A motion phantom study on helical tomotherapy: the dosimetric impacts of delivery technique and motion.
Helical tomotherapy (HT) can potentially be used for lung cancer treatment including stereotactic radiosurgery because of its advanced image guidance and its ability to deliver highly conformal dose distributions. However, previous theoretical and simulation studies reported that the effect of respiratory motion on statically planned tomotherapy treatments may cause substantial differences between the calculated and actual delivered radiation isodose distribution, particularly when the treatment is hypofractionated. In order to determine the dosimetric effects of motion upon actual HT treatment delivery, phantom film dosimetry measurements were performed under static and moving conditions using a clinical HT treatment unit. The motion phantom system was constructed using a programmable motor, a base, a moving platform and a life size lung heterogeneity phantom with wood inserts representing lung tissue with a 3.0 cm diameter spherical tumour density equivalent insert. In order to determine the effects of different motion and tomotherapy delivery parameters, treatment plans were created using jaw sizes of 1.04 cm and 2.47 cm, with incremental gantry rotation periods between the minimum allowed (10 s) and the maximum allowed (60 s). The couch speed varied from 0.009 cm s(-1) to 0.049 cm s(-1), and delivered to a phantom under static and dynamic conditions with peak-to-peak motion amplitudes of 1.2 cm and 2 cm and periods of 3 and 5 s to simulate human respiratory motion of lung tumours. A cylindrical clinical target volume (CTV) was contoured to tightly enclose the tumour insert. 2.0 Gy was prescribed to 95% of the CTV. Two-dimensional dose was measured by a Kodak EDR2 film. Dynamic phantom doses were then quantitatively compared to static phantom doses in terms of axial dose profiles, cumulative dose volume histograms (DVH), percentage of CTV receiving the prescription dose and the minimum dose received by 95% of the CTV. The larger motion amplitude resulted in more under-dosing at the ends of the CTV in the axis of motion, and this effect was greater for the smaller jaw size plans. Due to the size of the penumbra, the 2.47 cm jaw plans provide adequate coverage for smaller amplitudes of motion, +/-0.6 cm in our experiment, without adding any additional margin in the axis of motion to the treatment volume. The periodic heterogeneous patterns described by previous studies were not observed from the single fraction of the phantom measurement. Besides the jaw sizes, CTV dose coverage is not significantly dependent on machine and phantom motion periods. The lack of adverse synchronization patterns from both results validate that HT is a safe technique for treating moving target and hypofractionation.


Instant, multiscale dry transfer printing by atomic diffusion control at heterogeneous interfaces.
Transfer printing is a technique that integrates heterogeneous materials by readily retrieving functional elements from a grown substrate and subsequently printing them onto a specific target site. These strategies are broadly exploited to construct heterogeneously integrated electronic devices. A typical wet transfer printing method exhibits limitations related to unwanted displacement and shape distortion of the device due to uncontrollable fluid movement and slow chemical diffusion. In this study, a dry transfer printing technique that allows reliable and instant release of devices by exploiting the thermal expansion mismatch between adjacent materials is demonstrated, and computational studies are conducted to investigate the fundamental mechanisms of the dry transfer printing process. Extensive exemplary demonstrations of multiscale, sequential wet-dry, circuit-level, and biological topography-based transfer printing demonstrate the potential of this technique for many other emerging applications in modern electronics that have not been achieved through conventional wet transfer printing over the past few decades.


Cloning and identification of genes that associate with mammalian replicative senescence.
Cellular senescence and limited proliferative capacity of normal diploid cells has a dominant phenotype over immortality of cancerous cells, suggesting its regulation by the expression of a set of genes. In order to isolate the genes that associate with senescence, we have employed a clonal system of conditional SV40 T antigen rat embryo fibroblast cell lines which undergo senescence upon T antigen inactivation. Construction of cDNA libraries from two conditional cell lines and application of differential screening and subtractive hybridization techniques have resulted in the cloning of eight senescence-induced genes (SGP-2/Apo J, alpha 1-procollagen, osteonectin, fibronectin, SM22, cytochrome C oxidase, GTP-alpha, and a novel gene) and a senescence-repressed gene (FRS-2). Three of these genes encode for extracellular matrix proteins, others are involved in the calcium-dependent signal transduction pathways, while the SGP-2/Apo J gene may have a cellular protective function. RNA analysis has shown that the senescence-associated genes are overexpressed in both normal rat embryonic fibroblasts and human osteoblasts cell cultures undergoing aging in vitro. In comparison, the expression of these genes in a rat fibroblast immortalized cell line (208F cells) was down-regulated after both its partial and its full transformation by ras oncogenes. Thus, cloning of senescence-associated genes opens up new ways to elucidate and/or to modulate aging and cancer.


Single-Particle Catalytic Analysis by a Photon Burst Counting Technique Combined with a Microfluidic Chip.
Single-particle catalytic analysis plays an important role to understand the catalytic mechanism of nanocatalysts. Currently, some methods are used to study the relationship between single-particle catalytic activity and morphology. However, there is still lack of a simple and rapid analysis method for evaluating the catalytic activity of an individual nanocatalyst that freely moves in solution. Here, we proposed a novel single-particle catalytic analysis method for investigating the catalytic activity of a free nanocatalyst. Its working principle is based on the photon burst counting analysis on fluorescent catalytic products of an individual nanocatalyst combined with a microfluidic chip. In this study, we used the reduction reaction of resazurin (RZ) to resorufin (RF) catalyzed by gold nanoparticles (GNPs) as a model. When nonfluorescent RZ molecules in one microchannel of the microfluidic chip mixed with the GNPs flowing in another channel under the control of flow rates, each individual photon burst from the catalytic product RF by GNPs was measured in real time with a constructed flow single-particle catalytic analysis (SPCA) system. With the method, the obtained intensity of each photon burst reflects the capacity of a particle to catalyze RZ molecules into RF(s). The number of photon burst within sampling time reflects the particle number of GNPs with catalytic activity. The experimental conditions including the mixing mode of the nanocatalyst and the substrate, the flow rate, RZ concentration, and detection time were optimized. Finally, the method was successfully used to study the catalytic activity of GNPs with different sizes and morphologies.


Recent Progress in Single-Crystalline Perovskite Research Including Crystal Preparation, Property Evaluation, and Applications.
Organic-inorganic lead halide perovskites are promising optoelectronic materials resulting from their significant light absorption properties and unique long carrier dynamics, such as a long carrier lifetime, carrier diffusion length, and high carrier mobility. These advantageous properties have allowed for the utilization of lead halide perovskite materials in solar cells, LEDs, photodetectors, lasers, etc. To further explore their potential, intrinsic properties should be thoroughly investigated. Single crystals with few defects are the best candidates to disclose a variety of interesting and important properties of these materials, ultimately, showing the increased importance of single-crystalline perovskite research. In this review, recent progress on the crystallization, investigation, and primary device applications of single-crystalline perovskites are summarized and analyzed. Further improvements in device design and preparation are also discussed.


Detection of 123 bp fragment of insertion element IS6110 Mycobacterium tuberculosis for diagnosis of extrapulmonary tuberculosis.
Extrapulmonary tuberculosis (EPTB) is emerging problem in developing and developed countries. The diagnosis of EPTB in its different clinical presentations remains a true challenge. IS6110-based polymerase chain reaction (PCR) is used for rapid identification and positivity rate of the Mycobacterium tuberculosis complex in clinical isolates of different sites of EPTB. The present study was carried out to study the prevalence of M. tuberculosis complex in clinical isolates of EPTB at tertiary care centres in Lucknow. Seven hundred fifty-six specimens were collected from the suspected cases of EPTB which were processed for Mycobacteria by Ziehl Neelson (ZN) staining and BACTEC culture. All the specimens were also processed for IS6110-based PCR amplification with primers targeting 123 bp fragment of insertion element IS6110 of the M. tuberculosis complex. Of these 756 specimens, 71(9.3%) were positive for acid fast bacilli (AFB) by ZN staining, 227(30.1%) were positive for mycobacteria by BACTEC culture and IS6110 PCR were positive for M. tuberculosis complex in 165 (20.7%) isolates. We found a significant difference in sensitivities of different tests (P<0.05). This study reveals the positivity of M. tuberculosis complex in clinical isolates of EPTB case in tertiary care hospitals in Northern India. 72.7% of M. tuberculosis complex was confirmed by IS6110-PCR in culture isolates from different sites of EPTB. The high prevalence of the M. tuberculosis complex was seen in lymph node aspirate and synovial fluid. However, utility of PCR may play a potentially significant role in strengthening the diagnosis of EPTB especially targeting IS6110.


Spectral components of bioluminescence of aequorin and obelin.
Complex bioluminescence spectra of photoproteins from marine coelenterates - jellyfish Aequorea victoria and hydroid Obelia longissima, and photoluminescence spectra of the bioluminescent reaction products (Ca(2+)-discharged photoproteins) were deconvolved into components. The bioluminescence spectra of aequorin were found to include three, the bioluminescence spectra of obelin - four, and the photoluminescence spectra of the Ca(2+)-discharged photoproteins - only two components. The spectral components were assigned to one unionized and three ionized forms of coelenteramide. The changes in acidity of the excited coelenteramide molecule are discussed. The differences in bioluminescence and photoluminescence spectra are considered, with protonic environment of coelenteramide taken into account.


