation. Overexpression of C-MYC, BCL-2, BCL-6 protein suggests the possibility of translocation. Therefore, immunohistochemical detection of C-MYC, BCL-2, and BCL-6 are useful in diagnosis and prognosis of DLBCL.


Spatial Resolution and Imaging Encoding fMRI Settings for Optimal Cortical and Subcortical Motor Somatotopy in the Human Brain.
There is much controversy about the optimal trade-off between blood-oxygen-level-dependent (BOLD) sensitivity and spatial precision in experiments on brain's topology properties using functional magnetic resonance imaging (fMRI). The sparse empirical evidence and regional specificity of these interactions pose a practical burden for the choice of imaging protocol parameters. Here, we test in a motor somatotopy experiment the impact of fMRI spatial resolution on differentiation between body part representations in cortex and subcortical structures. Motor somatotopy patterns were obtained in a block-design paradigm and visually cued movements of face, upper and lower limbs at 1.5, 2, and 3 mm spatial resolution. The degree of segregation of the body parts' spatial representations was estimated using a pattern component model. In cortical areas, we observed the same level of segregation between somatotopy maps across all three resolutions. In subcortical areas the degree of effective similarity between spatial representations was significantly impacted by the image resolution. The 1.5 mm 3D EPI and 3 mm 2D EPI protocols led to higher segregation between motor representations compared to the 2 mm 3D EPI protocol. This finding could not be attributed to differential BOLD sensitivity or delineation of functional areas alone and suggests a crucial role of the image encoding scheme - i.e., 2D vs. 3D EPI. Our study contributes to the field by providing empirical evidence about the impact of acquisition protocols for the delineation of somatotopic areas in cortical and sub-cortical brain regions.


Jemboss reloaded.
Bioinformatics tools are freely available from websites all over the world. Often they are presented as web services, although there are many tools for download and use on a local machine. This tutorial section looks at Jemboss, a Java-based graphical user interface (GUI) for the EMBOSS bioinformatics suite, which combines the advantages of both web service and downloaded software.


[The significance of TU M2-PK tumor marker for lung cancer diagnostics].
The purpose of the study was to investigate significance of the tumor marker pyruvate kinase Tumor M2 (Tu M2-PK), in diagnostics, monitoring of treatment, and evaluation of its effectiveness in patients with lung cancer (LC). This is an isoform of the glycosile enzyme pyruvate kinase, existing as an active dimer and less active tetramer. The expression of the less active form is typical of tumor cells; its blood level can be measured. The subjects of the study were 140 patients with LC of various histologic types. Serum levels of certain tumor markers (Cyfra 21-1, NSE, SCC, and Tu M2-PK) were measured; Tu M2-PK level was determined by ELISA test from ScheBoTech, a two-stage sandwich immunoassay using one type of antibodies. The marker concentration was also determined in 195 healthy volunteers (control group.) The maximum concentration of Tu M2-PK was 12.9 U/ml, determined with 95% specificity. 78% of the patients with small-cell carcinoma, 73% of patients with adenocarcinoma, and 81% of patients with non-small cell lung carcinoma displayed increase of Tu M2-PK serum concentration; this concentration was within normal limits in patients with nonmalignant diseases (e.g. bronchitis or tuberculosis). Thus, patients with lung carcinoma display a pathologic increase of Tu M2-P level. Measurement of Tu M2-P may be useful in patients with suspected LC; this marker may be of greater diagnostic significance than SCC or NSE.


Primary adenocarcinoma of duodenum.
Primary duodenal adenocarcinoma (PDC) of the distal half of duodenum is extremely rare. We report a case of a young male with adenocarcinoma of third and fourth part of duodenum presenting with long standing proximal small bowel obstruction with associated weight loss and anemia. Esophago-gastro-duodeno-scopy showed a fungating intraluminal growth in third and fourth part of the duodenum. Computed tomography also showed a solid mass in the third and fourth part of the duodenum. Computed tomography also showed a solid mass in the third and fourth part of the duodenum. Segmental resection of the third and fourth part of the duodenum was performed with single layer extra mucosal duodenojejunal anastomosis.


[Immunologic findings in the newborn infant. I. Studies of cellular immunity].
Based on investigations of 133 healthy full-term newborns in the first 3 days of life parameters of cellular immunity are described. The lymphocyte count of 28.5 +/- 10.9% (mean +/- S.D.) or 4.45 +/- 1.99 Gpt/l respectively coincides with literature values. Estimation of T-lymphocytes (E-rosette method) yields a percentage of 67.5 +/- 10%, which is not different from adults, whereas the absolute number 2.99 +/- 1.42 Gpt/l is markedly higher. Measuring phytohemagglutinin induced lymphocyte transformation one often finds a high spontaneous activity in unstimulated controls. The transformation rate, then, is low. 14 of 129 samples had unstimulated control activities higher than with phytohemagglutinin so that stimulation indices could not be calculated. Fairly good lymphocyte transformation was found in more than a half of all newborns. There is no correlation between the absolute value of stimulation index and the phytohemagglutinin-concentration.


Bone cement extracts modulate the osteoprotegerin/osteoprotegerin-ligand expression in MG63 osteoblast-like cells.
The osteoprotegerin-ligand (OPG-L) has been identified as the essential factor required for osteoclastogenesis, and its effects are prevented by the osteoprotegerin (OPG). The OPG-L/OPG balance plays a crucial role in coordinating the sequence of osteoclast and osteoblast differentiation during the bone remodeling. The aim of the study was to investigate if polymethylmethacrylate-based cements are able to modulate the expression of OPG-L/OPG in MG63 cells, which are known to have high levels of OPG and inducible expression of OPG-L. Four radio-opaque cements. namely Sulfix-60, CMW1, CMW2 and CMW3, were polymerized for either 1 h or 7 d. MG63 were incubated for 24 h with culture medium only, cement extracts and 2 microg/ml of human recombinant IL-1beta as positive control. An RT-PCR was performed to detect the OPG and OPG-L expression, and the house-keeping gene, GAPDH, was used as a reference for the semi-quantitative analysis. An increase in the OPG-L band density was observed for all cements, and consequently, the OPG-L/OPG ratio also increased. The ability of bone cements to induce the expression of OPG-L could be a co-factor in the development of osteolysis at the bone-cement interface.


Eugenol inhibits sodium currents in dental afferent neurons.
Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents (I(Na)) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and I(Na) in both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on I(Na), suggesting no involvement of TRPV1. Two types of I(Na), tetrodotoxin (TTX)-resistant and TTX-sensitive I(Na), were inhibited by eugenol. Our results demonstrated that eugenol inhibits I(Na) in a TRPV1-independent manner. We suggest that I(Na) inhibition by eugenol contributes to its analgesic effect.


[Myositis ossificans localisata of the thenar muscles].
In a case report the difficult histologic differential diagnosis between Myositis ossificans and extra-osseous osteosarcoma is illustrated. For the patient, one diagnosis means the preservation, the other the loss of an extremity with all possible complications of a malignant growth.


Targeting NOX2 with Bivalent Small-Molecule p47phox-p22phox Inhibitors.
Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2) is an enzymatic complex whose function is the regulated generation of reactive oxygen species (ROS). NOX2 activity is central to redox signaling events and antibacterial response, but excessive ROS production by NOX2 leads to oxidative stress and inflammation in a range of diseases. The protein-protein interaction between the NOX2 subunits p47phox and p22phox is essential for NOX2 activation, thus p47phox is a potential drug target. Previously, we identified 2-aminoquinoline as a fragment hit toward p47phoxSH3A-B and converted it to a bivalent small-molecule p47phox-p22phox inhibitor (Ki = 20 μM). Here, we systematically optimized the bivalent compounds by exploring linker types and positioning as well as substituents on the 2-aminoquinoline part and characterized the bivalent binding mode with biophysical methods. We identified several compounds with submicromolar binding affinities and cellular activity and thereby demonstrated that p47phox can be targeted by potent small molecules.


