ANTIBACTERIAL AND ANTIOXIDANT POTENTIAL OF STEM BARK EXTRACT OF BOMBAX CEIBA COLLECTED LOCALLY FROM SOUTH PUNJAB AREA OF PAKISTAN.
Ethnic medication systems have been used extensively by humans since their origin. Now a day, in the developing countries these systems are being used due to their effectiveness and affordability. Especially inhabitants of rural areas still rely on these systems as first line of treatment against diseased conditions. Till now, majority of medicines is derived from the natural origin particularly plants owing to their little side effects and cost effectiveness. In the present work, we evaluated antibacterial and antioxidant activity of methanolic extract of Bombax ceiba stem bark. Total phenolic and flavonoid contents were also assessed in the extract. The antioxidant capacity was determined by DPPH, Nitric Oxide scavenging and reducing power activity. For antibacterial activity, Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi) and Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus) were used. Phenolic content was 133.21±1.56 μg GAE/mg of extract while Flavonoid content was 997.93±2.14 μg QE/mg. Plant extract demonstrated strong antiradical activity with EC50 18.78 ± 0.69 and 23.62 ± 1.99fg/ml for Nitric Oxide and DPPH assay respectively while EC50 in case of reducing power activity was 139.4 ± 0.98μg/ml. Plant extract displayed inhibitory effect against microbial growth with S. typhi as the most resistant strain and Staphylococcus aureus the most sensitive one. This study revealed that Bombax ceiba of local origin has broad spectrum antibacterial activity and it can also provide defense against oxidative stress.


Antioxidative biointerface: biocompatible materials scavenging reactive oxygen species.
Oxidative stress caused by reactive oxygen species (ROS) occurs as events in which living tissues contact certain materials. These events include cell cultures and implantation of materials. Because of the high reactivity of ROS, they damage cells by oxidizing DNA, lipids, and proteins. Conversely, ROS also act as signaling molecules regulating cellular morphology. In particular, mitochondrial ROS are involved in the regulation of cellular physiology, including differentiation, autophagy, metabolic adaptation, apoptosis, and immunity. The balance between generation and elimination of ROS is essential for signaling pathways and proper cell function, and redox imbalance leads to cellular dysfunction and disturbs cellular homeostasis. To reduce oxidative stress, versatile antioxidants, including natural compounds, have been used; however, their poor bioavailability and pro-oxidant effects have limited the versatility of these antioxidants. Recent developments of antioxidative biointerfaces may represent a potent solution to this issue. Designed biointerfaces composed of polymer antioxidants eliminate excessive ROS at the interface between living tissues and materials, and do not disturb regulated redox balance inside cells, thus eliminating unexpected cell responses, such as inflammation and dysfunction.


Racemization of (S)-profen thioesters by strong neutral bases in nonpolar organic solvents: implication for ion-pair kinetic basicity.
The racemization of (S)-profen 2,2,2-trifluoroethyl thioesters in isooctane with trioctylamine as base was carried out, in which the Hammett equation log(k(int)) = 3.584sigma - 3.745 was successfully applied to describe the electron-withdrawing effect of the substituents to the alpha-phenyl moiety of the thioesters. A combination of neutral strong organic bases with different nonpolar solvents was employed to determine the second-order interconversion constants for the racemization of (S)-naproxen 2,2,2-trifluoroethyl thioester, in which solvent hydrophobicity was found to have less effect on the racemization. Implication for ion-pair kinetic basicity scale for the neutral strong bases in isooctane was further discussed.


TETRODOTOXIN RESISTANCE IN GARTER SNAKES: AN EVOLUTIONARY RESPONSE OF PREDATORS TO DANGEROUS PREY.
The use of the "arms race" analogy as a conceptualization of evolutionary predator-prey interactions has been criticized because of the lack of evidence that predators can and do adapt to increased antipredator ability of prey. We present evidence that the garter snake Thamnophis sirtalis has evolved resistance to tetrodotoxin (TTX) in response to the toxicity of the newt Taricha granulosa on which the snake feeds. A bioassay (locomotor performance before and after injection of TTX) was used to obtain repeated measures of resistance for individual snakes. We studied interpopulation and interspecific variation by comparing resistance in Thamnophis sirtalis from populations occurring sympatrically and allopatrically with Taricha granulosa, and in Thamnophis ordinoides (which does not feed on the newt) occurring sympatrically with Taricha granulosa. We also examined intrapopulation variation in TTX resistance using snakes from a population known to feed on Taricha granulosa. Resistance differed significantly among individuals and litters; repeatability and heritability estimates of the assay were significantly different from zero, demonstrating the potential for response to selection. The population of Thamnophis sirtalis that occurs with Taricha granulosa exhibited levels of resistance much greater than either of the other groups. These results suggest that the predator-prey arms race analogy may be applicable to this system.


Serum protein electrophoresis by CZE 2000 clinical capillary electrophoresis system.
We compared the automated Paragon 2000 clinical capillary zone electrophoresis (CZE) system with two manual methods, agarose electrophoresis (AGE) and cellulose acetate electrophoresis (CAE). Reference intervals in healthy adults were determined for each method. When compared with AGE and CAE, CZE gave substantially higher reference values for the alpha1-globulin fraction. With CZE, within-run precision for fraction quantitation was between 0.5% (albumin) and 4.1% (alpha1-globulin). Total precision was between 0.8% (albumin) and 5.3% (beta-globulin). Data obtained from CZE showed poor linear correlation with results obtained by AGE but good linear correlation with data from CAE. Analysis of serum from patients with inter alia inflammation, nephrotic syndrome, or polyclonal gammopathy showed that clinical information obtained by CZE is comparable with information obtained by AGE and CAE. We conclude that CZE offers a clinically reliable alternative to AGE and CAE and has the advantages of automation, higher precision, and faster turnaround time.


Analysis of the effective point of measurement of a thimble chamber dosimeter set parallel to the X-ray beam axis.
To measure the narrow beam used in stereotactic irradiation, installation of the ionization chamber parallel to the X-ray beam axis has been used instead of perpendicular installation. However, the definition of the effective point is a major problem in the parallel installation. In this study, we analyzed the effective point in parallel installation, and considered the prediction and evaluation of measurement point displacement. Relative dosimetry was carried out by installing the thimble ionization chamber in both perpendicular and parallel configurations. We then searched for the measurement point that coincided with the PDD of the perpendicular installation by using the displacement of the measurement point of the parallel installation. We found that the effective point of measurement for relative photon beam dosimetry depends on every detail of the chamber design, including the cavity length and the cavity radius. Moreover, the effective point of measurement also depends on the beam quality and the field size. The amount of effective point displacement for the parallel installation was quantified with the linear expression of TPR(20,10). Our results showed that the amount of effective point displacement can be estimated by the ionization volume of the dosimeter and the energy used.


Hemodynamic consequences of resistance vessel rarification and of changes in smooth muscle sensitivity.
Alterations in resistance vessel design in form of an increased wall/lumen ratio appears to markedly influence the resistance control in primary hypertension (Folkow et al. 1973). The raised resistance has also been suggested to be a consequence of a rarification of resistence vessels or/and to an increased vascular smooth muscle sensitivity. Thus two series paired experiments were performed on matched normotensive rats, utilizing the responses of their hindquarter vascular beds during constant flow perfusion. In the first series, the precapillary resistance vessels section was first "rarified" by graded microplugging, thereby raising resistance at maximal dilatation about 50 per cent. Then the vascular responses to noradrenaline were studied to characterize the dose-response or "resistance curves". In the second series the vascular smooth muscle sensitivity to noradrenaline of one of the hindquarters was changed by infusion of phentolamine. The resistance responses were then recorded and the ensuing "resistance curves" compared. --These changes of resistance vascular architecture and vascular smooth muscle sensitivity, respectively, led to mutually different characters of the "resistance curves". Both of these differ, however, in virtually all important respects from those curves characterizing vascular beds of spontaneously or renal hypertensive rats.


Imaging Nerve Pathology of the Knee: Magnetic Resonance Imaging and Ultrasound.
Peripheral neuropathies are not uncommon, and the diagnostic evaluation includes a clinical assessment and electrophysiologic studies as well as diagnostic imaging. Magnetic resonance imaging (MRI) and high-resolution ultrasound (HRUS) are of special importance in providing the surgeon with information in the context of nerve trauma, entrapment, and nerve involvement by tumors. Peripheral neuropathy about the knee can occur in the context of associated knee pathology such as trauma, as part of a systemic disease, or as an isolated finding. In this review, we discuss the role of MRI and HRUS in the evaluation of peripheral neuropathy and present imaging examples of peripheral neuropathy involving the knee.


Euthanasia in The Netherlands: facts and moral arguments.
Some facts about euthanasia practices in The Netherlands are given. It is shown that there are several possible courses of action at the end of life, of which active euthanasia is the most problematic. Euthanasia is related to respect for the patient and the patient's right to refuse medical treatment. Some moral arguments against and in favour of euthanasia are discussed.


The pancreatic islet endothelial cell: emerging roles in islet function and disease.
The pancreatic islets are one of the most vascularized organs of the body. This likely reflects the requirements of the organ for a rich supply of nutrients and oxygen to the tissue, as well as the need for rapid disposal of metabolites and secreted hormones. The islet endothelium is richly fenestrated to facilitate trans-endothelial transport of secreted hormones, has a unique expression of surface markers, and produces a number of vasoactive substances and growth factors. The islet endothelial cells play a critical role in the early phase of type 1 diabetes mellitus by increasing the expression of surface leucocyte-homing receptors, thereby enabling immune cells to enter the endocrine tissue and cause beta-cell destruction. Following transplantation, pancreatic islets lack a functional capillary system and need to be properly revascularized. Insufficient revascularization may severely affect the transport properties of the islet endothelial system, resulting in a dysfunctional islet graft.


