Are the causes and presentation of chronic hepatitis changing? An analysis of 104 cases over 15 years.
We describe the features at presentation of 104 patients with biopsy-proven chronic hepatitis who presented in Brisbane in the period 1968-32. The mean period of follow-up was 59 months. Sex ratio (female : male) was 70 : 34 and the mean age was 37 years (range 3-83). Eighty-five (82 per cent) were born in Australia. Serological evidence of hepatitis B (HBV) infection was present in 24 (23 per cent). Analysis of the HBV marker positive and negative (non-B) groups revealed that the clinical and laboratory features of HBsAg positive chronic hepatitis were much less florid than those of non-B patients. However, the disturbances seen in hepatic histopathology were similar in severity, and the mortality in the HBsAg positive group exceeded that in the non-B group. The relative risk calculated on an actuarial basis was higher in HBsAg positive patients. In contrast to the experience of others, severe chronic active hepatitis remains an important problem in Brisbane but some features of the disease are altering. Several changes may be attributable to the increasing incidence of HBV-associated disease, and in addition, patients aged under 20 with non-B chronic hepatitis are now rarely seen. This is of interest in view of recent reports of decreased incidence of another disease of disordered immune response, rheumatoid arthritis.


Vinexin β Ablation Inhibits Atherosclerosis in Apolipoprotein E-Deficient Mice by Inactivating the Akt-Nuclear Factor κB Inflammatory Axis.
Vinexin β is a novel adaptor protein that regulates cellular adhesion, cytoskeletal reorganization, signal transduction, and transcription; however, the exact role that vinexin β plays in atherosclerosis remains unknown. Immunoblot analysis showed that vinexin β expression is upregulated in the atherosclerotic lesions of both patients with coronary heart disease and hyperlipemic apolipoprotein E-deficient mice and is primarily localized in macrophages indicated by immunofluorescence staining. The high-fat diet-induced double-knockout mice exhibited lower aortic plaque burdens than apolipoprotein E-/- littermates and decreased macrophage content. Vinexin β deficiency improved plaque stability by attenuating lipid accumulation and increasing smooth muscle cell content and collagen. Moreover, the bone marrow transplant experiment demonstrated that vinexin β deficiency exerts atheroprotective effects in hematopoietic cells. Consistent with these changes, the mRNA expression of proinflammatory cytokines were downregulated in vinexin β-/- apolipoprotein E-/- mice, whereas the anti-inflammatory M2 macrophage markers were upregulated. The immunohistochemical staining and in vitro experiments showed that deficiency of vinexin β inhibited the accumulation of monocytes and the migration of macrophages induced by tumor necrosis factor α-stimulated human umbilical vein endothelial cells as well as macrophage proliferation. Finally, the inhibitory effects exerted by vinexin β deficiency on foam cell formation, nuclear factor κB activation, and inflammatory cytokine expression were largely reversed by constitutive Akt activation, whereas the increased expression of the nuclear factor κB subset promoted by adenoviral vinexin β was dramatically suppressed by inhibition of AKT. Vinexin β deficiency attenuates atherogenesis primarily by suppressing vascular inflammation and inactivating Akt-nuclear factor κB signaling. Our data suggest that vinexin β could be a therapeutic target for the treatment of atherosclerosis.


Role of ceria in oxidative dehydrogenation on supported vanadia catalysts.
The effect of the suppport on oxidative dehydrogenation activity for vanadia/ceria systems is examined for the oxidation of methanol to formaldehyde by use of well-defined VO(x)/CeO(2)(111) model catalysts. Temperature-programmed desorption at low vanadia loadings revealed reactivity at much lower temperature (370 K) as compared to pure ceria and vanadia on inert supports such as silica. Density functional theory is applied and the energies of hydrogenation and oxygen vacancy formation also predict an enhanced reactivity of the vanadia/ceria system. At the origin of this support effect is the ability of ceria to stabilize reduced states by accommodating electrons in localized f-states.


Reconfigurable Light Imaging in Photonic Higher-Order Topological Insulators.
Topological phases of matter with robust edge states have revolutionized the fundamental intuitions for wave control. The recent development of higher-order topological insulators (HOTIs) realizes even lower dimensional topological states that enable versatile wave manipulations (e.g., light imaging). However, in conventional HOTIs, the topological states are usually protected by certain crystalline symmetries and therefore bounded at specific locations, hindering their applications in modern digital ears, which often prefer tunability and reconfigurability. Here, we report the reconfigurable light imaging based on topological corner states and anti-chiral edge states in a two-dimensional (2D) photonic HOTI with a honeycomb lattice of yttrium iron garnet (YIG, a ferrite material) rods. Sublattices A and B are applied with magnetic fields in opposite directions, which realize the so-called modified Haldane model that hosts anti-chiral edge modes. By further breaking the lattice's inversion symmetry via adjusting the radii of A and B rods, topological edge states with valley degrees of freedom emerge, which not only exhibit valley-dependence but also surprisingly show anti-chiral behaviors. In the valley edge gap, which is of nontrivial higher-order topology, corner states appear. With different combinations of corner states and anti-chiral edge states, versatile reconfigurable light imaging can be realized. As examples, a multiplexing waveguide-resonator device, a pine tree imaging that can be lit up or put out at will and selective imaging for partial objects in a two-heart pattern are demonstrated. The proposed HOTI shows high potential in future intelligent devices with exciting tunable and reconfigurable functions, which may inspire a wide range of applications such as topological switching, imaging processing, and nonreciprocal integrated photonics.


Drag force in bimodal cubic-quintic nonlinear Schrödinger equation.
We consider a system of two cubic-quintic nonlinear Schrödinger equations in two dimensions, coupled by repulsive cubic terms. We analyze situations in which a probe lump of one of the modes is surrounded by a fluid of the other one and analyze their interaction. We find a realization of D'Alembert's paradox for small velocities and nontrivial drag forces for larger ones. We present numerical analysis including the search of static and traveling form-preserving solutions along with simulations of the dynamical evolution in some representative examples.


Protein kinase Cdelta is associated with 14-3-3 phosphorylation in seizure-induced neuronal death.
Prolonged seizures cause significant damage to the brain, and cellular damage due to status epilepticus may be related to the pathogenesis of epilepsy. Protein kinase Cdelta (PKCδ) mediates multiple cell death signalings, and 14-3-3 proteins regulate survival pathways in brain, sequestering certain pro-apoptotic proteins. Presently, we examined the association between PKCδ and 14-3-3 with seizure-induced neuronal death using mouse model. Status epilepticus was induced by systemic kainic acid. Kainate-induced seizures caused an increase in levels of cleaved PKCδ in the hippocampus, along with up-regulation of cleaved caspase-3 and phospho-14-3-3ζ (Ser58), as well as extensive hippocampal cell death as visualized with Fluoro-Jade B and anti-active caspase-3 staining. Furthermore, co-immunoprecipitation or double immunofluorescence analysis revealed that PKCδ interacts with 14-3-3, and interaction between PKCδ and 14-3-3 was significantly enhanced in the hippocampus after seizures, paralleling increased interaction between Bad and Bcl-x(L). Moreover, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells had upregulated phospho-14-3-3ζ (Ser58) in the hippocampus after seizures. These findings suggest that PKCδ and phospho-14-3-3 are associated with apoptotic cell death in the hippocampus after seizures, and targeting PKCδ or phospho-14-3-3 may be potently protective against seizure-induced neuronal injury.


SQSTM1 and Paget's disease of bone.
Mutations in the Sequestosome 1 gene ( SQSTM1; also known as p62) have recently been identified as the cause of 5q35-linked Paget's disease of bone (PDB). All of the mutations identified to date affect the ubiquitin-associated (UBA) domain of SQSTM1, a region of the protein that binds noncovalently to ubiquitin. In this review we consider the possible functional significance of the SQSTM1-ubiquitin interaction, and consequences of the SQSTM1 UBA domain mutations. Clarification of the in vivo roles of SQSTM1 in bone-cell function will be central to improving our understanding of the molecular pathogenesis of PDB and related conditions.


Colorectal Infraperitoneal anastomosis: the effects of perioperative supplemental oxygen administration on the anastomotic dehiscence.
The role of supplemental oxygen therapy in the healing of colorectal anastomosis is still very much at an experimental stage. The aim of the present study, prospective randomized, was to assess the effect of administration of perioperative supplemental oxygen therapy on infraperitoneal anastomosis, where the risk of leakage is higher. We enrolled 72 patients between February, 2008 and February, 2011, who underwent elective open infraperitoneal anastomosis for rectal cancer (middle and low). Patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n = 37) or 80% (n = 35). Administration was commenced after induction of anesthesia and maintained for 6 h after surgery. The overall anastomotic leak rate was 16.6% (12 out of 72); 8 patients (21.6%) had an anastomotic dehiscence in the 30% FiO2 group and 4 (11.4%) in the 80% FiO2 group (p < 0.05). The risk of anastomotic leak was 46% lower in the 80% FiO2 group (RR, 0.63; 95% confidence interval, 0.42–0.98) vs. the 30% FiO2. Therefore, supplemental 80% FiO2 during and for 6 h after major rectal cancer surgery, reducing postoperative anastomotic dehiscence, should be considered part of ongoing quality improvement activities related to surgical care, with few risks to the patient and little associated cost.


[Decision making in geriatric oncology].
The decision making process, based on screening, diagnostic, staging, therapeutic and multidisciplinary decision procedures, is very well defined in oncology. Recently the same approach has been applied to the management of senior adult cancer patients. Screening of geriatric problems and evaluation of health status are linked to the oncologic evaluation. A comprehensive knowledge of the different health problems is discussed through a multidisciplinary approach. This needs a specific organization and collaboration between oncologists and geriatricians. It requires also the elaboration of specific decision trees of cancer adapted to the case of senior adult patients.


