PMID- 24175352 TI - Bone marrow metastases by alveolar rhabdomyosarcoma in a 31-year-old patient. PMID- 24175353 TI - Romiplostim-induced myelofibrosis. PMID- 24175358 TI - Women's organization nurtured, influenced. PMID- 24175359 TI - Human-animal interactions conference comes to U.S. AVMA convention is first U.S. venue; new award conferred. PMID- 24175360 TI - The trailblazer of veterinary specialty medicine. PMID- 24175361 TI - Needed for public health, despite constraints. Veterinarians needed, but debt hinders adaptability. PMID- 24175362 TI - Resisting heartworm prevention a small number of heartworms resistant to prophylaxis. PMID- 24175363 TI - Medicare program: conditions of participation (CoPs) for community mental health centers. Final rule. AB - This final rule establishes, for the first time, conditions of participation (CoPs) that community mental health centers (CMHCs) must meet in order to participate in the Medicare program. These CoPs focus on the care provided to the client, establish requirements for staff and provider operations, and encourage clients to participate in their care plan and treatment. The new CoPs enable CMS to survey CMHCs for compliance with health and safety requirements. PMID- 24175364 TI - Patient Protection and Affordable Care Act; program integrity: exchange, premium stabilization programs, and market standards; amendments to the HHS notice of benefit and payment parameters for 2014. Final rule. AB - This final rule implements provisions of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010 (collectively referred to as the Affordable Care Act). Specifically, this final rule outlines financial integrity and oversight standards with respect to Affordable Insurance Exchanges, qualified health plan (QHP) issuers in Federally facilitated Exchanges (FFEs), and States with regard to the operation of risk adjustment and reinsurance programs. It also establishes additional standards for special enrollment periods, survey vendors that may conduct enrollee satisfaction surveys on behalf of QHP issuers, and issuer participation in an FFE, and makes certain amendments to definitions and standards related to the market reform rules. These standards, which include financial integrity provisions and protections against fraud and abuse, are consistent with Title I of the Affordable Care Act. This final rule also amends and adopts as final interim provisions set forth in the Amendments to the HHS Notice of Benefit and Payment Parameters for 2014 interim final rule, published in the Federal Register on March 11, 2013, related to risk corridors and cost-sharing reduction reconciliation. PMID- 24175365 TI - [Stepping into the chamber]. PMID- 24175366 TI - [Socks for life - an art action for premature infants]. PMID- 24175367 TI - [Congratulations - Liliane Juchli. The grande dame of nursing celebrates her 80th birthday]. PMID- 24175368 TI - [Chronicity of attention deficit hyperactivity disorder]. PMID- 24175369 TI - [Sleepless in Germany: causes of sleep disorders as well as references for prevention]. PMID- 24175370 TI - [Risks and chances of immigration from the pediatric and adolescent psychiatric viewpoint]. PMID- 24175371 TI - [Patient safety in intensive care medicine: what preventive measures can be taken?]. PMID- 24175372 TI - [Women's health and immigration: needs - health care reality - perspectives]. PMID- 24175373 TI - [Federal election 2013: social pediatric personnel demand political implementation of child consciousness]. PMID- 24175374 TI - [High rate of athletic injuries in children. Boys break their bones, girls fall from the horse]. PMID- 24175375 TI - [Controlling dangerous hospital pathogens with uv light? US study proves effectiveness of special lamps in clinic rooms to control certain bacteria]. PMID- 24175376 TI - [Key qualifications for training spiritual health in the profession. Better equipped against stress and burnout]. PMID- 24175377 TI - [The physical development of children in Russia: the specification of means to evaluate and identify the problematic situation in process of growing and development of oncoming generation]. AB - The article deals with issue of physical development of children as an important summarizing health parameter and indicator of social well-being of society. The organism development in child age determines the main traits of health of this generation in older age including potential longevity and transferring of corresponding qualities to future generations. The analysis is presented concerning accumulation of factual data and development of methodical instruments to evaluate physical development of children in Russia and other countries. The universal application in Russia of corresponding WHO standards is proposed. The necessity to include the integrated indicators of physical development into official statistical reporting is emphasized. PMID- 24175378 TI - [The occupational health of medical personnel of psychiatric institutions]. AB - The article considers the issues of self-assessment of occupational health by medical personnel of psychiatric service. The main issues and areas of occupation health disorders are identified. The main directions of disorders prevention are presented. PMID- 24175379 TI - [The prevalence of main risk factors of development of cardio-vascular diseases in persons of young age]. AB - The article deals with results of study of main risk factors of development of cardio-vascular diseases in students of Stepanokert in 2007-2010. The main characteristics of prevalence of analyzed factors and their dynamics during established study period are presented are presented. The structure of prevalence of main risk factors predisposing to development of cardio-vascular diseases is determined. The predominance of risk factors of hypodynamia and higher psycho emotional stress is established. PMID- 24175380 TI - [The dynamics of heath indicators of population of industrial town]. AB - The article presents the results of analysis of dynamics of health indicators of population of industrial town (medical demographic indicators, disability, morbidity of social hygienically important diseases) during 1970-2010. The classified administrative territorial municipality of Seversk constructed near the Siberian chemical industrial center, the internationally first-rate complex of nuclear industry enterprises was used as a research base. It is demonstrated that dynamics of health indicators of studied population had such negative tendencies as rapid population ageing, population loss due to decrease of natality and increase of mortality (population of able-bodied age included), prevalence of cardio-vascular diseases, malignant neoplasms and external causes, chronization of diseases. The established tendencies are to be considered in management decision making targeted to support and promote population health in industrial towns. PMID- 24175381 TI - [The epidemiologic characteristic of diabetes mellitus and its complications]. AB - The article presents dynamics of prevalence, mortality and disability due to diabetes mellitus at the territory of Perm kraiy during last 10 years. The rate of diseases' complications and mean life interval are also considered. The materials of analysis made it possible to evaluate the epidemiological situation in kraiy and to develop activities to change it. PMID- 24175382 TI - [The prevention of tuberculosis in middle Volga and fore-Urals regions]. AB - The article presents last decade data concerning the level of tuberculosis in population of region, risk factors related to morbidity of tuberculosis in different groups of population. The activities of prevention of tuberculosis are discussed. PMID- 24175383 TI - [The model and stages of social hygienic evaluation of prevalence of pathology in population]. AB - The article presents the model of social hygienic evaluation of prevalence of pathology in population. The main information flows such as population morbidity according medical aid appealability, the results of patient examination in regional diagnostic center and self-assessment of patients of presence of disorders of organs and systems are considered. The stages of analysis of data information to be applied to evaluate prevalence of pathology, social hygienic value of diagnostic techniques and estimation of potential relevance of medical technologies are discussed. PMID- 24175384 TI - [The development of strategic management of high-tech surgical medical care]. AB - The high-tech surgical medical care is one of the most effective types of medical care in Russia. However high-tech surgical treatment very often is inaccessible for patients. The development of basics of strategic management of high-tech surgical care makes it possible to enhance availability of this type of care and to shorten the gap between volumes of rendered care and population needs. This approach can be resulted in decrease of disability and mortality of the most prevalent diseases of cardio-vascular diseases, malignant neoplasms, etc. The prerequisites can be developed to enhance life quality and increase longevity of population. PMID- 24175385 TI - [The justification of the level of public financing of health care to enhance health of population of the Russian Federation]. AB - The article discusses the justification of management of public financing of health care in Russia. The technique of comparative analysis and evaluation of dependences between public health care financing and indicators of population health has been applied. It is demonstrated that to achieve the values of 75.6 years of life expectancy at birth and 11 of total mortality as target indicators of population health up to 2018 the amount of public health care financing is to be increased up to 1.5 times or up to 6% of GDP per year in prices of 2011. The sources of additional health care financing are proposed. PMID- 24175386 TI - [The structure of hospital morbidity and enhancement of medical care in neurosurgery department]. AB - The article presents analysis of structure of hospital morbidity and indicators of activities of neurosurgery department of the Republic clinical hospital of emergency care of the Chechen Republic. The analysis date supports increasing quality of curative diagnostic processes and valuable development of algorithm of provision of medical care of this profile in curative preventive institution. PMID- 24175387 TI - [About reorganization of ambulatory polyclinic care of population in Moscow]. AB - The article presents main characteristics of development of ambulatory polyclinic care to population exemplified by North East administrative okrug of Moscow under implementation of three-level system according program of modernization of metropolitan health care. PMID- 24175388 TI - [The actual issues of personnel training in nursing care]. AB - The article presents results of questionnaire survey and testing of students of medical college and faculty of higher nursing education. The causes of choosing the profession of medical nurse are enumerated. The opinions of students concerning professional image of nurse are analyzed. The survey demonstrated that 9.3% of respondents noted that one's associates consider their profession as honorable one. About 9.3% of respondents indicated that the profession of medical nurse is to be considered with respect. About 39.3% of respondents assumed that medical nurse profession is publically needed. According the opinion of 8.6% the attitude to this profession is neutral and 4.8% indicated that one's associates have scornful attitude. The shortcomings of training quality of students are established. The directions of development of training process are indicated. PMID- 24175389 TI - [The becoming of public medicine in the second half of XVIII-first half of XIX centuries. Report IV. The state-run activities supporting healthy conditions of life, nutrition and occupational activities]. AB - The present report considers the activities of governmental authorities of European countries in the area of implementation of the concept of medical police. The target was to apply concrete activities concerning support of healthy conditions of life, nutrition and occupational activities of population of particular countries. The article considers the issues of application of sanitary education, sanitation and improvement of cities, liquidation of dumps, cemeteries and cesspits within the city limits, provision of population with sufficient amount of food and establishment of control of food quality, development and application of factory legislation, limitation of quarantine measures, implementation of specific measures of preventing diseases of smallpox and syphilis. PMID- 24175390 TI - [The input of the free economic society of study of problem of children mortality]. AB - The Free economic society is the first scientific society in Russia which, among many other problems, considered issues of medicine. The society possesses prominent accomplishments in spreading smallpox vaccination. In 1833 the Free economic society declared a competition for best writing about causes of high mortality among children at first year of life and measures of combatting. The work by I.R. Lichtenshtedt was approved as the best and published in 1840. PMID- 24175391 TI - [From the history of clinical town of the A.V. Vishnevskii Institute of Surgery]. AB - The article is dedicated to 150th anniversary of onset of medical and philanthropic activity of institutions of the Moscow merchant society at Schipok Street. Nowadays, in the buildings of society the A.V. Vishnevskiy Institute of surgery is situated. The archive documents were used to consider the characteristics of activity of precursors of the Institute, including the role of these structures in becoming of national public health. The value of private initiative in development of medicine and charity is demonstrated. The importance of historical traditions for contemporaries is emphasized. PMID- 24175392 TI - [The contribution of I.I. Molleson in becoming and development of sanitary service in the Saratov guberniia]. AB - The article presents in the historical perspective a brief biography data about I.I. Molleson. The main issues are covered concerning the development of sanitary service in the Saratov guberniya in the end of nineteenth century. The scientific and practical contribution of I.I. Molleson into becoming and development of sanitary business in Russia is demonstrated. PMID- 24175393 TI - [A.S. Puchkov as an organizer of the Moscow station of emergency medical care]. AB - The article is devoted to the 125th anniversary of outstanding Russian physician, health administrator, honored physician Aleksander Sergeyevitch Putchkov (1887 1952). During thirty years, from 1923, he continuously headed the Moscow station of emergency medical care based at the Sheremetoyevskiy hospital, nowadays the N.V. Sklifosofskiy research institute of emergency care. PMID- 24175394 TI - [The history of study of respiratory disorders of sleep]. AB - The pathologic breath during sleep was mentioned already by ancient historians. The respiratory disorders during sleep and particularly the syndrome of obstructive apnea in sleep were described in details already in early 1970s. Only 20 years later they became widely approved as a wide-spread and significant issue of public health. The considerable portion of society and even medical society has no enough knowledge of this problem. The article attempts to present in details historical aspects of its development. PMID- 24175395 TI - [I.P. Pavlov and L.A. Orbeli: new materials in stocks of the military medical museum]. AB - The article presents the previously unpublished letter of I.P. Pavlov to L.A. Orbeli being kept in stocks of the Military medical museum of military medical museum of the S.M. Kirov military medical academy. The needed commentaries are given. PMID- 24175396 TI - Association of Chairs of Departments of Physiology 2012 survey results. PMID- 24175397 TI - Mentoring 101: training for the future. PMID- 24175398 TI - APS suggests ways to reduce regulatory burden. PMID- 24175399 TI - Introduction. Dermatitis. PMID- 24175400 TI - Immunology of atopic dermatitis: novel insights into mechanisms and immunomodulatory therapies. AB - Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin condition that is associated with immune dysregulation and epidermal barrier dysfunction. The imbalance of the Th2 and Th1 pathways and their associated cytokines in AD presents as one facet of the pathogenic mechanisms. Changes in the T-cell populations and the associated cytokines during the acute and chronic phases of AD can cause variations in disease presentations and treatment responses. Continued discoveries in the immunopathogenesis of AD provide optimism for the development of efficacious therapeutic agents. Novel immunomodulatory therapies include apremilast, dupilumab, IL-37, omalizumab, rituximab, mepolizumab, infliximab, allergen-specific immunotherapy, Mycobacterium vaccae, and leflunomide. These agents serve as examples of how modulation in immunopathogenesis of AD can lead to therapeutic discoveries. PMID- 24175401 TI - Allergic contact dermatitis to plant extracts in cosmetics. AB - Topically applied cosmetics and medicaments containing botanical extracts are commonly used. Despite popular beliefs of their benignancy, some botanicals have been implicated in causing allergic contact dermatitis in susceptible patients. The offending allergen may be the botanical extract itself or another ingredient such as a fragrance, preservative, dye, or sunscreen found in the product. Specific botanicals implicated in causing cosmetic contact dermatitis include Compositae family plants, tea tree oil, peppermint, lavender, lichens, henna, and others. PMID- 24175402 TI - Hand dermatitis: review of clinical features and treatment options. AB - Hand dermatitis affects a significant portion of the population and can be caused by a variety of endogenous factors (ie, atopy) as well as occupational and environmental exposures. It is often a chronic problem with high costs to individuals, employers, and society. This review discusses subtypes of hand dermatitis based on their clinical features and pathogenesis. It also offers an approach to treatment. PMID- 24175403 TI - Basics of patch testing for allergic contact dermatitis. AB - Patch testing is essential for identification of culprit allergens responsible for allergic contact dermatitis. This manuscript reviews how to perform patch testing and how to read and interpret the results. PMID- 24175404 TI - Venous eczema and lipodermatosclerosis. AB - Cutaneous changes are a common feature of chronic venous insufficiency and include venous eczema and lipodermatosclerosis. This review will address the presumed pathophysiology of these conditions, their clinical findings, and important management strategies. PMID- 24175405 TI - Noninfectious granulomatous dermatitides: a review of 8 disorders (Part 1 of 3). AB - In this review we focus on 2 of the noninfectious granulomatous dermatitides, granuloma annulare and interstitial granulomatous dermatitis (the remaining 6 will be discussed in Parts 2 and 3), with an overview of their clinical and histological presentations, differential diagnoses, and treatment options. The disorders we discuss are polymorphic in their clinical and histopathological presentations, follow chronic or undulating disease courses, and are typically recalcitrant to therapeutic interventions. Although the clinical history may be helpful, careful and thorough histopathological examination is required. Established treatment algorithms for these disorders are lacking, and no randomized, placebo-controlled studies have been published. Future investigations should focus on the evaluation of larger cohorts, not only to establish treatment recommendations in randomized, placebo-controlled trials, but also to reach a greater understanding of disease pathogenesis and clinical-pathological presentation. PMID- 24175406 TI - Stormwater. PMID- 24175407 TI - Variations in highway stormwater runoff quality and stormwater treatment performance in relation to the age of porous friction courses. AB - A program of highway runoff sampling was conducted at four sites in Auckland, New Zealand. Concentrations of suspended solids, particulate copper, and zinc were significantly lower in runoff from a highway paved with a 1-year-old porous friction course (PFC) than in runoff at the other sites. Differences in total metal concentrations were less marked, reflecting relatively high concentrations of dissolved copper and zinc in runoff from the 1-year-old PFC. Runoff quality at a highway site that had been paved with a PFC 6 years previously was similar to that discharged from two impermeable roads, indicating a reduction over time in the quality of runoff discharged from PFCs. Runoff from the highways paved with 1 and 6-year-old PFCs was treated by a grass swale and wet pond, respectively. Both treatments were effective, the former predominantly through the lowering of dissolved metal concentrations and the latter through the lowering of particulate metal concentrations. These results indicate that stormwater treatment can improve the quality of runoff discharged from PFCs, irrespective of their age, provided that treatment is targeted to the predominant contaminant phase present. PMID- 24175408 TI - Effects of surface area and inflow on the performance of stormwater best management practices with uncertainty analysis. AB - The performance of stormwater best management practices (BMPs) is affected by BMP geometric and hydrologic factors. The objective of this study was to investigate the effect of BMP surface area and inflow on BMP performance using the k-C* model with uncertainty analysis. Observed total suspended solids (TSS) from detention basins and retention ponds data sets in the International Stormwater BMP Database were used to build and evaluate the model. Detention basins are regarded as dry ponds because they do not always have water, whereas retention ponds have a permanent pool and are considered wet ponds. In this study, Latin hypercube sampling (LHS) was applied to consider uncertainty in both influent event mean concentration (EMC), C(in), and the areal removal constant, k. The latter was estimated from the hydraulic loading rate, q, through use of a power function relationship. Results show that effluent EMC, C(out), decreased as inflow decreased and as BMP surface area increased in both detention basins and retention ponds. However, the change in C(out), depending on inflow and BMP surface area for detention basins, differed from the change in C(out) for retention ponds. Specifically, C(in) was more dominantly associated with the performance of the k-C* model of detention basins than were BMP surface area and inflow. For retention ponds, however, results suggest that BMP surface area and inflow both influenced changes in C(out) as well as C(in). These results suggest that sensitive factors in the performance of the k-C* model are limited to C(in) for detention basins, whereas BMP surface area, inflow, and C(in) are important for retention ponds. PMID- 24175409 TI - Size fractionation of metals present in highway runoff: beyond the six commonly reported species. AB - Highway runoff is an important non-point source of pollutants, especially metals. This study reports monitoring results from 17 storm events at three highway sites for six commonly sampled metals: cadmium, chromium, copper, lead, nickel, and zinc. The study also reports the results of eight additional metals: aluminum, arsenic, cobalt, iron, manganese, selenium, strontium, and vanadium. Soluble phase, defined as passing a 0.45 microm filter, and particulate phase concentrations on four size fractions from 0.45 to larger than 100 microm are reported. The greatest metal masses were typically observed in the 8 to 20 microm fraction. The size distribution shows that sedimentation as a treatment process typically found in stormwater management can remove only 65% of the mass of most particulate phase metal species. Additional processes, such as coagulation or filtration, are needed to obtain greater removal rates. The results indicate the need to study particle size distribution (PSD) in order to better select treatment alternatives or assess environmental impacts. PMID- 24175410 TI - Performance of compost filtration practice for green infrastructure stormwater applications. AB - Urban storm water runoff poses a substantial threat of pollution to receiving surface waters. Green infrastructure, low impact development, green building ordinances, National Pollutant Discharge Elimination System (NPDES) storm water permit compliance, and Total Maximum Daily Load (TMDL) implementation strategies have become national priorities; however, designers need more sustainable, low cost solutions to meet these goals and guidelines. The objective of this study was to determine the multiple-event removal efficiency and capacity of compost filter socks (FS) and filter socks with natural sorbents (NS) to remove soluble phosphorus, ammonium-nitrogen, nitrate-nitrogen, E. coli, Enterococcus, and oil from urban storm water runoff. Treatments were exposed to simulated storm water pollutant concentrations consistent with urban runoff originating from impervious surfaces, such as parking lots and roadways. Treatments were exposed to a maximum of 25 runoff events, or when removal efficiencies were < or = 25%, whichever occurred first. Experiments were conducted in triplicate. The filter socks with natural sorbents removed significantly greater soluble phosphorus than the filter socks alone, removing a total of 237 mg/linear m over eight runoff events, or an average of 34%. The filter socks with natural sorbents removed 54% of ammonium nitrogen over 25 runoff events, or 533 mg/linear m, and only 11% of nitrate nitrogen, or 228 mg/linear m. The filter socks and filter socks with natural sorbents both removed 99% of oil over 25 runoff events, or a total load of 38,486 mg/linear m. Over 25 runoff events the filter socks with natural sorbents removed E. coli and Enteroccocus at 85% and 65%, or a total load of 3.14 CFUs x 10(8)/ linear m and 1.5 CFUs x 10(9)/linear m, respectively; both were significantly greater than treatment by filter socks alone. Based on these experiments, this technique can be used to reduce soluble pollutants from storm water over multiple runoff events. PMID- 24175411 TI - Accuracy of a stormwater monitoring program for urban landuses. AB - This study examined the accuracy of an urban stormwater monitoring program in estimating the annual discharge load (L(T)) and the annual reduction rate by a stormwater treatment device (R(T)) for total suspended solids. A calibrated stormwater management model was used to generate the entire stormwater runoff events in one year and was used to estimate L(T) and R(T) under different monitoring strategies having limited numbers of runoff events, including random, wet season, antecedent dry days (ADD)-based, monthly, and seasonally weighted. For random monitoring, 12 storms were required to estimate the values of L(T) and R(T) with mean relative errors of 13.98 and 0.24%, respectively. Monthly monitoring had slightly greater mean relative errors compared to random monitoring. Wet season and ADD-based monitoring under- or overestimated both L(T) and R(T). Monitoring with equal numbers of storms from the wet and dry seasons best estimated L(T) and R(T). PMID- 24175412 TI - Nitrate and phosphate removal through enhanced bioretention media: mesocosm study. AB - Bioretention is an evolving type of Green Stormwater Infrastructure (GSI) designed to attenuate peak flows, reduce stormwater volume, and treat stormwater. This article examines the capabilities of a bioretention soil mixture of sand and compost enhanced with aluminum-based drinking water treatment residuals to reduce nutrients from stormwater runoff. Columns with and without a saturation zone and vegetation were compared to examine their role in removing nitrate and ortho phosphate from stormwater. Results show that utilization of a saturation zone can significantly reduce nitrate in effluent water (71% compared to 33% without a saturated zone), even in a newly constructed system. However, ortho-phosphate reduction was significantly better in the columns without a saturated zone (80%) compared to columns with (67%). Plants did not significantly improve removal. This suggests amendments such as aluminum-based water treatment residuals for phosphorus removal and a saturation zone for nitrogen removal are needed during the initial establishment period. PMID- 24175413 TI - The importance of particle characterization in stormwater runoff. AB - Treatment units for stormwater management are being routinely required for new construction and upgrading of older facilities. This paper shows how particle size distribution affects the removal of sedimentation units and how erroneous results are often obtained if one uses simple overall removal efficiency or if the particle size distribution is not considered. Two full-scale devices are used for demonstration. A hydrodynamic device, which generally have low, overall suspended solids removal efficiency, is used for the first case, and it is shown that it actually removes large particles very well but has virtually no removal of small particles. The second case is for a dry detention basin. It is shown that the removal rates are generally in accord with sedimentation theory, removing larger and medium size particles well. Using particle size distribution in evaluating treatment unit performance is a more accurate and precise way of determining the actual performance. PMID- 24175414 TI - Downscale methodology for determining priority orders of the sewer rehabilitation. AB - Although inflow/infiltration (I/I) is one of the main factors used to decrease efficiency in sewer capacity and wastewater treatment, due to budget constraints, it is sampled only at the outlet point. Accordingly, the rehabilitation orders of defected sewers are determined for each drainage area without the consideration of I/I in each sewer. This study focuses on the development of a sampled I/I distribution (I2D) model and a decision-making model for sewer rehabilitation. The I2D model is developed based on the unit sewer defect value. The decision making model, developed using a genetic algorithm, is simulated with the consideration of sewer rehabilitation, wastewater treatment cost, and distributed I/I amount in each sewer on the budget. When the simulation results are compared with those of a numerical weighting method, it is concluded that the integrated model provides a detailed and systematic sewer rehabilitation plan from watershed scale drainage areas to field-scale drainage areas. PMID- 24175415 TI - Nitrogen and COD removal from domestic and synthetic wastewater in subsurface flow constructed wetlands. AB - Comparisons of the performance of constructed-wetland systems (CWs) for treating domestic wastewater in the laboratory and field may use pathogen-free synthetic wastewater to avoid regulatory health concerns. However, little to no data are available describing the relative treatment efficiencies of CWs to both actual and synthetic domestic wastewaters so as to enable such comparison. To fill this gap, treatment performances with respect to organics (chemical organic demand; COD) and nitrogen (ammonium and nitrate) removal from domestic (septic tank) and a similar-strength synthetic wastewater under planted and non-planted subsurface flow CWs are determined. One pair of CWs was planted with cattails in May 2008, whereas the adjacent system was non-planted. Collected septic tank or synthesized wastewater was allowed to gravity feed each CWs, and effluent samples were collected and tested for COD and nitrogen species regularly during four different periods over six months. Overall, statistically significant greater removal of COD (-12%) and nitrogen (-5%) occurred from the synthetic as compared with the domestic wastewater from the planted and non-planted CWs. Effluent BOD5/COD ratios from the synthetic wastewater CWs averaged nearly twice that from the domestic wastewater CWs (0.17 vs 0.10), reflecting greater concentrations of readily degraded compounds. That removal fractions were consistent across the mid range loading rates to the CWs suggests that the synthetic wastewater can be used in testing laboratory CWs with reasonable success in application of their results to the field. PMID- 24175416 TI - Of: Sorption media for stormwater treatment--a laboratory evaluation of five low cost media for their ability to remove metals and phosphorus from artificial stormwater, T. Wium-Andersen, A. H. Nielsen, T. Hvitved-Jacobsen, N. K. Kristensen, H. Brix, C. Arias, J. Vollertsen, 84, 605-616 (2012). PMID- 24175417 TI - Immunomodulatory and therapeutic potentials of herbal, traditional/indigenous and ethnoveterinary medicines. AB - Herbs/Botanical plants are considered as God's gift to human beings in the form of natural medicines, like the one well known "Sanjeevani booti" described in Hindu Mythology. The traditional and ethno-veterinary practices have been in use for centuries, transferring the knowledge from generation to generation and they are accessible, easy to prepare and administer, with little or no cost at all. Even though the modern developments in therapeutic field brought about a rapid decline in traditional medicine, the plant-based remedies are still having a crucial role as potential source of therapeutic aids in health systems all over the world for both humans and animals. Among the 21,000 medicinal plants listed by the World Health Organization (WHO), 2500 species are native to India, which stands first in the production of medicinal herbs. This innumerable treasure of medicinal herbs brings India the distinction of 'the botanical garden of the world'. Nowadays immune-based therapies are gaining more importance than monovalent approaches which are having limited benefits. Apart from the actions like treating diseases, control of ecto- and endo-parasites, fertility enhancement, bone setting and poor mothering management, an array of herbal medicines have been reported which are having immunomodulatory effects like modulation of cytokine secretion, histamine release, immunoglobulin secretion, class switching, cellular co-receptor expression, lymphocyte expression, phagocytosis and so on. The present article describes in brief few of these important ones viz., ashwagandha, amla, tulsi, arjuna, aloe vera, garlic, turmeric, ginger, shatavari, neem, guduchi, kiwifruit, tut, kamala, palashlata, kokilaksha etc. being used for human and animal health benefits. PMID- 24175418 TI - Enhancement of Chlorella vulgaris growth and bioremediation ability of aquarium wastewater using diazotrophs. AB - Treatment of aquarium wastewater represents an important process to clean and recycle wastewater to be safely returned to the environment, used for cultivation or to minimize the multiple renewal of water. Chlorella vulgaris was an important freshwater microalgae which used in wastewater treatment, and increasing its potential of treatment can be achieved with existence of N2-fixing bacteria. Co culturing of Chlorella vulgaris with the diazotrophs, Azospirillum brasilense or Azotobacter chroococcum in three different media; aquarium wastewater (AWW), sterile enriched natural aquarium wastewater (GPM) and synthetic wastewater media (SWW) were studied. Biomass yield of the microalgae was estimated by determination of chlorophylls (a and b), total carotenoid and the dry weight of C. vulgaris. Also determination of ammonia, nitrite, phosphate and nitrate in the culture were done. The presence of diazotrophs significantly increased the biomass of C. vulgaris by increasing its microalgae pigments (chlorophylls a and b, and total carotenoids). The highest pigments percentage was reported due to addition of A. brasilense to C. vulgaris (18.3-133.5%) compared to A. chroococcum (23.9-56.9%). As well as increased dry weight from 12 to 50%. There was also improved removal of nitrate, nitrite, ammonia and phosphate; where, the highest removal percentage was reported due to addition of A. chroococcum to C. vulgaris (0.0-52%) compared to A. brasilense (0.6-16.4%). A. brasilense and A. chroococcum can support C. vulgaris biomass production and bioremediation activity in the aquarium to minimize the periodical water renewal. PMID- 24175419 TI - Contrasting cpDNA variation in two Indonesian endemic lowland dipterocarp species and implications for their conservation. AB - Shorea javanica (Dipterocarpaceae) is an economically important dammar-producing tree, endemic to the tropical lowland forests of Sumatra and Java, Indonesia. However, its total population size is limited and this species is endangered. Shorea selanica is one of the very limited numbers of species in genus Shorea (Dipterocarpaceae) that grows in Wallacean. This species can be found only in the central part of the Moluccas, eastern Indonesia. Six populations (77 individuals in total) were sampled for S. javanica while three populations (27 individuals in total) were sampled for S. selanica. To determine genetic variation and population structure, three non-coding chloroplast DNA regions of trnL-trnF, psbC trnS, trnS-trnfM and two non-coding chloroplast DNA regions of trnT-trnL, trnL trnF were sequenced from S. javanica and S. selanica, respectively. There was no variation in the chloroplast DNA regions from S. javanica, except for one unique indel polymorphism. Nucleotide diversity within S. selanica populations ranged from 0 (Seram) to 0.00044 (Buru), with a pooled value of 0.00041. S. javanica was determined as having no population structure while high levels of genetic differentiation was found among populations of S. selanica (F(ST) = 0.702). Different pattern of population structure among the two species in this study suggested the need for distinct management and conservation strategies for each species. For S. javanica, connectivity within and among populations, including augmentation of population size across the species range, should be promoted. For S. selanica, an in situ conservation plan that defines core areas completely free from perturbation within each population is necessary. PMID- 24175420 TI - Interventional therapy in diabetic foot: risk factors, clinical events and prognosis at one year follow-up (a study of 103 cases). AB - Diabetic foot is a common complication in diabetes mellitus course, able to increase the overall morbidity/mortality risk of such a disease. The aim was to investigate the outcomes, the incidence of clinical events, the number of recurrent ulcers in patients with diabetic foot during 1 year follow-up after angioplasty (PTA) revascularization. From January 2007 to August 2009, 103 diabetic patients with diabetic foot undergoing revascularization of a lower limb by PTA were recruited. At 1 year follow-up we assessed: "major" (death, stroke, Myocardial Infaction (MI) and "minor" (Deep Vein Thrombosis (DVT), renal failure, restenosis) events incidence; recurrent ulcers incidence; the predictive elements of all these events. At 1 year follow-up, "major"/"minor" events incidence was 15% (deaths: 5, stroke: 1, MI: 9%) and 34% (renal failure: 11, DVT: 9, restenosis: 14%), respectively. Obesity, high low density level-cholesterol levels and distal arterial lesions (at posterior tibial artery in particular) were statistically significantly associated with major events (p < 0.05); only obesity resulted statistically associated with minors (p = 0.043). High levels of C-reactive protein had a statistically significant relationship with the recurrence of ulcers (p = 0.006) while distal arterial obstructions showed a trend toward significance. To improve diabetic foot mortality and morbidity rate, our study underlines the importance of a prompt diagnosis and appropriate revascularization treatment. Other studies are needed to ascertain these. PMID- 24175421 TI - Efficiency of plant growth promoting rhizobacteria isolated from sand dunes of Chennai coastal area. AB - Plant Growth Promoting Rhizobacteria (PGPR) are beneficial bacteria that colonize the plant root and enhance the plant growth. The use of PGPR is steadily increasing in agriculture and offers an attractive way to replace chemical fertilizers, pesticides and supplements. In the present study, PGPR were isolated from 18 different rhizosphere soil samples of coastal sand dune plants, belonging to the genus Ipomoea sp. collected from the Chennai coastal area. For isolation of bacteria from soil samples, pour plate technique was followed. The rhizobacterial population was ranged from 4.4 x 10(6)-7.5 x 10(7) CFU g(-1). From that, 46 morphologically different bacterial strains were isolated. Among 46, 18 strains exhibited the production of Indole Acetic Acid. (IAA). When screened for phosphate solubilzing activity, six strains showed maximum activity. All these selected six strains were screened for seed germination among which these two strains (AMET1136 and AMET 1148) showed remarkable increase in the seed germination of black gram and green gram. For plant growth promotion, three types of treatments namely, seed bacterization, soil drenching and mixed (seed+soil) were carried out to check the potential of these two strains. Among that one strain which was identified as Pseudomonas sp. AMET1148 showed remarkable and significant increase in shoot length and root length of the tested plants. The study concluded that PGPR from coastal sand dund plants can be developed as plant growth promoters in agricultural crops. PMID- 24175422 TI - A novel study on carpet-dye-induced dermatitis and other changes in Rattus norvegicus. AB - It is known that humidity enhances the growth of mites in carpets, mattresses and other household items. The association between exposure to house dust and diseases such as asthma, chronic rhinitis and atopic dermatitis has been shown in many individuals. Large quantities of carpet dyes are used in carpet industry located in Eastern Uttar Pradesh India. Nearly 90% of the carpets are manufactured in Eastern Uttar Pradesh and remaining 10% is produced in Kashmir and other places of India. Therefore, this area is important in huge dyeing and washing industry in which nearly 760 metric tons of dyes and dye supporting chemicals as well as washing chemicals are used per year. Present study has been conducted to see the adverse health effects of carpet dye black T supra which is being greatly used in carpet industry. In the present study, Gram mixed with 20 mg kg(-1) of b.wt. day(-1) sub-lethal dose of Black T Supra carpet dye was fed to Rattus norvegicus for three months and the symptoms of dermatitis in the form of hair fall in patches on surface of body started from fifth week onward. The area of patches of hair fall increased between 6-12th weeks. In controls, such effect was not observed. In addition, a little increase in body weight, cataract in eyes and desperate walking in experimental animals were observed after fifth week of feeding Black T Supra dye. In some cases, the correlation between exposure to carpet dye black T supra and symptoms is obvious. PMID- 24175423 TI - Isolation and characterization of plant growth promoting traits of a rhizobacteria: Pantoea agglomerans lma2. AB - The use of microbial technology in agriculture is expanding quickly with the identification of new bacterial strains which are more effective in promoting the growth of plants. The rhizobacteria that promote the growth of plants can have a positive effect on the productivity of crops especially when subjected to salt stress. A nitrogen-fixing bacterium was isolated from the wheat rhizosphere of an arid region. The strain was identified on the basis of tests API20E and 16S rRNA sequencing, as Pantoea agglomerans lma2. This strain degraded several carbon sources: sugars (fructose, ribose, dextrin, salicin...), lipids (lecithin, tributyrin and tween 80), proteins (gelatin, casein), grew on KCN and could grow from pH 4 to 8 and had an optimum at pH 7. The growth temperature showed a maximum at 30 degrees C and the bacteria could tolerate from 4 to 41 degrees C and the growth rate was higher when the NaCl concentration was between 100 and 300 mM. The performance of activities enhancing the growth of plants of P. agglomerans lma2 was significantly better in the presence of salt. Rates of Indole Acetic Acid (IAA), siderophores production and solubilization of phosphate increased between 100 and 400 mM NaCl compared to the control without salt. The maximum values were saved to 300 mM for the production of siderophores (18.32%) and solubilization of phosphate (1061.49 microg mL(-1)) and 100 mM for the production of IAA (161 microg mL(-1)). A significant correlation existed between these three activities. These results showed that P. agglomerans lma2 with its Plant Growth Promoting Rhizobacteria (PGPR) and halophilic properties could constitute a good fertilizer in arid and saline zone. PMID- 24175424 TI - Immunomodulation by Hibiscus rosa-sinensis: effect on the humoral and cellular immune response of Mus musculus. AB - In West India, the Hibiscus rosa-sinensis L. (Malvaceae) is traditionally used as tea as a natural diuretic. Extract of this plant contains Vitamin C and is used traditionally as a mild medicine. In spite of a long history of traditional medicinal value of H. rosa-sinensis still no data are available for immunomodulatory activity. In present investigation, aqueous extract of H. rosa sinensis (AEHrs) (500 mg kg(-1) BW) was intraperitoneally (IP) injected to the male Swiss albino mice (Mus musculus) to evaluate the immunomodulatory property of extract. In addition for evaluation of phytochemical constituents of flowers of H. rosa-sinensis HPTLC was performed. The crude extract of H. rosa-sinensis has immunomodulatory activity. After the 15 days treatment, the number of plaque forming cells increased by 0.6%, antibody titre was increased 38.15% and significant increase of 52% was observed in DTH response. At the same concentration of dose the level of serum IL-1alpha enhanced significantly (14.27%) whereas a considerable decrease (32.70%) in the concentration of IL-2 was observed among AEHrs treated mice in comparison to the control mice. HPTLC chromatogram revealed that H. rosa-sinensis posses alkaloid (Rf 0.93) and flavonoids (Rf 0.02, 0.06, 0.14) on the basis of Rf values. Results of investigation supports for the immunomodulatory activity of H. rosa-sinensis aqueous extract. PMID- 24175425 TI - Gastrointestinal helminths are highly prevalent in scavenging chickens of selected districts of Eastern Shewa zone, Ethiopia. AB - A cross-sectional survey on gastrointestinal helminths was conducted on 124 chickens raised under traditional management system in two selected districts namely Ada'a and Adamitulu of Eastern Shewa zone, Ethiopia. Of these chickens, 111 (89.5%) were found to harbor one of the five different helminth parasites and 13 (10.48%) were free of helminths parasites. The study also found that 103 (83.0%) and 72 (58.0%) of the examined chickens were invariably infected by diverse species of cestodes and nematodes species, respectively. There was a statistically significant difference (p < 0.05) in the prevalence between cestodes and nematodes of helminths parasites within the same district. The major cestode species recovered form chickens were Raillietina echinobothrida 79 (63.7%), Raillietina tetragona 70 (56.5%), Raillietina cesticillus 50 (40.3%) and Choanotaenia infundibulum 17 (13.7%), Davainea proglottina 10 (8.1%), Hymenolepis contaniana 22 (17.7%) and Hymenolepis carioca 7 (17.7%). The major nematode species encountered were Heterakis gallinarum 47 (37.9%), Ascaridia galli 40 (32.0%), Gongylonema ingluvicola 32 (25.8%), Dispharynx nasuta 5 (4.0%), Heterakis isolonche 11 (8.9%), Allodapa suctoria 9 (7.3%), Capillaria anatis 4 (3.2%) and Heterakis dispar 8 (6.5%). The study also tried to see the prevalence of these parasites in relation with age and sex however, it has no significant difference (p > 0.05) with those risk factors. On the other hand district significantly affect the prevalence of some parasites (p < 0.05). This study strongly suggested that helminthosis is a very serious problem of backyard chickens in eastern Shewa zone of Oromia and appropriate control strategies need to be devised. PMID- 24175426 TI - Preparation and evaluation of gastroretentive floating pellets of metronidazole using Na-alginate and hydroxyl propyl methyl cellulose polymers. AB - Gastroretentive floating pellets of metronidazole were formulated to prolong the gastric residence time in order to obtain controlled release characteristics of the drug. Nine formulations of metronidazole floating pellets such as AX, BX, CX, AY, BY, CY, AZ, BZ and CZ were prepared by extrusion method using different quantities of hydroxyl propyl methyl cellulose (HPMC) polymers such as methocel K4M premium and methocel K100LV premium in the ratio of 2:1, 1:2 and 1.5:1.5 while the amount of Na-alginate used in the formulations was 3.50, 5.25 and 7.0 g, respectively. The in vitro dissolution studies were carried out in 900 mL of phosphate buffer (pH 1.2) at 37 +/- 0.5 degrees C and 50 rpm for 6 h using USP XXIV paddle method and the content of drug release was done by UV spectrophotometer at 277 nm. It was found that the percent release of metronidazole from different formulations was different with passing of time. The drug release profile of the formulation (AX) having Na-alginate 3.50 g methocel K4M premium and methocel K100LV premium in the ratio of 2:1 showed best fit to Higuchi release kinetics with R2 value of 0.994. Finally, it might be concluded that the polymers had significant effect on drug release kinetics of metronidazole from floating pellets. The selection and use of suitable polymers in appropriate ratio might be very important in designing floating pellets and using the capabilities of these polymers, suitable floating pellets of metronidazole with desirable release rate could be formulated. Thus, in vivo research studies by the future researchers will confirm the appropriateness of these formulated metronidazole floating pellets. PMID- 24175427 TI - Neuroendocrine control of water content and calcium concentration in the crab Ocypode macrocera (H. Milne-Edwards 1852) (Brachyura, Ocypodae). AB - The present study is focused to see the effect of crustacean neuroendocrine organs on the water and calcium metabolism which is very much important for the osmoregulatory functions. Since the experiments were carried out to investigate the control of water contents and calcium concentration in the crab, Ocypode macrocera. The animals were collected from the shore of the Bay of the Bengal near Annan Koil one among the biggest landing centers of south east coast of Tamil Nadu, India. The data revealed that water content in the hepatopancreas and thoracic muscle of the control crab were 70.16 and 79.86%, respectively, whereas in the experimental ones, the values were 80.32 and 87.44% after eyestalk removal and 54.52 and 66.98% after eyestalk extract injection. Calcium concentration in both the hepatopancreas and thoracic muscle of the control crab were 2.16 and 2.14 mg g(-1), respectively, whereas in the experimental animals the values were 2.76 and 3.52 mg g(-1) in the eyestalkless crabs and 1.52 and 1.57 mg g(-1) after eyestalk extract injection, respectively. Hence it was observed the % of water content is more in eyestalk less crabs as compared to that of control and injected. The roles of neurosecretory secretions, which control these parameters, were discussed. The ability for Ocypode macrocera to adapt rapidly and maintain homeostasis in a wide range of abnormality supports the fact that Ocypode macrocera are a suitable species for land-based aquaculture in ponds as well as critical condition where rapid fluctuation in salinity can occur. PMID- 24175428 TI - Sub-chronic concomitant ingestion of L-arginine and monosodium glutamate improves feed efficiency, lipid metabolism and antioxidant capacity in male Wistar rats. AB - The use of L-arginine (ARG) is common in supplements, whereas, Monosodium Glutamate (MSG) is widely used as flavor enhancing food additive. Thus, ARG and MSG may be present together in human diets, warranting this study aimed at investigating the effect of concomitant ingestion of ARG and MSG on some biochemical indices in male rats. Twelve male albino rats were grouped into three (n = 4) and concomitantly exposed to 0:0, 20:5 and 60:15 mg kg(-1) of ARG:MSG. Exposure was peroral and every twenty four h for 28 days. ARG plus MSG treatment caused a significant (p < or = 0.05) increase in Feed Efficiency (FE) (Low dose: 5.23 +/- 22%; High dose: 5.60 +/- 11%), whereas, it decreased (p < or = 0.05) the serum Total Cholesterol (T-Chol) (low dose: 80.83 +/- 0.11 mg/100 mL, high dose: 92.55 +/- 0.14 mg/100 mL), triacylglycerol (TAG) (low dose: 179.91 +/- 0.09 mg/100 mL, high dose: 119.77 +/- 0.32 mg/100 mL) and malondialdehyde (MDA) (low dose: 5.00 +/- 0.07 mg/100 mL, high dose: 24.36 +/- 0.10 mg/100 mL) concentrations of the rats in a dose dependent manner. However, (at the high dose) the increase in Body Weight (BW) (0.08 +/- 0.07 kg), Feed Intake (FI) (0.40 +/- 0.03 kg) and Water Intake (WI) (0.65 +/- 0.18 L) induced by ARG plus MSG exposure was not significant (p < or = 0.05), suggesting non treatment related effect on these routine parameters. However, exposure to ARG plus MSG may significantly improve feed efficiency, lipid metabolism and antioxidant capacity in the male rats. PMID- 24175429 TI - Scorpion anti-venom activity of botanicals: a pharmacological approach. AB - Scorpion bite is considered as one of the common and dangerous phenomenon throughout the world. The clinical manifestations include pulmonary edema, myocardial damage, intracerebral haemorrhage, brachial plexopathy, renal failure etc. which sometimes leads to mortality. The common antivenin therapy includes anti-scorpion venom serum or prazosin. In the vast rural areas of the third world countries phytotherapy is considered as an alternative system of medicine and scorpion sting is treated with the help of medicinal botanicals. As the safety and efficacy are considered as important aspects of anti venin therapy, conventional treatment can be supported by the herbal remedy. The present review compiles a number of medicinal plants pharmacologically evaluated in vitro and/or in vivo for scorpion antivenin properties. Considering the aspects like cost effectiveness, availability, lesser side effects and development of drug resistance, plant based anti venin therapy may be considered as a possible remedy against scorpion envenomation. PMID- 24175430 TI - Multiple rare opportunistic and pathogenic fungi in persistent foot skin infection. AB - Persistent superficial skin infection caused by multiple fungi is rarely reported. Recently, a number of fungi, both opportunistic and persistent in nature were isolated from the foot skin of a 24-year old male in Malaysia. The fungi were identified as Candida parapsilosis, Rhodotorula mucilaginosa, Phoma spp., Debaryomyces hansenii, Acremonium spp., Aureobasidium pullulans and Aspergillus spp., This is the first report on these opportunistic strains were co isolated from a healthy individual who suffered from persistent foot skin infection which was diagnosed as athlete's foot for more than 12 years. Among the isolated fungi, C. parapsilosis has been an increasingly common cause of skin infections. R. mucilaginosa and D. hansenii were rarely reported in cases of skin infection. A. pullulans, an emerging fungal pathogen was also being isolated in this case. Interestingly, it was noted that C. parapsilosis, R. mucilaginosa, D. hansenii and A. pullulans are among the common halophiles and this suggests the association of halotolerant fungi in causing persistent superficial skin infection. This discovery will shed light on future research to explore on effective treatment for inhibition of pathogenic halophiles as well as to understand the interaction of multiple fungi in the progress of skin infection. PMID- 24175431 TI - Recovery and purification of rapamycin from the culture broth of Mtcc 5681. AB - In this study of the recovery and purification of rapamycin from the culture broth of an actinomycetes strain MTCC 5681, we investigated various factors such as biomass separation, suitable solvents for extraction, normal phase and flash chromatographic conditions and selective precipitation to obtain rapamycin in substantially pure form of the product. Adsorption chromatography particularly with normal phase and flash chromatography, in combination with centrifugal decantation is found to be the most suitable for separation as well as purification of rapamycin. Centrifugal decantation technique is likely to emerge as an efficient, industrially scalable, high yielding and economical process for biomass separation. The purity of rapamycin obtained through the method described was 99.4% which has not been reported so far. PMID- 24175432 TI - Effects of plant growth substances on rooting of Hedychium spicatum under different temperature regimes. AB - Present study was carried out to develop a simple and efficient vegetative propagation protocol by applying various treatments to rhizome cuttings with different test solutions of auxins and phenolic compound. These were alpha naphthalene acetic acid (NAA), Indole-3-butyric acid (IBA), Indole Acetic Acid (IAA), phloroglucinol and coumarin. The concentrations for each treatment were 10.0, 50.0 and 100.0 microM. After treatments the rhizome cuttings were planted in polybags containing forest soil and kept under different temperature regimes i.e., inside polyhose (at 20-25 degrees C), inside mist chamber (at 15-20 degrees C) and under nethouse (nursery condition, at 14-18 degrees C). The maximum rooting percentage (74.06%) was achieved at 20-25 degrees C (inside polyhouse) by applying 50.0 microM IBA. Inside poly house condition, the various developmental parameters showed better responses compare to other conditions. On the basis of present study emphasizes that the temperature play a crucial role in rooting and further growth of the plants in this species. By using this simple and significant conventional method of propagation we could be propagate this vulnerable medicinal and aromatic species at large scale for commercial purpose. PMID- 24175433 TI - Insect predators and control of Aphis gossypii comparing to certain insecticides under caged-cotton plants conditions. AB - Numerous beneficial arthropods prey on aphid populations in cotton fields. Field experiments were conducted at Kafr El-Sheikh Governorate, Egypt in seasons of 2010 and 2011 to examine the impact of naturally occurring insect predators on cotton aphid, Aphis gossypii Glover (Homoptera: Aphididae) comparing to the impact of three insecticides; i.e., diafenthiuron, imidacloprid and thiamethoxam at their recommended rates using caged-plants technique. The toxicity of these insecticides to insect predators was determined likewise. Cotton aphid population on uncaged plants, where insect predators and aphids were allowed to develop undisturbed, declined gradually and consequently showed the lowest population density of aphids per cotton leaf at the last inspection. On the contrary, severe decrease in cotton aphid numbers occurred on caged plants that treated with insecticides and this decrease continued up to 15 days after spray, then increases in aphid numbers happened and significantly indicated the highest aphid population density at the last inspection. Density of aphid populations increased rapidly on caged-untreated plants, where insect predators were excluded and no insecticides were applied and declined only after exceeding the carrying capacity of cotton plants. Diafenthiuron was the most toxic to the insect predators. Imidacloprid and thiamethoxam significantly proved to be the least toxic to insect predators. Further studies are needed to establish the integration effect between selective insecticides and beneficial arthropods to control cotton aphids and other pests. PMID- 24175434 TI - An investigation of management effects on range functionality (case study: Karkaboud and Kouin, Taleghan). AB - Ecosystem function is affected by management activities in rangeland ecosystems. Hence, it is necessary to consider management effects on rangeland ecosystem to reduce its degradation. In order to determine the effects of management activities on rangeland ecosystem, four management treatments were chosen in Taleghan, Iran. Functionality characteristics including: stability, infiltration and nutrient cycling were calculated using Landscape Function Analysis (LFA). LFA calculates these parameters using 11 soil surface indicators. Results showed that stability, infiltration and nutrient cycle were higher in Karkaboud than the other locations because of low grazing pressure and non-accessibility conditions. As grazing pressure increased we witnessed less stability, infiltration and nutrient cycling in Karkaboud cascade, Kouin and Kouin-Marjan. Main causes of decline in stability, infiltration and nutrient cycling are perennial vegetation removal, soil trampling and decrease in soil organic matter and subsequent increase in erosion and soil instability. PMID- 24175435 TI - Topological organization and functional aspects of the olfactory epithelium of whipfin silver biddy Gerres filamentosus (Cuvier 1829). AB - The structural organization of different cells lining the olfactory epithelium of Gerres filamentosus (Cuvier 1829) were studied by light and scanning electron microscopy respectively to correlate their role in olfaction. The fan shaped olfactory rosette of G. filamentosus was more or less oval in outline and composed of 13 lamellae of different sizes in both sides. The olfactory epithelium was partitioned into sensory and non-sensory regions. The sensory epithelium was restricted on the flat apical end of the lamellae and embossed with two types of receptor cells bearing either cilia or microvilli. The non sensory epithelium, covering the middle and basal region of lamellae was comprised of stratified epithelial cells and mucous cells. The orientation of various cells in the surface contour of olfactory epithelium was discussed in light of their functional significance. PMID- 24175436 TI - Alarm fatigue: a growing problem. PMID- 24175437 TI - Take action: celebrate nephrology nursing. PMID- 24175438 TI - Fatal vascular access hemorrhage: reducing the odds. AB - Vascular access hemorrhage is not a frequently occurring complication associated with hemodialysis fistulas and grafts, but when it occurs, it can be fatal to patients and devastating to patients' families and dialysis unit staff members. The End Stage Renal Disease Notification of Death CMS-2746 forms indicated that between the years 2000 and 2006 (the most recent national data available), there were 1654 fatal vascular access hemorrhages. Specific issues that place patients at high risk for access rupture have been identified, and some are directly related to access physical assessment and cannulation. Recognizing at-risk accesses during physical assessment and improving site selection for needle placement can modify some risk factors for fatal vascular access hemorrhage and improve patient outcomes. PMID- 24175439 TI - Vitamin D deficiency in the sunshine state. AB - Vitamin D is well known for its skeletal and extraskeletal benefits. Chronic kidney disease (CKD), even in the early stages, may predispose patients to vitamin D deficiency, which may result in deleterious effects. Understanding the prevalence of vitamin D deficiency in the CKD population living in southern areas of the United States may help in early identification and implementation of preventative strategies. PMID- 24175440 TI - A self-care educational intervention to improve knowledge of dietary phosphorus control in patients requiring hemodialysis: a pilot study. AB - The purpose of this pilot study was to improve knowledge of dietary phosphorus control in patients requiring hemodialysis. The evidence-based literature suggests that nonadherence to phosphorous control in diets is a major health concern for patients who require hemodialysis because they have limited kidney function. Phosphorus tends to accumulate rather than be excreted. A self-care educational intervention was used in a pilot study (N = 10) to increase patients' knowledge about low phosphorous diets to promote dietary adherence. The outcome of this study was evaluated by a pre-test/post-test of patients' knowledge about phosphorus in the diet. A positive gain in knowledge was realized related to the intervention. PMID- 24175441 TI - Hemodialysis stressors and coping strategies among Jordanian patients on hemodialysis: a qualitative study. AB - The aim of this study was to examine the lived experiences of Jordanian patients with chronic kidney disease who received hemodialysis. Qualitative interviews were conducted to identify patients' lived experiences. Transcripts analyzed led to seven common themes: lifestyle change, time wasted, symptom-related suffering, marital and family role disruption, religious commitment disruption, motivators to alleviate stressors, and experience of healthcare providers' support. Findings revealed areas where nurses and other healthcare providers can improve care for this patient population and for patients with other chronic illnesses. PMID- 24175443 TI - Dialysis disequilibrium syndrome: rapid recognition and rapid intervention decrease the risk of mortality--a case study. AB - Dialysis disequilibrium syndrome is a potentially fatal complication of hemodialysis that is often undetected and under-reported. Early recognition and intervention are essential to prevent the potential deadly effects of this disorder and improve outcomes for patients with end stage renal disease (ESRD) on hemodialysis. Using a case study, this article discusses the pathophysiology, clinical manifestations, prevention, and management of dialysis disequilibrium syndrome. PMID- 24175442 TI - Survival in the Australian chronic kidney disease population: potential effects of the CHOIR and CREATE studies. AB - The CHOIR and CREATE studies led to changes in hemoglobin targets around the world for patients with chronic kidney disease. The aim of this study was to determine what effect these pivotal studies had on hemoglobin levels and survival Data were extracted from Australia's Renal Anaemia Database for patients with chronic kidney disease between October 2000 and December 2009. Survival was significantly longer in patients with chronic kidney disease who died between 2007 and 2009 compared to those who died between 2000 and 2006. PMID- 24175444 TI - Choice of GFR estimating equation influences dialysis initiation and mortality. AB - At least 12 observational studies of large databases since 2002 (greater than 1.2 million patients) have reported a survival disadvantage with higher estimated glomerular filtration rate (eGFR) or renal clearance at the time of dialysis initiation. This study found the association between mortality and early dialysis initiation is affected by which equation is used to estimate glomerular filtration rate. The mortality risk was related to time of dialysis initiation, which is influenced by the GFR estimating equation. Specifically, results suggest that use of the 4-variable Modification of Diet in Renal Disease (MDRD) eGFR equation in patients with end stage renal disease may provide an inaccurate estimation of eGFR relative to the 6-variable MDRD equation. The increased risk for mortality from "early" dialysis initiation reported in some recent observational studies may be the result of misclassifying sicker, sarcopenic patients as early starts when the 4-variable MDRD equation is used. PMID- 24175445 TI - We are better together: nurses' ability to affect change. AB - The Institute of Medicine has challenged nurses in recent years to practice to the fullest extent of their training and education. This article demonstrates application of this concept by use of example. It describes the processes that a group of nephrology nurses without graduate education who work in direct patient care followed to decrease the rate of transfusion reactions in clients undergoing apheresis receiving fresh frozen plasma fluid replacement. PMID- 24175446 TI - Menstrual cycle modulation of the late positive potential evoked by emotional faces. AB - The objective of the present study was to elucidate the time course and neural basis of facial expression recognition as modulated by the menstrual cycle in women. Event-related potentials (ERPs) associated with recognition of different emotional faces were assessed in 29 healthy women during the premenstrual, post menstrual, and periovulation phases of the menstrual cycle. Accuracy in recognizing different facial expressions was not affected by the menstrual cycle phase. ERP data indicated that only the late positive potential (LPP) was affected by the menstrual cycle phase for all facial expressions: during the periovulation phase, the amplitude of the LPP (750 to 1,000 msec. post-stimulus) was larger than that during the premenstrual phase. A positive correlation between the amplitude of the LPP and facial expression recognition performance was observed only during the periovulation phase. The present study provides electrophysiological evidence that the LPP evoked by emotional faces is modulated by the menstrual cycle, which may be correlated with fluctuations of ovarian hormones. PMID- 24175447 TI - Autobiographical remembering and individual differences in emotional intelligence. AB - The relationship between individual differences in Emotional Intelligence (EI) and self-reported arousal from remembering an autobiographical emotional or neutral event was examined. Participants (N = 235; 75 men; M age = 18.7 yr., SD = 0.9, range = 18-22) were required to complete the Japanese version of the Emotional Skills and Competence Questionnaire to assess EI. Participants were then asked to recall personal episodes from autobiographical memory, and then completed the Memory Characteristics Questionnaire (MCQ). A group with high EI rated, emotionally neutral episodes higher than did a group with low EI on several MCQ subscales: sound, participants, overall memory, and doubt/certainty. However, differences in ratings between the two groups were not observed for emotionally positive episodes. These results suggest that high EI is related to more effective use of weak retrieval cues when recalling neutral autobiographical memories. PMID- 24175448 TI - More to explore in music reading as a cross-modal process: a comment on Lee and Lei (2012). AB - Lee and Lei (2012) used a pitch task and a duration task in different blocks of trials and measured event-related potentials in 12 musicians and 24 non-musicians as they read musical scores. The authors claimed to disentangle pitch and duration processing. From the perspectives of cognitive neuropsychology there is great interest in studying the processes involved in reading musical scores. However, we argue that the design used by Lee and Lei (2012) does not allow disentangling pitch and duration processing because both are expressed within the musical score. Moreover, we emphasize the importance of longitudinal studies over cross-sectional studies to pinpoint the specific influence of musical expertise on score reading. PMID- 24175449 TI - Learning effects of self-controlled practice scheduling for children and adults: are the advantages different? AB - The benefit of providing learners control over their repetition schedule during multi-task learning has been limited to adult samples. Recently, differences in self-controlled strategies, such as frequent requests for knowledge of results by children (10 years) compared to adults have been reported. The purpose of the present experiment was to assess the benefits of a self-controlled repetition schedule during multi-task learning for children compared to adults. Twenty-four children (M age = 11.7 yr., SD = 2.0) and 24 adults (M age = 22.0 yr., SD = 2.2) completed 36 acquisition (12 per sequence) and 12 retention trials (4 per sequence) over two days for a key-pressing task. Half the adults (n = 12) and half the children (n = 12) chose the order in which to practice the three sequences during acquisition. The remaining participants practiced under the repetition schedule of a self-controlled counterpart. The dependent variables were the total time to complete the trial and the success of the motor trial (successful or unsuccessful). No differences were observed in the total number of times participants switched from one sequence to another in acquisition for the children and adults in the self-controlled condition. In retention, the proportion of error trials did not differ between the children and adults. The main effect for self-controlled vs yoked conditions indicated superior learning for the self-controlled conditions independent of age. PMID- 24175450 TI - Effect of practice distribution and experience on the performance and retention of a discrete sport skill. AB - This study examined how practice distribution influenced performance and learning of a discrete sport skill, the Australian Football (AF) handball pass. A secondary aim was to assess whether previous experience playing competitive Australian Football influenced learning. Participants performed the handball 50 times (5 blocks x 10 repetitions) using either a massed (1 sec. between repetitions or distributed (30 sec. between repetitions) practice schedule. Testing consisted of pre-test, acquisition, immediate retention (10 min.), and delayed retention (2 weeks) sessions. Performance accuracy scores improved in the massed practice condition from pre-test to immediate retention and from pre-test to delayed retention. Likewise, performance improved in the distributed practice group from pretest to immediate retention, but scores were not different from pre test to delayed retention, and decreased from immediate retention to delayed retention. While students with previous AF experience performed better overall, there were no differences between the massed and distributed groups based on experience. Results suggested that, regardless of previous related skill, massed practice of a discrete sport skill may lead to better retention of learning over a two-week period. PMID- 24175451 TI - The Manchester Colour Wheel: enhancing its utility. AB - The Manchester Colour Wheel was developed to investigate the role of colour in the perception of illness in gastroenterology. During validation it was found that positive, neutral, or negative connotations of the shade of a colour were more important than the colour itself. However, when asked to relate mood to a colour, the response rate was greater in individuals with mood disorders than healthy controls. This study assessed whether response rate could be made more uniform by changing the wording of the question. Mood/colour choice was compared, using two slightly different questions, in 105 and 203 healthy volunteers, resulting in response rates of 39% and 95% respectively, with the latter not associated with increased false positive responses. These results show that adjustment of the wording of a mood-related question may allow equal response rates irrespective of the mood status of participants. PMID- 24175452 TI - Validation of the OMNI Scale of Thermal Sensations. AB - Concurrent and construct validation of the OMNI Scale of Thermal Sensations was examined in a sample of 16 adult men and 5 adult women. Concurrent validity was established by regressing OMNI ratings of thermal sensation against core and skin temperatures obtained during treadmill walking while wearing firefighter thermal protective clothing in temperatures between 33 and 35 degrees C. Construct validity was established by regressing the OMNI scale against a construct specific visual analogue scale. OMNI scale responses accounted for statistically significant variance in both skin temperature and core temperature (48% and 51%, respectively) and visual analogue scale responses (84%). Concurrent and construct validity were established for the OMNI Scale of Thermal Sensations in healthy adults performing treadmill walking while wearing fire fighter thermal protective clothing. PMID- 24175453 TI - Effects of light, rotation, and texture on errors in the estimated length of a three-dimensional object in a two-dimensional display. AB - This study investigated the effects of light type (spot, directional, and point), forward-rotated stimulus angle (20 degrees, 45 degrees, and 70 degrees), and surface texture (wood, metal, transparent glass, dark brown leather, and translucent plastic) on errors in the estimated vertical diameter of a three dimensional object. Twenty female and 12 male Taiwanese college students, ages 18 22 years, participated in the current study. Participants were asked to judge the vertical diameter of an elliptical hole within a square plate that was displayed on an LCD monitor. Analysis indicated that the errors in estimated vertical diameter for rotated angles of 20 degrees and 45 degrees were greater than were those for 70 degrees. Additionally, the error of estimated vertical diameter for a rotated angle of 45 degrees was less than was that for 20 degrees. The surface texture also affected errors in estimated vertical diameter: transparent glass was associated with more errors than were wood and metal textures. However, light type had no effect on errors in estimated vertical diameter. These results have implications for the graphics-based design of interfaces. PMID- 24175454 TI - Simplest chronoscope. III. Further comparisons between reaction times obtained by meterstick versus machine. AB - The three classical Donders' reaction time (RT) tasks (simple, choice, and discriminative RTs) were employed to compare reaction time scores from college students obtained by use of Montare's simplest chronoscope (meterstick) methodology to scores obtained by use of a digital-readout multi-choice reaction timer (machine). Five hypotheses were tested. Simple RT, choice RT, and discriminative RT were faster when obtained by meterstick than by machine. The meterstick method showed higher reliability than the machine method and was less variable. The meterstick method of the simplest chronoscope may help to alleviate the longstanding problems of low reliability and high variability of reaction time performances; while at the same time producing faster performance on Donders' simple, choice and discriminative RT tasks than the machine method. PMID- 24175455 TI - Permeability theory and Palace Athena. AB - Permeability theory suggests that safety in environments depends on how far and how easily one can perceive or move through environments. Parts of environments that limit perception or retard locomotion elicit impressions of being enclosed, so properties of environments that influence perceived enclosure are important in permeability theory. One prediction of permeability theory is that the more permeable the boundary, the less enclosed the region within that boundary will seem to be. Another prediction is that boundary depth will have little influence on perceived enclosure. These predictions were tested in the venue of Greek temples. 30 participants were tested (14 men, 16 women; M age = 40 yr.), who rated perceived enclosure for 18 stimuli. The stimuli were constructed using a virtual scene from the Tholos in Delphi with the positions of the columns forming the boundaries. The boundaries were designed to have different levels of permeability and depth. Data were analyzed in terms of effect sizes and focused comparisons. Results indicated that perceived enclosure was most strongly influenced by the visual permeability of the boundary, while depth of boundary had a much smaller effect on perceived enclosure. PMID- 24175456 TI - A revision of the Academic Locus of Control Scale for College Students. AB - This study presents a revision of Trice's (1985) Academic Locus of Control Scale for College Students. A principal component analysis involving 322 college students produced four factors including 21 of the original 28 items. Inspection of the seven items not included in the four-factor solution suggested that they could be eliminated on both content and technical grounds. The resulting revised scale was similar to the original scale with respect to its relations with GPA, attendance, and measures of Academic Entitlement, procrastination, depression, and anxiety. PMID- 24175457 TI - Attachment pattern and cognitive skills: an exploratory study in an Italian non clinical sample. AB - Bowlby (1973) stated that the attachment relationship between a child and parents might help the child learn many skills important for survival, with a lifelong effect. However, there is a scarcity of research into attachment and intelligence in adulthood. This study examines the relationship between attachment status and cognitive skills in an Italian non-clinical sample of 101 young adults (M age = 22.6 yr.; SD = 1.8). The Adult Attachment Projective Picture Stimuli and the Wechsler Adult Intelligence Scale-Revised were administered to participants and four-way attachment classifications were analyzed regarding participants' IQ. Statistically significant differences were found for Full Scale IQ and Verbal IQ, with Dismissing participants scoring higher than Unresolved participants. Similar results were obtained for two-way attachment patterns with Resolved participants scoring higher than Unresolved. Implications regarding different attachment patterns and the concept of trauma are discussed. PMID- 24175458 TI - Document analysis of sports literature for individuals with disabilities. AB - A document analysis was conducted on published articles (data-based and review) relative to sports for individuals with disabilities. Data were directly compared to those published from a 10-year (1986 to 1996) document analysis by Reid and Prupas (1998). The current analysis consisted of the recent 10-year time period (2001 to 2011). Retrieved articles were assigned into one of eight categories. Reliability checks resulted in 90% for inter-rater and 93% for intra-rater agreement. The period 2001 to 2011 resulted in the greatest number of data-based articles published while the period 1986 to 1996 resulted in the greatest number of review articles published. Similarities and differences were discussed relative to the timeframes used as well as the method used to retrieve publications. Results were provided information for future research and writing in the area of sport for individuals with disabilities. PMID- 24175459 TI - Age-related changes of grip force control in physically active adults. AB - The age-related changes for controlling grip force in adults who practice regular and supervised physical activity have not been investigated. Fifty-five physically active adults ages 50 years and older and a group of 20 young adults (18-30 years old) performed a task of grasping and lifting an object. The grip force and the object's acceleration were recorded and used to calculate the parameters of grip force control. The levels of daily physical activities were also examined in all age groups. There were no differences in grip force control between the age groups. Conversely, the group over 76 years old used stronger grip force and increased latency (the time from grip force application to the time the object is lifted off the table) to manipulate the object. The results of this study suggest that middle-aged and older adults who exercise regularly can reduce or delay the possible grip force control deficits associated with aging. PMID- 24175460 TI - Effect of specific versus variable practice upon overhead throwing speed in children. AB - This study compared the effect of practice throwing with specific weights (specificity principle) or with variable weights (variability of practice) for a short practice period in children. Primary school children (N = 41; M age = 7.7 yr., SD = 0.5) were randomly divided into three homogenous groups. The first two groups used specific overhead throwing practice: throws with a soccer ball or 1 kg balls, while the third group used variable practice with 0.35, 0.45, 0.5, and 1 kg balls. All groups trained twice per week for six weeks. The same workload per session between the three groups varied from 24 throws (1 kg practice group) to 43 throws (soccer ball practice group). Throwing speed and distance with different balls was measured before and after the practice period. Statistically significant increases in performance in all three practice groups were found with no significant differences between groups. The results indicate that both specific and variable practice of throwing in children lead to increases in performance. However, it seems that the increased workload (practice) is a more important factor than the type of practice (specific or variable) in enhancing performance in children. PMID- 24175461 TI - Effect of interactions between a child and a robot on the imitation and praxis performance of typically devloping children and a child with autism: a preliminary study. AB - Interactions between a robot and a child (robot-child interactions) provide a unique context to engage children in whole body movements through a reciprocal imitation game. The effects of a novel, 8-session, robot-child interaction protocol on the imitation and praxis skills of 15 typically developing children and one child with autism between 4 and 7 years of age were examined. A quasi experimental observational comparison of pretest and posttest performance was conducted. A task-specific robot imitation test and a standardized praxis measure were coded for changes in imitation and praxis errors at pretest and posttest. All children showed improvements in task-specific imitation and generalized praxis. Interpretation is limited by the lack of a control group. These findings serve as a foundation for further investigation of robot-child interactions as a potential training tool for children with dyspraxia. PMID- 24175462 TI - Mental toughness of mixed martial arts athletes at different levels of competition. AB - This study investigated whether mental toughness distinguishes mixed martial arts (MMA) athletes competing at different levels. It was theorized that higher mental toughness would separate those competing at the professional level compared to lower levels. Male MMA competitors (N = 136, M age = 27.1 yr., SD = 4.8) were categorized as amateur, semi-professional, or professional and assessed by questionnaire using the Psychological Performance Inventory-A and the Sports Mental Toughness Questionnaire. There were statistically significant differences between the three groups on mental toughness. The professional group had higher scores compared to semi-professional and amateur groups with regard to confidence, positive cognition, and determination. The findings supported previous work that athletes performing at higher levels have superior mental toughness. PMID- 24175463 TI - Proactive and reactive effects of vigorous exercise on learning and vocabulary comprehension. AB - College students (N = 90) were randomly assigned to participate in vigorous, moderate or no physical exercise and vocabulary recall and comprehension learning activities under varying conditions to assess whether or not increased intensities of exercise, performed either before a vocabulary recall and comprehension learning activity (i.e., proactive effect) or after a vocabulary recall and comprehension learning activity (i.e., reactive effect), would improve vocabulary recall and comprehension. The results demonstrated that performing exercise at a vigorous intensity before or after rehearsing for a vocabulary comprehension test improved test results. PMID- 24175464 TI - Computerized measures of finger tapping: effects of hand dominance, age, and sex. AB - Computerized measures of digit tapping rate were obtained over 3 successive, 10 sec. periods in the right and left index fingers, from a community sample of 1,519 participants (ages 18 to 65 years; 607 men, 912 women). Differences between the dominant and non-dominant hands were found for tapping rate, movement initiation, and button down times, and the decline in tapping rate over the successive, 10-sec. periods. Declines were found in tapping rate in older participants in association with increased intertap variability. Men had higher tapping rates than women in all age ranges. The computerized finger tapping test is an efficient and precise measure of tapping speed and kinetics of potential utility in research and clinical studies of motor performance. PMID- 24175465 TI - Environmental context affects outcome and kinematic changes at different rates during skill learning. AB - Based on Gentile's learning model, this study used a dart-throwing task to investigate the influence of environmental context. Novice participants (N = 32) were trained in one of four conditions, while measuring outcomes and kinematics. The interaction of regulatory conditions (stationary/in motion) and intertrial variability (present/absent) created four target conditions: (1) stationary with one location, (2) stationary with five locations, (3) moving with one movement pattern, (4) moving with five starting locations. Performance outcome (radial error) and movement coordination (displacement of shoulder, elbow, and wrist) changes were investigated during three days of practice (480 trials). Radial error scores were analyzed using a 3 x 8 x 4 (Day x Trial Block x Condition) analysis of variance, repeated measures design. The transformed cross-correlation values of the kinematic trials were analyzed using a 3 x 3 x 4 (Joint x Day x Condition) analysis of variance, repeated measures design. Reducing the environmental context complexity of the skill (closed regulatory conditions and no inter-trial variability), decreased outcome errors and changed kinematics at different times in the learning. The environmental context influence was observed by a day x condition interaction on joint coordination. Inter-trial variability had its greatest influence on coordination. The environmental context should be taken into consideration when evaluating and assessing skill performance during learning. PMID- 24175466 TI - Postural control during pushing movement with risk of forward perturbation. AB - The purpose of this study was to investigate the effect of a forward bilateral pushing movement on postural control in a situation where known, unknown, and unpredictable perturbations may be induced. Participants stood upright and voluntarily pushed a handle with both hands. In the first task, the handle was free to be moved by the participant (perturbation; movable task) and in the second task, the handle was locked (stationary task). For each task, body displacement and observed applied force were recorded. Anticipatory postural control adjustment plays a vital role in body stability; however, in contrast to its role in maintaining stability, adjustment can generate a restricted voluntary movement because motor programming selects a postural control that gives priority to body stability over the target movement. PMID- 24175467 TI - Department of Sport Science, Seoul National University of Science and Technology, 172 Gongneung-dong, Nowon-gu, 139-743 Seoul, South Korea. AB - The current study investigated differences in physical activity and perceived benefits and barriers in normal-weight, overweight, and obese adolescents and tested the effect of BMI and perceived benefits and barriers on physical activity. Adolescents (N = 773) participated in the study; 381 were classified as having normal weight, 262 as overweight, and 130 as obese. Leisure Time Physical Activity Questionnaire, Decisional Balance Scale, and body composition analyzer were used to measure the study variables. Results indicated that there were no differences in self-reported physical activity in the three BMI groups. However, groups perceived benefits of and barriers to physical activity differed. BMI and 'better outlook', 'weight control', 'feeling confidence', 'physical dissatisfaction', and 'lack of confidence' accounted for nearly half the variance in self-reported physical activity. PMID- 24175468 TI - Environmental factors influencing pedestrian walking speed. AB - The present study investigated various factors influencing pedestrian speed. Undergraduate students who were registered in psychology courses participated in three studies (Study 1: N = 71, M age = 20.3 yr., 37 women; Study 2: N = 92, M age = 19.6 yr., 48 women; Study 3: N =108, M age = 20.4 yr., 56 women). They were required to walk within the city of Hradec Kralove (Czech Republic) along a route consisting of streets with various amounts of vegetation, traffic intensity, and noise. In Studies 1 to 3, participants tended to walk statistically significantly faster in sections without greenery and with more traffic, higher perceived noise, and more people than in sections with greenery and with less traffic, perceived noise, and fewer people. They also walked statistically significantly faster in less open spaces. In a fourth study, participants (N = 70, M age = 20.7 yr., 35 women) were asked to evaluate their emotional reactions to the environment (dimensions of pleasure, arousal, and dominance), as well as to the restorative qualities of the environment. In sections where participants reported more positive emotions and higher restoration, the walking speed was statistically significantly slower. The results are discussed in terms of the relationship between urban environmental design and stress reduction. PMID- 24175469 TI - Influence of chronotype on responses to a standardized, self-paced walking task in the morning vs afternoon: a pilot study. AB - The response to sub-maximal physical activity performed in the morning and late afternoon by individuals with different chronotypes was investigated. 22 participants filled out the Morningness-Eveningness Questionnaire and underwent a self-paced walking task that consisted of walking from the top to the bottom of a hill and back three times (1,836 meters, with a slope of 14.16%). The task was repeated twice: late afternoon (16:30) and early morning (08:30). Walking speed (time for completion in seconds), heart rate, and perceived exertion were measured during each task, with overall results given as a general descriptive analysis. Preliminary findings suggest that chronotype is likely to influence the responses to exercise, mostly with evening-types seeming at a disadvantage when performing a physical task in the morning. Individuals can be classified by circadian typology or chronotype, which is the propensity to be a morning-type, evening-type, or neither-type. The circadian typology, commonly referred to as being a morning person or an evening person or somewhere in between, is involved not only in the expression of physiological rhythms, but also in habits and lifestyles, such as sleeping patterns (Park, Matsumoto, Seo, & Shinkoda, 1999) that emerge especially during adolescence (Park, Matsumoto, Seo, Kang, & Nagashima, 2002) and remain throughout adult life (Koukkari & Sothern, 2006). PMID- 24175470 TI - Veridicality of self-concept of strength in male adolescents. AB - Changes in physical self-concept and veridicality (i.e., the appropriateness of one's self-perceptions to reality) during childhood and adolescence are related to performance in physical fitness, exercise, and global self-esteem, particularly in male adolescents. This cross-sectional study examined the relation between the self-concept of strength and actual strength in groups of male adolescents ages 12 to 15 years. For this purpose, 889 male adolescents (M age = 13.2 yr., SD = 1.0) were questioned about their self-concept of strength, after which a test of strength was carried out. The results showed that the correlation between self-concept of strength and actual strength was higher in older (14- and 15-year-old) than younger (12- and 13-year-old) adolescents. There was a statistically significant association between age group and veridicality, indicating that realistic self-concept is underrepresented among younger, but overrepresented among older adolescents. No association was found between the adolescents' physical activity and veridicality. The consequences for further research on the development of veridicality in the physical domain are discussed. PMID- 24175471 TI - [Effects of stimulation and blockade of the synthesis of endogenous hydrogen sulfide at myocardial ischemia-reperfusion]. AB - In experiments on isolated rat hearts, perfused according to Langendorff method, the effects of stimulation of the synthesis and blockade of endogenous hydrogen sulfide in myocardial ischemia-reperfusion (20 min/40 min) was studied. L cysteine (121 mg/kg), precursor of endogenous hydrogen sulfide was injected intraperitoneally 30 minutes before the experiment without and within 10 minutes after administration of DL-propargylglycine (11.3 mg/kg) ("Sigma", USA)- inhibitor of cystathionine-gamma-lyase. The heart function was assessed by measuring the LVDP, dP/dt, coronary flow, heart rate. The opening of mitochondria permeability transition (MPT) pore was estimated by releasing of a stable factor with UV absorbance (lambda(max) 250 nm) into the coronary outflow probes during the initial phase of reperfusion. Administration L-cysteine was accompanied by a decrease of reperfusion disorders in cardiac function compared to control rats. The results showed that L-cysteine pretreated hearts against the blockade of cystathionine-gamma-lyase with DL-propargylglycine exerted a powerful cardioprotective effect in ischemia-reperfusion injury. Significant post-ischemic recover of heart function and improving the efficiency of oxygen metabolism was accompanied with tiny quantity of mitochondrial factor releasing comparing to I/R group. Positive influence of the combined DL-propargylglycine and L-cysteine action was the prevention of MPT pore opening. PMID- 24175472 TI - [Biochemical mechanisms of the cardioprotective effect of the K(ATP) channels opener flocalin (medicinal form) in ischemia-reperfusion of myocardium]. AB - In experiments on the anaesthetized dogs with modeling of experimental ischemia (90 min) and reperfusion (180 min) of myocardium it was investigated changes of biochemical processes in arterial blood at intragastric introduction of medicinal form (tablets) of flocalin (the fluorine-containing opener of ATP-sensitive potassium channels) in a dose 2,2 mg/kg. The data analysis allowed to define a few possible mechanisms of cardioprotective action offlocalin, which prevented the opening of a mitochondrial permeability transition pore (MPTP) and inhibition of apoptosis induced by it. They consist, from one side, in activating of the constitutive de novo biosynthesis of nitric oxide by cNOS, from other side, in suppression of inducible nitric oxide de novo synthesis by iNOS in such way to prevent the formation of toxic peroxynitrite by co-operation of surplus nitric oxide with superoxide anion, thereby limits the generation of toxic active forms of nitrogen (*NO2) and oxygen (*OH). The first effect of flocalin takes place due to limitation the degradation of L-arginine by arginase which keeps substrat for cNOS, second--due to the inhibition of superoxide generation, in particular, by xanthine oxidase (marker uric acid), lipoxigenase (marker LTC4) and cyclooxygenase (marker TxB2). Because LTC4 have coronaroconstrictory, arrhythmogenic and chemoattractory properties in the conditions of myocardial ischemia, inhibition of its production both with superoxide generation (markers H2O2 and diene conjugates) may be the another mechanisms of flocalin's cardioprotection. Powerful antiischemic action of flocalin (marker nitrite anion) as the mechanisms of cardioprotection is possible as well as inhibition of ATP and GTP degradation (marker hypoxanthine+xanthine+inosine levels in the blood) and, possibly, stimulation ofhaem degradation by haem oxygenase (markers total bilirubin and Fe in the blood). Diminishing content of free arachidonic acid in arterial blood can testify inhibition of cellular membranes phospholipides degradation by phospholipase A2 as a result of flocalin cardioprotection. PMID- 24175473 TI - [The effect of Ca2+ on the properties of the large conductance cation channels of the nuclear envelope of the cerebellar neurons]. AB - Previously we have found the large conductance cation channels (LCCC) in the nuclear membranes, where inositol-1,4,5-triphosphate receptors (IP3Rs) were also observed. Probably IP3Rs and LCCC are functionally connected: LCCC may provide the counterflow of K+, which prevent the formation of the negative potential in the lumen of the nuclear envelope and in such way may prolong the Ca2+ releasing by IP3Rs. LCCC are poorly studied and their molecular nature is still unknown. We investigated the effect of Ca2+ on properties of these channels. Our results demonstrated the main biophysical properties of LCCC changed significantly neither in Ca(2+)-free solution, nor with high concentrations of Ca2+ in the nuclear lumen. So, the level of Ca2+ repletion of the store does not influence the activity of LCCC. PMID- 24175474 TI - [Development of a prediabetic state under chronic alcohol intoxication]. AB - We investigated the changes in key parameters of carbohydrate and lipid metabolism, which correspond to the clinical picture that accompanies the development of prediabetic condition on the background of chronic alcohol intoxication. From the analysis of glycemic curves obtained during the insulin glucose test, a speed of glucose uptake by peripheral tissues increased at the 1st day (1.5 fold) and the third day (1.3 fold) of administration of alcohol solution. At the later periods, at 7 and 11 days of ethanol administration, a decreased rate of glucose uptake in animals with chronic alcohol intoxication was detected. We also detected an increased content of serotonin in the blood serum and a decreased (1.2 fold) serotonin content in rat brain during the whole period of development of chronic alcohol intoxication. PMID- 24175475 TI - [The comparative pathomorphological evaluation of the mice-recipient's brain cell tissue reactions by the intracerebral imlantation of syngeneic and allogeneic neural cells]. AB - The aim of the study was to compare the mice-recipient's brain tissue cell structural reactions in response to intracerebral implantation of syngeneic and allogeneic cell suspensions of neural progenitor cells (NPC) (E13-15). The NPC suspensions from mice-donors of C57BL/6 and CBA containing 72.7 +/- 9.9% Vimentin+ and 81, 812, 5% GFAP+ cells were inoculated by standard procedure in right temporal segment of cerebral hemisphere of mice-recipients C57BL/6 (1 x 10(6) cells per animal). The certain part of mice-recipients of allogeneic NPC were immunosupressed by Sandimmune (100 mkg per animal) on day 0, 3, 6 after neurotransplantation. The standard histological preparations of mice brains were performed after 24 hours, 6, 12, 18 and 37 days after NPC neurotransplantation, which were investigated by cytoanalyzer "IBAS" (Germany). After intracerebral inoculation of allogeneic foetal NPC the signs of the pericellular edema and lymphocyte infiltration were detected in adjacent brain sections on day 12-18 and decreased on day 37. Allogeneic foetal NPC were reserved till day 18 and revealed the signs of primary differentiation. After immunosupression by "Sandimmune" the foetal NPC underwent the phoenotypic differentiation and infiltration in related brain sections. On the day 37 the implanted NPC were not detected. Focal reaction of the brain glial component to implanted NPC declined faster after syngeneic NPC neuroimplantation (up to day 18) than after allogeneic NPC neuroimplantation (up to day 37). After the syngeneic NPC inoculation on the 37th day at the site of implantation the formation of a small fragment of immature bone was fixed, which may indicate the possibility of NPC transdifferentiation in other cell types. PMID- 24175476 TI - [Mice myometrial contractility in conditions of mitochondrial functional changes]. AB - It has been investigated the temporal amplitude features of mice myometrium in conditions of action mitochondrial carriers inhibitor, the mitochondrial pore activator, calcium uniporters inhibitor. For the first time it is established that the functional condition of myometrium depends on a mitochondrial carriers functioning; the mitochondrial carrier is NO-dependent itself (on arginaze way of its formation); the carrier functions depending on mitochondrial membrane potential and mitochondrion nonspecific conductivity (mitochondrial pores). PMID- 24175477 TI - [Functional morphology of nucleated erythrocytes during hypoxia (in vitro experiments)]. AB - Changes in morphologic and functional properties of nucleic erythrocytes were observed during experimental hypoxia in vitro. It has been shown that erythrocytes volume and nuclei volume decrease in oxygen concentration of 1.76 4.03 mgO2 x l(-1) on 1.5-5.0% and 9-15% respectively. Both indexes increased significantly in case of deep hypoxia (0.57-1.76 mgO2 x l(-1)) when nucleo cytoplasmic ratio doesn't change. By this time erythrocytes shape modifies into extended ellipse because of elongation of large axis of cell (C1) and its width (h). Along with increase in nuclei volume the enhancement of SYBR Green I fluorescence is observed; the intensity correlates with volume magnitude of this cell structure (R2 = 0.81). PMID- 24175479 TI - [Stress-induced changes in the content of cytochrome P450 2E1 in the liver of mice with chronic psychoemotional overexertion]. AB - In this work we investigated changes in the cytochrome P450 2E1 (CYP2E1) expression level in the liver of mice that have been exposed to psycho-emotional stress (PES). It was shown twofold relative to control reduction of the enzyme, which does not normalize after termination of the stressor. The changes in level of Cyp2e1 mRNA is not observed at any time point of the experiment. At the same time it was found a significant decrease in the expression level of hsp90--one of the factors determines of the level of CYP2E1 degradation in the cell. Also it was shown, the oxidative stress develops in the liver of experimental animals, and this is indicated by a 3-fold increase in the malondialdehyde level on the background of a 5-fold decrease in catalase activity. A decrease in the level of expression of cytochrome P450 2E1 in the liver of mice that have been exposed to psycho-emotional stress is due to the intensification of the peroxide process and the development of oxidative stress. Reduction of protein content of CYP2E1 is apparently not related to the hsp90-dependent processes of its degradation in the cell. PMID- 24175478 TI - [Pathogenesis of skin injury in immunodeficient rats]. AB - We investigated the skin condition in rats with immunodeficit induced by cyclophosphane. Cyclophosphane induced in the blood the development of two phases pathological process. The first leukopenic phase is mediated by the action ofcytostatics, and the second hyperleucocytic phase is induced by liver injury and splenomegalia. Dysbiosis and inflammation are developed in the skin, especially during the second phase. PMID- 24175480 TI - [Glycoproteins of mucus of gastric and duodenal wall surface during ulcerogenesis and the impact of fenugreek]. AB - The comparative evaluation of qualitative and quantitative composition of glycoproteins of gastric and duodenal wall surface layer of protective mucus in the normal, at the modeling of ulcers in rats and at the introduction to animals with ulcerative lesions of fenugreek extract carried out. It was shown in control (normally) the general level of glycosylation of glycoproteins gastric mucus is 1.7 times more than the duodenum. Under acute stress model ulceration in the stomach mucus decrease in hexosamine (1.4 times), galactose (2.2 times), fucose (1.3-fold) and an increase in NANA (3.6 times) observed. Under cysteamine model ulceration in duodenal mucus increase galactose (2.7 times), NANA (2.4 times), fucose (1.8-fold) but significant decrease in the amount of hexosamines 3 times compared to the control occurred. It was proved the protective effect of fenugreek extract to the wall surface mucus of the stomach and duodenum mucosa under conditions modeling ulceration in rats. PMID- 24175481 TI - [Impact of renal dysfunction on clinical course of myocardial infarction complicated by acute heart failure in patients with preserved systolic function]. AB - Aiming to assess the relationships between renal function and ST-segment elevation myocardial infarction (MI) clinical course and remote outcomes in patients with preserved systolic left ventricular (LV) function (LV ejection fraction > 40%) estimated glomerular filtration rates (eGFR) were evaluated on 1st and 3rd -10th MI day (n = 491). On 3rd-10th day of MI in patients with acute heart failure (HF) symptoms on admission day (1st group, n = 153) eGFR < 70 ml/min x per body surface unit was independent marker of re-infarction (Hazzard Ratio (HR) with 95% confidence intervals (95% CI) = 4,08 [1,72 -11,73], P < 0,01) and cardiovascular death (CVD) (HR [95% CI] = 3,61 [1,09 - 11,99], P = <0,05) during three years of follow-up. In patient without acute HF (2nd group, n = 338) eGFR < 68 ml/min was predictive of CVD within three years post-MI (HR [95% CI] = 7,13 [2,06 - 24,74], P = 0,002). eGFR did not correlate with myocardial damage markers. In the 1st group eGFR on the 3rd MI day was negatively correlated with tumor-necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor levels. There were no correlation between systemic inflammation activation with eGFR in 2nd study group indicating different mechanisms of renal dysfucntion in patients with and without acute HF and preserved LV function. PMID- 24175482 TI - [Influence of professional conditions as risk factor for the development of vascular eye pathology in surgeons]. AB - This work was devoted to study of the peculiarities of morphology of the retina with ganglion cells complex and the peculiarities of regional and systemic blood circulation in surgeons and therapists. It was revealed that longtime work under operative microscope results in a decrease of all parameters of blood circulation, that with the data of optical coherent tomography of the retina and optic nerve in surgeons demonstrate the signs of the existence of more high risk of vascular eye pathology then that observed in therapists. PMID- 24175483 TI - [Endoplasmic reticulum stress and angiogenesis]. AB - The endoplasmic reticulum is a dynamic intracellular organelle with exquisite sensitivity to alterations in homeostasis, and provides stringent quality control systems to ensure that the only correctly folded proteins transit to the Golgi and unfolded or misfolded proteins are retained and ultimately degraded. The endoplasmic reticulum stress represents the unfolded protein response to cope with the accumulation of unfolded or misfolded proteins and is required to maintain the functional integrity of the endoplasmic reticulum. The endoplasmic reticulum stress is a fundamental phenomenon which provides a secure protection of the cells from different factors. This stress provides a wide spectrum of physiological roles in diverse developmental and metabolic processes, especially for professional secretory cells with high-level secretory protein synthesis, such as pancreatic beta cells, hepatocytes and osteoblasts and is required throughout the entire life. The endoplasmic reticulum stress and hypoxia are the obligate components of malignant tumor growth, are interconnected and activate angiogenesis via growth and metabolism control. The endoplasmic reticulum stress is mediated by three by three sensor and signaling pathways (PERK, ATF6 and ERN1), besides that blockade one (ERN1) leads to a decrease of tumor growth through suppression of angiogenesis and proliferation. The data concerning the interaction of signaling enzyme ERN1 and pro- and anti-angiogenic gene expressions is analyzed. PMID- 24175484 TI - The medicinal use of cannabis and cannabinoids--an international cross-sectional survey on administration forms. AB - Cannabinoids, including tetrahydrocannabinol and cannabidiol, are the most important active constituents of the cannabis plant. Over recent years, cannabinoid-based medicines (CBMs) have become increasingly available to patients in many countries, both as pharmaceutical products and as herbal cannabis (marijuana). While there seems to be a demand for multiple cannabinoid-based therapeutic products, specifically for symptomatic amelioration in chronic diseases, therapeutic effects of different CBMs have only been directly compared in a few clinical studies. The survey presented here was performed by the International Association for Cannabinoid Medicines (IACM), and is meant to contribute to the understanding of cannabinoid-based medicine by asking patients who used cannabis or cannabinoids detailed questions about their experiences with different methods of intake. The survey was completed by 953 participants from 31 countries, making this the largest international survey on a wide variety of users of cannabinoid-based medicine performed so far. In general, herbal non pharmaceutical CBMs received higher appreciation scores by participants than pharmaceutical products containing cannabinoids. However, the number of patients who reported experience with pharmaceutical products was low, limiting conclusions on preferences. Nevertheless, the reported data may be useful for further development of safe and effective medications based on cannabis and single cannabinoids. PMID- 24175485 TI - Marijuana as a predictor of concurrent substance use among motor vehicle operators. AB - Despite the adverse effects associated with marijuana abuse and dependence, marijuana is becoming more common-place in activities such as driving. Previous literature has discussed the high rates of cocaine, opioid and benzodiazepine use among users of marijuana, but no research has addressed the rates of concurrent use among drivers meeting abuse or dependence criteria. Each of these substances may produce effects detrimental to driving safety which may be compounded by concurrent substance use. This research examines rates of marijuana use, abuse, and dependence among an active sample of drivers (N = 7,734) in the 2007 National Roadside Survey. Mean age of participants was 36.89 years, and the majority were male (60.1%) and identified as White (59.2%). Participants who used marijuana but did not meet diagnostic criteria for abuse (n = 165) or dependence (n = 112) were significantly more likely to test positive for all substances than were those who did not use marijuana. Further, those that met criteria for marijuana abuse or dependence were more likely than those who did not meet criteria to test positive for THC, cocaine, and benzodiazepines and THC, cocaine, and opioids, respectively. The current research has implications for policy development and drugged driving interventions. PMID- 24175486 TI - Binge drinking, marijuana use, and friendships: the relationship between similar and dissimilar usage and friendship quality. AB - While it is commonly understood that the substance use of peers influences an individual's substance use, much less is understood about the interplay between substance use and friendship quality. Using a sample of 2,148 emerging adults nested within 1,074 dyadic friendships, this study separately investigates how concordance and discordance in binge drinking and marijuana use between friends is related to each friend's perceptions of friendship quality. Because "friendship quality" is a complex construct, we employ a measure containing five sub-elements--companionship, a lack of conflict, willingness to help a friend, relationship security, and closeness. Results for both binge drinking and marijuana use reveal that individuals in friendship pairs who are concordant in their substance use perceive significantly higher perceptions of friendship quality than individuals in dyads who are dissimilar in substance use. Specifically, concordant binge drinkers estimate significantly higher levels of companionship, relationship security, and willingness to help their friend than concordant non-users, discordant users, and discordant non-users. However, the highest amount of conflict in friendships is found when both friends engage in binge drinking and marijuana use. Several interpretations of these findings are discussed. Overall, concordance between friends' binge drinking and marijuana use appears to help some elements of friendship quality and harm others. PMID- 24175487 TI - Postoperative analgesia in the Jamaican cannabis user. AB - BACKGROUND: Anecdotal reports suggest that cannabis users require increased postoperative analgesia but there is insufficient supporting data. METHODS: A prospective randomized study was carried out in 73 patients undergoing elective operations. Postoperatively, all patients were assessed by a blinded investigator, who recorded pain intensity, sedation levels, mood, and hourly analgesia requirements. We calculated the mean pain intensity difference at the first postoperative hour (MPID1) and the sum of pain intensity differences (SPID1). The following end points were compared between cannabis users and non users using SPSS 16: MPIDI; SPID; patient mood; supplemental analgesia requirements and global assessment scores. RESULTS: There were 42 cannabis users and 31 non-users. Cannabis users had significantly higher supplemental pethidine requirements (82.7 mg, SD = 3.4 vs. 51.6 mg, SD = 42.7, p = 0.003) and significantly greater MPID1 scores (1.88, SD = 1.09 vs. 1.35, SD = 1.12, p = 0.001) compared to non-users. Female cannabis users required significantly more analgesia than males (93.3 mg, SD = 45.8 vs. 78.3 mg, SD = 44.3, p = 0.025). CONCLUSION: Cannabis users require significantly more opioid rescue analgesia in the immediate postoperative period. Further research is needed to elucidate the precise mechanism by which this occurs. PMID- 24175488 TI - Prevalence of substance use and mental distress among patients on waiting lists for substance use disorder treatment. AB - OBJECTIVE: The aim of this study was to examine the prevalence of illicit substance use, alcohol consumption, and psychosocial distress among Norwegian patients on waiting lists for substance use disorder treatment. METHODS: Patients on waiting lists at 16 Norwegian treatment clinics for substance use disorders received a mailed questionnaire or were recruited during pre-treatment meetings (response rate 40%, n = 203). The patients completed a questionnaire consisting of validated screening tools of substance use and psychosocial distress. When available, Norwegian norm data were used as a reference group in analyses. RESULTS: Among patients who reported use of illicit substances in the last month, 40% reported scores above cut-off. About 50% of those who had consumed alcohol reported a severe pattern of alcohol consumption. A total of 60% of the sample reported severe symptom loads and nearly 70% of the sample reported interpersonal problems above cut-off. Compared to the norm data, patients on waiting lists reported more psychosocial distress on all the symptom dimensions, as expected. CONCLUSIONS: Patients on waiting lists reported substantial substance use and psychosocial burden. Pre-treatment interventions should be conducted among these patients. Treatment could benefit from more standardized screening routines and clinical assessments before patients enter treatment. The findings may challenge the Norwegian policy of supply-driven treatment services. PMID- 24175491 TI - John or Jane? Exploring how clinical judgment is applied in managing access to opioid replacement therapy. AB - In Australia, access to Opioid Replacement Therapy (ORT) poses a problem for clinicians when confronted with multiple requests for ORT treatment. This article forms part of a broader grounded theory study exploring how clinicians apply clinical judgement in managing access to ORT programs. The focus of this article is to report on the codes generated from the study's data analysis and to discuss how they influence clinician responses to the process. From March to August 2012, 35 clinicians from 10 publicly funded ORT clinics within the states of Queensland and New South Wales were recruited. To stimulate clinicians to use their clinical judgment, a scenario was presented requiring participants to choose between two consumers for preferential access to ORT and explain why. Responses as to who should receive treatment first varied between clinicians. Reasoning for their decisions was diverse, except "prioritising" was a consistently presenting element. Previous education, training, work experience, and their peers were all factors identified as influencing their decision making. Not all clinicians were confident with their choice. This study examined how clinical judgement is applied in managing access to ORT, showing variation in clinician responses and the factors influencing those decisions. PMID- 24175490 TI - Developmental trajectories of alcohol use among monoracial and biracial Black adolescents and adults. AB - OBJECTIVE: The present study investigates developmental trajectories of alcohol use from early adolescence to adulthood by age and race/ethnicity among White, Black, Black-American Indian, Black-Hispanic, and Black-White individuals and associated sociodemograhphic correlates. METHOD: We used a subsample of nationally representative data obtained from the National Longitudinal Study of Adolescent Health (Add Health). The analytic sample consisted of 15,278 individuals in Wave 1 (ages 11 to 21 years). The sample consists of adolescents who were in Grades 7-12 at wave one and who were followed across four waves of data collection into adulthood. Respondents could report more than one race/ethnicity. RESULTS: We find distinct alcohol trajectories among monoracial and biracial/ethnic Blacks with all groups showing a cross-over or catch-up effect. Black-White adults demonstrated a cross-over effect by surpassing the alcohol drinking rates of Whites in adulthood, Black-American Indians showed a within-group catch-up effect by surpassing the alcohol drinking rates of monoracial and biracial/ethnic Blacks in adulthood, and monoracial Blacks were most likely to be non-drinkers in adulthood. We also show gender, socioeconomic status, and household structure differences in impact on alcohol use among monoracial and biracial/ethnic Blacks. CONCLUSIONS: Significant heterogeneity is observed regarding alcohol trajectories between monoracial and biracial/ethnic Blacks. PMID- 24175489 TI - The effects of alcohol problems and smoking on delay discounting in individuals with gambling problems. AB - Problem gambling is an addictive behavior with high comorbidity with alcohol problems and smoking. A common feature shared by these conditions is impulsivity. Past research shows that individuals with any of these addictions discount delayed money at higher rates than those without, and that the presence of gambling and substance use lead to additive effects on discounting. To date, however, no study examined the impact of smoking on these associations. The goals of this study were to compare the discounting rates of gamblers with and without histories of alcohol problems and smoking, and assess the associations these addictions might have on discounting. We analyzed the discounting rates of treatment-seeking gamblers categorized into four groups based on their histories of alcohol and smoking. Results revealed effects of history of alcohol problems, and an interaction between smoking and alcohol problems, on discounting. Never smokers with histories of alcohol problems discounted money less steeply than the other groups of gamblers. These results suggest that smoking does not produce additional increases on discounting rates in individuals with other addiction problems and the small subpopulation of gamblers with alcohol problems who never smoked is less impulsive and may have unique risk and/or protective behaviors. PMID- 24175492 TI - Early maladaptive schemas of substance abusers and their intimate partners. AB - The influence of intimate partners in the recovery of substance abuse has been increasingly recognized in the professional literature. Couples-based substance abuse treatment has demonstrated effectiveness in reducing substance abuse and increasing healthy couple functioning. Recently, research has begun to investigate enduring cognitive beliefs that may impact substance abusers and their intimate partners, which could advance our understanding of factors that may impact couple's functioning. The current study examined the early maladaptive schemas and substance use of a sample of adult substance abusers who have sought residential substance abuse treatment and their intimate partners (N = 102). Results demonstrated that the early maladaptive schemas of patients and their intimate partners may be interrelated and that patients scored significantly higher than their partners on 13 of the 18 early maladaptive schemas. Substance use was only associated with a few early maladaptive schemas. These findings highlight the potential importance of assessing early maladaptive schemas in couples where one partner has a substance abuse problem. Implications of these findings for future research are discussed. PMID- 24175494 TI - SDSMA Center for Physician Resources. PMID- 24175493 TI - Methoxetamine (MXE)--a phenomenological study of experiences induced by a "legal high" from the internet. AB - Methoxetamine (MXE), a ketamine analogue, is one of the new "legal highs" sold on the Internet. The aim of this qualitative study was to provide an initial understanding of what characterizes the experiences induced by MXE. Anonymously written reports (33 persons) on the effects of MXE were collected from public Internet forums and analyzed using the Empirical Phenomenological Psychological Method. The analysis generated 10 themes: (1) preparation, motivation and anticipation; (2) initial effects; (3) malfunction of cognitive processes stabilizing normal state; (4) inner personal processes and learning; (5) emotional processes; (6) altered sensory perception; (7) dissolution and transition; (8) spiritual and transcendental experiences; (9) effects and processes after the experience; (10) re-dosing and addiction. MXE induced a heavily altered state of consciousness. The effects were similar to those induced by classic hallucinogens (such as LSD, psilocybin) and the dissociative ketamine. MXE seemed to have quite a high abuse potential. Beside the positive effects described, negative effects like fear and anxiety were also reported. Acceptance was considered the best coping strategy. Dissolution of identity and body often culminated in spiritual and transcendental experiences. More research is needed on safety issues, how to minimize harm, and the motivation for using legal highs. PMID- 24175495 TI - Acute epiglottitis in adults: an under-recognized and life-threatening condition. AB - Epiglottitis is a potentially life-threatening condition resulting from infection of the epiglottis and surrounding structures, causing classical signs and symptoms related to inflammation and progressive airway obstruction. We briefly present two recent adult cases of epiglottitis, followed by a review of the literature concerning the subject. In diagnosing epiglottitis, direct visualization by laryngoscopy is the gold standard. Lateral neck X-rays also have great utility, but with less sensitivity than direct visualization. Though historically more of a burden for the pediatric population, epiglottitis does occur in adults, often with a milder clinical course. And while aggressive treatment in the pediatric population has driven mortality from 7 percent to about 1 percent, mortality in the adult population remains at about 7 percent. Some debate exists over how aggressively to approach the adult with epiglottitis due to the more variable nature of presentation in the adult population. Though prophylactic airway management is not necessarily indicated in the adult with epiglottitis, careful attention to the airway in a controlled intensive care environment is recommended. The severity of the clinical picture should guide the physician in his or her approach. Any clinical suspicion of epiglottitis warrants an aggressive approach until epiglottitis is ruled out or the patient is recovering well. PMID- 24175496 TI - Ipilimumab immune-related adverse reactions: a case report. AB - Ipilimumab is an immunomodulating agent approved by the Food and Drug Administration (FDA) as of March 2011 for the treatment of metastatic melanoma. The medication works by inhibiting cytotoxic T-lymphocyte antigen 4, which typically works to down-regulate the T-cell response and protects self-antigens from recognition by the immune system. Since the T-cells are no longer down regulated by this antigen, they are allowed to proliferate, thereby helping to prevent melanoma tumor evasion. As a result of the up-regulation of the immune system, numerous immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. Typically, these effects are treated with high-dose steroids and most eventually resolve. We present a case of autoimmune (lymphocytic) hypophysitis following treatment with four doses of ipilimumab 3mg/kg and discuss the work-up, treatment and prognosis of the event. PMID- 24175497 TI - Case report: treatment of subdural hematoma in the emergency department utilizing the subdural evacuating port system. AB - Patients with acute or chronic subdural hematomas may present with rapidly deteriorating neurological function and are at risk for irreversible brainstem injury. In such cases, rapid surgical intervention is required to evacuate the hematoma and reverse critically elevated intracranial pressure. A variety of surgical drainage methods are in existence, none of which are clearly superior to the others. This report presents the case of a 74-year-old woman who suffered an acute-on-chronic subdural hematoma which was evacuated in the emergency department utilizing the subdural evacuating port system (SEPS). The SEPS provides for a minimally invasive technique to drain subdural hematomas and is advantageous in that it can be performed at the bedside. The SEPS is relatively simple to use and may be especially useful to emergency department staff in outlying areas where there is a shortage of neurosurgical coverage. PMID- 24175498 TI - An update on influenza vaccines for the 2013-14 flu season. PMID- 24175499 TI - A doctor's story. PMID- 24175500 TI - Patient education: autism is from Mars. PMID- 24175501 TI - Extenuating circumstances--tobacco use and mental illness: treating addiction. PMID- 24175502 TI - DAKOTACARE update: what we did this summer. PMID- 24175503 TI - Quality focus: Clostridium difficile. PMID- 24175504 TI - [Distribution pattern of neutral sugar in forest soils along an altitude gradient in Changbai Mountains, Northeast China]. AB - In July 2010, soil samples were collected from five typical forests (Pinus koraiensis and broadleaved mixed forest, Picea and Abies forest, Larix and Abies forest, Betula ermanii forest, and alpine tundra) along an altitude gradient on the northern slope of Changbai Mountains to investigate the distribution and quantity of neutral sugar in the soils and related affecting factors. The origins of the neutral sugar were differentiated to probe into the biochemical accumulation mechanisms of soil organic matter. There was a significant difference in the neutral sugar content among the forest soils. The relative content of soil neutral sugar' s carbon to soil organic carbon ranged in 80.55 170.63 mg C x g(-1), and tended to be increased with elevated altitude. The multiple regression analysis showed that the mean temperature in growth season was the main factor affecting the relative content of soil neutral sugar, and low temperature was conducive to the accumulation of neutral sugar. The ratio of (galactose + mannose) / (arabinose + xylose) in the five soils was around 1.62 2.28, and had an increasing trend with elevated altitude, illustrating that the contribution of soil microbial neutral sugar to soil organic matter increased with elevated altitude. Soil microbial metabolic quotient declined significantly along elevated altitude, suggesting that in low temperature environment, soil microbial activity decreased but the carbon utilization efficiency enhanced. As a result, a significant portion of decomposed plant residues was transformed into microbial neutral sugar and accumulated stably in soil, and thus, increased the proportion of soil microbial neutral sugar. PMID- 24175505 TI - [Characteristics of soil microbial biomass and community composition in three types of plantations in southern subtropical area of China]. AB - By using fumigation-extraction method and phospholipid fatty acids (PLFAs) analysis, this paper studied the characteristics of soil microbial biomass and community composition in the Erythrophleum fordii, Castanopsis hystrix, and Pinus massoniana plantations in south subtropical China. The soil microbial biomass, total PLFAs, bacterial PLFAs, and fungal PLFAs in the plantations were significantly affected by the plantation type and season, and the soil microbial biomass, total PLFAs, and individual PLFA signatures were higher in dry season than in rainy season. The C. hystrix plantation had the highest soil microbial biomass carbon and total PLFAs, while the E. fordii plantation had the highest soil microbial biomass nitrogen. There was a significant positive correlation between the soil pH and arbuscular mycorrhizal fungal (AMF) PLFA (16:1omega5c). The soil total PLFAs, gram-positive bacterial PLFAs, saprophytic fungal PLFA (18:2omega6,9c), and the ratio of gram-positive to gram-negative bacterial PLFAs were significantly positively correlated with soil organic carbon, total nitrogen, and total phosphorus, suggesting that the soil organic carbon, total nitrogen, and total phosphorus contents were the most important nutrient factors affecting the numbers and types of the soil microorganisms. In addition, the ectomycorrhizae fungal PLFA (18:1omega9c) and AMF PLFA were significantly correlated with the soil C/N ratio. PMID- 24175506 TI - [Cleistogenes squarrosa population at different restorative succession stages in Inner Mongolia of China: a point pattern analysis]. AB - In this paper, the spatial pattern of Cleistogenes squarrosa population in different restorative succession communities of the typical steppe dominated by Stipa grandis and Leymus chinensis in Inner Mongolia was measured by photography orientation, and analyzed by complete spatial randomness model, Poisson cluster process, and nested double-cluster process. In severely degraded community, C. squarrosa population fitted well nested double-cluster process for all scales, i. e., high density small clusters existed at the centers of large clusters; whereas in 5-, 8-, and 21-year-old restored communities, C. squarrosa population fitted well Poisson cluster process for all scales, i. e. , high density small clusters did not exist at the centers of the clusters. It was suggested that facilitation was the dominant interaction in severely degraded community, while competition dominated in restored communities. The differences in the spatial pattern of C. squarrosa population during the restorative succession could be induced by the shift from facilitation to competition along the gradient of grazing stress. PMID- 24175507 TI - [Soil nutrient accumulation and its affecting factors during vegetation succession in karst peak-cluster depressions of South China]. AB - Taking the typical karst peak-cluster depressions in Huanjiang County of northwest Guangxi as the objects, and by using the method of replacing time with space, an analysis was made on the dynamic changes of top soil (0-15 cm) nutrients and their dominant controlling factors during the process of vegetation succession. With the positive succession of vegetation (herb-shrub-secondary forest-primary forest), the soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) contents increased significantly, with the soil SOC, TN, and TP increased from 29.1 g x kg(-1), 2.48 g x kg(-1), and 0.72 g x kg(-1) in herb community to 73.9 g x kg(-1), 8.10 g x kg(-1), and 1.6 g x kg(-1) in primary forest, respectively, which indicated that the positive succession of vegetation was helpful to the soil nutrient accumulation. The soil cation exchange capacity (CEC) had close relationships with the soil SOC and TN, being the primary controlling factor for the accumulation of the soil C and N. The litter P content, C/P ratio, and N/P ratio were the major factors controlling the P accumulation in the topsoil. The litters higher P content and N/P ratio and smaller C/P ratio were helpful for the P accumulation. Topographic indices (slope, aspect, and rock exposure ratio) had little effects on the soil nutrients. PMID- 24175508 TI - [Effects of drought stress on the growth, photosynthetic characteristics, and active oxygen metabolism of poplar seedlings]. AB - A pot experiment was conducted to study the effects of different water treatments (normal irrigation, light drought, moderate drought, and severe drought) on the growth, gas exchange, chlorophyll fluorescence characteristics, and active oxygen metabolism of poplar ( Populus x euramericana cv. 'Neva') seedlings in the experimental nursery of Shandong Forestry Academy from April to October, 2011. As compared with those under normal irrigation, the growth of the seedling' s basal diameter under light, moderate, and severe drought stress decreased by 12.8%, 44.5%, and 65.6%, and the height growth decreased by 12.2%, 43.1%, and 57.2%, respectively. With the increasing extent and duration of drought stress, the maximal photochemical efficiency of PS II , quantum yield, photochemical quenching coefficient, net photosynthetic rate, and stomatal conductance of the seedling leaves decreased gradually under light drought stress, while decreased rapidly under both moderate and severe drought stress. The non-photochemical quenching coefficient increased significantly under light drought stress, but decreased after an initial increase under moderate and severe drought. The leaf superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities under drought stress decreased after an initial increase, but definite differences existed in the responses of the three enzymes to drought stress and reactive oxygen. The leaf relative electric conductivity and malondialdehyde (MDA) content under drought stress increased significantly, plasma membrane was damaged, and massive ions leaked out. The most serious damage of plasma membrane was found under severe stress. Under light drought stress, the seedlings had higher photosynthetic efficiency and stronger oxidative enzyme defense system; under moderate and severe drought stress, the photosynthetic efficiency decreased significantly, and the oxidative enzyme defense system was damaged remarkably. PMID- 24175509 TI - [Effects of Eucalyptus grandis leaf litter at its early stage of decomposition on the growth and photosynthetic characteristics of Cichorium intybus]. AB - From March to May, 2010, a pot experiment was conducted to investigate the effects of Eucalyptus grandis leaf litter at its early stage of decomposition on the growth and photosynthetic characteristics of Cichorium intybus. Four treatments with different application rate of the leaf litter, i.e., 0 g x pot( 1) (CK), 30 g x pot(-1) (A1), 60 g x pot(-1) (A2), and 90 g x pot(-1) (A3), were installed. Each pot contained 12 kg soil mixed with the leaf litter, and then, C. intybus was sown. The growth indicators of the C. intybus were measured at the 30, 45, 60, and 75 d after sowing, and the photosynthetic characteristics of the C. intybus in treatment A3 were studied after the seedlings third leaf fully expanded. At each measured time, the biomass accumulation and leaf area growth of C. intybus in treatments A1, A2, and A3 were inhibited significantly. At the early stage of the leaf litter decomposition, the synthesis of photosynthetic pigments of the C. intybus seedlings was inhibited significantly, and the inhibition effect was getting stronger with the increasing amount of the leaf litter addition. The diurnal change of the seedlings photosynthetic rate in all treatments showed a bimodal curve with midday depression, the stomatal conductance and water use efficiency had the same variation trend with the net photosynthetic rate, and the total diurnal photosynthesis decreased in the order of CK > A1 > A2 > A3. The GC-MS analysis showed there were 33 kinds of small molecule compounds released gradually with the decomposition of the leaf litter, among which, allelopathic substance terpenoid dominated. PMID- 24175510 TI - [Evaluation index system of swamp degradation in Zoige Plateau of Sichuan, Southwest China under drainage stress]. AB - The evaluation index system of swamp degradation is one of the key scientific issues in the frontier field of international wetland science research. On the basis of long-term swamp field reconnaissance, and according to the fixed position ecological investigation of plant communities and the analysis of soil samples in 20 swamp plots in three belt transects of swamp degradation research under the stress of drainage in 2009, the swamps in the Zoige Plateau of Sichuan were classified into three groups with seven swamp communities, i. e., undisturbed (A type), disturbed by long-term and weak drainage (B-D type), and disturbed by short-term and strong drainage (E-G type), according to the species importance value and by Two-Way Indicator Species Analysis (TWINSPAN). The degradation degree of the swamps was graded by the method of Principal Components Analysis (PCA), and the swamp vegetation evaluation index (SVEI) and soil evaluation index (SSEI) were developed. Based on the SVEI, the swamps were classified as pristine swamp, lightly degraded swamp, moderately degraded swamp, and severely degraded swamp. Based on the SSEI, the swamps in Hongyuan County were divided into three grades, i. e. pristine swamp, lightly degraded swamp, and severely degraded swamp, while those in Ruoergai County were divided into lightly degraded swamp, moderately degraded swamp, and severely degraded swamp. The similarity of TWINSPAN classification results and SVEI/SSEI evaluation results was above 70%, indicating that both SVEI and SSEI were effective for the swamp degradation grading, and different classification methods should be combined to comprehensively evaluate the swamps in the Plateau. PMID- 24175511 TI - [Correlations between standing trees trunk decay degree and soil physical chemical properties in Korean pine-broadleaved mixed forest in Xiao Xing'an Mountains of Northeast China]. AB - Standing trees decay often causes vast loss of timber resources. To investigate the correlations between the standing trees decay and the site conditions is of importance to scientifically and reasonably manage forests and to decrease wood resources loss. By using Resistograph and meter ruler, a measurement was made on the decay degree of the trunk near root and the diameter at breast height (DBH) of 15 mature Korean pine standing trees in a Korean pine-broadleaved mixed forest in Xiao Xing' an Mountains in May, 2011. In the meantime, soil samples were collected from the root zones of standing trees and the upslope and downslope 5 meters away from the trunks, respectively. Five physical-chemical properties including moisture content, bulk density, total porosity, pH value, and organic matter content of the soil samples were tested. The regression equations concerning the trunk decay degree of the standing trees, their DBH, and the 5 soil properties were established. The results showed that the trunk decay degree of the mature Korean pine standing trees had higher correlations with the bulk density, total porosity, pH value, and organic matter content (R = 0.687), and significant positive correlation with the moisture content (R = 0.507) of the soils at the root zones of standing trees, but less correlation with the 5 properties of the soils at both upslope and downslope 5 meters away from the trunks. The trunk decay degree was decreased when the soil moisture content was below 18.4%. No significant correlation was observed between the trunk decay degree of mature Korean pine standing trees and the tree age. PMID- 24175512 TI - [Desorption characteristics of phosphorus in tea tree rhizosphere soil]. AB - In order to explore the phosphorus (P) release process and its supply mechanism in tea tree rhizosphere soil, an exogenous P adsorption and culture experiment was conducted to study the P desorption process and characters in the tea tree rhizosphere soils having been cultivated for different years and derived from different parent materials. The least squares method was used to fit the isotherms of P desorption kinetics. There was an obvious difference in the P desorption process between the rhizosphere soils and non-rhizosphere soils. The P desorption ability of the rhizosphere soils was significantly higher than that of the non-rhizosphere soils. As compared with non-rhizosphere soils, rhizosphere soils had higher available P content, P desorption rate, and beta value (desorbed P of per unit adsorbed P), with the average increment being 5.49 mg x kg(-1), 1.7%, and 24.4%, respectively. The P desorption ability of the rhizosphere soils derived from different parent materials was in the order of granite > quaternary red clay > slate. The average available P content and P desorption ability of the rhizosphere soils increased with increasing cultivation years. PMID- 24175513 TI - [Biological soil crust nitrogenase activity and its responses to hydro-thermic factors in different erosion regions on the Loess Plateau, China]. AB - Based on field survey, the biological soil crusts at their stable development stage were collected from the water erosion region, water-wind erosion region, and wind erosion region on the Loess Plateau, aimed to study the effects of the variations of moisture and temperature on the crusts nitrogenase activity (NA). The NA of the crusts in the erosion regions decreased in the order of water erosion region (127.7 micromol x m(-2) x h(-1)) > water-wind erosion region (34.6 micromol x m(-2) x h(-1)) > wind erosion region (6.0 micromol x m(-2) x h(-1)), and the optimal temperature for the crust nitrogen fixation was 35 degrees C, 25 degrees C, and 15 degrees C, respectively. At the optimal temperature and 100% 40% field water-holding capacity, the NA of the crusts from the water erosion and water-wind erosion regions had no significant difference. The NA of the crusts from the wind erosion region was more sensitive to the variation of moisture, showing a dramatic decline when the moisture decreased to 80% field water-holding capacity, and totally lost when the moisture decreased to 20% field water-holding capacity. The differences in the NA of the crusts from the three erosion regions and the responses of the NA to the variations of moisture and temperature were likely associated with the climate, environment, and the crust species composition. PMID- 24175514 TI - [Using 137Cs and 210Pb(ex) to trace the impact of soil erosion on soil organic carbon at a slope farmland in the black soil region]. AB - Soil cores were collected from a 28.5 hm2 slope farmland in the black soil region of Northeast China. Based on the sampled data of 137Cs, 210Pb(ex) and SOC, the potentials of applying 137Cs and 210Pb(ex) for assessing SOC redistribution were evaluated, aimed to approach the impact of soil erosion on soil organic carbon (SOC) in black soil region. At both planar and vertical directions, the 137Cs, 210Pb(ex) and SOC in the farmland had similar distribution patterns. Although there were large planar variations in the 137Cs and 210Pb(ex) areal activities and the SOC stock as affected by soil erosion and deposition, the 137Cs, 210Pb(ex) and SOC had similar changing trends over the landscape. Two depth distribution profiles were also used to study the relations of 137Cs and 210Pb(ex) with SOC. At eroded site, the radioactivities of 137Cs and 210Pb(ex) and the SOC mass fraction did not show large variations in 0-25 cm soil layer, but decreased sharply below 25 cm. For the deposition sample, the radioactivities of 137Cs and 210Pb(ex) in 0-100 cm soil increased firstly and then decreased. The SOC mass fraction also had similar depth distribution pattern in this soil layer. The 137Cs and 210Pb(ex) presented positive linear correlations with the SOC, indicating that 137Cs, 210Pb(ex) and SOC moved with the same physical mechanism in the farmland, and fallout 137Cs and 210Pb(ex) could be used to study spatio temporal distribution characteristics of SOC in the black soil region under the condition of soil erosion. PMID- 24175515 TI - [Effects of irrigation quota on moisture and salt redistribution in apple orchard soil in arid region]. AB - Taking the salinized apple orchard soil in Qin'an County of Gansu Province, Northwest China as test object, a field experiment was conducted to study the effects of different irrigation quota (0, 900, 1800, 2700, and 3600 m3 x hm(-2)) on the redistribution of moisture and salt in 0-100 cm soil profile on the 10, 20, and 30 d during apple florescence stage. With the increase of irrigation quota, the leached depth of Na+ increased and its hysteretic effect of redistribution was more obvious, "the zero flux plane" of Ca2+ disappeared gradually, the scope of "the zero flux plane" of Mg2+ increased gradually, the leaching-migration mode of Cl- changed from "fluctuation" to "straight-line" and the evaporation-migration changed from "fluctuation" to "ladder", the redistribution pattern of SO4(2-) showed "point", and the position of redistribution and accumulation of HCO3- shifted gradually from the bottom to upper layer in soil profile. In the middle of the soil profile with deeper groundwater table, there existed a "zero flux plane" of salt, which shifted gradually from the upper layer to the bottom during the redistribution of moisture in soil profile, embodying the characteristics of moisture depletion in upland soils. When the irrigation quota was between 2700 and 3600 m3 x hm(-2), irrigation was helpful to the leaching of salt and water-soluble Na+ in the 0-100 cm soil profile. However, when the irrigation quota was < 1800 m3 x hm(-2), irrigation accelerated the salt accumulation in surface soil. Therefore, from the viewpoints of salt leaching and water-saving, an irrigation quota of 1800-2700 m3 x hm(-2) in spring would be more appropriate for the salinized apple orchard soil in arid regions. PMID- 24175516 TI - [Effects of irrigation and planting pattern on winter wheat water consumption characteristics and dry matter production]. AB - Taking high-yield winter wheat cultivar 'Jimai 22' as test material, a field experiment was conducted in 2008-2010 to study the effects of different irrigation and planting modes on the water consumption characteristics and dry matter accumulation and distribution of winter wheat. Three planting patterns (uniform row, wide-narrow row, and furrow) and four irrigation schedules (no irrigation, W0; irrigation at jointing stage, W1; irrigation at jointing and anthesis stages, W2; and irrigation at jointing, anthesis, and milking stages, W3; with 60 mm per irrigation) were installed. With increasing amount of irrigation, the total water consumption and the ratio of irrigation water to total water consumption under different planting patterns all increased, while the soil water consumption and its ratio to total water consumption decreased significantly. As compared with W0, the other three irrigation schedules had a higher dry matter accumulation after anthesis and a higher grain yield, but a lower water use efficiency (WUE). Under the same irrigation schedules, furrow pattern had higher water consumption ratio, grain yield, and WUE. Taking the grain yield and WUE into consideration, furrow pattern combined with irrigation at jointing and anthesis stages would be the optimal water-saving and planting modes for the winter wheat production in North China Plain. PMID- 24175517 TI - [Effects of source-sink regulation on water soluble carbohydrates of vegetative organs and thousand-grain mass of wheat under different water conditions]. AB - Two winter wheat cultivars with different drought tolerance were selected to investigate the effects of source-sink regulation on the vegetative organs water soluble carbohydrates (WSC) content and 1000-grain mass (TGM) of wheat under drought stress (DS) and well watered (WW) conditions. Sink-cutting increased the WSC content of different vegetative organs significantly, and promoted the relative transportation of the WSC positively; while source-cutting caused opposite responses. The effects of source-sink regulation on the WSC content and its relative transportation amount (TA) and transportation rate (TR) were significantly higher under DS and sink-cutting than under WW and source-cutting, for drought-resistant cultivar (Longjian 19) than for drought-sensitive Q9086, and for peduncle internode and PedI than for penultimate internode and PenI. Under source-cutting, the superior organs of Longjian 19 in the TR of total WSC were sheath, PedI, and PenI, which also contributed to the fructan TR of the two cultivars, while those of Q9086 were the PenI and the third internode from top (ThiI). Source-cutting decreased the TGM of Longjian 19 and Q9086 significantly, with the decrement being 27.3% and 31.7% under DS and 25.3% and 12.1% under WW, respectively. The correlation coefficients of the WSC content and its TA and TR and the TGM were significantly higher under sink-cutting than under source cutting, and also, under DS than under WW. There existed a higher correlation coefficient (r2 > 0.900) of the TGM and the total WSC and fructan contents in different vegetative organs. The vegetative organs with closer correlation between their WSC content and its TA and TR and the TGM were mainly sheath and PedI. Under DS, the traits associated with the total WSC content had a higher correlation with TGM; under WW, the traits associated with sucrose and glucan contents generally showed a higher correlation with TGM. It was suggested that the effects of source-sink regulation on the WSC content of vegetative organs and the TGM were significantly affected by soil water environment, wheat genotype, and vegetative organs location. PMID- 24175518 TI - [Change characteristics of rice yield and soil organic matter and nitrogen contents under various long-term fertilization regimes]. AB - A long-term (1982-2010) field experiment was conducted in the Red Soil Experiment Station of Chinese Academy of Agricultural Sciences in Qiyang County of Hunan Province, South-central China to investigate the dynamic changes of rice yield and soil organic matter (OM) and nitrogen contents under different fertilization treatments. The treatments included NPK, NPKM (M: manure), NPM, NKM, PKM, M, and CK. Fertilization increased the soil OM, total N, and alkaline-hydrolysable N contents and the rice yield. In treatment NPKM, the rice yield across the 28 years maintained at the highest level; while in treatment NPK, the yield showed a decreasing trend, being lower than that in other fertilization treatments. In the treatments applied with manure only or in combining with chemical fertilizers, the soil OM content increased rapidly in the first 16 years, and then fluctuated around a constant level (29.42-39.32 g x kg(-1)). In the treatments of chemical fertilization, the soil OM content only had a quicker increase in the first 8 years, and then fluctuated within a relatively stable range. Fertilization with manure increased the soil OM significantly, as compared to fertilization with chemical fertilizers only. The soil total N content in all fertilization treatments showed a rapid increase in the first 8 years, and the increment was the highest in treatment NPKM. The soil alkaline-hydrolysable N content in all fertilization treatments had a slower increase in the first 12 years, with an average annual increment of 0.66-2.25 mg x kg(-1) x a(-1). In 1994-1998, the soil alkaline-hydrolysable N content in fertilization treatments had a quicker increase, with an average annual increment of 6.45-32.45 mg x kg(-1) x a(-1); but after 1998, the soil alkaline-hydrolysable N content had a slight decrease. It was concluded that organic fertilization was the key measure to stably improve the physical and chemical properties and the productivity of red paddy soils by increasing their OM and nitrogen contents, and to sustain the rice production in red soil region in subtropical China. PMID- 24175519 TI - [Effects of low temperature stress on photosynthetic performance of different genotypes wheat cultivars]. AB - Different genotypes wheat cultivars (spring wheat Yangmai 18, semi-spring wheat Zhengmai 9023, and semi-winter wheat Yannong 19) were chosen to study their photosynthetic and chlorophyll fluorescence characteristics at tillering and stem elongation stages under low temperature stress. After treated with low temperature (-10 degrees C at night) at tillering stage for 2 days, the net photosynthetic rate (Pn), stomata conductance (g(s)), maximum quantum yield of PSII (Fv/Fm), photochemical quenching (q(P)), non-photochemical quenching coefficient (NPQ), and acyclic photosynthetic electron transfer rate of PSII (ETR) of Yannong 19 were significantly higher than those of Yangmai 18 and Zhengmai 9023, the g(s), Fv/Fm, qP, and NPQ of Zhengmai 9023 were significantly higher than those of Yangmai 18, while the intercellular CO2 concentration (Ci) of Yannong 19 was significantly lower than that of Zhengmai 9023 and Yangmai 18. In addition, the minimal fluorescence (Fo) of Yangmai 18 was significantly higher than that of Zhengmai 9023 and Yannong 19. Similarly, after treated with low temperature (0 degrees C at night) at stem elongation stage for 3 days, the Pn, g(s), qP, and Fv/Fm of Yannong 19 were significantly higher than those of Yangmai 18 and Zhengmai 9023, and the NPQ and ETR of Yannong 19 were significantly higher than those of Yangmai 18. In addition, the Pn, g(s), Fv/Fm, and qP of Zhengmai 9023 were significantly higher than those of Yangmai 18, the Fo of Zhengmai 9023 was significantly higher than that of Yannong 19, and the Ci and Fo of Yangmai 18 were significantly higher than those of Zhengmai 9023 and Yannong 19. It was suggested that under low temperature stress at tillering and stem elongation stages, semi-winter wheat Yannong 19 had the highest photosynthetic activity and the best self-protection mechanism, followed by semi-spring wheat Zhengmai 9023, and spring wheat Yangmai 18. PMID- 24175520 TI - [Effects of tillage patterns on photosynthetic and chlorophyll fluorescence characteristics of maize in rainfed area of Northeast China]. AB - In 2010-2011, a field experiment was conducted in Northeast China to evaluate the effects of different tillage patterns on the temperature and moisture in topsoil layer and the leaf photosynthesis and chlorophyll fluorescence of maize. The effects of tillage patterns on the soil temperature and moisture mainly manifested at sowing-jointing stage. In treatments flat planting with ridging at early jointing stage (PL) and flat planting without ridging (PP), the soil moisture content at the depth of 0-40 cm was significantly higher than that in treatment ridge planting (LL), with the increment being 5.6% and 5.2%, 4.6% and 7.3%, and 3.9% and 4.8% at emergency, seedling, and jointing stages, respectively. The minimum temperature at the soil depth 5 cm at seedling stage in PL and PP was 1.4 and 1.3 degrees C higher than that in LL, respectively. Due to the improvement of soil water and thermal conditions, the leaf photosynthetic rate (Pn) and transpiration rate (Tr) at jointing stage in PL and PP were significantly higher than those in LL, whereas the PS II potential activity (Fv/Fo) and PS II maximal photochemical efficiency (Fv/Fm) had no significant differences among the treatments, indicating that the stomatal factors such as stomata conductivity and stomata limitation were the main factors inducing the photosynthesis differences among the treatments. Furthermore, the Pn and Tr at grain filling stage in LL and PL were higher than those in PP, mainly due to the high water-logging risk in PP in strong rainfall season. Consequently, treatment PL could promote maize photosynthesis through improving soil water and thermal conditions, and further, increase maize grain yield. PMID- 24175521 TI - [Dynamics of Cry1ab protein content in the rhizosphere soil and straw debris of transgenic Bt corn]. AB - By using ELISA test kits, a field investigation was conducted on the degradation dynamics of CrylAb protein in the rhizosphere soil of Bt corn MON810 at its different growth stages and in the MON810 straws returned into field after harvest. Three models (shift-log model, exponential model, and bi-exponential model) were used to fit the degradation dynamics of the Cry1 Ab protein from the straw debris, and the DT50 and DT90, values were estimated. There existed great differences in the CrylAb protein content in the rhizosphere soil of MON810 at its different growth stages, but overall, the CrylAb protein content was decreased remarkably with the growth of MON810. The degradation of Cry1 Ab protein from the straws covered on soil surface and buried in soil showed the same two-stage pattern, i.e., more rapid at early stage and slow-stable in later period. Within the first week after straw return, the degradation rate of the CrylAb protein from the straws covered on soil surface was significantly higher than that from the straws buried in soil. At 10 d, the degradation rate of the CrylAb protein from the straws covered on soil surface and buried in soil was basically the same, being 88.8% and 88.6%, respectively. After 20 days, the degradation of CrylAb protein entered slow-stable stage. Till at 180 d, a small amount of Cry1Ab protein could still be detected in the straw debris. All of the three models used in this study could fit the decay pattern of the CrylAb protein from the straw debris in field. By comparing the correlation coefficient (r) and the consistency between the measured and calculated DT90, bi-exponential model was considered to be the best. PMID- 24175522 TI - [Evaluation of cucumber' s chilling tolerance at germination and seedling stages]. AB - A total of 13 cucumber materials were used to study the relationships of cucumber's chilling tolerance with the 12 growth indices at germination and seedling stages. There existed significant differences in the relative germination rate, germination index, hypocotyl length, and vigor index at 17 degrees C among the 13 materials (P < 0.05), which also significantly correlated to the chilling tolerance. At seedling stage, the physiology among the materials after treated at 4 degrees C for 2 days had obvious difference. Chilling injury index had significant correlation with the survival rate after recovery, but less correlation with the soluble protein (SP) content, electric conductivity (EC), and superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activities. The chilling tolerance of the materials was classified into three levels by clustering analysis, and the cucumber' s chilling tolerance equations at the two stages were established through stepwise regression analysis. Based on confidence interval value, the chilling tolerance of cucumber could be well assessed. PMID- 24175523 TI - [Effects of different nitrogen forms and their ratios on broccoli yield, quality, and nutrient absorption]. AB - A field experiment was conducted to study the effects of different nitrogen forms ((NH2)2CO-N, NO(3-)-N, NH(4+)-N, and NO(3-)-NH4+) and their ratios on the yield formation, quality, and nutrient (N, P, and K) absorption of broccoli (Brassica oleracea). Fertilization with NO(3-)-N increased the accumulation of nitrate and soluble sugars in ball flower. When the NO(3-)-N: NH(4+)-N ratio was ranged from 3:7 to 5:5 and from 5:5 to 7:3, respectively, the accumulation of nitrate in the ball flower was reduced, while the soluble sugars content was promoted. Fertilization with (NH2)2CO-N and NH(4+)-N was conducive to the improvement of Vc content in the ball flower. N fertilization increased the accumulation of N, P, and K in plants, with the highest contents of N, P, and K observed at rosette stage. Throughout the entire growth period, NH(4+)-N fertilization improved the plant N content, whereas NO(3-)-N fertilization improved the plant K content. At different growth stages, the effects of different N sources on plant P content varied. As compared with applying single N forms, the NO(3-)-N:NH(4+)-N ratio ranged from 3:7 to 5:5 could improve the yield significantly. It was suggested that a combined application of NO(3-)-N and NH(4+)-N with an appropriate ratio could improve the productivity, quality, and economic return of broccoli. PMID- 24175524 TI - [Effects of applying pig manure on lettuce yield and nitrate content and soil nutrients]. AB - A pot experiment with two representative soils (purple soil and yellow soil) in Southwest China was conducted to study the effects of applying pig manure on the lettuce (Lactuca sativa L. var. capitata L. ) yield and nitrate content and the soil nutrients. Applying pig manure increased the lettuce yield significantly, and the increment was higher for yellow soil than for purple soil. The nitrate and total nitrogen, phosphorus, and potassium contents in lettuce plants were closely related to soil type and pig manure application rate. According to the evaluation standards of the nitrate pollution level of vegetables formulated by the Chinese Academy of Agricultural Sciences, the nitrate content in lettuce plants growing on purple soil was lower than the grade I (< or = 432 mg x kg(-1), slight pollution) in treatments CK (no pig manure application) and M1 ( applying 200 kg N x hm(-2) of pig manure), but generally higher than the grade II (< or = 758 mg x kg(-1), moderate pollution) while not exceeded the grade III (< or = 1440 mg x kg(-1), heavy pollution) in other treatments. The nitrate content in lettuce plants growing on yellow soil was lower than the grade I, except that in the treatments of chemical fertilizations and of M8 (applying 1600 kg N x hm(-2) of pig manure) where the plant nitrate content was exceeded the grade II. The critical value of Olsen-P characterizing the apparent leaching risk level of phosphorous in yellow soil and purple soil was 96.3 and 107.7 mg x kg(-1), respectively. The environmental safety capacity of pig manure was higher for yellow soil than for purple soil. Applying pig manure increased the organic carbon and total nitrogen contents of the two soils significantly. PMID- 24175525 TI - [Estimation model for daily transpiration of greenhouse muskmelon in its vegetative growth period]. AB - For developing an estimation method of muskmelon transpiration in greenhouse, an estimation model for the daily transpiration of greenhouse muskmelon in its vegetative growth period was established, based on the greenhouse environmental parameters, muskmelon growth and development parameters, and soil moisture parameters. According to the specific environment in greenhouse, the item of aerodynamics in Penman-Monteith equation was modified, and the greenhouse environmental sub-model suitable for calculating the reference crop evapotranspiration in greenhouse was deduced. The crop factor sub-model was established with the leaf area index as independent variable, and the form of the model was linear function. The soil moisture sub-model was established with the soil relative effective moisture content as independent variable, and the form of the model was logarithmic function. With interval sowing, the model parameters were estimated and analyzed, according to the measurement data of different sowing dates in a year. The prediction accuracy of the model for sufficient irrigation and water-saving irrigation was verified, according to measurement data when the relative soil moisture content was 80%, 70%, and 60%, and the mean relative error was 11.5%, 16.2% , and 16.9% respectively. The model was a beneficial exploration for the application of Penman-Monteith equation under greenhouse environment and water-saving irrigation, having good application foreground and popularization value. PMID- 24175526 TI - [Branch growth of Korean pine plantation based on nonlinear mixed model]. AB - Based on the branch analysis data from 36 sample trees in a Korean pine plantation in Mengjiagang Forest Farm of Heilongjiang Province, Northeast China, and by using Mitcherlich and Richards equations as the models of branch diameter and branch length growth, respectively, the effects of sampling plot and sample tree were investigated, and the nonlinear mixed models of branch diameter and branch length growth were established by the PROC NLMIXED procedure of SAS software. The evaluation statistics such as Akaike information criterion (AIC), Bayesian information criterion (BIC), -2Log likelihood, and likelihood ratio test (LRT) were used to compare the prediction precisions of the models. When considering plot effect, and taking alpha1 and alpha3 and beta1 and beta3 as the random parameters, respectively, the models of branch diameter and branch length growth had the best performance. When considering tree effect, and taking alpha2 and alpha3 and beta2 and beta3 as the random parameters, respectively, the models of branch diameter and branch length growth had the best performance. The nonlinear mixed model could not only reflect the mean variation of branch growth, but also show the differences among the individual trees. No matter considering plot effect or tree effect, the fitting precision of the nonlinear mixed model was better than that of the ordinary regression analysis model. Moreover, the fitting precision of the nonlinear mixed model was better when considering tree effect than considering plot effect. PMID- 24175527 TI - [Relationships between river water quality and land use type at watershed scale]. AB - Based on the remote sensing images of 54 water quality monitoring stations within the Suzi River watershed, the riparian buffer zones at 6 scales were constructed by ArcGIS, and the 8 landscape indices at landscape and class levels were calculated with FRAGSTATS software. A correlation analysis on the landscape indices and river water quality was made from the viewpoints of landscape space pattern and composition. In the watershed, the landscape pattern in different riparian buffer zones had different effects on the river water quality. When the distance of the buffer zones was less than 300 m, the main landscape types were dry land, construction land, and paddy filed, and their area ratio, patch number, patch density, maximum patch index, maximum shape index, and aggregation index were higher. In these buffer zones, farmlands had higher connectedness, and thus, had greater effects on the river water quality. When the distance of the buffer zones was more than 300 m, forest land had a larger area ratio and a higher connectedness, which would benefit the improvement of river water quality to some extent. In the watershed, farmland and construction land played a key role in affecting the river water quality. PMID- 24175528 TI - [Spatiotemporal distribution characteristics and causes of sunny days' heat island effect in Chengdu City of Southwest China]. AB - Based on 99 clear sky Terra satellite images of Chengdu City in 2005-2010, and by using a novel automatic extraction method of suburb temperature, i. e., each city circle temperature jump, this paper studied the spatiotemporal variation characteristics of the urban heat island (UHI) effect in the City in 2005-2010, and analyzed the causes of the variation characteristics. In the study period, the central area of the largest and strongest UHI was in the Jinhua Town located in the southwest of Chengdu. The UHI effect had no significant spatial variation, but the range and intensity of the UHI effect tented to be decreased. The intra annual UHI intensity and area within the ring roads showed a three-peak distribution pattern, with the peak values appeared in April, July, and October, and the intensity reached the maximum in July. The UHI intensity in Chengdu was attenuated by the decrease of air temperature and the increase of precipitation and urban vegetation cover. PMID- 24175529 TI - [Spatiotemporal patterns and driving forces of land use change in industrial relocation area: a case study of old industrial area in Tiexi of Shenyang, Northeast China]. AB - Based on the QuickBird remote sensing images and with the support of GIS, this paper analyzed the spatiotemporal characteristics of land use change and its driving forces in old industrial area of Tiexi, Shenyang City of Liaoning Province in 2000-2010. During the study period, the industrial and mining warehouse land pattern had the greatest change, evolving from the historical pattern of residential land in the south and of industrial land in the north into residential land as the dominant land use pattern. In the last decade, the residential land area increased by 9%, mainly transferred from the industrial and mining warehouse land located in the north of Jianshe Road, while the industrial and mining warehouse land area decreased by 20%. The land areas for the commercial service and for the administrative and public services were increased by 1.3% and 3.1%, respectively. The land area for construction had a greater change, with an overall change rate being 76.9%. The land use change rate in 2000 2005 was greater than that in 2005-2010. National development strategies and policies, regional development planning, administrative reform, and industrial upgrading were the main driving forces of the land use change in old industrial area of Tiexi. PMID- 24175530 TI - [Relationships between settlement morphology transition and residents commuting energy consumption]. AB - Settlement morphology transition is triggered by rapid urbanization and urban expansion, but its relationships with residents commuting energy consumption remains ambiguous. It is of significance to understand the controlling mechanisms of sustainable public management policies on the energy consumption and greenhouse gases emission during the process of urban settlement morphology transition. Taking the Xiamen City of East China as a case, and by using the integrated land use and transportation modeling system TRANUS, a scenario analysis was made to study the effects of urban settlement morphology transition on the urban spatial distribution of population, jobs, and land use, and on the residents commuting energy consumption and greenhouse gasses emission under different scenarios. The results showed that under the Business As Usual (BAU) scenario, the energy consumption of the residents at the morning peak travel time was 54.35 tce, and the CO2 emission was 119.12 t. As compared with those under BAU scenario, both the energy consumption and the CO2 emission under the Transition of Settlement Morphology (TSM) scenario increased by 12%, and, with the implementation of the appropriate policies such as land use, transportation, and economy, the energy consumption and CO2 emission under the Transition of Settlement Morphology with Policies (TSMP) scenario reduced by 7%, indicating that urban public management policies could effectively control the growth of residents commuting energy consumption and greenhouse gases emission during the period of urban settlement morphology transition. PMID- 24175531 TI - [Effects of precipitation variation on the distribution pattern of soil fungal diversity in broad-leaved Korean pine mixed forest]. AB - Broad-leaved Korean pine mixed forest is a kind of zonal climax vegetation with ecological significance in Northeast China, whereas Changbai Mountain is an ideal area to study the effects of precipitation variation on temperate forest. Taking the virgin broad-leaved Korean pine mixed forest in Changbai Mountain as the object, and based on T-RFLP method, this paper analyzed the spatial heterogeneity of fungal diversity in 0-5 cm and 5-10 cm soil layers and in rhizosphere soil at three different precipitation plots (30% increase, 30% decrease, and the control). Both the increase and the decrease of precipitation increased the diversity of soil fungi, but the dominant population changed. In 0-5 cm and 5-10 cm soil layers, the T-RFs over 500 bp increased with precipitation; in rhizosphere soil, the T-RFs responded to precipitation variation were 380 bp, 455 bp, and 487 bp, and the response mode was more complicated than that in surface soil layers. The results of CCA showed that the fungal community composition was significantly affected by soil pH, organic carbon, total nitrogen, and organic phosphorus. PMID- 24175532 TI - [Microecological mechanisms of red-leaf disease occurrence in Salvia miltiorrhiza Bge]. AB - A comparative study was made on the nutrient content in rhizosphere soil and the microflora in rhizosphere soil and on rhizoplane of healthy and red-leaf diseased Salvia miltiorrhiza plants, aimed to approach the microecological mechanisms of red-leaf disease occurrence in S. miltiorrhiza. The N, P, K, and Mn contents in the diseased plant leaves were significantly lower than those in the healthy plant leaves (P < 0.05). No significant difference was observed in the available P content in the rhizosphere soils of diseased and healthy S. miltiorrhiza, but the available N and K contents were significantly higher (P < 0.05) in the rhizosphere soil of diseased S. miltiorrhiza. These results indicated that the red-leaf disease occurrence in S. miltiorrhiza was related to plant P deficiency, but the lack of P in the plants was not caused by the insufficient soil P supply. As compared with those in healthy S. miltiorrhiza rhizosphere, the bacterial number in diseased S. miltiorrhiza rhizosphere soil decreased by 41.3% , while the fungal and actinomycetes numbers increased by 156.6% and 189.5% (P < 0.05), respectively. Similar variations in the numbers of bacteria, fungi, and actinomycetes were observed on diseased S. miltiorrhiza rhizoplane. In the rhizosphere soil and on the rhizoplane of diseased S. miltiorrhiza, the predominant microbial species that might be harmful included six fungi (Fusarium solani, Myrothecium roridum, F. tricinctum, Aspergillus calidoustus, F. oxysporum, and Dothideomycetes sp.), four actinomycetes (Streptomyces lateritius, Lentzea waywayandensis, S. stelliscabiei and S. collinus), and two bacteria (Bacillus aryabhattai and Piscinibacter aquaticus). These predominant soil microbes likely caused plant P deficiency via negatively affecting the growth of roots and their absorption of soil nutrients. It was suggested that the red-leaf disease occurrence in S. miltiorrhiza was closely related to the plant P deficiency caused by the abnormality of soil microflora in the rhizosphere soil and on the rhizoplane of S. miltiorrhiza. PMID- 24175533 TI - [Host preference and fitness of aphis citricola (Hemiptera: Aphididae) to mature and young apple leaves]. AB - In order to understand the differences of Aphis citricola in its original and final selectivity to the apple leaves with different leaf age, and to ascertain the effects of mature and young apple leaves on the growth and development, survival, and fecundity of A. citricola, this paper studied the host preference of A. citricola to mature and young apple leaves, with the related age-stage two type life tables constructed. A. citricola more preferred to oviposit on the young leaves. There existed differences in the behaviors between oriented selectivity and penetration selectivity, and the latter was the key factor determining whether A. citricola fed and oviposited on the host. The total development time of immature A. citricola on the mature leaves was significantly longer than that on the young leaves, and the survival rate was also lower, with the aphids died at the first and fourth instar stages and at mature stage. As compared with those on the young leaves, the apterae rate of A. citricola adults on the mature leaves was lower, and the longevity and fecundity were significantly shorter and lower. The population dynamic parameters suggested that the population growth of A. citricola was quicker on the young leaves than on the mature leaves, and it was difficult for A. citricola to establish a stable population on the mature leaves. PMID- 24175534 TI - [Stock assessment and management for Illex argentinus in Southwest Atlantic Ocean based on Bayesian Schaefer model]. AB - Abstract: Bayesian Schaefer model was applied to assess the stock of Illex argentinus in the Southwest Atlantic Ocean, with the risk of alternative management strategies for the squid analyzed. Under the scenarios of normal and uniform prior assumptions, the estimated model parameters and reference points were similar, and higher than the values under the scenario of logarithmic normal prior assumption. Under the three proposed scenarios, the fishing mortalities and the total catches in 2001-2010 were lower than the reference point F0.1 and the maximum sustainable yield (MSY), indicating that the I. argentinus was in an expected sustainable exploited level but not in over-fishing and over-fished. The results of decision analysis indicated that at the same harvest rate, the stock of the I. argentinus under the scenario of logarithmic normal prior assumption in 2025 would be the lowest, and the probability of collapse would be the highest. Under the three scenarios, the harvest rate in 2025 would be all 0.6 if the catch was the maximum. However, if the harvest rate was set to 0.6, the stock of the I. argentinus after 2025 would have definite risk, and thus, the harvest rate 0.4 and the catch 550000 t appeared to be the best management regulation or the baseline case. PMID- 24175535 TI - [Feeding habits of Trachurus japonicus in the East China Sea]. AB - A total of 453 Trachurus japonicus specimens with a fork length (FL) of 46-250 mm were sampled in the seasonal light seine net surveys in the East China Sea in May, August, and November, 2008 and in February, 2009. The stomach contents of the specimens were analyzed, and the seasonal and ontogenetic variations in the feeding habits of the T. japonicus were examined by the Kruskal-Wallis test, chi squared test, and cluster analysis. There were 124 prey species (including not identified) ingested by the T. japonicus, among which, planktonic crustaceans and small-scale marine fish made up the dominant prey groups. According to the percentage index of relative importance (IRI%), Bregmaceros macclellandi was the most dominant prey, accounting for 39.2%, followed by Macrura mysis larva (18.4%), brachyura zoea larva (7.6%), and Euphausia pacifica (6.6%). The feeding intensity of the T. japonicus varied significantly with its FL and season, being the highest for the T. japonicus with a FL of 140-159 mm, higher for the T. japonicus juveniles with a FL of 45-99 mm, while lower for the T. japonicus of other size classes, and the highest in spring and the lowest in winter. Cluster analysis revealed there was an abrupt change in the diet composition for the T. japonicus with a FL of about 100 mm FL. The average trophic level of the T. japonicus in four seasons was 3.51, indicating that the T. japonicus in the East China Sea was of low-level carnivores feeding on plankton and nekton. PMID- 24175536 TI - [Effects of aging time on the form transformation and eco-toxicity threshold (ECx) of added Zn in typical China soils]. AB - Six typical China soils with different properties were selected and added with seven concentrations of ZnCl2 to study the effects of different aging time (14, 90, 180, 360, and 540 days) on the form transformation and eco-toxicity threshold (ECx) of added Zn in the soils, with the main affecting factors analyzed. The results indicated that with the increase of aging time, the fraction of 0.01 mol x L(-1) CaCl2-extracted Zn in the soils decreased sharply initially, then slowed down, and reached the dynamic balance after 540 d incubation. The eco-toxicity thresholds (ECx, x = 10, 50) of Zn to bok choy increased significantly with aging time (P < 0.05), which implied the marked decrease of the phyto-toxicity of Zn. The measured aging factors AF10 and AF50 of Zn ranged from 1.077-1.743 and 1.174 1.441, respectively, and increased with aging time. The balanced concentration of Zn in the soils was significantly negatively correlated with soil pH, CEC, and organic carbon (Org-C) content, and soil pH was the most important controlling factor, followed by CEC and Org-C. It took shorter time to reach Zn balance in the soils with higher pH. The prediction model of the ECx of Zn was developed based on the aging factors and the main soil properties, and could be well validated by the measured ECx under field condition. This study would provide theoretical basis for the normalization of the eco-toxicity thresholds of added Zn in different soils and the formulation of the environmental criterion of Zn in China soils. PMID- 24175537 TI - [Ecological characteristics of Zostera japonica population in Swan Lake of Rongcheng, Shandong Province of China]. AB - In this study, a large area of well preserved Zostera japonica dominated meadow was found in a coastal lagoon, Swan Lake, in Rongcheng of Shandong Province. Due to its unique geographical position and high biomass, this meadow may act as a typical Z. japonica bed in the coastal area of Shandong. From September, 2011 to October, 2012, an annual investigation was conducted on the Z. japonica and its habitats in east coast of Swan Lake, and the distribution of the Z. japonica and its habitats ecological characteristics were preliminarily understood. The major ingredients of sediments particles in the Z. japonica bed was sand (81%) and silt (14%). The C and N contents in the sediments were the highest in winter, and the C/N ratio was the highest in autumn. The shoot density, shoot height, and biomass of the Z. japonica were all significantly correlated with water temperature (P < 0.05). There was an obvious change in the Z. japonica growth among seasons, with the peak biomass obtained in August-September. The C and N contents and C/N in Z. japonica leaves also varied with seasons. The leaf C content was significantly higher in autumn than in spring and summer (P < 0.05), the leaf N content was significantly lower in summer than in spring and autumn (P < 0.01), whereas the leaf C/N ratio was significantly higher in summer than in spring (P < 0.05). The annual carbon sequestration by the Z. japonica in the Swan Lake was estimated to be 111.4 g C x m(-2). PMID- 24175538 TI - [Deposition and burial of organic carbon in coastal salt marsh: research progress]. AB - Coastal salt marsh has higher potential of carbon sequestration, playing an important role in mitigating global warming, while coastal saline soil is the largest organic carbon pool in the coastal salt marsh carbon budget. To study the carbon deposition and burial in this soil is of significance for clearly understanding the carbon budget of coastal salt marsh. This paper summarized the research progress on the deposition and burial of organic carbon in coastal salt marsh from the aspects of the sources of coastal salt marsh soil organic carbon, soil organic carbon storage and deposition rate, burial mechanisms of soil organic carbon, and the relationships between the carbon sequestration in coastal salt marsh and the global climate change. Some suggestions for the future related researches were put forward: 1) to further study the underlying factors that control the variability of carbon storage in coastal salt marsh, 2) to standardize the methods for measuring the carbon storage and the deposition and burial rates of organic carbon in coastal salt marsh, 3) to quantify the lateral exchange of carbon flux between coastal salt marsh and adjacent ecosystems under the effects of tide, and 4) to approach whether the effects of global warming and the increased productivity could compensate for the increase of the organic carbon decomposition rate resulted from sediment respiration. To make clear the driving factors determining the variability of carbon sequestration rate and how the organic carbon storage is affected by climate change and anthropogenic activities would be helpful to improve the carbon sequestration capacity of coastal salt marshes in China. PMID- 24175539 TI - [Adaptation mechanisms of alpine plants photosynthetic apparatus against adverse stress: a review]. AB - Photosynthesis is one of the vital physiological processes easily affected by environmental changes. As a plant group growing in specific low temperature and strong irradiance environment, the photosynthetic apparatus of alpine plants have developed special morphologically and physiologically mechanisms in adapting to this extreme adverse environment. However, due to the high heterogeneity of habitats, there exist great differences in the photo-protection and adaptation mechanisms among different alpine plants. This paper reviewed the recent researches about the morphology and ultramicro-anatomical structure of the chloroplasts in photosynthetic apparatus of alpine plants and the photo protection and adaptation mechanisms of the plants, and proposed the further research directions on the physiological adaptation of the photosynthesis of alpine plants. PMID- 24175540 TI - [Effects of forest ownership regime on landscape pattern and animal habitat: a review]. AB - In some European and North American countries where forestry is highly developed, both public and private forest ownership regimes have being existed for a long time. Currently, the researches about both the dynamics of forest landscape and habitat pattern and the relationship between habitat pattern and biological conservation in multi-ownership forest landscape are increasingly becoming important. This paper reviewed the effects of multi-ownership regime on forest landscape pattern and animal habitat and emphasized on the ecological consequences of forest parcelization and land divestiture, including the provision of diverse habitats and fragmentation of the existing large-area habitat. This paper also summarized two ways (changing the ownership pattern and integrating the multi-ownership management by cross boundary coordination) for handling the conflicts between small-scaled multi-ownership management and biological conservation at large scale in forestry-developed countries and analyzed the reasons that those countries prefer to adopt the latter one. Furthermore, the methodological limitations in simulating ownership pattern were pointed out. Finally, the present status, challenges and opportunities in the above-mentioned research issues in China were discussed, and the suggestions for further researches were provided. PMID- 24175541 TI - [Assessment system for watershed ecological health in the United States: development and application]. AB - To meet the water quality goals of the Clean Water Act, the environmental agencies in the United States (U.S.) have developed a comprehensive ecological assessment system of watershed health in the last two decades. The system employs a watershed approach, and includes a large set of hydrological, chemical, and biological indices, having become an essential part of the watershed water quality management system in the U.S. and provided strong support for the protection of water environment and the restoration of aquatic system. In this paper, the development and application of the ecological assessment system of watershed health by the U.S. environmental regulators, especially the U.S. Environmental Protection Agency (US EPA), were overviewed from the aspects of related laws and regulations, ecosystem function analysis, ecological health indicators, comprehensive assessment system, and monitoring and data management systems, and the health assessment systems for the rivers, lakes, estuaries, coasts, and wetlands adopted by the National$t1-1-1 Aquatic Resource Surveys (NARS) were introduced. Some suggestions for the future development of the scientific ecological assessment system of watershed health in China were put forward based on the understanding of the protection and remediation practices of our water environment. PMID- 24175542 TI - [Effects of light on submerged macrophytes in eutrophic water: research progress]. AB - The restoration of submerged macrophytes is the key to remediate eutrophic water and maintain the health of aquatic ecosystem, while light is the main limiting factor. This paper summarized the factors affecting the light extinction in water and the mechanisms of light intensity affecting the physiology of submerged macrophytes, with the focuses on the metabolic mechanisms of carbon, nitrogen, and phosphorus, the responses of antioxidant enzyme system, and the feedbacks of pigment composition and concentration in the common submerged macrophytes under low light stress. Several engineering techniques applied in the ecological restoration of submerged macrophytes were presented, and the framework of the restoration of submerged macrophytes in eutrophic water was proposed. Some problems in current research and several suggestions on future research were addressed, which could help the related research and engineering practices. PMID- 24175543 TI - [Application potential of siderophore-producing rhizobacteria in phytoremediation of heavy metals-contaminated soils: a review]. AB - Siderophore-producing rhizobacteria (SPR) are a group of plant growth-promoting rhizobacteria, being able to play an important role in assisting the phytoremediation of heavy metals-contaminated soils. Based on the comprehensive analysis of related researches at home and abroad, this paper elaborated the functions of SPR in alleviating the heavy metals stress and toxicity to plants and the mechanisms of SPR in improving the heavy metals bioavailability in soil, and indicated that SPR had good application potential in promoting the plant growth in heavy metals-contaminated soils and reinforcing the heavy metals accumulation in plants. The contradictory phenomena of SPR in increasing or decreasing heavy metals accumulation in plants, which existed in current researches, were also analyzed. Aiming at the deficiencies in current researches, it was suggested that in the future researches, the mechanisms of the interactions between SPR and plants, especially hyperaccumulators, should be further studied, the key factors affecting the heavy metals complexation and mobilization in soil by siderophores should also be further clarified, the effects of siderophores on the heavy metals bioavailability and its subsequent influence on the heavy metals uptake by plants should be comprehensively considered, and the measures for improving the colonization of SPR in heavy metals-contaminated soil should be explored. PMID- 24175544 TI - [The protective effect of DR2 activation on hypoxia/reperfusion injury in the neonatal rat cardiomyocytes and related mechanism]. AB - OBJECTIVE: To observe the effect of dopamine receptor (DR2) activation on hypoxia/reperfusion injury (HRI) in the neonatal rat cardiomyocytes, and to explore its mechanism. METHODS: The hypoxia/reperfusion (H/R) injury model was established in primarily cultured neonatal rat cardiomyocytes, and randomly assigned: control, H/R, bromocriptine (Bro) and haloperidol (Hal) groups. The cell apoptosis was detected using inverted microscope, transmission electron microscope and flow cytometry (FCM). The lactate dehydrogenase(LDH) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in cell medium were analyzed. The expression of mRNA and protein of caspase-3, caspase-8, caspase-9, Fas, Fas-L, Cyt C and Bcl-2 were detected by RT-PCR and Western blot, respectively. RESULTS: Compared with the control group, apoptosis rate, LDH activity, MDA content and the expression of pro-apoptotic factors and anti apoptotic factors were increased, but SOD activity was decreased in H/R group. Compared with the H/R group, all index above-mentioned were down-regulated or reversed in Bro-group, and had no obvious differences in Hal-group. CONCLUSION: The neonatal rat cardiomyocytes injury and apoptosis caused by hypoxia/reperfusion can be inhibited with DR2 activation, which mechanism is related to scavenging oxygen radical. PMID- 24175545 TI - [Effects of retinol acid and triiodothyronine on alleviating the impairment of cognitive function by sleep deprivation]. AB - OBJECTIVE: To explore the effects of retinol acid (RA) and triiodothyronine (T3) on alleviating the impairment of cognitive function by sleep deprivation (SD). METHODS: Male Wistar rats were divided into 4 groups: control group (C group), sleep deprivation group (SD group), sleep deprivation + RA group (SD + RA group) and sleep deprivation + T3 group (SD + T3 group). Open field test (OFT) was used to observe the nervous behavior of the rats after SD and electrophysiological brain stereotactic method was used to test long-term potentiation (LTP) in dentate gyrus (DG) of the rats. Ng protein expression was determined by Western blot. RESULTS: Compared with the SD group, the number of crossing in OFT, the changes of amplitude of population spike (PS) and the expression of Ng protein in hippocampus were higher significantly in the SD + RA and SD + T3 groups. All of these had not significant difference comparing with the C group. CONCLUSION: RA and T3 may alleviate the restrain state of neural system after SD by augmenting the expression of Ng protein in hippocampus. PMID- 24175546 TI - [Protective effect of oxiracetam on traumatic brain injury in rats]. AB - OBJECTIVE: To study the role of oxiracetam on traumatic brain injury in rats. METHODS: Thirty Wistar rats were randomly divided into 3 groups: sham operation group, model group and treatment group. Feeney method were used to establish traumatic brain injury (TBI) model in rats in model and treatment group, and rats in sham group were only broached without hydraumatic fitted. Rats in treatment group were successive administration for 21 days with oxiracetam (100 mg/kg, ig). Neurologic impairment scores were undertook after operation of 1 d, 4 d, 7 d, 14 d and 21 d, and Morris water maze test were proceeded during 15 to 19 days after operation. Average escape latency, searching time in target quadrant and number of crossing target platform in rats were recorded. RESULTS: Neurologic impairment scores of rats in treatment group were significantly less than those of model group after operation of 7, 14 and 21 d (P < 0.05). Average escape latency of model group were significantly higher than those of sham operation group and treatment group (P < 0.05, P < 0.01). Searching time in target quadrant and number of crossing target platform of model group were lower than those of sham operation and treatment group (P < 0.05)). CONCLUSION: Oxiracetam could decrease neural injury and increase ability of learning, memory and space cognition in traumatic brain injury rats. PMID- 24175547 TI - [Effects of low temperature exposure on dermal microvascular endothelial cells function]. AB - OBJECTIVE: To explore the damage effects and expression of vascular endothelial growth factor (VEGF) exposed with different low-temperatures on rat dermal microvascular endothelial cells (DMVECs). METHODS: Primary DMVECs were obtained by discontinuous Percoll gradient centrifugation. The DMVECs were identified by phase contrast microscope and immunofluorescence studies for CD31 antigen. Applied 28 degrees C, 12 degrees C and 0 degrees C to interfere with rat DMVECs as cold-exposure model. The changes of cells morphology were observed under invert microscope. The membrane integrity was determined by lactate dehydrogenase (LDH) activity. RT-PCR was used to examine the expression of vascular endothelial growth factor mRNA in cells. RESULTS: The monolayer of cultured PMVECs displayed the shape of pavingstone. CD31 antigen and binding BSI results by fluorescence microscope identified the cultured cells were DMVECs. After 24 h cold exposure, the cell morphology of 0 degrees C group was shrunken, the other groups were "Fibroblast-like". The LDH activity (U/L) in the medium of 28 degrees C, 12 degrees C and 0 degrees C groups was 54.17 +/- 3.02, 64.66 +/- 3.03, 82.13 +/- 10.91 respectively, which was significantly higher than that of 37 degrees C group (12.23 +/- 3.0, P < 0.01). The VEGF mRNA expression level was up-regulated in 28 degrees C group and 12 degrees C group versus control group (P < 0.05), but unchanged in 0 degrees C group. CONCLUSION: The rat DMVECs injury severity are deteriorated with temperature decreasing, and VEGF might be involved in the regulation of membrane permeability in this period. PMID- 24175548 TI - [Inhibitory effects of 17beta-estradiol on spontaneous and activated contraction of rat uterus smooth muscle]. AB - OBJECTIVE: To observe and compare the effects of 17beta-estradiol (EST) on the phasic and tonic contractile activities of the uterine smooth muscles of SD rats in vitro. METHODS: Different concentrations of 17beta-estradiol were added into the perfusion muscular sockets containing uterine smooth muscles of SD rats, and the activities of muscle contraction were recorded at the same time. RESULTS: 17beta-estradiol had obvious depression effects on spontaneous rhythmic contraction of the uterine smooth muscles in a concentration-dependent manner, it could considerably decrease muscular tension, the mean amplitudes and frequencies of contractile waves (P < 0.01); it could also suppress the uterine contraction stimulated by KCl, CaCl2 or prostaglandin F2alpha (PGF2alpha). Based on the contraction of uterine smooth muscle stimulated by KCl, IC50 was 7.278 micromol/L and pD2 was -0.862 when calculated by linear regression method. 17beta-estradiol could also inhibit the maximal CaC12 contraction of uterine smooth muscle in the Ca2+ free Krebs solution, which the ECQ was 1.422 x 10(-3) mol/L, pD2 was 2.847 (control), but the E50 was 3.028 x 10(-3) mol/L, p2 was 2.519 (added with EST) when calculated by linear regression method. CONCLUSION: The depression effects of 17beta-estradiol on the spontaneous rhythmic contraction and activated contraction of the uterine smooth muscles of SD rats could be mediated through the blockage of C2+ influx through potential-dependent Ca2+ channels of plasma membrane. PMID- 24175549 TI - [Association between SNP/T3541G in 3' enhancer of erythropoietin gene and aerobic capacity]. PMID- 24175550 TI - [Expression of choline acetyltransferase in the rat barrel cortex by electrical stimulation]. AB - OBJECTIVE: To observe a turning performance in the rats excited by using a proper electrical stimuli of the barrel cortex region (BC), and the expression of choline acetyltransferase (ChAT) in the BC regions after electoral stimulation. METHODS: SD rats were divided into three groups. The stimulation electrodes were surgically implanted into the bilateral BC regions in the control group and the experimental group rats. The experiment group post surgery for seven days was given the electrical impulses via connection with the electrodes for three times each day through consecutive three days. Three groups of the rats were killed and the brains were quickly removed for frozen sections and then performed with conventional HE and immunohistochemistry staining. And protein samples were prepared from brain and the hippocampus tissues of the three groups to detect the level of the ChAT protein by Western blot. RESULTS: The experimental rats turn left or right when continuously stimulation in the bilateral BC regions with electric pulse. HE staining showed no significant damage around electrodes in the cerebral cortex. Compared with the control and blank groups, the ChAT positive rate in the brain section in the experimental rats was significantly high by immunohistochemistry assay; the level of the ChAT protein in the rats given the electrical stimulation increased. CONCLUSION: Turnings performance of the rat could be initiated hy electrical stimuli in the BC region. Expression of ChAT is significantly higher in the BC regions of rat under electrical stimulation, suggesting that acetylcholine might be associated with signal transmission between senses and movement behavior in the nervous central system. PMID- 24175551 TI - [Effects of dexmedetomidine on perioperative inflammatory response in patients undergoing valve replacement]. PMID- 24175552 TI - [Effects of curcumin on pneumocyte apoptosis and CHOP in pulmonary ischemia/reperfusion injury of mice]. AB - OBJECTIVE: To investigate the effects of curcumin (CUR) on pneumocyte apoptosis and CCAAT/enhancer binding protein homologous protein (CHOP) in pulmonary ischemia/reperfusion injury (PIRI) in mice. METHODS: Sixty C57BL/6J mice were randomly allocated into six groups (n = 10): Sham operation group (Sham group), ischemia/reperfusion group (I/R group), ischemia/reperfusion + dimethyl sulfoxide group (DMSO group), ischemia/reperfusion + curcumin pre-treated with respectively 100 mg/kg, 150 mg/kg and 200 mg/kg groups (CUR-100 group, CUR-150 group and CUR 200 group). Left lung tissue of each group was excised after reperfusion for 3 h. Wet lung weight to dry lung weight (W/D) and total lung water content (TLW) were tested. The morphological and ultrastructural changes of lung tissue were observed under light microscope and electron microscope, and index of quantitative evaluation for alveolar damage (IQA) was calculated. The expression levels of CHOP and glucose regulated protein 78 (GRP78) were detected by RT-PCR and Western Blot. Apoptosis index (AI) of lung tissue was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. RESULTS: Compared with Sham group, the expression levels of CHOP, GRP78 mRNA and protein were all significantly increased (P < 0.05) in I/R group and DMSO group, W/D, TLW, IQA and AI were all notably higher (P < 0.01); morphological and ultrastructural injury in lung tissue were notably observed in I/R group. Compared with DMSO group, the expression levels of GRP78 mRNA and protein were increased higher (P < 0. 05) in CUR-100 group, CUR-150 group, and CUR-200 group, but the expression levels of CHOP mRNA and protein were decreased lower (P < 0.05), W/D, TLW, IQA and AI were also decreased (P < 0.05, P < 0.01); morphological and ultrastructural injury in lung tissue were gradually alleviated in CUR groups. CONCLUSION: I/R induces excessive unfolded protein response (UPR) in lung tissue, in which CHOP participates in pneumocyte apoptosis, leading to lung injury; CUR has notable effects on lung protection against I/R injury, which may be related to inhibition of apoptosis mediated by CHOP in excessive UPR. PMID- 24175553 TI - [Corticotropin-releasing hormone modulates NO production, TNF-alpha and IL-6 release in rat primary microglia]. PMID- 24175554 TI - [Dynamic expression of toll like receptor 2 and 4 in a rat model of myocardial ischemia/reperfusion injury]. AB - OBJECTIVE: To explore the role of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) in myocardial ischemia/reperfusion injury (MI/RI) by observing the dynamic expression changes at mRNA and protein levels early after myocardial ischemia/reperfusion (I/ R). METHODS: The Wistar rats were randomly divided into Sham and I/R group (n = 42), and killed according to different reperfusion time (1, 2, 4, 6, 12, 24 h and 7 d). Structural and morphous changes of myocytes were observed under optical microscope. The mRNA and protein levels of TLR2 and TLR4 were detected using real-time PCR (RT-PCR). Monocyte chemokine protein-1 (MCP-1) and interleukine-6 (IL-6) mRNA levels were measured by reverse transcriptase polymerase chain reaction (rt-PCR). RESULTS: (1) With the extension of reperfusion time, the myocardial infarct size increased smoothly, and reached the plateau at 4 h, then stayed in the platform. After reperfusion for 7 d, the ventricular had been remodeled. (2) At the beginning of reperfusion, myocardial structure showed no significant change in Sham group, but had different degrees of injury in I/R group. In rats of the group reperfused for 7 d the left ventricular remodeling could be visible. (3) Compared to sham group,TIR2, TLR4, MCP-1, IL-6 mRNA level were increased in myocardium in I/R group. TLR2 and TLR4 both peaked at 4 h of reperfusion, IL6 peaked at 6 h, followed by a gradually decrease. TLR4 and IL-6 mRNA levels rose again at 7 d. MCP-1 level in I/R group remained fairly with sham group at the beginning of reperfusion, and markedly elevated at 7 d. CONCLUSION: Expression of TLRs mRNA in myocardium during early after myocardial ischemia/reperfusion increased rapidly and activated TLRs might play an important role in MI/RI through promoting the generation of inflammatory factors. At the late reperfusion, TLRs levels raise again and the expression of inflammatory factors increase once again, Those may probably affect the remodeling of ventricular, and injure myocardial structure and function. PMID- 24175555 TI - [Effect of hypericum perforatum extract on gap junction protein Cx43 of the dilated cardiomyopathy rats]. PMID- 24175556 TI - [The selective dilatation effects of iptakalim on pulmonary arterioles in hypoxic pulmonary hypertensive rat]. AB - OBJECTIVE: To study the selective dilatation effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener, on pulmonary arterioles in hypoxic pulmonary hypertensive rat. METHODS: SD male rats were divided into 3 groups, control group, the rest were fed in hypoxic and normobaric environment (O2 10% +/ 0.5%, 8 h/d and 6 d/week) and divided into hypoxia group and hypoxia plus acetazolamide (Acz) group (hypoxic rats were treated with ig acetazolamide (Acz) 80 mg x kg(-1) d(-1)) . After 12 weeks, pulmonary arteriole rings about (197 +/- 4) microm were isolated and the tension of hypoxic pulmonary arterioles pre contracted by 6 nmol/L endothelin-1 (FT-1) was observed with wire myograph system model (DMT 610 m). The relaxing response of hypoxic pulmonary arterioles induced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine. RESULTS: 10(-5) mol/L acetylcholine (ACh)-mediated vasodilatation was greatly reduced in the hypoxic group than those in control group (P < 0.01) and there was no significant difference between Acz treatment group and control group (P > 0.05). Ipt at the concentration ranging from 10(-11) mol/L to 10(-4) mol/L, caused dose dependent vasodilation on both hypoxic pulmonary arterioles and Acz treatment group (P > 0.05), but not on normal group. CONCLUSION: The endothelial function of pulmonary arterioles was damaged under hypoxic pulmonary hypertensive state, and Ipt showed selective dilatation effects on hypoxic pulmonary arterioles. Acz could improve the dysfunction of endothelial cells induced by hypoxic pulmonary hypertensive state, which didn't affect the selective dilatation effects of Ipt on hypoxic pulmonary arterioles. PMID- 24175557 TI - [Effects of hypericum perforatum extract on the autoimmune myocarditis of mice]. PMID- 24175558 TI - [Research on the mechanism and regulation of overtraining-related the function of neutrophils by the inhibitor of NADPH oxidase and glutamine supplementation]. AB - OBJECTIVE: To investigate the method and mechanism for exercise-related immunosuppression via the inhibitor of NADPH oxidase diphenyleneiodonium(DPI) and glutamine supplementation and on the function of neutrophils after overtraining. METHODS: Fifty male Wistar rats were randomly divided into five groups: a negative control group (C), an overtraining group (E), an overtraining + DPI intervention group (D), an overtraining+ glutamine supplementation group(G) and combined glutamine + DPI intervention group(DG). After 36 - 40 h from the last training, eight rats were randomly selected from each group, and blood was sampled from the orbital vein. ELISAs were used to measure serum cytokine levels and lipid peroxidation in blood plasma. Flow cytometry was used to measure neutrophil respiratory burst and phagocytosis. The activity of NADPH oxidase was assessed by chemiluminescence and the gene expression of gp91(phox) and p47(phox) of the NADPH-oxidase subunit was checked by Western blot. RESULTS: Compared with group C, the plasma concentrations of NO increased in group G, and the NO, cytokine-induced neutrophil chemoattractant (CINC) concentrations in group DG increased significantly. The respiratory burst and phagocytosis function of neutrophils were decreased in group E, but in group DG were increased when compared with those of group E. After overtraining the expression of gp91(phox) and p47(phox) was up regulated in group E. There were no significant changes in other groups except group DG, in which the expression of gp91(phox) was down regulated. Compared with group E, the expression of gp91(phox) and p47(phox) was up regulated in group D, group G and group DG. CONCLUSION: The activation of NADPH oxidase is responsible for the production of superoxide anions, which may be related to the decrease in neutrophil function after over training and is the mechanism of exercise-related immunosuppression. The DPI treatment combined glutamine supplementation can reverse the decrease neutrophils function after overtraining in vitro. PMID- 24175559 TI - [Zinc and IL-1beta concentration in serum and cerebrospinal fluid in children with febrile seizure]. PMID- 24175560 TI - [The Chinese medicine nutrient diet intervention prevent against the neurologic damage induce by EMF irradiation in rat hippocampus]. AB - OBJECTIVE: To observe the neurologic damage in rat hippocampus after electromagnetic field (EMF) acute or chronic irradiation and research the protective effects of Chinese medicine diet (CMD) which comprised ferulic acid, ginsenoside, astragalus polysaccharide and rhodiola sachalinensis. METHODS: Eighty rats were divided into ten groups (n = 8): normal diet with shame irradiation group (NS), normal diet with chronic irradiation group (NCI), three groups of normal diet with acute irradiation after 3 h, 24 h, 72 h (NAI), Chinese medicine diet with shame irradiation group (CS), Chinese medicine diet with chronic irradiation group (CCI), three groups of Chinese medicine diet with acute irradiation after 3 h, 24 h, 72 h (CAI). The chronic EMF irradiation were performed by electromagnetic wave at 15 W/cm2 for 20 min everyday for 8 weeks continuously. The acute EMF irradiation were performed by electromagnetic wave at 65 W/cm2 for 20 min after feeding with CMD for 8 weeks. The learning and memory were evaluated by Morris water maze before/after electromagnetic wave irradiation. The apoptotic cells in hippocampus was detected by Tunel staining. The peroxidation damage of EMF and the protective effect of CMD intervention were assayed by measuring superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and reactive oxygen species (ROS). RESULTS: The acute and chronic EMF irradiation disturbed the ability of learning and memory significantly (P < 0.05), CMD intervention markedly antagonized this effect. The apoptotic cells in hippocampus increased evidently after EMF irradiation (P < 0.05), but CMD intervention reduced the apoptotic cells. The acute and chronic EMF irradiation induced the oxidative stress by down-regulating SOD activity, GSH Px activity, ROS inhibiting and up-regulating the content of MDA obviously (P < 0.05), and CMD intervention reduced peroxidation damage significantly (P < 0.05). CONCLUSION: The acute and chronic EMF irradiation could initiate neurologic damage in hippocampus. CMD intervention has protective effect on the impaired learning and memory, the neuron apoptosis, the peroxidation damage induced by EMF irradiation. CMD intervention plays a significant protective role in antagonizing neurologic damage in the later stage of acute irradiation and chronic irradiation. PMID- 24175561 TI - [Experimental research on the anti-aging effects of astragalus polysaccharides]. PMID- 24175562 TI - [Study on the effect of ursolic acid (UA) on the myocardial fibrosis of experimental diabetic mice]. AB - OBJECTIVE: To investigate the effect of ursolic acid (UA) on the alloxan-induced myocardial fibrosis in mice and discuss the possible mechanism. METHODS: Diabetes was produced by a single injection of alloxan (70 mg/kg, i.v.) in mice. The mice were randomly divided into four groups: normal control group, model group, ursolic acid group (UA, 35 mg/kg, p.o.) and benazepril group (5 mg/kg, p. o.), and continuous administrated for 8 weeks. The blood glucose was measured 24 hours after the last administration. Detected the specific biochemical of myocardial tissue: superoxide dismutase (SOD), malondialdehyde (MDA) and hydroxyproline(HYP). Using masson staining to observe the morphology of the myocardial tissue. Immunohistochemistry was employed to determine the protein levels of TGF-beta1. RESULTS: Compared to normal group, the blood glucose, heart index, myocardial tissue MDA, HYP level were increased, and SOD activities were decreased in the diabetic mice, Masson stain showed that myocardial cells disarranged, myocardial collagen fibrosis hyperplasia. Meanwhile, the protein expression of TGF-beta1 was increased in model group. The UA group improved all the above significantly. CONCLUSION: UA improves the myocardial collagen fibrosis in diabetic mice induced by alloxan, its mechanism may be related to inhibiting the expression of TGF-beta1 and antioxidation. PMID- 24175563 TI - [Study of compound of Chinese traditional sturdy-positive-medicine prescriptions on the free radicals metabolism of rat cardiac muscle]. PMID- 24175564 TI - [The effects of ACEI on calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats]. AB - OBJECTIVE: To investigate the effects of angiotensin converting enzyme inhibitor (ACEI) captopril on Calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats. METHODS: Thirty adult male SD rats were randomly divided into 3 groups (n = 10), normal control group (NC group), diabetes mellitus group (DM group)and captopril treated group (Cap group). Streptozocin (STZ) were used to make the model of diabetes mellitus, captopril was administrated by gavage at the dose of 50 mg/kg every day, while in NC group and DM group the same volume of normal saline was administrated. Twelve weeks later, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVDEP), maximal rise rate of left ventricular pressure (+ dp/dtmax) and maximal fall rate of left ventricular pressure (- dp/dtmax) were detected; Western blot was used to detect the expression of Calpain-1 Calpain-2, Bcl-2, Bax and total Caspase3 protein; apoptosis index (AI) were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: Compared with NC group, LVDEP was significantly higher; LVSP, + dp/dtmax and - dp/dtmax were significantly decreased (P < 0.05); Bcl-2 protein expression was decreased; the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were increased; the value of AI was significantly increased. Compared with DM group, LVDEP was significantly lower; LVSP, + dp/dtmax and - dp/dtmax were significantly increased (P < 0.05); Bcl-2 protein expression was increased, the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were decreased; the value of AI was significantly decreased (P < 0.05). CONCLUSION: Captopril can protect diabetic myocardial structure through inhibiting activation of Calpain-1 and Calpain-2, up-regulating the expression of Bcl-2, down regulating the expression of Bax to inhibit Caspase3 dependent apoptosis, thereby improving the ventricular function and myocardial structure. PMID- 24175565 TI - [Effects of repeated fasting/refeeding on lipid metabolism and uncoupling proteins expression in rats]. AB - OBJECTIVE: To explore the expression changes of mRNA and protein of uncoupling protein 2 (UCP2) in adipose tissues and uncoupling protein 3 (UCP3) in muscle tissues of rats which were treated with repeated fasting/refeeding and followed by fed with high-fat diet, and their possible mechanism on lipid metabolism. METHODS: The model of repeating fasting/refeeding rats (repeated cycles of 1-day fasting and 1-day refeeding for 6 weeks fed with common-fat diet, RFR) was designed. At the end of the 6th week, the RFR rats were switched to high-fat diet every day (RFR-CF/HF). Moreover, the control rats were randomly divided into two groups and then fed with high-fat diet (HF) and common-fat diet (CF) respectively for 6 weeks. All rats were killed at the end of the 6th and the 12th week, serum and plasma samples were taken from abdominal aorta, and then the concentration of serum lipids, glucose, free fatty acid (FFA), and plasma insulin were measured. The histomorphological changes of liver tissues were observed by HE staining. The expression level of mRNA and protein of UCP2 in adipose tissues and UCP3 in muscle tissues was respectively measured by RT-PCR and Western blot. RESULTS: (1) The concentration of serum glucose in RFR group was significantly lower than that in control group (P < 0.05), while the concentration of serum FFA, expression level of UCP2 mRNA, UCP3 mRNA and protein were significantly higher than those in control group (P < 0.05). (2) The concentration of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and plasma insulin in RFR-CF/HF group was significantly lower than that in HF group, but significantly higher than that in CF group (P < 0.05). The concentration of serum FFA was significantly lower than that of HF and CF groups (P < 0.01). The expression level in UCP2, UCP3 mRNA and protein was significantly higher than that of HF group, but significantly lower than that of CF group (P < 0.05). CONCLUSION: The feeding pattern of repeated fasting/refeeding can decrease the obese degree induced by high-fat diet, increase the mRNA and protein expression of UCP2 in adipose tissues and UCP3 in muscle tissues, up-regulate the proton leak caused by obesity, and improve the rate of basic energy metabolism in rats. PMID- 24175566 TI - [Changes of sex hormones and risk factors associated with atherosclerosis in old patients with castrated prostatic cancer]. AB - OBJECTIVE: To detect the relationship between changes of sex hormone levels and risk factors for atherosclerosis in old patients with castrated prostatic cancer. METHODS: Two hundred and forty-seven patients, over 65 years old, were divided into three groups: 64 non-prostatic cancer patients (group I), 61 non-castrated prostatic cancer patients (group II) and 122 castrated prostatic cancer patients (group III). Group I and group II served as controls. Testosterone (T), estradiol (E2), luteal hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), progesterone (P), C-reactive protein (CRP), serum homocysteine (Hcy), glucose (GLU), uric acid (UA), total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL), were measured and compared between any two groups. RESULTS: In patients with castrated prostatic cancer, T, E2, and P levels decreased significantly, LH and FSH increased significantly, change of PRL was not significant, E2/T was elevated significantly; levels of CRP, Hcy, GLU, UA, TC, TG and LDL-C increased significantly compared with those in control groups. CONCLUSION: Sex hormone levels were imbalanced significantly after castration in old prostatic cancer patients, and the risk factors for atherosclerosis also increased accordingly. There might be relationship between decreased sex hormone levels and risk factors for atherosclerosis in old male patients. PMID- 24175567 TI - [Effect of HIF-1alpha on sex hormone levels and germ cell apoptosis of mice]. AB - OBJECTIVE: To study the effect of hypoxia on hypothalamus-adenohypophysis-testis axis hormone levels, germ cell apoptosis and hypoxia-inducible factor-1alpha (HIF 1alpha) expression in testis of adolescent mice, and explore HIF-1alpha regulation on the reproductive function of male mice. METHODS: Eighty SPF grade adolescent C57BL/6 mice were randomly divided into normoxia group, hypoxia 3, 7, 14 and 28 d groups. The level of serum testosterone (T), free testosterone (FT), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was analyzed by ELISA. Detected the sperm count, motility rate and abnormal sperm rate of epididymal sperm suspension. The apoptosis cells in testis were determined using TUNEL method. The expression of HIF-1alpha was analyzed using Western blot. RESULTS: Compared with corresponding normoxia group, serum T, FT, FSH and LH concentrations in hypoxia 3 d group were significantly higher (P < 0.05); T and LH concentrations in hypoxia 14 d group were significantly lower (P < 0.05). Sperm count and motility rate in hypoxia 7 and 14 d groups significantly declined (P < 0.05); abnormal sperm rate in all hypoxia groups significantly increased (P < 0.05). The apoptosis index (AI) of germ cells in hypoxia 7, 14 and 28 d groups significantly increased (P < 0.05), and the levels of HIF-1alpha protein expression were significantly higher (P < 0.05). CONCLUSION: HIF-1alpha protein highly expressed in mice testis could induce germ cell apoptosis increased in chronic hypoxia environment. PMID- 24175568 TI - [Effects of beta3-adrenergic receptor antagonist on myocardial UCP2 expression and energy metabolism in chronic heart failure rats]. AB - OBJECTIVE: To observe the effects of beta3-adrenergic receptor(beta3-AR) antagonist on myocardial uncoupling protein 2 (UCP2) expression and energy metabolism in chronic heart failure rats. METHODS: Seven weight-matched normal adult rats (control group), 18 isoproterenol (ISO) induced heat failure (HR) rats (ISO group) and 21 ISO induced heart failure rats but received specific beta3-AR inhibitor SR59230A (ISO+ SR59230A group) for 6 weeks were included in this research. At the end of the study, echocardiography was performed, the ratio of left ventricular weight and body weight (LVW/BW) was calculated. The expression of beta3-AR ad UCP2 mRNA in myocardium were detected by reverse transcription polymerase chain reaction (RT-PCR), the UCP2 protein in myocardium were detected by Western blot. The myocardial contents of creatine phosphate (PCr) and adenosine triphosphate (ATP) were measured by high performance liquid chromatography (HPLC). RESULTS: Compared with control group, the cardiac function was significantly reduced and myocardial beta3-AR mRNA significantly increased, UCP2 mRNA and protein were also significantly increased in ISO group, this change could be attenuated by the treatment with SR59230A, and the expression of myocardial UCP2 protein negatively correlated with the ratio of PCr/ATP. CONCLUSION: In the chronic stage of HF, the expression of UCP2 increases, which causes myocardial energy shortage, SR59230A improves myocardia energy efficiency and cardiac function by means of suppressing the expression of UCP2. PMID- 24175569 TI - [Effect of lycopene on oxidative stress and behavioral deficits in rotenone induced model of Parkinson's disease]. AB - OBJECTIVE: To investigate the neuroprotective potential of lycopene on oxidative stress and neurobehavioral abnormalities in rotenone induced Parkinson' disease (PD). METHODS: Forty adult C57BL/6 mice were randomly divided into four groups (n = 10): control, lycopene (10 mg/kg body weight, orally), rotenone (3 mg/kg bw, intraperitoneally) and rotenone plus lycopene, which were sacrificed for 5 weeks. The spectrophotometry was used to determine the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and the content of malondialdehyde (MDA) in substantia nigra and right striatum. At the same time, the number of tyrosine hydroxylase (TH), alpha-synuclein (alpha-SYN) and microtubule-associated protein 3 light chain (LC3-B) positive neurons were estimated by immunohistochemistry. We also examined neurobehavioral abnormalities by WT-200 water maze. RESULTS: Rotenone administration increased the MDA levels and significantly decreased the activities of SOD, GSH-Px and CAT. However, lycopene administration to the rotenone treated animals increased the activities of SOD, GSH-Px and CAT when compared to rotenone treated animals in substantia nigra and right striatum. The cognitive and motor deficits in rotenone administered animals, which were reversed on lycopene treatment. Along with this, the number of TH decreased, alpha-SYN increased and LC3-B positive neurons increased in rotenone administered animals, which were reversed on lycopene treatment. CONCLUSION: Collectively, these observations provide an evidence for beneficial effect of lycopene supplementation in rotenone-induced PD and suggest therapeutic potential in neurodegenerative diseases involving accentuated oxidative stress. PMID- 24175571 TI - Moving science into state child and adolescent mental health systems: Illinois' evidence-informed practice initiative. AB - In 2005, the Illinois State Mental Health Authority embarked on an initiative to close the gap between research and practice in the children's mental health system. A stakeholder advisory council developed a plan to advance evidence informed practice through policy and program initiatives. A multilevel approach was developed to achieve this objective, which included policy change, stakeholder education, and clinician training. This article focuses on the evidence-informed training process designed following review of implementation research. The training involved in-person didactic sessions and twice-monthly telephone supervision across 6 cohorts of community based clinicians, each receiving 12 months of training. Training content initially included cognitive behavioral therapy and behavioral parent training and was adapted over the years to a practice model based on common element concepts. Evaluation based on provider and parent report indicated children treated by training clinicians generally showed superior outcomes versus both a treatment-as-usual comparison group for Cohorts 1 to 4 and the statewide child population as a whole after 90 days of care for Cohorts 5 to 6. The results indicated primarily moderate to strong effects for the evidence-based training groups. Moving a large public statewide child mental health system toward more effective services is a complex and lengthy process. These results indicate training of community mental health providers in Illinois in evidence-informed practice was moderately successful in positively impacting child-level functional outcomes. These findings also influenced state policy in committing resources to continuing the initiative, even in difficult economic times. PMID- 24175572 TI - 6-Alkoxy-5-aryl-3-pyridinecarboxamides, a new series of bioavailable cannabinoid receptor type 1 (CB1) antagonists including peripherally selective compounds. AB - We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and 14g, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, 14h, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both 14h and 14g in the periphery but 10-fold lower exposure in the brain for 14h. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed. PMID- 24175573 TI - Utilizing carbon nanotube electrodes to improve charge injection and transport in bis(trifluoromethyl)-dimethyl-rubrene ambipolar single crystal transistors. AB - We have examined the significant enhancement of ambipolar charge injection and transport properties of bottom-contact single crystal field-effect transistors (SC-FETs) based on a new rubrene derivative, bis(trifluoromethyl)-dimethyl rubrene (fm-rubrene), by employing carbon nanotube (CNT) electrodes. The fundamental challenge associated with fm-rubrene crystals is their deep-lying HOMO and LUMO energy levels, resulting in inefficient hole injection and suboptimal electron injection from conventional Au electrodes due to large Schottky barriers. Applying thin layers of CNT network at the charge injection interface of fm-rubrene crystals substantially reduces the contact resistance for both holes and electrons; consequently, benchmark ambipolar mobilities have been achieved, reaching 4.8 cm(2) V(-1) s(-1) for hole transport and 4.2 cm(2) V(-1) s(-1) for electron transport. We find that such improved injection efficiency in fm-rubrene is beneficial for ultimately unveiling its intrinsic charge transport properties so as to exceed those of its parent molecule, rubrene, in the current device architecture. Our studies suggest that CNT electrodes may provide a universal approach to ameliorate the charge injection obstacles in organic electronic devices regardless of charge carrier type, likely due to the electric field enhancement along the nanotube located at the crystal/electrode interface. PMID- 24175574 TI - Mean platelet volume in patients undergoing percutaneous coronary intervention. PMID- 24175575 TI - Rice brans, rice bran oils, and rice hulls: composition, food and industrial uses, and bioactivities in humans, animals, and cells. AB - Rice plants produce bioactive rice brans and hulls that have been reported to have numerous health-promoting effects in cells, animals, and humans. The main objective of this review is to consolidate and integrate the widely scattered information on the composition and the antioxidative, anti-inflammatory, and immunostimulating effects of rice brans from different rice cultivars, rice bran oils derived from rice brans, rice hulls, liquid rice hull smoke derived from rice hulls, and some of their bioactive compounds. As part of this effort, this paper also presents brief summaries on the preparation of health-promoting foods including bread, corn flakes, frankfurters, ice cream, noodles, pasta, tortillas, and zero-trans-fat shortening as well as industrial products such bioethanol and biodiesel fuels. Also covered are antibiotic, antiallergic, anticarcinogenic, antidiabetic, cardiovascular, allelochemical, and other beneficial effects and the mechanisms of the bioactivities. The results show that food-compatible and safe formulations with desirable nutritional and biological properties can be used to develop new multifunctional foods as well as bioethanol and biodiesel fuel. The overlapping aspects are expected to contribute to a better understanding of the potential impact of the described health-promoting potential of the rice-derived brans, oils, and hulls in food and medicine. Such an understanding will enhance nutrition and health and benefit the agricultural and industrial economies. PMID- 24175576 TI - Mean platelet volume as a surrogate marker of low-grade inflammation in osteoarthritis. PMID- 24175577 TI - Activation of platelets by endocannabinoids: distinct agonists or arachidonate reservoirs? PMID- 24175578 TI - Atypical erythrocytes and platelets in a patient with a pro-thrombin mutation. AB - Prothrombin mutation G20210A, anti-phospholipid syndrome as well as iron overload has previously been shown to cause thrombotic events. The main reason for this is the involvement of these anomalies in causing hypercoagulability of the coagulation system, which frequently leads to venous and arterial thrombotic events. We report the case of a 37-year-old white female with prothrombin mutation G20210A, anti-phospholipid syndrome, as well as an increased serum ferritin level, who experienced two transient ischemic attacks and suffers from regular amaurosis fugax. We present an ultrastructural depiction of erythrocytes, platelets, and the fibrin network, to explain the clinical manifestations of the thrombotic state seen in this patient. PMID- 24175579 TI - Health-related quality of life in adult patients with chronic immune thrombocytopenia in Serbia. PMID- 24175580 TI - Mean platelet volume and platelet distribution width in vascular dementia and Alzheimer's disease. AB - Activated platelets play a substantial role in Alzheimer's disease (AD) and atherothrombosis. Mean platelet volume (MPV) is an early marker of platelet activation, which is linked to a variety of pro-thrombotic and pro-inflammatory diseases. This study is to examine the association between platelet indices and vascular dementia (VaD) and AD. In this cross-sectional study, we investigated the levels of platelet count, MPV, and platelet distribution width (PDW) in 150 VaD patients, 110 AD patients, and 150 non-demented controls. MPV and PDW were significantly lower in patients with VaD and AD as compared with controls. The decrease in PDW for AD patients as compared with VaD patients was also significant (p < 0.001). In addition, there was a positive correlation between Mini-Mental State Examination (MMSE) and MPV and PDW, after adjusting confounding factors (r = 0.532 for MPV and r = 0.425 for PDW, p < 0.001 for both). Multivariate regression analysis showed that MPV and PDW were significantly associated with MMSE (beta = 0.366 for MPV and beta = 0.273 for PDW, p < 0.001 for both). In conclusion, MPV and PDW were both decreased in VaD and AD. PDW levels were significantly lower in AD as compared to those in VaD. Our findings suggest that PDW in combination with MMSE scores could be potential indicators for distinguishing VaD from AD. PMID- 24175570 TI - Mechanistic aspects of carotenoid biosynthesis. PMID- 24175581 TI - Causative role of infection in chronic non-thromboembolic pulmonary hypertension following ventriculo-atrial shunt. AB - A severe complication of ventriculo-atrial (VA) shunt placement for treatment of hydrocephalus is chronic thromboembolic pulmonary hypertension (CTEPH). We report here a patient with a VA shunt for treatment of hydrocephalus who presented two consecutive episodes of VA shunt-induced infection by Staphylococcus epidermidis and who rapidly developed chronic PH. Extensive radiological investigations and normal ventilation/perfusion lung scan allowed us to rule out CTEPH. To our knowledge, no other case of chronic pulmonary hypertension (PH) related to VA shunt insertion has been reported so far. PH in this patient with VA shunt is clinically distinct from CTEPH and has been caused by VA shunt-induced S. epidermidis infection per se. PMID- 24175582 TI - Eyes on new product development. PMID- 24175583 TI - Impact properties of thiol-ene networks. AB - In this study, a series of thiol-ene networks having glass transition temperatures ranging from -30 to 60 degrees C were synthesized utilizing several multifunctional thiols and two trifunctional alkenes. Thermomechanical properties were determined using dynamic mechanical analysis, and impact properties were determined using pendulum impact and drop impact testing protocols. The impact behavior was found to directly correlate to the glass transition temperature, except when the temperature at which the impact event occurs overlaps with the range of temperatures corresponding to the viscoelastic dissipation regime of the polymer. Additionally, we discuss insight into the spatial limitations of energy dissipation for thiol-ene network polymers and establish a platform for predictability in similar systems. PMID- 24175584 TI - 5-Chlorothiophene-2-carboxylic acid [(S)-2-[2-methyl-3-(2-oxopyrrolidin-1 yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a selective and potent orally active dual thrombin and factor Xa inhibitor. AB - Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 MUM, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene P1 fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with Ki's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 MUM) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a. PMID- 24175585 TI - Degradation of rotenone in yam bean seeds ( Pachyrhizus sp.) through food processing. AB - The purpose of this research is to screen different processes that could potentially decrease or even eliminate rotenone, a toxic isoflavonoid, from Pachyrhizus seeds. Yam bean seeds have very interesting nutritional characteristics, especially their high protein and lipid contents, and could potentially increase food security in under-nourished populations. However, they contain rotenone, a natural molecule previously used as an insecticide inhibiting the respiratory mitochondrial chain. It was also proven to be toxic to mammals as chronic exposure leads to the development of Parkinson-like symptoms in rats. As the thermosensitivity of rotenone had been reported, this study tested different processes (drying, roasting, boiling, frying, alcohol extraction), tegument removal, and traditional Beninese culinary recipes. Rotenone was then quantified in end-products by a validated method, associating microwave extraction, solid phase extraction (SPE), and HPLC-UV. With these processes a rotenone removal of up to 80% was obtained. The most effective methods were the drying and roasting of the seeds and the maceration of their flour in local alcohol. Rotenone degradation and elimination were confirmed by cytotoxic assays, effectively inducing a decrease in sample toxicity. PMID- 24175586 TI - Dynamics of thermal electron emission from highly excited C60. AB - Gas-phase fullerenes emit thermal electrons after femtosecond laser excitation in the wavelength range 400-800 nm. We have used angular-resolved photoelectron spectroscopy (PES) to study the influence of the laser's electric field on the dynamics of the thermally emitted electrons. The laser field introduces an asymmetry in the thermal electron distributions with respect to the laser polarization direction, which was confirmed by carrying out experiments at different wavelengths. A simple model could reproduce the trends in measured apparent temperatures in the PES. The asymmetry effect was exploited in a pump probe experiment to estimate the time scale for thermal electron emission. It was found that, when 400 nm, 120 fs laser pulses of 2 TW cm(-2) intensity are used, thermal electrons are emitted up to ca. 300 fs after the peak of the laser pulse. The pump-probe scheme should be applicable to a wider range of complex molecules and clusters showing thermal electron emission on a femtosecond time scale. PMID- 24175587 TI - Direct work function measurement by gas phase photoelectron spectroscopy and its application on PbS nanoparticles. AB - Work function is a fundamental property of a material's surface. It is playing an ever more important role in engineering new energy materials and efficient energy devices, especially in the field of photovoltaic devices, catalysis, semiconductor heterojunctions, nanotechnology, and electrochemistry. Using ambient pressure X-ray photoelectron spectroscopy (APXPS), we have measured the binding energies of core level photoelectrons of Ar gas in the vicinity of several reference materials with known work functions (Au(111), Pt(111), graphite) and PbS nanoparticles. We demonstrate an unambiguously negative correlation between the work functions of reference samples and the binding energies of Ar 2p core level photoelectrons detected from the Ar gas near the sample surface region. Using this experimentally determined linear relationship between the surface work function and Ar gas core level photoelectron binding energy, we can measure the surface work function of different materials under different gas environments. To demonstrate the potential applications of this ambient pressure XPS technique in nanotechnology and solar energy research, we investigate the work functions of PbS nanoparticles with various capping ligands: methoxide, mercaptopropionic acid, and ethanedithiol. Significant Fermi level position changes are observed for PbS nanoparticles when the nanoparticle size and capping ligands are varied. The corresponding changes in the valence band maximum illustrate that an efficient quantum dot solar cell design has to take into account the electrochemical effect of the capping ligand as well. PMID- 24175590 TI - Further erosion of our moral compass: failure to expand Medicaid to low-income people in all states. AB - Expanding Medicaid eligibility to all of the 13 million U.S. citizens who do not have medical insurance and earn up to 138% of poverty is projected to reduce their annual death rate 30% and prevent 44,789 premature deaths a year. However 21 states representing 6.3 newly eligible people have confirmed that they will NOT expand Medicaid eligibility and 5 more, representing 1.8 million more, have not yet made a decision, despite the fact that the federal government will pay 100% of the cost the first 3 years, and 90% on an ongoing basis. Is the failure to expand because of party politics? Is it sound economic analysis? Is it beliefs about the role of government? The answers are, of course, maybe not, and probably...but it is not as simple as I first thought. PMID- 24175591 TI - The Science Stalwarts for wellness: the CDC (and P). PMID- 24175592 TI - Antiplatelet resistance in outpatients with monitored adherence. AB - Antiplatelet resistance with aspirin and clopidogrel has been associated with clinical, cellular and pharmacogenetic factors; and non-adherence has been considered as a major contributor to resistance in outpatients. We aimed at assessing factors to resistance when adherence to the antiplatelet drugs and all other oral solid drugs was controlled for. In a pilot study, we tested arachidonic acid and/or ADP-induced in vitro platelet aggregation of 82 outpatients with chronic aspirin and/or clopidogrel treatment before and after a one-week period of measuring the patient's adherence with the polymedication electronic monitoring system (POEMS). Resistance was found in 20% (aspirin; n = 69) and 25% (clopidogrel; n = 32) of the patients after monitored adherence. Mean platelet aggregation was not (aspirin) or non-significantly (clopidogrel) lowered when compared to baseline. Diabetes mellitus and inflammation were consistently associated with resistance to both drugs, but CYP2C19 polymorphisms could not be confirmed as predictors of clopidogrel response. Electronically compiled multidrug dosing histories allowed the concomitant intake of high-dose lipophilic statins to be identified as a risk factor of impaired response to clopidogrel and revealed that exposure to further potential drug-drug interactions (DDIs) was too low for analysis. Multidrug adherence monitoring allowed thus dismissing non adherence as a major contributor to resistance and inter-individual response variability in an outpatient setting. Additionally, it allowed analysing the impact of DDIs according to the actual exposure to the potentially interfering drugs. Further studies based on this methodology are essential to prevent misleading results due to incomplete adherence and gain additional insight into the impact of timing adherence on antiplatelet drug response. PMID- 24175593 TI - The association of foot arch posture and prior history of shoulder or elbow surgery in elite-level baseball pitchers. AB - STUDY DESIGN: Case-control. OBJECTIVES: The specific aim of this study was to examine the association between abnormal foot arch postures and a history of shoulder or elbow surgery in baseball pitchers. BACKGROUND: Pitching a baseball generates forces throughout the musculoskeletal structures of the upper and lower limbs. Structures such as the longitudinal arch of the foot are adaptable to stresses over time. Repeated pitching-related stresses may contribute to acquiring abnormal foot arch postures. Inversely, congenitally abnormal foot arch posture may lead to altered stresses of the upper limb during pitching. METHODS: A convenience sample of 77 pitchers was recruited from a Division I university team and a professional baseball franchise. Subjects who had a history of shoulder or elbow surgery to the pitching arm were classified as cases. Subjects who met the criteria for classification of pes planus or pes cavus based on longitudinal arch angle were classified as having abnormal foot arch posture. Odds ratios were calculated to examine the association between abnormal foot arch posture and pitching-arm injury requiring surgery. RESULTS: Twenty-three subjects were classified as cases. The odds of being a case were 3.4 (95% confidence interval: 1.2, 9.6; P = .02) times greater for subjects with abnormal foot arch posture and 2.9 (95% confidence interval: 1.0, 8.1; P = .04) times greater for subjects with abnormal foot posture on the lunge leg. CONCLUSION: Abnormal foot arch posture and a surgical history in the pitching shoulder or elbow may be associated. Because the foot and its arches are adaptable and change over time, the pathomechanics of this association should be further explored. PMID- 24175594 TI - Kinesiophobia after anterior cruciate ligament rupture and reconstruction: noncopers versus potential copers. AB - STUDY DESIGN: Secondary-analysis, longitudinal cohort study. OBJECTIVES: To compare kinesiophobia levels in noncopers and potential copers at time points spanning pre- and post-anterior cruciate ligament (ACL) reconstruction and to examine the association between changes in kinesiophobia levels and clinical measures. BACKGROUND: After ACL injury, a screening examination may be used to classify patients as potential copers or noncopers based on dynamic knee stability. Quadriceps strength, single-leg hop performance, and self-reported knee function are worse in noncopers. High kinesiophobia levels after ACL reconstruction are associated with poorer self-reported knee function and lower return-to-sport rates. Kinesiophobia levels have not been examined before ACL reconstruction, across the transition from presurgery to postsurgery, or based on potential coper and noncoper classification. METHODS: Quadriceps strength indexes, single-leg hop score indexes, self-reported knee function (Knee Outcome Survey activities of daily living subscale, global rating scale), and kinesiophobia (Tampa Scale of Kinesiophobia [TSK-11]) scores were compiled for potential copers (n = 50) and noncopers (n = 61) from 2 clinical trial databases. A repeated-measures analysis of variance was used to compare TSK-11 scores between groups and across 4 time points (before preoperative treatment, after preoperative treatment, 6 months post-ACL reconstruction, and 12 months post-ACL reconstruction). Correlations determined the association of kinesiophobia levels with other clinical measures. RESULTS: Presurgery TSK-11 scores were significantly higher in noncopers than in potential copers. Postsurgery, no group differences existed. TSK-11 scores in both groups decreased across all time points; however, TSK-11 scores decreased more in noncopers in the interval between presurgery and postsurgery. In noncopers, the decreases in TSK-11 scores from presurgery to postsurgery and after surgery were related to improvements in the Knee Outcome Survey activities of daily living subscale, whereas the association was only present in potential copers after surgery. CONCLUSION: Kinesiophobia levels were high in both noncopers and potential copers preoperatively. Restoration of mechanical knee stability with surgery might have contributed to decreased kinesiophobia levels in noncopers. Kinesiophobia is related to knee function after surgery, regardless of preoperative classification as a potential coper or noncoper. PMID- 24175595 TI - Whole-body vibration versus eccentric training or a wait-and-see approach for chronic Achilles tendinopathy: a randomized clinical trial. AB - STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To test the hypothesis that whole-body vibration training results in greater improvements in symptoms and pain, structural changes, and muscle flexibility and strength of the triceps surae muscle-tendon unit than those achieved with eccentric training or with a wait-and-see approach. BACKGROUND: The potential use of vibration training for the treatment of Achilles tendinopathy has not been explored. METHODS: Fifty eight patients (mean age, 46.0 years) with Achilles tendinopathy were randomly assigned to a 12-week intervention using whole-body vibration training, eccentric training, or a wait-and-see approach. Pain, tendon structure and path, and muscle flexibility and strength were assessed at baseline and follow-up, and compared using mixed-factor analyses of variance. RESULTS: Pain improvements at the midsection of the tendon were greater in the vibration- and eccentric-training groups than in the wait-and-see group (mean difference from the vibration training group, -18.0; 95% confidence interval [CI]: -35.0, -1.1; mean difference from the eccentric-training group, -27.0; 95% CI: -50.9, -3.1). Improvements in pain at the musculotendinous junction were greater in the eccentric-training group than in the other groups (mean difference from the vibration-training group, -31.4; 95% CI: -60.7, -2.0; mean difference from the wait-and-see group, 50.2; 95% CI: -82.3, -18.1). Improvements in most participants were achieved in the vibration-training group, followed by the eccentric-training group. CONCLUSION: Vibration training may be an alternative or a complementary treatment in patients who do not respond well to eccentric training, especially in those with insertional pain. LEVEL OF EVIDENCE: Therapy, level 2b-. PMID- 24175596 TI - Does quadriceps atrophy exist in individuals with patellofemoral pain? A systematic literature review with meta-analysis. AB - STUDY DESIGN: Systematic literature review. OBJECTIVES: To investigate whether quadriceps atrophy is present in the affected limb of individuals with patellofemoral pain (PFP). BACKGROUND: PFP is a common condition. Atrophy of the quadriceps femoris, in particular the vastus medialis obliquus, is often assumed to be present by clinicians, and its resolution may underpin the reported effectiveness of quadriceps strengthening intervention in PFP rehabilitation. METHODS: A systematic search of the literature was conducted to identify studies that measured the size of the quadriceps in individuals with PFP. Meta-analyses were performed to determine whether quadriceps size in limbs with PFP differed from that in comparison limbs. Separate meta-analyses were performed for quadriceps size measured as girth and quadriceps size measured with imaging (thickness, cross-sectional area, and volume). RESULTS: Ten studies were included in this review. The meta-analysis of girth measurements (3 studies) found no atrophy in limbs with PFP (P = .638). The meta-analyses for imaging techniques (thickness, cross-sectional area, or volume measurements) showed atrophy in the limb with PFP compared to both the asymptomatic limb (3 studies) (P = .036) and limbs from a comparison group (3 studies) (P = .001). The single study that compared the vastus medialis obliquus and vastus lateralis in individuals with PFP found atrophy of both the vastus medialis obliquus and vastus lateralis but no significant difference in the amount of atrophy between them (P = .179). CONCLUSION: Quadriceps muscle atrophy was shown to be present in PFP when analyzed by imaging, but not by girth measures. Insufficient data were available to determine if there was greater atrophy of the vastus medialis obliquus than the vastus lateralis. These findings support the rationale for use of quadriceps strengthening as part of a rehabilitation program for PFP. PMID- 24175597 TI - Recruitment of discrete regions of the psoas major and quadratus lumborum muscles is changed in specific sitting postures in individuals with recurrent low back pain. AB - STUDY DESIGN: Cross-sectional controlled laboratory study. OBJECTIVES: To investigate potential changes in the function of discrete regions of the psoas major (PM) and quadratus lumborum (QL) with changes in spinal curvatures and hip positions in sitting, in people with recurrent low back pain (LBP). BACKGROUND: Although the PM and QL contribute to control of spinal curvature in sitting, whether activity of these muscles is changed in individuals with LBP is unknown. METHODS: Ten volunteers with recurrent LBP (pain free at the time of testing) and 9 pain-free individuals in a comparison group participated. Participants with LBP were grouped into those with high and low erector spinae (ES) electromyographic (EMG) signal amplitude, recorded when sitting with a lumbar lordosis. Data were recorded as participants assumed 3 sitting postures. Fine-wire electrodes were inserted with ultrasound guidance into fascicles of the PM arising from the transverse process and vertebral body, and the anterior and posterior layers of the QL. RESULTS: When data from those with recurrent LBP were analyzed as 1 group, PM and QL EMG signal amplitudes did not differ between groups in any of the sitting postures. However, when subgrouped, those with low ES EMG had greater EMG signal amplitude of the PM vertebral body and QL posterior layer in flat posture and greater EMG signal amplitude of the QL posterior layer in short lordotic posture, compared to those in the pain-free group. For the group with high ES EMG, the PM transverse process and PM vertebral body EMG was less than that of the other LBP group in short lordotic posture. CONCLUSION: The findings suggest a redistribution of activity between muscles that have a potential extensor moment in individuals with LBP. The modification of EMG of discrete fascicles of the PM and QL was related to changes in ES EMG signal amplitude recorded in sitting. PMID- 24175598 TI - Physical examination tests for the diagnosis of posterior cruciate ligament rupture: a systematic review. AB - STUDY DESIGN: Systematic literature review. OBJECTIVES: To summarize and evaluate research on the accuracy of physical examination tests for diagnosis of posterior cruciate ligament (PCL) tear. BACKGROUND: Rupture of the PCL is a severe knee injury that can lead to delayed rehabilitation, instability, or chronic knee pathologies. To our knowledge, there is currently no systematic review of studies on the diagnostic accuracy of clinical examination tests to evaluate the integrity of the PCL. METHODS: A comprehensive systematic literature search was conducted in MEDLINE from 1946, Embase from 1974, and the Allied and Complementary Medicine Database from 1985 until April 30, 2012. Studies were considered eligible if they compared the results of physical examination tests performed in the context of a PCL physical examination to those of a reference standard (arthroscopy, arthrotomy, magnetic resonance imaging). Methodological quality assessment was performed by 2 independent reviewers using the revised version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. RESULTS: The search strategy revealed 1307 articles, of which 11 met the inclusion criteria for this review. In these studies, 11 different physical examination tests were identified. Due to differences in study types, different patient populations, and methodological quality, meta-analysis was not indicated. Presently, most physical examination tests have not been evaluated sufficiently enough to be confident in their ability to either confirm or rule out a PCL tear. CONCLUSIONS: The diagnostic accuracy of physical examination tests to assess the integrity of the PCL is largely unknown. There is a strong need for further research in this area. Level of Evidence Diagnosis, level 3a. PMID- 24175600 TI - Variability in diaphragm motion during normal breathing, assessed with B-mode ultrasound. AB - STUDY DESIGN: Clinical measurement, cross-sectional. OBJECTIVES: To establish a set of normal values for diaphragm thickening with tidal breathing in healthy subjects. BACKGROUND: Normal values for diaphragm contractility, as imaged sonographically, have not been described, despite the known role of the diaphragm in contributing to spinal stability. If the normal range of diaphragm contractility can be defined in a reliable manner, ultrasound has the potential to be used clinically and in research as a biofeedback tool to enhance diaphragm activation/contractility. METHODS: B-mode ultrasound was performed on 150 healthy subjects to visualize and measure hemi-diaphragm thickness on each side at resting inspiration and expiration. Primary outcome measures were hemi-diaphragm thickness and thickening ratio, stratified for age, gender, and body mass index. Interrater and intrarater reliability were also measured. RESULTS: Normal thickness of the diaphragm at rest ranged from 0.12 to 1.18 cm, with slightly greater thickness in men but no effect of age. Average +/- SD change in thickness from resting expiration to resting inspiration was 20.0% +/- 15.5% on the right and 23.5% +/- 24.4% on the left; however, almost one third of healthy subjects had no to minimal diaphragm thickening with tidal breathing. CONCLUSION: There is wide variability in the degree of diaphragm contractility during quiet breathing. B-mode ultrasound appears to be a reliable means of determining the contractility of the diaphragm, an important muscle in spinal stability. Further studies are needed to validate this imaging modality as a clinical tool in the neuromuscular re-education of the diaphragm to improve spinal stability in both healthy subjects and in patients with low back pain. PMID- 24175601 TI - Hyperemia in plantar fasciitis determined by power Doppler ultrasound. AB - STUDY DESIGN: Cross-sectional observational study. OBJECTIVES: To investigate the presence of soft tissue hyperemia in plantar fasciitis with power Doppler ultrasound. BACKGROUND: Localized hyperemia is an established feature of tendinopathy, suggesting that neurovascular in-growth may contribute to tendon associated pain in some patients. The presence of abnormal soft tissue vascularity can be assessed with Doppler ultrasound, and a positive finding can assist with targeted treatment plans. However, very little is known regarding the presence of hyperemia in plantar fasciitis and the ability of routine Doppler ultrasound to identify vascular in-growth in the plantar fascia near its proximal insertion. METHODS: This observational study included 30 participants with plantar fasciitis unrelated to systemic disease and 30 age- and sex-matched controls. Ultrasound examination was performed with a 13- to 5-MHz linear transducer, and power Doppler images were assessed by 2 blinded investigators. RESULTS: Hyperemia of the plantar fascia was present in 8 of 30 participants with plantar fasciitis and in 2 of 30 controls. The between-group difference for hyperemia, using a 4-point scale, was statistically significant, with participants with plantar fasciitis showing increased Doppler ultrasound signal compared to controls (Mann-Whitney U, P = .03). However, the majority of participants with plantar fasciitis with evidence of hyperemia demonstrated very mild color changes, and only 3 were found to have moderate or marked hyperemia. CONCLUSION: Mild hyperemia can occur with plantar fasciitis, but most individuals will not exhibit greater soft tissue vascularity when assessed with routine Doppler ultrasound. Clinicians treating plantar fasciitis should not consider a positive Doppler signal as essential for diagnosis of the condition but, rather, as a feature that may help to refine the treatment plan for an individual patient. PMID- 24175602 TI - Arthritis self-efficacy scale scores in knee osteoarthritis: a systematic review and meta-analysis comparing arthritis self-management education with or without exercise. AB - STUDY DESIGN: Systematic literature review and meta-analysis. OBJECTIVE: To evaluate studies that used arthritis self-management education alone or with exercise to improve Arthritis Self-Efficacy Scale scores of patients with knee osteoarthritis. BACKGROUND: Increasing self-efficacy may improve patient knee osteoarthritis symptom management and function. METHODS: MEDLINE (1946-March 2013), CINAHL (1981-March 2013), and PsycINFO (1967-March 2013) databases were searched. RESULTS: Twenty-four studies, including 3163 subjects (women, n = 2547 [80.5%]; mean +/- SD age, 65.3 +/- 6.5 years), met the inclusion criteria. A meta analysis was performed to compare the standardized mean difference effect sizes (Cohen d) of randomized controlled studies that used the Arthritis Self-Efficacy Scale pain (13 studies, n = 1906), other symptoms (13 studies, n = 1957), and function (5 studies, n = 399) subscales. Cohen d effect sizes were also calculated for cohort studies that used the Arthritis Self-Efficacy Scale pain (10 studies, n = 1035), other symptoms (9 studies, n = 913), and function (3 studies, n = 141) subscales. Both randomized controlled studies and cohort studies were grouped by intervention type (intervention 1, arthritis self management education alone; intervention 2, arthritis self-management education with exercise), and effect sizes were compared (Mann-Whitney U tests, P<.05). Interventions that used arthritis self-management education with exercise displayed higher methodological quality scale scores (76.8 +/- 13.1 versus 61.6 +/- 19.6, P = .03). Statistically significant standardized effect-size differences between intervention 1 and intervention 2 were not observed. CONCLUSION: Small to moderate effect sizes were observed regardless of whether the intervention included exercise. Exercise interventions used in conjunction with arthritis self-management education programs need to be developed to better enhance the self-efficacy of patients with knee osteoarthritis. LEVEL OF EVIDENCE: Therapy, level 2b-. PMID- 24175599 TI - Neuromuscular training to target deficits associated with second anterior cruciate ligament injury. AB - SYNOPSIS: Successful return to previous level of activity following anterior cruciate ligament (ACL) reconstruction is not guaranteed, and the prevalence of second ACL injury may be as high as 30%. In particular, younger athletes who return to sports activities within the first several months after ACL reconstruction may be at significantly greater risk of a second ACL rupture compared to older, less active individuals. Significant neuromuscular deficits and functional limitations are commonly identified in athletes following ACL reconstruction, and these abnormal movement and neuromuscular control profiles may be both residual of deficits existing prior to the initial injury and exacerbated by the injury and subsequent ACL reconstruction surgery. Following ACL reconstruction, neuromuscular deficits are present in both the surgical and nonsurgical limbs, and accurately predict second-ACL injury risk in adolescent athletes. While second ACL injury in highly active individuals may be predicated on a number of modifiable and nonmodifiable factors, clinicians have the greatest potential to address the modifiable postsurgical risk factors through targeted neuromuscular interventions. This manuscript will (1) summarize the neuromuscular deficits commonly identified at medical discharge to return to sport, (2) provide the evidence underlying second-ACL injury risk factors, (3) propose a method to assess the modifiable deficits related to second-ACL injury risk, and (4) outline a method of intervention to prevent second ACL injury. The program described in this clinical commentary was developed with consideration for the modifiable factors related to second-injury risk, the principles of motor learning, and careful selection of the exercises that may most effectively modify aberrant neuromuscular patterns. Future validation of this evidence-based, late-phase rehabilitation program may be a critical factor in maximizing return-to-activity success and reduction of second-injury risk in highly active individuals. LEVEL OF EVIDENCE: Therapy, level 5. PMID- 24175603 TI - The modified sleeper stretch and modified cross-body stretch to increase shoulder internal rotation range of motion in the overhead throwing athlete. AB - SYNOPSIS: Stretching techniques that focus on increasing posterior shoulder soft tissue flexibility are commonly incorporated into prevention and treatment programs for the overhead athlete. The cross-body and sleeper stretch exercises have been described as stretching techniques to improve posterior shoulder soft tissue flexibility and to increase glenohumeral joint internal rotation and horizontal adduction range of motion in the overhead athlete. But, based on the inability to stabilize the scapula and control glenohumeral joint rotation with the cross-body stretch and the potential for subacromial impingement with the sleeper stretch, the authors recommend modifications to both of these commonly performed stretches. This clinical commentary reviews the literature on posterior shoulder stretches, describes modifications to both of these commonly performed stretches, and outlines a strategy to maintain or improve posterior shoulder soft tissue flexibility and glenohumeral joint internal rotation range of motion in the overhead athlete. LEVEL OF EVIDENCE: Therapy, level 5. PMID- 24175604 TI - The effect of burst-duty-cycle parameters of medium-frequency alternating current on maximum electrically induced torque of the quadriceps femoris, discomfort, and tolerated current amplitude in professional soccer players. AB - STUDY DESIGN: Repeated-measures, within-subject crossover trial. OBJECTIVES: The primary objective was to assess the effect of the burst-duty-cycle parameters of medium-frequency alternating current on the maximum electrically induced torque of the quadriceps femoris. The secondary objectives were to evaluate the amount of discomfort tolerated and the maximum current amplitude delivered for each electrical-stimulation condition. BACKGROUND: Neuromuscular electrical stimulation used for muscle strengthening can improve functional performance. However, the electrical-stimulation parameters to achieve optimal outcomes are still unknown. Previous studies have demonstrated that the characteristics of the burst duty cycle of medium-frequency alternating current influence torque generation levels and perception of sensory discomfort. METHODS: The maximum electrically induced torque was assessed with a medium-frequency alternating current, with a carrier frequency of 2500 Hz and a modulated frequency of 50 Hz. The current amplitude was gradually increased to the point of the participant's maximum tolerance level. The testing sequence for the 3 burst duty cycles (20%, 35%, and 50%) was performed in a randomized order. RESULTS: Electrical stimulation using a 20% burst duty cycle produced an electrically induced torque greater than the 35% (P = .01) and 50% (P<.01) burst duty cycles, with no difference between the 35% and 50% burst duty cycles (P = .46). There was no difference in the amount of sensory discomfort produced by the 3 durations of burst duty cycles (P = .34). There was also no difference between the 3 conditions for the maximum current amplitude tolerated (P = .62). CONCLUSION: The burst duty cycle of 20% of medium-frequency alternating current, compared to burst duty cycles of 35% and 50%, produced higher peak torque of the quadriceps femoris in professional soccer players. There was no difference in discomfort produced and current amplitude tolerated between the different burst-duty-cycle conditions. PMID- 24175605 TI - Uncertainty in clinical prediction rules: the value of credible intervals. AB - SYNOPSIS: Decision making in physical therapy is increasingly informed by evidence in the form of probabilities. Prior beliefs concerning diagnoses, prognoses, and treatment effects are quantitatively revised by the integration of new information derived from the history, physical examination, and other investigations in a well-recognized application of Bayes' theorem. Clinical prediction rule development studies commonly employ such methodology to produce quantified estimates of the likelihood of patients having certain diagnoses or achieving given outcomes. To date, the physical therapy literature has been limited to the discussion and calculation of the point estimate of such probabilities. The degree of precision associated with the construction of posterior probabilities, which requires consideration of both uncertainty associated with pretest probability and uncertainty associated with test accuracy, remains largely unrecognized and unreported. This paper provides an introduction to the calculation of the uncertainty interval, known as a credible interval, around posterior probability estimates. The method for calculating the credible interval is detailed and illustrated with example data from 2 clinical prediction rule development studies. Two relatively quick and simple methods for approximating the credible interval are also outlined. It is anticipated that knowledge of the credible interval will have practical implications for the incorporation of probabilistic evidence in clinical practice. Consistent with reporting standards for interventional and diagnostic studies, it is equally appropriate that studies reporting posterior probabilities calculate and report the level of precision associated with these point estimates. PMID- 24175606 TI - Minimal clinically important difference of the disabilities of the arm, shoulder and hand outcome measure (DASH) and its shortened version (QuickDASH). AB - STUDY DESIGN: Prospective, single-group observational design. OBJECTIVES: To determine the minimal clinically important difference (MCID) for the Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure and its shortened version (QuickDASH) in patients with upper-limb musculoskeletal disorders, using a triangulation of distribution- and anchor-based approaches. BACKGROUND: Meaningful threshold change values of outcome tools are crucial for the clinical decision-making process. METHODS: The DASH and QuickDASH were administered to 255 patients (mean +/- SD age, 49 +/- 15 years; 156 women) before and after a physical therapy program. The external anchor administered after the program was a 7-point global rating of change scale. RESULTS: The test-retest reliability of the DASH and QuickDASH was high (intraclass correlation coefficient model 2,1 = 0.93 and 0.91, respectively; n = 30). The minimum detectable change at the 90% confidence level was 10.81 points for the DASH and 12.85 points for the QuickDASH. After triangulation of these results with those of the mean-change approach and receiver-operating-characteristic-curve analysis, the following MCID values were selected: 10.83 points for the DASH (sensitivity, 82%; specificity, 74%) and 15.91 points for the QuickDASH (sensitivity, 79%; specificity, 75%). After treatment, the MCID threshold was reached/surpassed by 61% of subjects using the DASH and 57% using the QuickDASH. CONCLUSION: The MCID values from this study for the DASH (10.83 points) and the QuickDASH (15.91 points) could represent the lower boundary for a range of MCID values (reasonably useful for different populations and contextual characteristics). The upper boundary may be represented by the 15 points for the DASH and 20 points for the QuickDASH proposed by the DASH website. PMID- 24175608 TI - Anterior talocrural joint laxity: diagnostic accuracy of the anterior drawer test of the ankle. AB - STUDY DESIGN: Prospective, blinded, diagnostic-accuracy study. OBJECTIVES: To investigate the diagnostic accuracy of the ankle anterior drawer test (ADT) to detect anterior talocrural joint laxity in adults with a history of lateral ankle sprain. BACKGROUND: The ADT is used to manually detect anterior talocrural joint laxity following lateral ankle sprain injury; however, the diagnostic accuracy of this test has not been established. METHODS: Sixty-six subjects with a history of lateral ankle sprain were examined with the ADT. Anterior talocrural joint laxity was measured digitally from ultrasound images of the talofibular interval during performance of the ADT. In addition, anterior talocrural joint laxity was measured digitally in 20 control subjects to establish a reference standard. ADT results were defined as "positive" or "negative," based on this and a second reference standard established from the literature. RESULTS: The group with a history of lateral ankle sprain had a mean +/- SD anterior talocrural joint laxity of 3.36 +/- 3.25 mm, compared with 0.17 +/- 1.87 mm in the control group. Thirty-five of 66 (53%) subjects demonstrated anterior talocrural joint laxity at a reference standard of 2.3 mm or greater, and 24 (36%) at a reference standard of 3.7 mm or greater. Sensitivity of the ADT was 0.74 (95% confidence interval [CI]: 0.58, 0.86) and 0.83 (95% CI: 0.64, 0.93) at the 2.3 mm or greater and 3.7 mm or greater reference standards, respectively. Specificity of the test was 0.38 (95% CI: 0.24, 0.56) and 0.40 (95% CI: 0.27, 0.56), respectively. Positive likelihood ratios were 1.2 and 1.4, whereas the negative likelihood ratios were 0.66 and 0.41, respectively. CONCLUSION: The ADT provides limited ability to detect excessive anterior talocrural joint laxity; however, it may provide useful information when used in side-to-side ankle comparisons and in conjunction with other physical exam procedures, such as palpation. LEVEL OF EVIDENCE: Diagnosis, level 3b. PMID- 24175607 TI - Quadriceps and hamstrings morphology is related to walking mechanics and knee cartilage MRI relaxation times in young adults. AB - STUDY DESIGN: Controlled laboratory study using a cross-sectional design. OBJECTIVES: To analyze the relationship of quadriceps-hamstrings and medial lateral quadriceps anatomical cross-sectional area (ACSA) ratios with knee loads during walking and articular and meniscal cartilage composition in young, healthy subjects. BACKGROUND: Muscle forces affect knee loading during walking, but it is not known if muscle morphology is associated with walking mechanics and cartilage composition in young subjects. METHODS: Forty-two knees from 27 young, healthy, active volunteers (age, 20-35 years; body mass index, <28 kg/m(2)) underwent 3-T magnetic resonance imaging (MRI) and 3-D motion capture. Standard MRI sequences were used for articular and meniscal cartilage T1rho and T2 relaxation times and for quadriceps and hamstrings muscle ACSA. Frontal plane kinetics during the stance phase of walking was calculated. Generalized estimating equation models were used to identify muscle variables that predicted MRI and gait parameters. RESULTS: Quadriceps-hamstrings and medial-lateral quadriceps ACSA ratios were positively related to frontal plane loading (beta = .21-.54, P<=.006), global articular cartilage relaxation times (beta = .22-.28, P<=.041), and the medial lateral ratio of meniscus T1rho relaxation time (beta = .26-.36, P<=.049). The medial-lateral quadriceps ACSA ratio was positively related to global meniscus T1rho relaxation times (beta = .30, P = .046). CONCLUSION: Higher quadriceps hamstrings and medial-lateral quadriceps ACSA ratios were associated with higher frontal plane loading during walking and with articular and meniscal cartilage T1rho and T2 relaxation times. These findings highlight the relationships between different knee tissues and knee mechanics in young, healthy individuals. PMID- 24175609 TI - Clinical rehabilitation guidelines for matrix-induced autologous chondrocyte implantation on the tibiofemoral joint. AB - SYNOPSIS: Autologous chondrocyte implantation (ACI) has become an established technique for the repair of full-thickness chondral defects in the knee. Matrix induced ACI (MACI) is the third and current generation of this surgical technique, and, while postoperative rehabilitation following MACI aims to restore normal function in each patient as quickly as possible by facilitating a healing response without overloading the repair site, current published guidelines appear conservative, varied, potentially outdated, and often based on earlier ACI surgical techniques. This article reviews the existing evidence-based literature pertaining to cell loading and postoperative rehabilitation following generations of ACI. Based on this information, in combination with the technical benefits provided by third-generation MACI in comparison to its surgical predecessors, we present a rehabilitation protocol for patients undergoing MACI in the tibiofemoral joint that has now been implemented for several years by our institution in patients with MACI, with good clinical outcomes. PMID- 24175610 TI - Middle and lower trapezius strengthening for the management of lateral epicondylalgia: a case report. AB - STUDY DESIGN: Case report. BACKGROUND: Addressing weakness of the shoulder region, especially the rotator cuff and scapular musculature, is often suggested clinically for the treatment of individuals with lateral epicondylalgia. However, to our knowledge, the clinical effectiveness of this approach has not been established. CASE DESCRIPTION: The patient was a 54-year-old woman with a 5-month history of right lateral elbow pain, whose symptoms were reproduced with clinical tests typically used to diagnose lateral elbow tendinopathy. The patient also demonstrated weakness in her middle and lower trapezius muscles, and the medial border of her scapula, measured with a tape measure, was 11 cm lateral from the spinous processes of the thoracic spine with the patient standing in relaxed stance. Based on improved grip strength and reduced associated elbow pain when tested with the scapula manually corrected in a more adducted position, treatment focused solely on strengthening of the middle and lower trapezius muscles over a 10-week period. OUTCOMES: Following the intervention, the patient presented with improved scapular position, with the medial border of the scapula being 9 cm lateral to the midthoracic spine. The patient's middle and lower trapezius strength improved from 3+/5 and 4-/5, respectively, to 5/5, and her grip strength from 26.1 to 42.2 kg. The patient's scores on the Disabilities of the Arm, Shoulder and Hand questionnaire also improved from 44.2 at the initial evaluation to 0 at the completion of therapy, with the patient being able to perform all of her daily activities in a pain-free manner. DISCUSSION: The results of this case report suggest that assessment and treatment of scapular musculature warrant consideration in the management of individuals with lateral epicondylalgia. LEVEL OF EVIDENCE: Therapy, level 4. PMID- 24175611 TI - Varied response to mirror gait retraining of gluteus medius control, hip kinematics, pain, and function in 2 female runners with patellofemoral pain. AB - STUDY DESIGN: Case report. BACKGROUND: The underlying mechanism of the changes in running mechanics after gait retraining is presently unknown. This case report assesses changes in muscle coordination and kinematics during treadmill running and step ascent in 2 female runners with patellofemoral pain after mirror gait retraining. CASE DESCRIPTION: Two female runners with chronic patellofemoral pain underwent 8 sessions of mirror gait retraining during treadmill running. Subjective measures and hip abductor strength were recorded at baseline and after the retraining phase. Changes in hip mechanics and electromyography data of the gluteus medius during treadmill running and step ascent were also assessed. OUTCOMES: Both runners reported improvements in pain and function that were maintained for at least 3 months. During running, peak contralateral pelvic drop (baseline-postretraining difference: runner 1, 2.6 degrees less; runner 2, 1.7 degrees less) and peak hip adduction (baseline-postretraining difference: runner 1, 5.2 degrees less; runner 2, 6.3 degrees less) were reduced after retraining. Kinematic reductions accompanied earlier activation of the gluteus medius relative to foot strike (baseline-postretraining difference: runner 1, 12.6 milliseconds earlier; runner 2, 37.3 milliseconds earlier) and longer duration of gluteus medius activity (runner 1, 55.8 milliseconds longer; runner 2, 44.4 milliseconds longer). Runner 1 transferred reduced contralateral pelvic drop to step ascent, whereas runner 2 did not (contralateral pelvic drop baseline postretraining difference: runner 1, 3.6 degrees less; runner 2, 1.5 degrees more; hip adduction baseline-postretraining difference: runner 1, 3.0 degrees less; runner 2, 0.5 degrees more). Both runners demonstrated earlier onset of gluteus medius activity during step ascent (baseline-postretraining difference: runner 1, 48.0 milliseconds earlier; runner 2, 28.3 milliseconds earlier), but only runner 1 demonstrated longer activation duration (runner 1, 25.0 milliseconds longer; runner 2, 69.4 milliseconds shorter). DISCUSSION: While changes in hip mechanics and gluteus medius activity during running were consistent with those noted during step ascent for runner 1, runner 2 failed to demonstrate similar consistency between the tasks. Earlier onset and longer duration of gluteus medius activity may have been necessary to alter step mechanics for runner 2. LEVEL OF EVIDENCE: Therapy, level 4. PMID- 24175612 TI - Identification and quantification of soluble free, soluble conjugated, and insoluble bound phenolic acids in durum wheat (Triticum turgidum L. var. durum) and derived products by RP-HPLC on a semimicro separation scale. AB - A straightforward semimicro separation scale RP-HPLC method was developed for the identification and quantification of phenolic acids (PAs) occurring as soluble free, soluble conjugated, and insoluble bound compounds, which were independently extracted from wholemeal of durum wheat and from its derived products coarse bran, semolina, and dried pasta. A narrow bore column and a semimicro photodiode array detector (PDA) cell, in conjunction with a single quadrupole mass spectrometer, equipped with an electrospray ionization source (ESI-MS), were employed. The method was validated in terms of linearity of calibration graphs, limits of detection, limits of quantification, repeatability, and accuracy, which was evaluated by a recovery study. In each sample (wholemeal, coarse bran, semolina, and dried pasta), the total amounts of the three different forms of PAs were in the order bound > conjugated > free, with bound PAs accounting for 61.0 83.6% of the total PAs. Ferulic acid was the most abundant PA in both soluble free and insoluble bound forms, whereas sinapic acid predominated in the conjugated ones. The highest PA content, calculated as the sum of total PAs quantified in the three forms, was found in coarse bran, followed by wholemeal, semolina, and dried pasta. PMID- 24175613 TI - Inducing secondary metabolite production by the endophytic fungus Fusarium tricinctum through coculture with Bacillus subtilis. AB - Coculturing the fungal endophyte Fusarium tricinctum with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium resulted in an up to 78-fold increase in the accumulation in constitutively present secondary metabolites that included lateropyrone (5), cyclic depsipeptides of the enniatin type (6-8), and the lipopeptide fusaristatin A (9). In addition, four compounds (1-4) including (-) citreoisocoumarin (2) as well as three new natural products (1, 3, and 4) were not present in discrete fungal and bacterial controls and only detected in the cocultures. The new compounds were identified as macrocarpon C (1), 2 (carboxymethylamino)benzoic acid (3), and (-)-citreoisocoumarinol (4) by analysis of the 1D and 2D NMR and HRMS data. Enniatins B1 (7) and A1 (8), whose production was particularly enhanced, inhibited the growth of the cocultivated B. subtilis strain with minimal inhibitory concentrations (MICs) of 16 and 8 MUg/mL, respectively, and were also active against Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis with MIC values in the range 2-8 MUg/mL. In addition, lateropyrone (5), which was constitutively present in F. tricinctum, displayed good antibacterial activity against B. subtilis, S. aureus, S. pneumoniae, and E. faecalis, with MIC values ranging from 2 to 8 MUg/mL. All active compounds were equally effective against a multiresistant clinical isolate of S. aureus and a susceptible reference strain of the same species. PMID- 24175615 TI - Pollution control on River Nile in the White Nile State sugar hub of Sudan. PMID- 24175614 TI - Quantitative proteome analysis of alveolar type-II cells reveals a connection of integrin receptor subunits beta 2/6 and WNT signaling. AB - Alveolar type-II cells (ATII cells) are lung progenitor cells responsible for regeneration of alveolar epithelium during homeostatic turnover and in response to injury. Characterization of ATII cells will have a profound impact on our understanding and treatment of lung disease. The identification of novel ATII cell-surface proteins can be used for sorting and enrichment of these cells for further characterization. Here we combined a high-resolution mass spectrometry based membrane proteomic approach using lungs of the SILAC mice with an Affymetrix microarray-based transcriptome analysis of ATII cells. We identified 16 proteins that are enriched in the membrane fraction of ATII cells and whose genes are highly expressed in these cells. Interestingly, we confirmed our data for two of these genes, integrin beta 2 and 6 (Itgb2 and Itgb6), by qRT-PCR expression analysis and Western blot analysis of protein extracts. Moreover, flow cytometry and immunohistochemistry in adult lung revealed that ITGB2 and ITGB6 are present in subpopulations of surfactant-associated-protein-C-positive cells, suggesting the existence of different types of ATII cells. Furthermore, analysis of the Itgb2(-/-) mice showed that Itgb2 is required for proper WNT signaling regulation in the lung. PMID- 24175616 TI - Theoretical and kinetic study of the hydrogen atom abstraction reactions of esters with H(O.)2 radicals. AB - This work details an ab initio and chemical kinetic study of the hydrogen atom abstraction reactions by the hydroperoxyl radical (HO2) on the following esters: methyl ethanoate, methyl propanoate, methyl butanoate, methyl pentanoate, methyl isobutyrate, ethyl ethanoate, propyl ethanoate, and isopropyl ethanoate. Geometry optimizations and frequency calculations of all of the species involved, as well as the hindrance potential descriptions for reactants and transition states, have been performed with the Moller-Plesset (MP2) method using the 6-311G(d,p) basis set. A validation of all of the connections between transition states and local minima was performed by intrinsic reaction coordinate calculations. Electronic energies for all of the species are reported at the CCSD(T)/cc-pVTZ level of theory in kcal mol(-1) with the zero-point energy corrections. The CCSD(T)/CBS (extrapolated from CCSD(T)/cc-pVXZ, in which X = D, T, Q) was used for the reactions of methyl ethanoate + HO2 radicals as a benchmark in the electronic energy calculations. High-pressure limit rate constants, in the temperature range 500-2000 K, have been calculated for all of the reaction channels using conventional transition state theory with asymmetric Eckart tunneling corrections. The 1-D hindered rotor approximation has been used for the low frequency torsional modes in both reactants and transition states. The calculated individual and total rate constants are reported for all of the reaction channels in each reaction system. A branching ratio analysis for each reaction site has also been investigated for all of the esters studied in this work. PMID- 24175618 TI - Wet-chemical approaches to porous nanowires with linear, spiral, and meshy topologies. AB - We report universal approaches for porous nanowires (NWs), and porous NWs with spiral and meshy topologies that have been developed via anodic aluminum oxide (AAO) confined wet-chemical synthesis. Materials such as CuOx, Pd, and Cu NWs are taken as examples for porous NWs and porous NWs with spiral and meshy topologies. Immediate benefits are demonstrated in hydrogen sensors as examples. We observed that hydrogen concentrations as low as 0.2% (v/v) were detected, that critical temperatures of the reverse sensing behavior as low as 239.9 K were measured and that better baseline-stability was confirmed compared with those fabricated with pure Pd NWs. Our approaches are anticipated to work on the synthesis of the porous NWs of other materials that could be obtained via wet-chemistry with potential as candidates for the next generation nanodevices (e.g., gas sensors) and other applications (e.g., catalysts). PMID- 24175619 TI - D-methionine pre-loading reduces both noise-induced permanent threshold shift and outer hair cell loss in the chinchilla. AB - OBJECTIVE: This study tested multiple dosing epochs of pre-loaded D-methionine (D met) for otoprotection from noise-induced hearing loss (NIHL). DESIGN: Auditory brainstem response (ABR) thresholds were measured at baseline, 1 day, and 21 days following a 6-hour 105 dB sound pressure level (SPL) octave band noise (OBN) exposure. Outer hair cell (OHC) counts were measured after day 21 sacrifice. STUDY SAMPLE: Three groups of five Chinchillas laniger each were given a 2-day regimen comprising five doses of D-met (200 mg/kg/dose) intraperitoneally (IP) starting 2, 2.5, or 3 days prior to noise exposure. A control group (n = 5) received five doses of equivalent volume saline IP starting 2.5 days prior to noise exposure. RESULTS: ABR threshold shifts from baseline to day-21 post-noise exposure were reduced in all D-met groups versus controls, reaching significance (p < 0.05) in the 3-day group. D-met groups showed reduced OHC loss relative to controls at day-21 post-noise exposure, reaching significance (p < 0.05) at all frequency regions in the 3-day group and at the 2, 4, and 8 kHz frequency regions in the 2.5-day group. CONCLUSIONS: D-met administration in advance of noise exposure, without further administration, significantly protects from noise induced ABR threshold shift and OHC loss. PMID- 24175617 TI - Biochemical characterization of protein quality control mechanisms during disease progression in the C22 mouse model of CMT1A. AB - Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary demyelinating neuropathy linked with duplication of the peripheral myelin protein 22 (PMP22) gene. Transgenic C22 mice, a model of CMT1A, display many features of the human disease, including slowed nerve conduction velocity and demyelination of peripheral nerves. How overproduction of PMP22 leads to compromised myelin and axonal pathology is not fully understood, but likely involves subcellular alterations in protein homoeostatic mechanisms within affected Schwann cells. The subcellular response to abnormally localized PMP22 includes the recruitment of the ubiquitin-proteasome system (UPS), autophagosomes and heat-shock proteins (HSPs). Here we assessed biochemical markers of these protein homoeostatic pathways in nerves from PMP22-overexpressing neuropathic mice between the ages of 2 and 12 months to ascertain their potential contribution to disease progression. In nerves of 3-week-old mice, using endoglycosidases and Western blotting, we found altered processing of the exogenous human PMP22, an abnormality that becomes more prevalent with age. Along with the ongoing accrual of misfolded PMP22, the activity of the proteasome becomes compromised and proteins required for autophagy induction and lysosome biogenesis are up-regulated. Moreover, cytosolic chaperones are consistently elevated in nerves from neuropathic mice, with the most prominent change in HSP70. The gradual alterations in protein homoeostatic response are accompanied by Schwann cell de-differentiation and macrophage infiltration. Together, these results show that while subcellular protein quality control mechanisms respond appropriately to the presence of the overproduced PMP22, with aging they are unable to prevent the accrual of misfolded proteins. PMID- 24175620 TI - The effects of pole walking on arm lymphedema and cardiovascular fitness in women treated for breast cancer: a pilot and feasibility study. AB - The benefit of exercise for breast cancer-treated women is well documented. However, studies of cardiovascular fitness training for women with breast cancer related arm lymphedema are rare. The purpose of this study was to investigate the effects of intensive pole walking on arm lymphedema in women treated for breast cancer. Thirty-five women with unilateral lymphedema were included and twenty three completed an eight-week exercise intervention consisting of pole walking 3 5 times per week, for 30-60 min, at 70%-80% of their maximum heart rate, preceded by a two-week control period. Measurements of arm lymphedema (water displacement method), body weight, cardiovascular fitness (sub-maximal bicycle ergometer test) and subjective assessments (disability of the arm, shoulder and hand (DASH) questionnaire; heaviness and tightness using a visual analogue scale (VAS); and well-being) were performed before the control period and before and after the exercise intervention. The results indicated a significant reduction in total arm volume of the lymphedema arm (p = 0.001), in lymphedema absolute volume (p = 0.014) and lymphedema relative volume (p = 0.015). Significant decreases of heart rate (p = 0.004), DASH score (p = 0.053) and rating of tightness in the arm (p = 0.043) were found. Positive and negative influences on well-being were reported. The conclusion of this study is that pole walking is feasible for breast cancer treated women with arm lymphedema. PMID- 24175621 TI - Anterior cruciate ligament surgery: optimize return to activity and minimize risk of a second injury. AB - A torn anterior cruciate ligament (ACL) can be a devastating injury for active individuals and athletes. After the injury, some individuals will recover with a good rehabilitation program and will not need surgery. However, if the injured knee feels like it gives way or if the knee is not stable, surgery to "reconstruct" the ACL may be required. After surgery, returning to preinjury activities can be challenging. In a review article published in the November 2013 issue of JOSPT, the authors' findings provide new insight and research-based strategies to help enhance performance and limit the risk of reinjury after ACL surgery. PMID- 24175622 TI - Triceps tendon tear in a middle-aged weightlifter. AB - The patient was a 47-year-old man who was evaluated by a physical therapist for a chief complaint of posterior right elbow pain. The patient routinely participated in weightlifting activities and reported a sudden onset of triceps weakness and posterior elbow pain while performing clap push-ups 3 days prior. A physician assistant ordered radiographs, which were initially interpreted as normal, and routine magnetic resonance imaging for the right elbow. Following examination by a physical therapist, due to concern for a triceps tendon tear, the previously ordered magnetic resonance imaging was expedited, which revealed a partial triceps tendon tear with partial tendon retraction medially. PMID- 24175623 TI - A cautionary note on endorsing the placebo effect. PMID- 24175624 TI - Kinetic study of aroxyl radical scavenging and alpha-tocopheroxyl regeneration rates of pyrroloquinolinequinol (PQQH2, a reduced form of pyrroloquinolinequinone) in dimethyl sulfoxide solution: finding of synergistic effect on the reaction rate due to the coexistence of alpha-tocopherol and PQQH2. AB - Measurements of aroxyl radical (ArO*)-scavenging rate constants (ks AOH) of antioxidants (AOHs: pyrroloquinolinequinol (PQQH2), alpha-tocopherol (alpha TocH), ubiquinol-10 (UQ10H2), epicatechin, epigallocatechin, epigallocatechin gallate, and caffeic acid) were performed in dimethyl sulfoxide (DMSO) solution, using stopped-flow spectrophotometry. The ks AOH values were measured not only for each AOH but also for the mixtures of two AOHs ((i) alpha-TocH and PQQH2 and (ii) alpha-TocH and UQ10H2). A notable synergistic effect that the ks AOH values increase 1.72, 2.42, and 2.50 times for alpha-TocH, PQQH2, and UQ10H2, respectively, was observed for the solutions including two kinds of AOHs. Measurements of the regeneration rates of alpha-tocopheroxyl radical (alpha-Toc*) to alpha-TocH by PQQH2 and UQ10H2 were performed in DMSO, using double-mixing stopped-flow spectrophotometry. Second-order rate constants (kr) obtained for PQQH2 and UQ10H2 were 1.08 * 105 and 3.57 * 104 M-1 s-1, respectively, indicating that the kr value of PQQH2 is 3.0 times larger than that of UQ10H2. It has been clarified that PQQH2 and UQ10H2 having two HO groups within a molecule may rapidly regenerate two molecules of alpha-Toc* to alpha-TocH. The result indicates that the prooxidant effect of alpha-Toc* is suppressed by the coexistence of PQQH2 or UQ10H2. PMID- 24175625 TI - IR and UV spectroscopy of vapor-phase jet-cooled ionic liquid [emim]+ [Tf2N]-: ion pair structure and photodissociation dynamics. AB - Small gas-phase clusters (ion pairs) of the ionic liquid [emim](+)[Tf2N](-) have been generated in a supersonic expansion. Clusters are investigated via UV photofragmentation and time-of-flight mass spectrometry. Spectra between 42,000 and 45,000 cm(-1) reveal dynamical branching between direct dissociation of the ion pair to the cation and anion and to radical species. The IR spectrum between 2800 and 3200 cm(-1) was measured by action spectroscopy. Multiple conformations of the ion pair are found to be present in the molecular beam, leading to broad spectral features, further complicated by hydrogen bonding and Fermi resonances. The measured and theoretical spectra compare well, and the jet-cooled ion pair structures present in the molecular beam are strongly hydrogen bonded "stacked" conformers. PMID- 24175626 TI - Identification of CB1/CB2 ligands from Zanthoxylum bungeanum. AB - In order to study cannabinoid receptor ligands, a novel plate-based assay was developed previously to measure internalization of CB1/CB2 receptors by determining the change in the intracellular levels of the radiolabeled agonists. This plate-based assay was also used for screening against complex matrices, specifically, in the present study screening for CB1/CB2 receptor activity of extracts for several species of the plant genus Zanthoxylum. The objective of this screen was to identify novel antagonists of the CB1 receptor, which simultaneously displayed agonist activity against the CB2 receptor, since compounds matching this criterion could be potential candidates for the treatment of type-1 diabetes. As a result, two Z. bungeanum extracts were deemed active, leading to the identification of eight compounds, of which compound 7 [(2E,4E,8E,10E,12E)-N-isobutyl-2,4,8,10,12-tetradecapentaenamide, gamma-sanshool] was obtained as a promising lead compound. PMID- 24175628 TI - Immunoregulatory effects of interferon-beta in suppression of Th17 cells. AB - To investigate the immunoregulatory effects of interferon (IFN)-beta on CD4+ T cells, we examined the response of CD4+ T cells from IFN-beta(+/+) and IFN-beta( /-) mice to CD3/CD28 activation and to differentiation to Th17 lineage, analyzing the expression of signaling effectors, cell surface receptors, production of IL 17, and gene expression profiles. We provide evidence of increased phosphorylation of the membrane proximal kinase associated with TCR activation, ZAP-70, in IFN-beta(-/-) T cells compared with IFN-beta(+/+) T cells. Anti CD3/anti-CD28 antibody stimulation of whole splenocytes or CD4+ T cells from IFN beta(-/-) mice results in secretion of IL-17A, in contrast to identical stimulation of cells from IFN-beta(+/+) mice, which fails to increase IL-17A production. After CD3/CD28 activation, IFN-beta(-/-) CD4+ T cells express higher levels of IRF-4, required for Th17 differentiation, and increased expression of CCR6, IL-23R, IL-6R, and CXCR4, compared with activated IFN-beta(+/+) T cells. Notably, cell surface expression of IL-6R and IL-23R is significantly higher in the IFN-beta(-/-) CD4+ T cells, with an increased number of double-positive CCR6+IL-23R+ and IL-6R+IL-23R+ CD4+ T cells. On polarization to Th17 lineage, CD4+ T cells from IFN-beta(-/-) mice exhibit a more Th17-primed transcriptome compared with CD4+ T cells from IFN-beta(+/+) mice. Indeed, when CD4+ T cells from IFN-beta(+/+) mice are polarized to Th17 lineage in the presence of IFN beta, many Th17-associated genes are down-regulated. Employing a MOG-peptide induced experimental autoimmune encephalomyelitis model of multiple sclerosis, we identify a greater proportion of Th17 cells in the lymph nodes of IFN-beta(-/-) mice compared with IFN-beta(+/+) mice, and increased numbers of CD4+ T cells in the central nervous system of IFN-beta(-/-) mice, regardless of the stage of disease. Taken together, our data indicate an immunoregulatory role for IFN-beta in the suppression of Th17 cells. PMID- 24175627 TI - Large-scale mass spectrometric detection of variant peptides resulting from nonsynonymous nucleotide differences. AB - Each individual carries thousands of nonsynonymous single nucleotide variants (nsSNVs) in their genome, each corresponding to a single amino acid polymorphism (SAP) in the encoded proteins. It is important to be able to directly detect and quantify these variations at the protein level to study post-transcriptional regulation, differential allelic expression, and other important biological processes. However, such variant peptides are not generally detected in standard proteomic analyses due to their absence from the generic databases that are employed for mass spectrometry searching. Here we extend previous work that demonstrated the use of customized SAP databases constructed from sample-matched RNA-Seq data. We collected deep-coverage RNA-Seq data from the Jurkat cell line, compiled the set of nsSNVs that are expressed, used this information to construct a customized SAP database, and searched it against deep-coverage shotgun MS data obtained from the same sample. This approach enabled the detection of 421 SAP peptides mapping to 395 nsSNVs. We compared these peptides to peptides identified from a large generic search database containing all known nsSNVs (dbSNP) and found that more than 70% of the SAP peptides from this dbSNP-derived search were not supported by the RNA-Seq data and thus are likely false positives. Next, we increased the SAP coverage from the RNA-Seq derived database by utilizing multiple protease digestions, thereby increasing variant detection to 695 SAP peptides mapping to 504 nsSNV sites. These detected SAP peptides corresponded to moderate to high abundance transcripts (30+ transcripts per million, TPM). The SAP peptides included 192 allelic pairs; the relative expression levels of the two alleles were evaluated for 51 of those pairs and were found to be comparable in all cases. PMID- 24175629 TI - Flash ignition of freestanding porous silicon films: effects of film thickness and porosity. AB - We report the first successful xenon flash ignition of freestanding porous Si films in air. The minimum flash ignition energy (Emin) first decreases and then increases with increasing the porous Si film thickness due to the competition between light absorption and heat loss. The Emin is lower for higher porosity film because high porosity reduces both the heat capacity and the thermal conductivity, facilitating the temperature rise. These results are important for initiating controlled porous Si combustion and preventing their unwanted combustion for safety reasons. PMID- 24175630 TI - Outcomes from an urban pediatric obesity program targeting minority youth: the Healthy Hawks program. AB - BACKGROUND: The aim of this study was to describe the outcomes of a family-based behavioral group treatment program with a group of urban, minority, low-income families. METHODS: Two hundred and ten families enrolled in a 12-week family based behavioral group treatment program for pediatric obesity. The program was offered in English and in Spanish and targeted the enrollment of low-income highly diverse youth and families. Primary outcome measures included child BMI z score (zBMI), maternal BMI, 3-day diet record, and accelerometer. RESULTS: Seventy-one percent of enrolled families completed the 12-week program. Significant 12-week outcomes were achieved for child zBMI (p<0.001) and for maternal BMI (p<0.001), as well as for child kcals (p<0.001), sugar-sweetened beverages (p=0.017), and red foods (p<0.001). Only change in child zBMI remained significant at 1 year (p<0.05). Physical activity outcomes were not significant and not in the expected direction. There were no differences in outcome by race/ethnicity, but by age, younger children had higher zBMI at baseline and were also more likely to decrease zBMI during the intervention. CONCLUSIONS: It is possible to enroll and maintain urban, minority, low-income families in a family based behavioral group treatment program for pediatric obesity. Outcome data indicate that these families achieve significant outcomes on zBMI, and that children who remain available for assessment maintain this at 1 year, which is an improvement over previous research using other intervention methodologies with this population. PMID- 24175631 TI - The cytokine-induced conformational switch of nuclear factor kappaB p65 is mediated by p65 phosphorylation. AB - The transcription factor NF-kappaB (nuclear factor kappaB) serves to up-regulate gene expression in response to precarious signals such as the pro-inflammatory cytokines TNF (tumour necrosis factor) and IL-1 (interleukin 1). In the present study we show that stimulation of cells with TNF or IL-1 results in a profound conformational switch of the NF-kappaB subunit p65, as revealed by limited proteolysis assays. We also describe the identification of a conformation specific monoclonal antibody that preferentially immunoprecipitates the inducibly refolded p65 protein. The cytokine-triggered reconfiguration of p65 mainly occurs for p65 contained in the nuclear fraction. Phosphorylations serve as the central driving force for the inducible reconfiguration of p65. Accordingly, mutation of single phosphorylation sites in the C-terminal transactivation domain led to large conformational changes which result in strongly decreased ubiquitination and also in differential protein-protein interactions. Induced conformational changes of p65 thus increase the intramolecular flexibility and therefore expand and specify the repertoire of possible protein-protein interactions. Constitutively bound chaperones of the Hsp (heat-shock protein)/Hsc70 (heat-shock cognate protein, 73 kDa) family are not important for the cytokine-induced conformational switch, but rather control the fidelity of protein rearrangement. Accordingly, pharmacological inhibition of Hsp/Hsc70 interferes with p65 triggered gene expression. PMID- 24175632 TI - Identification of pyroglutamyl peptides in Japanese rice wine (sake): presence of hepatoprotective pyroGlu-Leu. AB - Japanese rice wine, sake, is made from steamed rice, water, and lactic acid by "multiple parallel fermentation" with mold (Aspergillus oryzae) and yeast (Saccharomyces cerevisiae). Nineteen pyroglutamyl peptides were identified in commercially available sake. Among them, pyroGlu-Leu and pyroGlu-Gln were the major constituents. PyroGlu-Leu has been demonstrated to attenuate hepatitis and colitis in animal models. Commercial products (n = 5) contained pyroGlu-Leu at concentrations ranging from 40 to 60 MUM (10-15 mg/L). The pyroGlu-Leu content in sake mash increased during the fermentation processes. However, no pyroGlu-Leu was produced by yeast inoculated into preheated mash. Furthermore, addition of (13)C-Leu to the mash did not increase the ratio of pyroGlu-(13)C-Leu to pyroGlu (12)C-Leu. On the other hand, digestion of steamed rice with A. oryzae proteases increased the pyroGlu-Leu content. These results indicate that pyroGlu-Leu in sake is produced from rice proteins by digestion with A. oryzae proteases. PMID- 24175633 TI - Experimental verification of methane-carbon dioxide replacement in natural gas hydrates using a differential scanning calorimeter. AB - The methane (CH4) - carbon dioxide (CO2) swapping phenomenon in naturally occurring gas hydrates is regarded as an attractive method of CO2 sequestration and CH4 recovery. In this study, a high pressure microdifferential scanning calorimeter (HP MU-DSC) was used to monitor and quantify the CH4 - CO2 replacement in the gas hydrate structure. The HP MU-DSC provided reliable measurements of the hydrate dissociation equilibrium and hydrate heat of dissociation for the pure and mixed gas hydrates. The hydrate dissociation equilibrium data obtained from the endothermic thermograms of the replaced gas hydrates indicate that at least 60% of CH4 is recoverable after reaction with CO2, which is consistent with the result obtained via direct dissociation of the replaced gas hydrates. The heat of dissociation values of the CH4 + CO2 hydrates were between that of the pure CH4 hydrate and that of the pure CO2 hydrate, and the values increased as the CO2 compositions in the hydrate phase increased. By monitoring the heat flows from the HP MU-DSC, it was found that the noticeable dissociation or formation of a gas hydrate was not detected during the CH4 - CO2 replacement process, which indicates that a substantial portion of CH4 hydrate does not dissociate into liquid water or ice and then forms the CH4 + CO2 hydrate. This study provides the first experimental evidence using a DSC to reveal that the conversion of the CH4 hydrate to the CH4 + CO2 hydrate occurs without significant hydrate dissociation. PMID- 24175634 TI - Solvent versus temperature control over the infrared band shape and position in Fe(CO)3(eta(4)-ligand) complexes. AB - The solute-solvent interactions between Fe(CO)3(eta(4)-cyclooctatetraene) (FeCOT) and 27 solvents were examined by infrared (IR) spectroscopy. The observed change in band shape and position of the carbonyl bands as a function of solvent was found to be very similar to that previously observed in temperature-dependent IR experiments of Fe(CO)3(eta(4)-norborndiene) (FeNBD). While for FeNBD the change in band shape results from dynamic exchange of carbonyl ligands, temperature dependent IR experiments in ethyl acetate show that the observed changes are not a result of carbonyl ligand site exchange for FeCOT. We therefore concluded that the solvent dependence of the IR spectra must be a consequence of a static solute solvent interaction. We find that the linear solvation energy model (J. Am. Chem. Soc. 1977, 99, 6027-6038; Chem. Soc. Rev. 1993, 22, 409-416) provides a satisfactory account for the spectral changes due to the solvent. From this model, we are able to conclude that the solute-solvent interactions of this system are influenced by the solvent's polarizability and hydrogen bonding acidity. We also observed interdependence between the change in fwhm and band positions for all three carbonyl bands, which brings us to the conclusion that the observed changes in the IR carbonyl band shape of FeCOT are a consequence of the solute-solvent interactions, rather than any solvent friction effects. This implies that care must be taken to separate the effects of chemical dynamics and solvatochromism when examining IR spectra of molecules suspected of exhibiting dynamically broadened vibrational spectra. PMID- 24175635 TI - An interactive exercise in advance care planning for medical students. AB - BACKGROUND: With the growing need to train medical professionals how to engage their patients in advance care planning, this study examines medical students' experience using an interactive, online decision aid to help consenting adults complete an advance directive. METHODS: Third-year medical students at the University of California, Davis (UC Davis) used an online, multimedia decision aid to help an adult discuss his or her wishes for medical treatment and create a formal advance directive for health care. Students then wrote essays about their experiences, and an iterative analysis was used for thematic categorization. RESULTS: Four distinct thematic categories emerged from students' essays: 1) students' personal experiences with advance care planning; 2) participants' experiences; 3) recommendations for practice regarding advance care planning; and 4) feedback about the online decision aid. CONCLUSIONS: An interactive, online decision aid can play a meaningful role in educating medical professionals about advance care planning. PMID- 24175636 TI - The use of family conferences in the pediatric intensive care unit. AB - BACKGROUND: Data about pediatric intensive care unit (PICU) family conferences (FCs) are needed to enhance our understanding of the role of FCs in patient care and build a foundation for future research on PICU communication and decision making. OBJECTIVE: The study's objective was to describe the use and content of PICU FCs. DESIGN: The study design was a prospective chart review comparing patients who had conferences with those who did not, and a sub-analysis of patients with chronic care conditions (CCCs). SETTING/SUBJECTS: The study setting was an academic PICU from January 2011 through June 2011. MEASUREMENTS: Medical events under consideration were placement of tracheostomy or gastrostomy tube; initiation of chronic ventilation; palliative care involvement; use of extracorporeal membrane oxygenation, continuous renal replacement, or cardiopulmonary resuscitation; care limitation orders; death; length of stay; and discharge to a new environment. RESULTS: From 661 admissions, we identified 74 conferences involving 49 patients. Sixty-four conferences (86%) were held about 40 patients with CCCs. Having a conference was associated with (p<0.05): length of PICU admission; palliative care involvement; initiation of chronic ventilation; extracorporeal membrane oxygenation; cardiopulmonary resuscitation; death; discharge to a new environment; and care limitation orders. Twenty-nine percent of patients who had a new tracheostomy or gastrostomy tube placed had a conference. We identified two categories of discussion topics: information exchange and future management. CONCLUSIONS: Most identified FCs involved complex patients or patients who faced decisions affecting the child's quality of life or dying. For many patients who faced life changing decisions we did not identify a FC. Further research is needed to understand how to best utilize FCs and less formal conversations. PMID- 24175637 TI - Topological surface transport properties of single-crystalline SnTe nanowire. AB - SnTe has attracted worldwide interest since its theoretical predication as topological crystalline insulator. Because of promising applications of one dimensional topological insulator in nanoscale electronics and spintronics device, it is very important to realize the observation of topological surface states in one-dimensional SnTe. In this work, for the first time we successfully synthesized high-quality single crystalline SnTe nanowire via gold-catalyst chemical vapor deposition method. Systematical investigation of Aharonov-Bohm and Shubnikov-de Haas oscillations in single SnTe nanowire prove the existence of Dirac electrons. Further analysis of temperature-dependent Shubnikov-de Haas oscillations gives valuable information of cyclotron mass, mean-free path, and mobility of Dirac electrons in SnTe nanowire. Our study provides the experimental groundwork for research in low-dimensional topological crystalline insulator materials and paves the way for the application of SnTe nanowire in nanoelectronics and spintronics device. PMID- 24175638 TI - Gymnopalynes A and B, chloropropynyl-isocoumarin antibiotics from cultures of the basidiomycete Gymnopus sp. AB - A chlorinated isocoumarin with an acetylenyl side chain and its 3,4-dihydro derivative, named gymnopalynes A (1) and B (2), were isolated from cultures of a basidiomycete originating from the rain forest of Northern Thailand. The producing organism was identified as a species of Gymnopus (Marasmiaceae). Their structures were elucidated by spectroscopic methods including UV/vis and NMR spectroscopy as well as high-resolution mass spectrometry as 3-(3-chloroprop-1-yn 1-yl)-1H-isochromen-1-one (1) and 3-(3-chloroprop-1-yn-1-yl)-3,4-dihydro-1H isochromen-1-one (2). The absolute stereochemistry of 2 was assigned as S by CD spectroscopy. Both compounds showed weak to moderate antimicrobial and pronounced cytotoxic activities. PMID- 24175639 TI - Admission CTG test: "to be or not to be". PMID- 24175640 TI - Absorption mode FTICR mass spectrometry imaging. AB - Fourier transform ion cyclotron resonance mass spectrometry offers the highest mass resolving power for molecular imaging experiments. This high mass resolving power ensures that closely spaced peaks at the same nominal mass are resolved for proper image generation. Typically higher magnetic fields are used to increase mass resolving power. However, a gain in mass resolving power can also be realized by phase correction of the data for absorption mode display. In addition to mass resolving power, absorption mode offers higher mass accuracy and signal to-noise ratio over the conventional magnitude mode. Here, we present the first use of absorption mode for Fourier transform ion cyclotron resonance mass spectrometry imaging. The Autophaser algorithm is used to phase correct each spectrum (pixel) in the image, and then, these parameters are used by the Chameleon work-flow based data processing software to generate absorption mode "Datacubes" for image and spectral viewing. Absorption mode reveals new mass and spatial features that are not resolved in magnitude mode and results in improved selected ion image contrast. PMID- 24175641 TI - Intravitreal bevacizumab for treatment of choroidal neovascularization secondary to toxoplasmic retinochoroiditis: a case series. AB - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (Avastin) in treatment of choroidal neovascularization (CNV) secondary to toxoplasmic retinochoroiditis. DESIGN: Prospective case series. METHODS: Four patients affected by CNV secondary to inactive toxoplasmic retinochoroiditis received 1.25 mg intravitreal bevacizumab and were followed for at least six months. Patients underwent a full ophthalmic examination and fluorescein angiography (FA) and optical coherence tomography (OCT), revealing an active subfoveal CNV close to an old chorioretinal scar. All the patients were positive for toxoplasma immunoglobulins. Outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) and any adverse event related to the therapy. RESULTS: CNV regressed at eight weeks of follow-up and remained stable at six months of follow-up. Best-corrected visual acuity improved from mean 0.05 to 0.25. After six months, the BCVA improved in all patients (p < 0.05) and CMT decreased from 396 +/-7 micron to 253+/-17 micron. Metamorphopsia was resolved in all cases. CONCLUSIONS: Intravitreal bevacizumab seems to be an effective treatment for the long-term control of juxta/subfoveal CNV secondary to toxoplasmic retinochoroiditis. Further trials are mandatory to validate the data of our case series. PMID- 24175642 TI - Neurological symptoms associated with acute multifocal placoid pigment epitheliopathy: treatment dilemma and diagnostic issues. AB - Acute multifocal placoid pigment epitheliopathy (AMPPE) is thought to be caused by vasculitis of the choroid. Central nervous system involvement is rare. We report a case of a 28-year-old male who developed blurred vision (6/12 OD, 6/24 OS). Past medical history involved non-specific viral meningitis treated with intravenous antibiotics and antivirals. Subsequently, the patient complained of recurrent headaches. Based on typical clinical findings and fluorescein angiogram, he was diagnosed with AMPPE. Visual disturbance resolved without any systemic treatment. Six months later, visual symptoms recurred and resolved spontaneously, but his headache continued. A few months later, the patient developed acute progressive neurological signs and symptoms necessitating inpatient admission. Lacunar infarcts in the CNS were found, which had not been noted in previous neuro-imaging studies. Cerebral vasculitis associated with AMPPE was diagnosed and treated with systemic steroids and immune suppression. Currently, the patient remains asymptomatic under joined care of an ophthalmologist and a neurologist. PMID- 24175643 TI - Photographic essay: healing by secondary intention in oculoplastics. AB - This short report is written to demonstrate the usefulness of healing by secondary intention in oculoplastics. It shows photo strips of our patient outcomes, reflecting the excellent healing capacity of the face. The main point is to challenge misconceptions that healing by secondary intention is prone to infection and scarring, but instead, to show it is a safe and practical approach to our patients. PMID- 24175644 TI - Etanercept in methotrexate-resistant JIA-related uveitis. AB - We report our results with systemic Etanercept in patients with juvenile idiopathic arthritis in a joint ophthalmology-rheumatology clinic at a tertiary hospital. METHODS: Patients with JIA on Etanercept were identified from a dedicated uveitis database. A retrospective review of electronic and paper-based patient records was performed. RESULTS: Nine patients with JIA and current or previous treatment with Etanercept were identified, including six females and three males. Five patients with previous or current uveitis were noted. A further four were under observation for uveitis and required Etanercept for their joint disease. All nine patients had previously been taking Methotrexate, which had a suboptimal response in controlling arthritis or uveitis. Six out of nine patients did not show any uveitis activity at their last follow-up. Eyes of three patients still show signs of active inflammation in the anterior chamber (two on Etanercept and one off Etanercept). Severely impaired visual acuity (PL) was recorded in both eyes of one patient with long-standing persistent uveitis. Moderate visual loss in one eye of one patient was seen. The remaining seven patients did not show any significant loss of vision. Intraocular inflammation was not induced in any patient started on Etanercept. CONCLUSION: Etanercept may be useful in controlling JIA-related uveitis or arthritis in a pediatric patient when Methotrexate has had a suboptimal response in controlling the inflammatory activity. PMID- 24175645 TI - ExPRESS Shunt Surgery for Glaucoma with Post-Traumatic Aniridia. AB - A 76-year-old male presented with post-traumatic aphakia and aniridia in the right eye. The ocular pressure was 24 mmHg despite treatment with mixed eyedrops of timolol 0.5% and dorzolamide, brimonidine 0.1%, and Latananoprost 0.005%. The glaucomatous cup excavation was 0.8. Because it was his only eye, we informed him of the possibility of the Ex-PRESS implant as a possible prevention measure of possible postoperative hypotony. Seidel, hypotony, and choroidal detachment were not observed in the postoperative period. In the first two postoperative months, the pressure remained at 14 mmHg. The ocular pressure reached 20 mmHg at three months, so he was treated with mixed eyedrops of timolol 0.5% and brimonidine 0.1%. The ocular pressure decreased to 12 mmHg and remained at that level at the 10-month follow-up. The absence of serious postoperative complications suggest that this procedure may be an alternative in selected situations, such as for our patient. PMID- 24175646 TI - Technologies for anatomical and geometric characterization of the corneal structure and anterior segment: a review. AB - Corneal and anterior segment imaging techniques have become a crucial tool in the clinical practice of ophthalmology, with a great variety of applications, such as corneal curvature and pachymetric analysis, detection of ectatic corneal conditions, anatomical study of the anterior segment prior to phakic intraocular lens implantation, or densitometric analysis of the crystalline lens. From the Placido-based systems that allow only a characterization of the geometry of the anterior corneal surface to the Scheimpflug photography-based systems that provide a characterization of the cornea, anterior chamber, and crystalline lens, there is a great variety of devices with the capability of analyzing different anatomical parameters with very high precision. To date, Scheimpflug photography based systems are the devices providing the more complete analysis of the anterior segment in a non-invasive way. More developments are required in anterior segment imaging technologies in order to improve the analysis of the crystalline lens structure as well as the ocular structures behind the iris in a non-invasive way when the pupil is not dilated. PMID- 24175647 TI - Aspergillus tubingenesis endophthalmitis after cataract surgery with implantation of preloaded intraocular lens. AB - Abstract An 88-year-old man underwent uneventful phacoemulsification and aspiration with an implantation of a preloaded acrylic intraocular lens. Six months later, he developed endophthalmitis with negative aqueous cultures, and the inflammation was refractory to conventional antibacterial therapies. He was treated successfully with vitrectomy and removal of the IOL and the entire lens capsule. A combination of intravitreal voriconazole and systemic micafungin were prescribed, and the inflammation was resolved. As best we know, this is the first case of Aspergillus tubingenesis endophthalmitis that followed the implantation of a preloaded intraocular lens. PMID- 24175648 TI - Influence of harvest season on antioxidant activity and constituents of rabbiteye blueberry ( Vaccinium ashei ) leaves. AB - To select rabbiteye blueberry leaves from an appropriate harvest season to develop functional foods, this paper studied the bioactive secondary metabolites and the antioxidant capacity of rabbiteye blueberry leaves from May, September, and November. The results showed the leaves from May had the highest content of total flavonoids (114.21 mg/g) and the leaves from November had the highest content of total polyphenols and proanthocyanidins (425.24 and 243.29 mg/g, respectively). It was further found that blueberry leaves from different seasons have similar bioactive constituents, but their contents are obviously different by HPLC. The rabbiteye blueberry leaves from November had the highest antioxidant capacity, which was well correlated with their highest proanthocyanidin content. The results clarify that the blueberry leaves from different seasons have different contents of bioactive secondary metabolites and different antioxidant activities, which implied that leaves from November should be selected first for utilization in functional foods. PMID- 24175649 TI - 1,3-Aminoalkoxylation and phenolation/dimerization of maleimide-derived Morita Baylis-Hillman adduct of isatin via domino azidation-Michael addition/aza-Diels Alder reaction. AB - NaN3-ROH/ArOH has been found to be an efficient reagent for 1,3-amino alkoxylation and 1,3-amino phenolation of a maleimide-derived MBH adduct of isatin via domino azidation-Michael addition. Following this protocol, with NaN3 formalin, a one-pot synthesis of 3-spiro-1,2-dihydropyrrolooxazine-5,7-dione oxindole has been achieved. In an aprotic medium, the reaction underwent an unusual amino dimerization via an aza-Diels-Alder reaction of a common allylic imine intermediate. PMID- 24175652 TI - Realizing the potential of agricultural and environmental proteomics. PMID- 24175653 TI - Ambulatory blood pressure monitoring in spinal cord injury: clinical practicability. AB - Trauma to the spinal cord often results not only in sensorimotor but also autonomic impairments. The loss of autonomic control over the cardiovascular system can cause profound blood pressure (BP) derangements in subjects with spinal cord injury (SCI) and may therefore lead to increased cardiovascular disease (CVD) risk in this population. The use of ambulatory blood pressure monitoring (ABPM) allows insights into circadian BP profiles, which have been shown to be of good prognostic value for cardiovascular morbidity and mortality in able-bodied subjects. Past studies in SCI subjects using ABPM have shown that alterations in circadian BP patterns are dependent on the spinal lesion level. Tetraplegic subjects with sensorimotor complete lesions have a decreased daytime arterial BP, loss of the physiological nocturnal BP dip, and higher circadian BP variability, including potentially life-threatening hypertensive episodes known as autonomic dysreflexia (AD), compared with paraplegic and able-bodied subjects. The proposed underlying mechanisms of these adverse BP alterations mainly are attributed to a lost or decreased central drive to sympathetic spinal preganglionic neurons controlling the heart and blood vessels. In addition, several maladaptive anatomical changes within the spinal cord and the periphery, as well as the general decrease of physical daily activity in SCI subjects, account for adverse BP changes. ABPM enables the identification of adverse BP profiles and the associated increased risk for CVD in SCI subjects. Concurrently, it also might provide a useful clinical tool to monitor improvements of AD and lost nocturnal dip after appropriate treatments in the SCI population. PMID- 24175654 TI - Effect of Spirulina maxima and its protein extract on micronuclei induction by hydroxyurea in pregnant mice and their fetuses. AB - The purpose of the present report was to determine the inhibitory effect of Spirulina maxima (Sm) and its protein extract (PE), mainly consisting of C phycocyanin, on the increase in micronuclei and bone marrow cytotoxicity induced by hydroxyurea (HU) in pregnant mice and their fetuses. The two tested antimutagenic agents were administered daily from day 10 to day 18 of pregnancy, and HU (300 mg/kg) was administered once on day 16 of the assay. The experimental design also included mice that were administered only Sm or PE (1000 and 400 mg/kg, respectively), two control groups that were administered with vehicles (water and 0.5% Tween 80), and one additional group that was treated solely with HU. Blood samples from the pregnant mice and their fetuses were examined at day 19 of pregnancy. Significant increases in the number of micronucleated polychromatic erythrocytes and in the total number of micronucleated erythrocytes were observed in all HU-treated animals. In contrast, similarly low numbers of micronuclei were observed in the two control groups and in the groups treated with Sm and PE alone. The administration of Sm (100, 500, and 1000 mg/kg) and PE (100, 200, and 400 mg/kg) to HU-treated animals conferred moderate genotoxic protection (~30%) and some protection against the cytotoxicity induced by HU in mice. The obtained results provide new information regarding the capacity of the tested agents to confer protection to adult mice and transplacentally, as well as on a specific subclass of micronuclei. PMID- 24175655 TI - Water-soluble undenatured type II collagen ameliorates collagen-induced arthritis in mice. AB - Earlier studies have reported the efficacy of type II collagen (C II) in treating rheumatoid arthritis (RA). However, a few studies have investigated the ability of the antigenic collagen to induce oral tolerance, which is defined as active nonresponse to an orally administered antigen. We hypothesized that water-soluble undenatured C II had a similar effect as C II in RA. The present study was designed to examine the oral administration of a novel, water-soluble, undenatured C II (commercially known as NEXT-II) on collagen-induced arthritis (CIA) in mice. In addition, the underlying mechanism of NEXT-II was also identified. After a booster dose (collagen-Freund's complete adjuvant), mice were assigned to control CIA group, or NEXT-II treatment group, to which saline and NEXT-II were administered, respectively. The arthritis index in the NEXT-II group was significantly lower compared with the CIA group. Serum IL-6 levels in the NEXT-II group were significantly lower compared with the CIA group, while serum IL-2 level was higher. Furthermore, oral administration of NEXT-II enhanced the proportion of CD4+CD25+T (Treg) cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cells such as forkhead box p3 (Foxp3), transforming growth factor (TGF)-beta1, and CD25. These results demonstrated that orally administered water-soluble undenatured C II (NEXT-II) is highly efficacious in the suppression of CIA by inducing CD4+CD25+ Treg cells. PMID- 24175656 TI - Effects of brussels sprouts and their phytochemical components on oxidative stress-induced neuronal damages in PC12 cells and ICR mice. AB - In this study, the protective effects of Brussels sprouts extract and its major constituents against oxidative stress-induced damages were investigated in rat pheochromocytoma cells and Institute of Cancer Research mice. The major constituents of Brussels sprouts (3,4',5,7-tetrahydroxyflavone (kaempferol), indole-3-carbinol, and phenethyl isothiocyanate) were selectively tested. Of these, the flavonoid compound, kaempferol exhibited the highest potency in radical scavenging activity (1,1-diphenyl-2-picryl hydrazyl assay and oxygen radical absorbance capacity assay) and was most protective against oxidative stress in neuronal cell assays (measurement of intracellular oxidative stress levels and cell viability). In mice, after 4 weeks of kaempferol administration, significant protection against amyloid beta (Abeta) peptide-induced neurotoxicity was also observed, as assessed through the passive avoidance test. Taken together, the results suggest that Brussels sprouts could be protective against Abeta-induced neurotoxicity, possibly due to the antioxidative capacity of its major constituent, kaempferol. PMID- 24175657 TI - Preparation of chitosan-coated nanoliposomes for improving the mucoadhesive property of curcumin using the ethanol injection method. AB - Chitosan-coated curcumin nanoliposomes (CS-Cur-NLs) were fabricated by the ethanol injection method (EIM), and their physicochemical properties were compared with the properties of those fabricated by the dry thin film method (DTFM). The mean size and zeta potential of CS-Cur-NLs gradually increased with CS concentration. The encapsulation efficiency of Cur-NLs prepared by EIM was 54.70%, which was significantly improved compared to that (42.60%) of Cur-NLs prepared by DTFM. Further improvement of encapsulation efficiency was attained (up to 64.93%) by EIM with 0.1% CS coating. The mucoadhesive property of Cur-NLs improved from 33.60 to 56.47% with CS coating. The results indicate that the encapsulated curcumin will show prolonged adsorption in the gastrointestinal tract because of higher mucoadhesion. Thus, EIM can be considered to be effective for food-grade delivery carriers with higher encapsulation efficiency and absence of harmful solvents. EIM-generated CS-Cur-NLs showed higher bioavailability, with enhanced high mucoadhesive property, storage stability, and encapsulation efficiency. PMID- 24175658 TI - Quorum sensing-modulated AND-gate promoters control gene expression in response to a combination of endogenous and exogenous signals. AB - We have constructed and characterized two synthetic AND-gate promoters that require both a quorum-sensing (QS) signal and an exogenously added inducer to turn on gene expression. The engineered promoters, LEE and TTE, contain binding sites for the QS-dependent repressor, EsaR, and either LacI or TetR, and they are induced by an acyl-homoserine lactone (AHL) signal and IPTG or aTc. Although repression of both LEE and TTE by wild-type EsaR was observed, induction of gene expression at physiologically relevant concentrations of AHL required the use of an EsaR variant with higher signal sensitivity. Gene expression from both LEE and TTE was shown to require both signal molecules, and gene expression above background levels was not observed with either signal alone. We added endogenous production of AHL to evaluate the ability of the promoters to function in a QS dependent manner and observed that gene expression increased as a function of cell density only in the presence of exogenously added IPTG or aTc. Cell-cell communication-dependent AND-gate behaviors were demonstrated using an agar plate assay, where cells containing the engineered promoters were shown to respond to AHL produced by a second E. coli strain only in the presence of exogenously added IPTG or aTc. The promoters described in this work demonstrate that EsaR and its target DNA sequence can be used to engineer new promoters to respond to cell density or cell-cell communication. Further, the AND-gate promoters described here may serve as a template for new regulatory systems that integrate QS and the presence of key metabolites or other environmental cues to enable dynamic changes in gene expression for metabolic engineering applications. PMID- 24175659 TI - Privileged substructure-based diversity-oriented synthesis pathway for diverse pyrimidine-embedded polyheterocycles. AB - A new diversity-oriented synthesis pathway for the fabrication of a pyrimidine embedded polyheterocycles library was developed for potential interactions with diverse biopolymers. Five different pyrimidine-embedded core skeletons were synthesized from ortho-alkynylpyrimidine carbaldehydes by a silver- or iodine mediated tandem cyclization strategy. The resulting polyheterocycles possess diverse fused ring sizes and positions with potential functionalities for further modification. PMID- 24175661 TI - A longitudinal study of hearing and middle ear status of individuals with cleft palate with and without additional malformations/syndromes. AB - Objective : To describe and compare the middle ear status and hearing sensitivity in adolescence with isolated cleft palate plus additional malformations and/or syndromes with those with only an isolated cleft palate. Design : Retrospective and longitudinal. Two groups of individuals with isolated cleft palate were compared. Participants : A cohort of individuals born over 4 years in the western region of Sweden. The cohort was divided into one group with isolated cleft palate (n = 31; ICP) and one group with isolated cleft palate plus additional malformations and/or syndromes (n = 37; ICP+). Methods : Middle ear status and hearing thresholds were collected from the medical records at 7, 10, 13, and 16 years of age, examined, and compared within and between groups over time. Results : The ICP+ group demonstrated a significantly higher prevalence of abnormal middle ear status and elevated hearing thresholds as compared with the ICP group. As the individuals aged, the prevalence of abnormal middle ear status decreased. The hearing levels in both groups decreased in the low to middle frequencies as individuals aged; however, the hearing in the high frequencies did not. Conclusions : Individuals with cleft palate need to be followed routinely for middle ear status and hearing thresholds to ensure optimal audiological rehabilitation, with particular attention to those with additional malformations and/or syndromes. PMID- 24175662 TI - Caries-risk profile variations after short-term use of 5000 ppm fluoride toothpaste. AB - OBJECTIVE: To assess the caries risk following 6 weeks' use of 5000 ppm F toothpaste using 'Cariogram' software. MATERIALS AND METHODS: A total of 34 participants, 17 mothers and their teenage children, were enrolled in a 6-week clinical trial in which they were given 5000 ppm F toothpaste. They were followed consecutively for 6 weeks with visits that were 2 weeks apart (four in total). A clinical examination was done at baseline and salivary chair-side tests to record the buffer capacity and mutans streptococci (MS) and lactobacilli (LB) counts were performed at each visit. Based on these data, seven caries-related variables were collected and inserted into the Cariogram software to calculate the actual chance of avoiding caries. RESULTS: The use of 5000 ppm F toothpaste resulted in a statistically significant modification of the caries-risk profile, increasing the actual chance of avoiding caries in the future among the mothers and teenagers at each visit following baseline (p < 0.01). The changes essentially related to the salivary parameters (buffer capacity, MS and LB counts). A statistically significant linear trend was observed for MS counts (p < 0.01) and the number of subjects with a salivary concentration of MS < 10(3) increased at each visit. The same trend was also observed for LB and buffer capacity scores (p = 0.04 and p = 0.03, respectively). CONCLUSIONS: The short-term use of 5000 ppm F toothpaste is able to reduce the caries risk, which can be clearly demonstrated using 'Cariogram' software. PMID- 24175663 TI - Influence of air-particle deposition protocols on the surface topography and adhesion of resin cement to zirconia. AB - OBJECTIVES: This study evaluated the influence of air-particle abrasion protocols on the surface roughness (SR) of zirconia and the shear bond strength (SBS) of dual-polymerized resin cement to this ceramic. MATERIALS AND METHODS: Sintered zirconia blocks (n = 115) (Lava, 3M ESPE) were embedded in acrylic resin and polished. The specimens were divided according to the 'particle type' (Al: 110 um Al2O3; Si: 110 um SiO2) and 'pressure' factors (2.5 or 3.5 bar) (n = 3 per group): (a) Control (no air-abrasion); (b) Al2.5; (c) Si2.5; (d) Al3.5; (e) Si3.5. SR (Ra) was measured 3-times from each specimen after 20 s of air-abrasion (distance: 10 mm) using a digital optical profilometer. Surface topography was evaluated under SEM analyses. For the SBS test, 'particle type', 'pressure' and 'thermocycling' (TC) factors were considered (n = 10; n = 10 per group): Control (no air-abrasion); Al2.5; Si2.5; Al3.5; Si3.5; ControlTC; Al2.5TC; Si2.5TC; Al3.5TC; Si3.5TC. After silane application, resin cement (Panavia F2.0) was bonded and polymerized. Specimens were thermocycled (6.000 cycles, 5-55 degrees C) and subjected to SBS (1 mm/min). Data were analyzed using ANOVA, Tukey's and Dunnett tests (5%). RESULTS: 'Particle' (p = 0.0001) and 'pressure' (p = 0.0001) factors significantly affected the SR. All protocols significantly increased the SR (Al2.5: 0.45 +/- 0.02; Si2.5: 0.39 +/- 0.01; Al3.5: 0.80 +/- 0.01; Si3.5: 0.64 +/- 0.01 um) compared to the control group (0.16 +/- 0.01 um). For SBS, only 'particle' factor significantly affected the results (p = 0.015). The SiO2 groups presented significantly higher SBS results than Al2O3 (Al2.5: 4.78 +/- 1.86; Si2.5: 7.17 +/- 2.62; Al3.5: 4.97 +/- 3.74; Si3.5: 9.14 +/- 4.09 MPa) and the control group (3.67 +/- 3.0 MPa). All TC specimens presented spontaneous debondings. SEM analysis showed that Al2O3 created damage in zirconia in the form of grooves, different from those observed with SiO2 groups. CONCLUSIONS: Air abrasion with 110 um Al2O3 resulted in higher roughness, but air-abrasion protocols with SiO2 promoted better adhesion. PMID- 24175664 TI - Development of novel zein-sodium caseinate nanoparticle (ZP)-stabilized emulsion films for improved water barrier properties via emulsion/solvent evaporation. AB - This work attempted to develop novel high barrier zein/SC nanoparticle (ZP) stabilized emulsion films through microfluidic emulsification (ZPE films) or in combination with solvent (ethyl acetate) evaporation techniques (ZPE-EA films). Some physical properties, including tensile and optical properties, water vapor permeability (WVP), and surface hydrophobicity, as well as the microstructure of ZP-stabilized emulsion films were evaluated and compared with SC emulsion (SCE) films. The emulsion/solvent evaporation approach reduced lipid droplets of ZP stabilized emulsions, and lipid droplets of ZP-stabilized emulsions were similar to or slightly lower than that of SC emulsions. However, ZP- and SC-stabilized emulsion films exhibited a completely different microstructure, nanoscalar lipid droplets were homogeneously distributed in the ZPE film matrix and interpenetrating protein-oil complex networks occurred within ZPE-EA films, whereas SCE films presented a heterogeneous microstructure. The different stabilization mechanisms against creaming or coalescence during film formation accounted for the preceding discrepancy of the microstructures between ZP-and SC stabilized emulsion films. Interestingly, ZP-stabilized emulsion films exhibited a better water barrier efficiency, and the WVP values were only 40-50% of SCE films. A schematic representation for the formation of ZP-stabilized emulsion films was proposed to relate the physical performance of the films with their microstructure and to elucidate the possible forming mechanism of the films. PMID- 24175665 TI - Expression of HPV-related biomarkers and grade of cervical intraepithelial lesion at treatment. AB - OBJECTIVES: New human papillomavirus (HPV)-related biomarkers may allow better identification of clinically significant lesions that warrant excision and, conversely, identification of the false positive cases that have been overreported by traditional techniques. The aim of this study was to investigate how the expression of several HPV-related biomarkers correlates to the severity of the lesion at treatment. DESIGN: Prospective observational study. SETTING: University Hospital (2009-2011). POPULATION: All women submitted for excisional treatment. METHODS: A liquid-based cytology sample was obtained before treatment and was tested for HPV typing, mRNA E6 & E7 with NASBA or flow cytometry and p16. All women had histological diagnosis in the form of excisional cone (gold standard). MAIN OUTCOME MEASURES: Correlation of HPV biomarker positivity rates to the grade of the lesion at treatment histology. RESULTS: Two hundred women were recruited: 23 were found to have negative histology (11.5%), 79 (39.5%) CIN1, 50 (25.0%) CIN2 and 48 (24.0%) CIN3. All biomarkers (HPV DNA typing, HR HPV, single HPV 16/18, mRNA E6 & E7 expression and p16) revealed an increased linear positivity rate with increasing severity and grade of the lesion (chi squared test for trend p < 0.05). This was stronger for HPV (all and high-risk) followed by mRNA with NASBA, flow cytometry, HPV 16/18 and ultimately p16 immunostaining. CONCLUSIONS: The linear correlation between various HPV-related biomarkers and the grade of the lesion suggests that these biomarkers may prove to be useful in the prediction of CIN grade and, as a result, the need for treatment. PMID- 24175666 TI - Fluorination of aryl boronic acids using acetyl hypofluorite made directly from diluted fluorine. AB - Aryl boronic acids or pinacol esters containing EDG were converted in good yields and fast reactions to the corresponding aryl fluorides using the readily obtainable solutions of AcOF. In reactions with aryl boronic acids containing EWG at the para position, there are two competing forces: one directing the fluorination to take place ortho to the boronic acid and the other, toward an ipso substitution. With EWG meta to the boronic acid, substitution ipso to the boron moiety takes place in good yields. PMID- 24175667 TI - Phosphine-catalyzed domino reaction: an efficient method for the synthesis of bicyclo[3.2.0]heptenes skeleton. AB - Dienic sulfones and gamma-CH3 allenoates can be converted into bicyclo[3.2.0]heptene derivatives in moderate to good yield using trimethylphosphine as the catalyst under mild conditions. PMID- 24175668 TI - Comparative study of osteogenic differentiation potential of mesenchymal stem cells derived from bone marrow and adipose tissue of osteoporotic female rats. AB - Osteoporosis causes reduction of osteogenic differentiation of mesenchymal stem cells (MSCs) from bone marrow and adipose tissue. This study was designed to compare the osteogenic potential of bone marrow mesenchymal stem cells (BMMSCs) and adipose-derived stem cells (ADSCs) of ovariectomized (OVX) rats. MSC were harvested from bone marrow and inguinal fat pads of six OVX rats. The limitations of this report are that cells from different animals were pooled for the purpose of the experiments that were carried out in this study. At 7, 14 and 21 d of osteogenic differentiation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) conversion, alkaline phosphatase activity and gene expression for collagen I, osteocalcin, bone sialoprotein, osteopontin and bone morphogenetic protein-2 bone morphogenetic protein-2 (BMP-2) were analyzed. At 21 d, percentage of cells per field and percentage of mineralized nodule were analyzed. The data were subjected to analysis of variance, and the means were compared by Student Newman-Keuls test. The cells, regardless of group, showed phenotypic characteristics consistent with stem cells. MTT conversion, alkaline phosphatase activity, percentage of mineralized nodule and expression of collagen I, osteocalcin and BMP-2 of ADSCs from OVX rats were higher when compared to BMMSCs from OVX rats in at least one of the evaluated periods (p<0.05). However, bone sialoprotein and osteopontin expression were smaller than those observed in BMMSCs for all evaluated periods (p<0.05). It was concluded that the ADSCs from OVX rats have higher osteogenic potential when compared to BMMSCs from OVX rats. This result suggests that the treatment of osteoporosis with autologous ADSCs may be more efficient. PMID- 24175670 TI - Synthesis of an azido precursor to (2S,5R)-5-hydroxylysine using an asymmetric organocatalytic chlorination/reduction sequence. AB - An efficient, robust, and scalable synthesis of an azido precursor to the modified amino acid (2S,5R)-5-hydroxylysine was developed on the basis of the use of a highly stereoselective organocatalytic alpha-chlorination-reduction protocol. The final Fmoc-protected (2S,5R)-6-azido-5-hydroxylysine derivative can be used in solid-phase peptide synthesis, providing access to proteins that contain large quantities of post-translationally modified lysine (e.g., collagens). PMID- 24175669 TI - Site specific discrete PEGylation of (124)I-labeled mCC49 Fab' fragments improves tumor MicroPET/CT imaging in mice. AB - The tumor-associated glycoprotein-72 (TAG-72) antigen is highly overexpressed in various human adenocarcinomas and anti-TAG-72 monoclonal antibodies, and fragments are therefore useful as pharmaceutical targeting vectors. In this study, we investigated the effects of site-specific PEGylation with MW 2-4 kDa discrete, branched PEGylation reagents on mCC49 Fab' (MW 50 kDa) via in vitro TAG72 binding, and in vivo blood clearance kinetics, biodistribution, and mouse tumor microPET/CT imaging. mCC49Fab' (Fab'-NEM) was conjugated at a hinge region cysteine with maleimide-dPEG 12-(dPEG24COOH)3 acid (Mal-dPEG-A), maleimide-dPEG12 (dPEG12COOH)3 acid (Mal-dPEG-B), or maleimide-dPEG12-(m-dPEG24)3 (Mal-dPEG-C), and then radiolabeled with iodine-124 ((124)I) in vitro radioligand binding assays and in vivo studies used TAG-72 expressing LS174T human colon carcinoma cells and xenograft mouse tumors. Conjugation of mCC49Fab' with Mal-dPEG-A (Fab' A) reduced the binding affinity of the non PEGylated Fab' by 30%; however, in vivo, Fab'-A significantly lengthened the blood retention vs Fab'-NEM (47.5 vs 28.1%/ID at 1 h, 25.1 vs 8.4%/ID at 5 h, p < 0.01), showed excellent tumor to background, better microPET/CT images due to higher tumor accumulation, and increased tumor concentration in excised tissues at 72 h by 130% (5.09 +/- 0.83 vs 3.83 +/- 1.50%ID/g, p < 0.05). Despite the strong similarity of the three PEGylation reagents, PEGylation with Mal-dPEG-B or -C reduced the in vitro binding affinity of Fab'-NEM by 70%, blood retention, microPET/CT imaging tumor signal intensity, and residual 72 h tumor concentration by 49% (3.83 +/- 1.50 vs 1.97 +/- 0.29%ID/g, p < 0.05) and 63% (3.83 +/- 1.50 vs 1.42 +/- 0.35%ID/g, p < 0.05), respectively. We conclude that remarkably subtle changes in the structure of the PEGylation reagent can create significantly altered biologic behavior. Further study is warranted of conjugates of the triple branched, negatively charged Mal-dPEG-A. PMID- 24175671 TI - The British journal of dermatology: the early years. PMID- 24175672 TI - The three dimensions of skin disease burden: 'now', 'long term' and 'family'. PMID- 24175673 TI - Basal cell carcinoma incidence in the U.K. PMID- 24175675 TI - Reactivity umpolung in intramolecular ring closure of 3,4-disubstituted butenolides: diastereoselective total synthesis of paeonilide. AB - Remarkable reactivity reversal stratagem in 3,4-disubstituted butenolides under acidic conditions is described. Design of a suitably substituted multifunctional butenolide followed by an acid-catalyzed chemo- and diastereoselective intramolecular ring closure via the reactivity umpolung has been demonstrated to accomplish a concise total synthesis of paeonilide. Overall, the present protocol involves one-pot reduction of an alpha,beta-unsaturated carbon-carbon double bond and intramolecular nucleophilic insertion of oxygen function at the electron-rich gamma-position of butenolide. The involved mechanistic aspects have also been discussed. PMID- 24175676 TI - Direct dehydrative esterification of alcohols and carboxylic acids with a macroporous polymeric acid catalyst. AB - A macroporous polymeric acid catalyst was prepared for the direct esterification of carboxylic acids and alcohols that proceeded at 50-80 degrees C without removal of water to give the corresponding esters with high yield. Flow esterification for the synthesis of biodiesel fuel was also achieved by using a column-packed macroporous acid catalyst under mild conditions without removal of water. PMID- 24175677 TI - Oxidative dimerization of (hetero)aromatic amines utilizing t-BuOI leading to (hetero)aromatic azo compounds: scope and mechanistic studies. AB - A straightforward synthetic method of both symmetric and unsymmetric aromatic azo compounds through an efficient and cross-selective oxidative dimerization of aromatic amines using tert-butyl hypoiodite (t-BuOI) under metal-free and mild conditions has been developed. This method was also found applicable to the synthesis of heteroaromatic azo compounds. The spectroscopic study indicates the involvement of N,N-diiodoanilines in the oxidative reaction as the key intermediate. PMID- 24175679 TI - Evaluation and management of pulmonary nodules: state-of-the-art and future perspectives. AB - INTRODUCTION: The imaging evaluation of pulmonary nodules, often incidentally detected on imaging examinations performed for other clinical reasons, is a frequently encountered clinical circumstance. With advances in imaging modalities, both the detection and characterization of pulmonary nodules continue to evolve and improve. AREAS COVERED: This article will review the imaging modalities used to detect and diagnose benign and malignant pulmonary nodules, with a focus on computed tomography (CT), which continues to be the mainstay for evaluation. The authors discuss recent advances in the lung nodule management, and an algorithm for the management of indeterminate pulmonary nodules. EXPERT OPINION: There are set of criteria that define a benign nodule, the most important of which are the lack of temporal change for 2 years or more, and certain benign imaging criteria, including specific patterns of calcification or the presence of fat. Although some indeterminate pulmonary nodules are immediately actionable, generally those approaching 1 cm or larger in diameter, at which size the diagnostic accuracy of tools such as positron emission tomography (PET)/CT, single photon emission CT (SPECT) and biopsy techniques are sufficient to warrant their use. The majority of indeterminate pulmonary nodules are under 1 cm, for which serial CT examinations through at least 2 years for solid nodules and 3 years for ground-glass nodules, are used to demonstrate either benign biologic behavior or otherwise. The management of incidental pulmonary nodules involves a multidisciplinary approach in which radiology plays a pivotal role. Newer imaging and postprocessing techniques have made this a more accurate technique eliminating ambiguity and unnecessary follow-up. PMID- 24175678 TI - Biomarkers in IgA nephropathy: relationship to pathogenetic hits. AB - INTRODUCTION: IgA nephropathy, the most prevalent glomerular disease in the world, requires a renal biopsy for diagnosis. Reliable biomarkers are needed for the non-invasive diagnosis of this disease and to more fully delineate its natural history and risk for progression. AREAS COVERED: In this review, the authors examine serum levels of galactose-deficient IgA1 (Gd-IgA1) and glycan specific IgG and IgA autoantibodies that are integral to pathogenesis of IgA nephropathy. They also explore biomarkers related to alternative and lectin pathways of complement activation and serum and urinary peptide biomarkers detected by mass spectrometric methods. The literature search included review of all publications having IgA nephropathy in the title that were cited in PubMed and Scopus over the past 10 years and a non-systematic review of abstracts published for the annual meetings of the American Society of Nephrology and the International Symposia on IgA Nephropathy. EXPERT OPINION: Serum Gd-IgA1 level and glycan-specific autoantibody levels are prime candidates to become diagnostic biomarkers for IgA nephropathy because of their central role in the earliest stages of disease pathogenesis. Assays for serum levels of complement proteins C3 and factor H are readily available in clinical practice and deserve continued study, either alone or in tandem with total serum IgA or serum Gd-IgA1 levels, as prognostic biomarkers for patients with IgA nephropathy. Urinary peptidomic data are also reviewed because this approach can successfully differentiate patients with IgA nephropathy from healthy controls and from patients with other forms of renal disease. PMID- 24175681 TI - Statistics anxiety, state anxiety during an examination, and academic achievement. AB - BACKGROUND: A large proportion of students identify statistics courses as the most anxiety-inducing courses in their curriculum. Many students feel impaired by feelings of state anxiety in the examination and therefore probably show lower achievements. AIMS: The study investigates how statistics anxiety, attitudes (e.g., interest, mathematical self-concept) and trait anxiety, as a general disposition to anxiety, influence experiences of anxiety as well as achievement in an examination. SAMPLE: Participants were 284 undergraduate psychology students, 225 females and 59 males. METHODS: Two weeks prior to the examination, participants completed a demographic questionnaire and measures of the STARS, the STAI, self-concept in mathematics, and interest in statistics. At the beginning of the statistics examination, students assessed their present state anxiety by the KUSTA scale. After 25 min, all examination participants gave another assessment of their anxiety at that moment. Students' examination scores were recorded. Structural equation modelling techniques were used to test relationships between the variables in a multivariate context. RESULTS: Statistics anxiety was the only variable related to state anxiety in the examination. Via state anxiety experienced before and during the examination, statistics anxiety had a negative influence on achievement. However, statistics anxiety also had a direct positive influence on achievement. This result may be explained by students' motivational goals in the specific educational setting. CONCLUSIONS: The results provide insight into the relationship between students' attitudes, dispositions, experiences of anxiety in the examination, and academic achievement, and give recommendations to instructors on how to support students prior to and in the examination. PMID- 24175682 TI - Phonological awareness and oral language proficiency in learning to read English among Chinese kindergarten children in Hong Kong. AB - BACKGROUND: Learning to read is very challenging for Hong Kong children who learn English as a second language (ESL), as they must acquire two very different writing systems, beginning at the age of three. Few studies have examined the role of phonological awareness at the subsyllabic levels, oral language proficiency, and L1 tone awareness in L2 English reading among Hong Kong ESL kindergarteners. AIMS: This study aims to investigate L1 and L2 phonological awareness and oral language proficiency as predictors of English reading among children with Chinese as L1. SAMPLE: One hundred and sixty-one typically developing children with a mean age of 5.16 (SD=.35) selected from seven preschools in Hong Kong. METHOD: Participants were assessed for English reading, English and Chinese phonological awareness at different levels, English oral language skills, and letter naming ability. RESULTS: Hierarchical regression analyses indicated that both oral language proficiency and phonological awareness measures significantly predicted L2 word reading, when statistically controlled for age and general intelligence. Among various phonological awareness units, L2 phonemic awareness was the best predictor of L2 word reading. Cross-language transfer was shown with L1 phonological awareness at the tone level, uniquely predicting L2 word reading. CONCLUSIONS: The present findings show the important role of phonological awareness at the subsyllabic levels (rime and phoneme) and oral language proficiency in the course of L2 reading development in Chinese ESL learners. The significant contribution of L1 tone awareness to L2 reading suggests that phonological sensitivity is a general competence that ESL children need to acquire in early years. The findings have significant implications for understanding L2 reading development and curriculum development. PMID- 24175683 TI - Peer victimization and school disaffection: exploring the moderation effect of social support and the mediation effect of depression. AB - BACKGROUND: Peer victimization is associated with increased internalizing problems and reduced school adjustment. Research into the main effect and the buffering effect of social support on these internalizing problems has produced inconsistent findings, and none has tested the buffering effect of social support on school adjustment. Moreover, recent studies have underlined the importance of taking various sources of social support into account. AIMS: This study aims to test the relationships between peer victimization and school disaffection, the moderation effect of parental, peer and teacher social support, and the mediation effect of depression. SAMPLE: Four hundred seventh and eighth graders participated in this study. METHOD: Students filled out a questionnaire assessing peer victimization, depression, academic self-efficacy, school disaffection, and perceived social support from parents, peers, and teachers. RESULTS: Peer victimization was negatively associated with self-efficacy and positively associated with school disaffection. Regression analyses showed a main negative effect of social support (especially teacher support) on depression and school disaffection and a positive effect on self-efficacy. No significant interactions emerged between victimization and social support or between sources of social support. Path analyses indicated that the effects of victimization on self efficacy and school disaffection were fully mediated by depression, but that the effects of social support are partially independent of depression. Multigroup analyses indicated that these relationships were parallel among boys and girls. CONCLUSIONS: The results of this study are consistent with the main effect model of social support. They also highlight the importance of teacher support for school adjustment. PMID- 24175684 TI - Antecedents and consequences of situational interest. AB - BACKGROUND: There is a growing body of research on situational interest (SI). Yet, we still know relatively little about how SI is supported in the classroom and the academic benefits of SI. AIM: The current study investigated (1) contextual antecedents of SI; (2) potential benefits of SI for academic outcomes; and (3) SI as a mediator of classroom practices to academic outcomes. SAMPLE: Participants were 126 male and female adolescents (mean age = 14.6 years) who took part in a science course during a 3-week residential summer programme for talented adolescents. METHOD: Participants completed self-report measures prior to the start of the summer programme and at the end of the programme. Summer programme instructors completed ratings of students' engagement during the programme. RESULT: Multiple regression analyses were conducted to investigate the three study aims. After controlling for initial individual interest, perceived choice, instructor approachability, and course connections to real life were statistically significant predictors of SI during the summer programme, with varying associations observed based on the form of SI (triggered, maintained feeling, and maintained-value). SI was positively related to individual interest and perceived competence in science at the end of the programme as well as teacher-rated engagement; SI also mediated the associations of classroom practices with these outcomes. CONCLUSION: Results suggest that classroom practices shape SI. In turn, SI supports motivation and engagement. Moreover, differentiated antecedents and outcomes of the three sub-components of SI were identified, highlighting the utility of this three-component approach for studying SI. PMID- 24175685 TI - Is self-explanation worth the time? A comparison to additional practice. AB - BACKGROUND: Self-explanation, or generating explanations to oneself in an attempt to make sense of new information, can promote learning. However, self-explaining takes time, and the learning benefits of this activity need to be rigorously evaluated against alternative uses of this time. AIMS: In the current study, we compared the effectiveness of self-explanation prompts to the effectiveness of solving additional practice problems (to equate for time on task) and to solving the same number of problems (to equate for problem-solving experience). SAMPLE: Participants were 69 children in grades 2-4. METHODS: Students completed a pre test, brief intervention session, and a post- and retention test. The intervention focused on solving mathematical equivalence problems such as 3 + 4 + 8 = _ + 8. Students were randomly assigned to one of three intervention conditions: self-explain, additional-practice, or control. RESULTS: Compared to the control condition, self-explanation prompts promoted conceptual and procedural knowledge. Compared to the additional-practice condition, the benefits of self-explanation were more modest and only apparent on some subscales. CONCLUSIONS: The findings suggest that self-explanation prompts have some small unique learning benefits, but that greater attention needs to be paid to how much self-explanation offers advantages over alternative uses of time. PMID- 24175686 TI - Academic self-efficacy in study-related skills and behaviours: relations with learning-related emotions and academic success. AB - BACKGROUND: Academic self-efficacy, when operationalized as mastery over domain specific knowledge, has been found to be a predictor of academic achievement and emotions. Although academic emotions are also a predictor of academic achievement, there is limited evidence for reciprocal relations with academic achievement. AIMS: To examine whether academic self-efficacy, when operationalized as confidence in study-related skills and behaviours, is also a predictor of academic achievement and emotions and to test reciprocal relations between academic emotions and achievement. SAMPLE: Two hundred and six first-year undergraduate students. METHODS: Academic self-efficacy was measured at the beginning of the first semester and learning-related emotions (LREs) at the beginning of the second semester. Academic performance was aggregated across assessments in semester one and semester two. RESULTS: Self-efficacy in study related skills and behaviours predicted: (1) better semester one academic performance and (2) more pleasant and fewer unpleasant LREs at the beginning of the second semester directly and (3) indirectly through semester one academic performance. Reciprocal relations between academic performance and emotions were supported, but only for pleasant emotions. CONCLUSIONS: Self-efficacy in study related skills was the critical academic self-efficacy variable in this study. It may play an important role in maintaining challenge appraisals to maintain pleasant emotions and better academic performance. Accordingly, practitioners in higher education may wish to consider the value of assessing and developing students' self-efficacy in relation to their independent study skills. PMID- 24175687 TI - The relation between school entrance age and school achievement during primary schooling: evidence from Croatian primary schools. AB - BACKGROUND: Compulsory school entrance age and admission policies differ across countries and educational systems, and there is a continuing debate on the question whether and how the age at school entry affects various student outcomes. AIMS: This study explored the relation between school entrance age and school achievement among students attending fourth (ages 10-11) and eighth (ages 14-15) grade of Croatian primary schools. SAMPLE: Participants were 44,479 fourth and 43,338 eighth-grade students from all Croatian primary schools. Students were divided into groups of younger and older school entrants based on the difference between the year of birth and the year of school entry. METHODS: Differences in school achievement between students who were younger and those who were older when they entered school in subjects covered by the curriculum for respective grades were examined among fourth- and eighth-grade students. Two achievement measures were used for each subject-objective test results obtained during a national examination and final school marks appointed by teachers. RESULTS: Among fourth-grade students, older school entrants on average performed slightly better than the younger ones in all the subjects, irrespective of the achievement measure used. However, these differences in achievement are very small, and the effect of school entrance age on achievement is very weak. In the eighth-grade sample, younger and older school entrants did not differ in their achievement in the majority of subjects. CONCLUSIONS: Students who are older when they enter school perform slightly better than their older classmates in the lower grades of primary school, but these differences in achievement are very small and are probably no longer present by the end of primary schooling. PMID- 24175688 TI - Achievement goals in adult learners: evidence from distance education. AB - BACKGROUND: There is evidence that learners may adopt different kinds of achievement goals: mastery approach, mastery avoidance, performance approach, and performance avoidance. In higher education, this evidence has mainly come from young people who have recently gone straight from secondary education to higher education. However, higher education is increasingly populated by older students, and it has been theorised that the relationship between goals and achievement might be very different for adult learners. AIMS: The aim of the present study was to examine whether the relationships between achievement, drop-out rate, and goal orientation observed for non-adult populations are mirrored in adult learners. METHOD: The Achievement Goal Questionnaire (AGQ) was administered to adult learners taking courses by distance learning. SAMPLE: Respondents were 195 men and 586 women between the ages of 19 and 87. RESULTS: The results confirmed the reliability of the 2 * 2 version of the AGQ for this distinctive population. As in previous studies of younger students, mastery-approach goals were unrelated to attainment, performance-approach goals tended to facilitate attainment, and performance-avoidance goals tended to impair attainment. In addition, mastery avoidance goals tended to impair students' attainment and also increased the likelihood that they would drop out of their course altogether. CONCLUSION: The achievement-goal framework is as appropriate for understanding influences on attainment in adult learners as it is in younger students. Adult learners may be more sensitive to the deleterious effects of adopting mastery-avoidance achievement goals. PMID- 24175689 TI - Second-language learners' advantage in metalinguistic awareness: a question of languages' characteristics. AB - BACKGROUND: The awareness of the formal structure of language has been widely studied in the literature but less in a bilingualism context. Even less with second-language learners (SLL) who are acquiring their second language (L2) and are not considered as bilinguals. AIMS: This study aimed at providing an investigation of young SLL's skills in phonological, morphological and syntactic awareness. SAMPLES: Ninety-five French first graders participated in our study. Children were divided into two groups: monolinguals versus SLL of German (i.e., L1 = French, L2 = German). METHOD: Both groups completed two phonological tasks (i.e., phonological categorization and deletion). They also completed four morphological tasks evaluating their morphological awareness on two distinct aspects (i.e., affixes and compounds). Finally, they were evaluated on a syntactic awareness task. RESULTS: The main findings highlighted a bilingual superiority for compounds morphological and syntactic awareness but not for affixes morphological and phonological awareness. CONCLUSIONS: The second language learning advantage was observed on dimensions distinguishing the two languages (i.e., compounds morphology and syntax) but not on shared affixes morphological and phonological dimensions. Thus, results are discussed in light of languages' characteristics and bilingualism proficiency. PMID- 24175690 TI - Reigoselective arylation of thiazole derivatives at 5-position via Pd catalysis under ligand-free conditions. AB - An efficient regioselective arylation of thiazole derivatives via Pd-catalyzed C H activation is reported. The transformation was hypothesized through a Pd(0/II) catalytic cycle in the absence of special ligand sets. This method provided an efficient process to direct arylation of thiazoles at the 5-position. PMID- 24175691 TI - Complexation of imidazopyridine-based cations with a 24-crown-8 ether host: [2]pseudorotaxane and partially threaded structures. AB - A new series of linear molecules derived from 1,2-bis(imidazopyridin-2-yl)ethane can fully or partially penetrate the cavity of the dibenzo-24-crown-8 macrocycle to produce a new family of host-guest complexes. Protonation or alkylation of the nitrogen atoms on the pyridine rings led to an increase in the guest total positive charge up to 4+ and simultaneously generated two new recognition sites (pyridinium motifs) that are in competition with the 1,2-bis(benzimidazole)ethane motif for the crown ether. The relative position of the pyridine ring and the chemical nature of the N-substituent determined the preferred motif and the host guest complex geometry: (i) for linear guests with relatively bulky groups (i.e., a benzyl substituent), the 1,2-bis(benzimidazole)ethane motif is favored, leading to a fully threaded complex with a [2]pseudorotaxane geometry; (ii) for small substituents, such as -H and -CH3 groups, regardless of the guest shape, the pyridinium motifs are preferred, leading to external partially threaded complexes in a 2:1 host to guest stoichiometry. PMID- 24175702 TI - Oil-in-water emulsion system stabilized by protein-coated nanoemulsion droplets. AB - Nanoemulsion droplets (average size of about 150 nm) coated with micellar casein were used as an emulsifying agent to stabilize oil (n-hexadecane)-in-water emulsions. We found that these nanodroplets adsorbed at the oil-water interface and formed stable emulsions, with the size of the droplet-stabilized emulsions being dependent on the concentration of nanodroplets in the dispersions. Stable emulsions were still formed at low concentrations, even though the interface was not fully covered by the nanodroplets. The nanodroplets fully covered the interface at higher concentrations, resulting in a transition from a thick interfacial layer to a multilayer containing a network of assembled nanodroplets. Because of their soft and elastic nature, the adsorbed nanodroplets showed strong deformation at the oil-water interface. The morphology of the interfacial nanodroplets was dependent on their location inside the network interfacial layer. The adsorption and deformation of the droplets at the oil-water interface and the formation of network structures, as observed in the present study, provide new, useful fundamental knowledge with potential applications for microencapsulation and emulsion stabilization. PMID- 24175704 TI - Effect of cyclodextrin and membrane lipid structure upon cyclodextrin-lipid interaction. AB - Methyl-beta-cyclodextrin (MbetaCD) can be used to exchange membrane lipids between different vesicles in order to prepare model membrane vesicles with lipid asymmetry. To help define what factors influence lipid exchange, we studied how lipid interaction with cyclodextrins (CDs) was affected by lipid and CD structure. The decrease in light scattering upon CD-induced vesicle solubilization and the change in Forster resonance energy transfer of labeled lipids upon vesicle solubilization and lipid exchange were used to detect phospholipid-CD interaction. Of the CDs examined, MbetaCD, hydroxypropyl-alpha cyclodextrin (HPalphaCD), and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were the three with the most suitable phospholipid interaction properties. Only MbetaCD was observed to dissolve lipid vesicles (at least at CD concentrations below 125 mM). Solubilization of lipid vesicles was half complete at 10-80 mM MbetaCD with progressively higher MbetaCD concentrations required as phospholipid acyl chain length increased from 14 to 22 carbons. Phospholipid acyl chain unsaturation and lipid headgroup structure also affected the amount of MbetaCD needed for solubilization. All three CDs studied were able to carry out phospholipid exchange. MbetaCD, which retained the ability to carry out lipid exchange below MbetaCD concentrations needed for solubilization, exchanged lipid more efficiently than HPalphaCD or HPbetaCD. However, the ability of HPalphaCD to exchange phospholipids, coupled with its inability to interact with cholesterol, indicates that it will be useful for preparing asymmetric vesicles with controlled amounts of cholesterol. PMID- 24175706 TI - Understanding the interaction between trivalent lanthanide ions and stereoregular polymethacrylates through luminescence, binding isotherms, NMR, and interaction with cetylpyridinium chloride. AB - Complexation of isotactic, syndiotactic, and atactic poly(methacrylic acid), PMA, with trivalent lanthanide ions has been studied in water at a degree of neutralization 0.5. Metal ion binding is shown by quenching of cerium(III) fluorescence, enhancement of Tb(III) luminescence, and lanthanide-induced line broadening in the PMA (1)H NMR spectra. Comparison with lanthanide-acetate complexation suggests carboxylate binds in a bidentate fashion, while Ce(III) luminescence quenching suggests an ~3:1 carboxylate:metal ion stoichiometry, corresponding to charge neutralization. The presence of both free and bound Ce(III) cations in PMA solutions is confirmed from luminescence decays. Studies of Tb(3+) luminescence lifetime in H2O and D2O solutions show complexation is accompanied by loss of 5-6 water molecules, indicating that each bidentate carboxylate replaces two coordinated water molecules. The behavior depends on pH and polyelectrolyte stereoregularity, and stronger binding is observed with isotactic polyelectrolyte. Binding of cetylpyridinium chloride, CPC, in these systems is studied by luminescence, NMR, and potentiometry. NMR and Tb(3+) luminescence lifetime studies show the strongest binding with the isotactic polymer. Binding of surfactant to poly(methacrylate) in the presence of lanthanides is noncooperative, i.e., it binds to the free sites; binding isotherms in the presence of lanthanides are shifted to higher free surfactant concentrations, compared with sodium ions, have lower slopes and show a clear two step binding mechanism. While CPC readily replaces the Na(+) ions of poly(methacrylate) and binds very strongly (low critical association concentrations), exchange is much more difficult with the strongly bound trivalent lanthanide ions. Effects of tacticity are seen, with surfactant interacting most strongly with isotactic chains in the initial stages of binding, while in the final stages of binding the interaction is strongest with atactic poly(methacrylate). PMID- 24175707 TI - Efficient immobilization of colloidal particles from aqueous suspension by electrostatic interactions. AB - Anionically charged colloidal particles (beta-iron oxyhydroxide and smectite clay) were successfully removed from the suspension by the interactions with micrometer-sized hydrotalcite. The efficiency of the removal was evaluated by an examination of concentration-dependent experiments. PMID- 24175708 TI - First fluorinated zwitterionic micelle with unusually slow exchange in an ionic liquid. AB - The micellization of a fluorinated zwitterionic surfactant in ethylammonium nitrate (EAN) was investigated. The freeze-fracture transmission electron microscope (FF-TEM) observations confirm the formation of spherical micelles with the average diameter 25.45 +/- 3.74 nm. The micellization is an entropy-driven process at low temperature but an enthalpy-driven process at high temperature. Two sets of (19)F NMR signals above the critical micelle concentration (cmc) indicate that the unusually slow exchange between micelles and monomers exists in ionic liquid; meanwhile, surfactant molecules are more inclined to stay in micelle states instead of monomer states at higher concentration. Through the analysis of the half line width (Deltanu1/2), we can obtain the kinetic information of fluorinated zwitterionic micellization in an ionic liquid. PMID- 24175709 TI - Perfluoroalkane functionalization of NU-1000 via solvent-assisted ligand incorporation: synthesis and CO2 adsorption studies. AB - A new functionalization technique, solvent-assisted ligand incorporation (SALI), was developed to efficiently incorporate carboxylate-based functionalities in the Zr-based metal-organic framework, NU-1000. Unlike previous metal node functionalization strategies, which utilize dative bonding to coordinatively unsaturated metal sites, SALI introduces functional groups as charge compensating and strongly bound moieties to the Zr6 node. Utilizing SALI, we have efficiently attached perfluoroalkane carboxylates of various chain lengths (C1-C9) on the Zr6 nodes of NU-1000. These fluoroalkane-functionalized mesoporous MOFs, termed herein SALI-n, were studied experimentally and theoretically as potential CO2 capture materials. PMID- 24175710 TI - Location and membrane sources for autophagosome formation - from ER-mitochondria contact sites to Golgi-endosome-derived carriers. AB - Recent advances have revealed much about the signaling events and molecular components associated with autophagy. Although it is clear that there are multiple points of intersection and connection between autophagy and known vesicular membrane transport processes between membrane compartments, autophagy is modulated by a distinct set of molecular components, and the autophagosome has a unique membrane composition. A key question that has yet to be resolved with regards to autophagosome formation is its membrane source. Various evidences have indicated that membranes from the endoplasmic reticulum (ER), mitochondria, Golgi, endosomes and the plasma membrane could all potentially act as a source of autophagosomal membrane in non-specialized macroautophagy. Recent investigations have generated advances in terms of the mitochondria's involvement in starvation induced autophagy, and refined localization of autophagosome formation to ER mitochondria contact sites. On the other hand, data accumulates on the delivery of membrane sources to the pre-autophagosome structure by Atg9-containing mobile carriers, which likely originated from the Golgi-endosome system. The answer to the question on the origin of membrane materials for autophagosome biogenesis awaits further reconciliation of these different findings. PMID- 24175711 TI - Cyclic GMP regulates M3AChR activity at plasma membranes from airway smooth muscle. AB - Muscarinic acetylcholine receptors MAChRs from Bovine Tracheal Smooth Muscle (BTSM) plasma membranes are responsible for the cGMP rise and signal-amplitude peaks associated with smooth muscle contraction present in bronchial asthma. These MAChRs bind [(3)H]QNB and exhibit the classic G Protein Coupled-Receptor (GPCR) behavior towards muscarinic agonist and antagonists that is sensitive to sensitive to GTP analogs. Interestingly, the [(3)H]QNB binding activity was stimulated by cGMP and ATP, and was enhanced by IBMX and Zaprinast, inhibitors of cGMP-PDE. Cyclic GMP plus ATP affected the agonist-antagonist muscarinic binding activities. Thus, the high affinity agonist (Carbamylcholine) binding sites disappeared, whereas, 4-DAMP, a M3 selective antagonist displayed an additional high affinity-binding site. In contrast, non-selective (atropine) and M2 selective (methoctramine and gallamine) antagonists revealed one low binding site. Moreover, the 4-DAMP-mustard alkylation of the MAChRs blocked the cGMP effect indicating that the M3AChR is the main receptor target of cGMP. Interestingly, these cGMP effects were potentiated by an activator (Sp-8-pCPT cGMPS), and diminished by an inhibitor (Rp-8-pCPT-CGMPS), of cGMP-dependent protein kinase (PKG-II), which was detected by Western blotting using specific PKG II antibodies. Finally, plasma membrane M3AChRs were phosphorylated in a cGMP dependent manner and this novel post-translational reversible modification at M3AChRs may act as a feedback mechanism to terminate the cGMP dependent muscarinic signal transduction cascades at the sarcolema of BTSM. PMID- 24175712 TI - Ultrahigh magnetically responsive microplatelets with tunable fluorescence emission. AB - Tuning the optical properties of suspensions by controlling the orientation and spatial distribution of suspended particles with magnetic fields is an interesting approach to creating magnetically controlled displays, microrheology sensors, and materials with tunable light emission. However, the relatively high concentration of magnetic material required to manipulate these particles very often reduces the optical transmittance of the system. In this study, we describe a simple method of generating particles with magnetically tunable optical properties via sol-gel deposition and functionalization of a continuous layer of silica on ultrahigh magnetically responsive (UHMR) alumina microplatelets. UHMR microplatelets with tunable magnetic response in the range of 15-36 G are obtained by the electrostatic adsorption of 2 to 13% of superparamagnetic iron oxide nanoparticles (SPIONs) on the alumina surface. The magnetized platelets are coated with a 20-50 nm layer of SiO2 through the controlled hydrolysis and condensation reactions of tetraethylorthosilicate (TEOS) in an NH3/ethanol mixture. Finally, the silica surface is covalently modified with an organic fluorescent dye by conventional silane chemistry. Because of the anisotropic shape of the particles, control of their orientation and distribution using magnetic fields and field gradients enables easy tuning of the optical properties of the suspension. This strategy allows us to gain both spatial and temporal control over the fluorescence emission from the particle surface, making the multifunctional platelets interesting building blocks for the manipulation of light in colloid-based smart optical devices and sensors. PMID- 24175713 TI - Vascular Behcet's disease: new insights in the management of thrombosis. PMID- 24175714 TI - Global analysis of fluorescence decays to probe the internal dynamics of fluorescently labeled macromolecules. AB - The aim of this review is to introduce the reader first to the mathematical complexity associated with the analysis of fluorescence decays acquired with solutions of macromolecules labeled with a fluorophore and its quencher that are capable of interacting with each other via photophysical processes within the macromolecular volume, second to the experimental and mathematical approaches that have been proposed over the years to handle this mathematical complexity, and third to the information that one can expect to retrieve with respect to the internal dynamics of such fluorescently labeled macromolecules. In my view, the ideal fluorophore-quencher pair to use in studying the internal dynamics of fluorescently labeled macromolecules would involve a long-lived fluorophore, a fluorophore and a quencher that do not undergo energy migration, and a photophysical process that results in a change in fluorophore emission upon contact between the excited fluorophore and quencher. Pyrene, with its ability to form an excimer on contact between excited-state and ground-state species, happens to possess all of these properties. Although the concepts described in this review apply to any fluorophore and quencher pair sharing pyrene's exceptional photophysical properties, this review focuses on the study of pyrene labeled macromolecules that have been characterized in great detail over the past 40 years and presents the main models that are being used today to analyze the fluorescence decays of pyrene-labeled macromolecules reliably. These models are based on Birks' scheme, the DMD model, the fluorescence blob model, and the model free analysis. The review also provides a step-by-step protocol that should enable the noneducated user to achieve a successful decay analysis exempt of artifacts. Finally, some examples of studies of pyrene-labeled macromolecules are also presented to illustrate the different types of information that can be retrieved from these fluorescence decay analyses depending on the model that is selected. PMID- 24175715 TI - Applicability of non-halogenated methyl propionate to microencapsulation. AB - Applicability of methyl propionate to microencapsulation was evaluated with regard to volatility, capability of forming emulsions, and their quality. An emulsion-based technique was then developed to encapsulate progesterone into poly d,l-lactide-co-glycolide microspheres. Their characteristics were compared with those prepared using ethyl acetate. Our results demonstrated that methyl propionate had greater evaporative tendency and less water miscibility than ethyl acetate did. The former allowed us to prepare good microspheres. Their average volume mean diameter was 68.3 +/- 1.7 MUm with a span index of 0.91 +/- 0.13. Progesterone did not undergo polymorphic transition during microencapsulation, and its encapsulation efficiency ranged from 41.80 +/- 1.83 to 85.64 +/- 1.95%. Residual methyl propionate in various microspheres was found to be 0.97 +/- 0.03 to 1.54 +/- 0.07%. Such microsphere characteristics were quite similar to those prepared by the ethyl acetate-based microencapsulation process. Overall, our findings reflect that methyl propionate has a potential to become an invaluable solvent for microencapsulation. PMID- 24175716 TI - Hybrid bombesin analogues: combining an agonist and an antagonist in defined distances for optimized tumor targeting. AB - Radiolabeled hybrid ligands with defined distances between an agonist and an antagonist for the gastrin-releasing peptide receptor were found to have excellent tumor-targeting properties. Oligoprolines served as rigid scaffolds that allowed for tailoring distances of 10, 20, and 30 A between the recognition elements. In vitro and in vivo studies revealed that the hybrid ligand with a distance of 20 A between the recognition elements exhibits the highest yet observed tumor cell uptake and retention time in prostate cancer cells. PMID- 24175717 TI - Study of band structure at the Zn(S,O,OH)/Cu(In,Ga)Se2 interface via rapid thermal annealing and their effect on the photovoltaic properties. AB - This study focused on understanding the mechanisms of the photovoltaic property changes in Zn(S,O,OH)/Cu(In,Ga)Se2 solar cells, which were fabricated via annealing, using reflection electron energy loss spectroscopy (REELS), ultraviolet photoelectron spectroscopy (UPS), low temperature photoluminescence (LTPL), and secondary ion mass spectroscopy (SIMS). A pinhole-free Zn(S,O,OH) buffer layer was grown on a CIGS absorber layer using the chemical bath deposition (CBD). When the Zn(S,O,OH) film was annealed until 200 degrees C, the Zn-OH bonds in the film decreased. The band gap value of the annealed film decreased and the valence band offset (VBO) value at the Zn(S,O,OH)/CIGS interface with the annealed film increased. Both results contribute to the conduction band offset (CBO) value at the Zn(S,O,OH)/CIGS interface and, in turn, yield a reduction in the energy barrier at the interface. As a result of the annealing, the short circuit current (JSC) and quantum efficiency (QE) values (400-600 nm) of the cell increased due to the improvement in the electron injection efficiency. However, when the Zn(S,O,OH) film was annealed at 300 degrees C, the cell efficiency declined sharply due to the QE loss in the long wavelength region (800-1100 nm). The SIMS analysis demonstrated that the Cu content in the CIGS bulk decreased and the Cu element also diffused into CIGS/Mo interface. Through LTPL analysis, it was seen that the considerable drop of the Cu content in the CIGS bulk induced a 1.15 eV PL peak, which was associated with the transition from a deep donor defect to degrade the quality of the CIGS bulk. Accordingly, the series resistance (RS) and efficiency of the cell increased. PMID- 24175719 TI - Cariprazine, a new, orally active dopamine D2/3 receptor partial agonist for the treatment of schizophrenia, bipolar mania and depression. AB - Cariprazine is a novel drug with partial agonist activity at dopamine D2/3 receptors and six- to eightfold higher affinity for human dopamine D3 over D2 receptors. Results from several placebo-controlled Phase II/III trials in patients with a The Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of schizophrenia or bipolar I disorder suggest that cariprazine is superior to placebo with respect to antipsychotic and antimanic activity. Reports concerning safety and tolerability of cariprazine are mainly favorable, although the rates of treatment-associated adverse events, which most commonly included akathisia and extrapyramidal symptom, are rather high. However, only minor alterations of clinical laboratory values, prolactin concentrations and ECG parameters are reported in cariprazine-treated patients. A new drug application to the U.S. F DA for cariprazine for the treatment of both schizophrenia and manic or mixed episodes associated with bipolar I disorder was submitted in November 2012. A more precise assessment of the clinical properties of this new drug will require additional studies, aimed to compare and contrast cariprazine with other antipsychotic agents. PMID- 24175720 TI - The role of extended-release quetiapine fumarate monotherapy in the treatment of patients with major depressive disorder. AB - Pharmacotherapy, psychotherapy and other nonpharmacological interventions are used in patients with major depressive disorder (MDD). However, 50% of the patients with MDD fail to achieve a response to first-line antidepressant treatment. In four of five acute monotherapy studies, once-daily extended-release quetiapine fumarate (quetiapine XR) significantly improved depressive symptoms compared with placebo in patients with MDD. One acute monotherapy study demonstrated that neither quetiapine XR nor escitalopram had a statistically significant separation from placebo on the primary endpoint. Quetiapine XR maintenance therapy also significantly reduced the risk of recurrence of a depressive event. No significant improvement in overall quality of life was observed versus placebo except in the acute elderly study. Tolerability findings were consistent with the known pharmacological profile of quetiapine; the most common adverse events were dry mouth, sedation, somnolence and dizziness. Quetiapine XR monotherapy has been approved as a treatment for MDD in a limited number of countries. PMID- 24175721 TI - Extended-release quetiapine fumarate in the treatment of patients with major depressive disorder: adjunct therapy. AB - Approximately half of the patients with major depressive disorder (MDD) respond insufficiently to current antidepressants, resulting in increased risk of relapse and residual symptoms. Strategies available include dose increase, combination with a second agent, switching antidepressants, adjunct treatment, psychotherapy or exercise. Efficacy and tolerability of once-daily extended-release quetiapine fumarate (quetiapine XR) adjunct to index antidepressant therapy in patients with MDD and an inadequate response to treatment were assessed in two acute studies as part of a global clinical trial program. Quetiapine XR significantly improved depressive symptoms versus placebo. Significant improvement in quality of life versus placebo was confined to elderly patients with MDD. Tolerability was consistent with the known pharmacological profile of quetiapine: the most common adverse events were dry mouth, somnolence, sedation, dizziness and fatigue. Quetiapine XR is approved in the EU, USA and several other countries worldwide as adjunctive treatment for patients with MDD and an inadequate response to previous antidepressants. PMID- 24175722 TI - Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy. AB - Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP. PMID- 24175723 TI - Mild cognitive impairment. AB - Mild cognitive impairment is the term applied to the cognitive state that lies between normal aging and dementia. There has been significant controversy around describing, defining and characterizing mild cognitive impairment. This review will cover current understanding of the condition and discuss clinical features, research strategies and future directions. PMID- 24175725 TI - Differentiating the subtypes of social anxiety disorder. AB - Since the inclusion of subtypes of social anxiety disorder (SAD) in the DSM-III R, the most studied have been generalized versus specific subtypes. Previous research indicated that the generalized subtype was associated with greater severity, comorbidity and functional impairment compared to the specific subtype, but more recent evidence supports a dimensional conceptualization of SAD. Earlier studies also possessed limitations, such as heterogeneity in definitions of generalized SAD. Based on the more recent findings and the limitations of the earlier studies, the DSM-5 eliminated the generalized specifier. However, it also retained a categorical system by including a performance-based fear specifier, thus leaving an open debate on whether or not a dimensional or categorical system best describes SAD. Future research could examine other, more recent concepts as potential subtypes (e.g., attentional biases), or perhaps the larger question of the overall utility in subtyping SAD. PMID- 24175724 TI - Antiangiogenic therapy for high-grade gliomas: current concepts and limitations. AB - Glioblastoma (GBM) is associated with a high degree of angiogenesis. Therefore, antiangiogenic therapy could have a role in the treatment of this tumor. The currently available treatment approaches acting against angiogenesis are mainly directed toward three pathways: VEGF pathway, VEGF-independent pathways and inhibition of vascular endothelial cell migration. It has been demonstrated that antiangiogenic therapy can produce a rapid radiological response and a decrease of brain edema, without significantly influencing survival. Future studies should consider that: animal models are inadequate and cells used for animal models (mainly U87) are deeply different from patient GBM cells; GBM cells may become resistant to antiangiogenic therapy and some cells may be resistant to antiangiogenic therapy ab initio; and angiogenesis in the peritumor tissue has been poorly investigated. Therefore, the ideal target of angiogenesis is probably yet to be identified. PMID- 24175726 TI - Salvage stereotactic radiosurgery for brain metastases. AB - Recurrent or progressive brain metastases after initial treatment represent a common clinical entity mainly due to increased survival of cancer patients. From the various available treatment modalities, salvage stereotactic radiosurgery seems to be the most commonly used. Many clinical studies of class of evidence III have demonstrated satisfied results concerning the local brain control and survival of patients with relapsing brain disease. Also stereotactic radiosurgery is considered a relatively safe modality with low incidence of brain toxicity side effects. It is obvious that well-designed, randomized, prospective studies are necessary for the evaluation of the stereotactic radiosurgery as salvage treatment and for the establishment of guidelines for the selection of patients most suitable for this treatment option. The increasing number of patients with relapsing brain metastatic disease will act as a pressure to this direction. PMID- 24175727 TI - Adaptation of a membrane bioreactor to 1,2-dichloroethane revealed by 16S rDNA pyrosequencing and dhlA qPCR. AB - A pilot-scale membrane bioreactor (MBR) was tested for bioremediation of 1,2 dichloroethane (DCA) in groundwater. Pyrosequencing of 16S rDNA was used to study changes in the microbiology of the MBR over 137 days, including a 67 day initial adaptation phase of increasing DCA concentration. The bacterial community in the MBR was distinct from those in soil and groundwater at the same site, and was dominated by alpha- and beta- proteobacteria, including Rhodobacter, Methylibium, Rhodopseudomonas, Methyloversatilis, Caldilinea, Thiobacillus, Azoarcus, Hyphomicrobium, and Leptothrix. Biodegradation of DCA in the MBR began after 26 days, and was sustained for the remainder of the experiment. A quantitative PCR (qPCR) assay for the dehalogenase gene dhlA was developed to monitor DCA degrading bacteria in the MBR, and a positive correlation was seen between dhlA gene abundance and the cumulative amount of DCA that had entered the MBR. Genera previously associated with aerobic DCA biodegradation (Xanthobacter, Ancylobacter, Azoarcus) were present in the MBR, and the abundance of Azoarcus correlated well with dhlA gene abundance. This study shows that MBRs can be an effective method for removal of DCA from groundwater, and that the dhlA qPCR is a rapid and sensitive method for detection of DCA-degrading bacteria. PMID- 24175728 TI - APL@Voro: a Voronoi-based membrane analysis tool for GROMACS trajectories. AB - APL@Voro is a new program developed to aid in the analysis of GROMACS trajectories of lipid bilayer simulations. It can read a GROMACS trajectory file, a PDB coordinate file, and a GROMACS index file to create a two-dimensional geometric representation of a bilayer. Voronoi diagrams and Delaunay triangulations--generated for different selection models of lipids--support the analysis of the bilayer. The values calculated on the geometric structures can be visualized in a user-friendly interactive environment and, then, plotted and exported to different file types. APL@Voro supports complex bilayers with a mix of various lipids and proteins. For the calculation of the projected area per lipid, a modification of the well-known Voronoi approach is presented as well as the presentation of a new approach for including atoms into an existing triangulation. The application of the developed software is discussed for three example systems simulated with GROMACS. The program is written in C++, is open source, and is available free of charge. PMID- 24175729 TI - The correlates of meeting physical activity recommendations: a population-based cross-sectional study. AB - The aim of this study was to identify correlated factors which explain the recommended level of leisure time physical activity (LTPA) among Portuguese adults. Subjects aged 31-60 years (972 males, 1195 females) were categorized, based on LTPA data obtained using a questionnaire, into two groups according to the PA recommendation for PA: >= 10 or < 10 MET . hr . wk(-1). Chi-square and logistic regression analyses were applied to the results. For men, the perception of an active lifestyle [odds ratio (OR) = 4.61, 95% CI:3.13-6.81, p <0.001], having an excellent perception of health (OR = 3.14, 95% CI:1.28-7.71, p =0.013), perception of being sufficiently active (OR = 2.16, 95% CI:1.53-3.05, p <0.001), and having a high socio-economic status (SES) (OR = 1.86, 95% CI:1.22-2.81, p =0.004) were associated with attaining the recommended level of PA. For women, the perception of an active lifestyle (OR = 3.68, 95% CI:2.63-5.15, p <0.001), and middle SES (OR = 1.50, 95% CI:1.07-2.11, p =0.018) were positive and associated with meeting PA recommendations. Unlike men, women with body mass index (BMI) 25-29.9 kg/m(2) were more likely to attain the recommended level of PA than those with BMI <25 kg/m(2). The incidence of adults that met the recommended amount of PA is low. Men and women had different patterns of psychological and socio-demographic correlates. An intervention designed to improve the levels of PA among Portuguese adults may take these correlates into account. PMID- 24175730 TI - The cadence and water temperature effect on physiological responses during water cycling. AB - The aim of the study was to compare the maximal physiological responses during three protocols: maximal test on land cycle ergometer, maximal test on water cycling in an indoor pool at 27 degrees C (WC27) and at 31 degrees C (WC31). Moreover, the submaximal physiological responses were compared according cycling cadences and water temperatures during the water protocols. Ten young men were included and performed the protocols in separate days. Blood lactate (BL) concentration, heart rate (HR), oxygen uptake (VO2), ventilation (VE) and thermal comfort (TC) were collected during the exercise. The maximal HR and VO2 showed no significant differences between the protocols: HRmax: 189 +/- 7 (Land), 188 +/- 14 (WC27), 185 +/- 9 bpm (WC31) and VO2max: 4.2 +/- 0.4 (Land), 4.1 +/- 0.5 (WC27) and 4.3 +/- 0.5 l min(-1) (WC31). However, the maximal BL demonstrated significant lower values during the water protocols compared to the land protocol (p=0.018). All the submaximal physiological responses showed significant differences between the cadences (60, 70, 80 and 90 rpm). The effect of water temperature was significant for TC response (p=0.001) showing higher values at 31 degrees C than 27 degrees C (TCW27: 7 +/- 1 and TCW31:9 +/- 1). In conclusion, higher physiological responses were showed by increasing the cadence by 10 rpm and the subjects were more comfortable when cycling in the lower water temperature. PMID- 24175731 TI - Mechanisms of MS2 bacteriophage removal by fouled ultrafiltration membrane subjected to different cleaning methods. AB - An ultrafiltration unit with a polyvinylidene fluoride (PVDF) membrane of 40 nm nominal pore size was used to study bacteriophage MS2 removal under different membrane conditions: pristine membrane, membrane fouled by soluble microbial product (SMP) extracted from membrane bioreactor (MBR) feedwater, backwashed membrane, and chemically cleaned membrane. The order of MS2 removal by these membranes was as follows: fouled membrane > backwashed membrane > chemically cleaned membrane ~ pristine membrane. A linear correlation between membrane relative permeability and MS2 removal was found. Mass balance analysis showed a high percentage of MS2 in the concentrate for the fouled membrane as compared with the pristine membrane. Quartz crystal microbalance (QCM) results showed faster kinetics of MS2 adhesion to the pristine membrane than to the SMP-fouled membrane. In agreement with QCM results, an attractive force between MS2 and the pristine membrane was detected using an atomic force microscope (AFM), whereas a repulsive force was detected for the interaction between MS2 and the fouled membrane. The presence of SMP on the membrane surface led to higher rejection of MS2 due to both pore blocking and repulsion between MS2 and the SMP layer. Chemical cleaning removed most of the SMP foulant and as a result led to a lower MS2 removal. PMID- 24175732 TI - A systematic literature review of cardiovascular event utilities. AB - Cardiovascular disease (CVD) results in half of the non-communicable disease related deaths worldwide. Rising treatment costs have increased the need for cost utility models designed to compare the value of new and existing therapies. Cost utility models require utilities, values representing the strength of preferences for various health states. This systematic literature review aimed to identify and evaluate utilities reported for stroke, myocardial infarction (MI) and angina. In total, 83 unique studies were identified that reported utilities for these events. Approximately two-thirds reported utility values for stroke, and most used the EuroQoL five dimension to derive utilities. Utility values were lower in patients who experienced cardiovascular (CV) events than in patients who did not. The utility estimates for each condition varied greatly, likely due to differences in assessment methodologies and patient populations. This variability must be considered when choosing values for cost-utility models. Comparisons among reported utilities are further complicated by inconsistent CV event definitions. PMID- 24175733 TI - Risk equalization in The Netherlands: an empirical evaluation. AB - The Netherlands relies on risk equalization to compensate competing health insurers for predictable variation in individual medical expenses. Without accurate risk equalization insurers are confronted with incentives for risk selection. The goal of this study is to evaluate the improvement in predictive accuracy of the Dutch risk equalization model since its introduction in 1993. Based on individual-level claims data (n = 15.6 million), we estimate the risk equalization models that have been successively applied in The Netherlands since 1993. Using individual-level survey data (n = 8735), we examine the average under /overcompensation by these models for several relevant subgroups in the population. We find that in the course of years, the risk equalization model has been substantially improved. Even the current model (2012), however, does not eliminate incentives for risk selection completely. To achieve the public objectives, further improvement of the Dutch risk equalization model is crucial. PMID- 24175734 TI - Interactions of doxorubicin with organized interfacial assemblies. 1. Electrochemical characterization. AB - Doxorubicin is an anthracycline that has found wide use as a chemotherapeutic agent, with the primary target of its action being nuclear DNA. Despite the large body of knowledge on this family of compounds, the mechanism of doxorubicin penetration through the cellular or nuclear membrane remains understood to a limited extent. The plasma membrane acts as a barrier to the permeation of polar molecules, and this effect is mainly due to the hydrophobicity of membrane interior. The partitioning of DOX molecules into the lipid bilayer must thus be the basis for its passive transport across the biological membrane and therefore a key area of research activity lies in understanding how the structure of the anthracycline influences its interactions with amphiphilic interfaces. We have studied interactions between doxorubicin and Langmuir/Langmuir-Blodgett monomolecular films of octadecylamine (C18NH2), dihexadecylphosphate (DHP) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and DMPC bilayer films (Langmuir-Schaeffer) on a polycrystalline gold surface using ellipsometry, cyclic voltammetry, electrochemical impedance spectroscopy, and quartz crystal microbalance measurements. For all biomimetic films there is a substantial interaction between doxorubicin and the interface, and the extent of this interaction depends on the hydrophobic/hydrophilic properties of the film formed and its organization. PMID- 24175735 TI - Scalable and divergent total synthesis of (+)-colletoic acid, a selective 11beta hydroxysteroid dehydrogenase type 1 inhibitor. AB - An efficient and divergent total synthesis of (+)-colletoic acid, a selective 11 beta hydroxysteroid dehydrogenase 1 (11-betaHSD1) inhibitor, is presented along with its biological activity at the whole-cell level. A scalable, asymmetric synthetic strategy was designed featuring a diversity-oriented synthesis utilizing a diastereoselective intramolecular 5-exo-Heck reaction as the key step to provide the quaternary spirocenter intermediate 9 in multigram scale, thus establishing a platform for further structure-activity relationship studies and providing access to other acorane family members. PMID- 24175736 TI - Characterizing ion profiles in dynamic junction light-emitting electrochemical cells. AB - Organic semiconductors have the unique ability to conduct both ionic and electronic charge carriers in thin films, an emerging advantage in applications such as light-emitting devices, transistors, and electrochromic devices, among others. Evidence suggests that the profiles of ions and electrochemical doping in the polymer film during operation significantly impact the performance and stability of the device. However, few studies have directly characterized ion profiles within LECs. Here, we present an in-depth study of the profiles of ion distributions in LECs following application of voltage, via time-of-flight secondary ion mass spectrometry. Ion distributions were characterized with regard to film thickness, salt concentration, applied voltage, and relaxation over time. Results provide insight into the correlation between ion profiles and device performance, as well as potential approaches to tuning the electrochemical doping processes in LECs. PMID- 24175737 TI - Motor control, habits, complex motor stereotypies, and Tourette syndrome. AB - Tourette syndrome (TS) and primary complex motor stereotypies (CMS) are two relatively common, distinctly different movement disorders of childhood. Despite their frequency, the precise underlying pathophysiological mechanism(s) for tics and stereotypies remains unknown. Both are likely to involve cortical-striatal thalamo-cortical (CSTC) pathways or their interconnecting brain regions. In recent studies, distinct, separate cortical-striatal pathways have been identified for goal-directed and habitual behavioral activity with important influences from structures, such as the hippocampus, amygdala, dorsolateral prefrontal cortex, cerebellum, ventral tegmental area, and substantia nigra pars compacta. Determining the specific site of abnormality within these circuits remains an active area of research. At the synaptic level, numerous neurotransmitters are involved in the transmission of messages through CSTC pathways, and many have been proposed as potential pathophysiological mechanisms. Which, if any, transmitter is the primary pathological factor in TS and primary CMS remains to be definitively determined. PMID- 24175738 TI - Nocturnal non-invasive ventilation for cardio-respiratory disorders in adults. AB - Following the classic 'iron lung' non-invasive negative pressure ventilator, non invasive positive pressure ventilation (NIPPV), particularly used 'nocturnally' has developed a broad role in both the acute hospital setting and domiciliary long-term use for many cardio-respiratory disorders associated with acute and chronic ventilatory failure. This role is based in part upon the perceived relative ease of application and discontinuation of NIPPV, ability to avoid intubation or tracheostomy and their associated morbidities and availability of increasingly portable pressure and volume cycled NIPPV devices. Nevertheless, the many methodologies necessary for optimal NIPPV use are often underappreciated by health care workers and patients alike. This review focuses on the rationale, practice, and future directions for 'nocturnal' use of non-invasive positive pressure ventilation (nNIV) in cardio-respiratory disorders in adults which are commonly associated with sleep-related apnea, hypoventilation and hypoxemia: congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), cystic fibrosis (CF) and neuromuscular disorders. PMID- 24175739 TI - Isotopic analysis of oxidative pollutant degradation pathways exhibiting large H isotope fractionation. AB - Oxidation of aromatic rings and its alkyl substituents are often competing initial steps of organic pollutant transformation. The use of compound-specific isotope analysis (CSIA) to distinguish between these two pathways quantitatively, however, can be hampered by large H isotope fractionation that precludes calculation of apparent (2)H-kinetic isotope effects (KIE) as well as the process identification in multi-element isotope fractionation analysis. Here, we investigated the C and H isotope fractionation associated with the transformation of toluene, nitrobenzene, and four substituted nitrotoluenes by permanganate, MnO4(-), to propose a refined evaluation procedure for the quantitative distinction of CH3-group oxidation and dioxygenation. On the basis of batch experiments, an isotopomer-specific kinetic model, and density functional theory (DFT) calculations, we successfully derived the large apparent (2)H-KIE of 4.033 +/- 0.20 for the CH3-group oxidation of toluene from H isotope fractionation exceeding >13000/00 as well as the corresponding (13)C-KIE (1.0324 +/- 0.0011). Experiment and theory also agreed well for the dioxygenation of nitrobenzene, which was associated with (2)H- and (13)C-KIEs of 0.9410 +/- 0.0030 (0.9228 obtained by DFT) and 1.0289 +/- 0.0003 (1.025). Consistent branching ratios for the competing CH3-group oxidation and dioxygenation of nitrotoluenes by MnO4(-) were obtained from the combined modeling of concentration as well as C and H isotope signature trends. Our approach offers improved estimates for the identification of contaminant microbial and abiotic oxidation pathways by CSIA. PMID- 24175740 TI - Effects of ZnO nanoparticles on P3HT:PCBM organic solar cells with DMF-modulated PEDOT:PSS buffer layers. AB - In this study, we investigated hybrid bulk heterojunction organic solar cells containing ZnO nanoparticles blended with poly(3-hexylthiophene) (P3HT) and phenyl-C61-butyric acid methyl ester (PCBM) and having poly(3,4 ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) or N,N dimethylformamide (DMF)-modulated PEDOT:PSS buffer layers. The reference cell, which had a P3HT:PCBM active layer sandwiched between ITO?PEDOT:PSS and LiF?Al electrodes, exhibited an efficiency of 1.55%. The ZnO nanoparticle-doped active layer (ITO?PEDOT:PSS(DMF) ?ZnO:P3HT:PCBM?LiF?Al) exhibited a higher efficiency of 3.39% due to the modulated PEDOT:PSS buffer layer with low resistivity and the hybrid active layer containing ZnO nanoparticles. Here, we demonstrate that the low resistivity of the PEDOT:PSS layer can improve the Jsc value of hybrid solar cells, and ZnO nanoparticles can enhance the Voc value of organic solar cells. PMID- 24175741 TI - Amyloid fibrils in neurodegenerative diseases: villains or heroes? PMID- 24175743 TI - Synthesis and evaluation of antioxidant and trypanocidal properties of a selected series of coumarin derivatives. AB - This article describes the preparation and characterization of a selected series of coumarin derivatives with the aim of evaluating their antioxidant properties and their activity against Trypanosoma cruzi, the parasite responsible for Chagas disease. All the derivatives demonstrated moderate trypanocidal activity in the epimastigote and trypomastigote stages (clone Dm28c), with Compound 3 presenting the highest trypanocidal activity of the entire series, displaying higher activity than nifurtimox, which was used as a reference compound. In addition to the trypanocidal activity, this compound proved to have a very interesting antioxidant profile, as well as no cytotoxicity. These preliminary findings encouraged the authors to study the future structural optimization of this scaffold. PMID- 24175744 TI - Dual leucine zipper kinase as a therapeutic target for neurodegenerative conditions. AB - Dual leucine zipper kinase (DLK) is a serine/threonine protein kinase that is a member of the mixed lineage kinase subfamily. Mixed lineage kinases are upstream MAP3Ks that activate the JNK pathway. DLK is primarily responsible for activating JNK and mediating the apoptotic stress response in various cell types, specifically neurons. Inhibition and knockdown of DLK has been demonstrated to have neuroprotective effects in cellular and animal models of Alzheimer's disease, glaucoma, Parkinson's disease and other neurodegenerative conditions. Several series of ATP-binding site inhibitors have been identified through profiling efforts providing launch points for future medicinal chemistry programs. PMID- 24175745 TI - Development of lysophosphatidic acid pathway modulators as therapies for fibrosis. AB - Lysophosphatidic acid (LPA) is a class of bioactive phospholipid that displays a wide range of cellular effects via LPA receptors, of which six have been identified (LPAR1-6). In serum and plasma, LPA production occurs mainly by the hydrolysis of lysophosphatidylcholine by the phospholipase D activity of autotaxin (ATX). The involvement of the LPA pathway in driving chronic wound healing conditions, such as idiopathic pulmonary fibrosis, has suggested targets in this pathway could provide potential therapeutic approaches. Mice with LPAR1 knockout or tissue-specific ATX deletion have demonstrated reduced lung fibrosis following bleomycin challenge. Therefore, strategies aimed at antagonizing LPA receptors or inhibiting ATX have gained considerable attention. This Review will summarize the current status of identifying small-molecule modulators of the LPA pathway. The therapeutic utility of LPA modulators for the treatment of fibrotic diseases will soon be revealed as clinical trials are already in progress in this area. PMID- 24175746 TI - MS-based metabolomics facilitates the discovery of in vivo functional small molecules with a diversity of biological contexts. AB - In vivo small molecules as necessary intermediates are involved in numerous critical metabolic pathways and biological processes associated with many essential biological functions and events. There is growing evidence that MS based metabolomics is emerging as a powerful tool to facilitate the discovery of functional small molecules that can better our understanding of development, infection, nutrition, disease, toxicity, drug therapeutics, gene modifications and host-pathogen interaction from metabolic perspectives. However, further progress must still be made in MS-based metabolomics because of the shortcomings in the current technologies and knowledge. This technique-driven review aims to explore the discovery of in vivo functional small molecules facilitated by MS based metabolomics and to highlight the analytic capabilities and promising applications of this discovery strategy. Moreover, the biological significance of the discovery of in vivo functional small molecules with different biological contexts is also interrogated at a metabolic perspective. PMID- 24175748 TI - Targeting the redox metabolism of Plasmodium falciparum. AB - Targeting the redox metabolism of Plasmodium falciparum to create a fatal overload of oxidative stress is a route to explore the discovery of new antimalarial drugs. There are three main possibilities to target the redox metabolism of P. falciparum at the erythrocytic stage: selective targeting and inhibition of a redox P. falciparum protein or enzyme; oxidant drugs targeting essential parasite components and heme by-products; and redox cycler drugs targeting the parasitized red blood cell. Oxidants and redox cycler agents, with or without specific targets, may disrupt the fragile parasitized erythrocyte redox-dependent architecture given that: redox equilibrium plays a vital role at the erythrocytic stage; P. falciparum possesses major NADPH-dependent redox systems, such as glutathione and thioredoxin ones; and the protein-NADPH dependent phosphorylation-dephosphorylation process is involved in building new permeation pathways and channels for the nutrient-waste import-export traffic of the parasite. PMID- 24175747 TI - Small-molecule inhibitors of human LDH5. AB - The latest findings on the role played by human LDH5 (hLDH5) in the promotion of glycolysis in invasive tumor cells indicates that this enzyme subtype is a promising therapeutic target for invasive cancer. Compounds able to selectively inhibit hLDH5 hold promise for the cure of neoplastic diseases. hLDH5 has so far been a rather unexplored target, since its importance in the promotion of cancer progression has been neglected for decades. This enzyme should also be considered as a challenging target due the high polar character (mostly cationic) of its ligand cavity. Recently, significant progresses have been reached with small molecule inhibitors of hLDH5 displaying remarkable potencies and selectivities. This review provides an overview of the newly developed hLDH5 inhibitors. The roles of hLDH isoforms will be briefly discussed, and then the inhibitors will be grouped into chemical classes. Furthermore, general pharmacophore features will be emphasized throughout the structural subgroups analyzed. PMID- 24175751 TI - Antifungal activity and mechanism of palladium-modified nitrogen-doped titanium oxide photocatalyst on agricultural pathogenic fungi Fusarium graminearum. AB - Fusarium graminearum is the pathogen for Fusarium head blight (FHB) on wheat, which could significantly reduce grain quality/yield and produce a variety of mycotoxins posing a potential safety concern to human foods. As an environmentally friendly alternative to the commonly used chemical fugicides, a highly effective photocatalytic disinfection of F. graminearum macroconidia under visible light illumination was demonstrated on a visible-light-activated palladium-modified nitrogen-doped titanium oxide (TiON/PdO) nanoparticle photocatalyst. Because of the opposite surface charges of the TiON/PdO nanoparticles and the F. graminearum macroconidium, the nanoparticles were strongly adsorbed onto the macroconidium surface, which is beneficial to the photocatalytic disinfection of these macroconidia. The photocatalytic disinfection mechanism of TiON/PdO nanoparticles on these macroconidia could be attributed to their cell wall/membrane damage caused by the attack from reactive oxygen species (ROSs) as demonstrated by the fluorescence/phase contrast microscopy observations, while a breakage of their cell structure was not necessary for their loss of viability. PMID- 24175752 TI - Modeling the uptake of neutral organic chemicals on XAD passive air samplers under variable temperatures, external wind speeds and ambient air concentrations (PAS-SIM). AB - The main objective of this study was to evaluate the performance and demonstrate the utility of a fugacity-based model of XAD passive air samplers (XAD-PAS) designed to simulate the uptake of neutral organic chemicals under variable temperatures, external wind speeds and ambient air concentrations. The model (PAS SIM) simulates the transport of the chemical across the air-side boundary layer and within the sampler medium, which is segmented into a user-defined number of thin layers. Model performance was evaluated using data for polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) from a field calibration study (i.e., active and XAD-PAS data) conducted in Egbert, Ontario, Canada. With some exceptions, modeled PAS uptake curves are in good agreement with the empirical PAS data. The results are highly encouraging, given the uncertainty in the active air sampler data used as input and other uncertainties related to model parametrization (e.g., sampler-air partition coefficients, the influence of wind speed on sampling rates). The study supports the further development and evaluation of the PAS-SIM model as a diagnostic (e.g., to aid interpretation of calibration studies and monitoring data) and prognostic (e.g., to inform design of future passive air sampling campaigns) tool. PMID- 24175753 TI - Interactions of doxorubicin with organized interfacial assemblies. 2. Spectroscopic characterization. AB - Doxorubicin is an anthracycline that has found wide use as a chemotherapeutic agent, with the primary limitation to its use being cardiotoxicity. Depending on the identity and location of pendent side groups, the anthracyclines exhibit varying degrees of chemotherapeutic activity and toxicity, and a key area of research activity lies in understanding how the structure of the anthracycline influences its interactions with amphiphilic interfaces. We have studied interactions between doxorubicin and interfacial adlayers of octadecylamine (C18NH2), dihexadecylphosphate (DHP), and both monolayers and bilayers of 1,2 dimyristoyl-sn-glycero-3-phosphocholine (DMPC) on mica using time- and frequency resolved spectroscopic measurements. We report surface-enhanced resonance Raman data and fluorescence lifetime and anisotropy imaging data for doxorubicin at these interfaces. For all monolayers, there is a substantial interaction between doxorubicin and the interface. For DMPC bilayers, the extent of the interaction between doxorubicin and the interface depends on how the interface was formed. PMID- 24175754 TI - The future of tic disorder treatment. AB - Competing theories on the etiology and treatment of chronic tic disorders and Tourette syndrome have long made the search for efficacious intervention more challenging for patients and families seeking to reduce functional impairment related to tic symptoms. These symptoms were historically posited to be either psychological in origin, leading to the long tradition of psychoanalytic psychotherapy for tics, or biological in nature, particularly since the advent of successful treatments using neuroleptic medications. Current thinking about the phenomenology of tic disorders comes from growing empirical evidence as well as advances in neuroscience and genetics research and reveals a biological vulnerability that is exacerbated by physiological arousal related to environmental or interpersonal stress. This manuscript summarizes the evolution of this knowledge base and describes current best-practice recommendations for patients, families, and clinicians. PMID- 24175755 TI - Microfluidic templated mesoporous silicon-solid lipid microcomposites for sustained drug delivery. AB - A major challenge for a drug-delivery system is to engineer stable drug carriers with excellent biocompatibility, monodisperse size, and controllable release profiles. In this study, we used a microfluidic technique to encapsulate thermally hydrocarbonized porous silicon (THCPSi) microparticles within solid lipid microparticles (SLMs) to overcome the drawbacks accompanied by THCPSi microparticles. Formulation and process factors, such as lipid matrixes, organic solvents, emulsifiers, and methods to evaporate the organic solvents, were all evaluated and optimized to prepare monodisperse stable SLMs. FTIR analysis together with confocal images showed the clear deposition of THCPSi microparticles inside the monodisperse SLM matrix. The formation of monodisperse THCPSi-solid lipid microcomposites (THCPSi-SLMCs) not only altered the surface hydrophobicity and morphology of THCPSi microparticles but also remarkably enhanced their cytocompatibility with intestinal (Caco-2 and HT-29) cancer cells. Regardless of the solubility of the loaded therapeutics (aqueous insoluble, fenofibrate and furosemide; aqueous soluble, methotrexate and ranitidine) and the pH values of the release media (1.2, 5.0, and 7.4), the time for the release of 50% of the payloads from THCPSi-SLMC was at least 1.3 times longer than that from the THCPSi microparticles. The sustained release of both water-soluble and insoluble drugs together with a reduced burst-release effect from monodisperse THCPSi-SLMC was achieved, indicating the successful encapsulation of THCPSi microparticles into the SLM matrix. The fabricated THCPSi-SLMCs exhibited monodisperse spherical morphology, enhanced cytocompatibility, and prolonged both water-soluble and -insoluble drug release, which makes it an attractive controllable drug-delivery platform. PMID- 24175756 TI - Combined germline variations of thrombophilic genes promote genesis of lung cancer. AB - BACKGROUND: A large variety of familiar and non-familiar lung carcinomas (LC) are caused by long term exposure to chemical carcinogens that are present in tobacco smoke. We aimed to investigate the prevalence of 5 thrombophilic germ-line mutations in patients with lung carcinomas. MATERIALS AND METHODS: A total of 52 LC patients and 212 healthy controls from same population were analyzed for FV Leiden, factor V H1299R (R2), PAI-1, MTHFR C677T, MTHFR A1298C, ACE I/D, and Apo E genes and compared. RESULTS: Overall, heterozygous and/or homozygous point mutations in FV Leiden Apo E2, PAI-1 and MTHFR C677T genes were associated with LC in the current cohort. There was no meaningful association between LC and ACE I/D gene markers. CONCLUSIONS: The current results showed that LC is related to combined thrombophilic gene mutations and individuals with homozygosity of 4G in PAI-1 and MTHFR C677T genes and heterozygosity of FV Leiden, Apo E4 genes have a germ-line risk for LC tumorigenesis. PMID- 24175757 TI - Targeted silencing of inhibitors of apoptosis proteins with siRNAs: a potential anti-cancer strategy for hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a very poor prognosis. Despite significant improvements in diagnosis and treatment in recent years, the long-term therapeutic efficacy is poor, partially due to tumor metastasis, recurrence, and resistance to chemo- or radio-therapy. Recently, it was found that a major feature of tumors is a combination of unrestrained cell proliferation and impaired apoptosis. There are now 8 recognized members of the IAP-family: NAIP, c-IAP1, c-IAP2, XIAP, Survivin, Bruce, Livin and ILP-2. These proteins all contribute to inhibition of apoptosis, and provide new potential avenues of cancer treatment. As a powerful tool to suppress gene expression in mammalian cells, RNAi species for inhibiting IAP genes can be directed against cancers. This review will provide a brief introduction to recent developments of the application IAP-siRNA in tumor studies, with the aim of inspiring future treatment of HCC. PMID- 24175758 TI - Genetic factors, viral infection, other factors and liver cancer: an update on current progress. AB - Primary liver cancer is one of the most common cancers at the global level, accounting for half of all cancers in some undeveloped countries. This disease tends to occur in livers damaged through alcohol abuse, or chronic infection with hepatitis B and C, on a background of cirrhosis. Various cancer-causing substances are associated with primary liver cancer, including certain pesticides and such chemicals as vinyl chloride and arsenic. The strong association between HBV infection and liver cancer is well documented in epidemiological studies. It is generally acknowledged that the virus is involved through long term chronic infection, frequently associated with cirrhosis, suggesting a nonspecific mechanism triggered by the immune response. Chronic inflammation of liver, continuous cell death, abnormal cell growth, would increase the occurrence rate of genetic alterations and risk of disease. However, the statistics indicated that only about one fifth of HBV carries would develop HCC in lifetime, suggesting that individual variation in genome would also influence the susceptibility of HCC. The goal of this review is to highlight present level of knowledge on the role of viral infection and genetic variation in the development of liver cancer. PMID- 24175759 TI - Cancer care management through a mobile phone health approach: key considerations. AB - Greater use of mobile phone devices seems inevitable because the health industry and cancer care are facing challenges such as resource constraints, rising care costs, the need for immediate access to healthcare data of types such as audio video texts for early detection and treatment of patients and increasing remote aids in telemedicine. Physicians, in order to study the causes of cancer, detect cancer earlier, act in prevention measures, determine the effectiveness of treatment and specify the reasons for the treatment ineffectiveness, need to access accurate, comprehensive and timely cancer data. Mobile devices provide opportunities and can play an important role in consulting, diagnosis, treatment, and quick access to health information. There easy carriage make them perfect tools for healthcare providers in cancer care management. Key factors in cancer care management systems through a mobile phone health approach must be considered such as human resources, confidentiality and privacy, legal and ethical issues, appropriate ICT and provider infrastructure and costs in general aspects and interoperability, human relationships, types of mobile devices and telecommunication related points in specific aspects. The successful implementation of mobile-based systems in cancer care management will constantly face many challenges. Hence, in applying mobile cancer care, involvement of users and considering their needs in all phases of project, providing adequate bandwidth, preparation of standard tools that provide maximum mobility and flexibility for users, decreasing obstacles to interrupt network communications, and using suitable communication protocols are essential. It is obvious that identifying and reducing barriers and strengthening the positive points will have a significant role in appropriate planning and promoting the achievements of mobile cancer care systems. The aim of this article is to explain key points which should be considered in designing appropriate mobile health systems in cancer care as an approach for improving cancer care management. PMID- 24175760 TI - Alcohol consumption and risk of cancer: a systematic literature review. AB - This study aimed to discuss the consumption of alcohol as a risk factor for major cancers. We performed a search in the PubMed database, using the following inclusion criteria: meta-analysis published in English in the last 10 years that addressed the relationship between alcohol and the risk of developing cancer. The results indicate that moderate to heavy consumption of alcohol increases the risk of developing cancer of the oral cavity and pharynx, esophagus, stomach, larynx, colorectum, central nervous system, pancreas, breast and prostate. This review did not find any association between alcohol consumption and an increased risk of cancers of the lung, bladder, endometrium and ovary. It was also observed that alcohol consumption may be inversely related to thyroid cancer. Our systematic review has confirmed consumption of alcohol as a risk factor for the development of several types of cancer. PMID- 24175761 TI - Correlation between low Gleason score and prostate specific antigen levels with incidence of bone metastases in prostate cancer patients: when to omit bone scans? AB - BACKGROUND: To identify correlation and incidence of bone metastases in prostate cancer patient with low Gleason scores (GS) and prostate specific antigen (PSA) levels. MATERIALS AND METHODS: This descriptive restrospective study covered patients with prostate cancer in Cipto Mangunkusumo Hospital in 2006-2011. Of a total of 478, those who had PSA values, histological examination, and bone scan were included, resulting in 358 eligible cases. PSA values were measured using the sandwich electrochemiluminescent immunoassay. Histological examination was graded according to Gleason's grading system and divided into 3 categories: well differentiated (GS <= 6), moderately differentiated (GS 7) and poorly differentiated (GS 8-10). Bone scans were performed using a radiopharmaceutical agent (Tc 99m methylenen diphosphonate) with images captured by gamma camera. RESULTS: The mean age was 67.5 +/- 7.8, mean GS was 7.7 +/- 1.3 and median PSA was 56.9 (range: 0.48-17000 ng/ mL). There were 11 patients (3.0%) with positive bone scan with PSA<20 ng/mL and GS<8. Furthermore, there were 2 patients (0.6%) with GS <= 6 and PSA<10 ng/mL showing bone metastasis. CONCLUSIONS: In our study, there were still small percentage of patients with bone metastasis even when low values of PSA (PSA<10 ng/mL) and GS (GS <= 6) were applied. PMID- 24175762 TI - Barriers and facilitating factors perceived in Turkish women's behaviors towards early cervical cancer detection: a qualitative approach. AB - BACKGROUND: The aim of the present study was to investigate perceived inhibiting and facilitating factors concerning cervical cancer early diagnosis behavior in Turkish women over the age of 40. MATERIALS AND METHODS: The study was carried out by qualitative focus group interview with 35 participating women, in the period between April-June 2010. A semi-structured interview questionnaire based on the Health Belief Model and the Health Promotion Model was used. Content analysis was applied to the study data. RESULTS: Barriers such as lack of knowledge of women as regards to the cervical cancer and early detection, lack of sensitivity- negligence, forgetting, fear, inadequacy of health insurance and transportation, financial problems, inability to get an appointment, lack of female doctors, embarrassment, fatalist approach were frequently addressed. As for facilitating factors, these included provision of information, health professionals showing interest and tolerance, free services, provision of transportation means and reminding telephone calls. CONCLUSIONS: Focus group interviews were found to be effective in determining inhibiting and facilitating factors concerning cervical cancer early diagnosis behavior. In line with the results of the study, preparation of structured national and regional education programs and their addition to curriculum programs may be effective in realizing and maintaining positive early detection behavior. PMID- 24175763 TI - Mechanistic analysis of taxol-induced multidrug resistance in an ovarian cancer cell line. AB - OBJECTIVES: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. METHODS: The drug resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-alpha, Akt, ERK1/2, were detected by Western blotting. RESULTS: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p < 0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-alpha, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. CONCLUSION: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC alpha/ERK (JNK) signaling pathway. PMID- 24175764 TI - Comparison of p16INK4a immunocytochemistry with the HPV polymerase chain reaction in predicting high grade cervical squamous intraepithelial lesions. AB - AIM: To compare p16INK4a immunocytochemistry with the HPV polymerase chain reaction in predicting high grade cervical squamous intraepithelial lesions. MATERIALS AND METHODS: This diagnostic case-control study was conducted from January 2010 until December 2010. We obtained 30 samples, classified according to the degree of cervical intraepithelial neoplasia (CIN): 11 samples for CIN 1, 9 samples for CIN 2, and 10 samples for CIN 3. HPV PCR, p16INK4a immunocytochemistry, and histopathological examination were performed on all samples. Statistical analysis was conducted using SPSS 20.0. RESULTS: In predicting CIN 2-3, we found p16INK4a to have similar specificity and positive predictive value as HPV PCR (95%, 97.2% vs 96.7%), but better sensitivity (87.5% vs 72.5%) and negative predictive value (82.1% vs 67.6%). The most prevalent types of high-risk HPV in our study were HPV 33, 35, 58, 52, and 16. CONCLUSIONS: p16INK4a has better diagnostic values than HPV PCR and may be incorporated in the triage of ASCUS and LSIL to replace HPV PCR. Genotype distribution of HPV differs in each region, providing a challenge to develop HPV vaccines based on the epidemiology of HPV in that particular region. PMID- 24175765 TI - Audit of cancer patients from eastern Uttar Pradesh (UP), India: a university hospital based two year retrospective analysis. AB - BACKGROUND: A retrospective analysis of all cancer patients attending the radiotherapy outpatient department (OPD) of a single unit during the period of January 2005 till December 2006 was conducted to know the geographical distribution and incidence of the most common cancers, their stage of presentation, treatment compliance among the patients and follow-up. MATERIALS AND METHODS: A total of 4,484 patients were registered in the Institute of Medical Sciences, Banaras Hindu University during the period of January 2005- December 2006; of which 1,975 registered in an individual unit were included for the retrospective analysis. RESULTS: Most of the patients hailed from the various districts of UP and Bihar. Females outnumbered males with a ratio of 1.33:1. Females mostly belonged to the age group of 40-59 years; whilst males were a decade older. Major cancer sites in females were cervix and breast followed by head and neck. Leading cancer sites in males were head and neck, brain, bone, soft tissue and lung. Most of the cases presented in advanced stage of disease (74%). Squamous cell carcinoma was the most common histopathology (56%). A significant proportion of patients defaulted after undergoing preliminary investigations (16%). Only 53.9% of females and 58.5% of males took treatment out of which 68% and 63% completed the prescribed treatment. Compliance with follow up was poor. CONCLUSIONS: The outcome of this study will significantly help us to define region specific strategies needed for cancer management in eastern Uttar Pradesh. PMID- 24175766 TI - Expression of the proto-oncogene Pokemon in colorectal cancer--inhibitory effects of an siRNA. AB - OBJECTIVE: This study aimed to investigate expression of the proto-oncogene POK erythroid myeloid ontogenic factor (Pokemon) in colorectal cancer (CRC), and assess inhibitory effects of a small interference RNA (siRNA) expression vector in SW480 and SW620 cells. METHODS: Semi-quantitative reverse transcription polymerase chain reaction (PCR) and immunohistochemistry were performed to determine mRNA and protein expression levels of Pokemon in CRC tissues. Indirect immunofluorescence staining was applied to investigate the location of Pokemon in SW480 and SW620 cells. The siRNA expression vectors that were constructed to express a short hairpin RNA against Pokemon were transfected to the SW480 and SW620 cells with a liposome. Expression levels of Pokemon mRNA and protein were examined by real-time quantitative-fluorescent PCR and western blot analysis. The effects of Pokemon silencing on proliferation of SW480 and SW620 cells were evaluated with reference to growth curves with MTT assays. RESULTS: The mRNA expression level of Pokemon in tumor tissues (0.845 +/- 0.344) was significantly higher than that in adjacent tumor specimens (0.321 +/- 0.197). The positive expression ratio of Pokemon protein in CRC (87.0%) was significantly higher than that in the adjacent tissues (19.6%). Strong fluorescence staining of Pokemon protein was observed in the cytoplasm of the SW480 and SW620 cells. The inhibition ratios of Pokemon mRNA and protein in the SW480 cells were 83.1% and 73.5% at 48 and 72 h, respectively, compared with those of the negative control cells with the siRNA. In the SW620 cells, the inhibition ratios of Pokemon mRNA and protein were 76.3% and 68.7% at 48 and 72 h, respectively. MTT showed that Pokemon gene silencing inhibited the proliferation of SW480 and SW620 cells. CONCLUSION: Overexpression of Pokemon in CRC may have a function in carcinogenesis and progression. siRNA expression vectors could effectively inhibit mRNA and protein expression of Pokemon in SW480 and SW620 cells, thereby reducing malignant cell proliferation. PMID- 24175767 TI - HSP27 is commonly expressed in cervical intraepithelial lesions of Brazilian women. AB - Heat shock proteins are molecular chaperones that may be constitutively present in cells protecting them from various stresses, such as extreme temperature, anoxia or chemical agents. Cervical cancer is the second most prevalent malignancy of women. In this study, we analyzed the expression of Hsp27 by immunohistochemistry in cervical intraepithelial lesions of Brazilian women, along with samples from non neoplasic lesions (NN). Cervical intraepithelial neoplasia I (CIN I), II (CIN II) and III (CIN III)/in situ carcinoma and squamous cell carcinoma (SCC) were included. Immunostaining was observed in 30 (100%) samples of NN, 46 (92%) in CIN I, 50 (100%) in CIN II, 52 (98.11%) in CIN III/CIS, and 46 (98.11%) in SCC. In group NN Hsp27 immunostaining was heterogeneous, more intense in basal and parabasal layers of the epithelium and less or absent in the intermediate and superficial layer. The majority of the samples of CIS and SCC presented strong staining in allepithelial layers. Metaplasic cells, when present, were strongly stained. In this study, Hsp27 protein was found to be commonly expressed in cervical epithelial cells. PMID- 24175768 TI - Is there an association between variants in candidate insulin pathway genes IGF I, IGFBP-3, INSR, and IRS2 and risk of colorectal cancer in the Iranian population? AB - BACKGROUND: Several epidemiological studies have shown associations between colorectal cancer (CRC) risk and type 2 diabetes and obesity. Any effects would be expected to be mediated through the insulin pathway. Therefore it is possible that variants of genes encoding components of the insulin pathway play roles in CRC susceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated with risk of CRC. MATERIALS AND METHODS: The associations of four single nucleotide polymorphisms (SNPs) in IGF-I (rs6214), IGFBP-3 (rs3110697), INSR (rs1052371), and IRS2 (rs2289046) genes with the risk of CRC were evaluated using a case-control design with 167 CRC cases and 277 controls by the PCR-RFLP method. RESULTS: Overall, we observed no significant difference in genotype and allele frequencies between the cases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting for confounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotype compared with AA+AG genotypes has a protective effect for CRC in normal weight subjects (p=0.035, OR=0.259, 95%CI= 0.074-0.907). CONCLUSIONS: These findings do not support plausible associations between polymorphic variations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size. PMID- 24175769 TI - MicroRNA-122 promotes proliferation, invasion and migration of renal cell carcinoma cells through the PI3K/Akt signaling pathway. AB - OBJECTIVE: MicroRNAs (miRNAs) are a small class of non-coding, single-stranded RNAs with a critical role in genesis and maintenance of renal cancer mainly through binding to 3'-untranslated regions (3'UTR) of target mRNAs, which causes a block of translation and/or mRNA degradation. The aim of the present study was to investigate the potential effects of miR-122 in human renal cell carcinomas. METHODS: The expression level of miR-122 was quantified by qRT-PCR. MTT, colony formation, invasion and migration assays were used to explore the potential functions of miR-122 in human renal cell carcinoma cells. RESULTS: Cellular growth, invasion and migration in two A498 and 786-O cells were significantly increased after miR-122 transfection. Further experiments demonstrated that overexpression of miR-122 resulted in the increase of phospho-Akt (Ser473) and phospho-mTOR (Ser2448), then activation of mTOR targets, p70S6K and 4E-BP1. CONCLUSIONS: The up-regulation of miR-122 may play an important role in the progress of renal cancer through activating PI3K/Akt signal pathway and could be a potential molecular target for anti-cancer therapeutics. PMID- 24175770 TI - Screening in the era of economic crisis: misperceptions and misuse from a longitudinal study on Greek women undergoing benign vacuum-assisted breast biopsy. AB - BACKGROUND: To evaluate knowledge about screening tests and tests without proven screening value in a Greek Breast Unit population undergoing benign vacuum assisted breast biopsy (VABB). MATERIALS AND METHODS: This study included 81 patients. Three knowledge-oriented items (recommended or not, screening frequency, age of onset) were assessed. Regarding screening tests two levels of knowledge were evaluated: i). crude knowledge (CK), i.e. knowledge that the test is recommended and ii). advanced knowledge (AK), i.e. correct response to all three knowledge-oriented items. Solely CK was evaluated for tests without proven screening value. Risk factors for lack of knowledge were assessed with multivariate logistic regression. A second questionnaire was administered 18 months after VABB to assess its impact on the performance of tests. RESULTS: Concerning screening tests considerable lack of AK was noted (mammogram, 60.5%; Pap smear, 59.3%; fecal occult blood testing, 93.8%; sigmoidoscopy, 95.1%). Similarly lack of CK was documented regarding tests without proven screening value (breast self-examination, 92.6%; breast MRI, 60.5%; abdominal ultrasound, 71.6%; barium meal, 48.1%; urine analysis, 90.1%; chest X-Ray, 69.1%; electrocardiogram, 74.1%; cardiac ultrasound, 75.3%). Risk factors for lack of AK were: place of residence (mammogram), age (Pap smear), personal income (sigmoidoscopy); risk factors for lack of CK included number of offspring (breast MRI, chest X-Ray), BMI (abdominal ultrasound), marital status (urine analysis), current smoking status (electrocardiogram). VABB's only effect was improvement in mammogram rates. CONCLUSIONS: A considerable lack of knowledge concerning screening tests and misperceptions regarding those without proven value was documented. PMID- 24175771 TI - Nabag (Zizyphus spina-christi) extract prevents aberrant crypt foci development in colons of azoxymethane-treated rats by abrogating oxidative stress and inducing apoptosis. AB - Zizyphus spina-christi (ZSC) fruit is a rich source of bioactive compounds but any medicinal properties in chemoprevention of colon cancer have hitherto not been studied. The aim of the present study was to examine in vivo protective effects of ZSC water extract on colon carcinogenesis in azoxymethane (AOM) treated rats. Our results showed that ZSC significantly reduced AOM-induced colonic aberrant crypt foci development and AOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating the impairment of total antioxidant capacity. Caspase-3 cleavage, which has been considered as an apoptotic index, was almost undetectable in AOM-treated rats and ZSC exhibited pro-apoptotic effects evidenced by increased levels of cleaved caspase-3. In the studied model, our findings provide the first in vivo evidence that ZSC extract could inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis. PMID- 24175772 TI - rs12904 polymorphism in the 3'UTR of EFNA1 is associated with colorectal cancer susceptibility in a Chinese population. AB - Accumulated evidence has indicated that Ephrin A1 (EFNA1) is associated with angiogenesis and tumorigenesis in various types of malignancies, including colorectal cancer (CRC). In the current study, we performed an online search using the public microarray database to investigate whether EFNA1 expression might be altered in CRC tissues. We then conducted a case-control study including 306 subjects (102 cases and 204 well-matched controls) in Xiaoshan County to assess any association between genetic polymorphisms in EFNA1 and CRC susceptibility. Searches in the Oncomine expression profiling database revealed EFNA1 to be overexpressed in CRC tissue compared with adjacent normal tissue. The rs12904 G-A variant located in the 3' untranslated region (UTR) of EFNA1 was observed to be associated with CRC susceptibility. Compared with the AA homozygous genotype, those carrying GA genotype had a decreased risk of developing CRC (odds ratio (OR) =0.469, 95% confidence interval (CI): 0.225 0.977, and P =0.043). The association was stronger among smokers and tea drinkers, however, no statistical evidence of interaction between rs12904 polymorphism and smoking or tea drinking on CRC risk was found. Our results suggest that EFNA1 is involved in colorectal tumorigenesis, and rs12904 A>G polymorphism in the 3' UTR of EFNA1 is associated with CRC susceptibility. Larger studies and further mechanistic investigations are warranted to confirm our findings. PMID- 24175773 TI - Low income and rural county of residence increase mortality from bone and joint sarcomas. AB - BACKGROUND: This is a part of a larger effort to characterize the effects on socio-economic factors (SEFs) on cancer outcome. Surveillance, Epidemiology and End Result (SEER) bone and joint sarcoma (BJS) data were used to identify potential disparities in cause specific survival (CSS). MATERIALS AND METHODS: This study analyzed SEFs in conjunction with biologic and treatment factors. Absolute BJS specific risks were calculated and the areas under the receiver operating characteristic (ROC) curve were computed for predictors. Actuarial survival analysis was performed with Kaplan-Meier method. Kolmogorov-Smirnov's 2 sample test was used to for comparing two survival curves. Cox proportional hazard model was used for multivariate analysis. RESULTS: There were 13501 patients diagnosed BJS from 1973 to 2009. The mean follow up time (SD) was 75.6 (90.1) months. Staging was the highest predictive factor of outcome (ROC area of 0.68). SEER stage, histology, primary site and sex were highly significant pre treatment predictors of CSS. Under multivariate analysis, patients living in low income neighborhoods and rural areas had a 2% and 5% disadvantage in cause specific survival respectively. CONCLUSIONS: This study has found 2-5% decrement of CSS of BJS due to SEFs. These data may be used to generate testable hypothesis for future clinical trials to eliminate BJS outcome disparities. PMID- 24175774 TI - Cost of treatment for cancer: experiences of patients in public hospitals in India. AB - BACKGROUND: To assess the treatment pattern and expenditure incurred by cancer patients undergoing treatment at government tertiary hospitals in India. MATERIALS AND METHODS: A cross-sectional study of 508 cancer patients randomly selected from tertiary cancer hospitals funded by central/state governments located in major cities of five states in India, namely Kerala, Maharashtra, Rajasthan, West Bengal and Mizoram, during March - May 2011 was conducted. Information related to direct costs, indirect costs and opportunity costs incurred on investigations and treatment, major source of payment and difficulties faced by patients during the course of treatment was collected. RESULTS: About 45% of the patients used private health facilities as the first point of contact for cancer related diseases as against 32% in public hospitals. About 47% sought private health facilities for cancer investigations, 21% at district/sub-district hospitals, and about 4% contacted primary health care facilities. A majority of the patients (76%) faced financial problems while undergoing treatment. CONCLUSIONS: The results highlight the importance of involving the primary health care system in the cancer prevention activities. PMID- 24175775 TI - Overexpression of twist and matrix metalloproteinase-9 with metastasis and prognosis in gastric cancer. AB - OBJECTIVE: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. METHODS: Twist and MMP 9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopathologic features and to patients'outcome. RESULTS: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). CONCLUSIONS: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer. PMID- 24175776 TI - Early stage oral tongue cancer among non-tobacco users--an increasing trend observed in a South Indian patient population presenting at a single centre. AB - BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer diagnosed within the oral cavity worldwide. Many studies in India report OTSCC ranking among the top two most common subsites within the oral cavity. India is often labeled the oral cancer capital of the world. The incidence of tongue cancers in the population-based cancer registry (PBCR) of Chennai is showing an increasing trend. A majority of the oral cavity cancers (85%) in our cancer center present in advanced stages (III and IV). In contrast, early tongue cancers (stages I and II) constitute nearly 45% of all OTSCCs. AIM: The aim of this study was to analyze the clinical profile and epidemiological trends in our early stage tongue cancer patients with an emphasis on tobacco and alcohol habits. MATERIALS AND METHODS: This retrospective analysis was based on a prospectively collected database of 458 consecutive early stage OTSCC in-patients at a tertiary care oncology centre in Chennai between 1995 and 2008. RESULTS: Our study suggests that the earlier trends have clearly changed whereby nearly half of our patients are now never-tobacco users. The findings of the study indicate that a majority of the patients were never alcohol users (86.4%) and nearly half of them were never tobacco users (49.3%), and they had the best survival outcomes. This increasing trend of OTSCC among non-tobacco users is in contrast to our earlier experience of tongue cancer more than five decades ago.The median age of patients in our study was 53.3 years; the male to female ratio was approximately 2:1. The median follow up for the 458 patients was 53 months. CONCLUSIONS: Our study importantly as well as interestingly shows a conspicuous absence of association with the traditional risk factors, tobacco and alcohol. PMID- 24175777 TI - Phosphatidylinositol 3-kinase (PI3KCA) oncogene mutation analysis and gene expression profiling in primary breast cancer patients. AB - BACKGROUND: The phosphatidylinositol 3-kinase (PI3K) pathway plays a significant role in apoptosis, cellular proliferation and motility. The aim of the present study was to analyze mutations and gene expression profiles of the PI3KCA gene to determine any role in breast carcinomas. MATERIALS AND METHODS: We analyzed 38 breast cancers for mutations in the two PIK3CA hotspots in exons 9 and 20 by direct sequencing of DNA obtained from biopsy samples. We have also analyzed expression of the PI3KCA gene in 38 breast carcinoma tumor and corresponding control tissue samples at the mRNA level by RT-PCR. The Fisher's exact test (2?2 only) was performed using MedCalc software for to examine associations with mRNA levels. RESULTS: In the present study a total of 13 cases demonstrated somatic mutations. In 9/13 cases 1633 G>A (E545K) were found in exon 9, whereas in exon 20, 4/13 cases had 3140A>G mutation. Our combined analysis showed PI3KCA mutations present in 34% of human breast cancer patients. In our study, we have also clearly found significantly higher expression in breast cancer tissues in comparison with control tissues (p=0.001). CONCLUSIONS: PIK3CA mutation is an emerging tumor marker that, in the future, might be used in the process of choosing a treatment. The detection of PI3KCA mutation might have important clinical implications for diagnosis, progression and therapy. PMID- 24175778 TI - Involvement of microRNA-198 overexpression in the poor prognosis of esophageal cancer. AB - OBJECTIVE: This study aimed to investigate whether the miR-198 expression level is related to clinicopathological factors and prognosis of esophageal cancer. METHODS: MicroRNA was extracted from esophageal cancer patients who underwent surgery for assessment using the Taqman@ MicroRNA assay. The correlation between miR-198 expression and clinicopathological features was analyzed, and the significance of miR-198 as a prognostic factor and its relationship with survival was determined. RESULTS: MicroRNA-198 (miR-198) expression was higher in patients with poor prognosis than those with good prognosis (P < 0.05). Kaplan-Meier analysis results showed that the miR-198 expression level had a significant correlation with survival time (P = 0.030) and that patients with a higher expression of miR-198 had a shorter survival time. Cox multi-factor model analysis showed that patient prognosis (P = 0.014), tumor length (P = 0.040) and expression (P = 0.012), and survival time had a significant correlation; the corresponding risks were 7.268, 1.246, and 3.524, respectively. CONCLUSION: miR- 198 overexpression is involved in the poor prognosis of esophageal cancer and can be used as a biomarker for selection of cases requiring especial attention. PMID- 24175779 TI - Epidemiological correlates of breast cancer in South India. AB - BACKGROUND: Breast cancer is the most frequent cancer in women globally and represents the second leading cause of cancer death among women (after lung cancer). India is going through epidemiologic transition. It is reported that the incidence of breast cancer is rising rapidly as a result of changes in reproductive risk factors, dietary habits and increasing life expectancy, acting in concert with genetic factors. MATERIALS AND METHODS: In order to understand the existing epidemiological correlates of breast cancer in South India, a systematic review of evidence available on epidemiologic correlates of breast cancer addressing incidence, prevalence, and associated factors like age, reproductive factors, cultural and religious factors was performed with specific focus on screening procedures in southern India. RESULTS: An increase in breast cancer incidence due to various modifiable risk factors was noted, especially in women over 40 years of age, with late stage of presentation, lack of awareness about screening, costs, fear and stigma associated with the disease serving as major barriers for early presentation. CONCLUSIONS: Educational strategies should be aimed at modifying the life style, early planning of pregnancy, promoting breast feeding and physical activity. It is very important to obtain reliable data for planning policies, decision-making and setting up the priorities. PMID- 24175780 TI - High temperature of food and beverage intake increases the risk of oesophageal cancer in Xinjiang, China. AB - BACKGROUND: The north-western region of China has a high incidence of oesophageal cancer. This study aimed to investigate whether the intake of food and beverage at high temperature is associated with the risk of oesophageal cancer among adults residing in this remote part of China. MATERIALS AND METHODS: A case control study was undertaken in Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region of China, between 2008 and 2009. Participants were 359 incident oesophageal cancer patients and 380 hospital-based controls. Information on temperature of food and beverage intake was obtained by face-to-face interview. Logistic regression analyses were performed to ascertain the association between intake temperature and the risk of oesophageal cancer. RESULTS: The oesophageal cancer patients consumed foods and beverages at higher temperatures than controls, p<0.001. High temperature of tea, water and food intake appeared to increase the risk of oesophageal cancer by more than two-fold, with adjusted odds ratio (95% confidence intervals) of 2.86 (1.73-4.72), 2.82 (1.78-4.47) and 2.26 (1.49-3.45), respectively. CONCLUSIONS: Intake of food and beverage at high temperature was positively associated with the incidence of oesophageal cancer in north-western China. PMID- 24175781 TI - BCRP expression in VX2 rabbit liver tumours and its effects on tumour recurrence, metastasis and treatment tolerability. AB - OBJECTIVE: This study aimed to investigate the effects of BCRP expression on tumor recurrence, metastasis and treatment tolerability. METHODS: A VX2 rabbit liver tumor model was established. Division was randomly into 4 groups: namely saline control group; A group, given hydration lipiodol; B group, Ad-p53; and C group, Ad-p53+hydration lipiodol. After the intervention, samples were collected to detect the BCRP, MMP-2, VEGF and PCNA. RESULTS: The expression of BCRP, MMP-2, PCNA and VEGF in tumors in Group A had no significant difference when compared with the control group, while in B and C group, the values were significantly lower (P < 0.05). BCRP positive expression in metastatic lesions significantly increased (P < 0.05), and was correlated with MMP-2 (X2=6.172, P = 0.0131). CONCLUSIONS: BCRP may play an important role in mediating liver cancer multidrug resistance to chemotherapy, and may be correlated with tumor recurrence and metastasis, which leads to weakened treatment effect. Ad-P53 can down-regulate the expression of related genes, playing a role in multidrug resistance reversal and increased sensitivity in liver cancer treatment. PMID- 24175782 TI - Breast cancer in young women from a low risk population in Nepal. AB - BACKGROUND: The overall incidence of breast cancer in South Asian countries, including Nepal, is low compared to Western countries. However, the incidence of breast cancer among young women is relatively high. Breast cancer in such cases is characterized by a relatively unfavorable prognosis and unusual pathological features. The aim of this study was to investigate clinico-pathological and biological characteristics in younger breast cancer patients (<40 years) and compare these with their older counterparts. MATERIALS AND METHODS: Nine hundred and forty four consecutive female breast cancer patients, admitted to the Department of Surgery, Tribhuvan University Teaching Hospital, Kathmandu, Nepal between November 1997 and October 2012, were retrospectively analyzed. RESULTS: Out of the 944 female breast cancer patients, 263 (27.9%) were <40 years. The mean age was 34.6 +/- 5.0 years among younger patients compared to 54.1 +/- 9.9 for those >= 40 years. The mean age at menarche was also significantly lower (13.5 +/- 1.5 vs 14.2 +/- 1.5 years p=0.001) while the mean duration of symptoms was significantly longer (7.6 vs 6.5 months p=0.004). Family history of breast cancer was evident in 3.0% of the young women versus 0.3% in the older one. Mammography was performed less frequently in younger patients (59.7%), compared to older (74.4%), and was of diagnostic benefit in only 20% of younger patients compared to 85% of older ones. At diagnosis, the mean tumor diameter was significantly larger in young women (5.0 +/- 2.5 vs 4.5 +/- 2.4 cm, p=0.005). Axillary lymph nodes were positive in 73% of younger patients and 59% of older patients. In the younger group, the proportion of stage III or IV disease was higher (55.1% vs 47.1%, p <= 0.05). The proportion of breast conserving surgery was higher in young patients (25.1% vs 8.7%) and a higher proportion of younger patients receive neoadjuvant chemotherapy (9.9% vs 2.8%). The most common histological type was ductal carcinoma (93.1% vs 86%). The proportion of histological grade II or III was higher in younger patients (55.9% vs 24.5%). Similarly, in the younger group, lymphatic and vascular invasion was more common (63.2% vs 34.3% and 39.8% vs 25.4%, respectively). Patients in the younger age group exhibited lower estrogen and/ or progesterone receptor positivity (34.7% vs 49.8%). Although statistically not significant, the proportion of triple negative tumors in younger age group was higher (22.4% vs 13.6%). CONCLUSIONS: Breast cancer in young Nepalese women represents over one quarter of all female breast cancers, many being diagnosed at an advanced stage. Tumors in young women exhibit more aggressive biological features. Hence, breast cancer in young women is worth special attention for earlier detection. PMID- 24175783 TI - Opportunistic screening for cervical cancer in a tertiary hospital in Karnataka, India. AB - The incidence and mortality of cervical cancer remains high in India even after sixty years of introduction of the Pap smear (cervical cytology) which is an effective means of identifying preinvasive lesions of carcinoma cervix. The morbidity and mortality due to cervical cancer has come down drastically in countries with well established screening programmes at national level. This study aims at screening women for cervical cancer opportunistically during their visit to hospital and to study various types of neoplastic and non-neoplastic lesions of the cervix by cervical smear study (Pap smear study). In the present study, a total of 350 cervical smears were studied. The age of patients ranged from 19 years to 80 years with mean age being 37.5 years. Out of 350 cases, the diagnosis of neoplasia was given in 43 cases and 258 cases were diagnosed as inflammatory smears. Forty-cases were normal and 9 cases were inadequate to evaluate. Forty-three patients who were found to have neoplastic lesions on cytology were referred for further investigations like colposcopy and biopsy to confirm the diagnosis and avail proper treatment. Limitation of the present study was small sample size as all female patients aged between 20 and 60 years visiting hospital were not included in the screening, other screening tests like VIA (visual inspection with acetic acid test) and HPV DNA (human papilloma virus) tests were not done. Until the time centrally organised screening programmes for cervical cancer are established in India, arrangements should be made for hospital based opportunistic screening for all women attending hospital. The cost effectiveness of different screening tests for cervical cancer should be evaluated. PMID- 24175784 TI - Can reproductive characteristics predict bladder cancer in women with haematuria? AB - BACKGROUND: Among women with haematuria, defining individuals under high risk for bladder cancer based on reproductive factors prior to cystoscopy would be of great benefit in the management of this condition. The aim of this study was to compare age and reproductive factors such as menopausal status, parity, age at first delivery and age at the last delivery between women who have haematuria with or without bladder cancer. MATERIALS AND METHODS: A total of 463 patients underwent diagnostic cystoscopy in Duzce University Faculty of Medicine between 1 June 2008 and 1 June 2013. Female patients who presented with persistent microscopic or macroscopic haematuria and underwent standard evaluation for haematuria including urinalysis, urine culture, urine cytology, urinary tract imaging with excretory urography or computerized tomography with contrast enhancement and endoscopic evaluation of the urethra and bladder were included in this study. Exclusion criteria were tobacco use and high risk occupations for bladder cancer such as textile, dry cleaning, painting and etc. Fourteen women had hematuria due to benign conditions, and 18 due to bladder cancer. Data were retrospectively retrieved from the medical records of Duzce University Hospital. RESULTS: Patients with haematuria due to benign reasons did not significantly differ from patients who were found to have bladder cancer in terms of age (p=0.28), menopausal status (p=0.29), mean parity (p=0.38), being nulliparous (p=0.57), parity >= 3 (p=0.22), age <= 18 years at first delivery (p=1.00), age >= 30 years at last delivery (p=0.26), age >= 35 years at last delivery (p=0.23) and percentage of the patients with advanced age (>= 65 years) (p=0.18). CONCLUSIONS: It is difficult to predict a high risk for developing bladder cancer in women with haematuria based solely on reproductive factors. PMID- 24175785 TI - Social determinants of health and 5-year survival of colorectal cancer. AB - BACKGROUND: Early in the 21st century, cancers are the second cause of death worldwide. Colon cancer is third most common cancer and one of the few amenable to early diagnosis and treatment. Evaluation of factors affecting this cancer is important to increase survival time. Some of these factors affecting all diseases including cancer are social determinants of health. According to the importance of this disease and relation with these factors, this study was conducted to assess the relationship between social determinants of health and colon cancer survival. MATERIALS AND METHODS: This was a cross-sectional, descriptive study for patients with colon cancer registered in the Cancer Research Center of Shahid Beheshti University of Medical Science, from April 2005 to November 2006, performed using questionnaires filled by telephone interview with patients (if patients had died, with family members). Data was analyzed with SPSS software (version 19) for descriptive analysis and STATA software for survival analysis including log rank test and three step Cox Proportional Hazard regression. RESULTS: Five hundred fifty nine patients with ages ranging from 23 to 88 years with mean +/- standard deviation of 63 +/- 11.8 years were included in the study. The five year survival was 68.3%( 387 patients were alive and 172 patients were dead by the end of the study). The Cox proportional hazard regression showed 5 year survival was related to age (HR=0.53, p=0.042 for>50 years versus<50 years old) in first step, gender (HR=0.60, p=0.006 for female versus male) in second step, job (HR=1.7, p=0.001 for manual versus non manual jobs), region of residency (HR=3.49, p=0.018 for west versus south regions), parents in childhood (HR=2.87, p=0.012 for having both parents versus not having), anatomical cancer location (HR=2.16, p<0.033 for colon versus rectal cancer) and complete treatment (HR=5.96, p<0.001 for incomplete versus complete treatment). CONCLUSIONS: Social determinants of health such as job, city region residency and having parents during childhood have significant effects in 5-year survival of colon cancer and it may be better to consider these factors in addition to developing cancer treatment and to focus on these determinants of health in long-time planning. PMID- 24175786 TI - PIK3CA and AKT gene polymorphisms in susceptibility to osteosarcoma in a Chinese population. AB - PURPOSE: To explore the association between PIK3CA and AKT single nucleotide polymorphisms(SNP) and osteosarcoma susceptibility. METHODS: TaqMan polymerase chain reaction(PCR) was used to detect the genotypes of SNPs (rs7646409, rs6973569 and rs9866361) in peripheral blood samples from 59 patients with osteosarcoma and from 63 healthy controls. Unconditional logistic regression was used to analyze the correlation between SNPs and osteosarcoma risk. RESULTS: No statistically significant difference was found between osteosarcoma patients and healthy controls in the genotype of AKT rs6973569 (P = 0.7). However, after stratified analysis, the genotype AA of AKT rs6973569 carried a higher risk of osteosarcoma metastasis (OR:2.94, 95%CL:1.00-8.59); the difference of rs7646409 genotype distributions between the case and control groups was statistically significant (P = 0.032). Taking genotype TT as a reference, the risk of osteosarcoma increased three fold in patients with genotype CC (OR:3.47, 95%CL:1.26-9.56). A statistically significant difference was found between the alleles C and T (P=0.005). Further analysis showed that the risk factor was more pronounced in male patients with Enneking's stage IIB and osteoblastic osteosarcoma. PIK3CA rs9866361 did not fit Hardy-Weinberg equilibrium (P < 0.05). CONCLUSIONS: Genotype CC in locus PIK3CA rs7646409 may increase the risk of osteosarcoma in the Chinese population. PMID- 24175787 TI - Relationships between breast cancer and common non- communicable disease risk factors: an ecological study. AB - BACKGROUND: Breast cancer is one the most common cause of cancer-related deaths among women worldwide. The aims of this study were to investigate the impact of dietary factors and health status indicators on breast cancer (BC) incidence. MATERIALS AND METHODS: Risk factor data (RFD) of 89,404 individuals (15-64 years old) were gathered by questionnaire and laboratory examinations through a cross sectional study from the Non- Communicable Disease Surveillance Centre (NCDSC) of Iran. BC incidences of all provinces through 2001-2006 segregated by age and gender were obtained from the Cancer Registry Ministry of Health (CRMH). RESULTS: A significant positive relationship was seen between diabetes mellitus, fish consumption, percent of academic education and non-consumption of fruit, and breast cancer in women. However, non fish consumption, percent age illiteracy and taking fruit showed a significant negative relationship with the incidence of breast cancer. In addition, multiple linear regression analysis showed associations among percentage with academic education, fruit consumption and diabetes. CONCLUSIONS: We conclude that dietary factors such as fish and fruit consumption, dairy products, health status indicators, academic education, and some diseases like diabetes mellitus can affect the BC incidence, although the results of ecologic studies like this must naturally be interpreted with caution. PMID- 24175788 TI - Can capecitabine be used instead of concurrent bolus 5-FU in postoperative chemoradiotherapy for gastric adenocarcinoma? AB - BACKGROUND: 5-fluoro-uracil (FU) is a common agent in postoperative chemoradiation in gastric adenocarcinoma. However, FU is not well tolerated in a significant proportion of patients. Capecitabine (CA) is an orally administered fluoropyrimidine carbamate which is preferentially converted to active 5-FU and is one of the agents used instead of FU in such cases. We compared the toxicity, local and distant control and survival rates with FU or oral CA during the course of concurrent radiotherapy to assess the role of CA used instead of FU. MATERIALS AND METHODS: We conducted an analysis of survival, disease control and toxicity data in 46 patients treated with postoperative chemoradiation following total or subtotal gastrectomy for gastric adenocarcinoma with either FU or CA between January 2008 and December 2012. RESULTS: Median follow-up was 19 months (range: 3 59), median survival time was 23 (+/- 6.08) months and 1-3 years overall survival (OS) rates were 64.9- 39% for all patients. Compared with the CA regimen, the incidence of treatment interruption was higher with FU (p=0.023), but no significant differences were seen in local control (p=0.510), distant recurrences (p=0.721) and survival rates (p=0.866) among patients. CONCLUSIONS: Concurrent CA with radiotherapy seems to be a more tolerable and an equally effective regimen for the postoperative treatment of gastric adenocarcinoma when compared to FU. PMID- 24175789 TI - Influence of perineural invasion on survival and recurrence in patients with resected pancreatic cancer. AB - BACKGROUND: Perineural invasion (PNI) has been reported as one of the sources of locoregional recurrence in resected pancreatic cancer (PC). However the impact of PNI in resected pancreatic cancer remains controversial. The purpose of this study was to determine the association between PNI status and clinical outcomes. METHODS: Publications were identified which assessed prognostic significance of PNI status in resected pancreatic cancer up to February 2013. A meta-analysis was performed to clarify the association between PNI status and clinical outcomes. RESULTS: A total of 21 studies met the inclusion criteria, covering 4,459 cases. Analysis of these data showed that intrapancreatic PNI was correlated with reduced overall survival only in resected pancreatic ductal adenocarcinoma (PDAC) patients (HR=1.982, 95%CI: 1.526-2.574, p=0.000). Extrapancreatic PNI was correlated with reduced overall survival in all resected pancreatic cancer patients (HR=1.748, 95%CI: 1.372- 2.228, p=0.000). Moreover, intrapancreatic PNI status may be associated with tumor recurrence in all resected pancreatic cancer patients (HR=2.714, 95%CI: 1.885-3.906, p=0.000). CONCLUSION: PNI was an independent and poor prognostic factor in resected PDAC patients. Moreover, intrapancreatic PNI status may be associated with tumor recurrence. PMID- 24175790 TI - Outcomes of local excision for early rectal cancer: a 6-year experience from the largest university hospital in Thailand. AB - BACKGROUND: This study aimed to determine clinical outcomes of local excision for early rectal cancer from a University Hospital in Thailand. MATERIALS AND METHODS: We performed a retrospective review of 22 consecutive patients undergoing local excision for early rectal cancer (clinical and radiological T1/T2) from 2005-2010 at the Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok. Data were collected from patients' medical records, including demographic and clinical characteristics, pathological report and surgical outcomes. RESULTS: This study included 10 males and 12 females, with average age of 68 years. Nineteen patients (86%) underwent transanal excision and the others had trans-sacral excision. Median operative time was 45 minutes. Postoperative complications occurred in 2 patients (9%); 1 fecal fistula and 1 wound infection following trans-sacral excision. There was no 30-day postoperative mortality. Median hospital stay was 5 days. Pathological reports revealed T1 lesion in 12 cases (55%), T2 lesion in 8 cases (36%) and T3 lesion in 2 cases (9%). Eight patients received additional treatment; one re-do transanal excision, two proctectomies, and five adjuvant chemoradiation. During the median follow-up period of 25 months, local recurrence was detected in 4 patients (18%); two cases of T2 lesions with close or positive margins, and two cases of T3 lesions. Three patients with local recurrence underwent salvage abdominoperineal resection. No local recurrence was found in T1/T2 lesions with free surgical margins. CONCLUSIONS: Local excision is a feasible and acceptable alternative to radical resection only in early rectal cancer with free resection margins and favorable histopathology. PMID- 24175791 TI - Association of DNA base-excision repair XRCC1, OGG1 and APE1 gene polymorphisms with nasopharyngeal carcinoma susceptibility in a Chinese population. AB - BACKGROUND: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. AIMS: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. MATERIALS AND METHODS: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. RESULTS: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02- 3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1- 141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants ,was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). CONCLUSION: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1- 141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma. PMID- 24175792 TI - Reproductive risk factors for thyroid cancer: a prospective cohort study in Khon Kaen, Thailand. AB - BACKGROUND: Because of the gender disparity in the incidence of thyroid cancer, this study aimed to determine the association between reproductive factors and thyroid cancer. METHODS: A total of 10,767 eligible women from the Khon Kaen Cohort, recruited and interviewed between 1990 and 2001, were followed up until 2011. The data were linked to the Khon Kaen Population-Based Cancer Registry to detect thyroid cancer cases. RESULTS: There was 17 thyroid cancer cases detected, an incidence of 11.2 per 100,000 person-years, of which 70.6 % were papillary tumors. The incidence was apparently greater among those with an early age of menarche, nulligravida women, and oral contraceptive users. CONCLUSIONS: There was a trend for thyroid cancer to develop in relation to longer estrogen exposure. This evidence is inconclusive but warrants further investigation. PMID- 24175793 TI - Evaluation of the knowledge, behavior and health beliefs of individuals over 50 regarding colorectal cancer screening. AB - The aim of the study was to evaluate of the knowledge, behavior and health beliefs of individuals over 50 regarding colorectal cancer screening, with a descriptive and cross-sectional design at Karabuk Life and Health Center in Turkey. A total of 160 people meeting set criteria were included in the study. The questionnaire consisted of two parts. The first part was composed of questions on characteristics of participants and the second part of questions derived from the Champion's Health Belief Model Scale. Only 15.0% of participants (n=24) had undergone a fecal occult blood test (FOBT), 11.3% (n=18) had had colonoscopy and 4.4% (n=7) had had sigmoidoscopy. Some 90.6% of the participants had low levels of risk awareness about the colorectal cancer. It was found that the average point of severity subscale of participants over 65 is higher than that of participants under 65 (p<0.05). In conclusion, because of the many barriers and health beliefs for the colorectal cancer screening program, the rate of participation in screening programs is not sufficient. Healthcare providers have important responsibilities for increasing rate of attendance in colorectal cancer screening programs. PMID- 24175794 TI - Prognostic value of pathological characteristics of invasive margins in early stage squamous cell carcinomas of the uterine cervix. AB - BACKGROUND: To evaluate the pathological characteristics of invasive margins in early-stage cervical squamous cell carcinomas and their association with other clinicopathological features including clinical outcomes. MATERIALS AND METHODS: Patients with FIGO stage IB-IIA cervical squamous cell carcinomas who received surgical treatment and had available follow-up information were identified. Their histological slides were reviewed for prognostic variables including tumor size, grade, extent of invasion, lymphovascular invasion, involvement of vaginal margin or parametrium, and lymph node metastasis. The characteristics of invasive margins including invasive pattern (closed, finger-like, or spray-like type), degree of stromal desmoplasia, and degree of peritumoral inflammatory reaction were evaluated along the entire invasive fronts of tumours. Associations between the characteristics of invasive margins and other clinicopathological variables and disease-free survival were assessed. RESULTS: A total of 190 patients were included in the study with a median follow-up duration of 73 months. Tumour recurrence was observed in 18 patients (9%). Spray-like invasive pattern was significantly more associated as compared with closed or finger-like invasive pattern (p=0.005), whereas the degree of stromal desmoplasia or peritumoral inflammatory reaction was not. Low degree of peritumoral inflammatory reaction appeared linked with lymph node metastasis (p=0.021). In multivariate analysis, a spray-like invasive pattern was independently associated with marked stromal desmoplasia (p=0.013), whilst marked desmoplasia was also independently associated with low inflammatory reactions (p=0.009). Furthermore, low inflammatory reactions were independently associated with positive margins (p=0.022) and lymphovascular invasion (p=0.034). The patients with spray-like invasive pattern had a significantly lower disease-free survival compared with those with closed or finger-like pattern (p=0.004). CONCLUSIONS: There is a complex interaction between cancer tissue at the invasive margin and changes in surrounding stroma. A spray-like invasive pattern has a prognostic value in patients with early-stage cervical squamous cell carcinoma. PMID- 24175795 TI - No association of XRCC1 and CLPTM1L polymorphisms with non-small cell lung cancer in a non-smoking Han Chinese population. AB - BACKGROUND: This study aimed to explore potential associations between single nucleotide polymorphisms (SNPs) of the x-ray repair cross-complementing group 1 (XRCC1) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) and non small cell lung cancer (NSCLC) susceptibility in non-smoker Chinese patients. METHODS: A total of 200 NSCLC patients and 200 healthy controls with matched age and gender were recruited for genotyping of XRCC1 SNPs (rs2256507 and rs1001581) and CLPTM1L SNPs (rs401681 and rs4975616). Association of these SNPs with NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. RESULTS: The frequencies of genotype and allele in these four loci (rs2256507, rs1001581, rs401681, and rs4975616) were not significantly different between the cases and controls, or between either of the histological subgroups (adenocarcinoma and squamous cell carcinoma) and controls. CONCLUSIONS: Although these SNPs are associated with NSCLC risk in patients with a tobacco smoking habit, this study demonstrated that XRCC1 and CLPTM1L gene SPNs are not linked with NSCLC risk in non-smoking patients, indicating that molecular mechanisms of NSCLC betwee tobacco smokers and non-smokers may be different. Future studies are needed to uncover the underlying molecular mechanisms for NSCLC in non-smokers. PMID- 24175796 TI - Prognostic value of osteopontin in patients treated with primary radiotherapy for head and neck cancer. AB - BACKGROUND: The prognostic value of tumor osteopontin (OPN) in patients with squamous-cell head and neck cancer (SCHNC) was investigated. MATERIALS AND METHODS: OPN expression was assessed by immunohistochemical methods in 50 patients, who were treated with primary radiotherapy (RT) for locally advanced SCHNC. The effects of OPN on clinical parameters, local-regional control after RT and metastasis-free survival, was assessed. RESULTS: The rate of OPN expression in tumor tissue was 76%. OPN positive cases had lower Hb levels (p=0.088). Mean time to local recurrence was 53.8 months (SE 3.9) in OPN-negative cases and 39.1 months (SE 4.7) in OPN-positive cases (p=0.047). OPN increased the risk of local recurrence 5.9 times (p=0.085). It had no effect on metastasis-free (p=0.116) or overall survival (p=0.123). OPN was positive in 12 of 19 cases that developed grade 3-4 acute radiation dermatitis (p=0.096). CONCLUSIONS: OPN expression is associated with an increase in local recurrence in patients who were treated with primary RT for locally advanced SCHNC. PMID- 24175797 TI - Clinical effectiveness of preoperative embolization for cerebellar hemangioblastoma. AB - The cerebellar hemangioblastoma (CHB) has an abundant blood supply and deep anatomical location. Complete surgical resection is generally very difficult. This study investigated the safety and effectiveness of preoperative embolization followed by surgical resection of CHB in a large cohort of patients. A database of 125 CHB patients with surgical resection in Beijing Tiantan Hospital between July 2006 and July 2012 was reviewed. Of those, 46 cases (experimental group) received preoperative embolization, 79 cases (control group) underwent surgery without embolization. Patient demographics, tumor size, duration of surgery, blood loss, blood transfusion, complications and follow-up results were collected and analyzed retrospectively. In the experimental group, the Kamofsky score (KS) was 80-100 in 40 cases (86.9%), 40-70 in 4 cases (8.7%), and below 40 in 2 cases (4.3%). Among 31 cases with follow-up, KS was 80-100 in 27 cases (87.1%), 40-70 in 2 cases (6.5%), and 0 in 2 cases (6.5%). In control group, KS was 80 -100 in 65 cases (82.2%), 40-70 in 6 cases (7.6%), 10-30 in 3 cases (3.8%), and 0 in 3 cases (3.8%). Among 53 cases with follow-up, KS was 80-100 in 44 cases (83.0%), 40-70 in 4 cases (7.5%), 10-30 in 1 case (1.9%), and 0 in 4 cases (7.5%). There were statistically significant differences between the experimental and control groups in tumor size, duration of surgery, amount of intraoperative blood loss and transfusion (p <0.01). However, complications (p = 0.31) and follow-up results (p = 0.76) showed no significant differences between groups. Selective preoperative embolization of those CHB patients with richer blood supply, higher hemorrhage risk, is safe and effective, and is a reliable adjuvant therapy for complete surgical resection of CHB. PMID- 24175798 TI - Salvage treatment experience in advanced synovial sarcoma: a multicenter retrospective analysis of the Anatolian society of medical oncology. AB - BACKGROUND: We aimed to evaluate prognostic factors and response rates to various treatment approaches to patients with synovial sarcoma in an advanced setting. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 55 patients (18 pts; 32.7% women) diagnosed with synovial sarcomas. Twenty had metastatic disease at the time of diagnosis while the remainder of the study group consisted of patients who developed metastatic or inoperable locally advanced disease during follow up. RESULTS: The median follow up time was 15 months (range: 1-53). Regarding outcomes for the 55 patients, 3 and 5 year overall survival rates were 26% and 14%, respectively. In univariate analyses among demographic factors female gender was associated with a better outcome (p=0.030). Patients with early progressing disease (<2 years) had a worse prognosis when compared to patient group with late relapse, but this difference did not reach statistical significance (p=0.056). According to multivariate Cox regression analysis patients who had undergone metastasectomy had a significant survival advantage (p=0.044). The overall response rate to different salvage chemotherapy regimens given as second line treatment was around 42.9-53.9% for all regimes. There were no statistically significant differences between chemotherapy regimens given in either second or third line settings in terms of overall survival. CONCLUSIONS: We observed no major differences in terms of response rate and survival between different salvage chemotherapy regimens. Although metastatic disease still carries a poor prognosis, metastasectomy was found to be associated with improved survival. PMID- 24175799 TI - Association of dietary intake of folate, vitamin B6 and B12 and MTHFR genotype with breast cancer risk. AB - AIM: We aimed to investigate the associations of dietary intake of folate, vitamin B6 and B12 and MTHFR genotype with breast cancer in a Chinese population. METHODS: A matched case-control study was conducted, and 435 patients with newly diagnosed and histologically confirmed breast cancer and 435 controls were collected. The folate intake, vitamin B6 and vitamin B12 were calculated, and MTHFR C665T, C677T and A1298C were analyzed by PCR-RFLP. RESULTS: We found vitamin B12 was likely to reduce the risk of breast cancer, and MTHFR 665TT was associated with increased risk of breast cancer. Folate intake, vitamin B12 intake and variants of MTHFR C677T and MTHFR A1298C demonstrated no association with risk of breast cancer. However, we found patients with low intake of vitamin B6 and MTHFR 665TT genotype had a higher risk of breast cancer (OR=1.87, 95% CI=1.29-2.77), the association being less pronounced among subjects with a moderate intake of vitamin B6 and MTHFR 665TT genotype (OR=1.58, 95% CI=1.03 2.49, P=0.03). CONCLUSION: Our study indicated that the MTHFR C665T polymorphism and vitamin B6 are associated with risk of breast cancer, which indicated roles for nutrients in developing breast cancer. PMID- 24175800 TI - Glycemic index and glycemic load dietary patterns and the associated risk of breast cancer: a case-control study. AB - The glycemic index (GI) and glycemic load (GL) have been considered risk factors for breast cancer, but association studies of breast cancer risk using simple GI and GL might be affected by confounding effects of the overall diet. A total of 357 cases and 357 age-matched controls were enrolled, and dietary intake was assessed using a validated food frequency questionnaire (FFQ) with 103 food items. GI and GL dietary patterns were derived by reduced rank regression (RRR) method. The GI and GL pattern scores were positively associated with breast cancer risk among postmenopausal women [OR (95%CI): 3.31 (1.06-10.39), p for trend=0.031; 9.24 (2.93-29.14), p for trend<0.001, respectively], while the GI pattern showed no statistically significant effects on breast cancer risk, and the GL pattern was only marginally significant, among premenopausal women (p for trend=0.043). The GI and GL pattern scores were positively associated with the risk of breast cancer in subgroups defined by hormone receptor status in postmenopausal women. The GI and GL patterns based on all food items consumed were positively associated with breast cancer. PMID- 24175802 TI - Physical inactivity, water intake and constipation as risk factors for colorectal cancer among adults in Jordan. AB - BACKGROUND: Physical activity has been found to play a role in cancer prevention. The purpose of this matched case-control study was to investigate the association between physical activity levels, water intake, constipation and colorectal cancer (CRC). MATERIALS AND METHODS: Two hundred and thirty-two patients diagnosed with CRC (125 male, 107 female) were enrolled in this case-control study. Cases were matched to 271 population controls (137 male, 134 female). RESULTS: Drinking more than 4 cups of water daily decreased the risk of CRC by 33 42%; however, this effect was non-significant. Having constipation was found to be a significant risk factor for developing CRC with an OR=6.284 (95%CI=2.741 14.40). With reference to sedentary behavior, minimum activity (600-3000 Metabolic Equivalents Task (MET)) had 43% protection against CRC and the level of Health Enhancing Physical Activity OR was 0.58 (at 95%CI; 0.37-0.92). A significant negative association was found between CRC and physical activity levels expressed as both METs and MET-hours/week (p for trend=0.017 and 0.03, respectively). Among females, a significant trend of reduction in CRC by 62% was observed with increasing the level of physical activity expressed in MET (p for trend=0.04). CONCLUSIONS: The risk of CRC may be reduced by adopting a healthy lifestyle and practicing physically activity regularly, especially among females. Consuming adequate amounts of water and healthy bowel motility could also reduce the risk of CRC. PMID- 24175801 TI - Effects of the hippo signaling pathway in human gastric cancer. AB - BACKGROUND/AIM: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. METHODS: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. RESULTS: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1 ,YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). CONCLUSION: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer. PMID- 24175803 TI - Association of TAP1 and TAP2 gene polymorphisms with hematological malignancies. AB - Transporter associated with antigen presenting (TAP) 1 and TAP2 genes are localized in the major histocompatability complex (MHC) class II region and form a heterodimer playing a key role in endogenous pathways for antigen presentation. Defects of these genes have been reported to be common in different types of cancer. Polymorphisms identified in these loci have also been investigated and reported to be associated with several autoimmune disorders, viral infections and neoplasms. In the present study, for the first time, the allele and genotype frequencies of TAP1-333, TAP2-565, TAP2-651 and TAP2-665 were determined in patients with hematological malignancies (HM) using a PCR-RFLP method and compared with the frequencies in the control group. Our results suggested an association of TAP1-333 polymorphism with multiple myeloma-MM and TAP2- 565 polymorphism with chronic lymphoid leukemia-CLL. In addition, it could be concluded that the TAP2-665 GG genotype might be a risk factor for all types of hematological malignancies included in this study. PMID- 24175804 TI - Metastatic axillary lymph node ratio (LNR) is prognostically superior to pN staging in patients with breast cancer--results for 804 Chinese patients from a single institution. AB - The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer. The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor in predicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis was based on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008 in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile software and validated by bootstrapping. Patients were then divided into three groups (low , intermediate-, and high-risk) according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportional hazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log rank test. The 5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT , pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly different prognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor. Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category, but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore, LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routine clinical decision-making should take the LNR into consideration. PMID- 24175805 TI - Elevated serum IL-17A but not IL-6 in glioma versus meningioma and schwannoma. AB - BACKGROUND: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. MATERIALS AND METHODS: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. RESULTS: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera (0.29 +/- 0.54, 0.03 +/- 0.15 and 0.16 +/- 0.68 vs. 0.00 +/- 0.00 pg/ml; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls (2.34 +/- 4.35 vs. 4.67 +/- 4.32 pg/ml; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. CONCLUSIONS: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases. PMID- 24175806 TI - Nrf2 overexpression predicts prognosis and 5-FU resistance in gastric cancer. AB - OBJECTIVE: NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. MATERIALS AND METHODS: A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo. RESULTS: Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines. CONCLUSION: Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC. PMID- 24175807 TI - Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non small cell lung cancer associated with treatment response and prognosis? AB - BACKGROUND: Inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an essential participant in the neoplastic process, promoting proliferation, survival and migration. Platelets can release some growth factors such as platelet-derived growth factor, platelet factor 4, and thrombospondin. Such factors have been shown to promote hematogenous tumour spread, tumor cell adhesion and invasion, and angiogenesis and to play an important role in tumor progression. In this study, we aimed to investigate effects of the pretreatment neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on survival and response to chemoradiotherapy in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Ninety four patients with non-metastatic NSCLC were included and separated into two groups according to median value of NLR and PLR (low: <3.44 or high: >= 3.44 and low: <194 or high >= 194, respectively). RESULTS: Pretreatment high NLR and PLR were associated with significantly shorter disease-free and overall survival rates. Multivariate analysis revealed that the overall survival rates were significantly linked with PLR (OR: 1.87, CI: 1.20-2.91, p: 0.006) and response to chemoradiotherapy (OR: 1.80, CI: 1.14-2.81, p: 0.012) and the disease-free survival rates were significantly associated with NLR (OR: 1.81, CI: 1.16-2.82, p: 0.009) and response to chemoradiotherapy (OR: 2.30, CI: 1.45-3.66, p: 0.001). There was no significant difference between patients with high and low NLR in terms of response to chemoradiotherapy. Similarly, there was no significant influence of the PLR. CONCLUSIONS: Pretreatment NLR and PLR measurements can provide important prognostic results in patients with NSCLC and assessment of the two parameters together appears to better predict the prognosis in patients with NSCLC. The effect of inflammation, indicators of NLR and PLR, on survival seems independent of the response to chemoradiotherapy. PMID- 24175808 TI - Synergism of cytotoxicity effects of triptolide and artesunate combination treatment in pancreatic cancer cell lines. AB - BACKGROUND: Triptolide, extracted from the herb Tripteryglum wilfordii Hook.f that has long been used as a natural medicine in China, has attracted much interest for its anti-cancer effects against some kinds of tumours in recent years. Artesunate, extracted from the Chinese herb Artemisia annua, has proven to be effective and safe as an anti-malarial drug that possesses anticancer potential. The present study attempted to clarify if triptolide enhances artesunate-induced cytotoxicity in pancreatic cancer cell lines in vitro and in vivo. METHODS: In vitro, to test synergic actions, cell viability and apoptosis were analyzed after treatment of pancreatic cancer cell lines with the two agents singly or in combination. The molecular mechanisms of apoptotic effects were also explored using qRT-PCR and Western blotting. In vivo, a tumor xenograft model was established in nude mice, for assessment of inhibitory effects of triptolide and artesunate. RESULTS: We could show that the combination of triptolide and artesunate could inhibit pancreatic cancer cell line growth, and induce apoptosis, accompanied by expression of HSP 20 and HSP 27, indicating important roles in the synergic effects. Moreover, tumor growth was decreased with triptolide and artesunate synergy. CONCLUSION: Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications. PMID- 24175809 TI - A single measure of cancer burden in Korea from 1999 to 2010. AB - BACKGROUND: The purpose of this study was to develop a single measure of cancer burden (SMCB), which can prioritize cancer sites by considering incidence and mortality. MATERIALS AND METHODS: Incidence data from 1999 to 2010 were obtained from the Korea Central Cancer Registry. Mortality data from 1999 to 2010 were obtained from Statistics Korea. The SMCB was developed by adding incidence and mortality scores. The respective scores were given such that incidence and mortality were classified by ten ranges of equal intervals. RESULTS: According to the SMCB in 2010, stomach cancer ranked 1st in males with 20 points, and colorectal cancer was 2nd with 11 points. Breast cancer and thyroid cancer were joint 1st with 11 points for females. The SMCB for females was less than that for males. The burden of stomach cancer was 1st in males from 1999-2010. The incidences of lung cancer and liver cancer decreased, whereas thyroid cancer and colon cancer increased during the period. Breast cancer and thyroid cancer burden showed tendencies to increase in females. Comparison of SMCB with disability adjusted life years (DALY) and socioeconomic costs in 2005 showed that the top five cancer sites were similar, but there were differences in the size of the cancer burden. CONCLUSIONS: The SMCB indicated that the burdens of stomach cancer in males and thyroid and breast cancers in females were large. The single measure showed an advantage, reflected as the equivalent dimensions of incidence and mortality, whereas DALY and economic costs showed tendencies to reflect premature death. PMID- 24175810 TI - Micronucleus expression and acute leukemia prognosis. AB - The micronucleus frequency (MNF) in peripheral blood lymphocytes (PBL) is a biomarker of chromosomal damage and genome instability in human populations.The relationship of micronucleus frequency with prognosis of patients with acute leukemia is not clear. We therefore investigated MNF in mitogen-activated peripheral blood lymphocytes from patients with hematologic diseases and solid tumours. Patients included 50 with acute leukemia, 49 diagnosed with myelodysplastic syndrome (MDS), 54 with benign blood diseases, and 45 with solid tumours, examined with 50 healthy controls. The mean MNF was significantly higher in cases of hematologic diseases and solid tumor patients than in healthy controls (P<0.001). There was no evident difference between MNF in the acute leukemia (7.15 +/- 2.18) and solid tumor groups (7.11 +/- 1.47), but both were higher than in the MDS group (5.12 +/- 1.29) and benign blood diseases group (3.08 +/- 1.08). Taking 7.15%, the average MNF of the acute leukemia group as standard, and dividing 50 cases of acute leukemia patients into high MNF group (MNF >= 7.15%) and low MNF group (MNF<7.15%). The overall response (complete remission + partial remission) rates of the low MNF group were significantly higher than in the high MNF group (P=0.001). The high MNF group further showed lower overall survival rates than the low MNF group. MNF expression and progression-free survival seemed to have a opposite relationship, with a correlation coefficient of -0.702. These data indicate that MNF in peripheral blood lymphocytes is important for evaluation of prognosis of acute leukemia patients, and it can reflect progression of disease to a certain degree. PMID- 24175811 TI - Two-week combination chemotherapy with gemcitabine, high-dose folinic acid and 5 fluorouracil (GEMFUFOL) as first-line treatment of metastatic biliary tract cancers. AB - BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. MATERIALS AND METHODS: All patients received folinic acid 400 mg/m(2) on day 1, 5-fluorouracil bolus 400 mg/ m2 on day 1, IV infusion of 5-fluorouracil 2400 mg/m(2) over 46 hours, and gemcitabine 1250 mg/m(2) on day 1. RESULTS: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the first- line treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1 year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia in 2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. CONCLUSIONS: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer. PMID- 24175812 TI - Variants of interleukin-16 associated with gastric cancer risk. AB - AIM: We conducted a case-control matched study to investigate the role of IL-16 gene polymorphisms, rs4072111, rs1131445, rs4778889 and rs11556218, in the risk of gastric cancer in a Chinese population, also performing subgroup analysis by subsites. METHODS: To test the hypothesis of involvement, we analyzed the four SNPs of IL16 in 347 cancer patients and 368 controls. Demographic data and other information were collected using a newly designed questionnaire. Genotyping of IL16 (rs4072111, rs1131445, rs4778889 and rs11556218) was performed in a 384-well plate format on the MassARRAY(r) platform. RESULTS: In our study, we found the gastric cancer patients were more likely to be male and have a family history of cancer (P < 0.05). We found the rs4778889 CC and rs11556218 GG genotype was significantly associated with 1.97 and 1.84-fold increased risk of non-cardia gastric cancer, while we did not find significant association between the four IL 16 SNPs and cardia gastric cancer. CONCLUSIONS: In conclusion, our study indicated that IL-16 rs4778889 CC and rs11556218 GG genotypes are associated with an increased risk of non-cardia gastric cancer in a Chinese population. Our results offer insights into the influence of IL-16 on development of gastric cancer. PMID- 24175813 TI - The codon 399 Arg/Gln XRCC1 polymorphism is associated with lung cancer in Indians. AB - BACKGROUND: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. MATERIALS AND METHODS: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. RESULTS: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. CONCLUSIONS: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis. PMID- 24175814 TI - Identifying differentially expressed genes and small molecule drugs for prostate cancer by a bioinformatics strategy. AB - PURPOSE: Prostate cancer caused by the abnormal disorderly growth of prostatic acinar cells is the most prevalent cancer of men in western countries. We aimed to screen out differentially expressed genes (DEGs) and explore small molecule drugs for prostate cancer. MATERIALS AND METHODS: The GSE3824 gene expression profile of prostate cancer was downloaded from Gene Expression Omnibus database which including 21 normal samples and 18 prostate cancer cells. The DEGs were identified by Limma package in R language and gene ontology and pathway enrichment analyses were performed. In addition, potential regulatory microRNAs and the target sites of the transcription factors were screened out based on the molecular signature database. In addition, the DEGs were mapped to the connectivity map database to identify potential small molecule drugs. RESULTS: A total of 6,588 genes were filtered as DEGs between normal and prostate cancer samples. Examples such as ITGB6, ITGB3, ITGAV and ITGA2 may induce prostate cancer through actions on the focal adhesion pathway. Furthermore, the transcription factor, SP1, and its target genes ARHGAP26 and USF1 were identified. The most significant microRNA, MIR-506, was screened and found to regulate genes including ITGB1 and ITGB3. Additionally, small molecules MS-275, 8 azaguanine and pyrvinium were discovered to have the potential to repair the disordered metabolic pathways, abd furthermore to remedy prostate cancer. CONCLUSIONS: The results of our analysis bear on the mechanism of prostate cancer and allow screening for small molecular drugs for this cancer. The findings have the potential for future use in the clinic for treatment of prostate cancer. PMID- 24175815 TI - Prevalence and type distribution of human papillomavirus infection using the INNo Lipa assay, Kerman, Southeast Iran. AB - The human papilloma virus (HPV) causes skin and mucous membrane infections. It crosses from one person to another by skin-to-skin contact, such as sexual contact. There are more than 100 types of HPV that can influence different parts of the body. Some types of HPV can cause cancer (such as cervical or anal cancer) and others can cause warts (such as genital or plantar warts). HPV infection is one of the most common sexually transmitted infections (STIs) in Iran and around the world. Considerable molecular evidence suggests a role for human papilloma virus (HPV) in the pathogenesis of carcinoma. Epidemiological studies on human papilloma viruses (HPVs) infections in general population are critical for the performing of health policy guidelines for developing the strategies to hinder the primary and secondary different cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study was therefore to report the prevalence ratse of HPV types among Iranian patients. To study the risk of human papilloma virus (HPV) infection, we managed a retrospective study in Kerman province, southeast of Iran. For this purpose, 410 patients tested for the presence of HPV DNA using PCR and INNo- Lipa assays. HPV DNA was detected in 108 out of 410 patients (26.34%), while it was not detected in any of the control group samples. Patients included 23 (21.1%) males and 86 (78.8%) females. HPV type 6 was the most common (49%) followed by HPV type 16 (10.1%), and also HPV type11 (9.2%). The prevalence of HPV in Iran is comparable to those reported in other regions of the world. In a similar manner, it seems that HPV types 6, 16 and11 are the most common types in Kerman. Additional studies on larger group of patients, particularly in those with pre-invasive forms of disease, are needed to explain the roles of different HPV types in this location of Iran. PMID- 24175816 TI - Serum BMP-2 up-regulation as an indicator of poor survival in advanced non-small cell lung cancer patients. AB - PURPOSE: High levels of bone morphogenetic protein (BMPs) have been reported in patients with lung cancer. This study was conducted to assess correlations between serum BMP-2 levels and prognostic outcome in patients with non-small-cell lung cancer (NSCLC). METHODS: Blood samples from 84 patients with advanced NSCLC and 42 healthy controls were analyzed and quantitated for serum BMP-2 levels before and after two cycles of chemotherapy using a commercially available ELISA kit. RESULTS: The median level of BMP-2 was 146.9 pg/ml in patients with NSCLC vs. 87.7 pg/ml in healthy controls (P<0.01). A significant correlation was observed between pretreatment serum BMP-2 level and ECOG PS, disease stage and number of organs with metastases (P<0.05). Serum BMP-2 level decreased significantly in patients who achieved objective response after two cycles of chemotherapy. Multivariate analysis showed that increased BMP-2 level and advanced clinical stage were significantly correlated with poor prognosis. CONCLUSION: Thes erum BMP-2 level is positively correlated with clinical stage, ECOG PS and metastatic burden and may serve as an independent negative predictor for prognosis. Decreased BMP-2 after chemotherapy could be a reliable marker for efficacy of treatment. PMID- 24175817 TI - Relationships between clinical behavior of laryngeal squamous cell carcinomas and expression of VEGF, MMP-9 and E-cadherin. AB - The biological mechanisms of cancer and associations with behavior of tumours need to be studied to understand progression and determine appropriate treatments. Here we investigated expression of VEGF, MMP-9 and E-cadherin in laryngeal SCCs and their relations with clinical behavior. This prospective study was based on 38 surgical specimens from patients with primary laryngeal SCC and data recorded in their cards. Expression of the three factors in tumor tissue was examined using immunohistochemistry and correlations with clinical parameters of primary tumors, regional lymph node metastases, stage of disease, histopathologic differentiation, and vascular/cartilage invasion were investigated. Regarding the cases with positive MMP-9 expression, the difference between well and moderately/poorly differentiated tumors was statistically significant. However, differences between early stage (stage I and II) and late-stage (stage III and IV) tumours, and between positive and negative for pLN metastasis were not. No significant relationship between positive VEGF and tumor differentiation or stage was apparent, but E-cadherin levels significantly differed between well and moderately/ poorly differentiated tumours and with the presence of pLN metastasis. E-cadherin staining did not vary between MMP-9 positive and negative cases. In conclusion, MMP-9 may be a negative predictor of differentiation in laryngeal SCC, while E-cadherin is a predictor of differentiation and nodal metastases. Even if the difference between VEGF expression and tumor stage was not statistically significant, it seems that there exists some relationship, which might be clarified with a greater number of cases. PMID- 24175818 TI - Effects of the NQO1 609C>T polymorphism on leukemia susceptibility: evidence from a meta-analysis. AB - A functional polymorphism in the NQO1 gene, featuring a 609C>T substitution,leading to proline to serine amino-acid and enzyme activity changes, has been implicated in cancer risk. However, individually published investigations showed inconclusive results, especially for leukemia. In this study, we therefore performed a meta- analysis of 21 publications with a total of 3,634 cases and 4,827controls, mainly for leukemia. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of leukemia and performed subgroup analyses by ethnicity and leukemia type. We found that the variant TT homozygous genotype o was associated with a modestly increased risk of leukemia (TT versus CT/CC: OR = 1.23, 95%CI = 1.00 - 1.51, heterogeneity = 0.76; I2 = 0%). Following further stratified analyses, increased risk was only observed in subgroups of Caucasians. This meta-analysis suggests that the NQO1 609T allele is a high-penetrance risk factor for leukemia in Caucasians. The effect on leukemia may be modified by ethnicity and leukemia type, and the small sample sizes of the subgroup analyses suggest that further larger studies are needed. PMID- 24175819 TI - Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line. AB - Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of r(2)=0.997. Dose-dependent and anti proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an IC50 value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer. PMID- 24175820 TI - Clinical risk factor analysis for breast cancer: 568,000 subjects undergoing breast cancer screening in Beijing, 2009. AB - OBJECTIVES: Although there are many reports about the risk of breast cancer, few have reported clinical factors including history of breast-related or other diseases that affect the prevalence of breast cancer. This study explores these risk factors for breast cancer cases reported in Beijing in 2009. MATERIALS AND METHODS: Data were derived from a Beijing breast cancer screening performed in 2009, of 568,000 women, from 16 districts of Beijing, all aged between 40 and 60 years. In this study, multilevel statistical modeling was used to identify clinical factors that affect the prevalence of breast cancer and to provide more reliable evidence for clinical diagnostics by using screening data. RESULTS AND CONCLUSION: Those women who had organ transplants, compared with those with none, were associated with breast cancer with an odds ratio (OR) = 65.352 [95% confidence interval (CI): 8.488-503.165] and those with solid breast mass compared with none had OR = 1.384 (95% CI: 1.022- 1.873). Malignant tendency was strongly associated with increased risk of breast cancer, OR = 207.999(95% CI: 151.950-284.721). The risk of breast cancer increased with age, OR1 = 2.759 (95% CI: 1.837-4.144, 56-60 vs. 40-45), OR2 = 2.047 (95% CI: 1.394-3.077, 51-55 vs. 40 45), OR3 = 1.668 (95% CI: 1.145-2.431). Normal results of B ultrasonic examination show a lower risk among participants, OR= 0.136 (95% CI: 0.085 0.218). Those women with ductal papilloma compared with none were associated with breast cancer, OR=6.524 (95% CI: 1.871-22.746). Therefore, this study suggests that clinical doctors should pay attention to these high-risk factors. PMID- 24175821 TI - Chemopreventive effect of Amorphophallus campanulatus (Roxb.) blume tuber against aberrant crypt foci and cell proliferation in 1, 2-dimethylhydrazine induced colon carcinogenesis. AB - Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/ kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post- initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant (p <= 0.05) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-S- transferase and reduced glutathione. Whereas the supplementation of ACME significantly (p <= 0.05) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH. PMID- 24175822 TI - Associations between age, cytogenetics, FLT3-ITD, and marrow leukemia cells identified by flow cytometry. AB - OBJECTIVES: To explore the relationships between age, cytogenetic subgroups, molecular markers, and cells with leukemic aberrant immunophenotype in patients with acute myeloid leukemia (AML). METHODS: In this study, we evaluated the correlations between age, cytogenetic subgroups (normal, balanced and unbalance karyotype), molecular mutations (NPM1, FLT3-ITD, and CEBPA mutations) and marrow leukemia cells (LC) identified by flow cytometry in 256 patients with de novo AML. RESULTS: From age group 10-19 years to age group >= 60 years, the percentage of LC decreased from 67.0 +/- 18.4% to 49.0 +/- 25.1% (F = 2.353, P = 0.041). LC percentage was higher in patients with balanced karyotypes (65.7 +/- 22.4%), than those with unbalanced karyotypes (46.0 +/- 26.6%) (u = 3.444, P = 0.001) or a normal karyotype (49.9 +/- 22.1%) (u = 5.093, P < 0.001). Patients with FLT3-ITD (64.3 +/- 19.5%) had higher LC percentages compared with those without (54.2 +/- 24.3%) (u = 2.794, P = 0.007). CONCLUSIONS: Associations between age, cytogenetics, molecular markers, and marrow leukemia cells may offer beneficial information to understand the biology and pathogenesis of AML. PMID- 24175823 TI - Development of an educational program to prevent cervical cancer among immigrants in Korea. AB - BACKGROUND: This study developed and measured the effects of a cervical cancer prevention program for married women immigrants. MATERIALS AND METHODS: A nonequivalent control group pre-test/post-test design was used with a group of married women immigrants registered at the multi-cultural center in the city of "J. " Data on for 30 participants in the intervention group and 27 participants in the control group (N=57) were used for analysis. The intervention group attended a 4-session cervical cancer prevention program. RESULTS: The knowledge of the intervention and control groups about cervical cancer post-intervention was significantly different (F=12.55, p<0.001). The perceived susceptibility score before and after the experiment, for the intervention group, and 29.4 and 28 for the control group, was significantly different (t=2.063, p=0.043). After the program, cancer prevention behavior was significantly different in the intervention group (t=2.646, p=0.010). CONCLUSIONS: The results obtained in this study indicate that the cervical cancer preventive program was effective in increasing cervical cancer knowledge, perceived susceptibility, and cancer prevention behavior. PMID- 24175824 TI - Predictors of long-term abstinence among Chinese smokers following treatment: the role of personality traits. AB - Four hundred and thirty-five Chinese smokers who had attended the first smoking cessation clinic and received stage-matched individualized cessation counseling in Hong Kong during the period of August 2000 to January 2002 were successfully followed-up between February and August 2008. Some 38% of the participants (165/495) had stopped smoking during the 12-month follow-up after treatment. Participants with higher conscientiousness score (OR = 1.65, 95% CI: 1.09 - 2.48) and lower openness to experience score (OR = 0.64, 95% CI: 0.45 - 0.92) showed a greater likelihood of quitting smoking after controlling the effect of daily cigarettes smoked and stage of readiness at baseline. The study suggests an important role of conscientiousness and openness to experience on long-term quitting behaviors following treatment, and provides useful information for the development of matched intervention for smoking cessation among Chinese smokers. PMID- 24175825 TI - Prognostic impact of histology in patients with cervical squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma. AB - BACKGROUND: Clarifying the prognostic impact of histological type is an essential issue that may influence the treatment and follow-up planning of newly diagnosed cervical cancer cases. This study aimed to evaluate the prognostic impact of histological type on survival and mortality in patients with cervical squamous cell carcinoma (SCC), adenocarcinoma (ADC) and small cell neuroendocrine carcinoma (SNEC). MATERIALS AND METHODS: All patients with cervical cancer diagnosed and treated at Chiang Mai University Hospital between January 1995 and October 2011 were eligible. We included all patients with SNEC and a random weighted sample of patients with SCC and ADC. We used competing-risks regression analysis to evaluate the association between histological type and cancer specific survival and mortality. RESULTS: Of all 2,108 patients, 1,632 (77.4%) had SCC, 346 (16.4%) had ADC and 130 (6.2%) had SNEC. Overall, five-year cancer specific survival was 60.0%, 54.7%, and 48.4% in patients with SCC, ADC and SNEC, respectively. After adjusting for other clinical and pathological factors, patients with SNEC and ADC had higher risk of cancer-related death compared with SCC patients (hazard ratio [HR] 2.6; 95% CI, 1.9-3.5 and HR 1.3; 95% CI, 1.1-1.5, respectively). Patients with SNEC were younger and had higher risk of cancer related death in both early and advanced stages compared with SCC patients (HR 4.9; 95% CI, 2.7-9.1 and HR 2.5; 95% CI, 1.7-3.5, respectively). Those with advanced-stage ADC had a greater risk of cancer-related death (HR 1.4; 95% CI, 1.2-1.7) compared with those with advanced-stage SCC, while no significant difference was observed in patients with early stage lesions. CONCLUSION: Histological type is an important prognostic factor among patients with cervical cancer in Thailand. Though patients with SNEC were younger and more often had a diagnosis of early stage compared with ADC and SCC, SNEC was associated with poorest survival. ADC was associated with poorer survival compared with SCC in advanced stages, while no difference was observed at early stages. Further tailored treatment-strategies and follow-up planning among patients with different histological types should be considered. PMID- 24175826 TI - Association between the c.3751G>a genetic variant of MDR1 and hepatocellular carcinoma risk in a Chinese Han population. AB - The objective of this study was to evaluate the influence of a genetic variant in the multidrug resistance 1 gene (MDR1) on hepatocellular carcinoma (HCC) risk. This case-control study was conducted in a Chinese population of 645 HCC cases and 658 cancer-free controls. The genotype of the c.3751G>A genetic variant in the MDR1 gene was investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Our data demonstrated significantly differences detected in the allelic and genotypic frequencies between HCC cases and those of cancer-free controls. Association analyses indicated that there were statistically increased risk of HCC in the homozygote comparison (AA versus (vs.) GG: OR = 2.22, 95% CI 1.51-3.27, chi(2) = 16.90, P < 0.001), dominant model (AA/GA vs. GG: OR = 1.25, 95% CI 1.00-1.55, chi(2) = 3.98, P = 0.046), recessive model (AA vs. GA/GG: OR = 2.14, 95% CI 1.47-3.09, chi(2) = 16.68, P < 0.001) and allele comparison (A vs. G: OR = 1.33, 95% CI 1.13-1.57, chi(2) = 11.66, P = 0.001). The allele-A and genotype-AA may contribute to HCC susceptibility. These preliminary findings suggest that the c.3751G>A genetic variant in the MDR1 gene is potentially related to HCC susceptibility in a Chinese Han population, and might be used as a molecular marker for evaluating HCC susceptibility. PMID- 24175827 TI - Estimation of esophageal cancer incidence in Tehran by log- linear method using population-based cancer registry data. AB - BACKGROUND: Having knowledge or estimation of cancer incidence is necessary for planning and implementation of any cancer prevention and control programs. Population-based registries provide valuable information to achieve these objectives but require extra techniques to estimate the incidence rate. The present study aimed to estimate the esophageal cancer incidence using a log linear method based on Tehran population-based cancer registry data. MATERIALS AND METHODS: New cases of esophageal cancer reported by three sources of pathology reports, medical records, and death certificates to Tehran Metropolitan Area Cancer Registry Center during 2002-2006 were entered into the study and the incidence rate was estimated based on log-linear models. We used Akaike statistics to select the best-fit model. RESULTS: During 2002-2006, 1,458 new cases of esophageal cancer were reported by the mentioned sources to the population-based cancer registry. Based on the reported cases, cancer incidence was 4.5 per 100,000 population and this was estimated to be 10.5 per 100,000 by the log-linear method. CONCLUSIONS: Based on the obtained results, it can be concluded that an estimated incidence for 2004 of 8.3 per 100,000 population could be a good benchmark for the incidence of esophageal cancer in the population of Tehran metropolis. PMID- 24175828 TI - Efficacy of multiple low-dose photodynamic TMPYP4 therapy on cervical cancer tumour growth in nude mice. AB - OBJECTIVE: Photodynamic therapy (PDT) is an emerging therapeutic procedure suitable for the treatment of cervical cancer. However, the side effects of PDT are severe, including skin ulceration, so we designed an experiment to examine the effects of multiple low- dose photodynamic therapy of 5, 10, 15, 20 tetrakis(1- methylpyridinium-4-yl) porphyrin (Tmpyp4) on tumour growth by utilizing a model in nude mice implanted with Hela cervical cancer cells. MATERIALS AND METHODS: Female BALB/c nude mice (aged 5-6 weeks, weighing 18-20 g) were used. Hela cervical cancer cells were injected subcutaneously (1 x 10(7) cells/200 MUL). Ten days after injection, the mice were divided into three groups (n=6), the A group of controls without any treatment, the B group receiving a single-treatment with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation (blue laser, 108 J/cm(2)), and the C group given three-treatments with Tmpyp4 (10 mg/ kg, intratumor injection) and irradiation at intervals of two days. After starting treatment, tumours were measured every two days, to assess growth. At 2 weeks after the last treatment of C group, tumour tissue and organs were collected from each mouse to evaluate tumor histology and organ damage. RESULTS: Tumour growth in C group was significantly inhibited compared with A and B groups (P <0.05), without any injury to the skin and internal organs. CONCLUSION: Our novel findings demonstrated that multiple low-dose photodynamic therapy of Tmpyp4 could inhibit cervical cancer growth significantly with no apparent side effects. PMID- 24175829 TI - Surgical outcomes of patients with stage IA2 cervical cancer treated with radical hysterectomy. AB - BACKGROUND: This study was undertaken to evaluate the surgical outcomes of patients with stage IA2 cervical cancer treated with radical hysterectomy. Data for 58 patients who underwent modified radical hysterectomy or radical hysterectomy with pelvic lymphadenectomy between January 2003 and December 2012 at Chiang Mai University Hospital were retrospectively reviewed. The analysis included clinico-pathological risk factors (nodal metastasis, parametrial involvement), adjuvant treatment, 5-year disease-free survival and 5-year overall survival. All pathologic slides were reviewed by a gynecologic pathologist. Follow-up methods included at least cervical cytology and colposcopy with directed biopsy if indicated. Univariate analysis was performed to identify factors associated with median survival. At the median follow up time of 73 months, the 5-year disease-free survival and the 5-year overall survival were 97.4% and 97.4%, respectively. Two (3.4%) patients had pelvic lymph node metastases. In a univariate analysis, there was no statistically significant association between survival and prognostic factors such as age, histological cell type, lymph-vascular space invasion, vaginal margin status and lymph node status. Surgical and survival outcomes of women with stage IA2 cervical cancer are excellent. No parametrial involvement was detected in our study. Patients with stage IA2 cervical cancer may be treated with simple or less radical hysterectomy with pelvic lymphadenectomy. PMID- 24175830 TI - Stimulation of osteogenic differentiation in stromal cells of giant cell tumour of bone by zoledronic acid. AB - Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations (0 MUM, 0.01 MUM, 0.1 MUM, 1 MUM, 5 MUM, 30 MUM) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1 MUM in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery. PMID- 24175831 TI - Concurrent chemoradiation with weekly gemcitabine and cisplatin for locally advanced cervical cancer. AB - BACKGROUND: For more than 80 years, the standard treatment of locally advanced cervical cancer was radiotherapy. However, based on several phase III randomized clinical trials in the past decade, concurrent cisplatin-based chemoradiotherapy is the current standard for this disease. Gemcitabine has potent radiosensitizing properties in preclinical and clinical trials, so it can be utilized simultaneously with radiation. MATERIALS AND METHODS: Thirty women with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study in the Radiation Oncology Department of Imam Khomeini Hospital in Tehran from September 2009 to September 2010. Sixty mg/m2 gemcitabine followed by 35 mg/m(2) cisplatin were concurrently administered with radiotherapy to the whole pelvic region on day one of each treatment week for five weeks. One and three months after treatment, patients underwent a complete physical examination and MRI to determine the response to treatment. RESULTS: The mean age of patients was 58.1 +/- 11.8 (29-78) years. After 3 months of treatment, 73.3%had complete and 26.7% demonstrated partial response to treatment. Grade 3 anemia was seen in 10%, grade 3 thrombocytopenia in 3.3% and grade 3 leukopenia in 10% of the patients. CONCLUSIONS: According to the positive results of this study in stage IIB, further phase II and III clinical trials are suggested to evaluate the role of chemoradiation using Gemcitabine for advanced cervical cancers. PMID- 24175832 TI - Lentivirus mediated GOLPH3 shRNA inhibits growth and metastasis of esophageal squamous cancer. AB - AIM: To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer. METHODS: A lentiviral shRNA-vector was utilized to stably knockdown GOLPH3 in Eca-109 esophageal squamous cancer cells. mRNA transcription and protein expression of GOLPH3 were examined by real time quantitative PCR and Western blotting, respectively. Cell proliferation activity was assessed by MTT assay and invasion and migration potentials by matrigel invasion and transwell motility assays. RESULTS: Stable knockdown in the GOLPH3 cell line was established. PD-A gene expression was significantly suppressed by lentivirus-mediated RNAi, which resulted in reducing the capacity for cell proliferation, migration, invasion and adhesion in vitro. In vivo, GOLPH3 depletion resulted in inhibition of tumour growth, with stable decrease in the expression of GOLPH3 in tumor xenografts. CONCLUSIONS: Our findings suggest that lentivirus mediated silencing of the GOLPH3 gene has a significant anti tumour effect on esophageal squamous cancer in vitro and in vivo. In addition, the results indicate that GOLPH3 might be an effective molecular target for gene therapy in esophageal squamous cancer. PMID- 24175833 TI - Anti-metastatic potential of ethanol extract of Saussurea involucrata against hepatic cancer in vitro. AB - The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with 200 400 MUg/mL of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1 MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent. PMID- 24175834 TI - CXCL12-CXCR4 promotes proliferation and invasion of pancreatic cancer cells. AB - OBJECTIVE: CXCL12 exerts a wide variety of chemotactic effects on cells. Evidence indicates that CXCL12, in conjunction with its receptor, CXCR4, promotes invasion and metastasis of tumor cells. Our objective was to explore whether the CXCL12 CXCR4 biological axis might influence biological behavior of pancreatic cancer cells. METHODS: Miapaca-2 human pancreatic cancer cells were cultured under three different conditions: normal medium (control), medium + recombinant CXCL12 (CXCL12 group), or medium + CXCR4-inhibitor AMD3100 (AMD3100 group). RT-PCR was applied to detect mRNA expression levels of CXCL12, CXCR4, matrix metalloproteinase 2 (MMP-2), MMP-9, and human urokinase plasminogen activator (uPA). Additionally, cell proliferation and invasion were performed using CCK-8 colorimetry and transwell invasion assays, respectively. RESULTS: CXCL12 was not expressed in Miapaca-2 cells, but CXCR4 was detected, indicating that these cells are capable of receiving signals from CXCL12. Expression of extracellular matrix degrading enzymes MMP-2, MMP- 9, and uPA was upregulated in cells exposed to exogenous CXCL12 (P<0.05). Additionally, both proliferation and invasion of pancreatic cancer cells were enhanced in the presence of exogenous CXCL12, but AMD3100 intervention effectively inhibited these processes (P<0.05). CONCLUSIONS: The CXCL12-CXCR4 biological axis plays an important role in promoting proliferation and invasion of pancreatic cancer cells. PMID- 24175835 TI - Sonographic pattern recognition of endometriomas mimicking ovarian cancer. AB - BACKGROUND: To assess the accuracy of ultrasound in differentiating endometrioma from ovarian cancer and to describe pattern recognition for atypical endometriomas mimicking ovarian cancers. MATERIALS AND METHODS: Patients scheduled for elective surgery for adnexal masses were sonographically evaluated for endometrioma within 24 hours of surgery. All examinations were performed by the same experienced sonographer, who had no any information of the patients, to differentiate between endometriomas and non-endometriomas using a simple rule (classic ground-glass appearance) and subjective impression (pattern recognition). The final diagnosis as a gold standard relied on either pathological or post-operative findings. RESULTS: Of 638 patients available for analysis, 146 were proven to be endometriomas. Of them, the simple rule and subjective impression could sonographically detect endometriomas with sensitivities of 64.4% (94/146) and 89.7% (131/146), respectively. Of 52 endometriomas with false negative tests by the simple rule, 13 were predicted as benign masses and 39 were mistaken for malignancy. Solid masses and papillary projections were the most common forms mimicking ovarian cancer, consisting of 38.5% of the missed diagnoses. However, with pattern recognition (subjective impression), 32 from 39 cases mimicking ovarian cancer were correctly predicted for endometriomas. All endometriomas subjectively predicted for ovarian malignancy were associated with high vascularization in the solid masses. CONCLUSIONS: Pattern recognition of endometriomas by subjective assessment had a higher sensitivity than the simple rule in characterization of endometriomas. Most endometriomas mimicking ovarian malignancy could be correctly predicted by subjective impression based on familiarity of pattern recognition. PMID- 24175836 TI - P53 Arg72Pro and MDM2 SNP309 polymorphisms cooperate to increase lung adenocarcinoma risk in Chinese female non-smokers: a case control study. AB - BACKGROUND: Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressor gene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a key regulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancers including lung cancer. METHODS: We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female non- smokers. Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotyping assay. RESULTS: The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17-2.06) significantly correlated with an increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also noted for MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27-2.21) compared with the TT genotype. Combined p53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54-4.60) had a supermultiplicative interaction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, and passive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53 or MDM2 mutant alleles. CONCLUSIONS: P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers. PMID- 24175837 TI - Antioxidant effects of gamma-oryzanol on human prostate cancer cells. AB - BACKGROUND: To assess the antioxidant effects of gamma-oryzanol on human prostate cancer cells. MATERIALS AND METHODS: Cytotoxic activity of gamma-oryzanol on human DU145 and PC3 prostate cancer cells was determined by proliferation assay using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reagent. mRNA levels of genes involved in the intracellular antioxidant system, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GSR) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Cancer cell lysates were used to measure lipid peroxidation using thiobarbituric acid reactive substance (TBARS). Glutathione contents of the cell lysates were estimated by the reaction between sulfhydryl group of 5, 5'-dithio (bis) nitrobenzoic acid (DTNB) to produce a yellow- color of 5-thio-2-nitrobenzoic acid using colorimetric assay. Catalase activity was also analysed by examining peroxidative function. Protein concentration was estimated by Bradford's assay. RESULTS: All concentrations of gamma-oryzanol, 0.1 2.0mg/ml, significantly inhibited cell growth in a dose- and time-dependent fashion in both prostate cancer cell lines, DU145 and PC3. Gene expression of catalase in DU145 and PC3 exposed to gamma-orizanol at 0.5mg/ml for 14 days was down regulated, while mRNA of GPX was also down regulated in PC3. The MDA and glutathione levels including catalase activity in the cell lysates of DU145 and PC3 treated with gamma-oryzanol 0.1 and 0.5mg/ml were generally decreased. CONCLUSIONS: This study highlighted effects of gamma-oryzanol via the down regulation of antioxidant genes, catalase and GPX, not cytotoxic roles. This might be interesting for adjuvant chemotherapy to make prostate cancer cells more sensitive to free radicals. It might be useful for the reduction of cytotoxic agents and cancer chemoprevention. PMID- 24175838 TI - Alteration of runt-related transcription factor 3 gene expression and biologic behavior of esophageal carcinoma TE-1 cells after 5-azacytidine intervention. AB - 5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at 50 MUM had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5 azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5 azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells. PMID- 24175839 TI - Retrospective appraisal of cancer patients from Vientiane Capital City, Lao People's Democratic Republic (PDR), seeking treatment in Thailand. AB - BACKGROUND: Recent estimates suggest that in the Lao People's Democratic Republic (Lao PDR) the burden of cancer in terms of DALYs lost is amongst the highest in South East Asia. As such, increasingly cancer is becoming an important public health concern in the country. Lao PDR however has no population-based cancer registry and only one hospital-based registry. Cancer treatment within the country is extremely limited. Patients who can, may travel to neighboring countries for treatment, but little information about this is available in the country. The aim of this study was to estimate some of the otherwise largely unknown parameters of the cancer burden in Lao PDR. MATERIALS AND METHODS: This is a retrospective, descriptive study based on the records of 847 Lao cancer cases treated with surgery, radiation and chemotherapy at Srinagarind Hospital, Khon Kaen University, in Thailand between 1988 and 2010. RESULTS: The annual rate of registration of Lao cancer cases fluctuated, but showed an increasing trend. Most cancers were diagnosed by histology (65.2%), and a combination of endoscopy and radiology (15.6%). In most cases (70.2%) the stage of cancer at diagnosis could not be determined. In those whose stage could be identified, 54.0% were at the final stage (Stage IV). Among males, the commonest cancer sites were the liver (16.1%), blood (12.3%) and nasopharynx (10.6%). Those in female patients were the cervix (22.2%), breast (14.6%) and blood (8.1%). CONCLUSIONS: This study indicates that despite some fluctuations, the number of Lao cancer patients presenting at Srinagarind Hospital, Khon Kaen, gradually increased between 1988 and 2010. The unfavorable pattern of late-stage cancer diagnosis among male and female patients suggests a need for cancer control interventions and the establishment of cancer registration and treatment facilities within Lao PDR. PMID- 24175840 TI - Acidic pelvic drainage as a predictive factor for anastomotic leakage after surgery for patients with rectal cancer. AB - PURPOSE: To demonstrate the value of sequential determinations of pelvic drainage in the identification of increased risk of anastomotic leakage (AL) after anterior resection for rectal cancer with a double stapling technique. PATIENTS AND METHODS: Between January 2004 and December 2011, data for the daily postoperative pH of pelvic drainage fluid in 753 consecutive patients with rectal cancer who initially underwent anterior resection with a double stapling technique were reviewed. All patients experienced a total mesorectal excision. Patients with anastomotic leakage (Group AL, n=57) were compared to patients without leakage (Group nAL, n=696). Patients with perioperatively abdominopelvic implants that were likely to affect pH value (determined at 25 degrees ) other than leakage were excluded. Mean postoperative values were compared. RESULTS: Anastomotic leakage was noted in 57 (7.6%) of 753 patients with rectal cancer. The diagnosis of anastomotic leakage was made between the 6th and 12th postoperative day (POD; mean 8th POD). There was no significance of the daily average values of pH on POD1 and 2 in group AL while a significantly sharp declining mean pH value reached its diagnostic point of AL (p<0.001) on POD3. A cut-off value of 6.978 on the 3rd POD maximized the sensitivity (98.7.0%) and specificity (94.7%) in assessing the risk of leakage. CONCLUSION: According to these results, an early and persistent declining of pH value of pelvic drainage fluid after rectal surgery with anastomosis, is a marker of AL. A cut-off value of 6.798 on POD3 maximizes sensitivity and specificity. PMID- 24175841 TI - Should cut-off values of the risk of malignancy index be changed for evaluation of adnexal masses in Asian and Pacific populations? AB - BACKGROUND: The risk of malignancy index (RMI) for the evaluation of adnexal masses is a sensitive tool in certain populations. The best cut off value for RMI 1, 2 and 3 is 200. The cut off value of RMI-4 to differentiate benign from malignant lesions is 450. Our aim was to evaluate the efficiency of four different malignancy indexes (RMI1-4) in a homogeneous population. MATERIALS AND METHODS: We evaluated a total of 153 non-pregnant women with adnexal masses who did not have a history of malignancy and who were above 18 years of age. RESULTS: A cut-off value of 250 for RMI-1 provided 95.9% inter-observer agreement, yielding 95.9% specificity, 93.5% negative predictive value, 75.0% sensitivity and 82.8% positive predictive value. A cut-off value of 250 for RMI-1 showed high performance in preoperative diagnosis of invasive malignant lesions than cut-off value of 200 in our population. A cut-off value of 350 for RMI-2 provided 94.5% inter-observed agreement, yielding 94.2% specificity, 93.4% negative predictive value, 75.0% sensitivity and 77.4% positive predictive value. RMI-2 showed the higher performance when the cut-off value was set at 350 in our population. A cut off value of 250 provided 95.2% inter-observer agreement, yielding 95.0% specificity, 93.2% negative predictive value, 75.0% sensitivity, and 88.0% positive predictive value. RMI-3 showed the highest performance to diagnose malignant adnexal masses when the cut-off value was set at 250. In our study, RMI 4 showed similar statistical performance when the cut-off value was set at 400 [(Kappa: 0.684/p=0.000), yielding 93.8% inter-observer agreement, 93.4% specificity, 93.4% negative predictive value, 75.0% sensitivity, and 75.0% negative predictive value]. CONCLUSIONS: We showed successful utilization of RMIs in preoperative differentiation of benign from malignant masses. Many studies conducted in Asian and Pacific countries have reported different cut-off values as was the case in our study. We think that it is difficult to determine universally accepted cut-off values for RMIs for common use around the globe. PMID- 24175842 TI - Menadione (Vitamin K3) induces apoptosis of human oral cancer cells and reduces their metastatic potential by modulating the expression of epithelial to mesenchymal transition markers and inhibiting migration. AB - Oral cancer is one of the most commonly occurring cancers worldwide, decreasing the patient's survival rate due to tumor recurrence and metastasis. Menadione (Vitamin K3) is known to exhibit cytotoxicity in various cancer cells but the present study focused on its effects on viability, apoptosis, epithelial to mesenchymal transition (EMT), anchorage independent growth and migration of oral cancer cells. The results show that menadione is more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaT cells. Menadione treatment increased the expression of pro-apoptotic proteins, Bax and p53, with a concurrent decrease in anti-apoptotic proteins, Bcl-2 and p65. Menadione induced the expression of E-cadherin but reduced the expression of EMT markers, vimentin and fibronectin. Menadione also inhibited anchorage independent growth and migration in SAS cells. These findings reveal and confirm that menadione is a potential candidate in oral cancer therapy as it exhibits cytotoxic, antineoplastic and antimigratory effects besides effectively blocking EMT in oral cancer cells. PMID- 24175843 TI - Impact of Co-transfection with Livin and survivin shRNA expression vectors on biological behavior of HepG2 cells. AB - OBJECTIVE: To construct short hairpin RNA (shRNA) eukaryotic expression vectors targeting Livin and Survivin genes, and to explore the impact of co-transfection of Livin and Survivin shRNA expression vectors on the biological behavior of HepG2 cells. METHODS: shRNA eukaryotic expression vectors pSD11-Livin and pSD11- Survivin were designed and constructed then transfected into HepG2 cells separately or in combination. mRNA and protein expression in transfected cells was assessed by quantitative fluorescence PCR and Western blotting, respectively. Cell proliferation was measured by MTT assay and cell apoptosis by TUNEL assay. RESULTS: The Livin and Survivin shRNA eukaryotic expression vectors were successfully constructed and transfected into HepG2 cells. The relative mRNA expression levels of Livin and Survivin in HepG2 cells co-transfected with pSD11 Livin and pSD11-Survivin were 0.12 +/- 0.02 and 0.33 +/- 0.13, respectively, which was significantly lower than levels in cells transfected with either pSD11 Livin or pSD11-Survivin (P<0.05). The relative protein expression levels of Livin and Survivin in the co-transfected cells were also significantly decreased compared to single- transfection (P<0.05). The inhibition rate of cell growth in the co-transfection group was higher than that in the single-transfection groups at 48 h, 60 h, or 72 h after transfection (P<0.01). The apoptotic rate increased to the greatest extent in the co-transfection group relative to any other group (P<0.05). CONCLUSIONS: Co-transfection with pSD11-Livin and pSD11-Survivin was more efficient than transfection with either vector alone in reducing the mRNA and protein expression of Livin and Survivin genes in HepG2 cells. Co transfection also inhibited the proliferation of transfected cells more than the other groups, and induced cellular apoptosis more effectively. PMID- 24175844 TI - Prognostic significance of basic laboratory methods in non- small-cell-lung cancer. AB - BACKGROUND: In our study, the LDH, albumin, hemoglobin, neutrophile, thrombocyte, lymphocyte counts and prognostic significance of neutrophile-lymphocyte and thrombocyte-lymphocyte ratios in NSCLC derived from these counts obtained during regular examinations of patients were examined. MATERIALS AND METHODS: Histopathologically diagnosed non-small-cell-lung cancer patients between 2008 and 2010 were included in the study. Before the treatment, full blood count including routine lymphocyte count, blood biochemistry examinations including liver (AST, ALT, total protein, Albumin), LDH and kidney (BUN, Cre) function tests were performed. RESULTS: A total of 156 patients, 76 of whom (48.7%) were female and 80 of whom (51.3%) were male were included. Mean hemoglobin level was determined as 12. Overall survival was found to be significantly dependent on whether patients were anemic or not (p: 0.005). Mean LDH level was determined as 233.4. There was nosurvival difference between patients with and without high LDH (p: 0.532). In patients where NLR showed systemic inflammatory response, overall survival was 10.8 months whereas this duration was 19.6 months in patients where the systemic inflammatory response was negative (p: 0.012). In patients where TLR showed systemic inflammatory response, overall survival was 13.6 months whereas this duration was 21.9 months in patients where the systemic inflammatory response was negative (p: 0.04). CONCLUSIONS: Molecular methods have been changing rapidly in today's world and they manage the treatment besides defining the prognosis of patients. However, easily accessible and cheap laboratory parameters should be considered in the prognosis of patients besides these new methods. PMID- 24175845 TI - Exploring communication difficulties in pediatric hematology: oncology nurses. AB - BACKGROUND: Communication plays an important role for the well being of patients, families and also health care professionals in cancer care. Conversely, ineffective communication may cause depression, increased anxiety, hopelessness and decreased of quality life for patients, families and also nurses. OBJECTIVE: This study aimed to explore communication difficulties of pediatric hematology/oncology nurses with patients and their families, as well as their suggestions about communication difficulties. MATERIALS AND METHODS: It was conducted in a pediatric hematology/oncology hospital in Ankara, Turkey. Qualitative data were collected by focus groups, with 21 pediatric hematology/oncology nursing staff from three groups. Content analysis was used for data analysis. RESULTS: Findings were grouped in three main categories. The first category concerned communication difficulties, assessing problems in responding to questions, ineffective communication and conflicts with the patient's families. The second was about the effects of communication difficulties on nurses and the last main category involved suggestions for empowering nurses with communication difficulties, the theme being related to institutional issues. CONCLUSIONS: Nurses experience communication difficulties with children and their families during long hospital stays. Communication difficulties particularly increase during crisis periods, like at the time of first diagnosis, relapse, the terminal stage or on days with special meaning such as holidays. The results obtained indicate that pediatric nurses and the child/family need to be supported, especially during crisis periods. Feeling of empowerment in communication will improve the quality of care by reducing the feelings of exhaustion and incompetence in nurses. PMID- 24175846 TI - Associations between XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms and risk of differentiated thyroid carcinoma: a meta-analysis. AB - BACKGROUND: Associations between Arg399Gln, Arg194Trp and Arg280His polymorphisms of the XRCC1 gene and risk of differentiated thyroid carcinoma (DTC) have been widely studied but the findings are contradictory. METHODS: We performed a meta analysis in the present study using STATA 11.0 software to clarify any associations. Electronic literature databases and reference lists of relevant articles revealed a total of 10, 6 and 6 published studies for the Arg399Gln, Arg194Trp and Arg280His polymorphisms, respectively. RESULTS: No significant associations were observed between Arg399Gln and DTC risk in all genetic models within the overall and subgroup meta-analyses, while the Trp/Trp vs Arg/Arg and recessive model of the Arg194Trp polymorphism was associated with DTC susceptibility, and the dominant model of Arg280His polymorphism contributed to DTC susceptibility in Caucasians. CONCLUSIONS: Our meta-analysis suggests that XRCC1 Arg194Trp may be a risk factor for DTC development. PMID- 24175847 TI - Prevelance of common YMDD motif mutations in long term treated chronic HBV infections in a Turkish population. AB - In the current study we aimed to show the common YMDD motif mutations in viral polymerase gene in chronic hepatitis B patients during lamivudine and adefovir therapy. Forty-one serum samples obtained from chronic hepatitis B patients (24 male, 17 female; age range: 34-68 years) were included in the study. HBV-DNA was extracted from the peripheral blood of the patients using an extraction kit (Invisorb, Instant Spin DNA/ RNA Virus Mini Kit, Germany). A line probe assay and direct sequencing analyses (INNO-LIPA HBV DR v2; INNOGENETICS N.V, Ghent, Belgium) were applied to determine target mutations of the viral polymerase gene in positive HBV-DNA samples. A total of 41 mutations located in 21 different codons were detected in the current results. In 17 (41.5%) patients various point mutations were detected leading to lamivudin, adefovir and/ or combined drug resistance. Wild polymerase gene profiles were detected in 24 (58.5%) HBV positive patients of the current cohort. Eight of the 17 samples (19.5%) having rtM204V/I/A missense transition and/or transversion point mutations and resistance to lamivudin. Six of the the mutated samples (14.6%) having rtL180M missense transversion mutation and resistance to combined adefovir and lamivudin. Three of the mutated samples (7.5%) having rtG215H by the double base substituation and resistance to adefovir. Three of the mutated samples (7.5%) having codon rtL181W due to the missense transversion point mutations and showed resistance to combined adefovir and lamivudin. Unreported novel point mutations were detected in the different codons of polymerase gene region in the current HBV positive cohort fromTurkish population. The current results provide evidence that rtL180M and rtM204V/I/A mutations of HBV-DNA may be associated with a poor antiviral response and HBV chronicity during conventional therapy in Turkish patients. PMID- 24175848 TI - Alu hypomethylation in smoke-exposed epithelia and oral squamous carcinoma. AB - BACKGROUND: Alu elements are one of the most common repetitive sequences that now constitute more than 10% of the human genome and potential targets for epigenetic alterations. Correspondingly, methylation of these elements can result in a genome-wide event that may have an impact in cancer. However, studies investigating the genome-wide status of Alu methylation in cancer remain limited. OBJECTIVES: Oral squamous cell carcinoma (OSCC) presents with high incidence in South-East Asia and thus the aim of this study was to evaluate the Alu methylation status in OSCCs and explore with the possibility of using this information for diagnostic screening. We evaluated Alu methylation status in a) normal oral mucosa compared to OSCC; b) peripheral blood mononuclear cells (PBMCs) of normal controls comparing to oral cancer patients; c) among oral epithelium of normal controls, smokers and oral cancer patients. MATERIALS AND METHODS: Alu methylation was detected by combined bisulfite restriction analysis (COBRA) at 2 CpG sites. The amplified products were classified into three patterns; hypermethylation ((m)C(m)C), partial methylation (uC(m)C+(m)C(u)C), and hypomethylation ((u)C(u)C). RESULTS: The results demonstrate that the %(m)C(m)C value is suitable for differentiating normal and cancer in oral tissues (p=0.0002), but is not significantly observe in PBMCs. In addition, a stepwise decrease in this value was observed in the oral epithelium from normal, light smoker, heavy smoker, low stage and high stage OSCC (p=0.0003). Furthermore, receiver operating characteristic (ROC) curve analyses demonstrated the potential of combined %mC or %(m)C(m)C values as markers for oral cancer detection with sensitivity and specificity of 86.7% and 56.7%, respectively. CONCLUSIONS: Alu hypomethylation is likely to be associated with multistep oral carcinogenesis, and might be developed as a screening tool for oral cancer detection. PMID- 24175849 TI - Relationship between the body mass index and abnormal pap smears. AB - This cross-sectional analytic study aimed to investigate any relationship between the body mass index (BMI) and an abnormal Pap smear. The subjects were 7,720 women aged 30-69 years who lived in Khon Kaen Province, Thailand, and had been recruited as participants in the Khon Kaen Cohort Study during 1990-2001. All had received Pap smear screening for cervical cancer. The data were analyzed using descriptive and inferential statistics. Multiple logistic regression was used to determine the relationship between body mass index and an abnormal Pap smear. The mean BMI was 24.53 kg/m(2) (SD =3.98), and 2.14% had abnormal Pap smears. Compared with the reference group of women with a BMI <= 22.9 kg/m(2), those with a body mass index of 23.0- 24.9 kg/m(2) had a reduced risk of an abnormal smear (OR(adj) = 0.92, 95%CI: 0.57-1.47), but women with a BMI 25.0-29.9 kg/m(2) were found to have an approximately 1.24 times higher risk (OR(adj) = 1.24, 95%CI: 0.86-1.80), and those with a BMI >= 30.0 kg/m2 had an approximately 1.63 times higher risk (OR(adj)=1.63, 95%CI: 0.98-2.69). The results indicated that the risk of Pap smear abnormalities is increased in women who have a higher than normal body mass index, but this finding was not statistically significant. Nevertheless, public health personnel should encourage women to maintain their BMI in the normal range to reduce the possible future risk of cervical cancer. PMID- 24175850 TI - DNA repair capacity in peripheral blood lymphocytes predicts efficacy of platinum based chemotherapy in patients with gastric cancer. AB - OBJECTIVE: To investigate the correlation between ERCC1 expression levels in tumor tissue and peripheral blood lymphocytes (PBL) from patients with gastric cancer and assess the relationship between PBL DNA repair rate (DRR) and the efficacy of platinum chemotherapy. METHODS: A total of 53 patients with gastric cancer receiving surgery and 20 controls were studied. ERCC1 protein expression in tumour tissue and PBL were determined by immunohistochemical staining. The PBL DRRs of 47 advanced patients and 20 controls were estimated by comet assay. RESULTS: The positive expression rates of ERCC1 were 67. 9%, 56. 6% and 10.0% in tumour tissues, PBLs of gastric cancer patients, and PBLs of the control group. PBL ERCC1 expression correlated with that in tissue (chi(2) = 15. 463, p=0.000). Pearson contingency coefficient=0.475). DRRs of cancer patients by tail length (TL) (Z=4. 662, p=0.000) and tail moment (TM) (Z=3. 827, p=0.000) were significantly lower than that of control group. When TL was applied as an indicator, the correlation between DRR and chemotherapy efficacy was significant (Spearman rank correlation r=0.327, p=0.032). Patients with low levels of DRR in PBL presented better short-term efficacy of chemotherapy than those with high levels of DRR. CONCLUSIONS: The ERCC1 expression in PBLs may indirectly reflect ERCC1 expression in gastric cancer tissues. Compared with non-cancer populations, patients with gastric cancer may have lower DNA repair capacity. DRR in PBL may predict the short-term efficacy of platinum-based chemotherapy for patients with advanced gastric cancer. PMID- 24175851 TI - Anti-proliferation effects of interferon-gamma on gastric cancer cells. AB - IFN-gamma plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-gamma and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-gamma on apoptosis of cell lines and no effect on cell aging as assessed by beta-gal staining. Microarray assay revealed that IFN-gamma changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-gamma arrested the cells in the G1/S phase. IFN-gamma may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer. PMID- 24175852 TI - Detection of human papillomavirus in male and female urine by electrochemical DNA chip and PCR sequencing. AB - BACKGROUND: Cervical cancer is the second most common cancer in Thai women after breast cancer. Currently, the Papanicolaou (Pap) smear is the recommended procedure for cervical cancer screening in Thailand, but only a relatively small percentage of women follow this screening program. An alternative method to detect HPV genotypes associated with cervical cancer is self-sampling of urine, which is a more widely accepted method. Our study aimed to evaluate the prevalence of HPV in Thai women using urine and cervical swabs and prevalence of HPV in Thai men using urine samples. MATERIALS AND METHODS: Tumorigenic HPV detection was accomplished by electrochemical DNA chip and PCR/direct sequencing. In addition to HPV prevalence, we report the concordance between different methods and sample types. One-hundred and sixteen women and 100 men were recruited. Histological examination revealed normal cytology in 52 women, atypical squamous cells of undetermined significance (ASCUS) in 9, low-grade squamous intraepithelial lesions (LSIL) in 24, and high-grade squamous intraepithelial lesions (HSIL) in 31. One-hundred men were classified as heterosexuals (n=45) and homosexuals (n=55). RESULTS: The most prevalent HPV genotype in our study was HPV16. The HPV detection rate was generally lower in urine samples compared with cervical samples. Overall, there was good agreement for the detection of carcinogenic HPV from female cervical samples between the DNA chip and PCR/ sequencing, with 88.8% total agreement and a kappa value of 0.76. In male urine samples, the level of agreement was higher in heterosexuals compared with homosexuals. CONCLUSIONS: Further improvement is required to increase an overall yield of HPV DNA detection in urine samples before clinical application of a urine-based HPV screening program. The electrochemical DNA chip test is a promising technique for carcinogenic HPV detection. PMID- 24175853 TI - The blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced hepatocellular carcinoma receiving sorafenib. AB - BACKGROUND AND AIM: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy. METHODS: A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed. RESULTS: Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (<= 4) (P = 0.01). Age <= 65, NLR >4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). CONCLUSIONS: High baseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib. PMID- 24175854 TI - miR-10b promotes migration and invasion in nasopharyngeal carcinoma cells. AB - MicroRNA-10b (miR-10b) has been reported to play an important role in some types of cancer, but the effects and possible mechanisms of action of miR-10b in the metastasis of nasopharyngeal carcinoma cells (NPC) have not been explored. The aim of the present study was to investigate the function of miR-10b in nasopharyngeal carcinoma and to determine the molecular mechanisms underlying its action. The MTT assay was used to assess proliferation of CNE-2Z cells. Wound healing and transwell migration assays were applied to assess cell migration and invasion, while and expression of E-cadherin and MMP-9 were detected using Western blot analysis. Real-time PCR was employed to detect the expression of genes related to migration and invasion and the 2-??Ct method was used to calculate the degree of expression. MTT assay showed the expression of miR-10b to have no effect on the proliferation of NPC cell lines. The wound healing assay showed that miR-10b mimics promoted the mobility and invasion of NPC cell lines. Inhibitors of miR-10b reduced the ability of NPC cell lines to migrate and invade. In addition, the expression of genes related to migration and invasion, such as E-cadherin, vimentin, and MMP-9, were confirmed to be different in the CNE-2Z NPC cell line transfected with miR-10b mimics and with miR-10b inhibitors. In the present study, miR-10b was found to upregulate the expression of MMP-9 and knockdown of miR-10b was found to significantly downregulate the expression of E cadherin. On the whole, these results showed that miR-10b plays an important role in the invasion and metastasis of NPC cells. PMID- 24175855 TI - View point: How to make women familiar with their breasts? AB - There is a consensus among researchers about the fact that women should be familiar with their breasts but there is a lot of argument as to how to make them aware of what is normal for them. For over decades breast self examination (BSE) was advocated for the same but as an outcome of work conducted by researchers in various countires a controversy has been raised in the West. In a country like India, where breast cancer screening is not popular and limited resources are available we should question what would be the best strategy to make women familiar with their breasts to facilitate best use of BSE. PMID- 24175856 TI - Plasma IL-17, IL-35, interferon-gamma, SOCS3 and TGF-beta levels in pregnant women with preeclampsia, and their relation with severity of disease. AB - Abstract Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants. METHODS: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version. RESULTS: While IFN-gamma and TGF beta levels of preeclamptic women were significantly higher (p < 0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p < 0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age. CONCLUSIONS: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE. PMID- 24175857 TI - Monoterpene phenolic compound thymol prevents high fat diet induced obesity in murine model. AB - CONTEXT: Obesity has become a worldwide health problem. Most of the synthetic anti-obesity drugs have failed to manage the obesity due to either ineffectiveness or adverse effect. The research of prominent chemical constituents from herbal for the management of obesity has greatly increased. OBJECTIVE: The main objective of the present study was intended to examine the effects of thymol in high-fat diet (HFD)-induced obesity in murine model. METHODS: Male Wistar rats were fed HFD for 6 weeks to induce obesity. Thymol (14 mg/kg) administered orally twice a day to HFD-fed rats for 4 weeks. Alteration in body weight gain, visceral fat-pads weight and serum biochemical markers were assessed. RESULTS: At the end of study, rats fed with HFD exhibited significantly (p < 0.001) enhanced body weight gain, visceral pad weight, lipids, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), glucose, insulin and leptin levels compared with rats fed with normal diets. Thymol treatment showed significantly (p < 0.001) decreased body weight gain, visceral fat-pad weights, lipids, ALT, AST, LDH, BUN, glucose, insulin, and leptin levels in HFD-induced obese rats. Furthermore, thymol treatment showed significantly decreased serum lipid peroxidation and increased antioxidant levels in HFD-induced obese rats. DISCUSSION AND CONCLUSIONS: Thymol prevents HFD-induced obesity in murine model through several mechanisms including attenuation of visceral fat accumulation, lipid lowering action, improvement of insulin and leptin sensitivity and enhanced antioxidant potential. PMID- 24175858 TI - Mixed close-packed cobalt molybdenum nitrides as non-noble metal electrocatalysts for the hydrogen evolution reaction. AB - A two-step solid-state reaction for preparing cobalt molybdenum nitride with a nanoscale morphology has been used to produce a highly active and stable electrocatalyst for the hydrogen evolution reaction (HER) under acidic conditions that achieves an iR-corrected current density of 10 mA cm(-2) at -0.20 V vs RHE at low catalyst loadings of 0.24 mg/cm(2) in rotating disk experiments under a H2 atmosphere. Neutron powder diffraction and pair distribution function (PDF) studies have been used to overcome the insensitivity of X-ray diffraction data to different transition-metal nitride structural polytypes and show that this cobalt molybdenum nitride crystallizes in space group P63/mmc with lattice parameters of a = 2.85176(2) A and c = 10.9862(3) A and a formula of Co0.6Mo1.4N2. This space group results from the four-layered stacking sequence of a mixed close-packed structure with alternating layers of transition metals in octahedral and trigonal prismatic coordination and is a structure type for which HER activity has not previously been reported. Based on the accurate bond distances obtained from time of-flight neutron diffraction data, it is determined that the octahedral sites contain a mixture of divalent Co and trivalent Mo, while the trigonal prismatic sites contain Mo in a higher oxidation state. X-ray photoelectron spectroscopy (XPS) studies confirm that at the sample surface nitrogen is present and N-H moieties are abundant. PMID- 24175859 TI - Synthesis and isolation of methacrylate- and acrylate-functionalized polyhedral oligomeric silsesquioxanes (T8, T10, and T12) and characterization of the relationship between their chemical structures and physical properties. AB - Novel organic-inorganic hybrid nanobuilding blocks of methacrylate- and acrylate functionalized polyhedral oligomeric silsesquioxanes were easily prepared via nucleophilic substitution on octakis(3-chloropropyl)octasilsesquioxane, using sodium methacrylate and sodium acrylate, respectively. From a practical standpoint, these cage-rearranged silsesquioxanes (T8, T10, and T12) could be readily isolated in their pure form with conventional silica gel column chromatography. Octakis(3-propyl methacrylate)octasilsesquioxane (T8) is a colorless, crystalline solid with a melting point of 66.7-67.2 degrees C, while other cage products are colorless viscous liquids at room temperature. Moreover, we report that the chemical structure/physical property relationship of silsesquioxane cages not only is dependent on the symmetry of the inorganic silsesquioxane core at a given temperature but also is dictated by the organic substituent mobility. Structures of the products were confirmed by (1)H, (13)C, and (29)Si NMR spectroscopy and high resolution electrospray ionization mass spectrometry analysis. PMID- 24175860 TI - Biocompatibility and efficacy of oligomaltose-grafted poly(ethylene imine)s (OM PEIs) for in vivo gene delivery. AB - Polycationic polymers like poly(ethylene imine)s (PEIs) are extensively explored for the nonviral transfer of DNA or small RNAs (siRNAs). To enhance biocompatibility and alter pharmacokinetic properties, hyperbranched PEI was recently grafted with the nonligand oligosaccharides maltose or maltotriose at various degrees in a systematic study to yield (oligo-)maltose PEIs (OM-PEIs). In this paper, we investigate the in vivo biocompatibility and efficacy of a whole set of (OM-)PEIs and the corresponding (OM-)PEI-based DNA or siRNA complexes upon systemic (intravenous, i.v.) administration in mice. We determine the overall survival and animal welfare, hepatotoxicity, immune stimulation, erythrocyte aggregation, and the efficacy of DNA delivery in vivo. Higher-degree oligomaltose grafting of PEI substantially decreases weight loss, abolishes lethality upon repeated treatment with the free polymers or with complexes, and abrogates hepatotoxicity, as determined by serum levels of liver enzymes. Immunostimulatory effects (TNF-alpha, IFN-gamma) and erythrocyte aggregation are mainly observed upon treatment with partially maltotriose-grafted PEI or PEI-based complexes and are largely abolished upon higher-degree grafting. In vivo transfection experiments in mice bearing subcutaneous (s.c.) tumor xenografts reveal a strong dependence of reporter gene expression in a given organ on the mode of complex administration (i.v. vs intraperitoneal injection) and the OM-PEI architecture, with high-level maltose-grafted PEI (PEI-(2-Mal)) being most efficient for DNA delivery. We conclude that distinct differences between different patterns of maltose- or maltotriose-grafting are observed with regard to both biocompatibility and in vivo efficacy and identify optimal oligomaltose-PEIs for therapeutic applications. PMID- 24175861 TI - Deep brain stimulation: a mechanistic and clinical update. AB - Deep brain stimulation (DBS), the practice of placing electrodes deep into the brain to stimulate subcortical structures with electrical current, has been increasing as a neurosurgical procedure over the past 15 years. Originally a treatment for essential tremor, DBS is now used and under investigation across a wide spectrum of neurological and psychiatric disorders. In addition to applying electrical stimulation for clinical symptomatic relief, the electrodes implanted can also be used to record local electrical activity in the brain, making DBS a useful research tool. Human single-neuron recordings and local field potentials are now often recorded intraoperatively as electrodes are implanted. Thus, the increasing scope of DBS clinical applications is being matched by an increase in investigational use, leading to a rapidly evolving understanding of cortical and subcortical neurocircuitry. In this review, the authors discuss recent innovations in the clinical use of DBS, both in approved indications as well as in indications under investigation. Deep brain stimulation as an investigational tool is also reviewed, paying special attention to evolving models of basal ganglia and cortical function in health and disease. Finally, the authors look to the future across several indications, highlighting gaps in knowledge and possible future directions of DBS treatment. PMID- 24175862 TI - Regional trends and the impact of various patient and hospital factors on outcomes and costs of hospitalization between academic and nonacademic centers after deep brain stimulation surgery for Parkinson's disease: a United States Nationwide Inpatient Sample analysis from 2006 to 2010. AB - OBJECT: The aim of this study was to analyze the incidence of adverse outcomes, complications, inpatient mortality, length of hospital stay, and the factors affecting them between academic and nonacademic centers after deep brain stimulation (DBS) surgery for Parkinson's disease (PD). The authors also analyzed the impact of various factors on the total hospitalization charges after this procedure. METHODS: This is a retrospective cohort study using the Nationwide Inpatient Sample (NIS) from 2006 to 2010. Various patient and hospital variables were analyzed from the database. The adverse discharge disposition and the higher cost of hospitalization were taken as the dependent variables. RESULTS: A total of 2244 patients who underwent surgical treatment for PD were identified from the database. The mean age was 64.22 +/- 9.8 years and 68.7% (n = 1523) of the patients were male. The majority of the patients was discharged to home or self care (87.9%, n = 1972). The majority of the procedures was performed at high volume centers (64.8%, n = 1453), at academic institutions (85.33%, n = 1915), in urban areas (n = 2158, 96.16%), and at hospitals with a large bedsize (86.6%, n = 1907) in the West or South. Adverse discharge disposition was more likely in elderly patients (OR > 1, p = 0.011) with high comorbidity index (OR 1.508 [95% CI 1.148-1.98], p = 0.004) and those with complications (OR 3.155 [95% CI 1.202 8.279], p = 0.033). A hospital with a larger annual caseload was an independent predictor of adverse discharge disposition (OR 3.543 [95% CI 1.781-7.048], p < 0.001), whereas patients treated by physicians with high case volumes had significantly better outcomes (p = 0.006). The median total cost of hospitalization had increased by 6% from 2006 through 2010. Hospitals with a smaller case volume (OR 0.093, p < 0.001), private hospitals (OR 11.027, p < 0.001), nonteaching hospitals (OR 3.139, p = 0.003), and hospitals in the West compared with hospitals in Northeast and the Midwest (OR 1.885 [p = 0.033] and OR 2.897 [p = 0.031], respectively) were independent predictors of higher hospital cost. The mean length of hospital stay decreased from 2.03 days in 2006 to 1.55 days in 2010. There was no difference in the discharge disposition among academic versus nonacademic centers and rural versus urban hospitals (p > 0.05). CONCLUSIONS: Elderly female patients with nonprivate insurance and high comorbidity index who underwent surgery at low-volume centers performed by a surgeon with a low annual case volume and the occurrence of postoperative complications were correlated with an adverse discharge disposition. High-volume, government-owned academic centers in the Northeast were associated with a lower cost incurred to the hospitals. It can be recommended that the widespread availability of this procedure across small, academic centers in rural areas may not only provide easier access to the patients but also reduces the total cost of hospitalization. PMID- 24175863 TI - The added value of semimicroelectrode recording in deep brain stimulation of the subthalamic nucleus for Parkinson disease. AB - OBJECT: Accurate placement of the leads is crucial in deep brain stimulation (DBS). To optimize the surgical positioning of the lead, a combination of anatomical targeting on MRI, electrophysiological mapping, and clinical testing is applied during the procedure. Electrophysiological mapping is usually done with microelectrode recording (MER), but the relatively undocumented semimicroelectrode recording (SMER) is a competing alternative. In this study the added value and safety of SMER for optimal lead insertion in the subthalamic nucleus (STN) in a consecutive cohort of patients with Parkinson disease (PD) was assessed. METHODS: Between 2001 and 2010, a consecutive single-center cohort of 46 patients with PD underwent DBS of the STN (85 lead insertions). After exclusion of 11 lead insertions for mostly technical reasons, 74 insertions were included for the assessment. Anatomical target localization was based on either 1.5-T MRI or fused 3-T MRI with CT, with reference to anterior commissure posterior commissure coordinates. Electrophysiological mapping was performed with SMER. Intraoperative clinical testing was dominant in determining the final lead position. The target error was defined as the absolute distance between the anatomical or electrophysiological target and the final lead position. The effect of SMER on anatomical target error reduction and final target selection was analyzed. Also, the anatomical and electrophysiological target error was judged against the different imaging strategies. For safety evaluation, the adverse events related to all lead insertions were assessed. RESULTS: The use of SMER significantly reduced the anatomical target error from 1.7 (SD 1.6) mm to 0.8 (SD 1.3) mm (p < 0.0001). In particular, the anatomical target error based on 1.5-T MRI was significantly reduced by SMER, from 2.3 (SD 1.5) mm to 0.1 (SD 0.5) mm (p < 0.001). Anatomical target error reduction based on 3-T MRI fused with CT was not significantly influenced by SMER (p = 0.2), because the 3-T MRI-CT combination already significantly reduced the anatomical target error from 2.3 (SD 1.5) mm to 1.5 (SD 1.5) mm compared with 1.5-T MRI (p = 0.03). No symptomatic intracerebral hemorrhage was reported. Intracerebral infection was encountered in 1 patient following lead insertion. CONCLUSIONS: Semimicroelectrode recording has added value in targeting the STN in DBS for patients with PD based on 1.5-T MRI. The use of SMER does not significantly reduce the anatomical target error in procedures with fused 3-T MRI-CT studies and therefore might be omitted. With the absence of hemorrhagic complications, SMER-guided lead implantation should be considered a safe alternative to MER. PMID- 24175864 TI - The use of deep brain stimulation in Tourette's syndrome. AB - Tourette's syndrome (TS) is a childhood neuropsychiatric disorder characterized by multiple involuntary motor and vocal tics. It is commonly associated with other behavioral disorders including attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, depression, and self-injurious behaviors. Tourette's syndrome can be effectively managed with psychobehavioral and pharmacological treatments, and many patients experience an improvement in tics in adulthood. However, symptoms may persist and cause severe impairment in a small subset of patients despite available therapies. In recent years, deep brain stimulation (DBS) has been shown to be a promising treatment option for such patients. Since the advent of its use in 1999, multiple targets have been identified in DBS for TS, including the medial thalamus, globus pallidus internus, globus pallidus externus, anterior limb of the internal capsule/nucleus accumbens, and subthalamic nucleus. While the medial thalamus is the most commonly reported trajectory, the optimal surgical target for TS is still a topic of much debate. This paper provides a review of the available literature regarding the use of DBS for TS. PMID- 24175865 TI - Pallidotomy after chronic deep brain stimulation. AB - Recent publications have demonstrated that deep brain stimulation for Parkinson's disease still exerts beneficial effects on tremor, rigidity, and bradykinesia for up to 10 years after implantation of the stimulator. However with the progression of Parkinson's disease, features such as cognitive decline or "freezing" become prominent, and the presence of an implanted and functioning deep brain stimulator can impose a profound burden of care on the clinical team and family. The authors describe their experience in treating 4 patients who underwent removal of the implanted device due to either progressive dementia requiring full-time nursing or due to infection, and who subsequently underwent a unilateral pallidotomy. PMID- 24175866 TI - Selective dorsal rhizotomy for spasticity not associated with cerebral palsy: reconsideration of surgical inclusion criteria. AB - Children with spastic diplegia from cerebral palsy (CP) experience measurable improvement in their spasticity and motor function following selective dorsal rhizotomy (SDR). The role of this operation in the treatment of other spasticity causes is less well defined. A literature review was undertaken to survey outcomes from SDRs performed outside the CP population. Multiple sclerosis was the most common diagnosis found, accounting for 74 of 145 patients described. Selective dorsal rhizotomies have also been reported in patients with traumatic brain and spinal cord injuries, ischemic and hemorrhagic stroke, neurodegenerative disease, hypoxic encephalopathy, and other causes of spasticity. Outcomes from surgery are generally described as favorable, although postoperative assessments and follow-up times are not standardized across reports. Long-term outcomes are sparsely reported. Larger numbers of patients and more detailed outcomes data have the potential to form a basis for expanding the inclusion criteria for SDR. PMID- 24175867 TI - Deep brain stimulation in children and young adults with secondary dystonia: the Children's Hospital Los Angeles experience. AB - BACKGROUND: Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. It can be classified as primary or secondary. There is no cure for dystonia and the goal of treatment is to provide a better quality of life for the patient. Surgical intervention is considered for patients in whom an adequate trial of medical treatment has failed. Deep brain stimulation (DBS), specifically of the globus pallidus interna (GPi), has been shown to be extremely effective in primary generalized dystonia. There is much less evidence for the use of DBS in patients with secondary dystonia. However, given the large number of patients with secondary dystonia, the significant burden on the patients and their families, and the potential for DBS to improve their functional status and comfort level, it is important to continue to investigate the use of DBS in the realm of secondary dystonia. OBJECT: The objective of this study is to review a series of cases involving patients with secondary dystonia who have been treated with pallidal DBS. METHODS: A retrospective review of 9 patients with secondary dystonia who received treatment with DBS between February 2011 and February 2013 was performed. Preoperative and postoperative videos were scored using the Barry Albright Dystonia Scale (BADS) and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) by a neurologist specializing in movement disorders. In addition, the patients' families completed a subjective questionnaire to assess the perceived benefit of DBS. RESULTS: The average age at DBS unit implantation was 15.1 years (range 6-20 years). The average time to follow-up for the BADS evaluation from battery implantation was 3.8 months (median 3 months). The average time to follow up for the subjective benefit evaluation was 10.6 months (median 9.5 months). The mean BADS scores improved by 9% from 26.5 to 24 (p = 0.04), and the mean BFMDRS scores improved by 9.3% (p = 0.055). Of note, even in patients with minimal functional improvement, there seemed to be decreased contractures and spasms leading to improved comfort. There were no complications such as infections or hematoma in this case series. In the subjective benefit evaluation, 3 patients' families reported "good" benefit, 4 reported "minimal" benefit, and 1 reported no benefit. CONCLUSIONS: These early results of GPi stimulation in a series of 9 patients suggest that DBS is useful in the treatment of secondary generalized dystonia in children and young adults. Objective improvements in BADS and BFMDRS scores are demonstrated in some patients with generalized secondary dystonia but not in others. Larger follow-up studies of DBS for secondary dystonia, focusing on patient age, history, etiology, and patterns of dystonia, are needed to learn which patients will respond best to DBS. PMID- 24175868 TI - Hydrocephalus after meningioma surgery. PMID- 24175869 TI - Introduction: Evolving trends in movement disorder surgery. PMID- 24175870 TI - Copper-based conductive composites with tailored thermal expansion. AB - We have devised a moderate temperature hot-pressing route for preparing metal matrix composites which possess tunable thermal expansion coefficients in combination with high electrical and thermal conductivities. The composites are based on incorporating ZrW2O8, a material with a negative coefficient of thermal expansion (CTE), within a continuous copper matrix. The ZrW2O8 enables us to tune the CTE in a predictable manner, while the copper phase is responsible for the electrical and thermal conductivity properties. An important consideration in the processing of these materials is to avoid the decomposition of the ZrW2O8 phase. This is accomplished by using relatively mild hot-pressing conditions of 500 degrees C for 1 h at 40 MPa. To ensure that these conditions enable sintering of the copper, we developed a synthesis route for the preparation of Cu nanoparticles (NPs) based on the reduction of a common copper salt in aqueous solution in the presence of a size control agent. Upon hot pressing these nanoparticles at 500 degrees C, we are able to achieve 92-93% of the theoretical density of copper. The resulting materials exhibit a CTE which can be tuned between the value of pure copper (16.5 ppm/ degrees C) and less than 1 ppm/ degrees C. Thus, by adjusting the relative amount of the two components, the properties of the composite can be designed so that a material with high electrical conductivity and a CTE that matches the relatively low CTE values of semiconductor or thermoelectric materials can be achieved. This unique combination of electrical and thermal properties enables these Cu-based metal matrix composites to be used as electrical contacts to a variety of semiconductor and thermoelectric devices which offer stable operation under thermal cycling conditions. PMID- 24175871 TI - Integrative care therapies and pain in hospitalized children and adolescents: a retrospective database review. AB - BACKGROUND: Complementary or integrative care therapies are promising adjunctive approaches to pain management for pediatric inpatients that are currently underused and understudied. The purpose of this study was to examine the potential benefits of integrative care therapies delivered to hospitalized children and adolescents at a large Midwestern academic pediatric medical center over a 1-year period. METHODS: A retrospective chart review of an inpatient clinical database maintained by integrative care therapists over a 1-year period was used for the current study. Pre/post pain and relaxation scores associated with the delivery of inpatient integrative care therapies (primarily massage therapy and healing touch) were examined. RESULTS: Five-hundred nineteen hospitalized children and adolescents were treated by integrative care therapists for primarily pain or anxiety needs. Patients had a mean age of 10.2 years (standard deviation, 7.0), 224 were female (43%), 383 were white (74%), and most (393 [77%]) received massage therapy. Mean pain and relaxation scores decreased significantly from pre- to post-therapy across all demographic and clinical subgroups (p<=.001). CONCLUSIONS: Although integrative care therapies are increasingly requested and offered in children's hospitals, provision of these approaches is driven primarily by consumer demand rather than evidence-informed practice. Future controlled studies should examine the incremental effects of integrative care therapies as an adjunct to conventional treatment, assess how these therapies work mechanistically, and determine whether they improve outcomes, such as pain and cost, for hospitalized children and adolescents. PMID- 24175872 TI - A review of topical corrosive black salve. AB - Black salve is a compound derived from various inert ingredients, but it can be transformed into a corrosive ointment by the addition of bloodroot (Sanguinaria canadensis) or zinc chloride. Black salve products have been advertised as a natural remedy for many ailments, ranging from bee stings to skin cancer. This article reviews the current literature surrounding this compound, which in its corrosive form can be dangerous for use without medical supervision. Patients should be educated about the lack of objective evidence supporting the clinical efficacy of black salve as a skin cancer treatment, as well as the possible cosmetic defects resulting from tissue necrosis secondary to the effects of bloodroot and zinc chloride. PMID- 24175873 TI - Perinatal outcome of pregnancies following in vitro fertilization and ovulation induction. AB - OBJECTIVE: To investigate pregnancy outcome in patient who conceived by assisted reproductive techniques. METHODS: A retrospective population-based study was conducted, comparing obstetrical complications and neonatal outcomes of singleton pregnancies conceived by in vitro fertilization (IVF; n = 1296) and ovulation induction (n = 1988) as compared to singleton pregnancies conceived spontaneously (n = 172 288). Multivariable models were constructed to control for confounders. RESULTS: A significant linear association (using the chi-square test for trends) was documented among the three groups in adverse outcomes such as gestational diabetes mellitus (17.3% in the IVF, 14.2% in the ovulation induction, 6.6% in the comparison group, p < 0.001), severe preeclampsia (2.7% in the IVF, 1.8% in the ovulation induction, 1.1% in the comparison group, p < 0.001) and perinatal mortality (3.3% in the IVF, 2.1% in the ovulation induction, 1.3% in the comparison group, p < 0.001). In vitro fertilization and ovulation induction treatments were found to be independent risk factors for gestational diabetes mellitus, using two different multiple logistic regression models controlling for confounders such as maternal age (adjusted OR = 1.77, 95% CI:1.52-2.07, p < 0.001 and adjusted OR = 1.93, 95% CI:1.69-2.21, p < 0.001; respectively). CONCLUSIONS: Pregnancies conceiving following assisted reproductive techniques are at an increased risk for adverse obstetrics outcomes. The risk is higher for pregnancies following IVF compared with these conceived following ovulation induction. PMID- 24175874 TI - Trace metal contents of three tricalcium silicate materials: MTA Angelus, Micro Mega MTA and Bioaggregate. AB - AIM: To investigate the levels of nine metals [aluminium (Al), antimony (Sb), arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), iron (Fe), lead (Pb) and molybdenum (Mo)] in MTA Angelus, Micro Mega MTA and Bioaggregate using inductively coupled plasma-optical emission spectrometry (ICP-OES). METHODOLOGY: Each material (0.2 g) was digested using a mixture of hydrochloric and nitric acids and then filtered. The levels of nine metals in the resulting filtrates were measured by ICP-OES. The results were statistically analysed using one-way anova and the Bonferroni test. RESULTS: MTA Angelus contained more aluminium, beryllium and chromium than Micro Mega MTA (P < 0.05), whilst their levels of arsenic, cadmium and iron were similar. Antimony, lead and molybdenum were not detected in any of the three tested cements. Bioaggregate contained trace amounts of aluminium. CONCLUSIONS: MTA Angelus and Micro Mega MTA contained small amounts of seven tested metal oxides. Bioaggregate only contained trace amounts of aluminium. PMID- 24175875 TI - Selective synthesis of ternary copper-antimony sulfide nanocrystals. AB - Ternary copper-antimony sulfide nanocrystals (CAS NCs) have attracted increasing attention in photovoltaics and photoelectric nanodevices due to their tunable band gaps in the near-IR regime. Although much progress in the synthesis of CAS NCs has been achieved, the selective synthesis of CAS NCs with controllable morphologies and compositions is preliminary: in particular, a facile method is still in demand. In this work, we have successfully selectively synthesized high quality CAS NCs with diverse morphologies, compositions, and band gaps, including rectangular CuSbS2 nanosheets (NSs), trigonal-pyramidal Cu12Sb4S13 NCs, and rhombic Cu3SbS3 NSs, by cothermodecomposition of copper diethyldithiocarbamate trihydrate (Cu(Ddtc)2) and antimony diethyldithiocarbamate trihydrate (Sb(Ddtc)3). The direct and indirect band gaps of the obtained CAS NCs were systematically studied by performing Kubelka-Munk transformations of their solid state diffuse reflectance spectra. PMID- 24175876 TI - A dark-field scattering spectroelectrochemical technique for tracking the electrodeposition of single silver nanoparticles. AB - Dark-field scattering spectroelectrochemistry is used to analyze the electrochemical formation of individual Ag nanoparticles (NPs) at the surface of an indium tin oxide electrode. Heterogeneities in redox potentials among NPs not visible in bulk electrochemical measurements are presented for the first time. Through correlated electron microscopy, single NP light scattering intensity is related to particle size according to Mie theory, enabling rapid particle size determination and the construction of voltammetric curves for individual NPs. PMID- 24175877 TI - Fewer. Shorter. Better: Effective and efficient meetings for higher performing organizations. PMID- 24175878 TI - Sugar as part of a balanced breakfast? What cereal advertisements teach children about healthy eating. AB - Marketing that targets children with energy-dense, nutrient-poor foods is a likely contributor to the childhood obesity crisis. High-sugar ready-to-eat cereals are the packaged food most frequently promoted in child-targeted food advertising on television. The authors combined content analysis of product nutritional quality and messages presented in cereal television advertisements with syndicated data on exposure to those ads. The analysis quantifies children's exposure to specific products and messages that appear in advertisements and compares it with adult exposure. Children viewed 1.7 ads per day for ready-to-eat cereals, and 87% of those ads promoted high-sugar products; adults viewed half as many ads, and ads viewed were equally likely to promote high- and low-sugar cereals. In addition, the messages presented in high-sugar ads viewed by children were significantly more likely to convey unrealistic and contradictory messages about cereal attributes and healthy eating. For example, 91% of high-sugar cereal ads viewed by children ascribed extraordinary powers to these products, and 67% portrayed healthy and unhealthy eating behaviors. Given children's vulnerability to the influence of advertising, the emotional and mixed messages used to promote high-sugar cereals are confusing and potentially misleading. PMID- 24175880 TI - Maltreated youth display a blunted blood pressure response to an acute interpersonal stressor. AB - Although there is much evidence of hypothalamic-pituitary-adrenal axis dysfunction among individuals who have experienced child maltreatment, dysregulation of the autonomic nervous system (ANS) has received less attention. Understanding the role of the ANS in maltreated children may help clarify how these children respond to subsequent life stress. We explored ANS reactivity among 111 youth (ages 9-14), 34 of whom had experienced verified child maltreatment. ANS activity was assessed via blood pressure-a convenient, noninvasive physiological index-while youth underwent a social stress task. Blood pressure and subjective mood ratings were obtained prior to and following the task. Nonmaltreated youth experienced an increase in systolic blood pressure following the stressor, whereas maltreated youth did not. Self-reported subjective mood worsened for both groups. The current data suggest that children who experienced early stress exposure demonstrate blunted ANS reactivity. Results are discussed in terms of children's healthy adaptations to transient social stressors. In addition, we discuss the cost-effectiveness and benefits of physiological measures such as blood pressure for understanding risk for psychopathology. PMID- 24175881 TI - Italian risk factor-based screening for gestational diabetes. AB - There is a debate about whether universal or risk factors-based screening is most appropriate for gestational diabetes diagnosis. The aim of our retrospective study was to compare in our population the universal screening test recommended by the International Association of Diabetes in Pregnancy Study Group (IADPSG) panel and the American Diabetes Association (ADA) versus the selective screening proposed by the United Kingdom National Institute for Health and Clinical Excellence guidelines (NICE) but modified by the Italian National Institute of Health. From May 2010 to October 2011 all consecutive pregnant women were screened for gestational diabetes according to the IADPSG's panel criteria, while all the risk factors for each patient were registered. Of the 1015 pregnant women included in the study, 113 (11%) were diagnosed with gestational diabetes and 26 (23%) of them would not have been identified by the selective screening proposed by the Italian National Institute of Health. However, all the risk factors considered by the selective screening revealed a good predictive role except for maternal age >= 35 years (OR: 0.98). In the group without the risk factors considered, it was reported the predictive role for gestational diabetes of prepregnancy BMI and nulliparity. The selective risk factors-based screening proposed by the Italian National Institute of Health has detected 77% of gestational diabetes cases in our population, sparing the oral glucose tolerance test for more than 40% of pregnant women at the same time. More information on the clinical impact of this choice could be obtained by a strict analysis of treatment, perinatal outcome and follow-up of an adequate sample size of "missed" gestational diabetes. PMID- 24175882 TI - Alcohol binging exacerbates adipose tissue inflammation following burn injury. AB - BACKGROUND: Alcohol intoxication resulting from binge-drinking episodes is a leading cause of traumatic injury. Alcohol affects systemic responses critical for restoring homeostasis during the postinjury period. The lingering consequences of alcohol intoxication at time of injury are of relevance to the management of the trauma victim. METHODS: The study by Qin and colleagues (2013) used intraperitoneal alcohol administration to achieve blood alcohol concentrations of approximately 150 mg/dl to investigate its impact on adipose tissue inflammation following burn injury in a rodent model. The report and the pertinent literature were reviewed to provide perspective on the findings. RESULTS: Their results provide evidence of a marked increase in adipose inflammation during the postburn period. These findings identify a potential mechanism by which alcohol abuse and injury can synergize to promote a dysregulated environment conducive to insulin resistance, hyperglycemia, and potentially metabolic syndrome if the inflammatory changes in adipose tissue observed were to be sustained over prolonged periods. CONCLUSIONS: Adipose tissue inflammation potentially leading to metabolic dysregulation during the period following burn injury may further add to the complexities in the management of these patients. The underlying mechanisms need further investigation. The existence of an alcohol use disorder in burn or trauma victims should lead to increased awareness of possible metabolic complications during the recovery period that could be explained by enhanced adipose tissue inflammation. PMID- 24175883 TI - Vicinal bisheterocyclizations of alkynes via nucleophilic interception of a catalytic platinum carbene. AB - A novel platinum-catalyzed double heterocyclization of propargylic ethers is described. The transformation exploits the intermediacy of a key alpha,beta unsaturated carbene. The reactivity of this carbene is such that systems can be developed which avoid a complicating 1,2-hydrogen migration, allowing remarkable versatility in the selective syntheses of oxygen- and nitrogen-containing vicinal bis-heterocyclic compounds. PMID- 24175884 TI - Understanding the distributed cognitive processes of intensive care patient discharge. AB - AIMS AND OBJECTIVES: To better understand and identify vulnerabilities and risks in the ICU patient discharge process, which provides evidence for service improvement. BACKGROUND: Previous studies have identified that 'after hours' discharge and 'premature' discharge from ICU are associated with increased mortality. However, some of these studies have largely been retrospective reviews of various administrative databases, while others have focused on specific aspects of the process, which may miss crucial components of the discharge process. DESIGN: This is an ethnographic exploratory study. METHODS: Distributed cognition and activity theory were used as theoretical frameworks. Ethnographic data collection techniques including informal interviews, direct observations and collecting existing documents were used. A total of 56 one-to-one interviews were conducted with 46 participants; 28 discharges were observed; and numerous documents were collected during a five-month period. A triangulated technique was used in both data collection and data analysis to ensure the research rigour. RESULTS: Under the guidance of activity theory and distributed cognition theoretical frameworks, five themes emerged: hierarchical power and authority, competing priorities, ineffective communication, failing to enact the organisational processes and working collaboratively to optimise the discharge process. Issues with teamwork, cognitive processes and team members' interaction with cognitive artefacts influenced the discharge process. CONCLUSION: Strategies to improve shared situational awareness are needed to improve teamwork, patient flow and resource efficiency. Tools need to be evaluated regularly to ensure their continuous usefulness. RELEVANCE TO CLINICAL PRACTICE: Health care professionals need to be aware of the impact of their competing priorities and ensure discharges occur in a timely manner. Activity theory and distributed cognition are useful theoretical frameworks to support healthcare organisational research. PMID- 24175885 TI - Lungs, bone marrow, and adipose tissue. A network approach to the pathobiology of chronic obstructive pulmonary disease. AB - Patients with chronic obstructive pulmonary disease (COPD) often suffer other concomitant disorders, such as cardiovascular diseases and metabolic disorders, that influence significantly (and independently of lung function) their health status and prognosis. Thus, COPD is not a single organ condition, and disturbances of a complex network of interorgan connected responses occur and modulate the natural history of the disease. Here, we propose a novel hypothesis that considers a vascularly connected network with (1) the lungs as the main external sensor of the system and a major source of "danger signals"; (2) the endothelium as an internal sensor of the system (also a potential target tissue); and (3) two key responding elements, bone marrow and adipose tissue, which produce both inflammatory and repair signals. According to the model, the development of COPD, and associated multimorbidities (here we focus on cardiovascular disease as an important example), depend on the manner in which the vascular connected network responds, adapts, or fails to adapt (dictated by the genetic and epigenetic background of the individual) to the inhalation of particles and gases, mainly in cigarette smoke. The caveats and limitations of the hypothesis, as well as the experimental and clinical research needed to test and explore the proposed model, are also briefly discussed. PMID- 24175886 TI - Flexible queers, serious bodies: transgender inclusion in queer spaces. AB - Queer spaces are significant for understanding transgender inclusion as "queer spaces were places where individuals were expected to be attentive to or aware of alternative possibilities for being, including non-normative formulations of bodies, genders, desires and practices" ( Nash, 2011 , p. 203). Indeed, in this interview study of members of a queer leather group called the Club, members described a flexible "sexual landscape" that easily includes transgender members. However, these same queer spaces have been criticized for the way they regulate queer bodies and organize queer subjectivities. In this study, queer members of the Club also contrasted playful queer flexibility with serious transgender bodies. This article argues that, although there is a reiterative relation between transgender inclusion and queer spaces, the idealization of flexibility within queer spaces can also serve to marginalize and regulate transgender bodies. PMID- 24175887 TI - Emotional memories stemming from a crisis: a snapshot of AIDS activism in Washington, DC (1981-1986). AB - Emotional memories-described in this article as conscious, protracted memories that reference emotional events from the past-provide powerful qualitative data for social analysts. The reconfigured concept "emotional memories," a neuroscientific term, is utilized to help describe the long-term effects of affective, historically situated marginalization. The author highlights emotional memories of African American lesbian, gay, and bisexual activists involved in the early years of the AIDS crisis in Washington, DC, and connects these memories to documentation in the archives, which illuminate the source and power of these emotions. The author additionally uses an interdisciplinary lens to sociologically understand collective, yet individual, emotional responses to an epidemic. PMID- 24175888 TI - Measuring heterosexual LGBT ally development: a Rasch analysis. AB - An instrument was developed that measured heterosexual persons' level of lesbian, gay, bisexual, and transgender (LGBT) ally identity. Using a Rasch analysis, 2 dimensions were observed: (a) internal and interpersonal and (b) activity. Persons with high levels of LGBT ally identities endorsed items about having LGBT knowledge, attitudes, and skills; having interpersonal experiences with LGBT communities; and including LGBT ally as part of their identities. The instrument met criteria for the content, substantive, structural, generalizability, and responsiveness validity. The instrument can be used to assist persons to develop their abilities to support and advocate for equality for LGBT communities. PMID- 24175889 TI - Predictors of feminist activism among sexual-minority and heterosexual college women. AB - Engagement in activism is related to several aspects of social development in adolescence and emerging adulthood. Therefore, it is important to examine the correlates of different forms of activism, such as feminist collective action, among all youth. However, previous research has not investigated young sexual minority women's engagement with feminist collective action. This study examined predictors of college-aged heterosexual and sexual-minority women's commitment to and participation in feminist activism. Sexual orientation, number of years in college, social support, experiences with discrimination, and gender identity were tested as predictors of commitment to and participation in feminist activism with a sample of 280 college-aged women (173 heterosexuals and 107 sexual minorities). Similar predictors were related to both commitment to and participation in feminist activism. However, for sexual-minority women, but not heterosexual women, the number of years in college was correlated with participation in feminist activism. Young sexual-minority women reported more participation in feminist activism than did heterosexual women, even after controlling for social support, discrimination, and gender identity. PMID- 24175891 TI - Active form of the protein kinase CK2 alpha2beta2 holoenzyme is a strong complex with symmetric architecture. AB - CK2 is a protein kinase essential for cell viability whose activity is altered in several cancers. Its mechanisms of regulation differ from those common to other eukaryotic protein kinases and are not entirely established yet. Here we present crystal structures of the monomeric form of the alpha2beta2 holoenzyme that allow refining a formerly proposed structural model for activity regulation by oligomerization. Previous crystal structures of the CK2 holoenzyme show an asymmetric arrangement of the two alpha catalytic subunits around the obligate beta2 regulatory subunits. Asymmetric alpha2beta2 tetramers are organized in trimeric rings that correspond to inactive forms of the enzyme. The new crystal structures presented here reveal the symmetric architecture of the isolated active tetramers. The dimension and the nature of the alpha/beta interfaces configure the holoenzyme as a strong complex that does not spontaneously dissociate in solution, in accordance with the low dissociation constant (~4 nM). PMID- 24175892 TI - Familial intellectual disability in an Iranian family with a novel truncating mutation in CEP290. PMID- 24175893 TI - Diagnostic stifle joint arthroscopy using a needle arthroscope in standing horses. AB - OBJECTIVE: To assess use of an 18 g arthroscope for diagnostic stifle joint examination in the standing horse. STUDY DESIGN: Phase 1 used cadaver limbs and simultaneous ultrasonographic assessment. Phase 2 used 6 normal horses where stifles were assessed in both a standing and flexed position. Phase 3 used horses with suspected stifle injury or disease. ANIMALS: Normal horses (n = 6) to assess ability to perform diagnostic procedure (phase 2) and 3 clinical cases (phase 3). METHODS: Five cadaver limbs were used in phase 1 to assess all stifle joints. Phase 2 used standing sedated and locally anesthetized horses. Routine arthroscopic approaches were used in both weight bearing and flexed nonweight bearing positions. In both phase 1 and 2 simultaneous ultrasonographic and arthroscopic examinations were used to confirm extent of diagnostic examination. The methods developed in phase 2 were used to examine the stifle in 3 horses with suspected stifle disease. RESULTS: In cadaveric limbs and horses, all intra articular structures that constitute a complete arthroscopic examination were identified; no intra -or postoperative morbidity occurred. In phase 3, the needle arthroscope was used in accurate identification of pathologic change and in 1 horse, an osteochondral fragment not detected by ultrasonography and radiography was identified. CONCLUSIONS: This preliminary work indicates that an 18 g arthroscope can be used for diagnostic examination of the equine stifle in standing horses. PMID- 24175894 TI - A qualitative study of the relationships between residents and nursing homes nurses. AB - AIMS AND OBJECTIVES: To explore the relationships between residents and nurses in Spanish nursing homes. BACKGROUND: The nurses are one of the elements conditioning the life of the nursing home resident, influencing sense of security and mediating the relationships among residents. DESIGN: A qualitative phenomenological approach was applied. METHODS: An initial purposeful sampling of Spanish residents from nursing homes in the southern area of Madrid was conducted. The study included nursing home residents, aged 60 and over, with no cognitive impairment and who were able to communicate verbally in Spanish. Data were collected using unstructured and semi-structured interviews, researcher field notes, and personal diaries and letters from the residents. Data collection was concluded once theoretical saturation was reached, and data were analysed using the Giorgi proposal. RESULTS: Two main themes emerged: (1) 'meeting the nursing home nurses,' residents interact with nurses and establish relationships with them. The relationship is perceived as positive yet distant, and at times it is difficult to establish a closer relationship; and (2) 'managing relationships with the nursing home nurses,' residents learn to manage their relationships with the nurses, acquiring new behaviours to get closer to them, avoiding confrontations and helping each other. CONCLUSIONS: Residents manage their relationships with nurses using multiple behavioural strategies. They perceive these adjustments as necessary to facilitate daily life or avoid problems and/or confrontations. Deepening the relationships between residents and nurses could improve the management of nursing homes. RELEVANCE TO CLINICAL PRACTICE: Dialogue and active listening with residents must be incorporated into the daily nursing care. It should be given the same attention to all residents, with special attention to residents with cognitive and functional difficulties. PMID- 24175896 TI - Exercise intervention for the treatment of trismus in head and neck cancer. AB - BACKGROUND: The aim of this study was to investigate the impact of structured exercise with jaw mobilizing devices on trismus and its effect on trismus symptomatology and health-related quality of life (HRQL) in head and neck (H&N) cancer patients. MATERIAL AND METHODS: Fifty patients with H&N cancer and trismus, i.e. maximum interincisal opening (MIO) <= 35 mm participated in a structured intervention program with jaw exercise. The patients in the intervention group underwent a 10-week exercise program with regular follow-up. A control group comprising of 50 patients with trismus and H&N cancer were matched to the intervention group according to gender, tumor location, tumor stage, comorbidity and age. HRQL and trismus-related symptoms were assessed. RESULTS: The mean MIO improvement was 6.4 mm (4.8-8.0) and 0.7 (-0.3-1.7) mm in the intervention group and control group respectively, three months post-intervention commencement (p < 0.001). The intervention group demonstrated a statistically significant improvement in Role functioning, Social functioning and Global quality of life (EORTC QLQ C30) and in all Gothenburg Trismus Questionnaire (GTQ) domains, i.e. jaw-related problems (p < 0.001), eating limitation (p < 0.05) and muscular tension (p < 0.001). CONCLUSION: We found that a structured jaw exercise program was effective and improved the mouth opening capacity significantly. The objective effect on trismus (MIO) was also reflected in the patient-reported outcome questionnaires where the patients who underwent the structured exercise program after cancer treatment reported improvements in HRQL and less trismus related symptoms compared to the control group. PMID- 24175895 TI - Sugar-metal ion interactions: the complicated coordination structures of cesium ion with D-ribose and myo-inositol. AB - The novel cesium chloride-D-ribose complex (CsCl.C5H10O5; Cs-R) and cesium chloride-myo-inositol complex (CsCl.C6H12O6; Cs-I) have been synthesized and characterized using X-ray diffraction and FTIR, FIR, THz, and Raman spectroscopy. Cs(+) is eight-coordinated to three chloride ions, O1 and O2 from one D-ribose molecule, O1 from another D-ribose molecule, and O4 and O5 from the third D ribose molecule in Cs-R. For one D-ribose molecule, the oxygen atom O1 in the ring is coordinated to two cesium ions as an oxygen bridge, O2 is cocoordinated with O1 to one of the two cesium ions, and O4 and O5 are coordinated to the third cesium ion, respectively. O3 does not coordinate to metal ions and only takes part in forming hydrogen bonds. One chloride ion is connected to three cesium ions. Thus, a complicated structure of Cs-D-ribose forms. For Cs-I, Cs(+) is 10 coordinated to three chloride ions, O1 and O2 from one myo-inositol molecule, O3 and O4 from another myo-inositol molecule, O5 and O6 from the third myo-inositol molecule, and O6 from the fourth myo-inositol molecule. One metal ion is connected to four ligands, and one myo-inositol is coordinated to four Cs(+) ions, which is also a complicated coordination structure. Crystal structure results, FTIR, FIR, THz, and Raman spectra provide detailed information on the structure and coordination of hydroxyl groups to metal ions in the cesium chloride-D-ribose and cesium chloride-myo-inositol complexes. PMID- 24175897 TI - Psychosocial challenges and resource needs of young adult cancer survivors: implications for program development. AB - Young adult (YA) cancer survivors have specific needs because of their age and life stage. The authors investigated the challenges and resource needs of YA survivors, exploring the influence of age at diagnosis (i.e., diagnosis during childhood vs. young adulthood) and the diagnosis of a brain tumor. The authors conducted four focus groups with YA survivors (N = 22, age 18-35), treated for brain tumors or other cancers in childhood (mean age at diagnosis +/- SD: brain, 10.7 +/- 2.86; other cancers, 10.5 +/- 3.51) or as YAs (brain, 23.5 +/- 4.04; other cancers, 25.6 +/- 4.10). Transcripts of audiotaped sessions were coded using thematic analysis. Common challenges across the groups included physical appearance, fertility, late effects, social relationships, and changing priorities. Childhood cancer survivors struggled with identity formation, social isolation, and health care transitions. Concerns specific to survivors diagnosed as YAs included financial independence and protecting parents. Childhood brain tumor survivors struggled with cognitive deficits, limited career options, and poor social skills, whereas brain tumor survivors diagnosed as YAs emphasized cognitive decline, loss of autonomy, and living with an incurable disease. Despite the unique challenges identified, all groups described similar resource needs including peer support, age-specific information, and having health care providers proactively raise salient issues. Young adult cancer survivors have many similar psychosocial and information needs regardless of age at or type of diagnosis that differ from those of pediatric and older adult survivors. With improved survival rates, the small number of YA in any one institution will grow. It will become increasingly important to create comprehensive, age-appropriate YA programs that address overlapping and unique needs of survivors at this life stage. PMID- 24175898 TI - Screening for psychological well-being in childhood cancer survivors: a preliminary assessment of the feasibility of the strength and difficulties questionnaire as a parent-proxy report. AB - This article describes the feasibility of utilizing the Strengths and Difficulties Questionnaire (SDQ) as a brief psychosocial screener among survivors of pediatric cancer. Participants were parents of a child/adolescent diagnosed with cancer who were off treatment (n = 35) and a subset of adolescents (n = 14). Parent-proxy report using the SDQ was significantly associated with the Child Health Questionnaire. Parents who self-reported long-term uncertainty about their child's illness were more likely to report child psychosocial difficulties. A trend for concordance between patient and parent-proxy report of the SDQ was observed. These preliminary results highlight the potential utility of the SDQ as a screening tool for detection of child/adolescent psychosocial well-being. Further research, with larger samples, is needed to support these results. PMID- 24175899 TI - Moderators of psycho-oncology therapy effectiveness: meta-analysis of therapy characteristics. AB - As part of a larger meta-analysis seeking moderators of the effectiveness of psycho-oncological interventions, this report focuses on intervention types and characteristics, including protocol components, means of delivery (mode, dose, and therapist variables), and mechanisms of effectiveness. The data set comprised 146 published and unpublished prospective controlled trials with outcomes of anxiety, depression, and distress. Analyses took into account two moderators from analysis of study design features. The authors conclude that each of the four main professional therapy types (education, relaxation, cognitive behavior therapy (CBT), and expressive-support) has effect and that it is more important to focus on participant variables, notably, elevated baseline distress. Therapy components delivered by nonprofessionals and interventions that affect the patient indirectly show potential. Recommendations for practice and research are made. PMID- 24175900 TI - Factors associated with perceptions of the cancer care system: a multilevel modeling approach. AB - Perceptions about the health care system are a key driver of disparities and utilization. This study examined individual and contextual factors related to care and noncare dimensions and their relationship to perceptions of the cancer care system. A national sample of 877 cases was modeled using a multilevel modeling approach. Insurance complaints, number of treatments, and advocacy impact were negatively associated with satisfaction with the cancer care system at the individual level. Also, respondents in states where more Christians resided and lower hospital capacity were more likely to indicate satisfaction. Findings suggest implications for practitioners and health policy makers. PMID- 24175901 TI - Perspectives on psychosocial and spiritual cancer support services in New Zealand. AB - In New Zealand, support services have been developed in response to patient need but are variable. The benefits of psycho-social-spiritual care in reducing distress and enhancing quality of life for people with cancer and their families are well established yet unmet needs continue to feature. This project aimed to examine how health care professionals assessed for psycho-social-spiritual distress and unmet need, decisions on appropriate support, and identification of barriers in the referral process. A mixed-methods approach was used for this research. The qualitative phase entailed semistructured interviews with health care professionals working in cancer care. The quantitative phase was an online survey of oncologists and nurses. Thematic analysis was carried out by performing a side-by-side analysis of both sets of data. Nurses were most likely to assess for psycho-social-spiritual need and to refer to support services. Despite a clear mandate to provide regular psycho-social-spiritual assessment, there is no consistency of assessment and referral across New Zealand. There are clearly unmet psycho-social-spiritual needs among people affected by cancer in New Zealand, with health care professionals in this study noting structural impediments to adequate supportive care. There is a mismatch between the importance placed on such care and the capacity that is currently available. The results of this study provide evidence that can be used to argue for improvements in the infrastructure, funding allocation and policy that would allow for better psycho-social-spiritual care within the challenging context of increasing numbers of those affected by cancer. PMID- 24175902 TI - What is helpful to adolescents who have a parent diagnosed with cancer? AB - This research sought to identify what has been helpful for young people who have a parent diagnosed with cancer. Semistructured telephone interviews were conducted with young people (N = 15, age: M = 15.9 years) who had a parent diagnosed with cancer within the last 5 years. A phenomenological thematic data analysis distinguished three superordinate themes, identifying what helped adolescents cope with their parent's cancer diagnosis. These were parental behavior, specific coping strategies used by the young person, and community support. These results contribute to our knowledge of what can help young people whose parent has been diagnosed with cancer. PMID- 24175903 TI - Symptom communication in breast cancer: relationships of holding back and self efficacy for communication to symptoms and adjustment. AB - Adjuvant endocrine therapy improves overall survival for women with breast cancer. However, side effects may compromise patients' quality of life (QOL). This study examined how two communication variables (self-efficacy for symptom communication [SE] and holding back from discussing cancer-related concerns [HB]) relate to QOL, pain and menopausal symptoms. Participants with breast cancer (N = 61) completed questionnaires regarding symptoms, communication, and QOL. SE was positively related to QOL and negatively related to pain interference. HB from discussing cancer-related concerns was related negatively to QOL and positively to pain interference. HB mediated the relationship between SE and QOL as well as between SE and pain interference. Increased SE is beneficial among women on endocrine therapy for breast cancer. Future research should determine if interventions to improve SE are feasible and can improve QOL and symptom tolerability. PMID- 24175904 TI - Emotionally focused therapy with couples facing breast cancer: a theoretical foundation and descriptive case study. AB - Women with breast cancer experience a range of distressing emotions, and their partners experience increased distress as well. As a result, their relationship and the patient's health can be negatively affected. A theoretical foundation and specific techniques for applying Emotionally Focused Therapy in couples counseling for breast cancer is presented. A descriptive case study is used to illustrate the process. PMID- 24175906 TI - Inhibition of transglutaminase 2, a novel target for pulmonary fibrosis, by two small electrophilic molecules. AB - Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrotic destruction of normal lung architecture. Due to a lack of effective treatment options, new treatment approaches are needed. We previously identified transglutaminase (TG)2, a multifunctional protein expressed by human lung fibroblasts (HLFs), as a positive driver of fibrosis. TG2 catalyzes crosslinking of extracellular matrix proteins, enhances cell binding to fibronectin and integrin, and promotes fibronectin expression. We investigated whether the small electrophilic molecules 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) and 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2) inhibit the expression and profibrotic functions of TG2. CDDO and 15d-PGJ2 reduced expression of TG2 mRNA and protein in primary HLFs from control donors and donors with IPF. CDDO and 15d PGJ2 also decreased the in vitro profibrotic effector functions of HLFs including collagen gel contraction and cell migration. The decrease in TG2 expression did not occur through activation of the peroxisome proliferator activated receptor gamma or generation of reactive oxidative species. CDDO and 15d-PGJ2 inhibited the extracellular signal-regulated kinase pathway, resulting in the suppression of TG2 expression. This is the first study to show that small electrophilic compounds inhibit the expression and profibrotic effector functions of TG2, a key promoter of fibrosis. These studies identify new and important antifibrotic activities of these two small molecules, which could lead to new treatments for fibrotic lung disease. PMID- 24175907 TI - Gold-catalyzed rearrangements and beyond. AB - Cycloisomerizations of enynes are probably the most representative carbon-carbon bond forming reactions catalyzed by electrophilic metal complexes. These transformations are synthetically useful because chemists can use them to build complex architectures under mild conditions from readily assembled starting materials. However, these transformations can have complex mechanisms. In general, gold(I) activates alkynes in the presence of any other unsaturated functional group by forming an (eta(2)-alkyne)-gold complex. This species reacts readily with nucleophiles, including electron-rich alkenes. In this case, the reaction forms cyclopropyl gold(I) carbene-like intermediates. These can come from different pathways depending on the substitution pattern of the alkyne and the alkene. In the absence of external nucleophiles, 1,n-enynes can form products of skeletal rearrangement in fully intramolecular reactions, which are mechanistically very different from metathesis reactions initiated by the [2 + 2] cycloaddition of a Grubbs-type carbene or other related metal carbenes. In this Account, we discuss how cycloisomerization and addition reactions of substituted enynes, as well as intermolecular reactions between alkynes and alkenes, are best interpreted as proceeding through discrete cationic intermediates in which gold(I) plays a significant role in the stabilization of the positive charge. The most important intermediates are highly delocalized cationic species that some chemists describe as cyclopropyl gold(I) carbenes or gold(I)-stabilized cyclopropylmethyl/cyclobutyl/homoallyl carbocations. However, we prefer the cyclopropyl gold(I) carbene formulation for its simplicity and mnemonic value, highlighting the tendency of these intermediates to undergo cyclopropanation reactions with alkenes. We can add a variety of hetero- and carbonucleophiles to the enynes in the presence of gold(I) in intra- or intermolecular reactions, leading to the corresponding adducts with high stereoselectivity through stereospecific anti-additions. We have also developed stereospecific syn additions, which probably occur through similar intermediates. The attack of carbonyl groups at the cyclopropyl carbons of the intermediate cyclopropyl gold(I) carbenes initiates a particularly interesting group of reactions. These trigger a cascade transformation that can lead to the formation of two C-C and one C-O bonds. In the fully intramolecular process, this stereospecific transformation has been applied for the synthesis of natural sesquiterpenoids such as (+)-orientalol F and (-)-englerin A. Intra- and intermolecular trapping of cyclopropyl gold(I) carbenes with alkenes leads to the formation of cyclopropanes with significant increase in the molecular complexity, particularly in cases in which this process combines with the migration of propargylic alkoxy and related OR groups. We have recently shown this in the stereoselective total synthesis of the antiviral sesquiterpene (+)-schisanwilsonene by a cyclization/1,5-acetoxy migration/intermolecular cyclopropanation. In this synthesis, the cyclization/1,5-acetoxy migration is faster than the alternative 1,2-acyloxy migration that would result in racemization. PMID- 24175908 TI - Adult men's beliefs, values, attitudes and experiences regarding contraceptives: a systematic review of qualitative studies. AB - AIMS AND OBJECTIVES: To explore the men's beliefs, values, attitudes and experiences towards contraceptives. BACKGROUND: The promotion of male participation in contraceptive practices requires the knowledge and consideration of the beliefs, values, attitudes and experiences involved. The systematic review of the literature focusing on these themes can be useful for the evidence-based health care. DESIGN: A systematic review of qualitative studies. METHODS: Studies published between 1994 until 2011 (inclusive) were included. The participants included men from all cultures, ethnic backgrounds and religions who have expressed their beliefs, values, attitudes and experiences regarding male contraceptives. The databases CINAHL, PubMed, PsycINFO, SciELO, LILACS and MedCarib were explored. The appraisal of primary studies, carried out through the JBI-QARI (Qualitative Assessment and Review Instrument) resulted in the inclusion of 16 studies in this systematic review. RESULTS: The set of statements of beliefs, values, attitudes and experiences regarding contraceptives resulted in five synthesis: (1) contraceptive behaviour is influenced by religious, family and social backgrounds; (2) gendered, male-centred values predominate in contraceptive behaviours; (3) the sense of invulnerability influences contraceptive behaviours; (4) strong obstacles should be overcome to use contraceptives; (5) behaviours, decision-making and experiences regarding male contraceptives. CONCLUSIONS: The male beliefs and values regarding contraceptives are strongly influenced by religious, family and social backgrounds, and their attitudes in this scope are male centred. RELEVANCE TO CLINICAL PRACTICE: A deeper male consciousness regarding contraceptive responsibility should be promoted. It requires the knowledge of the men's personal backgrounds regarding contraceptives because they can be diverse according to family, social and cultural contexts. The consideration of the men's personal perspective is essential in the planning and implementation of reproductive health care. These aspects are essential for the concretisation of the evidence-based health care, a current challenge worldwide. PMID- 24175909 TI - Myosin Va is required for the transport of fragile X mental retardation protein (FMRP) granules. AB - BACKGROUND INFORMATION: Fragile X mental retardation protein (FMRP) is a selective RNA binding protein that functions as a translational inhibitor. It also plays a role in directing the transport of a subset of mRNAs to their site of translation and several recent reports have implicated microtubule motor proteins in the transport of FMRP-messenger ribonucleoprotein (mRNP) granules in neurons. Earlier work reported the association of the actin-based motor protein myosin Va with FMRP granules. RESULTS: Here, we follow up on this finding and confirm that myosin Va does in fact associate with FMRP and is required for its correct intracellular localisation. FMRP is concentrated in the perinuclear region of myosin Va-null mouse melanoma cells which contrasts starkly with the evenly distributed punctate pattern observed in wild-type cells. Similarly, overexpression of a dominant-negative mutant of myosin Va results in the accumulation of FMRP in large aggregate-like structures. FRAP experiments demonstrate that FMRP is largely immobile in the absence of myosin Va. CONCLUSIONS: Combining these data, we propose a model in which myosin Va and kinesin play key roles in the assembly and subsequent transport of FMRP granules along microtubules to the periphery of the cell. Myosin Va captures the complex onto peripheral actin structures and mediates the local delivery of the FMRP granule to the site of mRNA translation. PMID- 24175910 TI - Clinical, Histological and Cellular Evaluation of Vertico-Lateral Maxillary Reconstruction Associating Alveolar Osteogenic Distraction and Fresh-Frozen Bone Allograft. PMID- 24175911 TI - Recent progress in genome engineering techniques in the silkworm, Bombyx mori. AB - Rapid advances in genome engineering tools, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspaced palindromic repeats/CRISPR-associated (CRISPR/Cas) system, have enabled efficient gene knockout experiments in a wide variety of organisms. Here, we review the recent progress in targeted gene disruption techniques in the silkworm, Bombyx mori. Although efficiency of targeted mutagenesis was very low in an early experiment using ZFNs, recent studies have shown that TALENs can induce highly efficient mutagenesis of desired target genes in Bombyx. Notably, mutation frequencies induced by TALENs can reach more than 50% of G0 gametes. Thus, TALENs can now be used as a standard tool for gene targeting studies, even when mutant phenotypes are unknown. We also propose guidelines for experimental design and strategy for knockout experiments in Bombyx. Genome editing technologies will greatly increase the usefulness of Bombyx as a model for lepidopteran insects, the major agricultural pests, and lead to sophisticated breeding of Bombyx for use in sericulture and biotechnology. PMID- 24175912 TI - Gestational weight gain in overweight and obese women enrolled in a healthy lifestyle and eating habits program. AB - OBJECTIVES: To determine whether changes in lifestyle in women with BMI > 25 could decrease gestational weight gain and unfavorable pregnancy outcomes. METHODS: Women with BMI > 25 were randomized at 1st trimester to no intervention or a Therapeutic Lifestyle Changes (TLC) Program including diet (overweight: 1700 kcal/day, obese: 1800 kcal/day) and mild physical activity (30 min/day, 3 times/week). At baseline and at the 36th week women filled-in a Food Frequency Questionnaire. OUTCOMES: gestational weight gain, gestational diabetes mellitus, gestational hypertension, preterm delivery. Data stratified by BMI categories. RESULTS: Socio-demographic features were similar between groups (TLC: 33 cases, CONTROLS: 28 cases). At term, gestational weight gain in obese women randomized to TLC group was lower (6.7 +/- 4.3 kg) versus controls (10.1 +/- 5.6 kg, p = 0.047). Gestational diabetes mellitus, gestational hypertension and preterm delivery were also significantly lower. TLC was an independent factor in preventing gestational weight gain, gestational diabetes mellitus, gestational hypertension. Significant changes in eating habits occurred in the TLC group, which increased the number of snacks, the intake of fruits-vegetables and decreased the consumption of sugar. CONCLUSIONS: A caloric restriction associated to changes in eating behavior and constant physical activity, is able to reduce gestational weight gain and related pregnancy complications in obese women. PMID- 24175913 TI - Mossbauer spectroscopy as a probe of magnetization dynamics in the linear iron(I) and iron(II) complexes [Fe(C(SiMe3)3)2](1-/0.). AB - The iron-57 Mossbauer spectra of the linear, two-coordinate complexes, [K(crypt 222)][Fe(C(SiMe3)3)2], 1, and Fe(C(SiMe3)3)2, 2, were measured between 5 and 295 K under zero applied direct current (dc) field. These spectra were analyzed with a relaxation profile that models the relaxation of the hyperfine field associated with the inversion of the iron cation spin. Because of the lifetime of the measurement (10(-8) to 10(-9) s), iron-57 Mossbauer spectroscopy yielded the magnetization dynamics of 1 and 2 on a significantly faster time scale than was previously possible with alternating current (ac) magnetometry. From the modeling of the Mossbauer spectral profiles, Arrhenius plots between 5 and 295 K were obtained for both 1 and 2. The high-temperature regimes revealed Orbach relaxation processes with U(eff) = 246(3) and 178(9) cm(-1) for 1 and 2, respectively, effective relaxation barriers which are in agreement with magnetic measurements and supporting ab initio calculations. In 1, two distinct high temperature regimes of magnetic relaxation are observed with mechanisms that correspond to two distinct single-excitation Orbach processes within the ground state spin-orbit coupled manifold of the iron(I) ion. For 2, Mossbauer spectroscopy yields the temperature dependence of the magnetic relaxation in zero applied dc field, a relaxation that could not be observed with zero-field ac magnetometry. The ab initio calculated Mossbauer hyperfine parameters of both 1 and 2 are in excellent agreement with the observed hyperfine parameters. PMID- 24175914 TI - Strategies for designing supported gold-palladium bimetallic catalysts for the direct synthesis of hydrogen peroxide. AB - Hydrogen peroxide is a widely used chemical but is not very efficient to make in smaller than industrial scale. It is an important commodity chemical used for bleaching, disinfection, and chemical manufacture. At present, manufacturers use an indirect process in which anthraquinones are sequentially hydrogenated and oxidized in a manner that hydrogen and oxygen are never mixed. However, this process is only economic at a very large scale producing a concentrated product. For many years, the identification of a direct process has been a research goal because it could operate at the point of need, producing hydrogen peroxide at the required concentration for its applications. Research on this topic has been ongoing for about 100 years. Until the last 10 years, catalyst design was solely directed at using supported palladium nanoparticles. These catalysts require the use of bromide and acid to arrest peroxide decomposition, since palladium is a very active catalyst for hydrogen peroxide hydrogenation. Recently, chemists have shown that supported gold nanoparticles are active when gold is alloyed with palladium because this leads to a significant synergistic enhancement in activity and importantly selectivity. Crucially, bimetallic gold-based catalysts do not require the addition of bromide and acids, but with carbon dioxide as a diluent its solubility in the reaction media acts as an in situ acid promoter, which represents a greener approach for peroxide synthesis. The gold catalysts can operate under intrinsically safe conditions using dilute hydrogen and oxygen, yet these catalysts are so active that they can generate peroxide at commercially significant rates. The major problem associated with the direct synthesis of hydrogen peroxide concerns the selectivity of hydrogen usage, since in the indirect process this factor has been finely tuned over decades of operation. In this Account, we discuss how the gold-palladium bimetallic catalysts have active sites for the synthesis and hydrogenation of hydrogen peroxide that are different, in contrast to monometallic palladium in which synthesis and hydrogenation operate at the same sites. Through treatment of the support with acids prior to the deposition of the gold-palladium bimetallic particles, we can obtain a catalyst that can make hydrogen peroxide at a very high rate without decomposing or hydrogenating the product. This innovation opens up the way to design improved catalysts for the direct synthesis process, and these possibilities are described in this Account. PMID- 24175915 TI - Coronary heart disease patients transitioning to a normal life: perspectives and stages identified through a grounded theory approach. AB - AIMS AND OBJECTIVES: To explore how Iranian patients with coronary heart disease experience their lives. BACKGROUND: Coronary heart disease is a leading cause of death in Iran and worldwide. Understanding qualitatively how patients experience the acute and postacute stages of this chronic condition is essential knowledge for minimising the negative consequences of coronary heart disease. DESIGN: Qualitative study using grounded theory for the data analysis. METHODS: Data for this study were collected through individual qualitative interviews with 24 patients with coronary heart disease, conducted between January 2009 and January 2011. Patients with angina pectoris were selected for participation through purposive sampling, and sample size was determined by data saturation. Data analysis began with initial coding and continued with focused coding. Categories were determined, and the core category was subsequently developed and finalised. RESULTS: The main categories of the transition from acute phase to a modified or 'new normal' life were: (1) Loss of normal life. Experiencing emotions and consequences of illness; (2) Coming to terms. Using coping strategies; (3) Recreating normal life. Healthcare providers must correctly recognise the stages of transition patients navigate while coping with coronary heart disease to support and educate them appropriately throughout these stages. CONCLUSION: Patients with coronary heart disease lose their normal lives and must work towards recreating a revised life using coping strategies that enable them to come to terms with their situations. RELEVANCE TO CLINICAL PRACTICE: By understanding Iranian patients' experiences, healthcare providers and especially nurses can use the information to support and educate patients with coronary heart disease on how to more effectively deal with their illness and its consequences. PMID- 24175916 TI - The phytotoxic activity of the cerato-platanin BcSpl1 resides in a two-peptide motif on the protein surface. AB - Cerato-platanin family proteins are secreted and have been found in both the fungal cell wall and the extracellular medium. They elicit defence responses in a variety of plants and have been proposed to be perceived as pathogen-associated molecular patterns (PAMPs) by the plant immune system, although, in the case of the necrotroph Botrytis cinerea, the cerato-platanin BcSpl1 contributes to fungal virulence instead of plant resistance. In this study, we report that BcSpl1, which was previously found in the secretome as an abundant protein, is even more abundant in the fungal cell wall. By fusion to green fluorescent protein (GFP), we also show that BcSpl1 associates with the plant plasma membrane causing rapid morphological changes at the cellular level, such as the disorganization of chloroplasts, prior to macroscopic necrosis in the treated tissue. By a combination of serial deletion studies, synthetic peptides and chimeric proteins, we mapped the eliciting activity to a two-peptide motif in the protein surface. The expression of a chimeric protein displaying this motif in B. cinerea mutants lacking BcSpl1 undoubtedly showed that the motif is responsible for the contribution of BcSpl1 to virulence. PMID- 24175917 TI - In vitro metabolism of thyroxine by rat and human hepatocytes. AB - 1. The liver metabolizes thyroxine (T(4)) through two major pathways: deiodination and conjugation. Following exposure to xenobiotics, T(4) conjugation increases through the induction of hepatic uridine diphosphate glucuronosyltransferase (UGT) in rodents; however, it is uncertain to what degree different species employ deiodination and conjugation in the metabolism of T(4). The objective of this study was to compare the metabolism of T4 in untreated and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153)-treated primary sandwich-cultured hepatocytes from rat (SCRH) and human (SCHH). 2. Basal metabolite concentrations were 13 times higher in the medium of SCRH compared to SCHH. Metabolite distribution in the medium of SCRH versus SCHH was as follows: T(4)G, (91.6 versus 5.3%); T4S, (3.6 versus 4.4%) and T(3) + rT(3), (4.9 versus 90.3%). PCB 153 induced T(4)G in the medium of SCRH and SCHH; however, T(4)S and T(3) + rT(3) were changed but to a much lesser degree. 3. The results indicate that baseline T(4) glucuronidation is greater in SCRH compared to SCHH. These data also suggest that glucuronidation may be a more important pathway for T(4) metabolism in rats and deiodination may be a favored pathway in humans; however, with PCB 153 treatment these data support glucuronidation as a primary route of T(4) metabolism in both rat and humans. PMID- 24175918 TI - RegPrecise 3.0--a resource for genome-scale exploration of transcriptional regulation in bacteria. AB - BACKGROUND: Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in prokaryotes is one of the critical tasks of modern genomics. Bacteria from different taxonomic groups, whose lifestyles and natural environments are substantially different, possess highly diverged transcriptional regulatory networks. The comparative genomics approaches are useful for in silico reconstruction of bacterial regulons and networks operated by both transcription factors (TFs) and RNA regulatory elements (riboswitches). DESCRIPTION: RegPrecise (http://regprecise.lbl.gov) is a web resource for collection, visualization and analysis of transcriptional regulons reconstructed by comparative genomics. We significantly expanded a reference collection of manually curated regulons we introduced earlier. RegPrecise 3.0 provides access to inferred regulatory interactions organized by phylogenetic, structural and functional properties. Taxonomy-specific collections include 781 TF regulogs inferred in more than 160 genomes representing 14 taxonomic groups of Bacteria. TF-specific collections include regulogs for a selected subset of 40 TFs reconstructed across more than 30 taxonomic lineages. Novel collections of regulons operated by RNA regulatory elements (riboswitches) include near 400 regulogs inferred in 24 bacterial lineages. RegPrecise 3.0 provides four classifications of the reference regulons implemented as controlled vocabularies: 55 TF protein families; 43 RNA motif families; ~150 biological processes or metabolic pathways; and ~200 effectors or environmental signals. Genome-wide visualization of regulatory networks and metabolic pathways covered by the reference regulons are available for all studied genomes. A separate section of RegPrecise 3.0 contains draft regulatory networks in 640 genomes obtained by an conservative propagation of the reference regulons to closely related genomes. CONCLUSIONS: RegPrecise 3.0 gives access to the transcriptional regulons reconstructed in bacterial genomes. Analytical capabilities include exploration of: regulon content, structure and function; TF binding site motifs; conservation and variations in genome-wide regulatory networks across all taxonomic groups of Bacteria. RegPrecise 3.0 was selected as a core resource on transcriptional regulation of the Department of Energy Systems Biology Knowledgebase, an emerging software and data environment designed to enable researchers to collaboratively generate, test and share new hypotheses about gene and protein functions, perform large-scale analyses, and model interactions in microbes, plants, and their communities. PMID- 24175919 TI - Regulation of PKD1-mediated Golgi to cell surface trafficking by Galphaq subunits. AB - BACKGROUND INFORMATION: Heterotrimeric GTP-binding proteins play a key role in cell trafficking regulation. Above all, specific Gbetagamma subunits have been shown to be a major component of a signal transduction pathway, which also involves phospholipases C (PLC), protein kinases C (PKC) and D (PKD), whose main function is to regulate transport between Golgi and plasma membrane. It was the involvement of PLC which led us to study the role of the other member of this G protein family, the alpha subunits, in the regulation of membrane fission at the Golgi apparatus. RESULTS: Among constitutive active (QL) variants of different G protein alpha subunit sub-families, only GalphaqQL subunits were able to induce Golgi fragmentation, a phenotype that mainly reflects a membrane fission increase at this organelle. This phenotype was not observed with a GalphaqQL palmitoylation mutant, showing the need for a membrane-bounded subunit. Besides, GalphaqQL-dependent Golgi fission was blocked by specific PLC and PKC inhibitors, and in the presence of a PKD1-kinase dead variant. In addition, GalphaqQL was the only alpha subunit capable of inducing PKD1 phosphorylation. Finally, Vesicular Stomatitis Virus thermosensitive mutant glycoprotein (VSVG tsO45) transport assays have demonstrated that GalphaqQL acts directly on Golgi membranes to regulate trafficking between this organelle and plasma membrane. CONCLUSIONS: All these results indicate Galphaq subunits for the first time as a regulator of PKD mediated intracellular trafficking between Golgi apparatus and plasma membrane, opening new perspectives in the understanding of internal trafficking regulation by external signals through G protein-coupled receptors. PMID- 24175920 TI - Aggregation-induced emission enhancement in alkoxy-bridged binuclear rhenium(I) complexes: application as sensor for explosives and interaction with microheterogeneous media. AB - The aggregation-induced emission enhancement (AIEE) characteristics of the two alkoxy-bridged binuclear Re(I) complexes [{Re(CO)3(1,4-NVP)}2(MU2-OR)2] (1, R = C4H9; 2, C10H21) bearing a long alkyl chain with 4-(1-naphthylvinyl)pyridine (1,4 NVP) ligand are illustrated. These complexes in CH2Cl2 (good solvent) are weakly luminescent, but their intensity increased enormously by almost 500 times by the addition of poor solvent (CH3CN) due to aggregation. By tracking this process via UV-vis absorption and emission spectral and TEM techniques, the enhanced emission is attributed to the formation of nanoaggregates. The nanoaggregate of complex 2 is used as a sensor for nitroaromatic compounds. Furthermore, the study of the photophysical properties of these binuclear Re(I) complexes in cationic, cetyltrimethylammonium bromide (CTAB), anionic, sodium dodecyl sulfate (SDS), and nonionic, p-tert-octylphenoxypolyoxyethanol (TritonX-100, TX-100), micelles as well as in CTAB-hexane-water and AOT-isooctane-water reverse micelles using steady-state and time-resolved spectroscopy and TEM analysis reveals that the nanoaggregates became small and compact size. PMID- 24175921 TI - Uncorrelated dynamical processes in tetranuclear carboxylate clusters studied by variable-temperature 1H NMR spectroscopy. AB - Tetranuclear carboxylate clusters with the general structural formula [M4(L)2(O2CR)4] (M = Cd, Zn; LH2 = 2,6-bis(1-(2-hydroxyphenyl) iminoethyl)pyridine; R = CH3, C6H5) were studied by variable-temperature (VT) (1)H NMR spectroscopy. The dynamics of these clusters in solution can be described by two uncorrelated dynamical processes. The first dynamical process is the interconversion, both inter- as well as intramolecular, between syn-syn bridging and chelating carboxylate ligands. It is shown that this carboxylate interconversion mechanism is predominantly intramolecular for [Cd4(L)2(O2CCH3)4] (1a), whereas for [Zn4(L)2(O2CCH3)4] (2a) it is predominantly intermolecular. Two models for the second dynamic process, which involves the diiminepyridine ligand, are described. The first model comprises a nondissociative rotation around an internal axis, which changes the chirality of the cluster. The second model is based on the dissociation of the tetranuclear cluster into two dimeric species, which recombine again. This last model is supported by scrambling experiments between [Zn4(L)2(O2CCH3)4] (2a) and [Zn4(L3)2(O2CCH3)4] (5) (L3H2 = 2,6-bis(1-(2 hydroxyphenyl)-iminoethyl)4-chloropyridine). PMID- 24175922 TI - Esthetic Considerations for Reconstructing Implant Emergence Profile Using Titanium and Zirconia Custom Implant Abutments: Fifty Case Series Report. AB - Titanium and zirconia custom implant abutments are now commonly used for esthetic implant dentistry. Custom implant abutments allow the clinician to improve an implant's emergence profile, to customize cervical margins in accordance with the anatomy of the natural root, and to compensate for poor implant angulation. All of these are essential for optimum esthetic outcomes. Computer-aided design/computer-aided machining (CAD/CAM) technology allows the clinician to design custom implant abutment configurations and create natural-looking superstructures that are in harmony with the adjacent dentition and soft tissue. The CAD/CAM technique provides precise fit, reduces the cost of the procedure, and eliminates dimensional inaccuracies inherent in the conventional waxing and casting technique. The aim of this report is to describe a simplified technique for reconstructing emergence profiles during implant restoration using milled titanium and zirconia custom implant abutments. The results of 50 consecutive cases are reported. PMID- 24175923 TI - Mining of haplotype-based expressed sequence tag single nucleotide polymorphisms in citrus. AB - BACKGROUND: Single nucleotide polymorphisms (SNPs), the most abundant variations in a genome, have been widely used in various studies. Detection and characterization of citrus haplotype-based expressed sequence tag (EST) SNPs will greatly facilitate further utilization of these gene-based resources. RESULTS: In this paper, haplotype-based SNPs were mined out of publicly available citrus expressed sequence tags (ESTs) from different citrus cultivars (genotypes) individually and collectively for comparison. There were a total of 567,297 ESTs belonging to 27 cultivars in varying numbers and consequentially yielding different numbers of haplotype-based quality SNPs. Sweet orange (SO) had the most (213,830) ESTs, generating 11,182 quality SNPs in 3,327 out of 4,228 usable contigs. Summed from all the individually mining results, a total of 25,417 quality SNPs were discovered - 15,010 (59.1%) were transitions (AG and CT), 9,114 (35.9%) were transversions (AC, GT, CG, and AT), and 1,293 (5.0%) were insertion/deletions (indels). A vast majority of SNP-containing contigs consisted of only 2 haplotypes, as expected, but the percentages of 2 haplotype contigs varied widely in these citrus cultivars. BLAST of the 25,417 25-mer SNP oligos to the Clementine reference genome scaffolds revealed 2,947 SNPs had "no hits found", 19,943 had 1 unique hit / alignment, 1,571 had one hit and 2+ alignments per hit, and 956 had 2+ hits and 1+ alignment per hit. Of the total 24,293 scaffold hits, 23,955 (98.6%) were on the main scaffolds 1 to 9, and only 338 were on 87 minor scaffolds. Most alignments had 100% (25/25) or 96% (24/25) nucleotide identities, accounting for 93% of all the alignments. Considering almost all the nucleotide discrepancies in the 24/25 alignments were at the SNP sites, it served well as in silico validation of these SNPs, in addition to and consistent with the rate (81%) validated by sequencing and SNaPshot assay. CONCLUSIONS: High-quality EST-SNPs from different citrus genotypes were detected, and compared to estimate the heterozygosity of each genome. All the SNP oligo sequences were aligned with the Clementine citrus genome to determine their distribution and uniqueness and for in silico validation, in addition to SNaPshot and sequencing validation of selected SNPs. PMID- 24175926 TI - Dynamic anchoring of the 3'-end of the guide strand controls the target dissociation of Argonaute-guide complex. AB - Argonaute (Ago) is the catalytic core of small RNA-based gene regulation. Despite plenty of mechanistic studies on Ago, the dynamical aspects and the mechanistic determinants of target mRNA binding and dissociation of Ago-guide strand remain unclear. Here, by using single-molecule fluorescence resonance energy transfer (FRET) assays and Thermus thermophilus Ago (TtAgo), we reveal that the 3'-end of the guide strand dynamically anchors at and releases from the PAZ domain of Ago, and that the 3'-end anchoring of the guide strand greatly accelerates the target dissociation by destabilizing the guide-target duplex. Our results indicate that the target binding/dissociation of Ago-guide is executed through the dynamic interplays among Ago, guide, and target. PMID- 24175927 TI - Kinetic and structural features of a dyestuff coaggregation studied by time resolved static light scattering. AB - A binary dyestuff aggregate with a distinct stoichiometry is formed in dilute aqueous solution upon addition of Mg(2+) ions. The aggregation process was investigated with time-resolved multiangle static light scattering resulting in a sequence of static scattering curves. The scattering curves were analyzed with respect to the aggregation kinetics as well as the structure of the growing aggregates. The aggregation kinetics was based on the time evolution of the weight-averaged molar mass values extracted from the intercepts of the static scattering curves. A kinetic model that considers solely a nucleation step and monomer addition in its most simple form was developed in order to describe the evolution of time-dependent mass data. In addition, a kinetic model introduced by Lomakin et al. (Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 1125) for the description of beta-amyloid aggregation was adapted to the same experimental data. Application of the two kinetic models offered significant information on the role of magnesium ions within the aggregation process and provided a deeper understanding of the aggregation mechanism. Correlation of the size parameters extracted from the initial slopes of the scattering curves with the respective mass data as well as direct fitting of the scattering curves with the wormlike chain model yield a consistent set of model parameters. PMID- 24175924 TI - Contributions of thrombin targets to tissue factor-dependent metastasis in hyperthrombotic mice. AB - BACKGROUND: Tumor cell tissue factor (TF)-initiated coagulation supports hematogenous metastasis by fibrin formation, platelet activation and monocyte/macrophage recruitment. Recent studies identified host anticoagulant mechanisms as a major impediment to successful hematogenous tumor cell metastasis. OBJECTIVE: Here we address mechanisms that contribute to enhanced metastasis in hyperthrombotic mice with functional thrombomodulin deficiency (TM(Pro) mice). METHODS: Pharmacological and genetic approaches were combined to characterize relevant thrombin targets in a mouse model of experimental hematogenous metastasis. RESULTS: TF-dependent, but contact pathway-independent, syngeneic breast cancer metastasis was associated with marked platelet hyperreactivity and formation of leukocyte-platelet aggregates in immune competent TM(Pro) mice. Blockade of CD11b or genetic deletion of platelet glycoprotein Ibalpha excluded contributions of these receptors to enhanced platelet-dependent metastasis in hyperthrombotic mice. Mice with very low levels of the endothelial protein C receptor (EPCR) did not phenocopy the enhanced metastasis seen in TM(Pro) mice. Genetic deletion of the thrombin receptor PAR1 or endothelial thrombin signaling targets alone did not diminish enhanced metastasis in TM(Pro) mice. Combined deficiency of PAR1 on tumor cells and the host reduced metastasis in TM(Pro) mice. CONCLUSIONS: Metastasis in the hyperthrombotic TM(Pro) mouse model is mediated by platelet hyperreactivity and contributions of PAR1 signaling on tumor and host cells. PMID- 24175928 TI - Perceived learning needs of Syrian patients postcoronary artery bypass graft surgery. AB - AIMS AND OBJECTIVES: To describe the perceived learning needs of Syrian patients who underwent coronary artery bypass graft surgery before hospital discharge and to examine the differences in the mean scores of the categories (subscales) of the modified Cardiac Patients Learning Needs Inventory according to the demographic characteristics of the participants. BACKGROUND: Knowledge about the learning needs of patients who underwent coronary artery bypass graft surgery can help nurses in coronary care units to provide them with the information that they need. This might improve their quality of life through decreasing complications, length of stay in the hospital and hospital readmissions. DESIGN: A descriptive design was used for this study. METHODS: A convenience sample of 135 patients participated in this study and completed the demographic form and the modified Cardiac Patients Learning Needs Inventory. RESULTS: Information about chest and leg wound care, complications, medication and physical activity was the most important learning needs. There were significant differences between patients' perceptions of learning needs and their age, chronic illnesses and their working status. CONCLUSION: Syrian patients who underwent coronary artery bypass graft surgery were able to identify their learning needs that should be the focus of nursing practice. RELEVANCE TO CLINICAL PRACTICE: Meeting the needs of patients who underwent coronary artery bypass graft surgery should be emphasised in nursing practice. Meeting these needs might enhance their self-care behaviours. PMID- 24175929 TI - SmartArc-based volumetric modulated arc therapy for endometrial cancer: a dosimetric comparison with helical tomotherapy and intensity-modulated radiation therapy. AB - BACKGROUND: The purpose of the present study was to investigate the feasibility of using volumetric modulated arc therapy with SmartArc (VMAT-S) to achieve radiation delivery efficiency higher than that of intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) when treating endometrial cancer, while maintaining plan quality. METHODS: Nine patients with endometrial cancer were retrospectively studied. Three plans per patient were generated for VMAT-S, IMRT and HT. The dose distributions for the planning target volume (PTV), organs at risk (OARs) and normal tissue were compared. The monitor units (MUs) and treatment delivery time were also evaluated. RESULTS: The average homogeneity index was 1.06, 1.10 and 1.07 for the VMAT-S, IMRT and HT plans, respectively. The V40 for the rectum, bladder and pelvis bone decreased by 9.0%, 3.0% and 3.0%, respectively, in the VMAT-S plan relative to the IMRT plan. The target coverage and sparing of OARs were comparable between the VMAT-S and HT plans. The average MU was 823, 1105 and 8403 for VMAT-S, IMRT and HT, respectively; the average delivery time was 2.6, 8.6 and 9.5 minutes, respectively. CONCLUSIONS: For endometrial cancer, the VMAT-S plan provided comparable quality with significantly shorter delivery time and fewer MUs than with the IMRT and HT plans. In addition, more homogeneous PTV coverage and superior sparing of OARs in the medium to high dose region were observed in the VMAT-S relative to the IMRT plan. PMID- 24175931 TI - Current Approaches of Bone Morphogenetic Proteins in Dentistry. AB - Bone morphogenic proteins (BMPs) are a group of osteoinductive proteins obtained from nonmineralized bone matrix; they are capable of stimulating the differentiation of pluripotent mesenchymal cells to osteoprogenitor cells. They have become a likely treatment option, given their action on regeneration and remodeling of bone lesions and increasing the bone response around alloplastic materials. It may be feasible in the near future for BMPs to replace autologous and allogenic bone grafts. The application of specific growth factors for osteoinduction without using a bone graft constitutes a real impact on bone regeneration. The use of BMP is not only focused on osteogenic regeneration: There are a variety of studies investigating other properties, such as periodontal or dental regeneration from the conservative viewpoint. In this review, we will highlight the role of the BMP in bone, periodontal and dental regeneration. PMID- 24175930 TI - Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China. AB - BACKGROUND: Recent progress in malaria control has caused renewed interest in mass drug administration (MDA) as a potential elimination strategy but the evidence base is limited. China has extensive experience with MDA, but it is not well documented. METHODS: An ecological study was conducted to describe the use of MDA for the control and elimination of Plasmodium vivax in Jiangsu Province and explore the association between MDA and malaria incidence. Two periods were focused on: 1973 to 1983 when malaria burden was high and MDA administered to highly endemic counties province-wide, and 2000 to 2009, when malaria burden was low and a focal approach was used in two counties. All available data about the strategies implemented, MDA coverage, co-interventions, incidence, and adverse events were collected and described. Joinpoint analysis was used to describe trends in incidence and the relationship between MDA coverage and incidence was explored in negative binomial regression models. RESULTS: From 1973 to 1983, MDA with pyrimethamine and primaquine was used on a large scale, with up to 30 million people in target counties covered in a peak year (50% of the total population). Joinpoint analyses identified declines in annual incidence, -56.7% (95% CI -75.5 to -23.7%) from 1973-1976 and -12.4% (95% CI -24.7 to 2.0%) from 1976-1983. Population average negative binomial models identified a relationship between higher total population MDA coverage and lower monthly incidence from 1973-1976, IRR 0.98 (95% CI 0.97 to 1.00), while co-interventions, rainfall and GDP were not associated. From 2000-2009, incidence in two counties declined (annual change -43.7 to -14.0%) during a time when focal MDA using chloroquine and primaquine was targeted to villages and/or individuals residing near passively detected index cases (median 0.04% of total population). Although safety data were not collected systematically, there were rare reports of serious but non-fatal events. CONCLUSIONS: In Jiangsu Province, China, large-scale MDA was implemented and associated with declines in high P. vivax malaria transmission; a more recent focal approach may have contributed to interruption of transmission. MDA should be considered a potential key strategy for malaria control and elimination. PMID- 24175932 TI - Periosteal thickness and cellularity in mid-diaphyseal cross-sections from human femora and tibiae of aged donors. AB - Due to lack of access in healthy patients, the structural properties underlying the inherent regenerative power and advanced material properties of the human periosteum are not well understood. Periosteum comprises a cellular cambium layer directly apposing the outer surface of bone and an outer fibrous layer encompassed by the surrounding soft tissues. As a first step to elucidating the structural and cellular characteristics of periosteum in human bone, the current study aims to measure cambium and fibrous layer thickness as well as cambium cellularity in human femora and tibiae of aged donors. The major and minor centroidal axes (CA) serve as automated reference points in cross-sections of cadaveric mid-diaphyseal femora and tibiae. Based on the results of this study, within a given individual, the cambium layer of the major CA of the tibia is significantly thicker and more cellular than the respective layer of the femur. These significant intraindividual differences do not translate to significant interindividual differences. Further, mid-diaphyseal periosteal measures including cambium and fibrous layer thickness and cellularity do not correlate significantly with age or body mass. Finally, qualitative observations of periosteum in amputated and contralateral or proximal long bones of the lower extremity show stark changes in layer organization, thickness, and cellularity. In a translational context, these novel data, though inherently limited by availability and accessibility of human mid-diaphyseal periosteum tissue, provide important reference values for the use of periosteum in the context of facilitated healing and regeneration of tissue. PMID- 24175933 TI - Altitude-related cough. AB - Altitude-related cough is a troublesome condition of uncertain aetiology that affects many visitors to high altitude. The traditionally held belief that it was due solely to the inspiration of cold, dry air was refuted by observations and experiments in long duration hypobaric chamber studies. It is likely that altitude-related cough is a symptom of a number of possible perturbations in the cough reflex arc that may exist independently or together. These include loss of water from the respiratory tract; respiratory tract infections and sub-clinical high altitude pulmonary oedema. The published work on altitude-related cough is reviewed and possible aetiologies for the condition are discussed. PMID- 24175934 TI - Determining the active role of microscopists in community awareness-raising activities for malaria prevention: a cross-sectional study in Palawan, the Philippines. AB - BACKGROUND: Malaria remains one of the most prevalent and fatal diseases among the inhabitants of Palawan in the Philippines. Palawan, where healthcare services remain limited, has the highest malaria endemicity in the country. To eliminate malaria, effective prevention measures should be conducted alongside early diagnosis and prompt treatment, which are the major tasks of the trained microscopists in Palawan. However, while the microscopists have implemented community awareness-raising activities aimed at preventing transmission of malaria, the nature and quality of these activities have not been evaluated. The present study identified the factors associated with the strengthening of community awareness-raising activities for malaria prevention implemented by microscopists in Palawan. METHODS: A cross-sectional study was conducted among 127 microscopists in Palawan. Data were collected using self-administered questionnaires from November 2010 to February 2011. For data analysis, structural equation modelling was conducted, based on the questionnaire results, to identify the impact of factors associated with the number of community malaria awareness raising activities implemented by microscopists using the following assessment indicators: (1) place of assignment; (2) annual parasite index; (3) microscopists' capacity (service quality, knowledge on malaria, and ability in malaria microscopy); (4) self-preventive measures against malaria; and (5) job satisfaction. RESULTS: High microscopists' capacity was found to be a significant factor for a greater number of community awareness-raising activities for malaria prevention. High microscopists' capacity was significantly explained by its two sub-components: high service quality (active detection, diagnosis and treatment, prescription of anti-malarial, and follow-up) and high ability in malaria microscopy (preparation and documentation, slide preparation and observation, safe handling and disposal, and knowledge on the morphology of infected red blood cells). CONCLUSIONS: Microscopists' capacity was identified as a significant factor in community awareness-raising activities for malaria prevention. Thus, the strengthening of service quality and ability in malaria microscopy should be of the highest priority. PMID- 24175935 TI - Effects of quinapril on angiotensin converting enzyme and plasma renin activity as well as pharmacokinetic parameters of quinapril and its active metabolite, quinaprilat, after intravenous and oral administration to mature horses. AB - REASONS FOR PERFORMING STUDY: Angiotensin converting enzyme (ACE) inhibitors improve survival and quality of life in human patients and small animals with cardiovascular and renal disease. There is limited information regarding their effects in horses. OBJECTIVES: The purpose of this study was to determine the pharmacokinetics of quinapril and its effects on ACE and renin in horses. STUDY DESIGN: Experimental study using healthy mature horses. METHODS: Six healthy horses were administered quinapril at 120 mg i.v., 120 mg per os and 240 mg per os in a 3-way crossover design. Blood was collected for measurement of quinapril and quinaprilat concentrations using ultra-high pressure liquid chromatography with mass spectrometry. Angiotensin converting enzyme activity and renin activity were measured using a radioenzymatic assay. Noncompartmental pharmacokinetic modelling and statistical analyses were performed. RESULTS: No adverse effects were observed during the study period. Intravenous and oral administration significantly inhibited ACE activity. Renin concentrations increased in all groups, but this increase was not statistically significant. Following i.v. administration of quinapril, mean terminal half-life was 0.694 h and 1.734 h for quinapril and quinaprilat, respectively. The mean volume of distribution and clearance for quinapril were 0.242 l/kg bwt and 11.93 ml/kg bwt/min, respectively. Maximum concentration for quinaprilat was 145 ng/ml at 0.167 h. Bioavailability of quinapril following oral administration was <5%. Quinaprilat was detected in all horses following oral administration of quinapril; however, it was below the limit of quantification of the assay (2.5 ng/ml) for most horses in the 120 mg dosing group. CONCLUSIONS: These results suggest that, despite low plasma concentrations, quinapril has sufficient oral absorption to produce inhibition of ACE in healthy horses. Controlled studies in clinically affected horses are indicated. Quinapril provides a potential treatment alternative for horses with cardiovascular and renal disease. PMID- 24175937 TI - Changes in parafoveal retinal thickness and subfoveal choroidal thickness in a patient with dengue fever-associated maculopathy. AB - BACKGROUND: The time courses of retinal and choroidal thickness changes in dengue fever-associated maculopathy are not known. We measured central macular thickness (CMT), parafoveal retinal thickness (PRT), and subfoveal choroidal thickness (SCT), in one case, employing optical coherence tomography. FINDINGS: The patient was a 43-year-old man diagnosed with dengue fever in Sri Lanka. He became aware of blurred vision bilaterally and visited our department 2 weeks after the onset. He showed reduced visual acuity. The Amsler test revealed a doughnut-shaped relative scotoma. Based on the course of this condition, dengue fever-associated maculopathy was diagnosed. One month later, 20 mg triamcinolone was injected into sub-Tenon space of the left eye. Both eyes showed subsequent improvement. PRT of both eyes increased 1 week after the first visit and decreased thereafter, reaching a plateau 1 month after the first visit. The change in CMT was minimal. SCT changed markedly, with the similar pattern in both eyes, though no particular tendency was noted during the observation period. CONCLUSIONS: Dengue fever associated maculopathy appears to be closely associated with thickening of the inner layer of the retina, but not with changes in choroidal thickness. PMID- 24175936 TI - Is deep brain stimulation a treatment option for anorexia nervosa? AB - Anorexia nervosa (AN) is a severe psychiatric disorder with high rates of morbidity, comorbidity and mortality, which in a subset of patients (21%) takes on a chronic course. Since an evidence based treatment for AN is scarce, it is crucial to investigate new treatment options, preferably focused on influencing the underlying neurobiological mechanisms of AN. The objective of the present paper was to review the evidence for possible neurobiological correlates of AN, and to hypothesize about potential targets for Deep brain stimulation (DBS) as a treatment for chronic, therapy-refractory AN. One avenue for exploring new treatment options based on the neurobiological correlates of AN, is the search for symptomatologic and neurobiologic parallels between AN and other compulsivity or reward-related disorders. As in other compulsive disorders, the fronto striatal circuitry, in particular the insula, the ventral striatum (VS) and the prefrontal, orbitofrontal, temporal, parietal and anterior cingulate cortices, are likely to be implicated in the neuropathogenesis of AN. In this paper we will review the few available cases in which DBS has been performed in patients with AN (either as primary diagnosis or as comorbid condition). Given the overlap in symptomatology and neurocircuitry between reward-related disorders such as obsessive compulsive disorder (OCD) and AN, and the established efficacy of accumbal DBS in OCD, we hypothesize that DBS of the nucleus accumbens (NAc) and other areas associated with reward, e.g. the anterior cingulated cortex (ACC), might be an effective treatment for patients with chronic, treatment refractory AN, providing not only weight restoration, but also significant and sustained improvement in AN core symptoms and associated comorbidities and complications. Possible targets for DBS in AN are the ACC, the ventral anterior limb of the capsula interna (vALIC) and the VS. We suggest conducting larger efficacy studies that also explore the functional effects of DBS in AN. PMID- 24175939 TI - Living at home with eating difficulties following stroke: a phenomenological study of younger people's experiences. AB - AIMS AND OBJECTIVES: To explore and describe the experience of eating and eating related difficulties in stroke survivors living at home. BACKGROUND: The ability to consume food and to take pleasure in eating is an essential part of life. For people with stroke, eating difficulties are frequent. A phenomenological perspective of stroke survivors' experience of eating difficulties exceeding the acute stroke event and in-hospital rehabilitation is missing. DESIGN: A qualitative study founded on the Husslarian descriptive phenomenology. METHODS: Colaizzi's seven phases of data analysis provided a systematic approach to explore 17 in-depth interviews from seven participants and how eating difficulties influenced their daily lives. RESULTS: Eating difficulties revealed themselves in participants' relationship with the outer world in far-reaching disruptions of habits, capacities and actions. Four key themes illuminating the eating difficulties emerged: (1) preserving dignity by not conveying serious problems, (2) staying vigilant to bodily limitations, (3) stepping out of the security zone and (4) moving on without missing out. The findings exposed that eating difficulties might not only lead to serious consequences such as malnutrition but also, and equally importantly, lead to losses in the existential, social and cultural lifeworld. CONCLUSIONS: The experience of eating difficulties entails an ongoing readjustment process, which is strongly influenced by interactions with other people. The findings suggest that individualised long-term support is needed to facilitated the use of helpful strategies to manage eating difficulties. RELEVANCE TO CLINICAL PRACTICE: The long-term losses that people with eating difficulties experience are not reflected in conventional screening tools and interventions. To avoid haphazard identification presupposes professional knowledge of how eating difficulties are woven into daily life. This knowledge may inform innovative nursing strategies reaching beyond immediate rehabilitation. Partnership-based practice may provide an important framework to establish unique needs and to mobilise relevant actions and resources. PMID- 24175938 TI - Temporal expression patterns of insulin-like growth factor binding protein-4 in the embryonic and postnatal rat brain. AB - BACKGROUND: IGFBP-4 has been considered as a factor involving in development of the central nervous system (CNS), but its role needs to be further clarified. In present study, the localization of IGFBP-4 expression in the embryonic forebrain, midbrain and hindbrain was determined using immunohistochemistry, and the levels of IGFBP-4 protein and mRNA were semi-quantified using RT-PCR and Western blot in the embryonic (forebrain, midbrain and hindbrain) and postnatal brain (cerebral cortex, cerebellum and midbrain). RESULTS: A clear immunoreactivity of IGFBP-4 covered almost the entire embryonic brain (forebrain, midbrain, hindbrain) from E10.5 to E18.5, except for the area near the ventricle from E14.5. The change of IGFBP-4 mRNA level was regularly from E10.5 to E18.5: its expression peaked at E13.5 and E14.5, followed by gradual decreasing from E15.5. The expression of IGFBP-4 protein was similar to that of mRNA in embryonic stage. After birth, the pattern of IGFBP-4 expression was shown to be rather divergent in different brain areas. In the cerebral cortex, the IGFBP-4 mRNA increased gradually after birth (P0), while the protein showed little changes from P0 to P28, but decreased significantly at P70. In the cerebellum, the IGFBP-4 mRNA decreased gradually from P0, reached the lowest level at P21, and then increased again. However, its protein level gradually increased from P0 to P70. In the midbrain, the IGFBP-4 mRNA first decreased and reached its lowest level at P28 before it increased, while the protein remained constant from P0 to P70. At P7, P14, P21, P28 and P70, the levels of IGFBP-4 mRNA in the cerebral cortex were significantly higher than that in the cerebellum or in the midbrain. Differently, the protein levels in the cerebellum were significantly higher than that either in the cerebral cortex or in the midbrain at P14, P21, P28 and P70. CONCLUSIONS: The temporal expression pattern of IGFBP-4 in the embryonic brain from E10.5 to E18.5 was consistent with the course of neurogenesis in the ventricular zone, suggesting an important role of IGFBP-4 in regulating differentiation of neural stem cells. A strikingly higher abundance of the IGFBP-4 protein observed in the cerebellum from P14 to P70 suggests that IGFBP-4 may participate in the maintenance of cerebellar plasticity. PMID- 24175940 TI - Structural effects of the beta-vinyl linker in pyridinium porphyrins: spectroscopic studies in organic solvents and AOT reverse micelles. AB - Two isomeric beta-vinylpyridinium porphyrins, 2-[2-(2-methylpyridinium)vinyl] 5,10,15,20-tetraphenylporphyrin (1, ortho isomer) and 2-[2-(4 methylpyridinium)vinyl]-5,10,15,20-tetraphenylporphyrin (2, para isomer), which have shown different photodynamic behavior were investigated in organic solvents and sodium 1,4-bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelles. In organic systems, the absorption spectra present a red-shifted band that is more intense in the para isomer, in addition to the usual Soret band. This new band presents interesting solvatochromic effects which obey the multiparametric Kamlet-Taft equation. In AOT reverse micelles, the ortho isomer exhibits a strong dependence with the parameter omega0 = [H2O]/[AOT] which indicates that the molecule resides at the interface toward the organic phase. By contrast, no evidence was detected for the encapsulation of para isomer 2 in AOT reverse micelles. The hypothesis of two ground state isomers with different contributions of trans and quinoid structures is advanced on the basis of the overall data collected from electronic absorption, steady-state, and transient-state fluorescence emission. A charge transfer state in which an electron is fully transferred from the porphyrin to the pyridinium moiety is associated to a quinoid structure in isomer 2. The trans/quinoid relative proportions may be accounted for by the orientation of the ortho-/para-pyridinium isomers relatively to the porphyrin core. PMID- 24175941 TI - EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON OSSEOINTEGRATION: A REVIEW. AB - Abstract The purpose of this study was to review the effects of nonsteroidal antiinflammatory drugs on osseointegration and determine whether they cause failures in dental implants and whether patients who use them chronically can receive dental implants safely.A bibliographic electronic search was performed using the Cochrane Library, PubMed, and Medline databases, selecting articles published between January 1982 and December 2012. The search included the following keywords, either alone or combined: "non-steroidal anti-inflammatory drugs," "dental implants," "bone healing," and "osteoprogenitor cells." The inclusion criteria were the following: randomized, double-blind, placebo controlled clinical studies, in vivo animal model studies of osseointegration, and in vitro studies of the effects of these agents on osteoprogenitor cells. The literature search revealed 360 references. A total of 31 articles met the inclusion criteria, including two clinical trials, 20 animal studies, and nine osteoprogenitor cell studies. The clinical trials revealed that cyclooxygenase-1 (COX-1) inhibitors did not impair osseointegration. The animal studies showed that any drug that is capable of inhibiting COX-2 may impair the osseointegration process. The in vitro studies showed that COX-2 inhibitors are the most potent depressors of osseointegration at the cellular level. Caution must be taken when selecting COX-2 nonsteroidal antiinflammatory drugs during the postoperative period. PMID- 24175942 TI - Meaning-in-life in nursing-home patients: a valuable approach for enhancing psychological and physical well-being? AB - AIMS AND OBJECTIVES: To investigate the associations between meaning-in-life and physical, emotional, functional and social well-being in a cognitively intact nursing-home population. BACKGROUND: Meaning-in-life is understood as an influential psychological variable that promotes health and well-being; meaning in-life has been found to be a mediating variable in both psychological and physical health. DESIGN AND METHODS: The study employed a cross-sectional design. Data were collected in 2008 and 2009 using the purpose-in-life test and the FACT G quality-of-life questionnaire. A total of 250 cognitively intact nursing-home patients who met the inclusion criteria were approached and 202 attended. The hypothesised relationships between meaning and multidimensional well-being were tested by means of structural equation modelling. RESULTS: The structural equation modelling model fit well with the present data, showing significant direct relationships between meaning-in-life and emotional and functional well being, and a significant mediated influence of meaning on social and physical well-being. CONCLUSION: Meaning-in-life is associated with all dimensions of well being and likely plays an important role in both emotional and physical well being. RELEVANCE TO CLINICAL PRACTICE: Facilitating patients' perceived meaning in-life might help ease emotional distress and physical symptoms, thus fostering well-being in cognitively intact nursing-home patients. Therefore, advancing staff nurses' competence in facilitating meaningful involvement, connectedness, nurse-patient interaction and symptom management is important for care quality and global well-being in nursing homes. PMID- 24175943 TI - Meta-analysis shows limited evidence for using Lactobacillus acidophilus LB to treat acute gastroenteritis in children. AB - A meta-analysis of four randomised controlled trials of varying methodological quality, involving 304 children aged 1-48 months, showed that Lactobacillus acidophilus LB (LB) reduced the duration of diarrhoea in hospitalised, but not outpatient, children compared with a placebo. The chance of a cure on day three was similar in both groups, but LB increased the chance of cure on day four. CONCLUSION: There is limited evidence to recommend LB for treating paediatric diarrhoea. PMID- 24175944 TI - Early results of an integrated maternal, newborn, and child health program, Northern Nigeria, 2009 to 2011. AB - BACKGROUND: This paper describes early results of an integrated maternal, newborn, and child health (MNCH) program in Northern Nigeria where child mortality rates are two to three times higher than in the southern states. The intervention model integrated critical health systems changes needed to reinvigorate MNCH health services, together with community-based activities aimed at mobilizing and enabling women to make changes in their MNCH practices. Control Local Government Areas received less-intense statewide policy changes. METHODS: The impact of the intervention was assessed using a quasi-experimental design, comparing MNCH behaviors and outcomes in the intervention and control areas, before and after implementation of the systems and community activities. Stratified random household surveys were conducted at baseline in 2009 (n = 2,129) and in 2011 at follow-up (n = 2310), with women with births in the five years prior to household surveys. Chi-square and t-tests were used to document presence of significant improvements in several MNCH outcomes. RESULTS: Between baseline and follow-up, anti-tetanus vaccination rates increased from 69.0% to 85.0%, and early breastfeeding also increased, from 42.9% to 57.5%. More newborns were checked by trained health workers (39.2% to 75.5%), and women were performing more of the critical newborn care activities at follow-up. Fewer women relied on the traditional birth attendant for health advice (48.4% to 11.0%, with corresponding increases in advice from trained health workers. At follow-up, most of these improvements were greater in the intervention than control communities. In the intervention communities, there was less use of anti-malarials for all symptoms, coupled with more use of other medications and traditional, herbal remedies. Infant and child mortality declined in both intervention and control communities, with the greatest declines in intervention communities. In the intervention communities, infant mortality rate declined from 90 at baseline to 59 at follow-up, while child mortality declined from 160 to 84. CONCLUSIONS: These results provide evidence that in the context of ongoing improvements to the primary health care system, the participatory and community-based interventions focusing on improved newborn and infant care were effective at changing infant care practices and outcomes in the intervention communities. PMID- 24175945 TI - Comparative safety of artemether-lumefantrine and other artemisinin-based combinations in children: a systematic review. AB - BACKGROUND: The purpose of the study was to compare the safety of artemether lumefantrine (AL) with other artemisinin-based combinations in children. METHODS: A search of EMBASE (from 1974 to April 2013), MEDLINE (from 1946 to April 2013) and the Cochrane library of registered controlled trials for randomized controlled trials (RCTs) which compared AL with other artemisinin-based combinations was done. Only studies involving children <= 17 years old in which safety of AL was an outcome measure were included. RESULTS: Four thousand, seven hundred and twenty six adverse events (AEs) were recorded in 6,000 patients receiving AL. Common AEs (>= 1/100 and <1/10) included: coryza, vomiting, anaemia, diarrhoea, vomiting and abdominal pain; while cough was the only very commonly reported AE (>= 1/10). AL-treated children have a higher risk of body weakness (64.9%) than those on artesunate-mefloquine (58.2%) (p = 0.004, RR: 1.12 95% CI: 1.04-1.21). The risk of vomiting was significantly lower in patients on AL (8.8%) than artesunate-amodiaquine (10.6%) (p = 0.002, RR: 0.76, 95% CI: 0.63 0.90). Similarly, children on AL had a lower risk of vomiting (1.2%) than chlorproguanil-dapsone-artesunate (ACD) treated children (5.2%) (p = 0.002, RR: 0.63, 95% CI: 0.47-0.85). The risk of serious adverse events was significantly lower for AL (1.3%) than ACD (5.2%) (p = 0.002, RR: 0.45, 95% CI: 0.27-0.74). CONCLUSION: Artemether-lumefantrine combination is as safe as ASAQ and DP for use in children. Common adverse events are cough and gastrointestinal symptoms. More studies comparing AL with artesunate-mefloquine and artesunate-azithromycin are needed to determine the comparative safety of these drugs. PMID- 24175946 TI - Transfer of piano practice in fast performance of skilled finger movements. AB - BACKGROUND: Transfer of learning facilitates the efficient mastery of various skills without practicing all possible sensory-motor repertoires. The present study assessed whether motor practice at a submaximal speed, which is typical in sports and music performance, results in an increase in a maximum speed of finger movements of trained and untrained skills. RESULTS: Piano practice of sequential finger movements at a submaximal speed over days progressively increased the maximum speed of trained movements. This increased maximum speed of finger movements was maintained two months after the practice. The learning transferred within the hand to some extent, but not across the hands. CONCLUSIONS: The present study confirmed facilitation of fast finger movements following a piano practice at a submaximal speed. In addition, the findings indicated the intra manual transfer effects of piano practice on the maximum speed of skilled finger movements. PMID- 24175947 TI - Quinine binding by the cocaine-binding aptamer. Thermodynamic and hydrodynamic analysis of high-affinity binding of an off-target ligand. AB - The cocaine-binding aptamer is unusual in that it tightly binds molecules other than the ligand it was selected for. Here, we study the interaction of the cocaine-binding aptamer with one of these off-target ligands, quinine. Isothermal titration calorimetry was used to quantify the quinine-binding affinity and thermodynamics of a set of sequence variants of the cocaine-binding aptamer. We find that the affinity of the cocaine-binding aptamer for quinine is 30-40 times stronger than it is for cocaine. Competitive-binding studies demonstrate that both quinine and cocaine bind at the same site on the aptamer. The ligand-induced structural-switching binding mechanism of an aptamer variant that contains three base pairs in stem 1 is retained with quinine as a ligand. The short stem 1 aptamer is unfolded or loosely folded in the free form and becomes folded when bound to quinine. This folding is confirmed by NMR spectroscopy and by the short stem 1 construct having a more negative change in heat capacity of quinine binding than is seen when stem 1 has six base pairs. Small-angle X-ray scattering (SAXS) studies of the free aptamer and both the quinine- and the cocaine-bound forms show that, for the long stem 1 aptamers, the three forms display similar hydrodynamic properties, and the ab initio shape reconstruction structures are very similar. For the short stem 1 aptamer there is a greater variation among the SAXS-derived ab initio shape reconstruction structures, consistent with the changes expected with its structural-switching binding mechanism. PMID- 24175949 TI - Insulin therapy contributes to the increased risk of colorectal cancer in diabetes patients: a meta-analysis. AB - BACKGROUND: Recent epidemiological studies suggest that treatment with insulin may promote cancer growth. The present systematic review and meta-analysis of published observational studies was conducted to assess the risk of cancer during treatment with insulin. MATERIALS AND METHODS: A compressive search was conducted through MEDLINE, PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature databases (CBM). Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. RESULTS: A total of four studies with one case-controls study and three cohort studies comparing the insulin therapy and colorectal cancer susceptibility were identified. When all four studies were analyzed, the summary RRs were 1.61 (95% CI = 1.18-1.35) in a random-effects model for individuals with insulin therapy, compared with individuals without insulin therapy, which suggests a statistically significant association between insulin use and colorectal cancer. CONCLUSIONS: Our findings provides the evidence that insulin therapy may contribute to the risk of colorectal cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9339731010859509. PMID- 24175951 TI - Long-Term (9-12 Years) Outcomes of Titanium Implants With an Oxidized Surface: A Retrospective Investigation on 209 Implants. AB - The aim of this paper is to retrospectively assess the long-term clinical and radiological results in a group of patients treated with Branemark TiUnite implants supporting mostly single-tooth and partial restorations. The clinical records of 90 consecutive patients (mean age 55.9 years; range 21-82 years), treated with 209 Branemark System MkIII or MkIV TiUnite implants (72 maxillary/137 mandibular; 26 anterior intercanine/183 posterior sites), were analyzed. Indication types were single tooth (n = 21 implants), partial (n = 180) and full arches (n = 8). A delayed loading protocol was applied in 128 implants, while 81 were immediately loaded. Cumulative survival rate and marginal bone remodeling were evaluated. Marginal bone level was evaluated by an independent radiologist from periapical radiographs taken at implant insertion and at long term follow up. Plaque, probing pocket depth and peri-implant mucosa conditions were also assessed. The results showed the mean follow-up duration was 11.0 years (range 9.6-12.4 years): 181 implants (90.5%) reached at least 10 years follow-up, 100 implants 11 years, and 17 implants 12 years. Overall, 6 implants failed in 4 patients (5 during the first year and 1 after 2 years) resulting in a 97.1% survival rate after 12 years. Mean bone levels at implant insertion and at the last follow up were -0.90 +/- 1.16 mm (mean +/- SD; n = 169) and -1.49 +/- 0.95 mm (n = 195), respectively. Mean marginal bone remodeling from implant insertion to the last follow-up was -0.60 +/- 1.17 mm (n = 168). At the last available follow-up, mean pocket depth was 1.65 +/- 0.84 mm. Peri-implant mucosa was normal for the majority (97%) of implants. In conclusion, this retrospective long-term study showed excellent survival rate of TiUnite implants as well as favorable marginal bone response and soft tissue conditions. PMID- 24175948 TI - Hypersensitivity reactions to non beta-lactam antimicrobial agents, a statement of the WAO special committee on drug allergy. AB - Antibiotics are used extensively in the treatment of various infections. Consequently, they can be considered among the most important agents involved in adverse reactions to drugs, including both allergic and non-allergic drug hypersensitivity [J Allergy Clin Immunol 113:832-836, 2004]. Most studies published to date deal mainly with reactions to the beta-lactam group, and information on hypersensitivity to each of the other antimicrobial agents is scarce. The present document has been produced by the Special Committee on Drug Allergy of the World Allergy Organization to present the most relevant information on the incidence, clinical manifestations, diagnosis, possible mechanisms, and management of hypersensitivity reactions to non beta-lactam antimicrobials for use by practitioners worldwide. PMID- 24175953 TI - Sudden unexpected death study underlines risks of infants sleeping in sitting devices. PMID- 24175952 TI - The sensitive balance between the fully folded and locally unfolded conformations of a model peroxiredoxin. AB - To reduce peroxides, peroxiredoxins (Prxs) require a key "peroxidatic" Cys that, in a substrate-ready fully folded (FF) conformation, is oxidized to sulfenic acid and then, after a local unfolding (LU) of the active site, forms a disulfide bond with a second "resolving" Cys. For Salmonella typhimurium alkyl hydroperoxide reductase C (StAhpC) and some other Prxs, the FF structure is only known for a peroxidatic Cys->Ser variant, which may not accurately represent the wild-type enzyme. Here, we obtain the structure of authentic reduced wild-type StAhpC by dithiothreitol treatment of disulfide form crystals that fortuitously accommodate both the LU and FF conformations. The unique environment of one molecule in the crystal reveals a thermodynamic linkage between the folding of the active site loop and C-terminal regions, and comparisons with the Ser variant show structural and mobility differences from which we infer that the Cys->Ser mutation stabilizes the FF active site. A structure for the C165A variant (a resolving Cys to Ala mutant) in the same crystal form reveals that this mutation destabilizes the folding of the C-terminal region. These structures prove that subtle modifications to Prx structures can substantially influence enzymatic properties. We also present a simple thermodynamic framework for understanding the various mixtures of FF and LU conformations seen in these structures. On the basis of this framework, we rationalize how physiologically relevant regulatory post translational modifications may modulate activity, and we propose a nonconventional strategy for designing selective Prx inhibitors. PMID- 24175954 TI - Distraction test of the posterior superior iliac spine (PSIS) in the diagnosis of sacroiliac joint arthropathy. AB - BACKGROUND: The sacroiliac joint (SIJ) is a frequently underestimated cause of lower back (LBP). A simple clinical test of sufficient validity would be desirable. The aim of this study was to evaluate the diagnostic value of a new PSIS distraction test for the clinical detection of SIJ arthropathy and to compare it to several commonly used clinical tests. METHODS: Consecutive patients, where a SIJ pathology had been confirmed by an SIJ infiltration were enrolled (case group, 61 SIJs in 46 patients). Before infiltration, patients were tested for pain with PSIS distraction by a punctual force on the PSIS in medial to-lateral direction (PSIS distraction test), pain with pelvic compression, pelvic distraction, Gaenslen test, Thigh Thrust, and Faber (or Patrick's) test. In addition, these clinical tests were applied to both SIJs of a population of individuals without history of LBP (control group, 64 SIJs in 32 patients). RESULTS: Within the investigated cohort, the PSIS distraction test showed a sensitivity of 100% and a specificity of 89% for SIJ pathology. The accuracy of the test was 94%, the positive predictive value (PPV) was 90% and the negative predictive value (NPV) was 100%. Pelvic compression, pelvic distraction, Gaenslen test, Thigh Thrust, and Faber test were associated with a good specificity (> 90%) but a poor sensitivity (< 35%). CONCLUSIONS: Within our population of patients with confirmed SIJ arthropathy the PSIS distraction test was found to be of high sensitivity, specificity and accuracy. In contrast, common clinical tests showed a poor sensitivity. The PSIS distraction test seems to be an easy-to perform and clinically valuable test for SIJ arthropathy. PMID- 24175955 TI - Compassion satisfaction, compassion fatigue, anxiety, depression and stress in registered nurses in Australia: study 1 results. AB - AIM: To explore compassion fatigue and compassion satisfaction with the potential contributing factors of anxiety, depression and stress. BACKGROUND: To date, no studies have connected the quality of work-life with other contributing and co existing factors such as depression, anxiety and stress. METHOD: A self-report exploratory cross sectional survey of 132 nurses working in a tertiary hospital. RESULT: The reflective assessment risk profile model provides an excellent framework for examining the relationships between the professional quality of work factors and contributing factors within the established risk profiles. The results show a definite pattern of risk progression for the six factors examined for each risk profile. Additionally, burnout and secondary traumatic stress were significantly related to higher anxiety and depression levels. Higher anxiety levels were correlated with nurses who were younger, worked full-time and without a postgraduate qualification. Twenty percent had elevated levels of compassion fatigue: 7.6% having a very distressed profile. At-risk nurses' stress and depression scores were significantly higher than nurses with higher compassion satisfaction scores. IMPLICATIONS FOR NURSING MANAGERS: The employed nurse workforce would benefit from a psychosocial capacity building intervention that reduces a nurse's risk profile, thus enhancing retention. PMID- 24175956 TI - Two developmental switch points for the wing polymorphisms in the pea aphid Acyrthosiphon pisum. AB - BACKGROUND: In many insect taxa, wing polymorphism is known to be a consequence of tradeoffs between flight and other life-history traits. The pea aphid Acyrthosiphon pisum exhibits various morphs with or without wings associated with their complex life cycle including wing polyphenism in viviparous females, genetic wing polymorphism in males, and a monomorphic wingless phenotype in oviparous females and fundatrices. While wing differentiation has been investigated in some detail in viviparous females and males, these processes have not yet been elucidated in monomorphic morphs. The ontological development of the flight apparatus, including wings and flight muscles, was therefore carefully examined in oviparous females and fundatrices and compared with other morphs. RESULTS: The extensive histological examinations showed that flight-apparatus primordia were not at all produced throughout their postembryonic development in oviparous females and fundatrices, suggesting that during the embryonic stages the primordia are degenerated or not developed. In contrast, in viviparous females and males, the differentiation points to winged or wingless morphs occurred at the early postembryonic instars (first or second instar). CONCLUSIONS: Based on the above observations together with previous studies, we propose that there are two developmental switch points (embryonic and postembryonic) for the flight-apparatus development in A. pisum. Since there are multiple developmental trajectories for four wingless phenotypes (wingless viviparous females, oviparous females, fandatrices, wingless males), it is suggested that the developmental pathways leading to various morphs were evolutionarily acquired independently under selective pressures specific to each morph. Especially in viviparous females, the delay of determination is thought to contribute to the condition-dependent expressions of alternative phenotypes, that is, phenotypic plasticity. PMID- 24175957 TI - Conformation and dynamics at a flexible glycosidic linkage revealed by NMR spectroscopy and molecular dynamics simulations: analysis of beta-L-Fucp-(1->6) alpha-D-Glcp-OMe in water solution. AB - The intrinsic flexibility of carbohydrates facilitates different 3D structures in response to altered environments. At glycosidic (1->6)-linkages, three torsion angles are variable, and herein the conformation and dynamics of beta-L-Fucp-(1 >6)-alpha-D-Glcp-OMe are investigated using a combination of NMR spectroscopy and molecular dynamics (MD) simulations. The disaccharide shows evidence of conformational averaging for the psi and omega torsion angles, best explained by a four-state conformational distribution. Notably, there is a significant population of conformations having psi = 85 degrees (clinal) in addition to those having psi = 180 degrees (antiperiplanar). Moderate differences in (13)C R1 relaxation rates are found to be best explained by axially symmetric tumbling in combination with minor differences in librational motion for the two residues, whereas the isomerization motions are occurring too slowly to be contributing significantly to the observed relaxation rates. The MD simulation was found to give a reasonably good agreement with experiment, especially with respect to diffusive properties, among which the rotational anisotropy, D?/D?, is found to be 2.35. The force field employed showed too narrow omega torsion angles in the gauche-trans and gauche-gauche states as well as overestimating the population of the gauche-trans conformer. This information can subsequently be used in directing parameter developments and emphasizes the need for refinement of force fields for (1->6)-linked carbohydrates. PMID- 24175958 TI - The influence of a low glycemic index dietary intervention on maternal dietary intake, glycemic index and gestational weight gain during pregnancy: a randomized controlled trial. AB - BACKGROUND: Maternal diet is known to impact pregnancy outcome. Following a low glycemic index (GI) diet during pregnancy has been shown to improve maternal glycemia and reduce infant birthweight and may be associated with a higher fibre intake. We assessed the impact of a low GI dietary intervention on maternal GI, nutritional intake and gestational weight gain (GWG) during pregnancy. Compliance and acceptability of the low GI diet was also examined. METHOD: Eight hundred women were randomised in early pregnancy to receive low GI and healthy eating dietary advice or to receive standard maternity care. The intervention group received dietary advice at a group education session before 22 weeks gestation. All women completed a 3 day food diary during each trimester of pregnancy. Two hundred and thirty five women from the intervention arm and 285 women from the control arm returned complete 3x3d FDs and were included in the present analysis. RESULTS: Maternal GI was significantly reduced in the intervention group at trimester 2 and 3. The numbers of women within the lowest quartile of GI increased from 37% in trimester 1 to 52% in trimester 3 (P < 0.001) among the intervention group. The intervention group had significantly lower energy intake (P < 0.05), higher protein (% TE) (P < 0.01) and higher dietary fibre intake (P < 0.01) post intervention. Consumption of food groups with known high GI values were significantly reduced among the intervention group. Women in the intervention low GI group were less likely to exceed the Institute of Medicine's GWG goals. CONCLUSION: A dietary intervention in early pregnancy had a positive influence on maternal GI, food and nutrient intakes and GWG. Following a low GI diet may be particularly beneficial for women at risk of exceeding the GWG goals for pregnancy. PMID- 24175959 TI - Factors associated with smoking among adolescent males prior to incarceration and after release from jail: a longitudinal study. AB - BACKGROUND: The prevalence of cigarette smoking among incarcerated adult men and women is three-four times higher than in the general population, ranging from 70 80%. However, little is known about factors associated with smoking among incarcerated adolescents, especially upon their re-entry into communities after release from jail. The current study explores factors associated with smoking among adolescent males prior to incarceration and one year after their release from jail. METHODS: We conducted a secondary data analysis of the Returning Educated African-American and Latino Men to Enriched Neighborhoods (REAL MEN) study, which was designed to reduce HIV risk, substance use, and recidivism among 16-18 year old males leaving jail. We examined differences between smokers and non-smokers at the time of their incarceration (N = 552) and one year after their release from jail (N = 397) using t-tests and chi-square tests. Using logistic and linear regression we examined factors associated with current smoking status, frequency of smoking, and quantity of cigarettes smoked per day both prior to the young men's incarceration and one year after their release from jail. RESULTS: Prior to incarceration, 62% of the young men reported smoking, and one-year after jail release, 69% reported smoking. Prior to incarceration, foster care history, not living with parents, not attending school, drug sales, number of sex partners, gang involvement, current drug charges, and number of prior arrests were positively associated with smoking indicators prior to incarceration. Having violent charges was inversely associated with smoking indicators prior to incarceration. One-year after release from jail, foster care history and number of prior arrests before the index incarceration were associated with smoking indicators. CONCLUSIONS: Several problem behaviors may be associated with adolescent males' smoking behaviors prior to incarceration. However, the young men's histories of difficult life circumstances and engagement in illegal activity may have long-term consequences on smoking for these young men during their transition between jail and community. Findings suggest a need for comprehensive risk reduction interventions in settings in which disadvantaged young men are institutionalized, starting in childhood. PMID- 24175961 TI - On the statistical model of the two-stage designs in bioequivalence assessment. AB - OBJECTIVES: Two-stage clinical designs are currently recommended by the regulatory authorities for the assessment of bioequivalence (BE). A specific statistical methodology was recently proposed by the European Medicines Agency (EMA). The aims of this article are to elaborate on the suggested statistical design from the EMA and to compare it with the existing statistical methods reported in the literature. METHODS: Monte Carlo simulations were used to simulate the conditions of a two-stage BE design. The starting sample size was either 24 or 48, whereas the coefficient of variation of the within-subject variability was equal to 20% and 40%. Several geometric mean ratio levels of the BE metric were considered. Under each condition, 1,000,000 studies were simulated. KEY FINDINGS: The overall performance, in terms of percentage of BE acceptance, is identical. The additional term, 'sequence * stage', suggested in the EMA method is in most cases nonsignificant. The same results were obtained regardless of the type (fixed or random) of the effect applied to the 'subjects' term. CONCLUSIONS: Any BE study either finished or in progress which relies on the existing literature methodology leads to the same percentage of BE acceptance as if it was analysed with the recently proposed EMA method. PMID- 24175960 TI - The study of a barley epigenetic regulator, HvDME, in seed development and under drought. AB - BACKGROUND: Epigenetic factors such as DNA methylation and histone modifications regulate a wide range of processes in plant development. Cytosine methylation and demethylation exist in a dynamic balance and have been associated with gene silencing or activation, respectively. In Arabidopsis, cytosine demethylation is achieved by specific DNA glycosylases, including AtDME (DEMETER) and AtROS1 (REPRESSOR OF SILENCING1), which have been shown to play important roles in seed development. Nevertheless, studies on monocot DNA glycosylases are limited. Here we present the study of a DME homologue from barley (HvDME), an agronomically important cereal crop, during seed development and in response to conditions of drought. RESULTS: An HvDME gene, identified in GenBank, was found to encode a protein with all the characteristic modules of DME-family DNA glycosylase proteins. Phylogenetic analysis revealed a high degree of homology to other monocot DME glycosylases, and sequence divergence from the ROS1, DML2 and DML3 orthologues. The HvDME gene contains the 5' and 3' Long Terminal Repeats (LTR) of a Copia retrotransposon element within the 3' downstream region. HvDME transcripts were shown to be present both in vegetative and reproductive tissues and accumulated differentially in different seed developmental stages and in two different cultivars with varying seed size. Additionally, remarkable induction of HvDME was evidenced in response to drought treatment in a drought-tolerant barley cultivar. Moreover, variable degrees of DNA methylation in specific regions of the HvDME promoter and gene body were detected in two different cultivars. CONCLUSION: A gene encoding a DNA glycosylase closely related to cereal DME glycosylases was characterized in barley. Expression analysis during seed development and under dehydration conditions suggested a role for HvDME in endosperm development, seed maturation, and in response to drought. Furthermore, differential DNA methylation patterns within the gene in two different cultivars suggested epigenetic regulation of HvDME. The study of a barley DME gene will contribute to our understanding of epigenetic mechanisms operating during seed development and stress response in agronomically important cereal crops. PMID- 24175963 TI - Adverse respiratory outcome after premature rupture of membranes before viability. AB - AIM: To determine whether preterm premature rupture of membranes (PPROM) before 24 weeks is an independent risk factor for poor outcome in preterm neonates. METHODS: A retrospective comparative cohort study was conducted, including viable premature infants born between 25 and 34-weeks gestation. Each preterm case with early PPROM was matched with two preterm controls of the same gestational age at birth, sex and birth date and who were born spontaneously with intact membranes. Logistic regression was performed to identify independent risk factors associated with composite respiratory and perinatal adverse outcomes for the overall population of preterm infants. RESULTS: Thirty-five PPROM cases were matched with 70 controls. Extreme prematurity (26-28 weeks) was an independent risk factor for composite perinatal adverse outcomes [odds ratio (OR) 43.9; p = 0.001]. Extreme prematurity (OR 42.9; p = 0.001), PPROM (OR 7.1; p = 0.01), male infant (OR 5.2; p = 0.02) and intrauterine growth restriction (IUGR, OR 4.8; p = 0.04) were factors for composite respiratory adverse outcomes. CONCLUSION: Preterm premature rupture of membranes before viability represents an independent risk factor for composite respiratory adverse outcomes in preterm neonates. Extreme prematurity may represent the main risk factor for both composite respiratory and perinatal adverse outcomes. PMID- 24175964 TI - Adjunctive Orthodontic Applications in Dental Implantology. AB - Implant placement is often necessitated for replacement of teeth with pathologically damaged alveolar bone due to periodontitis or traumatic injury. Surgical augmentation of resorbed bone has many limitations, including lower efficacy of vertical augmentation than horizontal augmentation, as well as morbidity associated with grafting procedure. Orthodontic therapy has been proposed as a useful method for augmenting the resorbed alveolar bone and reforming aesthetically appealing gingival margin, prior to implant placement. This narrative review summarizes the available evidence for the application of orthodontic strategies that can be used as adjunct in selected cases to augment bone volume for the future implant site and maintain space for the prosthetic parts of the implant. These are (1) orthodontic extrusion of compromised teeth to generate vertical bone volume and enhance gingival architecture, (2) tooth preservation and postponing orthodontic space opening to maintain bone volume in future implant site, (3) orthodontic implant site switching to eliminate the deficient bone volume or risky implant sites, and (4) the provision of a rigid fixed-bonded retainer to maintain the implant site. Although there are no randomized controlled clinical trials to evaluate the efficacy of orthodontic therapy for implant site development, clinical case reports and experience document the efficacy of orthodontic therapy for this application. PMID- 24175966 TI - Consistent efficacy and safety of gemcitabine-paclitaxel in patients with metastatic breast cancer: a retrospective comparison of East Asian and global studies. AB - AIMS: The incidence of breast cancer in China is increasing at a rate greater than the global average. For treatment of metastatic breast cancer, a phase 3 trial of 529 patients (study JHQG) found that the combination of gemcitabine, a cytotoxic nucleoside analog, and paclitaxel, a taxane, significantly improved both overall and progression-free survival compared with paclitaxel monotherapy. As ethnic differences in the safety and efficacy of some anticancer therapies have been reported, this review provides oncologists treating East Asian patients with an evidence base to extrapolate results of the predominately Caucasian phase 3 JHQG study to their patients. METHODS: Three phase 2 studies in Chinese or Japanese patients with metastatic breast cancer are reviewed with reference to the global study JHQG. The results of pharmacokinetic, efficacy and safety analyses are descriptively compared between the global and Asian studies. RESULTS: Peak and total drug exposure values differed by less than 10% across the studies. Response rate, overall and progression-free survival values were similar, although values from the Asian studies for each of these parameters were slightly higher. Asian patients had higher rates of hematologic toxicities but lower rates of other adverse events. CONCLUSION: Examination of the data from three studies of the gemcitabine-paclitaxel combination reveals no clinically significant ethnic differences in efficacy and safety between East Asian patients and their global counterparts. Given its demonstrated efficacy and safety profile, the gemcitabine-paclitaxel regimen should be one of the standard treatments for East Asian patients with metastatic breast cancer. PMID- 24175967 TI - Variance of a potential of mean force obtained using the weighted histogram analysis method. AB - A potential of mean force (PMF) that provides the free energy of a thermally driven system along some chosen reaction coordinate (RC) is a useful descriptor of systems characterized by complex, high dimensional potential energy surfaces. Umbrella sampling window simulations use potential energy restraints to provide more uniform sampling along a RC so that potential energy barriers that would otherwise make equilibrium sampling computationally difficult can be overcome. Combining the results from the different biased window trajectories can be accomplished using the Weighted Histogram Analysis Method (WHAM). Here, we provide an analysis of the variance of a PMF along the reaction coordinate. We assume that the potential restraints used for each window lead to Gaussian distributions for the window reaction coordinate densities and that the data sampling in each window is from an equilibrium ensemble sampled so that successive points are statistically independent. Also, we assume that neighbor window densities overlap, as required in WHAM, and that further-than-neighbor window density overlap is negligible. Then, an analytic expression for the variance of the PMF along the reaction coordinate at a desired level of spatial resolution can be generated. The variance separates into a sum over all windows with two kinds of contributions: One from the variance of the biased window density normalized by the total biased window density and the other from the variance of the local (for each window's coordinate range) PMF. Based on the desired spatial resolution of the PMF, the former variance can be minimized relative to that from the latter. The method is applied to a model system that has features of a complex energy landscape evocative of a protein with two conformational states separated by a free energy barrier along a collective reaction coordinate. The variance can be constructed from data that is already available from the WHAM PMF construction. PMID- 24175965 TI - Sex differences in the expression of lupus-associated miRNAs in splenocytes from lupus-prone NZB/WF1 mice. AB - BACKGROUND: A majority of autoimmune diseases, including systemic lupus erythematosus (SLE), occur predominantly in females. Recent studies have identified specific dysregulated microRNAs (miRNAs) in both human and murine lupus, implying an important contribution of these miRNAs to lupus pathogenesis. However, to date, there is no study that examined sex differences in miRNA expression in immune cells as a plausible basis for sex differences in autoimmune disease. This study addresses this aspect in NZB/WF1 mice, a classical murine lupus model with marked female bias, and further investigates estrogen regulation of lupus-associated miRNAs. METHODS: The Taqman miRNA assay system was used to quantify the miRNA expression in splenocytes from male and female NZB/WF1 mice at 17-18, 23, and 30 weeks (wks) of age. To evaluate potential estrogen's effect on lupus-associated miRNAs, 6-wk-old NZB/WF1 male mice were orchidectomized and surgically implanted with empty (placebo) or estrogen implants for 4 and 26 wks, respectively. To assess the lupus status in the NZB/WF1 mice, serum anti-dsDNA autoantibody levels, proteinuria, and renal histological changes were determined. RESULTS: The sex differences in the expression of lupus-associated miRNAs, including the miR-182-96-183 cluster, miR-155, miR-31, miR-148a, miR-127, and miR 379, were markedly evident after the onset of lupus, especially at 30 wks of age when female NZB/WF1 mice manifested moderate to severe lupus when compared to their male counterparts. Our limited data also suggested that estrogen treatment increased the expression of aforementioned lupus-associated miRNAs, with the exception of miR-155, in orchidectomized male NZB/WF1 mice to a similar level in age-matched intact female NZB/WF1 mice. It is noteworthy that orchiectomy, itself, did not affect the expression of lupus-associated miRNAs. CONCLUSION: To our knowledge, this is the first study that demonstrated sex differences in the expression of lupus-associated miRNAs in splenocytes, especially in the context of autoimmunity. The increased expression of lupus-associated miRNA in female NZB/WF1 mice and conceivably in estrogen-treated orchidectomized male NZB/WF1 mice was associated with lupus manifestation. The notable increase of lupus associated miRNAs in diseased, female NZB/WF1 mice may be a result of both lupus manifestation and the female gender. PMID- 24175968 TI - Anaemia, iron deficiency and a common polymorphism of iron-regulation, TMPRSS6 rs855791, in Rwandan children. AB - Anaemia in children living in sub-Saharan Africa is common, but its causes are diverse. In 545 children below 5 years of age from rural southern Rwanda, we assessed the role of iron deficiency (ID) and of the TMPRSS6 736(V) (rs855791) allele, known to reduce iron status and haemoglobin (Hb) levels, in anaemia and Hb concentrations. Anaemia (Hb <11 g/dl) was present in 34.4% of the children and ID (ferritin <12 ng/ml) in 17.6%. The TMPRSS6 736(V) allele was uncommon (allele frequency, 0.096) and not associated with ID. In multivariate analysis, ID was positively associated with anaemia (adjusted odds ratio, 1.67) to an extent comparable with alpha(+) -thalassaemia, breastfeeding, inflammation and low household income, but the odds were substantially higher in Plasmodium falciparum infection (adjusted odds ratio, 10.3). These findings were verified in a multivariate analysis of Hb concentrations. The TMPRSS6 736(V) allele only tended to be associated with low Hb levels. TMPRSS6 736(V) is comparatively rare among Rwandan children and may only slightly contribute to low Hb concentrations. Preventable causes of anaemia, notably ID and P. falciparum infection, largely outweigh its impact and need to be addressed to improve the haematological status of children in the study area. PMID- 24175969 TI - Oleic acid inhibits lung Na/K-ATPase in mice and induces injury with lipid body formation in leukocytes and eicosanoid production. AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) can emerge from certain pathologies, such as sepsis, fat embolism and leptospirosis, in which the levels of unesterified fatty acids are increased in the patient's plasma. ARDS is characterized by edema formation, and edema resolution occurs mainly due to the pneumocyte Na/K-ATPase activity. As previously described, increased oleic acid (OA) plasma concentrations induce lung injury by interfering with sodium transport. The first aim of this study was to develop a radioactivity-free assay to detect Na,K-ATPase activity ex vivo using a model of OA-induced lung injury in mice. We also investigated the relationship between Na/K-ATPase inhibition and OA induced lung injury using ouabain-induced lung injury as a comparison, because of the well-described effect of ouabain as a Na/K-ATPase inhibitor. METHODS: We developed a Na/K-ATPase assay based on the capture of non-radioactive Rb+ ions by mice lung tissue in the absence or presence of ouabain, a specific Na/K-ATPase inhibitor. Rb+ incorporation into the lung was measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) after lung tissue mineralization. Na/K-ATPase activity was considered as the difference between Rb+ incorporation in the absence and in the presence of ouabain. Bronchoalveolar lavage fluid was collected for lung injury assessment. For this assessment, cell counting, lipid body enumeration and lipid mediator concentrations were measured. Histological analyses were used to determinate lung pathology. Whole body plethysmographic analysis was performed to assay lung function. RESULTS: The lung Na/K-ATPase activity of mice was completely inhibited by an OA dose of 10 MUmol, an effect also obtained with 10-3 MUmol of ouabain, as demonstrated by the decreased Rb+ incorporation in the lungs. The same OA dose induced lung edema and inflammation with cell influx, lipid body formation, and leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) production. Ouabain also induced lung inflammation, as detected by histological examinations. As far as we know, this is the first time that ouabain-induced lung injury was shown. Both OA and ouabain induced functional lung pathology in mice simultaneously with inhibition of the lung Na/K ATPase activity. CONCLUSIONS: We developed a new non-radioactive assay to quantified Na/K-ATPase in vivo. OA and ouabain inhibited in vivo Na/K-ATPase activity in the lungs and induced lung injury. Our data reinforce the idea that Na/K-ATPase inhibitors may worsen lung injury in specific pathological conditions. PMID- 24175970 TI - The capability of endophytic fungi for production of hemicellulases and related enzymes. AB - BACKGROUND: There is an imperative necessity for alternative sources of energy able to reduce the world dependence of fossil oil. One of the most successful options is ethanol obtained mainly from sugarcane and corn fermentation. The foremost residue from sugarcane industry is the bagasse, a rich lignocellulosic raw material uses for the production of ethanol second generation (2G). New cellulolytic and hemicellulytic enzymes are needed, in order to optimize the degradation of bagasse and production of ethanol 2G. RESULTS: The ability to produce hemicellulases and related enzymes, suitable for lignocellulosic biomass deconstruction, was explored using 110 endophytic fungi and 9 fungi isolated from spoiled books in Brazil. Two initial selections were performed, one employing the esculin gel diffusion assay, and the other by culturing on agar plate media with beechwood xylan and liquor from the hydrothermal pretreatment of sugar cane bagasse. A total of 56 isolates were then grown at 29 degrees C on steam-exploded delignified sugar cane bagasse (DEB) plus soybean bran (SB) (3:1), with measurement of the xylanase, pectinase, beta-glucosidase, CMCase, and FPase activities. Twelve strains were selected, and their enzyme extracts were assessed using different substrates. Finally, the best six strains were grown under xylan and pectin, and several glycohydrolases activities were also assessed. These strains were identified morphologically and by sequencing the internal transcribed spacer (ITS) regions and the partial beta-tubulin gene (BT2). The best six strains were identified as Aspergillus niger DR02, Trichoderma atroviride DR17 and DR19, Alternaria sp. DR45, Annulohypoxylon stigyum DR47 and Talaromyces wortmannii DR49. These strains produced glycohydrolases with different profiles, and production was highly influenced by the carbon sources in the media. CONCLUSIONS: The selected endophytic fungi Aspergillus niger DR02, Trichoderma atroviride DR17 and DR19, Alternaria sp. DR45, Annulohypoxylon stigyum DR47 and Talaromyces wortmannii DR49 are excellent producers of hydrolytic enzymes to be used as part of blends to decompose sugarcane biomass at industrial level. PMID- 24175972 TI - Osteoarthritis of the hand II: chemistry, pharmacokinetics and pharmacodynamics of naproxen, and clinical outcome studies. AB - OBJECTIVE: This article aims to review osteoarthritis of the hand and the role of the non-steroidal anti-inflammatory drug (NSAID) naproxen on its management. We discuss the chemical and pharmacological properties of naproxen and the NSAID class, with an emphasis on its mechanism and adverse reactions. In the context of part I of this paper in characterizing hand osteoarthritis (OA), we review clinical trials that have been conducted involving hand OA and naproxen. KEY FINDINGS: The therapeutic effect of NSAIDs stems from its role on inhibiting cyclo-oxygenase (COX)-1 or COX-2 enzyme activity in the body. These enzymes play a major role in maintaining several functions in the body and due NSAIDs' inhibitory effects; many principle adverse reactions occur with the use of NSAIDs such as: gastrointestinal tract issues, cardiovascular risks, renal, hepatic, central nervous system and cutaneous. Review of clinical trials involving naproxen and hand OA show that it is significantly more efficacious when compared with placebo. SUMMARY: These studies, along with the finding that naproxen is of least cardiovascular risk in the NSAID class, may show that it can be part of one of the approaches in managing the condition. It is important to note that the optimal NSAID to use varies for each individual. The finding that the use of naproxen leads to the smallest increase in cardiovascular risk appeals to those at-risk individuals who suffer from OA and require pharmacological treatment for relief. PMID- 24175971 TI - HIV-TAT mediated protein transduction of Cu/Zn-superoxide dismutase-1 (SOD1) protects skin cells from ionizing radiation. AB - BACKGROUND: Radiation-induced skin injury remains a serious concern during radiotherapy. Cu/Zn-superoxide dismutase (Cu/Zn-SOD, SOD1) is a conserved enzyme for scavenging superoxide radical in cells. Because of the integrity of cell membranes, exogenous molecule is not able to be incorporated into cells, which limited the application of natural SOD1. The aim of this study was to evaluate the protective role of HIV-TAT protein transduction domain mediated protein transduction of SOD1 (TAT-SOD1) against ionizing radiation. METHODS: The recombinant TAT-SOD1 and SOD1 were obtained by prokaryotic-based protein expression system. The transduction effect and biological activity of TAT-SOD1 was measured by immunofluorescence and antioxidant capability assays in human keratinocyte HaCaT cells. Mito-Tracker staining, reactive oxygen species (ROS) generation assay, cell apoptosis analysis and malondialdehyde (MDA) assay were used to access the protective effect of TAT- SOD1. RESULTS: Uptake of TAT-SOD1 by HaCaT cells retained its biological activity. Compared with natural SOD1, the application of TAT-SOD1 significantly enhanced the viability and decreased the apoptosis induced by X-ray irradiation. Moreover, TAT-SOD1 reduced ROS and preserved mitochondrial integrity after radiation exposure in HaCaT cells. Radiation-induced gammaH2AX foci, which are representative of DNA double strand breaks, were decreased by pretreatment with TAT-SOD1. Furthermore, subcutaneous application of TAT-SOD1 resulted in a significant decrease in 45 Gy electron beam induced ROS and MDA concentration in the skins of rats. CONCLUSIONS: This study provides evidences for the protective role of TAT-SOD1 in alleviating radiation induced damage in HaCaT cells and rat skins, which suggests a new therapeutic strategy for radiation-induced skin injury. PMID- 24175974 TI - Control of hyperbranched structure of polycaprolactone/poly(ethylene glycol) polyurethane block copolymers by glycerol and their hydrogels for potential cell delivery. AB - A series of biodegradable amphiphilic polyurethane block copolymers with hyperbranched structure were synthesized by copolymerizing poly(epsilon caprolactone) (PCL) and poly(ethylene glycol) (PEG) together with glycerol. The copolymers were characterized, and their composition and branch length were varied with the feeding ratio between PCL, PEG, and glycerol used. Hydrogels were formed from these copolymers by swelling of water at low polymer concentrations. The hydrogels were thixotropic, and their dynamic viscoelastic properties were dependent on the copolymer composition, branch length, and polymer concentration. Hydrolytic degradation of the hydrogels was evaluated by mass loss and changes in molecular structures. The porous morphology of the hydrogels provided good permeability for gas and nutrition. Together with the tunable rheological properties, the hydrogels were found to be suitable for 3D living cell encapsulation and delivery. The morphology of the solid copolymers was semicrystalline, while the hydrogels were totally amorphous without crystallinity, providing a mild aqueous environment for living cells. When the encapsulated cells were recovered from the hydrogels followed by subculture, they showed good cell viability and proliferation ability. The results indicate that the hyperbranched copolymers hydrogels developed in this work may be promising candidates for potential injectable cell delivery application. PMID- 24175973 TI - Perindopril treatment promote left ventricle remodeling in patients with heart failure screened positive for autoantibodies against angiotensin II type 1 receptor. AB - BACKGROUND: Autoantibodies specific to the angiotensin II type I receptor (anti AT1-AR) have been implicated in the pathology of congestive heart failure (CHF). Anti-AT1-AR may be associated with left ventricular function in CHF patients treated with perindopril. METHODS: Synthetic angiotensin II type 1 receptor (AT1 R) peptides served as the target antigen. ELISA was used to screen the sera of 156 CHF patients, which were divided into positive and negative groups based on their anti-AT1-AR reactivity. Echocardiography and a 6-minute walk test were performed at baseline and after one year of perindopril therapy. The end-point events were compared over a 5-year follow-up. RESULTS: Final analysis covered 138 patients, including 82 positive and 56 negative. The frequency and geometric mean titre of anti-AT1-AR were significantly lower in the positive group after one year of treatment (all P < 0.01, from 100% to 73.2% and from 1:125.3 +/- 1.0 to 1:69.2 +/- 1.1). Of these, 22 patients showed no antibodies. Both groups showed improvement in left ventricular end-diastole, end-systolic dimensions, ejection fraction, and a 6-minute walk test by perindopril in combination with standard treatment regime for one year (all P < 0.01). However, the 82 patients positive for anti-AT1-AR showed more pronounced improvement than the 56 negative patients (all P < 0.05). However, after 5 years of follow-up, the rate of all causes and cardiovascular mortality attributable to any cause and the re-hospitalisation rate showed no significant differences between the two groups (all P > 0.05). CONCLUSIONS: Perindopril treatment significantly decreased the frequency and geometric mean titre in patients positive for anti-AT1-AR, even to complete ablation. These patients showed greater improvement in left ventricular remodeling and heart function than negative that in patients after one year of perindopril treatment in combination with standard treatment, but no significant differences in endpoint events were observed in the following 5 years. Anti-AT1 AR might be a useful biomarker of over-activation of the renin-angiotensin aldosterone system for clinical medication. PMID- 24175975 TI - Neoadjuvant intra-arterial chemotherapy in advanced laryngeal and hypopharyngeal cancer. AB - AIM: To investigate whether neoadjuvant intra-arterial chemotherapy down-stages the tumors and predicts ultimate outcome in patients with advanced laryngeal and hypopharyngeal cancer. METHODS: Fifteen patients with stage III and IV cancers received two cycles of intra-arterial cisplatin (40 mg/m(2)) at days 1 and 15, infused super-selectively into superior thyroid artery. Interim evaluation using RECIST 1.1 and volumetry was done in all patients at day 25. Subsequently, the patients received concurrent chemoradiotherapy or surgery with radiotherapy. Final evaluation was done in 10 patients. RESULTS: At interim evaluation, five patients qualified as responders. Partial response, stable disease and progressive disease rates were 40, 33 and 27%, respectively. At final evaluation, complete response was noted in all patients. CONCLUSIONS: At interim evaluation, the response rates were lower compared to intravenous neoadjuvant chemotherapy and response to intra-arterial chemotherapy did not predict the ultimate outcome. Thus neoadjuvant intra-arterial chemotherapy offers no advantage over concurrent chemoradiotherapy. PMID- 24175976 TI - Design and evaluation of folate-appended alpha-, beta-, and gamma-cyclodextrins having a caproic acid as a tumor selective antitumor drug carrier in vitro and in vivo. AB - We reported that per-6-folic acid (FA)-appended beta-cyclodextrin (beta-CyD) possessing two caproic acids between FA and a beta-CyD molecule as a spacer (Fol c2-beta-CyD) could be useful as a promising antitumor drug carrier. However, the effects of the cavity size and the spacer length on the carrier ability are not still known. In this study, we designed and evaluated the FA-appended three kinds of CyDs possessing a caproic acid as a spacer between FA and a CyD molecule (Fol c1-CyDs) as a tumor targeting carrier for antitumor drugs. The stability constant of the Fol-c1-beta-CyD/doxorubicin (DOX) complex was much higher than those of Fol-c1-alpha-CyD and Fol-c1-gamma-CyD at pH 7.3. Antitumor activity of DOX was increased by the complexation with Fol-c1-beta-CyD, but not with Fol-c1-alpha-CyD or Fol-c1-gamma-CyD in KB cells, a folate receptor-alpha-positive cell line. Also, Fol-c1-beta-CyD increased antitumor activities of paclitaxel and vinblastine, but not 5-fluorouracil. Furthermore, Fol-c1-beta-CyD accelerated cellular uptake of DOX and inhibited its efflux from KB cells. The Fol-c1-beta CyD/DOX complex showed much higher antitumor activity than DOX alone after intratumoral and intravenous administrations to tumor-bearing mice with a negligible change of the blood chemistry values. These findings suggest that Fol c1-beta-CyD could be useful as a tumor-selective carrier for antitumor drugs. PMID- 24175977 TI - MG53's new identity. AB - Mitsugumin 53 (MG53) is a relatively newly identified tripartite motif-containing (TRIM) family muscle-specific E3 ubiquitin ligase that is expressed in skeletal muscle and the heart. It has been postulated to facilitate repair by targeting the site of an injury, and acting as a scaffold for assembly of a repair complex made up of dysferlin, annexin V, caveolin-3, and polymerase I and transcript release factor (PTRF). A recent letter published in Nature by Song et al. proposes an alternate function for MG53: as an E3 ligase that targets the insulin receptor and insulin receptor substrate 1 (IRS1) for degradation, therefore regulating muscle insulin signaling. This work is exciting, as it not only presents a novel role for MG53, but also suggests that muscle insulin signaling has a systemic influence on insulin resistance and the metabolic syndrome. PMID- 24175978 TI - Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment. AB - INTRODUCTION: While current treatment for acute myeloid leukemia is characterized by high response rates, patients' long-term outcome is still disappointing, due to frequent relapse and ineligibility of the often elderly patients for stem cell transplantation approaches. Considerable efforts have, thus, been made to incorporate immunotherapeutic approaches in the acute myeloid leukemia (AML) consolidation, with so far disappointing clinical benefit. The B7 family ligand programmed-death receptor-ligand 1 (PD-L1, B7-H1, CD274) has been recently described (with conflicting results) to be expressed on AML blast cells, and interaction with its receptor on T cells, programmed death receptor-1 (PD-1, CD279), has been shown to suppress T-cell functions and to allow survival of dormant AML cells in animal models. DESIGN AND METHODS: In this work, we analyzed freshly isolated myeloid precursor cells from healthy donors and from AML patients for PD-L1 expression with or without interferon-gamma exposure at different time points during their treatment. RESULTS: While without IFN exposure, only minor differences were observed, we found IFN-gamma-induced PD-L1 expression most prominent after initial treatment and independent of treatment outcome. CONCLUSIONS: Our observations support the recently suggested PD-L1 mediated adaptive immune resistance and argue for a targeting of the PD-L1/PD-1 pathway during the consolidation phase of AML treatment. PMID- 24175979 TI - Suppression of mast cell activity contributes to the osteoprotective effect of an herbal formula containing Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae. AB - OBJECTIVES: Mast cells are believed to contribute to the pathogenesis of osteoporosis as their number is increased in osteoporotic bones. Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae are three Chinese herbs traditionally for tonifying the 'kidney system' and a herbal formula (ELP) containing the respective herbs at the weight ratio of 5 : 4 : 1 was shown to prevent osteoporosis. This study evaluated if suppression of mast cell accumulation and activity contribute to the anti-osteoporotic action of ELP. METHODS: The herbs were boiled under reflux to produce the aqueous extract that was further concentrated under reduced pressure and lyophilized. An in-vivo rat osteoporosis model using hind limb unloading was employed for studying the accumulation of mast cells. The human mast cell line, LAD2, was employed to evaluate the mast cell modulating action of ELP. KEY FINDINGS: Mast cell number in the tibiae of hind limb unloaded rats increased significantly during the course of osteoporosis. ELP treatment (10 g/kg/day) prevented both osteoporosis and mast cell accumulation in these rats. Furthermore, ELP significantly inhibited histamine and tumour necrosis factor-alpha release from LAD2 cells. CONCLUSION: Mast cells contributed to hormone independent osteoporosis. The suppression of mast cell accumulation and activation may contribute to the anti osteoporotic action of ELP. PMID- 24175980 TI - Use of pedometer-driven walking to promote physical activity and improve health related quality of life among meat processing workers: a feasibility trial. AB - BACKGROUND: Current evidence supports the use of pedometers as effective motivational tools to promote physical activity and improve health-related quality of life in the general population. The aims of this study are to examine whether a pedometer-driven walking programme can improve health-related quality of life, and increase ambulatory activity in a population of meat processing workers when compared to a control group receiving educational material alone. METHODS/DESIGN: A feasibility study employing a randomized controlled trial (RCT) design will collect data at three time points. A sample of up to 60 meat workers will be recruited and randomly assigned to either an intervention group N = 30 (12-week pedometer-driven walking program, brief intervention, and educational material), or control group N = 30 (educational material only). The primary outcomes of ambulatory activity, health-related quality of life, and functional capacity, will be evaluated at baseline, immediately following the 12-week intervention and then at three month post-intervention. DISCUSSION: This paper describes the design of a feasibility randomized controlled trial, which aims to assess the effectiveness of the introduction of a workplace pedometer-driven walking program compared to normal lifestyle advice in meat processing workers. TRIAL REGISTRATION NUMBER (ANZCTR): 12613000087752. PMID- 24175981 TI - Dietary supply with polyunsaturated fatty acids and resulting maternal effects influence host--parasite interactions. AB - BACKGROUND: Interactions between hosts and parasites can be substantially modulated by host nutrition. Polyunsaturated fatty acids (PUFAs) are essential dietary nutrients; they are indispensable as structural components of cell membranes and as precursors for eicosanoids, signalling molecules which act on reproduction and immunity. Here, we explored the potential of dietary PUFAs to affect the course of parasitic infections using a well-established invertebrate host - parasite system, the freshwater herbivore Daphnia magna and its bacterial parasite Pasteuria ramosa. RESULTS: Using natural food sources differing in their PUFA composition and by experimentally modifying the availability of dietary arachidonic acid (ARA) and eicosapentaenoic acid (EPA) we examined PUFA-mediated effects resulting from direct consumption as well as maternal effects on offspring of treated mothers. We found that both host and parasite were affected by food quality. Feeding on C20 PUFA-containing food sources resulted in higher offspring production of hosts and these effects were conveyed to a great extent to the next generation. While feeding on a diet containing high PUFA concentrations significantly reduced the likelihood of becoming infected, the infection success in the next generation increased whenever the maternal diet contained PUFAs. We suggest that this opposing effect was caused by a trade-off between reproduction and immunity in the second generation. CONCLUSIONS: Considering the direct and maternal effects of dietary PUFAs on host and parasite we propose that host - parasite interactions and thus disease dynamics under natural conditions are subject to the availability of dietary PUFAs. PMID- 24175982 TI - Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer. AB - BACKGROUND: Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT. METHODS: Patients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients. RESULTS: Twelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years. CONCLUSIONS: This study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming. PMID- 24175983 TI - How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations?: A study in Polish primary care. AB - BACKGROUND: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. METHODS: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual's CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects' self-care behavior was examined. RESULTS: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. CONCLUSIONS: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR. PMID- 24175984 TI - Interaction of proteins associated with the magnetosome assembly in magnetotactic bacteria as revealed by two-hybrid two-photon excitation fluorescence lifetime imaging microscopy Forster resonance energy transfer. AB - Bacteria have recently revealed an unexpectedly complex level of intracellular organization. Magnetotactic bacteria represent a unique class of such organization through the presence of their magnetosome organelles, which are organized along the magnetosome filament. Although the role of individual magnetosomes-associated proteins has started to be unraveled, their interaction has not been addressed with current state-of-the-art optical microscopy techniques, effectively leaving models of the magnetotactic bacteria protein assembly arguable. Here we report on the use of FLIM-FRET to assess the interaction of MamK (actin-like protein) and MamJ, two magnetosome membrane associated proteins essential to the assembly of magnetosomes in a chain. We used a host organism (E. coli) to express eGFP_MamJ and MamK_mCherry, the latest expectedly forming a filament. We found that in the presence of MamK the fluorescence of eGFP_MamJ is distributed along the MamK filament. FRET analysis using the fluorescence lifetime of the donor, eGFP, revealed a spatial proximity of MamK_mCherry and eGFP_MamJ typical of a stable physical interaction between two proteins. Our study effectively led to the reconstruction of part of the magnetotactic apparatus in vivo. PMID- 24175985 TI - Glycated nail proteins: a new approach for detecting diabetes in developing countries. AB - OBJECTIVE: To assess glycation of nail proteins as a tool in the diagnosis of diabetes. METHODS: Glycation of nail proteins was assessed using a modified photometric nitroblue tetrazolium-based assay, which provides information about average glucose values of the last 6-9 months. Analysis is possible on 10 mg of nail clippings with a within-run coefficient of variation (CV) of 11%. The analyte is extremely stable. The reference range for glycated nail protein (0.55 3.60 MUmol/g nail) increases upon ageing. RESULTS: In diabetics (n = 112), values for glycated nail protein are significantly higher (median: 4.07 MUmol/g nail, IQR: 2.37-6.89 MUmol/g nail, P < 0.0001) than in non-diabetics (n = 116). ROC analysis shows an AUC of 0.848 (specificity 93.1%; sensitivity 68.9%). CONCLUSION: This affordable method is a simple alternative for diagnosing diabetes in remote areas as the pre-analytical phase (including all processes from the time a laboratory request is made by a physician until the sample is ready for testing) is extremely robust. PMID- 24175986 TI - Comparison of serial serum ferritin measurements and liver iron concentration assessed by MRI in adult transfused patients with sickle cell disease. AB - AIMS: Transfused patients with sickle cell disease (SCD) are at risk of iron overload and identifying such patients is important to prevent associated complications. Our aim was to assess the efficacy of serial serum ferritin (SF) measurements in identifying patients with hepatic iron overload as assessed by liver MRI and its usefulness in guiding decision making regarding chelation therapy. PATIENTS/METHODS: We retrospectively compared the results of 49 liver MRI scans (LS) with the median serum ferritin (MSF) values for 28 patients in our institution. RESULTS: We found a nonlinear increment of MSF with increasing liver iron concentration (LIC). 18.4% and 47.4% of abnormal LSs corresponded to MSF <1000 mcg/L and <2000 mcg/L, respectively. 30.4% of patients with LIC of 7 mg/g dry weight or higher had a MSF <2000 mcg/L. In 38.5% of patients receiving chelation, MSF offered little information regarding the efficacy of treatment and was sometimes misleading. CONCLUSION: Serial serum ferritin measurements in adult transfused patients with sickle cell disease have a low sensitivity for identifying patients with iron overload and are of limited value in guiding decision making regarding initiation or monitoring of chelation therapy. The iron status of such high risk patients should be assessed by more definitive ways such as MRI. PMID- 24175987 TI - Cerebral radiation necrosis. AB - Cerebral radiation-induced injury ranges from acute reversible edema to late irreversible radiation necrosis (RN). Cerebral RN is poorly responsive to treatment, is associated with permanent neurological deficits and occasionally progresses to death. We review the literature regarding cerebral RN after radiotherapy for various brain and head and neck lesions and discuss its clinical features, imaging characteristics, pathophysiology and treatment. For new enhancing lesions on computed tomography or magnetic resonance imaging, apart from tumor progression or recurrence, RN needs to be considered in the differential diagnosis. Further studies are required to design chemoradiotherapy protocols that are effective in treating tumors while minimizing risk of RN. Current available treatments for RN, steroid and surgery, only relieve the mass effect. None of the experimental treatments to date have consistently been shown to reverse the pathologic process of RN. PMID- 24175988 TI - General strategy for ordered noncovalent protein assembly on well-defined nanoscaffolds. AB - Here we develop a novel approach allowing the noncovalent assembly of proteins on well-defined nanoscaffolds such as virus particles. The antibody-binding peptide Z33 was genetically fused to the monomeric yellow fluorescent protein and 4 coumarate:CoA-ligase 2. This Z33 "tag" allowed their patterning on the surface of zucchini yellow mosaic virus by means of specific antibodies directed against the coat protein of the virus. The approach was validated by affinity assays and correlative microscopy. The coverage efficiency was ~ 87%. Fluorescence and enzymatic activity were fully retained after assembly. The principle of using the combination of a scaffold-specific antibody and Z33-fusion proteins can be extended to a wide variety of proteins/enzymes and antigenic scaffolds to support coupling for creating functional "biochips" with optical or catalytic properties. PMID- 24175990 TI - Interrelationships between maternal DHA in erythrocytes, milk and adipose tissue. Is 1 wt% DHA the optimal human milk content? Data from four Tanzanian tribes differing in lifetime stable intakes of fish. AB - Little is known about the interrelationships between maternal and infant erythrocyte-DHA, milk-DHA and maternal adipose tissue (AT)-DHA contents. We studied these relationships in four tribes in Tanzania (Maasai, Pare, Sengerema and Ukerewe) differing in their lifetime intakes of fish. Cross-sectional samples were collected at delivery and after 3 d and 3 months of exclusive breast feeding. We found that intra-uterine biomagnification is a sign of low maternal DHA status, that genuine biomagnification occurs during lactation, that lactating mothers with low DHA status cannot augment their infants' DHA status, and that lactating mothers lose DHA independent of their DHA status. A maternal erythrocyte-DHA content of 8 wt% was found to correspond with a mature milk-DHA content of 1.0 wt% and with subcutaneous and abdominal (omentum) AT-DHA contents of about 0.39 and 0.52 wt%, respectively. Consequently, 1 wt% DHA might be a target for Western human milk and infant formula that has milk arachidonic acid, EPA and linoleic acid contents of 0.55, 0.22 and 9.32 wt%, respectively. With increasing DHA status, the erythrocyte-DHA content reaches a plateau of about 9 wt%, and it plateaus more readily than milk-DHA and AT-DHA contents. Compared with the average Tanzanian-Ukerewe woman, the average US woman has four times lower AT-DHA content (0.4 v. 0.1 wt%) and five times lower mature milk-DHA output (301 v. 60 mg/d), which contrasts with her estimated 1.8-2.6 times lower mobilisable AT-DHA content (19 v. 35-50 g). PMID- 24175989 TI - The impact of frailty on oral care behavior of older people: a qualitative study. AB - BACKGROUND: Frailty has been demonstrated to negatively influence dental service use and oral self-care behavior of older people. The aim of this study was to explore how the type and level of frailty affect the dental service-use and oral self-care behavior of frail older people. METHODS: We conducted a qualitative study through 51 open interviews with elders of varying frailty in the East Netherlands, and used a thematic analysis to code transcripts, discussions and reviews of the attributes and meaning of the themes to the point of consensus among the researchers. RESULTS: Three major themes and five sub-themes emerged from our analyses. The major themes indicate that frail elders: A) favor long established oral hygiene routines to sustain a sense of self-worth; B) discontinue oral hygiene routines when burdened by severe health complaints, in particular chronic pain, low morale and low energy; and C) experience psychological and social barriers to oral health care when institutionalized. The subthemes associated with the discontinuation of oral care suggest that the elders accept more oral pain or discomfort because they: B1) lack belief in the results of dental visits and tooth cleaning; B2) trivialize oral health and oral care in the general context of their impaired health and old age; and B3) consciously use their sparse energy for priorities other than oral healthcare. Institutionalized elderly often discontinue oral care because of C1) disorientation and C2) inconveniencing social supports. CONCLUSION: The level and type of frailty influences people's perspectives on oral health and related behaviors. Frail elders associate oral hygiene with self-worth, but readily abandon visits to a dentist unless they feel that a dentist can relieve specific problems. When interpreted according to the Motivational Theory of Life Span Development, discontinuation of oral care by frail elderly could be viewed as a manifestation of adaptive development. Simple measures aimed at recognizing indicators for poor oral care behavior, and providing appropriate information and support, are discussed. PMID- 24175991 TI - The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors. AB - Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 +/- 0.06 vs. 0.20 +/- 0.03%, p < 0.001) and red cell distribution width (16.11 +/- 3.04 vs. 13.41 +/- 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 +/- 0.06 vs. 0.21 +/- 0.04%, p = 0.220) and mean platelet volume (8.94 +/- 1.44 vs. 8.68 +/- 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I. PMID- 24175992 TI - Risk factors for early postoperative cognitive dysfunction after non-coronary bypass surgery in Chinese population. AB - BACKGROUND: The present study was performed to investigate the incidence of early postoperative cognitive dysfunction (POCD) after non-coronary bypass surgery and the potential risk factors in Chinese population. METHODS: We performed a prospective study in a teaching tertiary hospital from May 2012 to August 2012. One hundred and seventy-six adult patients undergoing non-coronary bypass surgery were recruited. Mini-Mental State Examination (MMSE) score was evaluated before and 3 to 5 days after surgery. Patients with a MMSE score reduction of 2 was diagnosed with POCD. RESULTS: The general incidence of POCD was 33.0%, with no significant difference between the types of surgeries. In the univariate analysis, POCD associated factors included age, duration of surgery, anesthesia, cardiopulmonary bypass (CPB), cross-clamp and rewarming, and sevoflurane concentration. However, only age, cross-clamp duration and sevoflurane concentration were demonstrated to be independent risk factors for POCD. CONCLUSION: Incidence of early POCD after non-coronary bypass surgery was relatively high in Chinese population. Advanced age, longer aortic cross-clamp duration and lower sevoflurane concentration was associated with a higher incidence of POCD. PMID- 24175993 TI - Genome-wide binding of the basic helix-loop-helix myogenic inhibitor musculin has substantial overlap with MyoD: implications for buffering activity. AB - BACKGROUND: Musculin (MSC) is a basic helix-loop-helix transcription factor that inhibits myogenesis during normal development and contributes to the differentiation defect in rhabdomyosarcoma. As one of many transcription factors that impede myogenesis, its binding on a genome-wide scale relative to the widespread binding of the myogenic factor MyoD is unknown. METHODS: Chromatin immunoprecipitation coupled to high-throughput sequencing was performed for endogenous MSC in rhabdomyosarcoma cells and its binding was compared to that of MyoD in the same type of cells. RESULTS: MSC binds throughout the genome, in a pattern very similar to MyoD. Its binding overlaps strongly with regions enriched for acetylated histone H4, as well as regions that score high for DNase hypersensitivity in human myoblasts. In contrast to MyoD, MSC has a more relaxed binding sequence preference in the nucleotides that flank the core E-box motif. CONCLUSIONS: The myogenic inhibitor MSC binds throughout the genome of rhabdomyosarcoma cells, in a pattern highly similar to that of MyoD, suggesting a broad role in buffering the activity of MyoD in development and rhabdomyosarcomas. PMID- 24175994 TI - Family planning in Guinea: a need for better public commitment. AB - OBJECTIVE: To describe the evolution of family planning (FP) in Guinea and to identify strengths, weaknesses, opportunities and threats of the current FP programme. METHODS: Descriptive study of the evolution of FP in Guinea between 1992 and 2010. First, national laws as well as health policies and strategic plans related to reproductive health and family planning were reviewed. Second, FP indicators were extracted from the Guinean Demographic and Health Surveys (1992, 1999 and 2005). Third, FP services, sources of supply and data on FP funding were analysed. RESULTS: Laws, policies and strategic plans in Guinea are supportive of FP programme and services. Public and private actors are not sufficiently coordinated. The general government expenditure on health has remained stable at 6-7% between 2005 and 2011 despite a doubling of total expenditures on health, and contraceptives are supplied by foreign aid. Modern contraceptive prevalence slightly increased from 1.5% in 1992 to 6.8% in 2005 among women aged 15-49. CONCLUSION: A stronger national engagement in favour of repositioning FP should result in improved government funding of the FP programme and the promotion of long-acting and permanent methods. PMID- 24175995 TI - Calculation of the intrinsic solvation free energy profile of an ionic penetrant across a liquid-liquid interface with computer simulations. AB - We introduce the novel concept of an intrinsic free energy profile, allowing one to remove the artificial smearing caused by thermal capillary waves, which renders difficulties for the calculation of free energy profiles across fluid interfaces in computer simulations. We apply this concept to the problem of a chloride ion crossing the interface between water and 1,2-dichloroethane and show that the present approach is able to reveal several important features of the free energy profile which are not detected with the usual, nonintrinsic calculations. Thus, in contrast to the nonintrinsic profile, a free energy barrier is found at the aqueous side of the (intrinsic) interface, which is attributed to the formation of a water "finger" the ion pulls with itself upon approaching the organic phase. Further, by the presence of a nonsampled region, the intrinsic free energy profile clearly indicates the coextraction of the first hydration shell water molecules of the ion when entering the organic phase. PMID- 24175996 TI - Kinetics of photosynthetic response to ultraviolet and photosynthetically active radiation in Synechococcus WH8102 (cyanobacteria). AB - The picoplanktonic cyanobacteria, Synechococcus spp., (Nageli) are important contributors to global ocean primary production that can be stressed by solar radiation, both in the photosynthetically active (PAR) and ultraviolet (UV) range. We studied the responses of PSII quantum yield (active fluorescence), carbon fixation ((14)C assimilation) and oxygen evolution (membrane inlet mass spectrometry) in Synechococcus WH8102 under moderate UV and PAR. PSII quantum yield decreased during exposure to moderate UV and UV+PAR, with response to the latter being faster (6.4 versus 2.8 min, respectively). Repair processes were also faster when UV+PAR exposure was followed by moderate PAR (1.68 min response time) than when UV was followed by very low PAR (10.5 min response time). For the UV+PAR treatment, the initial decrease in quantum yield was followed by a 50% increase ("rebound") after 7 min exposure, showing an apparent photoprotection induction. While oxygen uptake increased with PAR, it did not change under UV, suggesting that this oxygen-dependent mechanism of photoprotection, which may be acting as an electron sink, is not an important strategy against UV. We used propyl gallate, an antioxidant, to test for plastid terminal oxidase (ptox) or ptox-like enzymes activity, but it caused nonspecific and toxic effects on Synechococcus WH8102. PMID- 24175997 TI - Factors associated with receipt of adjuvant chemotherapy among married women with breast cancer. AB - BACKGROUND: Adjuvant chemotherapies are recommended for most women after breast cancer surgery, and can greatly affect the patients' survival. We describe and evaluate possible factors influencing receipt of postoperative adjuvant chemotherapy among breast cancer patients in China. METHODS: A total of 1,431 women diagnosed with breast cancer from 1997 to 2005 were enrolled. We reviewed medical records and abstracted information about these patients. Details on social-demographic factors and clinical-pathological characteristics of participants were collected and analyzed. To meet our objectives, the patient's age at diagnosis, comorbidities, menstrual status, rural/urban status, tumor size, lymph node status, distant metastasis, tumor stage and hormone receptor status were estimated. RESULTS: Overall, 936 of these 1,431 patients (65.41%) received adjuvant chemotherapy. Receipt of chemotherapy was significantly associated with age at diagnosis, rural-urban disparities, and lymph node status of patients, though no significant difference was found between the age <50 and age 50 to 64 groups. Moderate association was also observed between hormone receptor status and receipt of adjuvant chemotherapy, though it was still not statistically significant. CONCLUSIONS: Our study suggests that age at diagnosis, rural-urban disparities and lymph node status of breast cancer patients are independent predictors for receipt of adjuvant chemotherapy among married Chinese women. Further investigations are warranted, and related public health education needs to be expanded in China. PMID- 24175998 TI - Understanding the relationship between stress, distress and healthy lifestyle behaviour: a qualitative study of patients and general practitioners. AB - BACKGROUND: The process of initiating and maintaining healthy lifestyle behaviours is complex, includes a number of distinct phases and is not static. Theoretical models of behaviour change consider psychological constructs such as intention and self efficacy but do not clearly consider the role of stress or psychological distress. General practice based interventions addressing lifestyle behaviours have been demonstrated to be feasible and effective however it is not clear whether general practitioners (GPs) take psychological health into consideration when discussing lifestyle behaviours. This qualitative study explores GPs' and patients' perspectives about the relationship between external stressors, psychological distress and maintaining healthy lifestyle behaviours. METHODS: Semi-structured telephone interviews were conducted with 16 patients and 5 GPs. Transcripts from the interviews were thematically analysed and a conceptual model developed to explain the relationship between external stressors, psychological distress and healthly lifestyle behaviours. RESULTS: Participants were motivated to maintain a healthy lifestyle however they described a range of external factors that impacted on behaviour in both positive and negative ways, either directly or via their impact on psychological distress. The impact of external factors was moderated by coping strategies, beliefs, habits and social support. In some cases the process of changing or maintaining healthy behaviour also caused distress. The concept of a threshold level of distress was evident in the data with patients and GPs describing a certain level of distress required before it negatively influenced behaviour. CONCLUSION: Maintaining healthy lifestyle behaviours is complex and constantly under challenge from external stressors. Practitioners can assist patients with maintaining healthy behaviour by providing targeted support to moderate the impact of external stressors. PMID- 24176000 TI - Safety and accuracy of core biopsy in retroperitoneal sarcomas. AB - AIM: Retroperitoneal sarcomas (RPSs) are large, rare tumors. The role of core biopsy for retroperitoneal masses identified by preoperative imaging is unclear and we report the safety and accuracy of core biopsies at a specialized sarcoma unit in Sydney, Australia. METHODS: A retrospective analysis of a prospectively collected database was performed to identify the safety and accuracy of core biopsies in patients who were confirmed to have RPS. RESULTS: Twenty-two patients underwent biopsies with no recorded morbidity or tumor seeding. RPS was correctly identified in 82%. Median follow-up was 19 months. CONCLUSION: We demonstrate that core biopsy is safe and can identify RPSs. PMID- 24176001 TI - Do pilocarpine drops help dry mouth in palliative care patients: a protocol for an aggregated series of n-of-1 trials. AB - BACKGROUND: It is estimated that 39,000 Australians die from malignant disease yearly. Of these, 60% to 88% of advanced cancer patients suffer xerostomia, the subjective feeling of mouth dryness. Xerostomia has significant physical, social and psychological consequences which compromise function and quality of life. Pilocarpine is one treatment for xerostomia. Most studies have shown some variation in individual response to pilocarpine, in terms of dose used, and timing and extent of response.We will determine a population estimate of the efficacy of pilocarpine drops (6 mg) three times daily compared to placebo in relieving dry mouth in palliative care (PC) patients. A secondary aim is to assess individual patients' response to pilocarpine and provide reports detailing individual response to patients and their treating clinician. METHODS/DESIGN: Aggregated n-of-1 trials (3 cycle, double blind, placebo-controlled crossover trials using standardized measures of effect). Individual trials will identify which patients respond to the medication. To produce a population estimate of a treatment effect, the results of all cycles will be aggregated. DISCUSSION: Managing dry mouth with treatment supported by the best possible evidence will improve functional status of patients, and improve quality of life for patients and carers. Using n-of-1 trials will accelerate the rate of accumulation of high grade evidence to support clinical therapies used in PC. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry Number: 12610000840088. PMID- 24176003 TI - Abstracts of the 24th Regional Congress of the International Society of Blood Transfusion in conjunction with the 6th Malaysian National Transfusion Medicine Conference of the Malaysian Blood Transfusion Society. Kuala Lumpur, Malaysia. December 1-4, 2013. PMID- 24176004 TI - Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice. AB - Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-alpha and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3 fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia. PMID- 24176005 TI - Quantum mechanics/molecular mechanics restrained electrostatic potential fitting. AB - We present a quantum mechanics/molecular mechanics (QM/MM) method to evaluate the partial charges of amino acid residues for use in MM potentials based on their protein environment. For each residue of interest, the nearby residues are included in the QM system while the rest of the protein is treated at the MM level of theory. After a short structural optimization, the partial charges of the central residue are fit to the electrostatic potential using the restrained electrostatic potential (RESP) method. The resulting charges and electrostatic potential account for the individual environment of the residue, although they lack the transferable nature of library partial charges. To evaluate the quality of the QM/MM RESP charges, thermodynamic integration is used to measure the pKa shift of the aspartic acid residues in three different proteins, turkey egg lysozyme, beta-cryptogein, and Thioredoxin. Compared to the AMBER ff99SB library values, the QM/MM RESP charges show better agreement between the calculated and experimental pK(a) values for almost all of the residues considered. PMID- 24176002 TI - Audio-visual speech perception: a developmental ERP investigation. AB - Being able to see a talking face confers a considerable advantage for speech perception in adulthood. However, behavioural data currently suggest that children fail to make full use of these available visual speech cues until age 8 or 9. This is particularly surprising given the potential utility of multiple informational cues during language learning. We therefore explored this at the neural level. The event-related potential (ERP) technique has been used to assess the mechanisms of audio-visual speech perception in adults, with visual cues reliably modulating auditory ERP responses to speech. Previous work has shown congruence-dependent shortening of auditory N1/P2 latency and congruence independent attenuation of amplitude in the presence of auditory and visual speech signals, compared to auditory alone. The aim of this study was to chart the development of these well-established modulatory effects over mid-to-late childhood. Experiment 1 employed an adult sample to validate a child-friendly stimulus set and paradigm by replicating previously observed effects of N1/P2 amplitude and latency modulation by visual speech cues; it also revealed greater attenuation of component amplitude given incongruent audio-visual stimuli, pointing to a new interpretation of the amplitude modulation effect. Experiment 2 used the same paradigm to map cross-sectional developmental change in these ERP responses between 6 and 11 years of age. The effect of amplitude modulation by visual cues emerged over development, while the effect of latency modulation was stable over the child sample. These data suggest that auditory ERP modulation by visual speech represents separable underlying cognitive processes, some of which show earlier maturation than others over the course of development. PMID- 24176006 TI - Report of a rare case: occult hemothorax due to blunt trauma without obvious injury to other organs. AB - Traumatic hemothorax commonly occurs accompanied by organ damage, such as rib fractures, lung injury and diaphragm rupture. Our reported patient was a 61-year old man who fell down from a stepladder about 1 meter in height, resulting in a heavy blow to the left abdomen. He consulted a clinic because of left chest pain the next day and was transported to the emergency center of our hospital on diagnosis of hemothorax with hemorrhagic shock.On computed tomography scanning with contrast medium, left hemothorax without rib fracture, diaphragm rupture or obvious organ injury was evident. We found only bleeding to the thoracic space from a branch of the left inferior phrenic artery without involvement of the abdomen. The patient underwent percutaneous angiography and embolization for hemostasis, and subsequently thoracotomy in order to check the active bleeding and remove the hematoma to improve respiratory. As thoracotomy findings, we found damage of a branch of the left inferior phrenic artery to the thoracic space without diaphragm rupture, and sutured the lesion. Such active intervention followed by surgical procedures was effective and should be considered for rare occurrences like the present case. We must consider not only traumatic diaphragm rupture, but also vascular damage by pressure trauma as etiological factors for hemothorax. PMID- 24176008 TI - Platelet and plasma bioactive scaffolds for stem cell differentiation: what are we missing? PMID- 24176007 TI - Potential association of pulmonary tuberculosis with genetic polymorphisms of toll-like receptor 9 and interferon-gamma in a Chinese population. AB - BACKGROUND: Association studies have been employed to investigate the relationships between host single nucleotide polymorphisms (SNPs) and susceptibility to pulmonary Tuberculosis (PTB). However, such candidate genetic markers have not been widely studied in Chinese population, especially with respect to the disease development from latent M. tuberculosis infection (LTBI). METHODS: In this case-control study, 44 candidate SNPs were examined in a total of 600 participants (PTB patients, LTBI controls and healthy controls without M. tuberculosis infection) from Zhengzhou, China. The two groups of controls were frequency matched on gender and age with PTB patients. Genotyping was carried out by the Illumina Golden Gate assay. RESULTS: When comparing PTB patients with LTBI controls but not healthy controls without M. tuberculosis infection, significant associations with disease development were observed for TLR9 1174 A/G, TLR9 1635 A/G and IFNG 2109G/A. The two loci in TLR9 were in LD in our study population (r(2)=0.96, D'=1.00). A combined effect of the genotypes associated with increased risk of PTB (i.e. TLR9 1174G/G and IFNG 2109 A/A) was found when comparing PTB patients with LTBI controls (p=0.004) but not with healthy controls without infection (p=0.433). CONCLUSIONS: Potential associations between TLR9 and IFN-gamma genetic polymorphisms and PTB were observed in a Chinese population which supports further study of the roles played by TLR9/IFN-gamma pathway during the development of PTB. PMID- 24176010 TI - Rhodiola crenulata extract for prevention of acute mountain sickness: a randomized, double-blind, placebo-controlled, crossover trial. AB - BACKGROUND: Rhodiola crenulata (R. crenulata) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet, but no scientific studies have previously examined its effectiveness. We conducted a randomized, double blind, placebo-controlled crossover study to investigate its efficacy in acute mountain sickness prevention. METHODS: Healthy adult volunteers were randomized to 2 treatment sequences, receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and 2 days during mountaineering, before crossing over to the alternate treatment after a 3-month wash-out period. Participants ascended rapidly from 250 m to 3421 m on two separate occasions: December 2010 and April 2011. The primary outcome measure was the incidence of acute mountain sickness, as defined by a Lake Louise score >= 3, with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness, or difficulty sleeping. RESULTS: One hundred and two participants completed the trial. There were no demographic differences between individuals taking Rhodiola-placebo and those taking placebo-Rhodiola. No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups (all 60.8%; adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) = 0.69-1.52). The incidence of severe acute mountain sickness in Rhodiola extract vs. placebo groups was 35.3% vs. 29.4% (AOR = 1.42, 95% CI = 0.90-2.25). CONCLUSIONS: R. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01536288. PMID- 24176011 TI - Pretreatment maximum standardized uptake value on 18F-fluorodeoxyglucose positron emission tomography is a predictor of outcome for stage I non-small cell lung cancer after stereotactic body radiotherapy. AB - AIMS: Stereotactic body radiotherapy (SBRT) is commonly considered an important treatment option for patients with stage I non-small cell lung cancer (NSCLC) who have contraindications for surgery or refuse surgery. Many studies have reported that the maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) of the primary tumor has prognostic value for resected NSCLC. The purpose of this study was to determine whether SUVmax is a predictor of disease-free survival (DFS) in patients with stage I NSCLC after SBRT. METHODS: In all patients, the diagnosis was pathologically or cytologically confirmed. The prescription dose was 48 Gy in four fractions at the isocenter. FDG-PET was performed before SBRT. RESULTS: Twenty-nine patients were enrolled in this study. The median follow-up period was 14 months (range, 2-56 months). Regional lymph node metastasis and distant metastasis were observed in 5 (17%) and 2 (7%), respectively. The median SUVmax was 5.6 (range, 2.2-22.0). DFS at 2 years was significantly different between the low SUVmax (<8.0) and high SUVmax (>=8.0) groups (85 versus 17%). In univariate analysis, SUVmax and gross tumor volume were significantly correlated with DFS. Multivariate analysis included variables with P-values <0.20 and showed that only SUVmax was significantly correlated with DFS. CONCLUSION: Pretreatment SUVmax on FDG-PET predicted the DFS in patients with stage I NSCLC after SBRT. PMID- 24176012 TI - Main considerable factors for correct laboratory test interpretation under DOA treatment. AB - SUMMARY: To avoid misinterpretation and mismanagement clinicians should be aware of the interference of new direct oral anticoagulants (DOA) on coagulation assays. A variety of oral anticoagulants targeting specific coagulation factors has already entered the market, and new indications for DOA will be released each year over the next few years. Due to their heterogeneous mode of action and different pharmacokinetic profile each DOA will vary in its effects on coagulations assays, and it is of current importance to recognize these variable effects.In this summary the main considerable factors for correct laboratory test interpretation under DOA treatment are described. PMID- 24176013 TI - Crystal structure of an HD-GYP domain cyclic-di-GMP phosphodiesterase reveals an enzyme with a novel trinuclear catalytic iron centre. AB - Bis-(3',5') cyclic di-guanylate (c-di-GMP) is a key bacterial second messenger that is implicated in the regulation of many crucial processes that include biofilm formation, motility and virulence. Cellular levels of c-di-GMP are controlled through synthesis by GGDEF domain diguanylate cyclases and degradation by two classes of phosphodiesterase with EAL or HD-GYP domains. Here, we have determined the structure of an enzymatically active HD-GYP domain protein from Persephonella marina (PmGH) alone, in complex with substrate (c-di-GMP) and final reaction product (GMP). The structures reveal a novel trinuclear iron binding site, which is implicated in catalysis and identify residues involved in recognition of c-di-GMP. This structure completes the picture of all domains involved in c-di-GMP metabolism and reveals that the HD-GYP family splits into two distinct subgroups containing bi- and trinuclear metal centres. PMID- 24176015 TI - Spontaneous membrane-translocating peptide adsorption at silica surfaces: a molecular dynamics study. AB - Spontaneous membrane-translocating peptides (SMTPs) have recently been shown to directly penetrate cell membranes. Adsorption of a SMTP, and some engineered extensions, at model silica surfaces is studied herein using fully atomistic molecular dynamics simulations in order to assess their potential to construct novel drug delivery systems. The simulations are designed to reproduce the electric fields above single, siloxide-rich charged surfaces, and the trajectories indicate that the main driving force for adsorption is electrostatic. An increase in the salt concentration slows down but does not prevent adsorption of the SMTP to the surface; it also does not result in peptide desorption, suggesting additional binding via hydrophobic forces. The results are used to design extensions to the peptide sequence which we find enhance adsorption but do not affect the adsorbed conformation. We also investigate the effect of surface hydroxylation on the peptide adsorption. In all cases, the final adsorbed conformations are with the peptide flattened to the surface with arginine residues, which are key to the peptide's function, anchoring it to the surface so that they are not exposed to solution. This conformation could impact their role in membrane translocation and thus has important implications for the design of future drug delivery vehicles. PMID- 24176014 TI - Nonlinear developmental trajectory of fear learning and memory. AB - The transition into and out of adolescence is a unique developmental period during which neuronal circuits are particularly susceptible to modification by experience. Adolescence is associated with an increased incidence of anxiety disorders in humans, and an estimated 75% of adults with fear-related disorders met diagnostic criteria as children and adolescents. Conserved neural circuitry of rodents and humans has facilitated neurodevelopmental studies of behavioral and molecular processes associated with fear learning and memory that lie at the heart of many anxiety disorders. Here, we review the nonlinear developmental aspects of fear learning and memory during a transition period into and out of adolescence and provide a discussion of the molecular mechanisms that may underlie these alterations in behavior. We provide a model that may help to inform novel treatment strategies for children and adolescents with fear-related disorders. PMID- 24176016 TI - Increasing the scale of peroxidase production by Streptomyces sp. strain BSII#1. AB - AIMS: To optimize peroxidase production by Streptomyces sp. strain BSII#1, up to 3 l culture volumes. METHODS AND RESULTS: Peroxidase production by Streptomyces sp. strain BSII#1 was optimized in terms of production temperature and pH and the use of lignin-based model chemical inducers. The highest peroxidase activity (1.30 +/- 0.04 U ml(-1) ) in 10 ml culture volume was achieved in a complex production medium (pH 8.0) at 37 degrees C in the presence of 0.1 mmol l(-1) veratryl alcohol, which was greater than those reported previously. Scale-up to 100 and 400 ml culture volumes resulted in decreased peroxidase production (0.53 +/- 0.10 and 0.26 +/- 0.08 U ml(-1) , respectively). However, increased aeration improved peroxidase production with the highest production achieved using an airlift bioreactor (4.76 +/- 0.46 U ml(-1) in 3 l culture volume). CONCLUSIONS: Veratryl alcohol (0.1 mmol l(-1) ) is an effective inducer of peroxidase production by Streptomyces sp. strain BSII#1. However, improved aeration increased peroxidase production in larger volumes without the use of an inducer, surpassing induced yields in an optimized small-scale process. SIGNIFICANCE AND IMPACT OF THE STUDY: Only a limited number of reports in literature have focused on the up-scaling of bacterial peroxidase production. There remains opportunity for feasible large-scale production of bacterial peroxidases with potentially novel biocatalytic properties. PMID- 24176017 TI - Fibroblast growth factor 19 entry into brain. AB - BACKGROUND: Fibroblast growth factor (FGF)-19, an endocrine FGF protein mainly produced by the ileum, stimulates metabolic activity and alleviates obesity. FGF19 modulates metabolism after either intravenous or intracerebroventricular injection, and its receptor FGFR4 is present in the hypothalamus. This led to the question whether blood-borne FGF19 crosses the blood-brain barrier (BBB) to exert its metabolic effects. METHODS: We determined the pharmacokinetics of FGF19 permeation from blood to brain in comparison with its distribution in peripheral organs. Multiple-time regression analysis after intravenous bolus injection, in situ brain perfusion, and HPLC assays were performed. RESULTS: FGF19 was relatively stable in blood and in the brain compartment. Significant influx was seen in the presence of excess unlabeled FGF19 in blood. This coincided with a slower decline of 125I-FGF19 in blood which suggested there was decreased clearance or peripheral tissue uptake. In support of an altered pattern of peripheral processing of 125I-FGF19 by excess unlabeled FGF19, the high influx to liver was significantly attenuated, whereas the minimal renal uptake was linearly accelerated. In the present setting, we did not detect a saturable transport of FGF19 across the BBB, as the entry rate of 125I-FGF19 was not altered by excess unlabeled FGF19 or its mouse homologue FGF15 during in-situ brain perfusion. CONCLUSION: FGF19 remained stable in the blood and brain compartments for up to 10 min. Its influx to the brain was non-linear, non-saturable, and affected by its blood concentration and distribution in peripheral organs. Liver showed a robust and specific uptake of FGF19 that could be inhibited by the presence of excess unlabeled FGF19, whereas kidney clearance was dose-dependent. PMID- 24176018 TI - Protective immunity against Toxoplasma gondii induced by DNA immunization with the gene encoding a novel vaccine candidate: calcium-dependent protein kinase 3. AB - BACKGROUND: Toxoplasma gondii can infect almost all warm-blood animals including human beings. The plant-like calcium-dependent protein kinases (CDPKs) harbored by T. gondii are involved in gliding motility, cell invasion, egress and some other developmental processes, and so have been implicated as important virulence factors. METHODS: In the present study, we constructed a DNA vaccine expressing T. gondii CDPK3 (TgCDPK3) and evaluated its protective efficacy against T. gondii infection in Kunming mice. The gene sequence encoding TgCDPK3 was inserted into the eukaryotic expression vector pVAX I, and mice were immunized with pVAX-CDPK3 intramuscularly. RESULTS: The results showed that mice immunized with pVAX-CDPK3 developed a high level of specific antibodies and a strong lymphoproliferative response. The significantly increased levels of IFN-gamma, IL-2, IL-12 (p70) and IL-23 and high ratio of IgG2a to IgG1 antibody titers indicated that a Th1 type response was elicited after immunization with pVAX-CDPK3. Furthermore, the percentage of CD4+ T cells in mice vaccinated with pVAX-CDPK3 was significantly increased. After lethal challenge with the tachyzoites of the virulent T. gondii RH strain, the mice immunized with pVAX-CDPK3 prolonged the survival time from 10 days to 24 days (13.5 +/- 4.89) compared to untreated mice or those received PBS or pVAX I which died within 7 days (P < 0.05). In chronic infection model (10 cysts of the T. gondii PRU strain), the numbers of brain cysts of the mice immunized with pVAX-CDPK3 reduced significantly when compared with those in control groups (P < 0.05), and the rate of reduction could reach to about 50%. CONCLUSIONS: TgCDPK3 can generate protective immunity against acute and chronic T. gondii infection in Kunming mice and is a promising vaccine candidate for further development of an effective vaccine against T. gondii. PMID- 24176019 TI - A complex regulatory network controlling intrinsic multidrug resistance in Mycobacterium smegmatis. AB - Mycobacteria are intrinsically resistant to a variety of stresses including many antibiotics. Although a number of pathways have been described to account for the observed resistances, the mechanisms that control the expression of genes required in these processes remain poorly defined. Here we report the role of a predicted anti-sigma factor, MSMEG_6129 and a predicted eukaryotic like serine/threonine protein kinase, MSMEG_5437, in the intrinsic resistance of Mycobacterium smegmatis to a variety of stresses including the genotoxic agent mitomycin C, hydrogen peroxide and at least four different antibiotics - isoniazid, chloramphenicol, erythromycin and tetracycline. We show that MSMEG_5437 influences the phosphorylation state of MSMEG_6129. Further, MSMEG_6129 controls the expression of a plethora of genes including efflux pumps, ABC transporters, catalases and transcription factors, either directly or via regulators like WhiB7, which account for the observed multi-drug resistance phenotypes. MSMEG_6129 in turn phosphorylates a contiguously located putative anti-anti-sigma factor, MSMEG_6127. We therefore propose that MSMEG_5437, MSMEG_6129 and MSMEG_6127 are components of a master regulatory network, upstream of whiB7, that controls the activity of one or more of the 28 sigma factors in M. smegmatis. Together, this network controls the expression of a regulon required for resistance to several unrelated antibiotics. PMID- 24176020 TI - Effect of exercising while fasting on eating behaviors and food intake. AB - BACKGROUND: Alternate day fasting combined with exercise is effective for weight loss. OBJECTIVE: The aim of this study was to examine the behavioral adaptations that occur when ADF is combined with exercise, and to determine how these changes affect weight loss. DESIGN: Obese subjects (n = 64) were randomized to 1 of 4 groups: 1) combination (ADF + endurance exercise), 2) ADF, 3) exercise, or 4) control, for 12 weeks. RESULTS: Body weight decreased (P < 0.05) in the combination group (6 +/- 4 kg), ADF (3 +/- 1 kg), exercise group (1 +/- 0 kg), with no change in the control group (0 +/- 0 kg). When given the choice, subjects chose to exercise the same amount (P = 0.790) on the fast days (48 +/- 2%) as feed days (52 +/- 2%). Percent of exercise sessions performed on fast day mornings (20 +/- 6%) did not differ (P = 0.453) from fast day afternoons (28 +/- 5%). Likeliness to cheat on the fast day was not higher if the subject exercised in the afternoon (17 +/- 7%) versus the morning (10 +/- 5%). Hunger decreased (P < 0.05) while satisfaction and fullness increased (P < 0.05) post-treatment in the ADF group only. Restrained eating increased (P < 0.05) and uncontrolled eating decreased (P < 0.05) in the combination and ADF groups. CONCLUSION: These findings suggest that endurance exercise is an excellent adjunct therapy to ADF, as it leads to positive behavioral changes that may contribute to long-term steady weight loss. PMID- 24176021 TI - Antidepressant-like activity of turmerone in behavioral despair tests in mice. AB - BACKGROUND: The present study was undertaken to evaluate the anti-depressive activity of turmerone after one-week administration by using a mouse forced swimming test (FST) and tail suspension test (TST). METHODS: Animals were divided into four groups (n = 10 /group): control (0.9% saline), the three doses of turmerone (1.25, 2.5, 5.0 mg/kg) for one-week treatment. To assess the effect of turmerone on locomotor activity, mice were evaluated in the open-field paradigm. Forced swimming test (FST) and Tail suspension test (TST) were used to take as a measure of antidepressant activity. The probable mechanisms of action of the anti depressive effect of turmerone was also investigated by measuring the activity of monoamine oxidase-A and corticosterone levels in the blood and the levels of monoamines in the cortex, striatum, hippocampus and hypothalamus of the mice. RESULTS: Turmerone (2.5, 5.0 mg/kg, p.o.) significantly reduced the immobility time of mice in both the FST and TST, but it did not significantly affect the ambulatory and total movements of mice. However, hyperactivity might explain the results. In addition, turmerone decreased the corticosterone level in the blood while it increased the levels of 5-HT in cortex, striatum, hippocampus, and hypothalamus, the level of NE in striatum and hippocampus, the levels of MHPG and DOPAC in hypothalamus, the level of 5-HIAA in striatum, and the level of DA in striatum, hippocampus, and hypothalamus. Turmerone (2.5, 5.0 mg/kg) decreased the activity of MAO-A in the frontal cortex and hippocampus of mouse brain. CONCLUSIONS: After one-week administration, turmerone produced antidepressant like effects. The mechanisms of action of anti-depressive effect of turmerone seemed to involve an increase of the monoamines level decreasing the MAO-A activity and the stress of mice. PMID- 24176022 TI - Poor agreement between light transmission aggregometry, Verify Now P2Y12 and vasodilatator-stimulated phosphoprotein for clopidogrel low-response assessment: a potential explanation of negative results of recent randomized trials. AB - Clopidogrel low response as assessed by several different biological tests correlates with poor prognosis after percutaneous coronary intervention (PCI). However, recent randomized clinical trials (RCT) testing the strategy of individual antiplatelet therapy tailoring based on one sole test have all shown negative results. Poor correlation between the different tests may explain the difficulties of patient selection and identification of "true poor responders" to clopidogrel. In this prospective study, clopidogrel response was assessed in 100 consecutive patients between 18 and 24 hours after a 600 mg clopidogrel loading dose using three different tests: light transmission aggregometry with 10 MUmol ADP (LTA, results expressed as platelet aggregation percentage: PAP), Verify Now P2Y12 (VN, results expressed as P2Y12 reaction unit: PRU) and vasodilatator stimulated phosphoprotein (VASP, results expressed as platelet reactivity index: PRI). Patients under chronic clopidogrel therapy were excluded. The mean PAP, PRU and PRI values were 38.6%, 176.1 PRU and 52.4%, respectively. When clopidogrel response was analyzed as continuous variable, there was a good correlation between the different tests: LTA/VN (R(2 )= 0.642, p < 0.001), LTA/VASP (R(2 )= 0.409, p < 0.001) and VN/VASP (R(2 )= 0.616, p < 0.001). However, when clopidogrel response was analyzed as pre-specified cut-off points to define patients as "poor or good responders" (according to the literature: 50% PAP for LTA, 235 PRU for VN and 50% PRI for VASP), only 47% of the patients were defined as "good" or "poor responders" by the three tests. Altogether, 33% of the patients were defined as "poor responders" by only one test, 20% by two tests and only 16% by the three tests. The correlation between the different tests is good when clopidogrel response is analyzed as continuous variable. Each individual is however rarely (less than 50%) defined as "poor or good responder" by all the three tests when pre-specified cut-off values are used. A sole test might not be sufficient to manage antiplatelet therapy in an individual patient and these results may explain the results of recent RCT showing the lack of benefit of systematic antiplatelet therapy monitoring strategy. PMID- 24176023 TI - Capturing the stories behind the numbers: the Auckland Regional Community Stroke Study (ARCOS IV), a qualitative study. AB - BACKGROUND: Qualitative data can add value and understanding to more traditional epidemiological studies. This study was designed to complement the quantitative data from the incidence study the Auckland Regional Community Stroke Study or ARCOS-IV by using qualitative methods to uncover the richer detail of life as a stroke survivor, thereby extending our understanding of the impact of stroke. AIMS: The aims of the study were to identify how the experience of recovery and adaptation changes over time after stroke; and to elicit the strategies people with stroke and their whanau/family use and find helpful in living life after stroke. The aim of this paper is to describe the methodology and also the challenges and advantages of embedding qualitative research into a large epidemiological study. METHODS: Longitudinal study utilizing a Qualitative Description design in a subset of those taking part in the incidence study. Participants will be interviewed at 6, 12, 24, and 36 months after stroke. Semistructured interviews will explore three key areas: (1) issues of importance to people following a stroke and their whanau/family; (2) the perceived impact on people's sense of recovery, adaptation, and hopes; and (3) key strategies that people with stroke and their whanau/family use and find most helpful in living life after stroke. Thematic analysis will be conducted using iterative constant comparative methods. CONCLUSIONS: This methodology paper demonstrates the application of mixed methods in epidemiology. It also considers some of the practical and methodological issues that have emerged and may provide a useful framework for other qualitative projects in population-based studies. PMID- 24176024 TI - TaqIB polymorphism in the cholesteryl ester transfer protein (CETP) gene influences lipid responses to the consumption of kiwifruit in hypercholesterolaemic men. AB - Fruit and vegetables are key elements of a cardioprotective diet, but benefits on plasma lipids, especially HDL-cholesterol (HDL-C), are inconsistent both within and between studies. In the present study, we investigated whether four selected HDL-C-related polymorphisms (cholesteryl ester transfer protein (CETP) Taq1B, APOA1 - 75G/A, hepatic lipase (LIPC) - 514C -> T, and endothelial lipase (LIPG) I24582) modulate the plasma lipid response to a kiwifruit intervention. This is a retrospective analysis of data collected during a 12-week randomised controlled cross-over trial. A total of eighty-five hypercholesterolaemic men completed a 4 week healthy diet run-in period before being randomised to one of two 4-week intervention sequences of two green kiwifruit/d plus healthy diet (kiwifruit intervention) or healthy diet alone (control intervention). The measurement of anthropometric parameters and collection of fasting blood samples were carried out at baseline 1 and after the run-in (baseline 2) and intervention periods. At baseline 2, B1/B1 homozygotes of the CETP Taq1B gene had significantly higher total cholesterol:HDL-C, TAG:HDL-C, and apoB:apoA1 ratios and small-dense LDL concentrations than B2 carriers. A significant CETP Taq1B genotype * intervention interaction was observed for the TAG:HDL-C ratio (P= 0.03). B1/B1 homozygotes had a significantly lower TAG:HDL-C ( - 0.23 (sd 0.58) mmol/l; P= 0.03) ratio after the kiwifruit intervention than after the control intervention, whereas the ratio of B2 carriers was not affected. The lipid response was not affected by other gene polymorphisms. In conclusion, the significant decrease in the TAG:HDL-C ratio in B1/B1 homozygotes suggests that regular inclusion of green kiwifruit as part of a healthy diet may improve the lipid profiles of hypercholesterolaemic men with this genotype. PMID- 24176025 TI - The regulatory implications of hydroquinone for the multifunctional enzyme dehaloperoxidase-hemoglobin from Amphitrite ornata. AB - Hydroquinone (H2Q) has been observed to compete with the oxidation of substrates 2,4,6-tribromophenol (2,4,6-TBP) and 2,4,6-trichlorophenol (2,4,6-TCP) catalyzed by the dehaloperoxidase-hemoglobin (DHP) from Amphitrite ornata in the presence of H2O2. This competition is observed as a lag phase during which H2Q is preferentially oxidized to 1,4-benzoquinone (1,4-BQ) while totally inhibiting either 2,4,6-TBP or 2,4,6-TCP oxidation. The inhibition by H2Q is distinct from that of the native competitive inhibitor 4-bromophenol (4-BP) since H2Q is itself oxidized and its product 1,4-BQ is not an inhibitor. Thus, once H2Q is completely consumed, the inhibition is removed, and normal substrate turnover is initiated, which explains the lag phase. To probe the mechanism of lag phase, the reactions between H2Q and DHP were both studied both in the presence and in the absence of H2O2. The reversible reactions between ferric/oxyferrous DHP A and H2Q/1,4-BQ are shown to involve a proton-coupled electron transfer (PCET) mechanism, where the distal histidine His(55) serves as the proton acceptor. The pKa of the distal histidine His(55) has been determined by resonance Raman spectroscopy in order to corroborate its involvement in this mechanism. Consistent with the proposed mechanism, kinetic assays have shown that H2Q serves as a substrate for DHP that follows the Michaelis-Menten kinetics. Unlike H2Q, the product 1,4-BQ has a relatively large Ki value and therefore has negligible inhibition. This study sheds light on understanding the difference between substrate and inhibitor binding sites and regulatory implication for the peroxidase and oxygen transporter functions in DHP. It also provides information on PCET in DHP, which is important for resolving the switching between the ferric peroxidase catalytic function and the ferrous oxygen transport function. PMID- 24176027 TI - Effects of light on secondary metabolism and fungal development of Fusarium graminearum. AB - AIMS: The objectives of this study were (i) to characterize white-collar (WC) orthologues of the filamentous fungus Fusarium graminearum, (ii) to investigate light-responsive phenotypes by the deletion of Fgwc-1 and Fgwc-2 genes and (iii) to examine the roles of those genes in constant light and darkness in relation to secondary metabolite synthesis and development. METHODS AND RESULTS: Production of secondary metabolites and asexual/sexual development of deletion mutants, DeltaFgwc-1 and DeltaFgwc-2, were assessed in constant light and darkness compared to the wild-type strain. The results showed that deletion of Fgwc-1 and Fgwc-2 impaired early onset of carotenogenesis, photoreactivation and the maturity of perithecia during sexual development. Conidiation of the DeltaFgwc-1 and DeltaFgwc-2 mutants was derepressed in constant light, but not in darkness. Moreover, the individual mutants produced more aurofusarin and trichothecenes than the wild-type strain in both constant light and darkness. CONCLUSIONS: Both Fgwc-1 and Fgwc-2 are required for light-dependent processes in F. graminearum, whereas light-independent processes such as aurofusarin and trichothecene biosynthesis are derepressed by deletion of these genes. Thus, Fgwc-1 and Fgwc-2 play roles as positive and negative regulators, depending on the requirement of light for biological activity. SIGNIFICANCE AND IMPACT OF THE STUDY: These results will extend the knowledge of the photobiology of Fusarium graminearum and will increase current understanding of light regulatory mechanisms mediated by white collar in secondary metabolism and fungal development. PMID- 24176028 TI - Pharmacological, experimental therapeutic, and transcranial magnetic stimulation treatments for compulsivity and impulsivity. AB - Obsessive-compulsive disorder (OCD) has been recently drawn apart from anxiety disorder by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and clustered together with related disorders (eg, hoarding, hair pulling disorder, skin picking), which with it seems to share clinical and neurophysiological similarities. Recent literature has mainly explored brain circuitries (eg, orbitofrontal cortex, striatum), molecular pathways, and genes (eg, Hoxb8, Slitrk5, Sapap3) that represent the new target of the treatments; they also lead the development of new probes and compounds. In the therapeutic field, monotherapy with cognitive behavioral therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs) is recommendable, but combination or augmentation with a dopaminergic or glutamatergic agent is often adopted. A promising therapy for OCD is represented by repetitive transcranial magnetic stimulation (rTMS), which is suitable to treat compulsivity and impulsivity depending on the protocol of stimulation and the brain circuitries targeted. PMID- 24176029 TI - Brain microabscesses in a porcine model of Staphylococcus aureus sepsis. AB - BACKGROUND: Sepsis caused by Staphylococcus aureus often leads to brain microabscesses in humans. Animal models of haematogenous brain abscesses would be useful to study this condition in detail. Recently, we developed a model of S. aureus sepsis in pigs and here we report that brain microabscesses develop in pigs with such induced S. aureus sepsis.Twelve pigs were divided into three groups. Nine pigs received an intravenous inoculation of S. aureus once at time 0 h (group 1) or twice at time 0 h and 12 h (groups 2 and 3). In each group the fourth pig served as control. The pigs were euthanized at time 12 h (Group 1), 24 h (Group 2) and 48 h (Group 3) after the first inoculation. The brains were collected and examined histopathologically. RESULTS: All inoculated pigs developed sepsis and seven out of nine pigs developed brain microabscesses. The microabscesses contained S. aureus and were located in the prosencephalon and mesencephalon. Chorioditis and meningitis occurred from 12 h after inoculation. CONCLUSIONS: Pigs with experimental S. aureus sepsis often develop brain microabscesses. The porcine brain pathology mirrors the findings in human sepsis patients. We therefore suggest the pig as a useful animal model of the development of brain microabscesses caused by S. aureus sepsis. PMID- 24176031 TI - Quality of life and correlation with musculoskeletal problems, hand disability and depression in patients with hemodialysis. AB - OBJECTIVES: The aims of this study were to assess the health-related quality of life (HRQOL) in patients with hemodialysis using the Kidney Disease Quality of Life (KDQOLTM) and to determine its relationships with conventional clinical measures, musculoskeletal problems, hand disability and depression. MATERIALS AND METHODS: This study was conducted in our tertiary hospital's dialysis unit. Fifty patients under hemodialysis treatment were included in the study. HRQOL, disability, pain and depression were assessed using KDQOL-36, Duruoz hand index (DHI), visual analog scale (VAS) and Beck Depression Inventory (BDI). RESULTS: It was seen that all of the patients included had one or more musculoskeletal problems, the most common of which were muscle cramps, myalgias and arthralgias. Depression was the second most common accompanying disease. It was also seen that older patients had much poorer physical functioning scores, DHI scores and BDI scores than younger patients. DHI score was found to be significantly lower in men than in women. Educational level, presence of arthrosis, myalgia, bone pain, arthralgia, CTS, VAS-hand and VAS-upper extremities scales, DHI and BDI scores significantly affected both physical and mental areas of KDQOL-36, whereas age, shoulder periarthritis, mobilization scores and presence of hypertension only had effects on physical areas. CONCLUSION: Physical functioning depends mainly on the age, severity of comorbid conditions, depression, locomotor findings and hand disability of hemodialysis patients. The KDQOL-36 is related to the clinical status and functional ability of hemodialysis patients and it can be used as a sensitive health status measure for clinical evaluation. PMID- 24176033 TI - Aberrant Mucin5B expression in lung adenocarcinomas detected by iTRAQ labeling quantitative proteomics and immunohistochemistry. AB - BACKGROUND: Lung cancer is the number one cause of cancer-related deaths in the United States and worldwide. The complex protein changes and/or signature of protein expression in lung cancer, particularly in non-small cell lung cancer (NSCLC) has not been well defined. Although several studies have investigated the protein profile in lung cancers, the knowledge is far from complete. Among early studies, mucin5B (MUC5B) has been suggested to play an important role in the tumor progression. MUC5B is the major gel-forming mucin in the airway. In this study, we investigated the overall protein profile and MUC5B expression in lung adenocarcinomas, the most common type of NSCLCs. METHODS: Lung adenocarcinoma tissue in formalin-fixed paraffin-embedded (FFPE) blocks was collected and microdissected. Peptides from 8 tumors and 8 tumor-matched normal lung tissue were extracted and labeled with 8-channel iTRAQ reagents. The labeled peptides were identified and quantified by LC-MS/MS using an LTQ Orbitrap Velos mass spectrometer. MUC5B expression identified by iTRAQ labeling was further validated using immunohistochemistry (IHC) on tumor tissue microarray (TMA). RESULTS: A total of 1288 peptides from 210 proteins were identified and quantified in tumor tissues. Twenty-two proteins showed a greater than 1.5-fold differences between tumor and tumor-matched normal lung tissues. Fifteen proteins, including MUC5B, showed significant changes in tumor tissues. The aberrant expression of MUC5B was further identified in 71.1% of lung adenocarcinomas in the TMA. DISCUSSIONS: A subset of tumor-associated proteins was differentially expressed in lung adenocarcinomas. The differential expression of MUC5B in lung adenocarcinomas suggests its role as a potential biomarker in the detection of adenocarcinomas. PMID- 24176032 TI - Poor agreement between interferon-gamma release assays and the tuberculin skin test among HIV-infected individuals in the country of Georgia. AB - BACKGROUND: Improved tests to diagnose latent TB infection (LTBI) are needed. We sought to evaluate the performance of two commercially available interferon-gamma release assays (IGRAs) compared to the tuberculin skin test (TST) for the diagnosis of LTBI and to identify risk factors for LTBI among HIV-infected individuals in Georgia, a country with high rates of TB. METHODS: HIV-patients were enrolled from the National AIDS Center in Tbilisi, Georgia. After providing informed consent, each participant completed a questionnaire, had blood drawn for QuantiFERON-TB Gold in-Tube (QFT-GIT) and T-SPOT.TB testing and had a TST placed. The TST was read at 48-72 hrs with >= 5 mm induration considered positive. RESULTS: Between 2009-2011, 240 HIV-infected persons (66% male) with a median age of 38 years and a median CD4 count of 255 cells/MUl (IQR: 124-412) had diagnostic testing for LTBI performed. 94% had visible evidence of a BCG scar. The TST was positive in 41 (17%) patients; QFT-GIT in 70 (29%); and T-SPOT.TB in 56 (24%). At least one diagnostic test was positive in 109 (45%) patients and only among 13 (5%) patients were all three tests positive. Three (1%) QFT-GIT and 19 (8%) T SPOT.TB test results were indeterminate. The agreement among all pairs of tests was poor: QFT-GIT vs. T-SPOT.TB (kappa = 0.18, 95% CI .07-.30), QFT-GIT vs. TST (kappa = 0.29, 95% CI .16-.42), and TST vs. T-SPOT.TB (kappa = 0.22, 95% CI .07 .29). Risk factors for LTBI varied by diagnostic test and none showed associations between positive test results and well-known risk factors for TB, such as imprisonment, drug abuse and immunological status. CONCLUSIONS: A high proportion of HIV patients had at least one positive diagnostic test for LTBI; however, there was very poor agreement among all tests. This lack of agreement makes it difficult to know which test is superior and most appropriate for LTBI testing among HIV-infected patients. While further follow-up studies will help determine the predictive ability of different LTBI tests, improved modalities are needed for accurate detection of LTBI and assessment of risk of developing active TB among HIV-infected patients. PMID- 24176034 TI - A new risk score model to predict the presence of significant coronary artery disease in renal transplant candidates. AB - BACKGROUND: Renal transplant candidates are at high risk of coronary artery disease (CAD). We sought to develop a new risk score model to determine the pre test probability of the occurrence of significant CAD in renal transplant candidates. METHODS: A total of 1,060 renal transplant candidates underwent a comprehensive cardiovascular risk evaluation. Patients considered at high risk of CAD (age >=50 years, with either diabetes mellitus (DM) or cardiovascular disease (CVD)), or having noninvasive testing suggestive of CAD were referred for coronary angiography (n = 524). Significant CAD was defined by the presence of luminal stenosis >=70%. A binary logistic regression model was built, and the resulting logistic regression coefficient B for each variable was multiplied by 10 and rounded to the next whole number. For each patient, a corresponding risk score was calculated and the receiver operating characteristic (ROC) curve was constructed. RESULTS: The final equation for the model was risk score = (age * 0.4) + (DM * 9) + (CVD * 14) and for the probability of CAD (%) = (risk score * 2) - 23. The corresponding ROC for the accuracy of the diagnosis of CAD was 0.75 (P <0.0001) in the developmental model. CONCLUSIONS: We developed a simple clinical risk score to determine the pre-test probability of significant CAD in renal transplant candidates. This model may help those directly involved in the care of patients with end-stage renal disease being considered for transplantation in an attempt to reduce the rate of cardiovascular events that presently hampers the long-term prognosis of such patients. PMID- 24176035 TI - Vascular endothelial growth factor secretion from pituitary folliculostellate cells: role of KATP channels. AB - Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen responsible for physiological and pathological angiogenesis. Abnormal regulation of VEGF expression in anterior pituitary folliculostellate (FS) cells has been implicated in pituitary tumour progression. FS and endocrine cells express VEGF, which is considered to be secreted by the constitutive pathway. The present study investigated the mechanism of VEGF secretion in TtT/GF cells, a mouse FS cell line. TtT/GF cells were shown to express VEGF(164), the most potent and bioavailable isoform of VEGF. Immunofluorescence and immunogold electron microscopy localised VEGF to the cytoplasm and small electron-lucent vesicles. Pituitary adenylate cyclase-activating polypeptide (PACAP), a well-documented stimulant of VEGF secretion, caused a robust increase in VEGF secretion over 24 h. Glyburide, an ABCA1 and K(ATP) channel blocker, also caused an increase in VEGF secretion when applied alone, and amplified the response to PACAP. Other ABCA1 transport blockers did not affect VEGF secretion. Exposure of TtT/GF cells to cycloheximide with PACAP or glyburide inhibited the increased secretion of VEGF, consistent with control of secretion at the transcription level. The SUR2B/Kir6.1 form of K(ATP) channels was shown to be expressed by TtT/GF cells. Diazoxide, a K(ATP) activator, inhibited PACAP- and PACAP + glyburide-stimulated VEGF secretion but not that of glyburide alone. These data suggest that K(ATP) channels are expressed by FS cells and play a significant role in the control of VEGF secretion, and also that activation of K(ATP) channels inhibits the secretion of VEGF at the level of transcription. PMID- 24176036 TI - In situ production of human beta defensin-3 in lager yeasts provides bactericidal activity against beer-spoiling bacteria under fermentation conditions. AB - AIMS: To examine the use of a natural antimicrobial peptide, human beta-defensin 3 (HBD3), as a means of preventing spoilage from bacterial contamination in brewery fermentations and in bottled beer. METHODS AND RESULTS: A chemically synthesised HBD3 peptide was tested for bactericidal activity against common Gram positive and Gram-negative beer-spoiling bacteria, including species of Lactobacillus, Pediococcus and Pectinatus. The peptide was effective at the MUmol l(-1) range in vitro, reducing bacterial counts by 95%. A gene construct encoding a secretable form of HBD3 was integrated into the genome of the lager yeast Saccharomyces pastorianus strain CMBS-33. The integrated gene was expressed under fermentation conditions and was secreted from the cell into the medium, but a significant amount remains associated with yeast cell surface. We demonstrate that under pilot-scale fermentation conditions, secreted HBD3 possesses bactericidal activity against beer-spoiling bacteria. Furthermore, when added to bottled beer, a synthetic form of HBD3 reduces the growth of beer-spoiling bacteria. CONCLUSIONS: Defensins provide prophylactic protection against beer spoiling bacteria under brewing conditions and also in bottled beer. SIGNIFICANCE AND IMPACT OF THE STUDY: The results have direct application to the brewing industry where beer spoilage due to bacterial contamination continues to be a major problem in breweries around the world. PMID- 24176037 TI - RISK FACTORS FOR ABDOMINAL OBESITY IN CHILDREN AND ADOLESCENTS FROM CRACOW, POLAND (1983-2000). AB - The aim of this study was to determine abdominal obesity risk factors in two successive cohorts of children and adolescents aged 4-18 from Cracow, Poland, examined during the years of political transformation. The influence of biological, socio-demographic and lifestyle factors on abdominal obesity was analysed by calculating odds ratios and 95% confidence intervals using logistic regression analysis. It was found that for girls obesity in both parents (OR=4.31; 95% CI 1.73-20.70) and high birth weight (OR=1.78; 95% CI 1.12-2.82) were significant risk factors for abdominal obesity in the 1983 cohort. In the 2000 cohort obesity in both parents for boys and girls (boys: OR=5.85; 95% CI 1.36-25.10; girls: OR=4.82; 95% CI 1.17-19.77), low level of parental education in girls (OR=2.06; 95% CI 1.15-3.69), having only one son (OR=1.96; 95% CI 1.36 3.40), parents' smoking habits in girls (OR=2.94; 95% CI 1.46-5.91) and lack of undertaking physical activity in sport clubs in boys (OR=6.11; 95% CI 1.46-25.47) were significant abdominal obesity risk factors. Higher number of hours of leisure time physical activity (OR=0.89; 95% CI 0.81-0.97) significantly lowered the risk of abdominal obesity in boys in the 2000 cohort. The greater differentiation of abdominal obesity risk factors in the 2000 cohort in comparison to the 1983 cohort may have resulted from the social and economic changes taking place in Poland at the end of the 20th century. PMID- 24176038 TI - The policy statement of the American Academy of Pediatrics -- children as hematopoietic stem cell donors -- a proposal of modifications for application in the UK. AB - BACKGROUND: With a view to addressing the moral concerns about the use of donor siblings, the Policy Statement of the American Academy of Pediatrics - Children as Hematopoietic Stem Cell Donors (the Policy) has laid out the criteria upon which tissue harvest from a minor would be permissible. DISCUSSION: Although tissue harvest serves the best interests of recipient siblings, parents are also obliged to act in the best interests of the donor sibling in the UK. Tissue harvest should proceed if and only if it serves the best interests of both the donor and recipient. Parents should be forbidden, and they are by UK law, to consent to tissue harvest unless there are substantial benefits for an incompetent minor that can outweigh the potential harm. There is no basis to subject a minor to the medical risks of tissue harvest if the recipient sibling can wait without significant risks of complications until the donor becomes Gillick competent. We also argue that the Policy fails to take into account recent advances in haematopoietic transplantation from haploidentical donors or related tissue-matched donors. SUMMARY: Unless a recipient sibling will suffer from serious complications or die without the transplantation and no other medically equivalent donors are available, there is no moral or legal basis to violate the donor sibling's right to bodily integrity. Accordingly, we propose that the Policy should be modified in order to fully satisfy the legal requirements for application in the UK and other commonwealth jurisdictions with similar statute laws protecting minors. PMID- 24176039 TI - Abnormal P-selectin localization during megakaryocyte development determines thrombosis in the gata1low model of myelofibrosis. AB - Patients with primary myelofibrosis have increased risk for bleeding and thrombosis. It is debated whether propensity to thrombosis is due to increased numbers of platelet microparticles and/or to pathological platelet-neutrophil interactions. Platelet neutrophil interactions are mediated by P-selectin and even though the megakaryocytes of myelofibrosis patients express normal levels of P-selectin, it remains abnormally localized to the demarcation membrane system rather than being assembled into the alpha-granules in platelets. Mice carrying the hypomorphic Gata1(low) mutation express the same megakaryocyte abnormalities presented by primary myelofibrosis patients, including abnormal P-selectin localization to the DMS and develop with age myelofibrosis, a disease that closely resembles human primary myelofibrosis. Whether these mice would also develop thrombosis has not been investigated as yet. The aim of this study was to determine whether Gata1(low) mice would develop thrombosis with age and, in this case, the role played by P-selectin in the development of the trait. To this aim, Gata1(low) mice were crossed with P-sel(null) mice according to standard genetic protocols and Gata1(low)P-sel(wt), Gata1(low)P-sel(null) and Gata1(WT)P-sel(null) or Gata1(wt)P-sel(wt) (as controls) littermates obtained. It was shown that platelet counts, but not hematocrit, are reduced in Gata1(low) mice. Moreover, platelet microparticles are reduced in Gata1(low) mice and P-selectin positive platelet microparticles were not found. To determine the phenotypic implications of the different mutations, bleeding time was estimated by a tail cut procedure. Mutant mice were sacrificed and presence of thrombosis was determined by immunohistological staining of organs. Gata1(low) mice with or without the P selectin null trait had a prolonged bleeding time compared to wild type mice. However, in Gata1(low) mice significantly higher frequency of thrombotic events was seen in adult and old Gata1(low) mice compared to Gata1(low)P-sel(null) mice. Thus, presence of the P-selectin null trait rescued Gata1(low) mice from the thrombotic phenotype, but did not change the level of platelet microparticles. Taken together these data indicate that abnormal localization of P-selectin, induced by the Gata1(low) mutation, and thus, increased pathological interactions with leucocytes, is responsible for the increased presence of thrombosis seen in these mice. PMID- 24176041 TI - Changes of predominant species/biovars and sequence types of Brucella isolates, Inner Mongolia, China. AB - BACKGROUND: Human brucellosis incidence in China was divided into 3 stages, high incidence (1950-1960s), decline (1970-1980s) and re-emergence (1990-2000s). Human brucellosis has been reported in all the 32 provinces, of which Inner Mongolia has the highest prevalence, accounting for over 40% of the cases in China. To investigate the etiology alteration of human brucellosis in Inner Mongolia, the species, biovars and genotypes of 60 Brucella isolates from this province were analyzed. METHODS: Species and biovars of the Brucella strains isolated from outbreaks were determined based on classical identification procedures. Strains were genotyped by multi locus sequence typing (MLST). Sequences of 9 housekeeping genes were obtained and sequence types were defined. The distribution of species, biovars and sequence types (STs) among the three incidence stages were analyzed and compared. RESULTS: The three stages of high incidence, decline and re emergence were predominated by B. melitensis biovar 2 and 3, B. abortus biovar 3, and B. melitensis biovar 1, respectively, implying changes in the predominant biovars. Genotyping by MLST revealed a total of 14 STs. Nine STs (from ST28 to ST36), accounting for 64.3% of all the STs, were newly defined and different from those observed in other countries. Different STs were distributed among the three stages. ST8 was the most common ST in 1950-1960s and 1990-2000s, while ST2 was the most common in 1970-1980s. CONCLUSIONS: The prevalence of biovars and sequence types of Brucella strains from Inner Mongolia has changed over time in the three stages. Compared with those from other countries, new sequence types of Brucella strains exist in China. PMID- 24176040 TI - Two major ruminant acute phase proteins, haptoglobin and serum amyloid A, as serum biomarkers during active sheep scab infestation. AB - Two ruminant acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid A (SAA), were evaluated as serum biomarkers (BMs) for sheep scab-a highly contagious ectoparasitic disease caused by the mite Psoroptes ovis, which is a major welfare and production threat worldwide. The levels of both APPs increased in serum following experimental infestation of sheep with P. ovis, becoming statistically significantly elevated from pre-infestation levels at 4 weeks post infestation. Following successful treatment of infested sheep with an endectocide, Hp and SAA serum levels declined rapidly, with half lives of less than 3 days. In contrast, serum IgG levels which specifically bound the P. ovis derived diagnostic antigen Pso o 2 had a half-life of 56 days. Taking into account pre-infestation serum levels, rapidity of response to infestation and test sensitivity at the estimated optimum cut-off values, SAA was the more discriminatory marker. These studies illustrated the potential of SAA and Hp to indicate current sheep scab infestation status and to augment the existing Pso o 2 serological assay to give disease-specific indications of both infestation and successful treatment. PMID- 24176042 TI - Antimicrobial stewardship auditing of patients reviewed by infectious diseases physicians in a tertiary university hospital. AB - BACKGROUND: The optimal way for antimicrobial stewardship programs (ASPs) to interact with existing infectious disease physician (IDP) services within the same institution is unknown. In our institution, IDPs and our prospective audit and feedback ASP operate independently, with occasionally differing recommendations offered for the same inpatient. We performed a retrospective audit on inpatients that had been reviewed by both IDPs and ASP within a 7-day period, focusing on cases where different therapy-modifying recommendations had been offered. We analyzed the outcomes in inpatients where the ASP recommendations were accepted and compared these with the inpatients where the IDP recommendations were accepted instead. Outcomes assessed were 30-day mortality post-ASP review, unplanned re-admission within 30 days post-discharge from hospital, and clinical deterioration at 7 days post-ASP review. FINDINGS: There were 143 (18.9%) patients where differing recommendations had been offered, with primary physicians accepting 69.9% of ASP recommendations. No significant differences in terms of demographics, clinical characteristics, 30-day mortality, and re-admission rates were observed, although clinical deterioration rates were lower in patients where the ASP recommendation was accepted (8.0% vs. 27.9%; p = 0.002). On multivariate analysis, hematology-oncology inpatients were associated with unplanned readmission. Increasing age and hematology-oncology inpatients were associated with clinical deterioration 7 days post-recommendation, whereas acceptance of ASP recommendations was protective. No characteristic was independently associated with 30-day mortality. CONCLUSION: In conclusion, independent reviews by both IDPs and ASPs can be compatible within large tertiary hospitals, providing primary physicians even in situations of conflicting recommendations viable alternative antimicrobial prescribing advice. PMID- 24176043 TI - Hypochondriasis and obsessive-compulsive disorder in schizophrenic patients treated with clozapine vs other atypical antipsychotics. AB - OBJECTIVE: The aim of the study was to investigate the prevalence rates of obsessive-compulsive disorder (OCD) and hypochondriasis in schizophrenic patients treated with atypical antipsychotics (AAPs) and to investigate the different comorbidity rates of OCD and hypochondriasis between clozapine-treated patients and patients treated with other AAPs. METHODS: We therefore recruited 60 schizophrenic patients treated with clozapine or other AAPs. We assessed the prevalence rates of OCD or OC symptoms and hypochondriasis or hypochondriac symptoms in the whole group of patients and in clozapine-treated patients versus patients treated with other AAPs. RESULTS: Schizophrenic patients had a higher comorbidity rate of OCD (26.6% vs 1-3%) and hypochondriasis (20% vs 1%) than the general population. These comorbidities were more frequent in schizophrenic patients treated with clozapine versus patients treated with other AAPs (36.7% vs 16.7% and 33.3% vs 6.7%). Clozapine-treated patients showed a higher mean Y-BOCS and HY-BOCS score when compared to patients treated with other AAPs (10.90 vs 5.90, p = .099; 15.40 vs 8.93, p = .166). A statistical significant correlation was found between the Y-BOCS and HY-BOCS scores of the whole group (r = .378, p = 0.03). Furthermore, we found an inverse correlation between the global level of functioning and the diagnosis of hypochondriasis (p = .048) and the severity of hypochondriac symptoms (p = .047). CONCLUSIONS: Hypochondriasis could represent an important clinical feature of schizophrenic patients treated with atypical antipsychotics, and further research is needed in this field. PMID- 24176044 TI - Identification of regulatory structure and kinetic parameters of biochemical networks via mixed-integer dynamic optimization. AB - BACKGROUND: Recovering the network topology and associated kinetic parameter values from time-series data are central topics in systems biology. Nevertheless, methods that simultaneously do both are few and lack generality. RESULTS: Here, we present a rigorous approach for simultaneously estimating the parameters and regulatory topology of biochemical networks from time-series data. The parameter estimation task is formulated as a mixed-integer dynamic optimization problem with: (i) binary variables, used to model the existence of regulatory interactions and kinetic effects of metabolites in the network processes; and (ii) continuous variables, denoting metabolites concentrations and kinetic parameters values. The approach simultaneously optimizes the Akaike criterion, which captures the trade-off between complexity (measured by the number of parameters), and accuracy of the fitting. This simultaneous optimization mitigates a possible overfitting that could result from addition of spurious regulatory interactions. CONCLUSION: The capabilities of our approach were tested in one benchmark problem. Our algorithm is able to identify a set of plausible network topologies with their associated parameters. PMID- 24176045 TI - Gender barriers to health promotion in middle-aged Iranian women. AB - This study explores the perceived socio-cultural factors that might be barriers to health-promoting behaviour in middle-aged women in the city of Yazd in Iran. The aim of this qualitative study was to explore the barriers to a healthy lifestyle in middle-aged women. Interviews with women aged 40-60 were audio taped, transcribed and analysed using content analysis. The interviews focused on socio-cultural factors and five main themes emerged: (a) giving higher priority to non-health-related needs; (b) the dominance of the husband's will in the family; (c) preference of children's needs to own needs; (d) having to fulfil multiple responsibilities; and (e) low access to community resources for health promotion. The multiple responsibilities of family and work, patriarchal societal attitudes and lack of exercise facilities are barriers to health in middle-aged Iranian women. PMID- 24176047 TI - Abstracts of the XXXI Annual Scientific Meeting of the British Blood Transfusion Society. October 16-18, 2013. Birmingham, United Kingdom. PMID- 24176048 TI - Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia). AB - BACKGROUND: Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. RESULTS: Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. CONCLUSIONS: The data corroborate the reports on circadian variation of NOS in the mammalian hippocampus and can be considered indicative of a dynamic interaction between hippocampus-dependent processes and circadian clock mechanisms. PMID- 24176049 TI - Clinical characteristics and treatment outcomes in patients with Helicobacter pylori-positive chronic immune thrombocytopenic purpura. AB - Immune thrombocytopenic purpura (ITP) is the condition caused by increased platelet destruction and or decreased platelet production. Previous studies have demonstrated the association and efficacy of Helicobacter pylori (H. pylori) eradication therapy in patients with chronic ITP. Data in Thai patients, however, are limited. A prospective cross-sectional analytic study was conducted in adult patients with chronic ITP to determine the prevalence and clinical predictive factors of H. pylori infection and evaluate the efficacy of H. pylori eradication therapy. H. pylori-infected patients received eradication therapy (omeprazole 40 mg/day, clarithromycin 1000 mg/day, amoxicillin 2000 mg/day) for 2 weeks. The platelet counts at baseline and monthly for 6 months after the end of treatment were evaluated. Of the 25 patients, 9 patients (36%) had H.pylori infection. H. pylori infection is higher among women than men. There were two clinical factors included 1) relapsed ITP 2) response after the first-line treatment statistically proven to be associated with H. pylori infection with an odds ratio and p value of 7.7, p = 0.035 and ND (not determined due to small sample size), p < 0.001. Nearly 80% of infected patients had the platelet count response after eradication therapy with the median time to response of 4 months. The prevalence of H. pylori infection is modest in Thai adult patients with chronic ITP. A history of relapsed ITP and high quality of response after first-line treatment indicated H. pylori infection. Therefore, the urea breath test should be recommended in patients who have a relapsed ITP condition with a history of good response after first-line therapy. PMID- 24176050 TI - Genomic testing to determine drug response: measuring preferences of the public and patients using Discrete Choice Experiment (DCE). AB - BACKGROUND: The extent to which a genomic test will be used in practice is affected by factors such as ability of the test to correctly predict response to treatment (i.e. sensitivity and specificity of the test), invasiveness of the testing procedure, test cost, and the probability and severity of side effects associated with treatment. METHODS: Using discrete choice experimentation (DCE), we elicited preferences of the public (Sample 1, N = 533 and Sample 2, N = 525) and cancer patients (Sample 3, N = 38) for different attributes of a hypothetical genomic test for guiding cancer treatment. Samples 1 and 3 considered the test/treatment in the context of an aggressive curable cancer (scenario A) while the scenario for sample 2 was based on a non-aggressive incurable cancer (scenario B). RESULTS: In aggressive curable cancer (scenario A), everything else being equal, the odds ratio (OR) of choosing a test with 95% sensitivity was 1.41 (versus a test with 50% sensitivity) and willingness to pay (WTP) was $1331, on average, for this amount of improvement in test sensitivity. In this scenario, the OR of choosing a test with 95% specificity was 1.24 times that of a test with 50% specificity (WTP = $827). In non-aggressive incurable cancer (scenario B), the OR of choosing a test with 95% sensitivity was 1.65 (WTP = $1344), and the OR of choosing a test with 95% specificity was 1.50 (WTP = $1080). Reducing severity of treatment side effects from severe to mild was associated with large ORs in both scenarios (OR = 2.10 and 2.24 in scenario A and B, respectively). In contrast, patients had a very large preference for 95% sensitivity of the test (OR = 5.23). CONCLUSION: The type and prognosis of cancer affected preferences for genomically-guided treatment. In aggressive curable cancer, individuals emphasized more on the sensitivity rather than the specificity of the test. In contrast, for a non-aggressive incurable cancer, individuals put similar emphasis on sensitivity and specificity of the test. While the public expressed strong preference toward lowering severity of side effects, improving sensitivity of the test had by far the largest influence on patients' decision to use genomic testing. PMID- 24176051 TI - Seed predators exert selection on the subindividual variation of seed size. AB - Subindividual variation among repeated organs in plants constitutes an overlooked level of variation in phenotypic selection studies, despite being a major component of phenotypic variation. Animals that interact with plants could be selective agents on subindividual variation. This study examines selective pressures exerted during post-dispersal seed predation and germination on the subindividual variation of seed size in hawthorn (Crataegus monogyna). With a seed offering experiment and a germination test, we estimated phenotypic selection differentials for average and subindividual variation of seed size due to seed predation and germination. Seed size affects germination, growth rate and the probability of an individual seed of escaping predation. Longer seeds showed higher germination rates, but this did not result in significant selection on phenotypes of the maternal trees. On the other hand, seed predators avoided wider seeds, and by doing so exerted phenotypic selection on adult average and subindividual variation of seed size. The detected selection on subindividual variation suggests that the levels of phenotypic variation within individual plants may be, at least partly, the adaptive consequence of animal-mediated selection. PMID- 24176052 TI - Effect of metallo-beta-lactamase production and multidrug resistance on clinical outcomes in patients with Pseudomonas aeruginosa bloodstream infection: a retrospective cohort study. AB - BACKGROUND: Blood stream infections (BSI) with Pseudomonas aeruginosa lead to poor clinical outcomes. The worldwide emergence and spread of metallo-beta lactamase (MBL) producing, often multidrug-resistant organisms may further aggravate this problem. Our study aimed to investigate the effect of MBL producing P. aeruginosa (MBL-PA) and various other resistance phenotypes on clinical outcomes. METHODS: A retrospective cohort study was conducted in three German hospitals. Medical files from 2006 until 2012 were studied, and a number of 113 patients with P. aeruginosa BSI were included. The presence of VIM, IMP and NDM genes was detected using molecular techniques. Genetic relatedness was assessed through multilocus sequence typing (MLST). The effect of resistance patterns or MBL production on clinical outcomes was investigated by using multivariate Cox regression models. RESULTS: In-hospital mortality was significantly higher in patients with MBL-PA and multidrug-resistant P. aeruginosa. However, neither BSI with MBL-PA nor BSI with various resistance phenotypes of P. aeruginosa were independently associated with mortality or length of hospital stay. In multivariate models, the SAPS II score (HR 1.046), appropriate definitive treatment (HR range 0.25-0.26), and cardiovascular disease (HR range 0.44-0.46) were independent predictors of mortality. Concomitant infections were associated with an excess length of stay (HR < 1). CONCLUSIONS: Medication with appropriate antimicrobial agents at any time during the course of infection remains the key for improving clinical outcomes in patients with P. aeruginosa BSI and should be combined with a strict implementation of routine infection control measures. PMID- 24176054 TI - Vitamin D intakes of adults differ by income, gender and race/ethnicity in the U.S.A., 2007 to 2010. AB - OBJECTIVE: To determine if dietary, supplemental and total vitamin D intakes in the USA are influenced by income, race/ethnicity or gender. DESIGN: Cross sectional. US vitamin D intakes were estimated by poverty income ratio (PIR), race/ethnicity and gender using 24 h dietary intake recalls and dietary supplement use questionnaires. Statistical analyses of weighted data were performed using SAS (version 9.2) to estimate means and their standard errors. Race and ethnic intake differences controlling for PIR, gender and age were assessed by ANCOVA. SUBJECTS: Adults aged >=19 years. SETTING: The 2007-2010 National Health and Nutrition Examination Survey, USA. RESULTS: Total (dietary and supplement) vitamin D intake was greater in the high (10.0 (se 0.30) MUg/d) v. the medium (7.9 (se 0.3) MUg/d) or the low (8.0 (se 0.3) MUg/d) PIR categories. Total vitamin D intake of non-Hispanic Whites (10.6 (se 0.4) MUg/d) was greater than that of Hispanics (8.1 (se 0.3) MUg/d) and non-Hispanic Blacks (7.1 (se 0.3) MUg/d). Supplemental vitamin D intake was greater by females (5.3 (se 0.2) MUg/d) than by males (3.3 (se 0.2) MUg/d). Participants with high income were more likely to be vitamin D supplement users (33.0%) than those with medium (22.5%) or low (17.6%) income. High-income non-Hispanic Whites had the lowest percentage (57%) not meeting the Estimated Average Requirement for vitamin D. Fortified milk and milk products provided 43.7% of the dietary vitamin D intake. CONCLUSIONS: Public health efforts should expand the number of vitamin D fortified foods and encourage the consumption of foods high in vitamin D and use of supplements. PMID- 24176053 TI - A novel porcine reproductive and respiratory syndrome virus vector system that stably expresses enhanced green fluorescent protein as a separate transcription unit. AB - Here we report the rescue of a recombinant porcine reproductive and respiratory syndrome virus (PRRSV) carrying an enhanced green fluorescent protein (EGFP) reporter gene as a separate transcription unit. A copy of the transcription regulatory sequence for ORF6 (TRS6) was inserted between the N protein and 3'-UTR to drive the transcription of the EGFP gene and yield a general purpose expression vector. Successful recovery of PRRSV was obtained using an RNA polymerase II promoter to drive transcription of the full-length virus genome, which was assembled in a bacterial artificial chromosome (BAC). The recombinant virus showed growth replication characteristics similar to those of the wild-type virus in the infected cells. In addition, the recombinant virus stably expressed EGFP for at least 10 passages. EGFP expression was detected at approximately 10 h post infection by live-cell imaging to follow the virus spread in real time and the infection of neighbouring cells occurred predominantly through cell-to-cell contact. Finally, the recombinant virus generated was found to be an excellent tool for neutralising antibodies and antiviral compound screening. The newly established reverse genetics system for PRRSV could be a useful tool not only to monitor virus spread and screen for neutralising antibodies and antiviral compounds, but also for fundamental research on the biology of the virus. PMID- 24176055 TI - Solving gap metabolites and blocked reactions in genome-scale models: application to the metabolic network of Blattabacterium cuenoti. AB - BACKGROUND: Metabolic reconstruction is the computational-based process that aims to elucidate the network of metabolites interconnected through reactions catalyzed by activities assigned to one or more genes. Reconstructed models may contain inconsistencies that appear as gap metabolites and blocked reactions. Although automatic methods for solving this problem have been previously developed, there are many situations where manual curation is still needed. RESULTS: We introduce a general definition of gap metabolite that allows its detection in a straightforward manner. Moreover, a method for the detection of Unconnected Modules, defined as isolated sets of blocked reactions connected through gap metabolites, is proposed. The method has been successfully applied to the curation of iCG238, the genome-scale metabolic model for the bacterium Blattabacterium cuenoti, obligate endosymbiont of cockroaches. CONCLUSION: We found the proposed approach to be a valuable tool for the curation of genome scale metabolic models. The outcome of its application to the genome-scale model B. cuenoti iCG238 is a more accurate model version named as B. cuenoti iMP240. PMID- 24176056 TI - The relative anthelmintic efficacy of plant-derived cysteine proteinases on intestinal nematodes. AB - We examined the in vitro and in vivo efficacy of plant cysteine proteinases (CPs) derived from pineapple (Ananas comosus) and kiwi fruit (Actinidia deliciosa), and compared their efficacy as anthelmintics to the known effects of CPs from the latex of papaya (Carica papaya) against the rodent intestinal nematode, Heligmosomoides bakeri. Both fruit bromelain and stem bromelain had significant in vitro detrimental effects on H. bakeri but in comparison, actinidain from kiwi fruit had very little effect. However, in vivo trials indicated far less efficacy of stem bromelain and fruit bromelain than that expected from the in vitro experiments (24.5% and 22.4% reduction in worm burdens, respectively) against H. bakeri. Scanning electron microscopy revealed signs of cuticular damage on worms incubated in fruit bromelain, stem bromelain and actinidain, but this was far less extensive than on those incubated in papaya latex supernatant. We conclude that, on the basis of presently available data, CPs derived from pineapples and kiwi fruits are not suitable for development as novel anthelmintics for intestinal nematode infections. PMID- 24176057 TI - AtRH57, a DEAD-box RNA helicase, is involved in feedback inhibition of glucose mediated abscisic acid accumulation during seedling development and additively affects pre-ribosomal RNA processing with high glucose. AB - The Arabidopsis thaliana T-DNA insertion mutant rh57-1 exhibited hypersensitivity to glucose (Glc) and abscisic acid (ABA). The other two rh57 mutants also showed Glc hypersensitivity similar to rh57-1, strongly suggesting that the Glc hypersensitive feature of these mutants results from mutation of AtRH57. rh57-1 and rh57-3 displayed severely impaired seedling growth when grown in Glc concentrations higher than 3%. The gene, AtRH57 (At3g09720), was expressed in all Arabidopsis organs and its transcript was significantly induced by ABA, high Glc and salt. The new AtRH57 belongs to class II DEAD-box RNA helicase gene family. Transient expression of AtRH57-EGFP (enhanced green fluorescent protein) in onion cells indicated that AtRH57 was localized in the nucleus and nucleolus. Purified AtRH57-His protein was shown to unwind double-stranded RNA independent of ATP in vitro. The ABA biosynthesis inhibitor fluridone profoundly redeemed seedling growth arrest mediated by sugar. rh57-1 showed increased ABA levels when exposed to high Glc. Quantitative real time polymerase chain reaction analysis showed that AtRH57 acts in a signaling network downstream of HXK1. A feedback inhibition of ABA accumulation mediated by AtRH57 exists within the sugar-mediated ABA signaling. AtRH57 mutation and high Glc conditions additively caused a severe defect in small ribosomal subunit formation. The accumulation of abnormal pre rRNA and resistance to protein synthesis-related antibiotics were observed in rh57 mutants and in the wild-type Col-0 under high Glc conditions. These results suggested that AtRH57 plays an important role in rRNA biogenesis in Arabidopsis and participates in response to sugar involving Glc- and ABA signaling during germination and seedling growth. PMID- 24176058 TI - The effect of rural-to-urban migration on renal function in an Indian population: cross-sectional data from the Hyderabad arm of the Indian Migration Study. AB - BACKGROUND: Urban migration is associated with an increased risk of hypertension, obesity and diabetes in Indian migrants. This study assessed the relationship between internal migration and renal function in the Hyderabad arm of the Indian Migration Study. METHODS: We assessed 841 subjects; urban non-migrants (n = 158), urban migrants (n = 424) and rural non-migrants (n = 259). Muscle mass was ascertained from DXA scanning. We derived urban life years for urban migrants and rural non-migrants. Multivariable linear regression was used to examine the association between tertiles of urban life years and 4-variable MDRD eGFR using Stata 11. RESULTS: Mean eGFR was lower in urban non-migrants and urban migrants compared to rural non-migrants. The prevalence of CKD 3-5 was higher in the rural non-migrant population (5.0%) than in the urban non-migrant populations (2.5%) due to a negatively skewed distribution of eGFR in rural non-migrants. As urban life years increased, eGFR declined (p = 0.008) though there was no obvious dose response effect. After adjustment for muscle mass, the association was attenuated and the trend was consistent with chance (p = 0.08). Further adjustment for vascular risk factors weakened the association to a small degree (p = 0.11). CONCLUSIONS: The high prevalence of reduced eGFR in rural areas requires further research. Urbanization was associated with reduced eGFR. This association appears mostly to be due to higher muscle mass with a small contribution from adverse vascular disease risk factors. PMID- 24176059 TI - "Be kind to young people so they feel at home": a qualitative study of adolescents' and service providers' perceptions of youth-friendly sexual and reproductive health services in Vanuatu. AB - BACKGROUND: Sexual activity during adolescence is common in Vanuatu, however many adolescents lack access to sexual and reproductive health (SRH) services and subsequently suffer a disproportionate burden of poor SRH. There is limited peer reviewed research describing adolescents' SRH service delivery preferences in Vanuatu to inform policy and programs. The aim of this qualitative study was to explore the barriers preventing adolescents from accessing SRH services in Vanuatu and the features of a youth-friendly health service as defined by adolescents. METHODS: Sixty-six focus group discussions were conducted with 341 male and female adolescents aged 15-19 years in rural and urban communities. Additionally, 12 semi-structured interviews were undertaken with policymakers and service providers. Data were analysed using thematic analysis. RESULTS: Socio cultural norms and taboos regarding adolescent sexual behaviour were the most significant factors preventing adolescents from accessing services. These contributed to adolescents' own fear and shame, judgmental attitudes of service providers, and disapproval from parents and community gate-keepers. Lack of confidentiality and privacy, costs, and adolescents' lack of SRH knowledge were also important barriers. Adolescents and service providers identified opportunities to make existing services more youth-friendly. The most important feature of a youth-friendly health service described by adolescents was a friendly service provider. Free or affordable services, reliable commodity supply, confidentiality and privacy were also key features. The need to address socio-cultural norms and community knowledge and attitudes was also highlighted. CONCLUSIONS: There are significant demand and supply-side barriers contributing to low utilisation of SRH services by adolescents in Vanuatu. However, there are many opportunities to make existing SRH services more youth-friendly, such as improving service provider training. Investment is also required in strategies that aim to create a more supportive environment for adolescent SRH. PMID- 24176060 TI - Longitudinal follow-up of implantable cardioverter defibrillator leads. AB - Although implantable cardioverter defibrillator (ICD) leads are prone to failure and Food and Drug Administration recall, comprehensive longitudinal studies investigating contemporary ICD lead survival rate in the United States are lacking. All patients receiving Medtronic, Boston Scientific, or St. Jude Medical transvenous ICD leads at the hospitals of the University of Pittsburgh Medical Center from 2000 to 2012 were included. Leads were classified as (1) functional lead, patient deceased; (2) functional lead, replaced; (3) failed lead, replaced; or (4) functional lead, active. Kaplan-Meier survival curves were constructed for all lead models separately and in aggregate. We followed 5,288 patients (1,020 Quattro, 623 Fidelis, 627 Riata, 828 Durata, and 2,190 Reliance) over 3.7 +/- 3.3 years. Functional leads that were replaced included 30 Quattro (3%), 99 Fidelis (16%), 24 Riata (4%), 24 Durata (3%), and 62 Reliance (3%). Leads replaced because of failure included 11 Quattro (1%), 47 Fidelis (8%), 38 Riata (6%), 18 Durata (2%), and 26 Reliance (1%; p <0.001 for Food and Drug Administration recalled vs nonrecalled leads). Overall survival rate of all leads was 89.3% at 5 years. Survival curves of Riata and Fidelis diverged from nonrecalled leads at approximately 2 years. In conclusion, the overall survival rate of ICD leads is nearly 90% at 5 years. Survival curves of recalled leads diverge from nonrecalled leads after 2 years of implantation. These data have important implications on postmarket release monitoring of ICD leads and physicians' choice of leads. PMID- 24176061 TI - Usefulness of T wave inversion in leads with ST elevation on the presenting electrocardiogram to predict spontaneous reperfusion in patients with anterior ST elevation acute myocardial infarction. AB - Inversion of the T waves (T-) in electrocardiographic leads with ST-segment elevation after the initiation of reperfusion therapy is considered a sign of reperfusion. However, the significance of T- on presentation before the initiation of reperfusion therapy is unclear. The aim of this study was to assess whether T- on presentation predicts patency of the infarct-related artery in patients with acute ST-segment elevation myocardial infarctions (STEMIs) who undergo primary percutaneous interventions. The medical records, electrocardiograms, and angiographic findings of 209 consecutive patients who underwent emergent coronary angiography as part of primary percutaneous coronary intervention protocol activation for STEMI were reviewed. A total of 179 patients (86%) had positive T waves (T+), 16 (8%) had biphasic T waves (T+/-), and 14 (7%) had T-. Patency of the infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] flow grades 2 and 3) was seen in 64.3% of the patients in the T group compared with only 31.2% in the T+/- group and 19.0% in the T+ group (p <0.001). Among patients with anterior STEMI, patency of the infarct-related artery was seen in all 7 patients in the T- group, compared with 50% of the 4 patients in the T+/- group and 10.1% of the 79 patients in the T+ group (p <0.001). There were no significant differences in TIMI flow grade among the groups in patients with nonanterior STEMIs (p = 0.985). In conclusion, T- in the leads with maximal ST-segment elevation on the presenting electrocardiogram was associated with higher prevalence of patency of the infarct-related artery before intervention (64.3%), especially in patients with anterior STEMIs (100%). PMID- 24176062 TI - Review of published cases of adverse cardiovascular events after ingestion of energy drinks. AB - Energy drink (ED) consumption has been linked to several adverse event reports, but there is limited data on related cardiovascular (CV) complications. We describe clinical characteristics, ED consumption profile, co-ingestions, and results of cardiovascular testing in a series of cardiovascular event reports temporally related to ED consumption from the literature. We searched PubMed and Embase for case reports in peer-reviewed journals from January 1, 1980, to February 1, 2013, in which an acute CV event was associated temporally with ED consumption. We identified 14 eligible articles involving 15 cases (5 atrial arrhythmias, 5 ventricular arrhythmias, 1 QT prolongation, 4 ST-segment elevations). Two additional cases of cardiac arrest from our institution are included. Of these 17 cases of ED-related acute CV events (13 male cases; 15 cases aged <30 years, age range 13 to 58 years), only 1 had minor previous cardiac disease. Cardiac investigations did not reveal any predisposing cardiac abnormality in the majority of cases. Of the 11 cases related to a serious event (i.e., cardiac arrest, ventricular arrhythmia, or ST-segment elevations), 5 reported acute heavy ED consumption, 4 reported co-ingestions with alcohol or other drugs, and 2 were found to have a channelopathy. Potential mechanisms of ED related cardiac events are reviewed. In conclusion, several adverse CV events after consuming ED have been reported in the literature. Although causality cannot be inferred from our series, physicians should routinely inquire about ED consumption in relevant cases, and vulnerable consumers such as youth should be advised that caution is warranted with heavy consumption and/or with concomitant alcohol or drug ingestion. PMID- 24176063 TI - Prognostic utility of the SYNTAX score in patients with single versus multivessel disease undergoing percutaneous coronary intervention (from the Acute Catheterization and Urgent Intervention Triage StrategY [ACUITY] trial). AB - The SYNergy between percutaneous intervention with TAXus drug-eluting stents and cardiac surgery (SYNTAX) score (SS) is an effective angiographic predictor of clinical outcomes in patients with multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention. It is not known whether this relation is independent of the number of diseased vessels. The aim of the present study was to assess the relation between the SS and major adverse cardiac events (MACE) in patients with single-vessel disease (SVD) and MVD undergoing percutaneous coronary intervention. In the ACUITY trial, the SS was determined in 2,627 patients undergoing percutaneous coronary intervention. The relation between the SS and the 1-year clinical outcomes was assessed according to SS tertiles: <5 (n = 441), >=5 but <10 (n = 525), and >=10 (n = 495) for SVD and <10 (n = 361), >=10 but <18 (n = 401), and >=18 (n = 404) for MVD. At 1 year of follow-up, the rate of MACE was 16.8%, 24.7%, and 23.7% for patients with MVD in the first, second and third tertiles, respectively (p = 0.02). The corresponding rates for those with SVD was 13.3%, 15.3%, and 19.1% (p = 0.01). In the patients with MVD, the SS independently predicted 1-year MACE (hazard ratio 1.02, 95% confidence interval 1.01 to 1.03; p = 0.002), myocardial infarction (hazard ratio 1.02, 95% confidence 1.00 to 1.04; p = 0.02), and cardiac death (hazard ratio 1.05, 95% confidence interval 1.02 to 1.09; p = 0.005). In patients with SVD, the SS independently predicted 1-year MACE (hazard ratio 1.03, 95% confidence interval 1.01 to 1.05; p = 0.0009) and myocardial infarction (hazard ratio 1.05, 95% confidence interval 1.02 to 1.07; p = 0.002). In the overall study cohort, the SS was an independent predictor of MACE and death, and MVD (vs SVD) was not. In conclusion, the SS is a useful angiographic predictive tool for patients with SVD and MVD. PMID- 24176064 TI - Comparison of the effect on right atrial pressure of abdominal compression versus the Valsalva maneuver. AB - When the right atrial pressure (RAP) exceeds the left atrial pressure, right-to left shunting can occur. Normally, the Valsalva maneuver is used to facilitate elevation of RAP. However, performing the Valsalva maneuver can be problematic in certain situations. The aim of this study was to test the hypothesis that the application of abdominal pressure would increase the pressure within the right atrium compared with the left atrium, making it an adequate alternative to the Valsalva maneuver. Twelve patients were prospectively evaluated during right sided cardiac catheterization with the application of abdominal pressure as well as a Valsalva maneuver. RAP and left atrial pressure were measured simultaneously. In 11 patients, the mean RAP was lower than the mean pulmonary capillary wedge pressure at baseline. The mean RAP was significantly higher than the mean pulmonary capillary wedge pressure during abdominal compression (24.8 +/ 9.9 vs 21.6 +/- 8.8 mm Hg, p = 0.001). When the Valsalva maneuver was performed, mean RAP was also significantly higher than the mean pulmonary capillary wedge pressure (25.3 +/- 10.9 vs 22.1 +/- 10.3 mm Hg, p = 0.008). In conclusion, abdominal compression is similar to an optimal Valsalva maneuver for increasing RAP and thus the right-to-left pressure gradient. Performing abdominal compression provides a simple alternative to the Valsalva maneuver for creating a transient increase in RAP. PMID- 24176065 TI - Magnetic resonance assessment of prevalence and correlates of right ventricular abnormalities in isolated left ventricular noncompaction. AB - The aim of the present study was to evaluate the prevalence and correlates of right ventricular (RV) noncompaction (RVNC), RV systolic dysfunction, and RV myocardial fibrosis in patients with isolated left ventricular (LV) noncompaction (LVNC). For this purpose, cine and contrast-enhanced cardiac magnetic resonance imaging (MRI) was used. A total of 56 consecutive patients with isolated LVNC were included in the study. The diagnosis of isolated LVNC was based on the presence of standard cardiac MRI and clinical criteria. For each patient, cine and contrast-enhanced cardiac MR images were analyzed to evaluate the prevalence and correlates of RVNC, RV dysfunction, and late gadolinium enhancement (a surrogate of myocardial fibrosis) involving the RV. Mean age of the patient population was 45 +/- 19 years; 35 patients (63%) were men. RVNC was observed in 5 patients (9%). Impaired RV systolic function was observed in 9 patients (16%). Late gadolinium enhancement was not observed in any RV segment. No association was found between wall motion abnormalities and noncompaction at RV segmental level (phi coefficient 0.041, p = 0.26). At multivariate analysis, LV ejection fraction was the only variable independently related to RV ejection fraction (beta = 0.62, p <0.001). In conclusion, RV systolic dysfunction is present in a non-negligible proportion of patients with isolated LVNC; LV systolic function is the only variable independently related to RV systolic function. PMID- 24176066 TI - Impact of atrial fibrillation in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention (from the HORIZONS-AMI [Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction] trial). AB - Atrial fibrillation (AF) has been associated with worse outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction. The aim of this study was to evaluate the incidence and impact of new-onset AF after primary PCI in patients with ST-segment elevation myocardial infarctions from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. HORIZONS-AMI was a large-scale, multicenter, international, randomized trial comparing different antithrombotic regimens and stents during primary PCI in patients with ST-segment elevation myocardial infarctions. Three-year ischemic and bleeding end points were compared between patients with and without new-onset AF after PCI. Of the 3,602 patients included in the HORIZONS-AMI study, 3,281 (91.1%) with sinus rhythm at initial presentation had primary PCI as their primary management strategy. Of these, new onset AF developed in 147 (4.5%). Compared with patients without AF after PCI, patients with new-onset AF had higher 3-year rates of net adverse clinical events (46.5% vs 25.7%, p <0.0001), mortality (11.9% vs 6.3%, p = 0.01), reinfarction (16.4% vs 7.0%, p <0.0001), stroke (5.8% vs 1.5%, p <0.0001), and major bleeding (20.9% vs 8.2%, p <0.0001). By multivariate analysis, new-onset AF after PCI was a powerful independent predictor of net adverse clinical events (hazard ratio 1.74, 95% confidence interval 1.30 to 2.34, p = 0.0002) and major adverse cardiac events (hazard ratio 1.73, 95% confidence interval 1.27 to 2.36) at 3 years. In conclusion, new-onset AF after PCI for ST-segment elevation myocardial infarction was associated with markedly higher rates of adverse events and mortality. PMID- 24176067 TI - Usefulness of serum unbound free fatty acid levels to predict death early in patients with ST-segment elevation myocardial infarction (from the Thrombolysis In Myocardial Infarction [TIMI] II trial). AB - Circulating total free fatty acid (FFA) levels are elevated early in myocardial infarction (MI) and have been associated with an increase in mortality. We investigated the association of serum unbound FFA (FFAu) levels with mortality in patients presenting with ST-segment elevation MI in the Thrombolysis In Myocardial Infarction II trial. The Thrombolysis In Myocardial Infarction II trial enrolled patients within 4 hours of chest pain onset. The patients were treated with a recombinant tissue plasminogen activator within 1 hour of enrollment. The FFAu concentration was evaluated in serum samples from 1,834 patients obtained at baseline, before therapy. The FFAu level was an independent risk factor for death as early as at 1 day of hospitalization and continued to be an independent risk factor for the >3.8 years of follow-up. When adjusted for other cardiovascular risk factors, the FFAu levels in the fourth versus the first quartile remained an independent risk factor for death from MI (hazard ratio 5.0, 95% confidence interval 1.9 to 13.0), all cardiac death (hazard ratio 2.4, 95% confidence interval 1.3 to 4.4), and all-cause death (hazard ratio 1.9, 95% confidence interval 1.2 to 3.1). Women were twice as likely to be in the upper 2 FFAu quartiles and had approximately twice the rate of death as men. In conclusion, FFAu elevation is 1 of the earliest molecular biomarkers of mortality in patients with ST-segment elevation MI and was independent of other risk factors known to affect the outcomes after ST-segment elevation MI. PMID- 24176068 TI - Effect of delayed inferior vena cava filter retrieval after early initiation of anticoagulation. AB - Retrievable inferior vena cava filters (IVCFs) were designed to provide temporary protection from pulmonary embolism in high-risk situations. However, little is known about their effectiveness, and many remain permanently implanted, leading to potential complications. The aim of this study was to determine patient characteristics, indications for IVCF placement, retrieval rates, complications, and post-IVCF anticoagulation (AC) practices in patients who have received IVCFs. A retrospective review of IVCF use by 3 specialty groups from January 1, 2009, to December 31, 2011, was conducted at a tertiary referral center. Indications for IVCF, procedural success and complications, post-IVCF AC practices, and patient outcomes were assessed. Seven hundred fifty-eight IVCFs were placed. Follow-up was available for 688 patients (90.7%) at a median of 342.0 days (interquartile range 81.5 to 758.0). Indications for IVCF placement included contraindication to AC in the presence of acute venous thromboembolism (n = 287 [41.7%]) and prophylaxis (n = 235 [34.2%]). Insertion-related complications occurred in 28 patients (4.1%). After IVCF placement, adequate AC was initiated in 454 patients (66.0%) <3.0 days (interquartile range 0 to 13.0) after insertion, but the overall retrieval rate was only 252 of 688 (36.6%) within a median of 134.0 days (interquartile range 72.50 to 205.8). Significant IVCF-related complications occurred in 122 patients (17.7%) within 32 days (interquartile range 13.0 to 116.8). The most common complication (72 of 131 [55.0%]) was deep vein thrombosis. In conclusion, in a large, modern cohort of patients receiving retrievable IVCFs for a variety of indications by various specialties, IVCF insertion remains safe. However, many patients have IVCF-related complications, and often, even when IVCFs are retrieved, there is a delay between AC and retrieval. Quality improvement initiatives that facilitate the expeditious retrieval of IVCF are needed. PMID- 24176069 TI - Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know. AB - Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects. PMID- 24176070 TI - Associations of dietary fiber intake with long-term predicted cardiovascular disease risk and C-reactive protein levels (from the National Health and Nutrition Examination Survey Data [2005-2010]). AB - Dietary fiber intake might reduce cardiovascular risk factor levels and, in turn, might lower the long-term risk of cardiovascular disease (CVD). A total of 11,113 subjects, aged 20 to 79 years with no history of CVD, from the 2005 to 2010 National Health and Nutrition Examination Survey were included in the present study to examine associations of dietary fiber intake with predicted lifetime CVD risk and C-reactive protein levels. Dietary fiber intake showed a significant gradient association with the likelihood of having a low or an intermediate predicted lifetime CVD risk among young and middle-age adults. In fully adjusted multinomial logistic models, dietary fiber intake was related to a low lifetime CVD risk with an odds ratio of 2.71 (95% confidence interval 2.05 to 3.59) in the young adults and 2.13 (95% confidence interval 1.42 to 3.20) in the middle-age adults and was related to an intermediate lifetime risk of 2.65 (95% confidence interval 1.79 to 3.92) in the young and 1.98 (95% confidence interval 1.32 to 2.98) in the middle-age adults compared with a high lifetime risk. A significant inverse linear association was seen between dietary fiber intake and log transformed C-reactive protein levels with a regression coefficient +/- standard error of -0.18 +/- 0.04 in the highest quartile of fiber intake compared with the lowest fiber intake. In conclusion, these data suggest that dietary fiber intake is independently associated with the predicted lifetime CVD risk, especially in young and middle-age adults. A greater amount of dietary fiber intake might be associated with lower C-reactive protein levels. PMID- 24176072 TI - Effect of electrocardiographic P-wave axis on mortality. AB - Although P-wave axis is routinely reported on the printouts of most contemporary electrocardiograms, the prognostic significance of its abnormality has not been systematically evaluated. We examined the association between abnormal P-wave axis and cardiovascular and all-cause mortality in 7,501 participants (53% women, mean age 59 years) from the United States Third National Health and Nutrition Examination Survey. P-wave axis of 0 degrees to 75 degrees was considered normal. Participants were linked to the National Death Index to identify the underlying cause of death listed on the death certificates using the International Classification of Disease. During a median follow-up of 13.8 years, a total of 2,541 deaths occurred; of which 1,077 were due to a cardiovascular cause. Abnormal P-wave axis was associated with 55% increased risk of all-cause mortality (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.43 to 1.69, p <0.01) and 41% increased risk of cardiovascular mortality (HR 1.41, 95% CI 1.24 to 1.62, p <0.01). After adjustment for age, gender, race/ethnicity, diabetes, systolic blood pressure, body mass index, smoking status, total/high-density lipoprotein cholesterol ratio, previous cardiovascular disease, chronic obstructive pulmonary disease, bronchial asthma, heart rate, and use of antiarrhythmic or atrioventricular nodal blocking drugs, the risk of mortality remained significantly high (HR 1.24 95% CI 1.13 to 1.36, p <0.01 for all-cause mortality and HR 1.19 95% CI 1.03 to 1.38, p = 0.02 for cardiovascular mortality) and was consistent across several subgroups of the participants. In conclusion, abnormal P-wave axis is associated with an increased risk of death, findings that call for attention to this routinely reported finding on contemporary electrocardiographic machines. PMID- 24176071 TI - Four- and seven-year outcomes of patients with congenital heart disease associated pulmonary arterial hypertension (from the REVEAL Registry). AB - Uncorrected congenital heart disease (CHD) frequently leads to pulmonary arterial hypertension (PAH), the most severe form of which is Eisenmenger syndrome (ES). We compared patients with idiopathic or heritable PAH (IPAH or HPAH; n = 1,626) against those with CHD-associated PAH (n = 353) who were enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL Registry). Of patients with CHD-associated PAH, 151 had ES. Compared with the IPAH or HPAH cohort, the ES cohort had greater systemic blood flow (2 +/- 1 vs 3 +/- 2 L/min/m(2), p <0.001), lower mean right atrial pressure (10 +/- 6 vs 7 +/- 4 mm Hg, p <0.001), higher mean pulmonary artery pressure (53 +/- 14 vs 65 +/- 17 mm Hg, p <0.001), higher pulmonary vascular resistance index (22 +/- 12 vs 32 +/- 31 Wood units * m(2), p <0.001), and lower systemic arterial oxygen saturation at rest (92 +/- 11% vs 84 +/- 13%, p <0.001). At 4 years from enrollment and 7 years from diagnosis, survival rate was similar between IPAH or HPAH and CHD-associated PAH cohorts. For the overall CHD-associated PAH cohort, longer 6-minute walk distance, lower mean right atrial pressure, brain natriuretic peptide level <50 pg/ml, and the presence of acute vasoreactivity were predictors of survival at 4 years from enrollment; younger age and lower mean right atrial pressure were predictors of survival at 7 years from diagnosis. In conclusion, these observations support predicted physiologic differences (e.g., hemodynamics) between patients with IPAH or HPAH and patients with CHD-associated PAH, with or without a systemic-pulmonary shunt. These differences, however, did not translate into significantly improved 4- and 7-year survival rates in patients with ES versus IPAH or HPAH and CHD-associated PAH. PMID- 24176073 TI - Relation of left ventricular mass at age 23 to 35 years to global left ventricular systolic function 20 years later (from the Coronary Artery Risk Development in Young Adults study). AB - Left ventricular (LV) mass and the LV ejection fraction (LVEF) are major independent predictors of future cardiovascular disease. The association of LV mass with the future LVEF in younger populations has not been studied. The aim of this study was to investigate the relation of LV mass index (LVMI) at ages 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CARDIA is a longitudinal study that enrolled young adults in 1985 and 1986. In this study, participants with echocardiographic examinations at years 5 and 25 were included. LVMI and the LVEF were assessed using M-mode echocardiography at year 5 and using M-mode and 2 dimensional imaging at year 25. Statistical analytic models assessed the correlation between LVMI and LV functional parameters cross-sectionally and longitudinally. A total of 2,339 participants were included. The mean LVEF at year 25 was 62%. Although there was no cross-sectional correlation between LVMI and the LVEF at year 5, there was a small but statistically significant negative correlation between LVMI at year 5 and the LVEF 20 years later (r = -0.10, p <0.0001); this inverse association persisted for LVMI in the multivariate model. High LVMI was an independent predictor of systolic dysfunction (LVEF <50%) 20 years later (odds ratio 1.46, p = 0.0018). In conclusion, LVMI in young adulthood in association with chronic risk exposure affects systolic function in middle age; the antecedents of heart failure may occur at younger ages than previously thought. PMID- 24176074 TI - Minimal changes in postoperative creatinine values and early and late mortality and cardiovascular events after coronary artery bypass grafting. AB - Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with adverse outcomes. This study investigated if already a minimal change of 0 to 0.3 mg/dl in postoperative serum creatinine values was associated with early death and long-term cardiovascular outcomes and death. From the SWEDEHEART registry, we included 25,686 patients who underwent elective, isolated, primary CABG in Sweden from 2000 to 2008. AKI was categorized according to increases in postoperative creatinine values: group 1, 0 to 0.3 mg/dl; group 2, 0.3 to 0.5 mg/dl; and group 3, >0.5 mg/dl. The primary outcome measure was death from any cause. During a mean follow-up of 6 years, there were 4,350 deaths (17%) and 7,095 hospitalizations (28%) for myocardial infarction, stroke, heart failure, or death (secondary outcome). The adjusted odds ratios (95% confidence interval [CI]) for early mortality in AKI groups 1 to 3 were 1.37 (0.84 to 2.21), 3.64 (2.07 to 6.38), and 15.4 (9.98 to 23.9), respectively. For long-term mortality, the corresponding hazard ratios (95% CI) were 1.07 (1.00 to 1.15), 1.33 (1.19 to 1.48), and 2.11 (1.92 to 2.32), respectively. There was a significant association between each AKI group and the composite outcome (HR 1.09, 95% CI 1.03 to 1.15; HR 1.39, 95% CI 1.27 to 1.52; and HR 1.99, 95% CI 1.84 to 2.16, respectively). In conclusion, already a minimal increase in the postoperative serum creatinine level after CABG was independently associated with long-term all-cause mortality and cardiovascular outcomes, regardless of preoperative renal function. PMID- 24176076 TI - Identifying the public health benefits of livestock-dependent, agro-ecosystems under climate change. AB - As the demand for meat continues to grow in South Asia and Africa and access to communal sources of water and forage shrinks, intensification of small-scale livestock systems in peri-urban areas is expected to expand. In South East Asia, smallholder transition to livestock intensification has been transformative, increasing economic opportunities while also introducing new disease risks. While we have an understanding of the emerging disease burden from livestock intensification; we have just begun to understand the possible public health benefits of sustainable landscapes and the potential health savings accrued from disease avoidance. To date, few studies have attempted to quantify the health benefits attributable to sustainable agro-ecosystems, especially in regard to livestock systems. In this paper, I will examine what is needed to measure and communicate the public health benefits and cost-savings (from disease avoidance) of sustainable agro-ecosystems. PMID- 24176075 TI - ADAMTS proteoglycanases in the physiological and pathological central nervous system. AB - ADAMTS-1, -4, -5 and -9 belong to 'a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)' family and more precisely to the proteoglycanases subgroup based on their common ability to degrade chondroitin sulfate proteoglycans. They have been extensively investigated for their involvement in inflammation-induced osteoarthritis, and a growing body of evidence indicates that they may be of key importance in the physiological and pathological central nervous system (CNS). In this review, we discuss the deregulated expression of ADAMTS proteoglycanases during acute CNS injuries, such as stroke and spinal cord injury. Then, we provide new insights on ADAMTS proteoglycanases mediating synaptic plasticity, neurorepair, angiogenesis and inflammation mechanisms. Altogether, this review allows us to propose that ADAMTS proteoglycanases may be original therapeutic targets for CNS injuries. PMID- 24176077 TI - Transposon variation by order during allopolyploidisation between Brassica oleracea and Brassica rapa. AB - Although many studies have shown that transposable element (TE) activation is induced by hybridisation and polyploidisation in plants, much less is known on how different types of TE respond to hybridisation, and the impact of TE associated sequences on gene function. We investigated the frequency and regularity of putative transposon activation for different types of TE, and determined the impact of TE-associated sequence variation on the genome during allopolyploidisation. We designed different types of TE primers and adopted the Inter-Retrotransposon Amplified Polymorphism (IRAP) method to detect variation in TE-associated sequences during the process of allopolyploidisation between Brassica rapa (AA) and Brassica oleracea (CC), and in successive generations of self-pollinated progeny. In addition, fragments with TE insertions were used to perform Blast2GO analysis to characterise the putative functions of the fragments with TE insertions. Ninety-two primers amplifying 548 loci were used to detect variation in sequences associated with four different orders of TE sequences. TEs could be classed in ascending frequency into LTR-REs, TIRs, LINEs, SINEs and unknown TEs. The frequency of novel variation (putative activation) detected for the four orders of TEs was highest from the F1 to F2 generations, and lowest from the F2 to F3 generations. Functional annotation of sequences with TE insertions showed that genes with TE insertions were mainly involved in metabolic processes and binding, and preferentially functioned in organelles. TE variation in our study severely disturbed the genetic compositions of the different generations, resulting in inconsistencies in genetic clustering. Different types of TE showed different patterns of variation during the process of allopolyploidisation. PMID- 24176078 TI - Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine. AB - Brucella melitensis Rev 1 is the best vaccine available for the prophylaxis of small ruminant brucellosis and, indirectly, for reducing human brucellosis. However, Rev 1 shows anomalously high rates of spontaneous dissociation from smooth (S) to rough (R) bacteria, the latter being inefficacious as vaccines. This S-R instability results from the loss of the O-polysaccharide. To overcome this problem, we investigated whether some recently described mechanisms promoting mutations in O-polysaccharide genes were involved in Rev 1 S-R dissociation. We found that a proportion of Rev 1 R mutants result from genome rearrangements affecting the wbo O-polysaccharide loci of genomic island GI-2 and the wbkA O-polysaccharide glycosyltransferase gene of the wbk region. Accordingly, we mutated the GI-2 int gene and the wbk IS transposase involved in those arrangements, and found that these Rev 1 mutants maintained the S phenotype and showed lower dissociation levels. Combining these two mutations resulted in a strain (Rev 2) displaying a 95% decrease in dissociation with respect to parental Rev 1 under conditions promoting dissociation. Rev 2 did not differ from Rev 1 in the characteristics used in Rev 1 typing (growth rate, colonial size, reactivity with O-polysaccharide antibodies, phage, dye and antibiotic susceptibility). Moreover, Rev 2 and Rev 1 showed similar attenuation and afforded similar protection in the mouse model of brucellosis vaccines. We conclude that mutations targeting genes and DNA sequences involved in spontaneous O-polysaccharide loss enhance the stability of a critical vaccine phenotype and complement the empirical stabilization precautions taken during S Brucella vaccine production. PMID- 24176080 TI - Tracking clinic performance to improve vascular care: Minnesota Department of Health. PMID- 24176079 TI - Iron deficiency during pregnancy: the consequences for placental function and fetal outcome. AB - This review examines the importance of the placenta in iron metabolism during development and the effect of iron deficiency on maternal and fetal physiology. Iron is an essential micronutrient, required for a wide variety of biological processes. During pregnancy, the mother has to deplete her iron stores in order to provide the baby with adequate amounts. Trans-placental iron transfer involves binding transferrin (Tf)-bound iron to the Tf receptor, uptake into an endosome, acidification, release of iron through divalent metal transporter 1, efflux across the basolateral membrane through ferroportin and oxidation of Fe(II) by zyklopen. An additional haem transport system has been hypothesised, which may explain why certain gene knockouts are not lethal for the developing fetus. Iron deficiency is a common phenomenon during pregnancy, and the placenta adapts by up regulating its transfer systems, maintaining iron at the expense of the mother. Despite these adaptations, deficiency cannot be completely prevented, and the offspring suffers both short- and long-term consequences. Some of these, at least, may arise from decreased expression of genes involved in the cell cycle and altered expression of transcription factors, such as c-myc, which in turn can produce, for example, kidneys with reduced numbers of nephrons. The mechanism whereby these changes are induced is not certain, but may simply be as a result of the reduced availability of iron resulting in decreased enzyme activity. Since these changes are so significant, and because some of the changes are irreversible, we believe that iron prophylaxis should be considered in all pregnancies. PMID- 24176081 TI - Impediments and facilitators to physical activity and perceptions of sedentary behavior among urban community residents: the Fair Park Study. AB - INTRODUCTION: Insufficient physical activity is an established risk factor for numerous chronic diseases and for premature death. Accumulating evidence reveals that prolonged sedentary time is detrimental, independent of the protective effects of physical activity. Although studies have explored correlates of physical activity among ethnic minority populations, few have examined factors related to sedentary behavior. Therefore, we conducted a preliminary investigation into urban adults' perceptions of sedentary behavior alongside perceived barriers and enablers to physical activity. METHODS: In-depth semi structured interviews were used to evaluate perceptions of physical activity and sedentary behavior in a sample of low-income, ethnic minority adults. The framework approach guided researchers in analyzing the qualitative data. RESULTS: Participants were well aware of the positive health benefits of physical activity. However, most admitted not regularly engaging in physical activity and cited numerous barriers to activity, such as lack of time, insufficient finances, and neighborhood crime. Enablers included weight loss, the presence of social support, and the availability of safe parks conducive to exercise. In comparison, participants were primarily unfamiliar with the term "sedentary behavior" and did not perceive a relationship between sedentary behavior and health outcomes. CONCLUSION: Our findings illustrate the need to increase the awareness of negative health implications of prolonged sedentary time while continuing to address the multiple impediments to physical activity as a way to combat chronic disease. PMID- 24176082 TI - Determinants of fruit, vegetable, and dairy consumption in a sample of schoolchildren, northern Serbia, 2012. AB - INTRODUCTION: Insufficient intake of fresh fruits, vegetables, and dairy products among children is a serious nutrition-related concern. The aim of our study was to determine behavioral and environmental factors that influence fruit, vegetable, and dairy consumption among Serbian schoolchildren. METHODS: We used 24-hour recall to measure fruit, vegetable, and dairy intake of schoolchildren (N = 212) aged 8 to 11 years from 2 elementary schools in a local community in Serbia. We evaluated potential determinants of intake by using a 48-item questionnaire that asked about children's behaviors, perceptions of others' expectations and behaviors, reinforcement of children's behaviors, and availability of fruits, vegetables, and dairy at home and school. Children completed written questionnaires during 1 school class under teacher supervision. Binary logistic regression was used to analyze determinants of fruit, vegetable, and dairy intake. RESULTS: Negative predictors of fruit intake were expectations from teacher and parents (P <.001) to eat fruit and availability of fruit in school. Vegetable intake was positively related to paternal modeling behavior (P <.001) and availability of vegetables at home (P = .04). Dairy intake was positively influenced by parental reinforcement (P = .03). CONCLUSION: Various personal and environmental factors are associated with children's intake of fruits, vegetables, and dairy. Interventions to promote fruit, vegetable, and dairy consumption in Serbian schoolchildren should focus on modeling and reinforcement by parents and teachers and increasing availability at school and at home. PMID- 24176083 TI - Patient satisfaction and perceived success with a telephonic health coaching program: the Natural Experiments for Translation in Diabetes (NEXT-D) Study, Northern California, 2011. AB - INTRODUCTION: Health coaching can improve lifestyle behaviors known to prevent or manage chronic conditions such as diabetes. However, little is known about the patient experience with telephonic coaching programs in real-world care settings. We examined patient satisfaction, patient's perceived success in achieving program goals, and the patient-level correlates of these outcomes in a voluntary telephonic coaching program at a large integrated health care delivery system in northern California. METHODS: Kaiser Permanente Northern California patients who participated in a telephonic coaching program in 2011 were sent a cross-sectional survey about their satisfaction with health coaching and perceived success with program goals. We examined associations with patient characteristics. RESULTS: The survey response rate was 34%; analyses were based on the 32% who completed the survey. Of those who had completed 2 or more sessions (n = 232 [52%]), most reported being satisfied (70%) or neutral (20%) with the program, and 71% would recommend health coaching. Healthy weight, healthful eating, and physical activity were the most common topics discussed (88%). Adjusting for demographic characteristics, 73% of those who had 2 or more sessions reported that health coaching helped achieve their weight-related goal. Outcomes were positively correlated with patient activation but not consistently correlated with patient demographic characteristics. CONCLUSION: Levels of satisfaction and perceived success with telephonic health coaching provided by a health plan were high and positively correlated with the number of sessions completed and patient activation. Voluntary telephonic health coaching programs should promote retention and assess patients' activation levels. PMID- 24176084 TI - Community-based interventions in prepared-food sources: a systematic review. AB - INTRODUCTION: Food purchased from prepared-food sources has become a major part of the American diet and is linked to increased rates of chronic disease. Many interventions targeting prepared-food sources have been initiated with the goal of promoting healthful options. The objective of this study was to provide a systematic review of interventions in prepared-food sources in community settings. METHODS: We used PubMed and Google Scholar and identified 13 interventions that met these criteria: 1) focused on prepared-food sources in public community settings, 2) used an impact evaluation, 3) had written documentation, and 4) took place after 1990. We conducted interviews with intervention staff to obtain additional information. Reviewers extracted and reported data in table format to ensure comparability. RESULTS: Interventions mostly targeted an urban population, predominantly white, in a range of income levels. The most common framework used was social marketing theory. Most interventions used a nonexperimental design. All made use of signage and menu labeling to promote healthful food options. Several promoted more healthful cooking methods; only one introduced new healthful menu options. Levels of feasibility and sustainability were high; sales results showed increased purchasing of healthful options. Measures among consumers were limited but in many cases showed improved awareness and frequency of purchase of promoted foods. CONCLUSION: Interventions in prepared-food sources show initial promising results at the store level. Future studies should focus on improved study designs, expanding intervention strategies beyond signage and assessing impact among consumers. PMID- 24176085 TI - The physical and mental health of Head Start staff: the Pennsylvania Head Start staff wellness survey, 2012. AB - INTRODUCTION: Despite attention to the health of low-income children in Head Start, little is known about the health of adults working for the program. The objective of our study was to compare the physical and mental health of women working in Pennsylvania Head Start programs with the health of US women who have similar sociodemographic characteristics. METHODS: We used data from a web-based survey in 2012 in which 2,199 of 3,375 (65.2%) staff in 66 Pennsylvania Head Start programs participated. For the 2,122 female respondents, we determined the prevalence of fair or poor health status, frequent (>=14 d/mo) unhealthy days, frequent (>=10 d/y) work absences due to illness, diagnosed depression, and 3 or more of 6 physical health conditions. We compared these prevalences with those found in 2 national samples of employed women of similar age, education, race/ethnicity, and marital status. RESULTS: Among Head Start staff, 85.7% were non-Hispanic white, 62.4% were married, and 60.3% had completed college. The prevalence (% [95% confidence interval]) of several health indicators was higher in Head Start staff than in the national samples: fair or poor health (14.6% [13.1%-16.1%] vs 5.1% [4.5%-5.6%]), frequent unhealthy days (28.3% [26.3%-30.2%] vs 14.5% [14.1%-14.9%]), diagnosed depression (23.5% [21.7%-25.3%] vs 17.6% [17.1%-18.0%]), and 3 or more physical health conditions (21.8% [20.0%-23.6%] vs 12.6% [11.7%-13.5%]). CONCLUSION: Women working with children in Head Start programs have poorer physical and mental health than do US women who have similar sociodemographic characteristics. PMID- 24176086 TI - Treatment patterns, clinical outcomes and health care costs associated with HER2 positive breast cancer with central nervous system metastases: a French multicentre observational study. AB - BACKGROUND: The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases. METHODS: This multicentre, retrospective, observational study was conducted on HER2-positive BC patients diagnosed with CNS metastases between 2006 and 2008. Data were extracted from patient medical records to estimate health care resource use. A partitioned estimator was used to adjust censoring costs by use of the Kaplan-Meier survival estimate. RESULTS: 218 patients were included and costs were estimated for 200 patients. The median time to detection of CNS metastases was 37.6 months. The first metastatic event involved the CNS in 39 patients, and this was the unique first metastatic site in 31 of these patients. Two years following diagnosis of CNS metastases, 70.3% of patients had died. The mean per capita cost of HER2 positive BC with CNS metastases in the first year following diagnosis was ?35,735 [95% CI: 31,716-39,898]. The proportion of costs attributed to expensive drugs and those arising from hospitalisation were in the same range. CONCLUSION: A range of individualised disease management strategies are used in HER2-positive BC patients with CNS metastases and the treatments used in the first months following diagnosis are expensive. The understanding of cost drivers may help optimise healthcare expenditure and inform the development of appropriate prevention policies. PMID- 24176087 TI - Nontransected ventral onlay-augmented urethroplasty using autologous saphenous vein graft in a rabbit model of urethral stricture. AB - OBJECTIVE: To evaluate the efficacy and feasibility of nontransected ventral onlay-augmented urethroplasty using an autologous saphenous vein graft in a rabbit model of urethral stricture. METHODS: Ten white male rabbits weighing 3.0 3.5 kg were selected, and a long tract urethral stricture was generated by excising an 0.8-cm wide and 2-cm long portion of the distal urethra. One month after the procedure, the rabbits were randomized into a urethral stricture group (n = 5) or urethroplasty with saphenous vein graft group (n = 5). Another 5 rabbits served as a normal control group. Retrograde urethrography was performed at 2, 4, 8, and 12 weeks after surgery in all groups, and the rabbits were killed at 12 weeks postoperatively for histopathologic and immunohistochemical evaluation. RESULTS: The mean operated urethral width of the normal, stricture, and vein graft group was 10.2 +/- 0.84, 4.3 +/- 0.97, and 10.04 +/- 2.35 mm at 2 weeks postoperatively, respectively (P = .008). The 4-, 8-, and 12-week postoperative urethrograms revealed results similar to those of the 2-week postoperative urethrograms. Histologic analysis showed the neourethra was epithelialized with urothelium in the vein graft group. All the rabbits survived throughout the study period without fistula formation or infection. CONCLUSION: Nontransected ventral onlay-augmented urethroplasty using an autologous saphenous vein graft can be an effective and feasible procedure for the surgical management of long tract urethral stricture. PMID- 24176088 TI - Translation of SBGN maps: Process Description to Activity Flow. AB - BACKGROUND: The Systems Biology Graphical Notation (SBGN) provides standard graphical languages for representing cellular processes, interactions, and biological networks. SBGN consists of three languages: Process Descriptions (PD), Entity Relationships (ER), and Activity Flows (AF). Maps in SBGN PD are often large, detailed, and complex, therefore there is a need for a simplified illustration. RESULTS: To solve this problem we define translations of SBGN PD maps into the more abstract SBGN AF maps. We present a template-based translation which allows the user to focus on different aspects of the underlying biological system. We also discuss aspects of laying out the AF map and of interactive navigation between both the PD and the AF map. The methods developed here have been implemented as part of SBGN-ED ( http://www.sbgn-ed.org). CONCLUSIONS: SBGN PD maps become much smaller and more manageable when translated into SBGN AF. The flexible translation of PD into AF and related interaction methods are an initial step in translating the different SBGN languages and open the path to future research for translation methods between other SBGN languages. PMID- 24176090 TI - Wedelolactone inhibits LPS-induced pro-inflammation via NF-kappaB pathway in RAW 264.7 cells. AB - BACKGROUND: Wedelolactone (WEL), a major coumestan ingredient in Wedelia chinensis, has been used to treat septic shock, hepatitis and venom poisoning in traditional Chinese medicines. The objective of the study was to elucidate the anti-inflammatory effects and mechanism of WEL with a cellular model of lipopolysaccharide (LPS)-induced RAW 264.7 cells. RESULTS: To study the role of WEL in pro-inflammation, we measured key inflammation mediators and end products including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF alpha) by using the Griess method, enzyme linked immunosorbent assay (ELISA) and Western blotting. Nuclear factor-kappaB (NF-kappaB) transcription activity was detected by luciferase reporter assay. The important pro-inflammatory transcription factors, NF-kappaB p65 and inhibitory kappaB alpha (IkappaB-alpha); and mitogen-activated protein kinases (MAPKs), including extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) were analyzed by Western blotting. Our study showed that WEL (0.1, 1, 10 MUM) significantly inhibited the protein expression levels of iNOS and COX-2 in LPS stimulated cells, as well as the downstream products, including NO, PGE2 and TNF alpha. Moreover, WEL also inhibited LPS-induced NF-kappaB p65 activation via the degradation and phosphorylation of IkappaB-alpha and subsequent translocation of the NF-kappaB p65 subunit to the nucleus. CONCLUSIONS: Our results revealed that WEL has a potential to be a novel anti-inflammatory agent targeting on the NF kappaB signaling pathway. PMID- 24176089 TI - Obesity associated alterations in the biology of adipose stem cells mediate enhanced tumorigenesis by estrogen dependent pathways. AB - INTRODUCTION: Obesity has been associated with increased incidence and mortality of breast cancer. While the precise correlation between obesity and breast cancer remains to be determined, recent studies suggest that adipose tissue and adipose stem cells (ASCs) influence breast cancer tumorigenesis and tumor progression. METHODS: Breast cancer cells lines were co-cultured with ASCs (n = 24), categorized based on tissue site of origin and body mass index (BMI), and assessed for enhanced proliferation, alterations in gene expression profile with PCR arrays, and enhanced tumorigenesis in immunocompromised mice. The gene expression profile of ASCs was assess with PCR arrays and qRT-PCR and confirmed with Western blot analysis. Inhibitory studies were conducted by delivering estrogen antagonist ICI182,780, leptin neutralizing antibody, or aromatase inhibitor letrozole and assessing breast cancer cell proliferation. To assess the role of leptin in human breast cancers, Oncomine and Kaplan Meier plot analyses were conducted. RESULTS: ASCs derived from the abdominal subcutaneous adipose tissue of obese subjects (BMI > 30) enhanced breast cancer cell proliferation in vitro and tumorigenicity in vivo. These findings were correlated with changes in the gene expression profile of breast cancer cells after co-culturing with ASCs, particularly in estrogen receptor-alpha (ESR1) and progesterone receptor (PGR) expression. Analysis of the gene expression profile of the four groups of ASCs revealed obesity induced alterations in several key genes, including leptin (LEP). Blocking estrogen signaling with ICI182,780, leptin neutralizing antibody, or letrozole diminished the impact of ASCs derived from obese subjects. Women diagnosed with estrogen receptor/progesterone receptor positive (ER+/PR+) breast cancers that also expressed high levels of leptin had poorer prognosis than women with low leptin expression. CONCLUSION: ASCs isolated from the abdomen of obese subjects demonstrated increased expression of leptin, through estrogen stimulation, which increased breast cancer cell proliferation. The results from this study demonstrate that abdominal obesity induces significant changes in the biological properties of ASCs and that these alterations enhance ER+/PR+ breast cancer tumorigenesis through estrogen dependent pathways. PMID- 24176091 TI - Fat source and dietary forage-to-concentrate ratio influences milk fatty-acid composition in lactating cows. AB - On the basis of the potential benefits to human health there is an increased interest in producing milk containing lower-saturated fatty acid (SFA) and higher unsaturated fatty acid (FA) concentrations, including cis-9 18:1 and cis-9, trans 11-conjugated linoleic acid (CLA). Twenty-four multiparous Holstein cows were used in two experiments according to a completely randomized block design, with 21-day periods to examine the effects of incremental replacement of prilled palm fat (PALM) with sunflower oil (SFO) in high-concentrate diets containing 30 g/kg dry matter (DM) of supplemental fat (Experiment 1) or increases in the forage-to concentrate (F : C) ratio from 39 : 61 to 48 : 52 of diets containing 30 g/kg DM of SFO (Experiment 2) on milk production, digestibility and milk FA composition. Replacing PALM with SFO had no effect on DM intake, but tended to increase organic matter digestibility, yields of milk, protein and lactose, and decreased linearly milk fat content. Substituting SFO for PALM decreased linearly milk fat 8:0 to 16:0 and cis-9 16:1, and increased linearly 18:0, cis-9 18:1, trans-18:1 (??4 to 16), 18:2 and CLA concentrations. Increases in the F : C ratio of diets containing SFO had no effect on intake, yields of milk, milk protein or milk lactose, lowered milk protein content in a quadratic manner, and increased linearly NDF digestion and milk fat secretion. Replacing concentrates with forages in diets containing SFO increased milk fat 4:0 to 10:0 concentrations in a linear or quadratic manner, decreased linearly cis-9 16:1, trans-6 to -10 18:1, 18:2n-6, trans-7, cis-9 CLA, trans-9, cis-11 CLA and trans-10, cis-12 CLA, without altering milk fat 14:0 to 16:0, trans-11 18:1, cis-9, trans-11 CLA or 18:3n-3 concentrations. In conclusion, replacing prilled palm fat on with SFO in high-concentrate diets had no adverse effects on intake or milk production, other than decreasing milk fat content, but lowered milk fat medium-chain SFA and increased trans FA and polyunsaturated FA concentrations. Increases in the proportion of forage in diets containing SFO increased milk fat synthesis, elevated short-chain SFA and lowered trans FA concentrations, without altering milk polyunsaturated FA content. Changes in fat yield on high-concentrate diets containing SFO varied between experiments and individual animals, with decreases in milk fat secretion being associated with increases in milk fat trans-10 18:1, trans-10, cis-12 CLA and trans-9, cis-11 CLA concentrations. PMID- 24176092 TI - Functional conservation of HIV-1 Gag: implications for rational drug design. AB - BACKGROUND: HIV-1 replication can be successfully blocked by targeting gag gene products, offering a promising strategy for new drug classes that complement current HIV-1 treatment options. However, naturally occurring polymorphisms at drug binding sites can severely compromise HIV-1 susceptibility to gag inhibitors in clinical and experimental studies. Therefore, a comprehensive understanding of gag natural diversity is needed. FINDINGS: We analyzed the degree of functional conservation in 10862 full-length gag sequences across 8 major HIV-1 subtypes and identified the impact of natural variation on known drug binding positions targeted by more than 20 gag inhibitors published to date. Complete conservation across all subtypes was detected in 147 (29%) out of 500 gag positions, with the highest level of conservation observed in capsid protein. Almost half (41%) of the 136 known drug binding positions were completely conserved, but all inhibitors were confronted with naturally occurring polymorphisms in their binding sites, some of which correlated with HIV-1 subtype. Integration of sequence and structural information revealed one drug binding pocket with minimal genetic variability, which is situated at the N-terminal domain of the capsid protein. CONCLUSIONS: This first large-scale analysis of full-length HIV-1 gag provided a detailed mapping of natural diversity across major subtypes and highlighted the considerable variation in current drug binding sites. Our results contribute to the optimization of gag inhibitors in rational drug design, given that drug binding sites should ideally be conserved across all HIV-1 subtypes. PMID- 24176093 TI - Diagnostic data for neurological conditions in interRAI assessments in home care, nursing home and mental health care settings: a validity study. AB - BACKGROUND: The interRAI suite of assessment instruments can provide valuable information to support person-specific care planning across the continuum of care. Comprehensive clinical information is collected with these instruments, including disease diagnoses. In Canada, interRAI data holdings represent some of the largest repositories of clinical information in the country for persons with neurological conditions. This study examined the accuracy of the diagnostic information captured by interRAI instruments designed for use in the home care, long-term care and mental health care settings as compared with national administrative databases. METHODS: The interRAI assessments were matched with an inpatient hospital record and emergency department (ED) visit record in the preceding 90 days. Diagnoses captured on the interRAI instruments were compared to those recorded in either administrative record for each individual. Diagnostic validity was examined through sensitivity, specificity and positive predictive value analysis for the following conditions: multiple sclerosis, epilepsy, Alzheimer's disease and other dementias, Parkinson's disease, traumatic brain injury, stroke, diabetes mellitus, heart failure and reactive airway disease. RESULTS: In the three large study samples (home care: n = 128,448; long-term care: n = 26,644; mental health: n = 13,812), interRAI diagnoses demonstrated high specificity when compared to administrative records, for both neurological conditions (range 0.80-1.00) and comparative chronic diseases (range 0.83-1.00). Sensitivity and positive predictive values (PPV) were more varied by specific diagnosis, with sensitivities and PPV for neurological conditions ranging from 0.23 to 0.94 and 0.14 to 0.77, respectively. The interRAI assessments routinely captured more cases of the diagnoses of interest than the administrative records. CONCLUSIONS: The interRAI assessment collected accurate information about disease diagnoses when compared to administrative records within three months. Such information is likely relevant to day-to-day care in these three environments and can be used to inform care planning and resource allocation decisions. PMID- 24176094 TI - Locomotion, cognition and influences of nutrition in ageing. AB - Gait and cognitive impairments in older adults can reflect the simultaneous existence of two syndromes that affect certain brain substrates and pathologies. Nutritional deficiencies, which are extremely common among elderly population worldwide, have potential to impact the existence and rehabilitation of both syndromes. Gait and cognition are controlled by brain circuits which are vulnerable to multiple age-related pathologies such as vascular diseases, inflammation and dementias that may be caused or accentuated by poor nutrition or deficiencies that lead to cognitive, gait or combined cognitive and gait impairments. The following review aims to link gait and cognitive classifications and provide an overview of the potential impact of nutritional deficiencies on both neurological and gait dysfunctions. The identification of common modifiable risk factors, such as poor nutrition, may serve as an important preventative strategy to reduce cognitive and mobility impairments and moderate the growing burden of dementia and disability worldwide. PMID- 24176095 TI - Jugular venous reflux and brain parenchyma volumes in elderly patients with mild cognitive impairment and Alzheimer's disease. AB - BACKGROUND: To determine whether or not jugular venous reflux (JVR) is associated with structural brain parenchyma changes in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: 16 AD patients (mean (SD): 81.9 (5.8) years), 33 MCI patients (mean (SD): 81.4 (6.1) years) and 18 healthy elderly controls (mean (SD): 81.5 (3.4) years) underwent duplex ultrasonography and magnetic resonance imaging scans to quantify structural brain parenchyma changes. Normalized whole brain (WB), gray matter (GM) and white matter (WM) volumes were collected, together with CSF volume. RESULTS: JVR was strongly associated with increased normalized WB (p = 0.014) and GM (p = 0.002) volumes across all three subject groups. There was a trend towards increased WB and GM volumes, which was accompanied by decreased CSF volume, in the JVR positive subjects in both the MCI and AD groups. When the MCI and AD subjects were aggregated together significant increases were observed in both normalized WB (p = 0.009) and GM (p = 0.003) volumes for the JVR-positive group. No corresponding increases were observed for the JVR-positive subjects in the control group. Through receiver operating characteristic analysis of the brain volumetric data it was possible to discriminate between the JVR-positive and negative AD subjects with reasonable accuracy (sensitivity = 71.4%; specificity = 88.9%; p = 0.007). CONCLUSIONS: JVR is associated with intracranial structural changes in MCI and AD patients, which result in increased WB and GM volumes. The neuropathology of this unexpected and counterintuitive finding requires further investigation, but may suggest that JVR retrogradely transmits venous hypertension into the brain and leads to brain tissues swelling due to vasogenic edema. PMID- 24176096 TI - Anatomical alterations of Phaseolus vulgaris L. mature leaves irradiated with X rays. AB - The cultivation of higher plants in Space involves not only the development of new agro-technologies for the design of ecologically closed Space greenhouses, but also understanding of the effects of Space factors on biological systems. Among Space factors, ionising radiation is one of the main constraints to the growth of organisms. In this paper, we analyse the effect of low-LET radiation on leaf histology and cytology in Phaseolus vulgaris L. plants subjected to increasing doses of X-rays (0.3, 10, 50, 100 Gy). Leaves irradiated at tissue maturity were compared with not-irradiated controls. Semi-thin sections of leaves were analysed through light and epi-fluorescence microscopy. Digital image analysis was applied to quantify anatomical parameters, with a specific focus on the occurrence of signs of structural damage as well as alterations at subcellular level, such as the accumulation of phenolic compounds and chloroplast size. Results showed that even at high levels of radiation, general anatomical structure was not severely perturbed. Slight changes in mesophyll density and cell enlargement were detected at the highest level of radiation. However, at 100 Gy, higher levels of phenolic compounds accumulated along chloroplast membranes: this accompanied an increase in number of chloroplasts. The reduced content of chlorophylls at high levels of radiation was associated with reduced size of the chloroplasts. All data are discussed in terms of the possible role of cellular modifications in the maintenance of high radioresistance and photosynthetic efficiency. PMID- 24176097 TI - Molecular phylogenetic analyses support the monophyly of Hexapoda and suggest the paraphyly of Entognatha. AB - BACKGROUND: Molecular phylogenetic analyses have revealed that Hexapoda and Crustacea form a common clade (the Pancrustacea), which is now widely accepted among zoologists; however, the origin of Hexapoda remains unresolved. The main problems are the unclear relationships among the basal hexapod lineages, Protura (proturans), Collembola (springtails), Diplura (diplurans), and Ectognatha (bristletails, silverfishes, and all winged insects). Mitogenomic analyses have challenged hexapod monophyly and suggested the reciprocal paraphyly of Hexapoda and Crustacea, whereas studies based on nuclear molecular data support the monophyletic origin of hexapods. Additionally, there are significant discrepancies with respect to these issues between the results of morphological and molecular studies. To investigate these problems, we performed phylogenetic analyses of Pancrustacea based on the protein sequences of three orthologous nuclear genes encoding the catalytic subunit of DNA polymerase delta and the largest and second largest subunits of RNA polymerase II from 64 species of arthropods, including representatives of all hexapod orders. RESULTS: Phylogenetic analyses were conducted based on the inferred amino acid (aa) sequences (~3400 aa in total) of the three genes using the maximum likelihood (ML) method and Bayesian inference. Analyses were also performed with additional datasets generated by excluding long-branch taxa or by using different outgroups. These analyses all yielded essentially the same results. All hexapods were clustered into a common clade, with Branchiopoda as its sister lineage, whereas Crustacea was paraphyletic. Within Hexapoda, the lineages Ectognatha, Palaeoptera, Neoptera, Polyneoptera, and Holometabola were each confirmed to be monophyletic with robust support, but monophyly was not supported for Entognatha (Protura + Collembola + Diplura), Ellipura (Protura + Collembola), or Nonoculata (Protura + Diplura). Instead, our results showed that Protura is the sister lineage to all other hexapods and that Diplura or Diplura + Collembola is closely related to Ectognatha. CONCLUSION: This is the first study to include all hexapod orders in a phylogenetic analysis using multiple nuclear protein-coding genes to investigate the phylogeny of Hexapoda, with an emphasis on Entognatha. The results strongly support the monophyletic origin of hexapods but reject the monophyly of Entognatha, Ellipura, and Nonoculata. Our results provided the first molecular evidence in support of Protura as the sister group to other hexapods. These findings are expected to provide additional insights into the origin of hexapods and the processes involved in the adaptation of insects to life on land. PMID- 24176098 TI - Clinical effectiveness and cost-effectiveness of minimally invasive techniques to manage varicose veins: a systematic review and economic evaluation. AB - BACKGROUND: Varicose veins are enlarged, visibly lumpy knotted veins, usually in the legs. Uncomplicated varicose veins can cause major discomfort and some complications. They are part of chronic venous disease (CVD), which is reported to have a substantial negative impact on health-related quality of life (HRQoL). Traditional treatments for varicose veins involve surgical stripping and ligation and liquid sclerotherapy (LS), but can be invasive and painful. New minimally invasive treatments offer an alternative. These treatments typically involve use of laser, radiofrequency or foam sclerosant. They are increasingly widely used and offer potential benefits such as reduced complications, faster recovery, fewer physical limitations and improved quality of life. OBJECTIVE: The aim of this report is to evaluate the clinical effectiveness, safety and cost effectiveness of the minimally invasive techniques of foam sclerotherapy (FS), endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in comparison with other techniques, including traditional surgical techniques, LS and conservative management, in the management of varicose veins. DATA SOURCES: A systematic search was made of 11 bibliographic databases of published and unpublished literature from their inception to July 2011: MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature; The Cochrane Library; Biological Abstracts; Science Citation Index (SCI); Social Sciences Citation Index; Conference Proceedings Citation Index-Science; UK Clinical Research Network; Current Controlled Trials; and ClinicalTrials.gov. REVIEW METHODS: A systematic review of randomised controlled trials (RCTs) to assess the clinical effectiveness of minimally invasive techniques compared with other treatments, principally surgical stripping, in terms of recurrence of varicose veins, retreatment and clinical symptoms, as measured by the Venous Clinical Severity Score (VCSS), pain and quality of life. Network meta-analysis and exploratory cost-effectiveness modelling were performed. RESULTS: The literature search identified 1453 unique citations, of which 34 RCTs (54 papers) satisfied the criteria for the clinical effectiveness review. The minimally invasive techniques reported clinical outcomes similar to surgery. Rates of recurrence were slightly lower for EVLA, RFA and FS, especially for longer follow-up periods; VCSS score was lower for EVLA and FS than for stripping, but slightly higher for RFA; short term pain was less for FS and RFA but higher for EVLA; higher quality-of-life scores were reported for all evaluated interventions than for stripping. Differences between treatments were therefore negligible in terms of clinical outcomes, so the treatment with the lowest cost appears to be most cost effective. Our central estimate is that total FS costs were lowest and FS is marginally more effective than stripping. However, this result was sensitive to the model time horizon. Threshold analysis indicated that EVLA and RFA might be considered cost-effective if their costs are equivalent to stripping. These findings are subject to uncertainty on account of the risk of bias present in the evidence base and the variation in costs. LIMITATIONS: The relative clinical effectiveness and cost-effectiveness of the techniques are principally based on rates of post-operative technical recurrence rather than symptomatic recurrence, as this was the reported outcome in all trials. The true proportion of treated individuals who are likely to present with symptoms of recurrence requiring retreatment is therefore not certain. A figure reflecting the likely proportion of treated individuals who would experience symptomatic recurrence requiring retreatment (with its associated costs), therefore, had to be calculated by the authors based on a small number of studies. The findings of this report also need to be verified by data from future trials with longer follow-up and using more standardised outcome measures. CONCLUSIONS: This assessment of the currently available evidence suggests there is little to choose between the minimally invasive techniques in terms of efficacy or cost, and each offers a viable, clinically effective alternative to stripping. FS might offer the most cost effective alternative to stripping, within certain time parameters. High-quality RCT evidence is needed. Future trials should aim to measure and report outcomes in a standardised manner, which would permit more efficient pooling of their results. STUDY REGISTRATION: PROSPERO number CRD42011001355. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 24176099 TI - The impact of continuous haemofiltration with high-volume fluid exchange during cardiopulmonary bypass surgery on the recovery of patients with impaired renal function: a pilot randomised trial. AB - BACKGROUND: There is widespread variability in clinical practice within cardiac surgery units worldwide on the use of haemofiltration. The clinical impact and safety of this modality is, however, unknown. OBJECTIVES: The primary pilot trial objectives were as follows: to assess the feasibility of randomising 60 patients with impaired kidney function undergoing on-pump coronary artery bypass graft (CABG) surgery within 6 months; to assess the suitability and reliability of our chosen outcome measures; to explore issues that may impact on recruitment into a definitive trial; and to undertake an exploratory economic evaluation. DESIGN: A pilot, single-centre, open-label randomised trial. SETTING: Liverpool Heart and Chest Hospital NHS Foundation Trust between November 2010 and March 2012. PARTICIPANTS: Men and women, aged > 18 years of age, undergoing on-pump CABG surgery, who had pre-operative impaired kidney function indicated by an estimated glomerular filtration rate (eGFR) of < 60 ml/minute adjusted for 1.73 m(2) of body surface area. INTERVENTIONS: Group 1: patients who received haemofiltration during bypass (experimental group). Group 2: patients who did not receive haemofiltration during bypass (control group). MAIN OUTCOME MEASURES: (1) Feasibility outcome measures: barriers to recruitment to a larger trial were documented as observations made during the recruitment period of the trial. Reliability of data collection methods was monitored using a 13-point case record form validation check for data entry against the patient clinical notes and the trial database. (2) The main clinical outcomes were frequency of intensive care unit (ICU) stay of duration > 3 days and the length of ICU stay days. (3) Other clinical outcomes were the need for postoperative haemofiltration in the ICU, mechanical ventilation time, hospital stay, composite of outcome of unfavourable perioperative events and eGFR values at 6 weeks' follow-up. (4) Secondary health economic feasibility outcomes. RESULTS: Recruitment into the pilot trial was from 21 November 2010 to 30 March 2012. Thirty-seven eligible patients were consented and successfully randomised into the trial arms (30%). The main issues impacting on recruitment were the high volume of off-pump CABG surgery within the centre; recruitment being restricted to research nurses' working hours of the week; issues arising associated with the screening process for identifying prospective eligible patients based on eGFR values; protocol deviations/treatment crossovers; and unexpected outbreaks of pandemic influenza and other infectious conditions. The data collection process was sufficiently robust, with few errors detected. The length of ICU stay days was deemed a suitable primary outcome. There was an overall trend towards reduction in the length of ICU stay for patients who were given intraoperative haemofiltration, more so for those with diabetes. The economic evaluation estimated that the incremental costs per person were L1744 lower for the intraoperative haemofiltration group, while the incremental benefits per person increased by 0.11. CONCLUSION: Given sufficient resources and broadening of the inclusion criteria, the recruitment into a larger multicentre trial is feasible and may demonstrate potential clinical and cost benefits of using intraoperative haemofiltration in this group of patients. However, owing to the small sample size in this pilot trial, no firm conclusions can be drawn from the findings at this stage. The outcomes of this pilot study are very encouraging and suggest that it is feasible to design a continuous superiority trial with the length of ICU stay days or time to tracheal extubation as the primary outcome measure, provided that guidelines for avoiding bias are implemented. An alternative primary outcome measure that avoids bias is mortality. The inclusion criteria should also be widened to include all cardiac surgery patients with impaired renal function. TRIAL REGISTRATION: ISRCTN49513454. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 49. See the HTA programme website for further project information. PMID- 24176100 TI - A systematic review of risk assessment strategies for populations at high risk of engaging in violent behaviour: update 2002-8. AB - BACKGROUND: This review systematically examines the research literature published in the period 2002-8 on structured violence risk assessment instruments designed for use in mental health services or the criminal justice system. It adopted much broader inclusion criteria than previous reviews in the same area in order to capture and summarise data on the widest possible range of available instruments. OBJECTIVES: To address two questions: (1) what study characteristics are associated with a risk assessment instrument score being significantly associated with a violent outcome? and (2) which risk assessment instruments have the highest level of predictive validity for a violent outcome? DATA SOURCES: Nineteen bibliographic databases were searched from January 2002 to April 2008, including PsycINFO, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, British Nursing Index, International Bibliography of the Social Sciences, Education Resources Information Centre, The Cochrane Library and Web of Knowledge. REVIEW METHODS: Inclusion criteria for studies were (1) evaluation of a structured risk tool; (2) outcome measure of interpersonal violence; (3) participants aged 17 years or over; and (4) participants with a mental disorder and/or at least one offence and/or at least one indictable offence. A series of bivariate analyses using either a chi-squared test or Spearman's rank-order correlation were conducted to explore associations between study characteristics and outcomes. Data from a subset of studies reporting area under the curve (AUC) analysis were combined to provide estimates of mean validity. RESULTS: For the overall set of included studies (n = 959), over three-quarters (77%) were conducted in the USA, Canada or the UK. Two-thirds of all studies were conducted with offenders who had either no formal mental health diagnosis (43%) or forensic samples with a formal diagnosis (25%). The Psychopathy Checklist-Revised was tested in the largest number of studies (n = 192). Most studies (78%) reported a statistically significant (p < 0.05) relationship between the instrument score and a violent outcome. Prospective data collection (chi-squared = 4.4, p = 0.035), number of people recruited (U = 27.8, p = 0.012) and number of participants at end point (U = 26.9, p = 0.04) were significantly associated with predictive validity. For those instruments tested in five or more studies reporting AUC values, the General Statistical Information on Recidivism instrument had the highest mean AUC (0.73). LIMITATIONS: Agreement between pairs of reviewers in the initial pilot exercises was good but less than perfect, so discrepancies may be present given the complexity and subjectivity of some aspects of violence research. Only five of the seven calendar years (2003-7) are completely covered, with partial coverage of 2002 and 2008. There is no weighting for sample or effect sizes when results from studies are aggregated. CONCLUSIONS: A very large number of studies examining the relationship between a structured instrument and a violent outcome were published in this relatively short 7-year period. The general quality of the literature is weak in places (e.g. over-reliance on cross-sectional designs) and a vast range of distinct instruments have been tested to varying degrees. However, there is evidence of some convergence around a small number of high performing instruments and identification of the components of a high-quality evaluation approach, including AUC analysis. The upper limits (AUC >= 0.85) of instrument-based prediction have probably been achieved and are unlikely to be exceeded using instruments alone. FUNDING: The National Institute for Health Research Health Technology Assessment and Research for Patient Benefit programmes. PMID- 24176101 TI - Molecular fingerprinting catches responders to therapeutic agents. AB - High-dimensional -omics profiling predicts responses to therapeutic agents in breast cancer cell lines that can be effectively applied to patient selection in clinical trials. PMID- 24176103 TI - Novel microwell assay with high throughput and minimum consumption for organic solvents in the charge transfer-based spectrophotometric determination of clarithromycin in pharmaceutical formulations. AB - BACKGROUND: Clarithromycin (CLM) is a semi-synthetic macrolide antibiotic with a broad antibacterial spectrum. It has a potent activity against Myc. Pneumonia, Legionella Spp., H. Influenza, and Mor. Catarrhalis. It is also used for prevention and treatment of disseminated M. Avium infections in patients with AIDS. The therapeutic importance and wide use of CLM promotes the growing interest in developing proper methods for its determination in bulk and pharmaceutical formulations. RESULTS: The present study describes the development and validation of a novel assay that can increase the throughput and reduce the consumption of organic solvents in the charge transfer (CT)-based spectrophotometric determination of CLM. In this assay, the CT reaction between CLM as n-electron donor and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a pi-electron acceptor was performed in the 96-microwells of an assay plate. The color signals of the CT complex were measured at 450 nm by microwell-plate absorbance reader. The linear range of the assay was 20-850 MUg mL-1. The limits of detection and quantitation were 15.5 and 51.2 MUg mL-1, respectively. The proposed assay gave very high precisions; the relative standard deviation (RSD) values did not exceed 1.82%. CONCLUSIONS: The assay described herein has a high throughput property that facilitates the processing of large number of samples in a reasonable time. As well, it consumes minimum volumes of organic solvents, thus it significantly reduces the exposures of the analysts to the toxic effects of organic solvents, and reduce the analysis cost by 50-folds. The results demonstrated that the proposed assay has great practical value in the routine analysis of CLM in quality control laboratories. PMID- 24176102 TI - Nonstructural protein P7-2 encoded by Rice black-streaked dwarf virus interacts with SKP1, a core subunit of SCF ubiquitin ligase. AB - BACKGROUND: Rice black-streaked dwarf virus (RBSDV), a member of the genus Fijivirus within the family Reoviridae, causes severe damage to cereal crops in South East Asia. The protein P7-2, encoded by the second open reading frame of segment S7, is conserved among most plant-infecting fijiviruses, but its function is still obscure. RESULTS: In this study, P7-2 was used as bait in two-hybrid screens of a cDNA library expressing Zea mays proteins. It was found that there is a strong interaction between P7-2 and Z. mays SKP1 (SKP1Maize), a core subunit of the multicomponent SCF (SKP1/Cullin1/F-box/Rbx1) E3 ubiquitin ligase. The interaction was then confirmed in leaf epidermal cells of Nicotiana benthamiana by bimolecular fluorescence complementation assay. Further investigations indicated that P7-2 also interacts with SKP1 proteins from other plants, including Arabidopsis thaliana, N. benthamiana,Oryza sativa and Saccharum sinense. The C-terminal fragment of SKP1Maize (residues 97-176) and the middle fragment of P7-2 (residues 79-214) are necessary to sustain the interaction, while the C-terminal putative alpha-helix domain spanning residues 214-295 of P7 2 greatly facilitates the interaction. Agrobacterium-mediated transient suppression assay showed that P7-2 has no obvious activity to suppress local RNA silencing. CONCLUSIONS: Taken together, our results indicated that RBSDV P7-2 can interact with SKP1 proteins from different plants. This is the first report linking a Fijivirus protein to a component of the ubiquitin proteasome system. P7 2 might be a potential F-box protein encoded by RBSDV and involved in the plant virus interaction through ubiquitination pathway. PMID- 24176104 TI - A comprehensive assessment of memory, delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: advancing beyond the three-pathway models. AB - BACKGROUND: Although attention deficit hyperactivity disorder (ADHD) has been associated with a broad range of deficits across various neuropsychological domains, most studies have assessed only a narrow range of neuropsychological functions. Direct cross-domain comparisons are rare, with almost all studies restricted to less than four domains. Therefore, the relationships between these various domains remain undefined. In addition, almost all studies included previously medicated participants, limiting the conclusions that can be drawn. We present the first study to compare a large cohort of medication-naive boys with ADHD with healthy controls on a broad battery of neuropsychological tasks, assessing six key domains of neuropsychological functioning. METHOD: The neuropsychological functioning of 83 medication-naive boys with well characterized ADHD (mean age 8.9 years) was compared with that of 66 typically developing (TYP) boys (mean age 9.0 years) on a broad battery of validated neuropsychological tasks. RESULTS: Data reduction using complementary factor analysis (CFA) confirmed six distinct neuropsychological domains: working memory, inhibition, delay aversion, decision making, timing and response variability. Boys with ADHD performed less well across all six domains although, for each domain, only a minority of boys with ADHD had a deficit [effect size (% with deficit) ADHD versus TYP: working memory 0.95 (30.1), inhibition 0.61 (22.9), delay aversion 0.82 (36.1), decision making 0.55 (20.5), timing 0.71 (31.3), response variability 0.37 (18.1)]. CONCLUSIONS: The clinical syndrome of ADHD is neuropsychologically heterogeneous. These data highlight the complexity of the relationships between the different neuropsychological profiles associated with ADHD and the clinical symptoms and functional impairment. PMID- 24176106 TI - Exploring inattention and distraction in the SafetyNet Accident Causation Database. AB - Distraction and inattention are considered to be very important and prevalent factors in the causation of road accidents. There have been many recent research studies which have attempted to understand the circumstances under which a driver becomes distracted or inattentive and how distraction/inattention can be prevented. Both factors are thought to have become more important in recent times partly due to the evolution of in-vehicle information and communication technology. This study describes a methodology that was developed to understand when factors such as distraction and inattention may have been contributors to crashes and also describes some of the consequences of distraction and inattention in terms of subsequent driver actions. The study uses data relating to distraction and inattention from the SafetyNet Accident Causation Database. This database was formulated as part of the SafetyNet project to address the lack of representative in-depth accident causation data within the European Union. Data were collected in 6 European countries using 'on-scene' and 'nearly on scene' crash investigation methodologies. 32% of crashes recorded in the database, involved at least one driver, rider or pedestrian, who was determined to be 'Inattentive' or 'Distracted'. 212 of the drivers were assigned 'Distraction' and 140 drivers were given the code 'Inattention'. It was found that both distraction and inattention often lead to missed observations within the driving task and consequently 'Timing' or 'Direction' become critical events in the aetiology of crashes. In addition, the crash types and outcomes may differ according to the type and nature of the distraction and inattention as determined by the in-depth investigations. The development of accident coding methodology is described in this study as is its evolution into the Driver Reliability and Error Analysis Model (DREAM) version 3.0. PMID- 24176105 TI - Solitary tumours associated with Jaagsiekte retrovirus in sheep are heterogeneous and contain cells expressing markers identifying progenitor cells in lung repair. AB - Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). This study examines immunohistochemically solitary lung nodules considered as early OPA lesions from 11 sheep infected naturally by JSRV. All 11 neoplastic nodules exhibited features of adenocarcinoma and in four of them mesenchymal growth was also observed. Both types of lesion were labelled with antibody specific for JSRV-Env. In two cases infiltrating lymphoreticular cells also contained JSRV-Env. All tumours had a high Ki67 labelling index and variably contained cells expressing CC10 (a marker of Clara cells (CCs)), SPC (a marker of type II pneumocytes), p63 and keratin 14 (markers for stem/progenitor cells of the lung airway epithelia). Tumours with mesenchymal growth had intense expression of vimentin and desmin, weak expression of smooth muscle actin and did not express pancytokeratin and p63. Both epithelial and mesenchymal proliferations did not express the stem cell markers CD90 and CD117, but some tumour infiltrating cells expressed CD133. Solitary OPA tumours can therefore be adenocarcinomas or mixed tumours and have a heterogeneous cellular composition, containing groups of cells expressing markers that characterize local progenitor cells involved in lung repair. PMID- 24176107 TI - Effect of different levels of crude glycerol on the morphology and some pathogenic bacteria of the small intestine in male broilers. AB - The gut health of poultry is closely associated with feeds and feeding. The experiment was conducted to the effect of crude glycerol addition to diets of male broilers on the bacterial microflora and morphology of their small intestines (duodenum, jejunum and ileum). A total of 120 Ross 308 broiler chicks received diets containing 0% (GLY 0), 4% (GLY 4) or 8% (GLY 8) crude glycerol for 42 days. The presence of Coliform bacteria and Enterobacteria was reduced in the duodenal tract of the broilers of GLY 4 (P<0.001); however, the presence of Staphylococci/Micrococci in the GLY 8 was reduced relative to the other groups (P<0.001). The presence of Salmonella spp. decreased in conjunction with the increasing quantities of glycerol (P<0.001). Analysis of the data regarding gut morphology (epithelial cell thickness, villi length and width, and crypt length and width) indicated that the glycerol levels fed to the different groups of broilers represented statistically different results in the small intestine. In general, whereas the diet with 4% glycerol statistically affected the investigated parameters of the gut, the diet with 8% glycerol statistically affected some segments of the broiler intestines. PMID- 24176108 TI - Progression of logopenic variant primary progressive aphasia to apraxia and semantic memory deficits. AB - BACKGROUND: Due to the nature of neurodegenerative disorders, patients with primary progressive aphasia develop cognitive impairment other than aphasia as the disorder progresses. The progression of logopenic variant primary progressive aphasia (lvPPA), however, has not been well described. In particular, praxic disorders and semantic memory deficits have rarely been reported. CASE PRESENTATIONS: We report three patients in the initial stage of lvPPA who subsequently developed apraxia in the middle stage and developed clinically evident semantic memory deficits in the advanced stages. CONCLUSIONS: The present case series suggests that some patients with lvPPA develop an atypical type of dementia with apraxia and semantic memory deficits, suggesting that these cases should be classified as a type of early-onset Alzheimer's disease. PMID- 24176109 TI - Effects of immigrant status on Emergency Room (ER) utilisation by children under age one: a population-based study in the province of Reggio Emilia (Italy). AB - BACKGROUND: The primary aim of this study was to assess the effect of immigrant status on Emergency Room (ER) utilisation by children under age one, considering all, non-urgent, very urgent, and followed by hospitalisation visits. The second aim was to investigate the role played by mother's educational level in the relationship between citizenship and ER utilisation. METHODS: The cohort study included all healthy singleton live births in the years 2008-2009 and residing in the province of Reggio Emilia, followed for the first year of life in order to study their ER visits. The outcomes were the ER utilisation rate for all, non urgent, very urgent, and followed by hospitalisation visits. The main explanatory variable was mother's citizenship. Other covariates were mother's educational level, maternal age, parity, and child gender. Multivariate analyses (negative binomial regression and zero inflated when appropriate) were performed. Adjusted utilisation Rate Ratios (RR) and their 95% Confidence Intervals (95% CI) were calculated. Trend for age in months by citizenship is depicted. RESULTS: There were 3,191 children (36.4%) with at least one ER visit in the first year of life. Adjusted RR show a significantly greater risk of ER visit for immigrants than for Italians: (RR 1.51; 95% CI 1.39-1.63). Immigrants also had a higher risk of non urgent visits (RR 1.72; 95% CI 1.48-2.00) and for visits followed by hospitalizations (RR 1.58; 95% CI 1.33-1.89). For very urgent visits, the immigrants had a slightly higher risk compared to Italians (RR 1.25; 95% CI 0.98 1.59).The risk of ER visits is higher in the first two months of life (RR(1st vs 3rd-12th) 2.08; 95% CI 1.93-2.24 and RR(2nd vs 3rd-12th) 1.45; 95% CI 1.33-1.58, respectively). Considering all visits, the ER utilisation rate was inversely related with maternal education only for Italians (low educational level 44.0 and high educational level 73.9 for 100 children; p value for trend test < 0.001). CONCLUSIONS: Our study observed a higher use of ER services by immigrant children and, to a lesser extent, by children of less educated Italian mothers. In immigrants, the excess is mostly due to non-urgent visits and only slightly to high acute conditions. PMID- 24176110 TI - Review of suicide-prevention programs in Queensland: state- and community-level activities. AB - OBJECTIVE: Information regarding the availability of suicide-prevention programs in Australia is sparse and rather difficult to obtain. This study aimed to report and describe suicide and/or self-harm-prevention programs in Queensland. METHODS: Programs were classified by type of intervention, predominant type of program, setting of delivery and targeted population-at-risk. RESULTS: Sixty-six organisations were identified, providing a total of 101 suicide-prevention programs. The majority of programs operated at the prevention or treatment level, with less than half providing continuing (long-term) care. The programs targeted 12 different risk groups and were most frequently delivered within community settings. CONCLUSIONS: The findings show a diverse distribution of activities across the levels of prevention and different risk populations. This survey demonstrates the existence of remarkable gaps in coverage and provision of programs for specific high-risk groups. PMID- 24176112 TI - Modeling precision treatment of breast cancer. AB - BACKGROUND: First-generation molecular profiles for human breast cancers have enabled the identification of features that can predict therapeutic response; however, little is known about how the various data types can best be combined to yield optimal predictors. Collections of breast cancer cell lines mirror many aspects of breast cancer molecular pathobiology, and measurements of their omic and biological therapeutic responses are well-suited for development of strategies to identify the most predictive molecular feature sets. RESULTS: We used least squares-support vector machines and random forest algorithms to identify molecular features associated with responses of a collection of 70 breast cancer cell lines to 90 experimental or approved therapeutic agents. The datasets analyzed included measurements of copy number aberrations, mutations, gene and isoform expression, promoter methylation and protein expression. Transcriptional subtype contributed strongly to response predictors for 25% of compounds, and adding other molecular data types improved prediction for 65%. No single molecular dataset consistently out-performed the others, suggesting that therapeutic response is mediated at multiple levels in the genome. Response predictors were developed and applied to TCGA data, and were found to be present in subsets of those patient samples. CONCLUSIONS: These results suggest that matching patients to treatments based on transcriptional subtype will improve response rates, and inclusion of additional features from other profiling data types may provide additional benefit. Further, we suggest a systems biology strategy for guiding clinical trials so that patient cohorts most likely to respond to new therapies may be more efficiently identified. PMID- 24176111 TI - Conditional testing of multiple variants associated with bone mineral density in the FLNB gene region suggests that they represent a single association signal. AB - BACKGROUND: Low bone mineral density (BMD) is a primary risk factor for osteoporosis and is a highly heritable trait, but appears to be influenced by many genes. Genome-wide linkage studies have highlighted the chromosomal region 3p14-p22 as a quantitative trait locus for BMD (LOD 1.1 - 3.5). The FLNB gene, which is thought to have a role in cytoskeletal actin dynamics, is located within this chromosomal region and presents as a strong candidate for BMD regulation. We have previously identified significant associations between four SNPs in the FLNB gene and BMD in women. We have also previously identified associations between five SNPs located 5' of the transcription start site (TSS) and in intron 1 of the FLNB gene and expression of FLNB mRNA in osteoblasts in vitro. The latter five SNPs were genotyped in this study to test for association with BMD parameters in a family-based population of 769 Caucasian women. RESULTS: Using FBAT, significant associations were seen for femoral neck BMD Z-score with the SNPs rs11720285, rs11130605 and rs9809315 (P = 0.004 - 0.043). These three SNPs were also found to be significantly associated with total hip BMD Z-score (P = 0.014 - 0.026). We then combined the genotype data for these three SNPs with the four SNPs we previously identified as associated with BMD and performed a conditional analysis to determine whether they represent multiple independent associations with BMD. The results from this analysis suggested that these variants represent a single association signal. CONCLUSIONS: The SNPs identified in our studies as associated with BMD appear to be part of a single association signal between the FLNB gene and BMD in our data. FLNB is one of several genes located in 3p14-p22 that has been identified as significantly associated with BMD in Caucasian women. PMID- 24176113 TI - Efficient bioconversion of 2,3-butanediol into acetoin using Gluconobacter oxydans DSM 2003. AB - BACKGROUND: 2,3-Butanediol is a platform and fuel biochemical that can be efficiently produced from biomass. However, a value-added process for this chemical has not yet been developed. To expand the utilization of 2,3-butanediol produced from biomass, an improved derivative process of 2,3-butanediol is desirable. RESULTS: In this study, a Gluconobacter oxydans strain DSM 2003 was found to have the ability to transform 2,3-butanediol into acetoin, a high value feedstock that can be widely used in dairy and cosmetic products, and chemical synthesis. All three stereoisomers, meso-2,3-butanediol, (2R,3R)-2,3-butanediol, and (2S,3S)-2,3-butanediol, could be transformed into acetoin by the strain. After optimization of the bioconversion conditions, the optimum growth temperature for acetoin production by strain DSM 2003 was found to be 30 degrees C and the medium pH was 6.0. With an initial 2,3-butanediol concentration of 40 g/L, acetoin at a high concentration of 89.2 g/L was obtained from 2,3-butanediol by fed-batch bioconversion with a high productivity (1.24 g/L . h) and high yield (0.912 mol/mol). CONCLUSIONS: G. oxydans DSM 2003 is the first strain that can be used in the direct production of acetoin from 2,3-butanediol. The product concentration and yield of the novel process are both new records for acetoin production. The results demonstrate that the method developed in this study could provide a promising process for efficient acetoin production and industrially produced 2,3-butanediol utilization. PMID- 24176115 TI - Reply: To PMID 23810152. PMID- 24176114 TI - Neurochemical characterisation of lamina II inhibitory interneurons that express GFP in the PrP-GFP mouse. AB - BACKGROUND: Inhibitory interneurons in the superficial dorsal horn play important roles in modulating sensory transmission, and these roles are thought to be performed by distinct functional populations. We have identified 4 non overlapping classes among the inhibitory interneurons in the rat, defined by the presence of galanin, neuropeptide Y, neuronal nitric oxide synthase (nNOS) and parvalbumin. The somatostatin receptor sst2A is expressed by ~50% of the inhibitory interneurons in this region, and is particularly associated with nNOS- and galanin-expressing cells. The main aim of the present study was to test whether a genetically-defined population of inhibitory interneurons, those expressing green fluorescent protein (GFP) in the PrP-GFP mouse, belonged to one or more of the neurochemical classes identified in the rat. RESULTS: The expression of sst2A and its relation to other neurochemical markers in the mouse was similar to that in the rat, except that a significant number of cells co expressed nNOS and galanin. The PrP-GFP cells were entirely contained within the set of inhibitory interneurons that possessed sst2A receptors, and virtually all expressed nNOS and/or galanin. GFP was present in ~3-4% of neurons in the superficial dorsal horn, corresponding to ~16% of the inhibitory interneurons in this region. Consistent with their sst2A-immunoreactivity, all of the GFP cells were hyperpolarised by somatostatin, and this was prevented by administration of a selective sst2 receptor antagonist or a blocker of G-protein-coupled inwardly rectifying K+ channels. CONCLUSIONS: These findings support the view that neurochemistry provides a valuable way of classifying inhibitory interneurons in the superficial laminae. Together with previous evidence that the PrP-GFP cells form a relatively homogeneous population in terms of their physiological properties, they suggest that these neurons have specific roles in processing sensory information in the dorsal horn. PMID- 24176116 TI - Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), pulmonary macrophages increase in number, release increased levels of inflammatory mediators, and respond poorly to glucocorticosteroids. Whether this is due to a change in macrophage phenotype or localized activation is unknown. OBJECTIVE: We sought to investigate whether macrophages from patients with COPD are a distinct phenotype. METHODS: Macrophage populations were isolated from human lung tissue from nonsmokers, smokers, and patients with COPD by using Percoll density gradients. Five macrophage populations were isolated on the basis of density (1.011-1.023, 1.023-1.036, 1.036-1.048, 1.048-1.061, and 1.061-1.073 g/mL), and cell-surface expression of CD14, CD16, CD163, CD40, and CD206 was assessed by using flow cytometry. Release of active matrix metalloproteinase 9, TNF-alpha, CXCL8, and IL-10 was measured by using ELISA. RESULTS: The 2 least dense fractions were more than 90% apoptotic/necrotic, with the remaining fractions greater than 70% viable. Macrophages from nonsmokers and smokers were CD163(+), CD206(+), CD14(+), and CD40(-), whereas macrophages from patients with COPD were less defined, showing significantly lower expression of all receptors. There were no differences in receptor expression associated with density. Macrophages from patients with COPD of a density of 1.036 to 1.048 g/mL released higher levels of active matrix metalloproteinase 9 compared with cells from nonsmokers, with no difference between the remaining fractions. This population of macrophages from patients with COPD was less responsive to budesonide compared with those from nonsmokers and smokers when stimulated with LPS. Glucocorticosteroid insensitivity was selective for proinflammatory cytokines because budesonide inhibition of LPS-stimulated IL-10 release was similar for all macrophages. CONCLUSIONS: This study identifies a specific macrophage phenotype in the lungs of patients with COPD who are glucocorticosteroid insensitive with a density of 1.036 to 1.048 g/mL but do not correspond to the current concept of macrophage phenotypes. PMID- 24176118 TI - Role of early egg ingestion in induction of tolerance: an unanswered question. PMID- 24176119 TI - Efficiency of different selection strategies against boar taint in pigs. AB - The breeding scheme of a Swiss sire line was modeled to compare different target traits and information sources for selection against boar taint. The impact of selection against boar taint on production traits was assessed for different economic weights of boar taint compounds. Genetic gain and breeding costs were evaluated using ZPlan+, a software based on selection index theory, gene flow method and economic modeling. Scenario I reflected the currently practiced breeding strategy as a reference scenario without selection against boar taint. Scenario II incorporated selection against the chemical compounds of boar taint, androstenone (AND), skatole (SKA) and indole (IND) with economic weights of 2.74, -1.69 and -0.99 Euro per unit of the log transformed trait, respectively. As information sources, biopsy-based performance testing of live boars (BPT) was compared with genomic selection (GS) and a combination of both. Scenario III included selection against the subjectively assessed human nose score (HNS) of boar taint. Information sources were either station testing of full and half sibs of the selection candidate or GS against HNS of boar taint compounds. In scenario I, annual genetic gain of log-transformed AND (SKA; IND) was 0.06 (0.09; 0.02) Euro, which was because of favorable genetic correlations with lean meat percentage and meat surface. In scenario II, genetic gain increased to 0.28 (0.20; 0.09) Euro per year when conducting BPT. Compared with BPT, genetic gain was smaller with GS. A combination of BPT and GS only marginally increased annual genetic gain, whereas variable costs per selection candidate augmented from 230 Euro (BPT) to 330 Euro (GS) or 380 Euro (both). The potential of GS was found to be higher when selecting against HNS, which has a low heritability. Annual genetic gain from GS was higher than from station testing of 4 full sibs and 76 half sibs with one or two measurements. The most effective strategy to reduce HNS was selecting against chemical compounds by conducting BPT. Because of heritabilities higher than 0.45 for AND, SKA and IND and high genetic correlations to HNS, the (correlated) response in units of the trait could be increased by 62% compared with scenario III with GS and even by 79% compared with scenario III, with station testing of siblings with two measurements. Increasing the economic weights of boar taint compounds amplified negative effects on average daily gain, drip loss and intramuscular fat percentage. PMID- 24176117 TI - A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients. AB - BACKGROUND: Peanut allergy is a major public health problem that affects 1% of the population and has no effective therapy. OBJECTIVE: To examine the safety and efficacy of oral desensitization in peanut-allergic children in combination with a brief course of anti-IgE mAb (omalizumab [Xolair]). METHODS: We performed oral peanut desensitization in peanut-allergic children at high risk for developing significant peanut-induced allergic reactions. Omalizumab was administered before and during oral peanut desensitization. RESULTS: We enrolled 13 children (median age, 10 years), with a median peanut-specific IgE level of 229 kU(A)/L and a median total serum IgE level of 621 kU/L, who failed an initial double-blind placebo-controlled food challenge at peanut flour doses of 100 mg or less. After pretreatment with omalizumab, all 13 subjects tolerated the initial 11 desensitization doses given on the first day, including the maximum dose of 500 mg peanut flour (cumulative dose, 992 mg, equivalent to >2 peanuts), requiring minimal or no rescue therapy. Twelve subjects then reached the maximum maintenance dose of 4000 mg peanut flour per day in a median time of 8 weeks, at which point omalizumab was discontinued. All 12 subjects continued on 4000 mg peanut flour per day and subsequently tolerated a challenge with 8000 mg peanut flour (equivalent to about 20 peanuts), or 160 to 400 times the dose tolerated before desensitization. During the study, 6 of the 13 subjects experienced mild or no allergic reactions, 5 subjects had grade 2 reactions, and 2 subjects had grade 3 reactions, all of which responded rapidly to treatment. CONCLUSIONS: Among children with high-risk peanut allergy, treatment with omalizumab may facilitate rapid oral desensitization and qualitatively improve the desensitization process. PMID- 24176120 TI - Prostate histotripsy: evaluation of prostatic urethral treatment parameters in a canine model. AB - OBJECTIVE: To assess the impact of histotripsy treatment parameters (pulse number and pulse-repetition frequency [PRF]) on the efficiency of histotripsy induced homogenisation of the prostatic urethra. MATERIALS AND METHODS: In all, 34 transabdominal prostate histotripsy treatments were applied along a perpendicular plane traversing the prostatic urethra of 21 dogs. Prostate histotripsy was applied with (i) escalating pulse number with fixed PRF or (ii) at fixed pulse number with varying PRFs. The development of urethral homognisation <=14 days of histotripsy was evaluated endoscopically and confirmed histologically. RESULTS: Within 14 days of histotripsy 50%, 83%, 83%, and 100% of dogs receiving 12 500, 25 000, 50 000, and 100 000 pulses/mm of treatment path (delivered at 500 Hz PRF), respectively developed prostatic urethral disintegration. Delivery of 100 000 pulses/mm was required to achieve urethral disintegration in all dogs within 24 h of histotripsy treatment. Increasing histotripsy PRF from 50 to 500 to 2000 Hz while applying a constant dose of 25 000 pulses/mm treatment was associated with increased rate of urethral disintegration (50% vs 75% vs 100% at 14 days, respectively). CONCLUSIONS: Increasing the number of histotripsy pulses and/or increasing the PRF of histotripsy treatment applied to the urethra may improve the rate and efficiency of prostatic urethral disintegration in the canine model. This understanding will aid in the development of treatment strategies for prostate histotripsy for benign prostatic hyperplasia in human trials. PMID- 24176121 TI - Impairment of small somatic and autonomic nerve fibres in intensive care unit patients with severe sepsis and critical illness polyneuropathy--a single center controlled observational study. AB - BACKGROUND: Axonal damage in large myelinated nerve fibres occurs in about 70% of patients with severe sepsis, known as critical illness polyneuropathy and contributes significantly to an increased short- and long-term morbidity and mortality in this population. Among other pathophysiological mechanisms, autonomic dysregulation, characterized by high concentrations of circulating catecholamines in the presence of impaired sympathetic modulation of heart and vessels have been discussed. We hypothesize that autonomic small fibre neuropathy play an important role in autonomic failure. METHODS/DESIGN: Single center, non randomized, controlled, observational study. Skin biopsies of patients with severe sepsis and/or septic shock are compared with those of age-matched controls. In order to assess impairment of small nerve fibres, skin biopsies are taken at onset of severe sepsis, and two and 16 weeks later. Intraepidermal nerve fibre densities are histologically analyzed using anti protein gene product (PGP) 9.5 immunostaining. In addition, standardized clinical examinations, as Medical Research Council (MRC) scores of muscle strength, Rankin scores, and standardized nerve conduction studies of the right median nerve, the right tibial nerve, the left fibular nerve, and both sural nerves are performed, to identify critical illness polyneuropathy and to neurophysiologically quantify the damage of large nerve fibres. DISCUSSION: The study will allow to describe the frequency of small fibre neuropathy in patients with severe sepsis up to four months after onset of severe sepsis and to evaluate its relationship to critical illness polyneuropathy. TRIAL REGISTRATION: The trial has been registered to the German Clinical Trials Register. The trial registration number is DRKS-ID: DRKS00000642. PMID- 24176124 TI - Predictors of obstructive coronary artery disease in otherwise 'healthy' individuals with ST-segment depression during paroxysms of atrial fibrillation. PMID- 24176125 TI - Round table on "Current evidence and future perspectives on n-3 PUFA": publication of the Proceedings as a supplement to the International Journal of Cardiology. PMID- 24176122 TI - Control analysis of the eukaryotic cell cycle using gene copy-number series in yeast tetraploids. AB - BACKGROUND: In the model eukaryote, Saccharomyces cerevisiae, previous experiments have identified those genes that exert the most significant control over cell growth rate. These genes are termed HFC for high flux control. Such genes are overrepresented within pathways controlling the mitotic cell cycle. RESULTS: We postulated that the increase/decrease in growth rate is due to a change in the rate of progression through specific cell cycle steps. We extended and further developed an existing logical model of the yeast cell cycle in order elucidate how the HFC genes modulated progress through the cycle. This model can simulate gene dosage-variation and calculate the cycle time, determine the order and relative speed at which events occur, and predict arrests and failures to correctly execute a step. To experimentally test our model's predictions, we constructed a tetraploid series of deletion mutants for a set of eight genes that control the G2/M transition. This system allowed us to vary gene copy number through more intermediate levels than previous studies and examine the impact of copy-number variation on growth, cell-cycle phenotype, and response to different cellular stresses. CONCLUSIONS: For the majority of strains, the predictions agreed with experimental observations, validating our model and its use for further predictions. Where simulation and experiment diverged, we uncovered both novel tetraploid-specific phenotypes and a switch in the determinative execution point of a key cell-cycle regulator, the Cdc28 kinase, from the G1/S to the S/G2 boundaries. PMID- 24176126 TI - Renal dysfunction and all-cause mortality in cardio-renal syndrome: calculation of glomerular filtration rate is crucial, independent of the equation. PMID- 24176123 TI - Genome-wide incorporation dynamics reveal distinct categories of turnover for the histone variant H3.3. AB - BACKGROUND: Nucleosomes are present throughout the genome and must be dynamically regulated to accommodate binding of transcription factors and RNA polymerase machineries by various mechanisms. Despite the development of protocols and techniques that have enabled us to map nucleosome occupancy genome-wide, the dynamic properties of nucleosomes remain poorly understood, particularly in mammalian cells. The histone variant H3.3 is incorporated into chromatin independently of DNA replication and requires displacement of existing nucleosomes for its deposition. Here, we measure H3.3 turnover at high resolution in the mammalian genome in order to present a genome-wide characterization of replication-independent H3.3-nucleosome dynamics. RESULTS: We developed a system to study the DNA replication-independent turnover of nucleosomes containing the histone variant H3.3 in mammalian cells. By measuring the genome-wide incorporation of H3.3 at different time points following epitope-tagged H3.3 expression, we find three categories of H3.3-nucleosome turnover in vivo: rapid turnover, intermediate turnover and, specifically at telomeres, slow turnover. Our data indicate that H3.3-containing nucleosomes at enhancers and promoters undergo rapid turnover that is associated with active histone modification marks including H3K4me1, H3K4me3, H3K9ac, H3K27ac and the histone variant H2A.Z. The rate of turnover is negatively correlated with H3K27me3 at regulatory regions and with H3K36me3 at gene bodies. CONCLUSIONS: We have established a reliable approach to measure turnover rates of H3.3-containing nucleosomes on a genome wide level in mammalian cells. Our results suggest that distinct mechanisms control the dynamics of H3.3 incorporation at functionally different genomic regions. PMID- 24176127 TI - In vitro developmental competence of prepubertal goat oocytes cultured with recombinant activin-A. AB - The present study was designed to evaluate the effect of activin-A during the in vitro oocyte maturation (IVM) and in vitro embryo culture (IVC) on nuclear maturation, blastocyst yield and blastocyst quality of prepubertal goat oocytes. In Experiment 1, three groups of oocytes were used during the IVM of prepubertal goat oocytes to determine the optimal concentration of recombinant human activin A added to the maturation medium. Cumulus-oocyte complexes were matured in an IVM medium containing 0, 10 and 100 ng/ml (groups A0, A10 and A100), fertilized and in vitro cultured using standard procedures. In Experiment 2, the addition of 10 ng/ml activin-A at IVM (A10A0), IVC (A0A10) or IVM+IVC (A10A10) was studied and compared with the control group (A0A0). Results of the first experiment demonstrated that the addition of activin-A yielded similar percentages of maturation (?71.0%) and blastocyst formation rates (?24.9%) than the control group (A0). Experiment 2 showed that exposure of prepubertal goat oocytes to an IVC medium containing 10 ng/ml activin-A (A0A10) significantly increased the rates of development to the blastocyst stage, as compared with the control group (A0A0) (19.5+/-2.21% v. 13.1+/-2.37%, respectively; P<0.05). With regard to the blastocyst quality, total number of cells, inner cell mass (ICM) and trophectoderm of prepubertal goat embryos produced in the presence of activin-A did not differ significantly among experimental groups. In summary, these results indicate that supplementation of the IVC medium with activin-A enhances embryo development of prepubertal goat oocytes. PMID- 24176128 TI - Thickened fluids: investigation of users' experiences and perceptions. AB - BACKGROUND & AIMS: Fluid thickeners are an important and commonly-used strategy to manage swallowing difficulties however there are no reports of the perceptions and experiences of parents of children using thickeners. METHODS: Semi-structured interviews of 14 parents having a child using fluid thickeners due to swallowing difficulties. RESULTS: Parents reported improvements in quality of life and health through the use of thickeners. They also reported persistent difficulties in the use of thickeners. CONCLUSIONS: Results showed unanimous goodwill and positive attitudes towards thickeners and their observed benefits, tempered by common difficulties with thickeners (variability and unpredictability). There remains scope for improvements of commercial thickeners and in information conveyed to users. PMID- 24176129 TI - Offspring death and subsequent psychiatric morbidity in bereaved parents: addressing mechanisms in a total population cohort. AB - BACKGROUND: It is unclear if psychiatric morbidity among parents bereaved of a child is related to major loss in general or if the cause of death matters. Whether such a link is consistent with a causal explanation also remains uncertain. METHOD: We identified 3,114,564 parents through linkage of Swedish nationwide registers. Risk of psychiatric hospitalization was assessed with log linear Poisson regression and family-based analyses were used to explore familial confounding. RESULTS: A total of 3284 suicides and 14,095 any-cause deaths were identified in offspring between 12 and 25 years of age. Parents exposed to offspring suicide had considerably higher risk of subsequent psychiatric hospitalization than unexposed parents [relative risk (RR) 1.90, 95% confidence interval (CI) 1.72-2.09], higher than parents exposed to offspring non-suicide death relative to controls (RR 1.18, 95% CI 1.11-1.26). We found no risk increase among stepfathers differentially exposed to biologically unrelated stepchildren's death or suicide, and the relative risk was notably lower among full siblings differentially exposed to offspring death or suicide. CONCLUSIONS: Parental psychiatric hospitalization following offspring death was primarily found in offspring suicide. Familial (e.g. shared genetic) effects seemed important, judging from both lack of psychiatric hospitalization in bereaved stepfathers and attenuated risk when bereaved parents were contrasted to their non-bereaved siblings. We conclude that offspring suicide does not 'cause' psychiatric hospitalization in bereaved parents. PMID- 24176130 TI - Prenatal diagnosis of two de novo 4q35-qter deletions characterized by array-CGH. AB - BACKGROUND: The 4q- syndrome is a well known genetic condition caused by a partial terminal or interstitial deletion in the long arm of chromosome 4. The great variability in the extent of these deletions and the possible contribution of additional genetic rearrangements, such as unbalanced translocations, lead to a wide spectrum of clinical manifestations. The majority of reports of 4q- cases are associated with large deletions identified by conventional chromosome analysis; however, the widespread clinical use of novel molecular techniques such as array comparative genomic hybridization (a-CGH) has increased the detection rate of submicroscopic chromosomal aberrations associated with 4q- phenotype. RESULTS: Herein we report two prenatal cases of 4qter deletions which presented the first with no sonographic findings and the second with brain ventriculomegaly combined with oligohydramnios. Standard karyotyping demonstrated a deletion at band q35.1 of chromosome 4 in both cases. The application of a-CGH confirmed the diagnosis and offered a precise characterization of the genetic defect. CONCLUSIONS: We provide a review of the currently available literature on the prenatal diagnostic approach of 4q- syndrome and we compare our results with other published cases. Our data suggest that the identification and the precise molecular characterization of new cases with 4q- syndrome will contribute in elucidating the genetic spectrum of this disorder. PMID- 24176131 TI - Long-term risk of mental health problems in women experiencing preterm birth: a longitudinal study of 29 mothers. AB - BACKGROUND: Several studies have reported significantly higher stress levels, both short and long terms, among mothers giving preterm birth compared with mothers giving birth at term. Stress, however, is a psychological phenomenon that may present as anxiety, depression and/or trauma reactions. In this study, the long-term mental health outcomes and the prevalence of anxiety, depression and trauma reactions in women experiencing preterm birth were explored. Interactional, main effect variables and predictors were identified. METHODS: Twenty-nine mothers of 35 premature children born before the 33rd week of pregnancy were assessed within 2 weeks postpartum (T0), 2 weeks after hospitalization (T1), 6 months post-term (T2), and 18 months post-term (T3). The standardized psychometric methods Impact of Event Scale (IES), General Health Questionnaire (GHQ) and State Anxiety Inventory (STAI-X1) assessed the maternal mental health outcomes. RESULTS: The maternal mental health problems except state anxiety decreased from T0 to T1, but remained high and stable at T3. The prevalence of posttraumatic stress reactions (PTSR) and posttraumatic stress disorder (PTSD) at T0 and T3 was 52% and 23%, respectively. We identified the time period between T0 and T1 to have a significant main effect on mental health outcomes. The predictors of higher levels of mental health problems were preeclampsia, previous psychological treatment, age, trait anxiety and infant's postnatal intraventricular haemorrhage. Bleeding in pregnancy predicted lower levels of mental health problems. CONCLUSIONS: The prevalence of maternal mental health problems remained high, emphasizing the importance of effective interventions. PMID- 24176132 TI - Gender norms and economic empowerment intervention to reduce intimate partner violence against women in rural Cote d'Ivoire: a randomized controlled pilot study. AB - BACKGROUND: Gender-based violence against women, including intimate partner violence (IPV), is a pervasive health and human rights concern. However, relatively little intervention research has been conducted on how to reduce IPV in settings impacted by conflict. The current study reports on the evaluation of the incremental impact of adding "gender dialogue groups" to an economic empowerment group savings program on levels of IPV. This study took place in north and northwestern rural Cote d'Ivoire. METHODS: Between 2010 and 2012, we conducted a two-armed, non-blinded randomized-controlled trial (RCT) comparing group savings only (control) to "gender dialogue groups" added to group savings (treatment). The gender dialogue group consisted of eight sessions that targeted women and their male partner. Eligible Ivorian women (18+ years, no prior experience with group savings) were invited to participate. 