Catastrophic expenditure and impoverishment of patients affected by 7 rare diseases in China.
China is actively promoting regulation of rare diseases, rare disease and orphan drugs have been formally incorporated into the national planning. However, few studies have been done to evaluate the affordability of rare disease patients in China. This study aims to provide policy recommendations for the establishment of social security mechanism for rare diseases in China, so as to address the problem of poverty caused by these diseases. A total of 7 rare diseases were selected by Delphi method. Affordability of treatment for the 7 rare diseases was assessed through annual per capital income, catastrophic expenditure and impoverishment expenditure among urban and rural residents in China. Assessed through annual per capital income, health expenditure for the 7 rare diseases are all rather high. The highest health expenditure is equivalent to income of 69.34 years of one urban resident, and the burden is heavier for rural residents. Through catastrophic expenditure assessment, proportions of the population experiencing catastrophic expenditure caused by the 7 rare diseases are all under 0.167 ‰. However, once one is ill and taking medications, he will suffer from catastrophic health expenditure. Through impoverishment expenditure assessment, the proportions of impoverishment payment are low among both urban and rural residents, but the 7 rare diseases could lead nearly 4.6 million people into poverty on a national scale. The affordability of treatment for rare disease as well as orphan drugs is rather poor. Residents of different income levels all have difficulties to afford the treatment for rare diseases, so poverty caused by rare diseases is quite widespread. Therefore, social security mechanism for rare disease patients should be established and specific payment pattern for orphan drugs should be set up.


Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications.
The diversity of body plans of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats, including terrestrial, aerial and aquatic habitats. However, the genetic basis of those phenotypic modifications, which have occurred during mammalian evolution, remains poorly explored. In the present study, we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and the main regulatory factors (Mll, Bmi1 and E2f6) that control the expression of Hox genes. A deflected density of repetitive elements and lineage-specific radical mutations of Mll have been determined in marine mammals with morphological changes, suggesting that evolutionary changes may alter Hox gene expression in these lineages, leading to the morphological modification of these lineages. Although no positive selection was detected at certain ancestor nodes of lineages, the increased ω values of Hox genes implied the relaxation of functional constraints of these genes during the mammalian evolutionary process. More importantly, 49 positively-selected sites were identified in mammalian lineages with phenotypic modifications, indicating adaptive evolution acting on Hox genes and regulatory factors. In addition, 3 parallel amino acid substitutions in some Hox genes were examined in marine mammals, which might be responsible for their streamlined body.


Effect of probenecid on blood levels and renal elimination of furosemide and endogenous compounds in rats: Discovery of putative organic anion transporter biomarkers.
Transporter-mediated drug-drug interactions (DDIs) are assessed using probe drugs and in vitro and in vivo models during drug development. The utility of endogenous metabolites as transporter biomarkers is emerging for prediction of DDIs during early phases of clinical trials. Endogenous metabolites such as pyridoxic acid and kynurenic acid have shown potential to predict DDIs mediated by organic anion transporters (OAT1 and OAT3). However, these metabolites have not been assessed in rats as potential transporter biomarkers. We carried out a rat pharmacokinetic DDI study using probenecid and furosemide as OAT inhibitor and substrate, respectively. Probenecid administration led to a 3.8-fold increase in the blood concentrations and a 3-fold decrease in renal clearance of furosemide. High inter-individual and intra-day variability in pyridoxic acid and kynurenic acid, and no or moderate effect of probenecid administration on these metabolites suggest their limited utility for prediction of Oat-mediated DDI in rats. Therefore, rat blood and urine samples were further analysed using untargeted metabolomics. Twenty-one m/z features (out of >8000 detected features) were identified as putative biomarkers of rat Oat1 and Oat3 using a robust biomarker qualification approach. These m/z features belong to metabolic pathways such as fatty acid analogues, peptides, prostaglandin analogues, bile acid derivatives, flavonoids, phytoconstituents, and steroids, and can be used as a panel to decrease variability caused by processes other than Oats. When validated, these putative biomarkers will be useful in predicting DDIs caused by Oats in rats.


Enhancement of relaxivity rates of Gd-DTPA complexes by intercalation into layered double hydroxide nanoparticles.
In this paper we report the preparation and characterization of [Gd(dtpa)](2-) intercalated layered double hydroxide (LDH) nanomaterials. [Gd(dtpa)](2-) (gadolinium(III) diethylene triamine pentaacetate) was transferred into LDH by anionic exchange. The intercalation of [Gd(dtpa)](2-) into LDH was confirmed by X-ray diffraction for the new phase with the interlayer spacing of 3.5-4.0 nm and by FTIR for the characteristic vibration peaks of [Gd(dtpa)](2-). The morphology of the nanoparticles was influenced by the extent of [Gd(dtpa)](2-) loading, in which the poly-dispersity quality decreased as the [Gd(dtpa)](2-) loading was increased. Compared with the morphology of the original Mg(2)Al-Cl-LDH nanoparticles (hexagonal plate-like sheets of 50-200 nm), the modified LDH-Gd(dtpa) nanoparticles are bar-like with a width of 30-60 nm and a length of 50-150 nm. LDH-Gd(dtpa) was expected to have an increased water proton magnetic resonance relaxivity due to the intercalation of [Gd(dtpa)](2-) into the LDH interlayer that led to slower molecular anisotropic tumbling compared with free [Gd(dtpa)](2-) in solution. Indeed, LDH-nanoparticle suspension containing approximately 1.6 mM [Gd(dtpa)](2-) exhibits a longitudinal proton relaxivity r(1) of approximately 16 mM(-1) s(-1) and a transverse proton relaxivity r(2) of approximately 50 mM(-1) s(-1) at room temperature and a magnetic field of 190 MHz, which represents an enhancement four times (r(1)) and 12 times (r(2)) that of free [Gd(dtpa)](2-) in solution under the same reaction conditions. We have thus tailored LDH-nanoparticles into a novel contrast agent with strong relaxivity, promising for great potential applications in magnetic resonance imaging.


[Effective delegation].
Ninety-seven percent of middle level managers feel they face work overload. The source of this problem may lie in a failure to delegate tasks effectively. If a manager does not effectively delegate, he/she is more likely to report fatigue, stress and depression. Conversely, effectively delegating tasks will improve overall job quality, professional growth in subordinates and cooperation within the team. While it is necessary for managers to delegate tasks effectively, few can be considered to be good natural 'delegators'. Learning and training is necessary for managers to develop the necessary confidence and maturity. This article describes the definitions, purpose and benefits of delegation; factors related to effective delegation; strategies related to successful delegation and skills related to performing cross-cultural delegations. Such issues have seldom been addressed in previous articles. Moreover, nursing implications and suggested applications in nursing practice, education, management and research are mentioned. This article is intended to provide directions to nursing managers and subordinates to promote delegation knowledge and skills.


Treatment of advanced breast cancer with chemotherapy.
Metastatic breast cancer continues to take thousands of lives each year despite the advances in screening and adjuvant therapy. Chemotherapy in advanced disease is an intervention which can successfully lead to palliation (prolongation of quality survival) in the majority of women who are treated, but it does not constitute a curative intervention. New agents or innovative modalities will be needed to make a significant impact on the survival of this group of women.


Hypophosphatasia in Adults: Clinical Assessment and Treatment Considerations.
Hypophosphatasia (HPP) is a rare inherited disorder of bone affecting approximately 500 to 600 known individuals in the United States. HPP is the result of mutations involving the gene for tissue nonspecific alkaline phosphatase. Five clinical types of HPP are recognized. The clinical presentation of HPP varies from devastating prenatal intrauterine disease to mild manifestations in adulthood. In adults, main clinical involvement includes early loss of primary or secondary teeth, osteoporosis, bone pain, chondrocalcinosis, and fractures. Treatment for HPP is limited. Asfotase alfa is a subcutaneously administered synthetic human alkaline phosphatase that is approved for treatment of patients, including adults, with perinatal/infantile- and juvenile-onset HPP. However, guidelines for the treatment of adults with HPP are not available. This discussion addresses diagnostic and treatment considerations for adults with HPP. © 2017 American Society for Bone and Mineral Research.


Conjoint analysis to understand preferences of patients with multiple sclerosis for disease-modifying therapy attributes in Spain: a cross-sectional observational study.
To assess patients' preferences for a range of disease-modifying therapy (DMT) attributes in multiple sclerosis (MS). A cross-sectional observational study. The data reported were from 17 MS units throughout Spain. Adult patients with relapsing-remitting MS. A conjoint analysis was applied to assess preferences. A total of 221 patients completed a survey with 10 hypothetical DMT profiles developed using an orthogonal design and rating preferences from 1 (most acceptable) to 10 (least acceptable). Medication attributes included preventing relapse, preventing disease progression, side effect risk, route and frequency of administration. Patients placed the greatest relative importance on the side effect risk domain (32.9%), followed by route of administration (26.1%), frequency of administration (22.7%), prevention of disease progression (10.0%) and prevention of relapse (8.3%). These results were independent of the Expanded Disability Status Scale score. The importance assigned to side effect risk was highest for patients with a recent diagnosis. Patients who had previously received more than one DMT gave a higher importance to relapse rate reduction than patients receiving their first DMT. Patient DMT preferences were mainly driven by risk minimisation, route of administration and treatment schedule. The risk-benefit spectrum of available DMT for MS is becoming increasingly complicated. Understanding which treatment characteristics are meaningful to patients may help to tailor information for them and facilitate shared decision-making in clinical practice.


Positioning Ustekinumab in Crohn's Disease: From Clinical Evidence to Clinical Practice.
Biological medicines have revolutionised the treatment of Crohn's disease [CD]. Yet, the management of patients not responding to tumour necrosis factor [TNF] antagonists remains a clinical challenge. Ustekinumab is a human monoclonal antibody blocking the biological activity of interleukins 12 and 23, which regulate the immune system and immune-mediated inflammatory disorders. Ustekinumab has recently been approved for the treatment of adult patients with moderately to severely active CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNF antagonist, or have medical contraindications to such therapies. Herein, we review the new biological drug's efficacy and safety data reported from randomised controlled trials and real-world observational studies conducted in populations with CD, in order to identify the patient groups most likely to benefit, and to appropriately place ustekinumab into treatment algorithms for CD.


