Monitoring the persistence of genes deriving from genetically modified plants in the soil environment.
To study the gene persistence in the soil environment, soil samples were collected from sugar beet (Beta vulgaris) and chicory (Cichorium intybus) experimental fields just before harvest. They were homogenized, mixed and stored at constant humidity in a non-heated room. Sub-samples of soils were subsequently collected at regular intervals, dried and sieved through a 1.8-mm mesh before DNA was extracted. Specific primers were then used for the detection of plant DNA by hot start PCR. Results reveal that, under laboratory conditions, transgenic and non-transgenic sugar beet DNA was still detected after 25 days incubation in the soil taken from a sugar beet experimental plot while detection of chicory DNA was still possible after 50 days incubation in soil taken from the chicory experimental plot. This might be in correlation with the stronger resistance of chicory radicles to decomposition as compared to radicles from sugar beets.


Brain Angiotensin II Type 1 Receptor Blockade Improves Dairy Blood Pressure Variability via Sympathoinhibition in Hypertensive Rats.
Abnormal blood pressure (BP) elevation in early morning is known to cause cardiovascular events. Previous studies have suggested that one of the reasons in abnormal dairy BP variability is sympathoexcitation. We have demonstrated that brain angiotensin II type 1 receptor (AT1R) causes sympathoexcitation. The aim of the present study was to investigate whether central AT1R blockade attenuates the excess BP elevation in rest-to-active phase in hypertensive rats or not. Stroke-prone spontaneously hypertensive rats (SHRSP) were treated with intracerebroventricular infusion (ICV) of AT1R receptor blocker (ARB), oral administration of hydralazine (HYD), or ICV of vehicle (VEH). Telemetric averaged mean BP (MBP) was measured at early morning (EM), after morning (AM), and night (NT). At EM, MBP was significantly lower in ARB to a greater extent than in HYD compared to VEH, though MBP at AM was the same in ARB and HYD. At NT, MBP was also significantly lower in ARB than in HYD. These results in MBP were compatible to those in sympathoexcitation and suggest that central AT1R blockade attenuates excess BP elevation in early active phase and continuous BP elevation during rest phase independent of depressor response in hypertensive rats.


A Ratiometric Fluorescent Sensor Based on Chelation-Enhanced Fluorescence of Carbon Dots for Zinc Ion Detection.
Zinc ion, one of the most important transition metal ions in living organisms, plays a crucial role in the homeostasis of the organism. The disorder of zinc is associated with many major diseases. It is highly desirable to develop selective and sensitive methods for the real-time detection of zinc ions. In this work, double-emitting fluorescent carbon dots (CDs) are prepared by a solvothermal method using glutathione, L-aspartic acid, and formamide as the raw materials. The carbon dots specifically recognize zine ions and produce a decrease in fluorescence intensity at 684 nm and an increase at 649 nm, leading to a ratiometric fluorescent sensor for zinc detection. Through surface modification and spectral analysis, the surface groups including carboxyl, carbonyl, hydroxyl, and amino groups, and C=N in heterocycles of CDs are revealed to synergistically coordinate Zn2+, inducing the structural changes in the emission site. The CDs can afford a low limit of detection of ~5 nM for Zn2+ detection with good linearity in the range of 0.02-5 μM, showing good selectivity as well. The results from real samples including fetal bovine serum, milk powder, and zinc gluconate oral solution indicated the good applicability of the CDs in the determination of Zn2+.


The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the alpha3beta1 integrin but not the alpha6beta4 integrin.
Laminin-5 is an important constituent of the basal lamina. The receptors for laminin-5, the integrins alpha3beta1 and alpha6beta4, have been associated with epithelial wound migration and carcinoma invasion. The signal transduction mechanisms that regulate these integrins are not well understood. We report here that the small GTPase Rap1 regulates the adhesion of a number of cell lines to various extracellular matrix proteins including laminin-5. cAMP also mediates cell adhesion and spreading on laminin-5, a process that is independent of protein kinase A but rather dependent on Epac1, a cAMP-dependent exchange factor for Rap. Interestingly, although both alpha3beta1 and alpha6beta4 mediate adhesion to laminin-5, only alpha3beta1-dependent adhesion is dependent on Rap1. These results provide evidence for a function of the cAMP-Epac-Rap1 pathway in cell adhesion and spreading on different extracellular matrix proteins. They also define different roles for the laminin-binding integrins in regulated cell adhesion and subsequent cell spreading.


Influence of hydrocarbon exposure on the course of glomerulonephritis.
Seventy-one patients with nonsystemic, nonacute glomerulonephritis were included in a follow-up study on the influence of hydrocarbon exposure on the course of their disease. A possible exposure was ruled out by interview performed by occupational hygienists unaware of the outcome of the disease. The patients were allocated to three groups according to their hydrocarbon exposure. One group consisted of patients who had never been exposed; the second of patients who were exposed during follow-up and the third of patients who had discontinued their previous exposure. Each group was subdivided into one group with a glomerular filtration rate (GFR) that remained normal, and one group with a GFR that was, or became, subnormal. Patients with a subnormal GFR who discontinued their exposure had a more favorable course than those who continued to be exposed in spite of an initially lower mean GFR and an initially higher frequency of hypertension. No significant difference was seen between the groups with a normal GFR.


Chronic graft-versus-host disease. Part II: Disease activity grading and therapeutic management.
Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 Federal Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of cGVHD. Part II discusses disease grading and therapeutic management.


A Robust Approach to TDMA Synchronization in Aerial Networks.
Unmanned Aerial Vehicles (UAVs) can be a powerful tool for live (interactive) remote inspection of large-scale structures or areas of interest. Instead of manual, local, and labor-intensive inspections, we envision human operators working together with networks of semi-autonomous UAVs. The current state-of-the-art for low-delay high-throughput inter-vehicle networking relies on Time-Division Multiple Access (TDMA) techniques that require accurate synchronization among all network nodes. In this paper, we propose a delay-tolerant synchronization approach that converges to the correct order of the TDMA slots implemented over COTS WiFi in a fully-distributed way and without resorting to a global clock. This highly flexible solution allows building an ad-hoc aerial network based on a backbone of relaying UAVs. We show several alternatives to achieve this synchronization in a concrete aerial network and compare them in terms of slots' overlap, throughput, and packet delivery. The results show that these alternatives lead to trade-offs in the referenced metrics. The results also provide insight into the delays caused by buffering in the protocol stack and especially in the WiFi interface.


Additional repulsion reduces the dynamical resilience in the damaged networks.
In this paper, we investigate the dynamical robustness of diffusively coupled oscillatory networks under the influence of an additional repulsive link. Such a dynamical resilience property is realized through the aging process of the damaged network of active and inactive oscillators. The aging process is one type of phase transition, mainly appearing at a critical threshold of a fraction of the inactive oscillator node where the mean oscillation amplitude of the entire network suddenly vanishes. These critical fractions of the failure nodes in the network are broadly used as a measure of network resilience. Here, we analytically derived the critical fraction of the aging process in the dynamical network. We find that the addition of the repulsive link enhances the critical threshold of the aging transition of diffusively coupled oscillators, which indicated that the dynamical robustness of the coupled network decreases with the presence of the repulsive interaction. Furthermore, we investigate the dynamical robustness of the network against the number of deteriorating repulsive links. We observed that a certain percentage of the repulsive link is enabled to produce the aging process in the entire network. Finally, the effect of symmetry-breaking coupling and the targeted inactivation process on the dynamical robustness property of damaged networks were investigated. The analytically obtained results are verified numerically in the network of coupled Stuart-Landau oscillators. These findings may help us to better understand the role of the coupling mechanism on the phase transition in the damaged network.


Review on Recent Progress in the Development of Tungsten Oxide Based Electrodes for Electrochemical Energy Storage.
Current progress in the advancement of energy-storage devices is the most important factor that will allow the scientific community to develop resources to meet the global energy demands of the 21st century. Nanostructured materials can be used as effective electrodes for energy-storage devices because they offer various promising features, including high surface-to-volume ratios, exceptional charge-transport features, and good physicochemical properties. Until now, the successful research frontrunners have focused on the preparation of positive electrode materials for energy-storage applications; nevertheless, the electrochemical performance of negative electrodes is less frequently reported. This review mainly focuses on the current progress in the development of tungsten oxide-based electrodes for energy-storage applications, primarily supercapacitors (SCs) and batteries. Tungsten is found in various stoichiometric and nonstoichiometric oxides. Among the different tungsten oxide materials, tungsten trioxide (WO3 ) has been intensively investigated as an electrode material for different applications because of its excellent charge-transport features, unique physicochemical properties, and good resistance to corrosion. Various WO3 composites, such as WO3 /carbon, WO3 /polymers, WO3 /metal oxides, and tungsten-based binary metal oxides, have been used for application in SCs and batteries. However, pristine WO3 suffers from a relatively low specific surface area and low energy density. Therefore, it is crucial to thoroughly summarize recent progress in utilizing WO3 -based materials from various perspectives to enhance their performance. Herein, the potential- and pH-dependent behavior of tungsten in aqueous media is discussed. Recent progress in the advancement of nanostructured WO3 and tungsten oxide-based composites, along with related charge-storage mechanisms and their electrochemical performances in SCs and batteries, is systematically summarized. Finally, remarks are made on future research challenges and the prospect of using tungsten oxide-based materials to further upgrade energy-storage devices.


Missed breast carcinoma: pitfalls and pearls.
Mammography is the standard of reference for the detection of breast carcinoma, yet 10%-30% of breast cancers may be missed at mammography. Possible causes for missed breast cancers include dense parenchyma obscuring a lesion, poor positioning or technique, perception error, incorrect interpretation of a suspect finding, subtle features of malignancy, and slow growth of a lesion. Recent studies have emphasized the use of alternative imaging modalities to detect and diagnose breast carcinoma, including ultrasonography (US), magnetic resonance imaging, and nuclear medicine studies. However, the radiologist can take a number of steps that will significantly enhance the accuracy of image interpretation at mammography and decrease the false-negative rate. These steps include performing diagnostic as well as screening mammography, reviewing clinical data and using US to help assess a palpable or mammographically detected mass, strictly adhering to positioning and technical requirements, being alert to subtle features of breast cancers, comparing recent images with earlier mammograms to look for subtle increases in lesion size, looking for additional lesions when one abnormality is seen, and judging a lesion by its most malignant features.


