Sensory-Motor Modulations of EEG Event-Related Potentials Reflect Walking-Related Macro-Affordances.
One fundamental principle of the brain functional organization is the elaboration of sensory information for the specification of action plans that are most appropriate for interaction with the environment. Using an incidental go/no-go priming paradigm, we have previously shown a facilitation effect for the execution of a walking-related action in response to far vs. near objects/locations in the extrapersonal space, and this effect has been called "macro-affordance" to reflect the role of locomotion in the coverage of extrapersonal distance. Here, we investigated the neurophysiological underpinnings of such an effect by recording scalp electroencephalography (EEG) from 30 human participants during the same paradigm. The results of a whole-brain analysis indicated a significant modulation of the event-related potentials (ERPs) both during prime and target stimulus presentation. Specifically, consistent with a mechanism of action anticipation and automatic activation of affordances, a stronger ERP was observed in response to prime images framing the environment from a far vs. near distance, and this modulation was localized in dorso-medial motor regions. In addition, an inversion of polarity for far vs. near conditions was observed during the subsequent target period in dorso-medial parietal regions associated with spatially directed foot-related actions. These findings were interpreted within the framework of embodied models of brain functioning as arising from a mechanism of motor-anticipation and subsequent prediction error which was guided by the preferential affordance relationship between the distant large-scale environment and locomotion. More in general, our findings reveal a sensory-motor mechanism for the processing of walking-related environmental affordances.


Attempted suicide and the lunar cycle.
An analysis of 383 cases of attempted suicide presented to the Accident and Emergency Department during 12 complete lunar cycles (one year) gave no support for an association between attempted suicide and the lunar cycle, especially the full moon. No control for weekends or holidays was made.


Rigors in tuberculosis.
Rigors are not a recognized characteristic of miliary tuberculosis. We report two patients presenting with persistent rigors, thought to be suggestive of acute pyogenic infection, who were subsequently found to have miliary tuberculosis. In both cases, there was significant diagnostic delay. Miliary tuberculosis should therefore be included in the differential diagnosis of any patient presenting with unexplained rigors.


Effect of Linc-POU3F3 on radiotherapy resistance and cancer stem cell markers of esophageal cancer cells.
Long non-coding RNA (LncRNA) is an important transcriptional and post-transcriptional regulatory molecule in the body. In recent years, relationship between LncRNA and malignant phenotype of tumor cells has been revealed gradually. This study aims to investigate the expression characteristics of pit-oct-unc class 3 homeobox 3 related long non-coding RNA (Linc-POU3F3) in esophageal cancer and its relationship with radiation resistance (IR) as well as the expressions of cancer stem cell (CSC) markers in esophageal cancer cells. The expression characteristics and potential interaction molecules of Linc-POU3F3 in esophageal cancer were collected from the public database via bioinformatics retrieval. Forty-two pair samples of esophageal cancer tissues and corresponding adjacent tissues were collected. Human normal esophageal epithelial cells (HEEC) and human esophageal cancer cell lines (ECA109, TE-1, TE-2, TE-13) were cultured. Real-time quantitative PCR (qPCR) was used to detect the expression level of Linc-POU3F3 in clinical tissues and cells. The formation of TE-13 IR cell line induced by different doses of radiation served as IR group cells, and the same condition treated with 0 Gy dose was set as control group (control) cells. Meanwhile, we used cell transfection technology to construct random interference sequence (siControl) cells and interference (siLinc-POU3F3) cells. In ECA109 cells, we transfected blank and over expressed Linc-POU3F3 plasmids as vector and over-expressed group (oeLinc-POU3F3). The mRNA and protein expressions of CD44, CD133 and CD90 were detected by qPCR and Western blotting, respectively. MTS [3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] was used to detect the cell viability under different radiation doses, and the resistance of IR cells was verified by clone formation experiment. The expression of Linc-POU3F3 was correlated with the tumor progression and poor prognosis of esophageal cancer. The level of Linc-POU3F3 mRNA expression was significantly higher in esophageal cancer tissues and cell lines than that in normal adjacent tissues and cell lines (all P<0.01). The expressions of Linc-POU3F3 mRNA and protein expressions of CD44, CD133, and CD90 in IR cells were significantly higher than those in control cells (all P<0.01). The expression of Linc-POU3F3 in siLinc-POU3F3 cell was significantly lower than that in the siControl cells (P<0.01), and the inhibition rate was 87.21%. The mRNA and protein expressions of CD44, CD133, and CD90 in the siLinc-POU3F3 cells were significantly lower than those in the siControl cells (all P<0.05). The expressions of linc-POU3F3, CD44, CD133, and CD90 mRNA and protein in the oeLinc-POU3F3 cells were significantly higher than those in the vector cells. The relative activity and clone formation ability in the IR cells were significantly higher than those in the control cells at 2, 4, and 8 Gy doses (all P<0.01). The relative activity in the siLinc-POU3F3 cells was significantly lower than that in the siControl cells at 4 and 8 Gy doses (P<0.01). The relative activity in the oeLinc-POU3F3 cells was significantly higher than that in the vector cells at 4 and 8 Gy doses (P<0.01). Linc-POU3F3 is up-regulated in esophageal cancer and can promote IR and the expression of CSC markers in esophageal cancer cells.


Predicting the risk of cardiovascular comorbidities in adult cancer survivors.
Data on how to identify cancer survivors (css) at the greatest risk for cardiovascular conditions are limited. We aimed to characterize the clinical factors associated with ischemic heart disease (ihd) and congestive heart failure (chf) in css and to develop a stratification schema for predicting the risk of cardiovascular comorbidities in css. Cancer survivors and non-cancer controls (nccs) were identified from the U.S. National Health and Nutrition Examination Survey. Independent factors associated with increased relative risk (rr) for cardiovascular conditions were determined. A risk stratification schema was devised that correlated risk score with the prevalence of cardiovascular comorbidities in cs. Baseline characteristics were similar for the 1869 css and 24,337 nccs included in the study. Compared with nccs, css were more likely to report ihd (13.7% vs. 5.2%), chf (7.9% vs. 2.1%), or both (4.2% vs. 1.2%; all p < 0.01). Based on multivariate analyses, risk factors for cardiovascular problems included ages 40-60 years (rr: 3.66; 95% ci: 1.87 to 7.17), 60-80 years (rr: 14.18; 95% ci: 7.65 to 26.30), and 80 years or older (rr: 25.34; 95% ci: 13.16 to 48.78); male sex (rr: 2.25; 95% ci: 1.72 to 2.94); U.S. citizenship (rr: 2.10; 95% ci: 1.08 to 4.08); annual incomes of $20,000-$45,000 (rr: 1.81; 95% ci: 1.21 to 2.70) and less than $20,000 (rr: 3.05; 95% ci: 1.81 to 5.14); comorbid diabetes mellitus (rr: 2.97; 95% ci: 2.05 to 4.32); and physical inactivity (rr: 1.98; 95% ci: 1.41 to 2.79). Independent risk factors for ihd and chf in css were identified. The risk stratification schema presented here may be helpful in developing a risk-based approach to preventive cardiovascular strategies for css.


Language Representation Models: An Overview.
In the last few decades, text mining has been used to extract knowledge from free texts. Applying neural networks and deep learning to natural language processing (NLP) tasks has led to many accomplishments for real-world language problems over the years. The developments of the last five years have resulted in techniques that have allowed for the practical application of transfer learning in NLP. The advances in the field have been substantial, and the milestone of outperforming human baseline performance based on the general language understanding evaluation has been achieved. This paper implements a targeted literature review to outline, describe, explain, and put into context the crucial techniques that helped achieve this milestone. The research presented here is a targeted review of neural language models that present vital steps towards a general language representation model.


Piezoelectric ribbons printed onto rubber for flexible energy conversion.
The development of a method for integrating highly efficient energy conversion materials onto stretchable, biocompatible rubbers could yield breakthroughs in implantable or wearable energy harvesting systems. Being electromechanically coupled, piezoelectric crystals represent a particularly interesting subset of smart materials that function as sensors/actuators, bioMEMS devices, and energy converters. Yet, the crystallization of these materials generally requires high temperatures for maximally efficient performance, rendering them incompatible with temperature-sensitive plastics and rubbers. Here, we overcome these limitations by presenting a scalable and parallel process for transferring crystalline piezoelectric nanothick ribbons of lead zirconate titanate from host substrates onto flexible rubbers over macroscopic areas. Fundamental characterization of the ribbons by piezo-force microscopy indicates that their electromechanical energy conversion metrics are among the highest reported on a flexible medium. The excellent performance of the piezo-ribbon assemblies coupled with stretchable, biocompatible rubber may enable a host of exciting avenues in fundamental research and novel applications.


Modified lip-repositioning technique for the treatment of gummy smile.
This article illustrates a new technique for repositioning the lip in the treatment of gummy smile. In particular, it introduces a formula to precisely calculate how much tissue should be eliminated to avoid the recurrence of gummy smile. The modified lip-repositioning technique (MLRT) also involves the microsurgical division of the tissue components (mucosa, periosteum, and bone) as well as the fixation of the surgically modified tissue to the periosteum component. The results of the technique are shown through case presentations of seven patients with follow-up of up to 3 years. Stable results were achieved with no recurrence of gummy smile.


Novel Consensus Gene Selection Criteria for Distributed GPU Partial Least Squares-Based Gene Microarray Analysis in Diffused Large B Cell Lymphoma (DLBCL) and Related Findings.
This paper proposes a novel consensus gene selection criteria for partial least squares-based gene microarray analysis. By quantifying the extent of consistency and distinctiveness of the differential gene expressions across different double cross validations (CV) or randomizations in terms of occurrence and randomization p-values, the proposed criteria are able to identify a more comprehensive genes associated with the underlying disease. A Distributed GPU implementation has been proposed to accelerate the gene selection problem and about 8-11 times speed up has been achieved based on the microarray datasets considered. Simulation results using various cancer gene microarray datasets show that the proposed approach is able to achieve highly comparable classification accuracy in comparing with many conventional approaches. Furthermore, enrichment analysis on the selected genes for Diffused Large B Cell Lymphoma (DLBCL) and Prostate Cancer datasets and show that only the proposed approach is able to identify gene lists enriched in different pathways with significant p-values. In contrast, sufficient statistical significance cannot be found for conventional SVM-RFE and the t-test. The reliability in identifying and establishing statistical significance of the gene findings makes the proposed approach an attractive alternative for cancer related researches based on gene expression profiling or other similar data.