Effect of climate change on Alternaria leaf spot of rocket salad and black spot of basil under controlled environment.
Plant responses to elevated CO2 and temperature have been much studied in recent years, but effects of climate change on pathological responses are still largely unknown. The pathosystems rocket (Eruca vesicaria subsp. sativa)--Alternaria leaf spot (Alternaria japonica) and basil (Ocimum basilicum)--black spot (Colletotrichum gloeosporioides) were chosen as models to assess the potential impact of increased CO2 and temperature on disease incidence and severity under controlled environment. Potted plants were grown in phytotrons under 4 different simulated climatic conditions: (1) standard temperature (ranging from 18 degrees to 22 degrees C) and standard CO2 concentration (400 ppm); (2) standard temperature and elevated CO2 concentration (800 ppm); (3) elevated temperature (ranging from 22 degrees to 26 degrees C, 4 degrees C higher than standard) and standard CO2 concentration; (4) elevated temperature and CO2 concentration. Each plant was inoculated with a spore suspension containing 1 x 10(5) cfu/ml of the pathogen. Disease incidence and severity were assessed 14 days after inoculation. Increasing CO2 to 800 ppm showed a clear increment in the percentage of Alternaria leaf spot on rocket leaves compared to standard conditions. Basil plants grown at 800 ppm of CO2 showed increased black spot symptoms compared to 400 ppm. Disease incidence and severity were always influenced by the combination of rising CO2 and increased temperature, compared to standard conditions (400 ppm of CO2 - 22 degrees C). Considering the rising concentrations of CO2 and global temperature, we can assume that this could increase the severity of Alternaria japonica on rocket and Colletotrichum gloeosporioides on basil.


Targeting eosinophils in allergy, inflammation and beyond.
Eosinophils can regulate local immune and inflammatory responses, and their accumulation in the blood and tissue is associated with several inflammatory and infectious diseases. Thus, therapies that target eosinophils may help control diverse diseases, including atopic disorders such as asthma and allergy, as well as diseases that are not primarily associated with eosinophils, such as autoimmunity and malignancy. Eosinophil-targeted therapeutic agents that are aimed at blocking specific steps involved in eosinophil development, migration and activation have recently entered clinical testing and have produced encouraging results and insights into the role of eosinophils. In this Review, we describe recent advances in the development of first-generation eosinophil-targeted therapies and highlight strategies for using personalized medicine to treat eosinophilic disorders.


Medullary carcinoma of the thyroid. Diagnostic problems.
Light microscopy is usually considered sufficient for the diagnosis of medullary carcinoma of the thyroid (MCT). As stromal amyloid is not always present and the tumor may exhibit great variation in growth pattern, light microscopy alone, however, may lead to misinterpretations. Of 1670 thyroid carcinomas registered durging a 15-year period in Norway, 42 were originally interpreted as MCT. The slides were reviewed and the diagnosis maintained in 33 cases only. Twenty-four additional cases were found by reviewing histopathologic slides from neoplasms originally registered as other types of thyroid tumors. Of 57 cases of MCT, stromal amyloid was demonstrated in 43. Calcitonin measurements and electron microscopy, even on formalin-fixed material, were valuable aids in establishing the correct diagnosis, though none of these methods are unequivocal. Different aspects of the problems concerning the diagnosis of MCT are discussed through the detailed presentation of five patients.


The combination of meropenem and levofloxacin is synergistic with respect to both Pseudomonas aeruginosa kill rate and resistance suppression.
New approaches are needed for the treatment of Pseudomonas aeruginosa infections. All available single agents are suboptimal, especially for resistance suppression. Classical beta-lactam/aminoglycoside combinations are not used often enough at least in part because of concern for nephrotoxicity. We evaluated the combination of meropenem and levofloxacin against the P. aeruginosa PAO1 wild type and its isogenic MexAB pump-overexpressed mutant. The drugs were studied using an in vitro hollow-fiber pharmacodynamic infection model. There were 16 different regimens evaluated for both isolates. Both total population and resistant subpopulations were quantified. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The impact of monotherapy versus that of combination therapy for attainment of a 3-log cell kill and for resistance suppression was examined using Kaplan-Meier analysis. Drug exposures were calculated by fitting the concentration-time data using the ADAPT II package of programs. For both isolates, monotherapy allowed resistance emergence with all but the largest exposure or with all exposures. In contrast, there was no resistance emergence with any combination regimen. Kaplan-Meier analysis showed significant differences in time to attainment of a 3-log cell kill as well as time to resistance emergence for monotherapy and combination therapy for both isolates, in favor of the combination regimens. Determination of the pharmacodynamic indices associated with resistance suppression demonstrated a 2- to 3-fold reduction with the use of combinations. Combination therapy with meropenem and levofloxacin provides a significantly faster time to attain a 3-log cell kill and significantly better resistance suppression than does either monotherapy. This combination should be evaluated in a clinical trial.


[Rupture of a gastroduodenal artery aneurysm caused by duodenal ulcer: a case report].
A 73-year-old man with a history of tarry stools was admitted to our hospital. Gastroduodenoscopy on admission revealed an ulcer with an exposed vessel at the duodenal bulb. During endoscopic clipping for prevention of re-bleeding, a large amount of bleeding from the vessel was observed. Hemostasis was achieved after the procedure. However, 7 days later, the patient passed a large amount of tarry stools and experienced hypovolemic shock. Endoscopic re-examination revealed a pulsatile aneurysmal vessel at the base of the duodenal ulcer. Abdominal contrast-enhanced computed tomography and abdominal angiography demonstrated an aneurysm of the gastroduodenal artery, which was successfully treated with transcatheter arterial embolization. Thus, here we report a rare case of an aneurysm of the gastroduodenal artery caused by a duodenal ulcer.


Trouble on takeoff: Crude oil on feathers reduces escape performance of shorebirds.
The ability to takeoff quickly and accelerate away from predators is crucial to bird survival. Crude oil can disrupt the fine structure and function of feathers, and here we tested for the first time how small amounts of oil on the trailing edges of the wings and tail of Western sandpipers (Calidris mauri) affected takeoff flight performance. In oiled birds, the distance travelled during the first 0.4s after takeoff was reduced by 29%, and takeoff angle was decreased by 10° compared to unoiled birds. Three-axis accelerometry indicated that oiled sandpipers produced less mechanical power output per wingbeat during the initial phase of flight. Slower and lower takeoff would make oiled birds more likely to be targeted and captured by predators, reducing survival and facilitating the exposure of predators to oil. Whereas the direct mortality of heavily-oiled birds is often obvious and can be quantified, our results show that there are significant sub-lethal effects of small amounts crude oil on feathers, which must be considered in natural resource injury assessments for birds.


Cerebral venous thrombosis revealing an ulcerative colitis.
Cerebral venous thrombosis (CVT) has been reported as an uncommon and devastating complication of ulcerative colitis (UC), with an annual incidence varying between 0,5 to 6,7%. It is suspected to be a consequence of the hypercoagulable state occurring during disease relapse. We report a case of 22-year-old female patient presenting with CVT revealing an UC. Our case raises the awareness among health professionals about the inflammatory bowel diseases (IBD) as a rare etiology of CVT, and signifies the importance of considering antithrombotic prophylaxis in all hospitalised IBD patients, especially those with active disease.


Frequency-Dependent Impedance of Nanocapacitors from Electrode Charge Fluctuations as a Probe of Electrolyte Dynamics.
The frequency-dependent impedance is a fundamental property of electrical components. We show that it can be determined from the equilibrium dynamical fluctuations of the electrode charge in constant-potential molecular simulations, extending in particular a fluctuation-dissipation relation for the capacitance recovered in the low-frequency limit and provide an illustration on water-gold nanocapacitors. This Letter opens the way to the interpretation of electrochemical impedance measurements in terms of microscopic mechanisms, directly from the dynamics of the electrolyte, or indirectly via equivalent circuit models as in experiments.


Nitric oxide metabolism in Neisseria meningitidis.
Neisseria meningitidis, the causative agent of meningococcal disease in humans, is likely to be exposed to nitrosative stress during natural colonization and disease. The genome of N. meningitidis includes the genes aniA and norB, predicted to encode nitrite reductase and nitric oxide (NO) reductase, respectively. These gene products should allow the bacterium to denitrify nitrite to nitrous oxide. We show that N. meningitidis can support growth microaerobically by the denitrification of nitrite via NO and that norB is required for anaerobic growth with nitrite. NorB and, to a lesser extent, the cycP gene product cytochrome c' are able to counteract toxicity due to exogenously added NO. Expression of these genes by N. meningitidis during colonization and disease may confer protection against exogenous or endogenous nitrosative stress.


Perceived stress among 20-21 year-olds and their future labour market participation - an eight-year follow-up study.
Labour market participation among young adults is essential for their future socioeconomic status and health. The aim of this study was to investigate the association between perceived stress among 20-21 year-olds and their labour market participation 8 years later as well as investigate any potential gender differences. A cohort of 1640 young adults born in 1983 completed a questionnaire in 2004 in which perceived stress was measured. The cohort was followed in a register of social benefits for 12 months in 2011-2012 and was categorized into active and passive labour market participation. Logistic regression was used to analyse the association between perceived stress and future labour market participation, taking into account effects of potential confounders. The analyses were stratified by gender. The effects of perceived stress on future labour market participation differed significantly among young women and young men (p = 0.029). For young men, higher levels of perceived stress reduced the risk of future passive labour market participation, when adjusting for socioeconomic factors, self-rated health and copings strategies (p = 0.045). For young women, higher levels of perceived stress increased the risk of future passive labour market participation, when adjusting for the same potential confounding factors, although unlike the men, this association was not statistically significant (p = 0.335). The observed gender difference has important implications from a public health point of view. Healthcare professionals might need to differentiate between the genders in terms of health communication, research and when developing preventive strategies.