A 13-week subchronic toxicity study of sodium iron chlorophyllin in F344 rats.
Sodium iron chlorophyllin (SIC), a water-soluble chlorophyll derivative, has been used as a food additive for green coloration. In the present study, a subchronic toxicity study of SIC was performed in male and female F344 rats with oral administration in diet at concentrations of 0%, 0.2%, 1.0%, and 5.0% for 13 weeks. No mortalities, abnormal clinical signs, and hematological changes were observed in any of the groups during the experiment. Significant reduction of body weight gain was noted in 5.0% males. In serum biochemistry, serum transferrin levels were significantly increased in 5.0% males and females. Relative spleen weights of both sexes were markedly reduced with 5.0% SIC as compared to the controls, and absolute weights of spleen were also significantly decreased in males. On histopathological assessment, diffuse hypertrophy of acinar cells in the parotid gland was observed in all examined 5.0% males and females, but not in the other groups. Based on the histopathology of the parotid glands, the no-observed-adverse-effect level (NOAEL) of SIC in the present study was estimated to be 1.0% (609 mg/kg bw/day for males and 678 mg/kg bw/day for females).


Hormonal regulation of the transformation phenotype in simian virus 40-transformed rat embryonic preadipose cell lines.
The regulation of transformed phenotypes was studied in newly isolated preadipose cell lines which were established after infection with simian virus 40 tsA58 dl2009. The clonal cell lines isolated exhibited most of the characteristics typical of transformed cells. The transformants, however, were able to differentiate into adipocytes in the presence of low calf serum (0.5%) and a combination of several hormones, including hydrocortisone and insulin. Treatment with insulin alone stimulated the growth of these cells but did not induce lipid accumulation without added hydrocortisone. The effect of hydrocortisone was accompanied by a restoration of growth control in the transformants after they reached high cell density. The blot hybridization analysis of cellular DNAs digested by restriction enzymes revealed that simian virus 40 genomes were integrated at multiple separate sites at which a head-to-tail oligomeric insertion took place. Large T antigen was synthesized in growing cells but was regulated at high cell density when cells were committed to differentiate by glucocorticoids. These results suggest that the glucocorticoid hydrocortisone is capable of restoring growth regulation at high cell densities to simian virus 40-transformed preadipose cell lines.


Use of common average reference and large-Laplacian spatial-filters enhances EEG signal-to-noise ratios in intrinsic sensorimotor activity.
Oscillations in the resting-state scalp electroencephalogram (EEG) represent various intrinsic brain activities. One of the characteristic EEG oscillations is the sensorimotor rhythm (SMR)-with its arch-shaped waveform in alpha- and betabands-that reflect sensorimotor activity. The representation of sensorimotor activity by the SMR depends on the signal-to-noise ratio achieved by EEG spatial filters. We employed simultaneous recording of EEG and functional magnetic resonance imaging, and 10-min resting-state brain activities were recorded in 19 healthy volunteers. To compare the EEG spatial-filtering methods commonly used for extracting sensorimotor cortical activities, we assessed nine different spatial-filters: a default reference of EEG amplifier system, a common average reference (CAR), small-, middle- and large-Laplacian filters, and four types of bipolar manners (C3-Cz, C3-F3, C3-P3, and C3-T7). We identified the brain region that correlated with the EEG-SMR power obtained after each spatial-filtering method was applied. Subsequently, we calculated the proportion of the significant voxels in the sensorimotor cortex as well as the sensorimotor occupancy in all significant regions to examine the sensitivity and specificity of each spatial-filter. The CAR and large-Laplacian spatial-filters were superior at improving the signal-to-noise ratios for extracting sensorimotor activity from the EEG-SMR signal. Our results are consistent with the spatial-filter selection to extract task-dependent activation for better control of EEG-SMR-based interventions. Our approach has the potential to identify the optimal spatial-filter for EEG-SMR. Evaluating spatial-filters for extracting spontaneous sensorimotor activity from the EEG is a useful procedure for constructing more effective EEG-SMR-based interventions.


Isolation and characterization of feruloylated arabinoxylan oligosaccharides from the perennial cereal grain intermediate wheat grass (Thinopyrum intermedium).
In comparison to the annual grain crops dominating current agricultural production, perennial grain species require fewer chemical and energy inputs and improve soil health and erosion control. The possibility for producing sustainable grain harvests from marginal land areas is motivating research initiatives to integrate perennial grains into commercial cropping and food processing systems. In this study, the feruloylated arabinoxylans from intermediate wheat grass (Thinopyrum intermedium, IWG), a promising perennial grain candidate in agronomic screening studies, were investigated. Insoluble fiber isolated from IWG whole grain flour was subjected to either mildly acidic (50 mM TFA, 100 °C, 2 h) or enzymatic (Driselase) hydrolysis. The liberated feruloylated arabinoxylan oligosaccharides were concentrated with Amberlite XAD-2, separated with gel chromatography (Sephadex LH-20, water), and purified with reversed-phase HPLC (C18, water-MeOH gradient). Thirteen feruloylated oligosaccharides were isolated (including eight structures described for the first time) and identified by LC-ESI-MS and NMR. Linkage-type analysis via methylation analysis, as well as the monosaccharide and phenolic acid profiles of the IWG insoluble fiber were also determined. IWG feruloylated arabinoxylans have a relatively simple structure with only short feruloylated side chains, a lower backbone substitution rate than annual rye and wheat varieties, and a moderate phenolic acid content.


Immigrant health access in Texas: policy, rhetoric, and fear in the Trump era.
Since the 2016 presidential election, reports have suggested that President Trump's rhetoric and his administration's proposed policies could be exacerbating barriers to accessing health care for undocumented as well as lawfully present immigrants and their families in the United States. However, very little empirical work has analyzed this possibility or detailed how these reports and rhetoric have altered the health seeking behavior of mixed immigration status families. Using a series of focus groups throughout Texas in both English and Spanish, this qualitative study analyzes changes to health access for immigrants. We consulted Community Health Workers to better understand the barriers encountered by their otherwise hard-to-reach undocumented clients and their families as they interface with the health system, revealing key insights about the changing nature of barriers to access under the Trump administration. We identify four key themes about the changing nature of immigrant health access in the United States: growing fear of interacting with health and social services; that social networks are paradoxically limiting health access in the current political climate; that the administration's rhetoric and proposed policies are impeding health seeking behavior; and that children are encountering new barriers to social program participation. The Trump administration, its proposed immigration policies, and his rhetoric are posing new and significant barriers to health access for immigrants and their families.


Understand, elucidate and rationalize the coordination mode of pyrimidylmethylamines: an intertwined study combining NMR and DFT methods.
Conception of new pyrimidylmethylamine (pyrma) ligands and their corresponding Pd(II) complexes has been described. Both symmetrical and non-symmetrical ligands were prepared and subjected to complexation. Two different coordination modes, Pd(N,N)- or Pd(C,N,N)-pyrma, have been evidenced depending on the substitution of the pyrimidine ring and the nature or the shape of the additional pendant arm. In a non-symmetrical pyrimidine series, the substituent-induced discrimination of each heterocyclic nitrogen atom provoked regio-controlled coordination to the metal center. The molecular structure of pyrma-Pd(II) complexes in the solution state has been elucidated thanks to combined NMR experiments and DFT calculations. This study highlights the potency of (15)N and (13)C NMR spectroscopy for the elucidation of the regio-selective coordination to the Pd(II) in the pyrma-based complex series. DFT calculations were highly relevant to the identification of crucial factors that govern the regio-selectivity and the complexation modes. Close predicted and experimental chemical shift values put into relief the reliability of coordination modes for the most stable complexes in solution, depicted by DFT approaches.


Improving the strategy and performance of molecularly imprinted polymers using cross-linking functional monomers.
A new strategy for monomer design has been investigated that combines interactive monomer functionality with a cross-linking format, giving as a result noncovalent molecularly imprinted polymers (MIPs) with improved performance. This strategy was explored under the premise that more functionality could be introduced without suffering performance losses due to reduced cross-linking. While this proved to be correct, equally important contributions to selectivity enhancement at the molecular level by conformation control and diastereomeric complexation were also discovered. Monomers derived from l-serine and l-aspartic acid were synthesized and used to prepare MIPs, with the best performance obtained for the MIP formulated with the serine-based cross-linker (N,O-bis-methacryloyl l-serine, 3), versus the aspartic-acid-based cross-linkers and the traditional methacrylic acid/ethylene glycol dimethacrylate (MAA/EGDMA) formulation. Quantitative structure-selectivity relationship (QSSR) studies revealed that the improved performance of 3 was due to three key factors: (1) the cross-linking nature of this monomer; (2) control of conformational flexibility; (3) a strong influence of monomer chirality on enantioselectivity in MIPs.


Association of portal hypertension and ruptured splenic artery aneurysm in pregnancy.
Spontaneous rupture of a splenic artery aneurysm is a rare, usually catastrophic event complicating pregnancy. Among risk factors for splenic artery aneurysm in nonpregnant patients is portal hypertension. The third case of rupture of splenic artery aneurysm in a patient with portal hypertension is reported, and previous reports are reviewed. In each of these cases the portal hypertension was due to hepatic cirrhosis. A previously unreported association between portal hypertension in pregnancy and rupture of a splenic artery aneurysm is presented.


Anti-epidermal growth factor receptor targeted therapy-associated ulcerations.
The well-studied role of epidermal growth factor receptor (EGFR) in metastatic colorectal cancer (mCRC) and non-small cell lung cancer (NSCLC) has enabled the development of drugs that target this molecule, including panitumumab for the former and osimertinib for the latter. Oral adverse events due to those agents are rarely described in the literature and their exact characterization is hampered by inadequate reporting and/or incorrect terminology used. We report two cases of panitumumab- and osimertinib-associated oral ulcerations with emphasis on their possible pathogenesis and optimal management.


