Flow cytometric assessment of morphology, viability, and production of reactive oxygen species of Crassostrea gigas oocytes. Application to toxic dinoflagellate (Alexandrium minutum) exposure.
The Pacific oyster Crassostrea gigas accounts for a large part of shellfish aquaculture production worldwide. Aspects of morphological and functional characteristics of oyster oocytes remain poorly documented, and traditional techniques, such as microscopic observations of shape or fertilization rate, are time and space consuming. The purpose of this study was to assess for the first time viability and reactive oxygen species (ROS) production of Pacific oyster oocytes using flow cytometry (FCM) and to apply this method to determine oocyte responses to in vitro exposure to the toxic dinoflagellate Alexandrium minutum. A culture of A. minutum caused a significant increase in oocyte ROS production, which gradually increased with the age of the culture, but viability was not affected. Effect of the supernatant of the same A. minutum culture did not cause any significant modifications of oocyte morphology, viability, or ROS level. This study confirmed that some oocyte cellular characteristics can be assessed using FCM techniques.


Resilient distributed control in the presence of misbehaving agents in networked control systems.
In this paper, we study the problem of reaching a consensus among all the agents in the networked control systems (NCS) in the presence of misbehaving agents. A reputation-based resilient distributed control algorithm is first proposed for the leader-follower consensus network. The proposed algorithm embeds a resilience mechanism that includes four phases (detection, mitigation, identification, and update), into the control process in a distributed manner. At each phase, every agent only uses local and one-hop neighbors' information to identify and isolate the misbehaving agents, and even compensate their effect on the system. We then extend the proposed algorithm to the leaderless consensus network by introducing and adding two recovery schemes (rollback and excitation recovery) into the current framework to guarantee the accurate convergence of the well-behaving agents in NCS. The effectiveness of the proposed method is demonstrated through case studies in multirobot formation control and wireless sensor networks.


Tremor and Quality of Life in Patients With Advanced Essential Tremor Before and After Replacing Their Standard Deep Brain Stimulation With a Directional System.
Patients with essential tremor treated with thalamic deep brain stimulation may experience increased tremor with the progression of their disease. Initially, this can be counteracted with increased stimulation. Eventually, this may cause unwanted side-effects as the circumferential stimulation from a standard ring contact spreads into adjacent regions. Directional leads may offer a solution to this clinical problem. We aimed to compare the ability of a standard and a directional system to reduce tremor without side-effects and to improve the quality of life for patients with advanced essential tremor. Six advanced essential tremor patients with bilateral thalamic deep brain stimulation had their standard system replaced with a directional system. Tremor rating scale scores were prospectively evaluated before and after the replacement surgery. Secondary analyses of quality of life related to tremor, voice, and general health were assessed. There was a significantly greater reduction in tremor without side-effects (p = 0.017) when using the directional system. There were improvements in tremor (p = 0.031) and voice (p = 0.037) related quality of life but not in general health for patients using optimized stimulation settings with the directional system compared to the standard system. In this cohort of advanced essential tremor patients who no longer had ideal tremor reduction with a standard system, replacing their deep brain stimulation with a directional system significantly improved their tremor and quality of life. Up-front implantation of directional deep brain stimulation leads may provide better tremor control in those patients who progress at a later time point.


Determination of non-steroidal estrogens in breast milk, plasma, urine and hair by gas chromatography/mass spectrometry.
It is suspected that all the natural estrogens occurring in the human body, as well as dietary and synthetic estrogens, diversely affect the endocrine system depending on their exposure patterns. More rapid, reliable and accurate measurements of these compounds in various biological matrices are thus becoming an important task. After solid-phase extraction using an Oasis HLB extraction cartridge, the estrogen concentrates were derivatized with a mixture of N-methyl-N-trifluorotrimethylsilylacetamide/ammonium iodide/dithioerythritol (1000:4:5, v/w/w) for analysis by gas chromatography/mass spectrometry in the selected ion-monitoring (SIM) mode. The qualitative identification of estrogens detected in SIM mode was further confirmed by tandem mass spectrometry using low-energy collision-induced dissociation (CID) mode. The method for the assay of the 20 estrogens was linear over the ranges of 1-1000 micro g/L for biological fluids and 1-200 micro g/kg for hair with high correlation coefficient (>0.99). The limits of quantitation (LOQ) ranged from 1.0-10 micro g/L (or micro g/kg) and the limit of detection ranged from 0.2-3 micro g/L (or micro g/kg). The average precision (% CV) and accuracy (% bias) of the method determined at the LOQ, low, and medium concentrations were in the ranges 2.6-9.2 and -4.1-7.7, respectively. The average extraction recovery of the estrogens from plasma and hair at the three concentration levels varied in the ranges 77-103% (1.9-14.3% CV) and 73-104% (3.1-14%), respectively. The distribution patterns of the estrogens were characteristic of each biosample. Five estrogens in the range 1.5-44.9 micro g/L were measured in breast milk, 8 estrogens in the range 3.5-322 micro g/L in plasma, 12 estrogens at 1.2-442 micro g/L in urine, and biochanin-A at 13.2-39.1 micro g/kg in hair. Because of its high sensitivity, good precision and specificity, the present method was found suitable for the trace analysis of dietary and synthetic estrogens in complex biosamples such as breast milk, plasma, urine and hair.


Is nitric oxide important in photodynamic therapy?
Photodynamic therapy (PDT) involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light and oxygen to destroy abnormal tissue. The transfer of energy from the activated photosensitizer to available oxygen results in the formation of toxic reactive oxygen species, such as singlet oxygen and free radicals, which can damage proteins, lipids, nucleic acids, and other cellular components. PDT is now commonly used in ophthalmology, dermatology and oncology however the therapeutic response to PDT exhibits variability, ranging from highly sensitive to extremely resistant. Over the last 10 years it has been suggested that nitric oxide (NO) may play a role in PDT, with evidence that NO is produced by both tumour and normal cells in addition to controlling important functions in tumour progression. NO may also influence the outcome of cancer therapies, such as PDT. PDT induces oxidative stress, vascular-mediated damage and leukocyte recruitment, processes all sensitive to NO. This review outlines the role of nitric oxide in PDT primarily focusing on vascular damage and how this may be modulated to improve therapeutic outcome.


Cloning of PCS gene (TpPCS1) from Tagetes patula L. and expression analysis under cadmium stress.
Phytochelatins (PCs) constitute an important mechanism for plants to resist heavy metal stress. Widely found in higher plants, they are small heavy metal binding peptides, synthesized through catalysis of phytochelatin synthase (PCS). We speculate that there may be PCS genes in Peacock grass (Tagetes patula L., Asteraceae), which is an important reason for its rich cadmium. In order to obtain the full-length cDNA sequence of the PCS gene from T. patula L. used rapid amplification of cDNA ends (RACE). Meanwhile, Relative expression of TpPCS1 under different concentrations of cadmium (Cd) stress was analysed using quantitative real-time polymerase chain reaction (qRT-PCR). Results found ORF of TpPCS1 genes with a length of 1970 bp, a gene coding area length of 1764 bp, coding for 587 amino acids. Expression of TpPCS1 under Cd stress was tissue specific. TpPCS1 in the root showed higher expression, while expression in the leaf and seed was relatively low. This research demonstrates that expression of TpPCS1 enhanced the enrichment of cadmium in T. patula L. roots and could be used to construct a plant hyperexpression carrier that would provide new avenues for plant restoration technology.


Who supports public employees strikes?
This research found that strikes by public employees are most likely to be tolerated by younger people, by citizens who feel city wages should be higher, by blue-collar workers, by black people and by citizens dissatisfied with their treatment by police officers. Respondents to this survey did not distinguish among categories of public employees when evaluating the desirability of strikes.


Comparison of the accuracy of quadriceps isometric exercise between using quadriceps education device (QED) and not using QED for osteoarthritic knee patients: a randomized controlled trial.
To compare the accuracy when osteoarthritic knee patients do quadriceps isometric exercise using quadriceps education device (QED) and not using QED after being instructed on the exercise program by doctors. A randomized controlled study was conducted. Sixty patients were divided into 2 groups, QED group (patients using QED) and non-QED group (patients not using QED). We developed the Quadriceps Educational Device (QED). All patients were instructed on the quadriceps exercise method. Patients in the QED group were instructed to use the QED device and received the QED to take back and conducted the exercises at home. After 2 weeks, both groups of patients were tested by asking them to do the quadriceps exercise without using the QED. The accuracy of the quadriceps exercise was analyzed to determine the statistical difference. Chi-square test was used for statistical analysis. The number of patients in the QED group that conducted accurate quadriceps exercise totaled 23 patients (79.3%), while the number of non-QED was reduced to 8 patients (28.6%). The results were significantly different in statistic (p < 0.01). Patients in the QED group conducted the quadriceps exercise more accurately than the non-QED group. The osteoarthritic knee patients, who used QED, can do the quadriceps isometric exercise more accurately than those who did not use the QED after being instructed on the exercise program by doctors.


A Case of Single Atrium, Mitral Valve Prolapse Spontaneously - Closed Inlet VSD with Polydactyly.
Single Atrium is a complex cardiac anomaly and generally a component of certain congenital syndromes. It is extremely rare for SA to be observed as an isolated defect. We report here a 14 year-old male patient with SA with MVP with spontaneously-closed inlet-VSD with polydactyly. He was examined first at "L. Harun Health Complex" 77 Sehora, Mymensingh, Bangladesh on 11th September 2016 and then at National Heart Foundation Hospital, Mirpur, Dhaka, Bangladesh on 17th October 2016.