Direct and correlated responses to divergent selection for serum cholesterol concentration on day 56 in swine.
Divergent selection for serum cholesterol concentration on d 56 was practiced in a four-breed, composite population for three generations. High and Low lines, representing high and low levels of serum cholesterol, respectively, were each maintained with approximately 10 males and 25 females per generation. Pigs from a contemporary Control line were evaluated only in the last generation. In the last generation, mean serum cholesterol concentration was significantly different among lines (107.1, 85.6, and 65.5 mg/dL for High, Control, and Low lines, respectively). Realized heritability was .31, .33, and .31 for high, low, and divergent selection (SE = .03), respectively. Terminal evaluation indicated that average birth and weaning (28 d of age) weight was lower (P < .05) for Low pigs (1.25 and 6.25 kg, respectively) than for High pigs (1.43 and 7.10 kg, respectively) and was intermediate for Control pigs (1.34 and 6.53 kg, respectively). At 56 d of age, High (15.1 kg) and Control (13.5 kg) pigs were heavier (P < .05) than Low pigs (11.9 kg). However, pigs sampled after 56 d did not differ (P > .05) in average daily gain, 164-d weight, feed consumption, or feed efficiency. Serum cholesterol concentration at 165 d of age was significantly different among lines (110.1, 98.5, and 85.6 mg/dL for High, Control, and Low pigs, respectively), although differences were smaller than at 56 d of age. When slaughtered at approximately 106 kg (188 to 195 d of age), Low pigs had significantly shorter carcasses than High and Control pigs (77.5 vs 78.7 and 78.9 cm, respectively). Low pigs had significantly more fat at the first rib (5.70 vs 5.28 cm) than High pigs. Lines did not differ significantly for fat thickness at the last rib, last lumbar vertebrae or 10th rib, or for longissimus muscle area. At 60 d of gestation, ovulation rate, measured as number of corpora lutea, was lower (P < .05) for High (9.84 eggs) than for Low (11.79 eggs) or Control (11.17 eggs) gilts. Differences in ovulation rate were reflected in smaller but nonsignificant differences in number of fetuses (7.97, 9.00, and 8.55 fetuses for High, Low, and Control, respectively).


Synthetic amphipathic helical peptides that mimic apolipoprotein A-I in clearing cellular cholesterol.
Clearance of excess cholesterol from cells by HDL is facilitated by the interaction of HDL apolipoproteins with cell-surface binding sites or receptors, a process that may be important in preventing atherosclerosis. In this study, synthetic peptides containing 18-mer amphipathic helices of the class found in HDL apolipoproteins (class A) were tested for their abilities to remove cholesterol and phospholipid from cultured sterol-laden fibroblasts and macrophages and to interact with cell-surface HDL binding sites. Lipid-free peptides containing two identical tandem repeats of class A amphipathic helices promoted cholesterol and phospholipid efflux from cells and depleted cellular cholesterol accessible for esterification by acyl CoA/cholesterol acyltransferase, similar to what was observed for purified apolipoprotein A-I. Peptide-mediated removal of plasma membrane cholesterol and depletion of acyl CoA/cholesterol acyltransferase-accessible cholesterol appeared to occur by separate mechanisms, as the latter process was less dependent on extracellular phospholipid. The dimeric amphipathic helical peptides also competed for high-affinity HDL binding sites on cholesterol-loaded fibroblasts and displayed saturable high-affinity binding to the cell surface. In contrast, peptides with a single helix had little or no ability to remove cellular cholesterol and phospholipid, or to interact with HDL binding sites, suggesting that cooperativity between two or more helical repeats is required for these activities. Thus, synthetic peptides comprising dimers of a structural motif common to exchangeable apolipoproteins can mimic apolipoprotein A-I in both binding to putative cell-surface receptors and clearing cholesterol from cells.


Purification and Characterization of Novel Antioxidative Peptides From Duck Liver Protein Hydrolysate as Well as Their Cytoprotection Against Oxidative Stress in HepG2 Cells.
This study aimed at mining antioxidant peptides derived from duck liver as a strategy for valorizing poultry byproducts utilization via the isolation and characterization of peptide molecules with great antioxidant potential and cytoprotective effects against hydrogen peroxide-induced oxidative stress. Six novel peptides, including GEHGDSSVPVWSGVN, HLDYYLGK, HLTPWIGK, DTYIRQPW, WDDMEKIWHH, and MYPGIAD were isolated and purified by Sephadex G-15 and reverse-phase high-performance liquid chromatography, followed by the identification with liquid chromatography-tandem mass spectrometry. Among the hydrolysates from different enzymes, the alcalase-originated peptides presented the strongest antioxidant capacity as revealed by DPPH and ABTS assays. The synthesized peptides were used to validate the antioxidant activities, identifying that DTYIRQPW and WDDMEKIWHH were the major antioxidative peptides capable of protecting HepG2 cells from H2O2-induced oxidative damage via stimulating antioxidant enzymes such as superoxide dismutase and catalase to eliminate free radicals and to decrease lipid peroxidation products. Molecular docking suggested that the antioxidative properties of the isolated peptides were related to the site and number of hydrogen bonds. This investigation indicated the great potential of duck liver protein hydrolysates as a base material for producing and developing dietary bioactive peptides.


Surface plasmon resonance tuning of silver nanoparticle array produced by nanosphere lithography through ion etching and thermal annealing.
It was demonstrated that size of the Ag nanoparticles array fabricated by nanosphere lithography (NSL) can be changed as needed by reactive ion etching (RIE) of the self-assembled polystyrene (PS) nanosphere template and post-annealing of the Ag particle array. A macroscopic 2D array of ordered Ag nanoparticles stretching over an area greater than 1 cm2 was achieved using a modified nanosphere lithography method. The wavelength corresponding to the extinction maximum of the surface plasmon resonance (SPR) from the Ag nanoparticle array was systematically tuned by RIE of the PS template. Additional tuning of SPR was achieved by post-annealing the Ag nanoparticles which induced shape-changes in the Ag nanoparticles. We demonstrated that SPR can be tuned over the entire visible spectrum by RIE of the PS mask and thermal annealing, which can be potentially used to display localized SPR spectrum (hence, different color) throughout the visible range.


Acid Catalysis with Alkane/Water Microdroplets in Ionic Liquids.
Ionic liquids are composed of an organic cation and a highly delocalized perfluorinated anion, which remain tight to each other and neutral across the extended liquid framework. Here we show that n-alkanes in millimolar amounts enable a sufficient ion charge separation to release the innate acidity of the ionic liquid and catalyze the industrially relevant alkylation of phenol, after generating homogeneous, self-stabilized, and surfactant-free microdroplets (1-5 μm). This extremely mild and simple protocol circumvents any external additive or potential ionic liquid degradation and can be extended to water, which spontaneously generates microdroplets (ca. 3 μm) and catalyzes Brönsted rather than Lewis acid reactions. These results open new avenues not only in the use of ionic liquids as acid catalysts/solvents but also in the preparation of surfactant-free, well-defined ionic liquid microemulsions.


Can timing of tracheal extubation predict improved outcomes after cardiac surgery?
Early tracheal extubation is a common goal after cardiac surgery. Our study aims to examine whether timing of tracheal extubation predicts improved postoperative outcomes and late survival after cardiac surgery. We also evaluated the optimal timing of extubation and its association with better postoperative outcomes. Between 2002 and 2006, 1164 patients underwent early tracheal extubation (<6 hours after surgery) and 1571 had conventional extubation (>6 hours after surgery). Propensity score adjustment and multivariable logistic regression analysis were used to adjust for imbalances in the patients' preoperative characteristics. Receiver operating characteristic curves (ROC) were used to identify the best timing of extubation and improved postoperative outcomes. Cox regression analysis was used to identify whether early extubation is a risk factor for decreased late mortality. Results - Early extubation was associated with lower propensity score-adjusted rate of operative mortality (Odds Ratio =0.55, 95% Confidence Intervals =0.31-0.98, p=0.043). Extubation within 9 hours emerged as the best predictor of improved postoperative morbidity and mortality (sensitivity =85.5%, specificity =52.7%, accuracy =64.5%). Early extubation also predicted decreased late mortality (Hazard Ratio =0.45, 95% Confidence Intervals 0.31-0.67, p<0.001). Early extubation may predict improved outcomes after cardiac surgery. Extubation within 9 hours after surgery was the best predictor of uncomplicated recovery after cardiac surgery. Those patients intubated longer than 16 hours have a poorer postoperative prognosis. Early extubation predicts prolonged survival up to 16 months after surgery.


Toxic Ipomeamarone accumulation in healthy parts of Sweetpotato (Ipomoea batatas L. Lam) storage roots upon infection by Rhizopus stolonifer.
Furanoterpenoid accumulation in response to microbial attack in rotting sweetpotatoes has long been linked to deaths and lung edema of cattle in the world. However, it is not known whether furanoterpenoid ipomeamarone accumulates in the healthy-looking parts of infected sweetpotato storage roots. This is critical for effective utilization as animal feed and assessment of the potential negative impact on human health. Therefore, we first identified the fungus from infected sweetpotatoes as a Rhizopus stolonifer strain and then used it to infect healthy sweetpotato storage roots for characterization of furanoterpenoid content. Ipomeamarone and its precursor, dehydroipomeamarone, were identified through spectroscopic analyses, and detected in all samples and controls at varying concentrations. Ipomeamarone concentration was at toxic levels in healthy-looking parts of some samples. Our study provides fundamental information on furanoterpenoids in relation to high levels reported that could subsequently affect cattle on consumption and high ipomeamarone levels in healthy-looking parts.


Sheng Zhu.
"In five years, I hope to be an experienced researcher studying the nanoconfinement effect in material synthesis, structure modulation, and emerging properties… My motto is: 'Diligence redeems stupidity.' " Find out more about Sheng Zhu in his Introducing… Profile.


Autoregulation of bacteriophage P2 repressor.
The immunity repressor of bacteriophage P2 regulates the two convergent promoters, Pe and Pc, located in the early control region. Pe is the early promoter which is negatively regulated by the repressor. It was found, by DNase I protection studies, that the P2 repressor enhances the binding of RNA polymerase to Pc. Furthermore, under in vivo conditions the transcription initiated at Pc, measured as chloramphenicol acetyl transferase gene expression, is low in the absence of repressor but is stimulated by low repressor levels. With increasing repressor concentrations transcription from the Pc promoter decreases. Thus, the P2 repressor both negatively and positively regulates its own promoter.


Newly Emerging Drugs of Abuse and Their Detection Methods: An ACLPS Critical Review.
Illicit drug abuse has reached an epidemic level in the United States. Drug overdose has become the leading cause of injury-related deaths since 2008 due to the recent surge of opioid overdose by heroin, controlled prescription drugs, and nonmethadone synthetic opioids. Synthetic designer drugs such as synthetic cathinones ("bath salts") and synthetic cannabinoids ("Spice" and "K2") continue to emerge and attract recreational users. The emergence of new drugs of abuse poses a steep challenge for clinical toxicology laboratories. Limited information about the emerging drugs and their metabolism, "rebranding" of the illicit drugs, and a lack of Food and Drug Administration-approved screening methods for these drugs contribute to this difficulty. Here we review detection methods that can aid in identifying emerging drugs of abuse. One promising approach is the utilization of untargeted drug screening by mass spectrometry. Historically, gas chromatography-mass spectrometry has been the gold standard. Liquid chromatography-tandem mass spectrometry and liquid chromatography-high-resolution mass spectrometry offer improved detection capability of new drugs with simplified sample preparation, making it the new standard.