Molecular dynamics study of β-cyclodextrin-phenylalanine (1:1) inclusion complex in aqueous medium.
Atomistic molecular dynamics (MD) simulations of host-guest inclusion complexes of β-cyclodextrin (BCD) and zwitterionic phenylalanine (zPHE) following two possible orientations of zPHE in aqueous solutions have been carried out. The guest induced structural changes of BCD and the microscopic properties of surrounding water have been explored. The results obtained for the complex molecules were compared with those obtained for free BCD and free zPHE molecules. It is found that irrespective of the orientation, the complexation of BCD and zPHE (1:1) is associated with loss of configurational entropy. Besides, the net configurational entropy is found to differ depending upon its orientation inside the BCD cavity. Interestingly, within the simulation length scale it is found that the relatively hydrophobic aromatic moiety of zPHE prefers to stay within the hydrophobic cavity of BCD, irrespective of its orientation. Further, nonuniform distribution and altered tetrahedral ordering of hydration water molecules around the complex molecules as compared to that around the free forms are correlated well with their conformational flexibilities.


Involvement of dopamine receptor in the actions of non-psychoactive phytocannabinoids.
Nematode Caenorhabditis elegans (C. elegans) exhibited a vigorous swimming behavior in liquid medium. Addition of dopamine inhibited the swimming behavior, causing paralysis in 65% of wild-type nematodes. Interestingly, phytocannabinoids cannabidiol (CBD) or cannabidivarin (CBDV), caused paralysis in 40% of the animals. Knockout of DOP-3, the dopamine D2-like receptor critical for locomotor behavior, eliminated the paralysis induced by dopamine, CBD, and CBDV. In contrast, both CBD and CBDV caused paralysis in animals lacking CAT-2, an enzyme necessary for dopamine synthesis. Co-administration of dopamine with either CBD or CBDV caused paralysis similar to that of either phytocannabinoid treatment alone. These data support the notion that CBD and CBDV act as functional partial agonists on dopamine D2-like receptors in vivo. The discovery that dopamine receptor is involved in the actions of phytocannabinoids moves a significant step toward our understanding of the mechanisms for medical uses of cannabis in the treatment of neurological and psychiatric disorders.


The antidiuretic neurohormone RhoprCAPA-2 downregulates fluid transport across the anterior midgut in the blood-feeding insect Rhodnius prolixus.
Osmotic balance in insects is regulated by the excretory system, consisting of Malpighian tubules and the gut under the control of diuretic and antidiuretic factors. Terrestrial insects must conserve water, and antidiuresis is the norm, only interrupted by brief diuretic periods. Surprisingly, little is known about antidiuresis in insects. Two antidiuretic strategies have been described. The first antidiuretic mechanism involves the reabsorption of fluid from the primary urine in the hindgut. More recently, a second antidiuretic strategy was reported, consisting of inhibition of primary urine formation by the Malpighian tubules. Recently, we isolated, characterized, and cloned the gene encoding for the antidiuretic neurohormone (the neuropeptide RhoprCAPA-2) acting on the Malpighian tubules of Rhodnius prolixus. Here we describe a third, novel mechanism central to the antidiuretic strategy of R. prolixus, the inhibition of ion and fluid transport across the anterior midgut by RhoprCAPA-2. Our results show that RhoprCAPA-2 (1 micromol/l) reduces serotonin-stimulated fluid transport from 83 +/- 11 to 12 +/- 12 nl/min and equivalent short-circuit current from 20 +/- 4 to 5 +/- 0.7 microA/cm(2) in diuretic hormone-stimulated anterior midgut. RhoprCAPA-2 appears to function independently of intracellular cGMP or Ca(2+) in the midgut. Thus, the antidiuretic neurohormone RhoprCAPA-2 has multiple target tissues, and we hypothesize that RhoprCAPA-2 functions to coordinate the transport activity of the anterior midgut and Malpighian tubules so that the rate of fluid transport into the haemolymph by the anterior midgut matches the transport rate of Malpighian tubules to maintain the volume and ion composition of haemolymph.


Purification and Characterization of Two Forms of Glutamine Synthetase from the Pedicel Region of Maize (Zea mays L.) Kernels.
Maize (Zea mays L.) kernel pedicels, including vascular tissues, pedicel parenchyma, placento-chalazal tissue, and the surrounding pericarp, contained two forms of glutamine synthetase (EC 126.96.36.199), separable by anion exchange chromatography under mildly acidic conditions. The earlier-eluting activity (GS(p1)), but not the later-eluting activity (GS(p2)), was chromatographically distinct from the maize leaf and root glutamine synthetases. The level of GS(p1) activity changed in a developmentally dependent manner while GS(p2) activity was constitutive. GS(p1) and GS(p2) exhibited distinct ratios of transferase to hydroxylamine-dependent synthetase activities (5 and 23, respectively), which did not change with kernel age. Purified pedicel glutamine synthetases had native relative molecular masses of 340,000, while the subunit relative molecular masses differed slightly at 38,900 and 40,500 for GS(p1) and GS(p2), respectively. Both GS forms required free Mg(2+) with apparent K(m)s = 2.0 and 0.19 millimolar for GS(p1) and GS(p2), respectively. GS(p1) had an apparent K(m) for glutamate of 35 millimolar and exhibited substrate inhibition at glutamate concentrations greater than 90 millimolar. In contrast, GS(p2) exhibited simple Michaelis-Menten kinetics for glutamate with a K(m) value of 3.4 millimolar. Both isozymes exhibited positive cooperativity for ammonia, with S(0.5) values of 100 and 45 micromolar, respectively. GS(p1) appears to be a unique, kernel-specific form of plant glutamine synthetase. Possible functions for the pedicel GS isozymes in kernel nitrogen metabolism are discussed.


Micromonohalimanes A and B: Antibacterial Halimane-Type Diterpenoids from a Marine Micromonospora Species.
Despite the fact that actinomycetes harbor the genetic potential to produce terpenes, terpenoid natural products tend to be a rare occurrence in fermentation broths. Here we report two new halimane-type diterpenoids, micromonohalimanes A (1) and B (2), that were isolated from a Micromonospora sp. cultivated from the marine ascidian Symplegma brakenhielmi. This is the first report of the halimane-type diterpenoids from Micromonospora. The structures were determined using spectroscopic methods including X-ray crystallography to establish the absolute configuration. Micromonohalimane B demonstrated moderate antibacterial activity against methicillin-resistant Staphylococcus aureus.


Serial structural and functional assessments of rotator cuff repairs: do they differ at 6 and 19 months postoperatively?
Some studies have shown that rotator cuff tendon (RCT) retears occur early after surgery and ultimate failure strength is reached at between 3 and 6 months. However, few clinical studies have been reported to support their theory. The purpose of this study was to determine whether the RCT integrity after repair showed any difference at 6 months and at 19 months postoperatively. Thirty-one patients who underwent complete repair for full-thickness RCT tears that were medium-sized tears or larger and had 2 postoperative follow-up magnetic resonance imaging (MRI) scans were included in this study. Retear, fatty degeneration, and muscle atrophy were evaluated during the first and second MRI sessions. Clinical assessment was performed by use of the American Shoulder and Elbow Surgeons score, Constant score, and pain visual analog scale preoperatively and at the time of the first and second MRI scans. The mean time for the two consecutive MRI scans was 5.9 months (range, 3.1-8.3 months) and 19.7 months (range, 10.1-24.3 months). On the first MRI scans, 24 patients had no retear, 5 had partial retears, and 2 had full-thickness retears. In terms of rotator cuff retears, the 2 sets of MRI scans showed exactly the same statuses. The only statistically significant improvement was a reduction in tendinosis on the second MRI scans. In addition, significant improvements in clinical status were observed between the 2 periods. Our study shows that the structural status of RCTs after arthroscopic repair can be assessed at 6 months after surgery. Furthermore, although functional status improved with time after 6 months, the structural status of repaired cuffs remained unchanged.


Computed Tomography Thermography for Ablation Zone Prediction in Microwave Ablation and Cryoablation: Advantages and Challenges in an Ex Vivo Porcine Liver Model.
The aim of this study was to investigate the diagnostic accuracy of computed tomography (CT) for the prediction of ablation zones from microwave ablation (MWA) and cryoablation (CA) in an ex vivo porcine liver model. Sequential (30 seconds) CT scans were acquired during and after MWA and CA in an ex vivo porcine liver model. We generated 120-kVp equivalent reconstructions of generic dual-energy CT data sets, and comprehensive region-of-interest measurements were statistically correlated with invasive temperature monitoring using Pearson correlation coefficient. Binary logistic regression was performed for prediction of successful ablation. With the use of pooled data from 6 lesions in 2 separate experiments, correlation analysis of attenuation in Hounsfield units (HU) and temperature yielded r = -0.79 [confidence interval (CI), -0.85 to -0.71] for MWA and r = 0.62 (CI, 0.55 to 0.67) for CA.For MWA, there was a linear association between attenuation and temperature up to 75°C; thus, linear regression yielded a slope of -2.00 HU/°C (95% CI, -1.58 to -2.41). For CA, a linear association between attenuation and temperature was observed in the cooling phase with a slope of 2.11 HU/°C (95% CI, 1.79 to 2.58). In MWA treatment, binary logistic regression separated less than 70°C and greater than 70°C with 89.2% accuracy. Within the ice ball, temperatures above and below -20°C were distinguished with 65.3% accuracy. Our experiments reveal several difficulties in predicting ablation zone temperature from CT attenuation. Microwave ablation leads to gas production in the tissue, which degrades the accuracy of noninvasive temperature measurement, especially at higher temperatures. In CA, CT thermometry is limited by ice ball formation, which leads to homogeneous attenuation, nearly independent of temperature. Further research is needed to define the role of CT thermography in ablation zone monitoring in liver malignancies.


Gliclazide directly inhibits arginine-induced glucagon release.
Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of gliclazide or was secondary to the paracrine effect of released somatostatin. To eliminate the paracrine effects of somatostatin, we first perfused isolated rat pancreata with a medium supplemented with 23% of the standard calcium content. Second, we perifused isolated rat islets with a novel and highly specific antagonist of type 2 somatostatin receptor, DC-41-33 (2 micro mol/l), which fully antagonizes the suppressive somatostatin effect on rat A cells. Gliclazide (30 micro mol/l) inhibited glucagon release by 54% in the perfusion experiments, whereas the somatostatin response was nearly abolished. In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell.