Renal Dysfunction among HIV-Infected Patients on Antiretroviral Therapy in Dar es Salaam, Tanzania: A Cross-Sectional Study.
HIV-associated renal dysfunction is common among infected patients; the growing burden of this condition may be partly accounted for by improved survival attributed to sustained viral suppression with antiretroviral therapies (ART). Some ART regimens are nephrotoxic and may potentially contribute to renal dysfunction observed in these patients. This study aimed at investigating the prevalence of renal dysfunction among people living with HIV (PLHIV) on ART attending the care and treatment clinic (CTC). A cross-sectional study was conducted between June and October 2019 among adults living with HIV on ART for 6 months or more attending CTC at Muhimbili National Hospital in Dar es Salaam, Tanzania. A total of 287 participants were screened for proteinuria and microalbuminuria using the Cybow 300 urine analyzer. Serum creatinine was tested for all participants, and it was used to estimate glomerular filtration rate (eGFR) using the CKD-EPI formula. Out of 287 participants (72.1% female, mean age ± SD: 46.7 ± 10.6 years), about one-third (32.8%) had eGFR less than 90 ml/min, whereas 7% had eGFR less than 60 ml/min. Microalbuminuria and proteinuria were detected in 38.6% and 25.1% of participants, respectively. In the multivariate analysis, predictive determinants for renal dysfunction were higher viral loads (OR 2.5 (1.1-5.8), p=0.031), diabetes mellitus (OR 5.5 (1.6-18.6), p=0.006), and age above 60 years (OR 2.8 (1.0-7.3), p=0.041); however, this was not the case for serum CD4 counts (OR 1.25 (0.7-2.3), p=0.46). High prevalence of renal dysfunction among PLHIV on ART was noted in this study. Viral loads above 1000 cp/ml and diabetes mellitus were noted to be associated with increased risk for renal dysfunction.


Detection of the Lowest-Lying Odd-Parity Atomic Levels in Actinium.
Two lowest-energy odd-parity atomic levels of actinium, 7s^{2}7p^{2}P_{1/2}^{o}, 7s^{2}7p^{2}P_{3/2}^{o}, were observed via two-step resonant laser-ionization spectroscopy and their respective energies were measured to be 7477.36(4) and 12 276.59(2) cm^{-1}. The lifetimes of these states were determined as 668(11) and 255(7) ns, respectively. In addition, we observed the effect of the hyperfine structure on the line for the transition to ^{2}P_{3/2}^{o}. These properties were calculated using a hybrid approach that combines configuration interaction and coupled-cluster methods, in good agreement with the experiment. The data are of relevance for understanding the complex atomic spectra of actinides and for developing efficient laser cooling and ionization schemes for actinium, with possible applications for high-purity medical-isotope production and future fundamental physics experiments.


Treatment outlines for the management of anxiety states. The Quality Assurance Project.
The Quality Assurance Project is developing explicit and detailed treatment outlines for each of the major psychiatric disorders. Three sources of information are used: a meta-analysis of the treatment outcome literature, the opinions of a sample of practising psychiatrists, and the views of a panel of nominated experts. The recommendations for the treatment of anxiety states were as follows: Phenelzine and then the tricyclic antidepressants were the treatments of choice for panic disorder. Behaviour therapy--cognitive anxiety management, relaxation and hyperventilation control--being recommended as an essential adjunct to drug therapy. Relaxation and dynamic psychotherapy separately, or in combination, were the treatments of choice for generalised anxiety disorder with cognitive procedures being of value and benzodiazepines only being recommended for short-term use. In complicated cases of either panic disorder or generalised anxiety disorder a long-term supportive psychotherapeutic relationship was regarded as essential to ensure smooth progress in treatment. In adjustment disorder with anxious mood, procedures to permit adaptation to the stressor were recommended, while in post-traumatic stress disorder psychotherapeutic techniques to allow the trauma to be re-experienced and worked through were favoured.


The male reproductive system in whip spiders (Arachnida: Amblypygi).
Whip spiders (Arachnida, Amblypygi), like many other soil arthropods, transfer their spermatozoa indirectly via a stalked spermatophore. While the complex courtship behavior as well as the morphological differences of spermatophores and corresponding female genitalia between taxa have received great attention in the past, comparative research on the internal reproductive system is lacking so far. In this study, the morphology of the male whip spiders of four neoamblypygid taxa has been comparatively studied via computer tomography and subsequent 3D reconstruction. We investigated four species belonging to the Neoamblypygi, that is, the phrynichid species Damon medius (Damoninae), and Euphrynichus bacillifer (Phrynichidae), the phrynid species Phrynus hispaniolae (Phrynidae), and the charontid species Charon grayi (Charontidae). The male reproductive organs consist of paired testes and two pairs of accessory glands, the ventral and lateral glands, which project their ducts anteriorly into the ventrally located unpaired spermatophore producing organ where the respective seminal and secretory reservoirs are located. While this general organization of the male reproductive system is similar among all investigated taxa, there are some notable differences in some structures. The most surprising findings include the complete absence of ventral glands in D. medius, the presence of unique spherical ventral gland reservoirs in C. grayi as well as differences in the organization of the seminal and secretory reservoirs and their connections to the inner genital slit. In addition, the secretory products of both, ventral and lateral glands, are stored in combined secretory reservoirs in E. bacillifer and P. hispaniolae. This study is the first to show that there is some morphological variation in the male reproductive system in Neoamblypygi. These results are the basis for the reconstruction of the Bauplan for the reproductive organs of the whip spiders.


[Cytologic diagnosis of thyroid gland adenoma and goiter].
Examinations of smear impressions of postoperative biopsy specimens of the thyroid from adenoma patients have revealed among polygonal structures 1 to 20 spherical complexes (per micropreparation) consisting of relatively monomorphic follicular cells with intensively blue cytoplasm. The 'ball' size was 200-900 micron or more. Cellular composition, specific features of cellular structure, and the presence of spherical structures permit differentiating adenoma from goiter.


Deep level transient spectroscopy for diodes with large leakage currents.
A Deep Level Transient Spectroscopy (DLTS) system is described for measuring deep levels in diodes exhibiting large leakage currents. A capacitance bridge employing the diode to be tested along with a dummy diode of similar characteristics is used. The DLTS spectrum of a leaky GaAs planar diode is measured and compared to experimental results obtained with two standard DLTS systems. It is shown that measurements with the standard systems are impossible in certain temperature ranges because of overloading problems. The approach described here, however, gives the DLTS spectrum between 77 degrees and 300 degrees K.


Effect of the Particle Size and Matrix Strength on Strengthening and Damage Process of the Particle Reinforced Metal Matrix Composites.
Roles of the particle, strengthening, and weakening during deformation of the particle reinforced metal matrix composite, were studied using in situ technique. Composites with three different strengths Al-Cu-Mg alloy matrices reinforced by three sizes SiC particles were manufactured and subjected to in situ tensile testing. Based on in situ observation, damage process, fraction and size distribution of the cracked particles were collected to investigate the behavior of the particle during composite deformation. The presence of the particle strengthens the composite, while the particle cracking under high load weakens the composite. This strengthening to weakening transformation is controlled by the damage process of the particle and decided by the particle strength, size distribution, and the matrix flow behavior together. With a proper match of the particle and matrix, an effective strengthening can be obtained. Finally, the effective match range of the particle and the matrix was defined as a function of the particle size and the matrix strength.


Cellular Activation Mediated by Nitric Oxide
Triggering of lymphocytes by mitogens leads to a complex biochemical cascade culminating in cellular activation. Data are accumulating that suggest that reactive free radicals participate in signal transduction. We have examined the effects of nitric oxide (NO) on some parameters of lymphocyte activation and have also performed mechanistic studies. Our data suggest that NO initiates a transductional cascade in lymphocytes by interacting directly with a G protein. These studies may help elucidate the biochemical basis by which reactive free radicals mediate signal transduction. Here, we review our findings and explore their biological significance.


Home care nurses' decisions about the need for and amount of service at the end of life.
We explore home care nurse decision-making about the need for and amount of service by clients and families at the end of life. We identify factors nurses refer to when describing these decisions, situated within contextual features of nursing practice. Home care nurses are often responsible for decisions which have an impact on the access of clients and families to services at the end of life. Understanding how these decisions, are made, factors that are considered, and contextual influences is critical for improving access and enhancing care. Qualitative data were collected between 2006 and 2008 from two samples of home care nurses: the first group (n = 29) recorded narrative descriptions of decisions made during visits to families. The second group (n = 27) completed in-person interviews focusing on access to care and their interactions with clients and families. Data were analysed with thematic coding and constant comparison. Participants described assessing client and family needs and capacity. These assessments, at times integrated with considerations about relationships with clients and families, inform predictive judgements about future visits; these judgments are integrated with workload and home health resource considerations. In describing decisions, participants referred to concepts such as expertise, practice ideals and approaches to care. Findings highlight the role of considerations of family caregiver capacity, the influence of relationships and the importance of the context of practice, as part of a complete understanding of the complexity of access to care at the end of life.


Manipulation of zebrafish's orientation using artificial cilia in a microchannel with actively adaptive wall design.
The zebrafish is a powerful genetic model organism especially in the biomedical chapter for new drug discovery and development. The genetic toolbox which this vertebrate possesses opens a new window to investigate the etiology of human diseases with a high degree genetic similarity. Still, the requirements of laborious and time-consuming of contemporary zebrafish processing assays limit the procedure in carrying out such genetic screen at high throughput. Here, a zebrafish control scheme was initiated which includes the design and validation of a microfluidic platform to significantly increase the throughput and performance of zebrafish larvae manipulation using the concept of artificial cilia actuation. A moving wall design was integrated into this microfluidic platform first time in literature to accommodate zebrafish inside the microchannel from 1 day post-fertilization (dpf) to 6 dpf and can be further extended to 9 dpf for axial orientation control in a rotational range between 0 to 25 degrees at the minimum step of 2-degree increment in a stepwise manner. This moving wall feature was performed through the deflection of shape memory alloy wire embedded inside the microchannel controlled by the electrical waveforms with high accuracy.