Technical recommendations for artificial insemination in sheep.
Artificial insemination (AI) was the first important biotechnology applied to improve the genetics of farm animals. It allows the rapid and massive diffusion of desirable characteristics of males with high productive potential. We describe the different types of estrus induction and synchronization techniques and the use of the AI with fresh, chilled or frozen semen. Through the adequacy of the protocols of estrus synchronization and AI to the different production systems, the efficient use of reproductive techniques is possible, reaching acceptable pregnancy rates. Summary of reproductive results obtained using cervical and laparoscopic AI are presented.


Allosteric activation of metabotropic glutamate receptor 5.
Metabotropic glutamate receptor 5 (mGluR5) is a class C G protein-coupled receptor (GPCR) with both an extracellular ligand binding site and an allosteric intrahelical chamber located similarly to the orthosteric ligand binding site of Class A GPCRs. Ligands binding to this ancestral site of mGluR5 can act as positive (PAM), negative (NAM) or silent (SAM) allosteric modulators, and their medicinal chemistry optimization is notoriously difficult, as subtle structural changes may cause significant variation in activity and switch in the functional response. Here we present all atom molecular dynamics simulations of NAM, SAM and PAM complexes formed by closely related ligands and analyse the structural differences of the complexes. Several residues involved in the activation are identified and the formation of a continuous water channel in the active complex but not in the inactive ones is recognized. Our results suggest that the mechanism of mGluR5 activation is similar to that of class A GPCRs.Communicated by Ramaswamy H. Sarma.


Charge Compensation Modulation of the Thermoelectric Properties in AgSbTe2 via Mn Amphoteric Doping.
In thermoelectric research, the introduction of a dopant can suppress lattice thermal conductivity (κ1) through phonon scattering and optimize the power factor (PF) by changing the behavior of carriers, which are the key prerequisites for high thermoelectric performance. However, the electrical thermal conductivity (κe) can also increase with the increase of electrical conductivity (σ), which may override the optimization in PF and be detrimental to the improvement of final ZT. In this work, we highlight an amphoteric doping method by using Mn atoms to substitute both Ag and Sb atoms in AgSbTe2. The MnSb positive doping in p-type AgSbTe2 can improve the σ through increasing the hole concentration while maintaining a relative high Seebeck coefficient (S), thus substantially improving the PF. On the other hand, the MnAg negative doping can introduce electrons into the matrix, which will recombine with the major hole carriers and lead to a decrease of σ to suppress exorbitant κe induced by the MnSb doping. The combination of the both functions by Mn amphoteric doping can further improve the thermoelectric property through charge compensation modulation. By virtue of amphoteric doping, though σ is decreased, PF is further optimized because of increased S, while the total thermal conductivity (κtotal) is further decreased due to suppressed κe and additional phonon scattering, which are beneficial for the improvement of the final ZT value. As a result, 5 mol % MnAg-MnSb amphoteric doping AgSbTe2 sample achieves a maximum ZT value of ∼0.74 at 550 K, which is higher than that of the pristine sample and other Mn monodoped counterparts. The present work suggests charge compensation modulation via amphoteric doping as an effective avenue to simultaneously achieve low thermal conductivity and high power factor for better thermoelectric performance.


Continuous Improvements of a Clinical Pathway Increased Its Feasibility and Improved Care Providers' Perception in TKA.
We aimed to determine 1) whether dropout rate decreased and 2) whether health care providers' perceptions were changed with continued improvements of contents of clinical pathway (CP) for total knee arthroplasty (TKA). This retrospective study included two separate analyses of patients and health care providers. In the analysis of patients, dropout rates and reasons were evaluated in two cohorts of patients who underwent TKA with CP applied at two different time periods (384 patients from 2009 to 2010 and 242 patients from 2012 to 2013). Contents of CP were continuously improved during the 3-year interval. Self-administered questionnaire surveys targeted to health care providers were carried out twice (2010 and 2013) and compared. Dropout rate decreased from 19.1% in the first time period to 10.4% in the second time period. Although overall satisfaction of care providers was high at both time-points, doctors had more favorable perceptions than nurses; most positive changes of perception were noted in nurses. The health care providers' perceptions for potential concerns of CP were improved while the perceptions for potential benefits and satisfaction were maintained. Continuously improved CP has increased feasibility for TKA patients and reduced health care providers' concern about its value. We propose that CP can be implemented and actively used to improve the outcomes and efficacy of patient care for TKA, regardless of the rotation of care providers.


Effect of modified alkaline supplementation on bone metabolic turnover in rats.
This study aims to determine the effects of a high protein diet and alkaline supplementation on bone metabolic turnover in rats. Eight-week-old male Sprague-Dawley rats were investigated by bone status, including bone mineral density (BMD) and biomechanical markers from blood and urine. Thirty rats were randomly divided into three groups and treated for 8 weeks as follows: baseline control group (n. 10, C), high-protein supplemented diet group (n. 10, chronic acidosis, CA group) and supplemented chronic acidosis (n.10, SCA). Diet-treated rats were fed an acidic high-protein diet and the supplementation consisted in a modified alkaline formula (Basenpulver, NaMed, Italy). At the end of the experimental period, the rats were sacrificed, blood samples were drawn and femur and tibia were removed for analysis of bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA). In the CA group, 24-hour urinary calcium (Ca) and phosphorus (P) excretion were increased 2.1-fold (p<0.05 vs normal diet controls) as well as kidney weight. However, serum Ca and P concentration, as well as urinary Dpd excretion were not significantly changed. Femural and tibial BMD was significantly decreased in the CA group (p<0.05), but alkaline supplementation prevented such phenomenon (p<0.05 vs CA). These results suggest that blood Ca and P concentrations in chronic acidosis condition during the 12-week supplementation might be maintained by hypercalciuria and hyperphosphaturia at the expenses of bone structure. However, modified alkaline supplementation is able to prevent such derangements.


Genetic modifiers of vision and hearing.
The identification of 'disease genes' and the mutations within them has greatly enhanced our understanding of normal function in the eye and ear. At the same time, it has become clear that these single-gene mutations must reside in a permissive genetic background for a disease phenotype to manifest. Segregating background genes can also modify the age of onset, rate of progression or severity of these diseases. These background genes that interact with the disease mutation and that are responsible for the specific phenotypes observed are commonly called genetic modifiers. Identification of these modifier genes may define the biological pathways that lead from the primary genetic defect to the aberrant phenotype. Once the identities of modifier genes that suppress vision or hearing loss become known, the door opens to new potential therapeutic targets, since these modifier genes may be more amenable to treatment than the primary mutant gene.


Haemopoietic tissue in Perinereis cultrifera Grübe: cytological identification and observations after treatment with lead.
A perivascular tissue made up of two different types of cells (one with a slightly basophilic cytoplasm and many Fe+++ ions, the other with haemopigments) has been demonstrated in Perinereis cultrifera Grübe by means of histochemical and cytochemical techniques. These two types of cells probably cooperate in the production of the respiratory pigment. Treatment with lead nitrate (0.02 ppm) for up to a maximum of five days caused a progressive cytological alteration with inhibition of haemoglobin synthesis.


MGRNN: Structure Generation of Molecules Based on Graph Recurrent Neural Networks.
Molecular structure generation is a critical problem for materials science and has attracted growing attention. The problem is challenging since it requires to generate chemically valid molecular structures. Inspired by the recent work in deep generative models, we propose a graph recurrent neural network model for drug molecular structure generation, briefly called MGRNN (Molecular Graph Recurrent Neural Networks). MGRNN combines the advantages of both iterative molecular generation algorithm and the efficiency of the training strategies. Moreover, MGRNN shows: (i) efficient computation for training; (ii) high model robustness for data; and (iii) an iterative sampling process, which allows to use chemical domain expertise for valency checking. Experimental results show that MGRNN is able to generate 69 % chemically valid molecules even without chemical knowledge and 100 % valid molecules with chemical rules.


Involvement of Small RNAs in Phosphorus and Sulfur Sensing, Signaling and Stress: Current Update.
Plants require several essential mineral nutrients for their growth and development. These nutrients are required to maintain physiological processes and structural integrity in plants. The root architecture has evolved to absorb nutrients from soil and transport them to other parts of the plant. Nutrient deficiency affects several physiological and biological processes in plants and leads to reduction in crop productivity and yield. To compensate this adversity, plants have developed adaptive mechanisms to enhance the acquisition, conservation, and mobilization of these nutrients under deficient or adverse conditions. In addition, plants have evolved an intricate nexus of complex signaling cascades, which help in nutrient sensing and uptake as well as to maintain nutrient homeostasis. In recent years, small non-coding RNAs such as micro RNAs (miRNAs) and endogenous small interfering RNAs have emerged as important component in regulating plant stress responses. A set of these small RNAs (sRNAs) have been implicated in regulating various processes involved in nutrient uptake, assimilation, and deficiency. In response to phosphorus (P) and sulphur (S) deficiencies, role of sRNAs, miR395 and miR399, have been identified to be instrumental; however, many more miRNAs might be involved in regulating the plant response to these nutrient stresses. These sRNAs modulate expression of target genes in response to P and S deficiencies and regulate their uptake and utilization for proper growth and development of the plant. This review summarizes the current understanding of uptake, sensing, and signaling of P and S and highlights the regulatory role of sRNAs in adaptive responses to these nutrient stresses in plants.


[Radiofrequency ablation of supraventricular tachycardia].
Most forms of supraventricular tachycardia are based on a reentry-mechanism which is maintained by a specific anatomic substrate (e.g., dual AV-nodal physiology, accessory pathway). Since this substrate is usually a very localized and well defined anatomical abnormality, focal thermocoagulation by radiofrequency energy is highly effective in restoring normal physiology, thereby offering definite cure to a high percentage of these patients. The present article summarizes pathophysiologic mechanisms as well as diagnostic electrophysiologic testing- and ablation-techniques. Clinical success and complications are discussed in the light of current indications for elective radiofrequency ablation of supraventricular tachycardias.