934 out of 981 (95.2%) partnered women completed baseline and endline data collection. The primary trial outcome measure was an overall measure of past-year physical and/or sexual IPV. Past year physical IPV, sexual IPV, and economic abuse were also separately assessed, as were attitudes towards justification of wife beating and a woman's ability to refuse sex with her husband. RESULTS: Intent to treat analyses revealed that compared to groups savings alone, the addition of gender dialogue groups resulted in a slightly lower odds of reporting past year physical and/or sexual IPV (OR: 0.92; 95% CI: 0.58, 1.47; not statistically significant). Reductions in reporting of physical IPV and sexual IPV were also observed (not statistically significant). Women in the treatment group were significantly less likely to report economic abuse than control group counterparts (OR = 0.39; 95% CI: 0.25, 0.60, p < .0001). Acceptance of wife beating was significantly reduced among the treatment group (beta = -0.97; 95% CI: -1.67, -0.28, p = 0.006), while attitudes towards refusal of sex did not significantly change Per protocol analysis suggests that compared to control women, treatment women attending more than 75% of intervention sessions with their male partner were less likely to report physical IPV (a OR: 0.45; 95% CI: 0.21, 0.94; p = .04) and report fewer justifications for wife beating (adjusted beta = -1.14; 95% CI: -2.01, -0.28, p = 0.01) ; and both low and high adherent women reported significantly decreased economic abuse (a OR: 0.31; 95% CI: 0.18, 0.52, p < 0.0001; a OR: 0.47; 95% CI: 0.27, 0.81, p = 01, respectively). No significant reductions were observed for physical and/or sexual IPV, or sexual IPV alone. CONCLUSIONS: Results from this pilot RCT suggest the importance of addressing household gender inequities alongside economic programming, because this type of combined intervention has potential to reduce levels of IPV. Additional large-scale intervention research is needed to replicate these findings. TRIAL REGISTRATION: REGISTRATION NUMBER: NCT01629472. PMID- 24176133 TI - Defining the role and scope of practice of allied health assistants within Queensland public health services. AB - BACKGROUND: The uptake and utilisation of allied health assistants as professional support staff has been variable across disciplines and jurisdictions. Although they are potentially very important in the current health workforce context, there is little agreement on their roles or the most suitable methods to define these roles. METHOD: Based on a review of literature, existing role descriptions and focus groups, a Delphi survey process was undertaken. This process comprising three rounds of discussion and clarification via email, with between 107 and 188 participants, was undertaken to define and establish consensus on allied health assistant roles at three levels. RESULTS: Three cycles of editing, qualitative feedback and rating of agreement with statements resulted in substantial clarification of roles and a meaningful degree of consensus regarding the role and scope of such positions. High levels of agreement were not reached for more high-level or contested clinical tasks. CONCLUSIONS: The Delphi process resulted in key tasks and roles being defined and contentious aspects clearly identified. The process facilitated engagement with workforce members most closely affected by these questions. It was a useful means of drawing together the opinions of the workforce and informing implementation trials to follow. PMID- 24176134 TI - Vitamin D intake in mid-pregnancy and child allergic disease - a prospective study in 44,825 Danish mother-child pairs. AB - BACKGROUND: Past studies suggest that maternal vitamin D intake during pregnancy may protect against child wheeze but studies on asthma are limited. Our objective was to examine the relation between intake of vitamin D in mid-pregnancy and child asthma and allergic rhinitis at 18 months and 7 years. METHODS: We examined data from 44,825 women enrolled during pregnancy in the longitudinal Danish National Birth Cohort (1996-2002). We estimated vitamin D intake from diet and supplements based on information from a validated food frequency questionnaire completed in gestational week 25. At 18 months, we evaluated child asthma using data from phone interviews. We assessed asthma and allergic rhinitis by self report at age 7 and asthma by using records from national registries. Current asthma at age 7 was defined as lifetime asthma diagnosis and wheeze in the past 12 months. We calculated multivariable risk ratios with 95% CIs comparing highest vs. lowest quintile of vitamin D intake in relation to child allergic disease outcomes. RESULTS: The median (5%-95%ile) intake of total vitamin D was 11.7(3.0 19.4) MUg/day (68% from supplements). In multivariable analysis, mothers in the highest (vs. lowest) quintile of total vitamin D intake were less likely to have children classified with current asthma at 7 years (Q5 vs. Q1: 0.74, 95% CI: 0.56, 0.96, P = 0.02) and they were less likely to have children admitted to the hospital due to asthma (Q5 vs. Q1: 0.80, 95% CI: 0.64, 1.00, P = 0.05). We found no associations with child asthma at 18 months or with allergic rhinitis at 7 years. CONCLUSIONS: Our findings suggest a weak inverse relationship between high total vitamin D and asthma outcomes in later, but not early, childhood. The data did not suggest a clear threshold of vitamin D intake above which risk of asthma was reduced. PMID- 24176135 TI - Analysis of expressed SNPs identifies variable extents of expression from the human inactive X chromosome. AB - BACKGROUND: X-chromosome inactivation (XCI) results in the silencing of most genes on one X chromosome, yielding mono-allelic expression in individual cells. However, random XCI results in expression of both alleles in most females. Allelic imbalances have been used genome-wide to detect mono-allelically expressed genes. Analysis of X-linked allelic imbalance in females with skewed XCI offers the opportunity to identify genes that escape XCI with bi-allelic expression in contrast to those with mono-allelic expression and which are therefore subject to XCI. RESULTS: We determine XCI status for 409 genes, all of which have at least five informative females in our dataset. The majority of genes are subject to XCI and genes that escape from XCI show a continuum of expression from the inactive X. Inactive X expression corresponds to differences in the level of histone modification detected by allelic imbalance after chromatin immunoprecipitation. Differences in XCI between populations and between cell lines derived from different tissues are observed. CONCLUSIONS: We demonstrate that allelic imbalance can be used to determine an inactivation status for X-linked genes, even without completely non-random XCI. There is a range of expression from the inactive X. Genes escaping XCI, including those that do so in only a subset of females, cluster together, demonstrating that XCI and location on the X chromosome are related. In addition to revealing mechanisms involved in cis-gene regulation, determining which genes escape XCI can expand our understanding of the contributions of X-linked genes to sexual dimorphism. PMID- 24176136 TI - The analysis--hierarchical models: past, present and future. AB - This paper discusses statistical modelling for data with a hierarchical structure, and distinguishes in this context between three different meanings of the term hierarchical model: to account for clustering, to investigate variability and separate predictive equations at different hierarchical levels (multi-level analysis), and in a Bayesian framework to involve multiple layers of data or prior information. Within each of these areas, the paper reviews both past developments and the present state, and offers indications of future directions. In a worked example, previously reported data on piglet lameness are reanalyzed with multi-level methodology for survival analysis, leading to new insights into the data structure and predictor effects. In our view, hierarchical models of all three types discussed have much to offer for data analysis in veterinary epidemiology and other disciplines. PMID- 24176137 TI - Does Rhipicephalus microplus tick infestation increase the risk for myiasis caused by Cochliomyia hominivorax in cattle? AB - The larval phase of Cochliomyia hominivorax (screwworm) is an obligate parasite of vertebrate animals, particularly mammals, and widespread in South America, where it remains one of the most important parasitic diseases of domestic animals. The skin of cattle highly infested by ticks, with cutaneous lesions, exudation of tissue fluid and blood scent seems to produce the ideal environment for fly attraction. However, an association between these parasites was never investigated. The aim of this work was to verify if there is an association between Rhipicephalus microplus tick load and the occurrence of C. hominivorax myiasis in cattle, and to quantify the risk. Sixty bovine (Bos taurus taurus, Angus breed) under field conditions were observed for 24 weeks, during which weekly tick counts and examination for the presence of myiasis were performed. There was a significant association between a high tick burden (24-week mean above 50 ticks per animal) and myiasis occurrence (P=0.0102). The calculated relative risk (RR) for C. hominivorax myiasis occurrence in cattle with high tick burden was 3.85 (CI95%=1.23-12.13); indicating that cattle highly parasitized by R. microplus have about four times more risk of myiasis than those with a low parasite load. As far as we aware, this is the first statistically based evidence of the relationship between R. microplus parasitic load and occurrence of myiasis by C. hominivorax. This result could be useful for the design of integrated control strategies for these parasites and to provide more information for the understanding of cattle tick parasitism in cattle production. PMID- 24176138 TI - Bias--is it a problem, and what should we do? AB - Observational studies are prone to two types of errors: random and systematic. Random error arises as a result of variation between samples that might be drawn in a study and can be reduced by increasing the sample size. Systematic error arises from problems with the study design or the methods used to obtain the study data and is not influenced by sample size. Over the last 20 years, veterinary epidemiologists have made great progress in dealing more effectively with random error (particularly through the use of multilevel models) but paid relatively little attention to systematic error. Systematic errors can arise from unmeasured confounders, selection bias and information bias. Unmeasured confounders include both factors which are known to be confounders but which were not measured in a study and factors which are not known to be confounders. Confounders can bias results toward or away from the null. The impact of selection bias can also be difficult to predict and can be negligible or large. Although the direction of information bias is generally toward the null, this cannot be guaranteed and its impact might be very large. Methods of dealing with systematic errors include: qualitative assessment, quantitative bias analysis and incorporation of bias parameters into the statistical analyses. PMID- 24176139 TI - Brain cholesterol homeostasis in Wilson disease. AB - Wilson disease (WD) is an autosomal recessive inherited disorder of copper (Cu) metabolism, resulting in pathological accumulation of Cu in many organs and tissues, predominantly in the liver and brain. There clearly is a close and complex relationship between Cu and the cholesterol's metabolic pathway; therefore any theory about the cholesterol metabolism in the brain of patients with WD must take it into account. The hypothesis presented in this paper is that the imbalance in cerebral copper homeostasis caused by WD may plays a key role in the derangement of the cholesterol homeostasis in the brain, and thus promoting the observed WD related neurological disorders. PMID- 24176140 TI - Neuroprotective effects of vagus nerve stimulation on hippocampal neurons in intractable epilepsy. AB - Vagus nerve stimulation (VNS) and electroacupuncture (EA) at specific acupoints have both shown promising anticonvulsant effects in intractable epilepsy patients. The differences between these therapies are target selection and stimulation parameter modulation. It has been demonstrated that EA of the extremities results in stimulation of the VN and protection of hippocampus neurons, possibly by an anti-inflammatory response. Similarly, VNS can also suppress neural inflammatory responses, implying that VNS may protect hippocampal neurons against seizure-induced damage. PMID- 24176141 TI - Stem cell science has made major strides in the last few years. Introduction. PMID- 24176142 TI - Temporal discounting in major depressive disorder. AB - BACKGROUND: Major depressive disorder (MDD) is associated with abnormalities in financial reward processing. Previous research suggests that patients with MDD show reduced sensitivity to frequency of financial rewards. However, there is a lack of conclusive evidence from studies investigating the evaluation of financial rewards over time, an important aspect of reward processing that influences the way people plan long-term investments. Beck's cognitive model posits that patients with MDD hold a negative view of the future that may influence the amount of resources patients are willing to invest into their future selves. METHOD: We administered a delay discounting task to 82 participants: 29 healthy controls, 29 unmedicated participants with fully remitted MDD (rMDD) and 24 participants with current MDD (11 on medication). RESULTS: Patients with current MDD, relative to remitted patients and healthy subjects, discounted large-sized future rewards at a significantly higher rate and were insensitive to changes in reward size from medium to large. There was a main effect of clinical group on discounting rates for large-sized rewards, and discounting rates for large-sized rewards correlated with severity of depressive symptoms, particularly hopelessness. CONCLUSIONS: Higher discounting of delayed rewards in MDD seems to be state dependent and may be a reflection of depressive symptoms, specifically hopelessness. Discounting distant rewards at a higher rate means that patients are more likely to choose immediate financial options. Such impairments related to long-term investment planning may be important for understanding value-based decision making in MDD, and contribute to ongoing functional impairment. PMID- 24176143 TI - Accelerometer measured daily physical activity and sedentary pursuits--comparison between two models of the Actigraph and the importance of data reduction. AB - BACKGROUND: Very few validation studies have been performed between different generations of the commonly used Actigraph accelerometers. We compared daily physical activity data generated from the old generation Actigraph model 7164 with the new generation Actigraph GT1M accelerometer in 15 young females for eight consecutive days. We also investigated if different wear time thresholds had any impact on the findings. Minutes per day of moderate and vigorous physical activity (MVPA), vigorous physical activity (VPA) and very vigorous physical activity (VVPA) were calculated. Moreover, minutes of sedentary pursuits per day were calculated. FINDINGS: There were significant (P < 0.05) differences between the Actigraph 7164 and the GT1M concerning MVPA (61 +/- 21vs. 56 +/- 23 min/day), VPA (12 +/- 8 vs. 9 +/- 3 min/day) and VVPA (3.2 +/- 3.0 vs. 0.3 +/- 1.1 min/day). The different wear time thresholds had little impact on minutes per day in different intensities. Median minutes of sedentary pursuits per day ranged from 159 to 438 minutes depending on which wear time threshold was used (i.e. 10, 30 or 60 minutes), whereas very small differences were observed between the two different models. CONCLUSIONS: Data from the old generation Actigraph 7164 and the new generation Actigraph GT1M accelerometers differ, where the Actigraph GT1M generates lower minutes spent in free living physical activity. Median minutes of sedentary pursuits per day are highly dependent on which wear time threshold that is used, and not by accelerometer model. PMID- 24176145 TI - Point-of-care diagnostics for tuberculosis elimination? PMID- 24176146 TI - Fetal imaging. PMID- 24176144 TI - Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial. AB - BACKGROUND: The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa. METHODS: In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from five primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT01554384. FINDINGS: Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not differ between groups at 2 months (2 [IQR 0 3] in the smear microscopy group vs 2 [0.25-3] in the MTB/RIF group; p=0.85) or 6 months (1 [0-3] vs 1 [0-3]; p=0.35), nor did median KPS at 2 months (80 [70-90] vs 90 [80-90]; p=0.23) or 6 months (100 [90-100] vs 100 [90-100]; p=0.85). Point of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0.0001) but similar specificity (517 [95%] 544 vs 540 [96%] of 560; p=0.25), and had similar sensitivity to laboratory-based MTB/RIF (292 [83%] of 351; p=0.99) but higher specificity (952 [92%] of 1037; p=0.0173). 34 (5%) of 744 tests with point-of-care MTB/RIF and 82 (6%) of 1411 with laboratory-based MTB/RIF failed (p=0.22). Compared with the microscopy group, more patients in the MTB/RIF group had a same-day diagnosis (178 [24%] of 744 vs 99 [13%] of 758; p<0.0001) and same-day treatment initiation (168 [23%] of 744 vs 115 [15%] of 758; p=0.0002). Although, by end of the study, more culture-positive patients in the MTB/RIF group were on treatment due to reduced dropout (15 [8%] of 185 in the MTB/RIF group did not receive treatment vs 28 [15%] of 182 in the microscopy group; p=0.0302), the proportions of all patients on treatment in each group by day 56 were similar (320 [43%] of 744 in the MTB/RIF group vs 317 [42%] of 758 in the microscopy group; p=0.6408). INTERPRETATION: Xpert MTB/RIF can be accurately administered by a nurse in primary-care clinics, resulting in more patients starting same-day treatment, more culture-positive patients starting therapy, and a shorter time to treatment. However, the benefits did not translate into lower tuberculosis-related morbidity, partly because of high levels of empirical evidence-based treatment in smear-negative patients. FUNDING: European and Developing Countries Clinical Trials Partnership, National Research Foundation, and Claude Leon Foundation. PMID- 24176147 TI - Overview of imaging in pregnancy: history to the present, including economic impact. PMID- 24176148 TI - Obstetric ultrasound utilization in the United States: data from various health plans. AB - There is currently a lack of published data on ultrasound utilization in obstetrics in the United States. In order to get some meaningful information on this topic, we analyzed de-identified data obtained from large insurance providers and underwriters that covered large segment of the United States population in various geographic areas of the country. Our results show an overall significant increase in utilization of obstetric ultrasound over the years, with pregnancies receiving around 4-5 ultrasounds per pregnancy. Another important aspect of the data is a higher than expected utilization of the targeted 76811 ultrasound examination, with utilization rates between 30% and 50%, beyond the original intention of the targeted code. Despite the fact that the data was not intended to shed light on indication of ultrasound or competency of ultrasound providers, in a healthcare world of shrinking reimbursement, as leaders of quality, we should ensure that ultrasound examinations that pregnant women receive are indicated and are performed by competent healthcare workers in ultrasound laboratories that meet accreditation standards. PMID- 24176149 TI - Benefits and risks of ultrasound in pregnancy. AB - Ultrasound is, arguably, the most commonly used diagnostic procedure in obstetrics. It is convenient, painless, yields immediate, extensive results, and is widely considered to be safe. Some (but not all) benefits described in the literature have been validated by evidence-based analysis, such as pregnancy dating. Others are considered clinically useful, although objective evidence may be less strong. As is the case with almost any medical procedure, however, its performance carries some risks: misdiagnosis on the one hand and possible undesired effects on the other. The general belief exists that diagnostic ultrasound (DUS) does not pose any risk to the pregnant patient nor to her fetus. Nonetheless, ultrasound is a form of energy and, as such, demonstrates effects in biological tissues it traverses (bioeffects). The physical mechanisms responsible for these effects are thermal or non-thermal (mechanical). It is the role of science to show whether any of these bioeffects may be harmful. A risk-benefit analysis may also be important, as well as education of the end users to assure patients' safety. PMID- 24176150 TI - Benefits and risks of MRI in pregnancy. AB - Ultrasound remains the modality of choice in imaging the fetus due to its availability, safety, and low cost. With advances in technology, however, magnetic resonance imaging (MRI) has become an important adjuvant in the evaluation of the fetus. MRI is not limited by fetal lie, oligohydramnios, overlying bone, or obesity. MRI can image the fetus in any plane, providing a large field of view of the fetus and placenta with excellent soft tissue resolution of the brain, airway, lungs, and abdomen. Advanced techniques are being developed that provide volumetric data, spectroscopy, and functional images. MRI has its own set of challenges with a lack of consensus regarding its utility and safety. Artifact from the moving fetus and breathing mother limits the sequences available. While there is currently no evidence that fetal MRI produces harmful effects, long-term safety regarding radiofrequency fields and the loud acoustic environment continues to be studied. In this review, the benefits and potential risks of fetal MRI will be discussed. PMID- 24176151 TI - Obstetric ultrasound terminology. AB - Obstetric ultrasound terminology currently varies between CPT book terminology and society guidelines. The major medical societies representing practitioners in this area have worked together to provide consistent guidelines for their members, in the interest of high-quality patient care. PMID- 24176152 TI - Should a first trimester dating scan be routine for all pregnancies? AB - Accurate pregnancy dating is important for diagnostic and management decisions during pregnancy. Dating by last menstrual period is less reliable than dating by ultrasound, since the former has memory-related and other sources of inaccuracy. Dating by first trimester ultrasound, via the crown-rump length, has a 95% confidence range of +/-5 days, slightly better than the +/-8 days for dating by second trimester ultrasound at 14-20 weeks. This small difference appears to be too small to justify a routine first trimester scan for the purpose of dating the pregnancy. PMID- 24176153 TI - Should the first trimester ultrasound include anatomy survey? AB - First trimester scanning has become routine since the introduction of nuchal translucency screening. While most scans have included dating and gross anatomical structures, recent reports have shown that with improvement of ultrasound technology, especially high-frequency transvaginal transducers, detailed analysis of the early fetal anatomy is now possible. Studies included in this manuscript demonstrate the ability to now being able to identify many fetal malformations including some very subtle ones. The literature presented has carefully conducted many prospective studies presenting timelines that show optimal periods to review the anatomical structures by a given gestational age especially noting when these anatomical structures are not optimally seen. PMID- 24176154 TI - Should second trimester ultrasound be routine for all pregnancies? AB - Ultrasound use has become ubiquitous in pregnancy. We review the evidence regarding the benefits of routine ultrasound use during pregnancy. Routine ultrasound use before 24 weeks improves detection of undiagnosed twins, reduces postdates inductions, and allows detection of fetal anomalies before birth. Wide variations exist in the sensitivity of ultrasound in detecting fetal anomalies. These may be related to equipment, training, and maternal characteristics, such as obesity. Standards have been developed for the performance of routine fetal ultrasonography in the second trimester. The benefits of routine first trimester ultrasound in the diagnosis of structural fetal anomalies or of routine ultrasonography after 24 weeks are not proven. As ultrasound technology improves and obstetrical care changes, new uses of routine ultrasonography may emerge. PMID- 24176155 TI - Timing of ultrasound in pregnancy--how often? At what intervals? AB - The second trimester fetal anatomic survey has continued to evolve over the past 27 years. This review will summarize the changes in the anatomic survey that have occurred and provide recommendations that serve to improve compliance with the components of the survey. In order to provide clarity and direction, the goals and limitations of the second trimester fetal anatomic survey should be defined. The visualization rate of specific fetal anatomic structures can be increased by specifying acceptable, alternative views. A single follow-up examination within 2 4 weeks of a fetal anatomic survey or before 22 weeks' gestation should be offered when specific components of the fetal anatomic survey cannot be visualized. The fetal anomalies that the anatomic survey seeks to identify should be defined along with an acceptable detection rate. PMID- 24176156 TI - Techniques, terminology, and indications for MRI in pregnancy. AB - Fetal MRI is now a well-established imaging modality for the diagnostic evaluation of fetuses with congenital anomalies. In this article, the authors provide a brief overview of the physical principles involved in fetal MRI imaging, the sequences that are used in clinical practice today, current indications, and limitations. A review of current evidence supports the following indications for fetal MRI: suspected central nervous system anomalies, neck and oropharyngeal masses, diaphragmatic hernia, abdominal masses or bowel pathology not fully characterized by ultrasonography, and suspected fetal infection. Other indications should be decided on a case-by-case basis with close collaboration between the departments of maternal-fetal medicine and radiology. More research is needed to determine the role of fetal MRI in functional neuroimaging at higher magnetic field strengths (3T). PMID- 24176157 TI - Timing of MRI in pregnancy, repeat exams, access, and physician qualifications. AB - This review addresses specific questions regarding performance and utility of fetal MR. The specific issues addressed are (1) physician qualifications; (2) MR safety; (3) access to fetal MR; (4) timing of MRI in pregnancy; (5) repeat exams; and (6) when MRI is most effective for prenatal diagnosis. Fetal MRI is a problem solving tool used for specific indications that are driven by ultrasound or at times by family history. Fetal MR should always be performed with knowledge of the sonographic findings from prior targeted scan. The best evidence for utility of MR is in assessment of CNS anomalies and assessment of the fetus with airway obstruction requiring decisions regarding mode of therapy. The type of information provided by MR can profoundly impact patient counseling and management. We recommend a team approach including specialists in obstetric imaging, fetal MRI, and postnatal care in interpreting MR so that the best information can be given to the pregnant patient. PMID- 24176158 TI - The use of obstetrical ultrasound in the obese gravida. AB - Obesity is an epidemic in the United States, especially among the pregnant population. Obesity is responsible for an increase in fetal anomalies and adverse outcome of both mother and fetus. Due to difficulty in penetrating to the depth of the uterus, the ultrasound image in obese patients is inadequate, fuzzy, and high in artifacts. Hence, obese patients often require multiple scans as well as special scanning techniques just to get borderline image quality. These techniques and the data regarding quality and frequency of scans for the obese pregnant population are discussed in this paper. PMID- 24176159 TI - Ultrasound in twins: dichorionic and monochorionic. AB - The objective of this review is to assess the evidence that supports the use of ultrasound in twin pregnancies. Although many of the indications for obstetric ultrasound are the same in both singleton and multiple gestations, there are special considerations as well as unique conditions in twins that require additional imaging studies. The reasons for ultrasound in twins include pregnancy dating, determination of chorionicity, nuchal translucency assessment, anatomical survey, placental evaluation, cervical length assessment, routine fetal growth, and serial surveillance of pregnancies complicated by anomalies, cervical shortening, fetal growth disturbances, and amniotic fluid abnormalities. Twins with monochorionic placentation require heightened scrutiny for monoamnionicity, conjoined twins, twin reversed arterial perfusion (TRAP) syndrome, twin-twin transfusion syndrome, unequal placental sharing with discordant twin growth or selective intrauterine fetal growth restriction (IUGR), twin anemia-polycythemia sequence (TAPS), and single fetal demise. Ultrasound is essential for the detection and management of conditions that can complicate dichorionic and monochorionic twin pregnancies. PMID- 24176160 TI - Morbidly adherent placenta. AB - Morbidly adherent placenta, which describes placenta accreta, increta, and percreta, implies an abnormal implantation of the placenta into the uterine wall. The incidence of placenta accreta has increased significantly over the past several decades, with the main risk factors include prior cesarean section and placental previa. Sonographic markers of placenta accreta can be present as early as the first trimester and include a low uterine implantation of a gestational sac, multiple vascular lacunae within the placenta, loss of the normal hypoechoic retroplacental zone, and abnormality of the uterine serosa-bladder interface, among others. Ultrasound has high sensitivity and specificity for the diagnosis of placenta accreta and MRI should be reserved for rare cases in which the ultrasound is non-diagnostic. The optimum time for planned delivery for a patient with placenta accreta is around 34-35 weeks following a course of corticosteroid injection. The successful management of placenta accreta includes a multidisciplinary care team approach with the successful management relying heavily on the prenatal diagnosis of this entity and preparing for the surgical management in a multidisciplinary approach by assuring the most skilled team is available for those patients. PMID- 24176161 TI - Follow-up of sonographically detected soft markers for fetal aneuploidy. AB - Sonographic soft markers of fetal Down syndrome were first reported in the 1980s. With improvements in aneuploidy screening, detection rates of 90% and higher are possible, and such screening is offered to women of all ages. The utility of sonographic detection and reporting of soft markers, particularly to women at low risk of fetal aneuploidy, is controversial. Some soft markers have no additional significance beyond an association with aneuploidy, while some potentially indicate other pathology, and therefore require sonographic follow-up or other evaluation. The definitions of soft markers vary among reported series, and any practice using such markers to adjust the risk of aneuploidy should carefully determine the most appropriate definitions as well as likelihood ratios and how to apply these in practice. PMID- 24176162 TI - Toward consistent terminology: assessment and reporting of amniotic fluid volume. AB - Amniotic fluid is typically measured by ultrasound using the amniotic fluid index (AFI) or the maximum vertical pocket (MVP). Although both parameters correlate poorly with the actual amniotic fluid volume measured with dye-dilution methods, cross-sectional studies have been used to establish gestational norms. The current acceptable definition of polyhydramnios in the late second and the third trimester in both singleton and multiple gestations is a MVP > 8 cm, while the definition of oligohydramnios is a MVP < 2 cm. The pocket to be measured should exclude the umbilical cord or fetal parts. Randomized clinical trials have indicated that defining oligohydramnios as a MVP < 2 cm will result in fewer obstetrical interventions and similar perinatal outcomes when compared to an AFI < 5 cm. PMID- 24176163 TI - Toward consistent terminology of placental location. AB - The diagnosis of placenta previa has shifted from clinical examination of the dilated cervix to sonographic assessment of the closed internal os, resulting in terminology confusion. If the cervix is closed, the distinction between a placental edge at the cervical margin and one partially covering the os is neither reliable nor clinically important. Cesarean delivery is recommended if the placenta reaches the cervical margin at time of delivery, and this entity may be grouped with placenta previa. Partial previa should probably be restricted to those with cervical dilatation. The terms marginal previa and low-lying placenta have been used interchangeably. However, if the placenta implants in the lower uterine segment but does not reach the cervix, low-lying placenta is preferred, and vaginal delivery may be achieved, depending on placental-os distance and presence of bleeding. Limited data suggest that if the placenta is within 2 cm of the os-low-lying placenta, cesarean delivery is performed for bleeding in one third of cases. PMID- 24176165 TI - Bridging genomics technology and biology. AB - A report on the UK Genome Science Meeting, held at the University of Nottingham, UK, 2-4 September 2013. PMID- 24176164 TI - Concurrent chemoradiotherapy with tomotherapy in locally advanced Non-Small Cell Lung Cancer: a phase I, docetaxel dose-escalation study, with hypofractionated radiation regimen. AB - BACKGROUND: Concurrent chemo-radiotherapy is demonstrately superior to sequential chemo-radiotherapy in the treatment of advanced Non-Small-Cell Lung Cancer not suitable for surgery. Docetaxel is considered to enhance the cytotoxic effect of radiotherapy on the tumour cells. Tomotherapy (HT) is a novel radiotherapeutic technique, which allows the delivery of Image Guided-IMRT (IG-IMRT), with a highly conformal radiation dose distribution.The goal of the study was to estimate tolerability of Docetaxel concurrent with IMRT and to find the maximum tolerated dose of weekly Docetaxel concurrent with IMRT delivered with HT Tomotherapy after induction chemotherapy with Cisplatin and Docetaxel in patients affected with stage III Non-Small Cell Lung Cancer. METHODS: We designed a phase I, dose-finding study to determine the dose of weekly Docetaxel concurrent with Tomotherapy after induction chemotherapy, in patients affected by Non-Small Cell Lung Cancer with Stage III disease, not suitable for surgery. RESULTS: Concurrent weekly Docetaxel and Tomotherapy are feasible; we did not reach a maximum tolerated dose, because no life-threatening toxicity was observed, stopping the accrual at a level of weekly docetaxel 38 mg/m2, a greater dose than in previous assessments, from both phase-I studies with weekly docetaxel alone and with Docetaxel concomitant with standard radiotherapy. CONCLUSIONS: Concurrent weekly Docetaxel and Tomotherapy are feasible, and even with Docetaxel at 38 mg/m2/week we did not observe any limiting toxicity. For those patients who completed the combined chemo-radio treatment, median progression-free survival (PFS) was 20 months and median overall survival (OS) was 24 months. PMID- 24176166 TI - Aged care nurse practitioners in Australia: evidence for the development of their role. AB - AIM: To consider evidence surrounding the emerging role of nurse practitioners in Australia with a particular focus on the provision of healthcare to older people. METHODS: Methods used included keyword, electronic database and bibliographic searches of international literature, as well as review of prominent policy reports in relation to aged care and advanced nursing roles. RESULTS: This paper reports on evidence from systematic reviews and international studies that show that nurse practitioners improve healthcare outcomes, particularly for hard to service populations. It also maps out the limited Australian evidence on the impact of nurse practitioners' care in aged care settings. CONCLUSIONS: If Australia is to meet the health needs of its ageing population, more evidence on the effectiveness, economic viability and sustainability of models of care, including those utilising nurse practitioners, is required. PMID- 24176167 TI - Modeling of cell sorting and rare cell capture with microfabricated biodevices. AB - In this paper, we review different aspects of computer modeling and simulation of lab-on-a-chip type bioanalytical devices, with special emphasis on cell sorting and rare cell capture, such as circulating tumor cells (CTCs). We critically review important fundamental concepts and innovative applications in addition to detailed analysis by multiphysics approaches. Relevant essentials of hydrodynamic, Newtonian, and non-Newtonian rheological behavior, single and multiphase models, together with various force field-mediated flows are discussed with respect to cell sorting. Furthermore, we provide a summary of techniques used to simulate electric and magnetic field-based rare cell capture methods, such as electrophoresis and magnetophoresis. Finally, we present simulations of practical applications to help non-specialists understand the basic principles and applications. PMID- 24176168 TI - Emerging rules for effective antimicrobial coatings. AB - In order to colonize abiotic surfaces, bacteria and fungi undergo a profound change in their biology to form biofilms: communities of microbes embedded into a matrix of secreted macromolecules. Despite strict hygiene standards, biofilm related infections associated with implantable devices remain a common complication in the clinic. Here, the application of highly dosed antibiotics is problematic in that the biofilm (i) provides a protective environment for microbes to evade antibiotics and/or (ii) can provide selective pressure for the evolution of antibiotic-resistant microbes. However, recent research suggests that effective prevention of biofilm formation may be achieved by multifunctional surface coatings that provide both non-adhesive and antimicrobial properties imparted by antimicrobial peptides. Such coatings are the subject of this review. PMID- 24176170 TI - Lifestyle and family history influence cancer prognosis in Brazilian individuals. AB - The aim of this research was to study prognostic parameters of CRC by analyzing clinical and pathological variables associated with cancer patients at a northeastern Brazilian Hospital. This was a retrospective study evaluating CRC diagnosed patients across a 10-year period (1995-2005) at Dr. Luiz Antonio Hospital in Natal, RN, Brazil. Data were collected from patients' medical files. A total of 358 patients were included over the 10-year period. The average age at diagnosis was 58.8 years (S.D.=15.26), 48.3% of the patients were males and 51.7% were females. Alcohol consumption significantly increased the chance of dying (p<0.023) from colorectal cancer; this increased risk of death was approximately 71%, compared to 52.2% of the non-alcoholics. In addition, tobacco increased the chance of developing high TNM stage tumors (level III, IV; p<0.001). Another risk factor for increased mortality was a family history for colorectal cancer (p<0.002). Our analysis found that patients with an unhealthy lifestyle and/or family history of colorectal cancer were more likely to develop advanced stage colorectal cancer and to have a poor disease prognosis compared to patients with healthy lifestyle and/or sporadic colorectal cancer. These data suggest that a mass screening program should be implemented in northeastern Brazil in order to better prevent and treat colorectal cancer. PMID- 24176169 TI - A low-cost, multiplexable, automated flow cytometry procedure for the characterization of microbial stress dynamics in bioreactors. AB - BACKGROUND: Microbial cell population heterogeneity is now recognized as a major source of issues in the development and optimization of bioprocesses. Even if single cell technologies are available for the study of microbial population heterogeneity, only a few of these methods are available in order to study the dynamics of segregation directly in bioreactors. In this context, specific interfaces have been developed in order to connect a flow cytometer directly to a bioreactor for automated analyses. In this work, we propose a simplified version of such an interface and demonstrate its usefulness for multiplexed experiments. RESULTS: A low-cost automated flow cytometer has been used in order to monitor the synthesis of a destabilized Green Fluorescent Protein (GFP) under the regulation of the fis promoter and propidium iodide (PI) uptake. The results obtained showed that the dynamics of GFP synthesis are complex and can be attributed to a complex set of biological parameters, i.e. on the one hand the release of protein into the extracellular medium and its uptake modifying the activity of the fis promoter, and on the other hand the stability of the GFP molecule itself, which can be attributed to the protease content and energy status of the cells. In this respect, multiplexed experiments have shown a correlation between heat shock and ATP content and the stability of the reporter molecule. CONCLUSION: This work demonstrates that a simplified version of on-line FC can be used at the process level or in a multiplexed version to investigate the dynamics of complex physiological mechanisms. In this respect, the determination of new on-line parameters derived from automated FC is of primary importance in order to fully integrate the power of FC in dedicated feedback control loops. PMID- 24176171 TI - Clinicopathological and molecular significance of Sumolyation marker (ubiquitin conjugating enzyme 9 (UBC9)) expression in breast cancer of black women. AB - The majority of breast cancers (BC) in Nigerian women are triple negative and show breast cancer-associated gene 1 (BRCA1) deficiency as well as the basal like phenotype, with a high mortality rate. In contrast to the well-defined predictive factors for the hormonal therapy, there is a paucity of information on the BRCA1 deficiency breast tumor biology, particularly among African women. BRCA1 Sumoylation (UBC9) has been speculated to be involved in the ER transcription activity, BRCA1 deficiency and triple negative BC. We therefore hypothesized that UBC9, a SUMOylation marker, may have contributed to the aggressive nature of BRCA1 tumor phenotype observed in Nigerian women. This study investigated the immunoprofiles of UBC9 in tissue microarray (TMA) of 199 Nigerian women and correlated their protein expression with clinical outcome, pathological responses and the expression of other biomarkers to demonstrate the functional significance in Nigerian women. The protein expression of UBC9, as compared with other biomarkers, showed an inverse correlation with steroid hormones (ER, progesterone (PgR)), BRCA1, p27, p21 and MDM4, and a positive correlation with triple negative, basal cytokeratins (CK14 and CK5/6), epidermal growth factor receptor (EGFR), basal-like breast cancer phenotype, p53, phosphoinositide-3-kinases (PI3KCA), placental cadherin, (P-cadherin) and BRCA1 regulators (metastasis tumor antigen-1 (MTA1). Survival analysis showed that those tumors positive for UBC9 expression had a significantly poorer breast cancer-specific survival (BCSS) as compared with those showing negative expression. UBC9 remained an independent predictor of outcome for BCSS. This study demonstrates that UBC9 appears to play an important role in the tumor biology of Nigerian women. Therefore, a novel UBC9 targeted therapy in black women with BC could enhance a better patient outcome. PMID- 24176172 TI - Chronic effects of clozapine administration on insulin resistance in rats: evidence for adverse metabolic effects. AB - Chronic treatment with the atypical antipsychotics clozapine has been associated with an increased risk for deterioration of glucose homeostasis, leading to hyperglycemia and insulin resistance diabetes. The present study mainly aimed to investigate possible mechanisms underlying clozapine-induced hyperglycemia. Male Wistar albino rats were randomly divided into two groups (each consists of 12 rats). The first group received clozapine orally at a dose of 10mg/kg body weight daily for 6 weeks, while the other group received the drug vehicle only and served as the control group. At the end of the six weeks, hyperglycemia, hyperinsulinemia and insulin resistance, as indicated by Homeostatic model assessment of insulin resistance (HOMA-IR), were observed in the clozapine group as compared with the control group. This disturbance in glucose regulation was associated with non-significant changes in body weight, serum cortisol level, and hepatic glycogen content. The Clozapine group showed a significant increase in hepatic phosphorylase activity and in the gene expression level of hepatic glucose-6-phosphatse (G6Pase) enzymes compared to the control group. It can be concluded that clozapine-induced hyperglycemia and insulin resistance occur in a manner mostly independent of weight gain, and may be attributed to an increase in hepatic phosphorylase activity and increased expression level of G6Pase. PMID- 24176173 TI - The relationship between drive to thinness, conscientiousness and bulimic traits during adolescence: a comparison between younger and older cases in 608 healthy volunteers. AB - BACKGROUND: Adolescence represents one of the critical transitions in the life span and is characterized by a tremendous pace in growth and change that is second only to that of infancy. Both biological and psychological changes occurring during early adolescence may also influence the definition of subsequent late adolescence or early adulthood physiological or (psycho) pathological features, including bulimia nervosa (BN) whenever occurring. Therefore, a pre-emptive assessment of suggestive psychological traits, including bulimic ones, during early and late years of adolescence, is recommended and represents the goal of the present study. METHODS: Six hundred and eight healthy volunteers attending mid- or high school, aged 14-19 years, were consecutively enrolled at multiple sites in Eastern Sicily, Italy. A systematic psychological assessment was performed, including McCrae and Costa' BigFive, the Eating Disorders Inventory (EDI), Bisantis's Assertivity test and the Liebowitz Social Anxiety Scale for Children and Adolescents. Demographic and general characteristics, including the body mass index, were also recorded. Based on hierarchical considerations, cases were then divided into 'younger' ('early' years, 14-16) and 'older' ('late' years, 17-19) adolescents. RESULTS: Upon descriptive and Pearson's correlation analyses, the following EDI constructs 'drive to thinness' and 'bulimia' scored significantly higher (both p = <.001) in 'early' vs. 'late' cases. Conversely, BigFive 'conscientiousness' was higher in older subjects vs. early cases (p = <.003). As expected, 'drive to thinness' positively correlated with BN both in early (r = .31) and late (r = .50) cases. In the 'late' group, age correlated with conscientiousness (r = .206) while BN correlated with drive to thinness (r = .505); finally, a negative correlation was observed with regard to consciousness and BN (r = -.19). CONCLUSIONS: Despite intrinsic methodological limits, our preliminary findings confirm that the transition between early and late years of adolescence is a critical phase of life span, with the consolidation of 'conscientiousness' eventually playing a protective role towards the onset of bulimic traits. If confirmed by replication studies, ideally providing long-term follow-ups too, an early acknowledgement of bulimic traits may play a major predictive role for subsequent BN, ultimately contributing to more effective pre-emptive interventions as well. PMID- 24176175 TI - Evaluation of DNA extraction from granulocytes discarded in the separation medium after isolation of peripheral blood mononuclear cells and plasma from whole blood. AB - BACKGROUND: Whole blood is generally processed for plasma and peripheral blood mononuclear cells (PBMCs) from granulocytes/erythrocytes using gradient centrifugation of blood with Histopaue-Ficoll. After separation of plasma and PBMCs, the residual erythrocytes/granulocytes, a rich source of DNA, is often discarded along with the separation medium. In order to isolate DNA from the granulocytes, current methods require the removal of the separation medium and subsequent purification of granulocytes. This report provides a method for extracting DNA using the PAXgene Blood DNA kit from granulocytes without purifying them from the separation medium. FINDINGS: Based on 719 erythrocyte/granulocyte samples stored frozen for approximately 10 years in Ficoll-Hypaque separation medium, the mean yield of DNA was 395 MUg (median = 281 MUg; range = 1.36 to 2077.2 MUg), with mean A260/A280 ratio of 1.84 (median = 1.84; range = 1.17 to 2.23). The quality of isolated DNA was sufficient for use as a template for restriction enzyme digestion, real-time PCR, pyrosequencing, and gel based variable number tandem repeats (VNTR) genotyping. CONCLUSIONS: By demonstrating the extraction of substantial amounts of high quality granulocytes DNA without purifying them from the separation medium, this method offers laboratories and biobanks a flexible and cost-effective approach to obtain plasma, PBMCs, and large amounts of DNA from a single blood collection for a variety of molecular genetics/epidemiologic studies. PMID- 24176176 TI - Revisiting default mode network function in major depression: evidence for disrupted subsystem connectivity. AB - BACKGROUND: Major depressive disorder (MDD) is characterized by alterations in brain function that are identifiable also during the brain's 'resting state'. One functional network that is disrupted in this disorder is the default mode network (DMN), a set of large-scale connected brain regions that oscillate with low frequency fluctuations and are more active during rest relative to a goal directed task. Recent studies support the idea that the DMN is not a unitary system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in depression, however, is unclear. METHOD: Here, we investigated the functional connectivity of distinct DMN subsystems and their interplay in depression using resting-state functional magnetic resonance imaging. RESULTS: We show that patients with MDD exhibit increased within-network connectivity in posterior, ventral and core DMN subsystems along with reduced interplay from the anterior to the ventral DMN subsystems. CONCLUSIONS: These data suggest that MDD is characterized by alterations of subsystems within the DMN as well as of their interactions. Our findings highlight a critical role of DMN circuitry in the pathophysiology of MDD, thus suggesting these subsystems as potential therapeutic targets. PMID- 24176177 TI - President's page: The perfect storm part 2: a rally cry for medical research funding. PMID- 24176178 TI - A technique for fabricating a hinged mandibular complete dental prosthesis with swing lock for a patient with microstomia. AB - Microstomia is defined as an acquired or congenital condition involving a reduction of the oral aperture severe enough to compromise esthetics, nutrition, and quality of life. This clinical report describes a technique for fabricating a mandibular swing-lock complete denture with a hinge for a patient with muscular dystrophy. A hinge in the midline allowed the denture to collapse. The collapsed denture could then be inserted into the mouth and locked into position. A sectional impression technique was used and the custom hinge was designed on the cobalt-chromium metal framework of the complete denture. The protocol presented can provide a viable treatment option for edentulous patients with microstomia. PMID- 24176179 TI - Effect of post translucency on bond strength of different resin luting agents to root dentin. AB - STATEMENT OF PROBLEM: Translucent fiber posts were developed to conduct light into the root canal more effectively, thereby contributing to the polymerization of dual-polymerized resin luting agents. However, there is no consensus in the literature regarding their effectiveness. PURPOSE: The purpose of this study was to evaluate the tensile bond strength of fiber posts with different degrees of translucency to bovine dentin with 3 types of resin luting agents. MATERIAL AND METHODS: Ninety bovine roots were endodontically treated and divided into 9 groups (n=10) according to the type of post (translucent, white, and black) and resin luting agent (dual-polymerized self-adhesive; dual-polymerized + etch-and rinse adhesive system; and autopolymerized + etch-and-rinse adhesive system). Tensile tests were performed on a universal testing machine (0.5 mm/min). To determine tensile stress, the bond area of each specimen was calculated. Data were statistically analyzed with ANOVA, Kruskal-Wallis, and Mann-Whitney tests (alpha=.05). RESULTS: Mean (standard deviation) tensile bond strength values (5.53 +/- 2.29 MPa) were significantly lower for translucent posts than for white (9.51 +/- 1.31 MPa) and black posts (10.12 +/- 3.44 MPa) with a dual-polymerized luting agent in combination with an adhesive system (P=.012). For white (6.02 +/- 1.88 MPa) and black posts (4.14 +/- 0.6 MPa), the self-adhesive luting agent led to lower tensile bond strength than the dual-polymerized luting agent in combination with an adhesive system (P=.003). Irrespective of post type, the autopolymerized luting agent provided the lowest tensile bond strength (P<.001). Microscopic analysis revealed that resin luting agents adhered more to the post surface than to the root dentin. CONCLUSION: Post translucency did not increase the tensile bond strength of dual-polymerized resin luting agents. PMID- 24176180 TI - A tooth-stabilized surgical template for alveolectomy. AB - The supraeruption of teeth and bone in patients with long-standing partial edentulism often results in compromised interarch distance. A method is presented for the fabrication and predictable use of a tooth-stabilized surgical template for alveolectomy in instances where teeth are present. PMID- 24176181 TI - In vitro comparison of the tensile bond strength of denture adhesives on denture bases. AB - STATEMENT OF PROBLEM: With several denture adhesives available, it is important for dentists to make appropriate patient recommendations. PURPOSE: The purpose of this study was to evaluate the tensile bond strength of denture adhesives on denture base materials at time intervals of up to 24 hours. MATERIAL AND METHODS: Fixodent, Super Poligrip, Effergrip, and SeaBond denture adhesives were tested with 3 denture base materials: 2 heat-polymerized (Lucitone 199 and SR Ivocap) and 1 visible-light-polymerized (shade-stable Eclipse). Artificial saliva with mucin was used as a control. Tensile bond strength was tested in accordance with American Dental Association specifications at 5 minutes, 3 hours, 6 hours, 12 hours, and 24 hours after applying the adhesive. Maximum forces before failure were recorded in megapascals (MPa), and the data were subjected to a 2-way analysis of variance (alpha=.05). RESULTS: All 4 adhesives had greater tensile bond strength than the control. Fixodent, Super Poligrip, and SeaBond had higher tensile bond strength values than Effergrip. All adhesives had the greatest tensile bond strength at 5 minutes and the least at 24 hours. The 3 denture bases produced significantly different results with each adhesive (P<.001). Lucitone 199 with the adhesives had the greatest tensile bond strength, followed by Ivocap and Eclipse. CONCLUSIONS: All 4 adhesives had greater tensile bond strength than the control, and all 4 adhesives were strongest at the 5-minute interval. On all 3 types of denture bases, Effergrip produced significantly lower tensile bond strength, and Fixodent, Super Poligrip, and SeaBond produced significantly higher tensile bond strength. At 24 hours, the adhesive-base combinations with the highest tensile bond strength were Fixodent on Lucitone 199, Fixodent on Eclipse, Fixodent on Ivocap, and Super Poligrip on Ivocap. PMID- 24176182 TI - Analysis of the misfit of dental implant-supported prostheses made with three manufacturing processes. AB - STATEMENT OF PROBLEM: The microgap between implant components has been associated with complications such as screw loosening or adverse biologic responses. PURPOSE: The purpose of this study was to quantify the microroughness of the mating surfaces of implant components manufactured with different processes, to quantify the microgap between implant components, and to determine whether a correlation exists between microroughness and the microgap. MATERIAL AND METHODS: Nine dental implants with a standard external connection were paired with 3 milled, 3 cast, and 3 sintered compatible cobalt-chromium alloy abutments. The abutment surface was examined, and the roughness parameter Sz was measured by using a white-light interferometric microscope at *10 to *100 magnification. The abutment surface and the microgap of the implant-abutment connection were observed with scanning electron microscopy, and the microgap width was quantified from micrographs made of each implant-abutment pair. The mean and standard deviation of roughness and microgap were evaluated. A 1-way ANOVA (alpha=.05) was used to assess the influence of the manufacturing process on roughness and microgap. The Pearson correlation was used to check dependence between roughness and microgap. RESULTS: The milled abutments possessed a connection geometry with defined edges and a mean roughness of 29 MUm, sintered abutments showed a blurred but functional connection with a roughness of 115 MUm, and cast abutments showed a connection with a loss of axial symmetry and a roughness of 98 MUm. A strong correlation was found between the roughness values on the mating surfaces and the microgap width. CONCLUSIONS: The milled components were smoother than the cast or sintered components. A correlation was found between surface roughness and microgap width. PMID- 24176183 TI - Influence of coping design on the cervical color of ceramic crowns. AB - STATEMENT OF PROBLEM: The replication of natural teeth, especially with single tooth restorations, represents a challenge. Similar to metal ceramic crowns, different designs of zirconia substructures have been suggested to improve the esthetic results of zirconia ceramic crowns. PURPOSE OF STUDY: The purpose of the study was to analyze the color of the cervical portion of single zirconia ceramic crowns fabricated with different zirconia coping designs. MATERIAL AND METHODS: The color, measured on the CIELAB color scale, of 3 different groups of restorations (n=10) fabricated with zirconia coping (Lava) and feldspathic porcelain (Noritake Super Porcelain) was analyzed with a spectrophotometer. Conventional zirconia crowns with zirconia facial margins were compared with ceramic crowns with porcelain facial margins and either a horizontal reduction of the zirconia coping (1.0 mm reduction) or an additional vertical reduction (1.0 mm additional reduction). The 3 groups, each with a different coping extension, were examined with a 1-way ANOVA and the Fisher exact test, and the differences of the groups were evaluated by applying DeltaE thresholds (alpha=.05). RESULTS: The mean color difference among all the groups was not clinically significant (DeltaE<3.7). Reduced color differences were present between the 2 porcelain butt margin groups of crowns (DeltaE=1.06, between group H and V). Increased differences were present between the zirconia margin group and the porcelain butt margin group (DeltaE=2.54 between group C and H; DeltaE=2.41 between group C and V). Lab* values were examined in all the groups of crowns to determine the clinical implications. CONCLUSIONS: Within the limitation of the study, no significant differences were present among the tested groups of crowns. Nevertheless, although some differences were present between the zirconia margin group and the porcelain butt margin group, reduced differences were present between the 2 different cutback designs. PMID- 24176185 TI - The influence of cadmium contamination and salinity on the survival, growth and phytoremediation capacity of the saltmarsh plant Salicornia ramosissima. AB - The major aim of this study was to evaluate the capacity of Salicornia ramosissima on Cadmium phytoremediation under distinct salinities and, consequently, the toxic effects on the plant's development. A greenhouse experiment was performed, using two Cd concentrations (50 and 100 MUg l(-1)) in different salinities (0, 5 and 10). Mortality and weight variation, observed at the end of the experiment, showed significant differences between some treatments, meaning that these variables were affected by the salinity and Cd concentrations. The highest Cd accumulation was detected in the roots, and decreased with the increase of salinity and Cd concentration. S. ramosissima is a potential candidate for Cd phytoremediation at salinities close to 0 and its capabilities in Cd phytoaccumulation and phytoestabilization proved to be quite interesting. The optimization of phytoremediation processes by S. ramosissima could turn possible the use of this plant in the recovery of contaminated ecosystems. PMID- 24176184 TI - Can we predict which patients are likely to develop severe complications following reconstruction for osteoradionecrosis? AB - High morbidity has been reported for free vascularised reconstruction for osteoradionecrosis (ORN) and there are no apparent risk factors. A single nucleotide polymorphism in the transforming growth factor beta 1 gene (TGF-beta1) has been implicated in the cause of ORN and may also predict these complications. We studied a series of 30 consecutive patients who had had reconstruction for severe ORN with free tissue transfer in relation to their outcomes and complications for a number of risk factors including TFG-beta1 genotype, age, sex, comorbidities, site and stage of tumour, type of initial operation, and dose of radiotherapy or chemoradiotherapy. Two patients died and 2 flaps failed. Using the Clavien-Dindo classification, 16 patients developed grade III complications and 6 grade II. Median (IQR) duration of inpatient stay was 19.5 (12-25) days and the median (IQR) duration of outpatient treatment was 6 (4-11) weeks. No specific risk factors for postoperative complications were identified. In view of the severity and unpredictability of the complications, careful preoperative counselling of patients is essential. PMID- 24176186 TI - Nurse-led supportive care management: a 6-month review of the role of a nurse practitioner in a chemotherapy unit. AB - OBJECTIVES: This case study evaluates the oncology nurse practitioner (NP) role in a chemotherapy unit. BACKGROUND: The NP works in the cancer centre of a major metropolitan public hospital. The NP role was established in the chemotherapy unit in 2007. The NP reviews all patients that have an unscheduled presentation to the unit, with symptoms relating either to their disease or treatment. METHODS: All unscheduled occasions of service provided by the NP in the chemotherapy unit over 6 months were recorded. Data were collected on patient demographic characteristics, medical problems and reason for presentation. Data on duration of care, interventions and outcomes administered by the NP were captured. RESULTS: There were 87 occasions of service (72 patients) during the study period. Nausea, vomiting or dehydration were the most common presenting problems and most presenting problems were moderate or severe (n = 73, 84%). The median time to review for the NP was 5 min and nearly all consultations (n = 83, 96%) took 30 min or less. Following NP consultation, most occasions of service did not require subsequent hospital admission (n = 52, 60%), medical advice (n = 61, 70%) or medical review (n = 75, 86%). CONCLUSIONS: The NP is a valuable asset to a busy department, increasing access to timely and appropriate healthcare for patients on chemotherapy. PMID- 24176187 TI - What it's like to be an editor at a conference. PMID- 24176189 TI - Tobacco smoking in schizophrenia: investigating the role of incentive salience. AB - BACKGROUND: Smoking is highly prevalent in people diagnosed with schizophrenia, but the reason for this co-morbidity is currently unclear. One possible explanation is that a common abnormality underpins the development of psychosis and independently enhances the incentive motivational properties of drugs and their associated cues. This study aimed to investigate whether incentive salience attribution towards smoking cues, as assessed by attentional bias, is heightened in schizophrenia and associated with delusions and hallucinations. METHOD: Twenty two smokers diagnosed with schizophrenia and 23 control smokers were assessed for smoking-related attentional bias using a modified Stroop task. Craving, nicotine dependence, smoking behaviour and positive and negative symptoms of schizophrenia were also recorded. RESULTS: Both groups showed similar craving scores and smoking behaviour according to self-report and expired carbon monoxide (CO), although the patient group had higher nicotine dependence scores. Attentional bias, as evidenced by significant interference from smoking-related words on the modified Stroop task, was similar in both groups and correlated with CO levels. Attentional bias was positively related to severity of delusions but not hallucinations or other symptoms in the schizophrenia group. CONCLUSIONS: This study supports the hypothesis that the development of delusions and the incentive motivational aspects of smoking may share a common biological substrate. These findings may offer some explanation for the elevated rates of smoking and other drug use in people with psychotic illness. PMID- 24176188 TI - Rationale and study design of ViPS - variable pressure support for weaning from mechanical ventilation: study protocol for an international multicenter randomized controlled open trial. AB - BACKGROUND: In pressure support ventilation (PSV), a non-variable level of pressure support is delivered by the ventilator when triggered by the patient. In contrast, variable PSV delivers a level of pressure support that varies in a random fashion, introducing more physiological variability to the respiratory pattern. Experimental studies show that variable PSV improves gas exchange, reduces lung inflammation and the mean pressure support, compared to non-variable PSV. Thus, it can theoretically shorten weaning from the mechanical ventilator. METHODS/DESIGN: The ViPS (variable pressure support) trial is an international investigator-initiated multicenter randomized controlled open trial comparing variable vs. non-variable PSV. Adult patients on controlled mechanical ventilation for more than 24 hours who are ready to be weaned are eligible for the study. The randomization sequence is blocked per center and performed using a web-based platform. Patients are randomly assigned to one of the two groups: variable PSV or non-variable PSV. In non-variable PSV, breath-by-breath pressure support is kept constant and targeted to achieve a tidal volume of 6 to 8 ml/kg. In variable PSV, the mean pressure support level over a specific time period is targeted at the same mean tidal volume as non-variable PSV, but individual levels vary randomly breath-by-breath. The primary endpoint of the trial is the time to successful weaning, defined as the time from randomization to successful extubation. DISCUSSION: ViPS is the first randomized controlled trial investigating whether variable, compared to non-variable PSV, shortens the duration of weaning from mechanical ventilation in a mixed population of critically ill patients. This trial aims to determine the role of variable PSV in the intensive care unit. TRIAL REGISTRATION: clinicaltrials.gov NCT01769053. PMID- 24176190 TI - [Treatment of colorectal cancer with unresectable metastasis with chemotherapy without primary tumor resection: analysis of tumor-related complications]. AB - INTRODUCTION: Although the conventional treatment of patients with stage iv colorectal cancer involves resection of the primary tumor followed by chemotherapy, several studies suggest that in patients with few symptoms the first and only treatment should be chemotherapy. The objective of this study is to analyze the complications related to the primary tumor in a series of patients with unresectable metastatic colorectal cancer treated with chemotherapy without surgery. MATERIAL AND METHODS: Retrospective descriptive study. The study included all patients with unresectable metastatic colorectal cancer treated with chemotherapy without resection of the primary tumor (January 2007-February 2011). RESULTS: The mean age of the 61 patients analyzed was 67+/-13 years and the performance status was 0-1 in 53 (87%). Twenty (33%) patients developed complications during follow-up. The most common complication was intestinal obstruction in 15 (25%) patients followed by perforation. Complications required surgery in 6 (10%) cases. We did not find differences in patient characteristics between those who had a complication and those without, although the complication rate in patients with a colonic stent (53%) was twice that of other patients (26%). CONCLUSIONS: Chemotherapy without surgery is a good option in most patients with unresectable metastatic colorectal cancer. However, although the percentage of patients requiring surgery is low, the total number of complications related to the primary tumor is not negligible. Studies are needed to identify those patients in whom a prophylactic colectomy could be indicated. PMID- 24176191 TI - [Surgical treatment of blunt liver trauma, indications for surgery and results]. AB - INTRODUCTION: The liver is the most frequently injured organ in blunt abdominal trauma. Patients that are hemodynamically unstable must undergo inmmediate surgical treatment. There are 2 surgical approaches for these patients; Anatomical Liver resection or non-anatomic liver resection. Around 80-90% of patients are candidates for non-operative management. -Several risk factors have been studied to select the patients most suited for a non operative management. MATERIALS AND METHODS: We performed a retrospective study based on a prospective database. We searched for risk factors related to immediate surgical management and failed non-operative management. We also described the surgical procedures that were undertaken in this cohort of patients and their outcomes and complications. RESULTS: During the study period 117 patients presented with blunt liver trauma. 19 patients (16.2%) required a laparotomy during the initial 24h after their admission. There were 11 deaths (58%) amongst these patients. Peri hepatic packing and suturing were the most common procedures performed. A RTS Score<7.8 (RR: 7.3; IC 95%: 1.8-30.1), and ISS Score >20 (RR 2,5 IC 95%: 1.0 6.7), and associated intra-abdominal injuries (RR: 2.95; IC 95%: 1.25-6.92) were risk factors for immediate surgery. In 98 (83.7%) patients a non-operative management was performed. 7 patients had a failed non-operative management. CONCLUSION: The need for immediate surgical management is related to the presence of associated intra-abdominal injuries, and the ISS and RTS scores. In this series the most frequently performed procedure for blunt liver trauma was peri hepatic packing. PMID- 24176192 TI - Recombinant polypeptide production in E. coli: towards a rational approach to improve the yields of functional proteins. AB - The development of complementary technologies enabled the successful production of recombinant polypeptides in bacteria and opened to biology researchers new avenues as obtaining suitable amounts of proteins necessary for their experimental work became easy, fast, and inexpensive. Nevertheless, the recombinant approach remained somehow unpredictable, since many constructs resisted to apparent production or accumulated as aggregates. Several factors and physical/chemical conditions that could improve the accumulation of native-like protein were identified. At the same time, it was acknowledged that the outcome of most of them was erratic and that almost any protein required its own specific optimized set of conditions to achieve its correct folding. The attempt to understand the critical points specific for recombinant protein production missed the goal of setting universally useful protocols, but contributed to the increase of the rate of success by proposing always new empiric combinations.Nevertheless, the results published in the recent literature allow for a better comprehension of some key mechanisms controlling protein production in E. coli and could enable the elaboration of rational methodologies for improving the quantitative and qualitative features of the produced polypeptides. This result will be achieved when the identification of the limiting step that impairs the accomplishment of the native folding for any single construct will become straightforward. This minireview will discuss how factors such as the expression rate, the folding machinery, and the secretion efficiency may impact the final protein yields. PMID- 24176193 TI - Specific cell targeting with APRPG conjugated PEG-PLGA nanoparticles for treating ovarian cancer. AB - Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol) poly (lactic acid) (PEG-PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG-PLA and mPEG-PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative zeta-potential (-14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic. PMID- 24176194 TI - A helix-PXXP-helix peptide with antibacterial activity without cytotoxicity against MDRPA-infected mice. AB - In response to the growing problem of multidrug-resistant pathogenic microbes, much attention is being paid to naturally occurring and synthetic antimicrobial peptides (AMPs) and the effects of their structural modification. Among these modifications, amino acid substitution is a simple approach to enhancing biological activity and reducing cytotoxicity. An earlier study indicated that HPA3, an analog of HP (2-20) derived from the N-terminus of Helicobacter pylori ribosomal protein L1, forms large pores and shows considerable cytotoxicity. However, HPA3P, in which a proline (Pro) is substituted for glutamic acid (Glu) at position 9 of HPA3, shows markedly less cytotoxicity. This may be attributable to the presence of a Pro-kink into middle of the HPA3P structure within the membrane environment. Unfortunately, HPA3P is not an effective antibacterial agent in vivo. We therefore designed a helix-PXXP-helix structure (HPA3P2), in which Pro was substituted for the Glu and phenylalanine (Phe) at positions 9 and 12 of HPA3, yielding a molecule with a flexible central hinge. As compared to HPA3P, HPA3P3 exhibited dramatically increased antibacterial activity in vivo. ICR mice infected with clinically isolated multidrug-resistant Pseudomonas aeruginosa showed 100% survival when administered one 0.5-mg/kg dose of HPA3P2 or three 0.1-mg/kg doses of HPA3P2. Moreover, in a mouse model of septic shock induced by P. aeruginosa LPS, HPA3P2 reduced production of pro-inflammatory mediators and correspondingly reduced lung (alveolar) and liver tissue damage. The changes in HPA3 behavior with the introduction of Pro likely reflects alterations of the mechanism of action: i) HPA3 forms pores in the bacterial cell membranes, ii) HPA3P permeates the cell membranes and binds to intracellular RNA and DNA, and iii) HPA3P2 acts on the outer cellular membrane component LPS. Collectively, these results suggest HPA3P2 has the potential to be an effective antibiotic for use against multidrug-resistant bacterial strains. PMID- 24176196 TI - Biomimetic macroporous PEG hydrogels as 3D scaffolds for the multiplication of human hematopoietic stem and progenitor cells. AB - Multiplication of hematopoietic stem cells (HSCs) in vitro with current standard methods is limited and mostly insufficient for clinical applications of these cells. They quickly lose their multipotency in culture because of the fast onset of differentiation. In contrast, HSCs efficiently self-renew in their natural microenvironment (their niche) in the bone marrow. Therefore, engineering artificial bone marrow analogs is a promising biomaterial-based approach for culturing these cells. In the current study, a straight-forward, easy-to-use method for the production of biofunctionalized, macroporous hydrogel scaffolds that mimic the spongy architecture of trabecular bones was developed. As surrogates for cellular components of the niche, mesenchymal stem cells (MSCs) from different sources (bone marrow and umbilical cord) and osteoblast-like cells were tested. MSCs from bone marrow had the strongest pro-proliferative effect on freshly isolated human hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood. Co-culture in the pores of the three-dimensional hydrogel scaffold showed that the positive effect of MSCs on preservation of HSPC stemness was more pronounced in 3D than in standard 2D cell culture systems. Thus, the presented biomimetic scaffolds revealed to meet the basic requirements for creating artificial HSC niches. PMID- 24176195 TI - Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model. AB - Alginate encapsulation reduces the risk of transplant rejection by evading immune mediated cell injury and rejection; however, poor vascular perfusion results in graft failure. Since existing imaging models are incapable of quantifying the vascular response to biomaterial implants after transplantation, in this study, we demonstrate the use of in vivo laser speckle imaging (LSI) and wide-field functional imaging (WiFI) to monitor the microvascular environment surrounding biomaterial implants. The vascular response to two islet-containing biomaterial encapsulation devices, alginate microcapsules and a high-guluronate alginate sheet, was studied and compared after implantation into the mouse dorsal window chamber (N = 4 per implant group). Images obtained over a 14-day period using LSI and WiFI were analyzed using algorithms to quantify blood flow, hemoglobin oxygen saturation and vascular density. Using our method, we were able to monitor the changes in the peri-implant microvasculature noninvasively without the use of fluorescent dyes. Significant changes in blood flow, hemoglobin oxygen saturation and vascular density were noted as early as the first week post-transplant. The dorsal window chamber model enables comparison of host responses to transplanted biomaterials. Future experiments will study the effect of changes in alginate composition on the vascular and immune responses. PMID- 24176197 TI - Optical imaging of tumor vascularity associated with proliferation and glucose metabolism in early breast cancer: clinical application of total hemoglobin measurements in the breast. AB - BACKGROUND: Near-infrared optical imaging targeting the intrinsic contrast of tissue hemoglobin has emerged as a promising approach for visualization of vascularity in cancer research. We evaluated the usefulness of diffuse optical spectroscopy using time-resolved spectroscopic (TRS) measurements for functional imaging of primary breast cancer. METHODS: Fifty-five consecutive TNM stage I/II patients with histologically proven invasive ductal carcinoma and operable breast tumors (<5 cm) who underwent TRS measurements were enrolled. Thirty (54.5%) patients underwent 18F-fluoro-deoxy-glucose (FDG) positron emission tomography with measurement of maximum tumor uptake. TRS was used to obtain oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (tHb) levels from the lesions, surrounding normal tissue, and contralateral normal tissue. Lesions with tHb levels 20% higher than those present in normal tissue were defined as "hotspots," while others were considered "uniform." The findings in either tumor type were compared with clinicopathological factors. RESULTS: "Hotspot" tumors were significantly larger (P= 0.002) and exhibited significantly more advanced TNM stage (P=0.01), higher mitotic counts (P=0.01) and higher levels of FDG uptake (P=0.0004) compared with "uniform" tumors; however, other pathological variables were not significantly different between the two groups. CONCLUSIONS: Optical imaging for determination of tHb levels allowed for measurement of tumor vascularity as a function of proliferation and glucose metabolism, which may be useful for prediction of patient prognosis and potential response to treatment. PMID- 24176199 TI - CANDIS treatment program for cannabis use disorders: findings from a randomized multi-site translational trial. AB - BACKGROUND: In a recent paper, we reported the efficacy of a modular cognitive behavioral intervention for treating adolescents and adults with cannabis use disorders (CUD). In this study, we examine the outcome of this intervention after translating it into clinical practice. METHODS: A multi-site, randomized controlled trial of 279 treatment seekers with ICD-10 cannabis use disorders aged 16- 63 years was conducted in 11 outpatient addiction treatment centers in Germany. Patients were randomly assigned to an Active Treatment (AT, n=149) or Delayed Treatment Control (DTC, n=130). Treatment consisted of 10 sessions of fully manualized individual psychotherapy that combined Cognitive-Behavioral Therapy, Motivational EnhancementTherapy and problem-solving training. Assessments were conducted at baseline, during each therapy session, at post treatment and at three and six month follow-ups. RESULTS: At post assessment 53.3% of AT patients reported abstinence (46.3% negative urine screenings) compared to 22% of DTC patients (17.7% negative drug screenings) (p<0.001, Intention-to-treat analysis). AT patients improved in the frequency of cannabis use, number of cannabis dependence criteria, severity of dependence, as well as number and severity of cannabis-related problems. Effect sizes were moderate to high. While abstinence rates in the AT group decreased over the 3-month (negative urine screenings: 32.4%) and 6-month (negative urine screenings: 35.7%) follow-up periods, the effects in secondary outcomes were maintained. CONCLUSIONS: The intervention can successfully be translated to and applied in clinical practice. It has the potential to improve access to evidence-based care for chronic CUD patients. PMID- 24176198 TI - Intrinsic foot muscle deterioration is associated with metatarsophalangeal joint angle in people with diabetes and neuropathy. AB - BACKGROUND: Metatarsophalangeal joint deformity is associated with skin breakdown and amputation. The aims of this study were to compare intrinsic foot muscle deterioration ratios (ratio of adipose to muscle volume), and physical performance in subjects with diabetic neuropathy to controls, and determine their associations with 1) metatarsophalangeal joint angle and 2) history of foot ulcer. METHODS: 23 diabetic, neuropathic subjects [59 (SD 10) years] and 12 age matched controls [57 (SD 14) years] were studied. Radiographs and MRI were used to measure metatarsophalangeal joint angle and intrinsic foot muscle deterioration through tissue segmentation by image signal intensity. The Foot and Ankle Ability Measure evaluated physical performance. FINDINGS: The diabetic, neuropathic group had a higher muscle deterioration ratio [1.6 (SD 1.2) vs. 0.3 (SD 0.2), P<0.001], and lower Foot and Ankle Ability Measure scores [65.1 (SD 24.4) vs. 98.3 (SD 3.3) %, P<0.01]. The correlation between muscle deterioration ratio and metatarsophalangeal joint angle was r=-0.51 (P=0.01) for all diabetic, neuropathic subjects, but increased to r=-0.81 (P<0.01) when only subjects with muscle deterioration ratios >1.0 were included. Muscle deterioration ratios in individuals with diabetic neuropathy were higher for those with a history of ulcers. INTERPRETATION: Individuals with diabetic neuropathy had increased intrinsic foot muscle deterioration, which was associated with second metatarsophalangeal joint angle and history of ulceration. Additional research is required to understand how foot muscle deterioration interacts with other impairments leading to forefoot deformity and skin breakdown. PMID- 24176200 TI - Effects of prenatal cocaine/polydrug exposure on substance use by age 15. AB - OBJECTIVE: Examined effects of prenatal cocaine exposure (PCE) on tobacco, alcohol, marijuana and cocaine use by age 15. METHODS: Adolescent (n=358; 183 PCE, 175 non-prenatally cocaine exposed; NCE) drug use was assessed using urine, hair, and/or blood spot samples and self-report (Youth Risk Behavior Surveillance System; YRBSS) at ages 12 and 15. Logistic regression assessed effects of PCE on drug use controlling for other drug exposures, environment and blood lead levels (BLL). RESULTS: Adjusted percentages of drug use (PCE vs. NCE) were: tobacco 35% vs. 26% (p<.04), marijuana 33% vs. 23% (p<.04), alcohol 40% vs. 35% (p<.01), and any drugs 59% vs. 50% (p<.005). PCE adolescents were twice as likely to use tobacco (OR=2.02, 95% CI=1.05-3.90, p<.04), 2.2 times more likely to use alcohol (OR=2.16, 95% CI=1.21-3.87, p<.01) and 1.8 times more likely to use marijuana (OR=1.81, 95% CI=1.02-3.22, p<.04) than NCE adolescents. A race-by-cocaine exposure interaction (p<.01) indicated PCE non-African American adolescents had greater probability of tobacco use (65%) than NCE non-African American youth (21%). PCE was associated with any drug use (OR=2.16, CI=1.26-3.69, p<.005), while higher BLL predicted alcohol use (p<.001). Violence exposure was a predictor of tobacco (p<.002), marijuana (p<.0007) and any drug (p<.04). CONCLUSIONS: PCE and exposure to violence increased the likelihood of tobacco, marijuana or any drug use by age 15, while PCE and higher early BLL predicted alcohol use. Prevention efforts should target high risk groups prior to substance use initiation. PMID- 24176201 TI - Excessive state switching underlies reversal learning deficits in cocaine users. AB - BACKGROUND: Markers of chronic cocaine exposure on neural mechanisms in animals and humans is of great interest. The probabilistic reversal-learning task may be an effective way to examine dysfunction associated with cocaine addiction. However the exact nature of the performance deficits observed in cocaine users has yet to be disambiguated. METHOD: Data from a probabilistic reversal-learning task performed by 45 cocaine users and 41 controls was compared and fit to a Bayesian hidden Markov model (HMM). RESULTS: Cocaine users demonstrated the predicted performance deficit in achieving the reversal criterion relative to controls. The deficit appeared to be due to excessive switching behavior as evidenced by responsivity to false feedback and spontaneous switching. This decision-making behavior could be captured by a single parameter in an HMM and did not require an additional parameter to represent perseverative errors. CONCLUSIONS: Cocaine users are characterized by excessive switching behavior on the reversal-learning task. While there may be a compulsive component to behavior on this task, impulsive decision-making may be more relevant to observed impairment. This is important in building diagnostic tools to quantify the degree to which each type of dysfunction is present in individuals, and may play a role in developing treatments for those dysfunctions. PMID- 24176202 TI - Impact of community participation in primary health care: what is the evidence? AB - Community participation is a foundational principle of primary health care, with widely reputed benefits including improved health outcomes, equity, service access, relevance, acceptability, quality and responsiveness. Despite considerable rhetoric surrounding community participation, evidence of the tangible impact of community participation is unclear. A comprehensive literature review was conducted to locate and evaluate evidence of the impact of community participation in primary health care on health outcomes. The findings reveal a small but substantial body of evidence that community participation is associated with improved health outcomes. There is a limited body of evidence that community participation is associated with intermediate outcomes such as service access, utilisation, quality and responsiveness that ultimately contribute to health outcomes. Policy makers should strengthen policy and funding support for participatory mechanisms in primary health care, an important component of which is ongoing support for Aboriginal Community Controlled Health Services as exemplars of community participation in Australia. Primary health-care organisations and service providers are encouraged to consider participatory mechanisms where participation is an engaged and developmental process and people are actively involved in determining priorities and implementing solutions. PMID- 24176203 TI - It's Sno'ing on Pol III at nuclear pores. AB - Integral nuclear pore proteins associate with subsets of snoRNA and tRNA genes transcribed by RNA polymerase III and promote 3' transcript processing in nematodes. PMID- 24176204 TI - Use of dextran sulfate in tourniquet-induced skeletal muscle reperfusion injury. AB - BACKGROUND: Lower extremity ischemia-reperfusion injury (IRI)-prolonged ischemia and the subsequent restoration of circulation-may result from thrombotic occlusion, embolism, trauma, or tourniquet application in surgery. The aim of this study was to assess the effect of low-molecular-weight dextran sulfate (DXS) on skeletal muscle IRI. METHODS: Rats were subjected to 3 h of ischemia and 2 or 24 h of reperfusion. To induce ischemia the femoral artery was clamped and a tourniquet placed under the maintenance of the venous return. DXS was injected systemically 10 min before reperfusion. Muscle and lung tissue samples were analyzed for deposition of immunoglobulin M (IgM), IgG, C1q, C3b/c, fibrin, and expression of vascular endothelial-cadherin and bradykinin receptors b1 and b2. RESULTS: Antibody deposition in reperfused legs was reduced by DXS after 2 h (P < 0.001, IgM and IgG) and 24 h (P < 0.001, IgM), C3b/c deposition was reduced in muscle and lung tissue (P < 0.001), whereas C1q deposition was reduced only in muscle (P < 0.05). DXS reduced fibrin deposits in contralateral legs after 24 h of reperfusion but did not reduce edema in muscle and lung tissue or improve muscle viability. Bradykinin receptor b1 and vascular endothelial-cadherin expression were increased in lung tissue after 24 h of reperfusion in DXS-treated and non-treated rats but bradykinin receptor b2 was not affected by IRI. CONCLUSIONS: In contrast to studies in myocardial infarction, DXS did not reduce IRI in this model. Neither edema formation nor viability was improved, whereas deposition of complement and coagulation components was significantly reduced. Our data suggest that skeletal muscle IRI may not be caused by the complement or coagulation alone, but the kinin system may play an important role. PMID- 24176205 TI - Perioperative cardiovascular system failure in South Asians undergoing cardiopulmonary bypass is associated with prolonged inflammation and increased Toll-like receptor signaling in inflammatory monocytes. AB - BACKGROUND: South Asian ethnicity is an independent risk factor for mortality after coronary artery bypass. We tested the hypothesis that this risk results from a greater inflammatory response to cardiopulmonary bypass (CPB). METHODS: This was a single-site prospective cohort study. We compared the inflammatory response to CPB in 20 Caucasians and 17 South Asians undergoing isolated coronary artery bypass grafting surgery. RESULTS: Plasma levels of proinflammatory cytokines (interleukin [IL]-6, IL-8, IL-12, interferon gamma, and tumor necrosis factor) and anti-inflammatory mediators (IL-10 and soluble TNF receptor I) were measured. The Toll-like receptor (TLR) signaling pathway was examined in peripheral blood monocytes by flow cytometry, measuring surface expression of TLR2, TLR4, and coreceptor CD14 and activation of downstream messenger molecules (interleukin-1 receptor-associated kinase 4, nuclear factor kappa from B cells (NF-kappaB), c-Jun amino-terminal kinase, p38 mitogen-activated protein kinase, and Protein Kinase B). South Asians had persistently higher plasma levels of IL-6 and exhibited increased TLR signaling through the p38 mitogen-activated protein kinase and Protein Kinase B pathways in inflammatory monocytes after CPB. This increased inflammatory response was paralleled clinically by a higher sequential organ failure assessment score (5.1 +/- 1.4 versus 1.5 +/- 1.6, P = 0.027) and prolonged cardiovascular system failure (23.5% versus 0%) 48 h after CPB. CONCLUSIONS: South Asians develop an exacerbated systemic inflammatory response after CPB, which may contribute to the higher morbidity and mortality associated with coronary artery bypass in this population. These patients may benefit from targeted anti-inflammatory therapies designed to mitigate the adverse consequences resulting from this response. PMID- 24176206 TI - Ghrelin decreases motor deficits after traumatic brain injury. AB - BACKGROUND: Pharmacologic therapy for traumatic brain injury (TBI) has remained relatively unchanged for decades. Ghrelin, an endogenously produced peptide, has been shown to prevent apoptosis and blood-brain barrier dysfunction after TBI. We hypothesize that ghrelin treatment will prevent neuronal degeneration and improve motor coordination after TBI. MATERIALS AND METHODS: A weight drop model created severe TBI in three groups of BALB/c mice: Sham, TBI, and TBI + ghrelin (20 MUg intraperitoneal ghrelin). Brain tissue was examined by hematoxylin and eosin and Fluoro-Jade B (FJB) staining to evaluate histologic signs of injury, cortical volume loss, and neuronal degeneration. Additionally, motor coordination was assessed. RESULTS: Ghrelin treatment prevented volume loss after TBI (19.4 +/- 9.8 mm(3)versus 71.4 +/- 31.4 mm(3); P < 0.05). Similarly, although TBI increased FJB-positive neuronal degeneration, ghrelin treatment decreased FJB staining in TBI resulting in immunohistologic patterns similar to sham. Compared with sham, TBI animals had a significant increase in foot faults at d 1, 3, and 7 (2.75 +/- 0.42; 2.67 +/- 0.94; 3.33 +/- 0.69 versus 0.0 +/- 0.0; 0.17 +/- 0.19; 0.0 +/- 0.0; P < 0.001). TBI + ghrelin animals had significantly decreased foot faults compared with TBI at d 1, 3, and 7 (0.42 +/- 0.63; 0.5 +/- 0.43; 1.33 +/- 0.58; P versus TBI <0.001; P versus sham = NS). CONCLUSIONS: Ghrelin treatment prevented post-TBI cortical volume loss and neurodegeneration. Furthermore, ghrelin improved post-TBI motor deficits. The mechanisms of these effects are unclear; however, a combination of the anti-apoptotic and inflammatory modulatory effects of ghrelin may play a role. Further studies delineating the mechanism of these observed effects are warranted. PMID- 24176207 TI - Ischemic preconditioning increased the intestinal stem cell activities in the intestinal crypts in mice. AB - BACKGROUND: Ischemic preconditioning (IPC) can protect against ischemia reperfusion injury in the small intestine. Because intestinal stem cells (ISCs) control the recovery and growth of intestinal villi, this study investigated whether IPC had any effects on the activity of ISCs. MATERIALS AND METHODS: The small intestines of mice were treated with IPC, laparotomy only (sham), or no surgery. The crypt fractions were isolated and the characteristics of ISCs among various groups were compared. The regenerative ability and the number of organoids grown from various crypt fractions were compared. The expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and the related proteins of the Wnt /beta-catenin pathway in the crypt fractions were studied. RESULTS: The IPC group had higher messenger RNA levels of various stem cell markers than the sham group at days 1 and 2 after surgery. The IPC group exhibited greater regenerative activity and more crypt organoids than the sham group (P < 0.05). The expression of HIF-1alpha, beta-catenin, and phosphoglycogen synthase kinase 3beta was increased in the IPC-treated crypt fractions in vivo and cultured crypt organoid cells with deferoxamine-mimicked hypoxia in vitro. CONCLUSIONS: IPC significantly upregulated the activity of ISCs, possibly through the HIF-1alpha response and Wnt-/beta-catenin signaling pathway. PMID- 24176208 TI - The effects of iloprost on ischemia-reperfusion injury in skeletal muscles in a rodent model. AB - PURPOSE: The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model. MATERIALS AND METHODS: Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses. RESULTS: Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL. CONCLUSIONS: These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model. PMID- 24176209 TI - The effect of arginine vasopressin on organ donor procurement and lung function. AB - BACKGROUND: Hormone replacement therapy (HRT) is becoming more common when managing brain-dead donors. Arginine vasopressin (AVP) is associated with benefits but is not consistently used. We hypothesize that AVP is associated with the maintenance of lung function and successful recovery in donors and enhanced lung graft performance in recipients. METHODS: The Organ Procurement and Transplantation Network database was used. Study donors were those treated with HRT and procured from January 1, 2009 to June 30, 2011. AVP (+) and AVP (-) donors were compared. Donor lung function, the rate of successful lung procurement, and the incidence of graft failure in recipients were studied. RESULTS: There were 12,322 donors included, of which 7686 received AVP (62.4%). Cerebrovascular accident (4722 [38.3%]) was the most common cause of donor death. There was a significant increase in high yield (>=4 organs) (51.0% versus 39.3%, <0.001), mean number of organs (3.75 versus 3.33, <0.001), and rate of successful lung recovery (26.3% versus 20.5%, <0.001) with AVP. Lung function was preserved to a greater degree in donors receiving AVP. Adjusting the significant factors, AVP was independently associated with lung procurement (1.220 [1.114-1.336], <0.001). The incidence of early graft failure was not changed. CONCLUSIONS: AVP with HRT is associated with the maintenance of lung function and a significant increase in successful organ recovery in donors without untoward effects in the recipient. AVP should be universally adopted as a component of HRT in the management of donors with neurologic death. PMID- 24176210 TI - Diagnosing angioedema. AB - Angioedema usually occurs within the setting of allergic diseases or urticaria, but situations occur in which angioedema itself represents a disease, such as in hereditary angioedema. Evaluation of patients for recurrent angioedema without wheals must take into account both specific clinical signs and symptoms and specialized laboratory testing. PMID- 24176211 TI - Hereditary angioedema with normal C1 inhibitor. AB - Until recently it was assumed that hereditary angioedema was a disease that results exclusively from a genetic deficiency of the C1 inhibitor. In 2000, families with hereditary angioedema, normal C1 inhibitor activity, and protein in plasma were described. Since then, numerous patients and families with that condition have been reported. Most of the patients were women. In many of the affected women, oral contraceptives, hormone replacement therapy containing estrogens, and pregnancies triggered the clinical symptoms. In some families mutations in the coagulation factor XII (Hageman factor) gene were detected. PMID- 24176212 TI - Creating a comprehensive treatment plan for hereditary angioedema. AB - Management of hereditary angioedema (HAE) has changed dramatically in recent years because of the availability of several HAE-specific medications. This paradigm shift in therapy provides the opportunity to dramatically improve the care of HAE patients, but has increased the complexity of treatment. Patient education and communication with health care providers is crucial. Early treatment of HAE attacks has been shown to improve clinical outcomes, highlighting the importance of rapid and reliable treatment. This review summarizes the current evidence for best practices in HAE management, and suggests practical steps toward developing a comprehensive treatment plan. PMID- 24176213 TI - On-demand therapy for hereditary angioedema. AB - Consensus guidelines on hereditary angioedema (HAE) recommend that all patients have access to on-demand treatment of acute attacks. A recent patientcentric guideline recommended that at least 2 on-demand therapies be available because patients often have heterogeneous responses to different medications. Self administration of therapeutic agents, or administration under supervision by a health care provider in the home setting, is the preferred treatment approach. Future studies are needed to show the benefits of acute on-demand therapies at improving quality of life and reducing morbidity and mortality in patients with HAE. PMID- 24176214 TI - Update on preventive therapy (prophylaxis) for hereditary angioedema. AB - Both prophylactic and acute treatment of hereditary angioedema have been revolutionized in the past decade. Effective prophylactic treatment has long been provided by the group of attenuated androgens and antifibrinolytic agents, but their use has been attended by side effects. Plasma derived C1 inhibitor has been added to the group of agents effective in prophylaxis and a group of agents, discussed elsewhere in this volume, has been added to the armamentarium for acute therapy. PMID- 24176215 TI - Hereditary angioedema in women: specific challenges. AB - Women with hereditary angioedema (HAE) present with more frequent and more severe attacks than men. The disease is often affected by estrogenic status. Estrogens increase kininogenase activities. Deliveries seem to be safe but it is advised to have C1 inhibitor (C1Inh) concentrate in the delivery room; in case of worsening during the pregnancy, it is recommended to use short-term prophylaxis with C1Inh concentrate. Women often badly tolerate attenuated androgen: 30% of women have weight gain, 30% irregular menstruations, and 6% virilization. Acid tranexamic and progestins are preferred for long-term prophylaxis for women with HAE. PMID- 24176216 TI - Contact system activation in patients with HAE and normal C1 inhibitor function. AB - In addition to hereditary angioedema (HAE) with C1 inhibitor (C1INH) deficiency, a type of HAE with dominant inheritance and normal C1INH function (HAE with normal C1INH) has been described. This relates to contact phase activation with exaggerated kinin formation, and mutations in the coagulation factor XII gene have been identified in some affected families, but the cause of the disease has remained elusive in a majority of families. Several triggering factors are responsible for developing kinin forming system, with participation of endothelium and mast cell component. Angioedema conditions meet the accumulation of kinins with failed kinin catabolism. PMID- 24176217 TI - Role of the B1 bradykinin receptor and gC1qR/p33 in angioedema. AB - Patients affected by angioedema (AE) are subject to asymmetric, nonerythematous, nonpruritic, localized, transient, episodic swelling of deeper layers or submucosal tissues of the skin, oropharyngolaryngeal tissue, and/or gastrointestinal wall. The nonapeptide bradykinin (BK) may be largely responsible for the vascular permeability seen in most AE. During AE attacks, activation of the serine proteases leads to the release of BK. Enzymes expressed on the endothelial cell membrane can metabolize BK, producing the agonist of the B1R, which can then be upregulated by proinflammatory stimuli, suggesting that the blockade of B1R and B2R, or gC1q/p33, may provide novel therapeutic targets. PMID- 24176218 TI - Rare disease partnership: the role of the US HAEA in angioedema care. AB - Rare diseases, including hereditary angioedema, present a unique set of challenges for clinicians and investigators. The most successful way to negotiate these difficulties has been to develop collaborative efforts among physicians and with patient advocacy organizations and pharmaceutical companies. The US Hereditary Angioedema Association is a large nonprofit patient advocacy organization that has been the catalyst for these types of collaborative arrangements involving hereditary angioedema. The dedication and unique structure of this patient advocacy organization has allowed it to make a substantial contribution to improving hereditary angioedema diagnosis and care. PMID- 24176219 TI - Angioedema: what we know and what we need to know. PMID- 24176220 TI - Immunology and Allergy Clinics of North America. Angioedema. Preface. PMID- 24176221 TI - PI3-kinase inhibition synergistically promoted the anti-tumor effect of lupeol in hepatocellular carcinoma. AB - BACKGROUND: Lup-20(29)-en-3H-ol (Lupeol), a dietary triterpene, has been shown to possess multiple pharmacological activities including anti-tumor effects METHODS: In the current study, we noted that low doses of lupeol (<40 MUM) promoted the growth of hepatocellular carcinoma (HCC) cells with a significant activation of the PI3-kinase/Akt signaling pathway. We further investigated the combined anti tumor effect of lupeol and S14161, a newly identified PI3-Kinase inhibitor in vitro and in vivo RESULTS: The results demonstrated that lupeol and S14161 could exert a synergistic antitumor effect resulting in chemo-sensitization of HCC to low doses of lupeol. Using an in vivo HCC model, we further demonstrated that lupeol and S14161 synergistically inhibited tumor growth without any adverse effects on body weight CONCLUSION: Our studies showed that the activation of PI3 kinase/Akt pathway resulted in the tumor-promoting effect with low doses of lupeol. Combining PI3-kinase inhibitor with lupeol could synergistically augment the anti-tumor effect of lupeol and might be an applicable strategy for HCC therapy. PMID- 24176222 TI - Oral versus intravenous antibiotics for patients with Klebsiella pneumoniae liver abscess: study protocol for a randomized controlled trial. AB - BACKGROUND: Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early (< one week) step-down to oral antibiotics, to continuing four weeks of intravenous antibiotics, in patients with Klebsiella liver abscess. METHODS/DESIGN: The study is designed as a multi-center randomized open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomized to active control will receive IV ceftriaxone 2 grams daily to complete a total of four weeks of IV antibiotics. Participants randomized to intervention will be immediately converted to oral ciprofloxacin 750 mg twice daily. At Week four, all participants will undergo abdominal imaging and be assessed for clinical response (CRP < 20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped; if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by Week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality of life analysis will be performed to assess whether treatment with oral antibiotics is less burdensome than prolonged IV antibiotics. DISCUSSION: Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction. TRIAL REGISTRATION: Clinical trials gov NCT01723150. PMID- 24176223 TI - Relationship between serum uric acid and all-cause and cardiovascular mortality in patients treated with peritoneal dialysis. AB - BACKGROUND: Although serum uric acid level appears to be associated with mortality in individuals treated with hemodialysis, the relationship between serum uric acid level and death is uncertain in patients treated with peritoneal dialysis (PD). STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 985 patients from a single PD center in South China followed up for a median of 25.3 months. PREDICTOR: Serum uric acid level. OUTCOMES & MEASUREMENTS: The association of baseline sex-specific uric acid level with all-cause and cardiovascular mortality was evaluated. Models were adjusted for age, body mass index, comorbidity score, residual kidney function, total Kt/V, allopurinol and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, and laboratory test results, including hemoglobin, serum albumin, creatinine, calcium, phosphorus, triglycerides, low-density lipoprotein cholesterol, and high-sensitivity C reactive protein. RESULTS: Mean age was 48.3+/-15.4 (SD) years, and 23% had diabetes. Mean uric acid level was 7.0+/-1.3 (range, 3.8-19.8) mg/dL. During follow-up, 144 deaths were recorded, of which 64 were due to cardiovascular events. In multivariable models, the highest sex-specific tertile of uric acid level was associated with increased risk of all-cause mortality (HR, 1.93; 95% CI, 1.27-2.93; P=0.004) and cardiovascular mortality (HR, 3.31; 95% CI, 1.70 6.41; P<0.001) compared to the lowest tertile. Adjusted Cox regression models showed that the HRs per 1-mg/dL higher uric acid level for all-cause and cardiovascular mortality were 1.33 (95% CI, 1.14-1.56; P<0.001) and 1.44 (95% CI, 1.17-1.77; P=0.001) for men and 1.03 (95% CI, 0.86-1.24; P=0.8) and 1.16 (95% CI, 0.97-1.38; P=0.1) for women, respectively. A formal test for interaction indicated that the association of uric acid level with all-cause and cardiovascular mortality differed by sex (beta = -0.06 [P=0.02] and beta = -0.10 [P=0.02], respectively). LIMITATIONS: Single measurement of uric acid at baseline. Cause of death determined by death certificates and expert consensus. CONCLUSIONS: Elevated serum uric acid level is an independent risk factor for all cause and cardiovascular mortality in men treated with PD. PMID- 24176225 TI - Differential role of visuospatial working memory in the propensity toward uncertainty in patients with obsessive-compulsive disorder and in healthy subjects. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with visuospatial working memory deficits. Intolerance of uncertainty is thought to be a core component of OCD symptoms. Recent findings argue for a possible relationship between abilities in visuospatial memory and uncertainty. However, this relationship remains unclear in both OCD patients and healthy subjects. To address this issue, we measured performance in visuospatial working memory and the propensity to express uncertainty during decision making. We assessed their relationship and the temporal direction of this relationship in both OCD patients and healthy subjects. METHOD: Baseline abilities in visuospatial working memory were measured with the Corsi block-tapping test. A delayed matching-to-sample task was used to identify explicit situations of certainty, uncertainty and ignorance and to assess continuous performance in visuospatial working memory. Behavioural variables were recorded over 360 consecutive trials in both groups. RESULTS: Baseline scores of visuospatial working memory did not predict the number of uncertain situations in OCD patients whereas they did in healthy subjects. Uncertain trials led to reduced abilities in visuospatial working memory to 65% of usual performance in OCD patients whereas they remained stable in healthy subjects. CONCLUSIONS: The present findings show an opposite temporal direction in the relationship between abilities in working memory and uncertainty in OCD patients and healthy subjects. Poor working memory performance contributes to the propensity to feel uncertainty in healthy subjects whereas uncertainty contributes to decreased continuous performance in working memory in OCD patients. PMID- 24176226 TI - Defining the paramedic process. AB - The use of a 'process of care' is well established in several health professions, most evidently within the field of nursing. Now ingrained within methods of care delivery, it offers a logical approach to problem solving and ensures an appropriate delivery of interventions that are specifically suited to the individual patient. Paramedicine is a rapidly advancing profession despite a wide acknowledgement of limited research provisions. This frequently results in the borrowing of evidence from other disciplines. While this has often been useful, there are many concerns relating to the acceptable limit of evidence transcription between professions. To date, there is no formally recognised 'process of care'-defining activity within the pre-hospital arena. With much current focus on the professional classification of paramedic work, it is considered timely to formally define a formula that underpins other professional roles such as nursing. It is hypothesised that defined processes of care, particularly the nursing process, may have features that would readily translate to pre-hospital practice. The literature analysed was obtained through systematic searches of a range of databases, including Ovid MEDLINE, Cumulative Index to Nursing and Allied Health. The results demonstrated that the defined process of care provides nursing with more than just a structure for practice, but also has implications for education, clinical governance and professional standing. The current nursing process does not directly articulate to the complex and often unstructured role of the paramedic; however, it has many principles that offer value to the paramedic in their practice. Expanding the nursing process model to include the stages of Dispatch Considerations, Scene Assessment, First Impressions, Patient History, Physical Examination, Clinical Decision-Making, Interventions, Re-evaluation, Transport Decisions, Handover and Reflection would provide an appropriate model for pre-hospital practices. PMID- 24176224 TI - TRPM7 triggers Ca2+ sparks and invadosome formation in neuroblastoma cells. AB - Cell migration depends on the dynamic formation and turnover of cell adhesions and is tightly controlled by actomyosin contractility and local Ca2+ signals. The divalent cation channel TRPM7 (Transient Receptor Potential cation channel, subfamily Melastatin, member 7) has recently received much attention as a regulator of cell adhesion, migration and (localized) Ca2+ signaling. Overexpression and knockdown of TRPM7 affects actomyosin contractility and the formation of cell adhesions such as invadosomes and focal adhesions, but the role of TRPM7-mediated Ca2+ signals herein is currently not understood. Using Total Internal Reflection Fluorescence (TIRF) Ca2+ fluorometry and a novel automated analysis routine we have addressed the role of Ca2+ in the control of invadosome dynamics in N1E-115 mouse neuroblastoma cells. We find that TRPM7 promotes the formation of highly repetitive and localized Ca2+ microdomains or "Ca2+ sparking hotspots" at the ventral plasma membrane. Ca2+ sparking appears strictly dependent on extracellular Ca2+ and is abolished by TRPM7 channel inhibitors such as waixenicin-A. TRPM7 inhibition also induces invadosome dissolution. However, invadosome formation is (functionally and spatially) dissociated from TRPM7 mediated Ca2+ sparks. Rather, our data indicate that TRPM7 affects actomyosin contractility and invadosome formation independent of Ca2+ influx. PMID- 24176227 TI - The role of gangliosides in brain development and the potential benefits of perinatal supplementation. AB - The maternal diet provides critical nutrients that can influence fetal and infant brain development and function. This review highlights the potential benefits of maternal dietary ganglioside supplementation on fetal and infant brain development. English-language systematic reviews, preclinical studies, and clinical studies were obtained through searches on PubMed. Reports were selected if they included benefits and harms of maternal ganglioside supplementation during pregnancy or ganglioside-supplemented formula after pregnancy. The potential benefits of ganglioside supplementation were explored by investigating the following: (1) their role in neural development, (2) their therapeutic use in neural injury and disease, (3) their presence in human breast milk, and (4) their use as a dietary supplement during or after pregnancy. Preclinical studies indicate that ganglioside supplementation at high doses (1% of total dietary intake) can significantly increase cognitive development and body weight when given prenatally. However, lower ganglioside supplementation doses have no beneficial cognitive effects, even when given throughout pregnancy and lactation. In human clinical trials, infants given formula supplemented with gangliosides showed increased cognitive development and an increase in ganglioside content. Ganglioside supplementation may promote brain development and function in offspring when administered at the optimum dosage. We propose that prenatal maternal dietary supplementation with gangliosides throughout pregnancy may promote greater long-term effects on brain development and function. Before this concept can be encouraged in preconception clinics, future research and clinical trials are needed to confirm the ability of dietary gangliosides to improve cognitive development, but available results already encourage this area of research. PMID- 24176228 TI - The polyphenol-rich baobab fruit (Adansonia digitata L.) reduces starch digestion and glycemic response in humans. AB - The baobab fruit (Adansonia digitata L.) is found throughout regions of Africa and is becoming increasingly recognized for its high nutrient and polyphenol content. Polyphenols have been beneficial for their effects on reducing the glycemic response (GR) and for improving various other metabolic parameters. Based on previous research, it was hypothesized that the baobab fruit extract would reduce starch digestion in vitro and would show potential for reducing the GR and for increasing satiety and diet-induced thermogenesis in humans. Six extracts of baobab from 6 different locations in Africa were measured for their antioxidant and polyphenol content using the ferric ion-reducing antioxidant power and the Folin-Ciocalteu methods, respectively. Baobab extract was baked into white bread at different doses to determine the optimal dose for reducing starch breakdown and sugar release from white bread after an in vitro digestion procedure. In vivo, baobab extract was consumed in solution at both a low-dose (18.5 g) and a high-dose (37 g) aqueous drink in 250 mL of water along with white bread, and resulting GR, satiety, and postprandial energy expenditure were measured. All extracts in this study were shown to be good sources of polyphenols. Baobab fruit extract added to white bread at 1.88 % significantly (P < .05) reduced rapidly digestible starch from white bread samples. In vivo, the baobab fruit extract at both low and high doses significantly (P < .05) reduced GR, although there was no significant effect on satiety or on energy expenditure. PMID- 24176229 TI - Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability. AB - There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway. PMID- 24176230 TI - Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins. AB - Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (<50 g carbohydrate/d) for 6 weeks would improve lipid profiles and insulin sensitivity, reduce blood pressure, decrease cellular adhesion and inflammatory biomarkers, and augment VEF (flow-mediated dilation and forearm blood flow) in statin users. Participants (n = 21; 59.3 +/- 9.3 y, 29.5 +/- 3.0 kg/m(2)) decreased total caloric intake by approximately 415 kcal at 6 weeks (P < .001). Daily nutrient intakes at baseline (46/36/17% carb/fat/pro) and averaged across the intervention (11/58/28% carb/fat/pro) demonstrated dietary compliance, with carbohydrate intake at baseline nearly 5-fold greater than during the intervention (P < .001). Compared to baseline, both systolic and diastolic blood pressure decreased after 3 and 6 weeks (P < .01). Peak forearm blood flow, but not flow-mediated dilation, increased at week 6 compared to baseline and week 3 (P <= .03). Serum triglyceride, insulin, soluble E-Selectin and intracellular adhesion molecule-1 decreased (P < .01) from baseline at week 3, and this effect was maintained at week 6. In conclusion, these findings demonstrate that individuals undergoing statin therapy experience additional improvements in metabolic and vascular health from a 6 weeks CRD as evidenced by increased insulin sensitivity and resistance vessel endothelial function, and decreased blood pressure, triglycerides, and adhesion molecules. PMID- 24176231 TI - Processed pork is the most frequently consumed type of pork in a survey of Australian children. AB - Pork represents a core food that provides key nutrients to the diet. Dietary guidelines recommend limiting processed meat intake because of adverse health outcomes. The aims of this study were to describe pork consumption, assess the contribution of pork to nutrient intakes, and compare anthropometric characteristics between pork consumers and nonconsumers in a survey of Australian children. We hypothesized that pork consumption will contribute to intakes of key nutrients and that the weight status of children who consume pork will be similar to nonconsumers. This study involved a secondary analysis of the 2007 Australian National Children's Nutrition and Physical Activity Survey. Pork and pork containing dishes were identified and classified as fresh or processed pork. The contributions of pork to nutrient intakes were calculated. Weight, waist circumference, and body mass index were compared between pork consumers and nonconsumers. Data from 4487 children were available for use. Of this sample, 2245 reported consuming pork, 14% (n = 310) of whom consumed fresh pork, whereas 93% (n = 2084) consumed processed pork. All types of pork contributed to intakes of protein, niacin, and zinc. In addition, fresh pork contributed to intakes of thiamine, long-chain omega-3, phosphorous, and potassium. Total and processed pork contributed 12.2% and 13.0% of sodium, respectively. There were no significant differences between weight, waist circumference, and body mass index in consumers and nonconsumers of total, fresh, or processed pork. In a survey of Australian children, processed pork was the most frequently consumed form of pork, suggesting a deviation from dietary guidelines. PMID- 24176232 TI - Cyclolepis genistoides D. Don (palo azul) promotes differentiation of adipocytes and regulates adipokine expression. AB - Cyclolepis genistoides D. Don is a herbaceous perennial belonging to the family Asteraceae, and its vernacular name is "palo azul" (palo). Palo has been reported to exhibit many physiological effects that contribute to the prevention of metabolic syndromes, although its mechanism is unclear. Among palo's various activities, we investigated the hypothesis that palo promotes adipocytes differentiation and regulates adipokine profiles in 3T3-L1 adipocytes by modulation of peroxisome proliferator-activated receptor (PPAR) gamma, a major regulator of adipose differentiation. 3T3-L1 adipocytes were cultured and differentiated in Dulbecco modified Eagle medium with 50 to 200 MUg/mL palo for 7 days or were cultured with palo without differentiation protocol for 14 days. Palo down-regulated the expression of 2 types of expressed/secreted adipokines, leptin and resistin, in a concentration-dependent manner. Under a nondifferentiated condition, palo promoted the accumulation of lipid droplets in cells. Real-time polymerase chain reaction and luciferase reporter assay showed that palo up-regulated expression and transcriptional activity of PPARgamma. Furthermore, palo increased the expression of insulin-sensitizing adipokine, adiponectin, which is a directly target of PPARgamma, both at the messenger RNA level and at the protein level. In summary, palo demonstrated the potential to improve insulin resistance by promoting adipocyte differentiation via PPARgamma activation. Results suggest an increase in adiponectin secretion and a decrease in insulin-resistant factors such as leptin and resistin. PMID- 24176233 TI - Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease. AB - Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-L-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial beta-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-L-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation. PMID- 24176235 TI - High-fat diet action on adiposity, inflammation, and insulin sensitivity depends on the control low-fat diet. AB - Animal studies using a high-fat diet (HFD) have studied the effects of lipid overconsumption by comparing a defined HFD either with a natural-ingredient chow diet or with a defined low-fat diet (LFD), despite the dramatic differences between these control diets. We hypothesized that these differences in the control diet could modify the conclusions regarding the effects that an increase of fat in the diet has on several metabolic parameters. For 11 weeks, C57bl6/J mice were fed a low-fat chow diet (8% energy from fat), a typical semisynthetic LFD (12%), or a semisynthetic HFD (sy-HF) (40%). Conclusions about the effect of sy-HF on body weight gain, subcutaneous adipose tissue, insulin sensitivity, and adipose tissue inflammation were modified according to the control LFD. Conversely, conclusions about epididymal and retroperitoneal adipose tissue; fat intake effects on liver and muscular lipids, cholesterol, free fatty acids, and markers of low-grade inflammation; and of adipose tissue macrophage infiltration were the same regardless of the use of low-fat chow diet or semisynthetic LFD. For some physiological outcomes, conflicting conclusions were even reached about the effects of increased fat intake according to the chosen low-fat control. Some deleterious effects of sy-HF may not be explained by lipid overconsumption but rather by the overall quality of ingredients in a semisynthetic diet. According to the control LFD chosen, conclusions on the lipid-related effects of HFDs must be formulated with great care because some end points are profoundly affected by the ingredient composition of the diet rather than by fat content. PMID- 24176234 TI - Olive leaf down-regulates the oxidative stress and immune dysregulation in streptozotocin-induced diabetic mice. AB - Type 1 diabetes is an endocrinologic disorder characterized by uncontrolled glucose regulation and oxidative stress. Olive leaves have been studied extensively for their antioxidant activity and capacity to improve immune function. We hypothesized that olive leaf powder supplementation will be effective in inhibiting the oxidative stress and immune dysregulation in streptozotocin (STZ)-induced diabetic mice. Mice were assigned to 1 of 5 groups: control (C), STZ-induced diabetes (D), and STZ-induced diabetes supplemented with very low dose (VLOL), low dose (LOL), or high dose of olive leaf powder (HOL). Blood glucose in the VLOL and LOL groups was lower than that in the D group (P < .05). Insulin levels were increased in all experimental groups in comparison with that in the D group, (P < .05). Superoxide dismutase, glutathione peroxidase, and catalase activities were shown to decrease in the D group, whereas these were increased in the VLOL and LOL groups. Nitric oxide levels decreased in the VLOL and LOL groups, as compared with the D group. The messenger RNA expression levels of inducible nitric oxide synthase were significantly decreased in the VLOL and HOL groups, and interferon-gamma levels were significantly decreased in the liver of the VLOL, LOL, and HOL groups compared with the levels in the D group. Interleukin-17 levels were significantly decreased in the VLOL and HOL groups. Th1 and Th17 cytokine levels were increased in the D group but decreased in all the experimental groups. Th2 cytokine levels were increased in all olive leaf supplemented groups compared with those in the D group. These results indicate a reduction in the levels of proinflammatory cytokines, suggesting that olive leaves have the potential to provide therapeutic inhibition of diabetic complications. PMID- 24176236 TI - A calcium-deficient diet in pregnant, nursing rats induces hypomethylation of specific cytosines in the 11beta-hydroxysteroid dehydrogenase-1 promoter in pup liver. AB - Prenatal undernutrition affects offspring phenotype via changes in the epigenetic regulation of specific genes. We hypothesized that pregnant females that were fed a calcium (Ca)-deficient diet would have offspring with altered hepatic glucocorticoid-related gene expression and altered epigenetic gene regulation. Female Wistar rats ate either a Ca-deficient or control diet from 3 weeks before conception to 21 days after parturition. Pups were allowed to nurse from their original mothers and then euthanized on day 21. Methylation of individual cytosine-guanine dinucleotides in the phosphoenolpyruvate carboxykinase (Pck1), peroxisome proliferator-activated receptor alpha (Ppara), glucocorticoid receptor (Nr3c1), 11beta-hydroxysteroid dehydrogenase-1 (Hsd11b1), and 11beta hydroxysteroid dehydrogenase-2 (Hsd11b2) promoters was measured in liver tissue using pyrosequencing. For each gene, quantitative real-time polymerase chain reaction was used to assess mRNA levels in liver tissue. Overall Hsd11b1 methylation was lower in the Ca-deficient group than in the control group; however, overall methylation of each other gene did not differ between groups. Serum corticosterone levels in male pups from Ca-deficient dams were higher than those in control pups. Expression of Pck1 and Nr3c1 was lower in the Ca-deficient group than in the control group. A Ca-deficient diet for a dam during gestation and early nursing may alter glucocorticoid metabolism and lead to higher intracellular glucocorticoid concentrations in the hepatic cells of her offspring; moreover, this abnormal glucocorticoid metabolism may induce the metabolic complications that are associated with Ca deficiency. These findings indicated that prenatal nutrition affected glucocorticoid metabolism in offspring in part by affecting the epigenome of offspring. PMID- 24176238 TI - Optimization of thermo-chemical pretreatment and enzymatic hydrolysis of kitchen wastes. AB - The use of abundant waste materials with high carbohydrate content may contribute substantially to reduction of biofuels production cost. The present study aimed at optimizing the combined effect of thermo-chemical pretreatment and enzymatic hydrolysis of kitchen wastes (KW) for maximizing the production of fermentable soluble sugars. To this end, acid pretreatment of KW samples was performed with hydrochloric acid (0-3% HCl) at 30-100 degrees C for 0-120 min treatment time. Alternatively, alkaline pretreatment of KW samples was performed with potassium hydroxide solution (0-11%) at constant temperature and time (0 degrees C and 20 min, respectively). KOH pretreatment at such conditions targets to degrade the resistant starch of KW samples. Both acid and alkaline pretreatments were followed by addition of variable levels of enzyme dosage (0-3.6% v/v alpha amylase and 0-3.2% v/v amyloglucosidase-AMG) at constant pH, temperature and time (pH = 5, T = 50 degrees C and t = 30 min, respectively). Based on our results, glucose concentration increased by ~300% after pretreatment with either acid or KOH in combination with enzymatic hydrolysis (2% HCl, 85 degrees C, 80 min, 0.1% alpha-amylase, AMG, and 1% KOH, 0 degrees C, 20 min, 1.1% alpha-amylase, 0.4% AMG) compared to raw (untreated) KW. Estimating the different YG yields at KW loading of 5%, an increase of 192% and 121% for total soluble monosugars and total soluble sugars, respectively, was succeeded compared to untreated KW. The effect of solids loading on the obtained sugar yields using the optimum conditions for thermo-chemical pretreatment followed by enzymatic hydrolysis was also tested resulting to 27.5% increase of the soluble glucose yield when half of the solids loading (2.5%) was used. A decrease of total soluble sugars yield by 32.2% was observed when solely acid hydrolysis at optimum conditions from our previous study was applied at 30% solids loading. PMID- 24176237 TI - Resveratrol prevents suppression of regulatory T-cell production, oxidative stress, and inflammation of mice prone or resistant to high-fat diet-induced obesity. AB - Consumption of a high-fat diet (HFD) is correlated with increased oxidative stress and chronic inflammation in many organs. Regulatory T cells (Tregs) are essential negative regulators of inflammation. We hypothesized that resveratrol (trans-3,5,4'-trihydroxystilbene) could protect against HFD-induced oxidative stress and inflammation. Therefore, we examined the effect of resveratrol on oxidative stress and the relevant peripheral immune-regulating mechanisms in HFD induced obese (DIO) and diet-resistant mice. C57BL/6 mice were fed a normal diet and an HFD for 13 weeks. Then the experimental group was subdivided into DIO and diet-resistant groups according to their body weights, which were further supplemented with 0.03% resveratrol and 0.06% resveratrol, respectively, for an additional 13 weeks. Resveratrol prevented the accumulation of chronic oxidative stress and suppression of Tregs production in HFD mice, modulated changes of cytokines in the plasma and spleen, and decreased expressions of inflammatory mediators compared with those of the DIO group. Our results indicate that resveratrol, as a feasible effective supplement for HFD, can relieve oxidative stress, inhibit inflammatory genes expression, and increase Tregs number via aryl hydrocarbon receptor activation inhibited by HFD, especially in DIO mice. PMID- 24176239 TI - Fluid bed gasification--plasma converter process generating energy from solid waste: experimental assessment of sulphur species. AB - Often perceived as a Cinderella material, there is growing appreciation for solid waste as a renewable content thermal process feed. Nonetheless, research on solid waste gasification and sulphur mechanisms in particular is lacking. This paper presents results from two related experiments on a novel two stage gasification process, at demonstration scale, using a sulphur-enriched wood pellet feed. Notable SO2 and relatively low COS levels (before gas cleaning) were interesting features of the trials, and not normally expected under reducing gasification conditions. Analysis suggests that localised oxygen rich regions within the fluid bed played a role in SO2's generation. The response of COS to sulphur in the feed was quite prompt, whereas SO2 was more delayed. It is proposed that the bed material sequestered sulphur from the feed, later aiding SO2 generation. The more reducing gas phase regions above the bed would have facilitated COS--hence its faster response. These results provide a useful insight, with further analysis on a suite of performed experiments underway, along with thermodynamic modelling. PMID- 24176240 TI - Eco-efficiency assessment of options for metal recovery from incineration residues: a conceptual framework. AB - Residues from municipal solid waste (MSW) incineration in Switzerland have been a hot topic in recent years, both in the research and practice communities. Regarded by many as an economically and environmentally sound solution to this issue, technological retrofitting of existing grate incinerators has the dual purpose of enhancing the metal recovery of bottom and fly ashes and improving the inertization of residues to be landfilled. How does context influence the economic and environmental performance of this particular technological option? Under which conditions would this technological option be implemented nationwide in the future? What are stakeholders' views on sustainable transitions of MSW incineration? We propose a three-stage methodological procedure to address these questions. PMID- 24176241 TI - Evaluation of multi-segmental kinematic modelling in the paediatric foot using three concurrent foot models. AB - BACKGROUND: Various foot models are used in the analysis of foot motion during gait and selection of the appropriate model can be difficult. The clinical utility of a model is dependent on the repeatability of the data as well as an understanding of the expected error in the process of data collection. Kinematic assessment of the paediatric foot is challenging and little is reported about multi-segment foot models in this population. The aim of this study was to examine three foot models and establish their concurrent test-retest repeatability in evaluation of paediatric foot motion during gait. METHODS: 3DFoot, Kinfoot and the Oxford Foot Model (OFM) were applied concurrently to the right foot and lower limb of 14 children on two testing sessions. Angular data for foot segments were extracted at gait cycle events and peaks and compared between sessions by intraclass correlation coefficient (ICC) with 95% confidence intervals (95%CI) and standard error of measurement (SEM). RESULTS: All foot models demonstrated moderate repeatability: OFM (ICC 0.55, 95% CI 0.16 to 0.77), 3DFoot (ICC 0.47, 95% CI 0.15 to 0.64) and Kinfoot (ICC 0.43, 95% CI -0.03 to 0.59). On the basis of a cut-off of 5 degrees , acceptable mean error over repeated sessions was observed for OFM (SEM 4.61 degrees +/- 2.86 degrees ) and 3DFoot (SEM 3.88 degrees +/- 2.18 degrees ) but not for Kinfoot (SEM 5.08 degrees +/- 1.53 degrees ). Reliability of segmental kinematics varied, with low repeatability (ICC < 0.4) found for 14.3% of OFM angles, 22.7% of 3DFoot angles and 37.6% of Kinfoot angles. SEM greater than 5 degrees was found in 26.2% of OFM, 15.2% of 3DFoot, and 43.8% of Kinfoot segmental angles. CONCLUSION: Findings from this work have demonstrated that segmental foot kinematics are repeatable in the paediatric foot but the level of repeatability and error varies across the segments of the different models. Information on repeatability and test-retest errors of three-dimensional foot models can better inform clinical assessment and advance understanding of foot motion during gait. PMID- 24176242 TI - Relative contribution of cognitive and physical disability components to quality of life in MS. AB - BACKGROUND: Information on the relative influence of cognitive and physical impairment on the quality of life in multiple sclerosis is currently limited and no scientific consensus has been reached yet. OBJECTIVE: For this reason, we wanted to examine the relative contribution of cognitive and physical impairment measures comprised in the MSFC test on quality of life in MS. METHODS: In the National MS Center Melsbroek, patients regularly undergo MSFC and EQ5D measurements. We investigated the correlations between the EQ5D, EQVAS and the MSFC and EDSS scores by the use of ANOVA and multilinear models. RESULTS: We found a significant correlation between the EQVAS score and cognition in a univariate model. When including EDSS score and MSFC outcomes into the model, cognition was, however, excluded based on the Akaike Information Criterion. Cognition was, on the other hand, a significant predictor for the "Usual Activities" question of the EQ5D. CONCLUSIONS: Although cognitive performance as measured on the PASAT-3s does not correlate with a patient's perceived quality of life in a multivariate model, it remains an important predictor for the patient's usual activities. PMID- 24176243 TI - Physical activity energy expenditure is associated with 2-h insulin independently of obesity among Inuit in Greenland. AB - AIMS: Indigenous populations throughout the Arctic are experiencing a rapid increase in the prevalence of obesity and type 2 diabetes. The role of physical activity in relation to glucose metabolism in Arctic populations is not well studied. We examined the association between objectively measured physical activity energy expenditure (PAEE) and glucose metabolism in a population-based study of adult Inuit in Greenland. METHODS: Cross-sectional data were collected by combined accelerometry and heart rate monitoring (ACC+HR) among Inuit (18+ years) in Greenland during 2005-2010 (n=1545). PAEE was calculated and the associations with fasting glucose, 2-h glucose, fasting insulin, 2-h insulin concentrations and body composition were analysed by linear regression. RESULTS: An inverse association between PAEE and fasting insulin, 2-h insulin, 2-h glucose, fat percentage, BMI and waist circumference (WC) was found after adjustments by age and sex. Only the association between PAEE and 2-h insulin remained significant after adjustment by WC (P=0.01), most pronounced at low levels of PAEE indicating a threshold around 35-40kJ/kg/day. No overall linear trend was found for fasting glucose and 2-h glucose. CONCLUSIONS: This population based study showed that PAEE was associated with 2-h insulin independently of obesity in an inverse dose-response relation. Insufficient physical activity may contribute to impaired glucose tolerance through a pathway including alterations in obesity and fat distribution. Both obesity and low levels of PAEE may be important contributing risk factors for the increasing prevalence of type 2 diabetes mellitus among Inuit in Greenland, but additional risk factors should be examined in this indigenous population. PMID- 24176244 TI - Hemoglobin A1C in non-diabetic patients: an independent predictor of coronary artery disease and its severity. AB - AIMS: To determine the association between glycated hemoglobin (HbA1c) and angiographically proven coronary artery disease (CAD) and its severity in nondiabetic individuals. METHODS: We enrolled 299 consecutive individuals undergoing coronary angiography for suspected ischemia. Patients were included if they had no history of prior revascularization or diabetes mellitus and had fasting blood glucose<126mg/dl (7.0mmol/l) and HbA1c<6.5% (47mmol/mol). The severity of the CAD was also evaluated using the Gensini score. Serum HbA1c (NGSP certified Method), highly sensitive C-reactive protein (hsCRP), lipid profile, insulin and APO lipoprotein A1 and B100 levels were measured. RESULTS: Mean age was 58.8+/-10.4 year; 60.9% men. One hundred forty seven patients had significant CAD (>=50% stenosis in any major vessel). With increasing HbA1c levels, there was a significant increase in the prevalence of CAD and number of vessels involved. In multivariate analysis, HbA1c emerged as an independent predictor of significant CAD (OR: 2.8, 95% CI: 1.3-6.2, p=0.009). Adjusted ORs for the occurrence of CAD were highest in subjects with both hsCRP and HbA1c in the upper 2 quartiles (OR: 4.183; 95% CI: 1.883-9.290, p<0.0001). There was a significant association between Gensini score and increasing HbA1c tertiles (p=0.038). The ideal cut-off value of HbA1c for prediction of the occurrence of CAD was 5.6% 38mmol/mol) (sensitivity: 60.5%, specificity: 52%). CONCLUSIONS: In non-diabetic subjects, HbA1c could be utilized for risk stratification of CAD and its severity, independent of traditional cardiovascular risk factors, insulin resistance and inflammatory markers. PMID- 24176245 TI - Reply to comments on 'conservative management of diabetic foot osteomyelitis' by Aragon-Sanchez. PMID- 24176246 TI - Effects of bacterial melanin on motor recovery and regeneration after unilateral destruction of Substantia Nigra pars compacta in rats. AB - We examined the potential neuroprotective action of bacterial melanin (BM) in rats after unilateral destruction of Substantia Nigra pars compacta (SNc) dopaminergic neurons. 24 rats were initially trained to an instrumental conditioned reflex (ICR) and then subjected to unilateral electrolytic destruction of SNc. Unilateral deficit in balancing hindlimb movements was observed in all rats after the destruction. On the next day after the destruction part of the animals (n=12) was intramuscularly injected with BM solution at the concentration 6 mg/ml (0.17 g/kg). The other 12 operated rats served as a control group. On the second day after the operation the testing of instrumental conditioned reflex was resumed in both groups. Comparison of recovery periods for the ICR in both groups showed that recovery of the reflex and balancing hindlimb movements in melanin treated rats took place in three postoperative testing days, whereas in control group the recovery was not complete after 23 testing days. Electrophysiological study was conducted in 12 intact rats to show the effects of BM on the activity of SNc neurons. The firing rate of neurons was significantly increased by the BM injection. Morpho-histochemical study of brain sections was conducted after the completion of behavioral experiments. In melanin injected rats the study revealed absence of destruction or electrode trace in Substantia Nigra pars compacta of melanin injected rats. BM stimulates regeneration and microcirculation in SNc. Increased electrical activity of SN neurons and regenerative efforts induced by BM accelerate motor recovery after unilateral SNc destruction. PMID- 24176247 TI - Local cortical thinning links to resting-state disconnectivity in major depressive disorder. AB - BACKGROUND: Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-modal imaging approach, we investigated the relationship between local cortical tissue abnormalities and intrinsic resting-state functional connectivity (RSFC) in MDD. METHOD: A total of 20 MDD in-patients and 20 healthy controls underwent magnetic resonance imaging at 3 T for structural and functional imaging. Whole-brain cortical thickness was calculated and compared between groups. Regions with reduced cortical thickness defined seeds for subsequent whole-brain RSFC analyses. Contributions of structural tissue abnormalities on inter-regional RSFC were explicitly investigated. RESULTS: Lower cortical thickness was observed in MDD in the right dorsomedial prefrontal cortex (PFC), superior temporal gyrus/temporal pole, middle-posterior cingulate cortex, and dorsolateral PFC. No differences in local fractional amplitude of low-frequency fluctuations were observed. Lower thickness in patients' dorsomedial PFC further directly and selectively affected its RSFC with the precuneus, which was unaffected by symptom severity. No effects of cortical thickness in other regions showing abnormal thickness were observed to influence functional connectivity. CONCLUSIONS: Abnormal cortical thickness in the dorsomedial PFC in MDD patients was observed to selectively and directly affect its intrinsic connectivity with the precuneus in MDD patients independent of depression severity, thereby marking a potential vulnerability for maladaptive mood regulation. Future studies should include an unmedicated sample and replicate findings using independent component analysis to test for morphometric effects on network integrity. PMID- 24176248 TI - Identification of forged Bank of England L20 banknotes using IR spectroscopy. AB - Bank of England notes of L20 denomination have been studied using infrared spectroscopy in order to generate a method to identify forged notes. An aim of this work was to develop a non-destructive method so that a small, compact Fourier transform infrared spectrometer (FT-IR) instrument could be used by bank workers, police departments or others such as shop assistants to identify forged notes in a non-lab setting. The ease of use of the instrument is the key to this method, as well as the relatively low cost. The presence of a peak at 1400 cm(-1) arising from nuasym (CO3(2-)) from the blank paper section of a forged note proved to be a successful indicator of the note's illegality for the notes that we studied. Moreover, differences between the spectra of forged and genuine L20 notes were observed in the nu(OH) (ca. 3500 cm(-1)), nu(C-H) (ca. 2900 cm(-1)) and nu(C=O) (ca. 1750 cm(-1)) regions of the IR spectrum recorded for the polymer film covering the holographic strip. In cases where these simple tests fail, we have shown how an infrared microscope can be used to further differentiate genuine and forged banknotes by producing infrared maps of selected areas of the note contrasting inks with background paper. PMID- 24176249 TI - [Calcium transport in the kidney]. PMID- 24176250 TI - Scope of family planning services available in Federally Qualified Health Centers. AB - OBJECTIVES: Federally Qualified Health Centers (FQHCs) are a major and growing source of primary care for low-income women of reproductive age; however, only limited knowledge exists on the scope of family planning care they provide and the mechanisms for delivery of these essential reproductive health services, including family planning. In this paper, we report on the scope of services provided at FQHCs including on-site provision, prescription only and referral options for the range of contraceptive methods. STUDY DESIGN: An original survey of 423 FQHC organizations was fielded in 2011. RESULTS: Virtually all FQHCs reported that they provide at least one contraceptive method (99.8%) at one or more clinical sites. A large majority (87%) of FQHCs report that their largest primary care site prescribes oral contraceptives plus one additional method category of contraception, with oral contraception and injectables being the most commonly available methods. Substantial variation is seen among other methods such as intrauterine devices (IUDs), contraceptive implants, the patch, vaginal ring and barrier methods. For all method categories, Title-X-funded sites are more likely to provide the method, though, even in these sites, IUDs and implants are much less likely to be provided than other methods. CONCLUSION: There is clearly wide variability in the delivery of family planning services at FQHCs in terms of methods available, level of counseling, and provision of services on site or through prescription or referral. Barriers to provision likely include cost to patients and/or additional training to providers for some methods, such as IUDs and implants, but these barriers should not limit on-site availability of inexpensive methods such as oral contraceptives. IMPLICATIONS: With the expansion of contraceptive coverage under private insurance as part of preventive health services for women, along with expanded coverage for the currently uninsured, and the growth of FQHCs as the source of care for women of reproductive age, it is critical that women seeking family planning services at FQHCs have access to a wide range of contraceptive options. Our study both highlights the essential role of FQHCs in providing family planning services and also identifies remaining gaps in the provision of contraception in FQHC settings. PMID- 24176251 TI - Immediate versus delayed initiation of the contraceptive patch after abortion: a randomized trial. AB - BACKGROUND: Immediate start of the contraceptive patch has not been studied in women after surgical abortion. STUDY DESIGN: Women presenting for surgical abortion who had chosen the transdermal patch for contraception were randomized to either delayed start of the patch (beginning the Sunday after their abortion) or immediate start (directly observed application of the patch in the clinic). Subjects were contacted at 2 and 6 months to assess contraceptive use. RESULTS: Two hundred ninety-eight women were randomized, and the follow-up rate was 71% at 2 months and 53% at 6 months. Method continuation did not differ by timing of initiation. At 2 months, 71% in the delayed-start group and 74% in the immediate start group were using the patch [p=.6, with a difference of 3.1%, 95% confidence interval (CI)=-17.2% to +11.2%]. At 6 months, 55% in the delayed-start group and 43% in the immediate-start group were using the patch (p=.13, with a difference of 11.9%, 95% CI=-19.2% to +34%). CONCLUSION: Immediate initiation of the contraceptive patch after surgical abortion was not associated with increased use of patch at 2 or 6 months. PMID- 24176254 TI - Survey of infectious agents in the endangered Darwin's fox (Lycalopex fulvipes): high prevalence and diversity of hemotrophic mycoplasmas. AB - Very little is known about the diseases affecting the Darwin's fox (Lycalopex fulvipes), which is considered to be one of the most endangered carnivores worldwide. Blood samples of 30 foxes captured on Chiloe Island (Chile) were tested with a battery of PCR assays targeting the following pathogens: Ehrlichia/Anaplasma sp., Rickettsia sp., Bartonella sp., Coxiella burnetti, Borrelia sp., Mycoplasma sp., Babesia sp., Hepatozoon canis, Hepatozoon felis, Leishmania donovani complex, and Filariae. Analysis of the 16S rRNA gene revealed the presence of Mycoplasma spp. in 17 samples (56.7%, 95% Confidence Intervals= 38.2-73.7). Of these, 15 infections were caused by a Mycoplasma belonging to the M. haemofelis/haemocanis (Mhf/Mhc) group, whereas two were caused by a Mycoplasma showing between 89% and 94% identity with different Candidatus Mycoplasma turicensis from felids and rodents hemoplasmas. The analysis of the sequence of the RNA subunit of the RNase P gene of 10 of the foxes positive for Mhf/Mhc showed that eight were infected with M. haemocanis (Mhc), one with a Mycoplasma showing 94% identity with Mhc, and one by M. haemofelis (Mhf). One of the foxes positive for Mhc was infected with a Ricketssia closely related to R. felis. All foxes were negative for the other studied pathogens. Our results are of interest because of the unexpectedly high prevalence of Mycoplasma spp. detected, the variability of species identified, the presence of a potentially new species of hemoplasma, and the first time a hemoplasma considered to be a feline pathogen (Mhf) has been identified in a canid. Though external symptoms were not observed in any of the infected foxes, further clinical and epidemiological studies are necessary to determine the importance of hemoplasma infection in this unique species. PMID- 24176253 TI - Vancouver At Home: pragmatic randomized trials investigating Housing First for homeless and mentally ill adults. AB - BACKGROUND: Individuals with mental illnesses are overrepresented among the homeless. Housing First (HF) has been shown to promote positive outcomes in this population. However, key questions remain unresolved, including: how to match support services to client needs, the benefits of housing in scattered sites versus single congregate building, and the effectiveness of HF with individuals actively using substances. The present study aimed to recruit two samples of homeless mentally ill participants who differed in the complexity of their needs. Study details, including recruitment, randomization, and follow-up, are presented. METHODS: Eligibility was based on homeless status and current mental disorder. Participants were classified as either moderate needs (MN) or high needs (HN). Those with MN were randomized to HF with Intensive Case Management (HF-ICM) or usual care. Those with HN were randomized to HF with Assertive Community Treatment (HF-ACT), congregate housing with support, or usual care. Participants were interviewed every 3 months for 2 years. Separate consent was sought to access administrative data. RESULTS: Participants met eligibility for either MN (n = 200) or HN (n = 297) and were randomized accordingly. Both samples were primarily male and white. Compared to participants designated MN, HN participants had higher rates of hospitalization for psychiatric reasons prior to randomization, were younger at the time of recruitment, younger when first homeless, more likely to meet criteria for substance dependence, and less likely to have completed high school. Across all study arms, between 92% and 100% of participants were followed over 24 months post-randomization. Minimal significant differences were found between study arms following randomization. 438 participants (88%) provided consent to access administrative data. CONCLUSION: The study successfully recruited participants meeting criteria for homelessness and current mental disorder. Both MN and HN groups had high rates of substance dependence, suicidality, and physical illness. Randomization resulted in no meaningful detectable differences between study arms. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN57595077 (Vancouver at Home study: Housing First plus Assertive Community Treatment versus congregate housing plus supports versus treatment as usual) and ISRCTN66721740 (Vancouver At Home study: Housing First plus Intensive Case Management versus treatment as usual). PMID- 24176255 TI - The impact of visual impairments in self-esteem and locus of control. AB - This study investigates the differences between adults with visual impairments and sighted adults with regard to locus of control (LOC) and self-esteem. One hundred and eight adults with visual impairments (blindness or low vision) and fifty-five sighted adults took part in this study. Sighted adults showed a higher score on the self-esteem scale than either the individuals with low vision or with blindness. Moreover, analysis indicated no significant differences amongst the three groups of participants regarding LOC. Significant predictors of self esteem were vision status and age at loss of sight. Significant predictors of LOC were vision status and independent movement. Findings are discussed with regard to their implications for parents, social workers, teachers, and rehabilitation specialists. PMID- 24176256 TI - Visual profile of children with handwriting difficulties in Hong Kong Chinese. AB - The purpose of this study was to find out the visual profiles of children with handwriting difficulties (HWD) in Hong Kong Chinese. Forty-nine children with HWD (mean age 8.4 +/- 1.1 years) and 27 controls (mean age 7.7 +/- 0.7 years) were recruited. All subjects received eye examination and vision assessment included ocular health, refraction, accommodative functions, binocularity, visual perception (by Gardner reversal frequency test: recognition subtest; Test of visual perceptual skills (non-motor)-revised) and motor skills (by The Beery Buktenica developmental test of visual motor integration; Detroit test of motor speed and precision). Higher percentages of tropia and phoria (of magnitude >6 prism dioptres) were found in children with HWD of 6.1% and 14.3% respectively. After adjusted for the effect of age, children with HWD showed significantly worse accommodative facility, directionality, visual discrimination, visual spatial relation, visual form constancy, visual sequential memory, visual figure ground, visual closure and visual motor integration. Studies reported the visual functions of children with HWD were mostly concerned with alphabetic languages, while studies concerning Chinese HWD were relatively less. This study provided the visual profiles of children with Chinese HWD. Based on the visual profile, further study is indicated to investigate the effect of optometric interventions on the assessment and remediation for children with HWD. PMID- 24176257 TI - Instability of delay classification and determination of early intervention eligibility in the first two years of life. AB - The purpose of this study was to determine the effectiveness of the Bayley Scales of Infant Development, Third Edition (Bayley-III) to track development and classify delays in low- and high-risk infants across the first two years of life. We assessed cognitive, language, and motor development in 24 low-risk full-term and 30 high-risk preterm infants via seven assessments performed between 3 and 24 months corrected age. The Bayley-III resulted in highly unstable delay classifications, low sensitivities, and poor positive predictive values across time. The results highlight that early intervention professionals, researchers, and policy makers should: (1) emphasize clinical opinion and prevalence of risk factors rather than standardized assessment findings when classifying delays and determining eligibility for services, and (2) develop more effective developmental assessments for infants and young children. PMID- 24176258 TI - Overweight in intellectually-disabled population: physical, behavioral and psychological characteristics. AB - Intellectually disabled (ID) people are at high risk of overweight and obesity. Prevalence and risk factors were assessed in a French population of ID adults attending specialized institutions, using a questionnaire focusing on demographic characteristics, physical activities, food habits and self-awareness about body and health. Data analysis included descriptive statistics, univariate and multivariate regression. Overall, 570 participants were included in the analysis (59% male), aged 19-59 years. The mean body mass index (BMI) was 24.9 kg/m(2); 45.6% of participants were overweight (BMI >= 25), including 17.2% who were obese (BMI >= 30). Participants practiced sports for 5.7h/week on average and were sedentary for 21.8h/week (time spent in front of some kind of screen). Most participants had food and self-care habits usually regarded as healthy. Eighty percent of them felt unhappy with their body and their physical capacities, but otherwise expressed a rather good opinion of themselves. Bivariate and multivariate analyses showed that some behavioral habits were associated with a reduced incidence of overweight and/or obesity, such as regular sport practice outside the institution, good personal body care or alcohol avoidance. The strongest risk factor was gender. Women were much more at risk than men of being overweight (53.9% versus 39.9%) and obese (28.2% versus 9.5%). Results suggest numerous ways to improve the health of institutionalized ID adults, related to sports education, nutrition and self-care, with particular attention paid to women. PMID- 24176259 TI - ASSERT--the Autism Symptom SElf-ReporT for adolescents and adults: bifactor analysis and validation in a large adolescent population. AB - With a view to developing a brief screening instrument for autism symptoms in a general population of adolescents, seven items from the Asperger syndrome (and high-functioning autism) diagnostic interview were adapted for use as self-report in an online questionnaire for youths aged 16-19 years (N=10,220). The selected items target lack of social understanding (4 items) and rigid and repetitive behavior and interests (RRBI; 3 items). Factor analyses were performed, and the seven items were also validated against self-reported ASD diagnosis. Best statistical model fit was found for a bifactor model with one general factor and two domain specific factors tied to social difficulties and RRBI. Both the general and the domain specific factors were associated with self-reported ASD diagnoses. The scale (referred to as the Autism Symptom SElf-ReporT for Adolescents and Adults--ASSERT) had good screening properties with a receiver operating curve-area under the curve (ROC-AUC) of 0.87 and a diagnostic odds ratio (DOR) of 15.8. Applying a modified scoring of the scale further improved the screening properties leading to a ROC-AUC of 0.89 and a DOR of 24.9. The ASSERT holds promise as a brief self-report screen for autism symptoms in adolescents, and further studies should explore its usefulness for adults. PMID- 24176260 TI - Gait profiles as indicators of domain-specific impairments in executive control across neurodevelopmental disorders. AB - In neurodevelopmental disorders, unique profiles of executive control and attention appear to co-occur with poor motor coordination. However, less is known about how syndrome-specific cognitive profiles interact with motor control and impact behavioural outcomes in neurodevelopmental disorders such as Williams syndrome (WS) and Down syndrome (DS). Here we aimed to examine the extent to which specific components of executive function interact with gait control when performing cognitive dual-tasks (verbal fluency, digit span) in WS and DS. Spatiotemporal gait characteristics and intra-individual variability of gait were assessed in individuals with WS who were matched on spatial ability to individuals with DS, and chronologically age (CA) matched controls. During the concurrent verbal fluency task, the WS group had greater dual-task costs on spatiotemporal gait parameters and variability than CA controls. Conversely, individuals with DS had selective gait interference during the concurrent digit span task when compared to CA controls, but only under increased demands on cognitive control where there was greater variability in step timing in DS. The interrelationships between cognitive-motor interference and behavioural measures of executive functioning appeared to differentiate between WS and DS, and emphasise the importance of task modality in unpacking the executive control profile in these neurodevelopmental disorders. These findings support the notion that associated cerebellar-cortico abnormalities may produce quite distinct profiles of executive control across cognitive and motor domains that impact on behavioural outcomes in neurodevelopmental disorders. PMID- 24176261 TI - Participation in leisure activities: differences between children with and without physical disabilities. AB - The aim of the current study was to compare varied dimensions of participation in leisure activities among school-aged children ages 10-16 with and without disabilities. The Children Leisure Activity Scale (CLASS) was administrated to 294 children, 81 with and 213 without physical disability. Two-way MANCOVA revealed significant differences between the frequency of participation in leisure activities of the study groups: an effect of disability F(4,265=239.57; p<0.001, eta(2)=0.78); an effect of gender F(4,265=3.35; p<0.01, eta(2)=0.05); and an interaction effect between gender and disability F(4,265=5.23; p<0.001, eta(2)=0.64). Children with disabilities, and mostly girls, were found at risk to participate in a narrower variety of activities that involved fewer social interactions. Using linear regressions for each group two different models were identified. Using the CLASS the study contributes evidence-based data regarding children at risk for leisure participation. In addition, the research further established the discriminate validity of the CLASS. PMID- 24176262 TI - Does relative body fat influence the Movement ABC-2 assessment in children with and without developmental coordination disorder? AB - Developmental coordination disorder (DCD) is a condition that results in an impairment of gross and/or fine motor coordination. Compromised motor coordination contributes to lower levels of physical activity, which is associated with elevated body fat. The impact of elevated body fat on motor coordination diagnostic assessments in children with DCD has not been established. The purpose of this study was to determine if relative body fat influences performance on the Movement Assessment Battery for Children, 2nd Edition (MABC-2) test items in children with and without DCD. A nested case control, design was conducted within the Physical Health Activity Study Team longitudinal cohort study. The MABC-2 was used to assess motor coordination to categorize cases and matched controls. Relative body fat was assessed using whole body air displacement plethysmography. Relative body fat was negatively associated with the MABC-2 "balance" subcategory after adjusting for physical activity and DCD status. Relative body fat did not influence the subcategories of "manual dexterity" or "aiming and catching". Item analysis of the three balance tasks indicated that relative body fat significantly influences both "2-board balance" and "zig-zag hopping", but not "walking heel-toe backwards". Children with higher levels of relative body fat do not perform as well on the MABC-2, regardless of whether the have DCD or not. Dynamic balance test items are most negatively influenced by body fat. Health practitioners and researchers should be aware that body fat can influence results when interpreting MABC-2 test scores. PMID- 24176263 TI - Prostate cancer testing: a snapshot of the attitudes and practice of Australian general practitioners. AB - The role of the General Practitioner (GP) in testing for and managing men with prostate cancer (PCa) is significant. Very few studies have explored the attitudes and practices of Australian GPs in the context of the role of PCa testing. In this study, a 46-item web-based questionnaire was used to assess self reported PCa testing attitudes and practices of GPs. This questionnaire was circulated to divisions of general practice and Medicare locals for further distribution to their GP members across Australia. GPs from all states and territories participated, and a total of 136 GPs completed the survey. Of the responding GPs, 57% always or usually offered PCa testing to asymptomatic men <= 70 years of age and 60% of GPs always or usually included a digital rectal examination (DRE). Many (80%) of the GPs stated that the current PCa testing guidelines were not clear. PCa testing was offered opportunistically by 56% while 39% offered testing at the patient's request. The results captured in this study represent a snapshot of GP attitudes and practices from across Australia. The results presented indicate a wide variation in the approaches to PCa testing in general practice across Australia, which in most part appear to be related to the lack of clarity of the current prostate cancer testing guidelines. PMID- 24176264 TI - Calcanectomy: avoiding major amputation in the presence of calcaneal osteomyelitis-A case series. AB - BACKGROUND: Calcaneal osteomyelitis is a surgical diagnosis that may be treated by local, resection or major amputation. OBJECTIVE: To determine the effectiveness of calcanectomy for treating calcaneal osteomyelitis. METHOD: We conducted a retrospective review of patients receiving calcanectomy between 1st April 2005 and 1st October 2011 for calcaneal osteomyelitis. We reviewed these cases to determine healing, rate, microbiological analysis, length of stay, limb salvage rate and survival rate. RESULTS: There were 10 patients included in this review. There were 7 with diabetes and 3 without. Mean age of group with diabetes was 64 years, of this group 5/7 healed at a mean of 64 days. Mean length of stay for this group was 49.3 +/- 39.4 days. 2 patients required a transtibial amputation. Mean age of group without diabetes was 77 years, healing at a mean of 19 days. Mean length of stay for this group was 14 +/- 16.8 days and all survived over 3 years. Microbiological analysis of suspected osteomyelitic bone typically isolated >4 organisms. CONCLUSIONS: Calcanectomy is a useful procedure for limb salvage. It may reduce morbidity rates for people with calcaneal osteomyelitis, those with diabetes can expect prolonged wound healing and longer length of stay. PMID- 24176266 TI - Predicting early left ventricular dysfunction after mitral valve reconstruction: the effect of atrial fibrillation and pulmonary hypertension. AB - OBJECTIVE: The preoperative ejection fraction (EF) and left ventricular (LV) end systolic dimension are known predictors of postoperative LV dysfunction after mitral valve repair. We investigated the effect of a preoperative history of atrial fibrillation and moderate pulmonary hypertension (defined as pulmonary artery systolic pressure >50 mm Hg) on early postoperative LV dysfunction. METHODS: From 2003 to 2010, 632 patients who had undergone successful mitral valve repair surgery for degenerative disease were included in the present study. The preoperative and postoperative echocardiographic data and postoperative outcomes were collected retrospectively. We analyzed the demographic, hemodynamic, and echocardiographic parameters to assess the predictors of early postoperative LV dysfunction, defined as an LVEF <50%. RESULTS: The mean age of the cohort was 57 +/- 13 years. All patients had less than mild mitral regurgitation on postoperative echocardiography. After mitral valve repair, a significant decrease in the LVEF (60% +/- 8% to 54% +/- 9%), LV end-systolic diameter (36 +/- 7 mm to 33 +/- 7 mm), and LV end-diastolic dimension (56 +/- 8 mm to 48 +/- 7 mm) was observed at early postoperative echocardiography (P < .001). On multivariate regression analysis, preoperative atrial fibrillation, pulmonary hypertension, and LV end-systolic dimension were independent predictors of the postoperative LVEF (P = .035 and P < .001, respectively). Preoperative atrial fibrillation (odds ratio, 1.97; 95% confidence interval, 1.28-3.02; P = .002) and pulmonary artery systolic pressure >50 mm Hg (odds ratio, 1.82; 95% confidence interval, 1.11-2.97; P = .017) increased the risk of postoperative LV dysfunction by almost twofold. CONCLUSIONS: In addition to the established predictors of postoperative LV dysfunction, the presence of preoperative pulmonary hypertension and a history of atrial fibrillation in patients undergoing mitral valve repair surgery increased the risk of early postoperative LV dysfunction by almost twofold. PMID- 24176267 TI - Implantable physiologic controller for left ventricular assist devices with telemetry capability. AB - OBJECTIVE: Rotary type left ventricular assist devices have mitigated the problem of durability associated with earlier pulsatile pumps and demonstrated improved survival. However, the compromise is the loss of pulsatility due to continuous flow and retained percutaneous driveline leading to increased mortality and morbidity. Lack of pulsatility is implicated in increased gastrointestinal bleeding, aortic incompetence, and diastolic hypertension. We present a novel, wirelessly powered, ultra-compact, implantable physiologic controller capable of running a left ventricular assist device in a pulsatile mode with wireless power delivery. METHODS: The schematic of our system was laid out on a circuit board to wirelessly receive power and run a left ventricular assist device with required safety and backup measures. We have embedded an antenna and wireless network for telemetry. Multiple signal processing steps and controlling algorithm were incorporated. The controller was tested in in vitro and in vivo experiments. RESULTS: The controller drove left ventricular assist devices continuously for 2 weeks in an in vitro setup and in vivo without any failure. Our controller is more power efficient than the current Food and Drug Administration-approved left ventricular assist device controllers. When used with electrocardiography synchronization, the controller allowed on-demand customization of operation with instantaneous flow and revolutions per minute changes, resulting in a pulsatile flow with adjustable pulse pressure. CONCLUSIONS: Our test results prove the system to be remarkably safe, accurate, and efficient. The unique combination of wireless powering and small footprint makes this system an ideal totally implantable physiologic left ventricular assist device system. PMID- 24176268 TI - Three-dimensional valve repair-the better care? Midterm results of a saddle shaped, rigid annuloplasty ring in patients with ischemic mitral regurgitation. AB - OBJECTIVES: Undersized ring annuloplasty is the treatment of choice for functional mitral regurgitation. However, recurrence of mitral regurgitation within the first years is frequent. The aim of this study was to analyze the functional and clinical outcome after mitral valve repair with the 3-dimensional saddle-shaped Edwards GeoForm (Edwards Lifesciences LLC, Irvine, Calif) annuloplasty ring in patients with ischemic mitral regurgitation. METHODS: Between November 2006 and November 2012, 70 patients (mean age, 68 +/- 10 years; mean left ventricular ejection fraction, 40% +/- 15%) with functional mitral regurgitation due to ischemic cardiomyopathy underwent mitral valve repair with the Edwards GeoForm annuloplasty ring. Concomitant procedures, such as coronary artery bypass grafting (75.7%), tricuspid valve repair (25.7%), aortic valve replacement (8.6%), and the Maze procedure (4.3%), were performed in 92.9% of patients. Follow-up is 97% complete (mean, 3.0 +/- 1.7 years). Transthoracic echocardiography was obtained 2.4 +/- 1.7 years postoperatively. RESULTS: Thirty day mortality was 5.9%. Overall survival at 5 years was 71.3% +/- 6.9%. At 4 years, overall freedom from recurrence of mitral regurgitation grade 3+ or greater was 92.5% +/- 3.6%, and freedom from recurrence of mitral regurgitation grade 2+ or greater was 71.0% +/- 8.7%. Three patients required a mitral valve related reoperation for ring dehiscence. New York Heart Association functional class improved from 3.6 +/- 0.6 to 1.6 +/- 0.6 during follow-up (P < .05). Mean mitral valve pressure gradient was 3.3 +/- 1.8 mm Hg across all ring sizes at the time of follow-up. CONCLUSIONS: Mitral valve repair with the 3-dimensional saddle shaped Edwards GeoForm annuloplasty ring in case of ischemic mitral regurgitation shows a low rate of recurrent regurgitation at 4 years. Clinically relevant mitral stenosis was not detected. The importance of secure anchoring of the device in the mitral annulus has to be emphasized to prevent ring dehiscence. PMID- 24176269 TI - Discussion. PMID- 24176270 TI - Preoperative percutaneous coronary intervention in patients undergoing open thoracoabdominal and descending thoracic aneurysm repair. AB - OBJECTIVE: Current guidelines have recommended against coronary revascularization before noncardiac surgery in patients with asymptomatic coronary artery disease. However, myocardial infarction after thoracic aneurysm (TA) repair dramatically increases the morbidity and mortality. Revascularization with coronary artery bypass grafting before TA repair minimizes the incidence of perioperative ischemia. However, the recovery can be prolonged, and a percentage of patients will either never return for aneurysm repair or will develop a rupture during convalescence. Percutaneous coronary intervention (PCI) before TA repair might be preferable. Previous studies examining PCI before major vascular surgery included few patients with TAs. We examined the outcomes of patients undergoing PCI before TA repair. METHODS: From 1997 to 2012, 592 patients underwent TA repair. Patients presenting for elective repair underwent cardiac catheterization before surgery. Those with significant single- or double-vessel coronary artery disease underwent PCI. The perioperative outcomes were examined and compared with those of patients undergoing TA repair without revascularization. RESULTS: A total of 44 patients (7.4%) underwent PCI with bare metal stents before surgery. No PCI-related complications occurred. Dual antiplatelet therapy was administered for 4 to 6 weeks. No instances of aneurysm rupture occurred in the interval between PCI and surgery. The incidence of stent thrombosis, myocardial infarction, and mortality for those undergoing PCI was 0. No bleeding complications occurred. CONCLUSIONS: PCI is safe and efficacious in patients undergoing TA repair. Aneurysm rupture did not occur in the interval before surgery. Antiplatelet therapy did not increase the risk of bleeding complications. Stent thrombosis was not seen. We recommend PCI those with significant single- or double-vessel coronary artery disease before elective TA repair. PMID- 24176271 TI - An alternative technique for surgical repair of pulmonary dissection. PMID- 24176272 TI - Acute inferior wall myocardial infarction secondary to ruptured sinus of Valsalva aneurysm in a 22-year-old man. PMID- 24176273 TI - Sequela-free long-term survival of a 65-year-old woman after 8 hours and 40 minutes of cardiac arrest from deep accidental hypothermia. PMID- 24176274 TI - One-year follow-up period after transumbilical thoracic sympathectomy for hyperhidrosis: outcomes and consequences. AB - OBJECTIVES: Thoracic sympathectomy is considered the most effective method to treat palmar hyperhidrosis. We developed a novel approach for thoracic sympathectomy in patients with palmar hyperhidrosis through the umbilicus, using an ultrathin gastroscope. The aim of this study was to evaluate the continuing efficacy and patient satisfaction of this innovative surgery. METHODS: All procedures were performed under general anesthesia and the patients were intubated with a dual-lumen endotracheal tube. After a 5-mm umbilical incision, the muscular parts of the diaphragmatic dome were incised with a needle-knife and the nasal gastroscope was advanced into the thoracic cavity. The sympathetic chain was identified at the desired thoracic level and ablated with hot biopsy forceps. All patients were followed up for at least 1 year after the procedure through clinic visits or telephone/e-mail interviews. RESULTS: From April 2010 to August 2011, a total of 35 patients underwent a transumbilical thoracic sympathectomy. Fifty-seven percent were male patients, with a mean age of 21.2 years (range, 16-33 years). The success rate after 12 months was 97.1% (34 of 35) for isolated palmar hyperhidrosis and 72.2% (13 of 18) for axillary hyperhidrosis. Compensatory sweating was reported in 28.6% of patients at the 1 year follow-up evaluation. There was no mortality, no diaphragmatic hernia, and no Horner syndrome was observed. Quality of life related to hyperhidrosis improved substantially in 27 (77.1%) patients, and improved in 4 (11.4%) patients at 12 months after surgery. A total of 94.3% of patients were satisfied with the excellent cosmetic results of the surgical incision. CONCLUSIONS: Transumbilical thoracic sympathectomy is an efficacious alternative to the conventional approach. This technique avoided the chronic pain and chest wall paresthesia associated with the chest incision. In addition, this novel procedure afforded maximum cosmetic benefits. PMID- 24176275 TI - Discussion. PMID- 24176276 TI - Discussion. PMID- 24176277 TI - Discussion. PMID- 24176278 TI - Incidence and progression of mild aortic regurgitation after Tirone David reimplantation valve-sparing aortic root replacement. AB - OBJECTIVE: The study objective was to determine whether recurrent or residual mild aortic regurgitation, which occurs after valve-sparing aortic root replacement, progresses over time. METHODS: Between 2003 and 2008, 154 patients underwent Tirone David-V valve-sparing aortic root replacement; 96 patients (62%) had both 1-year (median, 12 +/- 4 months) and mid-term (62 +/- 22 months) transthoracic echocardiograms available for analysis. Age of patients averaged 38 +/- 13 years, 71% were male, 31% had a bicuspid aortic valve, 41% had Marfan syndrome, and 51% underwent aortic valve repair, predominantly cusp free margin shortening. RESULTS: Forty-one patients (43%) had mild aortic regurgitation on 1 year echocardiogram. In 85% of patients (n = 35), mild aortic regurgitation remained stable on the most recent echocardiogram (median, 57 +/- 20 months); progression to moderate aortic regurgitation occurred in 5 patients (12%) at a median of 28 +/- 18 months and remained stable thereafter; severe aortic regurgitation developed in 1 patient, eventually requiring reoperation. Five patients (5%) had moderate aortic regurgitation at 1 year, which did not progress subsequently. Two patients (2%) had more than moderate aortic regurgitation at 1 year, and both ultimately required reoperation. CONCLUSIONS: Although mild aortic regurgitation occurs frequently after valve-sparing aortic root replacement, it is unlikely to progress over the next 5 years and should not be interpreted as failure of the valve-preservation concept. Further, we suggest that mild aortic regurgitation should not be considered nonstructural valve dysfunction, as the 2008 valve reporting guidelines would indicate. We need 10- to 15-year follow-up to learn the long-term clinical consequences of mild aortic regurgitation early after valve-sparing aortic root replacement. PMID- 24176279 TI - How does severe brachycephaly affect dog's lives? Results of a structured preoperative owner questionnaire. AB - Brachycephalic syndrome (BS) is a complex canine disease, which is characterized by diverse clinical signs primarily involving the respiratory and gastrointestinal systems. Through a structured owner questionnaire, the present study investigated how owners perceived the frequency and severity of a broad spectrum of welfare-relevant impairments caused by this hereditary disease. One hundred owners of brachycephalic dogs (Pugs and French bulldogs) referred for surgical treatment of BS completed the questionnaire. As a basis for comparison, 20 owners of mesocephalic dogs also completed part of the questionnaire. Questionnaire responses revealed that in addition to the well-known respiratory signs, brachycephalic dogs experienced severe exercise intolerance and prolonged recovery time after physical exercise (88%), significant heat sensitivity (more severe signs at temperatures above 19 degrees C; 50%) and a variety of sleep problems (56%). To our knowledge, this is the first study using a structured owner questionnaire specifically to investigate a broad range of problems caused by selective breeding for brachycephaly. In particular, decreased exercise tolerance, increased recovery time due to heat intolerance and the extent of sleep problems have either been underestimated in the past, or have severely worsened over recent generations of dogs. The extent and severity of clinical signs and their impact on quality of life greatly exceeded our expectations. This study emphasizes the major impact that selective breeding for extreme brachycephalic features has on animal welfare. PMID- 24176280 TI - Longitudinal development of equine forelimb conformation from birth to weaning in three different horse breeds. AB - There is limited published data on conformational changes in the forelimbs of growing foals. This study was designed to describe the changes in conformation of the carpus and distal forelimb from birth to weaning in foals of three different breeds. Evaluation of the conformation of the carpus, fetlock, pastern and foot was carried out in 134 Thoroughbreds, 162 French Trotters and 98 Selle Francais (French Warmblood) within 1 month of age and then at approximately 2 month intervals until weaning at approximately 6 months of age. The prevalence of limb deviations decreased from birth to weaning. Angular limb deformities were the predominant conditions in the first month (63.6% of all observed limb deviations) and flexural limb deformities were the most common abnormalities at weaning. The most frequent congenital abnormalities were carpal valgus (42.1% of the foals), fetlock valgus (31.2%), over-at-the-knee (30.8%) and dropped fetlocks (13.0%), with French Trotters and Thoroughbred foals being more affected than Selle Francais foals. During the study period, the carpal and fetlock conformation became less valgus. The predominant abnormalities at weaning were fetlock valgus (19.1%), club feet (13.0%) and fetlock varus (11.2%). These observations show that carpal, fetlock and foot conformations changed substantially from birth and weaning. There were significant conformational differences between the three breeds, especially in the first months of life. An understanding of the peculiarities of specific breeds may be useful for the evaluation of individual foal conformation. PMID- 24176281 TI - Development of postural balance in foals. AB - This study used stabilographic analysis to measure and describe changes in stability during standing in foals from birth to 5 months of age. Stabilographic analysis was performed on newborn foals immediately after first suckling then daily until 1 week of age, weekly until 1 month of age and monthly until 5 months of age. Ground reaction force (GRF) data were collected for periods of 8s with the foal standing on one or two force plates recording at 1000 Hz. Stabilographic variables describing the amplitude, velocity and frequency of center of pressure (COP) movements were derived from the GRF data. Amplitudes, which were initially larger in the craniocaudal direction, decreased over time in both directions, with craniocaudal amplitude becoming smaller than mediolateral amplitude by 1-2 months of age. At birth, COP velocity was larger in the craniocaudal direction, but decreased rapidly to become smaller than mediolateral velocity by 3 months of age. Mean frequency at birth was higher craniocaudally, but became similar in both directions at 2 months of age. The rapid reductions in craniocaudal amplitude and velocity were thought to reflect improvements in strength and coordination of the flexor/extensor musculature. Newborn foals splay their limbs to compensate for poor control of the abductor/adductor musculature and, after the limbs assumed a vertical posture, mediolateral sway velocity increased. PMID- 24176282 TI - Enhanced adhesion/migration and induction of Pyk2 expression in K562 cells following imatinib exposure. AB - Concern about extramedullary relapse (EMR) despite favorable response in the bone marrow has been raised with the use of imatinib for treatment of chronic myeloid leukemia (CML). In the present study we show an increase in adhesion, migration and invasion capabilities of the CML cell line K562 following imatinib administration. Imatinib induced upregulation of Pyk2 mRNA and protein levels. Pyk2 inhibition resulted in a reduction of K562 cells' adhesion and migration subsequent to imatinib treatment. This effect was similar to that shown by us previously with all trans retinoic acid (ATRA) in the acute promyelocytic leukemia (APL) cell line NB4. Our data pinpoint Pyk2 as a shared key mediator of targeted-therapy induced adhesion and migration and may implicate that targeting Pyk2 may serve as an effective therapeutic strategy to reduce EMR in APL and CML. PMID- 24176283 TI - Temporal characteristics of respiratory syncytial virus infection in children and its correlation with climatic factors at a public pediatric hospital in Suzhou. AB - BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral pathogen in infants and children. It is important to analyze RSV epidemic patterns and related relevant factors in order to prevent further infections and related complications. OBJECTIVE: To explore the relationship between RSV infection rate in hospitalized children from Suzhou area and climatic factors. STUDY DESIGN: 42,664 nasopharyngeal specimens from hospitalized children with acute respiratory infections were screened for RSV antigens using direct immunofluorescence. 472 RSV positive samples were randomly selected and performed real-time PCR to identify RSV subtype. Monthly meteorological data in Suzhou area was collected (average temperature, relative humidity, precipitation, total sunshine, and average wind speed) from 2001 to 2011. The relation between RSV infections and climatic factors was evaluated using correlation and stepwise regression analyses. RESULTS: The annual RSV infection rate in hospitalized children in Suzhou from 2001 to 2011 varied between 11.85% and 27.30%. The highest monthly infection rates occurred from November to April. The time interval from November to April was considered the infection season. Seasonal RSV infection rates from 2001 to 2010 were 40.75%, 22.72%, 39.93%, 27.37%, 42.71%, 21.28%, 38.57%, 19.86%, and 29.73%. The infection rate of any season was statistically different from the next season. There was no significant difference in RSV infection rates in the 2010-2011 and 2009-2010 epidemic seasons. Among the 472 randomly selected RSV positive samples, 412 were found to be RSV subtype A (RSV-A), while 60 subtype B (RSV-B). The monthly RSV infection rate was negatively correlated with monthly average temperature (r=-0.84), total sunshine (r=-0.47), precipitation (r=-0.31), relative humidity (r=-0.20), and average wind speed (r=-0.20), (P<0.05). Stepwise regression analysis showed monthly average temperature fit into a linear model (R(2)=0.64, P<0.01) with a regression coefficient of -1.52 (t=15.21, P<0.01). CONCLUSIONS: RSV infection in Suzhou occurred most frequently between November and April. The number of infections peaked every other year. Abnormally high infection rate in non-epidemic season only caused by RSV-A. Ambient temperature played an important role in the development of RSV infection. PMID- 24176284 TI - Morphohistological characteristics of rabbit oviduct: a proposal for a single regionalization. AB - In rabbits, like other mammals, there are proposals for the oviduct regionalization. Reports consider different regions with inconsistent tissue characteristics, which make it difficult to compare results between studies. Our aim was to analyze morphohistological characteristics of the rabbit oviduct, such as thickness of epithelium, proportion of secretory or ciliated epithelial cells, presence of submucosa or crypts, shape of transverse sections, and thickness of smooth muscle layer, in order to identify regions and discriminate the possible limits between them. To do this, Masson's thricrome was used to identify tissue characteristics along the oviduct. Both qualitative and quantitative analyses were performed. Additionally, Mann-Whitney-U or Kruskall-Wallis tests were used to determine significant differences (P <= 0.05) for variables between oviductal regions. Five regions were well distinguished: fimbria, infundibulum, ampulla, isthmus, and utero-tubal junction. Each region had particular histological characteristics that permit its identification. Fimbria and infundibulum had more ciliated cells, the ampulla had a similar proportion of secretory and ciliated cells, and isthmus and utero-tubal junction had more secretory cells. Crypts were observed in all oviductal regions, mainly in isthmus and utero-tubal junction. Fimbria presented packages of smooth musculature. Infundibulum and ampulla showed a thin smooth muscle layer (circular orientation of fibers). Isthmus and utero tubal junction had a thick smooth muscle layer (inner longitudinal and outer circular orientation of fibers). A single and precise regionalization of oviduct could be very useful to compare studies that analyze the influence of natural conditions or treatments for tissue components or regions. PMID- 24176285 TI - Mating activity of domestic geese ganders (Anser anser f. domesticus) during breeding period in relation to age, testosterone and thyroid hormones. AB - In breeding geese, natural mating applies. The objective of this study was to determine seasonal- and age-related changes in the sexual activity of ganders. Moreover, T, T4 and T3 plasma levels were evaluated. The study was conducted on 2/3-year-old males (n=15) and 1- or 2/3-year-old females (1?:4?). Sexual activity of ganders was characterized through the frequency of: courtship, attempts at and successful copulations and total mating activity (MA). Reproductive results manifested by egg production and fertility were recorded. Laying percentage (January-June) was 37.1 and 28.6% for 1-, and 2/3-year-old geese, respectively. MA was noted before the sexual maturity of females and the T level peak. MA was highest at the onset and during peak production (March) for ganders kept with 1-, and 2/3-year-old geese, respectively. From April to May a decrease in fertility with a reduction of the frequency of copulations was observed. At this time low levels of T were noted. The effect of goose age on the MA was shown, with higher frequency of copulations for ganders kept with 1-year-old geese. We suggest that in the successful seasonal mating in geese, social factors such as the presence of females and female age play an important role. The reduction in fertility during the spring period may be associated with decreases in the efficiency of successive mating sequences. The higher frequency of copulations without affecting fertility, for ganders kept with young geese, may be because of differences in sperm transfer or storage/transport efficiency. PMID- 24176286 TI - Preventing maternal and early childhood obesity: the fetal flaw in Australian perinatal care. AB - Almost half of Australian women of child-bearing age are overweight or obese, with a rate of 30-50% reported in early pregnancy. Maternal adiposity is a costly challenge for Australian obstetric care, with associated serious maternal and neonatal complications. Excess gestational weight gain is an important predictor of offspring adiposity into adulthood and higher maternal weight later in life. Current public health and perinatal care approaches in Australia do not adequately address excess perinatal maternal weight or gestational weight gain. This paper argues that the failure of primary health-care providers to offer systematic advice and support regarding women's weight and related lifestyle behaviours in child-bearing years is an outstanding 'missed opportunity' for prevention of inter-generational overweight and obesity. Barriers to action could be addressed through greater attention to: clinical guidelines for maternal weight management for the perinatal period, training and support of maternal health-care providers to develop skills and confidence in raising weight issues with women, a variety of weight management programs provided by state maternal health services, and clear referral pathways to them. Attention is also required to service systems that clearly define roles in maternal weight management and ensure consistency and continuity of support across the perinatal period. PMID- 24176287 TI - Between credit claiming and blame avoidance: the changing politics of priority setting for Korea's National Health Insurance System. AB - Priority-setting involves diverse parties with intense and often conflicting interests and values. Still, the political aspects of priority-setting are largely unexplored in the literature on health policy. In this paper, we examine how policy makers in Korea changed their strategies as the policy context for priority setting changed from only expanding benefits to a double burden of benefit expansion plus cost containment. This analysis shows that priority setting is a profoundly political process. The policy context shapes how policy makers choose their political strategies. In particular, we find that policy makers sway between "credit claiming" and "blame avoidance" strategies. Korean policy makers resorted to three types of political strategies when confronted with a double burden of benefit expansion and cost containment: delegating responsibility to other institutions (agency strategies), replacing judgment based decisions with automatic rules (policy strategies), and focusing on the presentation of how decisions are made (presentational strategies). The paper suggests implications for future studies on priority-setting in the Korean health care system and in other countries that face similar challenges, and concludes that Korean policy makers need to put more effort into developing transparent and systematic priority-setting processes, especially in times of double burden of benefit expansion and cost containment. PMID- 24176288 TI - Development of archetypes for non-ranking classification and comparison of European National Health Technology Assessment systems. AB - INTRODUCTION: European countries are increasingly utilising health technology assessment (HTA) to inform reimbursement decision-making. However, the current European HTA environment is very diverse, and projects are already underway to initiate a more efficient and aligned HTA practice within Europe. This study aims to identify a non-ranking method for classifying the diversity of European HTA agencies process and the organisational architecture of the national regulatory review to reimbursement systems. METHOD/RESULTS: Using a previously developed mapping methodology, this research created process maps to describe national processes for regulatory review to reimbursement for 33 European jurisdictions. These process maps enabled the creation of 2 HTA taxonomic sets. The confluence of the two taxonomic sets was subsequently cross-referenced to identify 10 HTA archetype groups. DISCUSSION: HTA is a young, rapidly evolving field and it can be argued that optimal practices for performing HTA are yet to emerge. Therefore, a non-ranking classification approach could objectively characterise and compare the diversity observed in the current European HTA environment. PMID- 24176289 TI - Sex-based differences in income and response to proposed financial incentives among general practitioners in France. AB - Women represent a growing proportion of the physician workforce, worldwide. Therefore, for the purposes of workforce planning, it is increasingly important to understand differences in how male and female physicians work and might respond to financial incentives. A recent survey allowed us to determine whether sex-based differences in either physician income or responses to a hypothetical increase in reimbursement exist among French General Practitioners (GPs). Our analysis of 828 male and 244 female GPs' responses showed that females earned 35% less per year from medical practice than their male counterparts. After adjusting for the fact that female GPs had practiced medicine fewer years, worked 11% fewer hours per year, and spent more time with each consultation, female GPs earned 11,194?, or 20.6%, less per year (95% CI: 7085?-15,302? less per year). Male GPs were more likely than female GPs to indicate that they would work fewer hours if consultation fees were to be increased. Our findings suggest that, as the feminization of medicine increases, the need to address gender-based income disparities increases and the tools that French policymakers use to regulate the physician supply might need to change. PMID- 24176290 TI - Austerity and health in Europe. AB - Many European governments have abundantly cut down public expenditure on health during the financial crisis. Consequences of the financial downturn on health outcomes have begun to emerge. This recession has led to an increase in poor health status, raising rates of anxiety and depression among the economically vulnerable. In addition, the incidence of some communicable diseases along with the rate of suicide has increased significantly. The recession has also driven structural reforms, and affected the priority given to public policies. The purpose of this paper is to analyse how austerity impacts health in Europe and better understand the response of European health systems to the financial crisis. The current economic climate, while challenging, presents an opportunity for reforming and restructuring health promotion actions. More innovative approaches to health should be developed by health professionals and by those responsible for health management. In addition, scientists and experts in public health should promote evidence-based approaches to economic and public health recovery by analyzing the present economic downturn and previous crisis. However, it is governance and leadership that will mostly determine how well health systems are prepared to face the crisis and find ways to mitigate its effects. PMID- 24176291 TI - Risk factors for susceptibility to varicella in newly arrived adult migrants in Canada. AB - Varicella occurs at an older age in tropical compared to cold climates. Migrants from tropical countries provide the opportunity to gain insights into observed global differences in varicella epidemiology. Severity of varicella increases with age thus, description of risk factors for varicella susceptibility will identify those who would benefit most from vaccination. A total of 1480 migrants, with a mean age of 32 years, were recruited in the pre-vaccination period (2002 2004) in Montreal, Canada. A questionnaire was administered and serum varicella antibodies were measured. Overall 6% were susceptible and ranged from 0.8% to 14.1% in subgroups. Risk factors for susceptibility were younger age, recent arrival, and originating from a tropical country. This could be modified by conditions that increased the probability of person-to-person spread of varicella through direct contact in source countries such as larger community size or household crowding. Many new young adult migrants would benefit from targeted varicella vaccination programmes. PMID- 24176292 TI - Hypersalinity reduces the risk of cyanide toxicosis to insectivorous bats interacting with wastewater impoundments at gold mines. AB - Wildlife and livestock that ingest bioavailable cyanide compounds in gold mining tailings dams are known to experience cyanide toxicosis. Elevated levels of salinity in open impoundments have been shown to prevent wildlife cyanide toxicosis by reducing drinking and foraging. This finding appears to be consistent for diurnal wildlife interacting with open impoundments, however the risks to nocturnal wildlife of cyanide exposure are unknown. We investigated the activity of insectivorous bats in the airspace above both fresh (potable to wildlife) and saline water bodies at two gold mines in the goldfields of Western Australian. During this study, cyanide-bearing solutions stored in open impoundments at both mine sites were hypersaline (range=57,000-295,000 mg/L total dissolved solids (TDS)), well above known physiological tolerance of any terrestrial vertebrate. Bats used the airspace above each water body monitored, but were more active at fresh than saline water bodies. In addition, considerably more terminal echolocation buzz calls were recorded in the airspace above fresh than saline water bodies at both mine sites. However, it was not possible to determine whether these buzz calls corresponded to foraging or drinking bouts. No drinking bouts were observed in 33 h of thermal video footage recorded at one hypersaline tailings dam, suggesting that this water is not used for drinking. There is no information on salinity tolerances of bats, but it could be assumed that bats would not tolerate salinity in drinking water at concentrations greater than those documented as toxic for saline-adapted terrestrial wildlife. Therefore, when managing wastewater impoundments at gold mines to avoid wildlife mortalities, adopting a precautionary principle, bats are unlikely to drink solutions at salinity levels >=50,000 mg/L TDS. PMID- 24176293 TI - Development of acute and chronic sediment bioassays with the harpacticoid copepod Quinquelaophonte sp. AB - Reliable environmentally realistic bioassay methodologies are increasingly needed to assess the effects of environmental pollution. This study describes two estuarine sediment bioassays, one acute (96 h) and one chronic (14 d), with the New Zealand harpacticoid copepod Quinquelaophonte sp. utilising behavioural and reproductive endpoints. Spiked sediments were used to expose Quinquelaophonte sp. to three reference compounds representing important categories of estuarine chemical stressors: zinc (a metal), atrazine (a pesticide), and phenanthrene (a polycyclic aromatic hydrocarbon). Acute-to-chronic ratios (ACR) were used to further characterise species responses. Acute sediment (sandy and low total organic content) 96 h EC50 values for the sublethal inhibition of mobility for zinc, atrazine and phenanthrene were 137, 5.4, and 2.6 ug/g, respectively. The chronic EC50 values for inhibition of reproduction (total offspring) were 54.5, 0.0083, and 0.067 ug/g for zinc, atrazine, and phenanthrene, respectively. For phenanthrene, a potentially novel mode of action was identified on reproduction. Quinquelaophonte sp. was found to be more sensitive than several other estuarine species indicating choice of test organism is important to characterising the effects of environmentally relevant levels of contamination. The bioassay sediment results demonstrate the sensitivity and suitability of Quinquelaophonte sp. as a tool for the assessment use of estuarine health. PMID- 24176295 TI - Sensory correlates of pain in peripheral neuropathies. AB - OBJECTIVE: To characterize sensory threshold alterations in peripheral neuropathies and the relationship between these alterations and the presence of pain. METHODS: Seventy-four patients with length-dependent sensory axonal neuropathy were enrolled, including 38 patients with painful neuropathy (complaining of chronic, spontaneous neuropathic pain in the feet) and 36 patients with painless neuropathy. They were compared to 28 age-matched normal controls. A standardized quantitative sensory testing protocol was performed in all individuals to assess large and small fiber function at the foot. Large fibers were assessed by measuring mechanical (pressure and vibration) detection thresholds and small fibers by measuring pain and thermal detection thresholds. RESULTS: Between patients with neuropathy and controls, significant differences were found for mechanical and thermal detection thresholds but not for pain thresholds. Patients with painful neuropathy and those with painless neuropathy did not differ regarding mechanical or thermal thresholds, but only by a higher incidence of thermal or dynamic mechanical allodynia in case of painful neuropathy. Pain intensity correlated with the alteration of thermal detection and mechanical pain thresholds. CONCLUSIONS: Quantitative sensory testing can support the diagnosis of sensory neuropathy when considering detection threshold measurement. Thermal threshold deterioration was not associated with the occurrence of pain but with its intensity. SIGNIFICANCE: There is a complex relationship between the loss or functional deficit of large and especially small sensory nerve fibers and the development of pain in peripheral neuropathy. PMID- 24176296 TI - Polarizing cerebellar neurons with transcranial Direct Current Stimulation. PMID- 24176297 TI - Modelling the electric field and the current density generated by cerebellar transcranial DC stimulation in humans. AB - OBJECTIVE: Transcranial Direct Current Stimulation (tDCS) over the cerebellum (or cerebellar tDCS) modulates working memory, changes cerebello-brain interaction, and affects locomotion in humans. Also, the use of tDCS has been proposed for the treatment of disorders characterized by cerebellar dysfunction. Nonetheless, the electric field (E) and current density (J) spatial distributions generated by cerebellar tDCS are unknown. This work aimed to estimate E and J distributions during cerebellar tDCS. METHODS: Computational electromagnetics techniques were applied in three human realistic models of different ages and gender. RESULTS: The stronger E and J occurred mainly in the cerebellar cortex, with some spread (up to 4%) toward the occipital cortex. Also, changes by +/-1cm in the position of the active electrode resulted in a small effect (up to 4%) in the E and J spatial distribution in the cerebellum. Finally, the E and J spreads to the brainstem and the heart were negligible, thus further supporting the safety of this technique. CONCLUSIONS: Despite inter-individual differences, our modeling study confirms that the cerebellum is the structure mainly involved by cerebellar tDCS. SIGNIFICANCE: Modeling approach reveals that during cerebellar tDCS the current spread to other structures outside the cerebellum is unlike to produce functional effects. PMID- 24176298 TI - Cyclin E1 (CCNE1) as independent positive prognostic factor in advanced stage serous ovarian cancer patients - a study of the OVCAD consortium. AB - Cyclin E, coded by the genes CCNE1 and CCNE2, is the main regulator for transition from G1 to S phase determining cell division. CCNE1 and CCNE2 are known oncogenes in many cancer entities. Especially CCNE1 has frequently been associated with gene amplifications in various malignancies, emphasising its role as a putative oncogene. We determined gene expression and copy number of CCNE1 and CCNE2 by quantitative polymerase chain reaction (PCR) from 172 International Federation of Obstetrics and Gynecology (FIGO) II/III/IV stage serous epithelial ovarian cancer (EOC) tissues and analysed its impact on outcome. Furthermore, whole transcriptome gene expression changes correlating with CCNE1 expression were determined by microarray technology, interpreted by Signalling Pathway Impact Analysis (SPIA), Tool for Inferring Network of Genes (TINGe), and illustrated by hive plots. Protein-protein interaction (PPI) networks were also used for the interpretation. Interestingly, and contradictory to most reports and intuitive expectations, high CCNE1 expression correlated with better overall survival (p=0.005) if corrected for usual clinicopathologic parameters and a molecular subclassification. Using different grading systems or only high graded tumours had no impact on this correlation. Copy number of CCNE1 was increased in 25% of cases which correlated highly significantly with expression but showed no impact on outcome. CCNE2 had no impact on outcomes at all. Whole genome transcriptome analysis revealed 1872 differentially expressed genes correlated to CCNE1 expression, which were significantly enriched with genes from five pathways (e.g. cell cycle and viral carcinogenesis pathway were up-regulated and the Fanconi anaemia pathway was down-regulated). High CCNE1 gene expression is a significant and independent predictor for prolonged overall survival in FIGO III/IV EOC patients. This upside down impact of CCNE1 on survival probably reflects the special characteristic of EOC with tumour dissemination in the near anaerobic peritoneal cavity as the predominant cause of death, compared to other cancer entities where distant metastasis are predominantly lethal. PMID- 24176299 TI - Barriers and enablers to good communication and information-sharing practices in care planning for chronic condition management. AB - Our aim was to document current communication and information-sharing practices and to identify the barriers and enablers to good practices within the context of care planning for chronic condition management. Further aims were to make recommendations about how changes to policy and practice can improve communication and information sharing in primary health care. A mixed-method approach was applied to seek the perspectives of patients and primary health-care workers across Australia. Data was collected via interviews, focus groups, non participant observations and a national survey. Data analysis was performed using a mix of thematic, discourse and statistical approaches. Central barriers to effective communication and information sharing included fragmented communication, uncertainty around client and interagency consent, and the unacknowledged existence of overlapping care plans. To be most effective, communication and information sharing should be open, two-way and inclusive of all members of health-care teams. It must also only be undertaken with the appropriate participant consent, otherwise this has the potential to cause patients harm. Improvements in care planning as a communication and information sharing tool may be achieved through practice initiatives that reflect the rhetoric of collaborative person-centred care, which is already supported through existing policy in Australia. General practitioners and other primary care providers should operationalise care planning, and the expectation of collaborative and effective communication of care that underpins it, within their practice with patients and all members of the care team. To assist in meeting these aims, we make several recommendations. PMID- 24176300 TI - Normative for motor speech profile in Kannada-speaking adults. AB - OBJECTIVE: The primary purpose of this study was to establish normative for 18 parameters of Motor Speech Profile (MSP; Computerized Speech Lab; KayPENTAX, Lincoln Park, NJ) in Indian population, specifically for Kannada-speaking adults across age and gender. STUDY DESIGN: Cross-sectional study. METHOD: Native Kannada speakers (n = 300) were divided into three age groups (20-40, 41-50, and 51-60 years) with 50 males and 50 females in each group. The obtained data are reported across age and gender for the parameters of diadochokinetic rate, second formant transition, and voice and tremor characteristics of MSP software. RESULTS: Across gender, a statistically significant difference (P < 0.05) was seen for seven parameters; whereas across age, a statistically significant variation was seen for nine parameters in the age group of 51-60 years than other groups (20-40 and 41-50 years). CONCLUSION: Establishment of the normative is essential for the effective use of acoustic analysis as an objective tool. The findings of the present study serve as a norm-based reference for MSP software in Indian population, aged between 20 and 60 years. PMID- 24176301 TI - Issues in forensic voice. AB - The following article provides a general review of an area that can be referred to as Forensic Voice. Its goals will be outlined and that discussion will be followed by a description of its major elements. Considered are (1) the processing and analysis of spoken utterances, (2) distorted speech, (3) enhancement of speech intelligibility (re: surveillance and other recordings), (4) transcripts, (5) authentication of recordings, (6) speaker identification, and (7) the detection of deception, intoxication, and emotions in speech. Stress in speech and the psychological stress evaluation systems (that some individuals attempt to use as lie detectors) also will be considered. Points of entry will be suggested for individuals with the kinds of backgrounds possessed by professionals already working in the voice area. PMID- 24176302 TI - Genetics of recessive cognitive disorders. AB - Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elucidation has lagged behind. Here we review recent progress in this field, show that ARID is not rare even in outbred Western populations, and discuss the prospects for improving its diagnosis and prevention. PMID- 24176303 TI - The new challenge in identifying the negative syndrome of schizophrenia. PMID- 24176304 TI - Response to the Letter to the Editor, "the definition of sleep duration and the risk for hypertension: caution for meta-analysis". PMID- 24176305 TI - Determination of chokeberry (Aronia melanocarpa) polyphenol components using liquid chromatography-tandem mass spectrometry: Overall contribution to antioxidant activity. AB - The type and content of plant polyphenols can be influenced by maturity. Korean chokeberry (Aronia melanocarpa) leaves of three different maturities (young, mature, and aged) were extracted with 70% aqueous methanol. The polyphenols in the leaves were analysed for the first time using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and comparison with reported data. Among the 12 characterised components, five flavonoids, 3, 4, and 10-12, and a dicaffeoylquinic acid derivative, 6, were characterised for the first time in chokeberry leaves. Each polyphenol component was validated and quantified using a representative polyphenol standard of the same group. The antioxidant activity of the three different mature leaf extracts was determined. The antioxidant activity was highest for young leaves, followed by mature and aged leaves. The results suggest that younger chokeberry leaves may be more favourable for processing a higher quality functional tea due to their higher polyphenol content. PMID- 24176306 TI - Development of naturally activated edible films with antioxidant properties prepared from red seaweed Porphyra columbina biopolymers. AB - The aim of this work was to study the physicochemical and antioxidant properties of phycobiliproteins-phycocolloids-based films, obtained from mixtures of two aqueous fractions extracted from Porphyra columbina red seaweed, one enriched in phycocolloids (PcF) and the other in phycobiliproteins (PF). Films with different ratios of PF:PcF (0, 25, 50, 75, 100% [w/w]) and without plasticizer addition were prepared by casting. PcF films had excellent mechanical properties (tensile strength ~50MPa, elongation at break ~3% and an elastic modulus ~17.5MPa). The addition of PF to formulations exerted a plasticizing effect on the PcF matrix, which was manifested in moisture content, water solubility and mechanical properties of the resulting films but not in its water vapour permeability. The antioxidant capacity (TEAC) of the PcF films was significantly increased by the addition of PF and a direct relationship between TEAC and the total phenolic compounds (r(2)=0.9998) and R-phycoerythrin (r(2)=0.9942) was observed. PMID- 24176307 TI - Profiling of anthocyanins for the taxonomic assessment of ancient purebred V. vinifera red grape varieties. AB - For the purpose of a varietal assessment, the berry skin anthocyanin profiles of 11 ancient native red grape varieties, sampled within the Irpinian area (Southern Italy), were compared to those of three reference Vitis vinifera cultivars and of a Kober 5BB rootstook hybrid (Vitisberlandieri*Vitisriparia). The 3,5-O diglucoside anthocyanins and their acylated derivatives were monitored as signature compounds of non-V. vinifera grapes, using both reversed phase-high performance liquid chromatography (RP-HPLC) and matrix assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry (MS). One variety (i.e. Tenta) was demonstrated to be an interspecific hybrid cross. Three additional varieties, namely Lacrima Nera, Aglianicone and a yet-unnamed variety, were classified as "late generation hybrids" (or non-V. vinifera*V. vinifera hybrids) because of a very diluted hybrid character, that was revealed only by MS methods. Five cultivars, i.e. Aglianico Lasco, Cannella, Coda di Volpe Rossa, Mentuonico, Olivella Nera, were catalogued as purebred V. vinifera. Due to the peculiar anthocyanin profile one variety (Tuccanese) remained unassigned. The methodology is of general applicability to support the process of varietal discrimination on a molecular basis with the objective of classifying autochthonous old grapevine varieties. PMID- 24176308 TI - Biotransformation of stevioside by Leuconostoc citreum SK24.002 alternansucrase acceptor reaction. AB - Stevioside (13-O-beta-sophorosyl-19-O-beta-d-glucosyl-steviol) is a non cariogenic and low-calorigenic diterpenoid glycoside. It has a slightly bitter taste and bad aftertaste. Enzymatic modification by alternansucrase from Leuconostoc citreum SK24.002 was utilised in the biotransformation of stevioside to fully or partially remove the bitter taste of the stevioside. The effect of the reaction conditions including, time (1-24h), temperature (20-40 degrees C), pH (4-7), donor concentration (10-100mg/ml) and enzyme concentration (0.5 2.5U/ml) were investigated in order to maximise the transglucosylation yield. The highest transglucosylation yield of approximately 43.7% was achieved at 20 degrees C, pH 5.4 for 24h using sucrose at 10mg/ml and alternansucrase at 1U/ml. LC/MS analysis confirmed that the product was composed of mono-di- and tri- glucosylated stevioside and their isomers. PMID- 24176309 TI - Composition of commercial truffle flavored oils with GC-MS analysis and discrimination with an electronic nose. AB - Truffles are among the most expensive foods and their quality depends on their unique aroma, composed of complex mixtures of lipophilic volatile organic compounds (VOCs). There are many foods flavored with truffle, and oils are particularly common. Using DHS-GC-MS and an electronic nose (MOS), 18 samples of olive oil flavored with white and black truffles from the Italian market were subjected to a blind analysis. Qualitative and quantitative analysis with DHS-GC MS detected the presence of 63 VOCs, 32 of which can be attributed to olive oil, also defective, and 19 to truffles, while 12 foreign compounds are of dubious origin (synthesis and/or demolition). The data obtained with the electronic nose (MOS), processed statistically, was able to discriminate the aromas coincident with the three species of truffle declared on the label (the white truffle Tuber magnatum and the black truffles Tuber melanosporum and Tuber aestivum), demonstrating the potential and reliability of this technique, confirming the established malpractice of the use of bismethyl(dithio)methane in black truffles flavorings. PMID- 24176310 TI - (13)C/(12)C isotope ratios of organic acids, glucose and fructose determined by HPLC-co-IRMS for lemon juices authenticity. AB - High performance liquid chromatography linked to isotope ratio mass spectrometry via an interface allowing the chemical oxidation of organic matter (HPLC-co-IRMS) was used to simultaneously determine carbon 13 isotope ratio (delta(13)C) of organic acids, glucose and fructose in lime and lemon juices. Because of the significant difference between organic acids and sugars concentrations, the experimental protocol was optimised by applying a "current jump" to the IRMS device. The filament current is increased of 300MUA during elution in order to enhance IRMS sensitivity. Then, analysis were performed on 35 lemon and lime fruits from various geographical origins and squeezed in the laboratory. An overall average delta(13)C values of -25.40+/-1.620/00, -23.83+/-1.820/00 and 25.67+/-1.720/00 is found for organic acids mixture mainly made up of citric acid, glucose and fructose, respectively. These authentic samples allowed the definition of a confidence domain to which have been confronted 30 commercial juices (24 "pure juices" and 6 coming from concentrate). Among these 30 samples, 10 present delta(13)C values outside the defined range revealing an added "C4" type organic acids or sugars, addition not specified on the label that is not in agreement with EU regulation. PMID- 24176311 TI - Relationship between skin cell wall composition and anthocyanin extractability of Vitis vinifera L. cv. Tempranillo at different grape ripeness degree. AB - The relationship between cell wall composition and extractability of anthocyanins from red grape skins was assessed in Tempranillo grape samples harvested at three stages of ripening (pre-harvest, harvest and over-ripening) and three different contents of soluble solids (22, 24 and 26 degrees Brix) within each stage. Cell wall material was isolated and analysed in order to determine cellulose, lignin, non-cellulosic polysaccharides, protein, total polyphenols index and the degree of esterification of pectins. Results showed the influence of ripeness degree and contents of soluble solids on cell wall composition. Furthermore, principal components analysis was applied to the obtained data set in order to establish relationships between cell wall composition and extractability of anthocyanins. Total insoluble material exhibits the biggest opposition to anthocyanin extraction, while the highest amounts of cellulose, rhamnogalacturonans-II and polyphenols were positively correlated with anthocyanin extraction. Moreover, multiple linear regression was performed to assess the influence of the cell wall composition on the extraction of anthocyanin compounds. A model connecting cell wall composition and anthocyanin extractabilities was built, explaining 96.2% of the observed variability. PMID- 24176312 TI - Epicatechin and epigallocatechin gallate inhibit formation of intermediary radicals during heating of lysine and glucose. AB - High concentrations of the tea catechins epicatechin (EC) or epigallocatechin gallate (EGCG) inhibited formation of highly reactive intermediary radicals appearing during the Maillard reactions (MR), that take place during heating glucose and lysine at 70 degrees C in EtOH/HEPES buffer at pH 7.0 and pH 8.0. Radicals were trapped by ethanol, which subsequently were converted into spin adducts of the spin trap alpha-(4-pyridyl N-oxide)-N-tert-butylnitrone (POBN). EGCG was found to be more efficient than EC as inhibitor of intermediary radicals during the MR. Based on UV/Vis-spectroscopy, measurement of oxygen consumption and LC-MS detection of intermediates, it is suggested that the quinone form of autoxidised EC reacts with lysine through either a Michael type addition or a "Strecker like" reaction and thereby influences the formation of intermediary MR products as well as radicals. PMID- 24176313 TI - Integration of magnetic solid phase fishing and off-line two-dimensional high performance liquid chromatography-diode array detector-mass spectrometry for screening and identification of human serum albumin binders from Radix Astragali. AB - Radix Astragali is one of the most popular traditional medicinal herb and healthy dietary supplement. Isoflavonoids and astragalosides are the main bioactive ingredients. However, the systematic bioactive component analysis is inadequate so far. Then a facile method based on Fe3O4@SiO2-human serum albumin (Fe3O4@SiO2 HSA) magnetic solid phase fishing integrated with two-dimensional high performance liquid chromatography-diode array detector-mass spectrometry (2D HPLC DAD-MS(n)) was developed to fish out and identify HSA binders from Radix Astragali. The immobilized HSA displayed a high stability with 96.2% retained after ten consecutive cycles. 