The Quality of Counseling for Headache OTC Medications in German Community Pharmacies Using a Simulated Patient Approach: Are There Differences between Self-Purchase and Purchase for a Third Party?
In Germany-as worldwide-headache is one of the most frequent causes of self-medication. The dispensing of over-the-counter (OTC) medications may only be carried out by community pharmacies (CPs). In doing so, CPs have to ensure "adequate" counseling, for both self-purchase and purchase for a third party, which also occurs in everyday pharmacy practice. The aim of this study was to evaluate the quality of counseling for headache OTC medications in German CPs and, as the first study worldwide, to analyze whether and to what extent there are differences in counseling between self-purchase and purchase for a third party. A cross-sectional study was carried out using the covert simulated patient methodology (SPM) in all 42 CPs in the German big city Potsdam. With the help of 8 trained simulated patients (SPs), each CP was visited four times by a different SP. The SPs simulated in each CP two scenarios two times with the demand for an OTC medication against headache, which differed only in whether the demand was for themselves or for their boyfriend/girlfriend. All 168 planned pharmacy visits (84 visits per scenario) were successfully carried out. Overall, the median counseling score was 3.0 out of 9 points (interquartile range [IQR 2.0]). There were no significant differences between the two scenarios (Wilcoxon signed-rank test; p=0.495, r = 0.053). In a multivariate binary logistic regression analysis, the counseling level and the different scenarios were not significantly associated (adjusted odds ratio [AOR] = 1.635, 95% CI = 0.673-3.972, p=0.278). Due to the partly considerable deficits in counseling of German CPs, policy-makers and the regional chambers of pharmacists are called upon to take appropriate measures to improve the quality of counseling. It is positive that no differences in counseling between self-purchase and purchase for a third party were found, but further verifying studies with a modified methodology are recommended.


Influence of acute volume loading on right ventricular function after cardiopulmonary bypass.
The influence of acute volume loading on right ventricular function immediately after extracorporeal circulation (ECC) was investigated in 25 patients undergoing elective aortocoronary bypass grafting. In addition to commonly monitored hemodynamic variables, right ventricular (RV) ejection fraction (EF) was measured by thermodilution technique using a new fast-response thermodilution catheter. In eight patients with concomitant severe stenosis (greater than 89%) of the right coronary artery (RCA), volume loading was followed by a decreased RVEF and cardiac output. In contrast, RVEF in the 17 patients without diseased RCA increased significantly, with an increase in cardiac output. Duration of aortic cross-clamping (i.e., ischemia) was more pronounced in the group with decreased RVEF due to RCA grafting. Increased end-diastolic volume and decreased RV contractility index indicated that patients with myocardial ischemia during cardiac surgery procedures sometimes were unable to make the adaptations required. We conclude that cardiocirculatory dysfunction associated with ECC may be caused by depressed RV function. Acute volume loading in this situation may lead to further deterioration of myocardial function due to RV failure, a condition which cannot be diagnosed readily at the bedside with the usual monitoring techniques.


Challenges in the Management of Complex Soft-Tissue Sarcoma Clinical Scenarios.
With nearly 15,000 new cases of soft-tissue sarcoma (STS) in the United States each year, early diagnosis and therapeutic management is imperative for successful patient outcomes. Primary STS is conventionally treated with a combination of wide-margin resection, neoadjuvant or adjuvant radiation therapy, and, in specific cases, adjuvant chemotherapy. However, in situations of complex disease presentation, guidelines for treatment are less clearly outlined. Limited metastatic disease, local recurrence, fungating STSs, and unplanned or incomplete resections of STSs present unique challenges for the multidisciplinary care team. The management of complex STS clinical scenarios usually involves limb-salvage resection or amputation as well as some combination of radiation therapy and/or ablative interventional radiology techniques. As a result, a multidisciplinary team approach is essential for treating patients in these challenging scenarios, with a recent focus on the integration of plastic and reconstructive surgery into the treatment algorithm.


Association between Sleep Traits and Lung Cancer: A Mendelian Randomization Study.
Multidimensional sleep trait, which is related to circadian rhythms closely, affects some cancers predominantly, while the relationship between sleep and lung cancer is rarely illustrated. We aimed to investigate whether sleep is causally associated with risk of lung cancer, through a two-sample Mendelian randomization study. The main analysis used publicly available GWAS summary data from two large consortia (UK Biobank and International Lung Cancer Consortium). Two-sample Mendelian randomization (MR) analysis was used to examine whether chronotype, getting up in the morning, sleep duration, nap during the day, or sleeplessness was causally associated with the risk of lung cancer. Additionally, multivariate MR analysis was also conducted to estimate the direct effects between sleep traits and lung cancer risks independent of smoking status including pack years of smoking or current tobacco smoking. There was no evidence of causal association between chronotype, getting up in the morning, or nap during the day and lung cancer. Sleeplessness was associated with higher risk of lung adenocarcinoma (odds ratio 5.75, 95% confidence intervals 2.12-15.65), while sleep duration played a protective role in lung cancer (0.46, 0.26-0.83). In multivariate MR analysis, sleeplessness and sleep duration remained to have similar results. In conclusion, we found robust evidence for effect of sleeplessness on lung adenocarcinoma risk and inconsistent evidence for a protective effect of sleep duration on lung cancer risk.


Tocilizumab for uncontrollable systemic inflammatory response syndrome complicating adult-onset Still disease: Case report and review of literature.
Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown etiology characterized by evanescent salmon-pink rash, fever spikes, arthralgia, and lymphadenopathy. AOSD usually has a good prognosis, but it can sometimes be fatal, especially when it is complicated by systemic inflammatory response syndrome (SIRS) and multiple organ failure. A previously healthy 26-year-old woman was referred to our hospital for persistent high fever and mild systemic edema. Five days later, the patient presented with dyspnea, hypotension, and anuria. Anasarca developed with massive pleural effusion, ascites, and systemic edema, resulting in an increase of 47 kg in body weight. The patient was diagnosed as AOSD after infection, malignancy, hematologic disorders, and other autoimmune diseases were excluded. We administered tocilizumab, an IL-6 receptor inhibitor, intravenously in addition to cyclosporine, prednisolone, plasma exchange, and continuous hemodiafiltration. The patient's systemic condition improved. After stabilization by all medications, the patient was managed and responded to tocilizumab alone. To the best of our knowledge, this was the first case of severe SIRS complicating AOSD that was successfully treated with an anti- IL-6 receptor antibody. SIRS should not be overlooked in a patient with steroid-resistant AOSD and edema. Inhibitors of the IL-6 receptor can be used safely and effectively to control AOSD complicated with severe SIRS.


Concerns in the Blurred Divisions between Medical and Consumer Neurotechnology.
Neurotechnology has traditionally been central to the diagnosis and treatment of neurological disorders. While these devices have initially been utilized in clinical and research settings, recent advancements in neurotechnology have yielded devices that are more portable, user-friendly, and less expensive. These improvements allow laypeople to monitor their brain waves and interface their brains with external devices. Such improvements have led to the rise of wearable neurotechnology that is marketed to the consumer. While many of the consumer devices are marketed for innocuous applications, such as use in video games, there is potential for them to be repurposed for medical use. How do we manage neurotechnologies that skirt the line between medical and consumer applications and what can be done to ensure consumer safety? Here, we characterize neurotechnology based on medical and consumer applications and summarize currently marketed uses of consumer-grade wearable headsets. We lay out concerns that may arise due to the similar claims associated with both medical and consumer devices, the possibility of consumer devices being repurposed for medical uses, and the potential for medical uses of neurotechnology to influence commercial markets related to employment and self-enhancement.