Microfluidic-enhanced 3D bioprinting of aligned myoblast-laden hydrogels leads to functionally organized myofibers in vitro and in vivo.
We present a new strategy for the fabrication of artificial skeletal muscle tissue with functional morphologies based on an innovative 3D bioprinting approach. The methodology is based on a microfluidic printing head coupled to a co-axial needle extruder for high-resolution 3D bioprinting of hydrogel fibers laden with muscle precursor cells (C2C12). To promote myogenic differentiation, we formulated a tailored bioink with a photocurable semi-synthetic biopolymer (PEG-Fibrinogen) encapsulating cells into 3D constructs composed of aligned hydrogel fibers. After 3-5 days of culture, the encapsulated myoblasts started migrating and fusing, forming multinucleated myotubes within the 3D bioprinted fibers. The obtained myotubes showed high degree of alignment along the direction of hydrogel fiber deposition, further revealing maturation, sarcomerogenesis, and functionality. Following subcutaneous implantation in the back of immunocompromised mice, bioprinted constructs generated organized artificial muscle tissue in vivo. Finally, we demonstrate that our microfluidic printing head allows to design three dimensional multi-cellular assemblies with an exquisite compartmentalization of the encapsulated cells. Our results demonstrate an enhanced myogenic differentiation with the formation of parallel aligned long-range myotubes. The approach that we report here represents a robust and valid candidate for the fabrication of macroscopic artificial muscle to scale up skeletal muscle tissue engineering for human clinical application.


Retrograde intramedullary osteosynthesis of femoral fracture: preliminary results of Maggiore Hospital.
The Distal Femoral Nail (DFN), Mathys Medical Ltd. Switzerland) was used in our division for the treatment of fractures of the distal metaepiphysis, and in some cases of the diaphysis, of the femur. A total of 16 cases treated over 30 months, between October 2000 and March 2003 (minimum 6, maximum 61 months), were analyzed retrospectively. A total of 11 metaepiphyseal fractures (65%) and 6 diaphyseal fractures (35%) were treated. Consolidation of the fracture was observed in 15 cases out of 16 (equal to 93.8%) with a mean time of 140 days (minimum 120 days, maximum 240 days) after surgery. Mean flexion of the knee equal to 90 degrees and 3 cases of stiffness with lower mobility at 45 degrees were observed: in 2 cases stiffness was of extra-articular origin caused by exuberant bone callus. There were no iatrogenic complications of the vascular type, nor were there infections, or cases of implant loosening. Shortening (1 cm) in a type B2 fracture (based on the AO classification) was observed. The results we obtained suggest that DFN represents a valid alternative to the open treatment of fractures of the distal metaphysis of the femur; in cases of patients with multiple trauma or in elderly patients where invasiveness is reduced, importance is awarded to less blood loss, a shorter amount of time required for surgery, and early mobilization and weight-bearing.


Effect of glutamine on change in early postoperative intestinal permeability and its relation to systemic inflammatory response.
To study the effects of glutamine (Gln) on the change of intestinal permeability and its relationship to systemic inflammatory response in early abdominal postoperative patients. A prospective, randomized, double-blind and controlled trial was taken. Twenty patients undergoing abdominal surgery were randomized into Gln group (oral administration of glutamine, 30 g/d, for 7 d, n=10) and placebo group (oral administration of placebo, 30 g/d, for 7 d, n=10). Temperatures and heart rates of all patients were daily recorded. White blood cell counts(WBC) and biochemical variables were measured before operation and 4 and 7 d after drug administration. Serum concentrations of glutamine, endotoxin, diamine oxidase and malondialdehyde and urine lactulose/mannito (L/M) ratio were measured before and 7 d after drug administration. The patients in the 2 groups were comparable prior to drug administration. Serum Gln concentration was significantly decreased in the placebo group and increased in the Gln group 7 d after drug administration. Urine L/M ratio was significantly increased in the placebo group and decreased in the Gln group. The serum concentration of endotoxin, diamine oxidase and malondialdehyde was significantly decreased in the Gln group compared with those in the placebo group. Temperatures, heart rates and WBC counts were significantly lower in the Gln group than those in the placebo group. Gut is one of the sources of systemic inflammatory response in abdominal postoperative patients and glutamine can decrease intestinal permeability, maintain intestinal barrier and attenuate systemic inflammatory response in early postoperative patients.


Adolescent obesity in the past decade: A systematic review of genetics and determinants of food choice.
As the incidence of global obesity increases, concerns about adverse health outcomes in adolescents continues to rise. The complexity and expense of this problem require early recognition and specific preventive treatments. Knowledge of genetics and determinants of food choices contributing to adolescent obesity warrants further examination. The primary goal was to appraise the literature from the past decade (2007-2017) on the current state of food choice and genetic determinants of adolescent overweight/obesity in the United States. The secondary goal was to determine trends in the literature and areas for future research. A systematic review of research studies in the United States from 2007 to 2017 was completed. Database searches were conducted using CINAHL, Embase, PsycINFO, PsycArticles, PubMed, Scopus, Academic Search Complete, Web of Science, BIOSIS, and the Cochrane Library. A total of 535 studies were selected. Of these, 283 studies focused on determinants of food choices and 165 studies focused on genetic factors. A total of 41 full-text articles included in this literature review contained studies limited exclusively to adolescents. Stress factors related to food choices demonstrated a new trend being explored. The need for precision health, the application of genetic information, could uncover ways food choices affect adolescent obesity. The etiology of adolescent obesity requires that nurses gain knowledge of genetics and food choice determinants to inform personalized treatments for adolescents, which may establish effective interventions that promote healthy weight achievement.


Attenuation of ANG II actions by adenovirus delivery of AT1 receptor antisense in neurons and SMC.
Both central and peripheral renin-angiotensin systems (RAS) are important in the development and establishment of hypertension. Thus, introducing genes relevant to RAS into neuronal and vascular smooth muscle (VSM) cells, two major targets for angiotensin (ANG) II action, is a prerequisite in considering a gene therapy approach for the control of ANG-dependent hypertension. In this study, we explored the use of adenoviral (Ad) vector to transfer AT1 receptor antisense cDNA (AT1R-AS) into neuronal and VSM cells with the anticipation of attenuation of ANG II-mediated cellular actions. Incubation of neurons and VSM cells with viral particles containing AT1R-AS (Ad-AT1R-AS) resulted in a robust expression of AT1R-AS in a majority (approximately 80%) of the cells. The expression was persistent for at least 28 days and was associated with decreases in the immunoreactive AT1 receptor protein and the maximal binding for AT1 receptor in a time- and dose-dependent manner in both cell types. ANG II stimulation of [3H]thymidine incorporation in VSM cells and norepinephrine transporter gene expression in neuronal cells were attenuated by Ad-AT1R-AS infection. Uninfected cells or cells infected with adenovirus particles containing a mutant AT1 receptor sense cDNA showed no effects on either AT1 receptor or on attenuation of ANG II's cellular affects. These observations show, for the first time, that adenovirus can be used to deliver AT1 receptor mutant sense and antisense cDNAs into two major ANG II target tissues. This consequently influences AT1 receptor-mediated cellular actions of ANG II.


An alphaTropomyosin mutation alters dimer preference in nemaline myopathy.
Nemaline myopathy is a human neuromuscular disorder associated with muscle weakness, Z-line accumulations (rods), and myofibrillar disorganization. Disease-causing mutations have been identified in genes encoding muscle thin filament proteins: actin, nebulin, slow troponin T, betaTropomyosin, and alphaTropomyosin(slow). Skeletal muscle expresses three tropomyosin (Tm) isoforms from separate genes: alphaTm(fast)(alphaTm, TPM1), betaTm (TPM2), and alphaTm(slow) (gammaTm, TPM3). In this article, we show that the level of betaTm, but not alphaTm(fast) protein, is reduced in human patients with mutations in alphaTm(slow) and in a transgenic mouse model of alphaTm(slow)(Met9Arg) nemaline myopathy. A postnatal time course of Tm expression in muscles of the mice indicated that the onset of alphaTm(slow)(Met9Arg) expression coincides with the decline of betaTm. Reduction of betaTm levels is independent of the degree of pathology (rods) within a muscle and is detected before the onset of muscle weakness. Thus, reduction in the level of betaTm represents an early clinical diagnostic marker for alphaTm(slow)-based mutations. Examinations of tropomyosin dimer formation using either recombinant proteins or sarcomeric extracts show that the mutation reduces the formation of the preferred alpha/beta heterodimer. We suggest this perturbation of tropomyosin isoform levels and dimer preference alters sarcomeric thin filament dynamics and contributes to muscle weakness in nemaline myopathy.


Streptococcus constellatus Tubo-ovarian Abscess in a Non-Sexually Active Adolescent Female.
Tubo-ovarian abscess (TOA) in non-sexually active female adolescents is a rare presentation to the pediatric emergency department. In the following case, bilateral TOA secondary to Streptococcus constellatus was diagnosed in a 13-year-old virginal female. The patient was seen 4 months before presentation for interventional radiology-guided drainage and antibiotic treatment for an intra-abdominal abscess due to suspected appendiceal rupture. Exploratory laparotomy on the most recent presentation demonstrated an appendix with inflammation and serositis on pathology report, a concern for chronic appendicitis with microperforation and subsequent bacterial translocation of the bilateral ovaries. This case report identifies a rare cause, pathogen, and the patient's demographics presenting with bilateral TOA. Most importantly, this case demonstrates the need for emergency medicine physicians to have a high index of suspicion for TOA in patients with a significant medical history of intra-abdominal pathology to promptly diagnose and treat high-morbidity pathology.