Cholesterol biosynthesis inhibitor RO 48-8071 reduces progesterone receptor expression and inhibits progestin-dependent stem cell-like cell growth in hormone-dependent human breast cancer cells.
Clinical trials and studies have shown that postmenopausal women undergoing combination hormone replacement therapy containing estrogen and progestin have an increased risk of breast cancer compared with women taking estrogen or placebo alone. Using animal models, we have previously shown that synthetic progestins, including medroxyprogesterone acetate (MPA), which is widely used clinically, accelerate breast cancer tumor growth and promote metastasis. Furthermore, we have found that MPA elevates CD44 protein expression and aldehyde dehydrogenase (ALDH) activity, two markers of cancer stem cells (CSCs), and increases mammosphere formation, another hallmark of stem cells, in hormone-dependent T47-D human breast cancer cells. Herein, we show that RO 48-8071 (RO), an inhibitor of cholesterol synthesis, reduced MPA-induced CD44 protein expression in two hormone-dependent human breast cancer cell lines, T47-D and BT-474. Because we have previously shown that MPA induction of CD44 is progesterone receptor (PR) dependent, we examined RO's effects on PR protein and mRNA expressions in T47-D cells. PR mRNA levels remained unchanged after RO treatment; however, RO significantly reduced the protein expression of both PR receptor isoforms, PR-A and PR-B. Using the proteasome inhibitor MG-132, we demonstrated that RO decreases PR protein expression in T47-D cells via the proteasomal degradation pathway. Importantly, treatment of T47-D cells with RO abolished MPA-induced mammosphere formation. Based on our observations, we contend that RO may represent a novel means of preventing MPA-induced CSC expansion. RO could be used clinically to both treat and prevent hormone-dependent breast cancers, which represent the majority of human breast cancers. RO may also have clinical utility in reducing resistance to antihormone therapy.


Classifying protein kinase structures guides use of ligand-selectivity profiles to predict inactive conformations: structure of lck/imatinib complex.
We report a clustering of public human protein kinase structures based on the conformations of two structural elements, the activation segment and the C-helix, revealing three discrete clusters. One cluster includes kinases in catalytically active conformations. Each of the other clusters contains a distinct inactive conformation. Typically, kinases adopt at most one of the inactive conformations in available X-ray structures, implying that one of the conformations is preferred for many kinases. The classification is consistent with selectivity profiles of several well-characterized kinase inhibitors. We show further that inhibitor selectivity profiles guide kinase classification. For example, selective inhibition of lck among src-family kinases by imatinib (Gleevec) suggests that the relative stabilities of inactive conformations of lck are different from other src-family kinases. We report the X-ray structure of the lck/imatinib complex, confirming that the conformation adopted by lck is distinct from other structurally-characterized src-family kinases and instead resembles kinases abl1 and kit in complex with imatinib. Our classification creates new paths for designing small-molecule inhibitors.


Higher fraction of inspired oxygen in anesthesia induction does not affect functional residual capacity reduction after intubation: a comparative study of higher and lower oxygen concentration.
Low fraction of inspired oxygen (FIO2) reduces the atelectasis area during anesthesia induction. However, atelectasis may occur during laryngoscopy and endotracheal intubation because lungs can collapse within a fraction of a second. We assessed the effects of ventilation with 100 and 40 % oxygen on functional residual capacity (FRC) in patients undergoing general anesthesia. Twenty patients scheduled for elective open abdominal surgery were randomized into 40 % oxygen (GI, n = 10) and 100 % oxygen (GII, n = 10) groups and FRC was measured. Preoxygenation and mask ventilation with 40 and 100 % oxygen were used in GI and GII, respectively. In both groups, 40 % oxygen was used for anesthesia maintenance after intubation. Bilateral lung ventilation was performed with volume guarantee and low tidal volume (7 ml/kg predicted body weight) using bilevel airway pressure. We measured FRC and blood gas in all patients during preoxygenation, after intubation, and during surgery. FRC decreased from during preoxygenation (GI 2380 ml, GII 2313 ml) to after intubation (GI 1569 ml, GII 1586 ml) and significantly decreased during surgery (GI 1338 ml, GII 1417 ml) (P < 0.05). PaO2/FIO2 decreased from during preoxygenation (GI 419 mmHg, GII 427 mmHg) to after intubation (GI 381 mmHg, GII 351 mmHg) and significantly decreased during surgery (GI 333 mmHg, GII 291 mmHg) (P < 0.05). No significant differences were found between the groups in both parameters. FRC significantly decreased from the awake state to surgery in both groups. FRC was not influenced by FIO2 elevation at anesthesia induction.


Virilizing ovarian dermoid cyst with peripheral steroid cells. A case study with immunohistochemical study of steroidogenesis.
A case of virilizing ovarian dermoid cyst with peripheral steroid cells and virilization is reported in a 62-year-old woman. The level of testosterone dropped to normal after oophorectomy. The cyst wall was bordered by a discontinuous band of steroid cells focally accompanied by smooth muscle cells. Immunohistochemically, the steroid cells were enzymatically active and displayed a profile similar to the internal theca cells of ovarian follicles. These steroid cells were most probably modified stromal cells associated with smooth muscle metaplasia of the ovarian stroma.


Therapist effects due to client racial/ethnic status when examining linear growth for client- and therapist-rated working alliance and real relationship.
Using data from 3,263 sessions nested within 144 clients, nested within 19 therapists, we examined client- and therapist-rated working alliance (WA) and real relationship (RR) at Session 3 and growth in WA and RR across the course of open-ended psychodynamic psychotherapy for clients who identified as racial/ethnic minority (REM) or as White. To be included in the analyses, therapists had to work with at least 2 REM and 2 White clients. There were no significant therapist effects for the interaction between client- or therapist-rated WA and client REM status at Session 3, or for client- or therapist-rated RR and client REM status at Session 3. There were, however, significant therapist effects due to client REM status on the interaction between client-rated linear growth in WA and RR, showing that some therapists had stronger WA and RR growth with REM than that with White clients, whereas other therapists had stronger alliance growth with White than that with REM clients. There were significant therapist effects on therapist-rated linear growth in both WA and RR, which indicated that some therapists reported stronger WA and RR growth with all of their clients, whereas other therapists reported weaker WA and RR growth for all of their clients, although this differential WA and RR growth was not related to clients' REM status. Implications for practice and research are discussed in this paper. (PsycINFO Database Record


Iron leakage owing to blood-brain barrier disruption in small vessel disease CADASIL.
To assess the relationship among iron accumulation, blood-brain barrier (BBB) damage, and cognitive function in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We enrolled 21 patients with NOTCH3 mutations and 21 age-matched healthy controls in this cross-sectional study. All participants underwent global physical and cognitive assessments and brain MRI using voxel-based quantitative susceptibility mapping (QSM; iron deposition measure) and dynamic contrast-enhanced MRI (BBB permeability measure). We compared behavioral and imaging data between the groups and analyzed the correlations in each group. Among 21 NOTCH3 mutation carriers, 10 were symptomatic and 11 asymptomatic. Montreal Cognitive Assessment scores were significantly different among the groups (symptomatic < asymptomatic < control participants). Voxel-based QSM analysis revealed that the symptomatic group had higher QSM values than did the asymptomatic group in the putamen, caudate nucleus, temporal pole, and centrum semiovale. These QSM values were positively correlated with regional BBB permeabilities (putamen: r = 0.57, p = 0.006; caudate nucleus: r = 0.51, p = 0.019; temporal pole: r = 0.48, p = 0.030; centrum semiovale: r = 0.45, p = 0.044) and negatively correlated with Montreal Cognitive Assessment scores (caudate nucleus: r = -0.53, p = 0.012; temporal pole: r = -0.56, p = 0.008). This study showed that cerebral iron burden was associated with regional BBB permeability and cognitive dysfunction in patients with CADASIL, highlighting the potential of these imaging techniques as auxiliary biomarkers to monitor the course of small vessel disease.


Molecular and cellular mechanisms of antidepressant drugs.
The mechanism of action of the antidepressants was reviewed through the summer of 1995. Antagonism of monoamine transport is the primary cellular action associated with many antidepressant medications. However, an increased synaptic concentration of monoamines is not the actual mechanism of antidepressant effects as suggested by the time lapse between treatment initiation and the onset of clinical antidepressant response. Chronic administration of all antidepressants increases the efficiency of 5-HT transmission in the synapse, albeit by different mechanisms. Serotonin transporter antagonists enhance serotonergic neurotransmission by decreasing the functional activity of the 5-HT1A and 5-HT1B autoreceptors. Tricyclic antidepressants and electroconvulsive therapy enhance 5-HT neurotransmission by increasing the responsiveness of postsynaptic 5-HT receptors. Monoamine oxidase inhibitors and the 5-HT1A agonists increase serotonergic function by desensitizing the somatodendritic autoreceptor; the terminal 5-HT autoreceptor is not affected by these agents. Evidence for both enhanced and diminished noradrenergic transmission following antidepressant treatment exists, although the evidence more strongly supports decreased noradrenergic transmission. Ongoing investigations into intracellular adaptations (e.g., steroid receptors, growth factors, etc.) during chronic antidepressant administration offer the promise of furthering our understanding of the mechanism of action of antidepressants.


Cellular correlates of proneural and Notch-delta gene expression in the regenerating zebrafish retina.
Fish can regenerate retinal neurons following ocular injury. Evidence is mounting that astrocytic glia function as inducible, regenerative stem cells in this process, but the underlying molecular events that enable neuronal regeneration are comparatively unclear. In the current study gene array, quantitative real-time PCR, in situ hybridization, and immunohistochemical approaches were used to identify, in the damaged retina of adult zebrafish, correlations between transcriptional events and entry into the cell cycle by Müller cells, a type of astrocytic cell present in all vertebrate retinas that is a candidate 'stem cell' of regenerated neurons. A proneural gene (achaete-scute homolog 1a, ash1a) and neurogenic components of the Notch signaling pathway, including notch3 and deltaA, were implicated. An injury-induced, enhanced expression of ash1a was observed in Müller cells, which is hypothesized to contribute to the transition of these cells, or their cellular progeny, into a notch3-expressing, regenerative progenitor. A model of vertebrate retinal repair is suggested in which damage-induced expression of proneural genes, plus canonical Notch-Delta signaling, could contribute to retinal stem cell promotion and subsequent regenerative neurogenesis.