Autophagy Contributes to the Induction of Anti-TNF Induced Macrophages.
Anti-tumour necrosis factor [TNF] antibodies induce regulatory macrophages which display a phenotype resembling M2 type macrophages. Anti-TNF induced macrophages [Mϕind] have immunosuppressive and wound healing properties. The factors that contribute to the induction of Mϕind remain to be explored. Autophagy has been described as a factor that is important for the induction and function of M2 type macrophages. We studied the contribution of autophagy to the induction of Mϕind. We studied the effect of autophagy on Mϕind in vitro using peripheral blood mononuclear cells. Interferon gamma [IFN-γ] induced macrophages [Mφ1] were generated by culturing monocytes in the presence of IFN-γ. Mϕind were generated by performing mixed lymphocyte reactions [MLR] in the presence of anti-TNF antibodies; 28 healthy donors were genotyped for rs_2241880 [ATG16L1]. Cells were analysed by autophagy gene array, immunofluorescence, western blot, flowcytometry, 3H-thymidine incorporation and MTS assay. Mϕind had a different expression profile of autophagy related transcripts with increased expression of 33/40 altered genes compared with Mφ1. In addition, autophagic activity was increased in Mϕind compared with Mφ1. Induction of Mϕind was positively correlated to the number of wild-type alleles for the ATG16L1 T300A risk allele present in the culture. Finally, the autophagy-related protein cathepsin S was highly expressed in Mφind and inhibition resulted in decreased viability as well as decreased expression of CD206. Mϕind have increased levels of autophagy compared with inflammatory Mφ1, and the induction of these macrophages is impaired in donors carrying the T300A risk allele for the ATG16L1. Given the association between Mϕind and clinical response, this suggests that an intact autophagy pathway may be important for an optimal response to anti-TNF therapy in inflammatory bowel disease.


The bone marrow in Hodgkin's disease--a two year study.
A total of forty bone marrow trephine biopsies and aspirates were studied from thirty five patients suffering from Hodgkin's disease during the two year period 1994 and 1995. Of these twenty five were at the time of diagnosis of the disease and fifteen after treatment. The biopsies were studied for incidence of involvement as well as associated findings in both the positive and negative biopsies. A comparison of the trephine biopsy with marrow aspirate with respect to yield of positivity was made. Five patients (20%) at the time of diagnosis and two (13.33%) after treatment showed involvement of the marrow. None of the seven corresponding aspirates were positive for involvement showing that biopsies were superior to aspirates in detecting marrow infiltration in Hodgkin's disease. Suppression of the marrow, fibrosis and lymphocytic aggregates were the other findings in positive biopsies. Eosinophilia and myelosuppression were notable changes in the negative biopsies. One biopsy also showed granulomas. The probable significance of these findings are also discussed.


SR4GN: a species recognition software tool for gene normalization.
As suggested in recent studies, species recognition and disambiguation is one of the most critical and challenging steps in many downstream text-mining applications such as the gene normalization task and protein-protein interaction extraction. We report SR4GN: an open source tool for species recognition and disambiguation in biomedical text. In addition to the species detection function in existing tools, SR4GN is optimized for the Gene Normalization task. As such it is developed to link detected species with corresponding gene mentions in a document. SR4GN achieves 85.42% in accuracy and compares favorably to the other state-of-the-art techniques in benchmark experiments. Finally, SR4GN is implemented as a standalone software tool, thus making it convenient and robust for use in many text-mining applications. SR4GN can be downloaded at: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/downloads/SR4GN.


[A double blind comparison of naproxen and indomethacin on the after-midnight-pain of patients with morbus bechterew].
27 patients with ascertained ankylosing spondylitis experiencing constant after-midnight-pain received, following three medication-free days, in a double blind, randomized, cross-over fashion indometacin (100 g/day) and d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) (500 mg/day), as suppositories, for a period of six days each. The intensity of the night-pain was recorded daily. Naproxen was shown to be equally effective as indometacin in alleviating the after-midnight backache of ankylosing spondylitis. Side effects occurred under indometacin in 5 cases, under naproxen in 3 cases.


[Presence of autoantibodies in patients infected with HIV].
The presence of serum autoantibodies directed against single-stranded DNA (ssDNA), RNA, histones, nuclear antigen SS-A, mitochondria and cardiolipin were investigated in 30 HIV-negative drug addicts (from years 1986-87), 30 addicts actually infected with HIV and 31 AIDS patients presenting with clinical symptoms indicating autoimmune disorders. Positive results were found in 12 (40%) drug addicts from years 1986-87, 5 (16.7%) actually infected and 16 (51.6%) AIDS patients. Autoantibodies were more often detectable in patients with thrombocytopenia 8/12 (66.7%) than in remaining 8 out of 19 subjects (42.1%) who presented dermatitis, hepatitis, pancarditis, ulcerative colitis and polyneuropathy. The prevalence of autoantibodies in all investigated groups were significantly higher than in controls-1/20 (3.3%).


[Radical operation for rectal cancer to preserve anorectal, urinary and sexual function].
Recently, preservation of physiological functions have become to be considered in the operative treatment for rectal cancer. Dysfunction caused following radical operation for rectal cancer is divided into two parts as follows, (1) disturbance or loss of anorectal function due to sacrifice of the anus in abdomino-perineal resection and decrease function as fecal reservoir following anal sphincter preserving resection of the rectum. (2) anorectal, urinary and sexual dysfunction following surgical injury to the autonomic nerves by pelvic lymph nodes dissection. Our conceptions of the indication for sphincter preserving operation and for wide dissection of pelvic lymph nodes which cause severe dysfunction of urinary and sexual functions postoperatively were discussed.


The Impact of Echocardiographic Screening for Rheumatic Heart Disease on Patient Quality of Life.
To assess the impact of rheumatic heart disease (RHD) on child-reported health-related quality of life (HRQOL) in the context of a Ugandan school-based echocardiographic screening program. Echocardiography-based screening has emerged as a tool for the early detection of RHD, but little is known about its impact on those screened. Participants included 358 children from Gulu and 28 children from Kampala Uganda. The Pediatric Quality of Life Inventory Version 4.0 was used to assess HRQOL in 4 groups of children: Gulu prescreen, Gulu postscreen, Gulu previously linked to care, and Kampala previously linked to care. Children in the pre- and postscreen groups were selected from a single school before and after screening occurred and matched by age and sex. Children previously linked to care were recruited from previous screening studies. When the echocardiogram was normal, there was no difference in HRQOL in the prescreen and postscreen groups. In the postscreen group, identification of latent RHD resulted in lower physical (75.3 vs 68.3, P = .03) and emotional (71.7 vs 63.4, P < .01) HRQOL, despite a lack of symptoms. The Kampala group had longer linkage to care (42 months vs 6 months, P < .01) and demonstrated greater HRQOL scores compared with the Gulu-linked group (70.7 vs 77.8, P < .01) and the combined Gulu cohort (77.8 vs 69.4, P = .02). Echocardiography-based screening for RHD does not diminish HRQOL in Ugandan children; rather, a diminished HRQOL score may be associated with being identified as RHD positive. Further investigation is needed to understand if longer linkage to care may ultimately normalize or improve HRQOL.


Complex formation in aqueous medium of partially hydrolysed oat cereal proteins with sodium stearoyl-2 lactylate (SSL) lipid surfactant and implications for bile acids activity.
Sodium stearoyl-2 lactylate (SSL) lipid surfactant molecules specifically bind partially hydrolysed oat proteins in aqueous medium and significantly enhance the dispersion stability of oat cereal preparations. The proposed complexation is composition dependent and a greater understanding of the role of both oat proteins and lipid surfactant in the effect was gained with data from high performance liquid chromatography (HPLC-UV), viscometry and differential scanning micro calorimetry. The effect of the lipid surfactant on the degree of association is primarily governed by the conformational activity of oat protein molecules related to the extent of protein hydrolysed state, as well as protein unfolded and subsequent aggregated structures. SSL does not dissociate oat proteins into subunits or destroy important hydrophobic contacts already stabilising the protein molecules. Although the exact mode of association is unknown, the present study demonstrates that such interactions occur in a specific manner and suggest selectivity of oat proteins for individual fatty acids. The effect of various amounts of bile acids on SSL-oat protein interaction was also investigated, as a first attempt to investigate the role of lipid surfactant molecules in the known cholesterol-lowering action of oat cereal ingredients and to elucidate favourable conditions by which oat cereal can elicit hypocholesterolemic effects.