Fusion activation through attachment protein stalk domains indicates a conserved core mechanism of paramyxovirus entry into cells.
Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. However, the sequence of events that closely links the timing of receptor recognition by HN, H, or G and the "triggering" interaction of the attachment protein with F is unclear. F activation results in F undergoing a series of irreversible conformational rearrangements to bring about membrane merger and virus entry. By extensive study of properties of multiple paramyxovirus HN proteins, we show that key features of F activation, including the F-activating regions of HN proteins, flexibility within this F-activating region, and changes in globular head-stalk interactions are highly conserved. These results, together with functionally active "headless" mumps and Newcastle disease virus HN proteins, provide insights into the F-triggering process. Based on these data and very recently published data for morbillivirus H and henipavirus G proteins, we extend our recently proposed "stalk exposure model" to other paramyxoviruses and propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion. Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes. We describe here the molecular mechanism by which HN activates the F protein such that virus-cell fusion is controlled and occurs at the right time and the right place. We extend our recently proposed "stalk exposure model" first proposed for parainfluenza virus 5 to other paramyxoviruses and propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion.


Excess densities and equimolar surfaces for spherical cavities in water.
For hard spheres with a radius up to 10 A in TIP4P water under ambient conditions, the author studies how the excess number of molecules at the accessible surface depends on the radius of the cavity. Simulation results derived from excess volumes are discussed in terms of radial distribution functions (rdfs), which compare well with extended simple point charge and theoretical rdfs from the literature. The excess number of molecules at the accessible surface inserted in the expression which refers to an arbitrary dividing surface enables one to find the position of the equimolar surface. The surface tension corresponding to this dividing surface was obtained from values of the free energy of cavity formation. For radii in the range of the simulation data, its behavior with curvature is quite different from that usually shown in the literature. A model, which describes how the excess number of molecules at the accessible surface changes with the radius, is discussed in the large length limit by examining consistent rdfs described by a simple analytical form. The inclusion in the model of a logarithmic term has also been considered. Comparison with theoretical results from the literature shows a good agreement for a cavity with a radius of 20 A. For a radius of 100 A and beyond, the model predicts instead sharper density profiles. Such differences have a poor effect on the surface tension at the equimolar surface.


Robust subgraph counting with distribution-free random graph analysis.
Subgraphs such as cliques, loops, and stars play a crucial role in real-world networks. Random graph models can provide estimates for how often certain subgraphs appear, which can be tested against real-world networks. These estimated subgraph counts, however, crucially depend on the assumed degree distribution. Fitting a degree distribution to network data is challenging, in particular, for scale-free networks with power-law degrees. Therefore, in this paper we develop robust subgraph counts that do not depend on the entire degree distribution but only on its mean and mean absolute deviation (MAD), summary statistics that are easy to obtain for most real-world networks. By solving an optimization problem, we provide tight (the sharpest possible) bounds for the subgraph counts, for all possible subgraphs, and for all networks with degree distributions that share the same mean and MAD. We identify the extremal random graph that attains these tight bounds as the graph with a specific three-point degree distribution. We leverage the bounds on the maximal subgraph counts to obtain robust scaling laws for how the number of subgraphs grows as a function of the network size. The scaling laws indicate that sparse power-law networks are not the most extreme networks in terms of subgraph counts but dense power-law networks are. The robust bounds are also shown to hold for several real-world data sets.


Development of a Clinical Decision Rule for the Early Safe Discharge of Patients with Mild Traumatic Brain Injury and Findings on Computed Tomography Brain Scan: A Retrospective Cohort Study.
International guidelines recommend routine hospital admission for all patients with mild traumatic brain injury (TBI) who have injuries on computed tomography (CT) brain scan. Only a small proportion of these patients require neurosurgical or critical care intervention. We aimed to develop an accurate clinical decision rule to identify low-risk patients safe for discharge from the emergency department (ED) and facilitate earlier referral of those requiring intervention. A retrospective cohort study of case notes of patients admitted with initial Glasgow Coma Scale 13-15 and injuries identified by CT was completed. Data on a primary outcome measure of clinically important deterioration (indicating need for hospital admission) and secondary outcome of neurosurgery, intensive care unit admission, or intubation (indicating need for neurosurgical admission) were collected. Multi-variable logistic regression was used to derive models and a risk score predicting deterioration using routinely reported clinical and radiological candidate variables identified in a systematic review. We compared the performance of this new risk score with the Brain Injury Guideline (BIG) criteria, derived in the United States. A total of 1699 patients were included from three English major trauma centers. A total of 27.7% (95% confidence interval [CI], 25.5-29.9) met the primary and 13.1% (95% CI, 11.6-14.8) met the secondary outcomes of deterioration. The derived clinical decision rule suggests that patients with simple skull fractures or intracranial bleeding <5 mm in diameter who are fully conscious could be safely discharged from the ED. The decision rule achieved a sensitivity of 99.5% (95% CI, 98.1-99.9) and specificity of 7.4% (95% CI, 6.0-9.1) to the primary outcome. The BIG criteria achieved the same sensitivity, but lower specificity (5%). Our empirical models showed good predictive performance and outperformed the BIG criteria. This would potentially allow ED discharge of 1 in 20 patients currently admitted for observation. However, prospective external validation and economic evaluation are required.


Compounds from gum ammoniacum with acetylcholinesterase inhibitory activity.
The use of herbal medicinal preparations in dementia therapy has been studied based on experience from traditional medicine. A dichloromethane extract of gum ammoniacum, the gum-resin from Dorema ammoniacum D. Don had shown acetylcholinesterase (AChE) inhibitory activity in a previous study. The aim of this study was the isolation and characterization of the active compounds from this resin. The extract was investigated by a respective colorimetric microplate assay and the active zones were identified via TLC bioautography and isolated using several chromatographic techniques. The structures of the active components were characterized by one- and two-dimensional (1)H and (13)C NMR spectroscopy and mass spectrometry as (2'S,5'S)-2'-ethenyl-5'-(3-hy-droxy-6-methyl-4-oxohept-5-en-2-yl)-7-methoxy-2'-methyl-4H-spiro[chromene-3,1'-cyclopentane]-2,4-dione (1), which is an analogue of doremone A and a new natural compound, and as (2'S,5'R)-2'-ethenyl-5'-[(2R,4R)-4-hydroxy-6-methyl-3-oxohept-5-en-2-yl]-7-methoxy-2'-methyl-4H-spiro[chromene-3,1'-cyclo-pentane]-2,4-dione (2 = doremone A), (4E,8E)-1-(2,4-dihydroxyphenyl)-5,9,13-trimethyltetradeca-4,8,12-trien-1-one (3 = dshamirone), and 4,7-dihydroxy-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]-2H-chromen-2-one (4 = am-moresinol). Dshamirone turned out to be the most active compound with an IC50 value for AChE inhibitory activity of 23.5 μM, whereas the other substances showed weak activity. The concentrations of the analytes in the resin were determined by HPLC as 3.1%, 4.6%, 1.9%, and 9.9%, respectively.


Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry.
The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis. A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M. tuberculosis genome promoted uptake into HeLa cells of polystyrene latex microspheres coated with the protein. N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity. Mce1 contained hydrophobic stretches at the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron microscopy indicated that the corresponding native protein is expressed on the surface of the M. tuberculosis organism. The complete M. tuberculosis genome sequence revealed that it contained four homologues of mce (mce1, mce2, mce3, mce4) and that they were all located within operons composed of genes arranged similarly at different locations in the chromosome. Recombinant Mce2, which had the highest level of identity (67%) to Mce1, was unable to promote the association of microspheres with HeLa cells. Although the exact function of Mce1 is still unknown, it appears to serve as an effector molecule expressed on the surface of M. tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells.


The generation of detergent-insoluble clipped fragments from an ERAD substrate in mammalian cells.
Proteostasis ensures the proper synthesis, folding, and trafficking of proteins and is required for cellular and organellar homeostasis. This network also oversees protein quality control within the cell and prevents accumulation of aberrant proteins, which can lead to cellular dysfunction and disease. For example, protein aggregates irreversibly disrupt proteostasis and can exert gain-of-function toxic effects. Although this process has been examined in detail for cytosolic proteins, how endoplasmic reticulum (ER)-tethered, aggregation-prone proteins are handled is ill-defined. To determine how a membrane protein with a cytoplasmic aggregation-prone domain is routed for ER-associated degradation (ERAD), we analyzed a new model substrate, TM-Ubc9ts. In yeast, we previously showed that TM-Ubc9ts ERAD requires Hsp104, which is absent in higher cells. In transient and stable HEK293 cells, we now report that TM-Ubc9ts degradation is largely proteasome-dependent, especially at elevated temperatures. In contrast to yeast, clipped TM-Ubc9ts polypeptides, which are stabilized upon proteasome inhibition, accumulate and are insoluble at elevated temperatures. TM-Ubc9ts cleavage is independent of the intramembrane protease RHBDL4, which clips other classes of ERAD substrates. These studies highlight an unappreciated mechanism underlying the degradation of aggregation-prone substrates in the ER and invite further work on other proteases that contribute to ERAD.


Sex-dependent prefrontal cortex activation in regular cocaine users: A working memory functional magnetic resonance imaging study.
Although two thirds of patients with a cocaine use disorder (CUD) are female, little is known about sex differences in the (neuro)pathology of CUD. The aim of this explorative study was to investigate sex-dependent differences in prefrontal cortex (PFC) functioning during a working memory (WM) functional magnetic resonance imaging (fMRI) task in regular cocaine users (CUs), as PFC deficits are implicated in the shift from recreational cocaine use to CUD. Neural activation was measured using fMRI during a standard WM task (n-back task) in 27 male and 28 female CUs and in 26 male and 28 female non-cocaine users (non-CUs). Although there were no main or interaction effects of sex and group on n-back task performance, WM-related (2-back > 0-back) PFC functioning was significantly moderated by sex and group: female compared with male CUs displayed higher WM-related activation of the middle frontal gyrus (MFG), whereas female compared with male non-CUs displayed lower WM-related MFG activation. Additionally, WM-related activation of the inferior frontal gyrus, insula, and putamen was negatively associated with cocaine use severity in female but not male CUs. These data support the hypothesis of sex-dependent PFC differences in CUs and speculatively suggest that PFC deficits may be more strongly implicated in the development, continuation, and possibly treatment of CUD in females. Most importantly, the current data stress the importance of studying both males and females in psychiatry research as not doing so could greatly bias our knowledge of CUD and other psychiatric disorders.