Synthesis and characterisation of enhanced barrier polyurethane for encapsulation of implantable medical devices.
Polymeric membranes have been used as interfaces between implantable devices and biological tissues to operate as a protective barrier from water exchanging and to enhance biocompatibility. Polyurethanes have been used as biocompatible membranes for decades. In this study, copolymers of polyether urethane (PEU) with polydimethylsiloxane (PDMS) were synthesised with the goal of creating materials with low water permeability and high elasticity. PDMS was incorporated into polymer backbone as a part of the soft segment during polyurethane synthesis and physical properties as well as water permeability of resulting copolymer were studied in regard to PDMS content. Increase in PDMS content led to increase of microphase separation of the copolymer and corresponding increase in elastic modulus. Surface energy of the polymer was decreased by incorporating PDMS compared to unmodified PEU. PDMS in copolymer formed a hydrophobic surface which caused reduction in water permeability and water uptake of the membranes. Thus, PDMS containing polyurethane with its potent water resistant properties demonstrated a great promise for use as an implantable encapsulation material.


Effects of Knee Position on the Reliability and Production of Maximal and Rapid Strength Characteristics During an Isometric Squat Test.
This study aimed to examine the effects of knee position on the reliability and production of peak force (PF) and rate of force development (RFD) characteristics during an isometric squat. Fourteen resistance-trained females performed isometric squats at 90, 120, and 150° knee angles (corresponding to parallel, half, and quarter squat positions, respectively) on 2 different occasions, from which PF, peak RFD, and early (RFD30, RFD50, RFD100) and late (RFD200) phase RFD variables were extracted. PF and RFD200 were highly consistent across trials for all 3 squat positions, with intraclass correlation coefficients (ICCs) ranging between 0.812-0.904 and coefficients of variation (CVs) between 6.6-19.4%. For peak and early RFD characteristics, higher ICCs and lower CV values were observed for the quarter squat (ICCs = 0.818-0.852, CVs = 17.3-19.4%) compared to the parallel (ICCs = 0.591-0.649, CVs = 30.1-55.9%) and half squats (ICCs = 0.547-0.598,CVs = 31.1-34.2%). In addition, isometric PF and RFD200 increased (P ≤ .001-0.04) with squat position (parallel < half < quarter); however, there were no differences for peak RFD (P ≥ .27), RFD30 (P ≥ .99), RFD50 (P ≥ .99), and RFD100 (P ≥ .09). These findings suggest that performing isometric squats at higher (150°) rather than lower knee joint angles (90-120°) may provide for an improved capacity to produce greater PF and RFD200 as well as a more reliable testing position for measuring peak and early RFD characteristics.


Development of a violence tool in the emergency hospital setting.
Violence against nurses is an on-going issue in healthcare settings, and is regularly documented in the literature. Assessing the potential for violence against nurses in the emergency department is essential to maintain their safety. The aim of this study was to develop a violence assessment tool by refining a list of predictive cues identified from both a previous study and existing literature. Using the Delphi technique, a panel of 11 expert nurse academics and clinicians developed a 37-item questionnaire and used three rounds of Delphi to refine the violence assessment questionnaire. The resulting tool comprises 17 cues of potential violence that can be easily observed and requires no prior knowledge of the perpetrators' medical history.


Purified human BRCA2 stimulates RAD51-mediated recombination.
Mutation of the breast cancer susceptibility gene, BRCA2, leads to breast and ovarian cancers. Mechanistic insight into the functions of human BRCA2 has been limited by the difficulty of isolating this large protein (3,418 amino acids). Here we report the purification of full-length BRCA2 and show that it both binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). BRCA2 acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. BRCA2 does not anneal ssDNA complexed with RPA, implying it does not directly function in repair processes that involve ssDNA annealing. Our findings show that BRCA2 is a key mediator of homologous recombination, and they provide a molecular basis for understanding how this DNA repair process is disrupted by BRCA2 mutations, which lead to chromosomal instability and cancer.


Measurement of the mechanical properties of skin with ballistometer and suction cup.
There is no consensus on the methodology for describing the mechanical properties of human skin in vivo. Current descriptions are generally method dependent. The mechanical properties of palmar skin of the hypothenar as well as dorsal and ventral forearm skin were studied in 17 healthy volunteers. Two methods were used: ballistometry [Dia-stron Torsional Ballistometer (Diastron Ltd., Andover, UK)] and suction cup [The Dermaflex machine (Cortex Technology, Hadsund, Denmark)]. A moderate degree of correlation was found between the methods (rs=0.315-0.540), while internal correlation between different measures obtained with one method was higher (rs=0.375-0.967). The suction cup method parameters (distensibility and elasticity) correlated significantly with the ballistometry parameters (indentation, alpha, area and coefficient of restitution), while the hysteresis did not correlate to ballistometry parameters. The coefficient of variation of both methods (CV=0.02-0.35) was within the range obtained with other non-invasive methods, e.g., TEWL. Regional differences were identified with both methods, while only the suction cup method identified age-related changes. The results suggest that while both methods may be useful, they describe related but not identical aspects of skin mechanics. The differences in measuring principle suggest that the suction cup method predominantly measures elasticity, while the ballistometer predominantly appears to measure stiffness. Hysteresis may be a unique measure of skin viscosity. Additional studies, however, are needed to specify the clinical significance of the various measures of skin mechanics.


Cryo-soft X-ray tomography: using soft X-rays to explore the ultrastructure of whole cells.
Cryo-soft X-ray tomography is an imaging technique that addresses the need for mesoscale imaging of cellular ultrastructure of relatively thick samples without the need for staining or chemical modification. It allows the imaging of cellular ultrastructure to a resolution of 25-40 nm and can be used in correlation with other imaging modalities, such as electron tomography and fluorescence microscopy, to further enhance the information content derived from biological samples. An overview of the technique, discussion of sample suitability and information about sample preparation, data collection and data analysis is presented here. Recent developments and future outlook are also discussed.


Elongating Nexus Between Workplace Factors and Knowledge Hiding Behavior: Mediating Role of Job Anxiety.
The study objective is to investigate the relationship between workplace ostracism, workplace incivility, and knowledge hiding behavior (evasive hiding, playing dumb, rationalized hiding) while considering the mediating role of job anxiety. The study collected data through structured questionnaires from 275 participants (ie, employees) working in the small to medium-sized enterprise of five big cities of Pakistan. The study adopted a structured equation modeling technique for data analysis. Significantly, the study results suggest a positive effect of workplace ostracism and workplace incivility on employees' knowledge hiding behavior, and job anxiety significantly mediates the relationship between workplace ostracism, workplace incivility, and knowledge hiding behavior of employees. The present study highlights the need to examine the personality disposition for understanding the relationship between the variables (eg, workplace ostracism, workplace incivility, knowledge hiding behavior). Employees' inappropriate behavior had suppressed by initiating a campaign for a realistic job preview, setting an exceptional example. The study significantly contributes to the current literature on knowledge hiding behavior by presenting valuable insight into organizational and individual variables, subsequently influencing the knowledge hiding behavior of individuals. Indeed, this study is the first to investigate the predictive effect of the proposed variables.


Rapid Diagnosis of Tuberculosis from Analysis of Urine Volatile Organic Compounds.
The World Health Organization has called for simple, sensitive, and non-sputum diagnostics for tuberculosis. We report development of a urine tuberculosis test using a colorimetric sensor array (CSA). The sensor comprised of 73 different indicators captures high-dimensional, spatiotemporal signatures of volatile chemicals emitted by human urine samples. The sensor responses to 63 urine samples collected from 22 tuberculosis cases and 41 symptomatic controls were measured under five different urine test conditions. Basified testing condition yielded the best accuracy with 85.5% sensitivity and 79.5% specificity. The CSA urine assay offers desired features needed for tuberculosis diagnosis in endemic settings.


Vitamin-Containing Antioxidant Formulation Reduces Carcinogen-Induced DNA Damage through ATR/Chk1 Signaling in Bronchial Epithelial Cells In Vitro.
Lung cancer has the highest mortality rate worldwide and is often diagnosed at late stages, requiring genotoxic chemotherapy with significant side effects. Cancer prevention has become a major focus, including the use of dietary and supplemental antioxidants. Thus, we investigated the ability of an antioxidant formulation (AOX1) to reduce DNA damage in human bronchial epithelial cells (BEAS-2B) with and without the combination of apple peel flavonoid fraction (AF4), or its major constituent quercetin (Q), or Q-3-O-d-glucoside (Q3G) in vitro. To model smoke-related genotoxicity, we used cigarette-smoke hydrocarbon 4-[(acetoxymethyl)nitrosamino]-1-(3-pyridyl)-1-butanone (NNKOAc) as well as methotrexate (MTX) to induce DNA damage in BEAS-2B cells. DNA fragmentation, γ-H2AX immunofluorescence, and comet assays were used as indicators of DNA damage. Pre-exposure to AOX1 alone or in combination with AF4, Q, or Q3G before challenging with NNKOAc and MTX significantly reduced intracellular reactive oxygen species (ROS) levels and DNA damage in BEAS-2B cells. Although NNKOAc-induced DNA damage activated ATM-Rad3-related (ATR) and Chk1 kinase in BEAS-2B cells, pre-exposure of the cells with tested antioxidants prior to carcinogen challenge significantly reduced their activation and levels of γ-H2AX (p ≤ 0.05). Therefore, AOX1 alone or combined with flavonoids holds promise as a chemoprotectant by reducing ROS and DNA damage to attenuate activation of ATR kinase following carcinogen exposure.


Healing men and community: predictors of outcome in a men's initiatory and support organization.
Men have poorer health and declining social outcomes when compared to women, and research suggests that behaviors related to restrictive and traditional male gender roles contribute to this disparity. This study is an examination of The ManKind Project International (MKPI), a community-based organization that provides alternative male gender norms and a community support system to help reinforce them. The MKPI runs an intensive, experiential "Training Adventure Weekend" (TAW), followed by voluntary, on-going peer-led support and integration groups (I-Groups). One hundred men completed a pre-TAW questionnaire, an interview, and a long-term follow-up (>18 mo.) questionnaire. The study examined if there was change on the primary study variables at follow-up, and the relationship of background characteristics (age, self-help group experience) and factors related to participation (MKPI beliefs, social support, I-Group participation) to the criterion variables (depression symptoms, gender role conflict, and life satisfaction) at follow-up. Results indicated significant change in the expected directions on the primary study variables, suggesting that for these men, participation has a positive impact. Most importantly, changes in MKPI-related beliefs and social support significantly predicted positive outcomes. Also, more positive outcomes were found among men 30-44 years of age, but not among those with more prior self-help experience or I-Group participation. Possible explanations for these findings and directions for further research are discussed.