Demographic and lifestyle factors associated with body mass index among children and adolescents.
Cases of overweight and obesity among adults, adolescents, and children are escalating in the United States. Using data from the Continuing Survey of Food Intake for Individuals (CSFII) 1994-1996 and 1998, and the National Health and Nutrition Examination Survey III (NHANES), we developed multivariate regression models to examine the association between demographic and lifestyle variables (gender, race/ethnicity, age, family income, diet, and television viewing) and the body mass index (BMI) of children aged 6-11 years, and adolescents aged 12-19 years for CSFII and aged 12-16 years for NHANES. In the children's model, the statistically significant demographic predictors of BMI were age, race, gender, and family income. Among adolescents, the demographic predictors were age, race, and gender. Among the lifestyle variables, dietary factors were not associated with BMI in children. On the contrary, carbohydrates (less added sugars) had a statistically significant inverse relationship to BMI among adolescents. In both children and adolescents, television viewing was markedly associated with BMI, and participation in team sports was negatively associated with BMI. The overall process by which overweight develops is complex, and our four models explained only a small portion of total variance of BMI. The CSFII models explained 8.5% of the variance for children and 11.4% of the variance for adolescents. The NHANES models explained 8.8% of the variance for children and 12.5% of the variance for adolescents. Demographic variables accounted for roughly one-half of the explained variance for both children and adolescents. The rest of the explained variance was accounted for by television viewing, diet, and family income.


Increased gene expression of Alzheimer disease beta-amyloid precursor protein in senescent cultured fibroblasts.
The pathological hallmark of Alzheimer disease is the accumulation of neurofibrillary tangles and neuritic plaques in the brains of patients. Plaque cores contain a 4- to 5-kDa amyloid beta-protein fragment which is also found in the cerebral blood vessels of affected individuals. Since amyloid deposition in the brain increases with age even in normal people, we sought to establish whether the disease state bears a direct relationship with normal aging processes. As a model for biological aging, the process of cellular senescence in vitro was used. mRNA levels of beta-amyloid precursor protein associated with Alzheimer disease were compared in human fibroblasts in culture at early passage and when the same fibroblasts were grown to senescence after more than 52 population doublings. A dramatic increase in mRNA was observed in senescent IMR-90 fibroblasts compared with early-passage cells. Hybridization of mRNA from senescent and early proliferating fibroblasts with oligonucleotide probes specific for the three alternatively spliced transcripts of the gene gave similar results, indicating an increase during senescence of all three forms. A similar, though more modest, increase in message levels was also observed in early-passage fibroblasts made quiescent by serum deprivation; with repletion of serum, however, the expression returned to previous low levels. ELISAs were performed on cell extracts from senescent, early proliferating, and quiescent fibroblasts, and quiescent fibroblasts repleted with serum for over 48 hr, using polyclonal antibodies to a synthetic peptide of the beta-amyloid precursor. The results confirmed that the differences in mRNA expression were partially reflected at the protein level. Regulated expression of beta-amyloid precursor protein may be an important determinant of growth and metabolic responses to serum and growth factors under physiological as well as pathological conditions.


Study on pharmacokinetics and bioequivalence of Vonoprazan pyroglutamate in rats by liquid chromatography with tandem mass spectrometry.
Vonoprazan Fumarate (TAK-438F) is a new and effective drug approved in Japan in 2014 for treatment and prevention of acid-related diseases (ARDs), which exhibits many advantages compared with traditional proton-pump inhibitors (PPIs). However, the clinical applications of TAK0-438F suffers limitation due to the lack of injection dosage form. Efforts to overcome this limitation lead to the systhesis of Vonoprazan pyroglutamate (TAK-438P) for its high water solubility and more potent antisecretory effect. This was the first report to establish and validate a reliable and sensitive LC-MS/MS method for the quantification of TAK-438P in rat plasma and tissues (heart, liver, spleen, liver, kidney, rain, stomach and small intestine). All the features of the developed method suggested it was within bioanalytical criteria recommended by regulatory authorities. Furthermore, the developed method was applied to the exploration of the bioequivalence between TAK-438P and TAK-438F, as well as the pharmacokinetics and tissue distribution of TAK-438P. The results showed that there was no significant differences between TAK-438P and TAK-438F after oral administration of the same dose. Besides, TAK-438P was rapidly absorbed and eliminated in rat plasma. And it was widely distributed and there was no long-term accumulation in most tissues. Notably, more than 2000ng/mL was observed in stomach 12h after oral administration. The high accumulation revealed that stomach was likely to be the target organs of TAK-438P.


Clip Migration in Common Bile Duct: An Uncommon Complication of Laparoscopic Cholecystectomy.
Laparoscopic cholecystectomy is the gold standard procedure for symptomatic cholelithiasis. During the procedure the cystic duct is ligated with titanium clips. Migration of these clips after cholecystectomy is a rare complication and may result in stone formation in common bile duct (CBD). We are here discussing a case of a 29 years female who presented with choledocholithiasis 10 years after laparoscopic cholecystectomy. The clip was incidentally discovered during endoscopic retrograde cholangiopancreatography (ERCP) and stone extraction. The patient was managed successfully at our center.


Inhibition of GLI1 gene activation by Patched1.
Patched1 (PTCH1) is a human tumour suppressor that acts as an HH (Hedgehog) receptor protein and is important for embryonic patterning. PTCH1 mediates its effects through SMO (Smoothened) and represses the expression of HH target genes such as the transcription factor GLI1 (glioma 1) as well as PTCH1. Up-regulation of these genes has been observed in several cancer forms, including basal cell carcinoma, digestive track tumours and small cell lung cancer. The fact that PTCH1 down-regulates its own expression via 'negative feedback' is an important feature in HH signalling, as it keeps the balance between HH and PTCH1 activities that are essential for normal development. In the present study, we provide evidence that a novel mechanism allowing PTCH1 to maintain this balance may also exist. We show that gene activation by GLI1, the transcriptional effector of the pathway, can be down-regulated by PTCH1 without involvement of the canonical cascade of HH signalling events. Specifically, the SMO antagonist cyclopamine has no appreciable effects in blocking this PTCH1-mediated inhibition. Moreover, the negative GLI1 regulator SUFU (Suppressor of Fused) was also found to be dispensable. Additionally, deletion mapping of PTCH1 has revealed that the domains encompassed by amino acids 180-786 and 1058-1210 are of highest significance in inhibiting GLI1 gene activation. This contrasts with the importance of the PTCH1 C-terminal domain for HH signalling.


Increased field resistance to Tilletia caries provided by a specific antifungal virus gene in genetically engineered wheat.
The field performance of a viral gene in two Swiss wheat (Triticum aestivum) varieties showed 10% increased fungal resistance against Tilletia caries (stinking smut). To the best of our knowledge, this is the first report of improved resistance against any fungus in the field achieved by genetic engineering in wheat. The genetically modified wheat lines previously showed a c. 30% decrease in symptoms of T. caries in the glasshouse (Clausen, M., Kräuter, R., Schachermayr, G., Potrykus, I. and Sautter, C. (2000) Antifungal activity of a virally encoded gene in transgenic wheat. Nat. Biotechnol. 18, 446-449), depending on the fungal strain inoculated. A glasshouse experiment run in parallel to the field test, and using the same collection of T. caries, gave the same results. In a dose-response experiment with isolated fungal strains, in which the infection pressure was varied via the spore concentration, the transgene behaved as a quantitative resistance gene and shifted the S-shaped dose-response curve towards higher resistance. The transgene was shown to be highly specific for fungi of the order Ustilaginales. Tests of the transgene using cell cultures of eukaryotes, including hamster and human, showed no significant side-effects with respect to biosafety. Endogenous pathogen-related genes were also activated on fungal infection in the presence of the kp4 transgene.


In operando spatiotemporal study of Li(2)O(2) grain growth and its distribution inside operating Li-O(2) batteries.
Nanocrystalline lithium peroxide (Li2 O2 ) is considered to play a critical role in the redox chemistry during the discharge-charge cycling of the Li-O2 batteries. In this report, a spatially resolved, real-time synchrotron X-ray diffraction technique was applied to study the cyclic formation/decomposition of Li2 O2 crystallites in an operating Li-O2 cell. The evaluation of Li2 O2 grain size, concentration, and spatial distribution inside the cathode is demonstrated under the actual cycling conditions. The study not only unambiguously proved the reversibility of the Li2 O2 redox reaction during reduction and evolution of O2 , but also allowed for the concentration and dimension growths of the peroxide nanocrystallites to be accurately measured at different regions within the cathode. The results provide important insights for future investigation on mass and charge transport properties in Li2 O2 and improvement in cathode structure and material design.


Rapid and sensitive biomolecular screening with encoded macroporous hydrogel photonic beads.
We present a new method to prepare inverse opaline photonic beads with good spherical shape and superior optical performance by simply introducing an interfacial tension system into a template replication method. When the scaffolds of these beads were composed of poly(ethylene glycol) diacrylate hydrogel, they could provide a homogeneous water surrounding, which remedied many shortcomings of biomolecular microcarriers introduced by the presence of the solid surface of them. The suspension array, which used these macroporous hydrogel photonic beads as coding elements, showed obvious advantages in multiplexed capability, rapid biomolecular screening (within 12 min), and highly sensitive detection (with limit of detection of approximately 10(-12) M).


Huguenots, Jacobites, Prisoners and the Challenge of Military Remittances in Early Modern Warfare.
Early modern states faced numerous challenges in supporting their prisoners of war, not least the problems of remitting them money for their subsistence, which had to pass across hostile borders. Examining how the British state achieved this in the War of the Spanish Succession (1702-13) shows the limits of modern scholarship on state formation and its focus on administrative reform and domestic resource mobilisation. The projection of power continued to rely on international Huguenot and even Jacobite financial networks, held together by personal trust and private interests, sometimes even while they were working for the enemy. Success was achieved because British officials were able to tap into these networks through hubs such as London, Amsterdam, Paris and Madrid, and use them to maintain the flow of money abroad.