Surgery for hydrocephalus in sub-Saharan Africa versus developed nations: a risk-adjusted comparison of outcome.
Surgery for children in developing nations is challenging. Endoscopic third ventriculostomy (ETV) is an important surgical treatment for childhood hydrocephalus and has been performed in developing nations, but with lower success rates than in developed nations. It is not known if the lower success rate is due to inherent differences in prognostic factors. We analyzed a large cohort of children (≤20 years old) treated with ETV in developed nations (618 patients from Canada, Israel, United Kingdom) and developing nations of sub-Saharan Africa (979 patients treated in Uganda). Risk-adjusted survival analysis was performed. The risk of an intra-operative ETV failure (an aborted procedure) was significantly higher in Uganda regardless of risk adjustment (hazard ratio (HR), 95% confidence interval (CI), 11.00 (6.01 to 19.84) P<0.001). After adjustment for patient prognostic factors and technical variation in the procedure (the use of choroid plexus cauterization), there was no difference in the risk of failure for completed ETVs (HR, 95% CI, 1.04 (0.83 to 1.29), P=0.74). Three factors account for all significant differences in ETV failure between Uganda and developed nations: patient prognostic factors, technical variation in the procedure, and intra-operatively aborted cases. Once adjusted for these, the response to completed ETVs of children in Uganda is no different than that of children in developed nations.


Changes in occupational class differences in leisure-time physical activity: a follow-up study.
Physical activity is known to have health benefits across population groups. However, less is known about changes over time in socioeconomic differences in leisure-time physical activity and the reasons for the changes. We hypothesised that class differences in leisure-time physical activity would widen over time due to declining physical activity among the lower occupational classes. We examined whether occupational class differences in leisure-time physical activity change over time in a cohort of Finnish middle-aged women and men. We also examined whether a set of selected covariates could account for the observed changes. The data were derived from the Helsinki Health Study cohort mail surveys; the respondents were 40-60-year-old employees of the City of Helsinki at baseline in 2000-2002 (n = 8960, response rate 67%). Follow-up questionnaires were sent to the baseline respondents in 2007 (n = 7332, response rate 83%). The outcome measure was leisure-time physical activity, including commuting, converted to metabolic equivalent tasks (MET). Socioeconomic position was measured by occupational class (professionals, semi-professionals, routine non-manual employees and manual workers). The covariates included baseline age, marital status, limiting long-lasting illness, common mental disorders, job strain, physical and mental health functioning, smoking, body mass index, and employment status at follow-up. Firstly the analyses focused on changes over time in age adjusted prevalence of leisure-time physical activity. Secondly, logistic regression analysis was used to adjust for covariates of changes in occupational class differences in leisure-time physical activity. At baseline there were no occupational class differences in leisure-time physical activity. Over the follow-up leisure-time physical activity increased among those in the higher classes and decreased among manual workers, suggesting the emergence of occupational class differences at follow-up. Women in routine non-manual and manual classes and men in the manual class tended to be more often physically inactive in their leisure-time (<14 MET hours/week) and to be less often active (>30 MET hours/week) than those in the top two classes. Adjustment for the covariates did not substantially affect the observed occupational class differences in leisure-time physical activity at follow-up. Occupational class differences in leisure-time physical activity emerged over the follow-up period among both women and men. Leisure-time physical activity needs to be promoted among ageing employees, especially among manual workers.


Fetomaternal bleeding following diagnostic amniocentesis.
The frequency of diagnostic amniocentesis is increasing. Fetal bleeding and trauma have long been recognized to be complications of amniocentesis. For detection of fetomaternal bleeding, efficacy of modified Kleihauer-Betke staining and alpha-fetoprotein elevation in maternal blood was assessed. Preamniocentesis ultrasound scanning was found useful in reducing the incidence of fetomaternal bleeding and bloody taps. Elevation of alpha-fetoprotein was found to be a more sensitive indicator of fetomaternal bleeding than was modified Kleihauer-Betke staining. The use of alpha-fetoprotein to detect fetomaternal bleeding associated with amniocentesis is suggested for the identification of Rh-negative patients requiring anti-D gamma-globulin to prevent sensitization.


Interleukin 7 regulates the survival and generation of memory CD4 cells.
Cytokines, particularly those of the common gamma chain receptor family, provide extrinsic signals that regulate naive CD4 cell survival. Whether these cytokines are required for the maintenance of memory CD4 cells has not been rigorously assessed. In this paper, we examined the contribution of interleukin (IL) 7, a constitutively produced common gamma chain receptor cytokine, to the survival of resting T cell receptor transgenic memory CD4 cells that were generated in vivo. IL-7 mediated the survival and up-regulation of Bcl-2 by resting memory CD4 cells in vitro in the absence of proliferation. Memory CD4 cells persisted for extended periods upon adoptive transfer into intact or lymphopenic recipients, but not in IL-7- mice or in recipients that were rendered deficient in IL-7 by antibody blocking. Both central (CD62L+) and effector (CD62L-) memory phenotype CD4 cells required IL-7 for survival and, in vivo, memory cells were comparable to naive CD4 cells in this regard. Although the generation of primary effector cells from naive CD4 cells and their dissemination to nonlymphoid tissues were not affected by IL-7 deficiency, memory cells failed to subsequently develop in either the lymphoid or nonlymphoid compartments. The results demonstrate that IL-7 can have previously unrecognized roles in the maintenance of memory in the CD4 cell population and in the survival of CD4 cells with a capacity to become memory cells.


Effects of undercover police stings of gun dealers on the supply of new guns to criminals.
To assess the effects of undercover police stings and lawsuits against gun dealers suspected of facilitating illegal gun sales in three US cities (Chicago, Detroit, Gary) on the flow of new firearms to criminals. An interrupted time series design and negative binomial regression analyses were used to test for temporal change in the recovery of guns used in crimes within one year of retail sale in both intervention and comparison cities. The stings were associated with an abrupt 46.4% reduction in the flow of new guns to criminals in Chicago (95% confidence interval, -58.6% to -30.5%), and with a gradual reduction in new crime guns recovered in Detroit. There was no significant change associated with the stings in Gary, and no change in comparison cities that was coincident with the stings in Chicago and Detroit. The announcement of police stings and lawsuits against suspect gun dealers appeared to have reduced the supply of new guns to criminals in Chicago significantly, and may have contributed to beneficial effects in Detroit. Given the important role that gun stores play in supplying guns to criminals in the US, further efforts of this type are warranted and should be evaluated.


Prophylactic antibiotics and evaluation scheme following febrile urinary tract infection in children: a nationwide Israeli survey.
Although febrile urinary tract infections are very common in young children, the need for antimicrobial prophylaxis and evaluation following a first event is controversial. To assess the approach of leading pediatric specialists throughout israel to antimicrobial prophylaxis. A questionnaire regarding the approach to antibiotic prophylaxis and diagnostic evaluation following a first event of febrile UTI, according to age and underlying renal abnormality, was sent to all 58 directors of departments of pediatrics, units of pediatric infectious diseases and pediatric nephrology in Israel. Fifty-six directors (96%) responded. Most prescribed prophylactic antibiotics after UTI. Heads of infectious disease departments prescribed less prophylaxis following UTI at the age of 18 months than heads of pediatrics or heads of pediatric nephrology units (34% vs. 72-75%, P = 0.018), but more often in cases of severe vesico-ureteral reflux without UTI. Cephalosporins were used prophylactically more often by directors of pediatrics compared to heads of pediatric nephrology units (71% vs. 38%, P = 0.048); the latter used non-beta-lactam prophylaxis (61% vs. 23%, P = 0.013) more often. Most pediatricians used renal sonography for evaluation; renal scan was used more commonly by pediatric nephrologists. The administration of prophylactic antibiotics after UTI is still common practice among pediatric opinion leaders, although the specific approach differs by subspecialty. According to the latest evidence-based data, educational efforts are needed to formulate and implement judicious guidelines.


Sca-1+ cardiac stem cells mediate acute cardioprotection via paracrine factor SDF-1 following myocardial ischemia/reperfusion.
Cardiac stem cells (CSCs) promote myocardial recovery following ischemia through their regenerative properties. However, little is known regarding the implication of paracrine action by CSCs in the setting of myocardial ischemia/reperfusion (I/R) injury although it is well documented that non-cardiac stem cells mediate cardioprotection via the production of paracrine protective factors. Here, we studied whether CSCs could initiate acute protection following global myocardial I/R via paracrine effect and what component from CSCs is critical to this protection. A murine model of global myocardial I/R was utilized to investigate paracrine effect of Sca-1+ CSCs on cardiac function. Intracoronary delivery of CSCs or CSC conditioned medium (CSC CM) prior to ischemia significantly improved myocardial function following I/R. siRNA targeting of VEGF in CSCs did not affect CSC-preserved myocardial function in response to I/R injury. However, differentiation of CSCs to cardiomyocytes (DCSCs) abolished this protection. Through direct comparison of the protein expression profiles of CSCs and DCSCs, SDF-1 was identified as one of the dominant paracrine factors secreted by CSCs. Blockade of the SDF-1 receptor by AMD3100 or downregulated SDF-1 expression in CSCs by specific SDF-1 siRNA dramatically impaired CSC-induced improvement in cardiac function and increased myocardial damage following I/R. Of note, CSC treatment increased myocardial STAT3 activation after I/R, whereas downregulation of SDF-1 action by blockade of the SDF-1 receptor or SDF-1 siRNA transfection abolished CSC-induced STAT3 activation. In addition, inhibition of STAT3 activation attenuated CSC-mediated cardioprotection following I/R. Finally, post-ischemic infusion of CSC CM was shown to significantly protect I/R-caused myocardial dysfunction. This study suggests that CSCs acutely improve post-ischemic myocardial function through paracrine factor SDF-1 and up-regulated myocardial STAT3 activation.