Constitutive binding of yeast heat shock factor to DNA in vivo.
We measured the binding of yeast heat shock factor (HSF) to DNA in vivo by using an interference assay in which HSF excludes GAL4 from a synthetic promoter element containing overlapping binding sites for each protein. The results show that HSF binds to DNA in unstressed cells and that binding is not sufficient for transcriptional activation.


Robotics versus laparoscopy--an experimental study of the transfer effect in maiden users.
Robot-assisted laparoscopy (RL) is used in a wide range of operative interventions, but the advantage of this technique over conventional laparoscopy (CL) remains unclear. Studies comparing RL and CL are scarce. The present study was performed to test the hypothesis that maiden users master surgical tasks quicker with the robot-assisted laparoscopy technique than with the conventional laparoscopy technique. 20 subjects, with no prior surgical experience, performed three different surgical tasks in a standardized experimental setting, repeated four times with each of the RL and CL techniques. Speed and accuracy were measured. A cross-over technique was used to eliminate gender bias and the experience gained by carrying out the first part of the study. The task "tie a knot" was performed faster with the RL technique than with CL. Furthermore, shorter operating times were observed when changing from CL to RL. There were no time differences for the tasks of grabbing the needle and continuous suturing between the two operating techniques. Gender did not influence the results. The more advanced task of tying a knot was performed faster using the RL technique than with CL. Simpler surgical interventions were performed equally fast with either technique. Technical skills acquired during the use of CL were transferred to the RL technique. The lack of tactile feedback in RL seemed to matter. There were no differences between males and females.


Clopidogrel reloading in patients undergoing percutaneous coronary intervention on chronic clopidogrel therapy: results of the ARMYDA-4 RELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) randomized trial.
To evaluate safety and effectiveness of clopidogrel reloading in patients on chronic clopidogrel therapy undergoing percutaneous coronary intervention (PCI). Five hundred and three patients on >10 days clopidogrel therapy (41% with non-ST-segment elevation acute coronary syndrome, ACS) randomly received 600 mg clopidogrel loading 4-8 h before PCI (n = 252) or placebo (n = 251). Primary endpoint was 30-day incidence of major adverse cardiac events (MACE). In the overall population primary endpoint occurred in 6.7% of patients in the reload vs. 8.8% in the placebo arm [odds ratios (OR) 0.75, 95% confidence intervals (CI) 0.37-1.52; P = 0.50]. In stable angina patients, 1-month MACE were not significantly different (7.0 vs. 3.9%; OR 1.84, 0.60-5.88; P = 0.36), whereas ACS patients had significant clinical benefit with reloading (6.4 vs. 16.3%; OR 0.34, 95% CI 0.32-0.90, P = 0.033 at multivariable analysis; interaction test: P = 0.01). There was no excess bleeding in the reload arm (6% in both groups). ARMYDA-4 RELOAD reveals no overall benefit from reloading patients on chronic clopidogrel therapy prior to PCI; the benefit observed in ACS patients is a hypothesis-generating finding that needs to be confirmed by larger studies.


Formulation and Characterization of Eplerenone Nanoemulsion Liquisolids, An Oral Delivery System with Higher Release Rate and Improved Bioavailability.
Because Eplerenone (EPL) is a Biopharmaceutical Classification System (BCS) class-II drug and is prone to extensive liver degradation, it suffers from poor bioavailability after oral administration. This work aimed to prepare liquisolids loaded with EPL-nanoemulsions (EPL-NEs) that have a higher drug release rate and improved bioavailability by the oral route. Based on solubility studies, mixtures of Triacetin (oil) and Kolliphor EL/PEG 400 surfactant/co-surfactant (Smix) in different ratios were used to prepare EPL-NE systems, which were characterized and optimized for droplet size, zeta potential, polydispersity index (PDI), and drug content. Systems were then loaded onto liquisolid formulations and fully evaluated. A liquisolid formulation with better drug release and tableting properties was selected and compared to EPL-NEs and conventional EPL oral tablets in solid-state characterization studies and bioavailability studies in rabbits. Only five NEs prepared at 1:3, 1:2, and 3:1 Smix met the specified optimization criteria. The drug release rate from liquisolids was significantly increased (90% within 45 minutes). EPL-NE also showed significantly improved drug release but with a sustained pattern for four hours. Liquisolid bioavailability reached 2.1 and 1.2 relative to conventional tablets and EPL-NE. This suggests that the EPL-NE liquisolid is a promising oral delivery system with a higher drug release rate, enhanced absorption, decreased liver degradation, and improved bioavailability.


Anisotropic ultrasonic backscatter from the renal cortex.
We have demonstrated a significant, directionally dependent, anisotropic, echogenicity from the cortices of two sheep kidneys and a normal human cadaver kidney. The anisotropy corresponds to the relationship of the sound field to the medullary rays and interlobular arteries. At 7.5 MHz, the backscatter from specimens of cortex of a sheep kidney was 4.7 +/- .7 dB (mean +/- SEM) greater in parts of the cortex where the field was perpendicular to these structures as opposed to where it was parallel to them. In addition, we measured the angular distribution of this anisotropy and compared it to the 5 dB inclusion angle of the 5 MHz linear array that was used in measurements on the whole kidney specimens. The transducer inclusion angle was 10 degrees +/- 2 degrees, while the angular distribution was 34 degrees +/- 22 degrees and 23 degrees +/- 11 degrees (mean +/- SD) for the intact sheep and human kidney, respectively, demonstrating some variation of the medullary rays from perfect specular reflectors. This anisotropy should be visible in standard diagnostic scanning, and its recognition could increase ultrasound's sensitivity for the detection of renal disease.


Malaria infection in pregnant women in Zaire: the effects and the potential for intervention.
In five maternity centres in urban and rural Zaire we evaluated the maternal prevalence of Plasmodium falciparum parasitaemia and recorded fever, the frequency of abortions and stillbirths, newborn birth weights and the feasibility of delivering antimalarial chemoprophylaxis. Women in their first and second pregnancy, compared to others (greater than or equal to third pregnancies), had a higher frequency of parasitaemia (38 v. 15%, respectively, P less than 0.001), higher parasite densities (geometric mean densities 927 per mm3 v. 277 per mm3, respectively, P = 0.01), higher rates of stillbirths and low birth weight babies (24% v. 6.4%, P less than 0.001). On average, pregnant women first attended prenatal clinics in the sixth to seventh month of gestation and made three to four visits before delivery. In these areas of Zaire, antimalarial interventions during pregnancy would have the largest impact if they were targeted to women in their first and second pregnancy. In the study areas, maternal attitudes and prenatal care-seeking behaviours do not appear to be barriers to providing an antimalarial intervention.


Factors associated with potentially harmful drug-drug interactions in older Korean people: A population-based study.
The present study investigated the status of potentially harmful drug-drug interactions (PHDI) in older adults, to obtain insight into factors that influence the risk of PHDI. The present study included Korean people aged ≥65 years who were prescribed one or more drugs included in the list of PHDI under the Beers Criteria 2015 from January to December, 2016 (n = 1 257 317). PHDI were defined based on the Beers Criteria 2015. Among 10 PHDI, a prevalence of >5% was taken to be clinically significant, and the relationships between multiple variables and PHDI were examined. The most frequent PHDI was corticosteroids and non-steroidal anti-inflammatory drugs (n = 259 499, 20.64%), followed by a combination of two or more anticholinergic drugs (n = 139 622, 11.1%), and three or more drugs acting on the central nervous system (n = 86 023, 6.84%). These three types of PHDI were more frequent in women (OR 1.066-1.141) and medical aid beneficiaries (OR 1.095-1.510). The risk of PHDI increased in proportion to the number of healthcare institutions used by the participants and their outpatient visits during the year (OR 1.043-1.079, 1.008-1.010, respectively). The risk of PHDI was low when patients took no more than five medications in a single prescription (OR 0.017-0.791). The findings of the present study highlight the three most frequent PHDI in Korea according to the Beers Criteria 2015. Healthcare providers should take PHDI into account when treating female patients, medical aid beneficiaries, patients using multiple healthcare institutions, frequent outpatient visitors and patients prescribed more than six medications in a single prescription. Geriatr Gerontol Int 2018; 18: 1378-1382.