Pediatric heart surgery in Ghana: three ethical questions.
When a group of doctors and nurses from Boston, Massachusetts, provided evaluation and heart surgery to children in Ghana, they encountered three rationing dilemmas: (1) What portion of surgery slots should they reserve for the simplest, most cost-effective surgeries? (2) How much time should be reserved for especially simple, nonsurgical interventions? (3) How much time should be reserved to training local staff to perform such surgeries? This article investigates these three dilemmas.


Cyclosporin A mediated immunosuppression in vitro: effect on high affinity interleukin-2 receptor expression and -turnover.
The effect of in vitro administration of Cyclosporin A (CsA) during mitogen, antigen and alloantigen activation of human T-lymphocytes on high affinity interleukin-2 (IL-2) receptor expression and -turnover and IL-2 production was investigated. The presence of CsA reduced 3H-thymidine incorporation and binding of radiolabelled human recombinant (ala125) IL-2 to high-affinity receptors in a dose-dependent fashion, although a pronounced inter- and intra-individual variation in sensitivity to CsA mediated immunosuppression was observed. Maximum inhibition was obtained when antigen and CsA were added to culture medium simultaneously. Preincubation with CsA did not influence the response. Although the number of IL-2 receptors was reduced, the turnover of the remaining high affinity IL-2 receptors on CsA treated cells was unaffected. Thus, binding, internalization and degradation were qualitatively unaltered by CsA administration. Finally, T cell activation in the presence of CsA reduced radioimmuno detectable IL-2 in cell culture supernatants to about 20%. CsA, added during antigen activation, reduced the number of Tac antigen presenting cells, but anti-Tac was unable to detect variations in the expression of high affinity IL-2 receptors. The present data indicate that CsA mediates immunosuppression by affecting early events during T-cell activation, and that variations in high affinity IL-2 receptor expression and IL-2 production are secondary to this affection.


Honor thy gut symbionts redux.
Exploring our gut microbial communities with new tools is allowing us to revisit old questions; to develop new concepts about our evolution, postnatal development, systems physiology, individuality, and definitions of health; and to further delineate the impact of our changing life-styles. It is also allowing us to envision exciting new ways for addressing global health problems. This area is inherently interdisciplinary, offering a wealth of opportunities to create new fields, partnerships, and educational initiatives. It is captivating to the public and carries substantial expectations. As such, participating scientists need to sponsor proactive, solution-focused discussions of its societal implications.


Monocyte function in IDDM patients and healthy individuals.
Interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) may be pathogenetically important in insulin-dependent diabetes mellitus (IDDM), which is associated with genes of the HLA region. Since a regulatory role of HLA region genes on monokine production may exist, we looked for an association between the monokine and prostaglandin E2 (PGE2) responses of monocytes (Mo) from 20 healthy males (18-50 years) with HLA-DR types relevant for IDDM susceptibility and resistance (DR1,2, DR1,3, DR1,4, DR3,4). Monokine assays were established and evaluated and the secretions of IL-1 beta, TNF-alpha, and PGE2 measured in Mo cultures (2h, 6h, 20h) prepared by endotoxin-free techniques and stimulated by low-dose E. coli lipopolysaccharides (LPS). There were no significant associations between Mo responses and HLA-DR phenotype. Likewise, Mo from DR2 (n = 5) and DR4 (n = 5) homozygous healthy males demonstrated no significant differences in monokine and PGE2 responses of Mo. In the HLA class III region a diallelic TNF-beta gene NcoI polymorphism consisting of alleles of 5.5 kb and 10.5 kb was recently described and associated with susceptibility to autoimmune diseases including IDDM. We report that IL-1 beta and TNF-alpha responses of Mo from TNF-beta 10.5 kb homozygous healthy individuals were significantly higher than for TNF-beta 5.5/10.5 kb heterozygotes. IL-1 beta and TNF-alpha responses of Mo from males (18-35 years) with newly diagnosed (n = 10) and long-standing IDDM (n = 10) and from age- and HLA-DR-matched healthy males (n = 10) were studied. LPS, gamma interferon (IFN), and TNF-alpha-stimulated Mo cultures were investigated. No significant differences were found between Mo responses of IDDM patients and controls. IFN (1000 U/ml) in the presence of LPS significantly potentiated LPS-stimulated Mo TNF-alpha secretion and reduced the levels of IL-1 beta immunoreactivity in Mo lysates. IFN and TNF-alpha did not have any effects on LPS-stimulated Mo secretion of IL-1 beta immunoreactivity. We conclude that Mo IL-1 beta and TNF-alpha production is normal in patients with recent-onset and long-standing IDDM. The interindividual differences in monokine responses may be accounted for by the diallelic human TNF-beta gene polymorphism rather than by HLA class II genes. This observation may be important for understanding the association of certain HLA haplotypes with autoimmune phenomena and disease.


[The role of radical oxygen species in airway inflammation].
Reactive oxygen species (ROS) are among numerous mediators of airway inflammation. They are playing a key role in asthma, chronic obturative pulmonary disease (COPD), adult respiratory distress syndrome (ARDS) and lung fibrosis (LF) pathogenesis. In view of very short half-life, their effects are local, related to the site of their formation. Generated either by epithelial or infiltrating cells, ROS cause epithelial damage, increase vascular leakage, induce smooth muscle proliferation and enhance pro-inflammatory gene expression. They also increase arachidonic acid mediator release through cytosolic phospholipase A2 phosphorylation. Drugs inhibiting ROS generation have become the first line of treatment of airway inflammatory disorders.


Molecular insights into the inhibitory potential of anthocyanidins on glucokinase regulatory protein.
Computational methods were used to investigate six anthocyanidins exhibiting antidiabetic activity by inhibiting glucokinase regulatory protein (GKRP) activity. Density functional theory was used to optimise the geometry of anthocyanidins and calculate their quantum chemical properties. A blind docking method was employed to conduct a molecular docking study, which revealed that delphinidin (Del), cyanidin (Cya), and pelargonidin (Pel) as potential GKRP inhibitors with the lowest binding free energy of -8.7, -8.6, and -8.6 kcal/mol, corresponding to high binding affinity. The molecular dynamics study further verified the blind docking results by showing high GKRP-F1P complex stability and high binding affinity calculated through the MM/GBSA method, upon the binding of pelargonidin. The lower RMSF values of pivotal GK-interacting residues for GKRP-F1P-Pel compared to GKRP-F1P, as a positive control, indicating pelargonidin ability to maintain the inactive conformation of GKRP through the inhibition of GK binding. The key residues that control the binding of the F1P to GKRP and anthocyanidin to GKRP-F1P were also identified in this study. Altogether, pelargonidin is anthocyanidins-derived natural products that have the most potential to act as inhibitors of GKRP and as antidiabetic nutraceuticals.


Qualitative interviews on substance abuse relapse and prevention among female trauma survivors.
Complex relationships among trauma, substance abuse, and mental disorders raise significant questions for the study of long-term recovery. The purpose of this qualitative study was to examine key themes in sustaining recovery among women with co-occurring disorders who had survived trauma. In semistructured interviews conducted at one of the nine sites of the Women, Co-occurring Disorders, and Violence Study, 27 female trauma survivors described the influences they considered most important in sustaining and hindering their recovery, with an emphasis on recovery from substance abuse. Recurring themes in the interviews were identified. Seven themes emerged from this analysis. Four of these themes supported recovery: connection, self-awareness, a sense of purpose and meaning, and spirituality. Three others served as obstacles to recovery: battles with depression and despair, destructive habits and patterns, and lack of personal control. The women in this study reported that, although caring relationships provided important supports for sustained recovery, some of these same relationships increased emotional stress and conflict and thus may impede recovery. It is important for women and clinicians to place a high priority on the development of boundary management and other relationship skills. In addition, clinicians need to attend to negative feelings such as boredom and loneliness and to help women develop a range of meaningful activities that are consistent with a strong sense of identity. Individual relapse prevention skills by themselves seem insufficient to sustained abstinence.


Lactoferrin, a versatile natural antimicrobial glycoprotein that modulates the host's innate immunity.
Lactoferrin is a multifunctional protein found in the secretions of mammals. The antimicrobial activity of lactoferrin was the first to be discovered and was assumed to be solely dependent on its iron-chelating ability. However, lactoferrin has been reported to display proteolytic activity towards bacterial virulence factors and to modulate the host defence by stimulating the immune system and balancing pathogen-induced inflammation. Here, we review the current understandings of the antimicrobial effect, interaction with host cells, and innate immune modulation of lactoferrin, and put forward this moonlighting protein as a possible alternative for antibiotics.


Interferon Alpha Favors Macrophage Infection by Visceral Leishmania Species Through Upregulation of Sialoadhesin Expression.
Type I interferons (IFNs) induced by an endogenous Leishmania RNA virus or exogenous viral infections have been shown to exacerbate infections with New World Cutaneous Leishmania parasites, however, the impact of type I IFNs in visceral Leishmania infections and implicated mechanisms remain to be unraveled. This study assessed the impact of type I IFN on macrophage infection with L. infantum and L. donovani and the implication of sialoadhesin (Siglec-1/CD169, Sn) as an IFN-inducible surface receptor. Stimulation of bone marrow-derived macrophages with type I IFN (IFN-α) significantly enhanced susceptibility to infection of reference laboratory strains and a set of recent clinical isolates. IFN-α particularly enhanced promastigote uptake. Enhanced macrophage susceptibility was linked to upregulated Sn surface expression as a major contributing factor to the infection exacerbating effect of IFN-α. Stimulation experiments in Sn-deficient macrophages, macrophage pretreatment with a monoclonal anti-Sn antibody or a novel bivalent anti-Sn nanobody and blocking of parasites with soluble Sn restored normal susceptibility levels. Infection of Sn-deficient mice with bioluminescent L. infantum promastigotes revealed a moderate, strain-dependent role for Sn during visceral infection under the used experimental conditions. These data indicate that IFN-responsive Sn expression can enhance the susceptibility of macrophages to infection with visceral Leishmania promastigotes and that targeting of Sn may have some protective effects in early infection.


Diagnosis of cardiac defects: where we've been, where we are and where we're going.
There has been tremendous development in the field of prenatal diagnosis of cardiac disease in the last 30 years. Early work centered on the technical aspects of providing an accurate assessment of cardiac structure and function. Techniques of fetal cardiac screening have been developed and utilized throughout the world. More recently, investigators have begun to explore the ramifications of fetal cardiac diagnosis by assessing measures of outcome. In this article, the field of fetal echocardiography, as a screening tool for identifying congenital heart disease, and its impact on disease outcome is reviewed.