Use of computer-assisted learning module to achieve ACGME competencies in orthopaedic foot and ankle surgery.
The Accreditation Council for Graduate Medical Education (ACGME) has charged academic institutions with finding methods to assess learning in specific areas of resident education. Computer-assisted education offers a reliable mode for teaching residents important information and skills. The CD-ROM "Fundamentals of Orthopaedic Foot Care," produced by the American Academy of Orthopaedic Surgeons, was tested as a tool to provide nonoperative foot and ankle care education for a group of orthopaedic residents (N = 14) and a group of family practice residents (N = 11). The CD-ROM's educational format includes an interactive tutorial on anatomy, video demonstrations on selected topics in physical examination and basic treatment of nonoperative problems of the foot and ankle, and patient education information sheets on multiple common foot disorders. Both resident groups scored significantly higher on their post-test exams after spending 1 hour with the computer program (p < or = .05). This study suggests that this program can be used reliably in an orthopaedic residency program to achieve ACGME required competency of "medical knowledge" in evaluation and nonoperative management of common foot and ankle problems.


Alternatives to tokamaks: a faster-better-cheaper route to fusion energy?
The use of thermonuclear fusion as a source for energy generation has been a goal of plasma physics for more than six decades. Its advantages are many: easy access to fuel and virtually unlimited supply; no production of greenhouse gases; and little radioactive waste produced. But heating fuel to the high temperature necessary for fusion-at least 100 million degrees Celsius-and containing it at that level has proved to be a difficult challenge. The ring-shaped magnetic confinement of tokamaks, which emerged in the 1960s, was quickly identified as the most promising approach and remains so today although a practical commercial reactor remains decades away. While tokamaks have rightly won most fusion research funding, other approaches have also been pursued at a lower level. Some, such as inertial confinement fusion, have emerged from nuclear weapons programs and others from academic efforts. A few have been spun out into start-up companies funded by venture capital and wealthy individuals. Although alternative approaches are less well studied, their proponents argue that they could provide a smaller, cheaper, and faster route to fusion energy production. This article will survey some of the current efforts and where they stand. This article is part of a discussion meeting issue 'Fusion energy using tokamaks: can development be accelerated?'.


Blood pressure in Hispanic women: the role of diet, acculturation, and physical activity.
The role of diet, acculturation, and physical activity on systolic and diastolic blood pressure was examined among 1,420 Mexican American, 388 Cuban American, and 542 Puerto Rican women who responded to the Hispanic Health and Nutrition Examination Survey collected in 1982-4. Dietary intake measures included sodium, potassium, calcium, magnesium, fiber, ethanol, and total kilocalories as estimated from 24-hour recall data. Serum sodium/potassium ratio was included as a measure of metabolic function. Acculturation was measured using language preference, speaking, reading and writing. Physical activity included recreational and non-recreational activities. Other correlates included age, education, and body composition. Final models indicated that age and body composition were significantly associated with blood pressure across all three Hispanic subgroups. Among Mexican-American women, acculturation had an impact on both systolic and diastolic blood pressure that was independent of diet, body composition, and physical activity. Furthermore, the dietary intake of specific nutrients such as sodium and potassium did not appear to be as important as the way the individual metabolized those nutrients, as indicated by the serum sodium/potassium ratio. The strong association of body mass index with both systolic and diastolic blood pressure among all three ethnic groups reinforces the need to maintain an appropriate body weight.


Quantitative Assessment of Vapor Molecule Adsorption to Solid Surfaces by Flow Rate Monitoring in Microfluidic Channels.
Measuring parameters related to gas adsorption on the effective surfaces of solid samples is important in catalyst studies. Further attention on the subject has appeared due to the materials and methods required to concentrate the gaseous biomarkers for detection. The conventional methods are mainly based on the volumetric and gravimetric analyses, which are applicable to bulk samples. No standard method has yet been provided for such measurements on thin films, which are the most commonly used samples for material screening. Here, a novel method is presented for the adsorption coefficient measurement on thin-film samples. This method comprises coating of the inner walls of a microfluidic channel with the thin film under test. The recorded diffusion rates for a trace gas along this microchannel are compared with the solutions of the adsorption-diffusion equation of the channel for determining the adsorption coefficient of the gas molecule to the inner walls of the channel. The high ratio of surface-to-volume in such channels magnifies the gas sorption effects and improves accuracy. The method is fast, versatile, and cost-effective, allowing measurements at different temperatures and atmospheric pressures. The adsorption coefficients of different isomers of butanol on poly(methyl methacrylate) sheets, zinc oxide thick films, and gold thin films are determined as examples.


Prognostic value of endothelial dysfunction in type 1 diabetes mellitus.
Patients with diabetes mellitus are at high risk of developing atherosclerosis, associated with higher rates of micro and macro vascular involvement such as coronary artery disease and renal disease. The role of hyperglycemia to induce synthesis of reactive oxygen species by the oxidation of glucose, leading to an increased production of advanced glycosylation end products, as well as inflammation and oxidative stress has been proposed as a possible mechanism in the pathogenesis of endothelial dysfunction (ED). The interaction between C-peptide - the connecting segment of pro-insulin-and nitric oxide in vasodilation is also discussed. Therefore, endothelial dysfunction has been identified as an early marker of vascular disorder in type 1 and type 2 diabetes mellitus. In some other diseases, ED has been considered an independent predictor of vascular disease, regardless of the method used. Studies have demonstrated the importance of endothelial dysfunction as an useful tool for identifying the risk of vascular complications in patients with type 1 diabetes mellitus, particularly as regards to renal impairment. The aim of this review is to clarify the prognostic value of endothelial dysfunction as a marker of vascular disease in these subjects.


Analysis of in vivo 1H MR spectra of normal brain tissue by means of second derivative method.
As follows from comparative studies conducted in a number of centres, meeting the repeatability and reliability conditions in MRS in vivo measurements depends mainly on system stability and operator-related external factors. The aim of the study was to check the usefulness of the automated fitting method offered by PeakFit 4.0 (by SPSS Inc., Chicago, USA). Short echo time in vivo PRESS 1H MR spectra (2T, TE = 35 ms) of normal brain were fitted in the frequency domain using the second derivative method. In this approach local maxima and hidden peaks are found as local minima of spectrum second derivative. The Lorentzian robust minimization procedure using Levenburg-Marquardt non-linear fitting engine was applied. Spectral lines were approximated under the assumption of the mixed Lorentzian/Gaussian lineshapes. The same procedure was applied to 18 proton spectra recorded from frontal lobe white matter. The number of peaks found within the range of 0.74 + 4.2 ppm was 52 +/- 3 and their positions were almost the same. The fitted lines were assigned on the basis of the J-pattern recalculated for the field strength of 2T and by comparing the chemical shifts with the shifts in single compound spectra. The ratios of main metabolites, such as NAA/Cr, Cho/Cr, Cho/NAA and mI/Cr, are in accordance with those obtained previously using the software supplied with the MR imager and the absolute concentrations of NAA, Cho, mI, Glc and Glu obtained from the fit agree with those reported in literature which confirms the usefulness of the second derivative method in routine analyses of 1H MR brain spectra. The automated fitting enables reasonable metabolite ratios and absolute concentrations to be obtained, however it should be kept in mind that the second derivative follows only the shape of the curve that represents the sum of all metabolites.


Prevention of selenite-induced cataractogenesis by rutin in Wistar rats.
To investigate whether rutin retards selenite-induced cataractogenesis in Wistar rat pups. On postpartum day ten, Group I rat pups received an intraperitoneal injection of saline. Group II and III rat pups received a subcutaneous injection of sodium selenite. Group III also received an intraperitoneal injection of rutin once daily on postpartum days 9-14. Both eyes of each pup were examined from day 16 up to postpartum day 30. After sacrifice, extricated pup lenses were analyzed for mean activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase. In addition, the mean concentrations of reduced glutathione (GSH) and of malondialdehyde were analyzed in samples of lenses and hemolysate. There was dense lenticular opacification in all of Group II, minimal opacification in 33.3% of Group III, no opacification in 66.7% of Group III, and no opacification in Group I. Significantly lower mean activities of lenticular antioxidant enzymes were noted in Group II, compared to Group I and III. Significantly lower mean concentrations of GSH and higher mean concentrations of malondialdehyde were noted in samples of hemolysate and lens from Group II, compared to the values in Group I and III. Rutin prevents experimental selenite-induced cataractogenesis in rat pups, possibly by preventing depletion of antioxidant enzymes and of GSH, and by inhibiting lipid peroxidation.


Genistein inhibits pro‑inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway.
Anaphylaxis is a rapidly occurring allergic reaction to any foreign substance, including venom from insects, foods and medications, which may cause fatalities. To prevent anaphylaxis, these triggers must be avoided. However, avoidance of numerous triggers is difficult. For this reason, the development of immunotherapeutic adjuvants that suppress the allergic response is important for anaphylaxis control. Mast cells are one of the major inflammatory cells involved in the inflammatory response, which secrete several inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, and recruits other immune cells. Mast cells are also involved in a number of diseases, such as sinusitis, rheumatoid arthritis and asthma. Genistein, a phytoestrogen, has been reported to have anti-oxidative and anti-inflammatory activities. However, the effects of genistein on the anti-inflammatory response of mast cells remain unknown. In the present study, the anti-inflammatory effects of genistein on mast cells were investigated. Genistein significantly decreased IL-6 and IL-1β mRNA levels, as well as IL-6 production in PMA/A23187-induced mast cells activation. In addition, genistein inhibited the phosphorylation of ERK 1/2 in PMA/A23187-induced mast cell activation. However, phosphorylation of p38 was not altered. Thus, these findings indicate that genistein inhibited the inflammatory status of mast cells through inhibition of the ERK pathway.


Scanning electrochemical microscopy: theory and application of the transient (chronoamperometric) SECM response.
A study of the transient (chronoamperometric) response of the scanning electrochemical microscope (SECM) is presented. SECM transients were simulated digitally with a novel integrator based on a Krylov algorithm. The transients observed with planar electrodes (PE), microdisks (MD), and thin-layer cells (TLC) are shown to be limiting cases that fit the simulated SECM transients at very short, intermediate, and long times, respectively. A procedure is established that, provided the tip radius is known, allows the determination of the diffusion coefficient of the species in solution independent of its concentration and the number of electrons transferred in the electrode reaction. Experimental SECM transients are reported for the electrochemical oxidation of Fe(CN)6(4-) in KCl; the diffusion coefficient of Fe(CN)6(4-) was found to agree very well with the literature value.