Physical inactivity and headache disorders: Cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
Physical inactivity has been linked to headache disorders but estimates based on the current World Health Organization physical activity guidelines are unknown. To test the associations between headache disorders and physical inactivity in the ELSA-Brasil cohort. In a cross-sectional analysis, linear (continuous variables) and logistic regression models (categorical variables) tested the associations of physical activity levels in the leisure time, commuting time, and combined leisure time physical activity + commuting time physical activity domains with headache disorders, adjusted for the effects of sociodemographic data, cardiovascular risk variables, psychiatric disorders, and migraine prophylaxis medication. Of 15,105 participants, 14,847 (54.4% women) provided data on physical activity levels and headache. Higher physical activity levels (continuous values) in the leisure time physical activity domain associated with lower migraine and tension-type headache occurrence and lower headache attack frequency, while in the commuting time physical activity domain it associated with more frequent headache attacks. Compared to people who met World Health Organization physical activity levels in the leisure time physical activity or combining leisure time physical activity + commuting time physical activity domains (i.e. ≥150 min.wk-1 of moderate and/or ≥75 min.wk-1 of vigorous physical activity), physical inactivity associated with higher migraine occurrence, while somewhat active (i.e. not meeting World Health Organization recommendations) associated with higher migraine and tension-type headache occurrence. Physical inactivity in the commuting time physical activity domain associated with higher tension-type headache in men and lower migraine in women. Physical inactivity within vigorous leisure time physical activity intensity, but not moderate leisure time physical activity, associated with higher migraine, mostly in women. Finally, physical inactivity associated with higher headache attack frequency regardless headache subtype. Physical inactivity and unmet World Health Organization physical activity levels associate with primary headaches, with heterogeneous associations regarding headache subtype, sex, physical activity domain/intensity, and headache frequency in the ELSA-Brasil study.


[Enhancive effect of histone deacetylase inhibitor trichostatin a on transfection efficiency of adenovirus in ovarian carcinoma cell line A2780].
The presence of Coxsackie and adenovirus receptor (CAR) on target cell surface is required for efficient adenovirus transfection; lack or down-regulated expression of CAR on cancer cells is the main cause of inefficiency of adenovirus-based gene therapy. This study was to evaluate enhancive effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on the transfection efficiency of adenovirus in ovarian carcinoma cell line A2780, and explore its possible application to adenovirus-based gene therapy. mRNA and protein levels of CAR on A2780 cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot before and after treatment of TSA. Transfection efficiency of adenovirus was valued by flow cytometry (FCM). In vitro antitumor effect of adenovirus/thymidine kinase (ADV/TK) was detected by MTT assay. After treatment of TSA, mRNA and protein levels of CAR on A2780 cells were obviously increased. Transfection rates of adenovirus were (1.24+/-0.14)% in untreated group, (7.58+/-0.32)% in 5 nmol/L of TSA treated group, and (7.94+/-0.28)% in 100 nmol/L of TSA treated groups. In vitro antitumor effect of ADV/TK was 4-10 folds in TSA (5 or 100 nmol/L) treated groups compared with that in untreated group. TSA could enhance transfection efficiency of adenovirus in ovarian carcinoma cells, and may be useful in gene therapy for ovarian carcinoma.


Adsorption of VOCs onto engineered carbon materials: A review.
Volatile organic compounds (VOCs) severely threaten human health and the ecological environment because most of them are toxic, mutagenic, and carcinogenic. The persistent increase of VOCs together with the stringent regulations make the reduction of VOC emissions more imperative. Up to now, numerous VOC treatment technologies have emerged, such as incineration, condensation, biological degradation, absorption, adsorption, and catalysis oxidation et al. Among them, the adsorption technology has been recognized as an efficient and economical control strategy because it has the potential to recover and reuse both adsorbent and adsorbate. Due to their large specific surface area, rich porous structure, and high adsorption capacity, carbonaceous adsorbents are widely used in gas purification, especially with respect to VOC treatment and recovery. This review discusses recent research developments of VOC adsorption onto a variety of engineered carbonaceous adsorbents, including activated carbon, biochar, activated carbon fiber, carbon nanotube, graphene and its derivatives, carbon-silica composites, ordered mesoporous carbon, etc. The key factors influence the VOC adsorption are analyzed with focuses on the physiochemical characters of adsorbents, properties of adsorbates as well as the adsorption conditions. In addition, the sources, health effect, and abatement methods of VOCs are also described.


Recent clinical research on the application of liquid biopsy in neuroblastoma.
Neuroblastoma (NB) is the most common extracranial solid tumor in children and has the features of high recurrence rate and low survival rate, and therefore, early diagnosis, treatment response evaluation, and recurrence monitoring are of great significance for NB patients. Liquid biopsy refers to the detection of cells and nucleic acids in fluid specimens, mainly blood. It is noninvasive and can overcome tumor heterogeneity, thus making it possible to achieve the early diagnosis and dynamic detection of NB. This review introduces the latest advances in clinical research on the application of liquid biopsy in NB.


[The Local Alternative Ti-6Al-4V Alloy Coating of Surgery Steel Instruments for Laser Deposition Forming].
Aiming at the medical practice problems of the surgical steel medical instruments, such as the crevice corrosion, the poor mechanical compatibility and the Ni, Cr plasma exudation, the laser deposition of Ti-6Al-4V alloy cladding layer at the local functional area as alternative coating was proposed and realized as a new process method. The accurate element content and good formability Ti-6Al-4V cladding powder was chosen, the low power and high duty cycle optimized laser process was adopt, the alternative coating of good fusion and low dilution was prepared. Through the elemental line scanning, the interface microstructure analysis and the experiments of basic mechanical properties, the basic properties of the cladding were characterized and verified. The experiments results showed that, the Ti, Al and V contents of the top coating were respectively about 88%, 4.9% and 3.9%, no sensitizing ions such as Cr and Ni were detected. Initial equiaxed α phase, flake β phase dist were distributed in the coating and interface, the α' martensite was precipitated at the boundary of the flake β phase, some refined granular β phase dispersion pinned to the grain boundary of basket structure. The microhardness of cladding layer was 352.08~312.76 HV0.1. The friction coefficient of the cladding layer was about 0.22~0.65. A new technology and method reference for improving and upgrading the performance of surgical medical devices is provided by this research.


Fermentative conditions modulating sweetness in dry wines: genetics and environmental factors influencing the expression level of the Saccharomyces cerevisiae HSP12 gene.
Yeast lees influence the organoleptic properties of wines by increasing their sweet taste. This effect is in part due to the protein Hsp12p, which is regulated by different stress response pathways in Saccharomyces cerevisiae. This work investigated the genetics and environmental factors influencing the expression level of the HSP12 gene in an enological context. RT-qPCR confirmed that the HSP12 expression level is regulated by temperature change and ethanol content during the alcoholic fermentation but not by the sugar content. Moreover, this gene shows an important variation according to the yeast strain used. For the first time yeast strain is demonstrated to play an important role in the perception of sweetness in red wine due to post-fermentation lees autolysis. Interestingly, a correlation between the expression level of HSP12 and the sweetness perception was found using yeast strains of different origins. All of the findings provide new insights on the contribution of yeast to wine taste.


Fabrication of two-dimensional photonic crystals with controlled defects by use of multiple exposures and direct write.
We have developed an approach for relatively rapid and easy fabrication of large-area two-dimensional (2-D) photonic crystal structures with controlled defects in the lattice. The technique is based on the combination of two lithographic steps in UV-sensitive SU-8 photoresist. First, multiple exposures of interference fringes are used in combination with precise rotation of the sample to define a 2-D lattice of holes. Second, a strongly focused UV laser beam is used to define line-defect waveguides by localized exposure in the recorded but not yet developed lattice from the first step. After development, the mask is transferred into a GaAs substrate with dry etching in chemically assisted ion-beam etching.