[Hypothalamic and pituitary function in brain death].
Hypothalamic and pituitary hormone levels were measured in 56 patients meeting the criteria of brain death proposed by the Japanese Ministry of Welfare. Pituitary hormone releasing tests were carried out in 39 patients. In addition, cerebral angiography and transcranial Doppler (TCD) were performed in 13 and six patients, respectively, just after hormone measurements. Serum hypothalamic and pituitary hormone levels were inconsistently high based on the half life time in the presumed absence of cerebral blood flow shown by angiography. The responses to releasing hormones were normal in 16 patients. TCD detected cerebral blood flow in the middle cerebral artery or ophthalmic artery in three patients who showed non-filling on angiography. Postmortem microscopic examination of the hypothalamus and anterior pituitary lobe revealed normal structure and cells intermingled with lytic changes and necrosis. This series suggests that some part of the hypothalamus and hypophysis may still be alive after brain death, although the function of these regions may be clinically insignificant.


Web-based interrogation of gene expression signatures using EXALT.
Widespread use of high-throughput techniques such as microarrays to monitor gene expression levels has resulted in an explosive growth of data sets in public domains. Integration and exploration of these complex and heterogeneous data have become a major challenge. The EXALT (EXpression signature AnaLysis Tool) online program enables meta-analysis of gene expression profiles derived from publically accessible sources. Searches can be executed online against two large databases currently containing more than 28,000 gene expression signatures derived from GEO (Gene Expression Omnibus) and published expression profiles of human cancer. Comparisons among gene expression signatures can be performed with homology analysis and co-expression analysis. Results can be visualized instantly in a plot or a heat map. Three typical use cases are illustrated. The EXALT online program is uniquely suited for discovering relationships among transcriptional profiles and searching gene expression patterns derived from diverse physiological and pathological settings. The EXALT online program is freely available for non-commercial users from http://seq.mc.vanderbilt.edu/exalt/.


The natural history of a novel, systemic, disseminated model of syngeneic mouse B-cell lymphoma.
Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates para-spinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics. Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates para-spinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics.


A model for human situs determination.
Alterations of human laterality range from situs reversal or consensus isometry to isolated anomalies of the cardiac, respiratory, gastrointestinal, skeletal, and central nervous systems. A mechanism for human situs determination has been derived from the general model of Brown and Wolpert (1990) , with steps involving A-P axis, D-V axis, midline, global situs, and local situs specification. Comparison with Drosophila segmentation is supported by maternal transmission of certain human situs defects and mutation of appropriate Drosophila gene homologues in the human Waardenburg and Greig syndromes. Anteroposterior gradients in expression of vertebrate homeotic genes may relate to a proposed hierarchy of regional laterality decisions. Early alterations in A-P or D-V axis polarity would produce situs reversal in 100 of individuals, as observed in pure situs inversus, homozygous inv mice or manipulated Xenopus embryos. Later alterations would permit random right-left decisions and account for heterotaxy in 50 of affected individuals, as observed in poly asplenia or homozygous iv mice. Randomisation of brain asymmetry could explain why situs but not brain laterality may be reversed in humans, with forebrain situs reversal or isometry leading to brain anomalies. Homologues of Drosophila genes regulating axis polarity, heart and gut development are attractive candidates in human laterality disorders, but none is uniquely localised to the 6q14-q21 or9q32-q34, 7q22, 10q21-22, 11q13 or 11q25, 12q13, 13qter, or Xq24-q27.1 chromosome regions highlighted by heterotaxic patients or mutant mice.


Orbit-Engineered Anisotropic Magnetoresistive Effect for Constructing a Magnetic Sensor with Ultrahigh Sensitivity.
A strong anisotropic magnetoresistance (AMR) effect induced by spin-orbit coupling is the basis for constructing a highly sensitive and reliable magnetic sensor. Presently, effective AMR enhancement in traditional films focuses on the modulation of the lattice or charge degree of freedom, leading to a general AMR ratio below 4%. Here, we demonstrate a different strategy to strengthen the AMR effect by tuning the orbital degree of freedom. By inserting an oxygen-affinitive Hf layer into a Ta/MgO/NiFe/MgO/Ta multilayer film, Fe-O orbital hybridization at the MgO/NiFe interface was modulated to trigger an effective orbital reconfiguration of Fe. In turn, the number of holes in the in-plane symmetric d orbits of Fe increased substantially, facilitating the s-d electron scattering to enhance the AMR ratio to 4.8%. By further micromachining the film into a Wheatstone bridge, we constructed a sensing element that displayed an ultrahigh sensitivity of 2.7 mV/V/Oe and a low noise detectability of 0.8 nT/√Hz. These findings help to advance the development of orbit-governed AMR sensors and provide an alternative method for tuning other orbit-related physical effects.


Two in one: patient-controlled epidural analgesia (PCEA) to prevent erection and control pain in adult hypospadias-surgery patients.
Following penile surgery, erections are painful and may prejudice the result, because the sutures may not withstand a rigid erection. Therefore, prevention of erection and management of pain are extremely important following hypospadias repair, especially in adult patients. In this prospective study, we aimed to achieve these goals by using an epidural block with patient-controlled analgesia. We allocated 20 adult patients scheduled for hypospadias repair randomly either to receive or not to receive epidural analgesia. Postoperative pain was scored according to a standardised scoring system, based on a 10 point visual analogue scale. In group I (n = 10), analgesia was provided by a 3 ml h(-1) continuous infusion of fentanyl (2 microg) and bupivacaine solution (0.125%) in 1 ml saline via an epidural catheter for the first 3 days. Patient-controlled epidural analgesia was administered with an additional 5 ml of the same solution when the pain score was high (> 4). After 3 days, fentanyl was excluded from the treatment protocol, and analgesia was maintained with bupivacaine (0.125%). In group II (n = 10, control group), an epidural catheter was not inserted, and analgesia was maintained with pethidine (1 mg kg(-1)). Pain management was found to be more effective in group I. No erections occurred in group I, but the erection rate in group II was mean +/- s.d. = 1.7 +/- 0.2. The differences were found to be statistically significant (P<0.05). We highly recommend the technique described here, which offers efficient analgesia and control of erection in adult hypospadias patients.


Risk differential between Medicare beneficiaries enrolled and not enrolled in an HMO.
Medicare provides incentive reimbursements to health maintenance organizations (HMOs) which enroll Medicare beneficiaries on a risk option and provide care at a lower cost than expected. The incentive reimbursements are tied to an actuarial calculation of Medicare Adjusted Average Per Capita Cost (AAPCC). The AAPCC adjusts for a number of variables which affect Medicare reimbursements and for which data are available: place of residence, age, sex, welfare status, and institutional status of beneficiaries. These factors account for much of the expected difference in health care reimbursements. They do not, however, account for differences in health status. Because of this, AAPCC calculations of expected costs may be too high if a selected group of beneficiaries is healthier than average, or too low if the selected group has a poorer health status than average. This case study examines the utilization behavior and reimbursement experience of a group of Medicare beneficiaries prior to their joining an HMO (during an open enrollment period) under a risk-sharing option. Their use was compared with a comparable Medicare population (the comparison group) to determine if their usage rates were greater, equal, or less than average. Results show that beneficiaries who joined during open enrollment had a rate of hospital inpatient use over 50 percent below the comparison group and a reimbursement rate for inpatient services 47 percent below the comparison group. These beneficiaries' use of Part B services also appears to be lower than the comparison group. These results must be interpreted with care. The information came from a single case study. Specific aspects of the open enrollment process, described in the paper, further limit the general liability of the findings. Also, while some studies of the same subject support the results, many others do not.


Magnetic shielding in a low-temperature torsion pendulum experiment.
A new type of ether drift experiment searches for anomalous torques on a permanent magnet. A torsion pendulum is used at liquid helium temperature so that superconducting cylinders can be used to shield magnetic fields. Lead shields attenuate the earth's field, while Nb-Sn shields fastened to the pendulum contain the fields of the magnet. The paper describes the technique by which the earth's field can be reduced below 10(-4) G while simultaneously the moment of the magnet can be reduced by a factor of 7 x 10(4).


Silicone Breast Implant and Automatic Implantable Cardioverter Defibrillator: Can They Coexist? A Case Report.
We present a case of a silicone breast implant rupture after insertion of an automatic implantable cardioverter defibrillator (AICD). A 51-year-old woman presented to our plastic surgery clinic to exchange her silicone breast implants. The patient underwent cosmetic mastopexy and breast augmentation in 2008. Because of recurrent myocardial infarctions and chronic heart failure, she underwent an insertion of an AICD in 2014 in which the left breast implant was hit. In this report, we discuss the first case of an AICD insertion, disrupting a breast implant. This case report illustrates the rare but real possibility of breast implant rupture after even minor surgical manipulation of the breast area.


Electrocatalytic Degradation of Levofloxacin, a Typical Antibiotic in Hospital Wastewater.
Presently, in the context of the novel coronavirus pneumonia epidemic, several antibiotics are overused in hospitals, causing heavy pressure on the hospital's wastewater treatment process. Therefore, developing stable, safe, and efficient hospital wastewater treatment equipment is crucial. Herein, a bench-scale electrooxidation equipment for hospital wastewater was used to evaluate the removal effect of the main antibiotic levofloxacin (LVX) in hospital wastewater using response surface methodology (RSM). During the degradation process, the influence of the following five factors on total organic carbon (TOC) removal was discussed and the best reaction condition was obtained: current density, initial pH, flow rate, chloride ion concentration, and reaction time of 39.6 A/m2, 6.5, 50 mL/min, 4‱, and 120 min, respectively. The TOC removal could reach 41% after a reaction time of 120 min, which was consistent with the result predicted by the response surface (40.48%). Moreover, the morphology and properties of the electrode were analyzed. The degradation pathway of LVX was analyzed using high-performance liquid chromatography-mass spectrometry (LC-MS). Subsequently, the bench-scale electrooxidation equipment was changed into onboard-scale electrooxidation equipment, and the onboard-scale equipment was promoted to several hospitals in Dalian.