Low-density lipoprotein inhibits receptor-mediated prostaglandin synthesis without affecting calcium and arachidonic acid mobilization in human endothelial cells.
Vascular serotonin 5-HT1 receptors have quiescent constrictor activity that is activated by other vasoactive agents such as histamine. Previously, we observed that the 5-HT1-selective agonist 5-carboxamidotryptamine (5-CT) potentiated histamine-stimulated arachidonic acid (AA) mobilization and prostaglandin production in human aortic endothelial cells (HAEC). In the present study, 5-CT was found to potentiate histamine-stimulated calcium mobilization but had no effect on intracellular calcium when added alone. Treatment of HAEC with human low-density lipoprotein (LDL) for 20 hours inhibited the histamine- plus 5-CT-stimulated production of prostaglandin F2alpha (PGF2alpha) and the prostacyclin metabolite 6-keto-PGF1alpha. However, the effects of histamine and histamine potentiation by 5-CT on intracellular Ca mobilization and AA release were resistant to LDL treatment. Conversely, the subsequent receptor-independent conversion of AA to prostaglandins was inhibited by LDL. These results demonstrate that histamine and serotonin receptor activity, measured as the stimulation of Ca and AA mobilization, is resistant to LDL exposure under mild oxidizing conditions, whereas the receptor-independent synthesis of prostaglandins is inhibited by LDL. The results also suggest that the LDL-stimulated mobilization of cellular AA is responsible for the LDL-mediated inhibition of prostaglandin synthesis. These findings suggest a mechanism by which LDL and/or atherosclerosis could promote the vascular liberation of AA that is not converted to endothelium-derived prostaglandins and is therefore available as substrate for the production of other eicosanoids.


[Screening hepatocellular carcinoma autoantibodies by serological proteome analysis].
To screen hepatocellular carcinoma (HCC) autoantibodies as diagnostic biomarkers or therapy targets by serologic proteome analysis (SERPA). Total proteins extracted from human HCC cell line HCCLM3 were separated by two-dimensional electrophoresis (2-DE) and then transferred onto PVDF membranes, which were subsequently incubated with sera from HCC, hepatitis B virus (HBV) infected patients or healthy volunteers. All immuno-reactive protein spots on blot films were matched to those on 2-DE gel maps by image analysis and identified by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS/MS). 2-DE gel maps of HCCLM3 and corresponding blot films of good quality and reproducibility were established. The number of spots on HCCLM3 2-DE reference gel totaled 603 and those on HCC, HBV and healthy sera blotted films were 70.75+/-24.25, 68.5+/-23.44 and 41.38+/-15.05, respectively. Blot films of HCC and HBV groups had more spots than those of the healthy group (P < 0.05) while no significance was found between films of HCC and HBV groups. By identification, those HCC autoantibodies could be classified as nuclear proteins, cytoskeleton proteins, heat shock proteins and metabolic enzymes. Serological proteome analysis is a high throughput technique for screening tumor autoantibodies. Those newly identified HCC associated tumor antigens and corresponding autoantibodies can be used in the early diagnosis or immuno-therapy of HCC.


Resveratrol has a positive effect on parameters of central hemodynamics and myocardial ischemia in patients with stable coronary heart disease.
Cardiovascular diseases, and primarily coronary heart disease (CHD), are the leading cause of mortality in the developing countries, including Ukraine. Prognosis for patients with CHD depends mainly on progression of coronary atherosclerosis (ASVD). Molecular mechanisms of atherogenesis are studied in detail in order to find new targets of pharmacological intervention. to study the effect of resveratrol on parameters of central hemodynamics and myocardial ischemia in patients with stable coronary heart disease (CHD). The research involved 85 patients with CHD: stable angina pectoris, FC II, and 30 healthy individuals made up the control group. Patients with CHD were randomized into the research group (30 people) and the comparison group (55 people). Patients of the comparison group were prescribed the standard therapy (Β-blockers, statins, aspirin). Resveratrol at a dose of 100 mg per os daily was added to standard treatment of the patients of the research group. The day before randomization and 2 months after the prescribing therapy to the patients, echocardiography (echo) and 24 hour Holter ECG monitoring were made. Diastolic dysfunction of the left ventricle (LV) in the form of violation of relaxation (type I) had been found in 100 % of patients with CHD. The 24 hour Holter ECG monitoring revealed episodes of myocardial ischemia (σt ST depr) (11.07+2.81 episodes a day), premature atrial contractions (PACs) and premature ventricular contractions (PVCs) in patients with stable CHD. After a two-month term of therapy in all patients with CHD, left ventricular systolic function in terms of ejection fraction (EF) of LV significantly improved (by 9.7 % in the research group and by 3.2 % in the comparison group). LV diastolic function improved in both groups in terms of the ratio of the phases of the transmitral flow E/A, dominating in the research group (р=0.004). DT value dropped significantly influenced by resveratrol (by 13 %), in the comparison group it didn`t change. In both groups IVRT significance decreased (р < 0.05). According to the 24 hour Holter ECG monitoring, in patients, additionally taking resveratrol, σt ST depr decreased by 45.9 %, that prevailed the result of the comparison group by 25.2 %. Under the influence of resveratrol, unlike in the comparison group, the number of PACs and PVCs was significantly reduced. The data have shown cardioprotective properties of resveratrol and its applicability in the treatment of patients with CHD.


UK quantitative WB-DWI technical workgroup: consensus meeting recommendations on optimisation, quality control, processing and analysis of quantitative whole-body diffusion-weighted imaging for cancer.
Application of whole body diffusion-weighted MRI (WB-DWI) for oncology are rapidly increasing within both research and routine clinical domains. However, WB-DWI as a quantitative imaging biomarker (QIB) has significantly slower adoption. To date, challenges relating to accuracy and reproducibility, essential criteria for a good QIB, have limited widespread clinical translation. In recognition, a UK workgroup was established in 2016 to provide technical consensus guidelines (to maximise accuracy and reproducibility of WB-MRI QIBs) and accelerate the clinical translation of quantitative WB-DWI applications for oncology. A panel of experts convened from cancer centres around the UK with subspecialty expertise in quantitative imaging and/or the use of WB-MRI with DWI. A formal consensus method was used to obtain consensus agreement regarding best practice. Questions were asked about the appropriateness or otherwise on scanner hardware and software, sequence optimisation, acquisition protocols, reporting, and ongoing quality control programs to monitor precision and accuracy and agreement on quality control. The consensus panel was able to reach consensus on 73% (255/351) items and based on consensus areas made recommendations to maximise accuracy and reproducibly of quantitative WB-DWI studies performed at 1.5T. The panel were unable to reach consensus on the majority of items related to quantitative WB-DWI performed at 3T. This UK Quantitative WB-DWI Technical Workgroup consensus provides guidance on maximising accuracy and reproducibly of quantitative WB-DWI for oncology. The consensus guidance can be used by researchers and clinicians to harmonise WB-DWI protocols which will accelerate clinical translation of WB-DWI-derived QIBs.


Conjoined twins--past, present, and future.
Conjoined twins are rare and complex anomalies of the newborn. They require a highly experienced team and a center equipped to deal with such challenging anatomy. A review of 31 sets of conjoined twins was managed by one team over a 15-year period. The spectrum of the anomalies, management strategies, and outcomes will be analyzed with future recommendations. Ten sets of complete conjoined twins and two sets of parasitic conjoined twins were successfully separated. Tissue expanders and prosthetic meshes were not required. A separation of one set of craniopagus parasiticus conjoined twins was attempted, but abandoned owing to major vascular and brain sharing. The remaining 18 sets were not separable owing to major cardiac anomalies and/or sharing, and all died within several weeks of birth. Careful planning, a multidisciplinary approach, rehearsal, and experience are important factors in dealing with conjoined twins. Tissue expanders and prosthetic meshes are not required in most cases. Selective abortion or fetal intervention may play a role in the future.


Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure.
Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb)] would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO ([Hb] = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in [Hb], peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in [Hb] produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of [Hb], O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.


Inhaled albuterol does not inhibit cellular influx or lung injury produced by segmental antigen challenge in humans.
Many experimental protocols and published guidelines for performing bronchoscopy, bronchoalveolar lavage (BAL), bronchial biopsies, and segmental antigen challenge (SAC) of allergic asthmatic subjects recommend treating subjects with a beta-agonist prior to the procedure. However, the effect of beta-agonist pretreatment has not been reported. In a retrospective analysis of ragweed allergic subjects undergoing bronchoscopy, SAC, and BAL, we examined the effect of albuterol pretreatment on cellular influx and lung injury produced by antigen challenge. Forty-eight subjects, 17 who received no pretreatment and 31 who received four puffs of albuterol prior to bronchoscopy, comprised the study groups. No parameter monitored in BAL fluid 24 h after SAC (total cells, macrophages, neutrophils, eosinophils, lymphocytes, total protein, albumin, or eosinophil cationic protein) differed in subjects pretreated with albuterol when compared with subjects who were not pretreated. Although additional, prospective studies are warranted, we conclude that beta-agonist pretreatment of experimental subjects does not alter many aspects of the inflammatory response produced by SAC.


Perceptions of Experiences of Recovery After Pancreaticoduodenectomy-A Phenomenographic Interview Study.
Pancreatic surgery in the context of enhanced recovery has mainly been evaluated using clinical variables. However, there is limited knowledge about patients' perceptions of recovery in this context. Hence, the aim of this study was to explore patients' perceptions of recovery after pancreatic surgery within an enhanced recovery program. To explore the variations in patients' perceptions, a qualitatively designed study was undertaken. Data in this phenomenographic study consisted of interviews with 19 patients at 4 to 6 weeks after surgery. Recovery after pancreatic surgery was classified into 5 categories, based on patients' perceptions: to be as before, affected by symptoms, physical activity, understanding the process, and facilitated by other people. The study focused on various areas of recovery, which took place between the in-hospital and after-discharge phases. Physical experiences were found to disturb recovery, in contrast to social and emotional experiences, which facilitated recovery. Variations in perceptions of recovery suggest that care may need to be more individualized, both in the preoperative and the postoperative phase. Working with realistic expectations and early patient education might better prepare patients to continue working on their own recovery after discharge from the hospital. Major cancer surgery needs to be perceived as a personal journey for the patient, even in enhanced recovery program care. Preoperative education is good, but adding continuous and individually adopted education during recovery is better. Knowledge about both hindering and facilitating factors for recovery is important for the healthcare personal.