Insights into future therapeutics for atopic dermatitis.
Atopic Dermatitis (AD) is a common chronic inflammatory skin disorder with a constellation of symptoms. Currently, there are numerous therapies in various phases of drug development that target the pathogenesis of AD. Our paper aims to examine small molecule therapies and other novel agents registered for clinical trial in the phase II and mainly phase III stages of development. A literature search using PubMed as well as Clinicaltrials.gov was conducted. Clinical trial evidence of these novel agents was compiled and assessed. Both topical and oral novel therapies with diverse range of mechanistic action are currently being studied, with varying success. These include phosphodiesterase-4 inhibitors, boron molecules, Janus kinase inhibitors, cannabinoid receptors agonists, kappa-opioid receptor agonists. A variety of compounds with yet undisclosed or unknown mechanisms of action are also being studied. Further research through extensive clinical trials will allow for more information about these targeted therapies and their potential place in the treatment algorithm of AD. Due to the success of such therapies in treating a spectrum of chronic inflammatory diseases, we remain hopeful that the successful development of targeted therapy for AD lies ahead.


Predictive factors for pulp necrosis in traumatized primary incisors: a longitudinal study.
This study aimed to assess factors associated with occurrence of pulp necrosis (PN) in traumatized primary incisors, which may contribute to the prognosis of this outcome. Data were collected by single examiner through the analysis of clinical files of traumatized patients. The occurrence of PN in traumatized teeth was the evaluated outcome. Poisson regression analysis was applied to calculate the relative risk (RR) and the respective 95% confidence interval. Five hundred and twenty-one files were assessed, summing up 727 traumatized primary incisors. The proportion of teeth affected by PN was 23.8%. Multiple regression analysis indicated the following factors as positively associated with PN: trauma with displacement, pulp exposure fracture, self-report of pain, yellow, grey and brown crown discoloration, internal root resorption, and bone loss. Trauma in 4- to 5-year old and more than 5-year-old children, pulp canal obliteration, and external root resorption with bone formation were negatively associated with PN. Teeth that suffered more aggressive injuries, pain, some types of discoloration, and other radiographic findings (for instance, internal root resorption) are positively associated with the occurrence of PN. On the other hand, trauma in older children, canal obliteration, or external resorption show less probability of PN.


Life events and personality characteristics in depression.
Evidence from many sources supports the view that stressful life events might be relevant for the onset and development of depression, but their pathogenic role is still only poorly understood. One approach in trying to elucidate the role of life events in depression, might be to study them from a multi-factorial point of view, taking into account the vulnerability of the individual experiencing them. As part of such an investigation, 138 depressed patients with a mean age of 45 years have participated in a study of life events and personality traits. In particular, it was tested whether aspects of aggression might interact with the occurrence and perception of external stressful events. Patients who scored high on outward aggression had experienced more stressful events, and patients who scored high on inhibition of aggression had experienced fewer, but more negatively. It is concluded that a combined study of the occurrence of life events and the personality characteristics of the patients experiencing them might enhance our understanding of the pathogenic role of life events in depression.


Renal cystic disease associated with tuberous sclerosis complex: renal failure treated by cadaveric kidney transplantation.
Chronic renal failure in patients with tuberous sclerosis may be secondary to diffuse cystic disease, a lesion less common than the better known hamartomatous angiomyolipomas. Uremia, in the case of a nineteen-year old female with end-stage renal disease, was associated with severely atrophic kidneys that contained numerous collapsed and scarred cysts. No hamartomas were present. The patient survived for more than three years following cadaveric renal transplantation.


Combined Therapy of ATRA and Imatinib Mesylate Decreases BCR-ABL and ABCB1/MDR1 Expression Through Cellular Differentiation in a Chronic Myeloid Leukemia Model.
Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease, and a major challenge for the eradication of CML is to understand the cause of the permanence of minimal residual disease (DRM). This work aimed to induce the maturation of leukemic stem cells with All-trans-retinoic acid (ATRA), making them sensitive to treatment with Imatinib (IM). K562 cells were treated with IM and with the combined therapy of ATRA together with IM for 48 and 72 h. The expression of BCR-ABL gene and multidrug resistance gene ABCB1 were evaluated using RT-qPCR. The combined ATRA and IM therapy showed a discreet cell differentiation pattern, evidenced by the panoptic morphology analysis at 48 and 72 h of treatment. The BCR-ABL expression showed no statistical difference when treated alone with IM, however in combination with ATRA, the expression was statistically significant in 48 and 72 h (p≤0.0001) and when the treatment groups were compared to each other (p≤0.001). The ABCB1 gene expression showed a decrease in isolated IM therapy (p≤0.05) and in the combination in 48 and 72 h (p≤0.0001). Combined ATRA and IM therapy was shown to be effective in decreasing BCR-ABL and ABCB1 genes, possibly through the differentiation of blast cells, demonstrating that the therapy could be potentially effective in the blast crisis of the disease and for those patients who develop resistance to available CML treatments.


Lack of sigma-1 receptor exacerbates ALS progression in mice.
The function of the sigma-1 receptor (S1R) has been implicated in modulating the activity of various ion channels. In the CNS S1R is enriched in cholinergic postsynaptic densities in spinal cord motoneurons (MNs). Mutations in S1R have been found in familial cases of amyotrophic lateral sclerosis (ALS). In this study we show that a knockout of S1R in the SOD1*G93A mouse model of ALS significantly reduces longevity (end stage). Electrophysiological experiments demonstrate that MN of mice lacking S1R exhibit increased excitability. Taken together the data suggest the S1R acts as a brake on excitability, an effect that might enhance longevity in an ALS mouse model.


Education Mitigates the Relationship of Stress and Mental Disorders Among Rural Indian Women.
Common mental disorders (CMD) are a constellation of mental health conditions that include depression, anxiety, and other related nonpsychotic affective disorders. Qualitative explanatory models of mental health among reproductive-aged women in India reveal that distress is strongly associated with CMD. The relationship of perceived stress and CMD might be attenuated or exacerbated based on an individual's sociodemographic characteristics. To screen for Common Mental Disorders (CMD) among reproductive-aged women from rural western India and explore how the relationship between perceived stress and CMD screening status varies by sociodemographic characteristics. Cross-sectional survey of 700 women from rural Gujarat, India. CMD screening status was assessed using Self-Reported Questionnaire 20 (SRQ-20). Factors associated with CMD screening status were evaluated using multivariable logistic regression. Effect modification for the relationship of perceived stress and CMD screening status was assessed using interaction terms and interpreted in terms of predicted probabilities. The analytic cohort included 663 women, with roughly 1 in 4 screening positive for CMD (157, 23.7%). Poor income, low education, food insecurity, and recurrent thoughts after traumatic events were associated with increased risk of positive CMD screen. Perceived stress was closely associated with CMD screening status. Higher education attenuated the relationship between high levels of stress and CMD screening status (82.3%, 88.8%, 32.9%; P value for trend: 0.03). Increasing income and age attenuated the link between moderate stress and CMD. Our findings suggest a high burden of possible CMD among reproductive-aged women from rural western India. Higher education might mitigate the association between elevated stress and CMD. Future efforts to improve mental health in rural India should focus on preventing CMD by enhancing rural women's self-efficacy and problem-solving capabilities to overcome challenging life events and stressors, thereby reducing the risk of CMD.


The question of nonlinearity in the dose-response relation between particulate matter air pollution and mortality: can Akaike's Information Criterion be trusted to take the right turn?
The shape of the dose-response relation between particulate matter air pollution and mortality is crucial for public health assessment, and departures of this relation from linearity could have important regulatory consequences. A number of investigators have studied the shape of the particulate matter-mortality dose-response relation and concluded that the relation could be adequately described by a linear model. Some of these researchers examined the hypothesis of linearity by comparing Akaike's Information Criterion (AIC) values obtained under linear, piecewise linear, and spline alternative models. However, at the current time, the efficacy of the AIC in this context has not been assessed. The authors investigated AIC as a means of comparing competing dose-response models, using data from Cook County, Illinois, for the period 1987-2000. They found that if nonlinearities exist, the AIC is not always successful in detecting them. In a number of the scenarios considered, AIC was equivocal, picking the correct simulated dose-response model about half of the time. These findings suggest that further research into the shape of the dose-response relation using alternative model selection criteria may be warranted.