Engineering of Synthetic Multiplexed Pathways for High-Level N-Acetylneuraminic Acid Bioproduction.
N-Acetylneuraminic acid (NeuAc) is widely used as a supplement to promote brain health and enhance immunity. However, the low efficiency of de novo NeuAc synthesis limits its cost-efficient bioproduction. Herein, a synthetic multiplexed pathway engineering (SMPE) strategy is proposed to improve NeuAc synthesis. First, we compare the key enzyme sources and optimize the expression levels of three NeuAc synthesis pathways in Bacillus subtilis; the AGE, NeuC, and NanE pathways, for which NeuAc production reached 3.94, 5.67, and 0.19 g/L, respectively. Next, these synthesis pathways were combined and modularly optimized via the SMPE strategy, with production reaching 7.87 g/L. Finally, fed-batch fermentation in a 5 L fermenter reached 30.10 g/L NeuAc production, the highest reported production using glucose as the sole carbon source. Using a generally regarded as safe strain as a production host, the developed NeuAc-producing approach should be favorable for efficient bioproduction, without the need for plasmids, antibiotics, or chemical inducers.


Investigating the Effect of Basic Amino Acids and Glucosamine on the Solubility of Ibuprofen and Piroxicam.
Poor aqueous solubility hampers the development of several compounds as pharmacological agents. Hence, preparing novel formulations with augmented absorption is a challenge in pharmaceutical industries. In this paper, we have examined the effect of basic amino acids including arginine (ARG), lysine (LYS), and glucosamine (GlucN) on the solubility of ibuprofen (IBU) and piroxicam (PXM) as drugs with limited solubility. We have also studied the effect of the dissolution media with the pH values 1.2 to 7.4. The saturation shake-flask method was used for solubility studies in the presence of amino acids. Briefly, buffer solutions containing different concentrations of amino acids were prepared. Then, an excess amount of each drug with these buffers was shaken to reach equilibrium. After 48 hours, the upper phase was separated, and solubility was calculated by reading their UV-Vis absorbance. The results illustrated that amino acids increased solubility of both drugs with different ratios, which were pH and concentration-dependent. Solubility improved as the amount of amino acids went up, and this upward pattern was more robust with ARG than LYS. The presence of GlucN in citrate buffer significantly enhanced IBU solubility. The solubility of PXM in accompany of GlucN in water did not change significantly while in citrate buffer solubility enhanced specially at pH 6. Overall, GlucN in citrate buffer and ARG in phosphate buffer could be introduced as the most suitable media for IBU and PXM solubility improvement, respectively.


Popliteal venous aneurysm: report of two cases and review of the world literature.
Two new cases of popliteal venous aneurysm are reported and added to the 22 other cases of popliteal venous aneurysm available for review. Both patients were first seen with acute pulmonary embolism and were treated with thrombolytic therapy followed by anticoagulation. Each had recurrent venous thromboembolism before discovery of the popliteal venous aneurysm. One popliteal venous aneurysm was diagnosed with phlebography and the second with venous duplex imaging, confirmed with phlebography. Both were surgically corrected with tangential aneurysmectomy and lateral venorrhaphy. Twenty-four cases of popliteal venous aneurysm are now available for review. Seventy-one percent (17 of 24) presented with pulmonary embolism, 88% (21 of 24) were saccular, and 96% (23 of 24) were located in the proximal popliteal vein. All but two were diagnosed by ascending phlebography. Three patients received no treatment: in two of these the outcome was not documented and the third had occasional pain. Two patients received anticoagulation without subsequent operative repair and both died of recurrent pulmonary emboli. Operative correction resulted in a 75% patency rate with 21% complications, most of which were related to postoperative anticoagulation. No patient who was operated on had subsequent pulmonary embolism, and there were no operative deaths. We suggest that all patients who have pulmonary embolism have lower-extremity venous duplex imaging. All popliteal venous aneurysms should be surgically repaired, inasmuch as nonoperative therapy results in recurrent thromboembolism and an unacceptably high mortality rate. Tangential aneurysmectomy with lateral venorrhaphy is the recommended procedure.


Immunological and virological markers in individuals progressing from seroconversion to AIDS.
Six men were selected from a large cohort of homosexual men participating in a study on HIV infection that was followed from seroconversion to AIDS. The patients were studied retrospectively for immunological functions of T cells, T-cell subset distribution and biological phenotype of HIV. A severe decrease in anti-CD3 monoclonal antibody (MAb)-induced T-cell proliferation at seroconversion was observed in two out of six men. After this acute phase, CD4+ T-cell numbers were in the normal range in the early asymptomatic period; the proliferative response was subnormal, whereas the capacity to generate cytotoxic T cells (CTL) was normal. From seroconversion on, CD4+CD29+ memory T-cell numbers were decreased to approximately 50% of normal values, which may contribute to loss of T-cell reactivity. In the asymptomatic phase only slow-replicating non-syncytium-inducing HIV variants were observed. The T-cell proliferative response further declined with the depletion of naive CD4+ CD45RA+ T cells and CD4+ T-cell numbers started to decline. This second decrease in T-cell function coincided with the emergence of more rapidly replicating, often (four out of six) syncytium-inducing variants. At diagnosis of AIDS, T-cell proliferation and CD4+ T-cell numbers were extremely low in five out of six patients and CTL function had declined in three out of five individuals tested. Circulating CD8+ cells had gradually shifted to an immature CD38+CD28- phenotype. Our findings support the theory that HIV-induced immune dysfunction allows for the emergence of virulent HIV variants associated with CD4+ cell loss and disease.


Activation of cell proliferation in Arabidopsis root meristem by isoprothiolane.
A plant growth regulating agent "Fuji-one" has been used to control non-parasitic damping-off (Murenae disease) of rice seedlings. Its active ingredient, isoprothiolane (diisopropyl 1,3-dithiolan-2-ylidenemalonate, IPT), enhances root elongation of rice and Arabidopsis. To understand the mechanisms of IPT's effect on root development, its effect on Arabidopsis root cells was investigated histologically. IPT at a lower concentration (12.5 µg/mL) had no effect on root cell elongation, whereas it enhanced cell division in the root meristem. Histological analysis using phytohormone-related mutants indicated that jasmonic acid and ethylene were involved in the enhanced cell division. In contrast, IPT at a higher concentration (75 µg/mL) suppressed both cell elongation and cell division, in which jasmonic acid and ethylene were not involved. In addition, root hair formation was suppressed by treatment with IPT. These analyses demonstrated that IPT (12.5 µg/mL) enhanced root elongation by activating cell division in a jasmonic acid- and ethylene-dependent manner.


Alcohol use severity and age moderate the effects of brief interventions in an emergency department randomized controlled trial.
The primary aim of this study was to examine the efficacy of two motivational interviewing-based alcohol brief interventions (BIs) among adults presenting to an emergency department (ED). The secondary aim was to evaluate moderators of intervention effects. Participants were 750 ED patients reporting recent alcohol misuse. Participants were randomly assigned to: 1) computer-delivered BI (Computer BI), 2) therapist-delivered BI with computer guidance (Therapist BI-CG), or 3) control. The BIs focused on reduction of alcohol use and risk behaviors. The outcome measure was trajectories of alcohol consumption (measured by the AUDIT-C) across baseline, 3-, 6- and 12-month follow-up assessments, analyzed using latent growth curve modeling. Moderation of intervention effect by gender, age, and baseline alcohol use disorder severity was examined. Across the full sample (40% males, mean age = 35.8, SD = 12.3), there was an overall reduction in alcohol consumption across 12 months. The main effects of the Therapist and Computer BI were not significant relative to control. Moderation analysis revealed that the impact of Therapist BI-CG, relative to control, was greater on reductions in alcohol consumption in participants with moderate to severe symptoms of alcohol use disorder compared to those with mild symptoms. The effect of the Computer BI on alcohol use, relative to control, was greater among younger participants compared to older participants. While no overall effect was shown, ED-based Therapist BI-CG with computer guidance may be effective among patients with moderate-severe drinking patterns, whereas Computer BIs may be more effective for younger participants.


Informed consent for case reports: the ethical dilemma of right to privacy versus pedagogical freedom.
A new international standard of editorial policy calls for written informed consent by the subject of every case report. Although this appears to be ethically appealing, the authors posit that in some situations, requesting informed consent may be unethical, can harm patients, and may erode the use of case reports as a valuable teaching method in psychiatry and psychotherapy. The authors discuss concerns regarding this new policy for mental health publication based on issues of transference, countertransference, best interest of the patient, and practicality.


The genome of Arabidopsis thaliana.
Arabidopsis thaliana is a small flowering plant that is a member of the family cruciferae. It has many characteristics--diploid genetics, rapid growth cycle, relatively low repetitive DNA content, and small genome size--that recommend it as the model for a plant genome project. The current status of the genetic and physical maps, as well as efforts to sequence the genome, are presented. Examples are given of genes isolated by using map-based cloning. The importance of the Arabidopsis project for plant biology in general is discussed.


Bimetallic phosphide AlP/SiP2 composite as an anode material for lithium-ion batteries with long cycle life.
AlP and SiP2 are promising alloy-type anode materials for lithium-ion batteries (LIBs), owing to their good conductivity, high storage capacity and appropriate working potential. However, they still suffer from rapid capacity decay due to the huge volume expansion and the resultant pulverization. Carbon modification can not only relieve volume changes but also provide a conducting matrix for the active material. Moreover, the charge transfer of the multi-phase composite can be accelerated owing to its electric field at the heterointerface. Hence, a bimetallic phosphide AlP/SiP2@C composite was synthesized for the first time via a facile and scalable high energy ball milling method and applied as an anode material for LIBs. Benefitting from the above combined advantages of the heterostructure and carbon layer protection, the AlP/SiP2@C electrode delivered a high reversible capacity (1482 mA h g-1 at the current density of 0.3 A g-1) and durable lifespan (516 mA h g-1 after 4000 cycles at a current density of 3 A g-1), which are superior to those of the binary AlP@C and SiP2@C composites.


Progress toward novel treatments for chronic kidney disease.
Chronic kidney failure remains a major health problem worldwide. Although current treatment is focused on the renin-angiotensin system, it is essential that new treatments targeted toward novel pathophysiological mechanisms are developed if we are to make significant progress in this area. In this review, we have outlined several promising new areas while emphasizing that large, randomized, well-controlled clinical trials are essential to reach a meaningful conclusion about the efficacy and safety of novel treatment.