Impact of pain and nonpain co-morbidities on opioid use in women with endometriosis.
Aim: To evaluate impact of co-morbidities on opioid use in endometriosis. Patients & methods: This was a retrospective analysis of data obtained from the Symphony Health database (July 2015-June 2018), which contains medical and pharmacy claims information on 79,947 women with endometriosis. Relative risk (RR) of postdiagnosis opioid use and supply duration associated with baseline co-morbidities were determined. Results: Women with endometriosis using opioids at baseline were 61% more likely to receive opioids postdiagnosis (RR: 1.61; 95% CI: 1.59-1.63). Risk of prolonged opioid supply postdiagnosis was highest for those with prolonged supply at baseline (RR: 21.14; 20.14-22.19), and was 1.32 (1.26-1.38) for patients with ≥1 co-morbidity, 1.37 (1.31-1.43) for pain co-morbidities and 1.07 (1.04-1.11) for psychiatric co-morbidities. Conclusion: Risk of opioid use after endometriosis diagnosis was greater in patients who used opioids before diagnosis. Risk of prolonged opioid use was greater if co-morbidities existed before diagnosis.


Socioeconomic factors and cardiovascular disease: a review of the literature.
Despite recent declines in mortality, cardiovascular diseases are the leading cause of death in the United States today. It appears that many of the major risk factors for coronary disease have been identified. Researchers are still learning about different modifiable factors that may influence cardiovascular diseases. Socioeconomic status may provide a new focus. The principal measures of SES have been education, occupation, and income or combinations of these. Education has been the most frequent measure because it does not usually change (as occupation or income might) after young adulthood, information about education can be obtained easily, and it is unlikely that poor health in adulthood influences level of education. However, other measures of SES have merit, and the most informative strategy would incorporate multiple indicators of SES. A variety of psychosocial measures--for example, certain aspects of occupational status--may be important mediators of SES and disease. The hypothesis that high job strain may adversely affect health status has a rational basis and is supported by evidence from a limited number of studies. There is a considerable body of evidence for a relation between socioeconomic factors and all-cause mortality. These findings have been replicated repeatedly for 80 years across measures of socioeconomic level and in geographically diverse populations. During 40 years of study there has been a consistent inverse relation between cardiovascular disease, primarily coronary heart disease, and many of the indicators of SES. Evidence for this relation has been derived from prevalence, prospective, and retrospective cohort studies. Of particular importance to the hypothesis that SES is a risk factor for cardiovascular disease was the finding by several investigators that the patterns of association of SES with coronary disease had changed in men during the past 30 to 40 years and that SES has been associated with the decline of coronary mortality since the mid-1960s. However, the declines in coronary mortality of the last few decades have not affected all segments of society equally. There is some evidence that areas with the poorest socioenvironmental conditions experience later onset in the decline in cardiovascular mortality. A number of studies suggest that poor living conditions in childhood and adolescence contribute to increased risk of arteriosclerosis. Some of these studies have been criticized because of their nature, and others for inadequate control of confounding factors.(ABSTRACT TRUNCATED AT 400 WORDS)


Water-accelerated tandem Claisen rearrangement-catalytic asymmetric carboalumination.
[reaction: see text] The addition of stoichiometric quantities of water accelerates both the trimethylaluminum-mediated aromatic Claisen reaction and the chiral zirconocene-catalyzed asymmetric carboalumination of terminal alkenes. The two reactions occur in a tandem sequence resulting in the selective formation of two new C-C and one C-O bond after oxidative quench of the intermediate trialkylalane.


p161, a murine membrane protein expressed on mast cells and some macrophages, is mouse CD13/aminopeptidase N.
pl6l is a membrane glycoprotein expressed on mast cells and on activated macrophages but on few if any other cells of hematopoietic lineages. Its lack of expression on basophils makes it useful to distinguish mast cells from basophils and aids in the analysis of mast cells and their precursors. p161 was purified from the mast cell line CFTL-12 by affinity chromatography and subjected to limited proteolysis. The sequences of the resultant peptides indicated that p161 is homologous with rat and human CD13/aminopeptidase N. Using oligonucleotide primers derived from rat CD13 cDNA, a mouse cDNA was obtained. Its deduced amino acid sequence displays 87% identity with rat CD13 and 76 % identity with human CD13. Expression of the mouse cDNA in M12 cells, which are p161 negative, renders these cells positive for staining with the monoclonal anti-p161 Ab, K-1. Furthermore, a mAb raised against partially purified mouse intestinal aminopeptidase N specifically blocked the binding of K-1 to both CFTL-12 cells and the transfected M12 cells. These results strongly indicate that mouse p161 is CD13/aminopeptidase N. Northern blot analysis shows that p161 mRNA is most abundantly expressed in the intestinal tract and kidney and is present in liver, lymph node, spleen, and brain.


The neural basis of disturbed efference copy mechanism in patients with schizophrenia.
Core psychopathological symptoms in patients with schizophrenia suggest that their sense of self may be disturbed. A disturbance in predictive motor mechanisms may be the cause of such symptoms. Ten patients with schizophrenia and ten healthy right-handed control subjects opened and closed their hand. This movement was filmed with an MRI compatible video camera and projected online onto a monitor. BOLD contrast was measured with fMRI. The temporal delay between movement and feedback was parametrically varied. Participants judged whether or not there was a delay. Patients were less sensitive to these delays than a matched control group. Comparing neural activation between the two groups showed a reduced attenuation of movement-sensitive perceptual areas in patients with increasing delay and a higher activation in the putamen in controls. The results provide further evidence that impaired efference copy mechanisms may contribute to the pathogenesis of schizophrenia and its first rank symptoms.


Global diversity and genetic contributions of chicken populations from African, Asian and European regions.
Genetic diversity and population structure of 113 chicken populations from Africa, Asia and Europe were studied using 29 microsatellite markers. Among these, three populations of wild chickens and nine commercial purebreds were used as reference populations for comparison. Compared to commercial lines and chickens sampled from the European region, high mean numbers of alleles and a high degree of heterozygosity were found in Asian and African chickens as well as in Red Junglefowl. Population differentiation (FST ) was higher among European breeds and commercial lines than among African, Asian and Red Junglefowl populations. Neighbour-Net genetic clustering and structure analysis revealed two main groups of Asian and north-west European breeds, whereas African populations overlap with other breeds from Eastern Europe and the Mediterranean region. Broilers and brown egg layers were situated between the Asian and north-west European clusters. structure analysis confirmed a lower degree of population stratification in African and Asian chickens than in European breeds. High genetic differentiation and low genetic contributions to global diversity have been observed for single European breeds. Populations with low genetic variability have also shown a low genetic contribution to a core set of diversity in attaining maximum genetic variation present from the total populations. This may indicate that conservation measures in Europe should pay special attention to preserving as many single chicken breeds as possible to maintain maximum genetic diversity given that higher genetic variations come from differentiation between breeds.


Five Plant Natural Products Are Potential Type III Secretion System Inhibitors to Effectively Control Soft-Rot Disease Caused by Dickeya.
Dickeya zeae, a plant soft-rot pathogen, possesses a type III secretion system (T3SS) as one of the major virulence factors, infecting a wide variety of monocotyledonous and dicotyledonous plants and causing serious losses to the production of economic crops. In order to alleviate the problem of pesticide resistance during bacterial disease treatment, compounds targeting at T3SS have been screened using a hrpA-gfp bioreporter. After screening by Multifunctional Microplate Reader and determining by flow cytometer, five compounds including salicylic acid (SA), p-hydroxybenzoic acid (PHBA), cinnamyl alcohol (CA), p-coumaric acid (PCA), and hydrocinnamic acid (HA) significantly inhibiting hrpA promoter activity without affecting bacterial growth have been screened out. All the five compounds reduced hypersensitive response (HR) on non-host tobacco leaves and downregulated the expression of T3SS, especially the master regulator encoding gene hrpL. Inhibition efficacy of the five compounds against soft rot were also evaluated and results confirmed that the above compounds significantly lessened the soft-rot symptoms caused by Dickeya dadantii 3937 on potato, Dickeya fangzhongdai CL3 on taro, Dickeya oryzae EC1 on rice, and D. zeae MS2 on banana seedlings. Findings in this study provide potential biocontrol agents for prevention of soft-rot disease caused by Dickeya spp.


New concepts in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability but has only recently been explored from a cellular and molecular perspective. In COPD, chronic inflammation leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterized by increased numbers of alveolar macrophages, neutrophils, and cytotoxic T lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). There is also a high level of oxidative stress, which may amplify this inflammation. There is increased elastolysis and probable involvement of matrix metalloproteinases. The inflammation and proteolysis in COPD is an amplification of the normal inflammatory response to cigarette smoke. Unlike asthma, this inflammation appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.


Interaction of adriamycin with a regulatory element of hmgb1: spectroscopic and calorimetric approach.
HMGB1 is a non-histone nuclear protein which plays important role in transcription, variable, diverse and joining (VDJ) recombination, chromatin remodeling, and DNA repair, etc. and its over expression is directly correlated with various human malignancies and inflammatory diseases. Because of the clear association between HMGB1 and cancer, we studied the binding of adriamycin (ADM), a well-known anticancer drug with the promoter region (-165 to -183) of hmgb1 by using a variety of spectroscopic, calorimetric techniques, and in-silico molecular modeling. Changes in UV and CD spectral characteristics (intensity and wavelength) of ADM and DNA associated with an induced peak (300 nm) in CD spectrum of DNA and a high binding constant of 2.0 × 10(5) M(-1) suggest a strong and stable complex formation between DNA and ADM. Scatchard analysis of spectroscopic data indicate that ADM binds to DNA in a non-cooperative nature. Further the quenching of fluorescence emission of ADM and isothermal titration calorimetry of ADM in presence of DNA points out to the intercalative mode of ADM binding to DNA which is enthalpically driven with additional small entropic contribution. Results from molecular modeling, Isothermal titration calorimetry, and Fourier transform infrared spectroscopy reveal that ADM has no marked preference between AT vs. GC base pair in binding to DNA. Therefore, hmgb1 can be considered as a novel potential chemotherapeutic target in treating cancers associated with HMGB1 upregulation.