Novel concepts for risk stratification in prostate cancer.
Since Partin introduced the analysis of prostate-specific antigen, clinical T-stage and Gleason scores to estimate the risk of progression in men with localised prostate cancer, our understanding of factors that modify this risk has changed drastically. There are now multiple risk stratification tools available, including look-up tables, risk stratification/classification analyses, regression-tree analyses, nomograms and artificial neural networks. Concurrently, descriptions of novel biopsy strategies, imaging modalities and biomarkers are frequently published with the aim of improving risk stratification. With an abundance of new information available, incorporating advances into clinical practice can be confusing. This article aims to outline the major novel concepts in prostate cancer risk stratification for men with biopsy confirmed prostate cancer. We will detail which of these novel techniques and tools are likely to be adopted to aid treatment decisions and enable more accurate post-diagnosis, pretreatment risk stratification.


Development and Evaluation of Ontologies in Traditional Medicine: A Review Study.
Development of ontologies in traditional medicine can be a foundation for other applications of informatics in this field. Despite the importance of the development of ontologies in traditional medicine, there are few review studies in this area. This study aims to review different methods for ontology development and evaluation in traditional medicine. This review study was performed in 2019. To find related papers, six databases including Scopus, Web of Science, PubMed, Embase, IEEE Xplore, and SpringerLink were searched. Initially, 761 articles were identified. After applying inclusion and exclusion criteria, 22 articles were selected to review different methods for ontology development and evaluation in traditional medicine. Five different methods were used for ontology development in traditional medicine, namely conventional, customized, semiautomatic, upper-level, and large-scale methods. The results showed that ontology evaluation was only considered in 32% of the studies. The common methods used for ontology evaluation were competency questions, expert-based evaluation, and automatic detection of inconsistency errors. Development of ontologies is of high importance for organizing knowledge in traditional medicine, as this branch of medicine is often not documented or is documented in local languages. The results of this study can help ontology developers to be familiar with the common methods of ontology development and evaluation in traditional medicine and use them for future research.


Embelin accelerates cutaneous wound healing in diabetic rats.
This study reports the effect of embelin (1) on cutaneous wound in streptozotocin (STZ)-induced diabetic rats. The effect was studied using excision, incision, and dead space models. In diabetic rats, topical application of embelin 5% (w/w) ointment showed a significant increase in wound contraction and better epithelialization, thereby facilitating the healing. Embelin was also active by the oral route (25 and 50 mg/kg) in the incision and dead space wound models. In incision wound model, wound granulation tissues were removed on 8th post-wounding day, and the hydroxyproline, hexosamine, total protein, and DNA contents were determined. In STZ diabetic rats, topical and oral applications of embelin showed an increase in hydroxyproline, hexosamine, total protein, and DNA contents. It also showed a significant increase in wound breaking strength. Embelin significantly increased granuloma tissue weight and breaking strength in dead space model. These results indicated that embelin accelerated wound healing in diabetic rat.


Common variable immunodeficiency in an adult with recurrent pneumonia.
Primary immunodeficiency syndromes are rarely diagnosed among adults. Common variable immunodeficiency (CVID) is a congenital immunological disorder characterized by defective antibody production. In this report, we describe a 35-year-old male suffering from a common variable immunodeficiency, referred to us because of a lobar pneumonia. He had a history of recurrent pulmonary infections, which was present months before presentation, suggesting hypogammaglobulinemia. We found a severe hypogammaglobulinemia, which confirmed the diagnosis of CVID. His immunoglobulin profiles upon admission before infusion of immunoglobulin (normal ranges) were: IgG < 1.41 (8-17) g/l, IgA 0.25 (0.85-4.9) g/l, IgM 0.182 (0.5-3.7) g/l, and IgE < 2 (< 120) IU/ml. His HLA profiles were HLA A2 A26, B18 B38, Cw7, DR11 and DQ7 DQ9. He was treated with intravenous immunoglobulin. After this regimen, his IgG was maintained at > 6.0 g/L. On follow up, he has been free of opportunistic infections. In conclusion, CVID should be considered in the differential diagnosis of recurrent pneumonia in adults.


Assessing attentional task-related electroencephalogram signal variations by using mobile electroencephalogram technology: An experimental study.
A better understanding of the network responses of cortical activities during rest and cognitive tasks is necessary. Therefore, in this study, we aimed to evaluate cerebral activities during attentional tasks by using mobile electroencephalography, identifying the types of attentional components and brain waves. In this experimental study, we enrolled 12 healthy young adults. The attentional tasks comprised parts A and B of the Trail-Making Test (TMT). Nineteen electroencephalography electrodes were placed over various brain regions. The Wilcoxon signed-rank test was used to examine the differences in power levels between the rest and TMT conditions. During TMT part A, the electroencephalography power level of the delta waves was significantly higher in the right frontal, left central, left occipital, left inferior frontal, right mid-temporal, right posterior temporal, and middle parietal areas (P < .05) than those during the resting state; that of the alpha waves was significantly lower in the left posterior temporal area (P = .006); and that of the high gamma waves was significantly lower in the left parietal (P = .05) and left occipital (P = .002) areas. During TMT part B, the electroencephalography power level of the beta waves was significantly higher in the right frontal area (P = .041) than that during the resting state, and that of the low gamma waves was significantly higher in the left frontal pole, right frontal, and right inferior frontal areas (P < .05). During the focused attentional task, the power level of the delta waves increased and that of the alpha waves decreased, and during the alternating attentional task, those of both the beta and gamma waves increased. The delta waves were related to the whole brain, the alpha and high gamma waves to the left posterior lobe, and the beta and low gamma waves to both frontal lobes. These findings contribute to the basic knowledge necessary to develop new attentional assessment methods for clinical situations.


Dysfunction of Sister Chromatids Separation Promotes Progression of Hepatocellular Carcinoma According to Analysis of Gene Expression Profiling.
Despite studying the various molecular mechanisms of hepatocellular carcinoma (HCC), effective drugs and biomarkers in HCC therapy are still scarce. The present study was designed to investigate dysregulated pathways, novel biomarkers and therapeutic targets for HCC. The gene expression dataset of GSE14520, which included 362 tumor and their paired non-tumor tissues of HCC, was extracted for processing by the Robust multi-array average (RMA) algorithm in the R environment. SAM methods were leveraged to identify differentially expressed genes (DEGs). Functional analysis of DEGs was performed using DAVID. The GeneMania and Cytohubba were used to construct the PPI network. To avoid individual bias, GSEA and survival analysis were employed to verify the results. The results of these analyses indicated that separation of sister chromatids was the most aberrant phase in the progression of HCC, and the most frequently involved genes, EZH2, GINS1, TPX2, CENPF, and BUB1B, require further study to be used as drug targets or biomarkers in diagnosis and treatment of HCC.


Establishment and characterization of Roberts syndrome and SC phocomelia model medaka (Oryzias latipes).
Roberts syndrome and SC phocomelia (RBS/SC) are genetic autosomal recessive syndromes caused by establishment of cohesion 1 homolog 2 ( ESCO 2) mutation. RBS/SC appear to have a variety of clinical features, even with the same mutation of the ESCO2 gene. Here, we established and genetically characterized a medaka model of RBS/SC by reverse genetics. The RBS/SC model was screened from a mutant medaka library produced by the Targeting Induced Local Lesions in Genomes method. The medaka mutant carrying the homozygous mutation at R80S in the conserved region of ESCO2 exhibited clinical variety (i.e. developmental arrest with craniofacial and chromosomal abnormalities and embryonic lethality) as characterized in RBS/SC. Moreover, widespread apoptosis and downregulation of some gene expression, including notch1a, were detected in the R80S mutant. The R80S mutant is the animal model for RBS/SC and a valuable resource that provides the opportunity to extend knowledge of ESCO2. Downregulation of some gene expression in the R80S mutant is an important clue explaining non-correlation between genotype and phenotype in RBS/SC.