Is gene therapy the answer for prostate cancer?
Prostate cancer is the third most common cancer, accounting for one in 10 cancer diagnoses in men worldwide during 2000. Despite this high burden of morbidity, there is a lack of curative treatments for locally advanced and metastatic disease. Good anatomical accessibility of the prostate combined with substantial molecular understanding of the disease makes prostate cancer an attractive target for gene therapy. Considerable progress has been made in the development of suitable gene transfer vectors and prostate-targeting strategies. Therapeutic approaches being explored fall into two broad categories: corrective and cytoreductive/cytolytic. There are currently 63 prostate cancer gene therapy clinical trials based on these approaches registered in the United States and United Kingdom. Although significant hurdles remain to be overcome, early clinical trial results are encouraging, suggesting that gene therapy may become an important treatment option for prostate cancer.


Adult growth hormone deficiency and bone mass.
Bone mineral density (BMD) is reduced in adults with growth hormone (GH) deficiency and the decrease in BMD appears more marked if the GH deficiency is childhood onset rather than adult onset. Recent epidemiological studies suggest an increased fracture rate in GH-deficient adults. The skeletal response to GH therapy depends on the variety of GH deficiency, the type of bone studied and the duration of therapy. In the childhood-onset, GH-deficient adult there is either no change or a reduction in cortical and integral bone mass over the first 6 months, whereas at 6 months there is an increase in vertebral trabecular BMD. Subsequently there is a steady rise in BMD at all sites over the next 12-18 months. In the adult-onset, GH-deficient adult, the long-term results are more contentious. It is too early to determine whether GH therapy modifies fracture risk.


Ab initio calculations of the electronic states of AsH2 including dissociation characteristics.
Multireference configuration interaction calculations have been carried out for low-lying electronic states of AsH(2). Bending potentials for the ten lowest states of AsH(2) are obtained in C(2v) symmetry for As-H distances fixed at the the ground state equilibrium value of 2.845 a(0), as well as for the minimum energy path constrained to R(1) = R(2). The calculated equilibrium geometries for the X̃(2)B(1) ground state and the Ã(2)A(1) excited state agree very well with the previous experimental and theoretical results, whereas the data for the higher-lying states are obtained for the first time. Asymmetric potential energy surface (PES) cuts (at R(1) = 2.845 a(0), θ = 90.7°) and two-dimensional (2D) PESs for the lowest three states are also new. The calculated ab initio data are used for analysis of possible AsH(2) photodissociation channels and predissociation effects. It is shown that the Ã(2)A(1)-X̃(2)B(1) transition dipole moment decreases with increasing bending angle, which influences the intensity distribution in the Ã(0,0,0)→X̃ emission spectrum (v(2)'' bending series), shifting its maximum to smaller v(2)'' quantum numbers.


Study of HMG-CoA Reductase Inhibition Activity of the Hydrolyzed Product of Snakehead Fish (Channa striata) Skin Collagen with 50 kDa Collagenase from Bacillus licheniformis F11.4.
Bioactive peptides produced from enzymatic hydrolysis fibrous protein have been proven to have several biological activities. Previous study showed that the hydrolysis product of snakehead fish skin collagen with 26 kDa collagenase from Bacillus licheniformis F11.4 showed HMG-CoA (HMGR) inhibition activity. The aim of this research was to determine the ability of the hydrolysis product produced from snakehead fish skin collagen hydrolysed by 50 kDa collagenase from B. licheniformis F11.4 in inhibiting HMGR activity. Snakehead fish skin collagen was extracted using an acid method and collagenase was produced from B. licheniformis F11.4 using half-strength Luria Bertani (LB) medium containing 5% collagen. Crude collagenase was concentrated and fractionated using the DEAE Sephadex A-25 column eluted with increasing gradient concentrations of NaCl. Collagen, collagenase, and fractions were analyzed using SDS-PAGE and collagenolytic activity was analyzed by the zymography method. Collagenase with 50 kDa molecular weight presented in fraction one was used to hydrolyze the collagen. The reaction was done in 18 hours at 50°C. The hydrolysis product using 3.51 μg collagen and 9 ng collagenase showed 25.8% inhibition activity against pravastatin. This work shows for the first time that the hydrolysis product of snakehead fish skin collagen and 50 kDa collagenase from B. licheniformis F11.4 has potential as an anticholesterol agent.


Single molecule force spectroscopy reveals that iron is released from the active site of rubredoxin by a stochastic mechanism.
Metal centers in metalloproteins involve multiple metal-ligand bonds. The release of metal ions from metalloproteins can have significant biological consequences, so understanding of the mechanisms by which metal ion dissociates has broad implications. By definition, the release of metal ions from metalloproteins involves the disruption of multiple metal-ligand bonds, and this process is often accompanied by unfolding of the protein. Detailed pathways for metal ion release from metalloproteins have been difficult to elucidate by classical ensemble techniques. Here, we combine single molecule force spectroscopy and protein engineering techniques to investigate the mechanical dissociation mechanism of iron from the active site of the simplest iron-sulfur protein, rubredoxin, at the single molecule level. Our results reveal that the mechanical rupture of this simplest iron center is stochastic and follows multiple, complex pathways that include concurrent rupture of multiple ferric-thiolate bonds as well as sequential rupture of ferric-thiolate bonds that lead to the formation of intermediate species. Our results uncover the surprising complexity of the rupture process of the seemingly simple iron center in rubredoxin and provide the first unambiguous experimental evidence concerning the detailed mechanism of mechanical disruption of a metal center in its native protein environment in aqueous solution. This study opens up a new avenue to investigating the rupture mechanism of metal centers in metalloproteins with unprecedented resolution by using single molecule force spectroscopy techniques.


Investigation of fluconazole heteroresistance in clinical and environmental isolates of Cryptococcus neoformans complex and Cryptococcus gattii complex in the state of Amazonas, Brazil.
Heteroresistance, defined as the occurrence of apparently homogeneous subpopulations of microbial cells showing different levels of antimicrobial susceptibility is a problem that has been associated with therapeutical failure in cryptococcosis. The purpose of the study was an investigation on the level of heteroresistance to fluconazole (LHF) as observed in clinical and environmental C. neoformans/C. gattii complex species isolates from Amazonas State (AM), Brazil. A total of 45 isolates and 9 type strains were analyzed. The assessments comprised testing for minimal inhibitory concentrations (MICs), for LHFs, for the strains' capacity of adaptation to high fluconazole (FLC) concentrations above the LHF, and for the stability of the heteroresistance phenomenon. The mean MICs for clinical isolates of C. gattii (6.4 µg/ml) were higher than those observed for environmental C. gattii strains (1.7 µg/ml) and clinical (3.7 µg/ml) as well as environmental (1.5 µg/ml) C. neoformans isolates. The phenomenon of heteroresistance to FLC was recorded for all isolates. On average, the LHF (8-256 µg/ml) of the isolates was 16 times higher than the FLC MICs (0.5-16 µg/ml) and a proportion of 85% isolates showed LHFs ≥ 16 µg/ml, 40% even ≥ 32 µg/ml. According to the adaptation assay, a considerable number of isolates (58%) showed the capacity of adaptation to MICs even higher than the initially recorded LHF. After the adaptation experiment, the adaptative-LHF values (8-512 µg/ml) were about 60 times higher than the original MIC values. After nine subsequent passages in drug-free broth, the isolates had their adaptative-LHF reduced. However, the LHF did not revert to the initially measured level. Our findings challenge the clinical interpretation of the antifungal MIC testing and motivate future studies correlating the levels of heteroresistance and parameters like LHF and adaptative-LHF with cryptococcosis-associated morbidity and mortality. Cryptococcosis affects many people and is caused by fungi of the Cryptococcus neoformans/Cryptococcus gattii complexes. These agents appear to become more resistant to antifungals when exposed to increasing concentrations of antifungals due to a phenomenon called heteroresistance.


Potential Risks of Poaceous Plants as Infectious Sources of Rice Black-Streaked Dwarf Virus Transmitted by the Small Brown Planthopper, Laodelphax striatellus.
The recent reemergence of rice black-streaked dwarf virus (RBSDV) has caused severe rice yield losses in several areas of East Asia. To identify the most important infectious sources of RBSDV, we compared the susceptibility of major poaceous plants to RBSDV infection and survival and the RBSDV acquisition efficiency of a vector insect, the small brown planthopper Laodelphax striatellus. RBSDV infection and survival rates of L. striatellus were significantly high in wheat (Triticum aestivum 'Norin61') and rice (Oryza sativa 'Reiho'), indicating that these crops can be important sources of RBSDV. Our results also showed that RBSDV can complete its infection cycle between Italian ryegrass (Lolium multiflorum 'Hataaoba') and L. striatellus. These results indicate that control of RBSDV and L. striatellus on winter-spring crops of wheat and Italian ryegrass may avoid an RBSDV epidemic on rice during the following summer. In addition to infections of wheat and Italian ryegrass, RBSDV infections were detected in Avena fatua, Avena sterilis subsp. ludoviciana, Cynosurus echinatus, Festuca arundinacea, Festuca pratensis, Lolium perenne, and Vulpia myuros var. megalura, although the infection efficiency varied.


A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity.
To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10-8), hospitalization (OR = 0.61, P = 8 × 10-8) and susceptibility (OR = 0.78, P = 8 × 10-6). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case-control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.


Obtaining the structure and bond rotational potential of a substituted ethane by NMR spectroscopy of solutions in nematic liquid-crystalline solvents.
Partially averaged dipolar couplings (also referred to as residual dipolar couplings) D(ij) can be obtained from the analysis of the NMR spectra of molecules dissolved in liquid-crystalline solvents. Their values for a nonrigid molecule depend upon the bond lengths and angles, the rotational potentials, and the orientational order of the molecules. The molecule studied, 1-chloro-2-bromoethane, is one of the simplest example of a substituted alkane in which the rotational potential has three minimum-energy positions, trans and gauche+/-conformations, and the present investigation explores the problems inherent in deriving the form of the potential and the molecular geometry from the set of partially averaged couplings between the protons, and between protons and (13)C nuclei. The geometrical parameters and the rotational potential obtained are compared with the results from a density-functional theory method.