Does lead play a role in the development of renal insufficiency in some patients with essential hypertension?
The association of excessive lead burden and essential hypertension has been a subject of much dispute. In particular, the potential detrimental effect of low level environmental exposure on BP has caused considerable concern. We studied the urinary excretion of lead following the infusion of EDTA (1 g of calcium disodium edetate) in 12 healthy controls (group I), 10 subjects with essential hypertension alone (Group II) and in 36 subjects with chronic renal insufficiency. Those subjects with renal insufficiency were further divided into three groups: group III, 12 patients with a history of 7-19 years of essential hypertension who subsequently developed into renal failure; group IV, patients with chronic renal failure alone; and group V, patients with chronic renal failure due to causes other than hypertensive nephropathy and associated with secondary hypertension. In comparison with other groups, subjects with hypertensive nephropathy (group III) had significantly elevated lead body burden. In addition, we found that five of the 12 subjects with hypertensive nephropathy had histories of acute gouty attacks after the development of renal function impairment. In conclusion, our observation of a higher EDTA postinfusional urinary lead excretion among some patients with essential hypertension with renal function impairment indicates that lead may play a crucial role in a subgroup of patients with hypertensive nephropathy.


Transjugular Liver Biopsy: Safe Even in Patients With Severe Coagulopathies and Multiple Biopsies.
To investigate the safety profile and diagnostic efficacy of transjugular liver biopsy (TJLB), with a focus on patients with severe coagulopathies and with multiple biopsies. Clinical, laboratory, and demographic information was collected on 1,321 TJLBs in 932 patients (mean age 43.5 ± 23.2 years) performed between January 2009 and May 2017 to determine the diagnostic success rate and incidence of both major and minor complications in the 3-day and 30-day period post-biopsies. These outcomes were also analyzed for severely coagulopathic patients and a subgroup of patients who underwent multiple biopsies. The overall success rate (diagnostic yield) of the TJLB procedure was 97.7% (1,291/1,321). Overall, the major and minor complication rates were 1.0% (13/1,321) and 9.5% (126/1,321), respectively. In patients with multiple biopsies, the overall complication rate was similar to the entire study cohort, which was 10.4% (57/550). Patients were also stratified according to the platelet counts of 0-50, 51-100, 101-200, 201-300 and >300 × 10 platelets/μL. The overall complication rates were 8.0% (10/124), 11.6% (36/310), 9.9% (54/547), 11.9% (28/235), and 14.3% (11/77), respectively, and these were not statistically significant from each other. Patients were also stratified by international normalized ratio into 0-1, 1.1-2, 2.1-3, and >3. The overall complication rates of these patients were 8.0% (19/237), 11.8% (113/954), 16.3% (7/43), and 0% (0/9), respectively, and were not statistically significant from each other. TJLB is a highly efficacious, well-tolerated and safe procedure. It can be safely performed multiple times in the same patient or in critically ill, severely coagulopathic patients with no significant increase in the rate of complication while maintaining an extremely favorable diagnostic yield.


The role of antimicrobial peptides in plant immunity.
Selective pressure imposed by millions of years of relentless biological attack has led to the development of an extraordinary array of defense strategies in plants. Among these, antimicrobial peptides (AMPs) stand out as one of the most prominent components of the plant immune system. These small and usually basic peptides are deployed as a generalist defense strategy that grants direct and durable resistance against biotic stress. Even though their name implies a function against microbes, the range of plant-associated organisms affected by these peptides is much broader. In this review, we highlight the advances in our understanding on the role of AMPs in plant immunity. We demonstrate that the capacity of plant AMPs to act against a large spectrum of enemies relies on their diverse mechanism of action and remarkable structural stability. The efficacy of AMPs as a defense strategy is evidenced by their widespread occurrence in the plant kingdom, an astonishing heterogeneity in host peptide composition, and the extent to which plant enemies have evolved effective counter-measures to evade AMP action. Plant AMPs are becoming an important topic of research due to their significance in allowing plants to thrive and for their enormous potential in agronomical and pharmaceutical fields.


Making it to the EHR promised land. How to solve common EHR adoption problems.
In the electronic health records (EHR) promised land, medical practices have integrated technology with their daily work flow. Charting is done electronically. Glitches occur rarely; if a problem does arise, practice staff and a supportive vendor handle it efficiently. Employees embrace the EHR and never want to return to paper. But if organizational and technological barriers prevent your group from reaching the EHR promised land, this article can help. The author offers solutions to the problems that keep your organization from enjoying the operational and economic benefits of automation.


The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review.
Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it. The keywords leptin, ghrelin, polymorphism, single-nucleotide polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar. Overall, 24 case-control studies, relevant to our topic, met the criteria and were included in the review. The most prevalent leptin/leptin receptor genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively. Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven studies on GHRL/GHSR showed significant relationships. In general, our study suggests that the association between LEP/LEPR and GHRL/GHSR with overweight/obesity and the related metabolic disturbances is inconclusive. These results may be due to unidentified gene-environment interactions. More investigations are needed to further clarify this association.


Granulocyte colony-stimulating factor-dependent growth of an acute myeloblastic leukemia cell line.
We report herein the establishment and characterization of a granulocyte colony-stimulating factor (G-CSF)-dependent acute myeloblastic leukemia (AML) cell line. The cell line, designated as OCI/AML 1a, has been cultured in the presence of G-CSF and has shown exponential growth for over two years. The cells growing in suspension culture resembled myeloblasts on the basis of morphologic, cytochemical and surface phenotypic analyses. Other CSFs, interleukin-3 and granulocyte-macrophage colony-stimulating factor did not support the growth of OCI/AML 1a cells so well as G-CSF. The effect on the growth of OCI/AML 1a cells of G-CSF was almost completely abolished by neutralizing monoclonal anti-G-CSF antibody. These findings showed that OCI/AML 1a cells required G-CSF for growth. OCI/AML 1a cell line will be valuable for studies of the biological nature, proliferation and differentiation of leukemic cells. Furthermore, OCI/AML 1a cells should be useful for determining the mechanism by which G-CSF induces the growth of hemopoietic cells.


Diabetes outpatient care before and after admission for diabetic foot complications.
To assess the number of patients admitted with a diabetic foot complication to a regional teaching hospital over a 12-month period (July 2005 to June 2006) and determine the percentage that went though an optimal diabetes outpatient management pathway before and after this admission. Diabetic inpatients with foot ulcers and infections were identified through the relevant International Classification of Diseases (ICD) codes. Both inpatient and outpatient data were obtained through the local electronic patient management system and review of clinical notes. Forty-nine patients were admitted to hospital with diabetic foot ulcers or infections during the audit period. Median age was 66 years and 67% were male. The most common admitting speciality was vascular surgery. The main associated procedure was toe amputation. In the six month period before and after the index admission, 63% of patients were seen by a health professional at the diabetes centre before or after the admission. 45% of patients were seen at the diabetes centre before and after the admission; 33% were seen by a podiatrist before and after the admission. However, 37% had no contact with the diabetes Centre and 51% did not see a podiatrist from the diabetes centre at any time during the six months before and after their admission. Despite the availability of a multidisciplinary high risk foot clinic, only 45% of patients admitted to our regional hospital during the audit period followed an interdisciplinary pathway that included specialist diabetes input of some form and only 33% were assessed by a specialist diabetes podiatrist both before and after their hospital admission. A formalised patient pathway is likely to improve clinical management and may minimise further admissions. In this way it will help reduce morbidity and mortality in this high-risk patient group. In the future, this might best be achieved using an electronic referral and decision support system.


Detection of glycosylated protein in glomeruli of STZ-induced diabetic rats using the nitroblue tetrazolium (NBT) reaction.
Detection of glycosylated protein in renal tissues was determined in streptozotocin (STZ)-induced diabetic rats using the nitroblue tetrazolium (NBT) reaction. The glycosylation of extra-cellular matrix (ECM) components such as laminin and fibronectin was examined in vitro using the same method. Immunofluorescence staining of laminin or type IV collagen was also performed in renal tissues of STZ-induced diabetic rats. There was no significant difference in the intensity of NBT in renal tissues between 4 week STZ-induced diabetic rats and control rats of the same age. The intensity of NBT staining in the glomerular mesangial areas and capillary walls was marked in 12 week diabetic rats. The mean values of fructosamine measured by the NBT reaction in the glycosylated-laminin and fibronectin were increased dose dependently. In immunofluorescence, laminin and type IV collagen were observed significantly in the glomerular mesangial areas and capillary walls of 12 week diabetic rats. However, there was no significant change in renal histopathology in 4 and 12 weeks diabetic rats. It appears that the non-enzymatic glycosylation and expression of ECM components in glomeruli increased in the early stage of diabetic nephropathy prior to the appearance of marked histologic alterations. In conclusion, non-enzymatic glycosylation of glomerular structural components may play an important role in the initiation of the early stage of renal injuries in diabetes.


Exponentially Enhanced Light-Matter Interaction, Cooperativities, and Steady-State Entanglement Using Parametric Amplification.
We propose an experimentally feasible method for enhancing the atom-field coupling as well as the ratio between this coupling and dissipation (i.e., cooperativity) in an optical cavity. It exploits optical parametric amplification to exponentially enhance the atom-cavity interaction and, hence, the cooperativity of the system, with the squeezing-induced noise being completely eliminated. Consequently, the atom-cavity system can be driven from the weak-coupling regime to the strong-coupling regime for modest squeezing parameters, and even can achieve an effective cooperativity much larger than 100. Based on this, we further demonstrate the generation of steady-state nearly maximal quantum entanglement. The resulting entanglement infidelity (which quantifies the deviation of the actual state from a maximally entangled state) is exponentially smaller than the lower bound on the infidelities obtained in other dissipative entanglement preparations without applying squeezing. In principle, we can make an arbitrarily small infidelity. Our generic method for enhancing atom-cavity interaction and cooperativities can be implemented in a wide range of physical systems, and it can provide diverse applications for quantum information processing.