A partially folded state of hen egg white lysozyme in trifluoroethanol: structural characterization and implications for protein folding.
The effect of 2,2,2-trifluoroethanol (TFE) on the solution conformation of hen egg white lysozyme has been investigated using circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) spectroscopy. Addition of TFE to lysozyme at pH 2.0, 27 degrees C, up to a concentration of 15% (v/v) induces only slight changes in the NMR spectrum. However, above this concentration a cooperative transition to a new but partially structured state of the protein is observed. This state shows no structural cooperativity against further denaturation and is characterized by an ellipticity in the far-UV CD greater than that of the native protein. Near-UV CD intensity is dramatically reduced compared with that of the native state, and 1H NMR studies indicate that side-chain interactions are substantially averaged in this denatured state. Solvent proton/deuterium exchange rates for 66 amide hydrogens were measured site-specifically by a combination of amide trapping experiments and 2D 1H NMR. Significant protection from exchange occurs for about 25 backbone amides, the majority of which are located in regions of the protein that are helical in the native enzyme. By contrast, amides located in a second region of the native protein which contains a beta-sheet and one 3(10)-helix as well as a long loop show little protection. This pattern of protection resembles that found in the stable molten globule state of alpha-lactalbumin and in an early kinetic intermediate detected in the refolding of hen lysozyme.


A report card on outcomes for surgically treated gastrointestinal cancers: are we improving?
Longitudinal analyses of cancer registries provide an opportunity for population-based explanations of epidemiology and survival-related outcomes. This study used two population-based data sets to report on nine surgery-related cancers over the past three decades. Using the SEER cancer database (1973-1999), all patients (>18 years old) with adenocarcinoma of esophagus, gastric, biliary system, pancreas, small bowel, colon, rectum; esophageal squamous cell carcinoma (ESC), or hepatocellular (HCC) carcinoma (n = 379,640) were analyzed. Changes in incidence rates, stage at diagnosis, and 5-year cancer and stage-specific survivals were determined. A separate database, the California inpatient database (1990-2000), was concurrently used to evaluate inpatient mortality after surgical resection (n = 34,057). Incidence rates increased for three cancers (esophageal, HCC, small bowel); decreased for three (rectal, gastric, ESC); and stayed constant for three (biliary, pancreatic, colon). More patients presented with local/regional disease in the 1990s versus 1970s for eight tumors (except small bowel, P < 0.05). Five-year overall survival improved for all but small bowel (P < 0.05); and local stage survival was improved for all except small bowel and biliary (P < 0.05). Finally, inpatient mortality rates improved significantly for liver, esophageal, pancreatic, and gastric resections (P < 0.05) over the past decade. For these nine surgically treated cancers, we are detecting disease at earlier and therefore more treatable stages, and surgical care and outcomes also appear to have improved. Continued reexamination of longitudinal trends of surgically relevant outcomes is important for future improvement of surgical care.


Bacterial Community Spacing Is Mainly Shaped by Unique Species in the Subalpine Natural Lakes of China.
Bacterial communities have been described as early indicators of both regional and global climatic change and play a critical role in the global biogeochemical cycle. Exploring the mechanisms that determine the diversity patterns of bacterial communities and how they share different habitats along environmental gradients are, therefore, a central theme in microbial ecology research. We characterized the diversity patterns of bacterial communities in Pipahai Lake (PPH), Mayinghai Lake (MYH), and Gonghai Lake (GH), three subalpine natural lakes in Ningwu County, Shanxi, China, and analyzed the distribution of their shared and unique taxa (indicator species). Results showed that the species composition and structure of bacterial communities were significantly different among the three lakes. Both the structure of the entire bacterial community and the unique taxa were significantly influenced by the carbon content (TOC and IC) and space distance; however, the structure of the shared taxa was affected by conductivity (EC), pH, and salinity. The structure of the entire bacterial community and unique taxa were mainly affected by the same factors, suggesting that unique taxa may be important in maintaining the spatial distribution diversity of bacterial communities in subalpine natural freshwater lakes. Our results provide new insights into the diversity maintenance patterns of the bacterial communities in subalpine lakes, and suggest dispersal limitation on bacterial communities between adjacent lakes, even in a small local area. We revealed the importance of unique taxa in maintaining bacterial community structure, and our results are important in understanding how bacterial communities in subalpine lakes respond to environmental change in local habitats.


Beneficial Effects of Slow-Release Large Neutral Amino Acids after a Phenylalanine Oral Load in Patients with Phenylketonuria.
The mainstay of phenylketonuria treatment is a low protein diet, supplemented with phenylalanine (Phe)-free protein substitutes and micronutrients. Adhering to this diet is challenging, and even patients with good metabolic control who follow the dietary prescriptions in everyday life ignore the recommendations occasionally. The present study explores the ability of slow-release large neutral amino acids (srLNAAs) to prevent Phe increase following a Phe dietary load. Fourteen phenylketonuric patients aged ≥13 years were enrolled in a 6-week protocol. Oral acute Phe loads of 250 and 500 mg were added to the evening meal together with srLNAAs (0.5 gr/kg). Phe and tyrosine were dosed before dinner, 2h-after dinner, and after the overnight fast. After oral Phe loads, mean plasma Phe remained stable and below 600 µmol/L. No Phe peaks were registered. Tyrosine levels significantly increased, and Phe/Tyrosine ratio decreased. No adverse events were registered. In conclusion, a single oral administration of srLNAAs at the dose of 0.5 gr/kg is effective in maintaining stable plasma Phe during acute oral loads with Phe-containing food and may be added to the dietetic scheme in situations in which patients with generally good adherence to diet foresee a higher than prescribed Phe intake due to their commitments.


Quality by Design for Optimizing a Novel Liposomal Jojoba Oil-Based Emulgel to Ameliorate the Anti-Inflammatory Effect of Brucine.
One of the recent advancements in research is the application of natural products in developing newly effective formulations that have few drawbacks and that boost therapeutic effects. The goal of the current exploration is to investigate the effect of jojoba oil in augmenting the anti-inflammatory effect of Brucine natural alkaloid. This is first development of a formulation that applies Brucine and jojoba oil int a PEGylated liposomal emulgel proposed for topical application. Initially, various PEGylated Brucine liposomal formulations were fabricated using a thin-film hydration method. (22) Factorial design was assembled using two factors (egg Phosphatidylcholine and cholesterol concentrations) and three responses (particle size, encapsulation efficiency and in vitro release). The optimized formula was incorporated within jojoba oil emulgel. The PEGylated liposomal emulgel was inspected for its characteristics, in vitro, ex vivo and anti-inflammatory behaviors. Liposomal emulgel showed a pH of 6.63, a spreadability of 48.8 mm and a viscosity of 9310 cP. As much as 40.57% of Brucine was released after 6 h, and drug permeability exhibited a flux of 0.47 µg/cm2·h. Lastly, % of inflammation was lowered to 47.7, which was significant effect compared to other formulations. In conclusion, the anti-inflammatory influence of jojoba oil and Brucine was confirmed, supporting their integration into liposomal emulgel as a potential nanocarrier.


Round table discussion 'gene therapy and society'--summary and conclusions.
An international group consisting of scientists, physicians, and one lawyer reported on the problems of gene therapy with regard to society in their respective countries and discussed ethical, legal and scientific aspects of gene therapy. Ethical questions and fear in society were addressed by Dr Odenbach, former Secretary General of the German Medical Association, member of the German Parliamentary Enquiry Commission, 'Prospects and Risks of Gene Technology' and present adviser of the Ethical Committee of the World Medical Association, and by PH Hofschneider, Professor of Virology at the Max-Planck-Institut for Biochemistry, Munich, with a long-time strong interest in medical ethics; legal aspects were addressed by H Hausheer, Professor of Civil Law with many years experience in constitutional law and jurisdiction in Switzerland. Medical and scientific aspects were discussed by R Strohman, Emeritus Professor of Molecular Biology, Berkeley, USA, F Takaku, President of the International Medical Center of Japan and Chairman of the Central Evaluation Committee of the Japanese government for gene therapy, Tokyo and J Goldman, Professor of Leukemia Biology at Hammersmith Hospital, London, and known for this pioneering work in bone marrow transplantation. The discussion was moderated by R Hehlmann, Professor of Medicine at the University of Heidelberg and member of the World Committee of the International Association.


[AIDS preventive work in Arusha and Kilimanjaro--health education].
Over the past five years the Tanzanian-Norwegian AIDS Project (MUTAN) has assisted the National AIDS Control Programme in creating and testing innovative HIV/AIDS educational programmes. These programmes, designed to reach a variety of target groups, have been implemented throughout the Arusha and Kilimanjaro regions and include: public meetings, intensive courses, information centres, radio programmes and school-based programmes. A recent survey of 996 participants (15-54 years old) was designed to assess public exposure to HIV/AIDS information. A total of 72% of the participants reported having heard about AIDS on the radio, 74% having read about AIDS in newspapers, and 52% having heard about AIDS from a health worker during the previous month. Furthermore, 26% had listened to MUTAN's weekly radio programme at least once. 31% knew of MUTAN's information centres, and 15% had visited one of these centres. The results indicate that large proportion of the population is receiving in-depth HIV/AIDS information. It is recommended that future work concentrate on how to reach people with no or little formal education, young adults and women.