[Vertebral body stenting. A method for repositioning and augmenting vertebral compression fractures].
Purpose of the study was to demonstrate the effectiveness of expanding a fractured vertebral body by transpedicular dilatation and stenting. 7 human cadaveric vertebral bodies from L2 to L5 underwent axia compression until a vertebral burst fracture was provoked. Then, by bilateral transpedicular approach, balloon-catheters were introduced, which were armed with stents, usually used for angioplasty. The catheters were inflated with radiolucent fluid and the stents expanded under radiologic control. After expansion, the balloon was deflated and removed, the stents resting inside the vertebral body, holding their inflated shape. Then, the resulting hole was filled with an injectable biodegradable calcium-phosphate. CT-scans were performed after destruction and after expansion. Morphology before and after expansion was judged, using 3-D reconstructions. Vertebral body strength was measured before destruction and after treatment with an Instron testing machine. Vertebral body shape could be restored. Also impressed central parts of the bony endplate could be elevated by using a convergent approach through the pedicles. There was no collapse of the vertebral body after removing the catheter-balloons The vertebral body strength could be restored up to a physiologic level. This procedure gives new perspectives in the treatment either of osteoporotic compression or traumatic vertebral fracture. By using CT-guided technique, it could be performed by a minimally invasive approach percutaneously.


[Current situation of patients with chronic filariasis in Lianshui County, Ji- angsu Province].
To understand the current situation of chronic filariasis patients in Lianshui County. The chronic filariasis patients registered were interviewed one by one to observe their clinical signs and episodes of illness during recent one year. There were 361 patients with chronic filariasis in Lianshui County up to 2014, and they distributed in 23 townships. Among all the patients, 128 were male and 233 were female. Most of the patients were farmers (98.34%) and aged ≥ 70 years (63.71%). The clinical signs of the patients including lymphedema of the lower limbs (87.81%), chyluria (18.56%), lymphangitis or lymphadenitis (12.74%) and hydrocele of tunica vaginalis (2.49%), and there were 8.86% of the patients showed more than two signs. Among the patients with lymphedema of lower limbs, 97.79% were in stage I to III, and 2.21% were in stage IV. In 2014, the ill condition of 28.36% of the patients with chyluria and 45.65% of the ones with lymphangitis or lymphadenitis relapsed. The concern and care to the patients with chronic filariasis should be continued, so as to reduce the pain as well as improve the quality of life of them.


Mouse mesenchymal stem cells can support human hematopoiesis both in vitro and in vivo: the crucial role of neural cell adhesion molecule.
We previously established a mesenchymal stem cell line (FMS/PA6-P) from the bone marrow adherent cells of fetal mice. The cell line expresses a higher level of neural cell adhesion molecule and shows greater hematopoiesis-supporting capacity in mice than other murine stromal cell lines. Since there is 94% homology between human and murine neural cell adhesion molecule, we examined whether FMS/PA6-P cells support human hematopoiesis and whether neural cell adhesion molecules expressed on FMS/PA6-P cells contribute greatly to the human hematopoiesis-supporting ability of the cell line. When lineage-negative cord blood mononuclear cells were co-cultured on the FMS/PA6-P cells, a significantly greater hematopoietic stem cell-enriched population (CD34(+)CD38(-) cells) was obtained than in the culture without the FMS/PA6-P cells. Moreover, when lineage-negative cord blood mononuclear cells were cultured on FMS/PA6-P cells and transplanted into SCID mice, a significantly larger proportion of human CD45(+) cells and CD34(+)CD38(-) cells were detected in the bone marrow of SCID mice than in the bone marrow of SCID mice that had received lineage-negative cord blood mononuclear cells cultured without FMS/PA6-P cells. Furthermore, we found that direct cell-to-cell contact between the lineage-negative cord blood mononuclear cells and the FMS/PA6-P cells was essential for the maximum expansion of the mononuclear cells. The addition of anti-mouse neural cell adhesion molecule antibody to the culture significantly inhibited their contact and the proliferation of lineage-negative cord blood mononuclear cells. These findings suggest that neural cell adhesion molecules expressed on FMS/PA6-P cells play a crucial role in the human hematopoiesis-supporting ability of the cell line.


[Nasal cytology in patients with non-seasonal atopic rhinitis].
The results of the cytological evaluation of the nasal smears taken from the patients with non-seasonal atopic rhinitis were presented. In 95% of smears a very abundant cytological material of the columnar epithelium cells was found. The smears taken by cyto-brushing (Medscand) showed the presence of the cytological material from the whole nasal mucosa, while those taken by the loop contained the cells from the small area of the mucosa.


Mathematical problem solving and working memory in children with learning disabilities: both executive and phonological processes are important.
The purpose of this investigation was to explore the relationship between working memory (WM) and mathematical problem solving in children with learning disabilities (LD). Children with LD (age 11.5 years) were compared to chronologically age-matched (CA-M) and younger comprehension/computation achievement-matched children (age 8.9 years) on measures of verbal and visual-spatial WM, phonological processing, components of problem solving, and word-problem solving accuracy. The results showed that (1) children with LD were inferior on measures of word solution accuracy, components of problem solving, phonological processing, domain-general WM, and verbal WM when compared to children who were CA-M, (2) children with LD were comparable to younger children on all processing measures, except measures of domain-general WM, visual-spatial WM, phonemic deletion, and identifying problem goals, (3) measures of verbal and visual-spatial WM contributed significant variance to solution accuracy independent of phonological processing, and (4) the influence of WM on solution accuracy was mediated by long-term memory (LTM) processes related to the knowledge of algorithms. The results support the notion that information activated from LTM, rather than phonological processing, mediates the relationship between executive processing and solution accuracy in children with LD.


Phosphorylation and activation of androgen receptor by Aurora-A.
Aurora-A kinase is frequently overexpressed/activated in various types of human malignancy, including prostate cancer. In this study, we demonstrate elevated levels of Aurora-A in androgen-refractory LNCaP-RF but not androgen-sensitive LNCaP cells, which prompted us to examine whether Aurora-A regulates the androgen receptor (AR) and whether elevated Aurora-A is involved in androgen-independent cell growth. We show that ectopic expression of Aurora-A induces AR transactivation activity in the presence and absence of androgen. Aurora-A interacts with AR and phosphorylates AR at Thr(282) and Ser(293) in vitro and in vivo. Aurora-A induces AR transactivation activity in a phosphorylation-dependent manner. Ectopic expression of Aurora-A in LNCaP cells induces prostate-specific antigen expression and cell survival, whereas knockdown of Aurora-A sensitizes LNCaP-RF cells to apoptosis and cell growth arrest. These data indicate that AR is a substrate of Aurora-A and that elevated Aurora-A could contribute to androgen-independent cell growth by phosphorylation and activation of AR.


Alignment method combining interference lithography with anisotropic wet etch technique for fabrication of high aspect ratio silicon gratings.
A method was developed for aligning interference fringes generated in interference lithography to the vertical {111} planes of <110> oriented silicon wafers. The alignment error is 0.036°. This high precision method makes it possible to combine interference lithography with anisotropic wet etch technique for the fabrication of high aspect ratio silicon gratings with extremely smooth sidewalls over a large sample area. With this alignment method, 320 nm and 2 μm period silicon gratings have been successfully fabricated. The highest aspect ratio is up to 100. The sample area is about 50 mm × 60 mm. The roughness (root mean square) of the sidewall is about 0.267 nm.


Chemical tools to probe cellular O-GlcNAc signalling.
Protein O-GlcNAcylation is an abundant, dynamic and reversible type of protein post-translational modification in animals that has been implicated in signalling processes linked to innate immunity, stress response, growth factor response, transcription, translation and proteosomal degradation. Only two enzymes, O-GlcNAc (O-linked N-acetylglucosamine) transferase and O-GlcNAcase, catalyse the reversible addition of the O-GlcNAc residue to over 1000 target proteins in the human cell. Recent advances in our understanding of the structures and mechanisms of these enzymes have resulted in the development of potent and selective inhibitors. The present review gives an overview of these inhibitors and how they have been used on cell lines, primary cells and animals to modulate O-GlcNAc levels and study the effects on signal transduction.


Inulin supplementation induces expression of hypothalamic antioxidant defence genes in weaned piglets.
Fibre plays an important role in diluting dietary energy density. Fibre is also implicated in the regulation of appetite, perhaps through direct effects in the brain. However, there is little information on this effect in pigs. Therefore, this study was conducted to investigate the effect of fibre type in regulating the expression of genes involved in appetite control, inflammation and antioxidant defence in the hypothalamus of weaned piglets. A total of 64 Duroc × Landrace × Yorkshire barrows at 37 days old were blocked by body weight and allotted to two dietary treatments, supplementation with either 0.25% cellulose (Solka-Floc) or inulin (INU) for 28 days, after which animals were killed for analysis. Pigs fed INU had a tendency (p = 0.06) for reduced feed intake in the first week, although this effect disappeared in subsequent weeks. Pigs supplemented with INU had lower expression of dopamine (dopamine receptor D2), serotonin (5-hydroxytryptamine receptor 1B), free fatty acid (GPR43) and neuropeptide Y receptor Y2 receptors in the hypothalamus (p < 0.05). Expression of the tryptophan hydroxylase 2 gene in the hypothalamus also tended (p = 0.09) to be lower for pigs fed INU. The abundance of antioxidant defence genes, superoxide dismutase (SOD1) and catalase, were greater (p < 0.05) but that of a proinflammatory gene, interleukin 1β, was lower (p < 0.05) in the hypothalamus of pigs fed INU. Therefore, consumption of INU causes downregulation of inflammation in the hypothalamus and regulation of the abundance of serotonin or dopamine receptors, and may also increase antioxidant defence through upregulation of SOD and catalase in weaned piglets.