Deleterious effects of non-synonymous single nucleotide variants of human IL-1β gene.
The IL-1β gene is currently topic of interest for its important role in the pathogenesis of intervertebral disk degeneration. The new sequencing technology makes it crucial to study the effects of variants in IL-1β. Thus, 714 IL-1β variants with evidence supporting were collected from the EMBL database. Among them, 62 were non-synonymous single nucleotide variants (nsSNVs). Furthermore, six common nsSNVs were predicted to have damaging effects by SIFT, PolyPhen, PROVEAN and SNPs&GO. Based on the constructed three-dimensional structure of pro-IL-1β, rs375479974 with a mutation of Phe to Ser was proposed to reduce the stability of the pro-IL-1β protein. The rs375479974 variant was found to cause least common stabilizing amino acid residues, decrease hydrophilic and increase hydrophobic surface areas in the greatest degree, and have the lowest free energy alterations in I-Mutant 2.0 sequence analysis. When analyzing the interaction between the experimental 3D structure of mature IL-1β and its neutralizing McAb canakinumab complex, the rs775174784 substitution of Leu with Phe was found to attenuate this interaction by reducing binding energy, while rs375479974 not. Molecular dynamics simulation results in intervertebral disk environment supported rs775174784's effects. These results suggest that both rs375479974 and rs775174784 may have potential clinical and drug target implications.


Multi-vehicle detection with identity awareness using cascade Adaboost and Adaptive Kalman filter for driver assistant system.
Vision-based vehicle detection is an important issue for advanced driver assistance systems. In this paper, we presented an improved multi-vehicle detection and tracking method using cascade Adaboost and Adaptive Kalman filter(AKF) with target identity awareness. A cascade Adaboost classifier using Haar-like features was built for vehicle detection, followed by a more comprehensive verification process which could refine the vehicle hypothesis in terms of both location and dimension. In vehicle tracking, each vehicle was tracked with independent identity by an Adaptive Kalman filter in collaboration with a data association approach. The AKF adaptively adjusted the measurement and process noise covariance through on-line stochastic modelling to compensate the dynamics changes. The data association correctly assigned different detections with tracks using global nearest neighbour(GNN) algorithm while considering the local validation. During tracking, a temporal context based track management was proposed to decide whether to initiate, maintain or terminate the tracks of different objects, thus suppressing the sparse false alarms and compensating the temporary detection failures. Finally, the proposed method was tested on various challenging real roads, and the experimental results showed that the vehicle detection performance was greatly improved with higher accuracy and robustness.


Long-term responses of higher and lower risk youths to smoking prevention interventions.
Adolescents at risk for cigarette smoking are difficult to reach with conventional interventions but have substantial exposure to the mass media. This study is the first to show that smoking prevention messages presented through the mass media can have large and durable effects on higher risk adolescents. Students in two communities received media and school interventions beginning in grades 5-7; those in matched comparison communities received school interventions. Media interventions were targeted to higher risk youths. School surveys were conducted before and after the interventions, in grades 4-6 and grades 8-10. Two years after interventions ended, when participants were in grades 10-12, school and telephone surveys were conducted to assess smoking status. Survey participants (n = 2,860) were classified at baseline as having higher or lower risk for becoming a smoker. Smoking prevalence within the higher risk sample was significantly lower for those receiving media-school interventions than for those receiving school interventions only (odds ratio = 0.71). Effects on the lower risk sample were similar in magnitude but marginally significant. Mass media and school interventions achieved lower smoking rates among higher risk youngsters 2 years following completion of the interventions. This strategy represents a uniquely effective method for communicating with a high-priority group.


Composite membranes of poly(lactic acid) with zinc-added bioactive glass as a guiding matrix for osteogenic differentiation of bone marrow mesenchymal stem cells.
This study aims to produce a degradable and bone-bioactive membrane for guiding bone regeneration by combining a degradable polymer, poly(lactic acid) (PLA), with a bioactive inorganic zinc-containing bioactive glass (ZnBG). The in vitro osteogenic development of rat bone marrow mesenchymal stem cells (rBMSCs) upon different membrane substrates (pure PLA control, PLA-BG, and PLA-ZnBG) was investigated in terms of bone cell phenotype syntheses and mineralization. Results showed significantly stimulated production of alkaline phosphatase and osteocalcin at days 14 and 21 in the membranes containing BG and ZnBG, with more in the samples containing ZnBG. The addition of ZnBG in PLA allowed the rBMSCs to express a high level of bone sialoprotein as confirmed by immunostaining. Cellular mineralization of the secreted extracellular matrix showed a significantly higher Ca level on the BG- and ZnBG-added membrane than on the PLA, and the more so in the ZnBG-added one. Based on the in vitro assessments using rBMSCs, the ZnBG-added PLA is considered to be of potential use in guiding active bone regeneration within the periodontal pocket.


Synthesis of Phenanthrothiazoles and 1,2-Di(heteroaryl)benzenes through Successive Pd-Catalyzed Direct Arylations.
Palladium-catalyzed direct arylation of 4-(2-bromophenyl)-2-methylthiazole proceeds with high efficiency at the thiazolyl C5 position using aryl bromides as the aryl source. This transformation provides simple access to 4-(2-bromophenyl)-2-methyl-5-arylthiazoles, which can be further converted into phenanthrothiazoles via palladium-catalyzed intramolecular direct arylation. When the direct arylation of 4-(2-bromophenyl)-2-methyl-5-arylthiazoles is conducted in the presence of an external heteroarene such as thiazoles, thiophenes, or imidazo[1,2-a]pyridines, the intermolecular arylation of such external heteroarenes proceeds faster than the intramolecular reaction, allowing the formation of 1,2-di(heteroaryl)benzene derivatives.


Detection of cocaine exposure in the neonate. Analyses of urine, meconium, and amniotic fluid from mothers and infants exposed to cocaine.
Cocaine and its metabolites were measured in urine, meconium, and amniotic fluid specimens collected from 30 maternal-infant pairs with histories of prenatal cocaine use. Cocaine, benzoylecgonine, and ecgonine methyl ester were measured by isotope dilution gas chromatography-mass spectrometry. Mothers were interviewed at delivery regarding their cocaine use during pregnancy. There was qualitative agreement between the results of drug determinations in maternal urine, amniotic fluid, infant urine, and meconium. Although all of the mothers in this study admitted to using cocaine during their pregnancy, cocaine or its metabolites were detected only in the 20 cases in which cocaine was used within 3 weeks before delivery. We conclude that when sufficiently sensitive analytic methods are used, maternal urine, infant urine, and meconium analyses yield equivalent results for detection of prenatal cocaine exposure. Importantly, neither meconium nor urinary drug measurements detected cocaine exposure when the last reported use was prior to 3 weeks before delivery.


Cancer chemoprevention and mitochondria: targeting apoptosis in transformed cells via the disruption of mitochondrial bioenergetics/redox state.
Cancer chemoprevention employs agents that block, hinder, or reverse tumorigenesis to prevent malignancy. Several putative cancer chemopreventive agents promote apoptosis in transformed cells initiated in animal carcinogenesis models or identified in human subjects, and/or in tumor cells cultured in vitro. Consequently, apoptosis induction is increasingly valued as a biologically significant anticancer mechanism in the arena of chemoprevention. In vitro studies suggest that the permeabilization of mitochondrial membranes is an important mechanistic determinant associated with the apoptosis induced by these agents. Mitochondrial membrane permeabilization (MMP) may occur via the control of proapoptotic Bcl-2 family members, and/or by the induction of the mitochondrial permeability transition. Both of these cell death-inducing regulatory mechanisms are ultimately responsive to the bioenergetic status/redox state of mitochondria. Interestingly, in addition to inducing MMP, various chemopreventive agents can directly modulate mitochondrial bioenergetics and/or redox tone in transformed cells. This review will examine prospective mechanisms associated with the disruption of mitochondrial function by chemopreventive agents that affect MMP and apoptosis. In doing so, we will construct a paradigm supporting the notion that the bioenergetic and/or redox characteristics of the mitochondria in transformed cells are important targets in the chemoprevention of cancer.


Business resilience: Reframing healthcare risk management.
The responsibility of risk management in healthcare is fractured, with multiple stakeholders. Most hospitals and healthcare systems do not have a fully integrated risk management system that spans the entire organizational and operational structure for the delivery of key services. This article provides insight toward utilizing a comprehensive Business Resilience program and associated methodology to understand and manage organizational risk leading to organizational effectiveness and operational efficiencies, with the fringe benefit of realizing sustainable operational capability during adverse conditions.


Effective components of treatment for the chemically dependent physician.
Physicians with substance use disorders have been documented throughout history. In 1973 the American Medical Association (AMA) acknowledged that physicians suffered from addiction with a landmark policy paper and subsequent Physician Health Conference. Since that time extensive information has been collected regarding the evaluation and treatment of physicians who have the disease of addiction. It is estimated that addiction affects ten percent of the current physician population. Effective treatment for these individuals centers around the fact that addiction is a chronic disease. Treatment initially requires intensive care for stabilization, education, and denial reduction. Ongoing treatment is then needed to help solidify gains made in primary treatment, modify self-care behaviors and attitudes, and to hopefully prevent relapse.


Multicritical points and topology-induced inverse transition in the random-field Blume-Capel model in a random network.
The interplay between quenched disorder provided by a random field (RF) and network connectivity in the Blume-Capel (BC) model is the subject of this paper. The replica method is used to average over the network randomness. It offers an alternative analytic route to both numerical simulations and standard mean field approaches. The results reveal a rich thermodynamic scenario with multicritical points that are strongly dependent on network connectivity. In addition, we also demonstrate that the RF has a deep effect on the inverse melting transition. This highly nontrivial type of phase transition has been proposed to exist in the BC model as a function of network topology. Our results confirm that the topological mechanism can lead to an inverse melting transition. Nevertheless, our results also show that as the RF becomes stronger, the paramagnetic phase is affected in such way that the topological mechanism for inverse melting is disabled.


[Circovirus infections in pigeons].
The first detection of circovirus infection in pigeons in Germany is described. The existing experiences with this still little known pigeon disease are summarized and similarities to circovirus infections in other species are shown.