2D HPLC system (size exclusion chromatography*reversed phase chromatography, SEC*RP) were developed and optimised. Forty-seven bioactive compounds including thirty-four isoflavonoids and thirteen astragalosides were screened and identified or tentatively deduced based on their retention time, ultraviolet (UV), accurate molecular weight and diagnostic fragment ions. The results indicated that the integrated method could be widely applied for systematical fishing and identification of bioactive compounds, especially for low-abundance and overlapped compounds, from complex mixtures. PMID- 24176314 TI - Contamination of cachaca by PAHs from storage containers. AB - Cachaca is a distiled beverage obtained from the fermentation of sugar cane syrup that, depending on the production procedures, may be susceptible to contamination by polycyclic aromatic hydrocarbons (PAHs). These compounds present carcinogenic and/or mutagenic properties and offer a risk to human health. Sixteen PAHs were determined in cachacas that had been stored in glass bottles and in polyethylene tank by gas chromatography coupled with mass spectrometry. The quantification of the PAHs utilised an internal standard. The limits of detection and quantification varied from 0.05 to 0.10MUgL(-)(1) and 0.20 to 0.30MUgL(-)(1), respectively. A total PAH concentration of 51.57MUgL(-)(1) was found in the beverages that were stored in the tank, while the concentration in the cachaca stored in glass jugs was 6.07MUgL(-)(1). These results indicate that the polyethylene tank is a source for PAHs in cachaca. PMID- 24176315 TI - Radical-scavenging-linked antioxidant activities of extracts from black chokeberry and blueberry cultivated in Korea. AB - The objective of this study was to investigate the radical-scavenging-linked antioxidant properties of the extracts from black chokeberry and blueberry cultivated in Korea. The 70% ethanol extracts were prepared from black chokeberry and blueberry, and evaluated for total phenolic content, total flavonoid content, total proanthocyanidin content, and antioxidative activities, using various in vitro assays, such as DPPH(2,2-diphenyl-1-picrylhydrazyl), ABTS(2,2-azino-bis-(3 ethylenebenzothiozoline-6-sulphonic acid)) radical-scavenging activity, FRAP(ferric-reducing antioxidant power) and reducing power. The major phenolic compounds, including cyanidin-3-galactoside, cyanidin-3-arabinoside, neochlorogenic acid, procyanidin B1, were analysed by HPLC with a photodiode array detector. Results showed that total phenol, flavonoid and proanthocyanidin contents of black chokeberry extract were higher than those of blueberry extract. In addition, black chokeberry extract exhibited higher free radical-scavenging activity and reducing power than did blueberry extract. Cyanidin-3-galactoside was identified as a major phenolic compound, with considerable content in black chokeberry, that correlated with its higher antioxidant and radical-scavenging effects. These results suggest that black chokeberry extracts could be considered as a good source of natural antioxidants and functional food ingredients. PMID- 24176316 TI - Hepatoprotection of sesquiterpenoids: a quantitative structure-activity relationship (QSAR) approach. AB - The relative hepatoprotection effect of fifteen sesquiterpenoids, commonly found in plants and plant-derived foods and beverages was assessed. Endogenous lipid peroxidation (assay A) and induced lipid peroxidation (assay B) were evaluated in liver homogenates from Wistar rats by the thiobarbituric acid reactive species test. Sesquiterpenoids with different chemical structures were tested: trans,trans-farnesol, cis-nerolidol, (-)-alpha-bisabolol, trans-beta-farnesene, germacrene D, alpha-humulene, beta-caryophyllene, isocaryophyllene, (+) valencene, guaiazulene, (-)-alpha-cedrene, (+)-aromadendrene, (-)-alpha neoclovene, (-)-alpha-copaene, and (+)-cyclosativene. Ascorbic acid was used as a positive antioxidant control. With the exception of alpha-humulene, all the sesquiterpenoids under study (1mM) were effective in reducing the malonaldehyde levels in both endogenous and induced lipid peroxidation up to 35% and 70%, respectively. The 3D-QSAR models developed, relating the hepatoprotection activity with molecular properties, showed good fit (Radj(2) 0.819 and 0.972 for the assays A and B, respectively) with good prediction power (Q(2)>0.950 and SDEP<2%, for both models A and B). A network of effects associated with structural and chemical features of sesquiterpenoids such as shape, branching, symmetry, and presence of electronegative fragments, can modulate the hepatoprotective activity observed for these compounds. PMID- 24176317 TI - Polyphenols in Barringtonia racemosa and their protection against oxidation of LDL, serum and haemoglobin. AB - The polyphenolic profiles and antioxidant activities of the water extracts of Barringtonia racemosa shoots (leaves and stems) were explored. Two methods, freeze drying and air drying, for preparation of the shoots, were also compared. Freeze drying was better as air drying caused 5-41% reduction of polyphenols. Three phenolic acids and three flavonoids were identified, using UHPLC. The descending order of polyphenols in the leaves and stems was gallic acid>ellagic acid>quercetin>protocatechuic acid>rutin>kaempferol. In vitro antioxidant analyses were performed using biological samples. In the LDL oxidation assay, B. racemosa leaf extract (IC50=73.0MUg/ml) was better than stem extract (IC50=226MUg/ml) at inhibiting the formation of TBARS and lipid hydroperoxides. Similar trends were observed for serum and haemoglobin oxidation. B. racemosa leaf extract was better than its stem extract in delaying the time required to oxidise haemoglobin to methaemoglobin. The high polyphenolic content of B. racemosa shoots could have contributed towards their antioxidative effects. PMID- 24176318 TI - Determination of free and bound riboflavin in cow's milk using a novel flavin binding protein. AB - A recently described putative protease from the gut bacterium Bacteroides thetaiotaomicron (termed ppBat) exhibits two tryptophan residues in the interface which enable specific binding of the isoalloxazine heterocycle of riboflavin and its two cofactor forms, FMN and FAD. Recombinant ppBat was used to capture riboflavin from bovine milk directly without any prior preparation steps. The flavin-loaded protein was then re-isolated by means of affinity chromatography to identify and quantify the captured flavins. Free riboflavin concentrations were determined to 197 and 151MUg/l for milk with 3.5% and 0.5% fat content, respectively. Total riboflavin concentrations were also determined after acid treatment of milk and were 4-5 times higher than for free riboflavin. Free FMN and FAD were not detectable and only trace amounts of FMN were found in milk following acid treatment. The method appears to be amenable to develop a direct assay for free riboflavin in milk and other foods. PMID- 24176319 TI - Geographical tracing of Xihu Longjing tea using high performance liquid chromatography. AB - Xihu Longjing tea (XHLJ) is one of the most famous green tea in China. Due to its high price, some inauthentic XHLJ from other tea producing areas appear on the market and hurt the interests of customers and producers. High-performance liquid chromatography (HPLC) combined with the principal component analysis (PCA) and linear discriminant analysis (LDA) methods were applied to the geographical tracing of XHLJ from two other types of Longjing teas and a non-Longjing flatten shaped tea (non-LJ). The chromatograms of the tea samples from four different regions were highly similar. It was difficult to classify 4 types of teas directly by PCA. However, high total accuracy rates of 94.8% and 87.6% for the training and test set were achieved for distinguishing XHLJ from the other three types of tea by stepwise discriminant analysis. The identification accuracy of XHLJ from non-LJ was the highest, suggesting geographical distance might play an important role in this process. In summary, a combination of chromatographic chemical fingerprints with LDA provides a simple and rapid approach for the identification of XHLJ from other teas. PMID- 24176320 TI - Analysis of anthocyanins in powdered berry extracts by planar chromatography linked with bioassay and mass spectrometry. AB - Major anthocyanins were extracted with acidified methanol and characterised in powdered berry extracts of bilberry, blueberry, chokeberry, acai berry and cranberry by HPTLC-Vis-MS for the first time. A combined 2-step normal phase separation was applied, first for separation of anthocyanins and secondly of anthocyanidins. Documentation was performed under white light illumination (transmission mode). In the powdered berry extracts, especially the 3-glucosides of delphinidin, cyanidin, malvidin and peonidin, further cyanidin glycosides and respective anthocyanidins were found. Calibration data revealed a good correlation, with r between 0.9988 and 0.9999. The repeatability of the sample analysis (n=3) was ?3.6%. Based on the results obtained, this method can be used for rapid routine quality control of powdered berry extracts. For confirmation of the results or characterisation of unknown anthocyanin zones, mass spectra were recorded. Chromatography was directly linked to the effect using DPPH(*) reagent and luminescent Aliivibrio fischeri bioassay. PMID- 24176321 TI - Structure elucidation of fucoidan composed of a novel tetrafucose repeating unit from sea cucumber Thelenota ananas. AB - Thelenota ananas is one of the most popular edible sea cucumber species consumed in China and some Southeast Asian countries. In this study, the delicate structure of fucoidan from T. ananas (Ta-FUC) was clarified. Oligosaccharides and low molecular weight polysaccharides of Ta-FUC were prepared by enzymatic degradation. Their structures, which retained primary structural features of Ta FUC, were investigated using tandem mass spectrometry and nuclear magnetic resonance. As a result, Ta-FUC was found to be composed of a novel tetrafucose repeating unit [->3-alpha-L-Fucp-1->3-alpha-L-Fucp-1->3-alpha-L-Fucp2,4(OSO3(-)) 1->3-alpha-L-Fucp2(OSO3(-))-1->]. Meanwhile, it was proven to possess a significant inhibitory effect on superoxide radicals with an IC50 of 17.46+/ 0.14MUg/ml. This effect was related to its sulphation pattern. PMID- 24176322 TI - Odour-active compounds in papaya fruit cv. Red Maradol. AB - Application of solid-phase microextraction and simultaneous distillation extraction combined with GC-FID, GC-MS, aroma extract dilution analysis, and odour activity value were used to analyse volatile compounds from papaya fruit cv. Red Maradol and to estimate the most odour-active compounds. The analyses led to the identification of 137 compounds; 118 of them were positively identified. Twenty-five odorants were considered as odour-active compounds and contribute to the typical papaya aroma, from which ethyl butanoate, benzyl isothiocyanate, 1 hexen-3-one, (E)-beta-ionone, and methyl benzoate were the most odour-active compounds. PMID- 24176323 TI - Atherogenicity index and health-related fatty acids in different stages of lactation from Friesian, Jersey and Friesian*Jersey cross cow milk under a pasture-based dairy system. AB - The objective of the study was to investigate the effect of stage of lactation on the fatty acid profiles of milk from Friesian, Jersey and Friesian*Jersey cows. Linoleic acid in pastures was highest in the second phase which coincided with mid-lactation days (p<0.05). Highest milk moisture content and lowest fat free dry matter content was seen in early lactation (p<0.05). Higher fat content was observed in late lactation than early lactation. Highest butyric, caproic, linoleic, omega-6 and polyunsaturated fatty acids were observed for milk from Friesian cows. Highest conjugated fatty acids, alpha-linolenic acid, linoleic acid, saturated fatty acids, polyunsaturated fatty acids, omega-6, and omega-3 were observed in early lactation. Atherogenicity index and desaturase activity indices were highest in late lactation. In conclusion, stage of lactation and genotype affected milk health-related fatty acid profiles. PMID- 24176324 TI - Role of moisture on the lipid oxidation determined by D(2)O in a linoleic acid model system. AB - The possibility of moisture, as an active substance for lipid oxidation, was determined in linoleic acid model systems containing deuterium oxide (D2O) and deuterium free H2O, by measuring the headspace oxygen content and headspace volatiles. Mixtures of D2O and H2O, at the ratio of 3:0, 2:1, 1:2, and 0:3 (w/w), were added to linoleic acid and oxidised at 60 degrees C. The existence of deuterium in headspace volatiles, was indirectly determined by comparing the amount of fragmented mass to charge ratio (m/z), which was 73.1/72.1 for d1 pentane/pentane, 57.0/56.0 for d1-2-propenal/2-propenal, 101.1/100.1 for d1 hexanal/hexanal, 113.1/112.1 for d1-t-2-heptenal-D/t-2-heptenal, and 153.2/152.2 for d1-2,4-decadieanl/2,4-decadieanl. As the oxidation time increased to 12h, the ratio of 73.1/72.1 (m/z) for pentane and 57.0/56.0 for 2-propenal increased significantly with a concentration dependent manner of deuterium oxide, which implies water was incorporated as a substrate during volatile formation. However, hexanal, t-2-heptenal, and 2,4-decadieanl did not follow the patterns of pentane and 2-propenal, implying that the formation mechanisms of these volatiles may not share the same pathways with pentane and 2-propenal. This study showed that moisture participates for the formation of volatiles and moisture may act as a substrate for lipid oxidation. PMID- 24176325 TI - Analytical performance of two miniaturised extraction methods for triclosan and methyltriclosan, in fish roe and surimi samples. AB - A new and reliable miniaturised QuEChERS-based extraction method combined with a dispersive SPE cleanup procedure for extracting triclosan and methyltriclosan from fish roe and surimi samples was proposed. The effectiveness of different extraction/partition conditions for QuEChERS method was systematically investigated, and the use of acetonitrile extraction solvent and MgSO4, PSA, C18 and Florisil as cleanup reagents was recommended in the final method. Other method based on ultrasonic extraction with ethylacetate and clean-up with SPE was also evaluated for these samples. Different polymeric and silica sorbents for clean up were tested and the combination of Florisil and PSA was finally selected. The performance of these miniaturised sample preparation methods combined with GC-MS with quadrupole detection were compared. Extraction efficiency as well as cleaning effectiveness, laboriousness and speed were taken as criteria for method evaluation. Satisfactory validation parameters, such as linearity, recovery, precision and LODs and LOQs for both developed analytical methods were obtained from fish roe and surimi samples. Finally, both methods were applied to real samples. The sensitivity of the proposed methods was good enough to ensure reliable determination of target analytes at concentration levels commonly found in this kind of samples. PMID- 24176326 TI - Atmospheric pressure chemical ionisation mass spectrometry analysis linked with chemometrics for food classification - a case study: geographical provenance and cultivar classification of monovarietal clarified apple juices. AB - In the present work, we have evaluated for first time the feasibility of APCI-MS volatile compound fingerprinting in conjunction with chemometrics (PLS-DA) as a new strategy for rapid and non-destructive food classification. For this purpose 202 clarified monovarietal juices extracted from apples differing in their botanical and geographical origin were used for evaluation of the performance of APCI-MS as a classification tool. For an independent test set PLS-DA analyses of pre-treated spectral data gave 100% and 94.2% correct classification rate for the classification by cultivar and geographical origin, respectively. Moreover, PLS DA analysis of APCI-MS in conjunction with GC-MS data revealed that masses within the spectral ACPI-MS data set were related with parent ions or fragments of alkyesters, carbonyl compounds (hexanal, trans-2-hexenal) and alcohols (1 hexanol, 1-butanol, cis-3-hexenol) and had significant discriminating power both in terms of cultivar and geographical origin. PMID- 24176327 TI - Anthocyanins content and antioxidant capacity of Corinthian currants (Vitis vinifera L., var. Apyrena). AB - Corinthian currants are dried vine products used in the Mediterranean diet. Currant is produced almost exclusively in Southern Greece; three commercial subcategories are recognised, i.e. Vostizza, Gulf, and Provincial. Thirty-five batches of Corinthian currants obtained over two crop years and belonging to the several subcategories, were evaluated in terms of total and individual anthocyanins, total phenolics and antioxidant capacity. Variations were observed among batches, cultivation regions, and subcategories with respect to the studied parameters. Up to five anthocyanidin-3-O-glucosides were identified and quantified in currants for the first time. Overall, Vostizza currants presented the higher total anthocyanins content and the lower total phenolics content and antiradical activity; reducing power showed no differentiation among currants subcategories and crop years studied. Though the contribution of currants to the daily anthocyanin intake is rather low, the combined presence of other phenolics as well, makes this product a source of hydrophilic antioxidants. PMID- 24176328 TI - Direct determination of Cd, Pb and Cr in honey by slurry sampling electrothermal atomic absorption spectrometry. AB - Slurry sampling electrothermal atomic absorption spectrometry was used for direct determination of Cr, Pb and Cd in honey without sample pretreatment. The honey slurries were prepared in aqueous solution containing hydrogen peroxide and nitric acid. The slurries were directly introduced in the pyrolytic graphite tubes. Pd-Mg was used as a chemical modifier only for Cd determination. Analytical curves were performed with aqueous standards for Pb and Cr and with addition of fructose for Cd. The quantification limits for Cd, Pb and Cr were 2.0, 5.4 and 9.4ngg(-1), respectively. Acceptable precision of the methodology was obtained through repeatability and intermediate precision. In the accuracy study, recoveries were satisfactory (94-101%) for the three elements. The methodology was applied in honey from Parana (Brazil). The concentrations of Pb, Cd and Cr ranged from 141 to 228ngg(-1), <2.0 to 8ngg(-1) and 83 to 94ngg(-1), respectively. PMID- 24176329 TI - Phytochemical markers of different types of red propolis. AB - Propolis is a resin that bees collect from different plant sources and use in the defense of the bee community. The intricate composition of propolis varies depending on plant sources from different geographic regions and many types have been reported. Red coloured propolis found in several states in Brazil and in other countries has known antimicrobial and antioxidant activity. Different analytical methods have been applied to studies regarding the chemical composition and plant origins of red propolis. In this study samples of red propolis from different regions have been characterised using direct infusion electrospray ionisation mass spectrometry (ESI(-)-MS) fingerprinting. Data from the fingerprints was extracted and analysed by multivariate analysis to group the samples according to their composition and marker compounds. Despite similar colour, the red coloured propolis samples were divided into three groups due to contrasting chemical composition, confirming the need to properly characterise the chemical composition of propolis. PMID- 24176330 TI - Study of XAD-2 adsorbent for the enrichment of trace levels of phthalate esters in hydroalcoholic food beverages and analysis by gas chromatography coupled with flame ionization and ion-trap mass spectrometry detectors. AB - An analytical method based on solid-phase extraction (SPE) with Amberlite XAD-2 adsorbent used as stationary phase for determining phthalate esters (PAEs) in hydroalcoholic food beverages by GC-FID (and peak confirmation by GC-IT/MS) has been set up. The XAD-2 resin shows excellent properties for determining PAEs in solutions at very large alcoholic range (10-40% v/v): 500mL of hydroalcoholic solution spiked with a PAE mixture solution (20pgMUL(-1) of each PAE) and containing 25gL(-1) of NaCl are passed onto a cartridge containing 500mg XAD-2 adsorbent and re-extracted for GC analysis. The effects of NaCl concentration (0, 12, 25 and 50gL(-1)) and different solvents (CS2, toluene, acetone, n-hexane, ethyl acetate) are extensively studied as well the PAE recoveries both in hydroalcoholic aqueous solutions (ranging between 94% and 103% with a Relative Standard Deviation, RSD, below 8.3) and spiked (5, 10 and 25pgMUL(-1) of each PAE) real samples (between 90% and 106% with a RSD below 9.9). The correlation coefficients (R(2)) of each PAE vary between 0.9830 and 0.9950 and they are calculated in the linear range 5-100pgMUL(-1). The limits of detection (LOD) in GC-FID vary between 1.21 and 2.51pgMUL(-1) (RSD?11.1) whereas the Limits of Quantification (LOQ) range between 2.42 and 5.03pgMUL(-1) (RSD?8.9) whereas the infra-day and inter-day repeatabilities calculated as RSD for hydroalcoholic solutions, are between 6.5% and 13.7%. PMID- 24176331 TI - Antioxidant activity and content of chlorophylls and carotenoids in raw and heat processed Jalapeno peppers at intermediate stages of ripening. AB - Jalapeno peppers at intermediate ripening stages (IRS) are typically discarded at the packinghouse because they are not demanded for fresh consumption or industrial processing. These peppers have been scarcely studied in terms of pigment composition and bioactivity. In this study, the profile of pigments (carotenoids and chlorophylls) and antioxidant activity were determined in raw and heat-processed Jalapeno peppers at three IRS (brown, 50% red, and 75% red). Peppers contained 64 different pigments. Chlorophylls were the most abundant pigments in raw brown peppers while capsanthin was the most abundant at the other IRS. The content of most pigments decreased due to heat treatments. Several pheophytins and cis isomers of carotenoids were generated by heat processing. Boiling and grilling consistently decreased and increased the antioxidant activity of peppers, respectively. Tested peppers showed a more complex/abundant pigment content and higher antioxidant activity than those typically reported for green and red peppers. PMID- 24176332 TI - As, Cd, Hg and Pb in four edible shellfish species from breeding and harvesting areas along the eastern Adriatic Coast, Croatia. AB - Four species of shellfish (Mytilus galloprovincialis, Ostrea edulis, Chlamis varia and Venus verrucosa) were collected during the autumn 2011 and spring 2012 along the eastern Adriatic coast from six shellfish harvesting areas (all species) and 13 breeding sampling areas (mussels) to assess As, Cd, Hg and Pb levels and the human risks of shellfish consumption. The mean metal concentrations (wet weight) in the examined species ranged from 1.420 to 9.575mg/kg for As, 0.034 to 1.270 for Cd, 0.005 to 0.680 for Hg and 0.140 to 2.072 for Pb. Examination of the spatial distribution of As, Cd, Hg and Pb revealed statistically significant differences among the studied areas. Since the concentrations were below the maximum prescribed by the laws of the EU and Croatia (the concentrations slightly exceeded the upper limits for three samples; Pb, Cd and Hg) and the hazard index, (HI) for Cd, Hg and Pb were below 1 and the target cancer risk (TR) for As was lower than 1*10(-6), there is no human health risk of consumption of shellfish from Croatian waters. PMID- 24176333 TI - Rapid and simple determination of acrylamide in conventional cereal-based foods and potato chips through conversion to 3-[bis(trifluoroethanoyl)amino]-3 oxopropyl trifluoroacetate by gas chromatography coupled with electron capture and ion trap mass spectrometry detectors. AB - A new, simple, rapid and fully validated method based on gas chromatography coupled with Electron capture and ion trap mass spectrometry detectors (GC-ECD and GC-IT/MS) is presented for quantitative analysis of acrylamide contaminant in conventional cereal-based foods and potato chips. Before analysis acrylamide was efficiently derivatized with trifluoroacetic anhydride, the effects of temperature, reaction time and catalyst on the acylation reaction were evaluated. Chromatographic analysis was performed on SE-54 capillary column; good retention and peak response of the acrylamide derivative achieved under the optimal conditions. The analytical method has been fully validated by assessment of the following parameters: LODs and LOQs (1 and 25ngg(-1) by GC-ECD and 2 and 36ngg( 1) by GC-IT/MS, with a Relative Standard Deviations <4 and <6, respectively), linearity (R(2) above 0.981 in the range 0.005-50MUgg(-1)) and extraction recovery (ranging between 91% and 99%, RSD below 4.0, for acrylamide spiked at levels of 1, 20, 50 and 100ngg(-1)). Furthermore, the method proposed requires no clean-up step of the acrylamide derivative to be performed prior to injection. The developed method has been successfully applied to determine acrylamide in different commercial cereal-based foods (including French fries and potato chips). PMID- 24176335 TI - Fast method of elements determination in slim coffees by ICP OES. AB - Six sample preparation procedures, i.e., the total decomposition in a HNO3 and H2O2 mixture by microwave-assisted or hot-plate heating, a partial decomposition by means of solubilisation in aqua regia or tetramethyl ammonium hydroxide and simple dissolution in diluted HNO3 or in H2O, for the determination of the total content of Ba, Ca, Cd, Cr, Cu, Fe, Mg, Mn, Ni, P, Pb, Sr and Zn in slim instant coffees using inductively coupled plasma optical emission spectrometry were compared. The performance of procedures was determined based on the precision and the accuracy of results and limits of detection of elements. It was found that the extraction with aqua regia provides the best results, i.e., limits of detection of elements within 0.11-108ngmL(-1), the precision of 0.6-5% and the accuracy better than 5%. Elements' concentrations agree with those after the wet digestion in the HNO3 and H2O2 mixture, therefore this procedure is a simple and fast alternative to complete sample decomposition procedures and can be easily applied for routine analyses. Six commercial slim coffee products were analysed with the proposed procedure. PMID- 24176334 TI - A survey of trichothecenes, zearalenone and patulin in milled grain-based products using GC-MS/MS. AB - An analytical protocol based on QuEChERS and gas chromatography-tandem mass spectrometry (GC-MS/MS) was successfully applied for the determination of trichothecenes, patulin and zearalenone in 182 milled grain-based samples. The analytical method was validated following the SANCO 1495/2011 document. LOQs were lower than 10MUgkg(-1) for the selected mycotoxins. Recoveries of fortified cereals ranged between 76-108% and 77-114% at 20 and 80MUgkg(-1), respectively, with relative standard deviation lower than 9%. More than 60% of the samples analysed showed deoxynivalenol contamination, followed by HT-2 toxin and nivalenol with frequencies of 12.1% and 10.4%, respectively. Co-occurrence of mycotoxins was also present in major cereals. A risk characterisation was carried out based on probable daily intake (PDI) and tolerable daily intake (TDI). Despite PDI of the average consumers were below TDI, special attention should be paid in high consumers as well as other susceptible population. PMID- 24176336 TI - Influence of type of amphora on physico-chemical properties and antioxidant capacity of 'Falanghina' white wines. AB - The present research was aimed to evaluate the effects of ageing and type of container on physico-chemical indices and on antioxidant compounds of 'Falanghina' wines. Wines were stored for 12months in raw, glazed, and engobe amphorae, and in stainless steel tanks. Lactic, acetic, citric, succinic, and hydroxycinnamoyl tartaric acids, and the antioxidant capacity (DPPH assay) were not affected by the type of container for the duration of the ageing. Flavonoids decreased by about 85% in all the containers. The concentrations of flavans reactive with vanilline were reduced by 100% in raw and glazed amphorae, 23% in engobe amphorae, and 59% in stainless steel tanks. The hydroxycinnamoyl tartaric acids decreased by about 11% in raw and engobe amphorae and by ~22% in glazed amphorae and in stainless steel tanks. During the whole ageing time, the decrease of the antioxidant capacity ranged from 28% (raw amphorae) to 43% (stainless steel tanks). PMID- 24176337 TI - Influence of new generation fungicides on Saccharomyces cerevisiae growth, grape must fermentation and aroma biosynthesis. AB - The influence of ten new generation fungicides (ametoctradin, benthiavalicarb isopropyl, boscalid, cyazofamid, dimethomorph, fenhexamid, kresoxim-methyl, mepanipyrim, metrafenone, and pyraclostrobin) on the fermentative activity of Saccharomyces cerevisiae yeast was initially evaluated in pasteurised red must. The presence of ametoctradin, dimethomorph and mepanipyrim seemed to affect sugars-to-ethanol yield in the stationary phase. The same fermentation experiments were carried out for these three fungicides in ecological red must from Vitis vinifera cv. Tempranillo. When ecological must was unfiltered, the fermentative activity of yeasts was unaffected by the presence of these selected fungicides. However, when ecological must was filtered beforehand, a slight decrease of biomass and ethanol production (in terms of biomass-to-ethanol yield and sugars-to-ethanol yield, respectively), as well as a decrease in fruity aroma, were registered with respect to the control wine. PMID- 24176338 TI - Simultaneous determination of aflatoxin M1, ochratoxin A, zearalenone and alpha zearalenol in milk by UHPLC-MS/MS. AB - In this study, a sensitive and rapid method has been developed for the simultaneous determination of aflatoxin M1, ochratoxin A, zearalenone and alpha zearalenol in milk by ultra high performance liquid chromatography combined with electrospray ionisation triple quadrupole tandem mass spectrometry (UHPLC-ESI MS/MS). The milk samples were purified using Oasis HLB cartridge. The matrix effects were evaluated by determining the signal suppression-enhancement (SSE) and corrected by external matrix-matched calibration. The limits of quantity (LOQ) of the mycotoxins were in the range of 0.003-0.015MUgkg(-1). The high correlation coefficients (R(2)?0.996) were obtained in the range of 0.01 1.00MUgkg(-1) of the mycotoxins, along with good recovery (87.0-109%), repeatability (3.4-9.9%) and intra-laboratory reproducibility (4.0-9.9%) at the concentrations of 0.025, 0.1 and 0.5MUgkg(-1). The detected rates of the mycotoxins were from 16.7% to 96.7% in raw milk, liquid milk and milk powder samples collected from the dairy farms and supermarkets in Beijing. The method proposed is suitable for the simultaneous determination of aflatoxin M1, ochratoxin A, zearalenone, and alpha-zearalenol, and could be performed for analysing the mycotoxins in milk. PMID- 24176339 TI - FTIR-ATR determination of solid non fat (SNF) in raw milk using PLS and SVM chemometric methods. AB - Fourier transform infrared spectroscopy (FTIR) attenuated total reflectance (ATR) spectroscopy, coupled with chemometrics methods have been applied to the fast and non-destructive quantitative determination of solid non fat (SNF) content in raw milk. Partial least squares regression (PLS) and support vector machine (SVM) regression methods were used to model and predict SNF contents in raw milk based on FTIR spectral transmission measurements. Both methods, PLS and SVM, showed good performances in SNF prediction with relative prediction errors in the external validation of between 0.2% and 0.3% depending on the spectral range and regression method. Coefficient of determination of the global fit was always above 0.99. Since, the relative prediction errors were low, it can be concluded that FTIR-ATR with chemometrics can be used for accurate quantitative determinations of SNF contents in raw milk within the investigated calibration range of 79-100g/L. The proposed procedure is fast, non-destructive, simple and easy to implement. PMID- 24176340 TI - Regulation of cytochrome P450 mRNA expression in primary porcine hepatocytes by selected secondary plant metabolites from chicory (Cichorium intybus L.). AB - Chicory (Cichorium intybus) has been shown to induce enzymes of pharmacokinetic relevance (cytochrome P450; CYP). The aim of this study was to investigate the effects of selected secondary plant metabolites with a global extract of chicory root, on the expression of hepatic CYP mRNA (1A2, 2A19, 2C33, 2D25, 2E1 and 3A29), using primary porcine hepatocytes. Of the tested secondary plant metabolites, artemisinin, scoparone, lactucin and esculetin all induced increased expression of specific CYPs, while esculin showed no effect. In contrast, a global extract of chicory root decreased the expression of CYP1A2, 2C33, 2D25 and 3A29 at high concentrations. The results suggest that purified secondary metabolites from chicory affect CYP expression and thereby might affect detoxification in general, and that global extracts of plants can have effects different from individual components. PMID- 24176341 TI - Determination of triterpenic acids in fruits by a novel high performance liquid chromatography method with high sensitivity and specificity. AB - A novel and interesting pre-column derivatisation method was developed for the analysis of triterpenic acids by high-performance liquid chromatography (HPLC) with fluorescence detection. Each triterpenic acid produced two HPLC peaks with similar peak areas after derivatising with chiral 1-(9H-carbazol-9-yl) propan-2 yl-methanesulfonate (CPMS), while the fatty acid derivative of CPMS had only one peak. This phenomenon greatly increased the confidence in analyte confirmation. Compound with only one peak or two peaks differing greatly in their peak areas could be excluded from the target compound list. CPMS was compared with five other derivatising reagents, four of which produced only one peak for one triterpenic acid, to study the possible mechanism. Analytes with different behaviours were also studied to better interpret the mechanism. The proposed method also showed the merits of high sensitivity and less sample consumption. It was successfully applied to the analysis of triterpenic acids in fruit peels and flesh. There is no prior report on the two peak phenomenon of triterpenic acids. The information provided in this study will be helpful for those who are also engaged in derivatisation study. PMID- 24176342 TI - Rapid characterisation and comparison of saponin profiles in the seeds of Korean Leguminous species using ultra performance liquid chromatography with photodiode array detector and electrospray ionisation/mass spectrometry (UPLC-PDA-ESI/MS) analysis. AB - The present work was reported on investigation of saponin profiles in nine different legume seeds, including soybean, adzuki bean, cowpea, common bean, scarlet runner bean, lentil, chick pea, hyacinth bean, and broad bean using ultra performance liquid chromatography with photodiode array detector and electrospray ionisation/mass spectrometry (UPLC-PDA-ESI/MS) technique. A total of twenty saponins were characterised under rapid and simple conditions within 15min by the 80% methanol extracts of all species. Their chemical structures were elucidated as soyasaponin Ab (1), soyasaponin Ba (2), soyasaponin Bb (3), soyasaponin Bc (4), soyasaponin Bd (5), soyasaponin alphag (6), soyasaponin betag (7), soyasaponin betaa (8), soyasaponin gammag (9), soyasaponin gammaa (10), azukisaponin VI (11), azukisaponin IV (12), azukisaponin II (13), AzII (14), AzIV (15), lablaboside E (16), lablaboside F (17), lablaboside D (18), chikusetusaponin IVa (19), and lablab saponin I (20). The individual and total saponin compositions exhibited remarkable differences in all legume seeds. In particular, soyasaponin betaa (8) was detected the predominant composition in soybean, cowpea, and lentil with various concentrations. Interestingly, soybean, adzuki bean, common bean, and scarlet runner bean had high saponin contents, while chick pea and broad bean showed low contents. PMID- 24176343 TI - Stability and conformational change of methoxypolyethylene glycol modification for native and unfolded trypsin. AB - The effect of succinimidyl carbonates activated methoxypolyethylene glycol (mPEG SC) on the catalytic properties and conformation of native trypsin and dynamic high-pressure microfluidisation (DHPM) induced unfolded trypsin was studied. The thermal stability of unfolded trypsin was enhanced more significantly than that of native trypsin between 45 and 70 degrees C. The autolysis analysis indicated that modified unfolded trypsin was markedly more resistant to autolysis compared to modified native trypsin between 40 and 180min. Upon mPEG-SC conjugation, the Km value of the enzyme decreased by about 2-fold, and the catalytic efficiency (Kcat/Km) increased by about 3-4-fold. Moreover, the increased thermal stability of unfolded trypsin might be due to the lower surface hydrophobicity and the higher hydrogen bond formation after mPEG-SC modification, which was reflected in the decrease of UV absorbance, the quenching and blue shift of fluorescence spectra, as well as the increase of beta-sheet content. PMID- 24176344 TI - Effect of ozone on aflatoxins detoxification and nutritional quality of peanuts. AB - Aflatoxins are a group of secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus with carcinogenicity, teratogenicity, and mutagenicity. Aflatoxins may be found in a wide range of agri-products, especially in grains, oilseeds, corns, and peanuts. In this study, the conditions for detoxifying peanuts by ozonation were optimised. Aflatoxins in peanuts at moisture content of 5% (w/w) were sensitive to ozone and easily degraded when reacted with 6.0mg/l of ozone for 30min at room temperature. The detoxification rates of the total aflatoxins and aflatoxin B1 (AFB1) were 65.8% and 65.9%, respectively. The quality of peanut samples was also evaluated in this research. No significant differences (P>0.05) were found in the polyphenols, resveratrol, acid value (AV), and peroxide value (PV) between treated and untreated samples. The results suggested that ozonation was a promising method for aflatoxin detoxification in peanuts. PMID- 24176345 TI - Profiling polyphenols of two diploid strawberry (Fragaria vesca) inbred lines using UHPLC-HRMS(n.). AB - Phenolic compounds in the fruits of two diploid strawberries (Fragaria vesca f. semperflorens) inbred lines-Ruegen F7-4 (a red-fruited genotype) and YW5AF7 (a yellow-fruited genotype) were characterised using ultra-high-performance liquid chromatography coupled with tandem high-resolution mass spectrometry (UHPLC HRMS(n)). The changes of anthocyanin composition during fruit development and between Ruegen F7-4 and YW5AF7 were studied. About 67 phenolic compounds, including taxifolin 3-O-arabinoside, glycosides of quercetin, kaempferol, cyanidin, pelargonidin, peonidin, ellagic acid derivatives, and other flavonols were identified in these two inbred lines. Compared to the regular octoploid strawberry, unique phenolic compounds were found in F. vesca fruits, such as taxifolin 3-O-arabinoside (both) and peonidin 3-O-malonylglucoside (Ruegen F7-4). The results provide the basis for comparative analysis of polyphenolic compounds in yellow and red diploid strawberries, as well as with the cultivated octoploid strawberries. PMID- 24176346 TI - Koelreuteria formosana extract impedes in vitro human LDL and prevents oxidised LDL-induced apoptosis in human umbilical vein endothelial cells. AB - Koelreuteria formosana ethanol extract (KFEE) is obtained from natural plants that are endemic in Taiwan. A study showed that KFEE has antioxidant activity in DPPH assay. In the current study, the antioxidative activity of KFEE, which contains polyphenols including gallic acid and caffeic acid, was evaluated. The manner by which KFEE protects human umbilical vein endothelial cells (HUVECs) from oxidised LDL (oxLDL)-mediated dysfunction in vitro was investigated as well. The results indicate that the antioxidative activity of KFEE is defined by the relative electrophoretic mobility of oxLDL, the fragmentation of ApoB, conjugated diene production, and malondialdehyde production through Cu(2+)-mediated oxidation of LDL. KFEE also inhibited ROS generation as well as the subsequent mitochondrial membrane potential collapse, chromosome condensation, cytochrome C release, and caspase-3 activation induced by oxLDL in HUVECs. Our results also indicate that KFEE may protect LDL oxidation and prevent oxLDL-induced cellular dysfunction in HUVECs. PMID- 24176347 TI - Methods of analysis for 2-dodecylcyclobutanone and studies to support its role as a unique marker of food irradiation. AB - Methods of analysis for 2-dodecylcyclobutanone (2-DCB) using gas chromatography with mass spectrometric detection (GC-MS), liquid chromatography with time-of flight mass spectrometric detection (LC-TOF-MS) and LC with tandem MS (MS/MS) detection have been developed and optimised for maximum sensitivity to allow very low irradiation doses to be detected. The LC-MS/MS method, following derivatisation with 2,4-dinitrophenylhydrazine, was found to be the most sensitive technique and was used to determine the amount of 2-DCB formed from the model compounds palmitic acid, glyceryl tripalmitate and 1,3-dipalmitoyl-2 oleoylglycerol irradiated over a range of doses by two different irradiation sources (gamma and electron beam). The model compounds were also treated with a number of non-irradiation based processing techniques including heating in the presence and absence of oxygen, light, and redox active metal salts, in a conventional oven, microwave oven and pressure cooker. No 2-DCB was detected in any of the processed non-irradiated model compounds, reaffirming the hypothesis that 2-DCB is a unique radiolytic product that can be used as a marker of irradiation in foodstuffs. PMID- 24176348 TI - Monoclonal antibody-quantum dots CdTe conjugate-based fluoroimmunoassay for the determination of aflatoxin B1 in peanuts. AB - A fluoroimmunoassay towards aflatoxin B1 (AFB1) was presented using quantum dots as the fluorescent label. The CdTe QDs were successfully linked to the monoclonal antibody against AFB1. Based on the conjugated complexes, a novel direct competitive fluorescence-linked immunosorbent assay (cFLISA) was developed for AFB1 detection. The 50% inhibition value (IC50) of the cFLISA was 0.149ng/mL in peanuts matrix. The method performance included the limit of detection (LOD) of 0.016ng/mL and considerable recoveries of 85-117% at three fortification levels (0.075, 0.15, and 0.3ng/g) from spiked AFB1 blank peanuts samples, along with coefficients of variation (CVs) below 10%. The cFLISA provided an alternative of rapid and sensitive detection for AFB1 and, moreover provided great potential for multiplexed mycotoxins determination simultaneously. PMID- 24176349 TI - Occurrence of toxigenic fungi and determination of mycotoxins by HPLC-FLD in functional foods and spices in China markets. AB - Twenty-four samples including 14 functional foods and 10 spices obtained from Chinese markets were examined for their mould profile. The mycotoxin contamination levels were also determined by an optimized HPLC-FLD method. 124 fungal isolates belonging to four different genera were recovered with Aspergillus and Penicillium as predominant fungi, with an incidence of 66.1% and 15.3%, respectively. In functional foods Aspergillus niger section (57.1%) was isolated more frequently, followed by Aspergillus flavi section (50.0%) and Aspergillus ochraceus section (21.4%), with the most contaminated samples being Coix seeds. Similar fungal presence and frequency were encountered in spice with A. niger section group (60.0%) and A. flavi section (40.0%) as main fungi. Cumin and Pricklyash peel samples showed the highest fungal contamination. Four functional foods and three spices were found to be positive at low levels for mycotoxins including aflatoxin B1 (up to 0.26MUg/kg) and ochratoxin A (OTA) (5.0MUg/kg). The more frequently detected mycotoxin was AFB1 (16.7%). PMID- 24176350 TI - Selenium-enriched Agaricus bisporus increases expression and activity of glutathione peroxidase-1 and expression of glutathione peroxidase-2 in rat colon. AB - The effect of dietary supplementation with Se-enriched Agaricus bisporus on cytosolic gluthathione peroxidase-1 (GPx-1), gastrointestinal specific glutathione peroxidase-2 (GPx-2), thioredoxin reductase-1 (TrxR-1) and selenoprotein P (SeP) mRNA expression and GPx-1 enzyme activity in rat colon was examined. Rats were fed for 5weeks with control diet (0.15MUg Se/g feed) or Se enriched diet fortified with selenised mushroom (1MUg Se/g feed). The mRNA expression levels were found to be significantly (P<0.01) up-regulated by 1.65 fold and 2.3-fold for GPx-1 and GPx-2, respectively, but were not significantly different for TrxR-1 and SeP between the 2 diet treatments. The up-regulation of GPx-1 mRNA expression was consistent with GPX-1 activity level, which was significantly (P<0.05) increased by 1.77-fold in rats fed with the Se-enriched diet compared to the control diet. The results showed that selenised A. bisporus can positively increase GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon. PMID- 24176351 TI - Structural investigation of a novel heteropolysaccharide from the fruiting bodies of Boletus edulis. AB - A novel water-soluble heteropolysaccharide, BEPF1, was isolated from the fruiting bodies of Boletus edulis with boiling water extraction and purified by Sephacryl S-300, with a molecular weight of 1.08*10(4)Da. Sugar composition of BEPF1 showed that it was composed of l-fucose, d-mannose, d-glucose and d-galactose in the ratio of 0.21:0.23:1.17:1.00. Methylation analysis together with (1)H, (13)C and 2D NMR spectroscopy established that BEPF1 was consisted of alpha-d-(1->6) galactopyranan backbone with a terminal of alpha-l-fucosyl unit on O-2 of the 2-d (2->6)-galactosyl units, beta-d-(1->6)-4-O-Me-glucopyranan and beta-d-(1->6) glucopyranan backbone with a terminal beta-d-glucosyl unit and it also contained a minor of 2,6-beta-d-Mannopyranan residues. PMID- 24176352 TI - Trace metals in wine and vineyard environment in southern Ukraine. AB - The study was focused on measuring the concentration levels of trace metals in the environment, vines and wine within the wine-growing region of Ukraine and comparing the findings to the data from well known wine-growing areas. Analysis was carried out of Cr, Cu, Ni, Pb and Zn in irrigation water, grape juice and wine, Cu, Pb and Zn in soil (pseudo-total and acid-soluble fractions) and Vitis vinifera L. in leaves and grapes. The accumulation levels of Cu and Zn from soil to leaves were significantly higher than from soil to grapes. Pb had lower potential to accumulate in aerial parts than Cu and Zn. Higher contents of Cu and Zn were observed in Muscat white grape juice compared to Chardonnay. The concentration levels of Zn and Cu were higher in wine than in juice. Trace metals were regulated by the soil composition and biological specificity of cultivars. The data obtained from the study area did not exceed the international limits. PMID- 24176353 TI - Isotope dilution liquid chromatography-tandem mass spectrometry for simultaneous identification and quantification of beta-casomorphin 5 and beta-casomorphin 7 in yoghurt. AB - A highly selective and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous identification and quantification of beta-casomorphin 5 (BCM5) and beta-casomorphin 7 (BCM7) in yoghurt. The method used deuterium labelled BCM5-d10 and BCM7-d10 as surrogate standards for confident identification and accurate and quantification of these analytes in yoghurt. Linear responses for BCM5 and BCM7 (R(2)=0.9985 and 0.9986, respectively) was observed in the range 0.01-10ng/MUL. The method limits of detection (MLDs) in yoghurt extracts were found to be 0.5 and 0.25ng/g for BCM5 and BCM7, respectively. Analyses of spiked samples were used to provide confirmation of accuracy and precision of the analytical method. Recoveries relative to the surrogate standards of these spikes were in the range of 95-106% for BCM5 and 103-109% for BCM7. Precision from analysis of spiked samples was expressed as relative standard deviation (%RSD) and values were in the range 1 16% for BCM5 and 1-6% for BCM7. Inter-day reproducibility was between 2.0-6.4% for BCM5 and between 3.2-6.1% for BCM7. The validated isotope dilution LC-MS/MS method was used to measure BCM5 and BCM7 in ten commercial and laboratory prepared samples of yoghurt and milk. Neither BCM5 nor BCM7 was detected in commercial yoghurts. However, they were observed in milk and laboratory prepared yoghurts and interestingly their levels decreased during processing. BCM5 decreased from 1.3ng/g in milk to 1.1ng/g in yoghurt made from that milk at 0day storage and 4)-beta-galactan chain and in the proportion of the arabinan side chain. Crude water extract (PWH) and fraction SF-50E were evaluated for their gastroprotective properties against ethanol-induced acute gastric lesions in rats. Oral administration of PWH (3 and 10mg/kg) reduced the gastric lesion area by 67+/-11% and 60+/-12%, respectively, while fraction SF-50E (10 and 30mg/kg) inhibited the lesion area by 84+/-12% and 83+/-12%, respectively. These results indicated that prune's polysaccharides act as gastroprotective agents in rats. PMID- 24176374 TI - Antioxidant properties of Australian canola meal protein hydrolysates. AB - Antioxidant activities of canola protein hydrolysates (CPHs) and peptide fractions prepared using five proteases and ultrafiltration membranes (1, 3, 5, and 10kDa) were investigated. CPHs had similar and adequate quantities of essential amino acids. The effective concentration that scavenged 50% (EC50) of the ABTS(+) was greatest for the <1kDa pancreatin fraction at 10.1MUg/ml. CPHs and peptide fractions scavenged DPPH(+) with most of the EC50 values being <1.0mg/ml. Scavenging of superoxide radical was generally weak, except for the <1kDa pepsin peptide fraction that had a value of 51%. All CPHs inhibited linoleic acid oxidation with greater efficiency observed for pepsin hydrolysates. The oxygen radical absorbance capacity of Alcalase, chymotrypsin and pepsin hydrolysates was found to be better than that of glutathione (GSH) (p<0.05). These results show that CPHs have the potential to be used as bioactive ingredients in the formulation of functional foods against oxidative stress. PMID- 24176375 TI - Influence of bottle storage time on colour, phenolic composition and sensory properties of sweet red wines. AB - Changes in colour and phenolic composition in sweet red wines made from Merlot, Syrah and Tempranillo grapes were studied in order to assess the influence of bottle storage over a period of 12months. For this purpose, wine colour parameters, sensory analysis and concentrations of monomeric anthocyanins, pyranoanthocyanins, methylmethine-mediated condensation adducts, flavan3-ol derivatives and flavonols were measured. Hue increased and red colours decreased with the storage time, particularly over the first 3months. The concentrations of low molecular weight flavan-3-ol derivatives decreased with time due to the effect of their conversion into tannins of high molecular weight. In addition, the glycosylated flavonols decreased through hydrolysis to give the corresponding aglycones. Overall, the concentration of phenolic compounds decreased markedly with storage time, whereas the antioxidant activity in the wines remained constant throughout. A panel of expert tasters judged the colour, aroma and flavour of all initial and final wines to be acceptable. PMID- 24176376 TI - Effect of delayed harvesting and pre-treatment methods on the antinutritional contents of trifoliate yam flour. AB - Effects of delayed harvesting and pre-treatment methods on the anti-nutritional contents of trifoliate yam flour were examined. Trifoliate yam tubers were washed, peeled, sliced and subjected to pre-treatment methods, such as soaking, pre-cooking and blanching/soaking. The phenols, phytate, oxalate, tannin and alkaloid profiles of the flours were evaluated and the values of phenols, tannin, oxalate and phytate contents were 0.02-0.32, 0.04-0.53, 0.11-4.32 and 0.20 1.05mg/100g, respectively. The predominant alkaloids in trifoliate yam flour were dioscorine and dihydrodioscorine. The white trifoliate yam flour had higher levels of anti-nutrients than the yellow trifoliate yam flour. Alkaloid contents of trifoliate yam flour increased slightly with delayed harvesting periods. Blanching/soaking method drastically reduced the anti-nutrient contents of trifoliate yam flour than other methods. PMID- 24176377 TI - Influence of cysteine and methionine availability on protein peroxide scavenging activity and phenolic stability in emulsions. AB - Plant phenolics are secondary metabolites that have been shown to confer beneficial health effects in humans. However, many of these compounds undergo metal-catalysed oxidation reactions, leading to the generation of hydrogen peroxide (H2O2) and other reactive oxygen species that may negatively impact product stability. In proteins, methionine (Met) and cysteine (Cys) are capable of reacting directly with peroxides. Thus, the dairy proteins, casein (CAS) and beta-lactoglobulin (BLG), were examined for their ability to scavenge H2O2 (400MUM) and influence (-)-epigallocatechin-3-gallate (EGCG) oxidation (400MUM) in Tween- or sodium dodecyl sulphate (SDS)-stabilised hexadecane emulsions. To examine the effect that the accessibility of these amino acids have on their peroxide scavenging activities, proteins were pre-treated with tert-butyl hydroperoxide (TBHP), a bulky peroxide, to oxidise only solvent accessible Met residues or H2O2, the smallest peroxide, to oxidise buried Met residues. In CAS treatments, higher Met content yielded greater peroxide scavenging activity and EGCG stability. CAS treatments also showed significantly higher peroxide scavenging activity compared to the corresponding BLG treatment. However, BLG peroxide scavenging activity was greatly enhanced in SDS-stabilised emulsions due to protein denaturation and subsequent exposure of previously buried Cys residues. PMID- 24176378 TI - Antioxidant activities of Se-SPI produced from soybean as accumulation and biotransformation reactor of natural selenium. AB - A study to compare the uptake, translocation, and distribution of selenium (Se) in soybean planted in natural seleniferous soil in Fengcheng city of China was conducted to clarify the relationship between the Se content levels of soybean proteins and their radical scavenging activity. The data showed that the total Se content in different parts of soybean plants varied with the growth periods. The selenoprotein (Se-SPI) content increased remarkably with the increase of Se content in seleniferous soils. The Se-SPI content obtained from the region with the highest Se level was almost 18 times higher than that of the control group, while antioxidant activities were about 4-fold compared to the control, suggesting that Se played a positive role in enhancing the antioxidant activity of Se-SPI. The increase in the Se level also led to changes in amino acids composition, but with nearly no effects on the subunit composition of soybean Se SPI. PMID- 24176379 TI - Effect of pulsed electric field treatment on enzyme kinetics and thermostability of endogenous ascorbic acid oxidase in carrots (Daucus carota cv. Nantes). AB - The objective of this research was to study the enzyme kinetics and thermostability of endogenous ascorbic acid oxidase (AAO) in carrot puree (Daucus carota cv. Nantes) after being treated with pulsed electric field (PEF) processing. Various PEF treatments using electric field strength between 0.2 and 1.2kV/cm and pulsed electrical energy between 1 and 520kJ/kg were conducted. The enzyme kinetics and the kinetics of AAO thermal inactivation (55-70 degrees C) were described using Michaelis-Menten model and first order reaction model, respectively. Overall, the estimated Vmax and KM values were situated in the same order of magnitude as the untreated carrot puree after being exposed to pulsed electrical energy between 1 and 400kJ/kg, but slightly changed at pulsed electrical energy above 500kJ/kg. However, AAO presented different thermostability depending on the electric field strength applied. After PEF treatment at the electric field strength between 0.2 and 0.5kV/cm, AAO became thermolabile (i.e. increase in inactivation rate (k value) at reference temperature) but the temperature dependence of k value (Ea value) for AAO inactivation in carrot puree decreased, indicating that the changes in k values were less temperature dependent. It is obvious that PEF treatment affects the temperature stability of endogenous AAO. The changes in enzyme kinetics and thermostability of AAO in carrot puree could be related to the resulting carrot puree composition, alteration in intracellular environment and the effective concentration of AAO released after being subjected to PEF treatment. PMID- 24176380 TI - Characterisation and classification of Greek pine honeys according to their geographical origin based on volatiles, physicochemical parameters and chemometrics. AB - The aim of the present study was to characterise and classify Greek pine honeys according to geographical origin, based on the determination of volatile compounds and physicochemical parameters using MANOVA and Linear Discriminant Analysis. Thirty-nine pine honey samples were collected during the harvesting period 2011 from 4 different regions in Greece known to produce good quality pine honey. The analysis of volatile compounds was performed by Headspace Solid Phase Microextraction-Gas Chromatography/Mass Spectroscopy. Fifty-five volatile compounds were tentatively identified and semi quantified. Physicochemical parameter analysis included the determination of pH, free, lactonic and total acidity, electrical conductivity, moisture, ash, lactonic/free acidity ratio and colour parameters L(*), a(*), b(*). Using 8 selected volatile compounds and 11 physicochemical parameters, the honey samples were satisfactorily classified according to geographical origin using volatile compounds (84.6% correct prediction), physicochemical parameters (79.5% correct prediction) and the combination of both (74.4% correct prediction). PMID- 24176381 TI - Doehlert design-desirability function multi-criteria optimal separation of 17 phenolic compounds from extra-virgin olive oil by capillary zone electrophoresis. AB - In Brazil, the consumption of extra-virgin olive oil (EVOO) is increasing annually, but there are no experimental studies concerning the phenolic compound contents of commercial EVOO. The aim of this work was to optimise the separation of 17 phenolic compounds already detected in EVOO. A Doehlert matrix experimental design was used, evaluating the effects of pH and electrolyte concentration. Resolution, runtime and migration time relative standard deviation values were evaluated. Derringer's desirability function was used to simultaneously optimise all 37 responses. The 17 peaks were separated in 19min using a fused-silica capillary (50MUm internal diameter, 72cm of effective length) with an extended light path and 101.3mmolL(-1) of boric acid electrolyte (pH 9.15, 30kV). The method was validated and applied to 15 EVOO samples found in Brazilian supermarkets. PMID- 24176382 TI - Effect of pesticide 1-[6-chloro-3-methyl-pyridyl-8-nitro-7-methyl-1 2 3 5 6 7 hexahydro imidazo (1,2a)]-pyridine when responding to a wheat plant's antioxidant defense system. AB - The purpose of this research was to establish an analytical method for analysing the 1-[6-chloro-3-methyl-pyridyl-8-nitro-7-methyl-1 2 3 5 6 7-hexahydro imidazo (1,2a)]-pyridine (IPP) residue levels and to evaluate the difference in plant growth and its physical condition. A high performance liquid chromatography connected to a diode array detector (HPLC-DAD) was also employed. The results showed that the content of protein and water soluble carbohydrate (WSC) treated by IPP were initially higher with a significant delayed decrease. The biomarker response showed, even at a lower dose rate, exposure to the IPP caused stress effects and modified the activity of superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT) and polyphenol oxidase (PPO). Different patterns of biomarker responses were observed by an increase in SOD and malondialdehyde (MDA), and differential effects for antioxidant enzymes with a decrease in CAT, POD and PPO. The conclusions show that this profile of biomarker variation could represent a useful method to characterise exposure to IPP in a wheat plant. PMID- 24176383 TI - Effect of limited enzymatic hydrolysis on linoleic acid binding properties of beta-lactoglobulin. AB - beta-Lactoglobulin (BLG) is a member of lipocalin family, proteins with ability to bind small hydrophobic ligands, such as retinol, vitamins and fatty acids. Moreover, BLG is susceptible to protease action producing a wide range of polypeptides depending on the hydrolysis degree (HD). In the present work, the effect of limited enzymatic hydrolysis on fatty acid binding properties of BLG was studied. Linoleic acid (LA) was used as a model fatty acid. Limited enzymatic hydrolysis was performed using alpha-chymotrypsin immobilised on agarose microparticles. BLG hydrolysates were produced at HD: 1%, 3% and 5%. In order to determine the influence of HD on BLG molecular weight SDS-PAGE was used. BLG structural modification and LA binding properties were monitored by means of fluorescence spectroscopic techniques. The increase in HD produced: (i) a BLG degradation and a molecular weight distribution of BLG hydrolysates and (ii) an increased exposition of buried hydrophobic residues, however it was observed a decrease in surface hydrophobicity possibly due to a deterioration of hydrophobic protein domains. It was observed that enzymatic hydrolysis treatment produced a decrease in BLG ability for binding LA. It was concluded that limited enzymatic hydrolysis could deteriorate the specific site on BLG structure necessary for binding LA. PMID- 24176384 TI - Tandem mass spectrometric analysis of human milk triacylglycerols from normal weight and overweight mothers on different diets. AB - The composition and structures of TAGs in the human milk from mothers with different food choices and prepregnancy body mass index were determined with two tandem mass spectrometric methods (negative APCI-MS/MS and positive UHPLC/ESI MS/MS) at the infant's age of three months. The normal weight mothers with recommended food choices had more 18:3n-3 and less 18:0 in their milk than normal weight mothers with non-recommended food choices. A significant difference between the normal weight mothers on the non-recommended food choices and the other groups was seen in acyl carbon number: number of double bond (ACN:DB) groups 54:6, 54:5, 54:3 and 54:2. In ACN:DB 52:7 and 52:6 the two recommended food choices-groups differed significantly from the two non-recommended food choices-groups. The regioisomerism of TAGs varied little despite differences in mother's weight and diet with sn-18:1-16:0-18:1 as the most prevalent regioisomer in the milk (13.8+/-2.7%). The results of this study highlight the importance of structure specific human milk substitutes and the careful selection of the MS/MS methods for analysis of mixtures of several isobaric TAGs. PMID- 24176385 TI - Characteristics and gelling property of phosphorylated gelatin from the skin of unicorn leatherjacket. AB - The characteristics and gelling property of gelatin from the skin of unicorn leatherjacket, phosphorylated with sodium tripolyphosphate (STPP) at various concentrations (0.25%, 0.50%, 0.75% and 1.00% w/w), for different times (1 and 3h) at 65 degrees C, were studied. With the increase of STPP concentration and time, no increase in bound phosphate was observed. The highest gel strength was obtained for gelatin phosphorylated using 0.25% STPP for 1h (P<0.05). When the effect of pH (5, 7, 9 and 11) on phosphorylation and gel property of gelatin was investigated, gelatin phosphorylated at pH 9 had the highest gel strength (204.3g) (P<0.05) and exhibited a finer and more compact network structure with smaller pores. Gelatin became negatively charged (-3.89mV) and might undergo an ionic interaction to a higher extent, thereby strengthening the gel network. Thus, the phosphorylation, under the appropriate condition, could improve the gelling property of gelatin from the skin of unicorn leatherjacket. PMID- 24176386 TI - Polycyclic aromatic hydrocarbons in rice grain dried by different processes: evaluation of a quick, easy, cheap, effective, rugged and safe extraction method. AB - This study aims at developing a method for the determination of 16 polycyclic aromatic hydrocarbons (PAHs) in rice grain samples by combining the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and determination by gas chromatography-mass spectrometry (GC-EI-MS). Quantification limits ranging from 1 to 5MUgkg(-1) were obtained. Recoveries ranged from 70% to 106% for most of the 16 PAHs under analysis. The optimised methodology was applied to assess safety concerning the content of PAHs in white and parboiled rice samples, dried by gas and wood burning. Although benzo(a)pyrene, the marker used for evaluating the carcinogenic risk of PAHs in food, was not detected in the samples, naphthalene and phenanthrene were detected in all of them. Since cereals have been shown to be an important source of PAHs in the diet, methods that perform the evaluation of the quality of this food group become relevant. PMID- 24176387 TI - Changes produced in oils during vacuum and traditional frying of potato chips. AB - In this study the effect of vacuum frying (VF) and traditional frying (TF) on oil degradation, fatty acid composition and alpha-tocopherol content was investigated. Two different refined sunflower oils were used: sunflower oil with high oleic acid content (HOSO) and sunflower oil with synthetic antioxidant (tertiary-butylhydroquinone) (TBHQ-SO). Oil degradation was monitored by measuring the free acidity (FFA), peroxide (PV), p-anisidine (p-AV),) total polar compounds (TPC) and oxidative stability (OE). Oils samples were taken every 4h of frying during 10 consecutive days. Values of FFA, p-AV, TPC using TBHQ-SO with traditional frying were (0.201, 207.0, 25.0) significantly higher than the obtained values with vacuum frying (0.073, 25.8, 11.2). The same parameters by using HOSO were (0.327, 82.0, 21.9) with traditional frying and (0.099, 33.3, 6.4) with vacuum frying. The EO was 2.44 and 7.95 with TBHQ-SO traditional and vacuum frying respectively, and with for HOSO 0.65 and 2.67, respectively. The polyunsaturated fatty acids percentage decreased in all treatments except in TBHQ SOv. The alpha-tocopherol content decreased in all treatments at different rates. At the end of the frying processes the percentages of alpha-tocopherol reduction were TBHQ-SOv (4.90%), TBHQ-SOt (53.62%), HOSOv (96.87%), HOSOt (99.76%). PMID- 24176388 TI - Effect of phenolic compound removal on rheological, thermal and physico-chemical properties of soybean and flaxseed proteins. AB - This study aimed to investigate the effect of removal of phenolics on physico chemical properties of protein isolates obtained from flaxseed and soybean. Proteins were isolated (I) from full-fat (F) and defatted (D) soybean (s) and flaxseed (f) using isoelectric precipitation. Free and bound phenolics were removed from the protein isolates. Thermal and gelation properties of protein isolates before and after removal of phenolics were investigated. Protein isolates from defatted soybean after removal of free and bound phenolics were showed a decrease in thermal stability of glycinin. For protein isolate from full fat soybean, the results showed the removal of free phenolics increase thermal stability of glycinin with increase water holding capacity (WHC) and produce more viscous and less elastic gels as compared to protein isolate after removal of bound phenolics. Removal of free and bound phenolics from flaxseed protein isolates decrease thermal stability, WHC and viscoelastic properties as compared to protein isolate after removal of free phenolics. PMID- 24176389 TI - Development of new active packaging film made from a soluble soybean polysaccharide incorporated Zataria multiflora Boiss and Mentha pulegium essential oils. AB - An active edible film from soluble soybean polysaccharide (SSPS) incorporated with different concentrations of Zataria multiflora Boiss (ZEO) and Mentha pulegium (MEO) essential oils was developed, and the film's optical, wettability, thermal, total phenol and antioxidant characteristics were investigated, along with their antimicrobial effectiveness against Staphylococcus aureus, Bacillus cereus, Escherichia coli O157:H7, Pseudomonas aeruginosa and Salmonella typhimurium. The film's colour became darker and more yellowish and had a lower gloss as the levels of ZEO or MEO were increased. Antioxidant activity of the films was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power assays. DPPH was reduced in the range of 19.84-74.12% depending on the essential oil type and concentration. Film incorporated with 3% (v/v) ZEO showed the highest DPPH radical scavenging activity and ferric reducing antioxidant power (IC50=4188.60+/-21.73mg/l and EC50=8.86+/-0.09mg/ml, respectively), compared with the control and MEO added film. Films containing ZEO were more effective against the tested bacteria than those containing MEO. S. aureus was found to be the most sensitive bacterium to both ZEO or MEO, followed by B. cereus and E. coli. A highest inhibition zone of 387.05mm(2) was observed for S. aureus around the films incorporated with 3% (v/v) ZEO. The total inhibitory zone of 3% (v/v) MEO formulated films was 21.98 for S. typhimurium and 10.15mm(2) for P. aeruginosa. Differential scanning calorimetry (DSC) analysis revealed a single glass transition temperature (Tg) between 16 and 31 degrees C. The contact angle increased up to 175% and 38% as 3% (v/v) of ZEO or MEO used: it clearly shows that films with ZEO were more hydrophobic than those with MEO. The results showed that these two essential oils could be incorporated into SSPS films for food packaging. PMID- 24176390 TI - Inhaled aztreonam for chronic Burkholderia infection in cystic fibrosis: a placebo-controlled trial. AB - BACKGROUND: Individuals with Burkholderia spp. infection have historically been excluded from efficacy trials of inhaled antibiotics, including aztreonam for inhalation solution (AZLI). METHODS: A double-blind, placebo-controlled, 24-week trial of continuous AZLI/placebo treatment was undertaken in individuals with cystic fibrosis (CF) and chronic Burkholderia spp. infection. All subjects also received usual medical care (determined by their physicians). Additional antibiotic use was not restricted. RESULTS: Baseline FEV1% predicted values ranged from 15.8% to 114.6%. No significant treatment differences (AZLI vs. placebo) were observed at week 24 for any endpoints, including FEV1% predicted, number of respiratory exacerbations requiring systemic/inhaled antibiotics, or hospitalizations. Continuous AZLI administration was well tolerated. Burkholderia spp. susceptibility to antibiotics commonly used in CF therapy showed little change. CONCLUSIONS: 24-weeks of continuous AZLI treatment did not significantly improve lung function in CF subjects with chronic Burkholderia spp. infection. Non-study antibiotic use may have confounded any potential AZLI effects. PMID- 24176391 TI - Effect of vehicle and route of administration of letrozole on ovarian function in a bovine model. AB - The objective of this study was to determine the effects of vehicle and route of administration of letrozole on ovarian function in sexually mature beef heifers. On Day 3 (Day 0=ovulation), heifers were assigned randomly to four treatment groups and given 1mgkg(-1) letrozole intravenously (iv, n=10) or intramuscularly (im, n=10) or given a placebo iv (control iv, n=5) or im (control im, n=5). The interwave interval was longer in heifers treated with letrozole im than in im and iv controls (11.7+/-0.30 vs 9.5+/-0.50 and 10+/-0.43, respectively; P<0.05). Corpus luteum diameter profiles and plasma progesterone concentrations were greater (P<0.03 and P<0.05, respectively) in heifers treated with letrozole im compared with control im. Plasma oestradiol concentrations were lower in both letrozole-treated groups compared with controls (P<=0.03). Plasma LH concentrations tended to be elevated at the time of wave emergence in heifers treated with letrozole im compared with other groups (group-by-day interaction, P=0.06) and plasma FSH concentrations tended to be greater (P<0.09) in heifers treated with letrozole by either route compared with a single control group. We conclude that intramuscular administration of letrozole in oil is a feasible route and vehicle for the development of a letrozole-based treatment protocol for herd synchronisation in cattle. PMID- 24176392 TI - Blockade of D3 receptors by YQA14 inhibits cocaine's rewarding effects and relapse to drug-seeking behavior in rats. AB - Preclinical studies suggest that dopamine D3 receptor (D3R) antagonists are promising for the treatment of drug abuse and addiction. However, few D3R antagonists have potential to be tested in humans due to short half-life, toxicity or limited preclinical research into pharmacotherapeutic efficacy. Here, we report on a novel D3R antagonist YQA14, which has improved half-life and pharmacokinetic profile and which displays potent pharmacotherapeutic efficacy in attenuating cocaine reward and relapse to drug-seeking behavior. Electrical brain stimulation reward (BSR) in laboratory animals is a highly sensitive experimental approach to evaluate a drug's rewarding effects. We found that cocaine (2 mg/kg) significantly enhanced electrical BSR in rats (i.e., decreased stimulation threshold for BSR), while YQA14 alone had no effect on BSR. Pretreatment with YQA14 significantly and dose-dependently attenuated cocaine-enhanced BSR. YQA14 also facilitated extinction from drug-seeking behavior in rats during early behavioral extinction, and attenuated cocaine- or contextual cue-induced relapse to drug-seeking behavior. YQA14 alone did not maintain self-administration in either naive rats or in rats experienced at cocaine self-administration. YQA14 also inhibited expression of repeated cocaine-induced behavioral sensitization. These findings suggest that YQA14 may have pharmacotherapeutic potential in attenuating cocaine-taking and cocaine-seeking behavior. Thus, YQA14 deserves further investigation as a promising agent for treatment of cocaine addiction. PMID- 24176393 TI - Psychosocial work factors and long sickness absence in Europe. AB - BACKGROUND: Studies exploring a wide range of psychosocial work factors separately and together in association with long sickness absence are still lacking. OBJECTIVES: The objective of this study was to explore the associations between psychosocial work factors measured following a comprehensive instrument (Copenhagen psychosocial questionnaire, COPSOQ) and long sickness absence (> 7 days/year) in European employees of 34 countries. An additional objective was to study the differences in these associations according to gender and countries. METHODS: The study population consisted of 16 120 male and 16 588 female employees from the 2010 European working conditions survey. Twenty-five psychosocial work factors were explored. Statistical analysis was performed using multilevel logistic regression models and interaction testing. RESULTS: When studied together in the same model, factors related to job demands (quantitative demands and demands for hiding emotions), possibilities for development, social relationships (role conflicts, quality of leadership, social support, and sense of community), workplace violence (physical violence, bullying, and discrimination), shift work, and job promotion were associated with long sickness absence. Almost no difference was observed according to gender and country. CONCLUSIONS: Comprehensive prevention policies oriented to psychosocial work factors may be useful to prevent long sickness absence at European level. PMID- 24176394 TI - Polycation-assisted DNA detection by reduction triggered fluorescence amplification probe. AB - We have developed a fluorescence detection system for DNA, assisted by a comb type cationic polymer (PLL-g-DX), for accelerating the reaction turnover. The combination of fluorogenic DNA probes with a comb-type cationic polymer has been demonstrated to be an effective means of signal amplification during the detection process. The method described herein represents a simple and enzyme free detection. PMID- 24176395 TI - 2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3beta inhibitors. AB - A series of 2-(2-phenylmorpholin-4-yl)pyrimidin-4(3H)-ones was synthesized and examined for their inhibitory activity against glycogen synthase kinase-3beta (GSK-3beta). We found 21, 29 and 30 to possess potent in vitro GSK-3beta inhibitory activity with good in vitro PK profiles. 21 demonstrated significant decrease of tau phosphorylation after oral administration in mice and excellent PK profiles. PMID- 24176396 TI - The discovery of novel N-(2-pyrimidinylamino) benzamide derivatives as potent hedgehog signaling pathway inhibitors. AB - Hedgehog signaling pathway inhibitors are emerging as new therapeutic intervention against cancer. A novel series of N-(2-pyrimidinylamino) benzamide derivatives as hedgehog signaling pathway inhibitors were designed and synthesized. Most compounds presented significant inhibitory effect on hedgehog signaling pathway, among which 21 compounds exhibited more potent than vismodegib. Furthermore, compound 6a showed moderate pharmacokinetic properties in vivo, representing a promising lead compound for further exploration. PMID- 24176397 TI - Antiproliferative activities and SAR studies of substituted anthraquinones and 1,4-naphthoquinones. AB - STAT3 is constitutively active in a large variety of cancers. The search for STAT3 inhibitors led to the discoveries of LLLs 3 and 12, which are substituted anthraquinones. LLL12 is an extremely potent compound that exhibits high levels of antiproliferative activity. Herein the synthesis and evaluation of compounds containing either an anthraquinone or 1,4-naphthoquinone moiety are reported. Analogs were evaluated in several cancer cell lines. Interestingly, it was found that the anthraquinones did not follow the same trends as the 1,4-naphthoquinones in regards to potency. LLL12, which contains a sulfonamide at position 1, was found to be the most potent of the anthraquinones. In contrast, the methyl ketone and methyl ester derivatives (LLLs 3.1 and 5.1) were found to be the most potent of the 1,4-naphthoquinones. Selected 1,4-naphthoquinones were also evaluated in the STAT3 fluorescence polarization assay in order to evaluate their abilities to bind to the STAT3 SH2 domain. They were found to have similar affinities, and their activities suggest that STAT3 is one of their molecular targets. PMID- 24176398 TI - Synthesis and initial biological evaluation of substituted 1-phenylamino-2-thio 4,5-dimethyl-1H-imidazole derivatives. AB - In this work, some new 2-[(4,5-dimethyl-1-(arylamino)-1H-imidazol-2-yl)thio]-1 (aryl)ethanone derivatives were synthesized and investigated for their antibacterial, antifungal and anticancer activities. Toxicity of the most effective compounds was established by performing Brine-Shrimp lethality assay. Antifungal activity of the compounds was found to be higher than antibacterial and anticancer activities of the compounds. PMID- 24176399 TI - Synthetic alpha-(aminomethyl)-gamma-butyrolactones and their anti-pancreatic cancer activities. AB - Aminated alpha-methylene-gamma-butyrolactones, which are readily synthesized with facile control of the diastereoisomerism, provide an economical and commercially viable alternative to the use of aminated natural products. These aminoloactones, which exhibit excellent activity against three pancreatic cancer cell lines when measured at 10 MUM-Panc-1, MIA PaCa-2, and BxPC-3-and are comparable to or better than parthenolide and dimethylaminoparthenolide (DMAPT, LC-1). It has also been shown that there is an effect on the biological activity depending on the identity of the amine. PMID- 24176401 TI - Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub micromolar potency in the cell-based replicon assay. AB - Optimization efforts on the anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors 1 and 2 resulted in the identification of multiple structural elements that contributed to improved cell culture potency. The additive effect of these elements resulted in compound 46, an inhibitor with enzymatic (IC50) and cell culture (EC50) potencies of less than 100 nanomolar. PMID- 24176400 TI - Synthesis of novel 7-substituted pyrido[2',3':4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues and evaluation of their inhibitory activity against Ser/Thr kinases. AB - The efficient synthesis of 7-substituted pyrido[2',3':4,5]furo[3,2-d]pyrimidin-4 amines and their N-aryl analogues is described. 3,5-Dibromopyridine was converted into 3-amino-6-bromofuro[3,2-b]pyridine-2-carbonitrile intermediate which was formylated with DMFDMA. Functionalization at position 7 of the tricyclic scaffold was accomplished, before or after cyclisation step, by palladium-catalyzed Suzuki Miyaura cross-coupling while the pyrimidin-4-amines and N-aryl counterparts were synthesized by microwave-assisted formamide degradation and Dimroth rearrangement, respectively. The final products were evaluated for their potent inhibition of a series of five Ser/Thr kinases (CDK5/p25, CK1delta/epsilon, CLK1, DYRK1A, GSK3alpha/beta). Compound 35 showed the best inhibitory activity with an IC50 value of 49 nM and proved to be specific to CLK1 among the panel of tested kinases. PMID- 24176402 TI - [Renal cancer and hereditary diseases]. AB - Renal tumors associated with hereditary diseases are a rare entity characterized by many renal tumors and other manifestations such as pulmonary, neurological and dermatological expressions. The management requires a close collaboration between surgical specialties and geneticists. Precocious, bilateral and/or multifocal tumors call to mind a hereditary disease. Early diagnosis and screening are essential to optimize a strict observation and a most conservative treatment. PMID- 24176403 TI - [Radiofrequency ablation of kidney tumors]. PMID- 24176404 TI - [Extracorporeal shock wave lithotripsy]. AB - Extracorporeal shock wave lithotripsy (ESWL) is a treatment of urinary stones with the uses of shock wave. The principle of ESWL will be exposed. The ways to localize the stones are then discussed with the mode of anesthesia. One session of ESWL will be presented in details. Contraindications, indications, prerequisit, complications and results will be briefly described. PMID- 24176405 TI - [Management of adult uretero-pelvic junction obstruction]. PMID- 24176406 TI - [Transurethral bladder resection of non muscle invasive bladder cancer with Hexvix (r)]. AB - Bladder neoplasms are the second most frequent urological cancer after prostate cancer. Bladder neoplasms arise from urothelial tissue and can either be restricted within the Mucosa and the Lamina Propria (i.e., non muscle invasive bladder cancer [NMIBC]) or invade the Muscularis Propria (i.e., muscle invasive bladder cancer [MIBC]). An exhaustive transuretral resection of the bladder tumor (TURBT) has always been seen a surrogate of quality for the initial step of the treatment. Although a large majority of bladder tumors can be easily identified macroscopically, there are flat lesions (i.e., carcinoma in situ [CIS]), which are more difficult to diagnose. To improve detection of flat lesions, a fluorescence diagnosis under blue light has been proposed during cystoscopy. Photodynamic diagnosis is performed using blue light after preoperative intravesical instillation of hexaminolaevulinic acid (Hexvix((r))) to enhance visual contrast between urothelial cancer and normal tissue. Thus, the quality of TURBT appears to be improved in selected cases with a controversial benefit on the recurrence free survival. Due to its medico-economical constraints, worldwide spread of fluorescence cystoscopy is still limited and restricted to specific cases. PMID- 24176407 TI - [Prognosis of neurological bladders]. AB - Numerous neurological diseases may hurt the neurological command of the miction and thus provoke the dysfunctions of the bladder and/or the urinary sphincter. These dysfunctions leads to annoying symptoms (incontinence, retention or both) but can also cause grave complications (renal infections, calculations, renal insufficiency, tumor of bladder). The forecast of the neurological bladders consists to prevent the urinary complications and to improve the comfort/quality of life. The initial care must be early and multidisciplinary. The objective of a low-pressure bladder emptied regularly without permanent drainage is common to all the situations. The objective of a dry and autonomous patient for the elimination of the urine is the main goal for the optimization of the quality of life. The restoration of a sexuality, a fertility, a control of the continence and the faecal exemption are also important parameters to improve of the quality of life. PMID- 24176408 TI - [Treatment of the urethral sphincter insufficiency]. AB - The intrinsic sphincter insufficiency is a cause of stress urinary incontinence. Its definition is clinical and based on urodynamics. It is mostly met with women, in context of the post-obstetrical period or older women in a multifactorial context. For men, it occurs mainly as complication of the surgery of the cancer of prostate or bladder. An initial, clinical and paraclinical assessment allows to confirm the diagnosis of intrinsic sphincter insufficiency, to estimate its severity, and to identify associated mechanisms of incontinence (urethral hypermobility, bladder overactivity) to choose the most adapted treatment. The perineal reeducation is the treatment of first intention in both sexes. At the menopausal woman, the local hormonotherapy is a useful additive. In case of failure or of incomplete efficiency, the treatment of the intrinsic sphincter insufficiency is surgical. Bulking agents, urethral slings, peri-urethral balloons and artificial sphincter are 4 therapeutic options to discuss according to history, the severity of the incontinence, the expectations of the patient. PMID- 24176409 TI - [Antibiotic prophylaxis in urologic surgery]. AB - Antibiotic prophylaxis is highly effective in prevention of postoperative infection. The aim is bacterial growth inhibition during operative procedure. To avoid side-effects, such as increase of bacterial resistant strains and modification of patient flora, some accurate rules are relevant and among them most important are: 1) never last more than 24 hours; 2) choose molecule active against bacteria generally responsible of infections according to the type of operation, but not used in therapeutic field; 3) of crucial importance is the timing of administration: it must start before operation, ideally 30 to 60 minutes before incision. Antibiotic prophylaxis cost must be considered as it accounts for more than 30% of total antibiotic use in hospital. PMID- 24176410 TI - The GRADE recommendations. weak recommendations are unhelpful to decision makers. PMID- 24176411 TI - Personal exposures to fine particulate matter and black carbon in households cooking with biomass fuels in rural Ghana. AB - OBJECTIVE: To examine cooking practices and 24-h personal and kitchen area exposures to fine particulate matter (PM2.5) and black carbon in cooks using biomass in Ghana. METHODS: Researchers administered a detailed survey to 421 households. In a sub-sample of 36 households, researchers collected 24-h integrated PM2.5 samples (personal and kitchen area); in addition, the primary cook was monitored for real-time PM2.5. All filters were also analyzed for black carbon using a multi-wavelength reflectance method. Predictors of PM2.5 exposure were analyzed, including cooking behaviors, fuel, stove and kitchen type, weather, demographic factors and other smoke sources. RESULTS: The majority of households cooked outdoors (55%; 231/417), used biomass (wood or charcoal) as their primary fuel (99%; 412/413), and cooked on traditional fires (77%, 323/421). In the sub-sample of 29 households with complete, valid exposure monitoring data, the 24-h integrated concentrations of PM2.5 were substantially higher in the kitchen sample (mean 446.8 ug/m3) than in the personal air sample (mean 128.5 ug/m3). Black carbon concentrations followed the same pattern such that concentrations were higher in the kitchen sample (14.5 ug/m3) than in the personal air sample (8.8 ug/m3). Spikes in real-time personal concentrations of PM2.5 accounted for the majority of exposure; the most polluted 5%, or 72 min, of the 24-h monitoring period accounted for 75% of all exposure. Two variables that had some predictive power for personal PM2.5 exposures were primary fuel type and ethnicity, while reported kerosene lantern use was associated with increased personal and kitchen area concentrations of black carbon. CONCLUSION: Personal concentrations of PM2.5 exhibited considerable inter-subject variability across kitchen types (enclosed, semi-enclosed, outdoor), and can be elevated even in outdoor cooking settings. Furthermore, personal concentrations of PM2.5 were not associated with kitchen type and were not predicted by kitchen area samples; rather they were driven by spikes in PM2.5 concentrations during cooking. Personal exposures were more enriched with black carbon when compared to kitchen area samples, underscoring the need to explore other sources of incomplete combustion such as roadway emissions, charcoal production and kerosene use. PMID- 24176412 TI - Variability in the correlation between nicotine and PM2.5 as airborne markers of second-hand smoke exposure. AB - The aim of this study was to assess the relationship between particulate matter of diameter<=2.5 um (PM2.5) and airborne nicotine concentration as markers of second-hand smoke exposure with respect to the setting studied, the intensity of exposure, and the type of environment studied (indoors or outdoors). Data are derived from two independent studies that simultaneously measured PM2.5 and nicotine concentrations in the air as airborne markers of second-hand smoke exposure in public places and workplaces, including health care centres, bars, public administration offices, educational centres, and transportation. We obtained 213 simultaneous measures of airborne nicotine and PM2.5. Nicotine in the air was measured with active samplers containing a sodium bisulphate-treated filter that was analysed by gas chromatography/mass spectrometry. PM2.5 was measured with a SidePak AM510 Personal Aerosol Monitor. We calculated Spearman's rank correlation coefficient and its 95% confidence intervals (95% CI) between both measures for overall data and stratified by setting, type of environment (indoors/outdoors), and intensity of second-hand smoke exposure (low/high, according to the global median nicotine concentration). We also fitted generalized regression models to further explore these relationships. The median airborne nicotine concentration was 1.36 ug/m3, and the median PM2.5 concentration was 32.13 ug/m3. The overall correlation between both markers was high (Spearman's rank correlation coefficient=0.709; 95% CI: 0.635-0.770). Correlations were higher indoors (Spearman's rank correlation coefficient=0.739; 95% CI: 0.666-0.798) and in environments with high second-hand smoke exposure (Spearman's rank correlation coefficient=0.733; 95% CI: 0.631-0.810). The multivariate analysis adjusted for type of environment and intensity of second hand smoke exposure confirmed a strong relationship (7.1% increase in geometric mean PM2.5 concentration per ug/m3 nicotine concentration), but only in indoor environments in a stratified analysis (6.7% increase; 95% CI: 4.3-9.1%). Although the overall correlation between airborne nicotine and PM2.5 is high, there is some variability regarding the type of environment and the intensity of second hand smoke exposure. In the absence of other sources of combustion, air nicotine and PM2.5 measures can be used indoors, while PM2.5 should be used outdoors with caution. PMID- 24176413 TI - The methodology of Dynamic Uncertain Causality Graph for intelligent diagnosis of vertigo. AB - Vertigo is a common complaint with many potential causes involving otology, neurology and general medicine, and it is fairly difficult to distinguish the vertiginous disorders from each other accurately even for experienced physicians. Based on comprehensive investigations to relevant characteristics of vertigo, we propose a diagnostic modeling and reasoning methodology using Dynamic Uncertain Causality Graph. The symptoms, signs, findings of examinations, medical histories, etiology and pathogenesis, and so on, are incorporated in the diagnostic model. A modularized modeling scheme is presented to reduce the difficulty in model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. We resort to the "chaining" inference algorithm and weighted logic operation mechanism, which guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal insights into underlying interactions among diseases and symptoms intuitively demonstrate the reasoning process in a graphical manner. These solutions make the conclusions and advices more explicable and convincing, further increasing the objectivity of clinical decision-making. Verification experiments and empirical evaluations are performed with clinical vertigo cases. The results reveal that, even with incomplete observations, this methodology achieves encouraging diagnostic accuracy and effectiveness. This study provides a promising assistance tool for physicians in diagnosis of vertigo. PMID- 24176414 TI - External fixator configurations in tibia fractures: 1D optimization and 3D analysis comparison. AB - The use of external fixation devices in orthopedic surgery is very common in open tibial fractures. A properly applied fixator may improve the healing process while one improperly applied might delay the healing process. The several external fixator systems used in clinical today, can be categorized into uniplanar-unilateral, uniplanar-bilateral, biplanar and multiplanar. The stability on the fracture focus and, therefore, the fracture healing process, is related with the type of external fixator configuration that is selected. The aim of this study is to discuss the principles for the successful application of unilateral-uniplanar external fixation, the assembly of its components, for the case of a transverse fractures using computational models. In this context, the fixation stiffness characteristics are evaluated using a simplified 1D finite element model for the tibia and external fixator. The beams are modeled with realistic cross-sectional geometry and material properties instead of a simplified model. The VABS (the Variational Asymptotic Beam Section analysis) methodology is used to compute the cross-sectional model for the generalized Timoshenko model, which was embedded in the finite element solver FEAP. The use of Timoshenko beam theory allows accounting for several kinds of loads, including torsion moments. Optimal design is performed with respect to the assembly of fixator components using a genetic algorithm. The optimization procedure is based on the evaluation of an objective function, which is dependent on the displacement at the fracture focus. The initial and optimal results are compared by performing a 3D analysis, for which different three-dimensional finite element models are created. The geometrical model of a tibia is created on the basis of data acquired by CAT scan, made for a healthy tibia of a 22 year old male. The 3D comparison of the 1D optimal results show a clear improvement on the objective function for the several load cases and, therefore, it is shown that appropriate selection of the external fixator geometrical features can lead to an improvement on the stability of the external fixator. The results obtained show that the optimal position of the side beam and the first pin should be as close as possible to the bone interface and as close as possible to the fracture focus, respectively. Concerning the second pin, it should be placed away from the first pin in case of flexion loads, to axial and torsion loads the second pin should be placed near the first pin. PMID- 24176415 TI - Clinical neurogenetics: recent advances in the genetics of epilepsy. AB - Epilepsy represents a diverse group of disorders with primary and secondary genetic etiologies, as well as non-genetic causes. As more causative genes are identified, genetic testing is becoming increasingly important in the evaluation and management of epilepsy. This article outlines the clinical approach to epilepsy patients, with emphasis on genetic testing. Specific targeted tests are available for numerous individual genetic causes of epilepsy. Broader screening tests, such as chromosome microarray analysis and whole exome sequencing, have also been developed. As a standardized protocol for genetic testing has not been established, individualized diagnostic approaches to epilepsy patients should be used. PMID- 24176416 TI - Clinical neurogenetics: stroke. AB - Understanding the genetic architecture of cerebrovascular disease holds promise of novel stroke prevention strategies and therapeutics that are both safe and effective. Apart from a few single-gene disorders associated with cerebral ischemia or intracerebral hemorrhage, stroke is a complex genetic phenotype that requires careful ascertainment and robust association testing for discovery and validation analyses. The recently uncovered shared genetic contribution between clinically manifest stroke syndromes and closely related intermediate cerebrovascular phenotypes offers effective and efficient approaches to complex trait analysis. PMID- 24176418 TI - Clinical neurogenetics: autism spectrum disorders. AB - Autism spectrum disorders are neurodevelopmental disorders characterized by deficits in social interactions, communication, and repetitive or restricted interests. There is strong evidence that de novo or inherited genetic alterations play a critical role in causing Autism Spectrum Disorders, but non-genetic causes, such as in utero infections, may also play a role. Magnetic resonance imaging based and autopsy studies indicate that early rapid increase in brain size during infancy could underlie the deficits in a large subset of subjects. Clinical studies show benefits for both behavioral and pharmacological treatment strategies. Genotype-specific treatments have the potential for improving outcome in the future. PMID- 24176419 TI - Clinical neurogenetics: dystonia from phenotype to genotype. AB - Dystonia can arise from genetic syndromes or can be secondary to nongenetic injuries; both causes can produce pure dystonia, dystonia plus other movement disorders, or paroxysmal mixed movement disorders. Genetic causes of dystonia are inherited through dominant, recessive, X-linked, and mitochondrial mechanisms, may show anticipation, are variably penetrant, and may be limited to small ethnic populations or single families. In this article, the genetic causes of dystonia, an algorithm for their diagnosis and management, information on common medications and surgical treatments, and resources for affected families and those interested in advancing research are presented. PMID- 24176417 TI - Clinical neurogenetics: amyotrophic lateral sclerosis. AB - Our understanding of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is expanding rapidly as its genetic causes are uncovered. The pace of new gene discovery over the last 5 years has accelerated, providing new insights into the pathogenesis of disease and highlighting biological pathways as targets for therapeutic development. This article reviews our current understanding of the heritability of ALS and provides an overview of each of the major ALS genes, highlighting their phenotypic characteristics and frequencies as a guide for clinicians evaluating patients with ALS. PMID- 24176421 TI - Muscular dystrophies and other genetic myopathies. AB - With advances in the genetics of muscle disease, the term, muscular dystrophy, has expanded to include mutations in an increasing large list of genes. This review discusses the genetics, pathophysiology, and potential treatments of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Other forms of muscular dystrophy and other genetic muscle disorders are also discussed to provide an overview of this complex clinical problem. PMID- 24176420 TI - Clinical neurogenetics: autosomal dominant spinocerebellar ataxia. AB - The autosomal dominant spinocerebellar ataxias are a diverse and clinically heterogeneous group of disorders characterized by degeneration and dysfunction of the cerebellum and its associated pathways. Clinical and diagnostic evaluation can be challenging because of phenotypic overlap among causes, and a stratified and systematic approach is essential. Recent advances include the identification of additional genes causing dominant genetic ataxia, a better understanding of cellular pathogenesis in several disorders, the generation of new disease models that may stimulate development of new therapies, and the use of new DNA sequencing technologies, including whole-exome sequencing, to improve diagnosis. PMID- 24176422 TI - Clinical neurogenetics: neurologic presentations of metabolic disorders. AB - This article reviews aspects of the neurologic presentations of selected treatable inborn errors of metabolism within the category of small molecule disorders caused by defects in pathways of intermediary metabolism. Disorders that are particularly likely to be seen by neurologists include those associated with defects in amino acid metabolism (organic acidemias, aminoacidopathies, urea cycle defects). Other disorders of small molecule metabolism are discussed as additional examples in which early treatments have the potential for better outcomes. PMID- 24176424 TI - Clinical neurogenetics: fragile x-associated tremor/ataxia syndrome. AB - This article summarizes the clinical findings, genetics, pathophysiology, and treatment of fragile X-associated tremor ataxia syndrome. The disorder occurs from a CGG repeat (55-200) expansion in the fragile X mental retardation 1 gene. It manifests clinically in kinetic tremor, gait ataxia, and executive dysfunction, usually in older men who carry the genetic abnormality. The disorder has distinct radiographic and pathologic findings. Symptomatic treatment is beneficial in some patients. The inheritance is X-linked and family members may be at risk for other fragile X-associated disorders. This information is useful to neurologists, general practitioners, and geneticists. PMID- 24176423 TI - Clinical neurogenetics: neuropathic lysosomal storage disorders. AB - The lysosomal storage disorders are a clinically heterogeneous group of inborn errors of metabolism, associated with the accumulation of incompletely degraded macromolecules within several cellular sites. Affected individuals present with a broad range of clinical problems, including hepatosplenomegaly and skeletal dysplasia. Onset of symptoms may range from birth to adulthood. Most are associated with neurologic features. Later-onset forms are often misdiagnosed as symptoms, which might include psychiatric manifestations, are slowly progressive, and may precede other neurologic or systemic features. Symptomatic care, which remains the mainstay for most subtypes, can lead to significant improvement in quality of life. PMID- 24176425 TI - Clinical neurogenetics: huntington disease. AB - Huntington disease (HD) is an autosomal dominant, adult-onset, progressive neurodegenerative disease characterized by the triad of abnormal movements (typically chorea), cognitive impairment, and psychiatric problems. It is caused by an expanded CAG repeat in the gene encoding the protein huntingtin on chromosome 4 and causes progressive atrophy of the striatum as well as cortical and other extrastriatal structures. Genetic testing has been available since 1993 to confirm diagnosis in affected adults and for presymptomatic testing in at-risk individuals. This review covers HD signs, symptoms, and pathophysiology; current genetic testing issues; and current and future treatment strategies. PMID- 24176426 TI - Clinical neurogenetics: friedreich ataxia. AB - Friedreich ataxia is the most common autosomal recessive ataxia. It is a progressive neurodegenerative disorder, typically with onset before 20 years of age. Signs and symptoms include progressive ataxia, ascending weakness and ascending loss of vibration and joint position senses, pes cavus, scoliosis, cardiomyopathy, and arrhythmias. There are no disease-modifying medications to either slow or halt the progression of the disease, but research investigating therapies to increase endogenous frataxin production and decrease the downstream consequences of disrupted iron homeostasis is ongoing. Clinical trials of promising medications are underway, and the treatment era of Friedreich ataxia is beginning. PMID- 24176427 TI - Clinical neurogenetics: behavioral management of inherited neurodegenerative disease. AB - Psychiatric symptoms often manifest years before overt neurologic signs in patients with inherited neurodegenerative disease. The most frequently cited example of this phenomenon is the early onset of personality changes in "presymptomatic" Huntington patients. In some cases the changes in mood and cognition are even more debilitating than their neurologic symptoms. The goal of this article is to provide the neurologist with a concise primer that can be applied in a busy clinic or private practice. PMID- 24176429 TI - Dual-energy x-ray absorptiometry scan autoanalysis vs manual analysis. AB - The measurement of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) is valuable for the determination of 10-yr fracture risk and for antifracture treatment follow-up. Ensuring patient scans are performed with accuracy, and reliability is imperative, requiring both technician competence and regular machine calibration. With DXA, analysis of each scan can be performed either with the machine's default autoanalysis or can be optimized manually. For 1 yr, all patients sent for DXA measurements to the Saskatoon Osteoporosis Center had each lumbar spine and hip scan analyzed with both manual and autoanalysis methods and the 2 sets of scans compared. We compared the concordance between the 2 analysis methods by calculating a BMD percent error for all of the scans, with the manually adjusted scans acting as the reference standard. Mann-Whitney U tests were completed to test for statistically significance differences between analysis types. In this investigation, scans completed with manual analysis were more accurate with respect to BMD (up to 4.7% error) and T-scores (up to 0.38 difference). In addition, many errors were identified with autoanalysis. Consequently, technicians using DXA should not rely on autoanalysis but rather be trained in and use manual analysis. PMID- 24176430 TI - The effect of extending femur scan length on BMD results on the Hologic Discovery W scanner. AB - A longer dual-energy X-ray absorptiometry scan field of the hip may be useful for the detection of atypical subtrochanteric femur fractures. It has been demonstrated in a Prodigy GE/Lunar scanner that extending the scan length does not affect bone mineral density (BMD) results at the total hip or femoral neck. We hypothesized that extending the scan field on a Hologic Discovery scanner would also have no effect on BMD results at the hip. Thirty subjects who presented for standard of care dual-energy X-ray absorptiometry scans underwent paired default (15.2 cm) and extended (24.1 cm) length hip scans. There was no significant difference in the total hip or any of the component subregions of femoral neck, greater trochanter, or intertrochanteric (shaft) BMD between the default and extended length scans. PMID- 24176431 TI - Combat sports practice favors bone mineral density among adolescent male athletes. AB - The aim of this study was to determine the impact of combat sports practice on bone mineral density (BMD) and to analyze the relationship between bone parameters and anthropometric measurements, bone markers, and activity index (AI). In other words, to detect the most important determinant of BMD in the adolescent period among combat sports athletes. Fifty athletes engaged in combat sports, mean age 17.1+/-0.2 yr, were compared with 30 sedentary subjects who were matched for age, height, and pubertal stage. For all subjects, the whole-body BMD, lumbar spine BMD (L2-L4), and BMD in the pelvis, arms, and legs was measured by dual-energy X-ray absorptiometry, and anthropometric measurements were evaluated. Daily calcium intake, bone resorption, and formation markers were measured. BMD measurements were greater in the combat sports athletes than in the sedentary group (p<0.01). Weight, body mass index, and lean body mass were significantly correlated with BMD in different sites. Daily calcium consumption lower than daily calcium intake recommended in both athletes and sedentary group. AI was strongly correlated with all BMD measurements particularly with the whole body, legs, and arms. Negative correlations were observed between bone markers and BMD in different sites. The common major predictor of BMD measurements was AI (p<0.0001). AI associated to lean body mass determined whole-body BMD until 74%. AI explained both BMD in arms and L2-L4 at 25%. AI associated to height can account for 63% of the variance in BMD legs. These observations suggested that the best model predicting BMD in different sites among adolescent combat sports athletes was the AI. Children and adolescents should be encouraged to participate in combat sports to maximize their bone accrual. PMID- 24176432 TI - Bilateral ophthalmic origin of the middle meningeal artery. AB - The origin of the middle meningeal artery (MMA) may vary although it can arise from the ophthalmic artery (OA) with a 0.5% prevalence. We report the exceptional bilateral asymmetric origin from the OAs that has not previously been reported in the literature. Surgeons should be aware of this variation as it could be crucial in the setting of an endovascular approach for meningeal lesions, as in our observation. A 50-year-old male underwent a preoperative cerebral digital subtracted angiography that incidentally revealed MMAs arising from the OA on both sides. In fact, the origin was asymmetric because it was complete on the right side with the anterior and posterior branches of the MMA arising from the OA, whereas it was partial on the left side, with only the anterior branch arising from the OA. The CT scan showed the absence of the foramen spinosum only on the right side. This paper discusses the unique anatomic variation in the light of MMA embryology and its different origins. Knowledge of this variation may have a practical impact in cases of cerebral embolization. PMID- 24176433 TI - Ultrafiltration therapy for acute decompensated heart failure: lessons learned from 2 major trials. PMID- 24176434 TI - Atypical is becoming typical in ST-elevation myocardial infarction presentation, but delays persist for women. PMID- 24176435 TI - Posttraumatic stress disorder and risk for coronary heart disease: a meta analytic review. AB - OBJECTIVE: The aim of this study was to estimate the association of posttraumatic stress disorder (PTSD) with risk for incident coronary heart disease (CHD). DESIGN: A systematic review and meta-analysis were used as study designs. DATA SOURCES: Articles were identified by searching Ovid MEDLINE, PsycINFO, Scopus, Cochrane Library, PILOTS database, and PubMed Related Articles and through a manual search of reference lists (1948-present). STUDY SELECTION: All studies that assessed PTSD in participants initially free of CHD and subsequently assessed CHD/cardiac-specific mortality were included. DATA EXTRACTION: Two investigators independently extracted estimates of the association of PTSD with CHD, as well as study characteristics. Odds ratios were converted to hazard ratios (HRs), and a random-effects model was used to pool results. A secondary analysis including only studies that reported estimates adjusted for depression was conducted. RESULTS: Six studies met our inclusion criteria (N = 402,274); 5 of these included depression as a covariate. The pooled HR for the magnitude of the relationship between PTSD and CHD was 1.55 (95% CI 1.34-1.79) before adjustment for depression. The pooled HR estimate for the 5 depression-adjusted estimates (N = 362,950) was 1.27 (95% CI 1.08-1.49). CONCLUSION: Posttraumatic stress disorder is independently associated with increased risk for incident CHD, even after adjusting for depression and other covariates. It is common in both military veterans and civilian trauma survivors, and these results suggest that it may be a modifiable risk factor for CHD. Future research should identify the mechanisms of this association and determine whether PTSD treatment offsets CHD risk. PMID- 24176436 TI - A large-scale cluster randomized trial to determine the effects of community based dietary sodium reduction--the China Rural Health Initiative Sodium Reduction Study. AB - BACKGROUND: Cardiovascular diseases are the leading cause of death and disability in China. High blood pressure caused by excess intake of dietary sodium is widespread and an effective sodium reduction program has potential to improve cardiovascular health. DESIGN: This study is a large-scale, cluster-randomized, trial done in five Northern Chinese provinces. Two counties have been selected from each province and 12 townships in each county making a total of 120 clusters. Within each township one village has been selected for participation with 1:1 randomization stratified by county. The sodium reduction intervention comprises community health education and a food supply strategy based upon providing access to salt substitute. Subsidization of the price of salt substitute was done in 30 intervention villages selected at random. Control villages continued usual practices. The primary outcome for the study is dietary sodium intake level estimated from assays of 24-hour urine. TRIAL STATUS: The trial recruited and randomized 120 townships in April 2011. The sodium reduction program was commenced in the 60 intervention villages between May and June of that year with outcome surveys scheduled for October to December 2012. Baseline data collection shows that randomisation achieved good balance across groups. DISCUSSION: The establishment of the China Rural Health Initiative has enabled the launch of this large-scale trial designed to identify a novel, scalable strategy for reduction of dietary sodium and control of blood pressure. If proved effective, the intervention could plausibly be implemented at low cost in large parts of China and other countries worldwide. PMID- 24176437 TI - Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial. AB - BACKGROUND: Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. CONCLUSIONS: LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 +/- 7.2 years, 64.3% were men, and mean body mass index was 32.5 +/- 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM. PMID- 24176438 TI - Randomized comparison of Zotarolimus-Eluting Endeavor Sprint versus bare-metal stent implantation in uncertain drug-eluting stent candidates: rationale, design, and characterization of the patient population for the Zotarolimus-eluting Endeavor Sprint stent in uncertain DES candidates study. AB - BACKGROUND: The use of drug-eluting stent (DES) instead of bare-metal stent (BMS) in patients at high stent thrombosis or bleeding risk as well as in those at low restenosis risk (ie, uncertain DES candidates) remains a matter of debate. Zotarolimus-Eluting Endeavor Sprint stent (E-ZES) (Santa Rosa, CA) is a hydrophilic polymer-based second-generation device with unique drug fast-release profile, which may allow for a shorter dual antiplatelet therapy (DAPT) duration without safety concerns. HYPOTHESIS: The primary objective is to assess whether E ZES implantation followed by a shorter than currently recommended course of DAPT will decrease the incidence of 12-month major adverse cardiovascular events as compared with BMS in undefined DES recipients. Actual duration of DAPT regimen will be dictated by patients' characteristics and not by stent type and, as such, can be as short as 30 days after intervention in both stent groups. STUDY DESIGN: The ZEUS study is an open-label randomized clinical trial conducted at 20 clinical sites in Italy, Switzerland, Portugal, and Hungary. With 1,600 individuals, this study will have 85% power to detect a 33% difference in the primary end point consisting of the composite of death, nonfatal myocardial infarction, or target vessel revascularization. SUMMARY: The ZEUS trial aims to assess whether the use of E-ZES, followed by a DAPT duration regimen based on patients' characteristics and not by stent type, is superior to conventional BMS implantation in undefined DES recipients who qualify for the presence of high thrombosis, bleeding, or low restenosis risk criteria. PMID- 24176439 TI - Gender-specific ambulance priority and delays to primary percutaneous coronary intervention: a consequence of the patients' presentation or the management at the emergency medical communications center? AB - BACKGROUND: Women with ST-elevation myocardial infarction (STEMI) tend to have longer treatment delays than men. This may partly be due to women delaying calling for help, difficulties for the emergency medical communication (EMC) service in interpreting a different constellation of presenting symptoms than men, or gender-specific ambulance delays due to differences in the management by the EMC service. METHODS AND RESULTS: We studied the EMC audio logs and medical records of 244 consecutive STEMI patients (65 women and 179 men) who contacted the EMC center at a single hospital directly. Patient demographics, clinical findings, and outcome after primary percutaneous coronary intervention were similar for the 2 genders. More women than men reported chest discomfort and discomfort in other areas of the upper body as debuting symptoms. The combined effects of longer patients delay and system delay led to longer total ischemic time in women (total ischemic time: median [interquartile range] 142 [180] vs 135 [83] minutes, women vs men, P = .024). Despite similar presentation, women had lower priority for emergent ambulance service (78.7% and 89.4% of women vs men, P = .035). Lower priority for ambulance service was associated with longer total ischemic time. CONCLUSION: Despite similar presentation and clinical findings, women with STEMI were given significantly lower priority for emergent ambulance service than men. PMID- 24176440 TI - Recent temporal trends for first-time hospitalization for acute myocardial infarction. Treatment patterns and clinical outcome in a large cohort study. AB - BACKGROUND: The objective was to report recent trends in the incidence, adoption of evidence-based treatment, and clinical outcomes for first-time hospitalization for acute myocardial infarction. METHODS: This is a large retrospective population-based cohort study using medical administrative data (International Classification of Diseases, Ninth Revision, Clinical Modification, codes) performed in the Emilia-Romagna Region of Italy (approximately 4.5 million inhabitants). We identified 60,673 patients with a first hospitalization for acute myocardial infarction from 2002 through 2009. RESULTS: The standardized incidence rate per 100,000 person-years of acute myocardial infarction increased from 173 cases in 2002 to a peak of 197 cases in 2004 and then decreased each year thereafter to 167 cases in 2009. The proportion of patients who underwent coronary angiography and angioplasty in the acute phase increased over time, respectively, from 45.4% and 27.1% to 72.3% and 57.2% (P < .001). Medication use within 12 months of discharge increased for aspirin, beta-blockers, and statins. A reduction in crude and adjusted in-hospital all-cause (16.1% in 2002 vs 12.8% in 2009, P < .001) and cardiovascular mortality (13.6% in 2002 vs 9.5% in 2009, P < .001) was observed over time. At 1 year after hospital discharge, no significant variations occurred in adjusted risk for all-cause mortality or cardiovascular mortality. Notably, crude and adjusted risk for in-hospital and postdischarge bleeding showed a significant increment. CONCLUSIONS: The utilization of evidence-based treatments in patients with myocardial infarction increased between 2002 and 2009. These changes in practice over time favored a reduction in early case fatality at the cost of a significant increase in bleeding. PMID- 24176441 TI - New-onset atrial fibrillation predicts malignant arrhythmias in post-myocardial infarction patients--a Cardiac Arrhythmias and RIsk Stratification after acute Myocardial infarction (CARISMA) substudy. AB - BACKGROUND: After myocardial infarction (MI) the risk of sudden cardiac death due to arrhythmias is substantial. OBJECTIVE: The purpose of this study was to investigate if new-onset atrial fibrillation (AF) is associated with development of potential malignant brady- and tachyarrhythmias after an acute MI. METHODS: The study included 277 post-MI patients from the CARISMA study with left ventricular ejection fraction <= 40%, New York Heart Association class I, II, or III and no history of AF. All patients were implanted with an implantable cardiac monitor within 4 to 27 days after an acute MI and followed every 3 months for 2 years. Time-dependent association between new-onset AF > 30 s and the development of bradyarrhythmias and/or ventricular tachyarrhythmias were investigated using Cox proportional hazard regressions. RESULTS: New-onset AF was associated with an increased risk of bradyarrhythmias when adjusting for male gender and baseline age, left ventricular ejection fraction and QRS width (HR = 2.8 [1.3-5.8], P = .006). Similarly, new-onset AF predicted ventricular tachyarrhythmias when adjusting for New York Heart Association class >= II and baseline QRS width (HR = 2.3 [1.2-4.4], P = .019). After dividing ventricular tachyarrhythmias into subgroups of non-sustained ventricular tachycardia (VT), sustained VT and ventricular fibrillation (VF), new-onset AF was significantly associated with an increased risk of non-sustained- and sustained VT but not VF (non-sustained VT: HR = 3.5 [1.7-7.2], P < .001, sustained VT: HR = 4.2 [1.1-15.7], P = .035, VF: HR = 1.1 [0.2-5.8], P = .877). CONCLUSION: In patients surviving a MI with reduced left ventricular systolic function, new-onset AF is associated with a significantly increased risk of developing ventricular brady- and tachyarrhythmias. PMID- 24176442 TI - Warfarin use among older atrial fibrillation patients with non-ST-segment elevation myocardial infarction managed with coronary stenting and dual antiplatelet therapy. AB - BACKGROUND: We sought to determine the risk of readmission for bleeding and major cardiac events in stented non-ST-segment elevation myocardial infarction (NSTEMI) atrial fibrillation (AF) patients. METHODS: For this patient population, selection of an antithrombotic strategy poses a unique challenge in clinical practice, and comparative outcome data are sparse. We linked NSTEMI patients aged >= 65 years in the CRUSADE Registry (2003-2006) to Medicare claims data. We examined patients with AF who received coronary stenting and either dual antiplatelet therapy (DAPT, aspirin + clopidogrel) or triple therapy (DAPT + warfarin) upon discharge. Multivariable Cox analysis was used to compare the 1 year risks of major cardiac events and readmission for bleeding. RESULTS: We identified 1,648 stented NSTEMI AF patients. Of these, 1,200 (73%) received DAPT, and 448 (27%) received triple therapy at hospital discharge. Predicted thromboembolic and bleeding risks did not appear to influence the decision to receive DAPT or triple therapy. At 1 year, 20.4% had a major cardiac event, and 13.5% were admitted for bleeding. Use of triple therapy relative to DAPT at discharge was associated with a similar adjusted risk of major cardiac events (adjusted hazard ratio 0.94, CI 0.73-1.21) but a trend toward increased risk of readmission for bleeding (hazard ratio 1.29, CI 0.96-1.74, P = .09). CONCLUSIONS: In routine practice and in contrast with practice recommendations, most elderly NSTEMI patients with AF who undergo percutaneous coronary intervention with stent placement receive DAPT rather than triple therapy at discharge. Those receiving triple therapy versus DAPT had a similar risk of an ischemic event but a trend toward increased bleeding. PMID- 24176443 TI - Adherence to guideline recommendations for antiarrhythmic drugs in atrial fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) guideline recommendations for antiarrhythmic drugs (AADs) are based on the effectiveness and safety of the AAD in patients with selected, concomitant heart disease. It is unknown to what extent these recommendations are being implemented in clinical practice. METHODS: Using commercial health claims, patients with AF were identified and then categorized into mutually exclusive, guideline-established subgroups based on their most serious concurrent heart disease: heart failure, coronary artery disease (CAD), hypertension, and no heart disease. Antiarrhythmic drug use after the first AF encounter and the identified concurrent heart disease encounter was determined from prescription claims, and this was compared with guideline recommendations. RESULTS: From January 2006 through December 2010, a total of 331,274 patients with AF aged < 65 years were identified: 18%, heart failure; 23%, CAD; 33%, hypertension; and 25%, no heart disease. Of these, 78,877 (24%) patients filled >= 1 qualifying AAD prescription. The median age was 57 years (interquartile range 52-61), and 69% were male. A total of 74,191 patients had AADs after both the AF and concurrent heart disease encounters: 27% with heart failure, 25% with CAD, 21% with hypertension, and 19% with no heart disease. In the heart failure and CAD subgroups, 45% and 31% of AADs were inconsistent with first- or second line guideline recommendations, respectively. CONCLUSION: More than one-third of the AADs used in patients with AF and CAD or heart failure did not conform to guideline recommendations. This highlights the potential need for increased clinician education and intervention to improve the safe use of AADs for AF management. PMID- 24176444 TI - Initiation of statin therapy after acute myocardial infarction is not associated with worsening depressive symptoms: insights from the Prospective Registry Evaluating Outcomes After Myocardial Infarctions: Events and Recovery (PREMIER) and Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) registries. AB - BACKGROUND: Whereas statins are considered the cornerstone of prevention after acute myocardial infarction (AMI), concerns about worsening depression in association with their use have been raised. METHODS: Using data from 2 prospective AMI registries (PREMIER and TRIUMPH), we examined the change in depressive symptoms from baseline and at 1, 6 and 12 months among statin-naive patients who were and were not discharged on a statin. Depressive symptoms were assessed with the 8-item Patient Health Questionnaire (PHQ-8). Within-group change in PHQ-8 scores from baseline to each follow-up period was assessed using paired t tests. A repeated-measures propensity-matched analysis examined whether changes in PHQ-8 scores from baseline were different between statin-treated and statin-untreated patients. RESULTS: Of 3,675 patients not previously treated with statins, 3,050 (83%) were discharged on a statin and 625 (17%) were not. Scores of PHQ-8 in the statin group decreased from baseline by a mean (+/- SD) of 0.9 (+/- 5.1), 1.2 (+/- 5), and 1.1 (+/- 5.1) at 1, 6, and 12 months, respectively. Corresponding changes in the nonstatin group were 0.9 (+/- 5.2), 1.3 (+/- 5.1), and 1.5 (+/- 5.8), respectively (P < .0001 for all comparisons). After propensity matching, 451 patients not discharged on statins with 1,240 patients discharged on statins, the mean change in PHQ-8 scores between baseline and the 3 follow-up time points was not significantly different between groups (mean between-group difference at 1 month: -0.13, 95% CI [-0.69 to 0.43], P = .65; at 6 months: 0.07, 95% CI [-0.66 to 0.52], P = .82; and at 12 months: -0.05, 95% CI [-0.67 to 0.58], P = .88). CONCLUSIONS: Initiation of statins after AMI was not associated with worsening depression. PMID- 24176445 TI - Frailty and risk for heart failure in older adults: the health, aging, and body composition study. AB - OBJECTIVE: The aim of this study was to assess the association between frailty and risk for heart failure (HF) in older adults. BACKGROUND: Frailty is common in the elderly and is associated with adverse health outcomes. Impact of frailty on HF risk is not known. METHODS: We assessed the association between frailty, using the Health ABC Short Physical Performance Battery (HABC Battery) and the Gill index, and incident HF in 2825 participants aged 70 to 79 years. RESULTS: Mean age of participants was 74 +/- 3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 466 participants developed HF. Compared to non-frail participants, moderate (HR 1.36, 95% CI 1.08-1.71) and severe frailty (HR 1.88, 95% CI 1.02-3.47) by Gill index was associated with a higher risk for HF. HABC Battery score was linearly associated with HF risk after adjusting for the Health ABC HF Model (HR 1.24, 95% CI 1.13-1.36 per SD decrease in score) and remained significant when controlled for death as a competing risk (HR 1.30; 95% CI 1.00-1.55). Results were comparable across age, sex, and race, and in sub-groups based on diabetes mellitus or cardiovascular disease at baseline. Addition of HABC Battery scores to the Health ABC HF Risk Model improved discrimination (change in C-index, 0.014; 95% CI 0.018-0.010) and appropriately reclassified 13.4% (net-reclassification-improvement 0.073, 95% CI 0.021-0.125; P = .006) of participants (8.3% who developed HF and 5.1% who did not). CONCLUSIONS: Frailty is independently associated with risk of HF in older adults. PMID- 24176446 TI - Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients. AB - BACKGROUND: Most heart failure (HF) risk stratification models were developed for inpatient use, and available outpatient models use a complex set of variables. We hypothesized that routinely collected clinical data could predict the 6-month risk of death and all-cause medical hospitalization in HF clinic outpatients. METHODS AND RESULTS: Using a quality improvement database and multivariable Cox modeling, we derived the Heart Failure Patient Severity Index (HFPSI) in the University of Michigan HF clinic (UM cohort, n = 1,536; 314 reached primary outcome). We externally validated the HFPSI in the Ann Arbor Veterans' Affairs HF clinic (VA cohort, n = 445; 106 outcomes) and explored "real-time" HFPSI use (VA RT cohort, n = 486; 141 outcomes) by tracking VA patients for 6 months from their most recently calculated HFPSI, rather than using an arbitrary start date for the cohort. The HFPSI model included blood urea nitrogen, B-type natriuretic peptide, New York Heart Association class, diabetes status, history of atrial fibrillation/flutter, and all-cause hospitalization within the prior 1 and 2 to 6 months. The concordance c statistics in the UM/VA/VA-RT cohorts were 0.71/0.68/0.74. Kaplan-Meier curves and log-rank testing demonstrated excellent risk stratification, particularly between a large, low-risk group (40% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 8%/12%/12%) and a small, high-risk group (10% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 57%/58%/79%). CONCLUSIONS: The HFPSI uses readily available data to predict the 6 month risk of death and/or all-cause medical hospitalization in HF clinic outpatients and could potentially help allocate specialized HF resources within health systems. PMID- 24176447 TI - Risk factors associated with the incidence and progression of mitral annulus calcification: the multi-ethnic study of atherosclerosis. AB - BACKGROUND: Significant cardiovascular morbidity has been associated with mitral annulus calcification (MAC), but limited data exist regarding its progression. The purpose of this study was to examine the natural history of and risk factors for MAC progression. METHODS: The MESA is a longitudinal cohort study of participants aged 45 to 84 years without clinical cardiovascular disease who underwent serial cardiac computed tomography studies with quantification of MAC. Regression models were used to identify risk factors associated with MAC incidence and progression. RESULTS: Prevalent MAC was observed in 534 (9%) of 5,895 participants. Over a median 2.3 years, 280 (5%) developed incident MAC. After adjustment, age was the strongest predictor of incident MAC (adjusted OR, 2.25 per 10 years; 95% CI, 1.97-2.58; P < .0001). Female gender, white ethnicity, body mass index, diabetes, hypertension, hyperlipidemia, serum cholesterol, smoking, and interleukin-6 were also significant predictors of incident MAC. In participants with prevalent MAC, the median rate of change was 10.1 [IQR, -6.7 to 60.7] Agatston units (AU)/year. Baseline MAC severity was the predominant predictor of rate of MAC progression (beta-coefficient per 10 AU, 0.88; 95% CI, 0.85-0.91; P < .0001), although ethnicity and smoking status possessed modest influence. CONCLUSIONS: Several cardiovascular risk factors predicted incident MAC, as did female gender. Severity of baseline MAC was the primary predictor of MAC progression, suggesting that, while atherosclerotic processes may initiate MAC, they are only modestly associated with its progression over these time frames. PMID- 24176448 TI - Prognostic implications of left ventricular end-diastolic pressure during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Findings from the Assessment of Pexelizumab in Acute Myocardial Infarction study. AB - BACKGROUND: Left ventricular end-diastolic pressure (LVEDP) is frequently measured during primary percutaneous coronary intervention (PCI). However, little is known of this measurement's utility in predicting outcomes or informing treatment decisions. We sought to determine the prognostic value of LVEDP measured during primary PCI for ST-segment elevation myocardial infarction (STEMI). METHODS: We studied 1,909 (33.2%) of 5,745 STEMI patients in whom LVEDP was measured during primary PCI in the APEX-AMI trial. Cox regression analysis was used to evaluate whether LVEDP was an independent predictor of mortality and the composite of death, cardiogenic shock, or congestive heart failure (CHF) at 90 days. RESULTS: The median (25th, 75th percentiles) LVEDP level was 22 mm Hg (16, 29); compared with patients with LVEDP <= 22 mm Hg, those with LVEDP > 22 mm Hg had higher rates of CHF (7.3% vs 3.1%, P < .001), cardiogenic shock (4.6% vs 1.7%, P < .001), and death (4.1% vs 2.2%, P = .014) at 90 days. After multivariable adjustment, LVEDP was associated with increased risk of mortality through 90 days (adjusted hazard ratio 1.22, 95% CI 1.02-1.46, per 5-mmHg increase, P = .044) and the composite of death, cardiogenic shock, or CHF within the first 2 days (adjusted hazard ratio 1.40, 95% CI 1.23-1.59, per 5-mm Hg increase, P < .001), but not from day 3 to 90 (P = .25). CONCLUSIONS: Left ventricular end-diastolic pressure measured during primary PCI for STEMI is an independent predictor of inhospital and longer term cardiovascular outcomes. Measuring LVEDP may be useful to stratify patient risk and guide postinfarct treatment. PMID- 24176449 TI - Elutax paclitaxel-eluting balloon followed by bare-metal stent compared with Xience V drug-eluting stent in the treatment of de novo coronary stenosis: a randomized trial. AB - BACKGROUND: Paclitaxel-eluting balloons (PEBs) are a promising alternative to drug-eluting stent (DES) in the treatment of coronary stenoses. The aim of our study was to compare the 9-month restenosis rates of a strategy of predilatation with PEB followed by bare-metal CoCr stent (PEB + BMS group) versus implantation of everolimus DES (DES group). METHODS: This randomized, single-center study planned to enroll 366 patients with stable angina (183 patients per arm) undergoing percutaneous coronary intervention of a de novo, native coronary artery stenosis <= 15 mm in length. Primary end point, in a noninferiority study design, was 9-month binary angiographic restenosis. A frequency-domain optical coherence tomography substudy investigated the percentage of uncovered stent struts per lesion, the percentage of malapposed/uncovered struts per lesion, and the percentage of net volume obstruction at 9-month follow-up among the first consecutive 30 patients enrolled in the PEB + BMS group. RESULTS: The study was prematurely halted after enrollment of 125 patients, 59 in the PEB + BMS group and 66 in the DES group, because of excess of ischemia-driven target lesion revascularization in the PEB + BMS group. When all the enrolled patients completed their follow-up, IDLTR rates were 14% in the PEB + BMS versus 2% in DES group (P = .001). Binary restenosis, either in-stent or in-segment, was significantly higher in the PEB + BMS compared with DES group (17% vs 3% [P = .01] and 25% vs 4% [P = .009] respectively). Frequency-domain optical coherence tomography demonstrated important neointimal regrowth in the PEB + BMS group, similar to historical BMS data. CONCLUSION: In the treatment of de novo coronary stenosis, a strategy of predilatation with PEB before BMS implantation was significantly inferior to implantation of an everolimus DES stent in terms of 9 month target lesion revascularization. Frequency-domain optical coherence tomography data confirm the lack of efficacy of this strategy. PMID- 24176450 TI - Cardiac biomarker measurement after elective percutaneous coronary interventions in older patients: insights from the National Cardiovascular Data Registry. AB - BACKGROUND: Guidelines recommend consideration of cardiac biomarker measurement after elective percutaneous coronary intervention (PCI), especially with complex cases or complicated procedures. However, the long-term prognostic implications of biomarker measurement after elective PCI have not been well characterized in older patients. METHODS: We examined 157,825 Medicare patients undergoing elective PCI in the United States from 2004 to 2008 at 711 hospitals in the CathPCI Registry. Clinical characteristics and 1-year mortality risk were studied, stratified by creatine kinase-muscle band measurement. RESULTS: Overall, 26% of patients on elective PCI had postprocedure biomarkers measured. These patients had more complex coronary anatomy and procedures but had similar rates of PCI success and inhospital mortality when compared with patients without biomarker measurement. The treating hospital was a significant factor associated with the likelihood of postprocedure biomarker surveillance. Hospitals that measured creatine kinase-muscle band in >= 90% of patients on elective PCI had lower associated 1-year mortality rates (adjusted hazard ratio 0.84, 95% CI 0.75 0.94) compared with hospitals that measured in < 10% of patients. CONCLUSIONS: Among older patients undergoing elective PCI, postprocedure cardiac biomarker measurement occurred infrequently and was concentrated at certain hospitals. Hospitals that routinely measured post-PCI biomarkers were associated with lower long-term mortality compared with hospitals without routine measurement. PMID- 24176451 TI - Incidence of atrial fibrillation in a population with impaired glucose tolerance: the contribution of glucose metabolism and other risk factors. A post hoc analysis of the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial. AB - BACKGROUND: The role of dysglycemia as an additional risk factor for atrial fibrillation (AF) is controversial. Therefore, it was of interest to assess risk factors for incident AF in a large, representative population of patients with cardiovascular risk factors and impaired glucose tolerance but not overt diabetes in NAVIGATOR. METHODS: Predictors of incident AF were analyzed in 8,943 patients without AF at baseline by Cox proportional hazards regression. Study treatments (valsartan vs no valsartan and nateglinide vs no nateglinide) and the time dependent covariate for progression to type 2 diabetes mellitus were added separately to the model. RESULTS: The median age of the 8,943 patients included in the present analysis of the NAVIGATOR trial was 63 years. Half of those patients were men, 6,922 (77.4%) had a history of hypertension, and 255 (2.9%) had heart failure. The median glycated hemoglobin was 6%. During the study, 613 of the 8,943 patients without AF at baseline presented with at least 1 episode of AF (6.9% 5-year incidence). Besides established predictors of incident AF, a 1 mmol/L increment of baseline fasting glucose, but not progression to diabetes, was found to be associated with a 33% increased risk of incident AF. Neither valsartan nor nateglinide affected AF incidence. CONCLUSIONS: In a trial population with impaired glucose tolerance, fasting plasma glucose and well-known risk factors (age, hypertension, and elevated body weight), but not progression to diabetes, predict risk of AF. PMID- 24176452 TI - Letter to the editor concerning the article by Kooiman et al. PMID- 24176453 TI - Reply to letter to the editor by Koza et al. PMID- 24176454 TI - Airway management: "the times they are a-changin". PMID- 24176455 TI - The role of physician assistants in pediatric emergency medicine: the physician's view. AB - OBJECTIVE: To define the range of clinical conditions Canadian emergency pediatricians consider appropriate for management by physician assistants (PAs) and the degree of autonomy PAs should have in the pediatric emergency department (PED). METHODS: We conducted a cross-sectional, pan-Canadian survey using electronic questionnaire technology: the Active Campaign Survey tool. We targeted PED physicians using the Pediatric Emergency Research Canada (PERC) network database (N = 297). Three outcome measures were assessed: demographic information, familiarity with PAs, and PA clinical roles in the PED. The level of PA involvement was assessed for 57 common nonemergent clinical conditions. RESULTS: Of 297 physicians, 152 completed the survey, for a response rate of 51.2%. None of the 57 clinical categories achieved at least 85% agreement regarding PA management without direct physician involvement. Twenty-four clinical conditions had >= 15% agreement that any PA involvement would be inappropriate. For the remaining 33 clinical conditions, more than 85% of respondents felt that PA could appropriately manage but were divided between requiring direct and only indirect physician supervision. Respondents' selection of the number of conditions felt to be appropriate for PA involvement varied between the size of the emergency department (ED) in which they work (larger EDs 87.7-89.1% v. smaller EDs 74.2%) and familiarity with the clinical work of PAs in the ED (90.5-91.5% v. 82.2-84.7%). CONCLUSION: This national survey of Canadian PED physicians suggests that they feel PAs could help care for a large number of nonemergent clinical cases coming to the PED, but these clinical encounters would have to be directly supervised by a physician. PMID- 24176456 TI - Parents' willingness to have their child receive care by physician assistants in a pediatric emergency department. AB - OBJECTIVE: To determine the willingness of parents of children visiting a pediatric emergency department to have a physician assistant (PA) assess and treat their child and the waiting time reduction sufficient for them to choose to receive treatment by a PA rather than wait for a physician. METHOD: After describing the training and scope of practice of PAs, we asked caregivers of children triaged as urgent to nonurgent if they would be willing to have their child assessed and treated by a PA on that visit: definitely, maybe, or never. We also asked the minimum amount of waiting time reduction they would want to see before choosing to receive treatment by a PA rather than wait for a physician. RESULT: We approached 320 eligible subjects, and 273 (85.3%) consented to participate. Regarding whether they would be willing to have their child receive treatment by a PA, 140 (51.3%) respondents answered definitely, 107 (39.2%) said maybe, and 26 (9.2%) said never. Most respondents (64.1%) would choose to have their child seen by a PA instead of waiting for a physician if the waiting time reduction were at least 60 minutes (median 60 minutes [interquartile range 60 minutes]). Respondents' perception of the severity of their child's condition was associated with unwillingness to receive treatment by a PA, whereas child's age, presenting complaint, and actual waiting time were not. CONCLUSION: Only a small minority of parents of children visiting a pediatric emergency department for urgent to nonurgent issues are unwilling to have their child treated by PAs. PMID- 24176457 TI - [Cohort study on the prevalence and risk factors of late pulmonary complications in adults following a closed minor chest trauma]. AB - OBJECTIVES: The objectives of this study are to determine the prevalence, risk factors, and time to onset of delayed hemothorax and pneumothorax in adults who experienced a minor blunt thoracic trauma. METHOD: A prospective cohort of 450 consecutive patients was recruited. Eligible patients had to be over 16 years of age, consulted within 72 hours for a trauma, and available for outpatient follow up at 2, 7, and 14 days posttrauma. The clinical outcome investigated was the presence of delayed pneumothorax or hemothorax on the follow-up chest x-ray. OUTCOMES: Delayed hemothorax occurred in 11.8% (95% CI 8.8-14.8), and delayed pneumothorax occurred in 0.9% (95% CI 0.2-2.3) of participants. During the 14-day follow-up period, 87.0% of these delayed complications developed in the first week. In the multivariate analysis, the only statistically significant risk factor for delayed complications was the location of fractures on the x-ray of the hemithorax. The adjusted odds ratio was 1.52 (95% CI 0.62-3.73) for the lower ribs (tenth to twelfth rib), 3.11 (95% CI 1.60-6.08) for the midline ribs (sixth to ninth rib), and 5.05 (95% CI 1.80-14.19) for the upper ribs (third to fifth rib) versus patients with no fractures. CONCLUSION: The presence of at least one rib fracture between the third and ninth rib on the x-ray of the hemithorax is a significant risk factor for delayed hemothorax and pneumothorax. PMID- 24176458 TI - Photodocumentation as an emergency department documentation tool in soft tissue infection: a randomized trial. AB - OBJECTIVES: Current documentation methods for patients with skin and soft tissue infections receiving outpatient parenteral anti-infective therapy (OPAT) include written descriptions and drawings of the infection that may inadequately communicate clinical status. We undertook a study to determine whether photodocumentation (PD) improves the duration of outpatient treatment of skin and soft tissue infections. METHODS: A single-blinded, prospective, randomized trial was conducted in the emergency departments of a community hospital and an academic tertiary centre. Participants included consecutive patients age >= 14 years presenting with noninvasive skin and soft tissue infections requiring OPAT. Patients in the intervention arm were treated with standard of care plus PD at each emergency physician assessment. Control subjects received care provided at the discretion of the treating physician and non-photographic documentation. The primary outcome was duration of therapy measured in half-days. The required sample size to detect a difference of one half-day was 253 patients per group (alpha = 0.05). Secondary outcomes included (1) completion and therapeutic failure rates, (2) patient satisfaction, and (3) physician and nurse satisfaction. RESULTS: Enrolment was slower and follow-up rates lower than anticipated, and the trial was terminated when funds were exhausted. A total of 468 subjects with similar age and gender characteristics were enrolled, with 244 receiving the intervention and 224 in the control arm. The mean OPAT duration was similar in the two groups (3.6 days v. 3.5 days, p = 0.73). No differences in the rate for completion and therapeutic failure were observed (71% v. 68% and < 1% for both, respectively). Survey response rates varied significantly: patients, 65%; nurses, 17%; and physicians, 87%. Physicians endorsed more comfort with their assessment and OPAT judgment with PD (65% and 64%, respectively). Physicians cited too much time lost with technological challenges, which would affect implementation in a busy ED. CONCLUSIONS: PD as an intervention is acceptable to patients and has reasonable endorsement by the majority of physicians. This trial had significant limitations that threatened the integrity of the study, so the results are inconclusive. PMID- 24176459 TI - Predictors of admission to hospital of patients triaged as nonurgent using the Canadian Triage and Acuity Scale. AB - OBJECTIVES: To identify factors known prior to triage that might have predicted hospital admission for patients triaged by the Canadian Triage Acuity Scale (CTAS) as level 5 (CTAS 5, nonurgent) and to determine whether inappropriate triage occurred in the admitted CTAS 5 patients. METHODS: We reviewed the triage records of patients triaged as CTAS 5 at the emergency departments (EDs) of three tertiary care hospitals between April 2002 and September 2009. Two triage nurses unaware of the study objective independently assigned the CTAS level in 20% of randomly selected CTAS 5 patients who were admitted. We used the kappa statistic (kappa) to measure the agreement among the raters in CTAS level between the assessment of the research nurses and the original triage assessment and regression analysis to identify independent predictors of admission to hospital. RESULTS: Of the 37,416 CTAS 5 patients included in this study, 587 (1.6%) were admitted. Agreement on CTAS assignment in CTAS 5 patients who were admitted was kappa -0.9, (95% confidence interval [CI] -0.96 to -0.84). Age over 65 (odds ratio [OR] 5.46, 95% CI 4.57 to 6.53) and arrival by ambulance (OR 7.42, 95% CI 6.15 to 8.96) predicted hospital admission in CTAS 5 patients. CONCLUSIONS: Most of the CTAS 5 patients who were subsequently admitted to hospital may have qualified for a higher triage category. Two potential modifiers, age over 65 and arrival by ambulance, may have improved the prediction of admission in CTAS 5 patients. However, the consistent application of existing CTAS criteria may also be important to prevent incorrect triage. PMID- 24176460 TI - Emergency department overcrowding and access block. PMID- 24176462 TI - In-flight arterial gas emboli from a ruptured bronchogenic cyst. PMID- 24176463 TI - Iatrogenic radial neck fracture on closed reduction of elbow dislocation. AB - Traumatic dislocation of the elbow is rare in children and can most often be managed in the emergency department using procedural sedation and closed reduction with good functional outcome. Radiographs must be evaluated for associated avulsions and fractures around the elbow. We present the case of a 14 year-old girl who sustained a fracture of the radial neck subsequent to repeated attempts at closed reduction of a pure posterior elbow dislocation that was missed on postreduction radiographs. Careful use of reduction techniques and avoidance of repeated forceful manipulations is emphasized. PMID- 24176464 TI - Surviving a stressful MIBI scan. AB - Dipyridamole/technetium sestamibi scans (more commonly known as MIBI scans, an acronym for methoxyisobutyl isonitrile) are used commonly for the diagnosis and risk stratification of coronary artery disease. Adverse events from MIBI scans are extremely rare. We present the case of a 64-year-old man who was successfully resuscitated after two asystolic episodes following dipyridamole infusion for a MIBI scan. The second asystolic episode occurred in the emergency department 40 minutes after the patient had been transferred from the Cardiac Stress Test Laboratory. To our knowledge, there are no previous reports of patients having two discrete asystolic episodes or an asystolic episode as delayed as we report after a MIBI scan. Our case illustrates why emergency physicians should be aware of the potential for asystole following MIBI scanning and why aminophylline, the antidote for dipyridamole, should be readily available in emergency departments that could see patients after pharmacologic stress testing. Patients who become asystolic following dipyridamole infusion likely require prolonged cardiac monitoring, given the potential for further episodes after periods of hemodynamic stability. PMID- 24176465 TI - Statin myotoxicity: a review of genetic susceptibility factors. AB - The 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (statins) are among the most common medications prescribed worldwide, but their efficacy and toxicity vary between individuals. One of the major factors contributing to intolerance and non-compliance are the muscle side-effects, which range from mild myalgia through to severe life-threatening rhabdomyolysis. One way to address this is pharmacogenomic screening, which aims to individualize therapy to maximize efficacy whilst avoiding toxicity. Genes encoding proteins involved in the metabolism of statins as well as genes known to cause inherited muscle disorders have been investigated. To-date only polymorphisms in the SLCO1B1 gene, which encodes the protein responsible for hepatic uptake of statins, and the COQ2 gene, important in the synthesis of coenzyme Q10, have been validated as being strongly associated with statin-induced myopathy. The aim of this review is to summarize studies investigating genetic factors predisposing to statin myopathy and myalgia, as the first step towards pharmacogenomic screening to identify at risk individuals. PMID- 24176466 TI - [Case report of Cogan-like dystrophy diagnosed as confirmed type I lattice corneal dystrophy in a 10-year-old child]. PMID- 24176467 TI - [Intravitreal and intravenous steroids in a case of Idiopathic Retinitis, Vasculitis and Neuroretinitis (IRVAN) syndrome]. PMID- 24176468 TI - [Assessing the feasibility and the acceptability of outpatient retinal detachment surgery]. AB - PURPOSE: To assess the feasibility and acceptability of outpatient care for patients undergoing surgery for retinal detachment. PATIENTS AND METHODS: Patients successively undergoing retinal detachment surgery between January and November 2012 were prospectively included. Patient age, distance from home, type of detachment, surgical technique, postoperative intravenous medications if applicable, pain as evaluated on the visual analogue scale (VAS), slit lamp findings on the day of surgery (D0) and the next day (D1), the presence of another person in the home, comprehension of instructions, the patient's physical abilities and adherence to outpatient treatment were recorded. RESULTS: Forty-six surgeries on 17 women and 28 men, including 2 one-eyed patients, with a mean age of 62 years (+/-16.6; 19-95), were studied. The mean distance from home was 78km (+/-108; 1-490 km). The surgery was performed ab-interno in 44 cases (40 transconjunctival, 4 cases of disinsertion with placement of a buckle) and ab externo in 2 cases; under general anesthesia in 40 cases and local/regional anesthesia in 6 cases. Five cases were recurrent detachments, lensectomy was performed in 6 cases, internal gas tamponade was performed in the majority of cases (4 with silicone oil and 1 without tamponade). Functional signs were absent or limited to simple discomfort in 95.7% of cases on D0 as well as D1. The mean VAS at D0 was very low, described as 0.32/10 (0-8) and 0.63/10 (0-5) at D1. Two patients vomited on D0 and one on D1. Mean intraocular pressure was 12.8mmHg (+/ 4.4; 4-24) at D0 and 17.6mmHg (+/-6.3; 8-34) at D1. The retina was visible in 91.3% of cases on D0 and 89.1% of cases on D1. Sleepiness was present in 3 cases (6.5%) at the D0 exam, and returning home was impossible without assistance from a third party in 4 cases (8.7%) (this incapacity was permanent or related to the patient's one-eyed status in all cases). The instructions for proper positioning were assimilated by all patients on D0, and no intravenous treatment was necessary after awakening. A companion was present at home in 78.3% (n=36) of cases; 87% (n=40) of the patients felt they could return home on D0 had it been necessary, with an early return home even desired by 32.6% (n=15) of the patients. DISCUSSION: The changes in surgical management of retinal detachment patients and the appearance in France of a specific fee schedule now make it possible to consider ambulatory treatment of patients with retinal detachment. CONCLUSION: Outpatient management of retinal detachment patients appears perfectly feasible and acceptable according to this study. PMID- 24176469 TI - Allergy to quince. PMID- 24176470 TI - When should we perform a repeat training on adrenaline auto-injector use for physician trainees? AB - BACKGROUND: Studies demonstrate that both doctors and patients may use adrenaline auto-injector improperly and the usage skills are improved by training. In this study, we aimed to determine the appropriate frequency of training to maintain skills for adrenaline auto-injector use. METHODS: We invited all interns of 2011 2012 training period. At baseline, all participants were given theoretical and practical training on adrenaline auto-injector use. The participants were randomly assigned into two groups. We asked those in group 1 to demonstrate the use of adrenaline auto-injector trainer in the third month and those in group 2 in the sixth month. RESULTS: One hundred and sixty interns were enrolled. Compared with the beginning score, demonstration of skills at all the steps and total scores did not change for the group tested in the third month (p=0.265 and p=0.888, respectively). However; for the group examined in the sixth month; the demonstration of skills for proper use of the auto-injector at all steps and the mean time to administer adrenaline decreased (p=0.018 and p<0.001, respectively). Besides, the group which was tested in the third month was better than the group which was tested in the sixth month in terms of demonstrating all steps (p=0.014), the total score (p=0.019), mean time of change to administer adrenaline (p<0.001) and presumptive self-injection into thumb (p=0.029). CONCLUSIONS: Auto-injector usage skills of physician trainees decrease after the sixth month and are better in those who had skill reinforcement at 3 months, suggesting continued education and skill reinforcement may be useful. PMID- 24176471 TI - Fever and signs of shock: the essential dangerous fever. AB - A common cause of fever with signs of shock is sepsis. Sepsis describes the spectrum of illness caused by severe infection. The incidence of sepsis is increasing and mortality can be high. Diagnosing the disease and implementing treatment early can decrease mortality. Early treatment includes empirical antibiotics and resuscitation. The diverse physiology present in sepsis can make the resuscitation complex; many different types of hemodynamic monitoring may be necessary. Even with this complexity, an organized approach can improve patient outcomes. PMID- 24176472 TI - Fever in the returning traveler. AB - Fever in ill travelers returning home from developing nations is common. Most travelers present with undifferentiated febrile syndromes. Regional proportionate morbidity rates and patients' travel histories are essential in narrowing the differential diagnosis. Most patients in whom a diagnosis is confirmed have malaria, dengue fever, enteric fever, or rickettsial disease. Empiric treatment based on the clinical presentation is required in many cases, because acquisition of confirmatory laboratory data is often delayed. The focus of this article is travel-related illness that falls within the spectrum of the acute febrile syndrome. PMID- 24176473 TI - Fever and the rational use of antimicrobials in the emergency department. AB - Any patient presenting to the emergency department (ED) with fever triggers consideration of the administration of an antimicrobial. Empiric antimicrobial therapy has become a cornerstone of treatment. Frequently, the decision to initiate empiric treatment needs to be made before the definitive diagnosis is known. In such cases, an organized approach is helpful. This article aims to provide a systems-based approach to prescribing antimicrobials to patients presenting to the ED with fever, while understanding the risk associated with overutilization. An understanding of the key considerations is needed to ensure that decisions are made well and appropriate treatment begins promptly. PMID- 24176474 TI - Endocrine causes of dangerous fever. AB - This article provides an overview of the pathogenesis and signs and symptoms of dangerous endocrine causes of hyperthermia. Treatment strategies based on specific causes are discussed. PMID- 24176475 TI - Fever and neurologic conditions. AB - Neurologic conditions are categorized as either those that cause a change in mental status or those that create a focal finding on physical examination. Neurologic abnormality associated with fever can be caused by a primary neurologic condition or one that does not originate in the central nervous system. Optimal management of such conditions requires high clinical suspicion and a broad differential diagnosis, which facilitates rapid recognition and effective treatment. A thorough history and physical examination are key determinants in accurately diagnosing neurologic conditions associated with fever, often requiring acquisition of collateral information from persons other than the patient. PMID- 24176476 TI - Drug-induced hyperthermic syndromes: part I. Hyperthermia in overdose. AB - Drugs and natural compounds that affect the thermoregulatory system can induce or contribute to hyperthermia when used in excess. Hyperthermia associated with drug overdose is dangerous and potentially lethal. This article reviews the body's process of maintaining thermodynamic equilibrium, and describes the mechanisms by which it is influenced by sympathomimetic and anticholinergic drugs, salicylates, and thyroid replacement medications. Appropriate treatment strategies such as cooling and the administration of counteractive medications are discussed. PMID- 24176477 TI - Hyperthermia caused by drug interactions and adverse reactions. AB - Drug-induced hyperthermic syndromes are similar to heat illness. The purpose of this article is to discuss the drugs associated with the development of these syndromes and to review their pathophysiology, clinical manifestations, and management. PMID- 24176478 TI - Fever in the postoperative patient. AB - Postprocedure fevers vary in the timing of their occurrence, duration, and severity. Such fevers do not all have an infectious cause, but they all require thorough investigation to rule out life-threatening conditions. This article summarizes the principles of diagnosis and management of postprocedure fevers for the emergency care provider. PMID- 24176479 TI - Fever in immunocompromised hosts. AB - Fever is one of the most common reasons for the emergency department presentation of immunocompromised patients. Their differential diagnosis can be broad and includes rare or unexpected pathogens. Certain infectious causes of fever portend true emergencies; if they are not managed appropriately, rapid progression and death may ensue. This article reviews the diagnosis and management of fevers in patients immunocompromised by human immunodeficiency virus/AIDS, solid-organ and hematopoietic transplants, chemotherapy-induced neutropenia, and tumor necrosis factor-alpha inhibitors. Prompt recognition of the type of immunosuppression and delineation of possible causes of fever are critical for management of these complex patients. PMID- 24176480 TI - Fever in the pediatric patient. AB - Fever is the most common reason that children and infants are brought to emergency departments. Emergency physicians face the challenge of quickly distinguishing benign from life-threatening conditions. The management of fever in children is guided by the patient's age, immunization status, and immune status as well as the results of a careful physical examination and appropriate laboratory tests and radiographic views. In this article, the evaluation and treatment of children with fevers of known and unknown origin are described. Causes of common and dangerous conditions that include fever in their manifestation are also discussed. PMID- 24176481 TI - Heat-related illness. AB - Environmental exposure to high temperatures can result in abnormalities ranging from mild heat exhaustion to heat stroke with multiorgan system failure. An understanding of the mechanisms of thermoregulation and how those mechanisms fail with extreme heat stress is critical for management of the patient with elevated body temperature in the emergency department. PMID- 24176482 TI - Dangerous fever in the emergency department. PMID- 24176483 TI - Dangerous fever in the emergency department. PMID- 24176484 TI - Characteristic CT features of heterotopic pancreas of the mesentery: "another pancreas" in the mesentery. AB - PURPOSE: To evaluate computed tomography (CT) findings of heterotopic pancreas of the mesentery (HPM). METHODS: Two radiologists reviewed CT scans of seven patients with HPM to determine the location, relationship with the adjacent bowel, presence of a duct-like structure, and the enhancement pattern of HPM in consensus. RESULTS: All HPMs were located in the jejunal mesentery and had morphologic features closely resembling those of the main pancreas and had unique relationship with the jejunum. Duct-like structures were observed in five lesions. The enhancement pattern varied. CONCLUSION: It is important to be aware of characteristic CT features of HPM to eliminate unnecessary surgeries. PMID- 24176485 TI - Heat acclimation decreases the growth hormone response to acute constant-load exercise in the heat. AB - OBJECTIVE: The major objective of this study was to elucidate the effect of heat acclimation on blood growth hormone (GH) response to moderate intensity exhausting exercise in the heat. In addition, the potential relationship between inter-individual differences in GH response to exercise and variability in exercise-induced sweat loss was investigated. DESIGN: Twenty young men completed three exercise tests on a treadmill: H1 (walk at 60% VO2peak until exhaustion at 42 degrees C), N (walk at 22 degrees C; duration equal to H1) and H2 (walk until exhaustion at 42 degrees C after a 10-day heat acclimation program). Core temperature (T(c)) was recorded continuously and venous blood samples were taken before, during and after each exercise test. Exercise-induced sweat production was calculated on the basis of body mass change taking into account water intake and the volume of blood samples drawn. RESULTS: Lower pre-exercise T(c), lower rate of rise in T(c) during exercise, and prolonged time to exhaustion in H2 compared with H1 revealed that the subjects successfully achieved an acclimated state. Overall, serum GH level was higher in H1 compared with both N and H2 (p<0.001) but did not differ between the two latter trials (p>0.05). T(c) correlated with serum GH concentration (r=0.615, p<0.01). Analysis of the individual data revealed a group (n=9) possessing a threshold-like pattern of the relationship between T(c) and blood GH response, whereas a plateau-like pattern was evident in the rest of the subjects (n=11). Both sweat production (r=0.596; p<0.001) and the rate of sweat production (r=0.457; p<0.001) correlated with the growth hormone area under the curve. CONCLUSION: Heat acclimation decreases the GH response to moderate intensity exhausting exercise in the heat. GH may have a modest stimulating effect on whole-body sweat production during exercise. PMID- 24176486 TI - A twist in the transradial coronary catheterisation. AB - The transradial approach for coronary angiography was first described in 1989. With the advent of modern equipment and improved technology it has recently gained significant interest amongst interventional cardiologists. As compared to femoral access, the radial approach has the major advantages of lower access site complication rates, cost-effectiveness, and shorter hospital stays. Further clinical benefits of lower morbidity and cardiac mortality in patients with ST elevation myocardial infarction have been shown recently. Rare vascular complications may include radial artery spasm, dissection, occlusion, perforation or compartment syndrome. Here, we present two unusual cases of an entrapped catheter in the radial artery and their outcomes. PMID- 24176487 TI - Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer. AB - OBJECTIVE: The incidence of thyroid gland invasion in patients with advanced laryngeal cancer was reported to be 0-50%. However there is a controversy in necessity and extent of routine thyroidectomy in these patients due to the difficulty in diagnosis of tumor invasion to thyroid gland and the risk of possible postoperative hypothyroidism and hypocalcemia. METHODS: The medical files of 47 patients who underwent thyroidectomy as part of surgical treatment for advanced laryngeal cancer were reviewed. RESULTS: Fourty-four (93.6%) patients underwent hemithyroidectomy, 3 (6.3%) patients underwent total thyroidectomy. Thyroid gland invasion was found in 2 (4.2%) patients. Hypothyroidism occurred in 15 (31.9%) patients, and their hormone levels were regulated with medical treatment during follow-up. Hypocalcemia was not found in any patients. CONCLUSION: We recommend that at least a hemithyroidectomy should be performed in patients with advanced laryngeal cancer, if they have any predictive factor (subglottic extension more than 1cm, invasion of paraglottic space, thyroid cartilage, cricoid cartilage and prelaryngeal tissue detected by radiological examination) for thyroid gland invasion. PMID- 24176488 TI - Effect of edaravone on acute brainstem-cerebellar infarction with vertigo and sudden hearing loss. AB - We report 2 cases with acute brainstem and brainstem-cerebellar infarction showed improvement of their signs and symptoms after administration of edaravone. Case 1, a 74-year-old woman who experienced sudden vertigo, also had dysarthria and left hemiplegia. Magnetic resonance imaging (MRI) showed an abnormal region in the right ventrolateral medulla oblongata. The patient's vertigo and hemiplegia improved completely after treatment. Case 2, a 50-year-old man who experienced sudden vertigo and sensorineural hearing loss (SNHL), developed dysarthria after admission. MRI revealed acute infarction in the right cerebellar hemisphere. Magnetic resonance angiography revealed dissection of the basilar artery and occlusion of the right anterior inferior cerebellar artery. The patient's vertigo and hearing remarkably improved. We have described 2 patients whose early symptoms were vertigo and sudden SNHL, but who were later shown to have ischemic lesions of the central nervous system. Edaravone is neuroprotective drug with free radical-scavenging actions. Free radicals in the ear are responsible for ischemic damage. Edaravone, a free radical scavenger, may be useful in the treatment of vertigo and SNHL. PMID- 24176489 TI - Infectious disease research investments: systematic analysis of immunology and vaccine research funding in the UK. AB - Financing for global health is a critical element of research and development. Innovations in new vaccines are critically dependent on research funding given the large sums required, however estimates of global research investments are lacking. We evaluate infectious disease research investments, focusing on immunology and vaccine research by UK research funding organisations. In 1997 2010, L2.6 billion were spent by public and philanthropic organisations, with L590 million allocated to immunology and vaccine research. Preclinical studies received the largest funding amount L505 million accounting for 85.6% of total investment. In terms of specific infection, "the big three" infections dominated funding: HIV received L127 million (21.5% of total), malaria received L59 million (10.0% of total) and tuberculosis received L36 million (6.0% of total). We excluded industry funding from our analysis, as open-access data were unavailable. A global investment surveillance system is needed to map and monitor funding and guide allocation of scarce resources. PMID- 24176490 TI - Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway. AB - The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the childhood immunisation programme in Norway in 2006 substantially decreased the incidence of vaccine-type (VT) invasive pneumococcal disease (IPD) in all age groups. Additionally, a slight increase in the non-vaccine (NVT) serotype IPD incidence (serotype replacement) was observed. After replacing PCV7 with PCV13 in 2011, a further decrease in IPD incidence is expected. However, the protection by the six additional serotypes opens new nasopharyngeal niches for colonisation, which favours conditions for serotype replacement. Close monitoring of IPD therefore remains important in order to quickly detect changes. In this observational retrospective population-based cohort study we used data notified nationally between 1 January 2004 and 31 December 2012 to determine the VT- and NVT-IPD incidences. The diversity in serotype distribution per year was analysed using the Simpson's index of diversity. Immunisation history of young children was obtained from the Norwegian Vaccination Registry to determine vaccine failure. The incidence of VT-IPD decreased in the targeted (<5 years) and non targeted (>=5) age groups since PCV7 introduction and further decreased after the replacement with PCV13. Only two cases of vaccine failure were identified. This indicates very high effectiveness of the 2+1 schedules with PCV7 or PCV13 and suggests that non-vaccinated individuals profit through indirect protection. The decrease in incidence of PCV7-IPD in non-targeted age groups became larger in later years, indicating a lag phase for the indirect effects, and suggests that the indirect protection of PCV13 will increase in coming years. The incidence of some NVT, specifically serotypes 23B and 15A, increased after PCV13 introduction. This coincided with an increased Simpson's index of diversity in the targeted age group. As this suggests that serotype replacement is again occurring, continues monitoring of IPD is important so that adaptations to vaccine recommendations can be promptly issued. PMID- 24176491 TI - Construction of a recombinant-attenuated Salmonella Enteritidis strain secreting Escherichia coli heat-labile enterotoxin B subunit protein and its immunogenicity and protection efficacy against salmonellosis in chickens. AB - A live attenuated Salmonella Enteritidis (SE) strain secreting Escherichia coli heat-labile enterotoxin B subunit (LTB) protein was constructed as a new vaccine candidate. The comparative effect of this vaccine candidate was evaluated with a previously reported SE vaccine, JOL919. An asd+, p15A ori plasmid containing eltB encoding LTB was introduced into a DeltalonDeltacpxRDeltaasd SE strain, and designated as JOL1364. In a single immunization experiment, group A chickens were orally inoculated with phosphate-buffered saline as a control, group B chickens were orally immunized with JOL919, and group C chickens were orally immunized with JOL1364. The immunized groups B and C showed significantly higher systemic, mucosal and cellular immune responses as compared to those of the control group. In addition, the immunized group C showed significantly higher mucosal and cellular immune responses as compared to those of the immunized group B at the 1st week post-immunization. In the examination of protection efficacy, the immunized groups B and C showed lower gross lesion scores in the liver and spleen, and lower bacterial counts of SE challenge strain in the liver, spleen, and caeca as compared to those of the control group. The number of SE-positive birds was significantly lower in the immunized group C as compared to that of the control group at the 14th day post-challenge. In addition, the number of birds carrying the challenge strain in the caeca was significantly lower in the immunized group C than those in the immunized group B and control group at the 7th and 14th day post-challenge. These results indicate that immunization with the JOL1364 vaccine candidate can induce higher mucosal and cellular immune responses than those of the JOL919 for efficient protection against salmonellosis. PMID- 24176492 TI - Increased efficacy of a trivalent nicotine vaccine compared to a dose-matched monovalent vaccine when formulated with alum. AB - Vaccination against nicotine is a potential treatment for tobacco smoking. Clinical trials show effect only in high antibody responders; therefore it is necessary to increase the effectiveness of nicotine vaccines. The use of a multivalent vaccine that activates several B cell populations is a possible approach to increase antibody response. The aim of this study was to investigate whether three different nicotine immunogens could be mixed to generate independent responses resulting in additive antibody titers, and whether this would alter nicotine distribution to a greater extent than antibodies generated by a monovalent vaccine. When immunogens were administered s.c. with alum adjuvant, the trivalent vaccine generated significantly higher titers and prevented the distribution of an i.v. nicotine dose to brain to a greater extent than an equivalent dose of a monovalent vaccine. The number of rats with antibody titers >1:10,000 was significantly increased in the trivalent group compared to the monovalent group. There were no correlations between the titers generated by the different nicotine immunogens in the trivalent vaccine, supporting the hypothesis that the immunogens generated independent responses from distinct populations of B cells. In contrast, when administered i.p. in Freund's adjuvant, the trivalent nicotine vaccine was not more immunogenic than its component monovalent vaccine. Vaccine immunogenicity was suppressed if unconjugated protein was added to the monovalent vaccine formulated in Freund's adjuvant, compared to monovalent vaccine alone. These data suggest a protein-protein interaction that affects titers negatively and is apparent when the vaccines are formulated with Freund's adjuvant. In summary, a trivalent nicotine vaccine formulated with alum showed significantly higher efficacy than a dose-matched monovalent vaccine and may offer a strategy for increasing nicotine vaccine immunogenicity. This approach may be generalizable to other nicotine immunogens or vaccines for other addictive drugs. PMID- 24176493 TI - Protective immunity induced by a recombinant BCG vaccine encoding the cyclophilin gene of Toxoplasma gondii. AB - The investigation of Toxoplasma gondii virulence factors can elucidate the immunopathology of T. gondii infection and identify potential candidates for effective human vaccines. The adjuvant is an important component of an effective vaccine. In this study, attenuated Mycobacterium bovis was used as a live vaccine vector with both antigen and adjuvant characteristics. Following amplification of the T. gondii cyclophilin gene, the shuttle expression plasmid pMV261-TgCyP and integrative expression plasmid pMV361-TgCyP were constructed, and their expression was stimulated after transfection into BCG. Both recombinant plasmids were highly immunogenic. Greater proliferation of CD4(+) and CD8(+) T cells was observed in the rBCG-vaccinated groups compared to the control groups. The levels of Th1-type IFN-gamma, IL-2 and IL-12 were significantly increased following immunisation with the rBCG vaccines via the i.v. or oral route, which indicated that catalytic activity against T. gondii infection was generated in the mice. rBCGpMV361-TgCyP i.v. inoculation resulted in a higher protection efficiency, as demonstrated by the increased survival time and survival rate (17%) of BALB/c mice. The present study demonstrates that a BCG vector expressing a target antigen, TgCyP, represent an alternative system for the production of effective vaccines to prevent toxoplasmosis. PMID- 24176494 TI - Adjuvant system AS02V enhances humoral and cellular immune responses to pneumococcal protein PhtD vaccine in healthy young and older adults: randomised, controlled trials. AB - BACKGROUND: The protection elicited by polysaccharide pneumococcal vaccines against community-acquired pneumonia in older adults remains debatable. Alternative vaccine targets include well-conserved pneumococcal protein antigens, such as pneumococcal histidine triad protein D (PhtD). OBJECTIVE: To evaluate humoral and cellular immune responses and safety/reactogenicity following immunisation with PhtD vaccine with or without adjuvant (alum or AS02V) in older (>=65 years) and young (18-45 years) healthy adults. METHODS: Two phase I/II, single-blind, parallel-group studies were conducted in 150 older and 147 young adults. Participants were randomised to receive 2 doses (months 0 and 2) of PhtD 30 MUg, PhtD 10 MUg plus alum, PhtD 30 MUg plus alum, PhtD 10 MUg plus AS02V or PhtD 30 MUg plus AS02V, or the 23-valent polysaccharide pneumococcal vaccine (23PPV) at month 0 with placebo (saline solution) at month 2. Safety/reactogenicity was assessed. PhtD-specific antibody, T cell and memory B cell responses were evaluated. RESULTS: Solicited adverse events were more common in young participants and with adjuvanted vaccines. No vaccine-related serious adverse events were reported. Although anti-PhtD geometric mean antibody concentrations (GMCs) were consistently lower in the older adult cohort than in young adults, GMCs in the older cohort following PhtD 30 MUg plus AS02V were comparable to those induced by plain PhtD or PhtD 30 MUg plus alum in the young cohort. Compared with alum adjuvant, AS02V adjuvant system was associated with an increased frequency of PhtD-specific CD4 cells in both cohorts and a significantly higher specific memory B cell response in the older cohort, similar to responses obtained in the young cohort. CONCLUSION: The improved immune response to PhtD vaccine containing the AS02V adjuvant system in comparison to alum suggests that the reduced immune response to vaccines in older adults can be partially restored to the response level observed in young adults. ClinicalTrials.gov identifiers: NCT00307528/NCT01767402. PMID- 24176495 TI - Serum antibody response to influenza virus vaccination during chemotherapy treatment in adult patients with solid tumours. AB - BACKGROUND: Higher rates of hospitalization and mortality are described in oncology patients with influenza virus infection compared to the general population. Yearly influenza vaccination is recommended for patients treated with chemotherapy. The optimal moment to administer the vaccine during a treatment cycle has not been studied extensively. PATIENTS AND METHODS: During the influenza season 2011-2012 we conducted a multicenter randomized controlled trial (OFLUVAC, NTR2858, no sponsoring) in the Netherlands. Patients receiving adjuvant chemotherapy for breast or colorectal cancer were randomized between early (day 5 after chemotherapy) and late (day 16 after chemotherapy) vaccination with the influenza virus vaccine (Influvac((r)) 2011/2012-Vaxigrip((r)) 2011/2012). Influenza virus-specific antibody titres were determined before, 3 and 12 weeks after vaccination by haemagglutination inhibition. RESULTS: Thirty-eight breast cancer patients (early=21; late=17) and 18 colorectal cancer patients (early=8; late=10) were analyzed. In breast cancer patients overall serologic responses were adequate. A statistically significant higher response in patients who received early compared to late vaccination in the chemotherapy cycle was observed. Geometric mean titres post vaccination on day 5 versus day 16 were 69.3 versus 27.4 (H3N2), 76.4 versus 17.5 (H1N1) and 34.4 versus 26.0 (B/Brisbane), respectively. In colorectal cancer patients overall serologic responses were adequate, no significant difference was found between early and late vaccination. Geometric mean titres post vaccination on day 5 versus day 16 were 170.1 versus 192.4 (H3N2), 233.0 versus 280.8 (H1N1) and 62.6 versus 75.9 (B/Brisbane), respectively. CONCLUSION: Overall antibody response to the influenza virus vaccine in patients treated with chemotherapy for breast or colorectal cancer patients is adequate. Breast cancer patients seem to mount the best antibody response when vaccinated early after a chemotherapy cycle (<=day 5). No difference was found between early and late vaccination in colorectal cancer patients. PMID- 24176496 TI - Cross-protection elicited by primary and booster vaccinations against Japanese encephalitis: a two-year follow-up study. AB - BACKGROUND: The inactivated Vero cell-derived vaccine (JE-VC, IXIARO) has replaced the traditional mouse brain-derived preparations (JE-MB) in travelers' vaccinations against Japanese encephalitis. We showed recently that a single JE VC dose efficiently boosts immunity in JE-MB-primed vaccinees, and that JE-VC elicits cross-protective immunity against non-vaccine genotypes, including the emerging genotype I. While these studies only provided short-term data, the present investigation evaluates the longevity of seroprotection in the same volunteers. METHODS: The study comprised 48 travelers who had received (1) JE-VC primary series, (2) JE-MB primary series followed by a single JE-VC booster dose, or (3) JE-MB primary series and a single JE-MB booster dose. Serum samples were collected two years after the last vaccine dose, and evaluated with the plaque reduction neutralization test against seven Japanese encephalitis virus strains representing genotypes I-IV. PRNT50 titers >= 10 were considered protective. RESULTS: Two years after the primary series with JE-VC, 87-93% of the vaccinees proved to be cross-protected against test strains representing genotypes II-IV and 73% against those of genotype I. After a single homologous or heterologous booster dose to JE-MB-primed subjects, the two-year seroprotection rates against genotype I-IV strains were 89-100%. CONCLUSIONS: After JE-VC primary series, seroprotection appeared to wane first against genotype I. The first booster should not be delayed beyond two years. In JE-MB-primed subjects, a single JE-VC booster provided cross-protective immunity against genotype I-IV strains in almost all vaccinees, suggesting an interval of two years or even longer for the second booster. These data further support the use of a single JE-VC dose for boosting JE-MB immunity. PMID- 24176497 TI - Cost-effectiveness of a new rotavirus vaccination program in Pakistan: a decision tree model. AB - BACKGROUND: Rotavirus gastroenteritis places a significant health and economic burden on Pakistan. To determine the public health impact of a national rotavirus vaccination program, we performed a cost-effectiveness study from the perspective of the health care system. METHODS: A decision tree model was developed to assess the cost-effectiveness of a national vaccination program in Pakistan. Disease and cost burden with the program were compared to the current state. Disease parameters, vaccine-related costs, and medical treatment costs were based on published epidemiological and economic data, which were specific to Pakistan when possible. An annual birth cohort of children was followed for 5 years to model the public health impact of vaccination on health-related events and costs. The cost-effectiveness was assessed and quantified in cost (2012 US$) per disability adjusted life-year (DALY) averted and cost per death averted. Sensitivity analyses were performed to assess the robustness of the incremental cost effectiveness ratios (ICERs). RESULTS: The base case results showed vaccination prevented 1.2 million cases of rotavirus gastroenteritis, 93,000 outpatient visits, 43,000 hospitalizations, and 6700 deaths by 5 years of age for an annual birth cohort scaled from 6% current coverage to DPT3 levels (85%). The medical cost savings would be US$1.4 million from hospitalizations and US$200,000 from outpatient visit costs. The vaccination program would cost US$35 million at a vaccine price of US$5.00. The ICER was US$149.50 per DALY averted or US$4972 per death averted. Sensitivity analyses showed changes in case-fatality ratio, vaccine efficacy, and vaccine cost exerted the greatest influence on the ICER. CONCLUSIONS: Across a range of sensitivity analyses, a national rotavirus vaccination program was predicted to decrease health and economic burden due to rotavirus gastroenteritis in Pakistan by ~40%. Vaccination was highly cost effective in this context. As discussions of implementing the intervention intensify, future studies should address affordability, efficiency, and equity of vaccination introduction. PMID- 24176498 TI - Interchangeability of Quinvaxem during primary vaccination schedules: results from a phase IV, single-blind, randomized, controlled, single-center, non inferiority study. AB - Combination vaccines against diphtheria, tetanus and pertussis (DTP) represent the core of childhood vaccination programs. Quinvaxem, a fully-liquid, pentavalent combination vaccine containing inactivated hepatitis B (HepB), Haemophilus influenzae type b (Hib) and whole-cell pertussis (wP) antigens, and tetanus and diphtheria toxoids, has been shown to be suitable for boosting children primed in infancy with another DTwP-HepB-Hib vaccine. This single-blind, randomized, controlled study was designed to demonstrate non-inferiority of a primary vaccination course (6-10-14 week schedule) of Tritanrix HB+Hib (first dose) and Quinvaxem (second/third doses) versus three doses of Quinvaxem with respect to the seroprotection/seroconversion rates for all antigens one month after vaccination course completion. Four hundred healthy subjects eligible for the local Expanded Program on Immunization were enrolled and equally randomized to the two treatment regimens. All subjects achieved seroprotection for tetanus and Hib, all except one for diphtheria, and all except two achieved seroconversion against Bordetella pertussis. Seroprotection against hepatitis B was achieved by 97.4% of Tritanrix HB+Hib followed by Quinvaxem and 94.9% of Quinvaxem subjects. Therefore, one month after vaccination course completion, seroprotection rates (seroconversion rate for B. pertussis) of Tritanrix HB+Hib followed by Quinvaxem were non-inferior to those elicited by Quinvaxem only, thus meeting the primary objective. Adverse events were comparable between the groups and were in line with the safety profile of the vaccines. The switch of vaccine had no apparent effect on safety endpoints. Our results support the use of Quinvaxem interchangeably with Tritanrix HB+Hib in a primary vaccination course and provides further evidence for the interchangeability of pentavalent vaccines (Clinical Trials.gov registry: NCT01357720). PMID- 24176499 TI - Different T cell memory in preadolescents after whole-cell or acellular pertussis vaccination. AB - To better understand vaccine-induced protection and its potential failure in light of recent whooping cough resurgence, we evaluated quantity as well as quality of memory T cell responses in B. pertussis-vaccinated preadolescent children. Using a technique based on flow cytometry to detect proliferation, cytokine production and phenotype of antigen-specific cells, we evaluated residual T cell memory in a cohort of preadolescents who received a whole-cell pertussis (wP; n=11) or an acellular pertussis vaccine (aP; n=13) during infancy, and with a median of 4 years elapsed from the last pertussis booster vaccine, which was aP for all children. We demonstrated that B. pertussis-specific memory T cells are detectable in the majority of preadolescent children several years after vaccination. CD4(+) and CD8(+) T cell proliferation in response to pertussis toxin and/or filamentous hemagglutinin was detected in 79% and 60% of the children respectively, and interferon-gamma or tumor necrosis factor-alpha producing CD4(+) T cells were detected in 65% and 53% of the children respectively. Phenotyping of the responding cells showed that the majority of antigen-specific cells, whether defined by proliferation or cytokine production, were CD45RA(-)CCR7(-) effector memory T cells. Although the time since the last booster vaccine was significantly longer for wP-compared to aP-vaccinated children, their proliferation capacity in response to antigenic stimulation was comparable, and more children had a detectable cytokine response after wP- compared to aP-vaccination. This study supports at the immunological level recent epidemiological studies indicating that infant vaccination with wP induces longer lasting immunity than vaccination with aP-vaccines. PMID- 24176500 TI - Metabolomics, peptidomics and proteomics applications of capillary electrophoresis-mass spectrometry in Foodomics: a review. AB - In the current post-genomic era, Foodomics has been defined as a discipline that studies food and nutrition through the application of advanced omics approaches. Foodomics involves the use of genomics, transcriptomics, epigenetics, proteomics, peptidomics, and/or metabolomics to investigate food quality, safety, traceability and bioactivity. In this context, capillary electrophoresis-mass spectrometry (CE-MS) has been applied mainly in food proteomics, peptidomics and metabolomics. The aim of this review work is to present an overview of the most recent developments and applications of CE-MS as analytical platform for Foodomics, covering the relevant works published from 2008 to 2012. The review provides also information about the integration of several omics approaches in the new Foodomics field. PMID- 24176501 TI - Activated sludge characterization through microscopy: a review on quantitative image analysis and chemometric techniques. AB - In wastewater treatment processes, and particularly in activated sludge systems, efficiency is quite dependent on the operating conditions, and a number of problems may arise due to sludge structure and proliferation of specific microorganisms. In fact, bacterial communities and protozoa identification by microscopy inspection is already routinely employed in a considerable number of cases. Furthermore, quantitative image analysis techniques have been increasingly used throughout the years for the assessment of aggregates and filamentous bacteria properties. These procedures are able to provide an ever growing amount of data for wastewater treatment processes in which chemometric techniques can be a valuable tool. However, the determination of microbial communities' properties remains a current challenge in spite of the great diversity of microscopy techniques applied. In this review, activated sludge characterization is discussed highlighting the aggregates structure and filamentous bacteria determination by image analysis on bright-field, phase-contrast, and fluorescence microscopy. An in-depth analysis is performed to summarize the many new findings that have been obtained, and future developments for these biological processes are further discussed. PMID- 24176502 TI - Handling large datasets of hyperspectral images: reducing data size without loss of useful information. AB - Hyperspectral Imaging (HSI) is gaining increasing interest in the field of analytical chemistry, since this fast and non-destructive technique allows one to easily acquire a large amount of spectral and spatial information on a wide number of samples in very short times. However, the large size of hyperspectral image data often limits the possible uses of this technique, due to the difficulty of evaluating many samples altogether, for example when one needs to consider a representative number of samples for the implementation of on-line applications. In order to solve this problem, we propose a novel chemometric strategy aimed to significantly reduce the dataset size, which allows to analyze in a completely automated way from tens up to hundreds of hyperspectral images altogether, without losing neither spectral nor spatial information. The approach essentially consists in compressing each hyperspectral image into a signal, named hyperspectrogram, which is created by combining several quantities obtained by applying PCA to each single hyperspectral image. Hyperspectrograms can then be used as a compact set of descriptors and subjected to blind analysis techniques. Moreover, a further improvement of both data compression and calibration/classification performances can be achieved by applying proper variable selection methods to the hyperspectrograms. A visual evaluation of the correctness of the choices made by the algorithm can be obtained by representing the selected features back into the original image domain. Likewise, the interpretation of the chemical information underlying the selected regions of the hyperspectrograms related to the loadings is enabled by projecting them in the original spectral domain. Examples of applications of the hyperspectrogram-based approach to hyperspectral images of food samples in the NIR range (1000-1700 nm) and in the vis-NIR range (400-1000 nm), facing a calibration and a defect detection issue respectively, demonstrate the effectiveness of the proposed approach. PMID- 24176503 TI - Vapor-phase testing of the memory-effects in benzene- and toluene-imprinted polymers conditioned at elevated temperature. AB - The preparation of polymers imprinted with common aromatic solvents such as benzene and toluene is an under-exploited subject of research. The present study was aimed at the understanding of whether true solvent memory effects can be achieved by molecular imprinting, as well as if they are stable at elevated temperature. A set of copolymers, comprising low and high cross-linking levels, was prepared from four different combinations of functional monomer and cross linker, namely methacrylic acid (MAA)/ethylene glycol dimethacrylate (EGDMA), methyl methacrylate (MMA)/EGDMA, MAA/divinyl benzene (DVB) and MMA/DVB. Each possible combination was prepared separately in benzene, toluene and acetonitrile. The obtained materials were applied as coatings onto nickel titanium (Ni-Ti) alloy wires which were incorporated into solid-phase microextraction devices and finally tested for their ability to competitively adsorb vapors from the headspace of an aqueous solution containing a few volatile organic compounds. Porosity analysis showed that, regardless of the solvent used, only a high cross-linking level permitted the preparation of mesoporous copolymers (BJH radius typically in the range 13-15 nm), a requirement for providing accessibility to the targeted nanoscale-imprinted cavities. A noticeable exception was, however, observed for the MMA/DVB copolymers which exhibited much diminished BJH radius. The porosity data correlated well with the extraction profiles found, which suggested the presence of benzene-imprinted sites in all the highly cross-linked copolymers prepared in benzene, except for the MMA/DVB copolymers. Concerning the effect of an elevated conditioning temperature on the memory-effects created by the imprinting process, the results were clearly indicative that the tested copolymers, including the more robust highly cross-linked ones, are not suitable for high temperature applications such as solid-phase microextraction coupled to gas chromatography. PMID- 24176504 TI - Molecular evaluation of soil organic matter characteristics in three agricultural soils by improved off-line thermochemolysis: the effect of hydrofluoric acid demineralisation treatment. AB - The molecular composition of soil organic matter (SOM) in three agricultural fields under different managements, was evaluated by off-line thermochemolysis followed by gas chromatography mass spectrometry analysis (THM-GC-MS). While this technique enabled the characterization of SOM components in coarse textured soil, its efficiency in heavy textured soils was seriously affected by the interference of clay minerals, which catalyzed the formation of secondary artifacts in pyrolysates. Soil demineralization with hydrofluoric acid (HF) solutions effectively improved the reliable characterization of organic compounds in clayey soils by thermochemolysis, while did not alter significantly the results of coarse textured soil. A wide range of lignin monomers and lipids molecules, of plant and microbial origin, were identified in the pyrograms of HF treated soils, thereby revealing interesting molecular differences between SOM management practices. Our results indicated that clay removal provided by HF pretreatment enhanced the capacity of thermochemolysis to be a valuable and accurate technique to study the SOM dynamics also in heavy-textured and OC-depleted cultivated soils. PMID- 24176505 TI - Steroid and steroid glucuronide profiles in urine during pregnancy determined by liquid chromatography-electrospray ionization-tandem mass spectrometry. AB - An ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-MS/MS) method was developed for the analysis of steroids and their glucuronides in urine samples. The method provides high sensitivity and fast analysis, as both steroids and their glucuronides can be analyzed directly without hydrolysis or complex sample preparation. The method was applied in profiling of targeted and nontargeted steroids and steroid glucuronides during pregnancy. The concentrations of 11 of 27 targeted steroids and steroid glucuronides and the concentrations of 25 nontargeted steroid glucuronides increased about 10-400 fold during the pregnancy. The concentrations of most of these 36 compounds began to increase in the first days of the pregnancy, increased gradually during the pregnancy, achieved a maximum in late pregnancy, and decreased sharply after delivery. Exceptionally, the concentrations of allopregnanolone and 17-hydroxypregnenolone started to increase later than those of the other steroids. Moreover, the concentrations of E2 glucuronides began to decrease one week before the delivery, in contrast to most of the steroids and steroid glucuronides, whose concentrations dropped sharply during the delivery. Concentrations of 34 compounds decreased noticeably when the subject was on sick leave owing a series of painful contractions. The results suggest that steroids and especially steroid glucuronides may provide a valuable diagnostic tool to follow the course of pregnancy. PMID- 24176506 TI - An ultrasensitive quantum dots fluorescent polarization immunoassay based on the antibody modified Au nanoparticles amplifying for the detection of adenosine triphosphate. AB - In this work, an ultrasensitive fluorescent polarization immunoassay (FPIA) method based on the quantum dot/aptamer/antibody/gold nanoparticles ensemble has been developed for the detection of adenosine triphosphate (ATP). DNA hybridization is formed when ATP is present in the PBS solution containing the DNA-conjugated quantum dots (QDs) and antibody-AuNPs. The substantial sensitivity improvement of the antibody-AuNPs-enhanced method is mainly attributed to the slower rotation of fluorescent unit when QDs-labeled oligonucleotides hybridize with antibody modified the gold nanoparticle. As a result, the fluorescent polarization (FP) values of the system increase significantly. Under the optimal conditions, a linear response with ATP concentration is ranged from 8*10(-12) M to 2.40*10(-4) M. The detection limit reached as low as 1.8 pM. The developed work provides a sensitive and selective immunoassay protocol for ATP detection, which could be applied in more bioanalytical systems. PMID- 24176507 TI - Simultaneous, real-time measurement of nitric oxide and oxygen dynamics during cardiac ischemia-reperfusion of the rat utilizing sol-gel-derived electrochemical microsensors. AB - In this study, we simultaneously measured nitric oxide (NO) and oxygen (O2) dynamics in the myocardium during myocardial ischemia-reperfusion (IR) utilizing sol-gel modified electrochemical NO and O2 microsensors. In addition, we attempted to clarify the correlation between NO release in the ischemic period and O2 restoration in the myocardium after reperfusion, comparing a control heart with a remote ischemic preconditioning (RIPC)-treated heart as an attractive strategy for myocardial protection. Rat hearts were randomly divided into two groups: a control group (n=5) and an RIPC group (n=5, with RIPC treatment). Myocardia that underwent RIPC treatment (182+/-70 nM, p<0.05) released more NO during the ischemic period than those of the control group (63+/-41 nM). The restoration value of oxygen tension (pO2) in the RIPC group significantly increased and was restored to pre-ischemic levels (92.6+/-36.8%); however, the pO2 of the control group did not increase throughout the reperfusion period (5.7+/-7.5%, p=0.001). Myocardial infarct size measurements revealed a significant decrease in cell death in the myocardium region of the RIPC group (41.44+/-6.42%, p=0.001) compared with the control group (60.05+/-10.91%). As a result, we showed that the cardioprotective effect of RIPC could be attributed to endogenous NO production during the ischemic period, which subsequently promoted reoxygenation in post-ischemic myocardia during early reperfusion. Our results suggest that the promotion of endogenous formation during an ischemic episode might be helpful as a therapeutic strategy for protecting the myocardium from IR injury. Additionally, our NO and O2 perm-selective microsensors could be utilized to evaluate the effect of drug or treatment. PMID- 24176508 TI - An ultrasensitive method for the determination of melamine using cadmium telluride quantum dots as fluorescence probes. AB - An ultrasensitive and simple method for the determination of melamine was developed based on the fluorescence quenching of thioglycolic acid (TGA) capped CdTe quantum dots (QDs) at pH 11.0. In strong alkaline aqueous solution, the selectivity of the method has been greatly improved due to most heavy metal ions show no interference as they are in the precipitation form or in their anion form. Furthermore, CdTe quantum dots have higher quantum yields at higher pH. The method has a wider concentration range and lower detection limit. The influence factors on the determination of melamine were investigated and the optimum conditions were determined. Under optimum conditions, the fluorescence intensity change of TGA coated CdTe quantum dots was linearly proportional to melamine over a concentration range from 1.0*10(-11) to 1.0*10(-5) mol L(-1) with a correlation coefficient of 0.9943 and a detection limit of 5*10(-12) mol L(-1). The mechanism of fluorescence quenching of the QDs has been proposed based on the infrared spectroscopy information and electrophoresis experiments in presence of melamine under alkaline condition. The proposed method was employed to detect trace melamine in milk powder and pet feeds with satisfactory results. PMID- 24176509 TI - Inkjet printing lanthanide doped nanorods test paper for visual assays of nitroaromatic explosives. AB - The facile and sensitive strategies for detections of nitroaromatic explosives are highly desirable in many challenging environments, especially for homeland security against terrorism. Here, we inkjet printed polyethylenimine (PEI)-coated Ce, Tb co-doped NaGdF4 nanorods (NaGdF4:Ce/Tb NRs) onto common filter paper to construct test paper for visual and instant detections of a typical explosive 2,4,6-trinitrophenol (TNP). Polyethylenimine molecules not only facilitate the formation of uniform NaGdF4 nanorods but also provide specific recognized sites for TNP by the acid-base pairing interaction. The resultant TNP bound at the surface of PEI-coated NaGdF4:Ce/Tb NRs can strongly quench the phosphorescence with a remarkably high quenching constant by the charge transfer mechanism from NaGdF4:Ce/Tb NRs to TNP. By printing of the probe on a piece of filter paper, trace amounts of TNP can be visually detected by the appearance of a dark color against a bright green background under a UV lamp. This test paper can detect TNP as low as 0.45 ng mm(-2) by the naked eye, which provides a potential application in the rapid, on-line detections of explosives. PMID- 24176510 TI - Quartz crystal microbalance with dissipation coupled to on-chip MALDI-ToF mass spectrometry as a tool for characterising proteinaceous conditioning films on functionalised surfaces. AB - Proteinaceous conditioning films (pCFs) are thought to play a key role in microbial adhesion, leading to the fouling of technical and biomedical devices and biofilm formation, which in turn causes material damage or persistent infections, respectively. However, little is definitively known about the process of surface conditioning via proteins. Herein, we demonstrate the potential of quartz crystal microbalance with dissipation coupled to MALDI-ToF mass spectrometry (QCM-D-MALDI) to investigate protein adsorption on different surfaces, enabling both the monitoring of CF formation and the determination of the molecular composition of CFs. After running QCM-D experiments, a subsequent tryptic on chip digestion step allows the identification of the proteins deposited on the sensor chip surface via MALDI-ToF mass spectrometry. Prominent blood plasma proteins, i.e., human serum albumin (HSA), fibrinogen (FG) and fibronectin (FN), were used. Chemically well defined sensor surfaces were prepared, among others, via self-assembled monolayer (SAM) technology. In cases where protein adsorption was observed by QCM-D, the adsorbed proteins were clearly detected and identified using MALDI-ToF/MS for both single-protein solutions of HSA, FG and FN as well as for protein mixtures. However, for equimolar protein mixtures on TiO2 surfaces, only signals attributed to FG and FN were observed in the mass spectra. No signals indicating the presence of HSA could be detected. This finding leads to the assumption that only FG and FN attach to the TiO2 sensor surface under the given experimental conditions. PMID- 24176511 TI - Loading of free radicals on the functional graphene combined with liquid chromatography-tandem mass spectrometry screening method for the detection of radical-scavenging natural antioxidants. AB - A novel free radical reaction combined with liquid chromatography electrospray ionization tandem mass spectrometry (FRR-LC-PDA-ESI/APCI-MS/MS) screening method was developed for the detection and identification of radical-scavenging natural antioxidants. Functionalized graphene was prepared by chemical method for loading free radicals (superoxide radical, peroxyl radical and PAHs free radical). Separation was performed with and without a preliminary exposure of the sample to specific free radicals on the functionalized graphene, which can facilitate reaction kinetics (charge transfers) between free radicals and potential antioxidants. The difference in chromatographic peak areas is used to identify potential antioxidants. The structure of the antioxidants in one sample (Swertia chirayita) is identified using MS/MS and comparison with standards. Thirteen compounds were found to possess potential antioxidant activity, and their free radical-scavenging capacities were investigated. The thirteen compounds were identified as 1,3,5-trihydroxyxanthone-8-O-beta-D-glucopyranoside (PD1), norswertianin (PD2), 1,3,5,8-tetrahydroxyxanthone (PD3), 3, 3', 4', 5, 8-penta hydroxyflavone-6-beta-D-glucopyranosiduronic acid-6'-pentopyranose-7-O glucopyranoside (PD4), 1,5,8-trihydroxy-3-methoxyxanthone (PD5), swertiamarin (PS1), 2-C-beta-D-glucopyranosyl-1,3,7-trihydroxylxanthone (PS2), 1,3,7 trihydroxylxanthone-8-O-beta-D-glucopyranoside (PL1), 1,3,8-trihydroxyl xanthone 5-O-beta-D-glucopyranoside (PL2), 1,3,7-trihydroxy-8-methoxyxanthone (PL3), 1,2,3 trihydroxy-7,8-dimethoxyxanthone (PL4), 1,8-dihydroxy-2,6-dimethoxy xanthone (PL5) and 1,3,5,8-tetramethoxydecussatin (PL6). The reactivity and SC50 values of those compounds were investigated, respectively. PD4 showed the strongest capability for scavenging PAHs free radical; PL4 showed prominent scavenging capacities in the lipid peroxidation processes; it was found that all components in S. chirayita exhibited weak reactivity in the superoxide radical scavenging capacity. The use of the free radical reaction screening method based on LC-PDA ESI/APCI-MS/MS would provide a new approach for rapid detection and identification of radical-scavenging natural antioxidants from complex matrices. PMID- 24176512 TI - Quality by Design approach in the development of a solvent-modified micellar electrokinetic chromatography method: finding the design space for the determination of amitriptyline and its impurities. AB - A solvent-modified micellar electrokinetic chromatography method was set up for the simultaneous determination of the tricyclic antidepressant amitriptyline (AMI) and its main impurities. The method was developed following Quality by Design (QbD) principles according to ICH Guideline Q8(R2). QbD approach made it possible to find the design space (DS), where quality was assured. After a scouting phase, aimed at selecting a suitable capillary electrophoresis pseudostationary phase, risk assessment tools were employed to define the critical process parameters (CPPs) to be considered in a screening phase (applied voltage, concentration and pH of the background electrolyte, concentration of the surfactant sodium dodecyl sulphate, of the cosurfactant n-butanol and of the organic modifiers acetonitrile and urea). The effects of the seven selected CPPs on critical quality attributes (CQAs), namely resolution values between critical peak pairs and analysis time, were investigated throughout the knowledge space by means of a symmetric screening matrix. Response surface study was then carried out on four selected CPPs by applying a Doehlert Design. Monte-Carlo simulations were performed in order to estimate the probability of meeting the desired specifications on CQAs, and thus to define the DS by means of a risk of failure map. Additional points at the edges of the DS were tested in order to verify the requirements for CQAs to be fulfilled. A control strategy was implemented by defining system suitability tests. The developed method was validated following ICH Guideline Q2(R1), including robustness assessment by Plackett-Burman design, and was applied to the analysis of real samples of amitriptyline coated tablets. PMID- 24176513 TI - Marijuana not ready for prime time as an analgesic. PMID- 24176514 TI - Arachnoid cyst masquerades as late onset obsessive-compulsive disorder. AB - Literature evidence suggests that onset of obsessive-compulsive disorder (OCD) at a later age is usually associated with brain lesions. However, none of previous reports suggest an association between arachnoid cyst and OCD. In this report, we present a case of OCD, starting at the age of 40 years, in which the obsessive symptoms were characteristically associated with fluctuating insight. Investigation revealed an arachnoid cyst, in the area of left fronto-parietal region, with broad base towards the falx. PMID- 24176515 TI - Escitalopram-induced Parkinsonism. AB - OBJECTIVE: Since the early reports associating extrapyramidal side effects (EPS) to serotonin reuptake inhibitors (SSRI), SSRIs have been pointed as more common offenders among antidepressants in producing EPS. The induction of EPS by SSRIs has been thought to be a consequence of serotonergically mediated inhibition of the dopaminergic system. We would like to present a case of escitalopram-induced Parkinsonism to increase awareness of this clinical problem. METHOD: A 29-year old male patient complaining of anger outbursts was started on escitalopram 10 mg/day without titration for impulse control in an outpatient clinic. Personal and family history was not significant for any chronic disorder, including movement disorders. RESULTS: Two weeks after the initiation of escitalopram, the patient started complaining of tremor, rigidity, slowness of movement, use of small steps when walking difficulty to rise when seated, disturbance of speech and along with the development of a mask-like facial expression. An MRI of the brain revealed normal findings. With a diagnosis of drug-induced Parkinsonism, he was started on 4-mg/day biperiden leading to full resolution of symptoms in 4 weeks, with no further complaints at follow up for 1.5 years. CONCLUSION: As described, drug-induced Parkinsonism may persist or remit slowly despite prompt discontinuation of the offending drug. Some patients may require medications temporarily to relieve symptoms. PMID- 24176517 TI - Plasticity, plasticity, plasticity...and the rigid problem of sex. AB - Why is popular understanding of female-male differences still based on rigid models of development, even though contemporary developmental sciences emphasize plasticity? Is it because the science of sex differences still works from the same rigid models? PMID- 24176518 TI - Co-targeting estrogen receptor and HER2 pathways in breast cancer. AB - The estrogen steroid hormone receptor (ER) and human epithelial growth factor receptor 2 membrane tyrosine kinase growth factor receptor (HER2) are the mediators of two key pathways involved in breast carcinogenesis, invasive behavior and cell growth. Co-expression of these receptors results in specific biological features that are not fully understood, but include relative resistance to hormonal therapy and chemotherapy as well as better long-term outcome imparted by ER and worse outcome by HER2 expression. The ER and HER2 signaling pathways interact with each other as do many biological networks, and this creates opportunities for therapeutic co-targeting with agents that modulate these respective pathways. However, relatively few studies have been conducted to test concurrent manipulation of ER and HER2. The avoidance of chemotherapy side effects is an attractive feature that has further spurred explorations in this strategy. Still, the only dually targeted strategy approved by some regulatory agencies is the combination of hormonal therapy using aromatase inhibition and the HER2 kinase inhibitor lapatinib. Other dual combinations have also demonstrated a benefit, although most of the testing has compared hormonal therapy with or without HER2-directed agents and not the other way around, limiting the applicability of this concept in routine clinical practice, especially when chemotherapy is also used. Newer generation signal transduction inhibitors can augment the efficacy of hormonal therapy, with one such example of mTOR blockade using everolimus now in the clinic. The logical extension of ER and HER2 co-targeting is the discovery and clinical testing of "synthetic lethal" combinations attacking diverse pathways that produce quantum improvements over either therapy alone. Molecular annotation of human cancers can further inform personalized combinatorial regimens based on the unique circuitry of an individual patient's tumor, with the potential to yield much more than incremental gains in survival. PMID- 24176519 TI - Partially involuting congenital hemangiomas: a report of 8 cases and review of the literature. AB - BACKGROUND: Congenital hemangiomas have been divided into 2 major subtypes based on clinical behavior: rapidly involuting congenital hemangioma (RICH) and noninvoluting congenital hemangioma (NICH). OBJECTIVE: We describe a clinical subtype of congenital hemangioma that begins as a RICH but fails to completely involute and persists as a NICH-like lesion. We propose the term "partially involuting congenital hemangioma" for this lesion with overlapping features. METHODS: A review of the medical charts, serial clinical photographs, imaging, and biopsies performed on children with a diagnosis of partially involuting congenital hemangioma between 2001 and 2012 at Centre Hospitalier Universitaire Sainte-Justine pediatric dermatology/vascular anomalies clinic was performed. RESULTS: Eight full-term, healthy infants presented at birth with vascular lesions typical of RICH. Affected locations included the head and neck, trunk, or extremities. Size varied from 2.0 * 1.5 cm to 13.0 * 8.5 cm. All had rapid involution during the first 12 to 30 months of life before stabilizing in size and appearance. LIMITATIONS: Only a small number of cases were identified. CONCLUSION: Partially involuting congenital hemangiomas are congenital hemangiomas with a distinct behavior, evolving from RICH to persistent NICH-like lesions. Their recognition and study will help us better understand whether RICH and NICH are indeed separate entities or simply part of a spectrum. PMID- 24176520 TI - Angiosarcoma of the scalp successfully treated with pazopanib. PMID- 24176521 TI - The MPATH-Dx reporting schema for melanocytic proliferations and melanoma. AB - BACKGROUND: The histologic diagnosis of melanoma and nevi can be subject to discordance and errors, potentially leading to inappropriate treatment and harm. Diagnostic terminology is not standardized, creating confusion for providers and patients and challenges for investigators. OBJECTIVE: We sought to describe the development of a pathology reporting form for more precise research on melanoma and a diagnostic-treatment mapping tool for improved patient care and consistency in treatment. METHODS: Three dermatopathologists independently reviewed melanocytic lesions randomly selected from a dermatopathology database. Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) reporting schema evolved from iterative case review and form revision. RESULTS: Differences in diagnostic thresholds, interpretation, and nomenclature contributed to development of the MPATH-Dx histology reporting form, which groups lesions by similarities in histogenesis and degrees of atypia. Because preliminary results indicate greater agreement regarding suggested treatments than for specific diagnoses, the diverse terminologies of the MPATH-Dx histology reporting form were stratified by commonalities of treatments in the MPATH-Dx diagnostic-treatment mapping scheme. LIMITATIONS: Without transformative advances in diagnostic paradigms, the interpretation of melanocytic lesions frequently remains subjective. CONCLUSIONS: The MPATH-Dx diagnostic-treatment mapping scheme could diminish confusion for those receiving reports by categorizing diverse nomenclature into a hierarchy stratified by suggested management interventions. PMID- 24176522 TI - Serum endocan levels as a marker of disease activity in patients with Behcet disease. AB - BACKGROUND: Endocan is a novel human endothelial cell-specific molecule. The central role of leukocytes and endothelial dysfunction in the development of Behcet disease (BD) led us to hypothesize that endocan might be a marker of this disease. OBJECTIVE: We investigated the relationship between serum levels of endocan and disease activity in patients with BD. METHODS: In all, 33 patients (16 active, 17 inactive) with BD and 35 healthy persons were included in the study. Endocan and C-reactive protein were measured in all subjects. RESULTS: Patients with BD had significantly higher serum endocan levels. Mean serum levels of endocan were 1.29 +/- 0.60 ng/mL (range: 0.58-2.99) in patients with BD and 0.75 +/- 0.16 ng/mL (range: 0.48-1.21) in control subjects (P < .001). In patients with BD, serum endocan levels correlated moderately but significantly with C-reactive protein, erythrocyte sedimentation rate, and disease activity. Receiver operating characteristic curve analysis suggested that the optimum endocan level cut-off point for patients with BD was 0.87 ng/mL, with a sensitivity and specificity of 75.8% and 80%, respectively (area under curve 0.835, 95% confidence interval 0.738-0.932). LIMITATIONS: The main limitation of our study is the relatively small sample size. CONCLUSIONS: Circulating endocan may be a marker of BD activity. PMID- 24176523 TI - Successful therapeutic transplantation of revertant skin in epidermolysis bullosa. AB - BACKGROUND: Epidermolysis bullosa (EB) is a group of genetic blistering diseases. Despite many efforts, treatment for EB remains symptomatic. Revertant mosaicism, coexistence of cells carrying disease-causing mutations with cells in which the inherited mutation is genetically corrected by a spontaneous genetic event (revertant cells) in 1 individual, can be found in EB. The naturally corrected revertant keratinocytes provide an opportunity for autologous cell therapy. OBJECTIVE: We sought to locally treat EB by transplantation of revertant skin. METHODS: Persistent ulcers in a patient with non-Herlitz junctional EB caused by mutations in the LAMB3 gene were treated by transplantation of split-thickness biopsy specimens from one of his revertant patches. RESULTS: All transplanted biopsy specimens were accepted and complete re-epithelialization occurred within 14 days. During 18 months of follow-up, the patient never experienced blisters or wounds in the grafted area, nor in the healed donor site. Immunofluorescence and DNA sequencing showed that acceptor sites healed with transplanted revertant keratinocytes. LIMITATIONS: Punch grafting allows only limited expansion of revertant skin. CONCLUSIONS: We demonstrate that phenotypical and genotypical correction of skin in patients with revertant mosaicism by expansion of revertant skin might be a promising therapeutic option for cutaneous manifestations of EB. PMID- 24176525 TI - The need for a physical basis of cognitive process: comment on "Consciousness in the universe. A review of the 'Orch OR' theory" by Hameroff and Penrose. PMID- 24176524 TI - Reliability assessment and validation of the postacne hyperpigmentation index (PAHPI), a new instrument to measure postinflammatory hyperpigmentation from acne vulgaris. AB - BACKGROUND: There are no validated outcome measures for postinflammatory hyperpigmentation (PIH). OBJECTIVE: We sought to determine the reliability and validity of an outcome measure for PIH after acne in patients with skin of color. METHODS: A postacne hyperpigmentation index (PAHPI) was developed. Six raters scored 21 patients with PIH twice. Reliability was determined within and between raters, whereas validity was evaluated by comparing scores with severity ranking by an independent dermatologist. The pigment intensity scores were compared with the melanin index of each patient using a narrowband reflectance spectrophotometer. A quality-of-life score (Skindex-29) was also compared with PAHPI scores. RESULTS: Total PAHPI scores showed good reliability within and between raters and were valid when compared with clinical severity and melanin indices. Good correlation was achieved between the total PAHPI score and the emotion subscale of the Skindex-29. LIMITATIONS: Generalizability of results is limited to African American females. CONCLUSION: The PAHPI shows good reliability and validity when scored on patients with PIH from acne vulgaris. The PAHPI also correlates well with the emotional impact of PIH as measured by the Skindex-29. Future studies should assess the ability of the PAHPI to change with improvement of PIH from acne after treatment. PMID- 24176527 TI - Design and synthesis of conformationally constrained analogues of cis-cinnamic acid and evaluation of their plant growth inhibitory activity. AB - 1-O-cis-Cinnamoyl-beta-D-glucopyranose is known to be one of the most potent allelochemical candidates and was isolated from Spiraea thunbergii Sieb by Hiradate et al. (2004), who suggested that it derived its strong inhibitory activity from cis-cinnamic acid, which is crucial for phytotoxicity. In this study, key structural features and substituent effects of cis-cinnamic acid (cis CA) on lettuce root growth inhibition was investigated. These structure-activity relationship studies indicated the importance of the spatial relationship of the aromatic ring and carboxylic acid moieties. In this context, conformationally constrained cis-CA analogues, in which the aromatic ring and cis-olefin were connected by a carbon bridge, were designed, synthesized, and evaluated as plant growth inhibitors. The results of the present study demonstrated that the inhibitory activities of the five-membered and six-membered bridged compounds were enhanced, up to 0.27 MUM, and were ten times higher than cis-CA, while the potency of the other compounds was reduced. PMID- 24176528 TI - Cassane diterpenes from Caesalpinia platyloba. AB - The dichloromethane extract from the leaves of Caesalpinia platyloba provided cassane diterpenes whose structures were determined as (-)-(5S,6R,8S,9S,10R,14R) 6-acetoxyvouacapane (1), (-)-(5S,6R,8S,9S,10R,12Z,14R)-6-acetoxycassa-12,15-diene (3), and (-)-(5S,6R,8S,9S,10R,13E)-6-acetoxycassa-13,15-diene (4). Compound 1 was chemically correlated with (-)-(5S,6R,8S,9S,10R,14R)-6-hydroxyvouacapane (2), (+) (5S,8S,9S,10R,14R)-6-oxovouacapane (5), and (+)-(5S,6S,8S,9S,10R,14R)-6 acetoxyvouacapane (6), the last one previously isolated from Dipteryx lacunifera. The absolute configurations of all six diterpenes 1-6 were established by comparison of DFT calculated vibrational circular dicroism spectra of 1, 2 and 5 with those obtained experimentally. In addition, several reported chemical shifts for 2 and 5 were reassigned based on two-dimensional NMR measurements. PMID- 24176529 TI - Maternal dietary counseling reduces total and LDL cholesterol postpartum. AB - OBJECTIVE: The aim of this study was to investigate the effects of dietary counseling on blood lipid concentrations during and after pregnancy. METHODS: Partcipants (N = 256) were randomized into three study groups: dietary counseling with probiotics or placebo and a control group at first trimester of pregnancy. Diet quality was evaluated from food records by an index of healthy eating and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, apolipoproteins A-I and B, and lipoprotein (a) were measured at the first and third trimesters of pregnancy and 1, 6, and 12 mo postpartum. RESULTS: During pregnancy, no differences in lipid values were noted among the groups, but postpartum TC and LDL-C were lower in both dietary counseling groups compared with controls (P = 0.027 and P = 0.012, respectively). Higher points on the healthy eating index, normal weight, and regular exercise were associated with a more favorable lipid profile at 12 mo after delivery. CONCLUSION: Maternal dietary counseling may lower maternal TC and LDL-C levels postpartum. A healthy lifestyle during pregnancy and postpartum may benefit women's cardiovascular health. PMID- 24176530 TI - Measurement of the apparent diffusion coefficient in paediatric mitochondrial encephalopathy cases and a comparison of parenchymal changes associated with the disease using follow-up diffusion coefficient measurements. AB - OBJECTIVES: To reveal the contribution of MRI and diffusion-weighted imaging (DWI) to the diagnosis of mitochondrial encephalopathy (ME) and to evaluate the parenchymal changes associated with this disease in the involved parenchymal areas using the apparent diffusion coefficient (ADC) parameter. METHODS: Ten patients who had undergone MRI and DWI analysis with a pre-diagnosis of neurometabolic disease, and who were subsequently diagnosed with ME in laboratory and/or genetic studies, were included in our study. ADC values were compared with a control group composed of 20 patients of similar age with normal brains. Evaluations involved measurements made in 20 different areas determined on the ADC map. The dominance or contribution of ADC coefficient measurements to the conventional sequences was compared with the controls. RESULTS: In the first examination, an increase in both diffusion and ADC values was detected in six cases and diffusion restriction and a decrease in ADC values in three patients. While an increase in both diffusion and ADC values was demonstrated in four cases, there was diffusion restriction and a decrease in ADC values in three cases in the control examinations. CONCLUSIONS: DWI provides information that complements conventional MRI sequences in the diagnosis of ME. PMID- 24176531 TI - Pulmonary artery pulsatility and effect on vessel diameter assessment in magnetic resonance imaging. AB - BACKGROUND: Information about thoracic vascular sizes can crucially affect clinical decision-making in cardiovascular disease. A variety of imaging techniques such as catheter angiography, contrast enhanced computed tomography (CT) and cardiac magnetic resonance imaging (CMR) are routinely used to measure vascular diameters. Traditionally, CMR black blood sequences were the main anatomical tool for visualization of vascular anatomy and still are in many centers. More recently, the vessel diameters are measured on multiplanar reconstructions derived from static magnetic resonance angiography (MRA). This study was performed to investigate the variation of vessel diameter measurements on different CMR techniques with respect to their data acquisition scheme. METHODS: We recruited two groups of patients for this prospective study. One group included patients with repaired tetralogy of Fallot (TOF), with at least moderate pulmonary insufficiency and another group of patients who underwent CMR as part of a diagnostic work-up for arrhythmogenic right ventricular cardiomyopathy (ARVC). Additional images of the right pulmonary artery (RPA) were acquired in the double inversion recovery (DIR) black blood, cine steady state free precession (SSFP) and MRA. All images were reviewed by two CMR trained readers using the electronic caliper provided within the picture archiving and communication system package. The maximum diameter of each artery was recorded in millimeters with up to one decimal point. Paired t-tests and Bland-Altman plots were used for comparison of measurements between different sequences. RESULTS: A total of 52 patients were recruited for this study, 26 patients in the TOF group (15 males, age 12.55+/-2.9) and 26 patients in the ARVC group (15 males, age 15.6+/-2.3). In both groups, the RPA sizes were not significantly different between the DIR images and diastolic cine SSFP (p>0.05). Measurements on DIR were significantly smaller than those made on systolic cine SSFP or MRA in both groups (p<0.0001). Vessel diameters measured on systolic SSFP were significantly larger than measurements made on diastolic SSFP (p<0.0001). There was no significant difference between vessel measurements on MRA and measurements on systolic cine SSFP (p=0.44 for the TOF group and p=0.79 for ARVC group). Measurements on the MRA datasets were significantly larger than those on diastolic SSFP images (p<0.0001). CONCLUSION: Black blood, white blood and MRA sequences are all reproducible CMR methods for the assessment of arterial diameters in children and adolescents. Measurements from systolic phase SSFP images are comparable to those from contrast-enhanced MRA. Therefore, the administration of contrast medium is not necessary in every case. Cine SSFP images offer the additional advantage over the other methods in such that both the largest and the smallest diameter of the vessel during the cardiac cycle can be assessed using this technique. This is even more relevant in highly pulsatile circulations, such as patients with repaired TOF and significant pulmonary insufficiency. PMID- 24176532 TI - Contrast-enhanced ultrasonography findings using a perflubutane-based contrast agent in patients with early hepatocellular carcinoma. AB - OBJECTIVE: We evaluated the contrast-enhanced ultrasonography (US) imaging features of early hepatocellular carcinomas (HCCs) and compared these findings with those obtained using contrast-enhanced computed tomography (CT). SUBJECTS AND METHODS: Forty-three patients with 52 early HCCs with a mean maximal diameter of 15.6mm were enrolled in this retrospective study. After confirming the location of the target lesion using fusion imaging combining conventional US and hepatobiliary phase of contrast-enhanced magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid, we evaluated findings of contrast-enhanced US using a perflubutane-based contrast agent. The contrast enhanced US detection rates for hyper-vascularity in early HCCs were compared with those obtained for contrast-enhanced CT. RESULTS: Transient hypo-vascularity subsequent to iso-vascularity during arterial phase and iso-vascularity during portal and post-vascular phases were the predominant contrast-enhanced US findings seen for 25 (48.1%) of the 52 early HCCs. Nine (17.3%) showed iso vascularity during all three phases, while 1 (1.9%) showed hypo-vascularity during all three phases. The remaining 17 (32.7%) showed partial or whole hyper vascularity during arterial phase, iso-vascularity during portal phase, and iso- or hypo-vascularity during post-vascular phase. The detection rate for the hyper vascularity of early HCCs using contrast-enhanced US (32.7%, 17/52) was significantly higher than that obtained using contrast-enhanced CT (21.2%, 11/52) (P<0.05 by McNemar test). CONCLUSION: Hypo-vascularity, iso-vascularity, and hyper-vascularity were observed during the arterial phase of contrast-enhanced US in 50.0%, 17.3%, and 32.7% of the early HCCs, respectively. Contrast-enhanced US was more sensitive than contrast-enhanced CT for the detection of hyper vascularity in early HCCs. Of note, early HCCs might not exhibit the early arterial enhancement that is generally considered to be a typical finding for HCCs. PMID- 24176533 TI - Simulation of real-time EPID images during IMRT using Monte-Carlo. AB - This study is part of a project concerned with real-time EPID-based verification of the incremental dose delivered during IMRT radiation treatments. Three automated Monte-Carlo methods are devised to calculate the differential dose delivered to the EPID during treatment. All methods break down the normalized total monitor units into a number of equally spaced segments. A method models the dynamic simulation as a series of static fields, each field corresponding to an IMRT segment or a sub-segment. Another method models each segment as a separate dynamic IMRT file. A third method, which modifies the DYNVMLC module of the BEAMnrc code, uses the full-MLC file. The MLC positions for the simulated photons are sequentially selected within DYNVMLC to correspond to individual segments of the delivery. A bash script calls the BEAM shared-library to calculate and store the EPID dose for each segment. Validation is performed by comparing the average dose contributed by all segments with the dose predicted by a canonical dynamic IMRT simulation that uses the same MLC file. The best results are achieved by the methods based on dynamic simulations (where leaf positions within a segment are interpolated for simulated photons) whose normalized root mean square error is at the most 0.2% over the focal area. EPID images can be predicted for individual segments (or smaller intervals) of an IMRT delivery using Monte-Carlo methods. The MLC file can be externally spliced or a simple modification of the DYNVMLC code can achieve accurate results. PMID- 24176534 TI - Changes in well-being and quality of life in a randomized trial comparing dynamic psychotherapy and pharmacotherapy for major depressive disorder. AB - BACKGROUND: Major depressive disorder (MDD) is associated with a decrease in quality of life (QOL) and well-being. Therefore, researchers are increasingly complementing traditional symptom measurements with QOL and well-being assessments in order to broaden the evaluation of treatment outcomes. The current prospective study investigated the effectiveness of supportive-expressive therapy (SET), antidepressant medication (MED) and placebo (PBO) in improving QOL and well-being in patients with MDD. METHODS: Data from a randomized controlled trial (trial registration: NCT00043550) comparing SET, MED and PBO for the treatment of depression (N=156) were analyzed. Outcome measures addressed patients' QOL and physical and mental well-being. Changes in outcomes were assessed across and between treatments using linear mixed models. RESULTS: Across treatments, patients showed significant improvement in QOL and mental and physical health measures, as well as a reduction in interpersonal distress and depressive and anxiety symptoms (p<=.002 for all measures). Those changes were not only the products of a decrease in depressive symptoms, but also predicted subsequent reduction in symptoms. No significant differences were found between the three treatment conditions. LIMITATIONS: The limitation is the study's moderate sample size. CONCLUSIONS: Current treatments for depression significantly improve patients' QOL and well-being. No significant differences were found between the three conditions examined in this study. The current study highlights the role of well-being in predicting subsequent symptomatic change. PMID- 24176535 TI - Polymorphism of Toll-like receptor 4 gene in bipolar disorder. AB - BACKGROUND: Bipolar disorder (BD) is considered as a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction is thought to play a key etiopathogenic role. In particular, excess of winter births associated with early-life infections raise the possibility of the implication of innate immunity. Given the pivotal role of Toll like receptor 4 (TLR-4), a major innate immune sensor molecule, we hypothesized that genetic variations of TLR-4 may be associated to BD. METHODS: Genomic DNAs from 572 BD patients and 202 healthy controls (HC) were analyzed for the distribution of six single nucleotides polymorphisms (SNPs) scattered along the TLR-4 locus (rs1927914, rs10759932, rs4986790, rs4986791, rs11536889 and rs11536891). Associations between BD and these polymorphisms were examined using the Chi-square test. RESULTS: We found that rs1927914 AA and rs11536891 TT genotype are more frequent in BD patients than in controls (corrected p; pc=.02 and .02 respectively) particularly in early-onset BD patients (pc=.004 and .006) born during the summer season (pc=.02 and .002 respectively). We also found that rs4986790 AG and rs4986791 CT genotypes were significantly associated with presence of autoimmune thyroiditis (pc=.002). LIMITATIONS: Our results are to be confirmed by replication in independent BD cohorts. CONCLUSIONS: We report for the first time a genetic association between BD and TLR-4 a major player of innate immunity. Possible mechanisms underlying bipolar disorders linking altered TLR-4 expression and increased susceptibility to infections and/or autoimmunity are discussed. PMID- 24176536 TI - Development and psychometrics of the five item daily index in a psychiatric sample. AB - BACKGROUND: Effective treatment of affective disorders requires the ability to reliably monitor patient progress and outcome. The current study aimed to establish the Daily Index-5 (DI-5) as a psychometrically sound and clinically valid measure of treatment response in psychiatric care for use as a companion measure with the WHO Wellbeing Index (WHO-5; Bech et al., 1996. Psychother. Psychosom. 