Leaf conductance as a function of photosynthetic photon flux density and absolute humidity difference from leaf to air.
FOR AN ENTIRE SEASON OF STOMATAL ACTIVITY, LEAF OR NEEDLE CONDUCTANCE WAS OBSERVED ON FOUR SPECIES, EACH IN A DIFFERENT GENUS: Engelmann spruce (Picea engelmannii Parry ex Engelm.), subalpine fir (Abies lasiocarpa [Hook.] Nutt.), lodgepole pine (Pinus contorta var. latifolia Engelm.), and aspen (Populus tremuloides Michx.). Conductance in the natural environment was described for all species by photosynthetic photon flux density (PPFD) and absolute humidity difference from leaf to air (DAH), as follows: Conductance = b(1) ( radicalPPFD/ radicalDAH) + b(2) ( radicalPPFD/DAH) + b(3) ( radicalPPFD/DAH(2)). The only data not fitting this relationship were conifer data collected after freezing nights or aspen data collected during a short period in August when water stress occurred. In both cases, leaf conductance was reduced. It is proposed that PPFD and DAH are primary factors controlling stomatal function for plants growing in their native range; secondary factors, such as temperature and water stress, affect conductance intermittently, except when plants are growing outside their normal environmental conditions.


Ion exchange chromatographic conditions for obtaining individual subunits of soybean beta-conglycinin.
Soybean beta-conglycinin is a complex protein possessing health-promoting properties. beta-Conglycinin is a trimeric glycoprotein. Little information related to methods for separation of the individual chains forming beta-conglycinin has been so far published and it is of great interest. As a consequence, less data on the bioactivities of alpha, alpha' and beta subunits of this glycoprotein have been published. The present research aimed to find out new alternative chromatographic conditions to obtain beta-conglycinin subunits that are free of contaminating proteins. In the present short communication, we propose the use of a two-step ion exchange chromatographic protocol to achieve this goal. Firstly, beta subunit was separated by means of anionic exchange fast protein liquid chromatography. Secondly, alpha and alpha' chains were separated from each other by cationic exchange. Our data indicated the feasibility of proposed fractionation protocol to separate soybean beta-conglycinin alpha and alpha' subunits from other contaminating proteins and to obtain enough amounts of the three individual chains forming this glycoprotein for further characterization and application. The procedure may be easily up-scaled.


[A case of difficult-to-diagnose hereditary angioedema].
Hereditary angioedema (HAE) due to an inherited C1-inhibitor (C1-INH) deficiency causes localized swelling of the oral cavity, pharynx, larynx, and face, that may be life-threatening when the larynx is involved. A 26-year-old woman seen 3 times previously for pharyngeal or laryngeal edema while in her teens, and seen this time for dyspnea was found in computed tomography (CT) to have esophageal edema and pleural effusion. Her C1-INH activity was low, yielding a definitive diagnosis of HAE for her 10-year-plus-disease history. n mind in th e f idiopathicedema. should be kept i While it is comparatively rare, HAE differential diagnosis o


Protein fibrillogenesis model tracked by its intrinsic time-resolved emission spectra.
The excited-state kinetics of the fluorescence of tyrosine in a de novo protein fibrillogenesis model was investigated as a potential tool for monitoring protein fibre formation and complexation with glucose (glycation). In stark contrast to insulin the time-resolved emission spectra (TRES) recorded over the period of 700 hours in buffered solutions of the model with and without glucose revealed no apparent changes in Tyr fluorescence responses. This indicates the stability of the model and provides a measurement-supported basis for its use as a reference material in fluorescence studies of protein aggregation.


Targeting polyIC to EGFR over-expressing cells using a dsRNA binding protein domain tethered to EGF.
Selective delivery of drugs to tumor cells can increase potency and reduce toxicity. In this study, we describe a novel recombinant chimeric protein, dsRBEC, which can bind polyIC and deliver it selectively into EGFR over-expressing tumor cells. dsRBEC, comprises the dsRNA binding domain (dsRBD) of human PKR (hPKR), which serves as the polyIC binding moiety, fused to human EGF (hEGF), the targeting moiety. dsRBEC shows high affinity towards EGFR and triggers ligand-induced endocytosis of the receptor, thus leading to the selective internalization of polyIC into EGFR over-expressing tumor cells. The targeted delivery of polyIC by dsRBEC induced cellular apoptosis and the secretion of IFN-β and other pro-inflammatory cytokines. dsRBEC-delivered polyIC is much more potent than naked polyIC and is expected to reduce the toxicity caused by systemic delivery of polyIC.


Evidence of guest encapsulation within G8 and G10 dendrimers using NMR techniques.
Encapsulation of guest molecules within the interior cavities of dendrimers is promising, but high generation dendrimers show limited encapsulation capacity due to their dense surface shell. Here, for the first time, we prove that high generation polyamidoamine dendrimers, such as generation 8 and generation 10, are able to encapsulate hydrophobic guests using NMR spectroscopy. Guest molecules such as phenylbutazone, dexamethasone sodium phosphate and 9-anthracenecarboxylic acid with molecular weights up to 516 Da are in close proximity to the interior scaffold protons of high generation dendrimers. This encapsulation behavior depends on guest hydrophobicity. Chemical defects and back-folding of terminal groups make it possible for these guest molecules to penetrate through the dense surface shell of high generation dendrimers. These results provide new insights into the host-guest chemistry of dendrimers.


Interactions of Nanosized Aggregates of Fullerene C60 with Electrolytes in Methanol: Coagulation and Overcharging of Particles.
Contrary to numerous studies on the stability of fullerene aqueous colloidal solutions in the presence of electrolytes, the corresponding issue for the organosols was until recently almost unexplored. In this article, the state of C60 in methyl alcohol and the regularities of the coagulation of colloidal solution in this solvent were examined in the presence of electrolytes. Alcosols with a fullerene concentration of 4 × 10-6 M were prepared by the dilution of the C60 saturated solution in toluene by methanol. The ca. 300 nm-sized aggregates possess a negative electrokinetic potential value, ζ = -37 ± 8 mV. To determine the critical coagulation concentrations, CCC, the size increase of the species was followed up using the dynamic light scattering method. The analysis of the coagulation in terms of the Fuchs function, W, was accompanied by zeta potential monitoring. The consideration of the data for 1:1 electrolytes NaClO4 and N(n-C4H9)4ClO4 allows a rough estimate of the Hamaker constant of fullerene-fullerene attraction. Whereas in the case of these two electrolytes the colloidal species are negatively charged at the CCC, expressed overcharging of up to ζ = +36 mV by H+, Ca2+, Ba2+, and La3+ ions was observed. The action of HClO4 should be attributed to the interfacial acid-base reaction, whereas the excessive attraction of metal cations is caused by poor solvation in methanol; the negative charge is restored when the metal cations are shielded by a macrocyclic ligand.


Depression of drug-metabolizing activity in the human liver by interferon-beta.
The depressant effect of interferon beta on drug-metabolizing activity in the human liver was investigated. Seven patients with chronic hepatitis C were treated with interferon beta at doses of 3 x 10(6) to 9 x 10(6) IU/day for 8 wk. The activities of 7-methoxycoumarin O-demethylase and 7-ethoxycoumarin O-deethylase in specimens obtained by liver biopsy were examined before and after interferon treatment. Theophylline pharmacokinetics were also examined before and after interferon treatment. Interferon beta treatment reduced the activities of both O-dealkylases from 6.0 (100%) to 3.2 (53%) nmol/gm liver per minute and from 1.9 (100%) to 1.1 (58%) nmol/gm liver per minute, respectively (p < 0.05). The total body clearance of theophylline was also decreased (from 0.76 to 0.56 ml/kg/min; p < 0.05), and its elimination half-life was increased (from 8.4 to 11.7 hr; p < 0.05); however, the volume of distribution was not significantly affected. The magnitude of the decreases in enzyme activities and in theophylline clearance varied widely in individual patients and did not correlate with the dose of interferon administered. This study provides the first direct evidence that interferon beta can depress the activity of drug-metabolizing enzymes in the human liver.


Colonic submucosal tumors: a new classification based on radiologic characteristics.
Despite advances in gastrointestinal radiologic techniques, findings from barium enema studies cannot be used reliably to predict the histologic nature of a colonic submucosal tumor. Therefore, we generated a new and comprehensive classification system for all colonic submucosal tumors based on a correlation between their radiologic characteristics and their histopathologic features. Between 1978 and 1990, 89 patients had 95 colonic submucosal tumors diagnosed on the basis of barium enema studies and confirmed by biopsy or surgery. Of these, 39 patients (44%) were symptomatic and 50 patients (56%) were asymptomatic. Single lesions (82 cases) and multiple lesions (12 cases of lymphoma and one case of blue rubber bleb nevus) were observed. The 95 lesions included 21 carcinoids, 27 malignant lymphomas, 17 lipomas, 10 lymphangiomas, six leiomyosarcomas, five leiomyomas, and nine others. We analyzed the radiologic findings and classified these lesions according to their appearance. All tumors were classified on the basis of their morphologic appearance into five types: (1) wide-based sessile lesion with gradually sloping margin and smooth surface (17 cases); (2) wide-based sessile lesion, more polypoid than the first type, with a smooth surface, with or without a central depression (49 cases); (3) wide-based sessile lesion with lobulated surface (six cases); (4) pedunculated lesion with smooth or granular surface (17 cases); (5) unclassified, not any of the previously mentioned types, may be diffusely stenotic or aneurysmal (six cases). The most common finding was the wide-based sessile lesion with a smooth surface and a possible central depression; next most common was the wide-based sessile lesion with gradually sloping margin and smooth surface; next was the pedunculated lesion with a smooth or granular surface. Eighty-six percent of the lesions were single; 14% were multiple. Histologic confirmation revealed mainly lymphoma (29%) and carcinoid (22%), of which the most common finding was a wide-based sessile lesion with a smooth surface, with or without a central depression. This new classification based on radiologic characteristics covers all varieties of colonic submucosal tumors. It can serve as a guideline for predicting a specific diagnosis of a colonic submucosal tumor on the basis of radiologic findings.