Differential determinants of patent ductus arteriosus closure for prematurity of varying birth body weight: A Retrospective Cohort Study.
Patent ductus arteriosus (PDA) remains a critical issue in prematurity care. To predict the PDA closure early, we aimed to clarify the association of PDA closure with the initial postnatal 24-hour clinical characteristics and maternal and gestational histories of preterm neonates. A retrospective cohort study was conducted in a pediatric-neonatal-intensive-care-unit from 2008 to 2013. Data relating to birth histories, maternal histories, and clinical data from the first 24 h of life were analyzed according to three types of PDA closure-non-treated, medically-responsive, and surgically-ligated PDA and birth body weights (BBWs). Univariate analysis was performed using non-parametric analysis and Chi-square test or Fisher's exact test. Multivariate analysis was performed using multinomial logistic regression to determine the independent risk factors for the PDA closure. This study involved 682 preterm infants with median gestational age of 31 (interquartile, IQR: 28-34) weeks and BBW of 1360 (IQR: 1085-1861) g. Inclusively, 16.7% of (P)DAs underwent medical and/or surgical treatment. For very low birth body weight (VLBW) neonates, surfactant use not only predicted the requirement of PDA treatment, but together with dopamine use and the larger amount of first 24-hour intravenous fluid (IVF) per kilogram of BBW, it also predicted the possibility of surgical ligation. Meanwhile, the cut-off values of the IVF amount (87 and 89.5 ml/kg/day, respectively) might predict the PDA treatment necessity and surgical ligation. For neonates with BBW ≥1500 g, placenta previa and lower BBW and systolic blood pressure (SBP) predicted the risk of treatment for PDA and its treatment response. Neonatal care for PDA in prematurity should be meticulously personalized. Surfactant use, dopamine administration and the first 24-hour IVF management may be critical for PDA closure in VLBW neonates. Antepartum history of placenta previa, BBW and SBP control may be important for BBW≥1500 g.


Ultrasonographic evaluation of adrenal gland size compared to body weight in normal dogs.
The accepted cut-off value for adrenal gland maximum diameter of 0.74 cm to distinguish adrenal gland enlargement in dogs regardless of body weight may not be appropriate for small to medium breed dogs. The purpose of the current retrospective study was to examine adrenal gland dimensions as a function of body weight in healthy dogs in three weight categories (< 10 kg, 10-30 kg, and > 30 kg) representing small, medium, and large breeds, respectively, to establish greater confidence in determining if adrenal gland size is abnormal. The measurements of length (sagittal plane), cranial and caudal pole thickness (sagittal and transverse planes), and caudal pole width (transverse plane) of both adrenal glands were obtained ultrasonographically in clinically healthy dogs (n = 45) with 15 dogs in each weight group. Findings support our hypothesis that adrenal gland size correlates with body weight in normal dogs, and more precise reference intervals should be created for adrenal gland size by categorizing dogs as small, medium, or large breed. The caudal pole thickness of either adrenal gland in a sagittal plane was the best dimension for evaluating adrenal gland size based on low variability, ease, and reliability in measurement.


Development of Johnston's organ in Drosophila.
Hearing is a specialized mechanosensory modality that is refined during evolution to meet the particular requirements of different organisms. In the fruitfly, Drosophila, hearing is mediated by Johnston's organ, a large chordotonal organ in the antenna that is exquisitely sensitive to the near-field acoustic signal of courtship songs generated by male wing vibration. We summarize recent progress in understanding the molecular genetic determinants of Johnston's organ development and discuss surprising differences from other chordotonal organs that likely facilitate hearing. We outline novel discoveries of active processes that generate motion of the antenna for acute sensitivity to the stimulus. Finally, we discuss further research directions that would probe remaining questions in understanding Johnston's organ development, function and evolution.


Modality-specific attention under imminent but not remote threat of shock: evidence from differential prepulse inhibition of startle.
Theories of animal defensive behavior postulate that imminent, predictable threat elicits highly focused attention toward the threat source, whereas remote, unpredictable threat elicits distributed attention to the overall environment. We used threat of shock combined with measurement of prepulse inhibition of the startle reflex to test these claims in humans. Twenty-seven participants experienced periods of threat and safety. Threat and safe periods were short or long, with the short threat periods conveying relatively predictable, imminent shocks and the long threat periods conveying unpredictable shocks. Startle reflexes were elicited with equal numbers of acoustic probes presented alone, preceded by a tactile prepulse, or preceded by an auditory prepulse. We observed enhanced tactile relative to auditory prepulse inhibition during short threat periods only. This finding supports the notion that imminent threat, but not remote threat, elicits attention focused toward the relevant modality, potentially reflecting preparatory activity to minimize the impact of the noxious stimulus.


Application of the analytic hierarchy process to a risk assessment of emerging infectious diseases in Shaoxing city in southern China.
This study aimed to assess the likelihood of an outbreak or epidemic of emerging infectious diseases (EIDs) in Shaoxing city, China, and its resulting impact to provide decision makers with quantitative, directive results. Factors related to the risk of EIDs were selected through meeting with experts and were arranged in a hierarchical structure. These evaluation factors were also weighted to allow the use of a point system for evaluation. As a result, 14 evaluation factors comprising a 3-layer hierarchy were generated. The riskiest top 10 EIDs were HIV/AIDS (consistency index [CI] = 3.206), cholera (CI = 3.103), SARS (CI = 2.804), acute schistosomiasis (CI = 2.784), malaria (CI = 2.777), legionellosis (CI = 2.743), avian influenza A/H5N1 (CI = 2.734), dengue fever (CI = 2.702), Escherichia coli O157:H7 enteritis (CI = 2.593), and plague (CI = 2.553). The risk assessment was specifically intended to support local and national government agencies in the management of high risk EIDs in their efforts to (i) make resource allocation decisions, (ii) make high-level planning decisions, and (iii) raise public awareness of the EID risk. The results showed that the EID risk in Shaoxing could be effectively assessed through an analytic hierarchy process.


Performance metrics for the objective assessment of capacitive deionization systems.
In the growing field of capacitive deionization (CDI), a number of performance metrics have emerged to describe the desalination process. Unfortunately, the separation conditions under which these metrics are measured are often not specified, resulting in optimal performance at minimal removal. Here we outline a system of performance metrics and reporting conditions that resolves this issue. Our proposed system is based on volumetric energy consumption (Wh/m3) and throughput productivity (L/h/m2) reported for a specific average concentration reduction, water recovery, and feed salinity. To facilitate and rationalize comparisons between devices, materials, and operation modes, we propose a nominal standard separation of removing 5 mM from a 20 mM NaCl feed solution at 50% water recovery. We propose this particular separation as a standard, but emphasize that the rationale presented here applies irrespective of separation details. Using our proposed separation, we compare the desalination performance of a flow-through electrode (fte-CDI) cell and a flow between membrane (fb-MCDI) device, showing how significantly different systems can be compared in terms of generally desirable desalination characteristics. In general, we find that performance analysis must be considered carefully so to not allow for ambiguous separation conditions or the maximization of one metric at the expense of another. Additionally, for context and clarity, we discuss a number of important underlying performance indicators and cell characteristics that are not performance measures in and of themselves but can be examined to better understand differences in performance.


Characterizing parasitic nematode faunas in faeces and soil using DNA metabarcoding.
Gastrointestinal parasitic nematodes can impact fecundity, development, behaviour, and survival in wild vertebrate populations. Conventional monitoring of gastrointestinal parasitic nematodes in wild populations involves morphological identification of eggs, larvae, and adults from faeces or intestinal samples. Adult worms are typically required for species-level identification, meaning intestinal material from dead animals is needed to characterize the nematode community with high taxonomic resolution. DNA metabarcoding of environmental samples is increasingly used for time- and cost-effective, high-throughput biodiversity monitoring of small-bodied organisms, including parasite communities. Here, we evaluate the potential of DNA metabarcoding of faeces and soil samples for non-invasive monitoring of gastrointestinal parasitic nematode communities in a wild ruminant population. Faeces and intestines were collected from a population of wild reindeer, and soil was collected both from areas showing signs of animal congregation, as well as areas with no signs of animal activity. Gastrointestinal parasitic nematode faunas were characterized using traditional morphological methods that involve flotation and sedimentation steps to concentrate nematode biomass, as well as using DNA metabarcoding. DNA metabarcoding was conducted on bulk samples, in addition to samples having undergone sedimentation and flotation treatments. DNA metabarcoding and morphological approaches were largely congruent, recovering similar nematode faunas from all samples. However, metabarcoding provided higher-resolution taxonomic data than morphological identification in both faeces and soil samples. Although concentration of nematode biomass by sedimentation or flotation prior to DNA metabarcoding reduced non-target amplification and increased the diversity of sequence variants recovered from each sample, the pretreatments did not improve species detection rates in soil and faeces samples. DNA metabarcoding of bulk faeces samples is a non-invasive, time- and cost-effective method for assessing parasitic nematode populations that provides data with comparable taxonomic resolution to morphological methods that depend on parasitological investigations of dead animals. The successful detection of parasitic gastrointestinal nematodes from soils demonstrates the utility of this approach for mapping distribution and occurrences of the free-living stages of gastrointestinal parasitic nematodes.


Protein Immunodepletion and Complementation in Xenopus laevis Egg Extracts.
The Xenopus egg extract system has been widely used to study cell cycle events, including DNA replication, nuclear envelope formation, spindle assembly, chromosome condensation and kinetochore formation. The functional roles of the proteins involved in these processes can be determined by immunodepleting a protein of interest from the extract. As immunodepletion may result in co-depletion of other proteins, the protein of interest can be added back to the extract to verify its function. Additionally, proteins harboring point mutations or domain deletions may be added to assess their functions. Here we outline the immunodepletion procedure and two separate methods for restoring a protein of interest: addition of either a recombinant protein or an mRNA that supports translation in egg extracts. The tradeoffs between these two methods are discussed.