[Clinical research of acupuncture at stellate ganglion in the treatment of posterior circulation ischemia and its impacts on blood pressure].
To compare the difference in the clinical efficacy on posterior circulation ischemia between acupuncture at stellate ganglion and conventional acupuncture as well as the impacts on blood pressure. Eighty cases of posterior circulation ischemia were randomized into an observation group (40 cases) and a control group (40 cases). In the observation group, acupuncture was applied to the bilateral stellate ganglions on the neck, stimulated with reinforcing technique by rotating the needles. In the control group, the acupuncture of reducing technique was applied to Fengchi (GB 20), Baihui (GV 20), Neiguan (PC 6) and Taichong (LR 3) in the excess syndrome. The even needling or reinforcing technique was applied to Fengchi (GB 20), Baihui (GV 20), Ganshu (BL 18), Shenshu (BL 23) and Zusanli (ST 36) for the deficiency syndrome. The treatment was given once every 3 days and 4 treatments were required totally in the two groups. The changes in total syndrome score, peak Systolic blood flow velocity (Vp) of vertebral artery and basilar artery, systolic and diastolic blood pressures were compared before and after treatment in the two groups. The clinical efficacy was compared between the two groups. The total syndrome score was reduced apparently after treatment compared with that before treatment in the two groups (P < 0.01), and the reducing was more obvious in the observation group as compared with that in the control group (P < 0.01). The total effective rate was 87.5% (35/40) in the observation group, higher than 67.5% (27/40, P < 0.05) in the control group. After treatment, the reduced Vp of vertebral artery was not improved apparently as compared with that before treatment in the control group, Vp in blood velocity abnormality (including vascular spasm, stenosis or reduced velocity) of vertebral artery and basilar artery was all improved as compared with that before treatment in the two groups (P < 0.01), and the improvements in the observation group were more obvious than those in the control group (P < 0.01). After treatment, the systolic and diastolic pressures were reduced as compared with those before treatment in the two groups, and the reduced systolic and diastolic pressures in the observation group were more apparent than those in the control group (P < 0.01). Acupuncture at stellate ganglion achieves the satisfactory efficacy in the treatment of posterior circulation ischemia and the significant efficacy of reducing blood pressure, more advanced than the conventional acupuncture.


Ultraviolet Radiation in Wound Care: Sterilization and Stimulation.
Wound care is an important area of medicine considering the increasing age of the population who may have diverse comorbidities. Light-based technology comprises a varied set of modalities of increasing relevance to wound care. While low-level laser (or light) therapy and photodynamic therapy both have wide applications in wound care, this review will concentrate on the use of ultraviolet (UV) radiation. UVC (200-280 nm) is highly antimicrobial and can be directly applied to acute wound infections to kill pathogens without unacceptable damage to host tissue. UVC is already widely applied for sterilization of inanimate objects. UVB (280-315 nm) has been directly applied to the wounded tissue to stimulate wound healing, and has been widely used as extracorporeal UV radiation of blood to stimulate the immune system. UVA (315-400 nm) has distinct effects on cell signaling, but has not yet been widely applied to wound care. Penetration of UV light into tissue is limited and optical technology may be employed to extend this limit. UVC and UVB can damage DNA in host cells and this risk must be balanced against beneficial effects. Chronic exposure to UV can be carcinogenic and this must be considered in planning treatments. New high-technology UV sources, such as light-emitting diodes, lasers, and microwave-generated UV plasma are becoming available for biomedical applications. Further study of cellular signaling that occurs after UV exposure of tissue will allow the benefits in wound healing to be better defined.


[Measles and its secondary pulmonary complications: prevention is better than treatment].
Recent measles outbreaks observed in North America and in several European countries, including Italy, raised the attention about the risks linked to this infection and the need of implementing and maintaining adequate preventive strategies. Measles may cause several respiratory complications such as chronic obstructive lung disease, pneumonia, with subsequent development of chronic suppurative lung disease, giant cells pneumonia or progressive respiratory insufficiency. The current preventive strategies aim to improve vaccination coverage rates with 2 doses of measles-mumps and rubella vaccine, and to catch up individuals who have not been previously vaccinated. The present review analyses pulmonary complications of measles and measles preventive strategies. Elimination of measles is a feasible goal. Since measles complications are preventable by vaccination, improvement in vaccination coverage is highly desirable.


Piper nigrum extract ameliorated allergic inflammation through inhibiting Th2/Th17 responses and mast cells activation.
Piper nigrum (Piperaceae) is commonly used as a spice and traditional medicine in many countries. P. nigrum has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the effect of P. nigrum on allergic asthma has not been known. This study investigated the effect of P. nigrum ethanol extracts (PNE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we analysed the number of inflammatory cells and cytokines production in bronchoalveolar lavage fluid (BALF) and lung tissue; histological structure; as well as the total immunoglobulin (Ig)E, anti-OVA IgE, anti-OVA IgG1 and histamine levels in serum. The oral administration (200 mg/kg) of PNE reduced the accumulation of inflammatory cells (eosinophils, neutrophils in BALF and mast cells in lung tissue); regulated the balance of the cytokines production of Th1, Th2, Th17 and Treg cells, specifically, inhibited the expressions of GATA3, IL-4, IL-6, IL-1β, RORγt, IL-17A, TNF-α and increased the secretions of IL-10, INF-γ in BALF and lung homogenate. Moreover, PNE suppressed the levels of total IgE, anti-OVA IgE, anti-OVA IgG1 and histamine release in serum. The histological analysis showed that the fibrosis and infiltration of inflammatory cells were also ameliorated in PNE treated mice. On the other hand, PNE inhibited the allergic responses via inactivation of rat peritoneal mast cells degranulation. These results suggest that PNE has therapeutic potential for treating allergic asthma through inhibiting Th2/Th17 responses and mast cells activation.


Proteomic Screen for Cellular Targets of the Vaccinia Virus F10 Protein Kinase Reveals that Phosphorylation of mDia Regulates Stress Fiber Formation.
Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. Although this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase. F10 is essential for virion morphogenesis, beginning with the poorly understood process of diversion of membranes from the ER for the purpose of virion membrane biogenesis. To better understand the function of F10, we generated a cell line that carries a single, inducible F10 transgene. Using uninduced and induced cells, we performed stable isotope labeling of amino acids in cell culture (SILAC) coupled with phosphopeptide analysis to identify cellular targets of F10-mediated phosphorylation. We identified 27 proteins that showed statistically significant changes in phosphorylation upon the expression of the F10 kinase: 18 proteins showed an increase in phosphorylation whereas 9 proteins showed a decrease in phosphorylation. These proteins participate in several distinct cellular processes including cytoskeleton dynamics, membrane trafficking and cellular metabolism. One of the proteins with the greatest change in phosphorylation was mDia, a member of the formin family of cytoskeleton regulators; F10 induction led to increased phosphorylation on Ser22 Induction of F10 induced a statistically significant decrease in the percentage of cells with actin stress fibers; however, this change was abrogated when an mDia Ser22Ala variant was expressed. Moreover, expression of a Ser22Asp variant leads to a reduction of stress fibers even in cells not expressing F10. In sum, we present the first unbiased screen for cellular targets of F10-mediated phosphorylation, and in so doing describe a heretofore unknown mechanism for regulating stress fiber formation through phosphorylation of mDia. Data are available via ProteomeXchange with identifier PXD005246.


Investigating the beneficial traits of Trichoderma hamatum GD12 for sustainable agriculture-insights from genomics.
Trichoderma hamatum strain GD12 is unique in that it can promote plant growth, activate biocontrol against pre- and post-emergence soil pathogens and can induce systemic resistance to foliar pathogens. This study extends previous work in lettuce to demonstrate that GD12 can confer beneficial agronomic traits to other plants, providing examples of plant growth promotion in the model dicot, Arabidopsis thaliana and induced foliar resistance to Magnaporthe oryzae in the model monocot rice. We further characterize the lettuce-T. hamatum interaction to show that bran extracts from GD12 and an N-acetyl-β-D-glucosamindase-deficient mutant differentially promote growth in a concentration dependent manner, and these differences correlate with differences in the small molecule secretome. We show that GD12 mycoparasitises a range of isolates of the pre-emergence soil pathogen Sclerotinia sclerotiorum and that this interaction induces a further increase in plant growth promotion above that conferred by GD12. To understand the genetic potential encoded by T. hamatum GD12 and to facilitate its use as a model beneficial organism to study plant growth promotion, induced systemic resistance and mycoparasitism we present de novo genome sequence data. We compare GD12 with other published Trichoderma genomes and show that T. hamatum GD12 contains unique genomic regions with the potential to encode novel bioactive metabolites that may contribute to GD12's agrochemically important traits.


Circadian expression of Bmal1 and serotonin-N-acetyltransferase mRNAs in chicken retina cells and pinealocytes in vivo and in vitro.
Unlike mammals, rhythmic changes in serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase [AANAT]) transcripts in chicken pineal cells are controlled by an oscillator located in the pinealocytes themselves, which is comprised of clock genes. Asimilar clock-dependent pathway has been postulated to regulate the retinal melatonin rhythm. In chicken retinal photoreceptor cells and pinealocytes, the chicken AANAT gene (cAANAT) is coexpressed with clock genes, including cBmal1 and cClock, which might regulate cAANAT transcription. Here, we have studied the temporal profile of cBmal1, cClock, and cAANAT mRNAexpressions in retinal cells in vivo with chickens housed in a 14/10-h light/dark (LD) cycle for 2 wk and in vitro cultured in a superfusion system for 4 LD cycles. mRNA levels of these genes were analyzed by RT-PCR and compared with their corresponding pineal transcripts. cBmal1 mRNA showed a peak during the light phase between Zeitgeber time (ZT) 8 and 10, preceding the amplitude of the nocturnal increase in cAANAT expression at ZT 16-17. Retinal cBmal1 and cAANAT mRNAs exhibited less robust cycling than their corresponding pineal transcripts in the same animal. cClock mRNAlevels failed to exhibit a well-detectable rhythm. The phase of the rhythms of retinal cBmal1 and cAANAT mRNAs suggests a link between retinal cBmal1 and cAANAT expressions similar to the regulation of pineal cAANAT transcription. Based on the highly conserved nature of the clockwork, it is reasonable to consider that chicken retina and pineal gland might serve as a useful tool for the development of drugs that could influence clock function in man.