Functional genomics and the comparative physiology of hypoxia.
Comparative physiology has proven a powerful approach to our understanding of how animals function under hypoxic conditions and to identifying potential adaptations to environmental oxygen levels. This review considers the potential for using a similar comparative approach with functional genomics to understand the genetic basis of such physiological processes and evolutionary adaptations. Comparative functional genomics is currently limited by genome data, which are available for only a few model organisms. However, comparative studies between model organisms of the same species having slightly different genomes (e.g., in-bred strains of laboratory rodents, transgenic mice, and consomic rats) demonstrate the types of results, as well as the analytical challenges, that are possible if comparative functional genomics is applied to more species. Results from wild and domestic animal studies suggest new models to investigate physiological and evolutionary responses to oxygen levels with functional genomics.


Dimensional influence of interproximal areas on existence of interdental papillae.
Restoring papillae in the gingival embrasures of the esthetic zone is a key consideration in periodontal, restorative, and orthodontic treatment. This study analyzes the existence of interdental papillae with regard to the vertical dimensions between the contact point and the alveolar crest and horizontal dimensions between adjacent roots. A total of 259 papillae, in 60 patients, were examined. All patients were indicated for full-thickness periodontal flap surgery. A mucoperiosteal flap was raised and, after thorough debridement, horizontal and vertical dimensions between adjacent roots were recorded. The incidence of papillae was analyzed using χ(2) for linear trend analysis. Interdental papillae were present in 85.7% of the cases when the vertical dimensions were 4 mm (P <0.05). Also, papillae were present in 78.5% of cases when the horizontal dimensions were between 0.5 and 1 mm (P <0.05). The vertical and horizontal dimensions of interproximal areas had a substantial, independent, and combined effect on the existence of interproximal papillae.


Human UDP-α-d-xylose synthase forms a catalytically important tetramer that has not been observed in crystal structures.
Human UDP-α-d-xylose synthase (hUXS) is a member of the extended short chain dehydrogenase/reductase (SDR) family of enzymes. Previous crystallographic studies have shown that hUXS conserves the same dimeric quaternary structure observed in other SDR enzymes. Here, we present evidence that hUXS also forms a tetramer in solution that is important for activity. Sedimentation velocity studies show that two hUXS dimers undergo a concentration-dependent association to form a tetramer with a Kd of 2.9 μM. The tetrameric complex is also observed in small-angle X-ray scattering (SAXS). The specific activity for the production of the reaction intermediate UDP-α-d-4-keto-xylose displays a hyperbolic dependence on protein concentration that is well modeled by an isotherm using the 2.9 μM Kd of the tetramer. Likewise, the rate of UDP-α-d-xylose production in the presence of increasing concentrations of the small molecule crowder trimethylamine N-oxide is consistent with the formation of a higher activity tetramer. We present several possible structural models of the hUXS tetramer based on (i) hUXS crystal packing, (ii) homology modeling, or (iii) ab initio simulated annealing of dimers. We analyze the models in terms of packing quality and agreement with SAXS data. The higher activity of the tetramer coupled with the relative instability of the complex suggests that an association-dissociation mechanism may regulate hUXS activity.


A simplified proof of the NP- and MAX SNP-hardness of multiple sequence tree alignment.
We give a simple proof which shows that the multiple sequence tree alignment problem from molecular biology is both NP-complete and MAX SNP-hard. Our proof of MAX SNP-hardness is simpler than that given previously by Wang and Jiang. These results suggest that it is unlikely that the multiple sequence tree alignment problem has polynomial-time algorithms that produce either optimal solutions or approximate solutions whose cost may be arbitrarily close to optimal.


Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis.
Mesothelial-to-mesenchymal transition (MMT) is an auto-regulated physiological process of tissue repair that in uncontrolled conditions such as peritoneal dialysis (PD) can lead to peritoneal fibrosis. The maximum expression of peritoneal fibrosis induced by PD fluids and other peritoneal processes is the encapsulating peritoneal sclerosis (EPS) for which no specific treatment exists. Tamoxifen, a synthetic estrogen, has successfully been used to treat retroperitoneal fibrosis and EPS associated with PD. Hence, we used in vitro and animal model approaches to evaluate the efficacy of Tamoxifen to inhibit the MMT as a trigger of peritoneal fibrosis. In vitro studies were carried out using omentum-derived mesothelial cells (MCs) and effluent-derived MCs. Tamoxifen blocked the MMT induced by transforming growth factor (TGF)-β1, as it preserved the expression of E-cadherin and reduced the expression of mesenchymal-associated molecules such as snail, fibronectin, collagen-I, α-smooth muscle actin, and matrix metalloproteinse-2. Tamoxifen-treatment preserved the fibrinolytic capacity of MCs treated with TGF-β1 and decreased their migration capacity. Tamoxifen did not reverse the MMT of non-epitheliod MCs from effluents, but it reduced the expression of some mesenchymal molecules. In mice PD model, we demonstrated that MMT progressed in parallel with peritoneal membrane thickness. In addition, we observed that Tamoxifen significantly reduced peritoneal thickness, angiogenesis, invasion of the compact zone by mesenchymal MCs and improved peritoneal function. Tamoxifen also reduced the effluent levels of vascular endothelial growth factor and leptin. These results demonstrate that Tamoxifen is a therapeutic option to treat peritoneal fibrosis, and that its protective effect is mediated via modulation of the MMT process.


Radiation Absorbed Dose to the Embryo and Fetus from Radiopharmaceuticals.
Nuclear medicine procedures are generally avoided during pregnancy out of concern for the radiation dose to the fetus. However, for clinical reasons, radiopharmaceuticals must occasionally be administered to pregnant women. The procedures most likely to be performed voluntarily during pregnancy are lung scans to diagnose pulmonary embolism and 18F-fluoro-2-deoxyglucose (18F-FDG) scans for the staging of cancers. This article focuses on the challenges of fetal dose calculation after administering radiopharmaceuticals to pregnant women. In particular, estimation of the fetal dose is hampered by the lack of fetal biokinetic data of good quality and is subject to the variability associated with methodological choices in dose calculations, such as the use of various anthropomorphic phantoms and modeling of the maternal bladder. Despite these sources of uncertainty, the fetal dose can be reasonably calculated within a range that is able to inform clinical decisions. Current dose estimates suggest that clinically justified nuclear medicine procedures should be performed even during pregnancy because the clinical benefits for the mother and the fetus outweigh the small and purely hypothetical radiation risk to the fetus. In addition, the fetal radiation dose should be minimized without compromising image quality, such as by encouraging bladder voiding and by using positron emission tomography (PET)/magnetic resonance imaging (MRI) devices or high-sensitivity PET scanners that generate images of good quality with a lower injected activity.


The F-BAR Protein NOSTRIN Dictates the Localization of the Muscarinic M3 Receptor and Regulates Cardiovascular Function.
Endothelial dysfunction is an early event in cardiovascular disease and characterized by reduced production of nitric oxide (NO). The F-BAR protein NO synthase traffic inducer (NOSTRIN) is an interaction partner of endothelial NO synthase and modulates its subcellular localization, but the role of NOSTRIN in pathophysiology in vivo is unclear. We analyzed the consequences of deleting the NOSTRIN gene in endothelial cells on NO production and cardiovascular function in vivo using NOSTRIN knockout mice. The levels of NO and cGMP were significantly reduced in mice with endothelial cell-specific deletion of the NOSTRIN gene resulting in diastolic heart dysfunction. In addition, systemic blood pressure was increased, and myograph measurements indicated an impaired acetylcholine-induced relaxation of isolated aortic rings and resistance arteries. We found that the muscarinic acetylcholine receptor subtype M3 (M3R) interacted directly with NOSTRIN, and the latter was necessary for correct localization of the M3R at the plasma membrane in murine aorta. In the absence of NOSTRIN, the acetylcholine-induced increase in intracellular Ca(2+) in primary endothelial cells was abolished. Moreover, the activating phosphorylation and Golgi translocation of endothelial NO synthase in response to the M3R agonist carbachol were diminished. NOSTRIN is crucial for the localization and function of the M3R and NO production. The loss of NOSTRIN in mice leads to endothelial dysfunction, increased blood pressure, and diastolic heart failure.


Inhibition of aggrecanases as a therapeutic strategy in osteoarthritis.
Over the last decade, there has been a large effort to target aggrecanases, which are responsible for the degradation of the aggrecan in the extracellular matrix of joints, in order to hopefully lead to new treatments for osteoarthritis. Only a few inhibitors have been effective in explants or rodent models and thus only a few have reached the clinic, none of which have proven to be effective. In this article, a survey of chemical series is described, covering historical and recent inhibitors and highlighting how some of their problems were resolved, with a critical overview of the challenges encountered. A large effort should be undertaken in designing smaller compounds with higher residence times, defining new interaction sites on the aggrecanases and exploiting target flexibility.


Coronary heart disease and periodontitis -- a case control study in Chilean adults.
To investigate the association between periodontal disease parameters and coronary ischemic disease among 30-50-year-old Chileans. Cases were 30-50-year-olds who were hospitalized in one of four Cardiologic Units in Santiago, Chile, for acute myocardial infarction, unstable angina or angina pectoris. Controls had undergone surgery due to gall bladder stones or abdominal hernia. Information on blood pressure, serum cholesterol, body weight and height, age, occupation, smoking, diabetes and use of antidepressants was obtained. A total of 86 persons participated based on informed consent, but the analysis is based on 61 persons, for whom a complete set of data was obtained. Cases and controls were given a clinical periodontal examination comprising assessment of number of teeth present, periodontal pocket depth and clinical attachment level at six sites per tooth. The association between mean attachment level; mean pocket probing depth; number of teeth present and case status was analyzed by conditional logistic regression controlling for known risk factors for CHD. The mean attachment level was positively associated with case status (OR = 3.17; 95% CI = [1.31; 7.65]), as was the mean pocket depth (OR = 8.64; 95% CI = [1.22; 61.20]). The number of teeth present was not statistically significantly associated with case status (OR = 0.93; 95% CI = [0.83; 1.04]). The results are in accordance with those of several previous reports. If the results reflect a causal link between periodontal diseases and CHD they emphasize the need for better control of periodontal diseases. If the associations are-non-causal, they still demonstrate that CHD and periodontal diseases cluster in the same sections of the population, which is important from a public health point of view.