Prevalence, Patterns, and Determinants of Intimate Partner Violence Experienced by Women Who Are Pregnant in Sanma Province, Vanuatu.
Violence perpetrated by an intimate partner (IPV) is an important human rights and public health problem worldwide and when experienced during pregnancy is of special concern due to the harmful impact on maternal and child health. Women living in Vanuatu, and especially Sanma Province, experience high rates of IPV, however little is known about their experiences of violence when pregnant. The aim was to describe the prevalence, patterns and determinants of IPV among women who are pregnant in Sanma Province, Vanuatu. A cross-sectional survey was used. All healthy adult women attending Northern Provincial Hospital antenatal clinic from late May to late July 2019 were eligible and invited to participate. Psychological, physical and sexual IPV and controlling behaviours were assessed with a modified version of the World Health Organization Violence Against Women Instrument administered as an individual interview. Descriptive statistics were used to analyse prevalence and patterns of IPV and logistic regression models to identify determinants. Of 214 women who expressed interest in participating, 192 women contributed data. Overall 64.2% of women had experienced any IPV during their lifetime and 42.2% had experienced IPV during their current pregnancy. Experience of co-occurrence of violence types was common, and it was more common for IPV to continue than to cease during pregnancy. Factors which increased likelihood of experiencing IPV included being employed, occupying a lower socioeconomic position, having a partner who was unemployed or used alcohol or illicit substances at least once a week. IPV, in all its forms, is a common problem faced by women who are pregnant and living in Vanuatu.


Sorbent-based sampling methods for volatile and semi-volatile organic compounds in air Part 1: Sorbent-based air monitoring options.
Sorbent tubes/traps are widely used in combination with gas chromatographic (GC) analytical methods to monitor the vapour-phase fraction of organic compounds in air. Target compounds range in volatility from acetylene and freons to phthalates and PCBs and include apolar, polar and reactive species. Airborne vapour concentrations will vary depending on the nature of the location, nearby pollution sources, weather conditions, etc. Levels can range from low percent concentrations in stack and vent emissions to low part per trillion (ppt) levels in ultra-clean outdoor locations. Hundreds, even thousands of different compounds may be present in any given atmosphere. GC is commonly used in combination with mass spectrometry (MS) detection especially for environmental monitoring or for screening uncharacterised workplace atmospheres. Given the complexity and variability of organic vapours in air, no one sampling approach suits every monitoring scenario. A variety of different sampling strategies and sorbent media have been developed to address specific applications. Key sorbent-based examples include: active (pumped) sampling onto tubes packed with one or more sorbents held at ambient temperature; diffusive (passive) sampling onto sorbent tubes/cartridges; on-line sampling of air/gas streams into cooled sorbent traps; and transfer of air samples from containers (canisters, Tedlar) bags, etc.) into cooled sorbent focusing traps. Whichever sampling approach is selected, subsequent analysis almost always involves either solvent extraction or thermal desorption (TD) prior to GC(/MS) analysis. The overall performance of the air monitoring method will depend heavily on appropriate selection of key sampling and analytical parameters. This comprehensive review of air monitoring using sorbent tubes/traps is divided into 2 parts. (1) Sorbent-based air sampling option. (2) Sorbent selection and other aspects of optimizing sorbent-based air monitoring methods. The paper presents current state-of-the-art and recent developments in relevant areas such as sorbent research, sampler design, enhanced approaches to analytical quality assurance and on-tube derivatisation.


Evaluation of cytokine gene expression in psoriasis.
Psoriasis is a chronic inflammatory disease affecting the skin with an unclear etiological significance. In this study, we determined the mRNA expression and circulating levels of T helper (Th)/T regulatory (Treg) cytokines in psoriasis and analyzed their association with disease severity and treatment response. 189 psoriasis patients and 189 controls were recruited. Circulating Th/Treg cytokines (IL-12, IFN-γ, IL-17, IL-23, TGF-β and IL-4) were measured at baseline and at follow-up after 12 weeks of methotrexate treatment by ELISA and their relative mRNA expression at baseline was estimated by quantitative PCR. We observed increased levels of Th1/Th17 cytokines (IFN-γ, IL-17, IL-12 and IL-23) and a decrease in levels of Th2/Treg cytokines (IL-4 and TGF-β) in psoriasis patients at baseline, as compared to controls. Further, we observed that there was a significant decrease in Th1/Th17 cytokines, whilst Th2/Treg cytokine levels were significantly increased on follow-up after treatment with systemic metho trexate, as compared to pre-treatment levels. Our results were further confirmed by the significantly higher mRNA expression of Th1/Th17 cytokine genes and significantly lower mRNA expression of Th2/Treg cytokine genes in patients with psoriasis, as compared to controls. A significant positive correlation of Th1/Th17 cytokines was observed with disease severity in cases, whilst Th2/Treg cytokines correlated negatively with disease severity. Our results show that increased Th1/Th17 cytokines and decreased Th2/Treg cytokines, both at the circulatory and gene expression level, play an important role in the immunopathogenesis and severity of psoriasis.


Synchronization of chaotic systems with different order.
The chaotic synchronization of third-order systems and second-order driven oscillator is studied in this paper. Such a problem is related to synchronization of strictly different chaotic systems. We show that dynamical evolution of second-order driven oscillators can be synchronized with the canonical projection of a third-order chaotic system. In this sense, it is said that synchronization is achieved in reduced order. Duffing equation is chosen as slave system whereas Chua oscillator is defined as master system. The synchronization scheme has nonlinear feedback structure. The reduced-order synchronization is attained in a practical sense, i.e., the difference e=x(3)-x(1)(') is close to zero for all time t> or =t(0)> or =0, where t(0) denotes the time of the control activation.


Thinner, smaller, faster: IR techniques to probe the functionality of biological and biomimetic systems.
New techniques in vibrational spectroscopy are promising for the study of biological samples as they provide exquisite spatial and/or temporal resolution with the benefit of minimal perturbation of the system during observation. In this Minireview we showcase the power of modern infrared techniques when applied to biological and biomimetic systems. Examples will be presented on how conformational changes in peptides can be traced with femtosecond resolution and nanometer sensitivity by 2D IR spectroscopy, and how surface-enhanced infrared difference absorption spectroscopy can be used to monitor the effect of the membrane potential on a single proton-transfer step in an integral membrane protein. Vibrational spectra of monolayers of molecules at basically any interface can be recorded with sum-frequency generation, which is strictly surface-sensitive. Chemical images are recorded by applying scanning near-field infrared microscopy at lateral resolutions better than 50 nm.


Combinatorial interpretation of Haldane-Wu fractional exclusion statistics.
Assuming that the maximal allowed number of identical particles in a state is an integer parameter, q, we derive the statistical weight and analyze the associated equation that defines the statistical distribution. The derived distribution covers Fermi-Dirac and Bose-Einstein ones in the particular cases q=1 and q--> infinity (n(i)/q-->1), respectively. We show that the derived statistical weight provides a natural combinatorial interpretation of Haldane-Wu fractional exclusion statistics, and present exact solutions of the distribution equation.


Delta-tubulin and epsilon-tubulin: two new human centrosomal tubulins reveal new aspects of centrosome structure and function.
The centrosome organizes microtubules, which are made up of alpha-tubulin and beta-tubulin, and contains centrosome-bound gamma-tubulin, which is involved in microtubule nucleation. Here we identify two new human tubulins and show that they are associated with the centrosome. One is a homologue of the Chlamydomonas delta-tubulin Uni3, and the other is a new tubulin, which we have named epsilon-tubulin. Localization of delta-tubulin and epsilon-tubulin to the centrosome is independent of microtubules, and the patterns of localization are distinct from each other and from that of gamma-tubulin. Delta-tubulin is found in association with the centrioles, whereas epsilon-tubulin localizes to the pericentriolar material. epsilon-Tubulin exhibits a cell-cycle-specific pattern of localization, first associating with only the older of the centrosomes in a newly duplicated pair and later associating with both centrosomes. epsilon-Tubulin thus distinguishes the old centrosome from the new at the level of the pericentriolar material, indicating that there may be a centrosomal maturation event that is marked by the recruitment of epsilon-tubulin.


Reliable method for calculating the center of rotation in parallel-beam tomography.
High-throughput processing of parallel-beam X-ray tomography at synchrotron facilities is lacking a reliable and robust method to determine the center of rotation in an automated fashion, i.e. without the need for a human scorer. Well-known techniques based on center of mass calculation, image registration, or reconstruction evaluation work well under favourable conditions but they fail in cases where samples are larger than field of view, when the projections show low signal-to-noise, or when optical defects dominate the contrast. Here we propose an alternative technique which is based on the Fourier analysis of the sinogram. Our technique shows excellent performance particularly on challenging data.


Recombinant human thrombopoietin increases platelet count in severe thrombocytopenic patients with hepatitis B-related cirrhosis: Multicentre real-world observational study.
Patients with hepatitis B-related cirrhosis complicated with thrombocytopenia have a higher risk of bleeding, which may lead to higher mortality. We aimed to explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of hepatitis B-related cirrhosis complicated with severe thrombocytopenia. Patients with hepatitis B-related compensated liver cirrhosis complicated with severe thrombocytopenia were divided into four groups according to the treatment method for thrombocytopenia. Platelet counts, the appearance of bleeding symptoms and adverse events were evaluated during the observation period. Also during the observational period, the platelet counts in the prednisone group, rhTPO group and prednisone plus rhTPO group were higher than those in the no treatment group. Patients without splenomegaly reacted better to rhTPO. Fewer bleeding events of grade 2 or worse were observed in the three treatment groups compared to the no treatment group. The platelet counts at baseline and treatment with rhTPO and/or prednisone were factors associated with bleeding events of grade 2 or worse in multivariate analysis. There could be a potential advantage for the use of rhTPO plus prednisone based on higher platelet counts and fewer bleeding events. Treatment with rhTPO was more effective in patients without splenomegaly.


[Cloning and sequencing of attacus ricini nuclear polyhedrosis virus polyhedrin gene].
Attacus ricini is a species of insect which only grows in China. It is expected to construct a new expression system for genetic engineering by using ArNPV as a vector. We have established an ArNPV gene library. The 1.1 kb DNA fragment containing ArNPV Ph gene was subcloned. Sequencing analysis shows that the 735 bp Ph structural gene has the homology of 76% and 81% with those of AcNPV and BmNPV respectively. The Rohrmann box in the ArNPV 5'-end regulation region is very similar to those of various other NPVs, but the 3'-end downstream sequence has almost no homology with those of AcNPV and BmNPV, demonstrating the characteristic property of the structure of ArNPV Ph gene. Other structural features of the Ph gene promoter are also discussed in this paper.