An evaluation of the aquatic hazard of cumene (isopropyl benzene).
Cumene manufacturers were required under a TSCA Section 4(a) test rule to evaluate the aquatic toxicity of cumene to daphnids, rainbow trout, mysid shrimp, and sheepshead minnows. Because of cumene's high volatility (vapor pressure, 3.2 mm Hg at 20 degrees C), all tests were conducted under flowthrough conditions using a proportional diluter system. The 96-hr LC50s for rainbow trout, sheepshead minnow, and mysid shrimp, based on mean measured concentrations, were 4.8, 4.7, and 1.3 mg/liter, respectively. The 48-hr daphnid EC50 was 4.0 mg/liter. Although cumene is considered moderately toxic to aquatic organisms under rigorous laboratory conditions, its volatility and biodegradability greatly reduce its hazard to the aquatic environment.


[Fecal microbiota transplantation: first case report in Chile and review].
Clostridium difficile (CD) infection is increasing in frequency and severity in in-hospital and outpatient clinical settings, with a recurrence that can reach 30% after first episode. The recurrences are usually treated with longer courses of metronidazole or vancomycin. Other treatments have been used, such as probiotics, fidaxomicin, rifaximin, immunoglobulins and monoclonal antibodies against toxins A and B. Fecal microbiota transplantation (FMT) has emerged as a promising strategy in this group of patients, with effectiveness greater than 90%. We present the first case reported in Chile of this therapeutic strategy in a patient with Crohn's disease and recurrent CD infection who presented after the fecal transplantation an Escherichia coli bacteremia, suggesting the need for caution in the use of this strategy. 10 months after the FMT the patient presented a new episode of E. coli bacteremia and two episodes of diarrhea due to CD infection, treated both of them with vancomycin with good clinical response.


Primary generalized seizure disorder: correlation of epileptiform discharges with seizure frequency.
The role of routine follow-up EEG in assessment of severity of a seizure disorder is not known. This retrospective chart review study of patients with primary generalized seizure disorders explored the relation between parameters of epileptiform discharge bursts on EEG and number of seizures experienced in the preceding months. Eighty-seven such patients were found, each with one to seven EEGs and corresponding clinical records, comprising a total of 201 clinicoelectrographic epochs. The 56 chronically attending patients (more than two attendances) differed from the 31 nonchronic attenders in receiving more antiepileptic drugs (AEDs) and having fewer EEG polyspikes; otherwise, the two groups were similar and were analyzed together. We noted a strong relation between number and maximum length of epileptiform bursts in the resting EEG record and number of absence seizures reported in the months preceding the EEG. Age did not affect this relation. After stepdown regression analysis, only the maximum length of epileptiform bursts remained significantly related to the reported number of absence seizures. These findings may prove useful in assessing clinical progress, e.g., in patients whose ability to estimate numbers of attacks is suspect. Neither number nor maximum length of epileptiform bursts in the resting EEG record had a significant relation with the number of generalized tonic-clonic seizures. Presence of polyspikes on resting or "activated" EEG had no added predictive value. The presence of epileptiform bursts after activation by sleep, hyperventilation, or photic stimulation was not associated with an increased likelihood of having had seizures.


Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection.
Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications.


Role of Cysteinyl Leukotrienes in Allergic Rhinitis.
Cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic rhinitis. Pharmacological studies using CysLTs indicate that two classes of receptor exist: CysLT1 receptor (CysLT1R) and CysLT2 receptor (CysLT2R). The CysLT1R is a high-affinity leukotriene D4 receptor with lower affinity for leukotriene C4 that is sensitive to the CysLT1R antagonist currently used to treat asthma and allergic rhinitis. Our previous immunohistochemical and autoradiographic studies have demonstrated the presence of anti-CysLT1R antibodies labeled in eosinophils, mast cells, macrophages, neutrophils and vascular endothelial cells in human nasal mucosa. Furthermore, we have revealed that the novel radioactive CysLT1R antagonist [3H]-pranlukast bound specifically to CysLT1R in human inferior turbinates and its binding sites were localized to vascular endothelium and the interstitial cells. These data suggest that the major targets of CysLT1R antagonists in allergic rhinitis are the vascular bed and infiltrated leukocytes such as mast cells, eosinophils and macrophages. Clinical trials have demonstrated that CysLT1R antagonists are as effective as antihistamines for the treatment of allergic rhinitis; however, they are less effective than intranasal steroids. The use of CysLT1R antagonists in combination with antihistamines has generally resulted in greater efficacy than when these agents were used alone.


Animal models of attention-deficit/hyperactivity disorder.
Attention-deficit hyperactivity disorder (AD/HD) is a clinically heterogenous disorder including hyperactivity, impulsivity, and inattention. Both psychostimulant and non-psychostimulant drugs such as methylphenidate and atomoxetine, respectively, to modulate catecholeamine neurotransmission are used as current pharmacotherapies for AD/HD. Multiple lines of evidence suggest that genetic factors play major roles in the etiology of AD/HD. meta-Analyses and pooled data analyses have suggested associations between AD/HD and polymorphisms in genes encoding monoamine neurotransmission molecules. There has been considerable research on this disorder using genetic, pharmacological, and neuroimaging approaches, and several animal models of AD/HD such as spontaneously hypertensive rat (SHR), dopamine transporter (DAT) knockout mice, coloboma mutant mouse, and Grin1 mutant mouse have been reported. These animal models are valuable tools for investigating molecular, cellular, and behavioral mechanisms as well as the neural development and circuit mechanisms of AD/HD. Here, we review the recent literature on animal models of AD/HD and discuss their advantages and limitations.


[[Work behavior of youth and recent changes in the fertility rate in Japan]].
"This paper observes and analyzes labor supply behavior and work attitude of...youth and discusses the impact they may have had on the recent change in [the] fertility rate in Japan." The author observes trends toward later marriage and a leisure-oriented life-style, and concludes that these shifts have helped to lower the fertility rate to 1.53 as of 1991. (SUMMARY IN ENG)


Pattern-reversal electroretinograms and visual evoked cortical potentials in multiple sclerosis.
Pattern-reversal and flash electroretinograms (ERG) and visual evoked cortical potentials (VECP) were recorded from 15 patients with definite multiple sclerosis (MS). All patients had prolonged VECP latency, indicating demyelination of one or both optic nerves. The pattern-reversal ERG amplitude was reduced below the level of normal variation (mean -2 SD) in 11 of the 22 eyes with prolonged VECP latency and in one of the eight eyes with normal VECP latency. The mean pattern-reversal ERG amplitude from eyes with prolonged VECP latencies was significantly lower than the mean amplitude from the normal controls. No abnormalities were observed in the flash ERGs. Degeneration of retinal ganglion cell axons has been demonstrated in MS patients. The amplitude reduction in the pattern-reversal ERG, observed in some 50% of the eyes with prolonged VECP latencies, is supposed to reflect retinal ganglion cell dysfunction or degeneration secondary to demyelination of the optic nerve.


Zinc-rich compounds of iron and cobalt: formation of [Fe2Zn(n)] (n = 2-4) and [Co2Zn3] cores.
The reactions of heteroleptic GaCp*/CO containing transition metal complexes of iron and cobalt, namely [(CO)(3)M(μ(2)-GaCp*)(m)M(CO)(3)] (Cp* = pentamethylcyclopentadienyl; M = Fe, m = 3; M = Co, m = 2) and [Fe(CO)(4)(GaCp*)], with ZnMe(2) in toluene and the presence of a coordinating co-solvent were investigated. The reaction of the iron complex [Fe(CO)(4)(GaCp*)] with ZnMe(2) in presence of tetrahydrofurane (thf) leads to the dimeric compound [(CO)(4)Fe{μ(2)-Zn(thf)(2)}(2)Fe(CO)(4)] (1). Reaction of [(CO)(3)Fe(μ(2)-GaCp*(3))Fe(CO)(3)] with ZnMe(2) and stoichiometric amounts of thf leads to the formation of [(CO)(3)Fe{μ(2)-Zn(thf)(2)}(2)(μ(2)-ZnMe)(2)Fe(CO)(3)] (2) containing {Zn(thf)(2)} as well as ZnMe ligands. Using pyridine (py) instead of thf leads to [(CO)(3)Fe{μ(2)-Zn(py)(2)}(3)Fe(CO)(3)] (3) via replacement of all GaCp* ligands by three{Zn(py)(2)} groups. In contrast, reaction of [(CO)(3)Co(μ(2)-GaCp*)(2)Co(CO)(3)] with ZnMe(2) in the presence of py or thf leads in both cases to the formation of [(CO)(3)Co{μ(2)-ZnL(2)}(μ(2)-ZnCp*)(2)Co(CO)(3)] (L = py (4), thf (5)) via replacement of GaCp* with {Zn(L)(2)} units as well as Cp* transfer from the gallium to the zinc centre. All compounds were characterised by NMR spectroscopy, IR spectroscopy, single crystal X-ray diffraction and elemental analysis.


Epileptiform EEG activity of the centromedian thalamic nuclei in children with intractable generalized seizures of the Lennox-Gastaut syndrome.
Centromedian thalamic nuclei (CM) epileptiform EEG activities were recorded in children with intractable generalized seizures of Lennox-Gastaut syndrome (LGS) through implanted recording-stimulating electrodes used for seizure control. Ictal CM epileptiform activities were consistently correlated to widespread surface cortical EEG activities and symptoms in all patients and all types of generalized seizures; i.e., fast spike discharges at CM correlated at onset of tonic and tonic-clonic generalized seizures; slow (1-2 Hz) spike-wave complex discharges at CM correlated for atypical absence seizures; slow polyspike-wave complex discharges correlated for myoclonic seizures; and spike bursts and suppression patterns correlated for combined tonic-atonic-myoclonic seizures. Ictal EEG activities occurred simultaneously at right and left CM and surface at onset of all seizure types, with the exception of myoclonic seizures where CM complete discharges and individual spike-wave complexes significantly lead those of the surface. Brief tonic-atonic spasms clinically undistinguishable from "real" epileptic seizures showed no EEG counterparts at CM and surface. Interictal CM spike-wave complete discharges and individual spike-wave complexes showed variable amplitude-temporal patterns. Amplitude emphasis on CM and frontopolar regions was observed in most of complete discharges, however, and phase shifts between CM and frontopolar regions were observed in individual spike-wave complexes.