Atomic Defects in Two-Dimensional Materials: From Single-Atom Spectroscopy to Functionalities in Opto-/Electronics, Nanomagnetism, and Catalysis.
Two-dimensional layered graphene-like crystals including transition-metal dichalcogenides (TMDs) have received extensive research interest due to their diverse electronic, valleytronic, and chemical properties, with the corresponding optoelectronics and catalysis application being actively explored. However, the recent surge in two-dimensional materials science is accompanied by equally great challenges, such as defect engineering in large-scale sample synthesis. It is necessary to elucidate the effect of structural defects on the electronic properties in order to develop an application-specific strategy for defect engineering. Here, two aspects of the existing knowledge of native defects in two-dimensional crystals are reviewed. One is the point defects emerging in graphene and hexagonal boron nitride, as probed by atomically resolved electron microscopy, and their local electronic properties, as measured by single-atom electron energy-loss spectroscopy. The other will focus on the point defects in TMDs and their influence on the electronic structure, photoluminescence, and electric transport properties. This review of atomic defects in two-dimensional materials will offer a clear picture of the defect physics involved to demonstrate the local modulation of the electronic properties and possible benefits in potential applications in magnetism and catalysis.


Tairyoku as a belief system of health and illness: a study of cancer patients in Japan.
The aim of this paper is to investigate the concept of tairyoku (body power) within the context of palliative care in contemporary Japan, and to explore its use by cancer patients at palliative care units (PCUs). Tairyoku is thought to be vital energy, analogous to qi in Chinese Medicine. In this paper it is shown that tairyoku is used to monitor bodily condition by patients and that it plays an important role in treatment decision-making for them. Medical professionals also use the word tairyoku; however, they do not agree with the patients' idea of increasing tairyoku in order to cure cancer. This situation causes disagreement about treatment between patients and medical staff at PCUs; however, this paper will show that tairyoku is the important concept to help patients manage their illness and sustain their autonomy, and finally accept imminent death.


Wrist swelling - Is it tuberculosis?
The hand and wrist are rare sites for tuberculosis (TB) and account for < 1% of all skeletal TB. Though rare, TB of the wrist is a cause of major morbidity. A common feature in the available reports on wrist TB is a delay in diagnosis causing residual stiffness and pain after treatment. Although TB of the wrist has a varied presentation, the majority of lesions respond to conservative treatment. We report a 12-year-old girl who presented with wrist swelling, having intercarpal, carpometacarpal, and radiocarpal joint involvement which turned out to be tuberculous and it healed with residual deformity.


[A short test for potential carcinogenicity of water soluble synthetic polymers].
The effect of synthetic water-soluble polymer with different structure on the appearance in SZNA mice of carcinogen-protein adducts (CPA) containing endogenous carcinogen, 3-oxyanthranilic acid (3-OAA), was investigated. CPA containing 3-OAA (3-OAA-CPA) were detected during the administration of 24 of 30 investigated polymers. The induction of 3-OAA-CPA and the character of their distribution in the organism (in all investigated tissues: serum, extracts of liver, spleen, lungs and kidneys tissues or in single tissues) depended on the chemical structure of polymers. It is concluded, that synthetic polymers represent potential cancerogenic danger, because their administration causes formation of 3-OAA-CPA in the organism of animals.


Partial purification and characterization of phosphoenolpyruvate carboxylase protein-serine kinase from illuminated maize leaves.
Following in situ renaturation and assay of protein kinase activity after denaturing electrophoresis of relatively impure samples of maize phosphoenolpyruvate carboxylase (PEPC) kinase, a approximately 30-kDa polypeptide was implicated as the best candidate for the PEPC kinase catalytic subunit. This kinase's apparent native molecular weight was estimated at 28,000 by gel filtration on a calibrated Superose 12 column (HR 10/30), suggesting that the isolated PEPC kinase is monomeric. This protein-serine kinase was partially purified about 4000-fold from illuminated maize leaves by ammonium sulfate precipitation and sequential chromatography on Ultrogel AcA 54, hydroxylapatite, blue dextran-agarose, and an analytical AcA 54 column. Analysis by denaturing electrophoresis revealed that a 30-kDa polypeptide copurified with PEPC kinase activity during the final step. This highly purified kinase had an apparent Km (PEPC subunit) of 2.5 microM and a Km (total ATP) of 40 microM at pH 8.0, its pH optimum. Upon in vitro phosphorylation of darkform (dephospho) C4 PEPC at Ser-15 (maize PEPC) or Ser-8 (sorghum), the malate sensitivity of the target enzyme decreased significantly. The maize PEPC kinase activity was markedly inhibited by L-malate, a negative allosteric effector of its protein substrate, in a concentration- and pH-dependent manner. Comparative phosphorylation studies with the catalytic subunit of mammalian cAMP-dependent protein kinase and casein revealed that a significant part of the malate inhibition of PEPC kinase activity in vitro was due to this effector's interaction with PEPC. The activity of both the highly purified PEPC kinase and a less pure sample prepared rapidly in the presence of various protease inhibitors was insensitive to Ca2+ chelation or addition. It is concluded that the approximately 30-kDa maize PEPC kinase is a low abundance, Ca(2+)-independent protein-serine kinase that activates its target enzyme by the exclusive phosphorylation of the regulatory serine residue near the N terminus and the resulting decrease in feedback inhibition by L-malate.


Acute expression of RET/PTC induces isozyme-specific activation and subsequent downregulation of PKCepsilon in PCCL3 thyroid cells.
Most papillary thyroid carcinomas (PTC) have an isozyme-specific reduction of protein kinase C (PKC)epsilon, which occurs through a post-transcriptional mechanism. Here, we test whether the oncoprotein RET/PTC could be responsible for this effect, since RET/PTC rearrangements are quite prevalent in PTC and RET/PTC activates PLCgamma, an upstream modulator of PKCs. At 3 h after induction of RET/PTC1 or RET/PTC3 expression, there was evidence of PKCepsilon activation. Activation was restricted to PKCepsilon, as acute expression of RET/PTC did not change the subcellular distribution of other PKC isozymes expressed in PCCL3 cells. Prolonged RET/PTC expression (2-6 days) produced an isozyme-specific change in PKCepsilon subcellular localization and a decrease in total PKCepsilon levels. The expression of RET/PTC3(Y541F), which does not interact with PLCgamma, but signals normally through other RET effectors, had no effect on PKCepsilon distribution at any of the time points examined. However, downregulation of total PKCepsilon levels was only partially prevented by expression of RET/PTC(Y541F). Cells with decreased PKCepsilon following prolonged expression of RET/PTC were relatively resistant to doxorubicin-induced apoptosis. Based on our previous observation that PCCL3 cells expressing a dominant-negative PKCepsilon are also markedly resistant to apoptosis, we propose that selective downregulation of PKCepsilon following prolonged RET/PTC activation promotes cell survival and clonal expansion.


Chlorate Levels in Dairy Products Produced and Consumed in Ireland.
In recent years, chlorate has become a residue of concern internationally, due to the risk that it poses to thyroid gland function. However, little is known about its occurrence in dairy products of Irish origin. To address this, a study was conducted in which samples of milk (n = 317), cream (n = 199), butter (n = 178), cheese (n = 144) and yoghurt (n = 440) were collected from grocery stores in the Republic of Ireland. Sampling was conducted across spring, summer, autumn and winter of 2021. Samples from multiple manufacturers of each respective dairy product were procured and analysed for chlorate using UPLC-MS/MS. Chlorate was detected in milk, cream, natural, blueberry, strawberry and raspberry yoghurts. Mean chlorate levels detected in these products were 0.0088, 0.0057, 0.055, 0.067, 0.077 and 0.095 mg kg-1, respectively. Chlorate was undetected in butter and cheese (<0.01 mg kg-1). All products sampled, except yoghurt, were found to be compliant with the EU limit for chlorate in milk (0.10 mg kg-1). Some manufacturers produced product with greater incidence and levels of chlorate. Chlorate levels from samples tested at different times of the year did not differ significantly, with the exception of strawberry and raspberry yoghurts which had higher chlorate levels in the winter period.