An integrated approach to assessing the viability of eradicating BVD in Scottish beef suckler herds.
The viability of eradicating bovine viral diarrhoea (BVD) in Scottish suckler herds is dependent on the continued compliance with eradication schemes. At the farm level, the costs of BVD have been identified in previous studies and show a substantial financial imperative to avoid infection. At a regional level the incentives of BVD eradication to individuals are unclear, for example the requirement for vaccination strategies despite achieving disease-free status. Ensuring farmer compliance with an eradication scheme is therefore difficult. Experience of eradicating BVD from beef-dominated areas is limited and theoretical models have tended to focus on the dairy sector. Here we present a stochastic epidemiological model of a typical beef suckler herd to explore the interaction of a farm with a regional pool of replacements, utilising information from a BVD virus seroprevalence survey of Scottish beef suckler herds. Our epidemiological model is then used to assess the relative costs to individuals assuming different regional endemic prevalences, which are used to represent the likelihood of BVD re-introduction. We explore the relative cost of BVD, taken as likelihood and consequence, at an endemic steady state in contrast to previous models that have assumed the introduction or control of BVD in an epidemic state (e.g. a closed and mostly susceptible population). Where endemic, BVD is unlikely to affect all farms evenly and will cost most farmers very little due to herd immunity or self-clearance of the virus. Compliance is likely to be boosted by pump-priming to initiate and complete eradication schemes with cost-sharing.


IMPROVED EXPERIMENTAL MODEL TO EVALUATE SUBMUCOSAL INJECTION SOLUTIONS FOR ENDOSCOPIC SUBMUCOSAL DISSECTION.
Endoscopic submucosal dissection carries an increased risk of bleeding and perforation. The creation of a long lasting submucosal cushion is essential for the safe and complete removal of the lesion. There is not a suitable experimental model for evaluation of the durability of the cushioning effect of different solutions. To describe an improved experimental model to evaluate submucosal injection solutions. A total of four domestic pigs were employed to evaluate two different submucosal fluid solutions in the gastric submucosa. After midline laparotomy, the anterior gastric wall was incised from the gastric body to the antrum and its mucosal surface was exposed by flipping inside out the incised gastric wall. Two different solutions (10% mannitol and normal saline) were injected in the submucosa of the anterior wall of the distal gastric body. All submucosal cushions were injected until they reach the same size, standardized as 1.0 cm in height and 2.0 cm in diameter. A caliper and a ruler were employed to guarantee accuracy of the measurements. All four animal experiments were completed. All submucosal cushions had the exact same size measured with caliper and a ruler. By using the mannitol solution, the mean duration of the submucosal cushion was longer than the saline solution: 20 and 22 min (mean, 21 min) vs 5 and 6 min (mean, 5.5 min) This experimental model is simple and evaluate the duration, size, and effect of the submucosal cushion, making it more reliable than other models that employ resected porcine stomachs or endoscopic images in live porcine models.


Variations of Surveillance Practice for Patients with Bone Sarcoma: A Survey of Australian Sarcoma Clinicians.
Introduction. After treatment, bone sarcoma patients carry a high chance of relapse and late effects from multimodal therapy. We hypothesize that significant variation in surveillance practice exists between pediatric medical oncology (PO) and nonpediatric medical oncology (NP) sarcoma disciplines. Methods. Australian sarcoma clinicians were approached to do a web based survey that assessed radiologic surveillance (RS) strategies, late toxicity assessment, and posttreatment psychosocial interventions. Results. In total, 51 clinicians responded. No differences were identified in local disease RS. In metastatic disease response assessment, 100% of POs (23/23) and 93% of NPs (24/26) conducted CT chest. However, this was more likely to occur for NPs in the context of a CT chest/abdomen/pelvis (NP: 10/26; PO: 1/23; p = 0.006). POs were more likely to use CXR for RS (p = 0.006). POs showed more prescriptive intensity in assessment of heart function (p = 0.001), hearing (p < 0.001), and fertility (p = 0.02). POs were more likely to deliver written information for health maintenance/treatment summary (p = 0.04). The majority of respondents described enquiring about psychosocial aspects of health (n = 33/37, 89%), but a routine formal psychosocial screen was only used by 23% (n = 6/26). Conclusion. There is high variability in bone sarcoma surveillance between PO and NP clinicians. Efforts to harmonize approaches would allow early and late effects recognition/intervention and facilitate improved patient care/transition and research.


An assessment of the impact of SiO2 nanoparticles of different sizes on the rest/wake behavior and the developmental profile of zebrafish larvae.
In this study, zebrafish larvae are introduced as an in vivo platform to examine the neurotoxicity and developmental toxicity associated with continuous exposure to a concentration gradient of different sizes of SiO2 nanoparticles (15 nm and 50 nm diameter) to determine the dose effect and size effect of SiO2 nanoparticle (NP)-induced toxicity. Bovine serum albumin (BSA-V) is utilized as a stabilizing agent to prevent coagulation of the SiO2 nanoparticles. To the best of our knowledge, this study is the first to describe locomotor activity assays linking rest/wake behavioral profiles for the purpose of investigating the neurotoxicity of NPs. In addition, developmental toxicological endpoints including mortality, LC50 , malformation, and cartilaginous deformity are assessed. The results show a concentration-dependent increase in behavioral neurotoxicity, mortality, and malformation among larvae treated with the SiO2 nanoparticles of 15 nm and 50 nm. A comparison of the 15 nm and 50 nm NPs by K-means clustering analysis demonstrates that the 15 nm NPs have a greater neurotoxic effect than the 50 nm NPs, with the 50 nm NPs exhibiting greater developmental toxicity on the zebrafish larvae than the 15 nm NPs.


Neuropeptide Y is involved in the regulation of quiescence of hematopoietic stem cells.
Differentiation, self-renewal and quiescence of Hematopoietic stem cells (HSCs) is tightly regulated in order to protect the HSCs from the strain of constant cell division and depletion of the stem cell pool. The neurotransmitter Neuropeptide Y (NPY) is released from sympathetic nerves in the bone marrow and has been shown to indirectly affect HSC function through effects on bone marrow (BM) multipotent Mesenchymal Stromal Cells (MSCs), osteoblasts (OBs) and macrophages. Although the absence of NPY has been shown to be accompanied by severe BM impairment and delayed engraftment of HSCs, the direct effects of NPY on HSCs have never been assessed. Here, we aimed to explore the effect of NPY on the regulation of HSCs. All NPY receptors Y1, Y2, Y4 and Y5 were found to be highly expressed on most HSCs and mature hematopoietic cell subsets. In culture, in particularly expression of the Y1 receptor was shown to decrease in time. Doses of 300 nM NPY suppressed HSC proliferation in cell cultures, as confirmed by an increase of HSCs in G0 phase and an increase in the gene expression levels of FOXO3, DICER1, SMARCA2 and PDK1, which all have been shown to play an important role in the regulation of cell quiescence. These data support the idea that NPY may have a direct effect on the regulation of HSC fate by modulating cell quiescence.


Kyphosis and review of the literature.
The term kyphosis is used to describe the spinal curve that results in an abnormally rounded back. Kyphosis may develop due to trauma, developmental anomalies, degenerative disc disease, inflammatory diseases, and infectious diseases and also iatrogenic. The aim of this paper is to review the etiopathognesis and the treatment management of kyphosis. A search in the National Library of Medicine (Pubmed) database using key word 'kyphosis' and was made. For the literature review, papers concerning etiopathogenesis, classification and treatment were selected among these papers. A search in the National Library of Medicine (Pubmed) database using key word 'kyphosis' yielded 7506 papers published between 1916 and 2013. The main papers about kyphosis were congenital, Scheuermann, tumour related, neuromuscular, posttraumatic, infectionrelated, iatrogenic kyphosis. Every patient with kyphosis should be treated based on her/his current state and needs. It should always be remembered that the patients with negative sagittal balance can compensate it with the hip flexion but it is far more difficult to compensate the positive sagittal balance. The main goal of surgery to treat the kyphotic patients is to correct the sagittal curve and also restore a spinal balance within an acceptable range above the hips and knees.


The role of telomeres in the ageing of human skin.
Skin is a self-renewing tissue that is required to go through extensive proliferation throughout the lifespan of an organism. Telomere shortening acts as a mitotic clock that prevents aberrant proliferation such as cancer. A consequence of this protection is cellular senescence and ageing. The telomerase enzyme complex maintains telomere length in germline cells and in cancer cells. Telomerase is also active in certain somatic cells such as those in the epidermis but is almost undetectable in the dermis. Increasing evidence indicates that telomerase plays a significant role in maintenance of skin function and proliferation. Mutations in telomerase component genes in the disease dyskeratosis congenita result in numerous epidermal abnormalities. Studies also indicate that telomerase activity in epidermal stem cells might have roles that go beyond telomere elongation. Telomeres in skin cells may be particularly susceptible to accelerated shortening because of both proliferation and DNA-damaging agents such as reactive oxygen species. Skin might present an accessible tissue for manipulation of telomerase activity and telomere length with the potential of ameliorating skin diseases associated with ageing.


The Draft Genome of Kochia scoparia and the Mechanism of Glyphosate Resistance via Transposon-Mediated EPSPS Tandem Gene Duplication.
Increased copy number of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene confers resistance to glyphosate, the world's most-used herbicide. There are typically three to eight EPSPS copies arranged in tandem in glyphosate-resistant populations of the weed kochia (Kochia scoparia). Here, we report a draft genome assembly from a glyphosate-susceptible kochia individual. Additionally, we assembled the EPSPS locus from a glyphosate-resistant kochia plant by sequencing select bacterial artificial chromosomes from a kochia bacterial artificial chromosome library. Comparing the resistant and susceptible EPSPS locus allowed us to reconstruct the history of duplication in the structurally complex EPSPS locus and uncover the genes that are coduplicated with EPSPS, several of which have a corresponding change in transcription. The comparison between the susceptible and resistant assemblies revealed two dominant repeat types. Additionally, we discovered a mobile genetic element with a FHY3/FAR1-like gene predicted in its sequence that is associated with the duplicated EPSPS gene copies in the resistant line. We present a hypothetical model based on unequal crossing over that implicates this mobile element as responsible for the origin of the EPSPS gene duplication event and the evolution of herbicide resistance in this system. These findings add to our understanding of stress resistance evolution and provide an example of rapid resistance evolution to high levels of environmental stress.