Untargeted metabolomics by liquid chromatography-mass spectrometry for food authentication: A review.
Food fraud is currently a growing global concern with far-reaching consequences. Food authenticity attributes, including biological identity, geographical origin, agricultural production, and processing technology, are susceptible to food fraud. Metabolic markers and their corresponding authentication methods are considered as a promising choice for food authentication. However, few metabolic markers were available to develop robust analytical methods for food authentication in routine control. Untargeted metabolomics by liquid chromatography-mass spectrometry (LC-MS) is increasingly used to discover metabolic markers. This review summarizes the general workflow, recent applications, advantages, advances, limitations, and future needs of untargeted metabolomics by LC-MS for identifying metabolic markers in food authentication. In conclusion, untargeted metabolomics by LC-MS shows great efficiency to discover the metabolic markers for the authenticity assessment of biological identity, geographical origin, agricultural production, processing technology, freshness, cause of animals' death, and so on, through three main steps, namely, data acquisition, biomarker discovery, and biomarker validation. The application prospects of the selected markers by untargeted metabolomics require to be valued, and the selected markers need to be eventually applicable at targeted analysis assessing the authenticity of unknown food samples.


Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation.
Regulation of mast cell degranulation is dependent on the subtle interplay of cellular signaling proteins. The Src homology 2 (SH2) domain-containing inositol-5'-phosphatase (SHIP), which acts as the gatekeeper of degranulation, binds via both its SH2 domain and its phosphorylated NPXY motifs to the adapter protein Shc via the latter's phosphorylated tyrosines and phosphotyrosine-binding domain, respectively. This theoretically leaves Shc's SH2 domain available to bind proteins, which might be part of the SHIP/Shc complex. In a search for such proteins, protein kinase C-delta (PKC-delta) was found to coprecipitate in mast cells with Shc and to interact with Shc's SH2 domain following antigen or pervanadate stimulation. Phosphorylation of PKC-delta's Y(332), most likely by Lyn, was found to be responsible for PKC-delta's binding to Shc's SH2 domain. Using PKC-delta(-/-) bone marrow-derived mast cells (BMMCs), we found that the antigen-induced tyrosine phosphorylation of Shc was similar to that in wild-type (WT) BMMCs while that of SHIP was significantly increased. Moreover, increased translocation of PKC-delta to the membrane, as well as phosphorylation at T505, was observed in SHIP(-/-) BMMCs, demonstrating that while PKC-delta regulates SHIP phosphorylation, SHIP regulates PKC-delta localization and activation. Interestingly, stimulation of PKC-delta(-/-) BMMCs with suboptimal doses of antigen yielded a more sustained calcium mobilization and a significantly higher level of degranulation than that of WT cells. Altogether, our data suggest that PKC-delta is a negative regulator of antigen-induced mast cell degranulation.


A 6-year clinical assessment of electronic facial thermography.
To report the findings a 6-year clinical application of ET on patients with orofacial pain. ET was conducted (in a blinded manner) using an Agema 870 unit at 0.1 degree C thermal accuracy. A newly devised thermal classification system was applied: 'normal' when zone delta T was from 0.0 to +/-0.25 degree C, "hot' when zone delta T was > +0.35 degree C, 'cold' when zone delta T was < -0.35 degree C, and 'equivocal' when zone delta T was +/-(0.26-0.35) degree C. Study populations consisted of 164 dental patients mainly with diagnostic problems and 164 matched (control) subjects. Our prospective, matched study determined that subjects with 'hot' thermograms had the clinical diagnoses of sympathetically maintained pain, peripheral nerve mediated pain, TMJ arthropathy, and maxillary sinusitis. Subjects with 'cold' thermograms were found to have the clinical diagnoses of peripheral nerve-mediated pain and sympathetically independent pain. Subjects with 'normal' thermograms were found to have the clinical diagnosis of cracked tooth syndrome, trigeminal neuralgia, pretrigeminal neuralgia, or psychogenic facial pain. The new system of thermal classification resulted in 92% (301 of 328) agreement in classification of pain patients and matched controls. These studies suggest that ET has promise in aiding the formation of a differential diagnosis of orofacial pain and may help in understanding mechanisms of pain as well as directing therapies.


Transformation of Aspergillus sp. and Trichoderma reesei using the pyrithiamine resistance gene (ptrA) of Aspergillus oryzae.
A pyrithiamine (PT) resistance gene (ptrA) was cloned from a PT resistant mutant of Aspergillus oryzae and was useful as a dominant selectable marker for transformation of all A. oryzae wild type strain as well as A. nidulans. For further study, we examined whether or not ptrA could be used as the transformation marker in other species of filamentous fungi. Two types of plasmid, which contain ptrA as a selectable marker, were constructed, and the transformation experiments were done with them. One is an integrative plasmid, pPTRI, and another is the autonomously replicating plasmid pPTRII, which contains AMA1. PT-resistant transformants were obtained in the cases of A. kawachii, A. terreus, A. fumigatus, and Trichoderma reesei as hosts with pPTRI and pPTRII. Furthermore, a beta-glucuronidase (GUS) gene was introduced into A. kawachii and A. fumigatus using pPTRII. Almost all the transformants turned blue on GUS assay plates. These results indicate that ptrA can also be used for some other filamentous fungi besides A. oryzae and A. nidulans.


Immune-activating properties of Panton-Valentine leukocidin improve the outcome in a model of methicillin-resistant Staphylococcus aureus pneumonia.
The Panton-Valentine leukocidin (PVL) is a cytotoxin expressed by many methicillin-resistant Staphylococcus aureus (MRSA) strains that cause community-acquired infections (CA-MRSA). Its role in virulence however, is controversial, with clinical data suggesting that PVL-producing strains may cause less severe disease in humans. PVL is capable of lysing human white blood cells, but at sublytic amounts, PVL can activate protective host immunity in the absence of cell damage. The concentration-dependent reactions it elicits from host cells could be the reason for seemingly contradictory results about PVL's role in virulence. We hypothesized that a key to understanding PVL's action on host cells and, possibly, outcomes from infection is the amount of toxin present, a hypothesis previously supported in studies using a low-inoculum skin infection model, where low levels of PVL augmented innate immune resistance to infection. Here, we present additional data supporting this hypothesis using a mouse model of MRSA pneumonia, wherein we found increased virulence of isogenic Δpvl strains and further confirmed PVL's capacity to activate proinflammatory responses from mouse and human neutrophils and pulmonary cells. Activation was measured as the production of phosphorylated p38 mitogen-activated protein kinase (MAPK) and proinflammatory cytokines interleukin-8 (IL-8) and KC (from human and mouse cells, respectively), as well as the release of antibacterial factors. Conversely, PVL lowered the levels of tumor necrosis factor alpha (TNF-α) produced in active pulmonary infection, while low doses induced apoptosis, suggesting that PVL also has the capacity to regulate inflammation. Our data indicate that, independent of its cytotoxic effects, PVL also plays an important and positive immunomodulatory role during MRSA infections.


Efficacy of Intravenous Immunoglobulin/Exchange Transfusion Therapy on Gestational Alloimmune Liver Disease.
Background: Gestational alloimmune liver disease (GALD) is a rare but critical cause of neonatal liver failure. After discovering the maternal-fetal alloimmune mechanism, intravenous immunoglobulin (IVIG) with or without exchange transfusion (ET) has gradually replaced antioxidant cocktails as the first-line therapy. Whether such therapy changes the outcome of neonates with GALD is yet to be defined. Method: We reported a pair of twins with discordant presentations, mild and self-limited in the older, whereas liver failure in the younger, who was successfully rescued by ET and IVIG. To investigate the outcome after therapeutic alteration, 39 cases between 2005 and 2020 from literature research were collected. Results: Half of the collected cases (47.1%) were preterm. Common presentations were ascites, jaundice, respiratory distress, hepatomegaly, and edema. Leading laboratory abnormalities were coagulopathy, hypoalbuminemia, and elevated serum ferritin. Salivary gland biopsy and magnetic resonance imaging detected extrahepatic siderosis in 70% (14/20) and 56% (14/25), respectively. IVIG, ET, and liver transplantation were performed in 19 (48.7%), 15 (38.5%), and 8 (20.5%) patients, respectively. The overall survival (OS) rate and native liver survival (NLS) rate were 64.1% (25/39) and 43.6% (17/39), respectively. Although the compiled results did not support a significant benefit, the OS and NLS were higher in the IVIG with/without ET group compared with those treated with conventional therapy [OS (70 vs. 57.9%) and NLS (55 vs. 31.6%), respectively]. Conclusion: A high index of suspicion for GALD is crucial when facing a neonate with liver failure. Despite no significant influence on the outcome over conventional therapy in such a rare and detrimental disease, IVIG with or without ET can be worth trying before resorting to liver transplantation, which is resource-demanding and technique-challenging in small infants.


[Mental health status of infertility patients with varicocele].
To study the mental health status of infertility patients with varicocele and its relationship with infertility. Using Hospital Anxiety and Depression scale (HAD), we assessed the psychological status of 110 infertility patients with varicocele, identified the risk factors of anxiety and depression in these patients, and analyzed the correlation among psychological and other relevant factors. Meanwhile, we recruited 61 age-matched normal fertile men as controls for comparative analysis. We also conducted logistic regression analysis on the mental health status of the 106 infertility patients with varicocele. The prevalence rates of anxiety were 61.32% and 13.79%, while those of depression 37.73% and 6.90% in the infertile patients and normal fertile controls, respectively, significantly higher in the former than in the latter (P < 0.05). Logistic regression analysis showed that the main risk factors of anxiety and depression of the infertile patients were the number of times they sought medical care and the severity of their testis disorders. Infertility patients with varicocele have psychological disorders, which are particularly associated with the frequency of the patients' clinic visit and the severity of their testis disorders.