[Comparative study of magnesium salts bioavailability in rats fed a magnesium-deficient diet].
The purpose of this study was to compare efficiency of compensation of alimentary Mg deficiency after administration of 12 organic and 8 inorganic magnesium salts and to evaluate the ability of vitamin B6 to accelerate their effect. Two hundred eighty rats were placed on a Mg-deficient diet (Mg content (15 mg/kg) and demineralized water for 7 weeks. Twelve control rats were fed a basal diet (Mg content 500 mg/kg). Starting from day 49 of the Mg-deficient diet, the rats were given magnesium salts (50 mg magnesium and 5 mg pyridoxine per kg): Mg chloride, Mg sulphate, Mg oxide, M nitrate, Mg thiosulphate, Mg hydrophosphate, Mg carbonate, Mg trisilicate, Mg (L-, D- and DL-) aspartate, Mg (L- and DL-) pyroglutamate, Mg succinate, Mg glycinate, Mg orotate, Mg taurate, Mg lactate or their combination with vitamin B6 (5 mg/kg b.w.). Erythrocyte and plasma Mg levels were measured by spectrophotometry following the colour reaction between Mg and titanium yellow. Mg L-aspartate compensated for magnesium deficit more effectively and faster than all other salts. Mg chloride showed the highest efficiency among inorganic magnesium salts. Both Mg chloride and Mg L-aspartate in combination with vitamin B6 caused statistically significant compensation of magnesium deficit.


A retrospective study of persistence, adherence, and health economic outcomes of fixed-dose combination vs. loose-dose combination of oral anti-diabetes drugs.
To compare outcomes between patients with type 2 diabetes mellitus (T2DM) using fixed-dose combination (FDC) and loose-dose combination (LDC) products. This retrospective cohort study used MarketScan Commercial and Medicare Supplemental data from January 1, 2009-December 31, 2013. The identified population included patients with T2DM and ≥1 additional oral anti-diabetic prescription (of the same regimen [FDC/LDC] as the index prescription) within 12 months following the fill date. Persistence (no ≥30-day gap) and adherence (medication possession ratio [MPR] ≥0.8) were assessed as primary end-points; secondary end-points included hypoglycemia, healthcare resource utilization, and costs. Of 23,361 patients identified, 12,590 (53.9%) were on FDC therapy and 10,771 (46.1%) were on LDC therapy. FDC patients had a significantly lower rate of non-persistence (67.9% vs. 73.4%, p < 0.0001) and a significantly higher rate of adherence to therapy (57.0% vs. 50.7%, p < 0.0001) when compared to LDC patients. Average time to non-persistence was significantly longer among FDC vs. LDC patients (207.1 vs. 186.3 days, p < 0.0001). After adjusting for baseline characteristics, the odds of non-persistence were 21% lower with FDC vs. LDC therapy (OR = 0.79, 95% CI = 0.74-0.85, p < 0.0001), with a 28% higher odds of adherence (OR = 1.28, 95% CI = 1.20-1.36, p < 0.0001). Differences in most secondary outcomes significantly favored FDC therapy, including total predicted monthly all-cause costs ($1008 vs. $1053; p = 0.006) and T2DM-related costs ($142 vs. $155; p < 0.001). Cohort classification was based on prescription claims data. The lack of clinical data limits assessment of potential influencers of FDC vs. LDC decisions, residual confounding was possible, and diabetes-related medical costs only captured claims with a primary diagnosis for diabetes. The results may not be generalizable to populations such as Medicaid. Management of T2DM using FDC therapies provides a compliance benefit relative to LDC therapies that may translate to reductions in healthcare utilization and costs.


Hesperidin Attenuates Titanium Dioxide Nanoparticle-Induced Neurotoxicity in Rats by Regulating Nrf-2/TNF-α Signaling Pathway, the Suppression of Oxidative Stress, and Inflammation.
Background: Titanium dioxide nanoparticles (TiO2NPs) are widely utilized and consumed mainly as food additives. Oxidative stress is considered to be the basic effect of TiO2NPs through biological interactions. Hesperidin (HSP) is a bioflavonoid (flavanone glycoside) with lipid-lowering, inflammation, oxidative stress suppression, antihypertensive, cancer-fighting, and antiedema effects. Objective: This study was to investigate the possible protective influences of HSP of subchronic oral TiO2NP exposure on the brains of rats, including neurotransmitters, oxidative stress/antioxidant parameters, inflammatory markers, and histological changes in the brains of adult male albino rats. Methodology: The experiment was executed on 80 albino rats. The animals were randomly divided into 4 equal groups. The first group served as a control; the second group was treated with oral doses of HSP (100 mg/kg Bw daily); the third group received TiO2NPs (200 mg/kg Bw orally daily); and the fourth group was treated with TiO2NPs and an oral dose of HSP daily for 8 weeks. Blood samples were obtained for biochemical analysis. Neurotransmitters, oxidative stress biomarker levels, and inflammatory markers were measured in brain homogenates. Histological examination of the brain was performed through H&E staining. Results: Coadministration of hesperidin with TiO2NPs orally for 8 weeks decreased the levels of MDA, TNF-α, AChE, and dopamine in brain homogenates, which were increased in the TiO2NP group. It increased the other oxidative biomarkers (SOD, CAT, and GPx) and Nrf-2 expression levels. Brain histological sections of the TiO2NP-treated group show degeneration, necrosis, congestion, and inflammatory cell infiltration that decreased markedly in the coadministration of hesperidin with the TiO2NP group. Conclusion: Hesperidin cotreatment offers significant protection against TiO2NP-induced oxidative stress and biochemical and histological alteration in the brain.


Stable propagation of an ordered array of cracks during directional drying.
We study the appearance and evolution of an array of parallel cracks in a thin slab of material that is directionally dried, and show that the cracks penetrate the material uniformly if the drying front is sufficiently sharp. We also show that cracks have a tendency to become evenly spaced during the penetration. The typical distance between cracks is mainly governed by the typical distance of the pattern at the surface, and it is not modified during the penetration. Our results agree with recent experimental work, and can be extended to three dimensions to describe the properties of columnar polygonal patterns observed in some geological formations.


Transcriptome Analysis Reveals Altered Expression of Memory and Neurotransmission Associated Genes in the REM Sleep Deprived Rat Brain.
Sleep disorders are associated with cognitive impairment. Selective rapid eye movement sleep (REMS) deprivation (REMSD) alters several physiological processes and behaviors. By employing NGS platform we carried out transcriptomic analysis in brain samples of control rats and those exposed to REMSD. The expression of genes involved in chromatin assembly, methylation, learning, memory, regulation of synaptic transmission, neuronal plasticity and neurohypophysial hormone synthesis were altered. Increased transcription of BMP4, DBH and ATP1B2 genes after REMSD supports our earlier findings and hypothesis. Alteration in the transcripts encoding histone subtypes and important players in chromatin remodeling was observed. The mRNAs which transcribe neurotransmitters such as OXT, AVP, PMCH and LNPEP and two small non-coding RNAs, namely RMRP and BC1 were down regulated. At least some of these changes are likely to regulate REMS and may participate in the consequences of REMS loss. Thus, the findings of this study have identified key epigenetic regulators and neuronal plasticity genes associated to REMS and its loss. This analysis provides a background and opens up avenues for unraveling their specific roles in the complex behavioral network particularly in relation to sustained REMS-loss associated changes.


The Whistleblower's Dilemma in Young Children: When Loyalty Trumps Other Moral Concerns.
When a group engages in immoral behavior, group members face the whistleblower's dilemma: the conflict between remaining loyal to the group and standing up for other moral concerns. This study examines the developmental origins of this dilemma by investigating 5-year-olds' whistleblowing on their in- vs. outgroup members' moral transgression. Children (n = 96) watched puppets representing their ingroup vs. outgroup members commit either a mild or a severe transgression. After the mild transgression, children tattled on both groups equally often. After the severe transgression, however, they were significantly less likely to blow the whistle on their ingroup than on the outgroup. These results suggest that children have a strong tendency to act on their moral concerns, but can adjust their behavior according to their group's need: When much is at stake for the ingroup (i.e., after a severe moral transgression), children's behavior is more likely to be guided by loyalty.


Chemical Structures of Polyphenols That Critically Influence the Toxicity of ZnO Nanoparticles.
Recent studies suggested that phytochemicals as natural antioxidants in food could alleviate nanoparticle (NP) toxicity. This study investigated the combined toxicity of ZnO NPs and a panel of polyphenols. Surprisingly, polyphenols with both high and almost no radical scavenging activities could elicit cytoprotective effects against NP exposure in Caco-2 cells, which were primarily influenced by the positions of the hydroxyl group. Polyphenols with different chemical structures variously influenced the hydrodynamic size, zeta potential, and solubility of ZnO NPs as well as NP-induced intracellular superoxide and Zn ions, which could all contribute to the combined effects. Responses of human endothelial cells appeared to be different from the responses of Caco-2 cells, which may indicate cell-type dependent responses to combined exposure of NPs and phytochemicals. In conclusion, the data from this study suggested a pivotal role of chemical structures of phytochemicals in determining their capacity to affect ZnO NP toxicity.


Detection and evolutionary analysis of soybean miRNAs responsive to soybean mosaic virus.
MicroRNAs (miRNA) are a class of non-coding RNAs that have important gene regulatory roles in various organisms. However, the miRNAs involved in soybean's response to soybean mosaic virus (SMV) are unknown. To identify novel miRNAs and biotic-stress regulated small RNAs that are involved in soybean's response to SMV, two small RNA libraries were constructed from mock-inoculated and SMV-infected soybean leaves and sequenced. This led to the discovery of 179 miRNAs, representing 52 families, among which five miRNAs belonging to three families were novel miRNAs in soybean. A large proportion (71.5 %) of miRNAs arose from segmental duplication, similar to the process that drives the evolution of protein-coding genes. In addition, we predicted 346 potential targets of these identified miRNAs, and verified 12 targets by modified 5'-RACE analysis. Finally, three miRNAs (miR160, miR393 and miR1510) that are involved in plant resistance were observed to respond to SMV infection. The interaction between miRNAs and resistance-related genes provides a novel mechanism for pathogens to evade host recognition.