Interferon induced with helicase C domain 1 (IFIH1) and virus-induced autoimmunity: a review.
In addition to genetic factors, environmental triggers, including viruses and other pathogens, are thought to play a major role in the development of autoimmune disease. Recent findings have shown that viral-induced autoimmunity is likely to be genetically determined. In large-scale genetic analyses, an association of interferon induced with helicase C domain 1 (IFIH1) gene variants encoding a viral RNA-sensing helicase with susceptibility to several autoimmune diseases was found. To date, the precise role of IFIH1 in pathogenic mechanisms of viral-induced autoimmunity has yet to be fully elucidated. However, recent reports suggest that IFIH1 may play a role in the etiology of type 1 diabetes. Rare IFIH1 alleles have been shown to be protective against diabetes, and their carriage correlates with lower production of this helicase and its functional disruption. In contrast, upregulation of IFIH1 expression by viruses is associated with more severe disease, and could exacerbate the autoimmune process in susceptible individuals.


[Receptor occupancy and antipsychotic drug action measured by PET and SPECT].
Positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies have demonstrated consistent findings of high dopamine D2 receptor occupancy (> 65-70%) in patients treated with antipsychotic drugs. Further, the risk of extrapyramidal side effects has been shown high in patients with occupancy above 80%. On the basis of these findings, an optimal interval for D2 receptor occupancy between 70% and 80% has been suggested. It has also been shown that several atypical antipsychotics induce marked occupancy of central 5-HT2 and D2 receptors in vivo. However, a low D2 occupancy has been observed in patients with clinical dose of clozapine or quetiapine. The antipsychotic effect of these atypical drugs with a low D2 receptor occupancy has been widely discussed with respect to actions on other receptor systems, limbic selectivity of antipsychotic action and episodic transient occupancy. The recent advances in PET/SPECT and developments of new radioligands have made it possible to evaluate antipsychotic drug actions directly in humans. The empirical data from occupancy measurements will enable us to open future directions of investigation of antipsychotic action and improvement of antipsychotic treatment.


Synthesis and characterization of self-assembled nanoscopic metallarectangles capable of binding fullerenes with size-selective responses.
Two new metallarectangles, 4 and 5, were obtained from the self-assembly of areneruthenium-based molecular clips 2 and 3 with a new dipyridyl donor ligand 1 containing a diamide core and ethynyl spacers. The metallarectangles were characterized by multinuclear NMR, electrospray ionization mass spectrometry, and UV-vis spectroscopy, and the molecular structure of 4 was unambiguously determined by single-crystal X-ray diffraction analysis. Because of the presence of an extended π-electron aromatic surface, the tetracene-containing molecular rectangle 5 was capable of binding C60 and C70 fullerenes as quantified by UV-vis, emission, and (1)H NMR experiments, providing an example of a supramolecular host capable of recognizing large guest molecules.


Use of second-generation platelet concentrate (platelet-rich fibrin) and hydroxyapatite in the management of large periapical inflammatory lesion: a computed tomography scan analysis.
Periapical surgery is required when periradicular pathosis associated with endodontically treated teeth cannot be resolved by nonsurgical root canal therapy (retreatment), or when retreatment was unsuccessful, not feasible or contraindicated. Endodontic failures can occur when irritants remain within the confines of the root canal, or when an extraradicular infection cannot be eradicated by orthograde root canal treatment. Foreign-body responses toward filling materials, toward cholesterol crystals or radicular cysts, might prevent complete periapical healing. We present here a case report wherein, combination of platelet-rich fibrin (PRF) and the hydroxyapatite graft was used to achieve faster healing of the large periapical lesion. Healing was observed within 8 months, which were confirmed by computed tomography, following improved bone density. PRF has many advantages over platelet-rich plasma. It provides a physiologic architecture that is very favorable to the healing process, which is obtained due to the slow polymerization process.


Induction of hematopoietic commitment and erythromyeloid differentiation in embryonal stem cells constitutively expressing c-myb.
To provide insight into the mechanisms by which c-myb regulates hematopoiesis, we analyzed the expression of markers for multiple hematopoietic lineages in differentiating parental embryonic stem (ES) cells and in ES cells transfected with c-myb or with a mutant c-myb deficient in DNA binding and assessed the ability of these cells to undergo hematopoietic commitment and colony formation. Undifferentiated ES cells transfected with intact c-myb, but not cells transfected with mutant c-myb, expressed CD34, c-kit, GATA1, and flt3 mRNA as well as surface CD34, c-kit, and flt3 product. In contrast, the kinetics of GATA-2 mRNA expression was identical in parental and Myb-transfected ES cells. Transient expression assays suggested transactivation of gene expression dependent on interaction with Myb binding sites in the CD34 and GATA1 5' flanking regions. Undifferentiated parental and c-myb mutant-transfected ES cells were not clonogenic, whereas c-myb transfectants formed erythromyeloid colonies in methylcellulose cultures in the absence of added hematopoietic growth factors and, at higher frequency, in the presence of kit and flt-3 ligands. Colony formation was suppressed by treatment with antisense oligodeoxynucleotides specifically downregulating c-kit and flt-3 expression. These findings indicate that c-myb regulates hematopoietic commitment and progenitor cell proliferation and differentiation through the activation of certain genes that define the stem/progenitor cell compartment.


Employer sponsored personal health record (PHR) systems.
Employers are providing systems to employees that enable them to keep track of their personal health care information. Personal health record (PHR) systems can help employees manage their health information and assist in making dependable health care decisions. This study focuses on identifying employee concerns and their expectations from an employer sponsored PHR system. The data collected from the survey will help to understand the utilization and adoption of PHR systems sponsored by the employer.


Structural features of a six-nucleotide RNA hairpin loop found in ribosomal RNA.
The hairpin loop GUAAUA occurs frequently in ribosomal RNA. Optical melting studies show that r(GGCGUAAUAGCC) folds into a hairpin containing this loop. The structural features of the r(GGCGUAAUAGCC) hairpin have been determined by NMR and molecular modeling. NOEs from G4-H1' to A9-H2 and from A9-H2 to G10-H1' show that G4 and A9 form a sheared base pair with two hydrogen bonds: A-N7 to G-NH2 and A-NH6 to G-N3. One-dimensional NOE data show no NOEs between the imino protons of U5 and U8, but NOEs are observed between the U5-H1' and the U8-H6 and U8-H5, thus orienting the U8 imino proton away from U5. Thus U5 and U8 do not form an imino hydrogen-bonded U.U pair. The U5-H2' exhibits NOEs to both the A6-H8 and A7-H8, and the 3' phosphorus resonances of U5 and A6 are shifted downfield. This suggests that the helix turn is between the U5 and A6 nucleotides. The JH1'-H2 and JH3'-H4' coupling constants indicate that the loop is dynamic, particularly at 35 degrees C, well below the melting temperature of 63 degrees C. Structures were generated using 75 distance and 46 dihedral angle restraints. In these structures, the U5 base is stacked on the sheared base pair formed by G4 and A9 and can initiate a uridine turn similar to that observed in the anticodon loop of tRNA. The A6, A7, and U8 bases can stack on one another with their hydrogen-bonding surfaces exposed to the solvent, suggesting that they are available for tertiary interactions or protein recognition in rRNA. A range of loop structures are consistent with the data, however. The lack of formation of a U.U mismatch is consistent with a recent model that predicts the stability of hairpin loops of six nucleotides on the basis of the closing base pair and first mismatch in the loop [Serra, M. J., Axenson, T. J., & Turner, D. H. (1994) Biochemistry 33, 14289-14296].


Circadian Rhythm of the Prokaryote Synechococcus sp. RF-1.
The prokaryotic Synechococcus sp. RF-1 exhibited a nitrogen fixation circadian rhythm with characteristics remarkably similar to the circadian rhythm of eukaryotes. The rhythm had a free-running period of about 24 hours when the length of the preen-trained cycle did not differ too much from 24 hours, and it was insensitive to changes in temperature from 22 degrees C to 33 degrees C. Because the endogenous rhythm of nitrogen fixation was not affected by a phase-shift of its previous cycles, the circadian rhythm in Synechococcus sp. RF-1 was not considered to be controlled simply by a feedback mechanism.


Anti-chromatin (anti-nucleosome) antibodies.
Chromatin is the native complex of histones and DNA found in the cell nucleus of eukaryotes. The fundamental subunit of chromatin is the nucleosome, which is composed of a core particle in which 146 bp of helical DNA are wrapped around an octamer made up of two H2A-H2B dimers that surround an H3-H4 tetramer. The prevalence of anti-chromatin (nucleosome) antibodies in systemic lupus erythematosus (SLE) varies from 50% to 90%, being similar to that of the classical positive LE cell. The presence of these antibodies can be used, in conjunction with clinical findings and other laboratory tests, to help in the diagnosis of SLE and drug induced lupus. The presence of anti-chromatin antibodies has also been linked to glomerulonephritis in SLE patients.


Algorithm and simulation for analysis of bio-images obtained by aperture diffraction based optical MEMS.
This paper proposes a novel method to detect transparent living cells in a transparent microfluidic chamber by optical diffraction of an aperture or an aperture array. Through the analysis of the far-field diffraction pattern, one of the parameters of the cells, including the size, refractive index, or position, can be extracted by the analysis software developed in this paper. Calculations are carried out to discuss the key issues of this MEMS device, and our simulation is verified by diffraction patterns of transparent microparticles on fabricated apertures, recorded via a digital camera.