What keeps you up at night? Genetics professionals' distressing experiences in patient care.
To explore specific patient care experiences that genetics professionals associate with distress and the emotions engendered by those experiences. We conducted semistructured telephone interviews with clinical geneticists, genetic counselors, and genetic nurses that focused on a single distressing experience. Fourteen clinical geneticists, 25 genetic counselors, and 14 nurses were interviewed. We categorized the situations that interviewees associated with distressing patient care experiences into seven major types: patient/family decisions (27% of total situations), giving bad news (17%), colleague behavior (15%), end-of-life issues (12%), unintended outcomes (12%), difficult patients (8%), and injustice/inhumanity (8%). Interviewees reported experiencing a variety of negative emotions during these situations, including anger, guilt, helplessness, and inadequacy. The distress and resulting emotions experienced by genetic service providers must be acknowledged. Interventions are needed to assist the clinician in becoming self-aware by reflecting on experienced emotions, examining belief systems and values, and understanding the connection between their emotions and behavior. Involvement in mindfulness meditation, reflective writing, peer support groups or additional communication skill-based training could address this need. In addition, clinicians should seek ways to increase personal meaning derived from providing patient care.


Applications of Fourier Transform-Infrared spectroscopy in microbial cell biology and environmental microbiology: advances, challenges, and future perspectives.
Microorganisms play pivotal roles in shaping ecosystems and biogeochemical cycles. Their intricate interactions involve complex biochemical processes. Fourier Transform-Infrared (FT-IR) spectroscopy is a powerful tool for monitoring these interactions, revealing microorganism composition and responses to the environment. This review explores the diversity of applications of FT-IR spectroscopy within the field of microbiology, highlighting its specific utility in microbial cell biology and environmental microbiology. It emphasizes key applications such as microbial identification, process monitoring, cell wall analysis, biofilm examination, stress response assessment, and environmental interaction investigation, showcasing the crucial role of FT-IR in advancing our understanding of microbial systems. Furthermore, we address challenges including sample complexity, data interpretation nuances, and the need for integration with complementary techniques. Future prospects for FT-IR in environmental microbiology include a wide range of transformative applications and advancements. These include the development of comprehensive and standardized FT-IR libraries for precise microbial identification, the integration of advanced analytical techniques, the adoption of high-throughput and single-cell analysis, real-time environmental monitoring using portable FT-IR systems and the incorporation of FT-IR data into ecological modeling for predictive insights into microbial responses to environmental changes. These innovative avenues promise to significantly advance our understanding of microorganisms and their complex interactions within various ecosystems.


Human coronavirus OC43 nucleocapsid protein binds microRNA 9 and potentiates NF-κB activation.
The human coronavirus OC43 is a major contributor to the common cold worldwide, though due to its low mortality rate, little research has focused on this human pathogen. The nucleocapsid is an essential structural protein with conserved functions across the coronavirus family. While a multitude of studies have examined nucleocapsid function, none have described the effects of OC43 nucleocapsid on the transcription factor NF-κB. We report that the nucleocapsid protein of OC43 causes potentiation of NF-κB activation. This prolonged activation is the direct result of the ability of the nucleocapsid to bind RNA, specifically microRNA 9 (miR-9), which is a negative regulator of NF-κB. This previously undescribed interaction between virus and host is a potential mechanism of immune evasion in RNA viruses.


Retrospective dose assessment for the population living in areas of local fallout from the Semipalatinsk nuclear test site Part I: External exposure.
A short analysis of all 111 atmospheric events conducted at the Semipalatinsk Test Site (STS) in 1949-1962 with regard to significant off-site exposure (more than 5 mSv of the effective dose during the first year after the explosion) has been made. The analytical method used to assess external exposure to the residents living in settlements near the STS is described. This method makes use of the archival data on the radiological conditions, including the measurements of exposure rate. Special attention was given to the residents of Dolon and Kanonerka villages exposed mainly as a result of the first test, detonated on August 29, 1949. For the residents of those settlements born in 1935, the dose estimates calculated according to the analytical method, are compared to those derived from the thermoluminescence measurements in bricks and electron paramagnetic resonance measurements in teeth. The methods described in this paper were used for external dose assessment for the cohort members at an initial stage of an ongoing epidemiological study conducted by the U.S. National Cancer Institute in the Republic of Kazakhstan. Recently revised methods and estimates of external exposure for that cohort are given in another paper (Simon et al.) in this conference.


The sodium-glucose cotransporter isoform 1 (SGLT-1) is important for sperm energetics, motility, and fertility†.
Glucose is a key substrate for supporting sperm energy production and function. Previous studies have demonstrated that sperm glucose uptake is facilitated by several isoforms of the glucose transporters (GLUT). Here, we report that sperm also expresses the Na+-dependent sodium glucose cotransporter (SGLT). This was first suggested by our observation that genetic deletion of the testis-specific Na,K-ATPase α4, which impairs the sperm plasma membrane Na+ gradient, reduces glucose uptake and ATP production. Immunoblot analysis revealed the presence of an SGLT in sperm, with specific expression of isoform 1 (SGLT-1), but not of isoform 2 (SGLT-2). Immunocytochemistry identified SGLT-1 in the mid- and principal piece of the sperm flagellum. Inhibition of SGLT-1 with the isotype-selective inhibitor phlorizin significantly reduced glucose uptake, glycolytic activity, and ATP production in noncapacitated and capacitated sperm from wild-type mice. Phlorizin also decreased total sperm motility, as well as other parameters of sperm movement. In contrast, inhibition of SGLT-1 had no significant effect on sperm hyperactivation, protein tyrosine phosphorylation, or acrosomal reaction. Importantly, phlorizin treatment impaired the fertilizing capacity of sperm. Altogether, these results demonstrate that mouse sperm express a functional SGLT transport system that is important for supporting sperm energy production, motility, and fertility.


Health human resources and public-private partnerships: understanding their contributions to Canada's transforming healthcare environment.
This article sets out some of the main elements that characterize Canada's transforming healthcare environment and that largely form the raison d'être for new approaches to health human resources and for the emergence of public-private partnerships. It then presents core findings from a meeting of healthcare CEOs held in Banff as well as the author's views based on his experiences as president and CEO of Kingston General Hospital.


Decreased tear lipocalin concentration in patients with meibomian gland dysfunction.
Recent studies have demonstrated that tear lipocalin (TL) and phospholipids have a crucial role in maintaining tear film stability. The level of TL in patients with meibomian gland dysfunction (MGD) was examined and these data were correlated with the severity of their clinical disorder. 12 patients with obstructive MGD, 12 patients with seborrhoeic MGD, and 12 age matched normal control subjects participated in this study. 3 mul of unstimulated tears were collected with a micropipette from the inferior tear meniscus in the right eye of all subjects. Tear samples were fractionated by high performance liquid chromatography, and TL concentrations were assayed with a bicinchoninic acid technique. The mean concentration of TL in patients with obstructive and seborrhoeic MGD was significantly lower than in normal controls. TL concentration correlated positively with tear film break up time and negatively with fluorescein staining scores. These results suggest that TL deficiency may be a predisposing factor for the manifestation of symptoms in MGD.


Focused ultrasound for immuno-adjuvant treatment of pancreatic cancer: An emerging clinical paradigm in the era of personalized oncotherapy.
Current clinical treatment regimens, including many emergent immune strategies (e.g., checkpoint inhibitors) have done little to affect the devastating course of pancreatic ductal adenocarcinoma (PDA). Clinical trials for PDA often employ multi-modal treatment, and have started to incorporate stromal-targeted therapies, which have shown promising results in early reports. Focused ultrasound (FUS) is one such therapy that is uniquely equipped to address local and systemic limitations of conventional cancer therapies as well as emergent immune therapies for PDA. FUS methods can non-invasively generate mechanical and/or thermal effects that capitalize on the unique oncogenomic/proteomic signature of a tumor. Potential benefits of FUS therapy for PDA include: (1) emulsification of targeted tumor into undenatured antigens in situ, increasing dendritic cell maturation, and increasing intra-tumoral CD8+/ T regulatory cell ratio and CD8+ T cell activity; (2) reduction in intra-tumoral hypoxic stress; (3) modulation of tumor cell membrane protein localization to enhance immunogenicity; (4) modulation of the local cytokine milieu toward a Th1-type inflammatory profile; (5) up-regulation of local chemoattractants; (6) remodeling the tumor stroma; (7) localized delivery of exogenously packaged immune-stimulating antigens, genes and therapeutic drugs. While not all of these results have been studied in experimental PDA models to date, the principles garnered from other solid tumor and disease models have direct relevance to the design of optimal FUS protocols for PDA. In this review, we address the pertinent limitations in current and emergent immune therapies that can be improved with FUS therapy for PDA.


How Long Does it Take to Diagnose Appendicitis? Time Point Process Mapping in the Emergency Department.
Appendicitis is the most common surgical emergency encountered in the pediatric emergency department (ED). We analyzed the time course of children evaluated for suspected appendicitis in relation to implementation of a risk-stratified ultrasound scoring system and structured reporting template (Appy-Score). In July 2013, a 6-level ultrasound (US)-based appendicitis scoring system was developed and implemented. The records of children (age ≤18 years) who underwent limited abdominal US exams for suspected appendicitis at a large academic pediatric ED were reviewed retrospectively. Time periods evaluated were from January 1 to April 1, 2013 (before implementation of the US scoring system, "PRE") and July 1 to October 1, 2013 (after implementation of the US scoring system, "POST"). Times are presented as medians with interquartile range. A total of 926 children were included (median age, 9.5 years [range, 0.1-18 years]; 49% female). Four hundred eighty-one patients were evaluated PRE and 445 POST. When comparing the 2 groups, there were no differences in the PRE and POST periods with regard to time from US ordered to first read (102 vs 112 minutes, P = 0.30), US ordered to disposition (215 vs 208 minutes, P = 0.40) and operating room posting (121 vs 122 minutes, P = 0.59), and overall ED stay (329 vs 333 minutes, P = 0.39). The development of a radiographic appendicitis score, although allowing for a standardized reporting method, did not significantly alter the ED process flow for evaluation of appendicitis. This reflects the complexities in ED throughput and reveals the need for additional factors to change to improve patient flow.