Mercury and the activity of erythrocyte and bone marrow glutathione reductase (E.C. 188.8.131.52.) and glucose-6-phosphate dehydrogenase (E.C. 188.8.131.52) in rats.
These studies were carried out on male Wistar rats. Erythrocyte and bone marrow activity of glutathione reductase (GR - E.C. 22.214.171.124) and glucose-6-phosphate dehydrogenase (G6PD - E.C. 18.104.22.168) were determined as affected by mercury. Under physiological conditions the above enzymes were found to be markedly more active in the bone marrow than in erythrocytes. The present experiments have revealed that within the first days there will be an increase in enzyme activity in the bone marrow as well as in glutathione reductase in erythrocytes. Simultaneously, a decline in the activity of erythrocytes could be observed which began within the very first days of the experiments as well as a decrease in the bone marrow, which occurred later in the course of the experiment.


Short-Term Treatment of Bothersome Bleeding for Etonogestrel Implant Users Using a 14-Day Oral Contraceptive Pill Regimen: A Randomized Controlled Trial.
To understand whether using oral contraceptive pills (OCPs) results in temporary interruption of bleeding for etonogestrel contraceptive implant users during a 14-day course. In this double-blind trial, we randomly assigned etonogestrel implant users reporting 7 consecutive days or more of bothersome bleeding to receive 14 pills of study drug (150 microgram levonorgestrel and 30 microgram ethinyl estradiol combined OCPs) or an identical-appearing placebo. The primary outcome was the proportion of women in each group who stopped bleeding during therapy and continued to report no bleeding at the end of therapy. Prespecified secondary outcomes were number of days until temporary interruption of bleeding occurred, number of days without bleeding during therapy, and number of days to recurrence of bleeding after discontinuation of therapy. We hypothesized that temporary interruption of bleeding would occur in 80% of the treatment group compared with 20% in the control group; using 80% power, we needed a sample size of 26 women. We performed intent-to-treat analysis. From November 2013 through December 2014, 66 women were screened and 32 were randomized: OCPs (n=16) or placebo (n=16). The majority was young, Caucasian women with reported bleeding as extremely or very annoying; groups had similar baseline characteristics. Participants randomized OCPs were more likely (14 of 16 [87.5%±16.2%] compared with six of 16 [37.5%±23.7%]) to have a temporary interruption of bleeding during the study drug period (odds ratio 11.7, 95% confidence interval 1.9-70.2). Of women in the OCP arm who had a temporary interruption, 85.7% had bleeding recurrence within 10 days after treatment. Bothersome bleeding in etonogestrel contraceptive implant users will usually stop with 14-day OCP treatment, but bleeding most often resumes within days of treatment cessation. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01968135. I.


The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study).
Gadobenate dimeglumine (MultiHance) has higher r1 relaxivity than gadoterate meglumine (Dotarem) which may permit the use of lower doses for MR imaging applications. Our aim was to compare 0.1- and 0.05-mmol/kg body weight gadobenate with 0.1-mmol/kg body weight gadoterate for MR imaging assessment of brain tumors. We performed crossover, intraindividual comparison of 0.1-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 1) and 0.05-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 2). Adult patients with suspected or known brain tumors were randomized to Arm 1 (70 patients) or Arm 2 (107 patients) and underwent 2 identical examinations at 1.5 T. The agents were injected in randomized-sequence order, and the 2 examinations were separated by 2-14 days. MR imaging scanners, imaging sequences (T1-weighted spin-echo and T1-weighted high-resolution gradient-echo), and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images for diagnostic information (degree of definition of lesion extent, lesion border delineation, visualization of lesion internal morphology, contrast enhancement) and quantitatively for percentage lesion enhancement and lesion-to-background ratio. Safety assessments were performed. In Arm 1, a highly significant superiority (P < .002) of 0.1-mmol/kg gadobenate was demonstrated by all readers for all end points. In Arm 2, no significant differences (P > .1) were observed for any reader and any end point, with the exception of percentage enhancement for reader 2 (P < .05) in favor of 0.05-mmol/kg gadobenate. Study agent-related adverse events were reported by 2/169 (1.2%) patients after gadobenate and by 5/175 (2.9%) patients after gadoterate. Significantly superior morphologic information and contrast enhancement are demonstrated on brain MR imaging with 0.1-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate. No meaningful differences were recorded between 0.05-mmol/kg gadobenate and 0.1-mmol/kg gadoterate.


Decline of serum human chorionic gonadotropin and spontaneous complete abortion: defining the normal curve.
We sought to estimate a standard curve of serum human chorionic gonadotropin (hCG) decline that characterizes spontaneous abortion. Data were extracted from a clinical database of women with symptomatic early pregnancies and nondiagnostic ultrasonography who required follow-up with serial hCG levels. The evaluation was restricted to women who had a pregnancy of unknown location, a decrease in serum levels, and who were ultimately diagnosed with miscarriage (a decrease in serum hCG to < 5 mIU/mL in the absence of surgical intervention or confirmation of products of conception after dilation and curettage). The starting point of the curve was the hCG concentration at presentation, with serial levels plotted until the time of definitive diagnosis. Semiparametric statistical techniques were used to characterize the shape of the curve. We present slopes for the decrease in log hCG levels and the projected rate of fall. Of the 1,543 patients, 710 were diagnosed with miscarriage. A quadratic curve for log hCG with a steeper rate of decline for large initial hCG values best described the pattern of change. One curve could not fully estimate the decline because the rate was dependent on the initial hCG level. In other words, more rapid decline was associated with a higher starting concentration. The rate of decline ranged from 21% to 35% at 2 days and 60% to 84% at 7 days, depending on initial hCG value. The rate of hCG decrease in spontaneous abortions is described by a quadratic profile, with a faster decline in hCG value with higher presentation levels. A rate of decline less than 21% at 2 days or 60% at 7 days suggests retained trophoblasts or an ectopic pregnancy.


Large cell neuroendocrine carcinoma of the ovary: a case report and a brief review of the literature.
Large cell neuroendocrine carcinoma (LCNC) of the ovary, or ovarian undifferentiated non-small cell carcinoma of neuroendocrine type, is a rare entity that is frequently associated with ovarian surface epithelial tumors. Few cases have been reported in the literature. LCNC is an aggressive tumor with tendency to present at advanced stages and to cause death after a short postoperative duration. We report three cases of LCNC diagnosed histopathologically. Immunohistochemically, the tumor cells were positive for chromogranin A, NSE, CD56, and pancytokeratin. The patients were treated postoperatively with combination chemotherapy. Due to the rarity of LCNC, the general consensus on standard therapy is not established. Although most patients are at stage I, the biological aggressiveness and poor prognosis of the tumors have been reported in previous reports despite extensive surgery and chemotherapy.


Increased expression of the cyclin-dependent kinase inhibitor p27 in cleavage-stage human embryos exhibiting developmental arrest.
It is accepted that approximately 50% of embryos obtained after IVF arrest during the first week. Traditionally, chromosome abnormality and suboptimal culture conditions have been proposed as factors commonly associated with embryo arrest. However, even when considering 'ideal' conditions and embryos of only excellent morphology in vitro, there is still a significant incidence of embryonic arrest. There is considerable evidence that the nuclear protein p27, a member of the Cip/Kip family of CDK inhibitors, plays an important role in multiple fundamental cellular processes, including cell proliferation, cell differentiation, and apoptosis. The present investigation, using immunocytochemical techniques coupled with confocal microscopy, was undertaken to determine whether p27 could play a role in the arrest of 4-8-cell human embryos. A total of 28 preimplantation embryos at the 4-8-cell stage were investigated. Of these, 16 were diploid embryos showing cleavage arrest with no further progression, and 12 were normally developing embryos. There was a 2-fold increased expression of the cell-cycle inhibitor p27 in arrested embryos compared with control normally developing embryos. This study represents the first demonstration of an increased expression of p27 in cleavage-stage human arrested embryos.


Facile Formation of Redox-Active Totally Organic Nanoparticles in Water by In Situ Reduction of Organic Precursors Stabilized through Aromatic-Aromatic Interactions by Aromatic Polyelectrolytes.
The formation of redox-active, totally organic nanoparticles in water is achieved following a strategy similar to that used to form metal nanoparticles. It is based on two fundamental concepts: i) complexation through aromatic-aromatic interactions of a water-soluble precursor aromatic molecule with polyelectrolytes bearing complementary charged aromatic rings, and ii) reduction of the precursor molecule to achieve stabilized nanoparticles. Thus, formazan nanoparticles are synthesized by reduction of a tetrazolium salt with ascorbic acid using polyelectrolytes bearing benzene sulfonate residues of high linear aromatic density, but cannot be formed in the presence of nonaromatic polyelectrolytes. The red colored nanoparticles are efficiently encapsulated in calcium alginate beads, showing macroscopic homogeneity. Bleaching kinetics with chlorine show linear rates on the order of tenths of milli-meters per minute. A linear behavior of the dependence of the rate of bleaching on the chlorine concentration is found, showing the potential of the nanoparticles for chlorine sensing.


Medicaid program; Medicaid management information system: revised definition of "mechanized claims processing and information retrieval system"--HCFA. Final rule with comment period.
We are making a number of revisions to regulations concerning mechanized claims processing and information retrieval systems ("system" or "systems"). We are revising definitions to show that we will not make available Federal funding at 75 and 90 percent of State Medicaid agency expenditures for eligibility determination systems because they do not meet the definition of a "mechanized claims processing and information retrieval system" or of an enhancement to that system. We are also conforming our regulations to changes made by section 9503(b)(2) and 9518 of the Consolidated Omnibus Budget Reconciliation Act (COBRA) of 1985 (Pub. L. 99-272), which involve technical changes. One change affects the frequency and scope of our system reviews, and the other involves the date by which States that are not exempt by law must have an operating system.


Observations of seating position of front seat occupants relative to the side of the vehicle.
This study was an on-road observational study of the seating position and limb position of front seat occupants relevant to the side of the car for a representative sample of occupants during straight road driving and turning manoeuvres. A video camera captured over 650 front-on images of passenger car occupants in Metropolitan Melbourne. Results showed a significant numbers of occupants were seated out-of-position while travelling on the road and that a number of these were seated in a manner that may possibly result in injury from the deployment of a side airbag. This was particularly so while turning, a situation common in many side impacts. A substantial number of front seat occupants' arms were exposed to severe injury in the event of a side impact crash. These findings highlight a number of aspects of seating behaviour of driver and front passengers that need to be taken into account when designing side impact airbags.