A lack of response of the financial behaviors of biodiversity conservation nonprofits to changing economic conditions.
The effectiveness of conservation organizations is determined in part by how they adapt to changing conditions. Over the previous decade, economic conditions in the United States (US) showed marked variation including a period of rapid growth followed by a major recession. We examine how biodiversity conservation nonprofits in the US responded to these changes through their financial behaviors, focusing on a sample of 90 biodiversity conservation nonprofits and the largest individual organization (The Nature Conservancy; TNC). For the 90 sampled organizations, an analysis of financial ratios derived from tax return data revealed little response to economic conditions. Similarly, more detailed examination of conservation expenditures and land acquisition practices of TNC revealed only one significant relationship with economic conditions: TNC accepted a greater proportion of conservation easements as donated in more difficult economic conditions. Our results suggest that the financial behaviors of US biodiversity conservation nonprofits are unresponsive to economic conditions.


Incremental predictive value of screening for anxiety and depression beyond current type 2 diabetes risk models: a prospective cohort study.
We sought to determine whether screening for anxiety and depression, an emerging risk factor for type 2 diabetes (T2D), adds clinically meaningful information beyond current T2D risk assessment tools. Prospective cohort. The 45 and Up Study is a large-scale prospective cohort of men and women aged 45 years and over, randomly sampled from the general population of New South Wales, Australia. 51 588 participants without self-reported diabetes at baseline (2006-2009) were followed up for approximately 3 years (2010). T2D status was determined by self-reported doctor who diagnosed diabetes after the age of 30 years, and/or current use of metformin. Current symptoms of anxiety and/or depression were measured by the 10-item Kessler Psychological Distress Scale (K10). We determined the optimal cut-off point for K10 for predicting T2D using Tjur's R2 and tested risk models with and without the K10 using logistic regression. We assessed performance measures for the incremental value of the K10 using the area under the receiver operating characteristic (AROC), net reclassification improvement (NRI) and net benefit (NB) decision analytics with sensitivity analyses. T2D developed in 1076 individuals (52.4% men). A K10 score of ≥19 (prevalence 8.97%), adjusted for age and gender, was optimal for predicting incident T2D (sensitivity 77%, specificity 53% and positive predictive value 3%; OR 1.70 (95% CI 1.41 to 2.03, P<0.001). K10 score predicted incident T2D independent of current risk models, but did not improve corresponding AROC, NRI and NB statistics. Sensitivity analyses showed that this was partially explained by the baseline model and the small effect size of the K10 that was similar compared with other risk factors. Anxiety and depressing screening with the K10 adds no meaningful incremental value in addition to current T2D risk assessments. The clinical importance of anxiety and depression screening in preventing T2D requires ongoing consideration.


MiR-29b-3p Reverses Cisplatin Resistance by Targeting COL1A1 in Non-Small-Cell Lung Cancer A549/DDP Cells.
To investigate the expression of miR-29b-3p in tissues and cells of non-small-cell lung cancer (NSCLC) and its effect on cisplatin resistance in NSCLC cells and its mechanism. The mRNA expression of miR-29b-3p and COL1A1 in NSCLC tissue, cell line A549 and cisplatin-resistant cell line A549/DDP was detected by RT-qPCR. MiR-29b-3p Mimics was transfected into A549/DDP cells, and the cell viability, proliferation, apoptosis and related protein expression were detected by CCK-8, flow cytometry and Western blot. Also, luciferase reporter gene assay was used to verify the targeting relationship between miR-29b-3p and COL1A1. Moreover, COL1A1 overexpression lentivirus and miR-29b-3p mimics (Mimics+COL1A1) were simultaneously transfected into A549/DDP cells, and then the cell viability and related protein expression were measured. In NSCLC tissue and its cell line, miR-29b-3p was downregulated and COL1A1 was upregulated (P<0.05). After A549/DDP cell was transfected by mimics, its cell viability and proliferation rate decreased, apoptosis rate and the expression of tumor suppressor gene PTEN and apoptosis-related protein BAX were increased (P<0.05), which could be reversed by Mimics+COL1A1 co-transfection. Luciferase reporter gene assay indicated that COL1A1 was the target gene of miR-29b-3p. All in all, miR-29b-3p can reverse the cisplatin resistance of A549/DDP cells by inhibiting the expression of COL1A1 gene and increasing the expression of PTEN and BAX.


An unusual no-reflow phenomenon due to neointimal tissue embolization during drug eluting balloon intervention in stent restenosis: A case report.
Acute coronary syndrome is one of the leading causes of death worldwide. Percutaneous coronary intervention (PCI), along with various devices, have been technically developed to dramatically improve mortality risk in patients with acute myocardial infarction. However, no-reflow phenomenon still remains a problematic complication during a PCI, even in the era of drug eluting stents. There are various hypotheses and mechanisms for no-reflow phenomenon, but none have been confirmed. Treatment for no-reflow phenomenon also depends on various underlying conditions, but have not yet shown effective improvement. We presented a case of no-reflow phenomenon caused by an unusual cause.


MAPT H1 Haplotype is Associated with Late-Onset Alzheimer's Disease Risk in APOEɛ4 Noncarriers: Results from the Dementia Genetics Spanish Consortium.
The MAPT H1 haplotype has been linked to several disorders, but its relationship with Alzheimer's disease (AD) remains controversial. A rare variant in MAPT (p.A152T) has been linked with frontotemporal dementia (FTD) and AD. We genotyped H1/H2 and p.A152T MAPT in 11,572 subjects from Spain (4,327 AD, 563 FTD, 648 Parkinson's disease (PD), 84 progressive supranuclear palsy (PSP), and 5,950 healthy controls). Additionally, we included 101 individuals from 21 families with genetic FTD. MAPT p.A152T was borderline significantly associated with FTD [odds ratio (OR) = 2.03; p = 0.063], but not with AD. MAPT H1 haplotype was associated with AD risk (OR = 1.12; p = 0.0005). Stratification analysis showed that this association was mainly driven by APOE ɛ4 noncarriers (OR = 1.14; p = 0.0025). MAPT H1 was also associated with risk for PD (OR = 1.30; p = 0.0003) and PSP (OR = 3.18; p = 8.59 × 10-8) but not FTD. Our results suggest that the MAPT H1 haplotype increases the risk of PD, PSP, and non-APOE ɛ4 AD.


Relationship between the use of intuition in clinical practice and the clinical competence of critical care nurses.
Clinical competency has been the main focus of nurse educational systems. To further it, the concept of intuition was introduced into nursing in the 1970s. Benner's theory proposed that greater use of intuition was linked to higher clinical competence; however, there is still a paucity of data to verify this theory. Therefore, the current study was conducted to assess the relationship between the use of intuition in clinical practice and the clinical competence of critical care nurses. In this correlational study, 88 critical care nurses were recruited as convenience. The tools included a 'use of intuition in clinical practice' scale devised by the researcher, and a 'clinical competence' instrument. The gathered data were analyzed by SPSS version 20.0 software, using descriptive and inferential statistics. Of the 88 participants, 73.9% were women and 93.2% were at undergraduate level. The mean and standard deviation of participants' age and work experience was 32.29 ± 6.75 and 7.40 ± 5.68 years, respectively. The Pearson correlation test revealed no significant connection between the use of intuition in clinical practice and the clinical competence of critical care nurses (r = 0.091, P = 0.398), and produced similar results from the various demographic groups (P > 0.05). In this study, no significant correlation between the use of intuition and clinical competence in critical care nurses was found. This could be attributed to intuition as a nursing skill being almost excluded from the educational curriculum of nursing schools, and some background factors.


Beware of the ulno-palmar distal radial fragment.
Five patients sustained isolated fractures of the ulnopalmar rim of the distal radius. In three cases the fragment was small and was classed as an avulsion fracture of the short radiolunate ligament. Palmar wrist subluxation occurred in all cases, four during treatment in a cast or splint. The ulnopalmar rim of the distal radius contributes to the stability of the radiocarpal joint and fractures in this region merit particular attention.


Delicate balance: 2003 salary survey.
Hospital boards are exercising more scrutiny than ever on executive pay, at a time when the disparity between salaries in health care and general industry has finally disappeared.


Analgesic Efficacy of Oral Dextrose and Breast Milk during Nasopharyngeal Suctioning of Preterm Infants on CPAP: A Blinded Randomized Controlled Trial.
Continuous positive airway pressure (CPAP) requires nasopharyngeal suctioning for airway patency, which is painful. Other procedures have used breast milk and 25% dextrose as analgesics. We aimed to compare their analgesic efficacy during nasopharyngeal suctioning in preterm neonates on CPAP. In this blinded randomized controlled trial, babies received 25% dextrose or breast milk orally. Pain before, during and after was assessed using the Premature Infant Pain Profile (PIPP) score. Analysis was done for 40 babies. The mean PIPP score in the 25% dextrose group during the procedure was 11.25 ± 2.73 and 13.2 ± 2.55 (p = 0.02) with the intervention and without. In the breast milk group the PIPP score during the procedure was 11.35 ± 3.05 and 13.45 ± 3.27 (p = 0.04); this difference persisted even after the procedure. There was no significant difference between the interventions. Both interventions significantly reduce pain. The analgesic effect of breast milk was sustained.


Carcinoembryonic antigen elevation due to bowel sequestration with mucocele formation following colonic resection.
Carcinoembryonic antigen (CEA) is recommended as a serologic marker to monitor colorectal carcinoma recurrence. Elevations of CEA due to causes other than carcinoma exist and may lead to a misdiagnosis of recurrent carcinoma. We report a case of bowel sequestration with mucocele formation at the site of previous colo-colic anastomosis causing a mild elevation in CEA. The patient exhibited increasing CEA levels 6 years after resection of a sigmoid colon carcinoma with end-to-end anastomosis. Subsequently, computed tomographic and positron emission tomographic scans documented the presence of a cystic mass showing increased uptake at the anastomotic site. At exploratory laparotomy a mass lesion with mucus-filled protrusions was resected. Pathologic examination documented the presence of sequestration of a segment of the bowel wall with a mucocele and no overlying defect at the mucosal anastomotic site by demonstrating the presence of all bowel layers. After resection of the lesion, the CEA level normalized.