[Treatment of hydrocephalus with endoscopic third ventriculocisternostomy].
Endoscopic third ventriculocisternostomy has gained widespread use in the treatment of hydrocephalus. In 1999 and 2000 endoscopic third ventriculostomy was performed in 120 patients (60 males) at Rikshospitalet, Oslo, Norway. Median age was 3.3 years (range 0.0 to 71.7). 69 procedures were done as primary treatment of hydrocephalus and 51 procedures for shunt failure. After one year, 62% of the patients older than 6 months at time of treatment and 8% of the patients younger than 6 months were successfully treated for their hydrocephalus with ventriculostomy only. The success rate for patients with hydrocephalus secondary to aqueductal stenosis or a space-occupying lesion in the posterior fossa was 72% and 31% for patients with other causes of hydrocephalus. The success rate of endoscopic third ventriculostomy as primary treatment of hydrocephalus was 55%; for the procedure at time of shunt failure 45%. The overall likelihood of success was significantly correlated to age, cause of hydrocephalus, and whether the procedure was done as primary treatment of hydrocephalus or at time of shunt failure. Endoscopic third ventriculostomy seems to be effective in treating hydrocephalus caused by aqueductal stenosis or a space-occupying lesion in the posterior fossa in patients older than 6 months. The procedure should not be routinely attempted on patients younger than 6 months.


Subdural Fluid Collection and Hydrocephalus After Foramen Magnum Decompression for Chiari Malformation Type I: Management Algorithm of a Rare Complication.
Chiari malformation type I is a hindbrain abnormality characterized by descent of the cerebellar tonsils beneath the foramen magnum, frequently associated with symptoms or brainstem compression, impaired cerebrospinal fluid circulation, and syringomyelia. Foramen magnum decompression represents the most common way of treatment. Rarely, subdural fluid collection and hydrocephalus represent postoperative adverse events. The treatment of this complication is still debated, and physicians are sometimes uncertain when to perform diversion surgery and when to perform more conservative management. We report an unusual occurrence of subdural fluid collection and hydrocephalus that developed in a 23-year-old patient after foramen magnum decompression for Chiari malformation type I. Following a management protocol, based on a step-by-step approach, from conservative therapy to diversion surgery, the patient was managed with urgent external ventricular drainage, and then with conservative management and wound revision. Because of the rarity of this adverse event, previous case reports differ about the form of treatment. In future cases, finding clinical and radiologic features to identify risk factors that are useful in predicting if the patient will benefit from conservative management or will need to undergo diversion surgery is only possible if a uniform form of treatment is used. Therefore, we believe that a management algorithm based on a step-by-step approach will reduce the use of invasive therapies and help to create a standard of care.


van der Waals epitaxy of highly (111)-oriented BaTiO3 on MXene.
We report on the high temperature thin film growth of BaTiO3 on Ti3C2Tx MXene flakes using van der Waals epitaxy on a degradable template layer. MXene was deposited on amorphous and crystalline substrates by spray- and dip-coating techniques, while the growth of BaTiO3 at 700 °C was accomplished using pulsed laser deposition in an oxygen rich environment. We demonstrate that the MXene flakes act as a temporary seed layer, which promotes highly oriented BaTiO3 growth along the (111) direction independent of the underlying substrate. The lattice parameters of the BaTiO3 films are close to the bulk value suggesting that the BaTiO3 films remains unstrained, as expected for van der Waals epitaxy. The initial size of the MXene flakes has an impact on the orientation of the BaTiO3 films with larger flake sizes promoting a higher fraction of the polycrystalline film to grow along the (111) direction. The deposited BaTiO3 film adopts the same morphology as the original flakes and piezoresponse force microscopy shows a robust ferroelectric behavior for individual grains. Transmission electron microscopy results indicate that the Ti3C2Tx MXene fully decomposes during the BaTiO3 deposition and the surplus Ti atoms are readily incorporated into the BaTiO3 film. Electrical measurements show a similar dielectric constant as a BaTiO3 film grown without the MXene seed layer. The demonstrated process has the potential to overcome the longstanding issue of integrating highly oriented complex oxide thin films directly on any desired substrate.


Outbreaks attributed to fresh leafy vegetables, United States, 1973-2012.
Leafy vegetables are an essential component of a healthy diet; however, they have been associated with high-profile outbreaks causing severe illnesses. We reviewed leafy vegetable-associated outbreaks reported to the Centers for Disease Control and Prevention between 1973 and 2012. During the study period, 606 leafy vegetable-associated outbreaks, with 20 003 associated illnesses, 1030 hospitalizations, and 19 deaths were reported. On average, leafy vegetable-associated outbreaks were larger than those attributed to other food types. The pathogens that most often caused leafy vegetable-associated outbreaks were norovirus (55% of outbreaks with confirmed aetiology), Shiga toxin-producing Escherichia coli (STEC) (18%), and Salmonella (11%). Most outbreaks were attributed to food prepared in a restaurant or catering facility (85%). An ill food worker was implicated as the source of contamination in 31% of outbreaks. Efforts by local, state, and federal agencies to control leafy vegetable contamination and outbreaks should span from the point of harvest to the point of preparation.


Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization.
Dystroglycan (DG) is a cell surface receptor for several extracellular matrix (ECM) molecules including laminins, agrin and perlecan. Recent data indicate that DG function is required for the formation of basement membranes in early development and the organization of laminin on the cell surface. Here we show that DG-mediated laminin clustering on mouse embryonic stem (ES) cells is a dynamic process in which clusters are consolidated over time into increasingly more complex structures. Utilizing various null-mutant ES cell lines, we define roles for other molecules in this process. In beta1 integrin-deficient ES cells, laminin-1 binds to the cell surface, but fails to organize into more morphologically complex structures. This result indicates that beta1 integrin function is required after DG function in the cell surface-mediated laminin assembly process. In perlecan-deficient ES cells, the formation of complex laminin-1 structures is defective, implicating perlecan in the laminin matrix assembly process. Moreover, laminin and perlecan reciprocally modulate the organization of the other on the cell surface. Taken together, the data support a model whereby DG serves as a receptor essential for the initial binding of laminin on the cell surface, whereas beta1 integrins and perlecan are required for laminin matrix assembly processes after it binds to the cell.


HIV-associated neuropathies: role of HIV-1, CMV, and other viruses.
The role of the human immunodeficiency virus (HIV) and other viruses in the development of neuropathies associated with HIV infection is controversial. Distal symmetric polyneuropathy (DSP), the most common subtype of HIV-associated neuropathy, is characterized by an abundance of reactive macrophages within the peripheral nerve, but HIV replication is limited to a small percentage of the macrophages. Thus, the pathological destruction may be mediated by pro-inflammatory signals amplified by activated glial elements within the nerve, similar to the proposed mechanism of damage caused by HIV within the central nervous system. In contrast, in mononeuropathy multiplex (MM) and progressive polyneuropathy (PP), cytomegalovirus (CMV) replication in the peripheral nerve is consistently demonstrable, and this replication likely results in direct damage to the infected cells (neurons and glia). The rarest form of HIV-associated neuropathy, the diffuse infiltrative lymphocytosis syndrome (DILS), is characterized by an intense CD8+ T lymphocyte infiltration into the nerve and abundant HIV infection of macrophages. Finally, while other viruses (varicella zoster, herpes simplex) are associated with myelitis in HIV-infected individuals, there is little support for a role for these viruses in HIV-associated neuropathy.


Generation properties of coherent infrared radiation in the optical absorption region of GaSe crystal.
We report a study of the effect of optical absorption on generation of coherent infrared radiation from mid-IR to THz region from GaSe crystal. The infrared-active modes of epsilon-GaSe crystal at 236 cm(-1) and 214 cm(-1) were found to be responsible for the observed optical dispersion and infrared absorption edge. Based upon phase matching characteristics of GaSe for difference-frequency generation (DFG), new Sellmeier equations of GaSe were proposed. The output THz power variation with wavelength can be properly explained with a decrease of parametric gain and the spectral profile of absorption coefficient of GaSe. The adverse effect of infrared absorption on (DFG) process can partially be compensated by doping GaSe crystal with erbium ions.


Lessons from comparative analysis of species-specific imprinted genes.
Genomic imprinting is generally believed to be conserved in all mammals except for egg-laying monotremes, suggesting that it is closely related to placental and fetal growth. As expected, the imprinting status of most imprinted genes is conserved between mouse and human, and some are imprinted even in marsupials. On the other hand, a small number of genes were reported to exhibit species-specific imprinting that is not necessarily accounted for by either the placenta or conflict hypotheses. Since mouse and human represent a single, phylogenetically restricted clade in the mammalian class, a much broader comparison including mammals diverged earlier than rodents is necessary to fully understand the species-specificity and variation in evolution of genomic imprinting. Indeed, comparative analysis of a species-specific imprinted gene Impact using a broader range of mammals led us to propose an alternative dosage control hypothesis for the evolution of genomic imprinting.


The role of glutathione in carboplatin ototoxicity in the chinchilla.
The role of glutathione in carboplatin ototoxicity was investigated in the chinchilla. Chinchillas hearing was tested with both distortion product otoacoustic emissions (DPOAE) and evoked potentials recorded from a chronic electrode in the inferior colliculus (IC). All subjects had an osmotic pump fitted to their right ear and it received buthionine sulfoximine (BSO) at a dose of 15 mM delivered at 5 ml per hour for 14 days. A group (N=4) was given a double dose of carboplatin (25 mg/kg i.p. for 2 days). The pump was implanted three days before the carboplatin dose. The BSO treated ears showed a greater loss in both evoked potential and DPOAE measures, as well as substantially fewer missing hair cells. The results implicate reactive oxygen species (ROS) as a common factor in ototoxic reactions because suppression of glutathione antioxidant leads to greater ototoxic reactions.