Oxidative stress increases phosphorylation of IkappaB kinase-alpha by enhancing NF-kappaB-inducing kinase after transient focal cerebral ischemia.
The IkappaB kinase (IKK) complex is a central component in the classic activation of the nuclear factor-kappaB (NF-kappaB) pathway. It has been reported to function in physiologic responses, including cell death and inflammation. We have shown that IKK is regulated by oxidative status after transient focal cerebral ischemia (tFCI) in mice. However, the mechanism by which oxidative stress influences IKKs after tFCI is largely unknown. Nuclear accumulation and phosphorylation of IKKalpha (pIKKalpha) were observed 1 h after 30 mins of tFCI in mice. In copper/zinc-superoxide dismutase knockout mice, levels of NF-kappaB-inducing kinase (NIK) (an upstream kinase of IKKalpha), pIKKalpha, and phosphorylation of histone H3 (pH3) on Ser10 were increased after tFCI and were higher than in wild-type mice. Immunohistochemistry showed nuclear accumulation and pIKKalpha in mouse brain endothelial cells after tFCI. Nuclear factor-kappaB-inducing kinase was increased, and it enhanced pH3 by inducing pIKKalpha after oxygen-glucose deprivation (OGD) in mouse brain endothelial cells. Both NIK and pH3 interactions with IKKalpha were confirmed by coimmunoprecipitation. Treatment with IKKalpha small interfering RNA significantly reduced cell death after OGD. These results suggest that augmentation of NIK, IKKalpha, and pH3 in response to oxidative stress is involved in cell death after cerebral ischemia (or stroke).


Environments of professional nursing practice in the context of the COVID-19 pandemic.
Although COVID-19 attracted attention to the environments of professional nursing practice, triggering a series of responses to address some of the most pressing problems, it is important to identify the size and scope of other weaknesses that have emerged. In an observational and cross-sectional study, using the Scale for the Evaluation of the Environment of Professional Nursing Practice, 752 nurses from a Portuguese university hospital, provided socio-demographic and professional data about the components structure, process and outcome of their professional nursing environment. Data collection took place from June 1-30, 2020, immediately after the first critical period of the COVID-19 pandemic in Portugal. In the analysed environment of professional nursing practice, Process factors were favourable to the quality of care, while the Structure and Outcome factors had a moderately favourable effect. Structure factors related to work contexts (P < .001) and nursing functions in patient care areas with COVID-19 (P = .001). Process factors related significantly to work contexts (P < .001). A significant association was found between Outcome factors and work contexts (P < .001) and nursing functions in patient care areas with COVID-19 (P = .005). The environments of professional nursing practice in the hospital under study are moderately favourable to the quality of care. However, the need to invest in nurses' participation, involvement and professional qualification is clear. Maintenance of a sustainable nursing workforce requires attention to be given to ensuring that practice environments are conducive to the quality of care and geared to promoting professional involvement and job satisfaction among nurses.


Improving providers' survival estimates and selection of prognosis- and guidelines-appropriate treatment for patients with symptomatic bone metastases: Development of the Bone Metastases Ensemble Trees for Survival Decision Support Platform.
In the management of symptomatic bone metastases, current practice guidelines do not provide clear methodology for selecting palliative radiotherapy (RT) regimens based on specific patient and disease features. Decision support aids may offer an effective means for translating the complex data needed to render individualised treatment decisions, yet no such tools are available for use in this setting. Thus, we describe the development of the Bone Metastases Ensemble Trees for Survival-Decision Support Platform (BMETS-DSP), which aims to optimise selection of evidence-based, individualised palliative RT regimens. The Ottawa Decision Support Framework was used as the theoretical basis for development of BMETS-DSP. First, we utilised stakeholder input and review of the literature to assess determinants underlying the provider decision. Based on this assessment and iterative stakeholder feedback, we developed the web-based, provider-facing BMETS-DSP. Consistent with the underlying theoretical framework, our design also included assessment of decision quality using the International Patient Decision Aids Standards (IPDAS) certification checklist. Stakeholder input and review of 54 evidence-based publications identified the following determinants of the provider decision: estimated prognosis, characteristics of the target symptomatic lesion and the primary cancer type, consideration of alternative interventions, access to patient-specific recommendations, and patient preferences. Based on these determinants, we developed the BMETS-DSP that (1) collects patient-specific data, (2) displays an individualised predicted survival curve, and (3) provides case-specific, evidence-based recommendations regarding RT, open surgery, systemic therapy, and hospice referral to aid in the decision-making process. The finalised tool met IPDAS quality requirements. Preliminary results of a pilot assessment suggest impact of clinical outcomes. We describe the successful development of a provider-facing decision support platform to aid in the provision of palliative RT in better alignment with patient and disease features. Impact of the BMETS-DSP on decision outcomes will be further assessed in a randomised, controlled study.


Transient Gene Expression in Intact and Organized Rice Tissues.
Regulated gene expression of chimeric genes has been studied extensively in electroporated protoplasts. The applicability of these assays is limited, however, because protoplasts are not always physiologically identical to the cells from which they are derived. We have developed a procedure to electroporate DNA into intact and organized leaf structures of rice. Optimization of the new gene delivery system mainly involved eliminating explant-released nucleases, prolonging the DNA/explant incubation time, and expanding the pulse time. Using a [beta]-glucuronidase gene under the control of constitutive promoters, we demonstrated that all cell types within a leaf base were susceptible to electroporation-mediated DNA uptake. Although the technique was initially developed for leaf bases of young etiolated rice seedlings, we proved that it was equally applicable both to other monocotyledons, including wheat, maize, and barley, and to other explants, such as etiolated and green sheath and lamina tissues from rice. Transient gene expression assays with electroporated leaf bases showed that the promoter from a pea light-harvesting chlorophyll a/b-binding protein gene displayed both light- and chloroplast-dependent expression in rice, and that the promoter from the Arabidopsis S-adenosylmethionine synthetase gene was, as in transgenic Arabidopsis and tobacco, preferentially expressed in cells surrounding the vascular bundles.


Effect of controlled-release Periochip™ on clinical and microbiological parameters in patients of chronic periodontitis.
The aim of the present study was to evaluate and compare the clinical and microbiological effectiveness of Periochip™ as an adjunct to scaling and root planing (SRP) with SRP alone in patients with chronic periodontitis. This randomized, split mouth, 3-month clinical and microbiological trial included 30 sites in 15 patients aged 30-50 years diagnosed with chronic periodontitis. In each patient, two bilateral pockets probing 5-7 mm were randomly assigned to test and control groups. The test group received SRP plus Periochip™, whereas the control group received SRP alone. Clinical indices and anaerobic culture analysis was done at baseline, 1 month, and 3 months interval. Total bacterial count and analysis of four major periodontopathogenic bacteria Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Fusobacterium nucleatum (Fn) was done. Significant improvement was obtained in all clinical variables in the test group as compared to the control group over the study period. Total colony counts were significantly reduced in the test group as compared to control over the period of time. At baseline Aa was recovered from 4 test group sites and 5 control group sites, Pg from 15 test group and 14 control group sites, Pi from 5 test group and 2 control group sites, Fn from 7 test and 7 control group sites. At 3 months, Aa was recovered from 1 test group and 4 control group sites, Pg from 4 test group and 8 control group sites, Pi from 1 test group and 1 control group site, Fn from 3 test and 4 control group sites. Periochip™ placement as an adjunct to SRP, showed promising results, when compared to SRP alone. Healthy microflora can be maintained for a longer period of time and delay in the repopulation by periodontopathic microorganisms was observed.


Ki-67 protein expression in smokeless tobacco (maras powder)-induced oral mucosal lesions.
ABSTRACT Objective: Many different forms of smokeless tobacco are used in the world. An interesting kind of smokeless tobacco (Maras powder) is used commonly in lieu of cigarettes in Kahramanmaras and its environs, in Turkey. The object of the present study was to investigate the effects of the Maras powder (MP) on oral mucosa and to examine the expression of Ki-67 in oral mucosa samples taken from MP users. Expression patterns for markers of cell proliferation (Ki-67) in oral mucosa of 84 MP users and 30 controls were analyzed by immunohistochemistry. Histologically, acanthosis, hyperorthokeratosis, and parakeratosis were found in all 84 formalin-fixed, paraffin-embedded oral mucosal samples of MP users. The spinous cell layer showed large pale staining epithelial cells with pyknotic nuclei. The subepithelial infiltrate was mild. The epithelium was hyperplastic in 17 cases and dysplastic in 67 cases. The dysplasia was mild in 25 cases, moderate in 35 cases, and severe in seven cases. Immunohistochemical findings revealed that with progression of lesions toward malignancy, there was a significant predilection for a basal-suprabasal staining pattern for Ki-67 antigen as compared with the strictly basal staining pattern seen in normal oral epithelium. Expression of Ki-67 antigen was significantly higher in MP users than in the controls (P < 0.001). Our study has shown that MP may induce epithelial cell proliferation, and that there was a significant positive association of Ki-67 expression and grade of dysplasia in MP users. MP, in contrast to other smokeless tobacco variants, seems to cause mucosal changes, which may transform into oral cancer.


Influence of Anomalous Changes in the Crystal Structure on the Transport Properties of YbNi1-xCuxAl Series of Alloys.
Results of the transport properties of the YbNi1-xCuxAl (x = 0, 0.2, 0.5, 0.8 and 1.0) series of alloys are reported. The previous analysis of X-ray diffraction patterns indicates that all compounds crystallize in the hexagonal ZrNiAl structure with a linear behavior of the unit cell volume as a function of the Cu concentration (x). This is not found in the unit cell parameters, showing a discontinuity between x = 0.5 and 0.8. Such discontinuities affect the behavior of the electrical resistivity, in which the position of the minimum temperature changes from 95 K to 175 K, and a rise in the low temperature slope in the magnetic contribution (with -lnT dependence) from 21 μΩcm to 212 μΩcm is observed. In addition, the electronic coefficient of the specific heat increases almost twofold from 125 mJ/mol·K2 (x = 0.5) to 246 mJ/mol·K2 (x = 0.8). These changes are attributed to the variation of the distance between Yb and transition metals (Ni and Cu) along the series and the different electronic properties of the transition metals (Ni and Cu).