Effects of acetylcholine and glutamate on isolated neurons of locomotory network of Clione.
In Clione limacina, locomotory rhythm is produced in the central pattern generator by reciprocal activity of two groups of interneurons. Dorsal (D) and ventral (V) phase interneurons activate neurons of the same phase and inhibit neurons of the opposite phase. Which neurotransmitters are used by these interneurons is not clear. In this study, identified follower neurons to V and D interneurons were isolated, and their responses to the local application of potential neurotransmitters were examined. Acetylcholine exerted inhibitory action on the isolated D-phase neurons and excitatory action on V-phase neurons. Glutamate produced excitation in D-phase neurons, and inhibition in V-phase neurons. These results suggest that acetylcholine is the neurotransmitter of D-phase interneurons, while glutamate might be the neurotransmitter of V-phase interneurons.


Experimental models of ventricular tachycardia and fibrillation caused by ischemia and infarction.
Experimental animal models of ventricular arrhythmias have been developed to elucidate mechanisms of arrhythmogenesis in humans. Studies of animal models have enabled the vulnerable period of the ventricles to be discovered and characterized and should eventually lead to improved techniques of defibrillation. Animal models of ischemic heart disease and myocardial infarction have also helped investigators elucidate the mechanisms of arrhythmias occurring at each stage of infarct development and healing. Data obtained from the experimental studies have been shown to apply to the clinical situation.


Investigation of the Utility of Features in a Clinical De-identification Model: A Demonstration Using EHR Pathology Reports for Advanced NSCLC Patients.
Electronic health record (EHR) systems contain a large volume of texts, including visit notes, discharge summaries, and various reports. To protect the confidentiality of patients, these records often need to be fully de-identified before circulating for secondary use. Machine learning (ML) based named entity recognition (NER) model has emerged as a popular technique of automatic de-identification. The performance of a machine learning model highly depends on the selection of appropriate features. The objective of this study was to investigate the usability of multiple features in building a conditional random field (CRF) based clinical de-identification NER model. Using open-source natural language processing (NLP) toolkits, we annotated protected health information (PHI) in 1,500 pathology reports and built supervised NER models using multiple features and their combinations. We further investigated the dependency of a model's performance on the size of training data. Among the 10 feature extractors explored in this study, n-gram, prefix-suffix, word embedding, and word shape performed the best. A model using combination of these four feature sets yielded precision, recall, and F1-score for each PHI as follows: NAME (0.80; 0.79; 0.80), LOCATION (0.85; 0.83; 0.84), DATE (0.86; 0.79; 0.82), HOSPITAL (0.96; 0.93; 0.95), ID (0.99; 0.82; 0.90), and INITIALS (0.97; 0.49; 0.65). We also found that the model's performance becomes saturated when the training data size is beyond 200. Manual de-identification of large-scale data is an impractical procedure since it is time-consuming and subject to human errors. Analysis of the NER model's performance in this study sheds light on a semi-automatic clinical de-identification pipeline for enterprise-wide data warehousing.


New carboxamides bearing benzenesulphonamides: Synthesis, molecular docking and pharmacological properties.
Ten new derivatives of benzenesulphonamide bearing carboxamide functionality were synthesized and investigated for their in vitro antimicrobial, antioxidant and in vivo anti-inflammatory activities. Compound 9d inhibited carrageenan induced rat-paw oedema at 93.81, 88.79 and 86.09% at 1 h, 2 h and 3 h administration respectively. In the antimicrobial activity, compound 9a (6.54, 6.69 and 6.64 mg/mL) was most potent against S. aureus, B. subtilis and C. albicans respectively, compound 9e (6.45 and 6.46 mg/mL) was most active against P. aeruginosa and A. niger respectively while compound 9i (6.24 mg/mL) was most active against E. coli. Only compound 9a (IC50 0.3052 mg/mL) had comparable activity with Vitamin C (IC50 0.2090 mg/mL) in the antioxidant assay.


Clinical utility of glatiramer acetate in the management of relapse frequency in multiple sclerosis.
Glatiramer acetate (GA) represents one of the most common disease-modifying therapies for multiple sclerosis. GA is currently approved for patients at high risk of developing clinically definite multiple sclerosis (CDMS) after having experienced a well-defined first clinical episode (clinically isolated syndrome or CIS) and for patients with relapsing-remitting multiple sclerosis (RRMS). GA's efficacy and effectiveness to reduce relapse frequency have been proved in placebo-controlled and observational studies. Comparative trials have also confirmed the lack of significant differences over other choices of treatment in the management of relapse frequency, and long-term studies have supported its effect at extended periods of time. Additionally, RRMS patients with suboptimal response to interferon β may benefit from reduced relapse rate after switching to GA, and those with clinically isolated syndrome may benefit from delayed conversion to CDMS. All these results, together with its proven long-term safety and positive effect on patients' daily living, support the favorable risk-benefit of GA for multiple sclerosis treatment.


CD8 expression in a case of chronic lymphocytic leukemia with trisomy 12.
We report a case of B-cell chronic lymphocytic leukemia (B-CLL) with aberrant expression of the T-cell-associated antigen CD8, as revealed by two-color flow-cytometric analysis. DNA studies showed immunoglobulin heavy-chain gene rearrangement, but not of gamma-chain T-cell receptor, confirming the B-cell origin of the neoplastic cells. Ploidy analysis showed a tetraploid population and high S-phase fraction. B-CLL cells also carried trisomy 12, detected by fluorescence in situ hybridization. The identification of more cases with the same features would be necessary to establish the prognosis of this subtype of B-CLL.


Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies.
To assess the efficacy and safety of VX-702, a p38 MAPK inhibitor, in patients with active, moderate-to-severe rheumatoid arthritis (RA). Two 12-week, double-blind, placebo-controlled studies of VX-702 were conducted in patients with active, moderate-to-severe RA. In the VeRA study, 313 patients received placebo or 2 daily doses of VX-702. In Study 304, 117 patients received placebo, daily VX-702, or twice weekly VX-702 in addition to concomitant methotrexate (MTX). Study end points included the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (an ACR20 response), ACR50 and ACR70 responses, changes in the serum levels of biomarkers of inflammation, and safety assessments. The numerically superior ACR20 response rates among patients receiving VX-702 compared with those receiving placebo in both studies did not reach pairwise statistical significance at the highest doses in either study. At week 12 in the VeRA study, ACR20 response rates were 40%, 36%, and 28% among patients receiving 10 mg of VX-702, 5 mg of VX-702, and placebo, respectively. In Study 304, the response rates were 40%, 44%, and 22% for patients receiving 10 mg VX-702 daily plus MTX, 10 mg VX-702 twice weekly plus MTX, and placebo, respectively. Reductions in the levels of C-reactive protein, soluble tumor necrosis factor receptor p55, and serum amyloid A were observed as early as week 1 in both studies, but these levels rapidly returned to baseline values by week 4. The overall frequency of adverse events was similar between the VX-702 and placebo groups. In the VeRA study, serious infections were more frequent in the VX-702 groups compared with the placebo group (2.4% versus 0%) but not in Study 304 (2.6% versus 4.9%). The modest clinical efficacy plus the transient suppression of biomarkers of inflammation observed in this study suggest that p38 MAPK inhibition may not provide meaningful, sustained suppression of the chronic inflammation seen in RA.


Synthesis and Bioactivities Study of Novel Pyridylpyrazol Amide Derivatives Containing Pyrimidine Motifs.
In this study, thirteen new pyridylpyrazolamide derivatives containing pyrimidine motifs were synthesized via six-step reactions. Bioassay results showed that some of the synthesized compounds revealed good antifungal properties against Sclerotinia sclerotiorum, Phytophthora infestans, Thanatephorus cucumeris, Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica, Botryosphaeria dothidea, and Phompsis sp. at 50 μg/mL, which were similar to those of Kresoxim-methyl or Pyrimethanil. Meanwhile, bioassay results indicated that the synthesized compounds showed a certain insecticidal activity against Spodoptera litura, Mythimna separata, Pyrausta nubilalis, Tetranychus urticae, Rhopalosiphum maidis, and Nilaparvata lugens at 200 μg/mL, which was lower than that of Chlorantraniliprole. To the best of our knowledge, this study is the first report on the antifungal and insecticidal activities of pyridylpyrazol amide derivatives containing a pyrimidine moiety.


Characteristics, perceptions, and factors influencing the decision making of physical therapy chairpersons in 2000.
The physical therapy (PT) profession is changing. A mailed survey elicited characteristics of current PT chairpersons, such as time spent on responsibilities, influences on decision making, perceptions of working relationships, and satisfaction with decision making, as well as information about their supervisors and the faculty they managed. Chairpersons of 115 (54.28%) accredited PT programs responded. They had been in their positions for a mean of 6.04 years; 63 (57.8%) held doctoral degrees. They had a mean of 25.6 years of experience in PT practice and 17.5 years in academic positions. Their levels of satisfaction and the power and influence they had in their positions were high. However, the time spent on faculty recruitment and mentoring, given the lack of seniority of their faculty, and the small percentage of time they devoted to their own professional development may be concerns. Long-range planning and accreditation duties take up most of the time of PT chairpersons. This information may be helpful to people who seek, or who are recruited for, chairperson positions. It provides a foundational database for longitudinal studies of PT chairpersons.


Ataxia, ocular telangiectasia, chromosome instability, and Langerhans cell histiocytosis in a patient with an unknown breakage syndrome.
An 8 year old boy who had Langerhans cell histiocytosis when he was 15 months old showed psychomotor regression from the age of 2 years. Microcephaly, severe growth deficiency, and ocular telangiectasia were also evident. Magnetic nuclear resonance imaging showed cerebellar atrophy. Alphafetoprotein was increased. Chromosome instability after x irradiation and rearrangements involving chromosome 7 were found. Molecular study failed to show mutations involving the ataxia-telangiectasia gene. This patient has a clinical picture which is difficult to relate to a known breakage syndrome. Also, the relationship between the clinical phenotype and histiocytosis is unclear.