Experimentation and Predictive Models for Properties of Concrete Added with Active and Inactive SiO₂ Fillers.
Cement is one of the main constituents of concrete material and it is one of the main sources of carbon dioxide emissions in the environment. Fillers within a range of 5⁻7% from different sources can be used as a replacement of cement without compromising the properties of concrete or even tailoring for required property. This paper investigates the influence of inactive silica filler and silica fume on the mechanical- and durability-related properties of concrete with different strengths. The investigated mechanical properties focused on compressive strength at different ages up to 400 days, while the durability-related properties focused on porosity and rapid chloride ion penetrability (RCPT). Two types of ultrafines, namely quartz ultrafine and silica fume, were used. Concrete mixtures with four different water/binder ratios (0.25, 0.30, 0.35, 0.40) were prepared for various dosages of quartz ultrafine (0%, 5%, 8%, 10%, 15%, 25%, and 35%) and different dosages of silica fume (0%, 8%, 10%, and 12%). The results revealed that the compressive strength and durability related properties of concrete with different dosages of ultrafines and silica fume were significantly affected; however, there was a negative impact of ultrafine filler on the compressive strength after replacement of more than 8% of ultrafines. The strength relationships for the concrete with different water-to-cement ratio were assessed and certain modifications were proposed for ultrafines and silica fume. Predictive models were proposed for predicting the compressive strength of concrete in terms of RCPT and porosity for different levels of replacements of ultrafines and silica fume.


Basal forebrain cholinergic system volume is associated with general cognitive ability in the elderly.
At the present, it is unclear whether association of basal forebrain cholinergic system (BFCS) volume with cognitive performance exists in healthy as well as in cognitively impaired elderly subjects. Whereas one small study reported an association of BFCS volume with general cognitive ability 'g' in healthy ageing, effects on specific cognitive domains have only been found in subjects with cognitive decline. Here we aim to clarify whether an association of BFCS volume and 'g' is present in a larger sample of elderly subjects without obvious symptoms of dementia and whether similar associations can also be observed in specific cognitive domains. 282 pre-surgical patients from the BioCog study (aged 72.7 ± 4.9 years with a range of 65-87 years, 110 women) with a median MMSE score of 29 points (range 24-30) were investigated. BFCS and brain volume as well as brain parenchymal fraction were assessed in T1-weighted MR images using SPM12 and a probabilistic map of the BFCS. Neuropsychological assessment comprised the CANTAB cognitive battery and paper-and-pencil based tests. For data analysis, generalised linear models and quantile regression were applied. Significant associations of BFCS volume with 'g' and several cognitive domains were found, with the strongest association found for 'g'. BFCS volume explained less variance in cognitive performance than brain volume. The association was not confounded by brain parenchymal fraction. Furthermore, the association of BFCS volume and 'g' was similar in high- and low-performers. Our results extend previous study findings on BFCS volume associations with cognition in elderly subjects. Despite the observed associations of BFCS volume and cognitive performance, this association seems to reflect a more general association of brain volume and cognition. Accordingly, a specific association of BFCS volume and cognition in non-demented elderly subjects is questionable.


TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy.
Cancer immunotherapy utilizing T-cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non-T-cell-inflamed tumors that lack markers associated with the activation of adaptive anti-tumor immune responses. Notably, elimination of cancer cells by T cells is critically dependent on the optimal activity of innate immune cells. Therefore, identifying new targets that regulate innate immune cell function and promote the engagement of adaptive tumoricidal responses is likely to lead to the development of improved therapies against cancer. Here, we review the TAM receptor tyrosine kinases-TYRO3, AXL, and MERTK-as an emerging class of innate immune checkpoints that participate in key steps of anti-tumoral immunity. Namely, TAM-mediated efferocytosis, negative regulation of dendritic cell activity, and dysregulated production of chemokines collectively favor the escape of malignant cells. Hence, disabling TAM signaling may promote engagement of adaptive immunity and complement T-cell checkpoint blockade.


Role of Emotion Reactivity to Predict Facial Emotion Recognition Changes with Aging.
Emotional intelligence includes an assortment of factors related to emotion function. Such factors involve emotion recognition (in this case via facial expression), emotion trait, reactivity, and regulation. We aimed to investigate how the subjective appraisals of emotional intelligence (i.e. trait, reactivity, and regulation) are associated with objective emotion recognition accuracy, and how these associations differ between young and older adults. Data were extracted from the CamCAN dataset (189 adults: 57 young/118 older) from assessments measuring these emotion constructs. Using linear regression models, we found that greater negative reactivity was associated with better emotion recognition accuracy among older adults, though the pattern was opposite for young adults with the greatest difference in disgust and surprise recognition. Positive reactivity and depression level predicted surprise recognition, with the associations significantly differing between the age groups. The present findings suggest the level to which older and young adults react to emotional stimuli differentially predicts their ability to correctly identify facial emotion expressions. Older adults with higher negative reactivity may be able to integrate their negative emotions effectively in order to recognize other's negative emotions more accurately. Alternatively, young adults may experience interference from negative reactivity, lowering their ability to recognize other's negative emotions.


Short- and long-term outcomes after conversion of laparoscopic total gastrectomy for gastric cancer: a single-center study.
Conversion of laparoscopic surgery for colorectal cancer has been fully studied. However, no study has investigated conversion of laparoscopic total gastrectomy for gastric cancer. We evaluated the effect of conversion to open total gastrectomy on short- and long-term outcomes among patients who underwent laparoscopic total gastrectomy for gastric cancer and identified factors predictive of survival. A prospective database of consecutive laparoscopic total gastrectomies for gastric cancer was reviewed. Patients who required conversion (converted group) were compared with those who had completed laparoscopic total gastrectomy (completed group). Kaplan-Meier method was used to compare and analyze survival. Univariate and multivariate analyses were performed to identify predictors of poor survival. The conversion rate was 17.4%, and the most common reason for conversion was a locally advanced tumor. Conversion was associated with significantly longer operative time and greater blood loss. No differences were observed in terms of postoperative morbidity or mortality between the converted and completed patients. The converted group had significantly worse 5-year overall survival (OS) and disease-free survival (DFS). Univariate analysis showed that conversion to open total gastrectomy, pathological (p) T4 disease, and pathological N2-N3 disease were significant risk factors for OS and DFS. In multivariate analysis, pT4 cancer was the only independent predictor of DFS and OS. Conversion to open total gastrectomy per se was not associated with worse short-term outcomes or worse long-term survival.


Susceptibility of Fourteen New Cucurbit Species to Gummy Stem Blight Caused by Stagonosporopsis citrulli Under Field Conditions.
At least 24 species of cucurbits from 13 genera are known to be susceptible to gummy stem blight, caused by three species of Stagonosporopsis. Cankers that are formed on crowns and stems play an important role in the disease cycle and the survival of the pathogen. Fourteen cucurbit species of unknown susceptibility representing 12 genera, four taxonomic tribes, and four geographic origins were inoculated with Stagonosporopsis citrulli in Charleston, SC, in spring 2015, spring 2016, and fall 2016 to evaluate their level of susceptibility to gummy stem blight and the ability of the pathogen to reproduce on crown cankers. An additional species, Cucumis melo, was included as a reference due to its known high susceptibility. Data sets of area under the disease progress curve (AUDPC) for foliar severity and crown cankers, final percentage of diseased leaf area, final percentage of plants with cankers, final percentage of plants with fruiting bodies, and rates of increase in canker incidence were analyzed to evaluate susceptibility. Results were similar for datasets of AUDPC and final ratings but there were more differences for AUDPC. In all experiments, Apodanthera sagittifolia, Ecballium elaterium, and Kedrostis leloja were at least as susceptible to foliar blight as the reference C. melo. K. leloja was as susceptible to crown cankers as C. melo in all experiments and A. sagittifolia and E. elaterium were among the species most susceptible to crown cankers in two experiments. Coccinia grandis was highly resistant to gummy stem blight and had a few cankers only in fall 2016. Sicana odorifera and Zehneria pallidinervia also consistently grouped with the most resistant species. Incidence of crown cankers on Cucumis melo and K. leloja increased at the fastest rate of all species in all experiments and had, along with E. elaterium, the highest incidence of crowns with fruiting bodies. In general, the most susceptible species also were most suitable for reproduction of the pathogen and had the fastest disease progression. The tribes Benincaseae and Cucurbiteae had consistently lower levels of foliar blight than Bryonieae and Coniandreae. The tribe Benincaseae had a consistently lower AUDPC for canker incidence than Bryonieae and Coniandreae. The species originating from Europe (E. elaterium) was consistently most susceptible to both symptoms, while African species grouped with the least susceptible species in all experiments. To the best of our knowledge, this is the first report of susceptibility to gummy stem blight of 14 species and the first report of susceptibility of the cucurbit tribes Coniandreae and Gomphogyneae. This expands the host range of Stagonosporopsis citrulli to 37 species representing 21 genera and seven tribes in the family Cucurbitaceae. This study demonstrates the importance of crown cankers as reproductive sites for S. citrulli.


Probing the anisotropy of Landau levels in phosphorene by magneto-capacitance with a parabolic potential confinement.
We theoretically investigate the Landau levels (LLs) and magneto-capacitance (MC) of monolayer black phosphorus under a perpendicular magnetic field, on which a parabolic potential is applied along with the armchair and zigzag directions, respectively. By both analytically perturbative calculation and numerical diagonalization based on an effective k ⋅ p Hamiltonian, we find that the LLs parabolically depend on the wave vectors and show strong anisotropy as the parabolic potential is applied along with different crystal directions. Specifically, the analytical LLs obtained by perturbative calculation from a decoupled single-band Hamiltonian are in good agreement with the numerical results. Importantly, the LLs are no longer linearly dependent on the magnetic field and level index even in the low energy regime due to the confinement of parabolic potential which repaints the cyclotron orbits. Moreover, the MC spectrum clearly reflects the structure of the LLs and exhibits strong anisotropic oscillating patterns. It can be used to determine the band parameters of phosphorene, i.e., the effective masses and inter-band coupling in the absence of magnetic and electric fields.


Integration of laser trapping for continuous and selective monitoring of photothermal response of a single microparticle.
Photothermal response (PTR) is an established pump and probe technique for real-time sensing of biological assays. Continuous and selective PTR monitoring is difficult owing to the Brownian motion changing the relative position of the target with respect to the beams. Integration of laser trapping with PTR is proposed as a solution. The proposed method is verified on red polystyrene microparticles. PTR is continuously monitored for 30 min. Results show that the mean relaxation time variation of the acquired signals is less than 5%. The proposed method is then applied to human red blood cells for continuous and selective PTR.


Tumor Promoting Function of DUSP10 in Non-Small Cell Lung Cancer Is Associated With Tumor-Promoting Cytokines.
Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.