Cystamine and Disulfiram Inhibit Human Transglutaminase 2 via an Oxidative Mechanism.
The catalytic activity of transglutaminase 2 (TG2), a ubiquitously expressed mammalian enzyme, is regulated by multiple post-translational mechanisms. Because elevated activity of TG2 in the extracellular matrix is associated with organ-specific diseases such as celiac disease and renal fibrosis, there is growing therapeutic interest in inhibitors of this enzyme. Cystamine, a symmetric disulfide compound, is one of the earliest reported TG2 inhibitors. Despite its widespread use as a tool compound to block TG2 activity in vitro and in vivo, its mechanism of action has remained unclear. Here, we demonstrate that cystamine irreversibly inhibits human TG2 ( kinh/ Ki = 1.2 mM-1 min-1) via a mechanism fundamentally distinct from those proposed previously. Through mass spectrometric disulfide mapping and site-directed mutagenesis, we show that cystamine promotes the formation of a physiologically relevant disulfide bond between Cys370 and Cys371 that allosterically abrogates the catalytic activity of human TG2. This discovery led us to evaluate clinically useful thiol → disulfide oxidants for TG2 inhibitory activity. It is demonstrated that disulfiram, a relatively safe oral thiuram disulfide, is a fairly potent TG2 inhibitor ( kinh/ Ki = 8.3 mM-1 min-1) and may therefore provide a practical tool for clinically validating this emerging therapeutic target in intestinal disorders such as celiac disease.


Real-time monitoring of the setting reaction of brushite-forming cement using isothermal differential scanning calorimetry.
The setting behavior of a brushite-forming cement (beta-tricalcium phosphate/mono calcium monophosphate) was investigated using an indentation technique (the Gillmore needles method) and isothermal differential scanning calorimetry (DSC). The two objectives of the study were to investigate whether DSC could be used to real-time monitor a fast-setting calcium phosphate cement (CPC) and to determine if it is possible to correlate DSC results directly with conventional setting-time measurements. Best-fit linear correlation analysis revealed that both the initial and final setting time (T(i) and T(f)) measured by indentation were strongly correlated to the maximum heat flow measured with DSC. It seems therefore possible to predict the setting times, usually achieved with user dependent indentation methods, of this specific fast setting CPC on the basis of objective DSC measurements. The drawbacks of DSC, however, are its overall complexity and expense and the fact that only exothermal reactions can be investigated in comparison to the Gillmore needles method, furthermore, it is not possible to monitor the complete reaction as the first 2 or 3 min are lost due to sample preparation and apparatus set up.


Neural correlates of successful costly punishment in the Ultimatum game on a trial-by-trial basis.
Costly punishment describes decisions of an interaction partner to punish an opponent for violating rules of fairness at the expense of personal costs. Here, we extend the interaction process by investigating the impact of a socio-emotional reaction of the opponent in response to the punishment that indicates whether punishment was successful or not. In a modified Ultimatum game, emotional facial expressions of the proposer in response to the decision of the responder served as feedback stimuli. We found that both honored reward following acceptance of an offer (smiling compared to neutral facial expression) and successful punishment (sad compared to neutral facial expression) elicited a reward positivity, indicating that punishment was the intended outcome. By comparing the pattern of results with a probabilistic learning task, we show that the reward positivity on sad facial expressions was specific for the context of costly punishment. Additionally, acceptance rates on a trial-by-trial basis were altered according to P3 amplitudes in response to the emotional facial reaction of the proposer. Our results are in line with the concept of costly punishment as an intentional act following norm-violating behavior. Socio-emotional stimuli have an important influence on the perception and behavior in economic bargaining.


Combined use of Kirschner wires and hinged external fixator for capitellar and trochlear fractures: a minimum 24-month follow-up.
Open reduction and internal fixation is the adequate treatment for capitellar and trochlear fractures. Given the low incidence of this type of fractures, it is difficult to constitute a universally accepted method for fixation. Thus, we hypothesised that combined use of Kirschner wires (K-wires), absorbable rods and sutures for fixation and post-operative hinged external fixator for early rehabilitation exercise can restore elbow joint function well. This retrospective study included 20 patients with a mean age of 48.3 (range 16-76) years. According to the Dubberley classification, fractures were classified on plain radiographs, computed tomography images and intra-operative findings. All patients were evaluated by the range of motion of the elbow and the Broberg-Morrey score. All fractures had healed without non-union, and the average time was 13.6 (range 8-17) weeks. The mean follow-up was 42.5 (range 24-80) months. The mean flexion was 117.1° (range 90°-135°), and the mean extension was 17.5° (range 0°-45°). The mean pronation was 74.4° (range 45°-85°), and the mean supination was 84.3° (range 60°-90°). The average Broberg-Morrey score was 86.2 (range 68-98) points with 10 excellent, 7 good and 3 fair results. K-wires, absorbable rods and sutures combined with hinged external fixator are feasible for fixation of capitellar and trochlear fractures. However, due to the absence of a control group (such as Herbert screw fixation), comparative studies are still needed to demonstrate the safety and reliability of K-wires for fixation.


Leaner, Healthier, Happier Together--A Family-Centred Approach to Weight Loss with the Overweight Dog and Her Caregivers.
Obesity represents a one of the most significant healthcare issues facing human and companion animal populations worldwide. A complex relationship commonly exists between owners and their companion animal, particularly around feeding behaviour. Obese companion animals commonly live alongside caregivers who are also struggling with their own body weight. This case report highlights the importance of a family-centred approach to canine obesity as a way to engage with the pet's caregivers to help maximize their compliance towards the successful implementation of a tailored weight loss programme. Lara, an overweight dog weighing 35 kilos with a body condition score (BCS) of 7-7.5/9, was referred for a nutritional assessment. A comprehensive, pro-active and multidisciplinary protocol, tailored towards a family-centred approach, was established. After a 16-week programme, Lara reached the target body weight. The caregivers' compliance was assessed as being excellent; they also reassessed their individual lifestyle and were able to increase awareness towards their own nutritional issues and body weight perception, resulting in weight loss in all caregivers. Lara's case report represents how a family-centred approach can lead to successful patient weight loss and to a modification in the caregivers' way of thinking about nutrition and their own lifestyle, with the final goal of living a healthier and longer life together.


Gold nanoparticles decorated by amphiphilic block copolymer as efficient system for drug delivery.
A drug delivery system based on gold nanoparticles (Au NPs) stabilized by an thiol-functionalized amphiphilic diblock copolymer was developed. The copolymer, poly(ethylene glycol)-b-poly(n-butyl acrylate) (MPEG-b-PBA), was synthesized by Reversible Addition-Fragmentation Transfer (RAFT) polymerization and the thiocarbonylthio group at the end of the hydrophobic block PBA was further reduced to thiol group. Pyrene, used as a model molecule for the hydrophobic drugs, was loaded in the hydrophobic interior of the shell around Au NPs by physical entrapment. The analysis performed by UV-Vis spectrophotometer show that the obtained Au NPs-pyrene nanocomposites have good stability in the aqueous solution and high drug loading capacity in comparison with Au NPs decorated with small molecular ligands. In addition, both their loading capacity and release behavior were found closely related to the chain length of hydrophobic block. In conclusion, we report here a versatile and simple procedure to fabricate Au NP-polymer hybrids that is applicable to various amphiphilic copolymers synthesized by RAFT polymerization and useful to produce efficient Au NP based drug carriers.


Human-Computer Interaction-Oriented African Literature and African Philosophy Appreciation.
African literature has played a major role in changing and shaping perceptions about African people and their way of life for the longest time. Unlike western cultures that are associated with advanced forms of writing, African literature is oral in nature, meaning it has to be recited and even performed. Although Africa has an old tribal culture, African philosophy is a new and strange idea among us. Although the problem of "universality" of African philosophy actually refers to the question of whether Africa has heckling of philosophy in the Western sense, obviously, the philosophy bred by Africa's native culture must be acknowledged. Therefore, the human-computer interaction-oriented (HCI-oriented) method is proposed to appreciate African literature and African philosophy. To begin with, a physical object of tablet-aid is designed, and a depth camera is used to track the user's hand and tablet-aid and then map them to the virtual scene, respectively. Then, a tactile redirection method is proposed to meet the user's requirement of tactile consistency in head-mounted display virtual reality environment. Finally, electroencephalogram (EEG) emotion recognition, based on multiscale convolution kernel convolutional neural networks, is proposed to appreciate the reflection of African philosophy in African literature. The experimental results show that the proposed method has a strong immersion and a good interactive experience in navigation, selection, and manipulation. The proposed HCI method is not only easy to use, but also improves the interaction efficiency and accuracy during appreciation. In addition, the simulation of EEG emotion recognition reveals that the accuracy of emotion classification in 33-channel is 90.63%, almost close to the accuracy of the whole channel, and the proposed algorithm outperforms three baselines with respect to classification accuracy.


[Surgical treatment of the primary cardiac rhabdomyoma in the neonate--a case report].
A successful surgical treatment of intracardiac rhabdomyoma in a 12-day-old female is reported. The neonate was first noted to have a cardiac murmur and she was diagnosed cardiac tumor by two dimensional echocardiography. It showed multiple cardiac tumors which occupied the right ventricular outflow tract and interventricular septum. Under the routine cardiopulmonary bypass the tumor of the right ventricular outflow tract was removed. Histological examination revealed a rhabdomyoma. Follow-up evaluation 7 years after operation showed normal growth and development of the patient. A repeated two dimensional echocardiogram revealed no sign of recurrence and the left ventricular cavity was not obstructed by the residual tumor in the interventricular septum. We reviewed 10 cases treated surgically in infancy including three neonate in Japan.


Deprescribing Guidelines: Value of an Interactive Mobile Application.
We developed a new channel on a mobile app as a continuing education tool to augment the use of deprescribing guideline content in clinical practice. In this research brief, we describe the reach and adoption of channel content, as well as user feedback. Using Google Analytics, we counted page views of the website (deprescribing.org) where the app was promoted. We calculated total app downloads, monthly active users, and guideline-specific page views. Users were invited to complete the embedded Information Assessment Method (IAM) Questionnaire to obtain feedback on the value of information presented on the Deprescribing Channel. Between March 2, 2019 and November 30, 2019, we documented 9,454 page views of the promotional web page across 40 countries. The Deprescribing Channel was downloaded 3,256 times with an average of 464 monthly users. In total, the guidelines on this channel were accessed 14,377 times with 49,721 views across all guideline pages. Thirty-seven IAM questionnaires were completed. Thirty-two responses indicated this deprescribing information was relevant for at least one of their patients. Regarding educational outcomes, 22 responses were of learning something new and/or being motivated to learn more. We documented international interest in a mobile app providing continuing education on deprescribing. App users generated sustained page views over the study period. Feedback from a small number of users was positive with the majority finding the content relevant, educational, and applicable to patient care. Further work is needed to improve the usability of the embedded feedback questionnaire and to evaluate its value in supporting learning.