65, 183-190.). METHOD: Eight hundred and ninety four consecutive inpatients and day-patients at a psychiatric facility completed the DI-5, WHO-5, SF-36 (Ware et al., 1993. SF-36 Health Survey: Manual and Interpretation Guide. The Health Institute, New England Medical Centre, Boston, MA.) and DASS-21 (Lovibond and Lovibond, 1995b. Manual for the Depression Anxiety Stress Scales. Psychology Foundation, Sydney, Australia.; Ware et al., 1993. SF-36 Health Survey: Manual and Interpretation Guide. The Health Institute, New England Medical Centre, Boston, MA.) routinely during treatment. RESULTS: The DI-5 was shown to be a measure with high reliability and validity. In addition criteria for clinically significant recovery are presented with an example implementation of a Clinical Significance Monitoring system. Finally, the latent structure of the DI-5 is established as a uni-dimensional index of affective disorder. LIMITATIONS: The results may be generalized to samples with primary diagnoses of depressive and/or anxiety disorders though assessment of the DI-5 as a measure of treatment response is warranted in patients with other primary diagnoses. CONCLUSIONS: The current study indicates that the DI-5 is a quick to administer and interpret, reliable and valid measure for assessing patient outcome that is appropriate for use in monitoring patient change. PMID- 24176537 TI - The neural representation of emotionally neutral faces and places in patients with panic disorder with agoraphobia. AB - BACKGROUND: Panic disorder with agoraphobia (PD-A) has been associated with abnormal neural activity for threat-related stimuli (faces, places). Recent findings suggest a disturbed neural processing of emotionally neutral stimuli at a more general level. METHODS: Using functional magnetic resonance imaging (fMRI) we investigated the neural processing of emotionally neutral faces and places in PD-A. Fifteen patients with PD-A and fifteen healthy subjects participated in the study. RESULTS: When they perceived neutral faces and places, the patients with PD-A showed significantly less brain activity in the fusiform gyrus, the inferior occipital gyrus, the calcarine gyrus, the cerebellum, and the cuneus compared with the healthy controls. However, the patients with PD-A showed significantly more brain activity in the precuneus compared with controls subjects. LIMITATIONS: It was not possible to distinguish the agoraphobia-associated effects from possible contributions due to general anxiety induced by fMRI. For future investigations, an additional clinical control group with patients suffering from panic disorder without agoraphobia would be of interest. In addition, the psychopathology concerning the agoraphobic symptoms needs to be investigated in more detail. CONCLUSIONS: The findings suggest altered neural processing of emotionally neutral faces and places in patients with PD-A. Reduced neural activity in different brain regions may indicate difficulties in recognizing the emotional content in face and place stimuli due to anxiety related hyper-arousal. PMID- 24176539 TI - Cardiac function in early onset small for gestational age and growth restricted fetuses. AB - OBJECTIVE: To examine cardiac function in appropriately grown, small for gestational age and intrauterine growth restricted fetuses and investigate the relationship between cardiac function and fetal arterial and venous Doppler parameters. STUDY DESIGN: Myocardial performance index, isovolumetric contraction time, isovolumetric relaxation time, ejection time, and umbilical artery, middle cerebral artery and ductus venosus Doppler pulsatility index were measured for women between 24 and 32 weeks with small for gestational age and intrauterine growth restricted fetuses. Forty-eight appropriately grown, 11 small for gestational age and 12 intrauterine growth restricted cases were included. The relationship between cardiovascular parameters and gestation was defined and Doppler values converted to Z-scores in relation to gestational age. RESULTS: In small for gestational age fetuses and fetuses with intrauterine growth restriction the myocardial performance index was 0.66 (0.63-0.7) and 0.64 (0.60 0.67), respectively, and compared to appropriately grown fetuses, at 0.45 (0.43 0.47), was significantly increased (p=0.001). No relationship was found between the myocardial performance index and arterial and venous Doppler Z-score. CONCLUSION: Small for gestational age and intrauterine growth restricted fetuses demonstrate altered cardiac function in the late second and early third trimester of pregnancy. Importantly, the myocardial performance index is raised in small for gestational age fetuses before the arterial and venous Doppler abnormalities that characterize hypoxia are evident. PMID- 24176538 TI - Pro-inflammatory cytokine associated with somatic and pain symptoms in depression. AB - BACKGROUND: More than two-thirds of depressed patients complain of somatic and pain symptoms, which are frequently regarded as a psychological reaction. Although there is a growing body of evidence showing that depression is related to immune abnormalities, few studies have investigated the association between inflammatory cytokines and somatic/pain symptoms. METHOD: Patients with depressive disorder but without any medical disorders, and age/gender/body mass index (BMI)-matched healthy subjects were enrolled. All the subjects completed the self-rating scales of the Beck Depression Inventory-II and the Depression and Somatic Symptoms Scale, which was comprised of depressive, somatic, and pain subscales. Pro-inflammatory cytokines, including C-reactive protein (CRP), interleukin-2 receptor (sIL-2R), soluble interleukin 6 receptor (sIL-6R), soluble TNF-receptors (sTNF-R), soluble P-selectin (sP-selectin), monocyte chemotactic protein-1 (MCP-1), and adiponectin, were assessed by enzyme-linked immunosorbent assays. RESULTS: In all, 109 patients with depressive disorder and 126 normal controls were enrolled. The patients with depressive disorder had significantly more severe depression, somatic and pain symptoms (all p<0.001), and higher levels of sIL-2R (p<0.0001), sTNF-R (p<0.001), and sP-selectin (p=0.005) than the normal control group. Using multivariate regression analysis with controlling of age, gender, BMI, and other pro-inflammatory cytokines, sIL-2R was the most significant predictor for depressive symptoms (p<0.0001); with further controlling of severity of depressive symptom, sP-selectin was the only predictor for somatic (p=0.002) and pain (p=0.059) symptoms. CONCLUSION: The elevated sP selectin associated with somatic symptoms in depression, may indicate early micro vascular changes occur subtly, and provide neurobiological evidence for somatic and pain symptom in depression. PMID- 24176540 TI - Clinical and pathological characteristics, pathological reevaluation and recurrence patterns of cellular leiomyomas: a retrospective study in 76 patients. AB - OBJECTIVES: To analyze clinical and pathologic features as well as recurrence patterns of cellular leiomyomas (CL) in women who underwent surgical therapy for symptomatic disease. STUDY DESIGN: This retrospective study was conducted at the Department of Obstetrics and Gynecology, University Women's Clinic, Tuebingen, Germany. We identified all women who had CL on final diagnosis after surgery between January 1, 2000, and December 31, 2010. RESULTS: Our study sample comprised 76 women with a diagnosis of CL. A single uterine mass was present in 51.3% of the cases; in uteri with both CL and uterine leiomyomas (UL), the CL constituted the largest uterine mass in 20 of 21 (95.2%) cases. Additionally, in 98% of the uteri, CL were either the largest or the only uterine mass. Five women (6.6%; 5/76) had reported surgical procedures for symptomatic leiomyoma before the index surgery in our analysis. Three women underwent hysteroscopic resection of the leiomyomas and 2 women underwent abdominal myomectomy. Mean time to recurrence was 14.0 months (median 6.0; range, 4.0-52.0). Over the follow-up period, 6 women who underwent uterus-conserving surgery (12.0%; 6/50) with CL had leiomyoma recurrence. Five women underwent abdominal myomectomy and one underwent hysteroscopic resection of the CL. One patient had recurrence of a CL 43 months after abdominal myomectomy and underwent vaginal hysterectomy; the other five women had recurrences of UL. Mean time to recurrence was 28.6 months (median 12.5; range, 4.0-83.0). CONCLUSIONS: Recurrence rates of CL in our study group resemble recurrence rates of UL. PMID- 24176541 TI - Clinical guidelines for management of thyroid nodule and cancer during pregnancy. AB - Special considerations are warranted in management of thyroid nodule and thyroid cancer during pregnancy. The diagnostic and therapeutic approach of thyroid nodules follows the standard practice in non-pregnant women. On the other hand, differentiated thyroid cancer management during pregnancy poses a number of challenges for the mother and fetus. The available data show that pregnancy is not a risk factor for thyroid cancer development or recurrence, although flare ups cannot be completely ruled out in women with active disease. If surgery is needed, it should be performed during the second term or, preferably, after delivery. A majority of pregnant patients with low-risk disease only need adjustment in levothyroxine therapy. However, women with increased serum thyroglobulin levels before pregnancy or structural disease require regular thyroglobulin measurements and neck ultrasound throughout pregnancy. Pregnancy is an absolute contraindication for radioactive iodine administration. PMID- 24176542 TI - Human multipotent adult progenitor cells transcriptionally regulate fucosyltransferase VII. AB - BACKGROUND AIMS: Targeted recruitment of leukocytes to sites of inflammation is a crucial event in normal host defense against pathogens, and attachment to and rolling on activated endothelial cells is a prerequisite first step for eventual leukocyte extravasation into sites of inflammation. These key events are mediated by interactions between glycosylated ligands expressed on leukocytes and selectins expressed on activated endothelium. Cell surface expression of selectin ligands on leukocytes is regulated by the rate-limiting enzyme fucosyltransferase VII (Fut7), and in its absence extravasation of leukocytes is severely inhibited. Multipotent adult progenitor cells (MAPCs) are an adherent cell population isolated from adult bone marrow. Intravenous administration of MAPCs provided functional improvement in multiple pre-clinical models of injury or disease, but the mechanisms by which these outcomes were achieved remain poorly understood. METHODS: In vitro cell analysis studies including fluorescence-activated cell sorting, messenger RNA analysis, T-cell proliferation assays and endothelial cell binding assays were performed. RESULTS: The in vitro cell analysis studies characterized the ability of MAPCs to secrete factors that transcriptionally attenuate expression of Fut7 in T cells, blocking the terminal fucosylation event in the biosynthesis of selectin ligands and reducing T-cell binding to endothelial cells. CONCLUSIONS: This study presents the first example of a distinct regulatory mechanism involving transcriptional down-regulation of Fut7 by MAPCs that could modulate the trafficking behavior of T cells in vivo. PMID- 24176543 TI - Genetically engineered fixed K562 cells: potent "off-the-shelf" antigen presenting cells for generating virus-specific T cells. AB - BACKGROUND AIMS: The human leukemia cell line K562 represents an attractive platform for creating artificial antigen-presenting cells (aAPC). It is readily expandable, does not express human leukocyte antigen (HLA) class I and II and can be stably transduced with various genes. METHODS: In order to generate cytomegalovirus (CMV) antigen-specific T cells for adoptive immunotherapy, we transduced K562 with HLA-A*0201 in combination with co-stimulatory molecules. RESULTS: In preliminary experiments, irradiated K562 expressing HLA-A*0201 and 4 1BBL pulsed with CMV pp65 and IE-1 peptide libraries failed to elicit antigen specific CD8+ T cells in HLA-A*0201+ peripheral blood mononuclear cells (PBMC) or isolated T cells. Both wild-type K562 and aAPC strongly inhibited T cell proliferation to the bacterial superantigen staphylococcal enterotoxin B (SEB) and OKT3 and in mixed lymphocyte reaction (MLR). Transwell experiments suggested that suppression was mediated by a soluble factor; however, MLR inhibition was not reversed using transforming growth factor-beta blocking antibody or prostaglandin E2 inhibitors. Full abrogation of the suppressive activity of K562 on MLR, SEB and OKT3 stimulation was only achieved by brief fixation with 0.1% formaldehyde. Fixed, pp65 and IE-1 peptide-loaded aAPC induced robust expansion of CMV-specific T cells. CONCLUSIONS: Fixed gene-modified K562 can serve as effective aAPC to expand CMV-specific cytotoxic T lymphocytes for therapeutic use in patients after stem cell transplantation. Our findings have implications for broader understanding of the immune evasion mechanisms used by leukemia and other tumors. PMID- 24176544 TI - Mobilization and engraftment of peripheral blood stem cells in healthy related donors >55 years old. AB - BACKGROUND AIMS: The increasing scarcity of young related donors has led to the use of older donors for related allogeneic hematopoietic stem cell transplantation (HSCT). This study analyzed the influence of age on the results of mobilization of peripheral blood stem cells (PBSCs) in healthy donors as well as on the engraftment and outcome of HSCT. METHODS: A retrospective analysis from a single center was performed comparing the results of PBSC mobilization from related healthy donors according to their age. RESULTS: The study included 133 consecutive related donors. The median age was 50 years (range, 4-77 years); 70 (53%) donors were males, and 44 (33%) were >55 years old. All donors were mobilized with granulocyte colony-stimulating factor for 5 days. The peak CD34(+) cell count in peripheral blood was higher in younger than in older donors (median, 90.5 CD34(+) cells/MUL [range, 18-240 CD34(+) cells/MUL] versus 72 CD34(+) cells/MUL [range, 20-172.5 CD34(+) cells/MUL], P = 0.008). The volume processed was lower in younger than in older donors (16,131 mL [range, 4424 36,906 mL] versus 18,653 mL [range, 10,003-26,261 mL], P = 0.002) with similar CD34(+) cells collected (579.3 * 10(6) cells [range, 135.14 * 10(6)-1557.24 * 10(6) cells] versus 513.69 * 10(6) cells [range, 149.81 * 10(6)-1290 * 10(6) cells], P = 0.844). There were no differences in time to recovery of neutrophils and platelets or in the incidences of acute and chronic graft-versus-host disease, overall survival, non-relapse mortality and relapse incidence. CONCLUSIONS: Donors >55 years old mobilized fewer CD34(+) cells and required a greater volume to collect a similar number of CD34(+) cells. The outcome of HSCT was not influenced by donor age. Donor age should not be a limitation for related allogeneic HSCT. PMID- 24176545 TI - Presence of osteoclast precursor cells during ex vivo expansion of bone marrow derived mesenchymal stem cells for autologous use in cell therapy. AB - BACKGROUND AIMS: To obtain a cell product competent for clinical use in terms of cell dose and biologic properties, bone marrow-derived mesenchymal stem cells (MSCs) must be expanded ex vivo. METHODS: A retrospective analysis was performed of records of 76 autologous MSC products used in phase I or II clinical studies performed in a cohort of cardiovascular patients. In all cases, native MSCs present in patient bone marrow aspirates were separated and expanded ex vivo. RESULTS: The cell products were classified in two groups (A and B), according to biologic properties and expansion time (ex vivo passages) to reach the protocol established cell dose. In group A, the population of adherent cells obtained during the expansion period (2 +/- 1 passages) was composed entirely of MSCs and met the requirements of cell number and biologic features as established in the respective clinical protocol. In group B, in addition to MSCs, we observed during expansion a high proportion of ancillary cells, characterized as osteoclast precursor cells. In this case, although the biologic properties of the resulting MSC product were not affected, the yield of MSCs was significantly lower. The expansion cycles had to be increased (3 +/- 1 passages). CONCLUSIONS: These results suggest that the presence of osteoclast precursor cells in bone marrow aspirates may impose a limit for the proper clinical use of ex vivo expanded autologous bone marrow-derived MSCs. PMID- 24176546 TI - Ascorbic acid induces osteoblast differentiation of human suspension mononuclear cells. AB - BACKGROUND AIMS: Suspension mononuclear cells (MNCs) can be differentiated into osteoblasts with the induction of ascorbic acid and beta-glycerophosphate. The aim of this study was to determine the ability of suspension MNCs to differentiate into osteoblasts using ascorbic acid only. METHODS: Suspension MNCs were obtained by a combination of gradient centrifugation and culture selection. Suspension MNCs were subjected to differentiation assay by culturing them inside proliferation medium supplemented with 10 MUg/mL, 30 MUg/mL, 50 MUg/mL, 60 MUg/mL, 90 MUg/mL and 500 MUg/mL of ascorbic acid. Proliferation medium supplemented with 50 MUg/mL ascorbic acid and 10 mmol/L beta-glycerophosphate was used as a positive control for osteoblast induction, and proliferation medium without ascorbic acid was used as a negative control. Differentiation analysis was performed using alkaline phosphatase (ALP) assay, von Kossa staining and expression of osteoblast-related genes. RESULTS: With all concentrations of ascorbic acid used, there was a significant increase (P < 0.05) in ALP-specific activity and mineralized nodule formation throughout the differentiation course compared with negative control. Ascorbic acid was also able to activate the expression of osteopontin (SPP1), osteonectin (SPARC) and runt-related transcription factor 2 (RUNX2) messenger RNA in positive control and ascorbic acid-induced MNCs (30 MUg/mL and 90 MUg/mL) but not in negative control. CONCLUSIONS: Ascorbic acid alone was sufficient to induce osteoblast differentiation from suspension MNCs; 30-90 MUg/mL of ascorbic acid was found to be the optimal concentration. Ascorbic acid can be used as a nutritional supplement for cellular therapy of bone-related disease. PMID- 24176547 TI - Bone sparing implant removal without trephine via internal separation of the titanium body with a carbide bur. AB - A novel technique was developed to remove osseointegrated implants without enlarging the bony socket. Immediate replacement was performed simultaneously using a same-size implant with good primary stability. The prosthesis was delivered after 6 months of healing with good loading function. Good bone stability was found at the 12-month follow-up. PMID- 24176550 TI - First report of NDM-1-producing Acinetobacter baumannii in East Africa. AB - BACKGROUND: The emergence of carbapenem-resistant Acinetobacter baumannii (CRAB) was observed in a Kenyan hospital from 2009 to 2010. Further investigation of the dissemination of CRAB isolates and the molecular characterization of associated resistance determinants were therefore performed. METHODS: Antibiotic susceptibilities were determined by broth microdilution and Etest. Metallo-beta lactamases were detected by Etest method. Clonal relationships were studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). beta-Lactam and aminoglycoside resistance determinants and the clonal relatedness to widespread European clones were studied by PCR and sequencing. RESULTS: Sixteen CRAB isolates from 10 patients possessed six pulsotypes; half of the isolates belonged to the European clone II (ECII) lineage. ECII strains were typed as MLST sequence type 2 (ST2) and ST109, and non-ECII strains as ST25 and ST113. All isolates harbored ISAba1-blaOXA-23, blaOXA-51-like, blaADC, and class 1 integron, including one that also harbored blaNDM-1. ADC-57 and two integron cassettes (arr-2-cmlA5 and aadB-aadA2-cmlA6-aadA15) were newly-identified. Non ECII isolates, designated non-ECII clone, carried armA and integron cassette arr 2-cmlA5. CONCLUSIONS: Two distinct clones of CRAB--ECII and non-ECII epidemic clones--were disseminated in Kenya. The concomitance of ISAba1-blaOXA-23 was the major mechanism contributing to CRAB. The first identification of ECII CRAB and New Delhi metallo-beta-lactamase 1 (NDM-1) extensively drug-resistant A. baumannii in East Africa is of concern. PMID- 24176549 TI - Staphylococcus haemolyticus disseminated among neonates with bacteremia in a neonatal intensive care unit in Rio de Janeiro, Brazil. AB - Oxacillin-resistant Staphylococcus haemolyticus (ORSH) was found as the most prevalent (77.5%) species of coagulase-negative staphylococci associated with bacteremia in neonates making use of intravenous catheters in an intensive care unit of a Brazilian teaching hospital. Thirty-one blood isolates were confirmed as S. haemolyticus by sequencing of the 16S and clustered in 6 pulsed-field gel electrophoresis types (with 58% of the strains belonging to 2 predominant types B and D). S. haemolyticus was mostly oxacillin-resistant (90.3%) displaying multiresistance profiles (70.4%). However, the mecA gene was undetected in 22.6% strains. ORSH exhibited slime production on Congo-Red agar (67.7%), adherence to polystyrene (96.7%), and glass (87%) surfaces. Interestingly, ica-operon was detected in 58% strains, mostly belonging to the B, D, and F genotypes, which is a significantly higher percentage when compared to other studies conducted at different parts of the globe. Data indicated that ica operon and biofilm-forming ORSH are endemic in Brazilian nosocomial environment. PMID- 24176551 TI - The relationship between ankle joint physiological characteristics and balance control during unilateral stance. AB - BACKGROUND: The role that the ankle's physiological characteristics play in maintaining balance during quiet stance has been well documented. However, the role of the ankle in maintaining balance during more challenging conditions is questionable. As such, the objectives of this study were to identify any significant relationships between the physiological characteristics of the ankle joint and the ability to maintain more challenging unilateral stance. PARTICIPANTS: 21 healthy, adult athletes (age = 24.67 +/- 5.42 years; height = 175.34 +/- 7.48 cms; weight = 79.09 +/- 14.07 kg). PROCEDURES: Passive resistance and joint position sense in the sagittal plane of the ankle, and active dorsiflexion range of motion of each subject was assessed, in addition to centre of pressure parameters during 20 s unilateral stance. RESULTS: Pearson's product moment correlation coefficient found significant positive correlations between D(peaktorque) and sway area (r = .554); A(x) range (r = .449); and A(y) range (r = .471). Significant negative correlations were found between P(peaktorque) angle and sway area (r = -.538, p = .012), A(x) range (r = -.590, p = .005) and A(y) range (r = -.439, p=.046). DISCUSSION: The results highlighted limited relationships between unilateral stance balance control and the ankle characteristics commonly associated with quiet stance balance control and has, thus, further questioned the role that the ankle plays during more challenging stance conditions. The majority of balance training protocols in the athletic community focuses on the distal joints, however, this needs re-addressing in order to maximise performance. PMID- 24176552 TI - Fgf receptors Fgfr1a and Fgfr2 control the function of pharyngeal endoderm in late cranial cartilage development. AB - Cranial cartilage derives mainly from cranial neural crest cells and its formation requires fibroblast growth factor (Fgf) signaling for early differentiation and survival of developing chondrocytes as well as patterning of the endodermal pouches. Here, we investigate the role of Fgf receptors in chondrocyte maturation at later stages, beyond 24 hpf. Using inducible expression of a dominant-negative Fgf receptor, we show that Fgf signaling is required around 30 hpf for correct cartilage formation. The receptor genes fgfr1a and fgr2 are expressed in pharyngeal endodermal pouches after 24 hpf or 26 hpf, respectively. Depletion of any of these two receptors by microinjection of antisense morpholinos results in severe defects in cartilage formation at 4 dpf and a decrease in expression of the late chondrocyte markers barx1 and runx2b. Although endodermal pouches are correctly formed and patterned, receptor knock down leads to decreased expression of runx3, egr1 and sox9b in this tissue, while expression of fsta, coding for a secreted BMP/Tgfbeta inhibitor, is clearly increased. Rescue experiments revealed that each Fgfr1a or Fgfr2 receptor is able to compensate for the loss of the other. Thus, we show that minimal amounts of Fgfr1a or Fgfr2 are required to initiate a regulatory cascade in pharyngeal endoderm reducing expression of fsta, thereby allowing correct BMP signaling to the maturing chondrocytes of the head cartilage. PMID- 24176553 TI - Celiac disease serum markers and recurrent pregnancy loss. AB - Celiac disease has been associated with numerous unfavorable health outcomes, including pregnancy complications such as infertility, preterm birth, and preeclampsia. However, the association between celiac disease and recurrent pregnancy loss (RPL) remains uncertain. Our purpose was to compare serum markers of celiac disease in women with and without RPL. Therefore, we performed a case control study of 116 women with unexplained recurrent pregnancy loss and 116 age matched controls. Maternal sera were analyzed for immunoglobulin A (IgA) and immunoglobulin G (IgG) tissue transglutaminase (tTG) antibodies and endomysial (EM) antibodies. Groups were similar with regard to age, race and ethnicity, and BMI. One case and one control tested positive (>=20 Units) for IgA tTG antibodies and mean levels of IgA tTG antibodies were similar in cases and controls (5.5+/ 2.86 versus 6.0+/-12.45; p=0.16). No cases or controls were positive for IgG tTG antibodies. However, cases had higher levels of IgG tTG antibody compared with controls (4.0+/-2.40 versus 3.3+/-1.30; p=0.0064). One subject (a control) tested positive for IgA EM antibodies and no subjects tested positive for IgG EM antibodies. In conclusion, positive results for tTG and EM antibodies were similar in women with and without RPL. Given these results, testing for occult celiac disease is not recommended in the evaluation of women with idiopathic RPL. PMID- 24176554 TI - Escaping the immune system: How the malaria parasite makes vaccine development a challenge. AB - Malaria is a major cause of morbidity and mortality. Immunity is acquired but is suboptimal, being slow to develop and incomplete. An inadequate understanding of natural immunity, host-parasite interactions, and a lack of reliable immune correlates of protection that could predict vaccine efficacy in the field have hindered development of a vaccine. With data from Phase III trials indicating that the leading malaria vaccine candidate, RTS,S, has limited efficacy, it is necessary to reconsider approaches to the development of a vaccine capable of inducing long-lived protection. PMID- 24176555 TI - [BIS bilateral: A simple way to detect cerebral ischemia... Yes but in a conscious patient]. PMID- 24176556 TI - Evidence-based methods to address disparities in global cancer control: the development of guidelines in Asia. PMID- 24176557 TI - Need for change in implementation of paediatric regulation. PMID- 24176558 TI - Waiting for prevention in Australia. PMID- 24176559 TI - Nuts and cancer: where are we now? PMID- 24176560 TI - Salvage treatment of relapsed or refractory germ-cell tumours. PMID- 24176561 TI - Salvage treatment of relapsed or refractory germ-cell tumours - authors' reply. PMID- 24176562 TI - BEACOPP or no BEACOPP? PMID- 24176563 TI - BEACOPP or no BEACOPP? - authors' reply. PMID- 24176564 TI - Dose-dense effect: other contributors - author's reply. PMID- 24176565 TI - Dose-dense effect: other contributors. PMID- 24176566 TI - Surgery versus SABR for NSCLC. PMID- 24176567 TI - Surgery versus SABR for NSCLC. PMID- 24176568 TI - Addressing questions about the HPV vaccine project in India. PMID- 24176569 TI - Cancer prevention in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013. AB - With economic growth in Asia, cancer has become increasingly prominent as a major health problem. However, discrepancies in infrastructure, economics, and development exist within and between Asian countries. We assess means of primary and secondary prevention for cervical, breast, colorectal, and hepatocellular cancer, and offer recommendations according to resource levels. Primary prevention by health education, lifestyle modification, and avoidance of risk factors should be made available at all resource levels. When resources allow, human papillomavirus and hepatitis B vaccinations should be given to reduce the risk of cervical and hepatocellular cancer, and genetic testing should be offered to detect increased susceptibility to colorectal and breast cancer. Secondary prevention by effective yet affordable screening for precancerous lesions or by early detection of cancer should be offered, followed by appropriate treatment. PMID- 24176571 TI - Management of prostate cancer in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013. AB - Many local and systemic options for prostate cancer have emerged in recent years, but existing management guidelines do not account for diversity in health resources between different countries. We present recommendations for the management of prostate cancer, stratified according to the extent of resource availability-based on a four-tier system of basic, limited, enhanced, and maximum resources-to enable applicability to Asian countries with differing levels of health-care resources. This statement of recommendations was formulated by a multidisciplinary panel from Asia-Pacific countries, at a consensus session on prostate cancer that was held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand. PMID- 24176570 TI - Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013. AB - Survival for adults and children with acute lymphoblastic leukaemia has risen substantially in recent years because use of improved risk-directed treatments and supportive care has widened. In nearly all developed countries, multidisciplinary panels of leukaemia experts have formulated clinical practice guidelines in which standard treatment approaches are recommended on the basis of current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, huge disparities in economy and infrastructure exist between countries, and even among different regions in some large countries. At a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand, a panel of experts summarised recommendations for management of adult and paediatric acute lymphoblastic leukaemia. Strategies were developed for Asian countries on the basis of available financial, skill, and logistical resources and were stratified in a four-tier system according to the resources available in a particular country or region (basic, limited, enhanced, and maximum). PMID- 24176572 TI - Management of gastric cancer in Asia: resource-stratified guidelines. AB - Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries. PMID- 24176573 TI - Management of B-cell non-Hodgkin lymphoma in Asia: resource-stratified guidelines. AB - Treatment of B-cell non-Hodgkin lymphomas has undergone substantial developments in the past 10 years. The introduction of rituximab has greatly improved survival outcomes in patients. Clinical practice guidelines based on current evidence have been developed to provide recommendations for standard treatment approaches. However, guidelines do not take into account resource limitations in resource poor countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs between Asian countries can hinder the delivery of optimum care to patients with lymphoma in Asia. We outline guidelines appropriate to different levels of health-care resources and expertise, aiming to provide advice on diagnosis and treatment, unify interpretation of results, and allow the design of future studies in Asia. In this resource-adapted consensus, we summarise recommendations for diagnosis, staging, risk stratification, and treatment of common B-cell non-Hodgkin lymphomas in Asia. PMID- 24176574 TI - Management of sarcoma in the Asia-Pacific region: resource-stratified guidelines. AB - Sarcomas are a rare and diverse set of cancers that disproportionately affect young people. The best possible outcome depends on access to highly specialised, multidisciplinary care. Although advances have been made in therapeutic techniques, access to some treatments might be limited by cost implications. This Review proposes an evidence-based, consensus recommendation for optimum management of bone and soft-tissue sarcoma across the Asia-Pacific region, taking into account variation in health-care resources, stratified according to the Breast Health Global Initiative resource levels. A web-based survey of 89 clinicians involved in the care of patients with sarcoma from 18 Asia-Pacific countries generated the recommendations for diagnosis, staging, and management, including supportive and palliative care, and research. PMID- 24176575 TI - Management of multiple myeloma in Asia: resource-stratified guidelines. AB - Treatment of multiple myeloma has undergone substantial developments in the past 10 years. The introduction of novel drugs has changed the treatment of the disease and substantially improved survival outcomes. Clinical practice guidelines based on evidence have been developed to provide recommendations on standard treatment approaches. However, the guidelines do not take into account resource limitations encountered by developing countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs in Asian countries hinder the delivery of optimum care to every patient with multiple myeloma in Asia. In this Review we outline the guidelines that correspond with different levels of health-care resources and expertise, with the aim to unify diagnostic and therapeutic guidelines and help with the design of future studies in Asia. PMID- 24176577 TI - Anticipated changes in reimbursements for US outpatient emergency department encounters after health reform. AB - STUDY OBJECTIVE: We study how reimbursements to emergency departments (EDs) for outpatient visits may be affected by the insurance coverage expansion of the Patient Protection and Affordable Care Act as previously uninsured patients gain coverage either through the Medicaid expansion or through health insurance exchanges. METHODS: We conducted a secondary analysis of data (2005 to 2010) from the Medical Expenditure Panel Survey. We specified multiple linear regression models to examine differences in the payments, charges, and reimbursement ratios by insurance category. Comparisons were made between 2 groups to reflect likely movements in insurance status after the Patient Protection and Affordable Care Act implementation: (1) the uninsured who will be Medicaid eligible afterward versus Medicaid insured, and (2) the uninsured who will be Medicaid ineligible afterward versus the privately insured. RESULTS: From 2005 to 2010, as a percentage of total ED charges, outpatient ED encounters for Medicaid beneficiaries reimbursed 17% more than for uninsured individuals who will become Medicaid eligible after Patient Protection and Affordable Care Act implementation: 40.0% versus 34.0%, mean absolute difference=5.9%, 95% confidence interval 5.7% to 6.2%. During the same period, the privately insured reimbursed 39% more than for uninsured individuals who will not be Medicaid eligible after Patient Protection and Affordable Care Act implementation: 54.0% versus 38.8%, mean absolute difference=15.2%, 95% confidence interval 12.8% to 17.6%. CONCLUSION: Assuming historical reimbursement patterns remain after Patient Protection and Affordable Care Act implementation, outpatient ED encounters could reimburse considerably more for both the previously uninsured patients who will obtain Medicaid insurance and for those who move into private insurance products through health insurance exchanges. Although our study does provide insight into the future, multiple factors will ultimately influence reimbursements after implementation of the act. PMID- 24176578 TI - Coadministration of glycogen-synthase kinase 3 inhibitor with morphine attenuates chronic morphine-induced analgesic tolerance and withdrawal syndrome. AB - BACKGROUND: Glycogen-synthase kinase 3 (GSK3) is involved in many signaling pathways and is associated with a host of high-profile pathophysiological states. However, its role in morphine tolerance, especially naloxone-precipitated withdrawal syndrome, has not been well investigated. The present study was undertaken to study the role of GSK3 in chronic morphine exposure. METHODS: Adult male Sprague-Dawley rats were subjected to intraperitoneal (i.p.) injections of morphine (10 mg/kg) twice daily for 6 consecutive days, and tail-flick tests were conducted to evaluate changes of morphine-induced antinociception. GSK3 inhibitor, SB216763 or SB415286, was i.p. injected prior to morphine to investigate the influences on morphine tolerance. There were four groups receiving morphine plus vehicle (2% dimethyl sulfoxide), morphine plus SB216763 (0.6 mg/kg) or SB415286 (1.0 mg/kg), GSK3 inhibitor alone, or dimethyl sulfoxide: as the control group. On Day 7, naloxone (i.p., 1 mg/kg) was administered and naloxone-precipitated withdrawal behaviors were individually compared between groups. RESULTS: Repeated morphine exposure in this study led to progressive shortening of tail-flick latencies and produced six of nine observed naloxone precipitated withdrawal behaviors. Coadministration with SB216763 or SB415286 significantly prevented antinociceptive tolerance and alleviated parts of withdrawal syndrome. Both inhibitors could similarly reverse withdrawal behaviors including grooming, chewing, and ptosis, but did not affect withdrawal behaviors of penis licking and defecation. CONCLUSION: The results demonstrate the importance of GSK3 in reducing chronic morphine-induced tolerance and withdrawal syndrome. Although GSK3 is involved in diverse physiological functions, aiming at GSK3-related pathway could still be a potential tool to improve therapeutic quality in clinical morphine treatment. PMID- 24176576 TI - Altered language network activity in young people at familial high-risk for schizophrenia. AB - BACKGROUND: Abnormalities in language and language neural circuitry are observed in schizophrenia (SZ). Similar, but less pronounced language deficits are also seen in young first-degree relatives of people with SZ, who are at higher familial risk (FHR) for the disorder than the general population. The neural underpinnings of these deficits in people with FHR are unclear. METHODS: Participants were 43 people with FHR and 32 comparable controls. fMRI scans were collected while participants viewed associated and unrelated word pairs, and performed a lexical decision task. fMRI analyses conducted in SPM8 examined group differences in the modulation of hemodynamic activity by semantic association. RESULTS: There were no group differences in demographics, IQ or behavioral semantic priming, but FHR participants had more schizotypal traits than controls. Controls exhibited the expected suppression of hemodynamic activity to associated versus unrelated word pairs. Compared to controls, FHR participants showed an opposite pattern of hemodynamic modulation to associated versus unrelated word pairs, in the left inferior frontal gyrus (IFG), right superior and middle temporal gyrus (STG) and the left cerebellum. Group differences in activation were significant, FWE-corrected for multiple comparisons (p<0.05). Activity within the IFG during the unrelated condition predicted schizotypal symptoms in FHR participants. CONCLUSIONS: FHR for SZ is associated with abnormally increased neural activity to semantic associates within an inferior frontal/temporal network. This might increase the risk of developing unusual ideas, perceptions and disorganized language that characterize schizotypal traits, potentially predicting which individuals are at greater risk to develop a psychotic disorder. PMID- 24176579 TI - Long-term outcome of ultrasound-guided percutaneous ethanol ablation of selected "recurrent" neck nodal metastases in 25 patients with TNM stages III or IVA papillary thyroid carcinoma previously treated by surgery and 131I therapy. AB - BACKGROUND: Ultrasound-guided percutaneous ethanol ablation (UPEA) of neck nodal metastases (NNM) has rarely been reported in papillary thyroid carcinoma (PTC) patients with advanced localized disease. METHODS: We ablated 25 PTC patients with stage III or IVA disease (mean age 58 years) who had "recurrent" NNM after surgery and 131I therapy. Diagnosis of 37 selected NNM was proven by ultrasound guided biopsy. UPEA was usually performed in 2 outpatient sessions. RESULTS: After UPEA, 35 of 37 NNM (95%) decreased in size. None had significant Doppler flow. Seventeen (46%) disappeared on rescanning. Serum thyroglobulin fell in 19 of 22 (86%) without thyroglobulin autoantibodies. None of the UPEA-treated NNM, followed on average for 5.4 years, required further intervention. Six patients (24%) subsequently developed 18 "new" recurrences. Of the 18, 15 (83%) were managed successfully by UPEA rather than operation. None of the 25 patients developed permanent hoarseness or have died from PTC. At our institution, where patients undergoing nodal dissections are charged $35-45,000, each outpatient UPEA procedure saves health providers approximately $38,400. Our 25 ablated patients, by avoiding 40 further neck reexplorations, on average, saved $61,440 in charges. CONCLUSION: UPEA for NNM in advanced localized PTC has proved safe and effective. It is also considerably less expensive than the conventional operative alternative of nodal dissection. PMID- 24176580 TI - Latent introduction to the Netherlands of multiple antibiotic resistance including NDM-1 after hospitalisation in Egypt, August 2013. AB - We describe the introduction of various multi-drug resistant bacterial strains, including an NDM-1-producing Klebsiella pneumoniae, through a traveller returning from Egypt, where they had been admitted to a private hospital. All family members of the patient were colonised with one or more extended-spectrum beta lactamase producing strains. These findings emphasise the importance of adherence to isolation precautions for returning patients and suggest the need for inclusion of Enterobacteriaceae in admission screening. PMID- 24176581 TI - Multidrug-resistant tuberculosis in Uzbekistan: results of a nationwide survey, 2010 to 2011. AB - Multidrug-resistant tuberculosis (MDR-TB; resistance to at least rifampicin and isoniazid) is a global public health concern. In 2010-2011, Uzbekistan, in central Asia, conducted its first countrywide survey to determine the prevalence of MDR-TB among TB patients. The proportion of MDR-TB among new and previously treated TB patients throughout the country was measured and risk factors for MDR TB explored. A total of 1,037 patients were included. MDR-TB was detected in 165 treatment-naive (23.2%; 95% confidence interval (CI) 17.8%-29.5%) and 207 previously treated (62.0%; 95% CI: 52.5%-70.7%) patients. In 5.3% (95% CI: 3.1% 8.4%) of MDR-TB cases, resistance to fluoroquinolones and second-line injectable drugs (extensively drug resistant TB; XDR-TB) was detected. MDR-TB was significantly associated with age under 45 years (adjusted odds ratio: 2.24; 95% CI: 1.45-3.45), imprisonment (1.93; 95% CI: 1.01-3.70), previous treatment (4.45; 95% CI: 2.66-7.43), and not owning a home (1.79; 95% CI: 1.01-3.16). MDR-TB estimates for Uzbekistan are among the highest reported in former Soviet Union countries. Efforts to diagnose, treat and prevent spread of MDR-TB need scaling up. PMID- 24176582 TI - Epidemiological investigation of Pseudomonas aeruginosa isolates from a six-year long hospital outbreak using high-throughput whole genome sequencing. AB - Although previous bacterial typing methods have been informative about potential relatedness of isolates collected during outbreaks, next-generation sequencing has emerged as a powerful tool to not only look at similarity between isolates, but also put differences into biological context. In this study, we have investigated the whole genome sequence of five Pseudomonas aeruginosa isolates collected during a persistent six-year outbreak at Nottingham University Hospitals National Health Service (NHS) Trust - City Campus, United Kingdom. Sequencing, using both Roche 454 and Illumina, reveals that most of these isolates are closely related. Some regions of difference are noted between this cluster of isolates and previously published genome sequences. These include regions containing prophages and prophage remnants such as the serotype converting bacteriophage D3 and the cytotoxin-converting phage phi CTX. Additionally, single nucleotide polymorphisms (SNPs) between the genomic sequence data reveal key single base differences that have accumulated during the course of this outbreak, giving insight into the evolution of the outbreak strain. Differentiating SNPs were found within a wide variety of genes, including lasR, nrdG, tadZ, and algB. These have been generated at a rate estimated to be one SNP every four to five months. In conclusion, we demonstrate that the single base resolution of whole genome sequencing is a powerful tool in analysis of outbreak isolates that can not only show strain similarity, but also evolution over time and potential adaptation through gene sequence changes. PMID- 24176583 TI - Hypokalemia-induced pseudoischemic electrocardiographic changes and quadriplegia. AB - Hypokalemia is a common biochemical abnormality. Severe hypokalemia can produce cardiac rhythm alterations and neurologic manifestations. Early detection and treatment allow clinician to prevent morbidity and mortality from cardiac arrhythmias and respiratory failure. Here, we describe a case of severe hypokalemia inducing pseudoischemic electrocardiographic (ECG) alterations and quadriplegia, in a patient affected by chronic diarrhea. Electrocardiographic alterations and neurologic manifestations completely disappeared after potassium replacement; however, prolonged potassium supplementation was required to achieve the normalization of plasmatic potassium levels. Consecutive figures show ECG improvement until normalization of ECG findings. PMID- 24176584 TI - B-type natriuretic peptide predicts complexity and severity of the coronary lesions in patients with ST-segment elevation myocardial infarction. PMID- 24176585 TI - Comparative analysis of airway scope and Macintosh laryngoscope for intubation primarily for cardiac arrest in prehospital setting. AB - STUDY OBJECTIVE: This study sought to determine and compare the utility of the Airway scope (AWS; Pentax Corporation, Tokyo, Japan) and the conventional Macintosh laryngoscope (MLS) for intubation in the prehospital setting. METHODS: In this randomized controlled trial in the prehospital setting, the primary outcome was time required for intubation, and the secondary outcomes were ultimate success, first attempt success, and difficulty of intubation. The intent to-treat principle was used to analyze time to intubation. Ultimate success was defined as intubation completed within 600 s regardless of the device ultimately used. RESULTS: A total of 109 patients, primarily with cardiac arrest, were randomly assigned to the AWS or MLS arms. Median time (interquartile range) to intubation was 155 (71-216) s with the AWS versus 120 (60-170) s with the MLS (P = .095). Ultimate success rate was slightly lower with the AWS (96.4%) than with the MLS (100%) (P = .496), while the first attempt success rate was significantly lower (46% and 75%, respectively; P = .002). There was no significant difference in difficulty of intubation (P = .066). Multivariate logistic regression analysis revealed that cervical immobilization and oral contamination, such as vomit, was associated with first attempt success (odds ratio [95% confidence interval]: 0.11 [0.01-0.87] and 0.43 [0.18-0.99], respectively). CONCLUSION: Despite its many advantages seen in other settings, the AWS did not show superior efficacy to the MLS in relation to time required for intubation, ultimate or first attempt success rate, or difficulty level of intubation in the prehospital setting. PMID- 24176586 TI - Central extracorporeal membrane oxygenation requiring pulmonary arterial venting after near-drowning. AB - Extracorporeal membrane oxygenation (ECMO) is an effective respiratory and circulatory support in patients in refractory cardiogenic shock or cardiac arrest. Peripheral ECMO sometimes requires left heart drainage; however, few reports state that pulmonary arterial (PA) venting is required during ECMO support. We present a case of a 14-year-old boy who required PA venting during ECMO support after resuscitation from near-drowning in freshwater. A biventricular assist device with an oxygenator implantation was intended on day 1; however, we were unable to proceed because of increasing of pulmonary vascular resistance from the acute lung injury. Central ECMO with PA venting was then performed. On day 13, central ECMO was converted to biventricular assist device with an oxygenator, which was removed on day 16. This case suggests that PA venting during ECMO support may be necessary in some cases of respiratory and circulatory failure with high pulmonary vascular resistance after near-drowning. PMID- 24176587 TI - Acquired factor VIII deficiency presenting with compartment syndrome. AB - Acquired factor VIII deficiency is a rare disease that has high rates of mortality and morbidity. Although this bleeding disorder has a classic presentation, its infrequency can make it difficult to identify. We present a case report of an elderly woman who came to an emergency department with spontaneous bilateral lower extremity compartment syndrome. Although she presented with tachycardia and hypotension, her only laboratory abnormalities were an elevated activated partial thromboplastin time and anemia. She underwent bilateral fasciotomies and had a postoperative course that was complicated by significant incisional bleeding. She was ultimately found to have acquired factor VIII deficiency. Emergency physicians must be familiar with this rare entity because its recognition can avoid serious complications, particularly in those requiring operative management. PMID- 24176588 TI - Acute left main coronary artery thrombosis as the first manifestation of systemic lupus erythematosus and catastrophic antiphospholipid syndrome. AB - Most coronary events in young adults are related to atherosclerosis; however, approximately 20% of coronary heart disease in young adults is related to nonatherosclerotic factors such as coronary abnormalities, connective tissue disorders, and autoimmune diseases. Different initial manifestations of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) have been reported. Myocardial infarction is observed in patients with SLE in all age groups; it appears during the course of the disease; and it is unusual in the APS. We present a unique case of a 28-year-old young man previously healthy who has an ST elevation myocardial infarction by total acute thrombosis of the left main coronary artery. Laboratory studies demonstrated the presence of antibodies for SLE and APS. The patient was treated successfully with percutaneous coronary intervention. He developed catastrophic APS despite an adequate anticoagulation and was treated with intravenous steroids and plasmapheresis. Clinical evolution was satisfactory, and he discharged from the hospital. This case highlights the importance of considering in the emergency department, the prothrombotic states such as SLE and APS in young patients presenting with acute myocardial infarction caused by an unexplained intracoronary thrombosis. Early diagnosis of catastrophic APS and aggressive therapies are essential to help such patients from succumbing to this potentially fatal condition. PMID- 24176589 TI - Reply to the letter to the editor. PMID- 24176590 TI - A new ST-segment elevation myocardial infarction equivalent pattern? Prominent T wave and J-point depression in the precordial leads associated with ST-segment elevation in lead aVr. AB - Certain acute coronary syndrome electrocardiographic (ECG) patterns, which do not include ST-segment elevation, are indicative of acute coronary syndrome caused by significant arterial occlusion; these patterns are, of course, associated with significant risk to the patient and mandate a rapid response from the health care team. One such high-risk ECG pattern includes the association of the prominent T wave and J-point depression producing ST-segment depression seen in the precordial leads coupled with ST-segment elevation in lead aVr. This ECG presentation is associated with significant left anterior descending artery obstruction. We report the case of a patient with this ECG presentation who progressed over a very short time to ST-segment elevation myocardial infarction of the anterior wall. PMID- 24176591 TI - Spontaneous coronary artery dissection and pseudoaneurysm: a case report. AB - Spontaneous coronary artery dissection (SCAD) is a very rare but potentially fatal condition, which often causes acute myocardial infarction and sudden cardiac death. Spontaneous coronary artery dissection associated with pseudoaneurysm has been rarely reported mostly managed with coronary artery bypass grafting. We report a female patient with SCAD and pseudoaneurysm who was treated by successful percutaneous coronary intervention. PMID- 24176592 TI - A fish-stunning wound infection with acute cardiac injury. AB - Vibrio vulnificus typically causes septicemia and necrotic wound infection. Among V vulnificus-related complications, acute nonthrombotic myocardial damage has not been reported. The most effective antibiotic treatment of V vulnificus infection includes combination of a third-generation cephalosporin and a tetracycline or its analogue. However, recommendations of a fourth-generation cephalosporinbased regimen for treating the disease are not established. A 67-year-old diabetic man acquired V vulnificus infection via a fish-stunning wound on the right foot. The patients developed septicemia and hemorrhagic bullous necrotic wounds and followed by acute nonthrombotic cardiac injury with low cardiac output. After initial resuscitation, we applied dobutamine inotropic therapy with combination of cefpirome and ciprofloxacin or minocycline, which achieved a good clinical outcome. PMID- 24176593 TI - The threshold of cortical electrical stimulation for mapping sensory and motor functional areas. AB - This study aimed to investigate the threshold of cortical electrical stimulation (CES) for functional brain mapping during surgery for the treatment of rolandic epilepsy. A total of 21 patients with rolandic epilepsy who underwent surgical treatment at the Beijing Institute of Functional Neurosurgery between October 2006 and March 2008 were included in this study. Their clinical data were retrospectively collected and analyzed. The thresholds of CES for motor response, sensory response, and after discharge production along with other threshold related factors were investigated. The thresholds (mean +/- standard deviation) for motor response, sensory response, and after discharge production were 3.48 +/ 0.87, 3.86 +/- 1.31, and 4.84 +/- 1.38 mA, respectively. The threshold for after discharge production was significantly higher than those of both the motor and sensory response (both p<0.05). A negative linear correlation was found between the threshold of after discharge production and disease duration. Using the CES parameters at a stimulation frequency of 50 Hz and a pulse width of 0.2 ms, the threshold of sensory and motor responses were similar, and the threshold of after discharge production was higher than that of sensory and motor response. PMID- 24176594 TI - The influence of shift work on cognitive functions and oxidative stress. AB - Shift work influences health, performance, activity, and social relationships, and it causes impairment in cognitive functions. In this study, we investigated the effects of shift work on participants' cognitive functions in terms of memory, attention, and learning, and we measured the effects on oxidative stress. Additionally, we investigated whether there were significant relationships between cognitive functions and whole blood oxidant/antioxidant status of participants. A total of 90 health care workers participated in the study, of whom 45 subjects were night-shift workers. Neuropsychological tests were administered to the participants to assess cognitive function, and blood samples were taken to detect total antioxidant capacity and total oxidant status at 08:00. Differences in anxiety, depression, and chronotype characteristics between shift work groups were not significant. Shift workers achieved significantly lower scores on verbal memory, attention-concentration, and the digit span forward sub-scales of the Wechsler Memory Scale-Revised (WMS-R), as well as on the immediate memory and total learning sub-scales of the Auditory Verbal Learning Test (AVLT). Oxidative stress parameters were significantly associated with some types of cognitive function, including attention-concentration, recognition, and long-term memory. These findings suggest that night shift work may result in significantly poorer cognitive performance, particularly working memory. PMID- 24176595 TI - Role of synaptosome-related (SNARE) genes in adults with attention deficit hyperactivity disorder. PMID- 24176596 TI - Reply from authors re: Guillaume Ploussard, James W. Catto. The quest for an optimal definition of prostate-specific antigen failure following radical prostatectomy: the risk of not seeing the forest for the trees. Eur Urol 2014;66:211-13: Identifying the candidates for early salvage therapy after radical prostatectomy. PMID- 24176597 TI - How to manage diabetes mellitus in older persons in the 21st century: applying these principles to long term diabetes care. PMID- 24176598 TI - Insulin use in long term care settings for patients with type 2 diabetes mellitus: a systematic review of the literature. AB - OBJECTIVE: To summarize currently available data about insulin therapy in patients with diabetes mellitus (DM), focusing on patients with type 2 DM (T2DM), in long term care (LTC) settings. DATA SOURCES: Ovid Medline, EMBASE, Cochrane Library databases, and United Kingdom National Health Service (NHS) Economic Evaluation Database, last accessed on November 12, 2012. STUDY ELIGIBILITY CRITERIA: We included studies that reported insulin use in patients with T2DM, and studies with combined samples of patients with type 1 DM or T2DM, that were conducted in LTC settings. Excluded were review articles and studies published before 2000. RESULTS: We identified 11 articles that met all inclusion and exclusion criteria. Insulin use in patients with DM in LTC settings varied widely, from 2.7% to 58.0%. It is difficult to draw conclusions from these proportions, as many studies did not define whether their populations were exclusively patients with T2DM. Despite recommendations against its use by the American Diabetes Association, the American Geriatrics Society, and the American Medical Directors Association, treatment with sliding-scale insulin (insulin injections adjusted to current blood glucose levels) was prevalent in the LTC setting. Although the recommended target hemoglobin A1c (A1C) for this patient population varies from <=6.5% to <=8.0%, higher A1C values (8.0%-8.9%) were associated with better patient outcomes in a study examining insulin treatment in community-dwelling elderly patients enrolled in an outpatient LTC setting. Insulin pen-devices seemed associated with a high incidence of needle-stick injuries in workers in LTC settings but, compared with insulin vials, showed cost advantages for use in very short-term (<=30 days) patients with DM in LTC settings. LIMITATIONS: Paucity of available data; only published studies for which full-text articles could be retrieved and which were identified by our search strategy were included; insufficient detail about patient samples were available in many included studies; and potential biases across studies might be introduced by funding sources or study designs. CONCLUSIONS: Available data about insulin therapy in patients with DM in LTC settings are very scarce and great treatment variability of this patient population seems to prevail in the current clinical practice. Additional, randomized, prospective clinical trials are needed to expand our knowledge and allow clinicians to make informed treatment decisions for patients with DM in LTC settings. PMID- 24176599 TI - Genetic analysis of Tn916-like elements conferring tetracycline resistance in clinical isolates of Clostridium difficile. AB - As an important clinically relevant pathogen, Clostridium difficile has a high multidrug resistance rate. Conjugative transposons play a vital role in its resistance phenotype. In the present study, 34 tetracycline-resistant clinical isolates of C. difficile were studied to detect tetracycline resistance genes and the presence of transposons. Thirty-two isolates were found to harbour Tn916-like elements carrying the tet(M) resistance gene, of which only one copy existed in the genome by Southern blot analysis. To characterise the genetic organisation of the Tn916-like elements, overlap PCR assays were performed with nine primer pairs, revealing three types of elements designated T1 to T3. The prevalent element T1 lacking PCRA (ORF23 to ORF21) and PCRB (ORF21 to ORF20) products, present in the epidemic ST37 clone, was further analysed by genome walking PCR in the left and right end sequences of the novel Tn916-like element. A gene coding for an FtsK/SpoIIIE family protein was found to replace the ORF24 to ORF21 region in Tn916. Moreover, the element could hardly conjugate between cells by filter mating experiments. These findings suggest that the dissemination of Tn916-like elements in epidemic ST37 strains in China was likely to have been conferred by clonal spread, signifying the importance of future surveillance and characterisation of conjugative transposons. PMID- 24176600 TI - The development of a model of education for casual academic staff who support nursing students in practice. AB - Nursing is predominantly a practice based profession where clinical placement for pre-registration nursing students is a significant component of their programme, as this is pivotal in achieving work readiness of the graduate registered nurse. It is therefore important to ensure nursing students have high quality clinical placements that are supervised by well-prepared experienced registered nurses. This paper discusses one component of the reconnaissance phase of a wider action research project being undertaken in a metropolitan university in NSW, Australia seeking to enhance the development and support of casual academic staff known as clinical supervisors who support students in clinical placement. The outcomes attributed to this project are the development of a participation model which has resulted in a collaborative partnership between the university and clinical supervisors and secondly, the embedding of solution focused ways of working and practice development into the program. The information from the reconnaissance phase of this project confirms the need for further research into the implementation of the participatory model to ensure that future education and support process are developed through collaboration. PMID- 24176601 TI - Association between health care workers' knowledge of influenza vaccine and vaccine uptake. AB - Immunization is the most effective measure available to prevent influenza and its complications, and health care workers (HCWs) play a pivotal role. We conducted a cross-sectional survey study to determine HCWs knowledge and opinions regarding influenza vaccine and its acceptance at our institution. The most important reason for vaccine uptake was because it required formal declination (33%); physicians were more likely to be vaccinated because of patient care, whereas nurses were more likely to be vaccinated because it required formal declination. PMID- 24176602 TI - Case-control analysis of endemic Acinetobacter baumannii bacteremia in the neonatal intensive care unit. AB - BACKGROUND: We aimed to characterize the clinical manifestations and outcomes of patients with Acinetobacter baumannii bacteremia in the neonatal intensive care unit (NICU). METHODS: All patients with A baumannii bacteremia in our NICU from 2004 to 2010 were reviewed. A matched case-control study was performed by comparing each case of A baumannii to 2 uninfected controls and all cases of Escherichia coli and Klebsiella bacteremia, respectively. RESULTS: Thirty-seven cases with A baumannii bacteremia were identified. Multidrug-resistant isolate was noted in only 2 cases (5.4%), and the overall mortality rate was 8.1%. Compared with matched, uninfected controls, infants with A baumannii were more likely to have had a central vascular catheter (CVC) (P = .009), use of total parenteral nutrition (TPN) (P = .021), longer duration of ventilator use (P = .002), and hospitalization (P = .010). Compared with E coli or Klebsiella bacteremia, infants with A baumannii bacteremia had lower birth weight (median of 1,090 g vs 1,300 g, P = .044) and a higher rate of CVC and TPN use (both P < .001) at the time of infection. CONCLUSION: A baumannii bacteremia occurs endemically or sporadically in the NICU, primarily in low-birth-weight infants on TPN use and with CVC in situ. Although A baumannii does not often cause mortality, and multidrug-resistant A baumannii is uncommon, it contributes significantly to longer hospitalization. PMID- 24176603 TI - Monitoring of health care personnel employee and occupational health immunization program practices in the United States. AB - Recent studies have identified concerns with various elements of health care personnel immunization programs, including the handling and management of the vaccine. The purpose of this study was to assess monitoring processes that support evaluation of the care of vaccines in health care settings. An 11 question survey instrument was developed for use in scripted telephone surveys. State health departments in all 50 states in the United States and the District of Columbia were the target audience for the surveys. Data from a total of 47 states were obtained and analyzed. No states reported an existing monitoring process for evaluation of health care personnel immunization programs in their states. Our assessment indicates that vaccine evaluation processes for health care facilities are rare to nonexistent in the United States. Identifying existing practice gaps and resultant opportunities for improvements may be an important safety initiative that protects patients and health care personnel. PMID- 24176604 TI - Hepatitis B outbreak associated with a home health care agency serving multiple assisted living facilities in Texas, 2008-2010. AB - We investigated a multifacility outbreak of acute hepatitis B virus infection involving 21 residents across 10 assisted living facilities in Texas during the period January 2008 through July 2010. Epidemiologic and laboratory data suggested that these infections belonged to a single outbreak. The only common exposure was receipt of assisted monitoring of blood glucose from the same home health care agency. Improved infection control oversight and training of assisted living facility and home health care agency personnel providing assisted monitoring of blood glucose is needed. PMID- 24176605 TI - Validation of the surveillance and reporting of central line-associated bloodstream infection denominator data. AB - BACKGROUND: While the main focus of validating central line-associated infections (CLABIs) has been applying strict definitions to identify cases, assessing the denominator counts has received less attention. This study evaluates the accuracy of the reporting of CLABSI denominator patient-day (PD) and central line-day (CLD) counts to the National Healthcare Safety Network (NHSN) system in one state. METHODS: The Connecticut Department of Public Health (CT DPH) performed a blinded retrospective chart review on the collection of CLABSI PD and CLD on 9 selected days during the fourth quarter of 2009 from 23 acute care hospitals. RESULTS: Overall, 1,988 intensive care unit patient charts were reviewed. Comparison of hospital and CT DPH counts identified over-reporting by 300 PD (17.2%) and 200 CLD (21.7%) with 17 hospitals (74%) collecting data manually. PD manual collection methods were more accurate than electronic methods (P < .01). For CLD, there was no significant difference in collection method (P > .05). Wednesday PD counts were more accurate than Monday (P < .05) or Saturday (P < .05). For CLD counts, there was no significant difference among the 3 days (P > .05). CONCLUSION: Our results provide some evidence for the prerequisite internal validation of denominator data by hospitals before reporting to the national surveillance system. PMID- 24176606 TI - Stethoscopes as potential intrahospital carriers of pathogenic microorganisms. AB - Stethoscopes can take part in the transmission of health care-associated infections. We cultured 112 stethoscopes by direct imprint on blood agar to estimate the prevalence of potentially pathogenic microorganisms. Forty-eight (47%) produced 50 potentially pathogenic microorganisms; from these, 43 (86%) were Staphylococcus aureus, of which 18 (42%) were methicillin-resistant S. aureus. We concluded that stethoscopes should be considered as potential fomites and must be disinfected routinely before and after each patient contact. PMID- 24176607 TI - [An a priori risk analysis study. Securisation of transfusion of blood product in a hospital: from the reception in the medical unit to its administration]. AB - Following an ABO accident after transfusion of red blood cells, an a priori risk analysis study is being performed in a hospital. The scope of this analysis covers from the reception of the blood product in the medical unit to its administration. The risk analysis enables to identify the potentially dangerous situations and the evaluation of the risks in order to propose corrective measures (precautionary or protective) and bring the system back to an acceptable risk level. The innovative concept of an a priori risk analysis in the medical field allows the extension of the analysis of this transfusion risk to other hospitals. In addition, it allows the extension of the use of this approach to other medical fields. PMID- 24176608 TI - Monitoring of geosmin producing Anabaena circinalis using quantitative PCR. AB - Geosmin is one of the most commonly detected off-flavor chemicals present in reservoirs and drinking water systems. Quantitative real-time PCR (qPCR) is useful for quantifying geosmin-producers by focusing on the gene encoding geosmin synthase, which is responsible for geosmin synthesis. In this study, several primers and probes were designed and evaluated to detect the geosmin synthase gene in cyanobacteria. The specificity of primer and probe sets was tested using 21 strains of laboratory cultured cyanobacteria isolated from surface waters in Australia (18) and Taiwan (2), including 6 strains with geosmin producing ability. The results showed that the primers designed in this study could successfully detect all geosmin producing strains tested. The selected primers were used in a qPCR assay, and the calibration curves were linear from 5 * 10(1) to 5 * 10(5) copies mL(-1), with a high correlation coefficient (R(2) = 0.999). This method was then applied to analyze samples taken from Myponga Reservoir, South Australia, during a cyanobacterial bloom event. The results showed good correlations between qPCR techniques and traditional methods, including cell counts determined by microscopy and geosmin concentration measured using gas chromatography (GC) coupled with a mass selective detector (MSD). Results demonstrate that qPCR could be used for tracking geosmin-producing cyanobacteria in drinking water reservoirs. The qPCR assay may provide water utilities with the ability to properly characterize a taste and odor episode and choose appropriate management and treatment options. PMID- 24176609 TI - Association between reported screening and counseling about energy drinks and energy drink intake among U.S. adolescents. AB - OBJECTIVE: Possible adverse health consequences of excessive energy drink (ED) consumption have led to recommendations by the American Academy of Pediatrics discouraging ED intake by youth. However, limited information on ED counseling by health care providers exists. METHODS: Data was obtained from the 2011 YouthStyles Survey administered to youth aged 12-17 (n=815). The outcome variable was ED consumption (none vs. >=1 time/week) and exposure variables were screening and counseling about ED (if doctor/nurse asked about ED consumption and if doctor/nurse recommended against ED consumption). RESULTS: Approximately 8.5% of youth consumed energy drinks weekly, 11.5% reported being asked by their doctor/nurse about frequency of ED consumption, and 11.1% were advised by their doctor/nurse against ED intake. Multivariable logistic regression analysis revealed that the odds for drinking ED >=1 time/week was significantly higher in youth who were asked how often they drank ED by their doctor/nurse (odds ratio=2.46) vs. those who were not asked. CONCLUSION: About 1 in 9 youth reported receiving counseling discouraging ED consumption from their doctor/nurse, and a greater proportion of youth who were screened about ED also reported ED consumption. PRACTICE IMPLICATIONS: Efforts by health care providers to educate youth about potential harms of consuming ED are needed. PMID- 24176610 TI - Implementation and effectiveness of a hospital smoking cessation service in Germany. AB - OBJECTIVE: Hospitalized smokers are often highly motivated to quit and receptive to assistance. There are few published accounts of hospital-based smoking cessation programmes implemented outside of a trial setting, particularly outside North America. We describe the implementation and effectiveness of a dedicated smoking cessation service in Freiburg, Germany. METHODS: Measures of implementation (e.g. number of patients referred and consenting to participate, receipt of post-discharge support) and effectiveness are presented. RESULTS: In the first 2 years of the service, 1432 patients were referred. Over half (55.3%) of counselled smokers agreed to participate. Sustained abstinence for 6 months was achieved by 28.0% (missing cases coded as smokers), whereas 7-day point prevalence rates were between 30 and 35% at 3, 6 and 12 months. Those who received 4+ post-discharge calls were more likely to achieve sustained abstinence, as were older smokers, those with higher self-efficacy, and cardiovascular patients. CONCLUSION: Hospitalized patients in Germany are receptive to the offer of bedside counselling and to phone support post discharge, and success rates are comparable to those achieved in other countries. PRACTICE IMPLICATIONS: The findings argue strongly for the routine identification of smokers upon hospital admission, and the availability of cessation support both during hospitalization and following discharge. PMID- 24176612 TI - A prospective study of methylnaltrexone for opioid-induced constipation in advanced illness: should we use it or not? PMID- 24176613 TI - Integrating new evidence about an old drug: growing pains as palliative medicine matures. PMID- 24176614 TI - Real time RT-PCR analysis of inflammatory mediator expression in recurrent airway obstruction-affected horses. AB - The goal of the present study was to investigate mRNA expression levels of several cytokines and inflammatory mediators in broncho-alveolar lavage (BAL) fluid and respiratory epithelium in recurrent airway obstruction (RAO)-affected horses. RAO, also called heaves, is a common, performance-limiting, equine respiratory disease with clinical signs and pathophysiological similarities to human asthma, and characterized by bronchospasm, neutrophilic infiltration and increased mucus in the airways. Six RAO-affected horses were examined twice within 15 days and seven clinically healthy horses were examined for comparison. Quantitative real-time RT-PCR was used to assess mRNA expression of the inflammatory mediators IL-1beta, IL-6, IL-8, IL-13, IL-17, TNFalpha, INFgamma, TGFbeta1, NFkappa-beta and TRL4 in bronchial biopsies and in BAL fluid. Gene expression levels were then compared with clinical signs, endoscopic examination, complete blood cell count, cytology of BAL fluid, histological examination of bronchial tissue and bacteriological and mycological examinations. Expression of IL1beta, IL8, TLR4, TNFalpha, TGFbeta1 and NFkbeta transcripts was significantly up-regulated in RAO-affected compared to healthy horses. A similar trend, albeit not significant, was showed for IL17 and INFgamma. A highly significant correlation was observed among IL-1beta, IL8, TGFbeta1, NFkbeta, TRL4, and INFgamma expression patterns as well as between expression levels of these genes and clinical parameters. In the present study, the comparison between clinically healthy and RAO-affected horses gave new insights on the cytokine expression in equine health and disease status. The identification of cytokines implicated in the pathogenesis of RAO may contribute to the diagnosis and treatment of this disease. PMID- 24176615 TI - The effects of ryanodine receptor 1 (RYR1) mutation on plasma cytokines and catecholamines during prolonged restraint in pigs. AB - In the current study, plasma cytokines, including interleukin (IL) 1, IL-2, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF alpha) and catecholamines (adrenaline and noradrenaline) were evaluated during 4h restraint and recovery phase in 60 male pigs. Blood samples were collected from three groups of pigs representing different RYR1 genotypes, namely NN homozygotes (wild-type), Nn heterozygous and nn homozygous (mutant). The 4h restraint evoked an increase in plasma cytokine concentrations in each of the RYR1 genotype groups. During the restraint, the greatest concentrations of plasma IL-6, IL-10, IL-12 and TNF-alpha in nn homozygous pigs and IFN-gamma in NN homozygous were observed. Interleukin 1, IL-2, IL-10, and TNF-alpha measures were positively intercorrelated in each of the three RYR1 genotype group. A positive correlation was seen between all measured cytokines (with the exception of IL-6) and plasma catecholamine concentrations in Nn heterozygous and nn homozygous pigs. The results suggest that of the cytokine parameters evaluated, IL-6, IL-10, IL-12 and TNF-alpha of the nn homozygous group seem to show a stronger stress-related response as compared with those of the other two (NN and Nn) groups. PMID- 24176617 TI - Study of a measles outbreak in Granada with preventive measures applied by the courts, Spain, 2010 to 2011. AB - Measles had practically been eliminated in Granada since the systematic vaccination of children with two doses introduced in 1984. However, in 2009 the disease returned in the form of small outbreaks. This study describes the measles outbreak that occurred in Granada from October 2010 to August 2011 and the measures imposed to control it. Information was sourced from the records of the Andalusian epidemiological surveillance system. A total of 308 cases were recorded, representing an incidence rate of 33.6 cases per 100,000 inhabitants. The first wave of the epidemic took place in Granada city, with the majority of cases occurring among families who lived in the Albaycin neighbourhood and were opposed to vaccination for ideological and/or religious reasons. The initial cases were in unvaccinated children aged 1 to 13 years. The outbreak later spread throughout the province. To control the outbreak, the vaccination schedule for the exposed children was brought up to date. The Regional Ministry of Health decided to take legal action in order to ensure vaccination of those in the initial nucleus of the outbreak. PMID- 24176616 TI - Human infection with avian influenza A(H7N9) virus re-emerges in China in winter 2013. AB - Through a national surveillance system for unexplained pneumonia, a severe case of influenza A(H7N9) in a man in his mid-30s was identified in Zhejiang Province, China on 14 October 2013. Epidemiological and clinical findings were consistent with the patterns reported during the outbreak in spring 2013, and laboratory findings showed that the virus had 99.6% identity with earlier H7N9 viruses identified in humans in the spring except for five mutations in the NA gene. PMID- 24176618 TI - Outbreak of West Nile virus infection among humans in Serbia, August to October 2012. AB - We describe the first reported outbreak of West Nile virus (WNV) infection in humans in Serbia in August to October 2012 and examine the association of various variables with encephalitis and fatal outcome. Enzyme-linked immunosorbent assay (ELISA) was used for detection of WNV-specific IgM and IgG antibodies in sera and cerebrospinal fluid. A total of 58 patients (mean age: 61 years; standard deviation: 15) were analysed: 44 were from Belgrade and its suburbs; 52 had neuroinvasive disease, of whom 8 had meningitis, while 44 had encephalitis. Acute flaccid paralysis developed in 13 of the patients with encephalitis. Age over 60 years and immunosuppression (including diabetes) were independently associated with the development of encephalitis in a multivariate analysis: odds ratio (OR): 44.8 (95% confidence interval (CI): 4.93-408.59); p=0.001 (age over 60 years); OR: 10.76 (95% CI: 1.06-109.65); p=0.045 (immunosuppression including diabetes). Respiratory failure requiring mechanical ventilation developed in 13 patients with encephalitis. A total of 35 patients had completely recovered by the time they were discharged; nine patients died. The presence of acute flaccid paralysis, consciousness impairment, respiratory failure and immunosuppression (without diabetes) were found to be associated with death in hospital in a univariate analysis (p<0.001, p=0.007, p<0.001 and p=0.010, respectively). PMID- 24176619 TI - Retrospective identification of human cases of West Nile virus infection in Austria (2009 to 2010) by serological differentiation from Usutu and other flavivirus infections. AB - There is increasing evidence for the spread of West Nile virus (WNV) in southern, eastern and central Europe. In parallel, another flavivirus, the antigenically closely related Usutu virus, was introduced from Africa and first detected in Austria (2001), followed by Spain (2003), Hungary (2005), Italy (2006), Switzerland (2006) and Germany (2007). In Austria, human WNV infections have not previously been documented, although the virus was isolated from birds and detected in mosquitoes in 2008 and 2009. We therefore conducted a retrospective search for human cases of WNV infection using serum and cerebrospinal fluid samples collected from patients with central nervous system (CNS) disease in the summers of 2009, 2010 and 2011. Although all samples were negative for WNV by polymerase chain reaction, quantitative evaluation of standardised antibody assays with purified flavivirus antigens (including Usutu virus, which cross reacts with WNV even in neutralisation assays) provided serological evidence for three autochthonous WNV infections in Austria: two in 2009 and one in 2010. Our data highlight the importance of raising awareness of WNV infections in Austria and neighbouring countries and suggest including testing for this infection in routine diagnostic practice of CNS diseases. PMID- 24176620 TI - Letter to the editor: seafarers: a new risk group for meticillin-resistant Staphylococcus aureus (MRSA). PMID- 24176621 TI - Molecular epidemiology of meticillin-resistant Staphylococcus aureus (MRSA): think regionally but use globally uniform typing languages. PMID- 24176622 TI - WHO publishes Global tuberculosis report 2013. PMID- 24176623 TI - X-ray solution structure of the native neuronal porosome-synaptic vesicle complex: Implication in neurotransmitter release. AB - Nanoportals at the cell plasma membrane called porosomes, mediate secretion from cells. In neurons porosomes are 15 nm cup-shaped lipoprotein structure composed of nearly 40 proteins. The size and complexity of the porosome has precluded determination of its atomic structure. Here we report at nanometer resolution the native 3D structure of the neuronal porosome-synaptic vesicle complex within isolated nerve terminals using small-angle X-ray solution scattering. In addition to furthering our understanding of the porosome structure, results from the study suggests the molecular mechanism involved in neurotransmitter release at the nerve terminal. PMID- 24176624 TI - Copper pathology in vulnerable brain regions in Parkinson's disease. AB - Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with alpha-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by alpha-synuclein pathology may display enhanced vulnerability and cell loss if Cu dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder. PMID- 24176626 TI - Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population. AB - We performed case-control studies using 2 Canadian cohorts to examine the role of 10 promising Alzheimer's disease (AD) loci identified in recent genomewide association studies. Patients age 65 years and older diagnosed with AD at baseline (prevalent cases) or who developed AD during follow-up assessments (incident cases) were compared with control subjects with no cognitive impairment. Our prevalent case study comparing prevalent AD cases (n = 428) with participants with no cognitive impairment (n = 524) revealed a significant association of rs6656401 and rs3818361 (CR1), rs2075650 (TOMM40), rs7561528 (BIN1), and rs3865444 (CD33) with late-onset AD that were robust to adjustment with age and apolipoprotein E epsilon4 genotype. The incident case study comparing patients who developed AD during longitudinal observation (n = 152) with participants with no cognitive impairment found that rs2075650 (TOMM40) and rs3865444 (CD33) influence the risk of developing AD in this population. In addition, pooled analysis of our AD patients confirmed that CR1, TOMM40, BIN1, and CD33 contribute to late-onset AD susceptibility, in addition to apolipoprotein E. PMID- 24176627 TI - Sexual dimorphism of root length on a Greek population sample. AB - Sexual dimorphism in teeth has been an area of research for osteoarchaeologists and forensic anthropologists studying human skeletal remains. As most studies have been based on the mesiodistal and buccolingual crown measurements, sexual dimorphism from root length dimensions remains "neglected" by comparison to crown dimensions. The aim of the present study was to test the existence of sexual dimorphism in the root length of single-rooted teeth with the purpose of investigating whether maximum root length can be reliably used to determine sex. A total of 774 permanent teeth in 102 individuals (58 males and 44 females) from the Athens Collection were examined. The maximum root length of each tooth was measured on the mesial, distal, buccal, and lingual side. Almost all teeth presented a high degree of sexual dimorphism with males showing numerically higher values in root length than females. The most dimorphic teeth were the maxillary second incisors followed by maxillary canines. The percentage of sexual dimorphism reached 16.56%, with maxillary teeth showing the highest degree of dimorphism. The classification results show that the overall correctly specified group percentage ranged from 58.6% to 90.0%. The data generated from this study suggest that root length measurements offer a reliable method for determining sex and are therefore useful in osteoarchaeological studies, particularly in cases of fragmented or cremated material, but also in forensic contexts. Moreover, root length can be used to separate the remains of female and male subadult individuals with a high level of accuracy thus addressing one of the most problematic issues in human osteoarchaeology and anthropology as immature skeletons are the most difficult to sex. PMID- 24176625 TI - Cholinergic basal forebrain atrophy predicts amyloid burden in Alzheimer's disease. AB - We compared accuracy of hippocampus and basal forebrain cholinergic system (BFCS) atrophy to predict cortical amyloid burden in 179 cognitively normal subjects (CN), 269 subjects with early stages of mild cognitive impairment (MCI), 136 subjects with late stages of MCI, and 86 subjects with Alzheimer's disease (AD) dementia retrieved from the Alzheimer's Disease Neuroimaging Initiative database. Hippocampus and BFCS volumes were determined from structural magnetic resonance imaging scans at 3 Tesla, and cortical amyloid load from AV45 (florbetapir) positron emission tomography scans. In receiver operating characteristics analyses, BFCS volume provided significantly more accurate classification into amyloid-negative and -positive categories than hippocampus volume. In contrast, hippocampus volume more accurately identified the diagnostic categories of AD, late and early MCI, and CN compared with whole and anterior BFCS volume, whereas posterior BFCS and hippocampus volumes yielded similar diagnostic accuracy. In logistic regression analysis, hippocampus and posterior BFCS volumes contributed significantly to discriminate MCI and AD from CN, but only BFCS volume predicted amyloid status. Our findings suggest that BFCS atrophy is more closely associated with cortical amyloid burden than hippocampus atrophy in predementia AD. PMID- 24176628 TI - Ankylosis of impacted canines: a retrospective post-surgical study. AB - Ankylosis is generally discovered following resistance to orthodontic displacement of an impacted canine. This retrospective study, drawing on direct perioperative observation of impacted teeth and of their sites, is intended, among other things, to analyze the causes of resistance to orthodontic movement and to report on the therapeutic interest of the surgical tooth displacement technique in this type of clinical situation. We demonstrate that primary coronal ankylosis can be detected by the orthodontic practitioner using radiographic records, that cervical ankylosis consequent to operative trauma during release is necessarily unpredictable and that it should be suspected when the tooth resists traction for more than 3 months in the absence of any other obvious cause of resistance. Hence, the risk of ankylosis linked to the level of surgical difficulty increases with the depth of coronal submergence within the bone. Moreover, the immediate placement of traction following release reduces the risk of ankylosis. In addition, temporarily suspending traction is a risk factor for secondary apical ankylosis. Finally, surgical positioning should be borne in mind as the final effective option when faced with any form of dental retention. PMID- 24176630 TI - Reproductive ageing and conflicting clocks: King Midas' touch. AB - The population attempting pregnancy and having babies is ageing. Gynaecological and obstetric complications worsen with age. Maternity services are struggling. Increasing rates of infertility and complications are not matched by the marvels in the laboratory. This paper argues that assisted reproduction treatment has had a damaging social impact. Despite its public acclaim, it helps few and fails many more. The assisted reproduction industry could take a new and revolutionary direction towards empowering men to experience pregnancy, producing babies from artificial gametes, with a final goal being the liberation of both women and men from the burdens and dangers of pregnancy through the development of artificial wombs. PMID- 24176631 TI - Profound acute limb ischemia affecting all four limbs following cocaine inhalation. AB - Recreational drug use is a recognized cause of a number of acute vascular events. Cocaine is associated with a number of cardiovascular diseases, including myocardial ischemia, arrhythmias, and aortic dissection. Cutting agents are commonly used to dilute the amount of cocaine required to enhance the profits of the seller. Such cutting agents themselves often provoke acute vascular disease. We present the case of a 34-year-old female presenting with profound ischemia affecting all four limbs secondary to cocaine inhalation. PMID- 24176632 TI - Extra-anatomic autologous reconstruction with hepatic-iliac artery bypass graft for aortic endograft infection. AB - We present a new intra-abdominal extra-anatomic bypass graft for a 64-year-old man treated with an abdominal aortic endograft and with signs of endograft infection. We performed surgical removal of the endograft and intra-abdominal extra-anatomic reconstruction of a hepatic-to-right external iliac artery bypass with autologous superficial femoral vein and a crossover graft between the right and left external iliac artery with the great saphenous vein. The later occlusion of the saphenous vein graft led us to perform a femoral-femoral prosthetic crossover. At 42 months from the intervention, the patient was in good health, and duplex scanning confirmed the patency of all grafts. PMID- 24176633 TI - Lateral approach to the peroneal artery without resection of the fibula for lower limb revascularization. AB - The peroneal artery is an important outflow vessel for lower limb revascularization and limb salvage. This vessel is commonly reached using a medial, posterior, or lateral approach with resection of the fibula. We present a technique of lateral approach to the peroneal artery without fibular resection. PMID- 24176634 TI - Impact of severe chronic kidney disease on outcomes of infrainguinal peripheral arterial intervention. AB - OBJECTIVE: Patients with severe chronic kidney disease (CKD) and peripheral vascular disease are at increased risk of major adverse limb events (MALEs) and death; however, patients with end-stage renal disease have been excluded in current objective performance goals. We evaluated the effect of severe (class 4 and 5) CKD on outcomes after infrainguinal endovascular arterial interventions. METHODS: All primary peripheral vascular interventions (PVIs) performed at a single institution (January 2002 through December 2009) were included. End points were defined by Society for Vascular Surgery objective performance goals for critical limb ischemia (CLI), which include all-cause mortality, reintervention, and composite end points of death or amputation and MALEs (reintervention or amputation). Univariate and multivariable analysis was used to examine the effect of severe CKD on study end points. RESULTS: A total of 879 PVIs were performed, with severe CKD in 125 (14%). Severe CKD patients were significantly (P < .05) more likely to have diabetes (64% vs 46%), CLI (72% vs 11%), and need a multilevel PVI (34% vs 19%) or tibial intervention (35% vs 20%) compared with the remainder of the cohort. Distribution of TransAtlantic Inter-Society Consensus C and D lesions were similar (19% severe CKD vs 15%; P = .2). Severe CKD predicted perioperative (30-day) reintervention (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.5-4; P = .05), amputation or death (OR, 3.1; 95% CI, 1.1-9; P = .04), and MALEs (OR, 2.8; 95% CI, 1.3-6.1; P = .04), which was independent of CLI in multivariable regression analysis. On Kaplan-Meier analysis, severe CKD was significantly (log-rank P < .05) associated with death (31% +/- 4% vs 7% +/- 1%), amputation (14% +/- 3% vs 3% +/- 1%), and MALEs (40% +/- 5% vs 26% +/- 2%) at 1 year. Freedom from reintervention was similar at 1 year (70% +/- 5% severe CKD vs 75% +/- 2%; P = .23). Risk-adjusted (age, CLI, diabetes, coronary artery disease) Cox proportional hazards regression showed that severe CKD increased the risk of late mortality (hazard ratio [HR], 2.4; 95% CI, 1.8-3.2; P < .01), amputation (HR, 2.1; 95% CI, 1.1-3.9; P = .02), and death or amputation (HR, 1.8; 95% CI, 1.3-2.4; P = .04), without increasing the risk of late reinterventions or MALEs. CONCLUSIONS: CKD independently predicts early and late adverse events after a PVI, in particular, excessive mortality. CKD should figure prominently in clinical decision making for patients with peripheral vascular disease. PMID- 24176636 TI - Processing the complexities of transcription. AB - Recent studies have revealed unexpected subunit diversity and specificity in the general transcription machinery for orchestrating multicellular differentiation. In this issue of Developmental Cell, Oyama et al. (2013) report a requirement for Taspase 1-dependent TFIIA proteolytic processing in the mouse testis to enable TRF2 targeting to genes regulating spermatogenic differentiation. PMID- 24176637 TI - Synaptic vesicle fusion without SNARE transmembrane regions. AB - Diverse roles in membrane fusion have been proposed for the transmembrane regions (TMRs) of SNARE proteins, including formation of channel-like transmembrane pores. Reporting in Neuron, Zhou et al. (2013) show that lipid-anchored SNAREs lacking TMRs can support neurotransmitter release, suggesting that SNAREs function primarily as power engines that force membranes together. PMID- 24176638 TI - Cilia grow by taking a bite out of the cell. AB - Autophagy and primary cilium assembly have long been known to be induced by the same conditions in cultured cells. Two recent studies in Nature-Tang et al. (2013) and Pampliega et al. (2013)-link the two processes, suggesting that a specialized autophagy pathway near the basal body regulates cilium assembly. PMID- 24176639 TI - Unfolding the mystery of olfactory receptor gene expression. AB - Reporting recently in Cell, Dalton et al. (2013) identify a central role for the unfolded protein response in the regulation of olfactory receptor expression, unveiling molecular players in an elaborate feedback loop that controls the stabilization and establishment of single olfactory receptor gene choice. PMID- 24176640 TI - External mechanical cues trigger the establishment of the anterior-posterior axis in early mouse embryos. AB - Mouse anterior-posterior axis polarization is preceded by formation of the distal visceral endoderm (DVE) by unknown mechanisms. Here, we show by in vitro culturing of embryos immediately after implantation in microfabricated cavities that the external mechanical cues exerted on the embryo are crucial for DVE formation, as well as the elongated egg cylinder shape, without affecting embryo intrinsic transcriptional programs except those involving DVE-specific genes. This implies that these developmental events immediately after implantation are not simply embryo-autonomous processes but require extrinsic factors from maternal tissues. Moreover, the mechanical forces induce a breach of the basement membrane barrier at the distal portion locally, and thereby the transmigrated epiblast cells emerge as the DVE cells. Thus, we propose that external mechanical forces exerted by the interaction between embryo and maternal uterine tissues directly control the location of DVE formation at the distal tip and consequently establish the mammalian primary body axis. PMID- 24176641 TI - Translation repressors, an RNA helicase, and developmental cues control RNP phase transitions during early development. AB - Like membranous organelles, large-scale coassembly of macromolecules can organize functions in cells. Ribonucleoproteins (RNPs) can form liquid or solid aggregates, but control and consequences of these RNP states in living, developing tissue are poorly understood. Here, we show that regulated RNP factor interactions drive transitions among diffuse, semiliquid, or solid states to modulate RNP sorting and exchange in the Caenorhabditis elegans oocyte cytoplasm. Translation repressors induce an intrinsic capacity of RNP components to coassemble into either large semiliquids or solid lattices, whereas a conserved RNA helicase prevents polymerization into nondynamic solids. Developmental cues dramatically alter both fluidity and sorting within large RNP assemblies, inducing a transition from RNP segregation in quiescent oocytes to dynamic exchange in the early embryo. Therefore, large-scale organization of gene expression extends to the cytoplasm, where regulation of supramolecular states imparts specific patterns of RNP dynamics. PMID- 24176642 TI - Cleavage of TFIIA by Taspase1 activates TRF2-specified mammalian male germ cell programs. AB - The evolution of tissue-specific general transcription factors (GTFs), such as testis-specific TBP-related factor 2 (TRF2), enables the spatiotemporal expression of highly specialized genetic programs. Taspase1 is a protease that cleaves nuclear factors MLL1, MLL2, TFIIAalpha-beta, and ALFalpha-beta (TFIIAtau). Here, we demonstrate that Taspase1-mediated processing of TFIIAalpha beta drives mammalian spermatogenesis. Both Taspase1(-/-) and noncleavable TFIIAalpha-betanc/nc testes release immature germ cells with impaired transcription of Transition proteins (Tnp) and Protamines (Prm), exhibiting chromatin compaction defects and recapitulating those observed with TRF2(-/-) testes. Although the unprocessed TFIIA still complexes with TRF2, this complex is impaired in targeting and thus activating Tnp1 and Prm1 promoters. The current study presents a paradigm in which a protease (Taspase1) cleaves a ubiquitously expressed GTF (TFIIA) to enable tissue-specific (testis) transcription, meeting the demand for sophisticated regulation of distinct subsets of genes in higher organisms. PMID- 24176644 TI - Treatment adherence and persistence in adult ADHD: results from a twenty-four week controlled clinical trial with extended release methylphenidate. AB - PURPOSE: The aim of this analysis is to describe medication adherence, and treatment persistence, in adults with attention deficit/hyperactivity disorder (ADHD) treated for 24 weeks with extended release methylphenidate (MPH-ER). Additionally, patient-, disorder- and treatment-related factors associated with adherence and persistence will be identified. METHOD: Post-hoc analysis of the active treatment group of a placebo-controlled, randomised, 24 week trial with MPH-ER with univariate description and multiple logistic regression models and Hosmer and Lemeshow tests. RESULTS: In the sample of 241 adults with ADHD (mean age of 35.2 +/- 10.1 years), 9.4% of the patients were non-adherent, taking less than 80% of the dispensed medication. Factors associated with non-adherence included age<25 years, education level lower than secondary education, lacking family history of ADHD, lower ADHD baseline severity and lower self- and observer rated medication efficacy. Lacking family history of ADHD, lower education level and lower self-rated medication efficacy, predicted non-adherence with a prediction accuracy of 16%. Seventeen percent of the patients discontinued early with most discontinuing within the first five weeks of the MPH-ER titration phase. Mean persistence in the discontinuing group was 63.4 +/- 49.4 days. Factors associated with discontinuation included male gender, lower education level, lacking family history of ADHD and lower self- and observer-rated medication efficacy. Treatment non-response, male gender and lower education level predicted treatment discontinuation with a prediction accuracy of 22.7%. CONCLUSION: Male adults without relatives with ADHD, with lower educational level and lower self- and observer-rated medication efficacy, who are newly treated with MPH-ER, are at increased risk of non-adherence and treatment discontinuation. Patients are at increased risk of treatment discontinuation during the medication titration phase. PMID- 24176645 TI - Method of assessment determines prevalence of suicidal ideation among patients with depression. AB - BACKGROUND: How different ways of assessing suicidal ideation influence its prevalence, correlates and predictive validity among patients with major depressive disorder (MDD) remains unclear. METHODS: Within the Vantaa Primary Care Depression Study (PC-VDS, 91 patients) and the Vantaa Depression Study (VDS, 153 psychiatric out-and 41 inpatients), suicidal ideation was assessed with the Scale for Suicidal Ideation (SSI), Hamilton Depression Scale (HAM-D) item 3 and Beck Depression Inventory (BDI) item 9, and by asking whether patients had seriously considered suicide during the episode. The positive and negative predictive values (PPV, NPV) for suicide attempts during a six-month follow-up were investigated. RESULTS: Depending on the setting, 56-88% of patients had suicidal ideation in some of the assessments, but only 8-44% in all of them. Agreement ranged from negligible to moderate (kappa 0.06-0.64), being lowest among primary care patients. The correlates of suicidal ideation overlapped. No assessment had optimal sensitivity, specificity, PPV and NPV. Nevertheless, PPVs ranged up to 43%. CONCLUSIONS: Which MDD patient is classified as having suicidal ideation depends strongly on the method of assessment, with the greatest variation likely in primary care. Differences in assessments may cause inconsistency in risk factors. Predicting suicide attempts is difficult, but not futile. PMID- 24176643 TI - A network of interactions enables CCM3 and STK24 to coordinate UNC13D-driven vesicle exocytosis in neutrophils. AB - Neutrophil degranulation plays an important role in acute innate immune responses and is tightly regulated because the granule contents can cause tissue damage. However, this regulation remains poorly understood. Here, we identify the complex of STK24 and CCM3 as being an important regulator of neutrophil degranulation. Lack of either STK24 or CCM3 increases the release of a specific granule pool without affecting other neutrophil functions. STK24 appears to suppress exocytosis by interacting and competing with UNC13D C2B domain for lipid binding, whereas CCM3 has dual roles in exocytosis regulation. Although CCM3 stabilizes STK24, it counteracts STK24-mediated inhibition of exocytosis by recruiting STK24 away from the C2B domain through its Ca(2+)-sensitive interaction with UNC13D C2A domain. This STK24/CCM3-regulated exocytosis plays an important role in the protection of kidneys from ischemia-reperfusion injury. Together, these findings reveal a function of the STK24 and CCM3 complex in the regulation of ligand stimulated exocytosis. PMID- 24176646 TI - Sustained antipsychotic effect of metacognitive training in psychosis: a randomized-controlled study. AB - Persistent psychotic symptoms represent a major challenge for psychiatric care. Basic research has shown that psychotic symptoms are associated with cognitive biases. Metacognitive training (MCT) aims at helping patients to become aware of these biases and to improve problem-solving. Fifty-two participants fulfilling diagnostic criteria of schizophrenia or schizoaffective disorders and persistent delusions and stabilized antipsychotic medication were enrolled in this study. Following baseline assessment patients were randomized either to treatment as usual (TAU) conditions or TAU+MCT. The intervention consisted of eight weekly 1 hour sessions (maximum: 8 hours). Participants were assessed at 8 weeks and 6 months later by blind assessors. Participants were assessed with the Psychotic Symptoms Rating Scales (PSYRATS) and the positive subscale of the PANSS. Between group differences in post- and pre-test values were significant at a medium effect size in favor of the MCT for the PSYRATS delusion scale and the positive scale of the PANSS both at post and follow-up. The results of this study indicate that MCT training has a surplus antipsychotic effect for patients suffering from schizophrenia-related disorders who demonstrate only a partial response to antipsychotic treatment and that the effect of the intervention persists for at least 6 months after the intervention. PMID- 24176647 TI - White matter hyperintensities and cognitive performance in adult patients with bipolar I, bipolar II, and major depressive disorders. AB - PURPOSE: We evaluate for the first time the associations of brain white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) with neuropsychological variables among middle-aged bipolar I (BPI), II (BPII) and major depressive disorder (MDD) patients and controls using a path model. METHODS: Thirteen BPI, 15 BPII, 16 MDD patients, and 21 controls underwent brain MRI and a neuropsychological examination. Two experienced neuroradiologists evaluated WMHs on the MRI scans. We constructed structural equation models to test the strength of the associations between deep WMH (DWMH) grade, neuropsychological performance and diagnostic group. RESULTS: Belonging in the BPI group as opposed to the control group predicted higher DWMH grade (coefficient estimate 1.13, P=0.012). The DWMH grade independently predicted worse performance on the Visual Span Forward test (coefficient estimate -0.48, P=0.002). Group effects of BPI and MDD were significant in predicting poorer performance on the Digit Symbol test (coefficient estimate -5.57, P=0.016 and coefficient estimate -5.66, P=0.034, respectively). LIMITATIONS: Because of the small number of study subjects in groups, the negative results must be considered with caution. CONCLUSIONS: Only BPI patients had an increased risk for DWMHs. DWMHs were independently associated with deficits in visual attention. PMID- 24176648 TI - VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. AB - Leucine-rich glioma inactivated 1 (LGI1) was recently identified as a target protein in autoimmune synaptic encephalitis, a rare condition associated with autoantibodies against structures in the neuronal synapse. Studies dealing with LGI1 are small in number and the various outcomes of different therapeutic regimens are not well studied. Here, we analyzed clinical characteristics of 14 patients with LGI1 antibodies, and outcomes according to therapeutic strategies. Most patients exhibited abnormal brain positron emission tomography and that patients treated with steroids alone were more likely to relapse and had less favorable outcomes than those treated with steroids and intravenous immunoglobulins. PMID- 24176649 TI - Mixed germ cell tumor complicating an intra-abdominal cryptorchidism. PMID- 24176650 TI - CT perfusion-guided versus time-guided mechanical recanalization in acute ischemic stroke patients. AB - OBJECTIVE: Perfusion studies are increasingly used to triage acute stroke patients for endovascular recanalization therapies. We compare the safety and efficacy of CT perfusion (CTP)-guided to time-guided mechanical recanalization in acute ischemic stroke (AIS) patients. METHODS: A review was conducted on 132 patients, 94 undergoing CTP-guided and 38 undergoing time-guided (maximum 8h from symptom onset) mechanical recanalization at our institution. RESULTS: The rate of partial-to-complete recanalization did not differ between the CTP and the non-CTP group (78.7% vs. 81.6%, respectively, p=0.71). ICH occurred respectively in 18.1% in the CTP group versus 31.6% in the non-CTP group (p=0.06). The overall in hospital mortality rate was significantly lower in the CTP group (15.9% vs. 36.8%, p=0.04). In multivariable analysis, CTP-guided patient selection was an independent negative predictor of in-hospital mortality (OR=3.2; p=0.01). CTP guided patient selection, however, was not a predictor of favorable outcome (Modified Rankin Scale 0-2 or 0-3). CONCLUSIONS: CTP-based patient selection was associated with lower ICH and mortality rates. Favorable outcomes, however, did not differ between the 2 groups. These results may suggest a possible benefit in terms of in-hospital mortality with CTP-guided triage of AIS patients for endovascular treatment. PMID- 24176651 TI - Rearrangement of motor centers and its relationship to the neurological status of low-grade glioma examined on pre- and postoperative fMRI. AB - OBJECTIVE: Well-developed compensatory mechanisms, based on the phenomenon of brain plasticity, exist in patients with neuroepithelial tumors, especially with highly differentiated gliomas (WHO grade II). We studied phenomenon of rearrangement of sensorimotor cortex using functional magnetic resonance imaging (fMRI), and verified relationship between observed changes and results of neurological and neuropsychological assessment. METHODS: Study group included 20 patients with WHO grade II gliomas located within motor or sensory cortex. fMRI examination, as well as clinical, neurological (Karnofsky performance score [KPS] and Lovett's scale [Lo]), and neuropsychological assessment (Digit Coding Symbol Test and Digit Span Test) were performed pre-operatively and 3 months post surgery. RESULTS: There were no significant differences in pre- and postoperative performance status of patients. Although statistically insignificant, an increase in frequency of activation of primary and secondary cortical motor centers was observed postoperatively (p>0.05). Prior to surgery, motor centers were characterized by lower values of t-statistics than in postoperative period (p>0.05). In contrast, values of parameters describing the size of examined centers, i.e. mean number of clusters, were lower, but not statistically significant on postoperative examination (p>0.05). Compared to individuals without motor deficit, patients with preoperative Lo3/Lo4 paralysis showed significantly higher mean values of t-statistics in the accessory motor area on postoperative examination (p<0.05). CONCLUSIONS: The processes of motor cortex rearrangement seemed to be associated with the pre- and postoperative neurological and neuropsychological status of patients. After contralateral primary motor cortex, accessory motor area was the second most frequently activated center, both pre- and postoperatively. PMID- 24176652 TI - [20% of living donor kidney transplantation in France? Yes, it's possible!]. PMID- 24176653 TI - [Mineral and bone disorders in renal transplantation]. AB - The deregulation of bone and mineral metabolism during chronic kidney disease (CKD) is a daily challenge for physicians, its management aiming at decreasing the risk of both fractures and vascular calcifications. Renal transplantation in the context of CKD, with pre-existing renal osteodystrophy as well as nutritional impairment, chronic inflammation, hypogonadism and corticosteroids exposure, represents a major risk factor for bone impairment in the post-transplant period. The aim of this review is therefore to provide an update on the pathophysiology of mineral and bone disorders after renal transplantation. PMID- 24176654 TI - Determining the number of intraparotid lymph nodes: postmortem examination. AB - BACKGROUND: The parotid gland is one of the metastatic drainage areas for malignant tumours of the head and neck area. In this study, we aimed to define the accurate number and distribution of intraparotid lymph nodes in the 84 glands of 42 fresh cadavers for implementing the data for the clinical practice. METHODS: Bilateral total parotidectomies were performed. The lobes were separated, fixed with formalin, cut into thick slices, embedded in paraffin and serially sectioned. 2 MUm thick sections were stained and examined histopathologically. RESULTS: No nodes were found in 4 of 84 superficial parotid lobes and in 58 of 84 deep parotid lobes. CONCLUSIONS: Sentinel lymph node biopsy failure may be related to the absence of intraparotid lymphoid tissue. Although the superficial intraparotid lymph nodes are a first echelon of head and neck tumours, involvement of these does not allow us to exclude the possibility of involvement of the deep lobes. PMID- 24176655 TI - Levels, profiles and gas-particle distribution of atmospheric PCDD/Fs in vehicle parking lots of a South China metropolitan area. AB - Vehicle exhaust is one important PCDD/F source in urban areas. In this study, occurrence and inhalation of atmospheric PCDD/Fs in three enclosed/semi-enclosed large-scale vehicle parks were investigated. The park for heavy-duty diesel trucks exhibited the highest atmospheric 2,3,7,8-PCDD/F concentrations (17.7 +/- 4.3 pg m(-3), 0.818 +/- 0.264 pg I-TEQm(-3)), followed sequentially by those for liquefied petroleum gas-buses and for unleaded gasoline-cars. High-chlorinated congeners/homologues dominated 2,3,7,8-PCDD/F profiles. Principal component analysis indicated their similarities with tailpipe studies. More than 70% of PCDD/Fs were particle-bound and their congener/homologue patterns differed from those of gaseous PCDD/Fs. In all studied parks logarithms of the gas/particle partitioning coefficients (Kps) of PCDD/F homologues were linearly correlated with those of their sub-cooled vapor pressures (pLs). Daily PCDD/F doses inhaled by park-workers were estimated to be between 0.099-0.227 pg I-TEQ kg(-1)d(-1). Their probabilistic incremental lifetime cancer risks were 1.08 * 10(-5)-2.07 * 10(-5), which were in the acceptable range (1.0 * 10(-4)-1.0 * 10(-6)). However, all data from the diesel-truck park significantly exceeded the upper limit for PCDD/Fs in ambient air of Japan (0.6 pg TEQm(-3)). Hence, air pollution and adequate ventilation should be considered during the design and construction of such enclosed/semi-enclosed parks. PMID- 24176656 TI - Behavior and fate of industrial zinc oxide nanoparticles in a carbonate-rich river water. AB - The present study precisely describes the solubility patterns of commercial uncoated and organic coated ZnO NPs (nc-NPs and c-NPs, respectively) in a natural carbonate-rich water and the physicochemical processes involved. NPs transformation rates were determined with the Donnan Membrane approach (DMT, to obtain Zn(2+) concentration) and ultrafiltration (i.e. Zn(2+) and Zn bound to small organic ligands) and modeled with VMinteQ. XPS measurements evidenced the presence on native nc-NPs of a Zn(OH)2 layer which accounts for almost 22% of total Zn. This Zn(OH)2 phase is more soluble than ZnO, and could control the early dissolution steps of the nc-NPs in our system. Indeed, nc-NPs display a fast (<1 h) dissolution step reaching 19 MUM Zn in solution (<1% of the total initial zinc concentration). Comparatively, c-NPs progressively release zinc during the first 48 h, to finally reach a maximum of 197 MUM (10% of total Zn), which is 10 times the maximum value measured for nc-NPs. Over the long term, dissolved Zn concentrations decrease in both systems, corresponding to the neoformation of carbonate phases observed by TEM imaging. The kinetic modeling allows highlighting two different ranges of time, corresponding to (i) first 10h with a fast precipitation (kp(')=-182.10(-4)) related to a highly oversaturated solution with respect to carbonate zinc mineral and (ii) a second slower precipitation step (kp(')=-8.10(-4)), related to the embedding of NPs in the precipitated carbonate matrix. The steady state is reached after 3 months of interaction. PMID- 24176657 TI - Monitoring West Nile virus (WNV) infection in wild birds in Serbia during 2012: first isolation and characterisation of WNV strains from Serbia. AB - West Nile virus (WNV), a neurovirulent mosquito-transmissible zoonotic virus, has caused recent outbreaks in Europe, including Serbia from August until October 2012. Although humans can be infected, birds are the main natural WNV reservoir. To assess WNV circulation in northern Serbia, 133 wild birds were investigated. These comprised resident and migratory birds, collected between January and September 2012 in the Vojvodina province. The birds belonged to 45 species within 27 families. Blood sera (n=92) and pooled tissues from respective birds (n=81) were tested by enzyme-linked immunosorbent assay (ELISA), plaque reduction neutralisation test (PRNT) and real-time reverse transcription-polymerase chain reaction (RT-qPCR). WNV antibodies were detected in seven (8%) sera: four from Mute Swans (Cygnus olor), two from White-tailed Eagles (Haliaeetus albicillas), and one from a Common Pheasant (Phasianus colchicus). Five sera neutralised WNV but not Usutu virus. For the first time in Serbia, WNV RNA was detected by RT qPCR in pooled tissue samples of eight respective birds. WNV RNA was also derived from an additional bird, after a serum sample resulted infective in cell culture. The total nine WNV RNA positive birds included three Northern Goshawks (Accipiter gentilis), two White-tailed Eagles, one Legged Gull (Larus michahelis), one Hooded Crow (Corvus cornix), one Bearded Parrot-bill (Panarus biramicus), and one Common Pheasant. Phylogenetic analysis of partial E region sequences showed the presence of, at least, two lineage 2 Serbian clusters closely related to those responsible for recent human and animal outbreaks in Greece, Hungary and Italy. Full genomic sequence from a goshawk isolate corroborated this data. These results confirm WNV circulation in Serbia and highlight the risk of infection for humans and horses, pointing to the need for implementing WNV surveillance programmes. PMID- 24176658 TI - Dramatic change in public attitudes towards vaccination during the 2009 influenza A(H1N1) pandemic in France. AB - We investigated the potential impact of the 2009 influenza A(H1N1) pandemic on attitudes towards vaccination among people aged 18 to 75 years and living in metropolitan France. We used data from three national telephone surveys conducted on representative samples in 2000, 2005 and 2010 (n=12,256, n=23,931, n=8,573 respectively). In France, unfavourable attitudes towards vaccination in general dramatically increased from 8.5% in 2000 and 9.6% in 2005 to 38.2% in 2010. In 2010, among respondents who held unfavourable attitudes towards vaccination, 50% mentioned specifically their opposition to the influenza A(H1N1) vaccine. The sociodemographic profile associated with these attitudes also changed greatly. In particular, unfavourable attitudes towards vaccination in general became significantly more frequent among less educated people in 2010. These attitudes were also correlated with vaccination behaviours. For example, parents who were unfavourable towards vaccination in general were more likely to report that they had at least one child who did not get the measlesmumps- rubella vaccine. As this shift in attitude may have a significant impact on future vaccination coverage, health authorities should urgently address the vaccine confidence gap. PMID- 24176659 TI - Plasmodium knowlesi infection imported to Germany, January 2013. PMID- 24176662 TI - [Hypofractionated radiotherapy, a standard in breast cancer?]. AB - In the era of high-tech radiotherapy, hypofractionated schema is more and more widely used regardless of tumour sites. In this article, we expose the role, techniques and indications of hypofractionated radiotherapy in adjuvant breast radiotherapy. PMID- 24176663 TI - [Evaluation and implementation of in vivo transit dosimetry with an electronic portal imaging device]. AB - PURPOSE: In vivo dosimetry is now widely recommended to avoid major treatment error. Transit dosimetry using portal imagers allows fast and accurate in vivo dose verifications. Several teams have published clinical studies but no recommendation has been proposed to define tolerance levels and validation criteria. This study proposes a simple methodology to assess the overall standard deviation of transit dosimetry and was applied to our transit dosimetry method. MATERIAL AND METHODS: In a first step, the uncertainties due to the dose reconstruction method are evaluated. Their estimation is based on a set of geometries, representative of clinical situations for which 45 points of measurement have been defined. In a second step, we studied the variations of our method in clinical situations. During the treatment session of the patient, the dose was reconstructed and the differences between reconstructed dose and prescribed dose were used to define a realistic tolerance level, adapted to the clinical routine. Then, a methodology is proposed to determine if the transit dosimetry method, with the defined tolerance level allows detecting significant treatment errors (>5% of the prescribed dose). RESULTS - CONCLUSION: Applying this methodology we concluded that a tolerance level of 6.5% (k=2) can be associated with our method. With this value, it is demonstrated that in many cases differences of 5% (or less) on the prescribed dose can be detected. This study demonstrates clearly that in vivo transit dosimetry is not able to detect all the treatment errors but remains an ultimate and efficient tool in many situations. PMID- 24176664 TI - Myeloma after local external beam radiotherapy jet: Is it a new entity? AB - Multiple myeloma, also known as Kahler's disease, is a cancer of plasma cells that abnormally accumulate in bone marrow. Radiation therapy may be indicated in multiple myeloma to relieve pain, alleviate spinal cord compression or reduce tumor mass. We report the case of a patient presenting a multiple myeloma, treated with radiation therapy for a spinal cord compression, who developed, eleven months later, an in-field subcutaneous relapse. We called this phenomenon myeloma appearance after local external beam radiotherapy jet (MAALEJ). A review of literature was performed trying to explain this uncommon relapse feature. PMID- 24176665 TI - Intrafraction variations in linac-based image-guided radiosurgery of intracranial lesions. AB - PURPOSE: This study investigated image-guided patient positioning during frameless, mask-based, single-fraction stereotactic radiosurgery of intracranial lesions and intrafractional translational and rotational variations in patient positions. PATIENTS AND METHODS: A non-invasive head and neck thermoplastic mask was used for immobilization. The Exactrac/Novalis Body system (BrainLAB AG, Germany) was used for kV X-ray imaging guided positioning. Intrafraction displacement data, obtained by imaging after each new table position, were evaluated. RESULTS: There were 269 radiosurgery treatments performed on 190 patients and a total of 967 setups within different angles. The first measured error after each table rotation (mean 2.6) was evaluated (698 measurements). Intrafraction translational errors were (1 standard deviation [SD]) on average 0.8, 0.8, and 0.7mm for the left-right, superior-inferior, and anterior-posterior directions, respectively, with a mean 3D-vector of 1.0mm (SD 0.9mm) and a range from -5mm to +5mm. On average, 12%, 3%, and 1% of the translational deviations exceeded 1, 2, and 3mm, respectively, in the three directions. CONCLUSION: The range of intrafraction patient motion in frameless image-guided stereotactic radiosurgery is often not fully mapped by pre- and post-treatment imaging. In the current study, intrafraction motion was assessed by performing measurements at several time points during the course of stereotactic radiosurgery. It was determined that 12% of the intrafraction values in the three dimensions are above 1mm, the usual safety margin applied in stereotactic radiosurgery. PMID- 24176667 TI - Autoregressive models for gene regulatory network inference: sparsity, stability and causality issues. AB - Reconstructing gene regulatory networks from high-throughput measurements represents a key problem in functional genomics. It also represents a canonical learning problem and thus has attracted a lot of attention in both the informatics and the statistical learning literature. Numerous approaches have been proposed, ranging from simple clustering to rather involved dynamic Bayesian network modeling, as well as hybrid ones that combine a number of modeling steps, such as employing ordinary differential equations coupled with genome annotation. These approaches are tailored to the type of data being employed. Available data sources include static steady state data and time course data obtained either for wild type phenotypes or from perturbation experiments. This review focuses on the class of autoregressive models using time course data for inferring gene regulatory networks. The central themes of sparsity, stability and causality are discussed as well as the ability to integrate prior knowledge for successful use of these models for the learning task at hand. PMID- 24176668 TI - Cascaded process model based control: packed absorption column application. AB - Nonlinear, adaptive, process-model based control is demonstrated in a cascaded single-input-single-output mode for pressure drop control in a pilot-scale packed absorption column. The process is shown to be nonlinear. Control is demonstrated in both servo and regulatory modes, for no wind-up in a constrained situation, and for bumpless transfer. Model adaptation is demonstrated and shown to provide process insight. The application procedure is revealed as a design guide to aid others in implementing process-model based control. PMID- 24176669 TI - A repeated syphilis infection imported from Thailand in an HIV positive couple of men-who-have-sex-with-men in Czech Republic. AB - Coinfection by HIV and syphilis has become a growing problem due to the re appearance of unsafe sexual practices in the era of potent anti-retroviral drugs. We describe a repeated import of syphilis by a couple of men-who-have-sex-with men from Thailand to Czech Republic likely due to non-adherence of the patients to physician recommendations. Such cases can become foci for dissemination of once locally rare infections and present a danger for the community. PMID- 24176670 TI - Arsenic exposure alters expression of cell cycle and lipid metabolism genes in the liver of adult zebrafish (Danio rerio). AB - Adult zebrafish (Danio rerio) were used to investigate mRNA expression in the liver following 7-day and 21-day exposures to 0, 10, 50, or 500 ppb sodium arsenite. Arsenic exposure has been linked to several human disorders including cancers and cardiovascular and metabolic diseases. Quantitative PCR was employed to determine the mRNA expression of genes involved in cell cycle regulation [cyclin E1 (ccne1), WEE1 A kinase (wee1)], DNA damage repair [breast cancer 2 (brca2)] and lipid transport and metabolism [carnitine O-octanoyltransferase (crot), fatty acid binding protein-3 (fabp3) and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (hmgcs1)]. Results from the 7-day exposure showed sex- and dose specific changes in expression of wee1, brca2, crot and hmgcs1. No significant differences from controls were observed in fish exposed for 21 days. Expression of all genes, except ccne1, was significantly different between the 7- and 21-day exposures. The results presented here correlate with prior findings from our lab and others, and offer further insight into potential mechanisms of low-dose arsenic exposure. PMID- 24176671 TI - Evora(r) chromium-cobalt dual mobility socket: results at a minimum 10 years' follow-up. AB - INTRODUCTION: The Evora chromium-cobalt alloy dual mobility socket claims to display a large articulation tribology different from that of stainless steel models, limiting the risk of intraprosthetic dislocation and wear. The present study reports a minimum of 10years' follow-up in a multicenter prospective series of 200 sockets previously reported on at 5years. HYPOTHESIS: The use of chromium cobalt in dual mobility sockets provides a low rate of failure at 10years, especially as regards to osteolysis and intraprosthetic dislocation. MATERIALS AND METHODS: Two hundred hydroxyapatite-coated molded chromium-cobalt sockets without titanium interface were implanted without cement in 194 patients with a mean age of 70 years (range, 32-91 years). Clinical results were assessed on Postel Merle d'Aubigne and Harris scores, plain radiographs and survival analysis. RESULTS: At a mean 11 years' follow-up (10-13 years), 56 patients had died and 31 were lost to follow-up. Four underwent surgical revision (3 femoral components, and 1 socket for migration at 9 years with complete disappearance of the hydroxyapatite). A total of 109 implants were analyzable in 107 patients with a mean age of 81 years (55-93 years). At follow-up, the mean Harris score was 90 (75-96) and the PMA score 16.3 (14-18). There were no cases of loosening (except for the case reoperated on at 9 years) and no acetabular radiolucency or cysts. There were 2 cases of non-evolutive femoral radiolucency and 10 of femoral granuloma, involving head size > 22 mm (P<0.0001) and a cemented titanium stem (P=0.004) as risk factors. There were no dislocations in the large or small articulation. Ten-year survival was 99% (95% CI: 97.3%-100%) with socket revision as censorship criterion. DISCUSSION: The absence of dislocation in both small and large articulations confirmed the efficacy of the dual mobility concept and suggested an advantage for chromium-cobalt sockets in reducing the rate of intraprosthetic dislocation and preventing blockage of the large articulation by a better performance in the friction couple. Granulomas were associated with wear in cemented titanium stems and with heads greater than 22 mm in diameter. Ten year survival was 99% (censorship criterion: revision for socket failure); there was, however, one case of socket loosening with disappearance of the hydroxyapatite, indicating that surveillance should be continued in this cohort. PMID- 24176672 TI - Circulating tumor cells in Hodgkin's lymphoma - a review of the spread of HL tumor cells or their putative precursors by lymphatic and hematogenous means, and their prognostic significance. AB - About 15% of patients diagnosed with classical Hodgkin's lymphoma (cHL) are considered high risk with unfavorable prognosis. The biology of the disease bears a direct relationship to its clinical course. However, some aspects of the disease are still being debated. Related topics include origin of neoplastic cells as circulating precursor versus germinal center B cell, and disease metastasis via hematogenous routes and the effect of HL circulation on relapse potential and further spread of the disease. The terminally differentiated giant neoplastic Hodgkin Reed-Sternberg (HRS) cells (HRSC) have limited proliferation and lack mobility. Therefore, they are unable to penetrate epithelium. Thus, the clinical aggressiveness of HRSCs that disseminate via both lymphatic and hematogenous may be determined by their molecular composition. This review discusses in detail the historical perspectives on scientific and clinical evidences of precursors of circulating HL cells and the prognostic importance of these circulating cells for predicting outcome. PMID- 24176674 TI - Periscapular amputation as treatment for brachial plexopathy secondary to recurrent breast carcinoma: a case series and review of the literature. AB - AIMS: Recurrent breast carcinoma with brachial plexus involvement is often misinterpreted as a radiation- or chemotherapy-induced brachial plexopathy. We review a case series of 4 patients at our institution within a 1-year period, and describe their diagnostic workup and treatment with a palliative periscapular amputation. Our aim is to describe this entity, indications and benefits of this procedure, when required for progressive disease, with the goal of raising a collective index of suspicion to aid in earlier diagnosis. METHODS: Four patients with recurrent axillary breast cancer and symptoms consistent with a brachial plexopathy were prospectively collected over a 1-year period. A Pubmed search was conducted; pertinent articles were reviewed and reported. RESULTS: Patients presented with intractable pain and flaccid paralysis of the ipsilateral limb. All had been previously treated with surgical resection, axillary lymph node dissection, chemotherapy, and radiation therapy. Average time from breast surgery to presentation was 78.75 months (range 11-216 months.) Workup included MRI and biopsy to confirm recurrence. Periscapular amputation was performed for each patient, all of who experienced subjective pain relief postoperatively. Three of the 4 patients are still living; one patient died of disease. CONCLUSION: Breast cancer survivors presenting with a brachial plexopathy should raise suspicion for recurrent disease. Close evaluation with MRI is the best first step in diagnosis. Although periscapular amputation is an aggressive surgical treatment, it is an acceptable option when disease has progressed to neurovascular involvement and a functionless limb. PMID- 24176673 TI - Stratified medicine for mental disorders. AB - There is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework programme for research and innovation of the European Commission (2014-2020), and in national funding agencies, clear advice on a potential strategy for mental health research investment is needed. The development of such a strategy is supported by the EC-funded "Roadmap for Mental Health Research" (ROAMER) which will provide recommendations for a European mental health research strategy integrating the areas of biomedicine, psychology, public health well being, research integration and structuring, and stakeholder participation. Leading experts on biomedical research on mental disorders have provided an assessment of the state of the art in core psychopathological domains, including arousal and stress regulation, affect, cognition social processes, comorbidity and pharmacotherapy. They have identified major advances and promising methods and pointed out gaps to be addressed in order to achieve the promise of a stratified medicine for mental disorders. PMID- 24176675 TI - Carbamylation and antibodies against carbamylated proteins in autoimmunity and other pathologies. AB - Carbamylation is a non-enzymatic post-translational modification in which cyanate binds to molecules containing primary amine or thiol groups and forms carbamyl groups. Cyanate is in equilibrium with urea in body fluid and increased carbamylation was first reported in patients with increased urea levels such as patients suffering renal diseases. Next, increased carbamylation related to inflammation has also been described in other conditions such as cardiovascular disease. Recently, a new consequence of carbamylation has been observed: induction of an autoantibody response. We identified anti-carbamylated protein (anti-CarP) antibodies in rheumatoid arthritis (RA) patients and in patients having 'pre-RA' symptoms, arthralgia. The presence of anti-CarP antibodies in arthralgia patients is associated with an increased risk of developing RA. The presence of anti-CarP antibodies in RA patients is associated with more severe joint damage in RA patients who do not have anti-citrullinated protein antibodies. It is currently unknown to what extent carbamylation and/or the formation of anti-CarP antibodies contributes to the disease processes of chronic diseases such as renal diseases, cardiovascular diseases and RA. This review summarizes the current knowledge on carbamylation and the formation of anti-CarP antibodies and discusses their possibly important implications. PMID- 24176676 TI - Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate. AB - The aim of this project was to study the effect of stainless steel solid microneedles and microneedle rollers on percutaneous penetration of verapamil hydrochloride and amlodipine besylate. Verapamil, 2-(3,4-dimethooxyphenyl)-5-[2 (3,4 dimethoxyphenyl)ethyl-methyl-amino]-2-propan-2-yl-pentanenitrile is a calcium channel blocker agent that regulates high blood pressure by decreasing myocardial contractilty, heart rate and impulse conduction. Amlodipine, (R, S)-2 [(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6 methyl-1, 4-dihydropyridine, is a calcium channel blocker that is used for the management of hypertension and ischemic heart disease. Passive penetration of verapamil and amlodipine across the skin is low. In vitro studies were performed with microneedle-treated porcine ear skin using vertical static Franz diffusion cells (PermeGear, Hellertown, PA, USA). The receiver chamber contained 5ml of PBS (pH7.4) and was constantly maintained at 37 degrees C temperature with a water circulation jacket. The diffusion area of the skin was 1.77cm(2). The donor compartment was loaded with 1ml of the solution containing 2.5mg/ml of amlodipine besylate. The donor chamber was covered with parafilm to avoid evaporation. Passive diffusion across untreated porcine skin served as control. Aliquots were taken every 2h for 12h and analyzed by liquid chromatography-mass spectrometry. Transcutaneous flux of verapamil increased significantly from 8.75MUg/cm(2)/h to 49.96MUg/cm(2)/h across microneedle-roller treated porcine skin. Percutaneous flux of amlodipine besylate following the use of stainless steel microneedles was 22.39MUg/cm(2)/h. Passive flux for the drug was 1.57MUg/cm(2)/h. This enhancement of amlodipine flux was statistically significant. Transdermal flux of amlodipine with microneedle roller was 1.05MUg/cm(2)/h in comparison with passive diffusion flux of 0.19MUg/cm(2)/h. The difference in flux values was also statistically significant. Stainless steel solid microneedles and microneedle rollers increased percutaneous penetration of verapamil hydrochloride and amlodipine besylate. It may be feasible to develop transdermal microneedle patches for these drugs. PMID- 24176677 TI - Selection of appropriate tumour data sets for Benchmark Dose Modelling (BMD) and derivation of a Margin of Exposure (MoE) for substances that are genotoxic and carcinogenic: considerations of biological relevance of tumour type, data quality and uncertainty assessment. AB - This article addresses a number of concepts related to the selection and modelling of carcinogenicity data for the calculation of a Margin of Exposure. It follows up on the recommendations put forward by the International Life Sciences Institute - European branch in 2010 on the application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic. The aims are to provide practical guidance on the relevance of animal tumour data for human carcinogenic hazard assessment, appropriate selection of tumour data for Benchmark Dose Modelling, and approaches for dealing with the uncertainty associated with the selection of data for modelling and, consequently, the derived Point of Departure (PoD) used to calculate the MoE. Although the concepts outlined in this article are interrelated, the background expertise needed to address each topic varies. For instance, the expertise needed to make a judgement on biological relevance of a specific tumour type is clearly different to that needed to determine the statistical uncertainty around the data used for modelling a benchmark dose. As such, each topic is dealt with separately to allow those with specialised knowledge to target key areas of guidance and provide a more in-depth discussion on each subject for those new to the concept of the Margin of Exposure approach. PMID- 24176678 TI - Impact of the severity of trauma on early retirement. AB - OBJECTIVE: To assess the association between Injury Severity Score (ISS) and subsequent risk of early retirement. DESIGN: Observational cohort study with follow-up based on prospectively collected data. Hospital-based data were linked to national register data on pension reception and vital status. SETTING: Level one urban trauma centre. PARTICIPANTS: Patients aged 18-64 years entering the trauma centre in Copenhagen during 1999-2007 who were alive after three days were followed until early retirement, death or emigration. MAIN OUTCOME MEASURES: Primary outcome was early retirement, defined as receiving disability pension (unintentional) or voluntary early retirement pension (intentional) before the regular age of retirement (65 years). Relative risk of early retirement according to ISS (low, ISS 1-15 vs. high, ISS 16-75) was assessed using Cox proportional hazards regression, adjusted for age and gender. RESULTS: Of all 6687 patients admitted to the trauma centre, a total of 1722 trauma patients were included and followed for a median of 6.2 years (interquartile range (IQR) 3.7-9.1). Of these, 1305 (75.8%) were males, median age was 35.0 years (IQR 25.4-46.5), and median ISS was 16 (IQR 9-25). Three hundred and twenty-two patients retired during follow-up. Patients with high ISS, compared to patients with low ISS, had an increased risk of early retirement, adjusted hazard ratio 2.60 (95% confidence interval (CI) 2.05-3.30; p<0.001). Relative increase in retirement risk was 1.04 (95% CI 1.03-1.05) per ISS point and 1.03 (95% CI 1.03-1.04) per year older. Gender was not found to be a significant risk factor (p=0.69). Five-year absolute risks of early retirement were 9.9% (95% CI 7.8-12.0%) for the low ISS group and 24.6% (95% CI 21.6-27.5%) for the high ISS group. CONCLUSIONS: The risk of early retirement is 2.6 times higher in severely injured patients (ISS 16-75) than the risk in low to moderately injured patients (ISS 1-15) and they have a high absolute 5-year risk as well. Early, targeted interventions to assist with return to work might be able to reduce this risk. PMID- 24176679 TI - Complications after volar locking plate fixation of distal radius fractures. AB - Volar locking plates are an increasingly popular treatment for distal radius fractures. We reviewed complications observed after volar locking plate fixation in a busy teaching hospital. The purpose of the study was to assess whether complication rates after volar locking plate use in general, routine trauma practice were higher than published literature from expert users. A retrospective review was carried out of patients treated with a volar locking plate between January 2009 and December 2010. The series included 206 procedures in 204 patients (77 males and 127 females) with mean age of 55 years (range 16-94). Surgery was performed by 18 different consultant surgeons and 11 registrars. A total of 22 complications were observed in 20 patients with an overall complication rate of 9.7%. Seven (3.4%) patients developed tendon problems including four (1.9%) tendon ruptures. Four (1.9%) patients required re-operation for metalwork problems; four patients developed complex regional pain syndrome (CRPS). Three fracture reduction problems were noted. A total of 16 further operations were carried out for complications. The overall complication rate was low even when surgery was done by many surgeons, suggesting that this is a safe and reproducible technique. This study provides information which can be used to counsel patients about risks, including those of tendon and metalwork problems. This allows patients to make an informed decision. Surgeons must have specific strategies to avoid these complications and remain vigilant so that these can be identified and managed early. PMID- 24176681 TI - [A randomised clinical trial to evaluate the effectiveness of an educational intervention developed for adult asthmatics in a primary care centre]. AB - OBJECTIVE: To assess the effect of an educational intervention on asthma control and quality of life. DESIGN: A randomised clinical trial of patients with asthma, with an intervention group (IG) and a control (GC). Asthma control and quality of life was measured in both groups at baseline and every three months for one a year. Blinding was only possible in the collection and analysis of data. LOCATION: Two urban Primary Care Health Centres PARTICIPANTS: A total of 163 patients aged 18 to 55 years were included: 84 were assigned to the IG and 79 to the CG. The follow-up was completed by 104 patients (GI: 55 and GC 49). INTERVENTION GI: Three educational sessions in small interactive groups. The first session was at the beginning of spring, the second 15 days later, and the third 6 months later, to recall the knowledge. MAIN MEASUREMENTS: Asthma control level and quality of life using ACT(Asthma Control Test) and the AQLQ (Asthma Quality of life Questionnaire). RESULTS: In the third month, statistically significant differences were detected in the percentage of patients with good control [(P=.0002), 75% in the GI, and 48.5% in the GC, Relative Risk (RR)=1.6 [1.2 to 2.1], Number Needed to Treat (NNT)=3.8 [2.4 to 9.4], and an improvement in levels of quality of life from baseline (P=.005), RR=2.3 [1.3 to 4.1], NNT: 4.3 [2.6 to 12.4]. No differences were detected in the remaining sessions. CONCLUSIONS: These interventions are effective in improving the control and quality of life in short-term, which can guide us in choosing the best time to do it. PMID- 24176682 TI - Glucocorticoid-induced osteoporosis: an update on effects and management. AB - Glucocorticoids remain a cornerstone of guideline-based management of persistent asthma and allergic diseases. Glucocorticoid-induced osteoporosis (GIO) is the most common iatrogenic cause of secondary osteoporosis and an issue of concern for physicians treating patients with inhaled or oral glucocorticoids either continuously or intermittently. Patients with GIO experience fragility fractures at better dual-energy x-ray absorptiometry T-scores than those with postmenopausal or age-related osteoporosis. This might be explained, at least in part, by the effects of glucocorticoids not only on osteoclasts but also on osteoblasts and osteocytes. Effective options to detect and manage GIO exist, and a management algorithm has been published by the American College of Rheumatology to provide treatment guidance for clinicians. This review will summarize GIO epidemiology and pathophysiology and assess the role of inhaled and oral glucocorticoids in asthmatic adults and children, with particular emphasis on the effect of such therapies on bone health. Lastly, we will review the American College of Rheumatology GIO guidelines and discuss diagnostic and therapeutic strategies to mitigate the risk of GIO and fragility fractures. PMID- 24176684 TI - Atopic dermatitis: scratching through the complexity of barrier dysfunction. PMID- 24176685 TI - Reply: To PMID 23154083. PMID- 24176686 TI - Induction of severe systemic lupus erythematosus by TNF blockade and response to an anti-IL-6 strategy: role of IL-17? PMID- 24176687 TI - In vitro leukocyte response of three-spined sticklebacks (Gasterosteus aculeatus) to helminth parasite antigens. AB - Helminth parasites of teleost fish have evolved strategies to evade and manipulate the immune responses of their hosts. Responsiveness of fish host immunity to helminth antigens may therefore vary depending on the degree of host parasite counter-adaptation. Generalist parasites, infective for a number of host species, might be unable to adapt optimally to the immune system of a certain host species, while specialist parasites might display high levels of adaptation to a particular host species. The degree of adaptations may further differ between sympatric and allopatric host-parasite combinations. Here, we test these hypotheses by in vitro exposure of head kidney leukocytes from three-spined sticklebacks (Gasterosteus aculeatus) to antigens from parasites with a broad fish host range (Diplostomum pseudospathaceum, Triaenophorus nodulosus), a specific fish parasite of cyprinids (Ligula intestinalis) and parasites highly specific only to a single fish species as second intermediate host (Schistocephalus pungitii, which does not infect G. aculeatus, and Schistocephalus solidus, infecting G. aculeatus). In vitro responses of stickleback leukocytes to S. solidus antigens from six European populations, with S. solidus prevalence from <1% to 66% were tested in a fully crossed experimental design. Leukocyte cultures were analysed by means of flow cytometry and a chemiluminescence assay to quantify respiratory burst activity. We detected decreasing magnitudes of in vitro responses to antigens from generalist to specialist parasites and among specialists, from parasites that do not infect G. aculeatus to a G. aculeatus-infecting species. Generalist parasites seem to maintain their ability to infect different host species at the costs of relatively higher immunogenicity compared to specialist parasites. In a comparison of sympatric and allopatric combinations of stickleback leukocytes and antigens from S. solidus, magnitudes of in vitro responses were dependent on the prevalence of the parasite in the population of origin, rather than on sympatry. Antigens from Norwegian (prevalence 30-50%) and Spanish (40-66%) S. solidus induced generally higher in vitro responses compared to S. solidus from two German (<1%) populations. Likewise, leukocytes from stickleback populations with a high S. solidus prevalence showed higher in vitro responses to S. solidus antigens compared to populations with low S. solidus prevalence. This suggests a rather low degree of local adaptation in S. solidus populations, which might be due to high gene flow among populations because of their extremely mobile final hosts, fish-eating birds. PMID- 24176690 TI - Biangular fractures of the mandible. AB - INTRODUCTION: Bifocal fractures of the mandible often associate the angle and condyle or symphysis. Little data is available on biangular fractures. The authors had for aim to study their characteristics and to suggest an adapted management. MATERIAL AND METHODS: We retrospectively reviewed the records of patients operated on for a biangular fracture from January 2005 to December 2009. The impact of a third molar was evaluated using Pell and Gregory's and Shiller's classifications. RESULTS: Six hundred and forty patients underwent surgery for a mandibular fracture, seven of whom (1.1%) for biangular fractures. The patients' mean age was 27.6 years. Patients were predominantly men (85.7%). Assaults or brawls were the most frequent etiology (85.7%). The mechanism was direct impact in every case. The inferior alveolar nerve was injured in 57.1% of cases. There was an impacted third molar in 71.4% of cases. Most of the time, a single miniplate was sufficient for each angle. Two cases of postoperative infection were noted. The mean follow-up was 52.2months. The occlusion was restored in every case. Three patients presented with neurological sequels in the V3 area. DISCUSSION: Biangular fractures are rare and present a high risk of infection and neurological sequels. The presence of a mesioangular impacted third molar seems to be a predisposing factor. The risk of neurological sequels requires performing surgery rapidly. PMID- 24176688 TI - Alterations in functional connectivity between the hippocampus and prefrontal cortex as a correlate of depressive symptoms in temporal lobe epilepsy. AB - Depression is a common comorbidity in temporal lobe epilepsy (TLE) that is thought to have a neurobiological basis. This study investigated the functional connectivity (FC) of medial temporal networks in depression symptomatology of TLE and the relative contribution of structural versus FC measures. Volumetric MRI and functional connectivity MRI (fcMRI) were performed on nineteen patients with TLE and 20 controls. The hippocampi and amygdalae were selected as seeds, and five prefrontal and five cingulate regions of interest (ROIs) were selected as targets. Low-frequency blood-oxygen-level-dependent signals were isolated from fcMRI data, and ROIs with synchronous signal fluctuations with the seeds were identified. Depressive symptoms were measured by the Beck Depression Inventory II. The patients with TLE showed greater ipsilateral hippocampal atrophy (HA) and reduced FC between the ipsilateral hippocampus and the ventral posterior cingulate cortex (vPCC). Neither HA nor hippocampal-vPCC FC asymmetry was a robust contributor to depressive symptoms. Rather, hippocampal-anterior prefrontal FC was a stronger contributor to depressive symptoms in left TLE (LTLE). Conversely, right amygdala FC was correlated with depressive symptoms in both patient groups, with a positive and negative correlation in LTLE and right TLE (RTLE), respectively. Frontolimbic network dysfunction is a strong contributor to levels of depressive symptoms in TLE and a better contributor than HA in LTLE. In addition, the right amygdala may play a role in depression symptomatology regardless of the side of the epileptogenic focus. These findings may inform the treatment of depressive symptoms in TLE and inspire future research to help guide surgical planning. PMID- 24176692 TI - [Angiolymphoid hyperplasia with eosinophilia]. AB - INTRODUCTION: Angiolymphoid hyperplasia with eosinophilia (HALE) is a rare, benign proliferative vascular disorder of unknown etiology which typically presents as tumor-like nodules of the skin or subcutaneous tissue. It concerns mostly young female adults. We report a case of HALE located on the ear auricle diagnosed by biopsy. The outcome was total regression. OBSERVATION: An 81-year old male patient presented with a lesion of the whole ear auricle. A diagnosis of HALE was confirmed histologically on biopsy. The evolution was marked by spontaneous and complete regression in 2 months. There was no recurrence after 1 year of follow-up. DISCUSSION: The etiology of this disease remains hypothetical. It poses real diagnostic problems with other types of proliferation, but its main differential diagnosis is Kimura disease. Its treatment has not been codified yet. Spontaneous regression is possible and justifies following the patient from 3 to 6 months, before a possible surgery. PMID- 24176691 TI - [Horseshoe Le Fort I osteotomy]. AB - INTRODUCTION: Performing Le Fort I impaction osteotomy can be compromised or impossible. The intranasal volume of the lower turbinates prevents an important maxillary impaction. In this case, horseshoe osteotomy is an alternative. SURGICAL TECHNIQUE: The first step is to lower the inferior edge of the pyriform aperture and the anterior floor of the nasal fossae with a bur. The palatine alveolar wall is cut through resection of the maxillary sinus anterior and lateral walls. The maxillary dental arch may be impacted without freeing the vomer or cutting through lateral walls of the nasal fossa, after having dissected the palatine fibrous mucosa and disjoined the pterygomaxillary suture. DISCUSSION: This technique has mainly been used in pre-implantation surgery to lower the maxillary crest in edentulate patients, and to increase the crestal height after bone grafting without modifying the position of the hard palate. It is a good alternative to the usual Le Fort I osteotomy for important impactions when the alveolar bone height is sufficient. PMID- 24176693 TI - [Burkitt's leukemia presenting as atypical acute mastoiditis in a 7-month-old child]. AB - A 7-month-old girl presented with left acute mastoiditis and a white blood cell count of 79,000/mm(3). A surgically obtained bacteriological sample showed Streptococcus pneumoniae. Direct blood examination revealed leukemic blast cells. Histological samples showed leukemic infiltration of the left temporal bone. The final diagnosis was Burkitt's leukemia with left temporal bone leukemic infiltration. The patient received chemotherapy according to the LMB 2001 protocol from the Societe francaise d'oncologie pediatrique. Clinical, biological, and imaging follow-up 30 months after the end of treatment showed remission with complete recovery in the left temporal bone. Atypical presentation of acute mastoiditis (AM) should prompt investigation into whether there is a rare underlying pathology, such as a hemopathy, histiocytosis, or solid tumor. The first sign of leukemia may be acute middle ear disease. To our knowledge, no other cases of Burkitt's leukemia with temporal bone leukemic infiltration presenting as AM have been reported in a child under 1 year of age. PMID- 24176694 TI - Examining the interrelationship between DOC, bromide and chlorine dose on DBP formation in drinking water--a case study. AB - During drinking water treatment aqueous chlorine and bromine compete to react with natural organic matter (NOM). Among the products of these reactions are potentially harmful halogenated disinfection by-products, notably four trihalomethanes (THM4) and nine haloacetic acids (HAAs). Previous research has concentrated on the role of bromide in chlorination reactions under conditions of a given NOM type and/or concentration. In this study different concentrations of dissolved organic carbon (DOC) from U.K. lowland water were reacted with varying amounts of bromide and chlorine in order to examine the interrelationship between the three reactants in the formation of THM4, dihaloacetic acids (DHAAs) and trihaloacetic acids (THAAs). Results showed that, in general, molar yields of THM4 increased with DOC, bromide and chlorine concentrations, although yields did fluctuate versus chlorine dose. In contrast both DHAA and THAA yields were mainly independent of changes in bromide and chlorine dose at low DOC (1 mg.L(-1)), but increased with chlorine dose at higher DOC concentrations (4 mg.L(-1)). Bromine substitution factors reached maxima of 0.80, 0.67 and 0.65 for the THM4, DHAAs and THAAs, respectively, at the highest bromide/chlorine ratio studied. These results suggest that THM4 formation kinetics depend on both oxidation and halogenation steps, whereas for DHAAs and THAAs oxidation steps are more important. Furthermore, they indicate that high bromide waters may prove more problematic for water utilities with respect to THM4 formation than for THAAs or DHAAs. While mass concentrations of all three groups increased in response to increased bromide incorporation, only the THMs also showed an increase in molar yield. Overall, the formation behaviour of DHAA and THAA was more similar than that of THM4 and THAA. PMID- 24176695 TI - Environmental behaviour of airborne Amaranthaceae pollen in the southern part of the Iberian Peninsula, and its role in future climate scenarios. AB - The Amaranthaceae family includes a number of species which, through a series of specific adaptations, thrive in salty soils, arid environments and altered human settlements. Their ability to tolerate high temperatures favours summer flowering, giving rise to the widespread involvement of Amaranthaceae pollen grains in summer allergies, both in Mediterranean Europe and in areas with arid climates. This study analysed a 21-year set of historical airborne Amaranthaceae pollen records for an area located in the southern part of the Iberian Peninsula, in order to chart species' environmental reaction to changing climate conditions which occurred in the last decades. Airborne pollen data were collected from January 1991 to December 2011 using a Hirst-type volumetric impact sampler. Results showed that Amaranthaceae pollen remained in the atmosphere for over 6 months along the year, from early spring until early autumn. The annual Pollen Index ranged from barely 200 grains to almost 2000 grains, and was strongly influenced by rainfall during the flowering period, which prompted the development of new individuals and thus an increase in pollen production. A trend was noted towards increasingly early pollen peak dates; peaks were recorded in August-September in years with summer rainfall, but as early as May-June in years when over 50% of annual rainfall was recorded in the months prior to flowering. The gradual decline in the annual Pollen Index over later years is attributable not only to growing urbanisation of the area but also to a change in rainfall distribution pattern. High maximum temperatures in spring were also directly related to the peak date and the Pollen Index. This ability to adapt to changeable and occasionally stressful and restrictive, environmental conditions places Amaranthaceae at a competitive advantage with respect to other species sharing the same ecological niche. An increased presence of Amaranthaceae is likely to have a greater impact on future scenarios for pollen allergy diseases associated with climate change. PMID- 24176696 TI - Effects of river morphology, hydraulic gradients, and sediment deposition on water exchange and oxygen dynamics in salmonid redds. AB - Fine sediment decreasing gravel permeability and oxygen supply to incubating salmonid embryos, is often considered the main contributing factor for the observed decline of salmonid populations. However, oxygen supply to salmonid embryos also depends on hydraulic conditions driving water flow through the redd. A more generalized perspective is needed to better understand the constraints on successful salmonid incubation in the many heavily modified fluvial ecosystems of the Northern Hemisphere. The effects of hydraulic gradients, riverbed and redd morphology as well as fine sediment deposition on dissolved oxygen (DO) and water exchange was studied in 18 artificial redds at three sites along a modified river. Fifty percent of the redds in the two downstream sites were lost during high flow events, while redd loss at the upstream site was substantially lower (8%). This pattern was likely related to increasing flood heights from up- to downstream. Specific water infiltration rates (q) and DO were highly dynamic and driven on multiple temporal and spatial scales. Temporally, the high permeability of the redd gravel and the typical pit-tail structure of the new built redds, leading to high DO, disappeared within a month, when fine sediment had infiltrated and the redd structure was leveled. On the scale of hours to days, DO concentrations and q increased during high flows, but decreased during the falling limb of the water level, most likely related to exfiltration of oxygen depleted groundwater or hyporheic water. DO concentrations also decreased under prolonged base flow conditions, when increased infiltration of silt and clay particles clogged the riverbed and reduced q. Spatially, artificial log steps affected fine sediment infiltration, q and interstitial DO in the redds. The results demonstrate that multiple factors have to be considered for successful river management in salmonid streams, including riverbed structure and local and regional hydrogeological conditions. PMID- 24176697 TI - Linking heavy metal bioavailability (Cd, Cu, Zn and Pb) in Scots pine needles to soil properties in reclaimed mine areas. AB - This work deals with bioaccumulation of Zn, Pb, Cu and Cd in foliage of Scots pine, grown on mine soils. Regression models were used to describe relationships between pine elements bioavailability and biological (dehydrogenase activity) and physico-chemical properties of mine soils developed at different parental rocks. Concentration of trace elements in post-mine ecosystems did not differ from data for Scots pine on natural sites. We conclude that, in this part of Europe in afforested areas affected by hard coal, sand, lignite and sulphur mining, there is no risk of trace element concentrations in mine soils. An exception was in the case of Cd in soils on sand quarry and hard coal spoil heap located in the Upper Silesia region, which was more due to industrial pressure and pollutant deposition than the original Cd concentration in parental rocks. PMID- 24176698 TI - Use of biofilm-dwelling ciliate communities to determine environmental quality status of coastal waters. AB - It has increasingly been recognized that the ecological features of protozoan communities have many advantages as a favorable bioindicator to evaluate environmental stress and anthropogenic impact in many aquatic ecosystems. The ability of biofilm-dwelling ciliate communities for assessing environmental quality status was studied, using glass slides as an artificial substratum, during a 1-year cycle (August 2011-July 2012) in coastal waters of the Yellow Sea, northern China. The samples were collected monthly at a depth of 1m from four sampling stations with a spatial gradient of environmental stress. Environmental variables, e.g., salinity, dissolved oxygen (DO), chemical oxygen demand (COD), nitrate nitrogen (NO3-N), ammonium nitrogen (NH4-N) and soluble reactive phosphates (SRP), were measured synchronously for comparison with biotic parameters. Results showed that: (1) the community structures of the ciliates represented significant differences among the four sampling stations; (2) spatial patterns of the ciliate communities were significantly correlated with environmental variables, especially COD and the nutrients; (3) five dominant species (Hartmannula angustipilosa, Metaurostylopsis sp.1, Discocephalus ehrenbergi, Stephanopogon minuta and Pseudovorticella paracratera) were significantly correlated with nutrients or COD; and (4) the species richness measure was significantly correlated with the nutrient NO3-N. It is suggested that biofilm-dwelling ciliate communities might be used as a potentially robust bioindicator for discriminating environmental quality status in coastal waters. PMID- 24176699 TI - Historical trends of concentrations, source contributions and toxicities for PAHs in dated sediment cores from five lakes in western China. AB - In this work, sixteen U.S. EPA priority PAH compounds in the dated sediment cores were detected from five lakes in western China. In most lakes, the concentrations of the total PAHs (SigmaPAHs) increased from the deep layers to the surface sediments. Two source categories, i.e. vehicular emission and biomass & domestic coal combustion were identified by Unmix, a factor analysis receptor model to explore the source contributions of PAHs in the dated sediments. The source apportionment results showed that biomass & domestic coal combustion contributed larger proportion of PAHs in the five lakes. The toxicities of PAHs in the dated sediments, assessed by BaP equivalent (BaPE) values showed that the BaPE increased gradually from the deep layers to the surface sediments in most lakes. For the first effort, the contribution of each source to BaPE was apportioned by Unmix-BaPE method, and the result indicated that the vehicular emission posed the highest toxic risk. The percentage contribution of vehicular emission for PAHs and BaPE also increased from the deep layers to the surface sediments, while biomass & domestic coal combustion exhibited the opposite tendency. PMID- 24176700 TI - Emissions of two phthalate esters and BDE 209 to indoor air and their impact on urban air quality. AB - Estimated emissions of decabrominated diphenyl ether (BDE 209) and the two phthalate esters diethylhexyl phthalate (DEHP) and diisononyl phthalate (DINP) to indoor air in the Stockholm conurbation, Sweden were used to assess the contribution of chemical outflows from the indoor environment to urban outdoor air pollution for these substances, by applying the recently developed Stockholm MUltimedia URban fate (SMURF) model. Emission rates of DINP from PVC materials were measured and published emission rates of DEHP were adapted to Swedish conditions. These were used as input to the model, as well as recently reported estimates of BDE 209 emissions to indoor air in Stockholm. Model predicted concentrations were compared to empirical monitoring data obtained from the literature and from additional measurements of phthalates in ventilation outlets and urban air performed in the current study. The predicted concentrations of the phthalates DINP and DEHP in indoor air and dust were within a factor of 1.5-10 of the measured concentrations. For BDE 209, predicted indoor concentrations were within the measured ranges, but measured concentrations showed a much larger variability. An adjusted emission scenario to better fit observed concentrations indoors was employed for DEHP and final outcomes resulted in estimated indoor emissions of 250 (50-1250), 2.9 (0.58-15), and 0.068 (0.014-0.34) kg year(-1) for DEHP, DINP and BDE 209. These emissions could not explain the observed concentrations in urban air of the phthalates, suggesting an underestimation of background inflow or existence of additional sources in the outdoor environment. For BDE 209, the assessment indicates that the Stockholm indoor environment contributes about 25% to the air pollution load in inflowing background air, but additional monitoring data in urban air are needed to confirm this conclusion. PMID- 24176701 TI - Fourier transform infrared spectroscopy and partial least square regression for the prediction of substrate maturity indexes. AB - Traditional methods to evaluate the stability and maturity of organic wastes and composting matrices are laborious, time-consuming and generate laboratory chemical wastes. This study focused on the development of partial least square (PLS) regression models for the prediction of the stability and maturity of compost-based substrates based on Fourier transform infrared (FTIR) spectroscopy. The following parameters, selected as conventional maturity indexes, were modeled and used as dataset: dissolved organic carbon (DOC), C/N and NH4(+)/NO3(-) ratios, cation exchange capacity (CEC), degree of polymerization (DP), percentage of humic acid (PHA), humification index (HI) and humification ratio (HR). Models were obtained by using data from a wide range of compost based growing media of diverse origin and composition, including 4 commercially available substrates and 11 substrates prepared in our facilities with varying proportions of different organic wastes. The PLS models presented correlation coefficient of calibration (R(2)cal) close to 0.90 and correlation coefficient (R(2)) of cross validation (R(2)cv) presented acceptable values (>0.6), ranging from 0.67 (HR) to 0.92 (C/N). The good performance of the method was also confirmed by the low correlation obtained from the Y-randomization test. R(2) for test samples (R(2)pred) ranged from 0.66 (C/N) to 0.97 (HI) confirming the good correlation between measured and PLS predicted maturity indexes. FTIR spectroscopy combined with PLS regression represents, after modeling process, a fast and alternative method to assess substrate maturity and stability with reduction of time, lower generation of laboratory chemical wastes residues and lower cost per sample than conventional chemical methods. All models adjusted for maturity indexes are predictive, robust and did not present chance correlation. PMID- 24176702 TI - Sulphate leaching from diffuse agricultural and forest sources in a large central European catchment during 1900-2010. AB - Using dynamic, mass budget, and empirical models, we quantified sulphate-sulphur (SO4-S) leaching from soils in a large central European catchment (upper Vltava river, Czech Republic) over a 110-year period (1900-2010). SO4-S inputs to soils with synthetic fertilisers and atmospheric deposition increased in the 1950s 1980s, then rapidly decreased (~80%), and remained low since the middle 1990s. The proportion of drained agricultural land rapidly increased from 4 to 43% between the 1950s and 1990s; then the draining ability of the system slowly decreased due to its ageing. Sulphate concentrations in the Vltava exhibited similar trends as the external SO4-S inputs, suggesting that they could be explained by changes in atmospheric and fertiliser S inputs. The available data and modelling, however, showed that (i) internal SO4-S sources (mineralization of soil organic S in the drained agricultural land), (ii) a hysteresis in SO4-S leaching from forest soils (a net S retention at the high S inputs and then a net release at the lowered inputs), and (iii) hydrology must be taken into account. An empirical model was then employed, based on parameters representing hydrology (discharge), external SO4-S sources (inputs by synthetic fertilisers and atmospheric deposition), and internal SO4-S sources (mineralization related to soil drainage). The model explained 84% of the observed variability in annual SO4 S concentrations in the Vltava river during 1900-2010 and showed that forest soils were a net sink (105 kg ha(-1)) while agricultural land was a net source (55 kg ha(-1)) of SO4-S during 1960-2010. In the late 1980s, forest soils changed from a sink to a source of S, and the present release of SO4-S accumulated in forest soils thus delays recovery of surface waters from acidification, while S losses from agricultural soils increase the risk of future S deficiency in S demanding crops. PMID- 24176703 TI - Evaluation of wastewater contaminant transport in surface waters using verified Lagrangian sampling. AB - Contaminants released from wastewater treatment plants can persist in surface waters for substantial distances. Much research has gone into evaluating the fate and transport of these contaminants, but this work has often assumed constant flow from wastewater treatment plants. However, effluent discharge commonly varies widely over a 24-hour period, and this variation controls contaminant loading and can profoundly influence interpretations of environmental data. We show that methodologies relying on the normalization of downstream data to conservative elements can give spurious results, and should not be used unless it can be verified that the same parcel of water was sampled. Lagrangian sampling, which in theory samples the same water parcel as it moves downstream (the Lagrangian parcel), links hydrologic and chemical transformation processes so that the in-stream fate of wastewater contaminants can be quantitatively evaluated. However, precise Lagrangian sampling is difficult, and small deviations - such as missing the Lagrangian parcel by less than 1h - can cause large differences in measured concentrations of all dissolved compounds at downstream sites, leading to erroneous conclusions regarding in-stream processes controlling the fate and transport of wastewater contaminants. Therefore, we have developed a method termed "verified Lagrangian" sampling, which can be used to determine if the Lagrangian parcel was actually sampled, and if it was not, a means for correcting the data to reflect the concentrations which would have been obtained had the Lagrangian parcel been sampled. To apply the method, it is necessary to have concentration data for a number of conservative constituents from the upstream, effluent, and downstream sites, along with upstream and effluent concentrations that are constant over the short-term (typically 2-4h). These corrections can subsequently be applied to all data, including non conservative constituents. Finally, we show how data from other studies can be corrected. PMID- 24176704 TI - Soluble salt sources in medieval porous limestone sculptures: a multi-isotope (N, O, S) approach. AB - The sources and mechanisms of soluble salt uptake by porous limestone and the associated degradation patterns were investigated for the life-sized 15th century "entombment of Christ" sculpture group located in Pont-a-Mousson, France, using a multi-isotope approach on sulphates (delta(34)S and delta(18)O) and nitrates (delta(15)N and delta(18)O). The sculpture group, near the border of the Moselle River, is within the potential reach of capillary rise from the alluvial aquifer. Chemical analyses show a vertical zonation of soluble salts with a predominance of sulphates in the lower parts of the statues where crumbling and blistering prevail, and higher concentrations of nitrates and chloride in the high parts affected by powdering and efflorescence. Isotope fingerprints of sulphates suggest a triple origin: (1) the lower parts are dominated by capillary rise of dissolved sulphate from the Moselle water with characteristic Keuper evaporite signatures that progressively decreases with height; (2) in the higher parts affected by powdering the impact of atmospheric sulphur becomes detectable; and (3) locally, plaster reparations impact the neighbouring limestone through dissolution and re-precipitation of gypsum. Nitrogen and oxygen isotopes suggest an organic origin of nitrates in all samples. N isotope signatures are compatible with those measured in the alluvial aquifer of the Moselle River further downstream. This indicates contamination by sewage or organic fertilisers. Significant isotopic contrasts are observed between the different degradation features depending on the height and suggest historical changes of nitrate sources. PMID- 24176705 TI - Assessment of the water supply:demand ratios in a Mediterranean basin under different global change scenarios and mitigation alternatives. AB - Spatial differences in the supply and demand of ecosystem services such as water provisioning often imply that the demand for ecosystem services cannot be fulfilled at the local scale, but it can be fulfilled at larger scales (regional, continental). Differences in the supply:demand (S:D) ratio for a given service result in different values, and these differences might be assessed with monetary or non-monetary metrics. Water scarcity occurs where and when water resources are not enough to meet all the demands, and this affects equally the service of water provisioning and the ecosystem needs. In this study we assess the value of water in a Mediterranean basin under different global change (i.e. both climate and anthropogenic changes) and mitigation scenarios, with a non-monetary metric: the S:D ratio. We computed water balances across the Ebro basin (North-East Spain) with the spatially explicit InVEST model. We highlight the spatial and temporal mismatches existing across a single hydrological basin regarding water provisioning and its consumption, considering or not, the environmental demand (environmental flow). The study shows that water scarcity is commonly a local issue (sub-basin to region), but that all demands are met at the largest considered spatial scale (basin). This was not the case in the worst-case scenario (increasing demands and decreasing supply), as the S:D ratio at the basin scale was near 1, indicating that serious problems of water scarcity might occur in the near future even at the basin scale. The analysis of possible mitigation scenarios reveals that the impact of global change may be counteracted by the decrease of irrigated areas. Furthermore, the comparison between a non monetary (S:D ratio) and a monetary (water price) valuation metrics reveals that the S:D ratio provides similar values and might be therefore used as a spatially explicit metric to valuate the ecosystem service water provisioning. PMID- 24176706 TI - Shifts in the abundance and community structure of soil ammonia oxidizers in a wet sclerophyll forest under long-term prescribed burning. AB - Fire shapes global biome distribution and promotes the terrestrial biogeochemical cycles. Ammonia-oxidizing bacteria (AOB) and archaea (AOA) play a vital role in the biogeochemical cycling of nitrogen (N). However, behaviors of AOB and AOA under long-term prescribed burning remain unclear. This study was to examine how fire affected the abundances and communities of soil AOB and AOA. A long-term repeated forest fire experiment with three burning treatments (never burnt, B0; biennially burnt, B2; and quadrennially burnt, B4) was used in this study. The abundances and community structure of soil AOB and AOA were determined using quantitative PCR, restriction fragment length polymorphism and clone library. More frequent fires (B2) increased the abundance of bacterium amoA gene, but tended to decrease archaeal amoA genes. Fire also modified the composition of AOA and AOB communities. Canonical correspondence analysis showed soil pH and dissolved organic C (DOC) strongly affected AOB genotypes, while nitrate-N and DOC shaped the AOA distribution. The increased abundance of bacterium amoA gene by fires may imply an important role of AOB in nitrification in fire-affected soils. The fire-induced shift in the community composition of AOB and AOA demonstrates that fire can disturb nutrient cycles. PMID- 24176707 TI - Surface emission determination of volatile organic compounds (VOC) from a closed industrial waste landfill using a self-designed static flux chamber. AB - Closed landfills can be a source of VOC and odorous nuisances to their atmospheric surroundings. A self-designed cylindrical air flux chamber was used to measure VOC surface emissions in a closed industrial landfill located in Cerdanyola del Valles, Catalonia, Spain. The two main objectives of the study were the evaluation of the performance of the chamber setup in typical measurement conditions and the determination of the emission rates of 60 different VOC from that industrial landfill, generating a valuable database that can be useful in future studies related to industrial landfill management. Triplicate samples were taken in five selected sampling points. VOC were sampled dynamically using multi-sorbent bed tubes (Carbotrap, Carbopack X, Carboxen 569) connected to SKC AirCheck 2000 pumps. The analysis was performed by automatic thermal desorption coupled with a capillary gas chromatograph/mass spectrometry detector. The emission rates of sixty VOC were calculated for each sampling point in an effort to characterize surface emissions. To calculate average, minimum and maximum emission values for each VOC, the results were analyzed by three different methods: Global, Kriging and Tributary area. Global and Tributary area methodologies presented similar values, with total VOC emissions of 237 +/- 48 and 222 +/- 46 g day(-1), respectively; however, Kriging values were lower, 77 +/ 17 gd ay(-1). The main contributors to the total emission rate were aldehydes (nonanal and decanal), acetic acid, ketones (acetone), aromatic hydrocarbons and alcohols. Most aromatic hydrocarbon (except benzene, naphthalene and methylnaphthalenes) and aldehyde emission rates exhibited strong correlations with the rest of VOC of their family, indicating a possible common source of these compounds. B:T ratio obtained from the emission rates of the studied landfill suggested that the factors that regulate aromatic hydrocarbon distributions in the landfill emissions are different from the ones from urban areas. Environmental conditions (atmospheric pressure, temperature and relative humidity) did not alter the pollutant emission fluxes. PMID- 24176708 TI - Daily variations of Zn and Pb concentrations in the Deule River in relation to the resuspension of heavily polluted sediments. AB - Sediments in the Deule River (northern France) are severely polluted by metals in the vicinity of several metallurgical plants. The aim of this paper is to identify the role played by the recurrent resuspension of these polluted sediments by boat traffic on the dissolved Pb and Zn concentrations in the river. For that purpose, several high-frequency on-line monitoring campaigns were performed. Our results clearly suggest that the resuspension of sedimentary particles into the overlying water significantly increased the dissolved electrolabile Pb and Zn contents. This increase does not persist for a long time because at night and during weekends and holidays, when the boat traffic strongly slows down, Pb and Zn concentrations drop again quickly. Our data also indicate that the biological processes (such as photosynthetic and respiration activities), diffusive and benthic fluxes, as well as dilution of pore water into the overlying water during sediment remobilization do not contribute significantly to the sharp increase of dissolved Pb and Zn concentrations in the river during the day. The good correlation between turbidity and electrolabile metal concentration allows us to discard slow AVS (Acid Volatile Sulfides) oxidation as well. Desorption of metals from sediment particles was clearly the most relevant process, responsible for the increase of dissolved Pb and Zn concentrations in the water column. PMID- 24176709 TI - Mass balance and decontamination times of Polycyclic Aromatic Hydrocarbons in rural nested catchments of an early industrialized region (Seine River basin, France). AB - Accumulation of Polycyclic Aromatic Hydrocarbons (PAHs) in soils and their subsequent release in rivers constitute a major environmental and public health problem in industrialized countries. In the Seine River basin (France), some PAHs exceed the target concentrations, and the objectives of good chemical status required by the European Water Framework Directive might not be achieved. This investigation was conducted in an upstream subcatchment where atmospheric fallout (n=42), soil (n=33), river water (n=26) and sediment (n=101) samples were collected during one entire hydrological year. PAH concentrations in atmospheric fallout appeared to vary seasonally and to depend on the distance to urban areas. They varied between 60 ng.L(-1) (in a remote site during autumn) and 2,380 ng.L( 1) (in a built-up area during winter). PAH stocks in soils of the catchment were estimated based on land use, as mean PAH concentrations varied between 110 ng.g( 1) under woodland and 2,120 ng.g(-1) in built-up areas. They ranged from 12 to 220 kg.km(-2). PAH contamination in the aqueous phase of rivers remained homogeneous across the catchment (72 +/- 38 ng.L(-1)). In contrast, contamination of suspended solid was heterogeneous depending on hydrological conditions and population density in the drainage area. Moreover, PAH concentrations appeared to be higher in sediment (230-9,210 ng.g(-1)) than in the nearby soils. Annual mass balance calculation conducted at the catchment scale showed that current PAH losses were mainly due to dissipation (biodegradation, photo-oxidation and volatilization) within the catchments (about 80%) whereas exports due to soil erosion and riverine transport appeared to be of minor importance. Based on the calculated fluxes, PAHs appeared to have long decontamination times in soils (40 to 1,850 years) thereby compromising the achievement of legislative targets. Overall, the study highlighted the major role of legacy contamination that supplied the bulk of PAHs that are still found nowadays in the environment. PMID- 24176710 TI - Occurrence, fate and ecotoxicological assessment of pharmaceutically active compounds in wastewater and sludge from wastewater treatment plants in Chongqing, the Three Gorges Reservoir Area. AB - The occurrence, removal and ecotoxicological assessment of 21 pharmaceutically active compounds (PhACs) including antibiotics, analgesics, antiepileptics, antilipidemics and antihypersensitives, were studied at four municipal wastewater treatment plants (WWTP) in Chongqing, the Three Gorges Reservoir Area. Individual treatment unit effluents, as well as primary and secondary sludge, were sampled and analyzed for the selected PhACs to evaluate their biodegradation, persistence and partitioning behaviors. PhACs were identified and quantified using high performance liquid chromatography/tandem mass spectrometry after solid-phase extraction. All the 21 analyzed PhACs were detected in wastewater and the target PhACs except acetaminophen, ibuprofen and gemfibrozil, were also found in sludge. The concentrations of the antibiotics and SVT were comparable to or even higher than those reported in developed countries, while the case of other target PhACs was opposite. The elimination of PhACs except acetaminophen was incomplete and a wide range of elimination efficiencies during the treatment were observed, i.e. from "negative removal" to 99.5%. The removal of PhACs was insignificant in primary and disinfection processes, and was mainly achieved during the biological treatment. Based on the mass balance analysis, biodegradation is believed to be the primary removal mechanism, whereas only about 1.5% of the total mass load of the target PhACs was removed by sorption. Experimentally estimated distribution coefficients (<500 L/kg, with a few exceptions) also indicate that biodegradation/transformation was responsible for the removal of the target PhACs. Ecotoxicological assessment indicated that the environment concentrations of single compounds (including sulfadiazine, sulfamethoxazole, ofloxacin, azithromycin and erythromycin-H2O) in effluent and sludge, as well as the mixture of the 21 detected PhACs in effluent, sludge and receiving water had a significant ecotoxicological risk to algae. Therefore, further control of PhACs in effluent and sludge is required before their discharge and application to prevent their introduction into the environment. PMID- 24176711 TI - Clustering cities with similar fine particulate matter exposure characteristics based on residential infiltration and in-vehicle commuting factors. AB - Epidemiological studies have observed between city heterogeneity in PM2.5 mortality risk estimates. These differences could potentially be due to the use of central-site monitors as a surrogate for exposure which do not account for an individual's activities or ambient pollutant infiltration to the indoor environment. Therefore, relying solely on central-site monitoring data introduces exposure error in the epidemiological analysis. The amount of exposure error produced by using the central-site monitoring data may differ by city. The objective of this analysis was to cluster cities with similar exposure distributions based on residential infiltration and in-vehicle commuting characteristics. Factors related to residential infiltration and commuting were developed from the American Housing Survey (AHS) from 2001 to 2005 for 94 Core Based Statistical Areas (CBSAs). We conducted two separate cluster analyses using a k-means clustering algorithm to cluster CBSAs based on these factors. The first only included residential infiltration factors (i.e. percent of homes with central air conditioning (AC) mean year home was built, and mean home size) while the second incorporated both infiltration and commuting (i.e. mean in-vehicle commuting time and mean in-vehicle commuting distance) factors. Clustering on residential infiltration factors resulted in 5 clusters, with two having distinct exposure distributions. Cluster 1 consisted of cities with older, smaller homes with less central AC while homes in Cluster 2 cities were newer, larger, and more likely to have central AC. Including commuting factors resulted in 10 clusters. Clusters with shorter in-vehicle commuting times had shorter in-vehicle commuting distances. Cities with newer homes also tended to have longer commuting times and distances. This is the first study to employ cluster analysis to group cities based on exposure factors. Identifying cities with similar exposure distributions may help explain city-to-city heterogeneity in PM2.5 mortality risk estimates. PMID- 24176712 TI - Desorption kinetics of PAHs from aged industrial soils for availability assessment. AB - Persistent organic pollutants (POPs), such as polycyclic aromatic hydrocarbons (PAHs), may be found in high concentrations in soils of former industrial sites including manufactured gas plants or coking plants. Techniques using moderate solvent extraction, biological tests or solid phase extraction have proved useful for pollution availability estimation. However, more accurate and reliable measurement tools specifically adapted to low concentrations are still needed. Based on a solid-liquid extraction using a Tenax(r) resin, we suggest a protocol to assess the bioavailability of PAHs, dedicated to aged industrial wasteland soils. Desorption kinetics were measured on three representative contaminated industrial soils. Results were modeled using a first order two-compartment model that provided an estimate of the rapidly desorbing fraction, which was considered to be available, over a 30 h extraction period. In conclusion, this method, allowing the measurement of the available fraction, might prove more relevant than the total concentration value when assessing soil contamination related risks. It may also predict achievable bioremediation performances. PMID- 24176713 TI - Snow in the city as a spore bank of potentially pathogenic fungi. AB - This study evaluates the role of snow as a specific ecological niche and a vector in fungal spreading with particular emphasis on potential pathogens in seasonally and daily changing conditions. The experimental material was fungi isolated from the atmospheric air, snow cover, and fragments of ice and soil from underneath the snow cover. The total count of microfungi in the air before snowfall, i.e. in the autumn, reached 1756.1 CFU/m(3) on average. After the first snowfalls, it dropped to 85.2 CFU/m(3). The analyzed samples of snow cover contained from 101.6 to 8500.0 CFU/m(3) of fungi. Furthermore, 26 species of yeast and yeast-like fungi were isolated from the experimental material. Amongst the analyzed species, 13 were potential anthropopathogens. Though another three species were isolated from organ ontocenoses, i.e. Candida intermedia, Saccharomyces bayanus and Zygosaccharomyces rouxii, their pathogenic potential has not yet been explicitly confirmed. The results of the presented study may be applied in predicting concentrations of fungal spores responsible for mycoses. The first snowfalls significantly reduced the number of colony-forming units of fungi in the air. Under conditions of temperate climate, snow becomes a temporary bank of yeast like fungi spores and while it melts cells of deposited microfungi migrate to the atmosphere. Hence, individuals with impaired immunity or in the course of immunosuppression or recovery should avoid long walks during periods of snow melting. The count of fungi in urban bioaerosol during the melt may be reduced through systematic removal of snow cover, which is a significant reservoir of potential pathogens. In addition, it should be noted that even a typical psychrophilic strain, capable of surviving at a temperature of 37 degrees C, may bear a significant pathogenic potential. PMID- 24176714 TI - A web-based tool to engage stakeholders in informing research planning for future decisions on emerging materials. AB - Prioritizing and assessing risks associated with chemicals, industrial materials, or emerging technologies is a complex problem that benefits from the involvement of multiple stakeholder groups. For example, in the case of engineered nanomaterials (ENMs), scientific uncertainties exist that hamper environmental, health, and safety (EHS) assessments. Therefore, alternative approaches to standard EHS assessment methods have gained increased attention. The objective of this paper is to describe the application of a web-based, interactive decision support tool developed by the U.S. Environmental Protection Agency (U.S. EPA) in a pilot study on ENMs. The piloted tool implements U.S. EPA's comprehensive environmental assessment (CEA) approach to prioritize research gaps. When pursued, such research priorities can result in data that subsequently improve the scientific robustness of risk assessments and inform future risk management decisions. Pilot results suggest that the tool was useful in facilitating multi stakeholder prioritization of research gaps. Results also provide potential improvements for subsequent applications. The outcomes of future CEAWeb applications with larger stakeholder groups may inform the development of funding opportunities for emerging materials across the scientific community (e.g., National Science Foundation Science to Achieve Results [STAR] grants, National Institutes of Health Requests for Proposals). PMID- 24176715 TI - The potential of using the Ecosystem Approach in the implementation of the EU Water Framework Directive. AB - The Ecosystem Approach provides a framework for looking at whole ecosystems in decision making to ensure that society can maintain a healthy and resilient natural environment now and for future generations. Although not explicitly mentioned in the Water Framework Directive, the Ecosystem Approach appears to be a promising concept to help its implementation, on the basis that there is a connection between the aims and objectives of the Directive (including good ecological status) and the provision of ecosystem services. In this paper, methodological linkages between the Ecosystem Approach and the Water Framework Directive have been reviewed and a framework is proposed that links its implementation to the Ecosystem Approach taking into consideration all ecosystem services and water management objectives. Individual River Basin Management Plan objectives are qualitatively assessed as to how strong their link is with individual ecosystem services. The benefits of using this approach to provide a preliminary assessment of how it could support future implementation of the Directive have been identified and discussed. Findings also demonstrate its potential to encourage more systematic and systemic thinking as it can provide a consistent framework for identifying shared aims and evaluating alternative water management scenarios and options in decision making. Allowing for a broad consideration of the benefits, costs and tradeoffs that occur in each case, this approach can further improve the economic case for certain measures, and can also help restore the shift in focus from strict legislative compliance towards a more holistic implementation that can deliver the wider aims and intentions of the Directive. PMID- 24176716 TI - Neutralization of cobra venom by cocktail antiserum against venom proteins of cobra (Naja naja naja). AB - Naja naja venom was characterized by its immunochemical properties and electrophoretic pattern which revealed eight protein bands (14 kDa, 24 kDa, 29 kDa, 45 kDa, 48 kDa, 65 kDa, 72 kDa and 99 kDa) by SDS-PAGE in reducing condition after staining with Coomassie Brilliant Blue. The results showed that Naja venom presented high lethal activity. Whole venom antiserum or individual venom protein antiserum (14 kDa, 29 kDa, 65 kDa, 72 kDa and 99 kDa) of venom could recognize N. naja venom by Western blotting and ELISA, and N. naja venom presented antibody titer when assayed by ELISA. The neutralization tests showed that the polyvalent antiserum neutralized lethal activities by both in vivo and in vitro studies using mice and Vero cells. The antiserum could neutralize the lethal activities in in-vivo and antivenom administered after injection of cobra venom through intraperitoneal route in mice. The cocktail antiserum also could neutralize the cytotoxic activities in Vero cell line by MTT and Neutral red assays. The results of the present study suggest that cocktail antiserum neutralizes the lethal activities in both in vitro and in vivo models using the antiserum against cobra venom and its individual venom proteins serum produced in rabbits. PMID- 24176717 TI - Registered nurses' perceptions of their professional work in nursing homes and home-based care: a focus group study. AB - BACKGROUND: In Sweden, as well as in most industrialised countries, an increasing older population is expected to create a growing demand for health care staff. Previous studies have pointed to lack of proficient medical and nursing staff specialised in geriatric care, which poses serious threats to the care of a vulnerable population. At the same time, there are studies describing elderly care as a low-status career choice, attracting neither nurses nor student nurses. Judging from previous research it was deemed important to explore how nurses in elderly care perceive their work, thus possibly provide vital knowledge that can guide nurse educators and unit managers as a means to promote a career in elderly care. OBJECTIVE: The aim of the present study was to illuminate how nurses, working in nursing homes and home-based care, perceived their professional work. METHOD: This was a qualitative study using focus groups. 30 registered nurses in seven focus groups were interviewed. The participants worked in nursing homes and home-based care for the elderly in rural areas and in a larger city in southern Sweden. The interviews were analysed in line with the tradition of naturalistic inquiry. RESULTS: Our findings illustrate how nurses working in elderly care perceived their professional work as holistic and respectful nursing. Three categories of professional work emerged during analysis: (1) establishing long term relationships, (2) nursing beyond technical skills, and (3) balancing independence and a sense of loneliness. CONCLUSIONS: The findings are important as they represent positive alternatives to the somewhat prevailing view on elderly care as depressing and undemanding. Nurse educators might use the key aspects as good examples, thus influencing student nurses' attitudes towards elderly care in a positive way. Elderly care agencies might find them helpful when recruiting and retaining nurses to a much needed area. PMID- 24176718 TI - Attitudes of nurses towards the use of physical restraints in geriatric care: a systematic review of qualitative and quantitative studies. AB - OBJECTIVES: To examine nurses' attitudes towards the use of physical restraints in geriatric care. DESIGN: Systematic review and synthesis of qualitative and quantitative studies. DATA SOURCES: The following databases were searched: Medline, CINAHL, EMBASE, Psyndex, PsychInfo, Social SciSearch, SciSearch, Forum Qualitative Social Research (1/1990 to 8/2013). We performed backward and forward citation tracking to all of the included studies. REVIEW METHODS: We included in the present review all qualitative and quantitative studies in English and German that investigated nurses' attitudes towards the use of physical restraints in geriatric care. Two independent reviewers selected the studies for inclusion and assessed the study quality. We performed a thematic synthesis for the qualitative studies and a content analysis of the questionnaires' items as well as a narrative synthesis for the quantitative surveys. RESULTS: We included 31 publications in the review: 20 quantitative surveys, 10 qualitative and 1 mixed method study. In the qualitative studies, nurses' attitudes towards the use of physical restraints in geriatric care were predominately characterised by negative feelings towards the use of restraints; however, the nurses also described a perceived need for using restraints in clinical practice. This discrepancy led to moral conflicts, and nurses described several strategies for coping with these conflicts when restraints were used. When nurses were in doubt regarding the use of restraints, they decided predominantly in favour of using restraints. The results of the quantitative surveys were inconsistent regarding nurses' feelings towards the use of restraints in geriatric care. Prevention of falls was identified as a primary reason for using restraints. However, the items of the questionnaires focussed primarily on the reasons for the use of restraints rather than on the attitudes of nurses. CONCLUSIONS: Despite the lack of evidence regarding the benefits of restraints and the evidence on the adverse effects, nurses often decided in favour of using restraints when in doubt and they used strategies to cope with negative feelings when they used restraints. A clear policy change in geriatric care institutions towards restraint-free care seems to be warranted to change clinical practice. The results of this review should also be considered in the development of interventions aimed at reducing the use of restraints. PMID- 24176719 TI - EXTL2 controls liver regeneration and aortic calcification through xylose kinase dependent regulation of glycosaminoglycan biosynthesis. AB - The gene products of two members of the EXT gene family, EXT1 and EXT2, function together as a polymerase in the biosynthesis of heparan sulfate. EXTL2, one of the three EXT-like genes in the human genome that are homologous to EXT1 and EXT2, encodes an N-acetylhexosaminyltransferase. However, both the role of EXTL2 in glycosaminoglycan (GAG) biosynthesis and the biological significance of EXTL2 remain unclear. Interestingly, EXTL2 can transfer a GlcNAc residue to the tetrasaccharide linkage region when this region is phosphorylated by a xylose kinase 1 (FAM20B) and thereby terminate chain elongation. Production of GAGs was significantly higher in EXTL2-knockout mice than in wild-type mice. EXTL2 knockout mice are viable and apparently healthy during development and after birth. Therefore, EXTL2-knockout mice were analyzed following the experimental induction of two separate pathological conditions. Carbon tetrachloride (CCl4) was used to induce liver failure, and 5/6th nephrectomy in combination with a high-phosphate diet was used to induce chronic kidney disease (CKD). Under conditions of CCl4-induced liver failure, hepatocyte proliferation following CCl4 treatment was lower in EXTL2-knockout mice than in wild-type mice; consequently, liver regeneration was impaired in EXTL2-knockout mice. This reduction in hepatocyte proliferation resulted partially because EXTL2-knockout mice experienced less hepatocyte-growth-factor-mediated signaling than did wild-type mice. Under conditions of induced CKD, matrix mineralization in vascular smooth muscle cells (VSMCs) in aortic rings of EXTL2-knockout mice was enhanced relative to that in wild-type mice. Altered biosynthesis of GAGs in EXTL2-knockout mice affected bone-morphogenetic-protein signaling, and consequently enhanced the differentiation of VSMCs into osteoblasts. Taken together, these results indicated that the EXTL2-dependent mechanism that regulates GAG biosynthesis is important for the maintenance of tissue homeostasis under pathological conditions, that is, lack of EXTL2 causes GAG overproduction and structural changes of GAGs associated with pathological processes. PMID- 24176720 TI - [Minimally invasive procedure doesn't mean no complications...]. PMID- 24176721 TI - [Endotracheal intubation with the GlideScope(r), the Airtraq(r), the McGrath(r) videolaryngoscope and direct laryngoscopy: a comparative study on an infant manikin]. AB - OBJECTIVE: The primary purpose of this experimental study was to compare intubation times for direct laryngoscopy with a Miller blade and for 3 VL: GlideScope(r) videolaryngoscope, Airtraq(r), and McGrath(r). METHODS: Seventy seven operators, with various experience of pediatric tracheal intubation (from none to expert), performed 10 attempts of orotracheal intubation with each device on an infant manikin. The main outcome was intubation time and secondary outcome was failure rate. RESULTS: There was a significant decrease in intubation time from the first to the 10th intubation attempt with all devices (P<0.05). This decrease was no more significant following the third attempt with VL and following the fifth attempt with DL. At the time of the 10th attempt, intubation time was significantly shorter with Airtraq(r) as compared with all the other devices (P<0.05), but the differences were tight. Failure was significantly more frequent with DL. CONCLUSION: In this infant manikin model, the learning curve of the different VL was 3 attempts and the Airtraq(r) VL appears the airway device enabling the quickest orotracheal intubation. These experimental results need to be confirmed by clinical studies in infants and children. PMID- 24176723 TI - The impact of an intervention package promoting effective neonatal resuscitation training in rural China. AB - OBJECTIVE: To evaluate an intervention package promoting effective neonatal resuscitation training at county level hospitals across China. METHODS: The intervention package was implemented across 4 counties and included expert seminars, training workshops, establishment of hospital-based resuscitation teams, and supervision of training by national and provincial instructors. Upon completing the activities, a survey was conducted in all county hospitals in the 4 intervention counties and 4 randomly selected control counties. Data on healthcare providers' knowledge and self-confidence, and incidence of deaths from birth asphyxia from 2009 to 2011 in all hospitals were collected and compared between the two groups. RESULTS: Eleven intervention and eleven control hospitals participated in the evaluation, with 97 and 87 health providers, respectively, completing the questionnaire survey. Over 90% of intervention hospitals had implemented neonatal resuscitation related practice protocols, while in control hospitals the proportion was less than 55%. The average knowledge scores of health providers in the intervention and control counties taking a written exam were 9.2+/-1.2 and 8.4+/-1.5, respectively (P<0.001) out of maximum possible score of 10, and the average self-confidence scores were 57.3+/-2.5 and 54.1+/ 8.2, respectively (P<0.001). Incidence of birth asphyxia (defined as 1-min Apgar score<=7) decreased from 8.8% to 6.0% (P<0.001) in the intervention counties, and asphyxia-related deaths in the delivery room decreased from 27.6 to 5.0 per 100,000 (P=0.076). There was no difference over time in asphyxia rates for the control counties. CONCLUSIONS: The intervention has not only improved skills of health providers, decreased the mortality and morbidity of birth asphyxia, but also resulted in effective implementation of guidelines and protocols within hospitals. PMID- 24176722 TI - [Impact of sugammadex on neuromuscular blocking agents use: a multicentric, pharmaco-epidemiologic study in French university hospitals and military hospitals]. AB - INTRODUCTION: Seven Neuromuscular Blocking Agents (NMBA) are commercialized in France. Four of them have an intermediate duration of action. Sugammadex required the use of NMBA slightly employed in clinical practice in France. Its introduction in routine practice could have an impact on NMBA use in clinical practice. This study was then conducted to assess and compare NMBA use before and after the commercialization of sugammadex. MATERIALS AND METHODS: A longitudinal, retrospective, observational study was conducted between 2008 and 2011 in French university hospitals and military hospitals. The consumption data for sugammadex and NMBA were collected using a collection grid which was filled by pharmacists or anesthesiologists. Drug use was measured by the number of vials used divided by the annual number of hospitalizations in surgery and obstetrics (HSO). An overall analysis of the annual frequency of NMBA use was firstly performed, then individual data of each hospital were analyzed. Descriptive statistical analysis including mean, standard deviation, median, minimum and maximum was achieved. RESULTS: Thirty-four out of 39 hospitals participated in the study (87%) and analysis was performed on 26 of them (7%). The data of eight institutions were excluded due to missing values or because of the non-admission of sugammadex in their formulary. The NMBA mostly used were non-steroidal NMBA (75% of market share) with an increased use between 2008 and 2011 concerning atracurium (from 41 to 51 vials of 50mg atracurium used per 100 HSO). The overall analysis revealed an increase of the occurrence of rocuronium (between 2008 and 2011: from 1 to 4.8 vials of 50mg rocuronium used per 100 HSO). Individual analyses on each hospital showed a possible effect of sugammadex introduction on NMBA use in nine hospitals. DISCUSSION AND CONCLUSIONS: The commercialization of sugammadex seems to have induced a discrete increase of steroidal NMBA but non-steroidal NMBA remain the leading agent in France. A long-term follow-up is deserved. PMID- 24176724 TI - Are we ready to put the SQUEEZE into all IO placements? PMID- 24176726 TI - Laparoscopic transgastric partial gastrectomy for a posterior fundic gastrointestinal stromal tumor. PMID- 24176725 TI - Biological magnetic cellular spheroids as building blocks for tissue engineering. AB - Magnetic nanoparticles (MNPs), primarily iron oxide nanoparticles, have been incorporated into cellular spheroids to allow for magnetic manipulation into desired shapes, patterns and 3-D tissue constructs using magnetic forces. However, the direct and long-term interaction of iron oxide nanoparticles with cells and biological systems can induce adverse effects on cell viability, phenotype and function, and remain a critical concern. Here we report the preparation of biological magnetic cellular spheroids containing magnetoferritin, a biological MNP, capable of serving as a biological alternative to iron oxide magnetic cellular spheroids as tissue engineered building blocks. Magnetoferritin NPs were incorporated into 3-D cellular spheroids with no adverse effects on cell viability up to 1 week. Additionally, cellular spheroids containing magnetoferritin NPs were magnetically patterned and fused into a tissue ring to demonstrate its potential for tissue engineering applications. These results present a biological approach that can serve as an alternative to the commonly used iron oxide magnetic cellular spheroids, which often require complex surface modifications of iron oxide NPs to reduce the adverse effects on cells. PMID- 24176727 TI - Temporal dynamics of error correction in a double step task in patients with a lesion to the lateral intra-parietal cortex. AB - Five patients with lesions involving intra-parietal cortex (IPCx) were tested in a rapid version of the double step paradigm to investigate the role of the IPCx in the rapid, online, updating of a saccade program. Saccades were executed to a single target in either the contra- or the ipsilesional visual field. In two thirds of the trials, a step change in target position required that the saccade shifted to a new location within the same field but in the contra- or the ipsilesional direction, allowing us to investigate whether patients are able to update their saccade program given new exogenous information about the required endpoint of the saccade. This set-up resulted in three types of initial saccades: saccades to the target on no-step trials, uncorrected saccades to the original target location on step trials and corrected saccades to the new target location on step trials. Furthermore, if the updating of the original eye movement program failed, patients performed a second saccade to the new target location that required a rapid error correction. The analysis of the double-step task on a group level indicated that latencies for all trial types were longer when saccades were directed to the contralesional versus the ipsilesional field. Furthermore, longer latencies were required for patients to initiate a corrective second saccade after making an uncorrected first saccade in their contralesional compared to ipsilesional field. There were no differences in the ultimate landing positions of the eye movements for such corrected saccades. These results reveal that deficits in updating of saccade programs only seem to be present if the updating must occur after the gaze has shifted to a new location, pointing to a role of intra-parietal cortex in the processes involved in updating information when the current reference frame has to be updated. In conclusion, the paradigm deployed in the current study allows for a refinement of the role of the intra parietal cortex in the updating of saccade programs. PMID- 24176728 TI - Prospective duration judgments: the role of temporality and executive demands of concurrent tasks. AB - It is known that concurrent non-temporal tasks shorten reproduced temporal durations in prospective duration judgments. Two experiments were carried out, one comparing a concurrent temporal task to a minimally demanding concurrent task (Experiment 1) and one comparing an executive concurrent (Simon) task with a less demanding non-executive concurrent task (Experiment 2). An effect of the concurrent task type on temporal reproductions was found. Furthermore, a duration length effect was found, where longer durations were underestimated more than shorter durations. This effect tended to be stronger for the experiments that included a concurrent task that demanded high attention. PMID- 24176730 TI - A case of bilateral trochleitis in adult-onset Still's disease. AB - OBJECTIVES: We describe the first case of adult-onset Still's disease (AOSD) presenting with trochleitis and successfully treated with an interleukin-1 receptor antagonist. METHODS: This is a descriptive case report of one patient, identified in consultation with the inpatient ophthalmology consult service. RESULTS: A 23-year-old Caucasian male initially presented with complaints of sore throat, myalgias, rash, and fever. After he failed to respond to antibiotic therapy for presumed streptococcal pharyngitis and developed left eye pain with upgaze, he was admitted to the hospital. Laboratory workup revealed elevated inflammatory markers and liver enzymes. He was eventually diagnosed with AOSD. During his hospitalization he developed binocular vertical diplopia, worsening of left eye pain on upgaze, and exquisite tenderness over the region of the left trochlea, consistent with trochleitis. This diagnosis was supported by magnetic resonance imaging (MRI). Soon after onset of left eye symptoms, the right eye developed identical symptoms. He was started on intravenous corticosteroids, which led to the rapid resolution of his ocular and systemic symptoms. However, after transition to oral corticosteroids, his symptoms recurred. He was started on anakinra, an interleukin-1 (IL-1) receptor antagonist, which led to resolution of his ocular and systemic symptoms. CONCLUSIONS: Trochleitis is an unusual form of orbital inflammation localized to the superior oblique tendon and trochlea complex. It has been associated with a number of systemic inflammatory conditions including systemic lupus erythematous, rheumatoid arthritis, and juvenile idiopathic arthritis. This is the first case of a patient with AOSD presenting with trochleitis. Treatment with IV corticosteroids and anakinra resulted in rapid resolution of his ocular and systemic symptoms. PMID- 24176729 TI - Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis-results from the International Scleroderma Renal Crisis Survey. AB - OBJECTIVE: To determine whether exposure to angiotensin-converting enzyme (ACE) inhibitors prior to the onset of scleroderma renal crisis (SRC) leads to worse outcomes of SRC. METHODS: Prospective cohort study of incident SRC subjects. The exposure of interest was ACE inhibitors prior to the onset of SRC. The outcomes of interest were death or dialysis during the first year after the onset of SRC. RESULTS: A total of 87 subjects with incident SRC were identified and 1-year follow-up data were obtained in 75 (86%) subjects. Overall, 27 (36%) subjects died within the first year and an additional 19 (25%) remained on dialysis 1 year after the onset of SRC. In adjusted analyses, exposure to ACE inhibitors prior to the onset of SRC was associated with an increased risk of death (hazard ratio 2.42, 95% CI 1.02, 5.75, p < 0.05 in the primary analysis and 2.17, 95% CI 0.88, 5.33, p = 0.09 after post-hoc adjustment for pre-existing hypertension). CONCLUSION: Overall, the 1-year outcomes of SRC were poor. Prior exposure to ACE inhibitors was associated with an increased risk of death after the onset of SRC, although there was uncertainty around the magnitude of the risk and the possibility of residual confounding could not be ruled out. Further studies will be needed to confirm these findings. PMID- 24176731 TI - Vertebral fracture assessment-detected abdominal aortic calcification and cardiovascular disease in rheumatoid arthritis. AB - OBJECTIVE: Individuals with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Traditional prediction tools underestimate this risk. Vertebral fracture assessment (VFA)-detected aortic calcification enhances CVD risk stratification in the general population but its relationship in RA is unclear. We assessed the presence of abdominal aortic calcification (AAC) on VFA images, and its association with CVD in RA patients. METHODS: We determined the prevalence of cardiovascular events in a cohort of RA patients aged 40 years and older fulfilling the 1987 American College of Rheumatology classification criteria. Two blinded radiologists independently reviewed all VFA scans to determine the presence/severity of AAC using an established 24-point scale. Logistic regression analyses were performed to determine whether AAC could discriminate between RA patients with and without CVD, and to compare the ability of VFA-detected AAC to predict CVD to conventional CVD risk factors and the Framingham Risk Score. RESULTS: 603 subjects fulfilled study inclusion criteria. 230 (38%) subjects had 1 or more documented CVD event and 211 (35%) had AAC detected on VFA scans. Significantly more subjects with cardiovascular events had AAC on their VFA scans than controls (76% versus 10%; P < 0.05). VFA-detected AAC was a better predictor of CVD than traditional risk factors, and significantly out-performed the Framingham Risk Score for discriminating between the presence and absence of CVD (AUC 0.85 versus 0.58; P < 0.001). CONCLUSION: There was a significant association between VFA-detected AAC and CVD in our study population. This finding may enhance cardiovascular disease risk prediction in RA patients. PMID- 24176732 TI - Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin. AB - Eighteen symmetrical bis-Schiff base derivatives of isatin were synthesized by condensation of the natural or synthetic isatins with hydrazine and were evaluated for their in vitro and in vivo antitumor activities. More than half of the obtained compounds showed potent cytotoxicity according to the MTT assay on five different human cancer cell lines (i.e. HeLa, SGC-7901, HepG2, U251, and A549), with compound 3b 3,3'-(hydrazine-1,2-diylidene)bis (5-methylindolin-2-one) being the most potent compound on HepG2 (IC50 ~ 4.23 MUM). 3b was also found to be able to inhibit substantially the tumor growth on the HepS-bearing mice at a dose of 40 mg/kg. The real-time live cell imaging and tracking in the H2B-labeled HeLa cells revealed that 3b could induce mitosis interference and apoptosis associated cell death. In mechanism study, 3b arrested the cell cycle at the G2/M phase in HepG2 cells by down-regulating the expression of cyclin B1 and cdc 2. PMID- 24176733 TI - Acquired resistance to targeted therapies against oncogene-driven non-small-cell lung cancer: approach to subtyping progressive disease and clinical implications. AB - In the emerging era of targeted therapy for advanced-stage non-small-cell lung cancer, it is becoming increasingly important to anticipate underlying driver oncogene alterations at the time of initial diagnosis and tumor-tissue acquisition, so that patients can be selected in a timely fashion for first-line tyrosine kinase inhibitor (TKI) therapy if their cancers are found to harbor tyrosine-kinase-activating mutations in the epidermal growth factor receptor gene or gain-of-function rearrangements in the anaplastic lymphoma kinase gene. However, despite the clear benefits of TKI therapy over chemotherapy in these settings, the eventual emergence of acquired resistance and progressive disease (PD) is universal. How to best approach oncogene-driven non-small-cell lung cancer at the time of acquired resistance to initial TKI therapy is an increasingly complex question because of variability in mechanisms of resistance, extent of PD, and inter- and intrapatient tumor heterogeneity. Here we propose an approach to subtyping PD in the setting of acquired resistance as well as subsequent clinical implications. PMID- 24176734 TI - [Stab wounds in emergency department]. AB - Stab wounds represent the most common cause of penetrating wounds, occurring mainly in case of aggression or suicide attempt. Clinical severity depends on the superficial or penetrating aspect of the wound, its location and damaged organs. Medical management must be known because the vital risk is involved in penetrating wounds. Hemodynamically unstable patients should be operated without delay after performing a chest X-ray and ultrasound Focus assisted sonography for trauma (FAST) to guide the surgery. In the stable patients, the general clinical examination, exploration of the wound and medical imaging detect injuries requiring surgical management. Stab penetrating wounds require close and rapid collaboration between medical teams, tailored to the institution's resources. PMID- 24176735 TI - Is osteoarthritis a metabolic disease? AB - Obesity, together with aging and injury, is among the main risk factors for osteoarthritis. Obesity-related osteoarthritis can affect not only the weight bearing joints, but also the hands, suggesting a role for circulating mediators released by the adipose tissue and known as adipokines. Thus, osteoarthritis may have a systemic metabolic component. Evidence from both epidemiological and biological studies support the concept of metabolic osteoarthritis, defined as a broad clinical phenotype that includes obesity-related osteoarthritis. Thus, osteoarthritis can be related to metabolic syndrome or to an accumulation of metabolic abnormalities. In addition, studies have demonstrated associations linking osteoarthritis to several components of the metabolic syndrome, such as hypertension and type 2 diabetes, independently from obesity or any of the other known risk factors for osteoarthritis. Both in vitro and in vitro findings indicate a deleterious effect of lipid and glucose abnormalities on cartilage homeostasis. Chronic low-grade inflammation is a feature shared by osteoarthritis and metabolic disorders and may contribute to the genesis of both. Thus, osteoarthritis is emerging as a disease that has a variety of phenotypes including a metabolic phenotype, in addition to the age-related and injury related phenotypes. PMID- 24176736 TI - Recommendations for using TNFalpha antagonists and French Clinical Practice Guidelines endorsed by the French National Authority for Health. AB - The use of TNFalpha antagonists must follow specific guidelines to ensure optimal effectiveness and safety. The French Society for Rheumatology (SFR) and Task Force on Inflammatory Joint Diseases (CRI), in partnership with several French learned societies, asked the French National Authority for Health (HAS) to develop and endorse good practice guidelines for the prescription and monitoring of TNFalpha antagonist therapy by physicians belonging to various specialties. These guidelines were developed, then, validated by two multidisciplinary panels of experts based on an exhaustive review of the recent literature and in compliance with the methodological rules set forth by the HAS. They pertain to the initial prescription of TNFalpha antagonists and to a variety of clinical situations that can arise during the follow-up of patients receiving TNFalpha antagonists (infections, malignancies, pregnancy, vaccination, paradoxical adverse events, surgery, use in older patients, and vasculitides). PMID- 24176737 TI - Infection of the sigmoid colon during TNFalpha antagonist therapy for chronic inflammatory joint disease. AB - We report 7 cases of sigmoid colon infection in patients taking TNFalpha antagonist therapy to treat chronic inflammatory joint disease. There were 5 women and 2 men with a mean age of 57.5 years (range, 21-77 years). The presenting symptoms were abdominal pain, bowel habit changes, and a fever. These symptoms developed within 6 months after starting TNFalpha antagonist therapy in 5 of the 7 patients. Empirical antibiotic therapy was used in all 7 patients. Surgical colectomy was performed in 4 patients, including 1 who required a temporary Hartmann's procedure. The risk of infection associated with TNFalpha antagonist therapy is well documented. However, few cases of colon infection have been reported and little is known about this potentially severe complication. Glucocorticoids or non-steroidal anti-inflammatory drugs may worsen the infection, particularly as they can attenuate the clinical symptoms, thereby delaying the diagnosis. A history of sigmoid colon infection, diverticulosis, and/or diverticulitis must be sought before starting treatment with a biological agent. Prophylactic treatment may be considered if such a history is found. Diagnostic investigations are in order to develop a standardized management strategy in patients with a history of intestinal tract infection. PMID- 24176738 TI - Inhibition of glycogen synthase kinase-3beta suppresses inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes and collagen-induced arthritis. AB - OBJECTIVES: Glycogen synthase kinase (GSK)-3beta, a serine/threonine protein kinase, has been implicated as a regulator of the inflammatory response. This study was performed to evaluate the effect of selective GSK-3beta inhibitors in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and collagen-induced arthritis (CIA). METHOD: FLS from RA patients were treated with selective GSK 3beta inhibitors, including lithium chloride, 6-bromoindirubin-3'-oxime (BIO), or 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). The effects of GSK 3beta inhibition on pro-inflammatory mediators were determined by real-time PCR and ELISA. The levels of NF-kappaB, phosphorylated JNK, c-jun, ATF-2 and p-38 proteins were evaluated by western blot analysis. The in vivo effects of GSK 3beta inhibitors were examined in mice with CIA. RESULTS: Treatment of RA FLS with GSK-3beta inhibitors induced dose-dependent reductions in gene expression and the production of pro-inflammatory mediators. The levels of NF-kappaB, phosphorylated JNK, c-jun, ATF-2 and p-38 were decreased following treatment with GSK-3beta inhibitors. GSK-3beta inhibitors treatment attenuated clinical and histological severities of CIA in mice. Infiltration of T-cells, macrophages, and tartrate-resistant acid phosphatase positive cells was decreased in joint sections of CIA mice by GSK-3beta inhibitors treatment. Serum levels of IL-1beta, IL-6, TNF-alpha and IFN-gamma in CIA mice were also significantly decreased in dose-dependent manners by treatment with GSK-3beta inhibitors. CONCLUSION: Treatment with GSK-3beta inhibitors suppressed inflammatory responses in RA FLS and CIA mice. These findings suggest that the inhibition of GSK-3beta can be used as an effective therapeutic agent for RA. PMID- 24176739 TI - Overestimation of flavonoid aglycones as a result of the ex vivo deconjugation of glucuronides by the tissue beta-glucuronidase. AB - Flavonoid glucuronides are the main circulating metabolites of flavonoids in humans and animals. There has been a growing interest in the biological function of glucuronides. In order to differentiate biological activity and to assess efficacy it is essential to accurately determine the levels of flavonoid aglycone and metabolic conjugate in vivo. Many organs and body fluids of humans and animals exhibit beta-glucuronidase against flavonoid glucuronides. Studies have shown that beta-glucuronidase within the tissues hydrolyzes glucuronides to their aglycones during the tissue extraction, leading to artificially higher reported tissue levels of aglycone than actual in vivo concentrations. The aims of this study were to estimate the extent by which the aglycones were overestimated and to investigate the use of saccharo-1,4-lactone, a beta-glucuronidase inhibitor, to block the ex vivo hydrolysis of flavonoid glucuronides. Our data demonstrate that in mouse liver tissues and human tumor xenografts levels of quercetin and methylated quercetin aglycones could be over-estimated by 7-fold. The inhibition of deconjugation of quercetin and baicalein glucuronides by saccharo-1,4-lactone is dose-dependent. The amount of saccharo-1,4-lactone used to produce optimal inhibition of the enzyme activity is in the range of 15-24MUmol per gram of liver tissue. The use of beta-glucuronidase inhibitor blocks the ex vivo deconjugation resulting in an accurate estimation of tissue levels of aglycone and conjugate. Our study described here can be extended to other animal models and human studies with different types of substrates of beta-glucuronidase. PMID- 24176740 TI - Liquid chromatographic determination of CPZEN-45, a novel anti-tubercular drug, in biological samples. AB - CPZEN-45 is a new drug candidate being considered for the treatment of tuberculosis (TB). The aim of this study was to develop and validate a reverse phase high-performance liquid chromatographic (HPLC) method suitable to determine CPZEN-45 concentrations in biological samples. CPZEN-45 was extracted from biological fluids and tissues (plasma, lung and spleen from guinea pig) by sequential extraction with acetonitrile and quantified by a Waters HPLC Alliance System coupled with a ZORBAX Bonus-RP column, guard column and UV detection at 263nm. The mobile phase was 20:80 acetonitrile:ultrapure-water with 0.05% TFA. The CPZEN-45 peak was eluted at 5.1min with no interference from the inherent peaks of plasma, bronchoalveolar lavage (BAL), lung or spleen tissues. Recovery of CPZEN-45 from biological samples was >96% of the spiked amount. The limit of detection was 0.05MUg/ml and the limit of quantitation was 0.29MUg/ml which was more than 5 and 21 times lower than the reported minimal inhibitory concentration of CPZEN-45 (MIC=1.56MUg/ml for Mycobacterium tuberculosis and 6.25MUg/ml for MDR TB, respectively). Thus, HPLC method was deemed reliable, sensitive, reproducible and accurate for the determination of CPZEN-45 concentrations in plasma, BAL, lung and spleen tissues. Therefore, this method was used in subsequent studies in the guinea pig model to determine the disposition of CPZEN-45 after administration of solutions by the IV and SC routes. PMID- 24176741 TI - Determination of macro and trace elements in multivitamin dietary supplements by high-resolution continuum source graphite furnace atomic absorption spectrometry with slurry sampling. AB - In this research, three different commercially available multivitamin dietary supplements were analyzed by high-resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS GFAAS) with slurry sampling. The concentrations of Cr, Cu, Fe, Mn, and Se were determined and compared to the amounts stated by producers. The safety of multivitamin dietary supplements depends on various factors including the manufacturing process and the purity and origins of the raw ingredients. For this reason, this research determined concentrations of several toxic elements (As, Cd, and Pb). Microwave-assisted high pressure Teflon bomb digestion was used to determine total amounts of elements in samples. Samples were prepared as slurries at a concentration of 0.1% (m/v) for macro elements (Cr, Cu, Fe, Mn, and Se) and at a concentration of % (m/v) for trace elements (As, Cd, and Pb) in acidic media (3M HNO3). The influence of acid concentration, Triton X-100 addition, sonication time, and sonication power on absorbance was investigated. The accuracy of this method was validated by analyses of NRCC LUTS-1 (Lobster hepatopancreas), NRCC DORM-1 (Dogfish Muscle), NRCC DOLT-2 (Dogfish Liver), NBS SRM 1570 (Spinach Leaves) and NBS SRM 1573 (Tomato Leaves) certified reference materials. The measured elements contents in these reference materials (except NRCC DOLT-2) were in satisfactory agreement with the certified values according to the t-test for a 95% confidence level. PMID- 24176742 TI - Identification, isolation and characterization of process related impurities in ezetimibe. AB - During the synthesis of ezetimibe, two process related impurities were detected were HPLC analysis at levels ranging from 0.05 to 0.8%. These two impurities were isolated by column chromatography and co-injected with ezetimibe sample to confirm the retention times in HPLC. These two impurities were characterized as 2 (4-hydroxybenzyl)-N,5-bis(4-fluorophenyl) pentanamide (impurity-I) and 1-(4 fluorophenyl)-3(3-(4-fluorophenyl)propyl)-4-(4-hydroxyphenyl)azetidin-2-one (impurity-II). Isolation, structural elucidation of these impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and probable mechanism of their formation have been discussed. PMID- 24176743 TI - A high performance liquid chromatography fingerprinting and ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry chemical profiling approach to rapidly find characteristic chemical markers for quality evaluation of dispensing granules, a case study on Chuanxiong Rhizoma. AB - A high performance liquid chromatography-photodiode array detector (HPLC-PDA) fingerprinting and ultra high performance liquid chromatography-photodiode array detector coupled with quadrupole time-of-flight mass spectrometry (UHPLC-PDA-QTOF MS/MS) based chemical profiling approach was developed to rapidly find characteristic chemical markers for quality control of dispensing granules, taking Chuanxiong Rhizoma (CR) as a model herb. Firstly, CR crude drugs, their traditional decoctions and CR dispensing granules were analyzed by HPLC-PDA to rapidly establish the fingerprints and thereby generate the simulative median chromatograms of CR crude drugs, decoctions and dispensing granules, and by comparing the simulative median chromatograms, major characteristic peaks of CR decoctions and dispensing granules could be determined. Secondary, UHPLC-PDA-QTOF MS/MS was used to identify the major characteristic peaks of CR decoctions and dispensing granules. The identities of three major peaks were elucidated and confirmed to be ferulic acid (1), senkyunolide I (2) and senkyunolide H (3) by comparing the mass/UV spectra and retention times with that of the reference compounds. Thirdly, an HPLC-PDA method was validated to quantify the three characteristic components in commercial CR dispensing granules. The average contents of ferulic acid and senkyunolide H were found to be less than 1.0mg/g, whereas that of senkyunolide I was 4.40mg/g in CR dispensing granules, which indicated that senkyunolide I might be chosen as a suitable quantitative marker, while ferulic acid and senkyunolide H as qualitative markers for the quality evaluation of CR dispensing granules. It is suggested that this newly established approach could be used to practically and rapidly find suitable marker compounds for quality control of dispensing granules derived from other medicinal herbs. PMID- 24176744 TI - Improvement of a stability-indicating method by Quality-by-Design versus Quality by-Testing: a case of a learning process. AB - The understanding of the method is a major concern when developing a stability indicating method and even more so when dealing with impurity assays from complex matrices. In the presented case study, a Quality-by-Design approach was applied in order to optimize a routinely used method. An analytical issue occurring at the last stage of a long-term stability study involving unexpected impurities perturbing the monitoring of characterized impurities needed to be resolved. A compliant Quality-by-Design (QbD) methodology based on a Design of Experiments (DoE) approach was evaluated within the framework of a Liquid Chromatography (LC) method. This approach allows the investigation of Critical Process Parameters (CPPs), which have an impact on Critical Quality Attributes (CQAs) and, consequently, on LC selectivity. Using polynomial regression response modeling as well as Monte Carlo simulations for error propagation, Design Space (DS) was computed in order to determine robust working conditions for the developed stability-indicating method. This QbD compliant development was conducted in two phases allowing the use of the Design Space knowledge acquired during the first phase to define the experimental domain of the second phase, which constitutes a learning process. The selected working condition was then fully validated using accuracy profiles based on statistical tolerance intervals in order to evaluate the reliability of the results generated by this LC/ESI-MS stability-indicating method. A comparison was made between the traditional Quality-by-Testing (QbT) approach and the QbD strategy, highlighting the benefit of this QbD strategy in the case of an unexpected impurities issue. On this basis, the advantages of a systematic use of the QbD methodology were discussed. PMID- 24176745 TI - Validated LC-MS/MS assay for quantitative determination of deoxypodophyllotoxin in rat plasma and its application in pharmacokinetic study. AB - A rapid and sensitive liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of deoxypodophyllotoxin (DPT) concentration in rat plasma with diazepam as internal standard (IS). DPT and IS were extracted with ethyl acetate, and the chromatographic separation was accomplished by using a Waters Symmetry C18 analytical column (2.1mm*150mm, 5MUm) with a mobile phase consisting of acetonitrile and deionized water (70:30, v:v) containing 0.1% formic acid at a flow rate of 0.2mL/min. Multiple Reaction Monitoring (MRM), using electrospray ionization in positive ion mode, was employed to quantitatively detect DPT and IS. The monitored transitions were set at m/z 399.05-231.00 and m/z 285.00-154.00 for DPT and IS, respectively. The calibration curve was linear over the concentration range of 7.8-1000ng/mL (R(2)>=0.9999). The intra- and inter-day precision values were less than 7%. Similarly, the mean intra- and inter-day accuracy were found to be within -2.8% to 1.9% of the interval, with all samples locating within general assay acceptability criteria for QC samples according to FDA guidelines. This method was further and successfully applied in the pharmacokinetics study of DPT in rat. PMID- 24176746 TI - Determination of monoamine and amino acid neurotransmitters and their metabolites in rat brain samples by UFLC-MS/MS for the study of the sedative-hypnotic effects observed during treatment with S. chinensis. AB - Schisandra chinensis (Turcz.) Baill. has been used as a sedative and hypnotic agent in traditional Chinese medicine for centuries. The purpose of this study was to reveal the influence of insomnia on the levels of the neurotransmitters: glutamate (Glu), gamma-aminobutyric acid (GABA), noradrenaline (NE), dopamine (DA), serotonin (5-HT) and their metabolites (5-HIAA, DOPAC and HVA), and to study the role of S. chinensis in the treatment of insomnia. To achieve this goal, an efficient, sensitive and selective method was developed and validated for the simultaneous determination of these five neurotransmitters and their metabolites in rat brain samples using ultra fast liquid chromatography/tandem mass spectrometry (UFLC-MS/MS). The analysis was performed on a Synergi Fusion-RP 80A ODS column (150mm*2.0mm, 4.0MUm) using gradient elution, with the mobile phase consisting of acetonitrile and 0.05% formic acid in water. The method was validated using rat brain homogenate samples and showed a good linearity over a wide concentration range (r(2)>0.99) with a lower limit of quantification (LLOQ) at 4-16ngmL(-1). The intra and inter-day assay variability was less than 15% for all analytes. The results indicated that the condition of insomnia elevated GABA, NE, DA, DOPAC and HVA, and reduced 5-HT, 5-HIAA levels in rat brain. The oral administration of S. chinensis (7.5gkg(-1)day(-1), eight days) influenced insomnia by significantly increasing or reducing the levels of the neurotransmitters parameters mentioned above. These results suggested that S. chinensis could alter the levels of these brain neurotransmitters and their metabolites through its sedative-hypnotic effects. PMID- 24176747 TI - Double-bed-type extraction needle packed with activated-carbon-based sorbents for very volatile organic compounds. AB - A novel needle-type sample preparation device was developed for the determination of very volatile organic compounds (VVOCs) in gaseous samples by gas chromatography-mass spectrometry (GC-MS). Two types of activated-carbon-based sorbents, Carbopack X and a carbon molecular sieve (CMS), were investigated as the extraction medium. A double-bed-type extraction needle showed successful extraction and desorption performance for all investigated VVOCs, including acetaldehyde, isoprene, pentane, acetone, and ethanol. Sensitive and reliable determination of VVOCs was achieved by systematically optimizing several desorption conditions. In addition, the effects of sample humidity on the extraction and desorption of analytes were investigated with the needle-type extraction devices. Only the CMS packed extraction needle was adversely affected by sample humidity during the desorption process; on the other hand the double bed-type extraction needle was unaffected by sample humidity. Finally, the developed double-bed-type extraction needle was successfully applied to the analysis of breath VVOCs of healthy subjects. PMID- 24176748 TI - Structural characterization of in vitro metabolites of the new anticancer agent EAPB0503 by liquid chromatography-tandem mass spectrometry. AB - EAPB0503, belonging to the imidazo[1,2-a]quinoxaline series, is an anticancer drug with antitumoral activity against a variety of tumors. Previous studies have shown that this drug undergoes demethylation and oxygenation reactions. In this paper, liquid chromatography-electrospray ionization-tandem mass spectrometry (LC ESI-MS/MS) was employed to assess the structures of unknown oxygenated metabolites of EAPB0503. EAPB0503 and its identified demethylated metabolites, EAPB0502 and EAPB0603, were incubated with human, rat, dog and mouse liver microsomes, as well as human, rat and dog hepatocytes. After separation on a C8 analytical column with a gradient elution of acetonitrile-formate buffer, positive ESI-MS/MS experiments were performed. To facilitate metabolite identification, the detailed fragmentation pathways of the parent compounds were first studied using high-resolution MS/MS. Additional hydrogen/deuterium exchange LC-MS/MS experiments were used to support the identification and structural characterization of metabolites. Four hydroxylated metabolites were identified: M'4 and its demethylated derivative M'1 (OH in ortho position on the phenyl substituent in position 1), and M'6 and its demethylated derivative M'3 (OH on the imidazole ring at the C2 position). Three phase II metabolites (Met A, EAPB0602 glucuronide; Met B, M'4 glucuronide; Met C, EAPB0603 glucuronide) were also evidenced. Elucidation of the metabolite structures was performed by comparing the chromatographic behaviors (changes in retention times), by measuring the molecular masses (mass increment), by studying the MS(2) spectral patterns of metabolites with those of parent drugs and for M'1 and M'4 by co analysis with synthetic standards. The results of the present study provided important structural information relating to the metabolism of EAPB0503. PMID- 24176749 TI - Saliva metabolomics by NMR for the evaluation of sport performance. AB - The paper reports preliminary results of a study in order to verify that saliva is a bio-fluid sensitive to metabolite variations due to stress and fatigue in soccer athletes, and possibly, to identify potential markers of test of performance. Saliva samples of fourteen professional soccer players were collected before and after the stressful physical activity of the level 1 Yo-Yo intermittent recovery test and, also, physiological parameters were evaluated. The NMR spectra of saliva offer a metabolites profiling which was analyzed by Principal Component Analysis as a blind test. The results of NMR pre and post test shows that it was possible to cluster the best and the worst performing athletes and that the role of the actual player may be diagnosed by a different cluster of metabolites profile. Thus saliva can be considered a biofluid metabolically sensitive to the induced physical stress and, in the future, deeper investigated to monitor the performances in athletes. PMID- 24176750 TI - Determination of selected biogenic amines in Acacia rigidula plant materials and dietary supplements using LC-MS/MS methods. AB - Extracts of Acacia rigidula leaves are used in weight-loss products sold in vitamin shops and over the internet with little or no published data about their potential biological effects. In our chemical investigations on authenticated A. rigidula plant material, we established a rapid and sensitive LC-MS/MS method for the quantitative determination of several phenethylamine, tyramine and tryptamine derivatives. Stable isotopically labeled compounds were used as internal standards for quantitative analysis. We found total calculated contents of 6 biogenic amines in A. rigidula leaf of 18.6 and 32.9MUg/g. The content of selected amines in 21 dietary supplements labeled as containing A. rigidula was determined by a second LC-MS/MS method. Our study revealed significant differences in the amine profiles of authenticated plant materials and dietary supplements. beta-Methylphenethylamine, a non-natural compound, was found in 9 of the 21 dietary supplement products. beta-Methylphenethylamine was found at levels of 960-60,500MUg/g while phenethylamine was found at levels of 710-171,620MUg/g. beta-Methylphenethylamine is a positional isomer of amphetamine and our results showed that it can be misidentified as amphetamine during LC-MS analysis. An independent GC-MS analysis was used to confirm the presence of beta methylphenethylamine and the absence of amphetamine in dietary supplements labeled as containing A. rigidula. This study demonstrates that confirmations by independent analytical methods are essential to verify findings of unusual or unexpected compounds in dietary supplements. PMID- 24176751 TI - A fast and feasible microextraction by packed sorbent (MEPS) procedure for HPLC analysis of the atypical antipsychotic ziprasidone in human plasma. AB - An original high-performance liquid chromatographic method coupled to microextraction by packed sorbent (MEPS) was developed for the therapeutic drug monitoring (TDM) of psychiatric patients treated with the recent atypical antipsychotic ziprasidone. The chromatographic separation was achieved on a RP C18 column, using an isocratic mobile phase and setting the wavelength at 320nm. The analyte was extracted from human plasma by means of a fast and feasible innovative MEPS procedure, optimised on C2 sorbent and requiring only 100MUL of biological sample. A second pre-treatment procedure, based on solid phase extraction (SPE), has been also developed for comparison. The availability of different pre-treatment procedures allows the choice of the one best suiting the specific clinical, economic and scientific needs. The extraction yield values were always higher than 90% and sensitivity was also good, with a limit of quantitation (LOQ) of 1ng/mL. The method was successfully applied to plasma samples from ten subjects undergoing therapy with ziprasidone, thus confirming its suitability for the TDM of psychiatric patients, in order to personalise their pharmacological treatments. PMID- 24176752 TI - Quantitative determination of triterpenoid glycosides in Fatsia japonica Decne. & Planch. using high performance liquid chromatography. AB - Fatsia japonica Decne. & Planch. is a triterpenoid glycoside-rich herb with anti inflammatory activity for the treatment of rheumatoid arthritis. A method for quantitative analysis of the complex triterpenoid glycosides in this medicinal plant has not been established so far. In this study, a high performance liquid chromatography (HPLC) method was developed for simultaneous qualification of 11 glycosides in F. japonica. The analysis was performed on an ODS-2 Hypersil column (250mm*4.6mm, 5MUm) with a binary gradient mobile phase of water and acetonitrile. The established HPLC method was validated in terms of linearity, sensitivity, stability, precision, accuracy, and recovery. Results showed that this method had good linearity with R(2) at 0.99992-0.99999 in the test range of 0.04-9.00MUg/MUL. The limit of detection (LOD) and limit of quantification (LOQ) for the standard compounds were 0.013-0.020MUg/MUL and 0.040-0.060MUg/MUL. The relative standard deviations (RSDs%) of run variations were 0.83-1.40% for intra day and 0.84-3.59% for inter-day. The analyzed compounds in the samples were stable for at least 36h, and the spike recoveries of the detected glycosides were 99.67-103.11%. The developed HPLC method was successfully applied for the measurements of the contents of 11 triterpenoid glycoside in different parts of F. japonica. Taken together, the HPLC method newly developed in this study could be used for qualitative and quantitative analysis of the bioactive triterpenoid glycosides in F. japonica and its products. PMID- 24176753 TI - Analytics of the therapeutic peptide aviptadil by sheathless CE-MS and comparison with nanoRP-HPLC-MS. AB - Purification and quality control of therapeutic peptides is often performed by one single method, RP-HPLC. As usage of an orthogonal technique is highly advisable for quality assurance, capillary electrophoresis (CE) employing a coated capillary coupled via a sheathless interface to a mass spectrometer was applied in parallel. The basic therapeutic peptide aviptadil served as a model substance to study the impurity profiles revealing 15 detectable impurities using CE-MS, two were detected by an appropriate nanoRP-HPLC-MS method. None of the impurities detected by CE were observed in LC and vice versa. The LOD in CE-MS was determined in the base peak electropherogram at ~1fmol, a value 2500 times smaller than the LOD found in nanoRP-HPLC-MS (3pmol). In nanoRP-HPLC-MS only 0.2% of the extrapolated CE-MS signal for a 25ng aviptadil load was observed. We conclude that both, the LOD as well as the impurity profile of aviptadil, as analyzed by nanoRP-HPLC are influenced by both, the ligand-derivatized silica matrix and the flow-rate. Peptides may disappear completely and their variable emergence may lead to the determination of incorrect ratios as present in the sample. PMID- 24176754 TI - Quantitative determination of Lx2-32c, a novel taxane derivative, in rat plasma by liquid chromatography-tandem mass spectrometry. AB - A sensitive and reliable LC-MS/MS method for the determination of Lx2-32c, a novel taxane derived from cephalomannine, has been developed and validated. Plasma samples containing Lx2-32c and paclitaxel (internal standard) were prepared based on a simple protein precipitation by the addition of two volumes of acetonitrile. The analyte and internal standard were separated on a Zorbax SB C18 column (3.5MUm, 2.1mm*100mm) with the mobile phase of acetonitrile/water containing 0.1% formic acid (v/v) with gradient elution at a flow rate of 0.2ml/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with atmospheric pressure chemical ionization (APCI) by multiple reactions monitoring (MRM) of the transitions at m/z 887.5->264.3 for Lx2-32c and 854.5->286.2 for IS. Linear detection responses were obtained for Lx2 32c ranging from 1 to 1000ng/ml. Inter- and intra-day precision (R.S.D.%) were all within 15% and the accuracy (R.E.%) was equal or lower than 8%. The lower limit of quantitation (LLOQ) was 1ng/ml and the average recovery was greater than 91.5%. The method was successfully applied to the pharmacokinetic study of Lx2 32c in rat plasma. PMID- 24176755 TI - Bioinformatical analysis of nuclear localisation sequences in penaeid densoviruses. AB - Nuclear location sequences (NLSs) link proteins to importation molecules for transportation into the nucleus. A bioinformatical search of the penaeid parvoviruses was undertaken to look for NLS. All three ORFs of Penaeus merguiensis densovirus (PmergDNV) have functional NLS whilst only the two non structural proteins of Penaeus stylirostris densovirus (PstDNV) appear to. In PmergDNV, NS1 has a NLS similar to DNA helicase Q1, NS2 is similar to Dorsal and VP1 is similar to SV40 T-antigen signal. In PstDNV, NS2 has a NLS that is an unrecognised pattern unless it is a monopartite Chelsky signal whilst NS1 has both a Dorsal and minute virus of mouse signals. The capsid protein NLS of PstDNV is likely to be inefficient. Spawner isolated mortality virus has a NLS like DNA helicase Q1. These NLSs affect the nature of inclusion bodies seen with light microscopy, basophilic in PmergDNV; eosinophilic in PstDNV and the site of encapsidation, nuclear in PmergDNV; cytoplasmic in PstDNV as seen with TEM. Many possible NLSs in penaeid parvoviruses are homologues to those in eukaryotic organisms and need to be tested experimentally. PMID- 24176756 TI - Three-dimensional insights into dermal tissue as a cue for cellular behavior. AB - Scar formation after injury is a big problem, which influences the skin function and esthetic appearances. Recent researchers have hinted many directions, one of which has shown that scar formation is related to the loss of integrity in dermal tissues. The structure of dermal tissue, which contains mostly collagen, is not only crucial for the mechanical stability of skin, but also acts as a dermal template, providing contact guidance for regulating cell behavior and restoring normal structure and function to skin that has been damaged by injury. These findings suggest a series of questions. How does contact guidance regulate cell behavior? What is the three-dimensional (3D) architecture of the dermal tissue? How does the native 3D architecture influence cell behavior in vivo? In this paper, combing our recent research, we will review the recent advances in this field, that is, the phenomenon of contact guidance and explore the possible mechanism behind it. PMID- 24176757 TI - Validation of predictive factors of dysphagia risk following thermal burns: a prospective cohort study. AB - PURPOSE: The objective of this study was to prospectively evaluate the validity and reliability of a risk factor model developed for use in predicting dysphagia risk within the first 24 h after injury/hospitalisation in patients with thermal burns. METHOD(S): Three hundred and fifty six patients with thermal burns, with or without inhalation injury, who were consecutively admitted to and received management at a quaternary state-wide burn center over a 12 month period, were included. Patients were reviewed for dysphagia risk by nursing staff using an established set of predictive factors. If risk factors for dysphagia were present, referral to speech-language pathology was initiated to investigate swallow function. RESULT(S): Of the 356 admissions, 83 patients were identified as meeting one or more risk criteria for dysphagia after burn. Of these, 24.9% (n = 30; 8.42% of the total cohort) presented with dysphagia. Using these criteria, sensitivity and specificity for detection of dysphagia risk were high (100% and 83.74%, respectively). The criteria over identify patients who may be at risk of dysphagia and who require dysphagia assessment (positive predictive value = 36.14%). However, as a set of predictors of dysphagia risk when thermal burn is the only complaint, a negative result reassures that a patient does not have dysphagia (negative predictive value = 100%). CONCLUSION: Overall, the risk factor model provided a valid measure for predicting dysphagia risk. Incorporating these criteria into a dysphagia screening assessment can ensure an evidence-based pathway for early detection and timely referral to speech-language pathology for patients at risk of dysphagia after thermal burns. PMID- 24176758 TI - Mutation of KCNJ8 in a patient with Cantu syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition. AB - KCNJ8 (NM_004982) encodes the pore forming subunit of one of the ATP-sensitive inwardly rectifying potassium (KATP) channels. KCNJ8 sequence variations are traditionally associated with J-wave syndromes, involving ventricular fibrillation and sudden cardiac death. Recently, the KATP gene ABCC9 (SUR2, NM_020297) has been associated with the multi-organ disorder Cantu syndrome or hypertrichotic osteochondrodysplasia (MIM 239850) (hypertrichosis, macrosomia, osteochondrodysplasia, and cardiomegaly). Here, we report on a patient with a de novo nonsynonymous KCNJ8 SNV (p.V65M) and Cantu syndrome, who tested negative for mutations in ABCC9. The genotype and multi-organ abnormalities of this patient are reviewed. A careful screening of the KATP genes should be performed in all individuals diagnosed with Cantu syndrome and no mutation in ABCC9. PMID- 24176759 TI - A proteomic approach on the effects of TX527, a 1alpha,25-dihydroxyvitamin D3 analog, in human T lymphocytes. AB - 1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3), and its analogs (i.e. 14,20-bis epi-19-nor-23-yne-1alpha,25(OH)2D3 - TX527) have been shown to prevent autoimmunity and prolong islet graft survival in the non-obese diabetic (NOD) mouse. Their effects are mediated by their action on various immune cell types, such as dendritic cells (DC) and T cells. We have previously reported important direct effects of TX527 on human T cells, on their cytokine/chemokine profiles, T regulatory cell markers, homing characteristics and chemotaxis. In order to fully understand the molecular mechanisms underlying the beneficial properties of TX527 on human T cells, we applied here 2-dimensional difference gel electrophoresis (2 D DIGE) to analyze the global protein alterations induced by TX527 on human synchronized T cells. We detected differential expression of 64 protein spots upon TX527 treatment, of which 65.6% could be successfully identified using tandem mass spectrometry (MALDI-TOF/TOF). The identified proteins function in various processes, such as metabolism and energy pathways, cytoskeleton and protein metabolism. When comparing the proteomics data to our previously performed microarray data on the same set of cells, we found an overlap of 17 different mRNAs/proteins. For some of these (e.g. PSME2, HSPA8), the direction of regulation was not similar, hereby reinforcing the important role of post transcriptional/translational processes in the functionality of proteins. In addition, although 2-D DIGE offers the possibility of picking up post translational processes, it lacks the ability to detect molecules with extreme molecular weight (MW) and isoelectrical point (pI) values, or very low abundant/hydrophobic proteins. This study highlights therefore the importance of combining different experimental approaches to obtain a complete picture of the underlying mechanisms and general processes being affected in T cells upon TX527 treatment. These processes lead altogether to the generation of T cells with interesting immunomodulatory features for clinical applications in the treatment of autoimmune diseases or in the prevention of graft rejection. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID- 24176760 TI - Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells. AB - Anti-proliferative effects of calcium in the colon are mediated, at least in part, via the calcium-sensing receptor (CaSR), a vitamin D target gene. The expression of CaSR decreases during colorectal tumor progression and the mechanisms regulating its expression are poorly understood. The CaSR promoter harbors vitamin D elements responsive to 1,25-dihydroxyvitamin D3 (1,25D3) and NF kappaB, STAT, and SP1 binding sites accounting for responsiveness to proinflammatory cytokines. Therefore, in the current study we investigated the impact of 1,25D3, tumor necrosis factor alpha (TNFalpha), and interleukin (IL)-6 on CaSR expression in a differentiated (Caco2/AQ) and in a moderately differentiated (Coga1A) colon cancer cell line. 1,25D3 induced CaSR expression in both cell lines. Treatment with TNFalpha was accompanied by a 134-fold induction of CaSR in Coga1A (p<0.01). In Caco2/AQ cells the expression of CaSR was upregulated also by IL-6 (3.5-fold). Our data demonstrated transcriptional and translational activation of the CaSR by 1,25D3, TNFalpha, and IL-6 in a time- and cell line-dependent manner. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID- 24176762 TI - Quantifying the non-food sources of basal vitamin D input. AB - Unsupplemented vitamin D status is determined by cutaneous synthesis and food inputs; however, their relative magnitudes are largely unknown. In a cohort of 780 non-supplement-taking adults with a mean serum 25-hydroxyvitamin D [25(OH)D] of 33 (+/-14)ng/ml we assessed the relationship between serum 25(OH)D and non food environmental variables. Serum 25(OH)D concentration was adjusted for seasonal influence (which removed 2% of the total variance) and these adjusted values were regressed against factors involved in cutaneous synthesis. Indoor tanning use, sun exposure, and percent of work performed outdoors were significantly positively associated and body mass index (BMI) was significantly negatively associated with 25(OH)D values (P<0.03 for each). Latitude, gender, and age were not significantly correlated (P>0.10). Season and non-food predictors together explained 13% of the total variance in serum 25(OH)D concentration. Non-traditional food sources need to be investigated as possible vitamin D inputs. This article is part of a Special Issue entitled 'Vitamin D Workshop'. PMID- 24176761 TI - Prevention and treatment of postmenopausal osteoporosis. AB - In the beginning, that is from the 1960's, when a link between menopause and osteoporosis was first identified; estrogen treatment was the standard for preventing bone loss, however there was no fracture data, even though it was thought to be effective. This continued until the Women's Health Initiative (WHI) study in 2001 that published data on 6 years of treatment with hormone therapy that showed an increase in heart attacks and breast cancer. Even though the risks were small, 1 per 1500 users annually, patients were worried and there was a large drop off in estrogen use. In later analyses the WHI study showed that estrogen reduced fractures and actually prevented heart attacks in the 50-60 year age group. Estrogen alone appeared to be safer to use than estrogen+the progestin medroxyprogesterone acetate and actually reduced breast cancer. At the same time other drugs were being developed for bone that belong to the bisphosphonate group and the first generation of compounds showed moderate potency on bone resorption. The second and third generation compounds were much more potent and in a series of large trials were shown to reduce fractures. For the last 15 years the treatment of osteoporosis belonged to the bisphosphonate compounds, most of which reduce fracture rates by 50 percent. With the exception of gastrointestinal irritation the drugs are well tolerated and highly effective. The sophistication of the delivery systems now allow treatment that can be given daily, weekly, monthly and annually either orally or intravenously. Bone remodeling is a dynamic process that repairs microfractures and replaces old bone with new bone. In the last 10 years there has been a remarkable understanding of bone biology so that new therapies can be specifically designed on a biological basis. The realization that RANKL was the final cytokine involved in the resorption process and that marrow cells produced a natural antagonist called Osteoprotegerin (OPG) quickly led to two lines of therapy. First OPG was used as a therapy to block RANKL was initially successful but later antibodies against OPG developed and this line of treatment had to be discontinued. The next step was to develop a monoclonal antibody against RANKL and this proved to be highly effective in blocking bone resorption. It led to development of a drug Denosumab that successfully reduces fractures and is now one of the therapeutic options for osteoporosis treatment. On the anabolic side bone biology research showed that osteocytes produces sclerostin an inhibitor of the anabolic WNT signaling pathway. Recent development of a monoclonal antibody against sclerostin has shown remarkable anabolic activity in bone showing large increases in bone density and fracture trials are now underway. The newer treatments for osteoporosis are likely to be based on our understanding of bone biology and the design of new highly specific compounds with fewer side effects. This review summarizes the diagnosis of postmenopausal osteoporosis and various available non-pharmacological and pharmacological therapies available for its management. This article is part of a Special Issue entitled 'Menopause'. PMID- 24176763 TI - Pharmacology of conjugated equine estrogens: efficacy, safety and mechanism of action. AB - Oral conjugated equine estrogens (CEE) are the most used estrogen formulation for postmenopausal hormone therapy either alone or in combination with a progestin. CEE is most commonly used for the management of early menopausal symptoms such as hot flashes, vaginitis, insomnia, and mood disturbances. Additionally, if used at the start of the menopausal phase (age 50-59 years), CEE prevents osteoporosis and may in some women reduce the risk of cardiovascular disease (CVD) and Alzheimer's disease (AD). There appears to be a common mechanism through which estrogens can protect against CVD and AD. CEE is a natural formulation of an extract prepared from pregnant mares' urine. The product monogram lists the presence of only 10 estrogens consisting of the classical estrogens, estrone and 17beta-estradiol, and a group of unique ring B unsaturated estrogens such as equilin and equilenin. The ring B unsaturated estrogens are formed by an alternate steroidogenic pathway in which cholesterol is not an obligatory intermediate. Both the route of administration and structure of these estrogens play a role in the overall pharmacology of CEE. In contrast to 17beta-estradiol, ring B unsaturated estrogens express their biological effects mainly mediated by the estrogen receptor beta and not the estrogen receptor alpha. All estrogen components of CEE are antioxidants, and some ring B unsaturated estrogens have several fold greater antioxidant activity than estrone and 17beta-estradiol. The cardioprotective and neuroprotective effects of CEE appear to be, to some extent, due to its ability to prevent the formation of oxidized LDL and HDL, and by inhibiting or modulating some of the key proteases involved in programmed cell death (apoptosis) induced by the excess neurotransmitter glutamate and other neurotoxins. Selective combinations of ring B unsaturated estrogens have the potential of being developed as novel therapeutic agents for the prevention of cardiovascular disease and Alzheimer's disease in both aging women and men. This article is part of a Special Issue entitled 'Menopause'. PMID- 24176764 TI - Neurosteroid allopregnanolone attenuates high glucose-induced apoptosis and prevents experimental diabetic neuropathic pain: in vitro and in vivo studies. AB - Hyperglycemia plays a critical role in the development of diabetic neuropathy. Hyperglycemia induces oxidative stress in neurons, resulting in neuronal cell apoptosis and dysfunction. Anti-apoptotic properties of neurosteroids have been demonstrated in numerous cellular models of neurodegenerative studies. Here, the protective effects of neurosteroid allopregnanolone were investigated in in vitro and in vivo models of diabetic neuropathy. The data show that glucose decreased the viability of PC12 cells in a concentration-dependent manner. Allopregnanolone at concentrations of 2.5, 5 and 10MUM markedly prevented high glucose-induced toxicity in naive and NGF-treated (neuron-like) PC12 cells. Furthermore, treatment of diabetic rats with allopregnanolone (5 and 20mg/kg) significantly ameliorated diabetic-induced thermal hyperalgesia. Moreover, this neurosteroid inhibited caspase 3 and decreased Bax/Bcl2 ratio in high glucose-treated cells and spinal cord of diabetic rats. In conclusion, the data revealed that allopregnanolone has protective effects against hyperglycemic-induced cellular damage and prevention of cell apoptosis is involved in its mechanisms. Our findings suggest that allopregnanolone has protective effect against pro apoptotic challenges such as diabetes and hyperglycemia and propose therapeutic potential of neurosteroids in attenuation of diabetic side effects such as neuropathy. PMID- 24176766 TI - Kinetic Monte Carlo simulation of the initial phases of chlorophyll fluorescence from photosystem II. AB - Kinetic Monte Carlo (KMC) simulation is employed to represent the photochemical reactions involved in the initial phases of chlorophyll fluorescence (ChlF) emission from photosystem II (PSII). Comparison with a differential equation representation reveals similarities and differences. Both KMC and differential equation models can describe the kinetic variations and show the main characteristics of ChlF emission. Differential equation models are simpler to implement but have limitations that warrant future improvements. PMID- 24176768 TI - Understanding the burden of influenza infection among adults in Canadian hospitals: a comparison of the 2009-2010 pandemic season with the prepandemic and postpandemic seasons. AB - BACKGROUND: The degree to which the 2009-2010 influenza pandemic season differed from previous and subsequent influenza seasons in Canadian hospitals has not yet been assessed. METHODS: Surveillance for laboratory-confirmed influenza among adults in 51 Canadian Nosocomial Infection Surveillance Program hospitals was conducted between November 1, 2006, and May 31, 2011. Inpatient characteristics, treatment, and outcomes of influenza cases in the pandemic season (2009-2010) were compared with those in the prepandemic (2006-2007 to 2008-2009) and postpandemic (2010-2011) seasons. RESULTS: The incidence of influenza infection was lower in the postpandemic season (1.59/1,000 admissions) compared with the prepandemic seasons (2.00/1,000 admissions; P < .001) and the pandemic season (1.80/1,000 admissions; P < .001). The proportion of cases classified as health care-associated was much smaller during the pandemic season (6.6%) than in either the prepandemic season (23.2%; P < .001) or the postpandemic season (23.6%; P < .001). Inpatients in the pandemic season were significantly younger compared with those in the prepandemic and postpandemic seasons (P < .001). Inpatients in the pandemic season were less likely to have been vaccinated (P < .001), but more likely to be treated with antiviral agents (P < .001), than inpatients in both the prepandemic and postpandemic seasons. Intensive care unit admission was greater during the pandemic season, but there were no significant differences in 30-day mortality among the seasons. CONCLUSIONS: Among adult inpatients, the pH1N1 pandemic season differed from seasonal influenza in terms of age, vaccination status, antiviral use, and intensive care unit admission, but not in terms of 30-day mortality. PMID- 24176765 TI - The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions. AB - Research over the last decade has revealed that CYP11A1 can hydroxylate the side chain of vitamin D3 at carbons 17, 20, 22 and 23 to produce at least 10 metabolites, with 20(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3, 17,20(OH)2D3 and 17,20,23(OH)3D3 being the main products. However, CYP11A1 does not act on 25(OH)D3. The placenta, adrenal glands and epidermal keratinocytes have been shown to metabolize vitamin D3 via this CYP11A1-mediated pathway that is modified by the activity of CYP27B1, with 20(OH)D3 (the major metabolite), 20,23(OH)2D3, 1,20(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3 being detected, defining these secosteroids as endogenous regulators/natural products. This is supported by the detection of a mono-hydroxyvitamin D3 with the retention time of 20(OH)D3 in human serum. In new work presented here we demonstrate that the CYP11A1-initiated pathways also occurs in Caco-2 colon cells. Our previous studies show that 20(OH)D3 and 20,23(OH)2D3 are non-calcemic at pharmacological doses, dependent in part on their lack of a C1alpha hydroxyl group. In epidermal keratinocytes, 20(OH)D3, 20(OH)D2 and 20,23(OH)2D3 inhibited cell proliferation, stimulated differentiation and inhibited NF-kappaB activity with potencies comparable to 1,25(OH)2D3, acting as partial agonists on the VDR. 22(OH)D3 and 20,22(OH)2D3, as well as secosteroids with a short or no side chain, showed antiproliferative and prodifferentiation effects, however, with lower potency than 20(OH)D3 and 20,23(OH)2D3. The CYP11A1-derived secosteroids also inhibited melanocyte proliferation while having no effect on melanogenesis, and showed anti-melanoma activities in terms of inhibiting proliferation and the ability to grow in soft agar. Furthermore, 20(OH)D3 and 20,23(OH)2D3 showed anti-fibrosing effects in vitro, and also in vivo for the former. New data presented here shows that 20(OH)D3 inhibits LPS-induced production of TNFalpha in the J774 line, TNFalpha and IL-6 in peritoneal macrophages and suppresses the production of proinflammatory Th1/Th17-related cytokines, while promoting the production of the anti-inflammatory cytokine IL-10 in vivo. In summary, CYP11A1 initiates new pathways of vitamin D metabolism in a range of tissues and products could have important physiological roles at the local or systemic level. In the skin, CYP11A1-derived secosteroids could serve both as endogenous regulators of skin functions and as excellent candidates for treatment of hyperproliferative and inflammatory skin disorders, and skin cancer. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID- 24176769 TI - Veterans Affairs methicillin-resistant Staphylococcus aureus prevention initiative associated with a sustained reduction in transmissions and health care associated infections. AB - Implementation of a methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative was associated with significant declines in MRSA transmission and MRSA health care-associated infection rates in Veterans Affairs acute care facilities nationwide in the 33-month period from October 2007 through June 2010. Here, we show continuing declines in MRSA transmissions (P = .004 for trend, Poisson regression) and MRSA health care-associated infections (P < .001) from July 2010 through June 2012. The Veterans Affairs Initiative was associated with these effects, sustained over 57 months, in a large national health care system. PMID- 24176770 TI - Developing a new national approach to surveillance for ventilator-associated events: executive summary. AB - In September 2011, the Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group to organize a formal process for leaders and experts of key stakeholder organizations to discuss the challenges of VAP surveillance definitions and to propose new approaches to VAP surveillance in adult patients (Table 1). The charges to the Working Group were to (1) critically review a draft, streamlined VAP surveillance definition developed for use in adult patients; (2) suggest modifications to enhance the reliability and credibility of the surveillance definition within the critical care and infection prevention communities; and (3) propose a final adult surveillance definition algorithm to be implemented in the CDC's National Healthcare Safety Network (NHSN), taking into consideration the potential future use of the definition algorithm in public reporting, interfacility comparisons, and pay-for-reporting and pay-for-performance programs. PMID- 24176771 TI - Variability in hand hygiene practices among internal medicine interns. AB - Hand hygiene compliance remains suboptimal among physicians despite quality improvement efforts. We observed hand hygiene compliance among 29 medicine interns at 2 large academic institutions. Overall compliance was 75%. Although 4 interns averaged <40% compliance, 14 averaged at least 80%. Given variability observed among individuals in the same training programs, targeting those with poor performance may be important in improving overall compliance. PMID- 24176772 TI - Adherence to hand hygiene in high-risk units of a tertiary care hospital in India. AB - To improve the compliance to hand hygiene in our health care workers, 3 hand hygiene awareness weeks have been conducted over the past one-and-a-half years in our hospital. This observational audit conducted from October 2011 to March 2012 was planned to assess the impact of the above awareness drives. Although overall compliance increased significantly in 7 intensive care units from 23.1% to 41.2% (P < .0001), several deficiencies were noticed both in technique used as well as during specific opportunities of hand hygiene. PMID- 24176773 TI - Automated label-free quantification of metabolites from liquid chromatography mass spectrometry data. AB - Liquid chromatography coupled to mass spectrometry (LC-MS) has become a standard technology in metabolomics. In particular, label-free quantification based on LC MS is easily amenable to large-scale studies and thus well suited to clinical metabolomics. Large-scale studies, however, require automated processing of the large and complex LC-MS datasets. We present a novel algorithm for the detection of mass traces and their aggregation into features (i.e. all signals caused by the same analyte species) that is computationally efficient and sensitive and that leads to reproducible quantification results. The algorithm is based on a sensitive detection of mass traces, which are then assembled into features based on mass-to-charge spacing, co-elution information, and a support vector machine based classifier able to identify potential metabolite isotope patterns. The algorithm is not limited to metabolites but is applicable to a wide range of small molecules (e.g. lipidomics, peptidomics), as well as to other separation technologies. We assessed the algorithm's robustness with regard to varying noise levels on synthetic data and then validated the approach on experimental data investigating human plasma samples. We obtained excellent results in a fully automated data-processing pipeline with respect to both accuracy and reproducibility. Relative to state-of-the art algorithms, ours demonstrated increased precision and recall of the method. The algorithm is available as part of the open-source software package OpenMS and runs on all major operating systems. PMID- 24176775 TI - Clitoral anesthesia disrupts paced copulation in the female rat. AB - Clitoral stimulation produced by sexual contact with a partner or during manual stimulation is associated with pleasure in humans, and produces conditioned place preference in rats. The present experiment investigated the effect of blocking genitosensory stimulation of the clitoris with lidocaine during copulation in female rats on a measure of female sexual motivation: pacing behavior. Sexually naive, ovariectomized female rats were treated with 10MUg estradiol benzoate 48h and 500MUg progesterone 4h prior to a 30-min copulatory trial with a sexually vigorous stimulus male scheduled every 4days. A total of 10 copulatory sessions were divided into two phases of 5 trails each. In the first phase, females received an injection (0.05ml) of either 2% lidocaine, saline, or no injection to the clitoral sheath under isoflurane anesthesia immediately prior to the start of a copulatory session, and were then placed on one side of a paced mating chamber and allowed to copulate for 30min. In the second phase, females previously injected with lidocaine were switched to saline and vice versa, and the no injection group remained the same. Variables measured included overall time spent with the males, number of solicitations, contact-return latencies following male mounts, intromissions, and ejaculations; the frequency of entrances and exits from the male chamber, and frequency of mounts, intromissions, ejaculations. Sexual behavior was examined at session 1, session 5, and session 10. At test 5, females that received LID had a greater number of entrances/exits but spent significantly less time in the presence of the male during the copulatory bout than CNTL animals. These females also displayed a trend for longer contact return latencies s after ejaculations than VEH and CNTL groups. On session 10, females that received LID and subsequently switched to VEH treatment no longer differed from controls in entrance/exit numbers, time spent with males or ejaculation contact return latency. They did however, receive a greater number of intromissions and displayed shorter inter intromission intervals compared to CNTLs. We suggest that clitoral stimulation in the rat serves as both a reward signal and may contribute to the detection of differences in copulatory stimuli that are critical to pacing and potentially, the initiation of pregnancy. PMID- 24176774 TI - Identification of lysine succinylation substrates and the succinylation regulatory enzyme CobB in Escherichia coli. AB - Lysine succinylation is a newly identified protein post-translational modification pathway present in both prokaryotic and eukaryotic cells. However, succinylation substrates and regulatory enzyme(s) remain largely unknown, hindering the biological study of this modification. Here we report the identification of 2,580 bacterial lysine succinylation sites in 670 proteins and 2,803 lysine acetylation (Kac) sites in 782 proteins, representing the first lysine succinylation dataset and the largest Kac dataset in wild-type E. coli. We quantified dynamic changes of the lysine succinylation and Kac substrates in response to high glucose. Our data showed that high-glucose conditions led to more lysine-succinylated proteins and enhanced the abundance of succinyllysine peptides more significantly than Kac peptides, suggesting that glucose has a more profound effect on succinylation than on acetylation. We further identified CobB, a known Sir2-like bacterial lysine deacetylase, as the first prokaryotic desuccinylation enzyme. The identification of bacterial CobB as a bifunctional enzyme with lysine desuccinylation and deacetylation activities suggests that the eukaryotic Kac-regulatory enzymes may have enzymatic activities on various lysine acylations with very different structures. In addition, it is highly likely that lysine succinylation could have unique and more profound regulatory roles in cellular metabolism relative to lysine acetylation under some physiological conditions. PMID- 24176776 TI - Overexpression of pituitary tumor transforming gene (PTTG) is associated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma. AB - Pituitary tumor transforming gene (PTTG) is a newly identified proto-oncogene that has been shown to be aberrantly overexpressed in a subset of human cancers. The aim of the present study was to examine PTTG expression in patients with esophageal squamous cell cancer (ESCC) and explore its clinical significance. PTTG protein expression was analyzed in 108 archived, paraffin-embedded primary ESCC specimens by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Overexpression of PTTG was observed in 38.0% (41/108) of primary ESCC tissues and significantly correlated with differentiation, TNM stage, lymph node metastasis, and depth of invasion (P<0.05). Kaplan-Meier curves showed that ESCC patients with tumors expressing high levels of PTTG had substantially shorter overall survival compared with patients expressing low levels of PTTG (P=0.022, log-rank test). Cox multivariate regression analysis revealed that overexpression of PTTG was an independent prognostic factor in overall survival for ESCC patients (hazard ratio was 2.35, P=0.009). Overall, our data suggest that overexpression of PTTG may contribute to the malignant progression of ESCC and serve as a novel prognostic indicator for patients with ESCC. PMID- 24176777 TI - Nipple areola reconstructing reduction mammaplasty. AB - BACKGROUND: The pigment density and texture of breast skin are not uniform. Especially in patients with massive breasts, lower pole skin can be significantly darker and coarser than the upper pole skin. Nipple areola reconstructing (NAR) reduction mammaplasty is a technical modification of the "free nipple" procedure in which the original nipple areola complex (NAC) is discarded and the new NAC is reconstructed from coarse pigmented lower pole skin using a modified skate flap purse-string technique. OBJECTIVES: The authors review their initial clinical experience with NAR reduction mammaplasty. METHODS: Between 2010 and 2012, 16 patients (31 breasts) underwent the NAR procedure, and these cases were retrospectively reviewed for patient demographics, preoperative topographic breast measurements, amount of reduction per breast, and complications. The operative goal was to obtain the smallest breast size that can be achieved with tension-free wound closure. Patient satisfaction was also assessed. RESULTS: Breast reductions varied from 1150 to 2850 g/breast (average, 1590 g/breast), and patients were followed up for a minimum of 1 year (average, 15.9 months). No major local or systemic complications were encountered. Two patients required touch-ups for the correction of minor periareolar irregularities resulting mainly from the inversion of wound closure. At 1 year, average score for general satisfaction was 4.6, and the average score for NAC satisfaction was 3.9, on a scale from 1 (not satisfied) to 5 (extremely satisfied). CONCLUSIONS: NAR reduction mammaplasty enables the surgeon to perform massive reductions, design different non-NAC-bearing glandular pedicles for breast shaping, and obtain tension-free closure without the fear of ischemic complications. PMID- 24176778 TI - Treatment of a symptomatic trapezial dysplasia with metacarpal instability following thumb metacarpal lengthening with an addition-subtraction osteotomy. AB - The most important problem of trapezial dysplasia with thumb metacarpal instability is of bony origin. Together with the progressive capsuloligamentous decompensation it evolves in a progressive adduction deformity of the thumb metacarpal secondary to the dysplasia of the trapezium with its increased articular slope. The addition-subtraction osteotomy restores the anatomy combining two techniques: an abduction-extension osteotomy of the first metacarpal to correct the axis of the first metacarpal and an opening wedge osteotomy of the trapezium to reorientate the trapezial saddle. We present a case of an addition-subtraction osteotomy in a case of symptomatic trapezial dysplasia with metacarpal instability following a thumb metacarpal lengthening in a severely mutilated hand. This technique was especially effective in reducing the instability and pain but mainly in maintaining mobile the only remaining joint of the thumb. PMID- 24176779 TI - Reply to comment on "Efficacy of sublingual Lorazepam for prolonged convulsions beyond sub-Saharan Africa". PMID- 24176781 TI - Use of an intraoperative ultrasonography-guided localization and tissue fixation device demonstrates less margin positivity during breast-conserving surgery for invasive breast cancer than standard preoperative needle-wire localization: a retrospective comparative analysis in a consecutively treated case series. AB - PURPOSE: To retrospectively compare 2 methods of pre-resection, image-guided tumor localization-preoperative needle-wire localization (PNWL) and intraoperative ultrasonography-guided localization and tissue fixation (IUGLTF) for patients with invasive breast cancer at the time of breast-conserving surgery (BCS). PATIENTS AND METHODS: We identified 118 cases in which image-guided localization was required for nonpalpable and questionably palpable tumors from a series of 204 consecutive invasive breast cancers treated by BCS. We defined a positive margin as tumor at the inked surface. We defined a close margin as tumor within 1 mm or less of the inked surface. RESULTS: Of those 118 cases requiring pre-resection, image-guided localization, 54 patients underwent PNWL and 64 underwent IUGLTF placement. A positive margin was identified in 6 of 54 (11.1%) undergoing PNWL compared with 1 of 64 (1.6%) undergoing IUGLTF (P = .046). A positive or close margin was identified in 9 of 54 (16.7%) undergoing PNWL compared with 3 of 64 (4.7%) undergoing IUGLTF (P = .032). The mean volume and mean weight of the BCS specimens were not different in the 2 groups. CONCLUSION: Based on the finding of less margin positivity associated with the IUGLTF technique than the PNWL technique, we believe that the use of an IUGLTF device by surgeons during BCS could be highly advantageous in the surgical management of nonpalpable and questionably palpable invasive breast cancers. PMID- 24176780 TI - Predicting adherence of adults to a 12-month exercise intervention. AB - BACKGROUND: The purpose of this study was to (a) examine demographic, psychosocial, and physiological predictors of exercise adherence in a yearlong exercise intervention and (b) describe the trajectory of adherence over time. METHODS: Participants were 51 men and 49 women aged 40 to 75 years. The supervised and home-based intervention consisted of 60 minutes/day, 6 days/ week of moderate-to-vigorous intensity exercise. Three adherence measures were used: (1) minutes/week, (2) MET-hours/week, and (3) change in cardiopulmonary fitness (VO2max). Predictors of adherence were determined separately by sex using mixed models and multivariable regression. RESULTS: Participants performed 287 +/- 98 minutes/week of moderate-to-vigorous activity with 71% adhering to at least 80% (288 minutes/week) of the prescription. Men adhered better than women (P < .001). Among women, adiposity-related variables were significantly related to poorer adherence on all 3 measures (P < .05). A less consistent pattern was observed among men but in follow-up analyses, adiposity was associated with fewer MET hours/week of exercise. Social support, pain, and perceived benefits were predictive in some models. Men and nonobese women experienced peak adherence at 4 to 6 months, while obese women peaked during months 0 to 3. CONCLUSIONS: When provided with supervision and support, previously sedentary men and women can achieve and maintain high levels of aerobic activity. PMID- 24176782 TI - Success of different knee arthrodesis techniques after failed total knee arthroplasty: is there a preferred technique? AB - Arthrodesis is a widely accepted treatment for failed total knee arthroplasty when further revision is contraindicated. In this study, we retrospectively review the pre-operative characteristics, operation techniques, treatment plans, and eventual outcomes in 42 consecutive patients (43 knees) who underwent knee arthrodesis at a single institution. Femorotibial fusion was achieved in 30 cases (75.0%). No cases of implant failure were recorded. Post-operative complications occurred in 20 cases (46.5%). Repeat arthrodesis was performed in 4 cases, and 2 patients eventually required above-the-knee amputation. Comparing the cases with successful vs. unsuccessful outcomes, there was a significant difference in days until hospital discharge following arthrodesis (P = .026), mean erythrocyte sedimentation rate prior to arthrodesis (P = .012), and the proportion of patients with post-operative wound complications (P = .021). PMID- 24176783 TI - Measuring structure - What's the point in counting? PMID- 24176784 TI - 2013 SYR Accepted Poster Abstracts. AB - SYR 2013 Accepted Poster abstracts: 1. Benefits of Yoga as a Wellness Practice in a Veterans Affairs (VA) Health Care Setting: If You Build It, Will They Come? 2. Yoga-based Psychotherapy Group With Urban Youth Exposed to Trauma. 3. Embodied Health: The Effects of a Mind?Body Course for Medical Students. 4. Interoceptive Awareness and Vegetable Intake After a Yoga and Stress Management Intervention. 5. Yoga Reduces Performance Anxiety in Adolescent Musicians. 6. Designing and Implementing a Therapeutic Yoga Program for Older Women With Knee Osteoarthritis. 7. Yoga and Life Skills Eating Disorder Prevention Among 5th Grade Females: A Controlled Trial. 8. A Randomized, Controlled Trial Comparing the Impact of Yoga and Physical Education on the Emotional and Behavioral Functioning of Middle School Children. 9. Feasibility of a Multisite, Community based Randomized Study of Yoga and Wellness Education for Women With Breast Cancer Undergoing Chemotherapy. 10. A Delphi Study for the Development of Protocol Guidelines for Yoga Interventions in Mental Health. 11. Impact Investigation of Breathwalk Daily Practice: Canada?India Collaborative Study. 12. Yoga Improves Distress, Fatigue, and Insomnia in Older Veteran Cancer Survivors: Results of a Pilot Study. 13. Assessment of Kundalini Mantra and Meditation as an Adjunctive Treatment With Mental Health Consumers. 14. Kundalini Yoga Therapy Versus Cognitive Behavior Therapy for Generalized Anxiety Disorder and Co-Occurring Mood Disorder. 15. Baseline Differences in Women Versus Men Initiating Yoga Programs to Aid Smoking Cessation: Quitting in Balance Versus QuitStrong. 16. Pranayam Practice: Impact on Focus and Everyday Life of Work and Relationships. 17. Participation in a Tailored Yoga Program is Associated With Improved Physical Health in Persons With Arthritis. 18. Effects of Yoga on Blood Pressure: Systematic Review and Meta analysis. 19. A Quasi-experimental Trial of a Yoga based Intervention to Reduce Stress and Promote Health and Well-being Among Middle School Educators. 20. A Systematic Review of Yoga-based Interventions for Objective and Subjective Balance Measures. 21. Disparities in Yoga Use: A Multivariate Analysis of 2007 National Health Interview Survey Data. 22. Implementing Yoga Therapy Adapted for Older Veterans Who Are Cancer Survivors. 23. Randomized, Controlled Trial of Yoga for Women With Major Depressive Disorder: Decreased Ruminations as Potential Mechanism for Effects on Depression? 24. Yoga Beyond the Metropolis: A Yoga Telehealth Program for Veterans. 25. Yoga Practice Frequency, Relationship Maintenance Behaviors, and the Potential Mediating Role of Relationally Interdependent Cognition. 26. Effects of Medical Yoga in Quality of Life, Blood Pressure, and Heart Rate in Patients With Paroxysmal Atrial Fibrillation. 27. Yoga During School May Promote Emotion Regulation Capacity in Adolescents: A Group Randomized, Controlled Study. 28. Integrated Yoga Therapy in a Single Session as a Stress Management Technique in Comparison With Other Techniques. 29. Effects of a Classroom-based Yoga Intervention on Stress and Attention in Second and Third Grade Students. 30. Improving Memory, Attention, and Executive Function in Older Adults with Yoga Therapy. 31. Reasons for Starting and Continuing Yoga. 32. Yoga and Stress Management May Buffer Against Sexual Risk-Taking Behavior Increases in College Freshmen. 33. Whole-systems Ayurveda and Yoga Therapy for Obesity: Outcomes of a Pilot Study. 34. Women?s Phenomenological Experiences of Exercise, Breathing, and the Body During Yoga for Smoking Cessation Treatment. 35. Mindfulness as a Tool for Trauma Recovery: Examination of a Gender-responsive Trauma-informed Integrative Mindfulness Program for Female Inmates. 36. Yoga After Stroke Leads to Multiple Physical Improvements. 37. Tele-Yoga in Patients With Chronic Obstructive Pulmonary Disease and Heart Failure: A Mixed-methods Study of Feasibility, Acceptability, and Safety. 38. Effects of an Ashtanga Yoga based Health and Wellness Curriculum on Physical and Emotional Well-being, Engagement Toward School, and Academic Performance of K-6 Students. 39. Yoga as a Facilitator for Participation Following an 8-week Yoga for Individuals With Chronic Stroke. 40. Standardization of Design and Reporting of Yoga Interventions for Musculoskeletal Conditions: A Delphi Approach. 41. Creating S.P.A.C.E. Through Yoga: Africa Yoga Project Teachers Promote Personal Transformation, Peaceful Communities, and Purpose-filled Service. PMID- 24176785 TI - Regulation of the HIF-system in human macrophages--differential regulation of HIF alpha subunits under sustained hypoxia. AB - Macrophages are often associated to pathophysiological processes and were found at hypoxic areas. However, cell adaption greatly depends on hypoxia-inducible factors (HIF). Activation of these transcription factors is induced by heterodimerization of an alpha-(HIF-1alpha, -2alpha, -3alpha) and HIF-1beta subunit. The main regulatory pathway is represented by alpha-subunit stability. Beside, little is known about the exact mechanisms of fine-tuning in Hif regulation. The present study characterizes the hypoxia-induced regulation of HIF 1alpha and -2alpha in human macrophages. The hypoxic increase of both subunits is initially mediated by protein stabilization. Sustained hypoxia caused a distinct regulation of HIF-1alpha and -2alpha. The striking increase of HIF-2alpha protein expression was contrasted by a dramatic decrease of HIF-1alpha. The long-term downregulation of HIF-1alpha is due to downregulation of its mRNA. This decrease was accompanied by increased expression of ahif, a natural cis-antisense transcript of HIF-1alpha. The ahif-transcript was strongly inducible by hypoxia and rapidly degraded under reoxygenation. Using an adenoviral overexpression and siRNA silencing approach revealed that the targeted regulation of ahif is mediated by the HIF-system itself. Furthermore it could be shown that ahif indeed is able to modulate the hypoxic expression of HIF-1alpha and influences the expression of the HIF-target gene Enolase-2. Taken together, this study characterizes a new regulation process of the HIF-transcription factor-system in human macrophages under hypoxia. For the first time evidence is provided that ahif is regulated by the HIF-system and influences HIF-1alpha expression in primary human macrophages. PMID- 24176786 TI - A metaproteomic pipeline to identify newborn mouse gut phylotypes. AB - In order to characterize newborn mouse gut microbiota phylotypes in very early life stages, an original metaproteomic pipeline, based on LC-MS(2)-spectra and Mascot driven NCBI non-redundant repository database interrogation was developed. An original computational analysis assisted in the generation of a taxonomic gut architecture from protein hits to operational taxonomic units (OTUs) and related functional categories. Regardless of the mouse's genetic background, a prevalence of Firmicutes (Lactobacillaceae) and Proteobacteria (Enterobacteriaceae) was observed among the entire Eubacteria taxonomic node. However, a higher abundance of Firmicutes was retrieved for Balb/c gut microbiota compared to Rag2(ko) mice, the latter was mainly characterized by a Proteobacteria enriched microbiota. The metaproteomic-obtained OTUs were supported, for the identification (ID) of the cultivable bacteria fraction, corroborated by axenic culture-based MALDI-TOF MS IDs. Particularly, functional analysis of Rag2(ko) mice gut microbiota proteins revealed the presence of abundant glutathione, riboflavin metabolism and pentose phosphate pathway components, possibly related to genetic background. The metaproteomic pipeline herein presented may represent a useful tool to investigate the highly debated onset of the human gut microbiota in the first days of life, when the bacterial composition, despite its very low diversity (complexity), is still very far from an exhaustive description and other complex microbial consortia. BIOLOGICAL SIGNIFICANCE: The manuscript deals with a "frontier" topic regarding the study of the gut microbiota and the application of a metaproteomic pipeline to unveil the complexity of this fascinating ecosystem at the very early stages of life. Indeed during these phases, its diversity is very low but the bacterial content is highly "instable", and the relative balance between mucosal and fecal bacteria starts its dynamics of "fight" to get homeostasis. However, in the neonatal period, especially immediately after birth, a comprehensive description of this microbial eco-organ is still lacking, while it should be mandatory to highlight its first mechanisms of homeostasis and perturbation, while it co-develops with and within the host species. In order to unravel its low but almost unknown microbial community multiplicity, the newborn mouse gut, characterized by a "very" low complexity, was herein selected as model to design a LC-MS(2)-based shotgun metaproteomic approach, potentially suitable to study onset and shaping in human newborns. A microbiological semi-automatic computational analysis was performed to infer gut phylotypes; such as proof of evidence, related OTUs were compared to axenic-culture-based MALDI-TOF MS IDs showing consistency at family and phyla levels for the bacterial cultivable fraction. This article is part of a Special Issue entitled: Trends in Microbial Proteomics. PMID- 24176787 TI - Activation of Bothrops jararaca snake venom gland and venom production: a proteomic approach. AB - Viperidae venom glands have a basal-central lumen where the venom produced by secretory cells is stored. We have shown that the protein composition of venom gland changes during the venom production cycle. Here, we analyzed the venom gland proteins during the venom production cycle by proteomic approach. We identified specific proteins in each stage of the cycle. Protein species from endoplasmic reticulum (PDI and GPR78) and cytoplasm (actin, vimentin, tropomyosin, proteasome subunit alpha type-1, thioredoxin, and 40S ribosomal protein) are more abundant in the activated stage, probably increasing the synthesis and secretion of toxins. We also showed for the first time that many toxins are present in the secretory cells during the quiescent stage. C-type lectin-like and serine proteinases were more abundant in the quiescent stage, and GPIb-BP and coagulation factor IX/X were present only in this stage. Metalloproteinases, L-amino acid oxidases, PLA2 and snake venom metalloproteinase and PLA2 inhibitors, and disintegrins were more abundant in the activated stage. Regarding metalloproteinases, the presence of peptides corresponding to the pro domain was observed. These results allow us to better understand the mechanism of venom gland activation and venom production, contributing to studies about snake toxins and their diversity. BIOLOGICAL SIGNIFICANCE: In this study we identified, for the first time, the presence of different toxins in the snake venom gland in its quiescent stage. Furthermore, we showed that not all toxins are synthesized during the activated stage of the gland, suggesting an asynchronous synthesis for different toxins. Besides, the synthesis of some protein species from endoplasmic reticulum and cytoplasm, which are related to the synthesis and secretion processes, are more abundant in the activated stage of this gland. The knowledge of the proteomic composition of the venom gland in different stages of the venom production cycle will give us new insights into the mechanism of venom gland activation and venom production, contributing to studies about snake toxins and their diversity. PMID- 24176788 TI - Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition. AB - Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice (referred to as 3xTg AD/mtauKO mice). Therefore, this new model allows us to determine the pathological consequences of the murine tau. Here, we show that 3xTg-AD/mtauKO mice have lower tau loads in both soluble and insoluble fractions, and lower tau hyperphosphorylation level in the soluble fraction relative to 3xTg-AD mice. In the 3xTg-AD model endogenous mouse tau is hyperphosphorylated and significantly co-aggregates with human tau. Despite the deletion of the endogenous tau gene in 3xTg-AD/mtauKO mice, cognitive dysfunction was equivalent to 3xTg-AD mice, as there was no additional impairment on a spatial memory task, and thus despite increased tau phosphorylation, accumulation and NFTs in 3xTg-AD mice no further effects on cognition are seen. These findings provide better understanding about the role of endogenous tau to Alzheimer's disease (AD) pathology and for developing new AD models. PMID- 24176789 TI - Targeted therapies for squamous cell carcinoma of the head and neck: current knowledge and future directions. AB - Despite progress in the therapeutic management of patients with squamous cell carcinoma of the head and neck (SCCHN), the mortality rate of patients presenting with advanced disease remains high. One approach to improve treatment efficacy is to add novel molecular targeted agents to the classical treatment regimens. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have shown clinical benefits in palliative and curative settings. However, only a minority of patients presenting with recurrent or metastatic (R/M) SCCHN have meaningful tumor regression with these agents and virtually all who do develop acquired tumor resistance after a few months of treatment. For these reasons, other inhibitors of EGFR or molecules that interfere with known molecular pathways activated in SCCHN are of considerable interest, either as single agents or in combination with other treatment modalities. In this review, we discuss the different molecular therapeutic approaches explored in SCCHN. We also briefly outline new trial designs that could be used to accelerate the investigation of emerging therapeutic agents in this disease. PMID- 24176790 TI - The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. AB - Non-small cell lung cancer (NSCLC) accounts for >80% of lung cancer cases and currently has an overall five-year survival rate of only 15%. Patients presenting with advanced stage NSCLC die within 18-months of diagnosis. Metastatic spread accounts for >70% of these deaths. Thus elucidation of the mechanistic basis of NSCLC-metastasis has potential to impact on patient quality of life and survival. Research on NSCLC metastasis has recently expanded to include non-cancer cell components of tumors-the stromal cellular compartment and extra-cellular matrix components comprising the tumor-microenvironment. Metastasis (from initial primary tumor growth through angiogenesis, intravasation, survival in the bloodstream, extravasation and metastatic growth) is an inefficient process and few released cancer cells complete the entire process. Micro-environmental interactions assist each of these steps and discovery of the mechanisms by which tumor cells co-operate with the micro-environment are uncovering key molecules providing either biomarkers or potential drug targets. The major sites of NSCLC metastasis are brain, bone, adrenal gland and the liver. The mechanistic basis of this tissue-tropism is beginning to be elucidated offering the potential to target stromal components of these tissues thus targeting therapy to the tissues affected. This review covers the principal steps involved in tumor metastasis. The role of cell-cell interactions, ECM remodeling and autocrine/paracrine signaling interactions between tumor cells and the surrounding stroma is discussed. The mechanistic basis of lung cancer metastasis to specific organs is also described. The signaling mechanisms outlined have potential to act as future drug targets minimizing lung cancer metastatic spread and morbidity. PMID- 24176791 TI - Molecular and cellular biology of gonadotropes: an integrated view with new horizons. PMID- 24176792 TI - An alternative explanation of hypertension associated with 17alpha-hydroxylase deficiency syndrome. AB - The syndrome of 17alpha-hydroxylase deficiency is due to the inability to synthesize cortisol and is associated with enhanced secretion of both corticosterone and 11-deoxy-corticosterone (DOC). In humans, corticosterone and its 5alpha-Ring A-reduced metabolites are excreted via the bile into the intestine and transformed by anaerobic bacteria to 21-dehydroxylated products: 11beta-OH-progesterone or 11beta-OH-(allo)-5alpha-preganolones (potent inhibitors of 11beta-HSD2 and 11beta-HSD1 dehydrogenase). Neomycin blocks the formation of these steroid metabolites and can blunt the hypertension in rats induced by either ACTH or corticosterone. 3alpha,5alpha-Tetrahydro-corticosterone, 11beta hydroxy-progesterone, and 3alpha,5alpha-tetrahydro-11beta-hydroxy-progesterone strongly inhibit 11beta-HSD2 and 11beta-HSD1 dehydrogenase activity; all these compounds are hypertensinogenic when infused in adrenally intact rats. Urine obtained from a patient with 17alpha-hydroxylase deficiency demonstrated markedly elevated levels of endogenous glycyrrhetinic acid-like factors (GALFs) that inhibit 11beta-HSD2 and 11beta-HSD1 dehydrogenase activity (>300 times greater, and >400 times greater, respectively, than those in normotensive controls). Thus, in addition to DOC, corticosterone and its 5alpha-pathway products as well as the 11-oxygenated progesterone derivatives may play a previously unrecognized role in the increased Na(+) retention and BP associated with patients with 17alpha hydroxylase deficiency. PMID- 24176793 TI - The trends and the risk of type 1 diabetes over the past 40 years: an analysis by birth cohorts and by parental migration background in Sweden. AB - OBJECTIVE: To investigate the trends and the risk of developing type 1 diabetes in the offspring of Swedes and immigrants by specific parental migration background, age, sex and birth cohort. DESIGN: Registry-based cohort study. SETTING: Using Swedish nationwide data we analysed the risk of developing type 1 diabetes in 3 457 486 female and 3 641 304 male offspring between 0 and 30 years of age, born to native Swedes or immigrants and born and living in Sweden between 1969 and 2009. We estimated incidence rate ratios (IRRs) with 95% CIs using Poisson regression models. We further calculated age-standardised rates (ASRs) of type 1 diabetes, using the world population as standard. RESULTS: We observed a trend of increasing ASRs among offspring below 15 years of age born to native Swedes and a less evident increase among offspring of immigrants. We further observed a shift towards a younger age at diagnosis in younger birth cohorts in both groups of offspring.Compared with offspring of Swedes, children (0-14 years) and young adults (15-30 years) with one parent born abroad had an overall 30% and 15-20% lower IRR, respectively, after multivariable adjustment. The reduction in IRR was even greater among offspring of immigrants if both parents were born abroad. Analysis by specific parental region of birth revealed a 45-60% higher IRR among male and female offspring aged 0-30 years of Eastern Africa. CONCLUSIONS: Parental country of birth and early exposures to environmental factors play an important role in the aetiology of type 1 diabetes. PMID- 24176794 TI - Adherence to antiretroviral drug therapy in adult patients who are HIV-positive in Northwest Ethiopia: a study protocol. AB - INTRODUCTION: Achievement of optimal medication adherence and management of antiretroviral toxicity pose great challenges among Ethiopian patients with HIV/AIDS. There is currently a lack of long-term follow-up studies that identify the barriers to, and facilitators of, adherence to antiretroviral therapy (ART) in the Ethiopian setting. Therefore, we aim to investigate the level of adherence to ART and a wide range of potential influencing factors, including adverse drug reactions occurring with ART. METHODS AND ANALYSIS: We are conducting a 1-year prospective cohort study involving adult patients with HIV/AIDS starting on ART between December 2012 and March 2013. Data are being collected on patients' appointment dates in the ART clinics. Adherence to ART is being measured using pill count, medication possession ratio and patient's self-report. The primary outcome of the study will be the proportion of patients who are adherent to their ART regimen at 3, 6 and 12 months using pill count. Taking 95% or more of the dispensed ART regimen using pill count at given points of time will be considered the optimal level of adherence in this study. Data will be analysed using descriptive and inferential statistical procedures. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Tasmania Health and Medical Human Research Ethics Committee and Bahir-Dar University's Ethics Committee. The results of the study will be reported in peer-reviewed scientific journals, conferences and seminar presentations. PMID- 24176795 TI - The increased risks of death and extra lengths of hospital and ICU stay from hospital-acquired bloodstream infections: a case-control study. AB - OBJECTIVES: Hospital-acquired bloodstream infections are known to increase the risk of death and prolong hospital stay, but precise estimates of these two important outcomes from well-designed studies are rare, particularly for non intensive care unit (ICU) patients. We aimed to calculate accurate estimates, which are vital for estimating the economic costs of hospital-acquired bloodstream infections. DESIGN: Case-control study. SETTING: 9 Australian public hospitals. PARTICIPANTS: All the patients were admitted between 2005 and 2010. PRIMARY AND SECONDARY OUTCOME MEASURES: Risk of death and extra length of hospital stay associated with nosocomial infection. RESULTS: The greatest increase in the risk of death was for a bloodstream infection with methicillin resistant Staphylococcus aureus (HR=4.6, 95% CI 2.7 to 7.6). This infection also had the longest extra length of stay to discharge in a standard bed (12.8 days, 95% CI 6.2 to 26.1 days). All the eight bloodstream infections increased the length of stay in the ICU, with longer stays for the patients who eventually died (mean increase 0.7-6.0 days) compared with those who were discharged (mean increase: 0.4-3.1 days). The three most common organisms associated with Gram negative infection were Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia. CONCLUSIONS: Bloodstream infections are associated with an increased risk of death and longer hospital stay. Avoiding infections could save lives and free up valuable bed days. PMID- 24176796 TI - Estimation of net muscle volume in patients with muscular dystrophy using muscle CT for prospective muscle volume analysis: an observational study. AB - OBJECTIVES: Muscle volume in patients with muscle disease is an index of disease progression. The aim of this study was to demonstrate a new method of muscle volumetry using CT of thigh muscles. DESIGN: Observational study. PARTICIPANTS: (1) For muscle volumetry using CT and dual-energy X-ray absorptiometry (DXA), 13 patients with muscle disease participated. (2) For prospective CT volumetry, 12 patients participated over 4 years. PRIMARY AND SECONDARY OUTCOME MEASURES: To establish the new CT volumetry, the results of which were correlated with the muscle mass calculated from DXA (primary outcome). To show the decrease in muscle volume using our method over 4 years (secondary outcome) METHODS: (1) Helical CT imaging of the thigh was performed. CT images were analysed by applying estimated functions, and the accumulation of outcomes resulted in muscle volumes. We refer to this method as 'net muscle volumetry'. Simultaneously, DXA was performed in these patients, and the muscle mass of the thigh was calculated with vendor provided software. (2) To evaluate longitudinal changes in muscle volume, net muscle volumetry at the 14 cm section of the middle part of the thigh was performed repeatedly over a 4-year period. RESULTS: (1) Volumes of the thigh muscle on one side were calculated to be 300-3400 cm(3) using CT. Muscle mass of the thigh was calculated from DXA to be 1100-5000 g. These results correspond closely, with a Pearson correlation coefficient of 0.993. (2) Thigh net muscle volumes of seven patients with gait disturbance decreased over the 4-year study period (p<0.01). CONCLUSIONS: A method of measuring net muscle volume using CT, which was validated by muscle mass calculated from DXA, was developed. Decrements in net muscle volume over 4 years support the reliability of this method. This less arbitrary method is suitable for assessment of muscle volume in patients with muscular dystrophy. PMID- 24176797 TI - The effect of a glucagon-like peptide-1 receptor agonist on glucose tolerance in women with previous gestational diabetes mellitus: protocol for an investigator initiated, randomised, placebo-controlled, double-blinded, parallel intervention trial. AB - INTRODUCTION: Pregnancy is associated with decreased insulin sensitivity, which is usually overcome by a compensatory increase in insulin secretion. Some pregnant women are not able to increase their insulin secretion sufficiently, and consequently develop gestational diabetes mellitus (GDM). The disease normally disappears after delivery. Nevertheless, women with previous GDM have a high risk of developing type 2 diabetes (T2D) later in life. We aim to investigate the early development of T2D in women with previous GDM and to evaluate whether treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, may modify their risk of developing T2D. METHODS AND ANALYSES: 100 women with previous GDM will be randomised to either liraglutide or placebo treatment for 1 year (blinded) with an open-label extension for another 4 years. Additionally, 15 women without previous GDM will constitute a baseline control group. Women will be tested with an oral glucose tolerance test (primary endpoint: area under the curve for plasma glucose) and an isoglycaemic intravenous glucose infusion at baseline, after 1 year and after 5 years. Additional evaluations include a glucagon test, dual-energy X-ray absorptiometry, imaging of the liver (ultrasound elastography and fibroscanning), an ad libitum meal for food intake evaluation and questionnaires related to appetite, quality of life and alcohol consumption habits. ETHICS AND DISSEMINATION: The protocol has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark, and the Danish Data Protection Agency and will be carried out under the surveillance and guidance of the GCP unit at Copenhagen University Hospital Bispebjerg in compliance with the ICH-GCP guidelines and in accordance with the Helsinki Declaration. Positive, negative and inconclusive results will be published at scientific conferences and as one or more scientific manuscripts in peer-reviewed journals. REGISTRATIONS: The trial is registered at https://eudract.ema.europa.eu (2012-001371-37) and http://www.clinicaltrials.gov (NCT01795248). PMID- 24176799 TI - Incubation pit analysis and calculation of the hydrodynamic impact pressure from the implosion of an acoustic cavitation bubble. AB - An experimental study to evaluate cavitation bubble dynamics is conducted. The aim is to predict the magnitude and statistical distribution of hydrodynamic impact pressure generated from the implosion of various individual acoustic cavitation bubbles near to a rigid boundary, considering geometrical features of the pitted area. A steel sample was subjected to cavitation impacts by an ultrasonic transducer with a 5mm diameter probe. The pitted surface was then examined using high-precision 3D optical interferometer techniques. Only the incubation period where surface is plastically deformed without material loss is taken into account. The exposure time was adjusted in the range of 3-60 s to avoid pit overlapping and a special procedure for pit analysis and characterisation was then followed. Moreover, a high-speed camera device was deployed to capture the implosion mechanisms of cavitation bubbles near to the surface. The geometrical characteristics of single incubation pits as well as pit clusters were studied and their deformation patterns were compared. Consequently, a reverse engineering approach was applied in order the hydrodynamic impact pressure from the implosion of an individual cavitation bubble to be determined. The characteristic parameters of the cavitation implosion process such as hydrodynamic impact pressure and liquid micro-jet impact velocity as well as the hydrodynamic severity of the cavitation impacts were quantified. It was found that the length of the hypotenuse of the orthographic projections from the center of the pit, which basically represents the deformed area of the pit, increases with the hydrodynamic impact aggressiveness in a linear rate. Majority of the hydrodynamic impacts were in the range of 0.4-1 GPa while the corresponding micro jet velocities were found to be in the range of 200-700 m/s. Outcomes of this study, contribute to further understanding the cavitation intensity from the implosion of acoustically generated bubbles and could certainly represent a significant step towards developing more accurate cavitation models. PMID- 24176798 TI - Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions. AB - OBJECTIVE: Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions. DESIGN: Cross-sectional design. SETTING: Hospital-based and community-based screening settings. PARTICIPANTS: A hospital-based deviation cohort of 3172 participants to evaluate test performance and a community-based validation cohort of 3621 to verify the findings. INTERVENTIONS: Three types of stool tests with bidirectional endoscopy as the reference standard. OUTCOMES: Sensitivity, specificity and positive and negative likelihood ratios. RESULTS: For detecting upper gastrointestinal lesions in cases with negative immunochemical tests, the sensitivity, specificity, and positive and negative likelihood ratios of the guaiac-based and H pylori antigen tests were 16.3% (95% CI 13.3% to 19.8%), 90.1% (88.9% to 91.2%), 1.64 (1.31 to 2.07), and 0.93 (0.89 to 0.97), respectively, and 52.5% (48.1% to 56.9%), 80.6% (79.0% to 82.1%), 2.71 (2.41 to 3.04) and 0.59 (0.54 to 0.65), respectively. For detecting upper gastrointestinal lesions in cases with normal colonoscopy, the results of the guaiac-based and H pylori antigen tests were 17.9% (14.8% to 21.5%), 90.1% (88.9% to 91.2%), 1.81 (1.45 to 2.26) and 0.91 (0.87 to 0.95), respectively, and 53.1% (48.6% to 57.4%), 80.7% (79.1% to 82.2%), 2.75 (2.45 to 3.08) and 0.58 (0.53 to 0.64), respectively. Within the community, positive predictive values of the immunochemical and H pylori antigen tests were 36.0% (26.0% to 46.0%) and 31.9% (28.3% to 35.5%), respectively, for detecting lower and upper gastrointestinal lesions, which were similar to expected values. CONCLUSIONS: The H pylori stool antigen test is more accurate than the guaiac based test in the screening of upper gastrointestinal lesions in a population with high prevalence of H pylori infection and upper gastrointestinal lesions. It is applicable to add the H pylori antigen test to the immunochemical test for pan detection. TRIAL REGISTRATION: NCT01341197 (ClinicalTrial.gov). PMID- 24176800 TI - Sector activities and lessons learned around initial implementation of the United States national physical activity plan. AB - BACKGROUND: National plans are increasingly common but infrequently evaluated. The 2010 United States National Physical Activity Plan (NPAP) provided strategies to increase population levels of physical activity. This paper describes (i) the initial accomplishments of the NPAP sector teams, and (ii) results from a process evaluation to determine how the sectors operated, their cross-sector collaboration, challenges encountered, and positive experiences. METHODS: During 2011, a quarterly reporting system was developed to capture sector-level activities. A year-end interview derived more detailed information. Interviews with 12 sector leads were recorded, transcribed verbatim, and analyzed for common themes. RESULTS: The 6 sectors worked on goals from the implementation plan that focused broadly on education, promotion, intervention, policy, collaboration, and evaluation. Through year-end interviews, themes were generated around operations, goal setting, and cross-sector collaboration. Challenges to the NPAP work included lack of funding and time, the need for marketing and promotion, and organizational support. Positive experiences included collaboration, efficiency of work, enhanced community dynamic, and accomplishments toward NPAP goals. CONCLUSIONS: These initial results on the NPAP sector teams can be used as a baseline assessment for future monitoring. The lessons learned may be useful to other practitioners developing evaluations around state- or national-level plans. PMID- 24176802 TI - Surface deformations as a necessary requirement for resistance switching at the surface of SrTiO3:N. AB - Atomic force microscopy (AFM), conductive AFM and electrochemical strain microscopy were used to study the topography change at the defect surface of SrTiO3:N, breakdown in the electrical conduction of the tip/sample/electrode system and ionic motion. The IV curves show resistance switching behavior in a voltage range +/-6 V < U <+/- 10 V and a current of maximum +/-10 nA. A series of sweeping IV curves resulted in an increase in ionically polarized states (surface charging), electrochemical volume (surface deformations) and sequential formations of stable surface protrusions. The surface deformations are reversible (U <+/- 5 V) without IV pinched hysteresis and remained stable during the resistance switching (U >+/- 6 V), revealing the additional necessity (albeit insufficient due to 50% yield of working cells) of surface protrusion formation for resistance switching memory. PMID- 24176801 TI - Shape in migration: quantitative image analysis of migrating chemoresistant HCT-8 colon cancer cells. AB - Unsuccessful cytotoxic anticancer treatments may contribute to tumor morphologic instability and consequent tissue invasion, promoting the selection of a more malignant phenotype. Indeed, morphological changes have been demonstrated to be more pronounced in strongly vs. weakly metastatic cells. By means of normalized bending energy, we have previously quantitatively defined the link between cell shape modifications and the acquisition of a more malignant phenotype by 5-FU resistant colon cancer cells (HCT-8FUres). Such changes were significantly correlated with an increase in motility speed. Herein, we propose a method to quantitatively analyze the shape of wild and chemoresistant HCT-8 migration front cells during wound healing assay. We evaluated the reliability of parameters (area/perimeter ratio [A/p], circularity, roundness, fractal dimension, and solidity) in describing the biological behavior of the two cell lines, enabling hence in distinguishing the chemoresistant line from the other one. We found solidity index the parameter that better described the difference between chemoresistant and wild cells. Moreover, solidity is able to capture the differences between chemoresistant and wild cells at each time point of the migration process. Indeed, motility speed was found to be inversely correlated with solidity, a quantitative index of cell deformability. Deformability is an outstanding hallmark of the process leading to metastatic spread; consequently, solidity may be considered a marker of acquired metastatic property. PMID- 24176803 TI - What do we know today about the prospective long-term course of social anxiety disorder? A systematic literature review. AB - While we know that social anxiety disorder (SAD) is today's most common anxiety disorder knowledge on its prospective long-term course is sparse. We conducted a systematic literature search using databases Medline and PsycINFO for naturalistic and psychotherapy outcome studies with follow-up durations of at least 24 months. Four naturalistic cohorts and nine psychotherapy trials were included in the review. The naturalistic course in clinical was less favorable than in non-clinical samples (27% vs. 40% recovery rate after 5 years). Psychotherapy trials, all applying (cognitive) behavioral methods, yielded stable outcomes with overall large pre- to follow-up effect sizes on self-report scales. Observer rated remission rates varied considerably (36% to 100%) depending on study design and follow-up length. The results of psychotherapy trials and that of naturalistic studies can hardly be compared due to differences in methodology. More standardized remission and recovery criteria are needed to enhance the understanding of the longitudinal course. PMID- 24176804 TI - Longitudinal course of anxiety sensitivity and PTSD symptoms in cognitive behavioral therapies for PTSD. AB - Anxiety sensitivity (AS) has been conceptualized as trait-like vulnerability and maintenance factor for PTSD. Although recent literature has demonstrated its malleability during treatment, few have examined its influence on and effect from PTSD treatment. Using multilevel regression analyses we examined: (a) changes in AS during treatment and (b) whether pre-treatment AS predicted PTSD treatment response, in sample of female victims of interpersonal trauma receiving one of three treatments (cognitive processing therapy, cognitive processing therapy cognitive, and written accounts). Participants exhibited reductions in total ASI scores from pre- to post-treatment. Growth curve modeling revealed slightly different trajectories of PTSD symptoms as a function of pre-treatment AS, and overall decreases in PTSD symptoms during treatment were not associated with pretreatment AS. Pretreatment AS dimensions impacted PTSD total scores and symptoms clusters differentially. Clinical and theoretical implications for these results are discussed. PMID- 24176805 TI - The role of sleep disturbance in the relationship between post-traumatic stress disorder and suicidal ideation. AB - We tested if the risk of suicidal ideation in individuals with PTSD symptoms was dependent on comorbid sleep disturbance. Our cross-sectional sample included 2465 participants with complete data from the 21 year follow-up of the Mater University Study of Pregnancy (MUSP), a birth cohort study of young Australians. Using structural equation modelling with indirect pathways we found that 12 month PTSD symptoms did not directly predict suicidal ideation at 21 when adjusting for major depression symptoms, polyvictimization and gender. However, PTSD symptoms had an indirect effect on suicidal ideation via past-month sleep disturbance. Our results suggest that increased suicidal ideation in those with PTSD may result from the fact that PTSD sufferers often exhibit other comorbid psychiatric conditions which are themselves known to predict suicidal behaviours. Sleep disturbance may be targeted in those who experience PTSD to help prevent suicidal ideation. PMID- 24176806 TI - Unstaged versus staged posterior-only thoracolumbar fusions in deformity: a retrospective comparison of perioperative complications. AB - BACKGROUND CONTEXT: Improvements in surgical techniques and medical support have made reconstruction of adult scoliosis more feasible. In an attempt to reduce the risk of complications, some surgeons have chosen to stage these procedures. PURPOSE: We sought to compare a staged group versus an unstaged group of patients undergoing posterior-only instrumentation and fusion from the thoracic spine to the pelvis by a single surgeon for degenerative kyphoscoliosis or residual, progressive adolescent idiopathic scoliosis to assess for a difference in complications. STUDY DESIGN/SETTING: Retrospective chart review. PATIENT SAMPLE: We included 143 consecutive patients treated between January 1, 2000, and December 31, 2010. OUTCOME MEASURE: The primary outcome assessed was perioperative complications. Secondary outcomes included intraoperative blood loss, intraoperative transfusions, ICU stay, and disposition. METHODS: After institutional review board approval, records were analyzed to identify comorbidities and determine whether the management of each patient was planned in an unstaged or staged fashion. "Failures" were identified in which the plan was for an unstaged procedure but were converted to a staged procedure. Complications were defined as unplanned additional procedures or unexpected medical outcomes within 90 days of surgery. We considered p<.005 to be significant. RESULTS: Fifty two patients underwent planned staged surgery and 90 underwent planned unstaged surgical procedures. Baseline demographics including American Society of Anesthesiologists (ASA) score, body mass index, and preoperative diabetic and cardiac status were not different between the two groups. Age was greater in the staged group (68 vs. 63 y; p=.001). Intraoperative transfusion and invasiveness index as defined by Mirza, were also higher in the staged group (p<.005). No difference was identified between the two intent-to-treat groups for complications including infection rate, death, myocardial infarction, stroke, pulmonary embolism, other pulmonary complication, or blindness. Eleven of the 90 unstaged patients were unable to have their surgical procedure completed at the time of the index procedure. The 11 "failures" demonstrated a higher ASA compared with the 79 successfully treated unstaged procedures (p<.005), although no differences in complications. CONCLUSIONS: There were no differences in complications between the intent-to-treat groups of staged and unstaged procedures, nor was there a difference comparing the "failures" of unstaged care to successful unstaged patients. Although fraught with potential complications, both techniques may be reasonable approaches. PMID- 24176807 TI - Paraspinal desmoid-type fibromatosis as a cause of low back pain. PMID- 24176809 TI - Successful conservative management of an intrathecal catheter-associated inflammatory mass. PMID- 24176808 TI - Bone morphogenetic protein-7 antagonizes tumor necrosis factor-alpha-induced activation of nuclear factor kappaB and up-regulation of the ADAMTS, leading to decreased degradation of disc matrix macromolecules aggrecan and collagen II. AB - BACKGROUND CONTEXT: Tumor necrosis factor-alpha (TNF-alpha) is a regulatory cytokine that can increase the activity of enzymes such as ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), which degrade disc matrix. ADAMTS are enzymes that break down disc matrix and thereby mediate disc degeneration. Bone morphogenetic protein-7 (BMP-7), on the other hand, stimulates synthesis of the disc extracellular matrix and is a potential therapeutic molecule for the treatment of disc degeneration. However, the effects of BMP-7 on TNF-alpha and ADAMTS are unknown. PURPOSE: We investigated the effects of BMP-7 on the catabolic regulators such as TNF-alpha and ADAMTS and evaluated the molecular mechanism by which BMP-7 affects the catabolic regulators. STUDY DESIGN: This was an in vitro study in which we used human intervertebral disc cells cultured in alginate beads. METHODS: Human intervertebral disc cells were cultured in alginate beads, and treated with TNF-alpha, or TNF- alpha plus BMP-7, pharmacological inhibitor of ERK1/2 (U0126), p38 (SB203580), or NFkappaB (BAY 11 7082). The mRNA levels of target genes were measured by real-time polymerase chain reaction, and the protein levels were determined by the Western blots. The nuclear factor (NF)kappaB activity was analyzed by measured phosphorylation and nuclear translocation of the NFkappaB protein p65. RESULTS: TNF-alpha activated NFkappaB signaling and induced up-regulation of the catabolic regulators ADAMTS-4 and ADAMTS-5, contributing to degradation of the disc matrix macromolecules aggrecan and collagen II. BMP-7 antagonized the TNF-alpha-induced activation of NFkappaB protein p65 and blocked TNF-alpha-induced up-regulation of ADAMTS-4 and ADAMTS-5, leading to reversing TNF-alpha-mediated degradation of aggrecan and collagen II. Moreover, BMP-7 antagonized the TNF-alpha-induced activation of NFkappaB signaling by suppressing phosphorylation and nucleus translocation of NFkappaB protein p65. CONCLUSION: BMP-7 antagonizes TNF-alpha-induced activation of NFkappaB and up-regulation of ADAMTS, leading to decreased degradation of disc matrix macromolecules. These data indicate that BMP-7 has a dual mechanism of action on disc metabolism: (1) the previously well-described positive effect on disc matrix synthesis and (2) an anticatabolic effect that is described here. This understanding is important as BMP-7 is being considered for treatment of disc degeneration. PMID- 24176810 TI - The influence of cervical spinal cord compression and vertebral displacement on somatosympathetic reflexes in the rat. AB - BACKGROUND CONTEXT: One theory within chiropractic proposes that vertebral subluxation in the upper cervical region induces spinal cord compression sufficient to alter spinal cord efferent output. We report on the feasibility of three different experimental approaches to test this theory. METHODS: A high threshold electrical-evoked somatosympathetic reflex was recorded in adrenal or renal nerves of 10 anaesthetized adult male rats before and after (1) graded pressure was applied directly to the C1/C2 spinal cord segment in eight rats by the use of either direct compression or inflation of an extradural balloon and (2) displacement, less than a dislocation applied posterior to anterior, to the C2 vertebra in two rats. The latency and amplitude of the pre- and postintervention reflex responses were compared. RESULTS: The reflex amplitude was not significantly changed by pressure (26 mmHg) from an extra-dural balloon or direct compression of the dura mater onto the dorsal spinal cord. Additional pressure, at least sufficient to occlude the dorsal vessels, induced a significant reduction in the amplitude of the reflex, and this reduction persisted for 20 minutes after removal of the pressure (Dunn's method for all pairwise multiple comparison Q stat=3.437; critical value for k=6 with alpha=0.05 is 2.936). Maximal vertebral (C2) displacement (4 mm), without dislocation did not induce significant changes compared with the control period. CONCLUSIONS: Although this feasibility study suggests it is unlikely that upper cervical vertebral subluxation, displacement less than a dislocation, compromises the sympathetic outflow in the adrenal or renal nerves, further vertebral displacement studies are necessary to formally test this. PMID- 24176811 TI - Delayed hinge fracture after plate-augmented, cervical open-door laminoplasty and its clinical significance. AB - BACKGROUND CONTEXT: Among the various forms of laminoplasty fixation, plate augmentation provides a semirigid arch reconstruction and is gaining popularity as the result of its safety and effectiveness. However, the effects of this procedure on hinge status and subsequent bony healing remain unclear. PURPOSE: We sought to evaluate the status and time course of bony healing of the hinge gutter and to determine the effect on postoperative clinical course of plate-only, open door cervical laminoplasty. STUDY DESIGN: This was a retrospective clinical series. PATIENT SAMPLE: A total of 79 adult men and women undergoing cervical laminoplasty in a university hospital setting were studied. OUTCOME MEASURES: Time-dependent changes in hinges observed on computed tomography (CT) were used to measure the radiological outcome. A numerical rating scale of axial neck pain and arm pain was used to evaluate the clinical outcome. METHODS: Patients who underwent plate-only, open-door laminoplasty for cervical myelopathy and had available postoperative CT scans were enrolled in this study. Neck pain intensity before and 1 year after surgery was assessed with questionnaires. CT scans (n=125) obtained after surgery were assessed in terms of bony healing of the hinge. RESULTS: Most of the hinges were initially well-bent. Only 9% were found to be "fractured" or "in danger of fracture" at 1 week. Primary healing without callus formation, which is the next step of bony healing of well-bent hinges, was observed in 62% of cases at month 4. The remaining 38% were classified as "fractured" or in the process of "secondary healing." A similar number of hinges was classified as "secondarily healed" after 1 or 2 years of follow-up. All except one hinge were well united and incorporated at the final follow-up, and the number of hinges classified as "fractured or secondarily healed" related to postoperative axial neck pain with respect to the 1-year visual analog scale for the neck and the Neck Disability Index. CONCLUSIONS: Although plate-only, open door laminoplasty is a safe and reliable surgery for decompression of multilevel cervical disease, the fixation that it provides on the open side may not be sufficiently stable to allow successful primary healing. Additional attention should be paid to the hinged side to prevent delayed fracture in the early postoperative period and to reduce postoperative axial pain. PMID- 24176812 TI - Efficacy and safety of peginterferon plus ribavirin for patients aged >= 65 years with chronic hepatitis C: a systematic review and meta-analysis. AB - METHODS: Studies up to August 30, 2012 of the efficacy and safety of peginterferon plus ribavirin therapy in CHC patients aged>=65 years were systematically identified in PubMed, Ovid, Web of Knowledge and Cochrane Library databases. A meta-analysis was performed using both fixed- and random-effects models based on heterogeneity across studies. RESULTS: The overall sustained virological response (SVR) in CHC patients aged>=65 years was significantly lower than in patients aged<65 years on both intention-to-treat (ITT; 42.0% vs. 60.1%, respectively; P<0.00001) and per-protocol (PP; 54.4% vs. 67.4%, respectively; P=0.002) analyses, including treatment-naive patients. Subgroup analysis showed that patients>=65 years with either hepatitis C virus (HCV) genotype 1/4 or 2/3 had lower SVR rates than younger patients. No statistically significant differences were observed between the two groups in terms of rapid virological response (RVR) and early virological response (EVR) rates (both P>=0.05). However, the end-of-treatment virological response (ETR) rate was lower in patients>=65 years, who also had a significantly higher risk of relapse than those aged<65 years (39.8% vs. 26.9%, respectively; P<0.00001). The discontinuation rate in the older patients was also significantly higher than in the younger patients (25.5% vs. 14.8%, respectively; P<0.00001). Ribavirin dose reduction in the older patients treated with peginterferon plus ribavirin was also significantly higher than in younger patients (44.5% vs. 32.8%, respectively; P<0.00001). CONCLUSION: Peginterferon plus ribavirin therapy was effective for older patients with CHC, particularly those with HCV genotype 2/3. Response-guided therapy can be used for older patients with genotype 1/4, but such patients had poorer treatment adherence, leading to poorer treatment efficacy. PMID- 24176813 TI - Neuroendocrine tumor of the small intestine. PMID- 24176814 TI - Mean platelet volume is not a predictive marker of histopathological changes of the liver in patients with chronic hepatitis B. PMID- 24176815 TI - Role of allelochemicals in plant growth promoting rhizobacteria for biocontrol of phytopathogens. AB - Soil borne fungal diseases pose serious constraints on agro-productivity. Biological control is non-hazardous strategy to control plant pathogens and improve crop productivity. PGPR (plant growth promoting rhizobacteria) have long been used as plant disease control agents. PGPR produced a wide range of secondary compounds that may act as signals--that is, allelochemicals that include metabolites, siderophores, antibiotics, volatile metabolites, enzymes and others. Their mode of action and molecular mechanisms provide a great awareness for their application for crop disease management. The present review highlights the role of PGPR strains, specifically referring to allelochemicals produced and molecular mechanisms. Further research to fine tune combinations of allelochemicals, plant-microbe-pathogen interaction will ultimately lead to better disease control. PMID- 24176816 TI - Diversity of Candida zemplinina isolates inferred from RAPD, micro/minisatellite and physiological analysis. AB - Among non-Saccharomyces wine yeasts, Candida zemlpinina is one of the frequently isolated and oenologically important species. It is mostly known from European winemaking areas and it has become one of the key species of non-Saccharomyces wine yeasts to study. Investigating the diversity of C. zemplinina isolates is important for a deeper understanding of the non-Saccharomyces wine yeasts and for the yeast starter industry, as numerous researches have pointed to the potential use of this species in winemaking. For assessing the biodiversity of a larger number of strains, RAPD and micro/minisatellite PCR is often the method of choice, however, this technique is often unstandardized. Whereas some laboratories use these methods for species identifications, others apply RAPD primers for determining intraspecies diversity. In this study, we have tested 5 different RAPD and micro/minisatellite primers on strains of C. zemplinina isolated from different locations. We show that after a rigorous PCR-optimization aimed at reproducibility and comparability of band patterns with these PCR reactions, diversity of different strains from a wide range of geographic locations is relatively low. The analysis of several oenologically important physiological traits of the strains showed a relatively low level of diversity as well. We also demonstrate that the intraspecific diversity of C. zemplinina observable with different techniques (RAPD, micro/minisatellite or physiological analysis) may be fairly different and not necessarily comparable. PMID- 24176817 TI - Probiotics-pathogen interactions elicit differential regulation of cutaneous immune responses in epidermal cells of Atlantic cod Gadus morhua. AB - Little is known on the cutaneous immune responses during probiotics-pathogen interactions in fish. Thus, this study employed Atlantic cod primary epidermal (EP) cell cultures as a model to understand this interaction. The probiotics pathogen interactions in the EP cell cultures were elucidated using Vibrio anguillarum 2133 (VA) as the pathogen and two host-derived bacteria (GP21 and GP12) as the probiotics. There was a regional size difference on the EP cells; i.e., EP cells from the dorsal region were significantly larger than the EP cells at the ventral side. VA significantly decreased viability of EP cells. In the presence of probiotics, this inhibition was mitigated. The probiotics reduced VA induced cellular apoptosis and the probiotics-pathogen interactions influenced cellular myeloperoxidase activity during the latter stage of co-incubation. The probiotics-pathogen interactions triggered differential regulation of immune related genes and the effects of the interaction were dependent on the region where the cells were isolated and the length of the co-incubation period. In most cases, the presence of probiotics alone showed no significant change on the mRNA level of immune genes in the EP cells but triggered immunostimulatory activity when incubated with VA. This study showed that the virulence of VA in EP cells could be modulated by host-derived probiotics and the immunomodulatory characteristics of the two candidate probionts advanced their immune-related probiotic potential. PMID- 24176818 TI - Modulatory effects of deltamethrin-exposure on the immune status, metabolism and oxidative stress in gilthead seabream (Sparus aurata L.). AB - Deltamethrin, a sintetic pyrethroid, is the insecticide that has been replacing recently to others like organochlorines, organophosphates and carbamates which are less toxic for birds and mammals, although, unfortunately, all of them are highly toxic to various non-targeted aquatic organisms including fish. In the present study, the consequences of the exposition of gilthead seabream (Sparus aurata L.) specimens to sublethal bath dose of deltamethrin (0.1 ppb) on organo somatic indexes, immunity, seric metabolic parameters, oxidative stress and liver histology were determined after 1, 3, 7 and 14 days of exposure. Deltamethrin alters gilthead seabream immune status, the hepato-somatic index and various seric metabolic parameters since the first exposure day while important progressive deleterious morphological changes in liver were also observed. However, no statistically significant deviation was detected in the expression of oxidative stress-related genes whilst the expression of cytochrome P450 gene was up-regulated in head-kidney and liver of exposed fish. Overall, the present results indicate severe immunotoxicological and metabolic effects of deltamethrin in gilthead seabream, the species with the highest rate of production in Mediterranean aquaculture. In general, the values obtained for the tested parameters during the trial seem to indicate that specimens try to adapt to this adverse situation although the continuous presence of the toxic impede the hypothetic recovery of homoeostasis. The use of deltamethrin in the proximities of seabream farms should be carefully considered. PMID- 24176819 TI - Grouper interleukin-12, linked by an ancient disulfide-bond architecture, exhibits cytokine and chemokine activities. AB - Interleukin-12 (IL-12) is a pleiotropic cytokine which bridges innate and adaptive immunity in defense against pathogens. IL-12 proved to be an effective and successful adjuvant to enhance both the innate and adaptive immune responses and could be applicable for a rationale vaccine formulation in fish against pathogen infection. We have cloned the p35 and p40 cDNAs of IL-12 from orange spotted grouper (Epinephelus coioides). Grouper IL-12 most resembles with sea bass orthologues; moderate to low identity with other teleost and mammalian counterparts. The structural model of grouper IL-12 heterodimer revealed NC(141)F three amino acid patch of grouper p35, which is present in teleost p35 but absent in mammalian and avian p35, and is spatially nearby the conserved cysteine residue located at A-helix of p35 to form a disulfide bond when the 14aa peptide located at loop 1 of grouper p35 was aligned with human corresponding exon 4, instead of exon 5. The results indicated that the loss of this 3aa patch during evolution was compensated by the duplication of exon 4 in mammalian p35 to gain another cysteine residue to form a disulfide bond, evidenced by chicken p35 which does not contain NCF corresponding 3-aa patch nor exon 4 duplication. Accordingly, the inter-chain disulfide bond of IL-12 heterodimer is conserved from teleost to mammalian IL-12. A single chain grouper IL-12 (scgIL-12) construct linked by (G4S)3 was successfully expressed in baculovirus-insect cell system; its identity has been confirmed by LC/MS/MS. In addition, the biological activity of recombinant scgIL-12 (rscgIL-12) are demonstrated for its stimulation of PBL proliferation, chemotactic migration, induction of TNF-alpha gene expression and a plausible adjuvant effect of prolonged protection against parasite infection in fish. We illustrated the first time in lower vertebrate that grouper IL-12 possesses both cytokine and chemokine activities. PMID- 24176821 TI - Consumption of red and processed meat and risk for esophageal squamous cell carcinoma based on a meta-analysis. AB - PURPOSE: To provide a quantitative assessment of the association between red and processed meat intake and the risk of esophageal squamous cell carcinoma (ESCC), we summarized the evidence from observational studies. METHODS: Relevant studies were identified in MEDLINE and EMBASE until October 31, 2012. Summary relative risks with 95% confidence intervals (CIs) were pooled with high versus low and linear dose-response random-effects models. RESULTS: A total of 21 studies (19 case-control and two cohort studies) with 6499 ESCC cases were included in this meta-analysis. Based on high versus low analysis, the summary relative risks of ESCC were 1.57 (95% CI, 1.26-1.95; Pheterogeneity = .003, I(2) = 56.0%) for red meat intake and 1.55 (95% CI, 1.22-1.97; Pheterogeneity = .029, I(2) = 45.3%) for processed meat intake. Subgrouped and sensitivity analyses revealed that the increment of ESCC risk with intakes of red meat and processed meat was stable and robust. These results are consistent with the results of the dose-response analyses. There was evidence of a nonlinear association of processed meat intake and ESCC risk (Pnonlinearity = .019). CONCLUSIONS: Intake of red and processed meat may be associated with significantly increased risk of ESCC. Further investigations with prospective designs are warranted. PMID- 24176820 TI - Plasma lactate and diabetes risk in 8045 participants of the atherosclerosis risk in communities study. AB - PURPOSE: Determinants of oxidative capacity, such as fitness and level of adiposity, are strongly associated with type 2 diabetes. Whether decreased oxidative capacity itself is a cause or consequence of insulin resistance and diabetes is unknown. METHODS: We examined the association of plasma lactate, a marker of oxidative capacity, with incident diabetes in 8045 participants from the Atherosclerosis Risk in Communities (ARIC) Study with no history of subclinical or diagnosed diabetes at baseline (1996-1998). Incident diabetes was self-reported during annual telephone calls. RESULTS: During a median follow-up of 12 years, there were 1513 new cases of diabetes. In Cox proportional hazards models, baseline plasma lactate (per 10 mg/dL) was significantly associated with diabetes (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43), even after adjustment for diabetes risk factors, fasting glucose, and insulin. The upper quartile of baseline lactate (>= 8.1 mg/dL) was also significantly associated with diabetes risk (hazard ratio, 1.20; 95% confidence interval, 1.02-1.41) compared with the lowest quartile (<= 5.1 mg/dL). Significant associations persisted among persons without insulin resistance (homeostatic model assessment insulin resistance index < 2.6 U) (P-trend < .01). CONCLUSIONS: These findings suggest that low oxidative capacity may precede diabetes. Future studies should evaluate the physiological origins of elevated lactate to better understand its possible role in the pathogenesis of diabetes. PMID- 24176822 TI - Embryos of the zebrafish Danio rerio in studies of non-targeted effects of ionizing radiation. AB - The use of embryos of the zebrafish Danio rerio as an in vivo tumor model for studying non-targeted effects of ionizing radiation was reviewed. The zebrafish embryo is an animal model, which enables convenient studies on non-targeted effects of both high-linear-energy-transfer (LET) and low-LET radiation by making use of both broad-beam and microbeam radiation. Zebrafish is also a convenient embryo model for studying radiobiological effects of ionizing radiation on tumors. The embryonic origin of tumors has been gaining ground in the past decades, and efforts to fight cancer from the perspective of developmental biology are underway. Evidence for the involvement of radiation-induced genomic instability (RIGI) and the radiation-induced bystander effect (RIBE) in zebrafish embryos were subsequently given. The results of RIGI were obtained for the irradiation of all two-cell stage cells, as well as 1.5 hpf zebrafish embryos by microbeam protons and broad-beam alpha particles, respectively. In contrast, the RIBE was observed through the radioadaptive response (RAR), which was developed against a subsequent challenging dose that was applied at 10 hpf when <0.2% and <0.3% of the cells of 5 hpf zebrafish embryos were exposed to a priming dose, which was provided by microbeam protons and broad-beam alpha particles, respectively. Finally, a perspective on the field, the need for future studies and the significance of such studies were discussed. PMID- 24176823 TI - Roles for GP IIb/IIIa and alphavbeta3 integrins in MDA-MB-231 cell invasion and shear flow-induced cancer cell mechanotransduction. AB - Adhesion of cancer cell to endothelial cells and the subsequent trans-endothelial migration are key steps in hematogenous metastasis. However, the molecular mechanisms of cancer cell/endothelial cell interaction under hemodynamic shear flow and how shear flow-induced cancer cell mechanotransduction are yet to be fully defined. In this study, we identified that the integrins of both platelet glycoprotein IIb/IIIa (GP IIb/IIIa) and alphavbeta3 were crucial for hematogenous metastasis of human breast carcinoma MDA-MB-231 cells. The cell migration and invasion were studied by using Millicell cell culture insert system. The numbers of invaded MDA-MB-231 cells significantly increased by thrombin-activated platelets and reduced by eptifibatide, a platelet inhibitor. Meanwhile, RGDWE peptides, a specific inhibitor of alphavbeta3 integrin, also inhibited MDA-MB-231 cell invasion. We further used a parallel-plate flow chamber to investigate MDA MB-231 cell adhesion under flow conditions. Alike in static condition, the adhesion capability of MDA-MB-231 cells to endothelial monolayer was also significantly affected by GP IIb/IIIa and alphavbeta3 integrins. The expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and alphavbeta3 integrin in MDA-MB 231 cells were up-regulated after low shear stress exposure (1.84 dynes/cm(2), 2 h). Moreover, we also demonstrated that low shear stress induced a sustained activation of p85 (a regulatory subunit of PI3K) and Akt. Pre-treating MDA-MB-231 cells with the specific PI3K inhibitor of LY294002 abolished the shear stress induced-Akt activation, and the expression of MMP-2, MMP-9, vascular endothelial growth factor (VEGF) and alphavbeta3 integrin were also down-regulated. Immunofluorescence assay showed that low shear stress also induced alphavbeta3 integrin clustering and nuclear factor-kappaB (NF-kappaB) activation. Interestingly, shear stress-induced activation of Akt and NF-kappaB was attenuated by LM609, a specific antibody of alphavbeta3 integrin. It suggests that alphavbeta3 integrin might be as a mechanosensor to trigger both PI3K/Akt and NF-kappaB signaling pathways. Taken together, these results establish that GP IIb/IIIa and alphavbeta3 integrins are essential mediators, and provide insight into how shear stress-induced alphavbeta3 integrin activation and the downstream pathways for contribution to MDA-MB-231 cell adhesion, migration and invasion. PMID- 24176824 TI - Impulsivity and drinking motives predict problem behaviours relating to alcohol use in university students. AB - AIMS: This study used a four-factor model of impulsivity to investigate inter relationships between alcohol consumption, impulsivity, motives for drinking and the tendency to engage in alcohol-related problem behaviours. METHODS: 400 University students aged 18-25 completed an online survey consisting of the following measures: Urgency, Premeditation, Perseverance and Sensation Seeking Scale (UPPS) to measure impulsivity; Student Alcohol Questionnaire to assess drinking quantity, frequency and rates of problem behaviours; Drinking Motives Questionnaire to assess motives for drinking. RESULTS: The majority of the sample (94.5%) drank alcohol at least monthly. Path analysis revealed direct effects of urgency, sensation seeking and premeditation, as well as the quantity of alcohol consumed, on the tendency to engage in risky behaviours with negative consequences. The effect of urgency was mediated by drinking for coping motives and by a combined effect of drinking for social motives and consumption of wine or spirits. Conversely the effect of sensation seeking was mediated by the quantity of alcohol consumed, irrespective of drink type, and the effect of premeditation was mediated by the consumption of wine and spirits, in combination with enhancement motives. CONCLUSIONS: Sensation seeking, urgency and lack of premeditation are related to different motives for drinking and also demonstrate dissociable relationships with the consumption of specific types of alcohol (beer, wine and spirits) and the tendency to engage in risky behaviours associated with alcohol consumption. Screening for high levels of urgency and for severe drinking consequences may be useful predictors of alcohol-related problems in UK University students aged 18 to 25 years. PMID- 24176825 TI - ENP-BC is here! PMID- 24176826 TI - Complications associated with oral anticoagulation therapy. AB - Review of recent evidence with translation to practice for the advanced practice nurse (APN) role is presented using a case study module for "Complications Associated With Oral Anticoagulation Therapy." The study results showed that bleeding complications were most often due to gastrointestinal bleeding associated with anticoagulants (dabigatran 80% and warfarin 48%). The implications and clinical relevance of these findings for APNs are discussed highlighting best evidence. PMID- 24176827 TI - Proximal fifth metatarsal fractures. AB - The most common fracture of the foot is a fracture of the proximal fifth metatarsal. In general, there are 3 types of fractures involving the proximal fifth metatarsal area, including a proximal diaphyseal stress fracture, a Jones fracture, and an avulsion fracture of the tuberosity. Some fractures of the fifth metatarsal heal without difficulty, whereas some have the potential for nonunion or delayed healing. Each fracture has some variation in the anatomical location on the fifth metatarsal, the mechanism of injury, the radiographic findings, and the treatment plan. Avulsion fractures of the tuberosity often heal without difficulty, yet fractures distal to the area of insertion of the peroneus brevis tendon are prone to nonunion and delayed healing (). Differential diagnosis of a fifth metatarsal midfoot injury includes ankle sprains, midfoot sprains, plantar facial ruptures, peroneus tendon ruptures, and other foot fractures. PMID- 24176828 TI - Coagulation and complications of left ventricular assist device therapy: a primer for emergency nurses. AB - Implantation of left ventricular assist devices (LVADs) is becoming more common with the advancement of mechanical circulatory support technology and the continued insufficient number of organ donors available for heart transplantation. Modern LVADs provide a mechanically induced, nonpulsatile, continuous blood flow that drastically alters the hemodynamic and coagulation profile of patients using these devices. In addition to the risk of bleeding and thrombotic events, LVAD support can also lead to arrhythmias and infection. Although LVAD therapy can prolong life, the majority of patients will experience an adverse event following implantation and many of these complications can result in emergency department visits. By understanding the pathophysiology and management of LVAD complications, emergency nurses will be able to provide prompt and quality care for this unique patient population. PMID- 24176830 TI - Pediatric sepsis: a case study. AB - Abdominal pain with vomiting is a common pediatric complaint in the emergency department setting that can lead to a more insidious disease state. The article depicts a case study of a 21-month-old male child presenting with these signs and symptoms that ultimately resulted in a diagnosis of septic shock. The importance of physical assessment, rapid response to findings with time-constrained empirical interventions, the relevance of pediatric sepsis to the provider, the consideration of access to health care, and a holistic approach to treatment of the patient and the family are highlighted. The application and explanation of evidence-based guidelines is also depicted in the management of the patient. PMID- 24176831 TI - Strangulation forensic examination: best practice for health care providers. AB - Strangulation is one of the most dangerous forms of interpersonal violence (IVP), yet it is often not reported and missed by the health care provider because of lack of visible injury. The victim of strangulation can have critical injuries and a late onset symptoms. Victims of IVP should be directly asked whether they were choked or whether during the assault they felt like they could not breathe because of pressure on their neck. The objective of this article is to summarize "best practice" for health care providers so that they are better prepared to care for victims who report a history of strangulation. A summary of how to perform a forensic examination of the strangled patient is provided along with important documentation takeaways and useful forms to ensure that the severity of the strangulation is assessed, that critical injuries are identified, and that all injuries and findings are accurately documented for legal proceedings. PMID- 24176832 TI - Is this case an EMTALA violation? AB - The advanced practice registered nurse (APRN) working in the emergency department (ED) is asked to see a patient with an "eye infection." The patient has a severe retrobulbar orbital abscess requiring complex multidisciplinary specialty management and is ultimately transferred to a tertiary care center. The patient had first presented to a community ED per the recommendation of her ear, nose, and throat (ENT) specialist. The patient was advised to leave the first ED during triage and to go to a second community ED. Although the referring physician was made aware of the recommendation to have the patient drive to another facility, the APRN questions whether this is a case of an Emergency Medical Treatment and Active Labor Act (EMTALA) violation. This article defines EMTALA and evaluates the case. PMID- 24176833 TI - Provider in triage: is this a place for nurse practitioners? AB - The role of nurse practitioners (NPs) in emergency care continues to evolve. A new and exciting role is the provider-in-triage (PIT) role. This innovative role has been implemented in many emergency departments (EDs) across the country. It was developed primarily as a front-end strategy to improve throughput of patients receiving emergency care. The PIT process uses a provider, physician, NP, or physician assistant in the triage area. Patient satisfaction, quality measures, and financial improvements have been attributed to using a PIT. The emergency NP is an optimal choice for this role. Advanced emergency nursing knowledge, skills, and decision making confer the NP a cost-effective provider to improve throughput in the ED while providing quality emergency care. PMID- 24176834 TI - Reproducibility and variability of dynamic cerebral autoregulation during passive cyclic leg raising. AB - Dynamic cerebral autoregulation (dCA) estimates require mean arterial blood pressure (MABP) fluctuations of sufficient amplitude. Current methods to induce fluctuations are not easily implemented or require patient cooperation. In search of an alternative method, we evaluated if MABP fluctuations could be increased by passive cyclic leg raising (LR) and tested if reproducibility and variability of dCA parameters could be improved. Middle cerebral artery cerebral blood flow velocity (CBFV), MABP and end tidal CO2 (PetCO2) were obtained at rest and during LR at 0.1 Hz in 16 healthy subjects. The MABP-CBFV phase difference and gain were determined at 0.1 Hz and in the low frequency (LF) range (0.06-0.14 Hz). In addition the autoregulation index (ARI) was calculated. The LR maneuver increased the power of MABP fluctuations at 0.1 Hz and across the LF range. Despite a clear correlation between both phase and gain reproducibility and MABP variability in the rest condition, only the reproducibility of gain increased significantly with the maneuver. During the maneuver patients were breathing faster and more irregularly, accompanied by increased PetCO2 fluctuations and increased coherence between PetCO2 and CBFV. Multiple regression analysis showed that these concomitant changes were negatively correlated with the MABP-CBFV phase difference at 0.1 Hz Variability was not reduced by LR for any of the dCA parameters. The clinical utility of cyclic passive leg raising is limited because of the concomitant changes in PetCO2. This limits reproducibility of the most important dCA parameters. Future research on reproducibility and variability of dCA parameters should incorporate PetCO2 variability or find methods to keep PetCO2 levels constant. PMID- 24176835 TI - Enabling community through social media. AB - BACKGROUND: Social network analysis provides a perspective and method for inquiring into the structures that comprise online groups and communities. Traces from interaction via social media provide the opportunity for understanding how a community is formed and maintained online. OBJECTIVE: The paper aims to demonstrate how social network analysis provides a vocabulary and set of techniques for examining interaction patterns via social media. Using the case of the #hcsmca online discussion forum, this paper highlights what has been and can be gained by approaching online community from a social network perspective, as well as providing an inside look at the structure of the #hcsmca community. METHODS: Social network analysis was used to examine structures in a 1-month sample of Twitter messages with the hashtag #hcsmca (3871 tweets, 486 unique posters), which is the tag associated with the social media-supported group Health Care Social Media Canada. Network connections were considered present if the individual was mentioned, replied to, or had a post retweeted. RESULTS: Network analyses revealed patterns of interaction that characterized the community as comprising one component, with a set of core participants prominent in the network due to their connections with others. Analysis showed the social media health content providers were the most influential group based on in-degree centrality. However, there was no preferential attachment among people in the same professional group, indicating that the formation of connections among community members was not constrained by professional status. CONCLUSIONS: Network analysis and visualizations provide techniques and a vocabulary for understanding online interaction, as well as insights that can help in understanding what, and who, comprises and sustains a network, and whether community emerges from a network of online interactions. PMID- 24176836 TI - Academic productivity in today's training climate: a fellowship's impact. PMID- 24176837 TI - Endothelialization of platinum-based coils: a new frontier of endosaccular aneurysm therapy. PMID- 24176838 TI - Advanced imaging techniques in cervical spinal cord trauma. PMID- 24176840 TI - Berberine in combination with doxorubicin suppresses growth of murine melanoma B16F10 cells in culture and xenograft. AB - Melanoma is very aggressive and major cause of mortality due to skin cancer. Herein, we studied the anticancer effects of berberine, a plant alkaloid, in combination with doxorubicin on murine melanoma B16F10 cells in vitro and in vivo. This drug combination strongly inhibited cell growth and induced cell death, and caused G2/M arrest in cell cycle together with a decrease in Kip1/p27. Berberine showed stronger inhibitory effect on ERK1/2 phosphorylation as compared to Akt phosphorylation, whereas the combination of the drugs showed greater inhibitory effect on Akt phosphorylation. In murine B16F10 xenograft, cells were implanted into mice and treated with vehicle (methyl cellulose) or berberine (100mg/kg of body weight/day by oral gavage) or doxorubicin (4 mg/kg of body weight/week by intraperitoneal injection) or combination of berberine and doxorubicin. Berberine alone did not show any considerable effect on tumor growth as observed with doxorubicin, however, the combination of the two drugs resulted in a significant and strong decrease in tumor volume (85%, p<0.005) and tumor weight (78%, p<0.05) as compared to control. Immunohistochemical analysis of tumor samples showed that drug combination decreased PCNA-positive cells (82%, p<0.001) and increased cleaved caspase-3 positive cells (3-fold, p<0.05) indicating inhibition of proliferation and an increase in apoptosis, respectively. Overall, our findings suggest that berberine and doxorubicin could be a novel combination to inhibit melanoma tumor growth. PMID- 24176839 TI - Effect of Silymarin in Pdx-1 expression and the proliferation of pancreatic beta cells in a pancreatectomy model. AB - In type 1 Diabetes Mellitus (DM) there is a destruction of pancreatic beta-cells (80-90%) at the time of detection, in DM type 2 these cells are decreased significantly. The Pdx1 transcription factor plays a central role in pancreatic development and in insulin gene expression. Previously, we have demonstrated that Silymarin recovers the normal morphology and endocrine function of damaged pancreatic tissue in alloxan induced diabetic rats. The aim of this study was to analyze the effect of Silymarin in Pdx1 gene expression and its repercussion on insulin gene expression and beta-cell proliferation. 72 Wistar rats were partially pancreatectomized (60%) and divided into 12 groups. Six groups were treated daily with Silymarin (200mg/kg p.o.) for 3, 7, 14, 21, 42 and 63 day periods. Also, an unpancreatectomized control group was performed. At each time interval three animals from each group were administered BrdU 18 h before the sacrifice. Insulin and Pdx-1 gene expression were assessed by RT-PCR assay in total pancreatic RNA. beta-Cell proliferation was determined by immunoperoxidase assay. In contrast to the animals that were only pancreatectomized, the Silymarin treatment induced an increase in both Pdx1 and insulin gene expression as well as beta-cell proliferation in pancreatic tissue (control=2.6+/-0.28%; untreated=14.25+/-0.56%; treated=39.08+/-4.62%). Consequently, serum insulin levels rose (control=1.01+/-0.02 ng/ml; untreated=1.18+/-0.42 ng/ml; treated=4.58+/-0.58 ng/ml) and serum glucose levels decreased in these animals (control=6.2+/-0.01 mM; untreated=9.02+/-0.41 mM; treated=6.41+/-0.32 mM). These results suggest that Silymarin may induce the proliferation of insulin-producing cells. PMID- 24176841 TI - Improvement of anti-inflammatory and anti-angiogenic activity of berberine by novel rapid dissolving nanoemulsifying technique. AB - Berberine, an isoquinoline alkaloid, has wide biological and pharmacological actions. Despite the promising pharmacological effects and safety of berberine, poor oral absorption due to its extremely low aqueous solubility results in poor oral systemic bioavailability. This limits its clinical usage. This study describes the development and characterization of self-nanoemulsifying drug delivery system (SNEDDS) of berberine in liquid as well as solid form with improved solubility, dissolution and in vivo therapeutic efficacy. The SNEDDS of berberine were prepared using Acrysol K-150, Capmul MCM and polyethylene glycol 400. The formulations were characterized for various in vitro physicochemical characteristics. In vivo efficacy was evaluated in acetic acid induced inflammatory bowel model in rats. Anti-angiogenic activity of the developed SNEDDS of berberine was studied using chick chorioallantoic membrane assay. SNEDDS of berberine rapidly formed nanoemulsions with globule size of 17-45 nm. The in vitro rate and extent of release of berberine from SNEDDS was significantly higher than berberine alone. Chick chorioallantoic membrane assay revealed potent anti-angiogenic activity of SNEDDS of berberine. These studies demonstrate that the SNEDDS of berberine is a promising strategy for improving its therapeutic efficacy and have potential application in the treatment of chronic inflammatory conditions and cancer. PMID- 24176842 TI - Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer. AB - Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. Harmine is reported as a promising drug candidate for cancer therapy; however, effects and action mechanism of harmine on the human gastric cancer cells remain unclear. This study evaluated the anti-tumor effects of harmine on human gastric cancer both in vitro and in vivo. The cell proliferation was determined using MTT colorimetric assay. Apoptosis was measured by DAPI staining and flow cytometry analysis. The wound healing and transwell invasion assays were performed to evaluate the effects of harmine on the migration and invasion of gastric cancer cells. The expression of COX-2, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax and matrix metalloproteinase-2 (MMP-2) was detected by Western blot analysis. Our results showed that harmine significantly inhibited cellular proliferation, migration, invasion and induced apoptosis in vitro, as well as inhibited tumor growth in vivo. In addition, harmine significantly inhibited the expression of COX-2, PCNA, Bcl-2 and MMP-2 as well as increased Bax expression in gastric cancer cells. These results collectively indicate that harmine induces apoptosis and inhibits proliferation, migration and invasion of human gastric cancer cells, which may be mediated by down-regulation of COX-2 expression. PMID- 24176843 TI - Reproductive and developmental toxicity of the Ginkgo biloba special extract EGb 761(r) in mice. AB - Extracts from leaves of Ginkgo biloba are among the most widely used and best investigated phytopharmaceuticals worldwide. Almost all clinical trials and the majority of preclinical studies have been performed with a specifically defined extract (EGb 761((r))) standardized to contain confined concentrations of active ingredients and limited quantities of potentially harmful substances. Besides pharmaceutical grade extracts poorly characterized Ginkgo preparations are now increasingly appearing on the market as nutraceuticals. While the safety of EGb 761((r)) has been evaluated in an extensive set of toxicology studies, adverse effects of Ginkgo extracts of non-pharmaceutical quality on reproductive functions in mice have been reported in several publications in recent years. As this species has not previously been used in reproductive toxicity studies with EGb 761((r)), the present investigation was conducted to examine the influence of EGb 761((r)) (100, 350 and 1225mg/kg/day) on embryo-fetal development in mice during the critical period of organogenesis. During external and internal inspection of the fetuses as well as examination of skeletal and soft tissues no embryotoxic properties were noted. In particular, the incidence of malformations, variations or retardations was not increased and the general condition of dams was not influenced. Thus, the no-observed-effect level (NOEL) was above 1225mg/kg/day for the dams and the fetuses. PMID- 24176844 TI - Antioxidant and intestinal anti-inflammatory effects of plant-derived coumarin derivatives. AB - BACKGROUND: Coumarins, also known as benzopyrones, are plant-derived products with several pharmacological properties, including antioxidant and anti inflammatory activities. Based on the wide distribution of coumarin derivatives in plant-based foods and beverages in the human diet, our objective was to evaluate both the antioxidant and intestinal anti-inflammatory activities of six coumarin derivatives of plant origin (scopoletin, scoparone, fraxetin, 4-methyl umbeliferone, esculin and daphnetin) to verify if potential intestinal anti inflammatory activity was related to antioxidant properties. METHODS: Intestinal inflammation was induced by intracolonic instillation of TNBS in rats. The animals were treated with coumarins by oral route. The animals were killed 48 h after colitis induction. The colonic segments were obtained after laparotomy and macroscopic and biochemical parameters (determination of glutathione level and myeloperoxidase and alkaline phosphatase activities) were evaluated. The antioxidant properties of these coumarins were examined by lipid peroxidation and DPPH assays. RESULTS: Treatment with esculin, scoparone and daphnetin produced the best protective effects. All coumarin derivatives showed antioxidant activity in the DPPH assay, while daphnetin and fraxetin also showed antioxidant activity by inhibiting lipid peroxidation. Coumarins, except 4-methyl-umbeliferone, also showed antioxidant activity through the counteraction of glutathione levels or through the inhibition of myeloperoxidase activity. DISCUSSION: The intestinal anti-inflammatory activity of coumarin derivatives were related to their antioxidant properties, suggesting that consumption of coumarins and/or foods rich in coumarin derivatives, particularly daphnetin, esculin and scoparone, could prevent intestinal inflammatory disease. PMID- 24176845 TI - Microenvironment mesenchymal cells protect ovarian cancer cell lines from apoptosis by inhibiting XIAP inactivation. AB - Epithelial ovarian carcinoma is characterized by high frequency of recurrence (70% of patients) and carboplatin resistance acquisition. Carcinoma-associated mesenchymal stem cells (CA-MSC) have been shown to induce ovarian cancer chemoresistance through trogocytosis. Here we examined CA-MSC properties to protect ovarian cancer cells from carboplatin-induced apoptosis. Apoptosis was determined by Propidium Iodide and Annexin-V-FITC labelling and poly-ADP-ribose polymerase cleavage analysis. We showed a significant increase of inhibitory concentration 50 and a 30% decrease of carboplatin-induced apoptosis in ovarian cancer cells incubated in the presence of CA-MSC-conditioned medium (CM). A molecular analysis of apoptosis signalling pathway in response to carboplatin revealed that the presence of CA-MSC CM induced a 30% decrease of effector caspases-3 and -7 activation and proteolysis activity. CA-MSC secretions promoted Akt and X-linked inhibitor of apoptosis protein (XIAP; caspase inhibitor from inhibitor of apoptosis protein (IAP) family) phosphorylation. XIAP depletion by siRNA strategy permitted to restore apoptosis in ovarian cancer cells stimulated by CA-MSC CM. The factors secreted by CA-MSC are able to confer chemoresistance to carboplatin in ovarian cancer cells through the inhibition of effector caspases activation and apoptosis blockade. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and the phosphorylation of its downstream target XIAP underlined the implication of this signalling pathway in ovarian cancer chemoresistance. This study reveals the potentialities of targeting XIAP in ovarian cancer therapy. PMID- 24176846 TI - Cyclophilin A: a key player for human disease. AB - Cyclophilin A (CyPA) is a ubiquitously distributed protein belonging to the immunophilin family. CyPA has peptidyl prolyl cis-trans isomerase (PPIase) activity, which regulates protein folding and trafficking. Although CyPA was initially believed to function primarily as an intracellular protein, recent studies have revealed that it can be secreted by cells in response to inflammatory stimuli. Current research in animal models and humans has provided compelling evidences supporting the critical function of CyPA in several human diseases. This review discusses recently available data about CyPA in cardiovascular diseases, viral infections, neurodegeneration, cancer, rheumatoid arthritis, sepsis, asthma, periodontitis and aging. It is believed that further elucidations of the role of CyPA will provide a better understanding of the molecular mechanisms underlying these diseases and will help develop novel pharmacological therapies. PMID- 24176847 TI - Autophagy triggered by magnolol derivative negatively regulates angiogenesis. AB - Angiogenesis has a key role in the tumor progression and metastasis; targeting endothelial cell proliferation has emerged as a promising therapeutic strategy for the prevention of cancer. Previous studies have revealed a complex association between the process of angiogenesis and autophagy and its outcome on tumorigenesis. Autophagy, also known as type-II cell death, has been identified as an alternative way of cell killing in apoptotic-resistant cancer cells. However, its involvement in chemoresistance and tumor promotion is also well known. In this study, we used a derivate of natural product magnolol (Ery5), a potent autophagy inducer, to study the association between the autophagy and angiogenesis in both in vitro and in vivo model system. We found that the robust autophagy triggered by Ery5, inhibited angiogenesis and caused cell death independent of the apoptosis in human umbilical cord vein endothelial cells and PC-3 cells. Ery5 induced autophagy effectively inhibited cell proliferation, migration, invasion and tube formation. We further demonstrated that Ery5 mediated autophagy and subsequent inhibition of angiogenesis was reversed when autophagy was inhibited through 3-methyl adenine and knocking down of key autophagy proteins ATG7 and microtubule-associated protein light chain 3. While evaluating the negative regulation of autophagy on angiogenesis, it was interesting to find that angiogenic environment produced by the treatment of VEGF and CoCl2 remarkably downregulated the autophagy and autophagic cell death induced by Ery5. These studies, while disclosing the vital role of autophagy in the regulation of angiogenesis, also suggest that the potent modulators of autophagy can lead to the development of effective therapeutics in apoptosis resistant cancer. PMID- 24176848 TI - Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27. AB - The small chaperone protein Hsp27 confers resistance to apoptosis, and therefore is an attractive anticancer drug target. We report here a novel mechanism underlying the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitizing activity of the small molecule LY303511, an inactive analog of the phosphoinositide 3-kinase inhibitor inhibitor LY294002, in HeLa cells that are refractory to TRAIL-induced apoptosis. On the basis of the fact that LY303511 is derived from LY294002, itself derived from quercetin, and earlier findings indicating that quercetin and LY294002 affected Hsp27 expression, we investigated whether LY303511 sensitized cancer cells to TRAIL via a conserved inhibitory effect on Hsp27. We provide evidence that upon treatment with LY303511, Hsp27 is progressively sequestered in the nucleus, thus reducing its protective effect in the cytosol during the apoptotic process. LY303511-induced nuclear translocation of Hsp27 is linked to its sustained phosphorylation via activation of p38 kinase and MAPKAP kinase 2 and the inhibition of PP2A. Furthermore, Hsp27 phosphorylation leads to the subsequent dissociation of its large oligomers and a decrease in its chaperone activity, thereby further compromising the death inhibitory activity of Hsp27. Furthermore, genetic manipulation of Hsp27 expression significantly affected the TRAIL sensitizing activity of LY303511, which corroborated the Hsp27 targeting activity of LY303511. Taken together, these data indicate a novel mechanism of small molecule sensitization to TRAIL through targeting of Hsp27 functions, rather than its overall expression, leading to decreased cellular protection, which could have therapeutic implications for overcoming chemotherapy resistance in tumor cells. PMID- 24176849 TI - Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasis in a xenograft model of breast cancer. AB - Triple-negative breast cancers (TNBCs) are clinically aggressive forms associated with a poor prognosis. We evaluated the cytotoxic effect exerted on triple negative MDA-MB231 breast cancer cells both by parthenolide and its soluble analogue dimethylamino parthenolide (DMAPT) and explored the underlying molecular mechanism. The drugs induced a dose- and time-dependent decrement in cell viability, which was not prevented by the caspase inhibitor z-VAD-fmk. In particular in the first hours of treatment (1-3 h), parthenolide and DMAPT strongly stimulated reactive oxygen species (ROS) generation. The drugs induced production of superoxide anion by activating NADPH oxidase. ROS generation caused depletion of thiol groups and glutathione, activation of c-Jun N-terminal kinase (JNK) and downregulation of nuclear factor kB (NF-kB). During this first phase, parthenolide and DMAPT also stimulated autophagic process, as suggested by the enhanced expression of beclin-1, the conversion of microtubule-associated protein light chain 3-I (LC3-I) to LC3-II and the increase in the number of cells positive to monodansylcadaverine. Finally, the drugs increased RIP-1 expression. This effect was accompanied by a decrement of pro-caspase 8, while its cleaved form was not detected and the expression of c-FLIPS markedly increased. Prolonging the treatment (5-20 h) ROS generation favoured dissipation of mitochondrial membrane potential and the appearance of necrotic events, as suggested by the increased number of cells positive to propidium iodide staining. The administration of DMAPT in nude mice bearing xenografts of MDA-MB231 cells resulted in a significant inhibition of tumour growth, an increment of animal survival and a marked reduction of the lung area invaded by metastasis. Immunohistochemistry data revealed that treatment with DMAPT reduced the levels of NF-kB, metalloproteinase-2 and -9 and vascular endothelial growth factor, while induced upregulation of phosphorylated JNK. Taken together, our data suggest a possible use of parthenolide for the treatment of TNBCs. PMID- 24176850 TI - Survival or death: disequilibrating the oncogenic and tumor suppressive autophagy in cancer. AB - Autophagy (macroautophagy) is an evolutionarily conserved lysosomal degradation process, in which a cell degrades long-lived proteins and damaged organelles. Recently, accumulating evidence has revealed the core molecular machinery of autophagy in carcinogenesis; however, the intricate relationship between autophagy and cancer continue to remain an enigma. Why does autophagy have either pro-survival (oncogenic) or pro-death (tumor suppressive) role at different cancer stages, including cancer stem cell, initiation and progression, invasion and metastasis, as well as dormancy? How does autophagy modulate a series of oncogenic and/or tumor suppressive pathways, implicated in microRNA (miRNA) involvement? Whether would targeting the oncogenic and tumor suppressive autophagic network be a novel strategy for drug discovery? To address these problems, we focus on summarizing the dynamic oncogenic and tumor suppressive roles of autophagy and their relevant small-molecule drugs, which would provide a new clue to elucidate the oncosuppressive (survival or death) autophagic network as a potential therapeutic target. PMID- 24176851 TI - Light-controlled inhibition of malignant glioma by opsin gene transfer. AB - Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light controllable optogenetic approach. PMID- 24176852 TI - killerFLIP: a novel lytic peptide specifically inducing cancer cell death. AB - One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killerFLIP as its sequence was derived from the C-terminal domain of c FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using electron microscopy demonstrated that killerFLIP-E triggers cell death accompanied by rapid (within minutes) plasma membrane permeabilization. Studies of the structure of the active core of killerFLIP (-E) indicated that it possesses amphiphilic properties and self-assembles into micellar structures in aqueous solution. The biochemical properties of killerFLIP are comparable to those of cationic lytic peptides, which participate in defense against pathogens and have also demonstrated anticancer properties. We show that the pro-cell death effects of killerFLIP are independent of its sequence similarity with c-FLIPL as killerFLIP-induced cell death was largely apoptosis and necroptosis independent. A killerFLIP-E variant containing a scrambled c FLIPL motif indeed induced similar cell death, suggesting the importance of the c FLIPL residues but not of their sequence. Thus, we report the discovery of a promising synthetic peptide with novel anticancer activity in vitro and in vivo. PMID- 24176853 TI - Transcriptome analysis of glioma cells for the dynamic response to gamma irradiation and dual regulation of apoptosis genes: a new insight into radiotherapy for glioblastomas. AB - Ionizing radiation (IR) is of clinical importance for glioblastoma therapy; however, the recurrence of glioma characterized by radiation resistance remains a therapeutic challenge. Research on irradiation-induced transcription in glioblastomas can contribute to the understanding of radioresistance mechanisms. In this study, by using the total mRNA sequencing (RNA-seq) analysis, we assayed the global gene expression in a human glioma cell line U251 MG at various time points after exposure to a growth arrest dose of gamma-rays. We identified 1656 genes with obvious changes at the transcriptional level in response to irradiation, and these genes were dynamically enriched in various biological processes or pathways, including cell cycle arrest, DNA replication, DNA repair and apoptosis. Interestingly, the results showed that cell death was not induced even many proapoptotic molecules, including death receptor 5 (DR5) and caspases were activated after radiation. The RNA-seq data analysis further revealed that both proapoptosis and antiapoptosis genes were affected by irradiation. Namely, most proapoptosis genes were early continually responsive, whereas antiapoptosis genes were responsive at later stages. Moreover, HMGB1, HMGB2 and TOP2A involved in the positive regulation of DNA fragmentation during apoptosis showed early continual downregulation due to irradiation. Furthermore, targeting of the TRAIL/DR5 pathway after irradiation led to significant apoptotic cell death, accompanied by the recovered gene expression of HMGB1, HMGB2 and TOP2A. Taken together, these results revealed that inactivation of proapoptotic signaling molecules in the nucleus and late activation of antiapoptotic genes may contribute to the radioresistance of gliomas. Overall, this study provided novel insights into not only the underlying mechanisms of radioresistance in glioblastomas but also the screening of multiple targets for radiotherapy. PMID- 24176854 TI - Loss of Yme1L perturbates mitochondrial dynamics. AB - Yme1L is an AAA protease that is embedded in the mitochondrial inner membrane with its catalytic domain facing the mitochondrial inner-membrane space. However, how Yme1L regulates mammalian mitochondrial function is still obscure. We find that endogenous Yme1L locates at punctate structures of mitochondria, and that loss of Yme1L in mouse embryonic fibroblast (MEF) cells results in mitochondrial fragmentation and leads to significant increased 'kiss-and-run' type of mitochondrial fusion; however, Yme1L knockdown (shYme1L (short hairpin-mediated RNA interference of Yme1L)) cells still remain normal mitochondrial fusion although shYme1L mitochondria have a little bit less fusion and fission rates, and the shYme1L-induced fragmentation is due to a little bit more mitochondrial fission than fusion in cells. Furthermore, shYme1L-induced mitochondrial fragmentation is independent on optic atrophy 1 (OPA1) S1 or S2 processing, and shYme1L results in the stabilization of OPA1 long form (L-OPA1); in addition, the exogenous expression of OPA1 or L-OPA1 facilitates the shYme1L-induced mitochondrial fragmentation, thus this fragmentation induced by shYme1L appears to be associated with L-OPA1's stability. ShYme1L also causes a slight increase of mitochondrial dynamics proteins of 49 kDa and mitochondrial fission factor (Mff), which recruit mitochondrial key fission factor dynamin-related protein 1 (Drp1) into mitochondria in MEF cells, and loss of Drp1 or Mff inhibits the shYme1L-induced mitochondrial fragmentation. In addition, there is interaction between SLP-2 with Yme1L and shYme1L cells retain stress-induced mitochondrial hyperfusion. Taken together, our results clarify how Yme1L regulates mitochondrial morphology. PMID- 24176855 TI - Irradiation to the young mouse brain impaired white matter growth more in females than in males. AB - Modern therapy cures 80% of all children with brains tumors, but may also cause long-lasting side effects, so called late effects. Radiotherapy is particularly prone to cause severe late effects, such as intellectual impairment. The extent and nature of the resulting cognitive deficits may be influenced by age, treatment and gender, where girls suffer more severe late effects than boys. The reason for this difference between boys and girls is unknown, but very few experimental studies have addressed this issue. Our aim was to investigate the effects of ionizing radiation on the corpus callosum (CC) in both male and female mice. We found that a single dose of 8 Gray (Gy) to the brains of postnatal day 14 mice induced apoptosis in the CC and reduced the number of proliferating cells by one third, as judged by the number of phospho-histone H3 positive cells 6 h after irradiation (IR). BrdU incorporation was reduced (62% and 42% lower in females and males, respectively) and the number of oligodendrocytes (Olig2(+) cells) was lower (43% and 21% fewer in females and males, respectively) 4 months after IR, so the lack of developing and differentiated cells was more pronounced in females. The number of microglia was unchanged in females but increased in males at this late time point. The density of microvessel profiles was unchanged by IR. This single, moderate dose of 8 Gy impaired the brain growth to some extent (8.1% and 0.4% lower brain/body weight ratio in females and males, respectively) but the CC growth was even more impaired (31% and 19% smaller in females and males, respectively) 4 months after IR compared with non-irradiated mice. In conclusion, this is the first study to our knowledge demonstrating that IR to the young rodent brain affects white matter development more in females than in males. PMID- 24176856 TI - Retinoic acid alters the proliferation and survival of the epithelium and mesenchyme and suppresses Wnt/beta-catenin signaling in developing cleft palate. AB - Retinoic acid (RA) contributes to cleft palate; however, the cellular and molecular mechanisms responsible for the deleterious effects on the developing palate are unclear. Wnt signaling is a candidate pathway in the cleft palate and is associated with RA in organ development; thus, we aim to investigate whether RA-induced cleft palate also results from altered Wnt signaling. Administration of RA to mice altered cell proliferation and apoptosis in craniofacial tissues by regulating molecules controlling cell cycle and p38 MAPK signaling, respectively. This altered cell fate by RA is a crucial mechanism contributing to 100% incidence of cleft palate. Moreover, Wnt/beta-catenin signaling was completely inhibited by RA in the early developing palate via its binding and activation with RA receptor (RAR) and is responsible for RA-induced cleft palate. Furthermore, PI3K/Akt signaling was also involved in actions of RA. Our findings help in elucidating the mechanisms of RA-induced cleft palate. PMID- 24176857 TI - miR-125b transcriptionally increased by Nrf2 inhibits AhR repressor, which protects kidney from cisplatin-induced injury. AB - MicroRNAs (miRNAs) have a role in the cellular defense mechanism. Nuclear factor erythroid-2-related factor 2 (Nrf2) increases antioxidant enzyme capacity. However, miRNA transcriptionally controlled by Nrf2 had been uncharacterized. Here we report that miR-125b is transactivated by Nrf2 and inhibits aryl hydrocarbon receptor (AhR) repressor (AhRR). Bioinformatic approaches enabled us to extract six candidate miRNAs. Of them, only miR-125b was increased in the kidney of mice treated with oltipraz. Nrf2 overexpression enhanced primary, precursor and mature miR-125b levels. Functional assays revealed MIR125B1 is a bona fide target gene of Nrf2. Oltipraz treatment protected the kidney from cisplatin toxicity with increase of miR-125b. Consistently, Nrf2 knockout abrogated an adaptive increase of miR-125b elicited by cisplatin, augmenting kidney injury. An integrative network of miRNA and messenger RNA changes enabled us to predict miR-125b as an inhibitor of AhRR for the control of AhR activity and cell survival. In our molecular study, miR-125b inhibited AhRR and thereby activated AhR, leading to the induction of mdm2. Consistently, p53 activation by cisplatin was diminished by either miR-125b or oltipraz treatment. The results of experiments using miR-125b mimic or small interfering RNA of AhRR verified the role of miR-125b in AhRR regulation for kidney protection. In conclusion, miR 125b is transcriptionally activated by Nrf2 and serves as an inhibitor of AhRR, which contributes to protecting kidney from acute injury. PMID- 24176858 TI - Gene miles-apart is required for formation of otic vesicle and hair cells in zebrafish. AB - Hearing loss is a serious burden to physical and mental health worldwide. Aberrant development and damage of hearing organs are recognized as the causes of hearing loss, the molecular mechanisms underlining these pathological processes remain elusive. Investigation of new molecular mechanisms involved in proliferation, differentiation, migration and maintenance of neuromast primordium and hair cells will contribute to better understanding of hearing loss pathology. This knowledge will enable the development of protective agents and mechanism study of drug ototoxicity. In this study, we demonstrate that the zebrafish gene miles-apart, a homolog of sphingosine-1-phosphate receptor 2 (s1pr2) in mammals, has an important role in the development of otic vesicle, neuromasts and survival of hair cells. Whole-mount in situ hybridization of embryos showed that miles apart expression occurred mainly in the encephalic region and the somites at 24 h.p.f. (hour post fertilization), in the midbrain/hindbrain boundary, the brainstem and the pre-neuromast of lateral line at 48 h.p.f. in a strict spatiotemporal regulation. Both up- and downregulation of miles-apart led to abnormal otoliths and semicircular canals, excess or few hair cells and neuromasts, and their disarranged depositions in the lateral lines. Miles-apart (Mil) dysregulation also caused abnormal expression of hearing-associated genes, including hmx2, fgf3, fgf8a, foxi1, otop1, pax2.1 and tmieb during zebrafish organogenesis. Moreover, in larvae miles-apart gene knockdown significantly upregulated proapoptotic gene zBax2 and downregulated prosurvival gene zMcl1b; in contrast, the level of zBax2 was decreased and of zMcl1b enhanced by miles-apart overexpression. Collectively, Mil activity is linked to organization and number decision of hair cells within a neuromast, also to deposition of neuromasts and formation of otic vesicle during zebrafish organogenesis. At the larva stage, Mil as an upstream regulator of bcl-2 gene family has a role in protection of hair cells against apoptosis by promoting expression of prosurvival gene zMcl1b and suppressing proapoptotic gene zBax2. PMID- 24176859 TI - Phosphorylated SATB1 is associated with the progression and prognosis of glioma. AB - Special AT-rich sequence-binding protein 1 (SATB1) is a global chromatin organizer and gene regulator, and high expression of SATB1 is associated with progression and poor prognosis in several malignancies. Here, we examine the expression pattern of SATB1 in glioma. Microarray analysis of 127 clinical samples showed that SATB1 mRNA was expressed at lower levels in highly malignant glioblastoma multiforme (GBM) than in low-grade glioma and normal brain tissue. This result was further confirmed by real-time RT-PCR in the clinical samples, three GBM cell lines, primary SU3 glioma cells and tumor cells harvested by laser capture microdissection. Consistent with the mRNA levels, SATB1 protein expression was downregulated in high-grade glioma, as shown by western blotting. However, phospho-SATB1 levels showed an opposite pattern, with a significant increase in these tumors. Immunohistochemical analysis of phospho-SATB1 expression in tissue microarrays with tumors from 122 glioma cases showed that phospho-SATB1 expression was significantly associated with high histological grade and poor survival by Kaplan-Meier analysis. In vitro transfection analysis showed that phospho-SATB1 DNA binding has a key role in regulating the proliferation and invasion of glioma cells. The effect of SATB1 in glioma cell is mainly histone deacetylase (HDAC1)-dependent. We conclude that phospho-SATB1, but not SATB1 mRNA expression, is associated with the progression and prognosis of glioma. By interaction with HDAC1, phospho-SATB1 contributes to the invasive and proliferative phenotype of GBM cells. PMID- 24176860 TI - Excitotoxic cell death induces delayed proliferation of endogenous neuroprogenitor cells in organotypic slice cultures of the rat spinal cord. AB - The aim of the present report was to investigate whether, in the mammalian spinal cord, cell death induced by transient excitotoxic stress could trigger activation and proliferation of endogenous neuroprogenitor cells as a potential source of a lesion repair process and the underlying time course. Because it is difficult to address these issues in vivo, we used a validated model of spinal injury based on rat organotypic slice cultures that retain the fundamental tissue cytoarchitecture and replicate the main characteristics of experimental damage to the whole spinal cord. Excitotoxicity evoked by 1 h kainate application produced delayed neuronal death (40%) peaking after 1 day without further losses or destruction of white matter cells for up to 2 weeks. After 10 days, cultures released a significantly larger concentration of endogenous glutamate, suggesting functional network plasticity. Indeed, after 1 week the total number of cells had returned to untreated control level, indicating substantial cell proliferation. Activation of progenitor cells started early as they spread outside the central area, and persisted for 2 weeks. Although expression of the neuronal progenitor phenotype was observed at day 3, peaked at 1 week and tapered off at 2 weeks, very few cells matured to neurons. Astroglia precursors started proliferating later and matured at 2 weeks. These data show insult-related proliferation of endogenous spinal neuroprogenitors over a relatively brief time course, and delineate a narrow temporal window for future experimental attempts to drive neuronal maturation and for identifying the factors regulating this process. PMID- 24176861 TI - Physical activity matters: associations among body mass index, physical activity, and health-related quality of life trajectories over 10 years. AB - BACKGROUND: The objective of this study was to assess the associations among body mass index (BMI), leisure time physical activity (LTPA) and health-related quality of life (HRQL) trajectories among adults. METHODS: Self-reported data were drawn from the Canadian National Population Health Survey, with respondents being interviewed every 2 years between 1996-97 and 2006-07. Using growth curve modeling, HRQL trajectories for individuals aged 18 and over were associated with measures of BMI and LTPA. Growth models were constructed separately for males and females. RESULTS: Findings suggested that, for males, BMI categories had little impact on baseline HRQL, and no impact on the rate of change in HRQL. Among women, higher BMI categories were associated with significantly lower baseline HRQL. However, BMI had no impact on the rate of change of HRQL. Conversely, for both men and women and regardless of BMI category, LTPA had significant impacts on baseline HRQL, as well as the rate of change in HRQL. Individuals who were inactive or sedentary had much steeper declines in HRQL as they aged, as compared with individuals who were active in their leisure time. CONCLUSIONS: The results underscore the importance of LTPA in shaping trajectories of HRQL. PMID- 24176863 TI - Template-based high-dose-rate interstitial brachytherapy in gynecologic cancers: a single institutional experience. AB - PURPOSE: To report the outcome and toxicities of radical external beam radiotherapy (EBRT) and template-based high-dose-rate interstitial brachytherapy (ISBT) in patients diagnosed with cervical cancer undergoing inadvertent surgery, vault cancers, and vaginal cancers at our institution. METHODS AND MATERIALS: Between January 2000 and December 2008, 113 patients (37 patients of cervical cancer post-inadvertent surgery, 57 patients with vault cancers, and 19 patients with primary vaginal cancers) were treated with Martinez Universal Perineal Interstitial Template brachytherapy boost after EBRT. The median EBRT dose was 50 Gy, median ISBT dose was 20 Gy, whereas median total dose was 73 Gy equivalent dose at 2 Gy per fraction in all three groups. RESULTS: Median followup of surviving patients for the whole group was 43 months (interquartile range, 19-67 months). The 3-year actuarial disease-free survival and overall survival for three groups was 61%, 61%, 59% and 64%, 64%, and 56%, respectively. Grade III/IV rectal toxicity was seen in 11 (10%) patients, bladder toxicity in 5 (4.5%) patients, whereas 7 (6%) patients developed Grade III small bowel toxicity. Residual disease at brachytherapy had significant impact on DFS and OS. Other factors such as age, disease volume, parametrial extension, and vaginal extension did not impact the survivals. CONCLUSIONS: Martinez Universal Perineal Interstitial Template-based high-dose-rate ISBT boost in gynecologic cancer results in a reasonable outcome in terms of survivals with acceptable late toxicities. The use of template-based ISBT is associated with a definite learning curve. PMID- 24176864 TI - Touchless intra-operative display for interventional radiologist. PMID- 24176865 TI - Tension pneumomediastinum secondary to thoracic air-leak syndrome in chronic graft versus host disease. PMID- 24176866 TI - Peritoneal hydatidosis and hepatic hydatid cyst perforation. PMID- 24176867 TI - Atypical presentation of ovarian metastases of a gastric cancer. PMID- 24176868 TI - Hippocampal sleep spindles preceding neocortical sleep onset in humans. AB - The coexistence of regionally dissociated brain activity patterns -with some brain areas being active while other already showing sleep signs- may occur throughout all vigilance states including the transition from wakefulness to sleep and may account for both physiological as well as pathological events. These dissociated electrophysiological states are often characterized by multi domain cognitive and behavioral impairment such as amnesia for events immediately preceding sleep. By performing simultaneous intracerebral electroencephalographic recordings from hippocampal as well as from distributed neocortical sites in neurosurgical patients, we observed that sleep spindles consistently occurred in the hippocampus several minutes before sleep onset. In addition, hippocampal spindle detections consistently preceded neocortical events, with increasing delays along the cortical antero-posterior axis. Our results support the notion that wakefulness and sleep are not mutually exclusive states, but rather part of a continuum resulting from the complex interaction between diffuse neuromodulatory systems and intrinsic properties of the different thalamocortical modules. This interaction may account for the occurrence of dissociated activity across different brain structures characterizing both physiological and pathological conditions. PMID- 24176871 TI - Rolling in the deep: a quaint sphere rolling in the deep pancreatic duct. PMID- 24176872 TI - An ALTer ego of serum ALT: is it more than a marker of liver inflammation? PMID- 24176869 TI - Analysis of sampling techniques for imbalanced data: An n = 648 ADNI study. AB - Many neuroimaging applications deal with imbalanced imaging data. For example, in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, the mild cognitive impairment (MCI) cases eligible for the study are nearly two times the Alzheimer's disease (AD) patients for structural magnetic resonance imaging (MRI) modality and six times the control cases for proteomics modality. Constructing an accurate classifier from imbalanced data is a challenging task. Traditional classifiers that aim to maximize the overall prediction accuracy tend to classify all data into the majority class. In this paper, we study an ensemble system of feature selection and data sampling for the class imbalance problem. We systematically analyze various sampling techniques by examining the efficacy of different rates and types of undersampling, oversampling, and a combination of over and undersampling approaches. We thoroughly examine six widely used feature selection algorithms to identify significant biomarkers and thereby reduce the complexity of the data. The efficacy of the ensemble techniques is evaluated using two different classifiers including Random Forest and Support Vector Machines based on classification accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity measures. Our extensive experimental results show that for various problem settings in ADNI, (1) a balanced training set obtained with K-Medoids technique based undersampling gives the best overall performance among different data sampling techniques and no sampling approach; and (2) sparse logistic regression with stability selection achieves competitive performance among various feature selection algorithms. Comprehensive experiments with various settings show that our proposed ensemble model of multiple undersampled datasets yields stable and promising results. PMID- 24176873 TI - Single cell analysis of HCV-infected patient hepatocytes: the science is no longer science fiction. PMID- 24176874 TI - The skinny on eosinophilic esophagitis. PMID- 24176875 TI - Some unusual cystic lesions of the liver. PMID- 24176876 TI - High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics. AB - Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. PMID- 24176877 TI - Palaeoclimate reconstructions reveal a strong link between El Nino-Southern Oscillation and Tropical Pacific mean state. AB - The El Nino-Southern Oscillation (ENSO) is one of the most important components of the global climate system, but its potential response to an anthropogenic increase in atmospheric CO2 remains largely unknown. One of the major limitations in ENSO prediction is our poor understanding of the relationship between ENSO variability and long-term changes in Tropical Pacific oceanography. Here we investigate this relationship using palaeorecords derived from the geochemistry of planktonic foraminifera. Our results indicate a strong negative correlation between ENSO variability and zonal gradient of sea-surface temperatures across the Tropical Pacific during the last 22 ky. This strong correlation implies a mechanistic link that tightly couples zonal sea-surface temperature gradient and ENSO variability during large climate changes and provides a unique insight into potential ENSO evolution in the future by suggesting enhanced ENSO variability under a global warming scenario. PMID- 24176878 TI - Open loop Kelvin probe force microscopy with single and multi-frequency excitation. AB - Conventional Kelvin probe force microscopy (KPFM) relies on closed loop (CL) bias feedback for the determination of surface potential (SP). However, SP measured by CL-KPFM has been shown to be strongly influenced by the choice of measurement parameters due to non-electrostatic contributions to the input signal of the bias feedback loop. This often leads to systematic errors of several hundred mV and can also result in topographical crosstalk. Here, open loop (OL)-KPFM modes are investigated as a means of obtaining a quantitative, crosstalk free measurement of the SP of graphene grown on Cu foil, and are directly contrasted with CL-KPFM. OL-KPFM operation is demonstrated in both single and multi-frequency excitation regimes, yielding quantitative SP measurements. The SP difference between single and multilayer graphene structures using OL-KPFM was found to be 63 +/- 11 mV, consistent with values previously reported by CL-KPFM. Furthermore, the same relative potential difference between Al2O3-coated graphene and Al2O3-coated Cu was observed using both CL and OL techniques. We observed an offset of 55 mV between absolute SP values obtained by OL and CL techniques, which is attributed to the influence of non-electrostatic contributions to the input of the bias feedback used in CL-KPFM. PMID- 24176879 TI - CST recovery in pediatric hemiplegic patients: Diffusion tensor tractography study. AB - Many diffusion tensor imaging (DTI) studies have reported an association between corticospinal tract (CST) injury and motor dysfunction. In this study, we investigated CST recovery in 29 pediatric patients with clinical hemiplegia using DTI. We measured the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and asymmetric anisotropy (AA) of both CSTs. The patients were classified into three groups according to severity of CST disruption of the more affected hemisphere. DTI was followed up for 9.34 +/- 2.07 months after initial evaluation. The FA value of the more affected CST showed a significant decrease compared to the opposite side at initial and follow up evaluation, respectively (p<0.05). The FA value of both CSTs showed a significant increase at follow up compared to the initial evaluation, while more changes were observed on the more affected side, compared with the less affected side (p<0.05). AA showed a significant decrease at follow up, and showed significant correlation with interval change of FA value of the more affected side, not with that of the less affected side (r=0.543, p<0.05). 19 patients showed change of CST integrity. In the current study, the results of DTI showed recovery of the CST and provided radiologic evidence for a scientific basis of brain plasticity in pediatric patients. PMID- 24176880 TI - Paraventricular nucleus of hypothalamus participates in the sympathetic modulation and spontaneous fluctuation of baroreflex during head up tilt in unanesthetized rats. AB - The autonomic nervous system is importantly involved in the maintenance of arterial pressure during orthostatic challenges. However, little is known about the specific central areas involved in these cardiovascular compensations. It has been proposed that the paraventricular nucleus of the hypothalamus (PVN) is involved in cardiovascular reflex responses related to blood volume. Our hypothesis is that PVN is involved in autonomic modulation during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to the PVN and femoral artery and vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR) recordings in conscious state. After baseline parameters the rats were submitted to HUT. The spectral analysis during HUT showed an increase in low-frequency oscillation of systolic arterial pressure (SAP) (LF: 14.21+/-2.73-32.44+/-8.43 mmHg(2)) and pulse interval (PI) (LF: 14.05+/-4.25-51.79+/-10.64 n.u.) and a decrease in high-frequency oscillation (HF; 84.52+/-4.82-47.49+/-10.30 n.u.). Previous bilaterally microinjection of cobalt chloride (1 mM/100 nl), a calcium channel blocking agent, into the PVN decreased LF oscillations of SAP (LF: 32.44+/-8.43-13.23+/-1.87 mmHg(2)) as well as in PI (LF: 12.38+/-3.76-5.03+/-1.20 ms(2)). Muscimol microinjection (40 mM), a GABAA agonist, decreased LF component of PI oscillations (LF: 51.79+/-10.64 25.76+/-5.34 n.u.). The baroreflex gain was not altered by HUT, but during tilt, with PVN previously inhibited by muscimol or cobalt chloride, the gain was reduced. Our data suggest that the PVN participates in the brain circuitry involved in autonomic adjustment during orthostatic challenges. PMID- 24176881 TI - Characterization of the APP/PS1 mouse model of Alzheimer's disease in senescence accelerated background. AB - The APP/PS1 mouse model of Alzheimer's disease (AD) exhibits remarkable elevation of beta-amyloid production associated with certain behavioral abnormalities, while the senescence accelerated mouse prone 8 (SAMP8) is characterized by early and age-related deterioration of learning and memory. In order to obtain an AD model that develops earlier pathological changes and cognitive impairment, we generated SAMP8-APP/PS1, a novel senescence accelerated APP/PS1 transgenic mouse model of AD. Standard histological staining and immunohistochemistry using an amyloid beta (Abeta) antibody showed an age, genotype and strain-dependent progression of amyloid deposition and neuron loss in the cerebral cortex and hippocampus of SAMP8-APP/PS1 mice. Results from the cognitive behavioral tests revealed early deficits in learning and memory in SAMP8-APP/PS1 mice in the two way active avoidance and Morris water maze tests compared with C57-APP/PS1, SAMP8 wild-type and control mice. These results suggest that accelerated senescence exacerbates amyloid deposition and cognitive dysfunction in APP/PS1 mice and the senescence accelerated-APP/PS1 (SAMP8-APP/PS1) mouse model might be a valuable tool to study AD progression and to evaluate the effect of drugs on AD. PMID- 24176882 TI - Remodeling of the dendritic structure of the striatal medium spiny neurons accompanies behavioral recovery in a mouse model of Parkinson's disease. AB - Medium spiny neurons (MSNs) are the major type of neurons found in the striatum. The dendritic spines on these cells contain glutamatergic synaptic contacts between the cortex (or the thalamus) and the striatum. The complexity of the dendritic structure of MSNs may therefore reflect the functional status of the basal ganglia because the striatum is the major input structure in which signals from different regions are integrated. We examined the structural alterations in the dendrites of striatal MSNs in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). Acute MPTP treatment rapidly damaged dopaminergic neurons and their terminals within the striatum and caused behavioral impairments. However, mice injected with MPTP spontaneously recovered from these behavioral impairments within one week. This recovery was accompanied by the restoration of dendritic structures on MSNs, but the damage to dopaminergic neurons remained extensive. Furthermore, we demonstrated that rasagiline, a monoamine oxidase-B (MAO-B) inhibitor that has been shown to be efficacious for PD, could enhance the dendritic complexity of cultured MSNs. The effect of rasagiline on the spine-like structures of dendrites, however, appears not to require DA availability because the small protrusions of dendrites in cultured MSNs without major source of DA input was similarly changed by rasagiline. Our data suggest that the dendritic structures of striatal MSNs change dynamically, reflecting the progression of motor-related symptoms in PD, and the restoration of functional synapses in the MSNs of PD patients may constitute a clinical target for symptomatic alleviation. PMID- 24176884 TI - Who benefits most from adjuvant interferon treatment for melanoma? AB - Metastatic melanoma has a poor prognosis; the median survival for patients with stage IV melanoma ranges from 8 to 18 months after diagnosis. Interferon-alpha provides significant improvement in disease-free survival at the cost of poor tolerability. Identifying patients who benefit the most may improve the cost:benefit ratio. In addition, no data exist for the role of adjuvant therapy in noncutaneous melanoma. Molecular profiles may help to identify patients who benefit the most from adjuvant interferon therapy. In this review, the American Joint Commission on Cancer 2009 staging criteria and emerging biomarker data to guide adjuvant treatment decisions will be discussed. Several criteria to guide selection of patients are discussed in detail. These include Breslow thickness, number of positive lymph nodes, whether or not the primary lesion has ulcerated, immunologic markers, and cytokine profiles. Substantial progress has been made in deciding which patients benefit from interferon-alpha adjuvant therapy. Interferon-alpha is the only agent currently approved for the adjuvant treatment of this deadly disease, despite its side effect profile. More effective drugs with better tolerability are needed. PMID- 24176883 TI - DJ1 analysis in a large cohort of Italian early onset Parkinson Disease patients. AB - We analyzed the DJ1 gene in a large consecutive series (N=163) of Italian unrelated Early Onset Parkinson Disease (EOPD: onset <=40 years of age) patients and 100 healthy controls (mean age 64 +/- 7 years). No homozygous or compound heterozygous mutations with an obvious pathogenic effect were found. Several variants were identified, some of which were novels. All variants had similar frequency in patients and in controls. Our data suggest that DJ1 mutations are very rare in Italian EOPD. Other genes and risk factors for PD are still to be identified. PMID- 24176885 TI - Biosorption of Pb(II) from aqueous solution by Solanum melongena leaf powder as a low-cost biosorbent prepared from agricultural waste. AB - Solanum melongena leaves are relatively galore and used as inexpensive material. This paper presents the characterization and evaluation of potential of S. melongena leaf powder (SMLP) for removal of Pb(II) from aqueous solution as a function of pH, biomass dosage, initial metal ion concentration, contact time and temperature. Experimental data were analyzed in terms of three kinetic models such as the pseudo-first-order, pseudo-second-order and intraparticle diffusion models and the results showed that the biosorption processes of Pb(II) followed well pseudo-second-order kinetics. Langmuir and Freundlich isotherm models were applied to describe the biosorption process. Langmuir isotherm described the equilibrium data very well, with a maximum monolayer sorption capacity of 71.42 mg/g for Pb(II) ions at 323 K. The biosorption process was spontaneous and endothermic in nature with negative DeltaG degrees (-8.746, -8.509 and -7.983 kJ/mol) and positive value for DeltaH degrees (3.698 kJ/mol). PMID- 24176886 TI - Co-encapsulation of antioxidants into niosomal carriers: gastrointestinal release studies for nutraceutical applications. AB - Recently niosomes have been used as nutraceutical vehicles of functional components, useful in the prevention of many diseases caused by oxidative stress, with the aim to control their delivery into the body and to increase the nutritional quality of food dairy products with which these products can be enriched. We decided to develop novel niosomal formulations containing nutritional supplements such as gallic acid, ascorbic acid, curcumin and quercetin as single agents and in combination, to evaluate the effect of the active molecules co-encapsulation on the physico-chemical properties of the carriers, on their antioxidant properties and capability of releasing the encapsulated materials. Results suggest that the co-encapsulations of gallic acid/curcumin and ascorbic acid/quercetin mix influence their physico-chemical properties and their entrapment efficiencies respect to the formulations containing the single antioxidant; also the antioxidants releases appeared to improve and their combinations resulted in a promoted ability of reducing free radicals, due to a synergic antioxidant action. PMID- 24176887 TI - Simultaneous determination of codeine and caffeine using single-walled carbon nanotubes modified carbon-ceramic electrode. AB - In the present paper, the simultaneous determination of codeine (CO) and caffeine (CF) is described by the use of single-walled carbon nanotubes modified carbon ceramic electrode (SWCNT/CCE); prepared via a simple and rapid method. The results show that the SWCNT/CCE exhibits excellent electrochemical catalytic activity toward the oxidation of these compounds with respect to the bare CCE and offers two anodic peaks at 1.05 and 1.38 V vs. saturated calomel electrode for oxidation of CO and CF, respectively. Differential pulse voltammetry was used for simultaneous determination of CO and CF at micromolar concentration level. In the optimum conditions, it is found that the calibration graphs for CO and CF are linear in the concentration ranges 0.2-230 and 0.4-300 MUM with detection limits of 0.11 and 0.25 MUM for CO and CF, respectively. The SWCNT/CCE presents good stability, reproducibility, and repeatability and the proposed method has been successfully applied for determination of CO and CF in some pharmaceutical, drinking and biological samples with high recovery rate. PMID- 24176888 TI - Biofunctional quantum dots as fluorescence probe for cell-specific targeting. AB - We describe here the synthesis, characterization, bioconjugation, and application of water-soluble thioglycolic acid TGA-capped CdTe/CdS quantum dots (TGA-QDs) for targeted cellular imaging. Anti-human epidermal growth factor receptor 2 (HER2) antibodies were conjugated to TGA-QDs to target HER2-overexpressing cancer cells. TGA-QDs and TGA-QDs/anti-HER2 bioconjugates were characterized by fluorescence and UV-Vis spectroscopy, X-ray diffraction (XRD), hydrodynamic sizing, electron microscopy, and gel electrophoresis. TGA-QDs and TGA-QDs/anti-HER2 were incubated with cells to examine cytotoxicity, targeting efficiency, and cellular localization. The cytotoxicity of particles was measured using an MTT assay and the no observable adverse effect concentration (NOAEC), 50% inhibitory concentration (IC50), and total lethal concentration (TLC) were calculated. To evaluate localization and targeting efficiency of TGA-QDs with or without antibodies, fluorescence microscopy and flow cytometry were performed. Our results indicate that antibody-conjugated TGA-QDs are well-suited for targeted cellular imaging studies. PMID- 24176889 TI - Synthesis of poly(N-isopropylacrylamide) particles for metal affinity binding of peptides. AB - Temperature-sensitive poly(N-isopropylacrylamide) (PNIPAM) microgel particles with metal affinity ligands were prepared for selective binding of peptides containing the His6-tag (six consecutive histidine residues). The PNIPAM particles were copolymerized with the functional ligand vinylbenzyl iminodiacetic acid (VBIDA) through a two-stage dispersion polymerization using poly(N-vinyl pyrrolidone) (PVP) as a steric stabilizer. The resulting particles were monodisperse in size and colloidally stable over a wide range of temperature and ionic strength due to chemically grafted PVP chains. The particle size was also found to be sensitive to ionic strength and pH of the aqueous environment, likely due to the electrostatic repulsion between ionized VBIDA groups. Divalent nickel ions were chelated to the VBIDA groups, allowing selective metal affinity attachment of a His6-Cys peptide. The peptide was released upon the addition of the competitive ligand imidazole, demonstrating that the peptide attachment to the particles is reversible and selective. PMID- 24176890 TI - Fabrication of a composite system combining solid lipid nanoparticles and thermosensitive hydrogel for challenging ophthalmic drug delivery. AB - The purpose of this study was to explore a composite thermosensitive in situ gelling formulation using the distribution of solid lipid nanoparticles (SLNs) among poloxamer-based hydrogels as a potential carrier for novel ocular drug delivery. SLNs containing the model drug Resina Draconis were prepared using a melt-emulsion ultrasonication method. A central composite design (CCD) was adopted to screen the thermosensitive hydrogel (THG) formulation. After aqueous SLNs were dispersed into the THG matrices, the physicochemical properties of the SLNs were characterized before and after their incorporation into hydrogels. The in vitro corneal penetration experiment, ocular irritant test and transcorneal mechanism across the cornea have been previously described to predict the feasibility for the proposed ophthalmic application. Finally, the optimal THGs consisted of 27.8% (w/v) poloxamer 407 and 3.55% (w/v) poloxamer 188. The particle size of the SLNs remained within the colloidal range. In vitro corneal penetration studies revealed a nearly steady sustained drug release. The hen's egg test-chorioallantoic membrane (HET-CAM) test indicated that all of the tested polymer systems were non-irritant. Coumarin-6 labeled SLNs formulated into THGs displayed a more homogeneous fluorescence with a deeper penetration intensity into the cornea at various times. Taken together, these results suggest that the SLN-based THG system can be used as a potential vehicle for ocular application. PMID- 24176891 TI - Resveratrol stabilized gold nanoparticles enable surface loading of doxorubicin and anticancer activity. AB - The green synthesis of gold nanoparticles was achieved by exploiting the antioxidant property of resveratrol (R). The formation of resveratrol stabilized gold nanoparticles (R-GNPs) was confirmed by the observation of the surface plasmon resonance band at 537 nm. The average size of R-GNPs produced in resveratrol medium was ~35nm. The geometrical shape and zeta potential of the gold nanoparticles were spherical and -21.2 mV, respectively. R-GNPs showed excellent stability in saline and other buffers mimicking the physiological pH. The MTT assay using fibroblast cells from explants tissue revealed the biocompatibility of R-GNPs. The cytotoxic activity of doxorubicin loaded R-GNPs against glioma carcinoma cell line (LN 229), showed the suitability of R-GNPs as a carrier for anticancer drugs. PMID- 24176892 TI - Co-encapsulation of lipophilic antioxidants into niosomal carriers: percutaneous permeation studies for cosmeceutical applications. AB - Niosomal vesicular systems containing resveratrol, alpha-tocopherol and curcumin as single agents and in combination, were designed with the aim to develop novel cosmeceutical formulations. The effects of antioxidants co-encapsulation on the physico-chemical properties of the carriers, their antioxidant properties and in vitro percutaneous permeation profiles were evaluated. Results showed that the co encapsulation of resveratrol/curcumin and alpha-tocopherol/curcumin affected the physico-chemical properties of niosomes and the entrapment efficiencies values, respect to the formulations containing the single antioxidant. The antioxidants in vitro percutaneous permeations appeared to be controlled and improved respect to the corresponding free solutions used as control. Moreover the antioxidants combinations resulted in a promoted ability to reduce free radicals, due to a synergic antioxidant action. PMID- 24176893 TI - A physical activity program for Swedish physically inactive female high school students: a controlled intervention study. AB - BACKGROUND: Physical activity and sport participation often decline during adolescence. AIM: To investigate if physical exercise during 6 months could lead to a positive behavior of physical activity, improve physical fitness and self related health in physically inactive female high school students. METHODS: A prospective cluster-randomized controlled intervention study included 104 physically inactive female high school students, 60 in an intervention group and 44 controls. At baseline there were no group differences regarding self-related health. The intervention group exercised at least once per week. A questionnaire and physical fitness tests were used for evaluation, at baseline and 6 months later. RESULTS: The intervention group improved their self-related health compared with the controls (P = .012). When divided into a regular (n = 27) and an irregular training group (n = 33) the regular training group improved their self-related health compared with the controls, while the irregular training group did not differ from the other groups. Maximal oxygen consumption was improved in the intervention group compared with the controls (P < .001). No group differences were found in muscle strength and endurance. CONCLUSION: Physical exercise at least once per week during 6 months improved physical fitness (maximal oxygen consumption) and self-related health in physically inactive female high school students. PMID- 24176894 TI - Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV. AB - Vesicular stomatitis virus (VSV) is neuropathogenic in rodents but can be attenuated 50-fold by engineering the mouse interferon-beta (IFN-beta) gene into its genome. Intravenously administered VSVs encoding IFN-beta have potent activity against subcutaneous tumors in the 5TGM1 mouse myeloma model, without attendant neurotoxicity. However, when 5TGM1 tumor cells were seeded intravenously, virus-treated mice with advanced myeloma developed clinical signs suggestive of meningoencephalitis. Co-administration of a known active antimyeloma agent did not prolong survival, further suggesting that deaths were due to viral toxicity, not tumor burden. Histological analysis revealed that systemically administered 5TGM1 cells seed to the CNS, forming meningeal tumor deposits, and that VSV infects and destroys these tumors. Death is presumably a consequence of meningeal damage and/or direct transmission of virus to adjacent neural tissue. In light of these studies, extreme caution is warranted in clinical testing of attenuated VSVs, particularly in patients with CNS tumor deposits. PMID- 24176895 TI - Survival analysis of robotic versus traditional laparoscopic surgical staging for endometrial cancer. AB - OBJECTIVE: The purpose of this study was to compare the survival of women with endometrial cancer managed by robotic- and laparoscopic-assisted surgery. STUDY DESIGN: This was a retrospective study conducted at 2 academic centers. Primary outcomes were overall survival, disease-free survival (DFS), and disease recurrence. RESULTS: From 2003 through 2010, 415 women met the study criteria. A total of 183 women had robotic and 232 women had laparoscopic-assisted surgery. Both groups were comparable in age, body mass index, comorbid conditions, histology, surgical stage, tumor grade, total nodes retrieved, and adjuvant therapy. With a median follow-up of 38 months (range, 4-61 months) for the robotic and 58 months (range, 4-118 months) for the traditional laparoscopic group, there were no significant differences in survival (3-year survival 93.3% and 93.6%), DFS (3-year DFS 83.3% and 88.4%), and tumor recurrence (14.8% and 12.1%) for robotic and laparoscopic groups, respectively. Univariate and multivariate analysis showed that surgery is not an independent prognostic factor of survival. CONCLUSION: Robotic-assisted surgery yields equivalent oncologic outcomes when compared to traditional laparoscopic surgery for endometrial adenocarcinoma. PMID- 24176896 TI - Teaching ethics: when respect for autonomy and cultural sensitivity collide. AB - Respect for autonomy is a key ethical principle. However, in some cultures other moral domains such as community (emphasizing the importance of family roles) and sanctity (emphasizing the sacred and the spiritual side of human nature) hold equal value. Thus, an American physician may sometimes perceive a conflict between the desire to practice ethically and the wish to be sensitive to the mores of other cultures. For example, a woman may appear to be making what the physician thinks is a bad clinical choice because her spouse is speaking on her behalf. That physician may find it difficult to reconcile the sense that the patient had not exercised freely her autonomy with the desire to be culturally sensitive. In this article, the means by which a physician can reconcile respect for other cultures with respect for autonomy is explored. The question of whether physicians must always defer to patients' requests solely because they are couched in the language of cultural sensitivity is also addressed. PMID- 24176897 TI - Reply: To PMID 23727040. PMID- 24176898 TI - A transpersonal approach to care: a qualitative study of performers' experiences with DooR to DooR, a hospital-based arts program. AB - The arts have a history of relaxing and calming patients in the hospital setting, yet research is limited on how arts may aid in the healing process. DooR to DooR was established to bring comfort, respite, and healing to hospitalized patients, family members, and health care staff. DooR to DooR is located in the University of North Carolina Hospitals at Chapel Hill, North Carolina; professional performing artists visit there, spending 5 to 10 minutes with each patient, family member, and health care staff. The purpose of this qualitative study is to understand performers' experiences and of how arts-based programs can facilitate improved patient outcomes in the hospitalized setting to help nurses better use the arts in their care of patients and families. Three overarching themes were identified: (a) the arts are therapeutic for all involved, (b) the arts transform the hospital environment, and (c) nurses and the other medical staff play an important role. The significance of this study for nursing practice is that the arts are a plausible intervention for the hospital because they may help improve patient outcomes by reducing pain and depression and by relieving stress among staff and family members. More research is needed to determine the level of arts as-an-intervention knowledge among nurses. PMID- 24176899 TI - Retinal vascular parameter variations in patients with human immunodeficiency virus. AB - PURPOSE: To compare the retinal vascular parameters in patients with human immunodeficiency virus (HIV) infection with normal controls, and to determine the relationship between retinal vascular parameters and HIV-related blood biomarkers (CD4(+) T-lymphocytes count, presence of HIV RNA). METHODS: Case-control study of eighty-five patients with HIV on follow-up at the Communicable Disease Center, Singapore, and 251 age-, sex-, and race-matched normal healthy controls (case: control matching ~ 1:3) selected from the Singapore Epidemiology of Eye Disease program were included in this study. Standardized retinal photographs were taken from patients and controls. Trained technicians measured quantitative retinal vascular parameters (retinal vascular caliber, branching angle, tortuosity, and fractal dimension) with a semiautomated computer-based program following a standardized protocol. RESULTS: HIV-patients had more tortuous arterioles (0.77 * [10(4)] vs. 0.59 * [10(4)], P < 0.001) and venules (0.90 * [10(4)] vs. 0.74 * [10(4)], P < 0.001), compared with healthy normal subjects. Amongst the HIV patients, increasing HIV viral loads were associated with decreased retinal arteriolar caliber (P trend = 0.009) and decreased arteriolar-venular ratio (P trend = 0.025). CONCLUSIONS: Our study showed that patients with HIV have significant variations in retinal vasculature. Retinal vascular imaging may offer further insight into the pathophysiology behind HIV-related vascular disease in future. PMID- 24176900 TI - Reduction of steroid-induced intraocular pressure elevation in sheep by tissue plasminogen activator. AB - PURPOSE: To investigate whether tissue plasminogen activator (tPA) can prevent and/or reverse steroid-induced IOP elevation in an ovine model. METHODS: Three animal groups were subjected to bilateral steroid-induced IOP elevation using thrice daily topical ocular prednisolone administration. In the first group (N = 8), one eye each of two sheep was injected intravitreally with 100 MUg, 200 MUg, 500 MUg, or 1 mg human recombinant tPA, while contralateral eyes received vehicle. In the second group (N = 2), one eye was injected intravitreally with tPA (100 MUg), while contralateral eyes received vehicle containing L-arginine. In the third group (N = 4), each animal received intravitreal tPA in one eye concurrently with initiation of bilateral steroid administration. IOP was monitored for the duration of the experiment. Tissues from eyes of the third group were used to determine relative gene expression. RESULTS: In the first and second groups, IOP decreased by 9.7 (+/-2.8) and 9.7 (+/-1.6) mm Hg, respectively, 24 hours after tPA administration. In the third group, tPA-treated eyes did not develop IOP elevation with DeltaIOP of 11.8 (+/-1.3) mm Hg 8 days later. In all tPA-treated eyes, IOP remained low until the end of the study. mRNA levels in the trabecular meshwork were decreased for plasminogen activator tissue (PLAT), increased for matrix-metalloproteinase 1 (MMP-1), and stable for plasminogen activator inhibitor 1 (PAI-1), MMP-2, MMP-9, and MMP-13 in tPA treated eyes compared with contralateral controls. PAI-1 mRNA levels in ciliary processes also remained similar. CONCLUSIONS: Recombinant human tPA is effective in both preventing and reversing steroid-induced IOP elevation in sheep. Tissue plasminogen activator may be useful as a therapeutic agent in steroid-induced glaucoma. PMID- 24176901 TI - Efficacy and safety of intra-arterial thrombolysis in central retinal artery occlusion. AB - PURPOSE: To investigate the efficacy and safety of intra-arterial thrombolysis (IAT) for acute central retinal artery occlusion (CRAO). METHODS: Records from 101 CRAO patients treated with either IAT (n = 57) or standard treatment (ST; n = 44) were retrospectively reviewed. ST consisted of ocular massage and intraocular pressure-lowering agents. We used fundoscopic and angiographic findings to categorize CRAO as incomplete (diminished visual acuity [VA] with slight retinal edema, slight cherry-red spot), subtotal (severe VA reduction, cherry-red spot, distinct retinal edema), or total (massive edema, occluded perimacular arterioles, additional choroidal blood flow interruption). One-month and final best-corrected VA (BCVA) of the IAT group were compared with those of the ST group. Early (<=3-day) and final (1-month) reperfusion (improvement of retinal perfusion) rates were compared between groups. Subgroup analyses were performed according to CRAO stage. RESULTS: Overall, VA did not significantly differ between groups, but early reperfusion was greater in the IAT group (74.1% vs. 42.9%, P = 0.005). In incomplete CRAO, the IAT group exhibited greater visual improvement after 1 month (1.08 +/- 0.21 vs. 0.23 +/- 0.26 logarithmic values of the minimum angle of resolution [logMAR], P < 0.001) and at the final visit (1.08 +/- 0.53 vs. 0.08 +/- 0.57 logMAR, P < 0.001). However, in subtotal and total CRAO, no significant differences in visual outcomes were observed between groups. IAT resulted in clinically insignificant cerebral infarcts, detectable on brain imaging, in 8% of patients. Hemorrhagic transformation was not noted. CONCLUSIONS: The IAT treatment may provide early restoration of retinal perfusion and offer functional benefits in the management of incomplete CRAO. PMID- 24176902 TI - Does visual impairment affect mobility over time? The Salisbury Eye Evaluation Study. AB - PURPOSE: To determine if the odds of mobility disability increases at a different rate among visually impaired (VI) as compared with nonvisually impaired (NVI) over an 8-year period. METHODS: A total of 2520 Salisbury Eye Evaluation Study participants were followed 2, 6, and 8 years after baseline. VI was defined as best-corrected visual acuity worse than 20/40, or visual field of approximately less than 20 degrees . Self-reported difficulty with three tasks was assessed at each visit: walking up 10 steps, walking down 10 steps, and walking 150 feet. Generalized estimating equation models included a 6-year spline, and explored differences in mobility difficulty trajectories by including an interaction between VI status and the spline terms. Odds ratios (OR) and 95% confidence intervals (CI) compared mobility difficulty for each task by VI status. RESULTS: At baseline, the VI were significantly more likely to report difficulty mobility tasks than the NVI (OR(difficultywalkingup10steps) = 1.37, CI: 1.02-1.80; OR(difficultywalkingdown10steps) = 1.55, CI: 1.16-2.08; OR(difficultywalking150feet) = 1.50, CI: 1.10-2.04). The trajectory of mobility disability did not differ by VI status from baseline to the 6-year visit. However, the difference between the VI and NVI declined at the 8-year visit, which may be due to loss of VI participants at risk of developing mobility difficulty. CONCLUSIONS: The VI were more likely to report mobility disability than the NVI, but the trajectory of mobility disability was not steeper among the VI as compared to the NVI over the study period. PMID- 24176903 TI - Choroidal thickness in myopic and nonmyopic children assessed with enhanced depth imaging optical coherence tomography. AB - PURPOSE: We examined choroidal thickness (ChT) and its topographic variation across the posterior pole in myopic and nonmyopic children. METHODS: A total of 104 children aged 10 to 15 years (mean age, 13.1 +/- 1.4 years) had ChT measured using enhanced depth imaging optical coherence tomography (OCT). Of these children 40 were myopic (mean spherical equivalent, -2.4 +/- 1.5 diopters [D]) and 63 were nonmyopic (mean, +0.3 +/- 0.3 D). Two series of 6 radial OCT line scans centered on the fovea were assessed for each child. Subfoveal ChT and ChT across a series of parafoveal zones over the central 6 mm of the posterior pole were determined through manual image segmentation. RESULTS: Subfoveal ChT was significantly thinner in myopes (mean, 303 +/- 79 MUm) compared to nonmyopes (mean, 359 +/- 77 MUm, P < 0.0001). Multiple regression analysis revealed refractive error (r = 0.39, P < 0.001) and age (r = 0.21, P = 0.02) were associated positively with subfoveal ChT. Also, ChT exhibited significant topographic variations, with the choroid being thicker in more central regions. The thinnest choroid was observed typically in nasal (mean, 286 +/- 77 MUm) and inferior-nasal (306 +/- 79 MUm) locations, and the thickest in superior (346 +/- 79 MUm) and superior-temporal (341 +/- 74 MUm) locations. The difference in ChT between myopic and nonmyopic children was significantly greater in central foveal regions compared to more peripheral regions (>3 mm diameter, P < 0.001). CONCLUSIONS: Myopic children have significantly thinner choroids compared to nonmyopic children of similar age, particularly in central foveal regions. The magnitude of difference in choroidal thickness associated with myopia appears greater than would be predicted by a simple passive choroidal thinning with axial elongation. PMID- 24176905 TI - Intronic deletions in the SLC34A3 gene: a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria. AB - Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25 dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6-1/2 year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24-hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH), and elevated 1,25(OH)2D. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440-1469del). The single base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. PMID- 24176906 TI - The onset of type 2 diabetes: proposal for a multi-scale model. AB - BACKGROUND: Type 2 diabetes mellitus (T2D) is a common age-related disease, and is a major health concern, particularly in developed countries where the population is aging, including Europe. The multi-scale immune system simulator for the onset of type 2 diabetes (MISSION-T2D) is a European Union-funded project that aims to develop and validate an integrated, multilevel, and patient-specific model, incorporating genetic, metabolic, and nutritional data for the simulation and prediction of metabolic and inflammatory processes in the onset and progression of T2D. The project will ultimately provide a tool for diagnosis and clinical decision making that can estimate the risk of developing T2D and predict its progression in response to possible therapies. Recent data showed that T2D and its complications, specifically in the heart, kidney, retina, and feet, should be considered a systemic disease that is sustained by a pervasive, metabolically-driven state of inflammation. Accordingly, there is an urgent need (1) to understand the complex mechanisms underpinning the onset of this disease, and (2) to identify early patient-specific diagnostic parameters and related inflammatory indicators. OBJECTIVE: We aim to accomplish this mission by setting up a multi-scale model to study the systemic interactions of the biological mechanisms involved in response to a variety of nutritional and metabolic stimuli and stressors. METHODS: Specifically, we will be studying the biological mechanisms of immunological/inflammatory processes, energy intake/expenditure ratio, and cell cycle rate. The overall architecture of the model will exploit an already established immune system simulator as well as several discrete and continuous mathematical methods for modeling of the processes critically involved in the onset and progression of T2D. We aim to validate the predictions of our models using actual biological and clinical data. RESULTS: This study was initiated in March 2013 and is expected to be completed by February 2016. CONCLUSIONS: MISSION-T2D aims to pave the way for translating validated multilevel immune-metabolic models into the clinical setting of T2D. This approach will eventually generate predictive biomarkers for this disease from the integration of clinical data with metabolic, nutritional, immune/inflammatory, genetic, and gut microbiota profiles. Eventually, it should prove possible to translate these into cost-effective and mobile-based diagnostic tools. PMID- 24176907 TI - Keratocystic odontogenic tumor: a commentary. PMID- 24176908 TI - Evidence for massive bulk Dirac fermions in Pb1-xSnxSe from Nernst and thermopower experiments. AB - Topological surface states protected by mirror symmetry are of interest for spintronic applications. Such states were predicted to exist in the rocksalt IV VI semiconductors, and several groups have observed the surface states in (Pb,Sn)Te, (Pb,Sn)Se and SnTe using photoemission. An underlying assumption in the theory is that the surface states arise from bulk states describable as massive Dirac states, but this assumption is untested. Here we show that the thermoelectric response of the bulk states displays features specific to the Dirac spectrum. By relating the carrier density to the peaks in the quantum oscillations, we show that the first (N=0) Landau level is non-degenerate. This finding provides robust evidence that the bulk states are indeed massive Dirac states. In the lowest Landau level, Sxx displays a striking linear increase versus magnetic field characteristic of massive Dirac fermions. In addition, the Nernst signal displays a sign anomaly in the gap-inverted phase at low temperatures. PMID- 24176909 TI - Crosstalk between second messengers predicts the motility of the growth cone. AB - Axon guidance involves multiple second messenger signal transduction pathways. Although each signal transduction pathway has been characterized, only a few studies have examined crosstalk between these cascades. Here, we applied a simultaneous second messenger imaging method to the growth cone and demonstrated correlations between cAMP, cGMP, and Ca(2+). The levels of cAMP and cGMP in non stimulated freely extending growth cones showed a negative correlation without delay. Although there was no direct correlation between cAMP and Ca(2+), examination of cross correlations using small time windows showed frequent switching behavior from negative to positive and vice versa. Furthermore, spatially asymmetric cAMP and cGMP signals in freely deviating growth cones were visualized directly. These results indicate that we succeed in relating second messenger crosstalk to growth cone deviation and extension, and also indicate the possibility of predicting axon guidance from this second messenger crosstalk. PMID- 24176911 TI - Practical use of near-infrared spectroscopy in carotid surgery. AB - Carotid endarterectomy (CEA) is the gold standard for the treatment of symptomatic patients with atherosclerotic carotid disease. However, benefit of the CEA procedure depends on the rate of peri- and postoperative adverse neurological events. Therefore, brain monitoring is important in detecting cerebral ischemia during and after CEA and also allows to prompt appropriate action. Traditional methods of cerebral monitoring are being replaced by novel, easy-to-use techniques that allow continued monitoring of regional cerebral oxygen saturation. In this review, we present the recent literature data related to the mechanism of cerebral oximetry and its practical use during and after CEA. PMID- 24176912 TI - Low-density lipoprotein cholesterol targeting: a continued controversy. PMID- 24176910 TI - Intriguing mechanistic labyrinths in gold(I) catalysis. AB - Many mechanistically intriguing reactions have been developed in the last decade using gold(I) as catalyst. Here we review the main mechanistic proposals in gold catalysed activation of alkynes and allenes, in which this metal plays a central role by stabilising a variety of complex cationic intermediates. PMID- 24176913 TI - Co nanostructures in ordered templates: comparative FORC analysis. AB - A comparative study on the structural and magnetic properties of highly ordered hexagonal arrays of Co nanoholes, nanowires, nanopillars and nanotubes, with tuned pore/wire/tube diameters, is here presented. The magnetic interactions and their dependence on the geometric features of the arrays were studied using first order reversal curves (FORCs). For all nanostructures we observe an increase of the magnetostatic interactions with the templates' pore diameter, with the higher (smaller) values found for the nanowire (nanohole) arrays. For the smallest diameters studied (35 nm), all types of arrays could be considered as almost isolated nanostructures, where local interactions prevail. In particular, both nanotube and nanohole arrays exhibit considerable local magnetostatic interactions coming from the stray fields within each void or empty core. On the other hand, the coercivity is found to decrease with diameter for the elongated nanostructures, while it increases with the pore diameter for the nanohole arrays. This behavior is associated with the magnetization reversal mechanisms present in each array. This work highlights a versatile route to tailor the size, geometrical arrangement and magnetostatic interactions of ordered arrays and demonstrates their importance for the tuning of the magnetic behavior of nanometric devices. PMID- 24176914 TI - COUP-TFII regulates human endometrial stromal genes involved in inflammation. AB - Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII; NR2F2) is an orphan nuclear receptor involved in cell-fate specification, organogenesis, angiogenesis, and metabolism. Ablation of COUP-TFII in the mouse uterus causes infertility due to defects in embryo attachment and impaired uterine stromal cell decidualization. Although the function of COUP-TFII in uterine decidualization has been described in mice, its role in the human uterus remains unknown. We observed that, as in mice, COUP-TFII is robustly expressed in the endometrial stroma of healthy women, and its expression is reduced in the ectopic lesions of women with endometriosis. To interrogate the role of COUP-TFII in human endometrial function, we used a small interfering RNA-mediated loss of function approach in primary human endometrial stromal cells. Attenuation of COUP-TFII expression did not completely block decidualization; rather it had a selective effect on gene expression. To better elucidate the role of COUP-TFII in endometrial stroma cell biology, the COUP-TFII transcriptome was defined by pairing microarray comparison with chromatin immunoprecipitation followed by deep sequencing. Gene ontology analysis demonstrates that COUP-TFII regulates a subset of genes in endometrial stroma cell decidualization such as those involved in cell adhesion, angiogenesis, and inflammation. Importantly this analysis shows that COUP-TFII plays a role in controlling the expression of inflammatory cytokines. The determination that COUP-TFII plays a role in inflammation may add insight into the role of COUP-TFII in embryo implantation and in endometrial diseases such as endometriosis. PMID- 24176916 TI - Physiotherapists' knowledge, attitudes and practices regarding clinical prediction rules for low back pain. AB - Clinical Prediction Rules (CPRs) have been developed to assist in the physiotherapy management of low back pain (LBP) although little is known about the factors that may influence their implementation in clinical practice. This study used qualitative research methodology to explore the knowledge, attitudes and practices/behaviours of physiotherapists in relation to these tools. Four semi-structured focus groups involving 26 musculoskeletal physiotherapists were conducted across three Australian geographic regions. A fictitious LBP case scenario was developed and used to facilitate group discussion. Participant knowledge of CPRs was found to be mixed, with some clinicians never having previously encountered the term or concept. LBP CPRs were often conceptualised as a formalisation of pattern recognition. Attitudes towards CPRs expressed by study participants were wide-ranging with several facilitating and inhibiting views identified. It was felt that more experienced clinicians had limited need of such tools. Only a small number of participants expressed that they had ever used LBP CPRs in clinical practice. To optimise the successful adoption of an LBP CPR, researchers should consider avoiding the use of the term 'rule' and ensure that the tool and its interface are uncomplicated and easy to use. Understanding potential barriers, the needs of clinicians and the context in which CPRs will be implemented will help facilitate the development of tools with the highest potential to positively influence physiotherapy practice. PMID- 24176915 TI - M-protein is down-regulated in cardiac hypertrophy driven by thyroid hormone in rats. AB - Although it is well known that the thyroid hormone (T3) is an important positive regulator of cardiac function over a short term and that it also promotes deleterious effects over a long term, the molecular mechanisms for such effects are not yet well understood. Because most alterations in cardiac function are associated with changes in sarcomeric machinery, the present work was undertaken to find novel sarcomeric hot spots driven by T3 in the heart. A microarray analysis indicated that the M-band is a major hot spot, and the structural sarcomeric gene coding for the M-protein is severely down-regulated by T3. Real time quantitative PCR-based measurements confirmed that T3 (1, 5, 50, and 100 physiological doses for 2 days) sharply decreased the M-protein gene and protein expression in vivo in a dose-dependent manner. Furthermore, the M-protein gene expression was elevated 3.4-fold in hypothyroid rats. Accordingly, T3 was able to rapidly and strongly reduce the M-protein gene expression in neonatal cardiomyocytes. Deletions at the M-protein promoter and bioinformatics approach suggested an area responsive to T3, which was confirmed by chromatin immunoprecipitation assay. Functional assays in cultured neonatal cardiomyocytes revealed that depletion of M-protein (by small interfering RNA) drives a severe decrease in speed of contraction. Interestingly, mRNA and protein levels of other M-band components, myomesin and embryonic-heart myomesin, were not altered by T3. We concluded that the M-protein expression is strongly and rapidly repressed by T3 in cardiomyocytes, which represents an important aspect for the basis of T3 dependent sarcomeric deleterious effects in the heart. PMID- 24176917 TI - Articular dysfunction patterns in patients with mechanical neck pain: a clinical algorithm to guide specific mobilization and manipulation techniques. AB - In view of a didactical approach for teaching cervical mobilization and manipulation techniques to students as well as their use in daily practice, it is mandatory to acquire sound clinical reasoning to optimally apply advanced technical skills. The aim of this Masterclass is to present a clinical algorithm to guide (novice) therapists in their clinical reasoning to identify patients who are likely to respond to mobilization and/or manipulation. The presented clinical reasoning process is situated within the context of pain mechanisms and is narrowed to and applicable in patients with a dominant input pain mechanism. Based on key features in subjective and clinical examination, patients with mechanical nociceptive pain probably arising from articular structures can be categorized into specific articular dysfunction patterns. Pending on these patterns, specific mobilization and manipulation techniques are warranted. The proposed patterns are illustrated in 3 case studies. This clinical algorithm is the corollary of empirical expertise and is complemented by in-depth discussions and knowledge exchange with international colleagues. Consequently, it is intended that a carefully targeted approach contributes to an increase in specificity and safety in the use of cervical mobilizations and manipulation techniques as valuable adjuncts to other manual therapy modalities. PMID- 24176918 TI - A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-kappaB activation pathway. AB - The compound with R=CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R=CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activities and human apoptosis PCR-array analysis, both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. While both compounds activate mitochondrial and FAS apoptotic pathways, compound 1 was also found to induce another death receptor dependent pathway by induction of CD40, CD40L and TNF-R1 (p55). Further, 1 highly expressed DAPK1, a tumour suppressor, with concomitant down-regulation of XIAP and NF-kappaB. Cell cycle arrest at the S and G2/M phases correlates with the inhibition of the growth of HepG2 cells. The cell invasion rate of 2 is 10-fold higher than that of 1, a finding correlated with the down-regulation of survivin and XIAP expression by 1. Compounds 1 and 2 interact with DNA through different binding motifs with 1 interacting with AT- or TA-specific sites followed by inhibition of restriction enzyme digestion; 2 did not interfere with any of the studied restriction enzymes. PMID- 24176919 TI - Complex forming competition and in-vitro toxicity studies on the applicability of di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) as a metal chelator. AB - Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) is a potential candidate in chelation therapy as an iron chelator. This study showed that a combined treatment with 2MUM easily available Fe(II), Cu(II) and Zn(II) each and 5MUM Dp44mT on eight different cancer cell lines resulted in a 10-40-fold increase in the intracellular Cu content compared to control samples. The uptake of Cu and Cu-dependent cytotoxicity strictly depend on the Cu concentration of the culture medium. Even as low concentration of Dp44mT as 0.1MUM can transport high amounts of copper inside the cells. The Cu accumulation and toxicity through Dp44mT can hardly be influenced by Fe. Copper uptake and toxicity triggered by 2MUM extracellular Cu(II) and 5MUM Dp44mT could not be influenced by Fe(II) extracellular concentrations even 50-times higher than that of Cu(II). A 50-times higher Co(II) extracellular concentration hindered the Cu(II) uptake almost completely and a 10-times higher Co(II) concentration already decreased the Dp44mT-mediated Cu toxicity. Conditional complex stability constant determinations for Dp44mT with Cu(II), Co(II), Fe(II), Ni(II) and Zn(II) revealed that the metal-to-ligand ratio is 1:1 in [Cu(II)Dp44mT] complex, while for Co(II), Fe(II) and Ni(II) is 1:2. The highest stability constant was obtained for Cu(II) (lg beta=7.08+/-0.05) and Co(II) (lg beta2=12.47+/-0.07). According to our results, Dp44mT in combination with Cu is highly toxic in vitro. Therefore, the use of Dp44mT as an iron chelator is limited if biologically available Cu is also present even at low concentrations. PMID- 24176920 TI - Engineering a well-ordered, functional protein-gold nanoparticle assembly. AB - The study of interactions between proteins and nanoparticles is important to advancing applications of nanoparticles in biology, medicine, and materials science. Here, we report the encapsulation of a 5-nm diameter gold nanoparticle (AuNP) by thermophilic ferritin (tF), achieved in nearly quantitative yield under mild conditions that preserved the secondary structure, ferroxidase activity, and thermal stability of the native, 4-helix bundle protein subunits. Chromatography based assays determined that stable protein assembly around AuNPs occurred on long time scales (~48h) and was reversible. Apparent association constants were determined at 25 degrees C for equilibrated tF-BSPP-capped AuNP samples (KA=(2.1+/-0.4)*10(78)M(-11)) and compared favorably to salt-assembled tF samples (KA=(2.2+/-0.5)*10(68)M(-11)) at the same protein concentration (0.3mg/mL). Finally, addition of gold ions and mild reducing agent to the tF-AuNP assembly produced 8-nm diameter AuNPs with surface plasmon resonance band unchanged at 520nm, indicative of templating by the protein shell. PMID- 24176921 TI - Synthesis, crystallographic characterization and electrochemical property of a copper(II) complex of the anticancer agent elesclomol. AB - Elesclomol is a novel anticancer agent that has been evaluated in a number of late stage clinical trials. A new and convenient synthesis of elesclomol and its copper complex is described. X-ray crystallographic characterization and the electrochemical properties of the elesclomol copper(II) complex are discussed. The copper(II) cation is coordinated in a highly distorted square-planar geometry to each of the sulphur and amide nitrogen atoms of elesclomol. Electrochemical measurements demonstrate that the complex undergoes a reversible one-electron reduction at biologically accessible potentials. In contrast the free elesclomol is found electrochemically inactive. This evidence is in strong support of the mechanism of action we proposed for the anticancer activity of elesclomol. PMID- 24176922 TI - The synergetic antibacterial activity of Ag islands on ZnO (Ag/ZnO) heterostructure nanoparticles and its mode of action. AB - Sliver nanoparticles (NPs) possess wonderful antibacterial activity while ZnO is a promising photocatalyst. Although it has been reported that the photocatalytic activity of Ag/ZnO heterostructure nanoparticles (HNPs) was better than that of pure ZnO NPs, the existing comparisons on their antibacterial activity were all taken between Ag-doped ZnO HNPs and pure Ag NPs (or pure ZnO NPs), and were still controversial. Ag islands on ZnO, another type of Ag/ZnO HNPs, were synthesized by a two-step preparation and characterized in this work. The antibacterial activity of as-synthesized Ag/ZnO HNPs, especially with 5.0wt.% of Ag, against Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) was enhanced greatly in contrast with that of the simple mixture of Ag and ZnO NPs. The enhancement was found to be mainly due to the obvious increase in the reactive oxidative species (especially superoxide) and the increased damage to plasmid DNA induced by Ag/ZnO HNPs. PMID- 24176923 TI - (-)-Epicatechin regenerates the chlorinating activity of myeloperoxidase in vitro and in neutrophil granulocytes. AB - The heme-containing enzyme myeloperoxidase (MPO) is mainly expressed in polymorphonuclear leukocytes (PMNs), the most abundant immune cell type in the blood. Accordingly, MPO is classically attributed to the innate immune response against pathogens. Yet, new results also show immune-regulatory functions of the halogenating MPO activity including the formation of anti-inflammatory mediators. In this work we tested the ability of the flavonoid (-)-epicatechin to regenerate this enzymatic activity both in vitro at the isolated MPO-H2O2-Cl(-) system and ex vivo in human PMNs. For all experiments the non-fluorescent dye aminophenyl fluorescein (APF) was used. Upon oxidation by the MPO, the halogenation product hypochlorous acid (HOCl) fluorescein is formed which can be detected e.g. by flow cytometry. The in vitro- and ex vivo-results concordantly show that (-) epicatechin is a suitable substrate to overcome a compound II accumulation of MPO which was experimentally forced by applying excess hydrogen peroxide. Thereby concentration-dependent effects of the flavan-3-ol were found in both cases and confirmed the proposed mode of action of (-)-epicatechin. The results are in accordance with previous stopped-flow kinetic studies which showed a high reactivity of the polyphenol with MPO compound II. The obtained data may contribute to the explanation of the well-known health promoting effects of (-) epicatechin. Moreover, the presented study provides new insights into the role of MPO during inflammation. PMID- 24176924 TI - Nature and causes of the immediate extinction deficit: a brief review. AB - Recent data in both rodents and humans suggests that the timing of extinction trials after conditioning influences the magnitude and duration of extinction. For example, administering extinction trials soon after Pavlovian fear conditioning in rats, mice, and humans results in minimal fear suppression - the so-called immediate extinction deficit. Here I review recent work examining the behavioral and neural substrates of the immediate extinction deficit. I suggest that extinction is most effective at some delay after conditioning, because brain systems involved in encoding and retrieving extinction memories function sub optimally under stress. PMID- 24176925 TI - What are the elements of motivation for acquisition of conditioned taste aversion? AB - The pond snail Lymnaea stagnalis is capable of being classically conditioned to avoid food and to consolidate this aversion into a long-term memory (LTM). Previous studies have shown that the length of food deprivation is important for both the acquisition of taste aversion and its consolidation into LTM, which is referred to as conditioned taste aversion (CTA). Here we tested the hypothesis that the hemolymph glucose concentration is an important factor in the learning and memory of CTA. One-day food deprivation resulted in the best learning and memory, whereas more prolonged food deprivation had diminishing effects. Five-day food deprivation resulted in snails incapable of learning or remembering. During this food deprivation period, the hemolymph glucose concentration decreased. If snails were fed for 2days following the 5-day food deprivation, their glucose levels increased significantly and they exhibited both learning and memory, but neither learning nor memory was as good as with the 1-day food-deprived snails. Injection of the snails with insulin to reduce glucose levels resulted in better learning and memory. Insulin is also known to cause a long-term enhancement of synaptic transmission between the feeding-related neurons. On the other hand, injection of glucose into 5-day food-deprived snails did not alter their inability to learn and remember. However, if these snails were fed on sucrose for 3min, they then exhibited learning and memory formation. Our data suggest that hemolymph glucose concentration is an important factor in motivating acquisition of CTA in Lymnaea and that the action of insulin in the brain and the feeding behavior are also important factors. PMID- 24176926 TI - In vitro effects on human heart and skeletal cells of the venom from two cubozoans, Chironex fleckeri and Carukia barnesi. AB - Although Chironex fleckeri and Carukia barnesi cause significant human envenomation, research into their effects in human models or human cells has been limited. In this in vitro study we have presented data that shows that although C. fleckeri is highly cytotoxic to human cardiac and skeletal muscle cells, C. barnesi is not cytotoxic at all concentrations tested to both cardiac and skeletal muscles cells. We also demonstrate that in vitro C. fleckeri venom cardiocytotoxic activity is significantly attenuated when heated to 44 degrees C for 20 min. There is a similar attenuation with skeletal cells at 46 degrees C. PMID- 24176927 TI - Long-term effects of transcranial direct current stimulation combined with computer-assisted cognitive training in healthy older adults. AB - The aim of the present study was to analyze the long-term effects of transcranial direct current stimulation (tDCS) of the bilateral prefrontal cortex combined with computer-assisted cognitive training on working memory and cognitive function in healthy older adults aged at least 65 years. Forty healthy older adults were enrolled and randomly assigned to two groups: anodal and sham tDCS. All participants completed 10 sessions of computer-assisted cognitive training, combined with tDCS of the bilateral prefrontal cortex. The accuracy of the verbal working memory task and performance of the digit span forward test were significantly improved after computer-assisted cognitive training combined with bifrontal anodal tDCS as compared with that after computer-assisted cognitive training combined with sham tDCS. Moreover, the effect lasts for 4 weeks in the verbal working memory task. We suggest that the tDCS-induced changes in the bilateral prefrontal excitability during computer-assisted cognitive training may have beneficial effects on age-related cognitive decrement in healthy older adults. PMID- 24176928 TI - Analgesic treatment with pregabalin does not prevent persistent pain after peripheral nerve injury in the rat. AB - Reducing the risk of chronic postoperative pain through preventive analgesia is an attractive therapeutic concept. Because peripheral nerve lesions are a major cause of chronic pain after surgery, we tested in rats whether analgesic treatment with pregabalin (PGB) has the capacity to mitigate the development of persistent neuropathic pain-like behavior. Starting on the day of spared nerve injury or 1week later, we treated rats with a continuous intrathecal infusion of PGB (300 or 900MUg/24hours) or vehicle for up to 28days. Rats receiving early PGB treatment had almost normal withdrawal thresholds for punctate mechanical stimuli and were clearly less sensitive to pinprick or cold stimulation. The responses to punctate mechanical and cold stimulation were still reduced for a brief period after the infusion was terminated, but the difference from vehicle-treated rats was minor. Essentially, the analgesic effect of PGB was limited to the duration of the infusion, whether analgesia started at the time of surgery or with a delay of 1week, independently of the length of the treatment. PGB did not suppress the activation of spinal microglia, indicating that analgesia alone does not eliminate certain pain mechanisms even if they depend, at least partially, on nociceptive input. Unexpectedly, intrathecal infusion of PGB did not inhibit the nerve injury-induced accumulation of its binding target, the voltage-gated calcium channel subunit alpha2delta1, at primary afferent terminals in the spinal cord. Interference with the synaptic trafficking of alpha2delta1 is not required to achieve analgesia with PGB. PMID- 24176929 TI - Trends in leisure-time physical activity in a southern Brazilian city: 2003-2010. AB - BACKGROUND: Most of physical activity surveillance data are derived from high income countries. The aim of the current study was to report time trends in leisure-time physical activity. METHODS: Population-based surveys were conducted in the city of Pelotas, Brazil in 2003 and 2010, including individuals aged 20+ years. Physical activity was assessed using the leisure-time section of the long version of the IPAQ. A cut-off point of 150 min/wk was used in the analyses. Methodologies were virtually identical in both surveys. RESULTS: In 2003, 26.8% (95% CI 24.3; 29.2) of the participants were classified as active in leisure time, as compared with 24.4% (95% CI 22.6; 26.2) in 2010. The proportion of subjects reporting 0 minutes per week of walking, moderate- and vigorous intensity physical activity practice also did not vary between 2003 and 2010. However, the proportion of active adults decreased from 39.9% (95% CI 33.0; 42.7) in 2003 to 29.7% (95% CI 24.9; 34.5) in 2010 among high-income participants. Males were more active than females in both surveys. CONCLUSIONS: Leisure-time physical activity is stable among adults living in the South of Brazil, but high income participants are becoming less active over time. Scaling up effective and promising physical activity interventions is urgently needed in Brazil. PMID- 24176930 TI - Flexible and twistable non-volatile memory cell array with all-organic one diode one resistor architecture. AB - Flexible organic memory devices are one of the integral components for future flexible organic electronics. However, high-density all-organic memory cell arrays on malleable substrates without cross-talk have not been demonstrated because of difficulties in their fabrication and relatively poor performances to date. Here we demonstrate the first flexible all-organic 64-bit memory cell array possessing one diode-one resistor architectures. Our all-organic one diode-one resistor cell exhibits excellent rewritable switching characteristics, even during and after harsh physical stresses. The write-read-erase-read output sequence of the cells perfectly correspond to the external pulse signal regardless of substrate deformation. The one diode-one resistor cell array is clearly addressed at the specified cells and encoded letters based on the standard ASCII character code. Our study on integrated organic memory cell arrays suggests that the all-organic one diode-one resistor cell architecture is suitable for high-density flexible organic memory applications in the future. PMID- 24176931 TI - Thirteen follies and fallacies about alternative medicine. PMID- 24176932 TI - Loss of iron triggers PINK1/Parkin-independent mitophagy. AB - In this study, we develop a simple assay to identify mitophagy inducers on the basis of the use of fluorescently tagged mitochondria that undergo a colour change on lysosomal delivery. Using this assay, we identify iron chelators as a family of compounds that generate a strong mitophagy response. Iron chelation induced mitophagy requires that cells undergo glycolysis, but does not require PINK1 stabilization or Parkin activation, and occurs in primary human fibroblasts as well as those isolated from a Parkinson's patient with Parkin mutations. Thus, we have identified and characterized a mitophagy pathway, the induction of which could prove beneficial as a potential therapy for several neurodegenerative diseases in which mitochondrial clearance is advantageous. PMID- 24176933 TI - MxB/Mx2: the latest piece in HIV's interferon puzzle. PMID- 24176934 TI - Semi-quantitative colony immunoassay for determining and optimizing protein expression in Saccharomyces cerevisiae and Escherichia coli. AB - This work describes a quick semi-quantitative colony immunoassay (QSCI) method for immunoblot detection of intracellularly expressed proteins in both yeast and bacterial cells. After induction of protein expression, only 4.5 h is required for cell breakage, protein detection, and data analysis. This protocol was used to screen and unambiguously identify Saccharomyces cerevisiae cells efficiently overexpressing glutathione S-transferase (GST)-tagged Yih1 in addition to cells expressing the myc-tagged large 297-kDa Gcn1 protein. In addition, the method was used to identify Escherichia coli cells efficiently expressing His6-tagged Yih1 and a GST-tagged Gcn1 fragment, respectively. The protocol allows the use of both epitope-specific and protein-specific antibodies. The same colony immunoassay can also be used to determine the minimal concentration of inducing agent sufficient for induction of optimal protein expression (e.g., galactose for yeast, isopropyl beta-D-1-thiogalactopyranoside [IPTG] for E. coli). To our knowledge, this is the first report on a rapid low-cost procedure that allows the calibration of inducing agent on solid medium. PMID- 24176935 TI - Levoglucosan indicates high levels of biomass burning aerosols over oceans from the Arctic to Antarctic. AB - Biomass burning is known to affect air quality, global carbon cycle, and climate. However, the extent to which biomass burning gases/aerosols are present on a global scale, especially in the marine atmosphere, is poorly understood. Here we report the molecular tracer levoglucosan concentrations in marine air from the Arctic Ocean through the North and South Pacific Ocean to Antarctica during burning season. Levoglucosan was found to be present in all regions at ng/m(3) levels with the highest atmospheric loadings present in the mid-latitudes (30 degrees -60 degrees N and S), intermediate loadings in the Arctic, and lowest loadings in the Antarctic and equatorial latitudes. As a whole, levoglucosan concentrations in the Southern Hemisphere were comparable to those in the Northern Hemisphere. Biomass burning has a significant impact on atmospheric Hg and water-soluble organic carbon (WSOC) from pole-to-pole, with more contribution to WSOC in the Northern Hemisphere than in the Southern Hemisphere. PMID- 24176937 TI - Thrill and adventure seeking as a modifier of the relationship of perceived risk with risky driving among young drivers. AB - Risky driving contributes to road trauma, a leading cause of mortality among young people. Health-relevant behaviour models suggest a negative relationship between risky driving and perceived risk of its outcomes. However, high sensation seekers may value the "thrill" of the risk, and positive associations between sensation seeking and risky driving have been observed. This is the first study to examine whether aspects of sensation seeking modify the relationship between perceived risk and risky driving. Young drivers in metropolitan Sydney and rural New South Wales [NSW] (n=797) completed a survey relating to one of the four risky driving behaviours (speeding, drink-driving, driving while fatigued, and failing to wear a seatbelt). Results suggest that the Thrill and Adventure Seeking subscale of Zuckerman's (1994) Sensation Seeking Scale moderate the relationship of perceived risk with risky driving - indicating a negative relationship for low-scores, but not high-scorers, on the TAS subscale. Thus, road safety campaigns that emphasize the riskiness of a particular behaviour may be of limited benefit to thrill and adventure seekers. PMID- 24176936 TI - Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes. AB - An unresolved problem in biological signal transduction is how particular branches of highly interconnected signaling networks can be decoupled, allowing activation of specific circuits within complex signaling architectures. Although signaling dynamics and spatiotemporal mechanisms serve critical roles, it remains unclear if these are the only ways cells achieve specificity within networks. The transcription factor Steroidogenic Factor-1 (SF-1) is an excellent model to address this question, as it forms dynamic complexes with several chemically distinct lipid species (phosphatidylinositols, phosphatidylcholines and sphingolipids). This property is important since lipids bound to SF-1 are modified by lipid signaling enzymes (IPMK & PTEN), regulating SF-1 biological activity in gene expression. Thus, a particular SF-1/lipid complex can interface with a lipid signaling enzyme only if SF-1 has been loaded with a chemically compatible lipid substrate. This mechanism permits dynamic downstream responsiveness to constant upstream input, disentangling specific pathways from the full network. The potential of this paradigm to apply generally to nuclear lipid signaling is discussed, with particular attention given to the nuclear receptor superfamily of transcription factors and their phospholipid ligands. PMID- 24176938 TI - Self-reported barriers and facilitators to preventive human papillomavirus vaccination among adolescent girls and young women: a systematic review. AB - OBJECTIVE: Widespread uptake of preventive human papillomavirus vaccination among target groups is an important public health goal. To evaluate barriers and facilitators to human papillomavirus vaccination, we conducted a systematic review of self-reported views of adolescent girls and young women. METHODS: Twenty-two studies including 8079 females aged 9-26 years in North America, published between 2008 and 2011 (representing studies conducted post-vaccine availability), were included. Two reviewers performed all levels of screening and data abstraction in duplicate. We collated findings pertaining to vaccination barriers and facilitators, study characteristics, and study quality. RESULTS: Participants were mainly unvaccinated (70%) and sexually active. Twenty-one barriers to vaccination were identified. Cost was the most frequently reported barrier, followed by feelings that vaccination was unnecessary, and concerns regarding vaccine safety and side effects. Facilitators included perceived benefit of vaccination, health care provider recommendations, and social norms. Few studies specifically sought to isolate the views of adolescents, though not being sexually active was the most commonly reported barrier among this group. CONCLUSION: Understanding factors which arbitrate in vaccination decisions among key target groups can improve the success of health promotion interventions. Additional studies of superior methodological quality are needed to produce reliable data to inform health promotion strategies. PMID- 24176939 TI - Melanotic schwannoma: a case of renal origin. PMID- 24176940 TI - Outcomes and tolerance of human immunodeficiency virus--positive U.S. veterans undergoing dose-escalated external beam radiotherapy for localized prostate cancer. AB - INTRODUCTION: There are little data on the outcomes and tolerance, as well as the impact on the CD4 counts, of human immunodeficiency virus (HIV)-positive patients with prostate cancer who undergo high-dose external beam radiotherapy. MATERIALS AND METHODS: We identified 15 HIV-positive patients with prostate cancer who were treated with external beam radiation to a dose >= 75.6 Gy at the New York Harbor Department of Veterans Affairs between 2003 and 2010. Kaplan-Meier analyses were used to measure biochemical control outcomes. Toxicity and CD4 counts before, after, and during treatments were analyzed. RESULTS: A total of 15 patients were identified, with a median follow-up period of 49 months. There were 2 biochemical failures, which occurred at 28 months and 63 months, respectively. In neither of these 2 patients was there evidence of metastatic disease. The overall 5-year biochemical control was 92.3%. There appeared to be a consistent decline in the CD4 counts both during and immediately after the radiation treatments. Most of these patients had a subsequent improvement in their CD4 counts. Toxicity was mild overall, though there was 1 patient who developed rectal bleeding 11 months post treatment, which required argon plasma coagulation. CONCLUSION: Dose escalated external beam radiation is well tolerated in HIV-positive patients with durable biochemical control and mild toxicity. A substantial decline in CD4 counts is associated with the radiation; therefore, these counts need to be monitored closely, in conjunction with the infectious-disease specialist. PMID- 24176942 TI - Transient adhesion and conductance phenomena in initial nanoscale mechanical contacts between dissimilar metals. AB - We report on transient adhesion and conductance phenomena associated with tip wetting in mechanical contacts produced by the indentation of a clean W(111) tip into a Au(111) surface. A combination of atomic force microscopy and scanning tunneling microscopy was used to carry out indentation and to image residual impressions in ultra-high vacuum. The ~7 nm radii tips used in these experiments were prepared and characterized by field ion microscopy in the same instrument. The very first indentations of the tungsten tips show larger conductance and pull off adhesive forces than subsequent indentations. After ~30 indentations to a depth of ~1.7 nm, the maximum conductance and adhesion forces reach steady state values approximately 12 * and 6 * smaller than their initial value. Indentation of W(111) tips into Cu(100) was also performed to investigate the universality of tip wetting phenomena with a different substrate. We propose a model from contact mechanics considerations which quantitatively reproduces the observed decay rate of the conductance and adhesion drops with a 1/e decay constant of 9-14 indentation cycles. The results show that the surface composition of an indenting tip plays an important role in defining the mechanical and electrical properties of indentation contacts. PMID- 24176941 TI - Immunological profiles determine neurological involvement in Sjogren's syndrome. AB - BACKGROUND: Up to 68% of patients with primary Sjogren's syndrome (pSS) undergo neurological complications, and evidence for distinct immunological subgroups is emerging. We sought to determine systemic and immunological profiles associated with neurological manifestations. METHODS: 420 patients fulfilling the 2002 American-European pSS criteria were retrospectively analyzed. Neurological manifestations were diagnosed through clinical, biological, electrophysiological, and imaging findings. Biographical, clinical, and laboratory data were compared. RESULTS: Within 93 (22%) patients with neurological manifestations, peripheral and central nervous systems were involved in 66% and 44%, respectively. Raynaud's phenomenon, cutaneous vasculitis, renal involvement, and cryoglobulinemia were associated with sensorimotor neuropathy and mononeuritis multiplex (p<0.05). Conversely, pure sensory neuropathy occurred without extraglandular manifestation, and without anti-Ro/SSA antibodies (p<0.05). All neurological manifestations were associated with increased use of corticosteroids and immunosuppressive drugs (p<0.05). CONCLUSIONS: In pSS, patients with sensorimotor neuropathies and pure sensory neuropathies have distinct extraglandular and immunological profiles. PMID- 24176944 TI - Managing severe aggression in frontotemporal dementia. AB - OBJECTIVE: The aim of this paper is to present a case and discussion illustrating the limitations in the evidence base to guide practice in relationship to managing severe aggression in people with dementia. It also calls attention to the association between haloperidol use and increased mortality in dementia. METHOD: Case report and review of the literature. RESULTS: A 60-year-old man with rapidly progressive frontotemporal dementia complicated by severe aggression was managed in specialised psychogeriatric services and high-dose haloperidol was used. This treatment decision was made following literature review, consultation with experts and a detailed risk-benefit analysis. Unfortunately, his physical condition deteriorated swiftly and he died soon after. CONCLUSIONS: Haloperidol is associated with increased mortality in patients with dementia. This case exposes the difficulties in managing severe aggression in dementia, with few safe and effective treatment options and a lack of consensus guidance in the area of very severe aggression in dementia. PMID- 24176943 TI - Changes to antiretroviral drug regimens during integrated TB-HIV treatment: results of the SAPiT trial. AB - BACKGROUND: Frequency of drug changes in combination antiretroviral therapy among patients starting both tuberculosis (TB) and HIV therapy, as a result of treatment-limiting toxicity or virological failure, is not well established. METHODS: Patients in the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) trial were randomized to initiate antiretroviral therapy (ART) either early or late during TB treatment or after completion of TB treatment. Drug changes due to toxicity (defined as due to grade 3 or 4 adverse events) or virological failure (defined as viral load >1,000 copies/ml on two occasions, taken >=4 weeks apart) were assessed in these patients. RESULTS: A total of 501 TB-HIV-coinfected patients were followed for a mean of 16.0 months (95% CI 15.5, 16.6) after ART initiation. The standard first-line antiretrovirals used were efavirenz, lamivudine and didanosine. Individual drug switches for toxicity occurred in 14 patients (incidence rate 2.1 per 100 person-years, 95% CI 1.1, 3.5), and complete regimen changes due to virological failure in 25 patients (incidence rate 3.7 per 100 person-years, 95% CI 2.4, 5.5). The most common treatment limiting toxicities were neuropsychiatric effects (n=4, 0.8%), elevated transaminase levels and hyperlactataemia (n=3, 0.6%), and peripheral neuropathy (n=2, 0.4%). Complete regimen change due to treatment failure was more common in patients with CD4(+) T-cell count <50 cells/mm(3) (P<0.001) at ART initiation and body mass index >25 kg/m(2) (P=0.01) at entry into the study. CONCLUSIONS: Both drug switches and complete regimen change were uncommon in patients cotreated for TB-HIV with the chosen regimen. Patients with severe immunosuppression need to be monitored carefully, as they were most at risk for treatment failure requiring regimen change. PMID- 24176945 TI - Effect of dietary protein supply originating from soybean meal or casein on the intestinal microbiota of piglets. AB - Dietary composition is a major factor influencing the intestinal microbial ecosystem of pigs. To alleviate weaning-associated disorders, variations in dietary protein supply may beneficially affect microbial composition in the gastrointestinal tract of piglets. A total of 48 piglets, fitted with simple ileal T-cannulas, was used to examine the effect of protein supply of either highly digestible casein or less digestible, fiber-rich soybean meal (SBM) on the composition of the intestinal microbiota. Gene copies of 7 bacteria groups were determined by real-time PCR in ileal digesta and feces. Ileal counts of total eubacteria, the Bacteroides-Prevotella-Porphyromonas group, Enterobacteriaceae and Clostridium Cluster XIVa were higher (P < 0.001) in the casein-based diets. Fecal counts of all analyzed bacterial groups were higher for the SBM-based diets (P < 0.001), apart from Enterobacteriaceae (P < 0.05) which were higher in the casein-based diets. Ileal counts of lactobacilli linearly increased as the crude protein level was increased up to 335 g/kg (P < 0.01). The Bacteroides-Prevotella Porphyromonas group linearly decreased in ileal samples (P < 0.01) and increased in fecal samples (P < 0.05) as the crude protein level in the SBM-based diet was increased. Both, protein level and protein source may affect intestinal microbial balance. Higher dietary protein levels in combination with diets low in fiber contents might stimulate proliferation of protein fermenting bacteria in piglet's large intestine. Further studies are warranted to clarify, whether this would be associated with intestinal disturbances. PMID- 24176946 TI - Early results from a United States trial of prostatic artery embolization in the treatment of benign prostatic hyperplasia. AB - PURPOSE: To report early findings from a prospective United States clinical trial to evaluate the efficacy and safety of prostatic artery embolization (PAE) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: From January 2012 to March 2013, 72 patients were screened and 20 patients underwent treatment. Patients were evaluated at baseline and selected intervals (1, 3, and 6 mo) for the following efficacy variables: American Urological Association (AUA) symptom score, quality of life (QOL)-related symptoms, International Index of Erectile Function score, peak urine flow rate, and prostate volume (on magnetic resonance imaging at 6 mo). Complications were monitored and reported per Society of Interventional Radiology guidelines. RESULTS: Embolization was technically successful in 18 of 20 patients (90%); bilateral PAE was successful in 18 of 19 (95%). Unsuccessful embolizations were secondary to atherosclerotic occlusion of prostatic arteries. Clinical success was seen in 95% of patients (19 of 20) at 1 month, with average AUA symptom score improvements of 10.8 points at 1 month (P < .0001), 12.1 points at 3 months (P = .0003), and 9.8 points at 6 months (P = .06). QOL improved at 1 month (1.9 points; P = .0002), 3 months (1.9 points; P = .003), and 6 months (2.6 points; P = .007). Sexual function improved by 34% at 1 month (P = .11), 5% at 3 months (P = .72), and 16% at 6 months (P = .19). Prostate volume at 6 months had decreased 18% (n = 5; P = .05). No minor or major complications were reported. CONCLUSIONS: Early results from this clinical trial indicate that PAE offers a safe and efficacious treatment option for men with BPH. PMID- 24176947 TI - [3-(Trifluoromethyl)-3H-diazirin-3-yl]coumarin as a carbene-generating photocross linker with masked fluorogenic beacon. AB - A coumarin-fused diazirine photolabeling agent exhibited dramatic enhancement in fluorescence after cross-linking with the target protein. Fluorescence emission from the coumarin moiety was efficiently quenched by the diazirine group, and was then intensively recovered from photolysis treatment by irradiation with light at a wavelength of 365 nm. PMID- 24176948 TI - The efficacy of SPA0355 in protecting beta cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes. AB - Cytokines activate several inflammatory signals that mediate beta-cell destruction. We recently determined that SPA0355 is a strong anti-inflammatory compound, thus reporting its efficacy in protecting beta cells from various insults. The effects of SPA0355 on beta-cell survival were studied in RINm5F cells and primary islets. The protective effects of this compound on the development of type 1 diabetes were evaluated in non-obese diabetic (NOD) mice. SPA0355 completely prevented cytokine-induced nitric oxide synthase (iNOS) expression and cytotoxicity in RINm5F cells and isolated islets. The molecular mechanism of SPA0355 inhibition of iNOS expression involves the inhibition of nuclear factor kappaB and Janus kinase signal transducer and activator of transcription pathways. The protective effects of SPA0355 against cytokine toxicity were further demonstrated by normal insulin secretion and absence of apoptosis of cytokine-treated islets. In experiments with NOD mice, the occurrence of diabetes was efficiently reduced when the mice were treated with SPA0355. Therefore, SPA0355 might be a valuable treatment option that delays the destruction of pancreatic beta cells in type 1 diabetes. PMID- 24176950 TI - Changes in response to antiaggregatory treatment in patients with myeloproliferative neoplasms: a sequential study using multiple electrode aggregometry. AB - In the present study, we used multiple electrode aggregometry (MEA) to investigate the response to aspirin and clopidogrel treatment, and its potential changes over a long-time disease course in patients with myeloproliferative neoplasms (MPNs). arachidonic acid (ASPI), ADP, and thrombin receptor activating peptide (TRAP) tests were performed at two timepoints between 32-50 months in 21 patients with MPN and 1-46 months in 29 controls. We further checked the medical records of the participants to identify a potential correlation of changes in the treatment response with clinical events. In MPN, four out of 13 patients treated with 100 mg of aspirin, no patients receiving 50 mg of aspirin, and one out of five clopidogrel-treated patients showed a therapeutic antiplatelet effect. In the subsequent examinations, five patients changed from response to nonresponse or vice versa. Initial nonresponse and changes from an initial response to nonresponse were observed in six patients with thrombotic events. In the controls, 25 out of 26 aspirin-treated patients and two out of three clopidogrel treated patients showed an initially adequate in-vitro response. Except from one patient changing from initial aspirin nonresponse to response, all controls showed a stable response state. One control with two ischemic strokes showed a nonresponse to clopidogrel. In conclusion, MEA detects the response to antiaggregatory treatment, as well as its changes during the disease course in patients with MPN. An initial or subsequent nonresponse was observed in patients with thrombotic events. PMID- 24176949 TI - Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2 overexpressing gastric cancer xenografts than individual blockade. AB - Gastric cancer overexpressing the human epidermal growth factor 2 (HER2) protein has a poor outcome, although a combination of chemotherapy and the anti-HER2 antibody trastuzumab has been approved for the treatment of advanced gastric cancer. Vascular endothelial growth factor (VEGF) expression in gastric cancer is correlated with recurrence and poor prognosis; however, the anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trials. In this study, we evaluated the antitumor effects of trastuzumab; VEGF-Trap binding to VEGF-A, VEGF-B and placental growth factor (PlGF); and a combination of trastuzumab and VEGF-Trap in a gastric cancer xenograft model. Although trastuzumab and VEGF-Trap each moderately inhibited tumor growth, the combination of these agents exerted greater inhibition compared with either agent alone. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation and increased apoptosis of tumor cells and decreased tumor vascular density. The combined treatment resulted in fewer proliferating tumor cells, more apoptotic cells and reduced tumor vascular density compared with treatment with trastuzumab or VEGF-Trap alone, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. These data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach to treating HER2-overexpressing gastric cancer. PMID- 24176951 TI - Pulmonary embolism risk stratification: the intermediate-risk group. AB - Despite all the advances on acute pulmonary embolism risk stratification, a grey area still justifies ongoing debate. Although growing scientific evidence has clarified the extremes of pulmonary embolism risk continuum and has given support to every day's clinical practice decisions, on who may be sent home or needs promptly aggressive measures, the intermediate-risk pulmonary embolism patients are still a challenging group. Moreover, recent studies reported most interesting findings, exposing weaknesses of traditional markers of pulmonary embolism prognosis (e.g. right-ventricular dysfunction), and shed some light on how we can potentially overcome the difficulties of risk assessment in these cases. Our intention is to briefly discuss the recent developments in pulmonary embolism risk stratification, aiming at clarifying their usefulness in current pulmonary embolism management. PMID- 24176952 TI - Mean platelet volume and mitral annular calcification. PMID- 24176953 TI - Association of XRCC1 Arg399Gln polymorphism with bladder cancer susceptibility: a meta-analysis. AB - Genetic variations in DNA repair genes are thought to modify DNA repair capacity and may to be related to cancer susceptibility. However, epidemiological study results have been inconsistent. In this meta-analysis, we assessed 24 case control studies of association between the X-ray repair cross complementing group 1 (XRCC1) Arg399Gln polymorphism and bladder cancer susceptibility in the general population and in Asian and non-Asian subgroups. A moderately significant association with bladder cancer risk was found for AG vs GG (OR=1.110, 95% CI=1.018-1.210). No significant associations with bladder cancer risk were found for AA vs GG (OR=0.942, 95% CI=0.823-1.077), the dominant model AA/AG vs GG (OR=1.075, 95% CI=0.990-1.167) and the recessive model AA vs AG/GG(OR=0.890, 95% CI=0.788-1.005). In subgroup analysis, a moderately significant association was also found for AG vs GG (OR=1.091, 95% CI=1.008-1.180) in non-Asian subgroup. The analysis suggests that the XRCC1 Arg399Gln polymorphism might be a moderate risk factor for bladder cancer, especially in non-Asian population. PMID- 24176955 TI - Does 30-day readmission affect long-term outcome among glioblastoma patients? AB - BACKGROUND: Research on readmissions has focused mainly on the economic and resource burden it places on hospitals. OBJECTIVE: To evaluate the effect of 30 day readmission on overall survival among newly diagnosed glioblastoma multiforme (GBM) patients. METHODS: A nationwide cohort of GBM patients diagnosed between 1991 and 2007 was studied using the Surveillance, Epidemiology and End Results Medicare database. Multivariate models were used to determine factors associated with readmission and overall survival. Odds ratio, hazard ratio, 95% confidence interval, and P values were reported. Complete case and multiple imputation analyses were performed. RESULTS: Among the 2774 newly diagnosed GBM patients undergoing surgery at 442 hospitals nationwide, 437 (15.8%) were readmitted within 30 days of the index hospitalization. Although 63% of readmitted patients returned to the index hospital where surgery was performed, a significant portion (37%) were readmitted to nonindex hospitals. The median overall survival for readmitted patients (6.0 months) was significantly shorter than for nonreadmitted (7.6 months; P < .001). In a confounder-adjusted imputed model, 30-day readmission increased the hazard of mortality by 30% (hazard ratio, 1.3; P < .001). Neurological symptoms (30.2%), thromboembolic complications (19.7%), and infections (17.6%) were the leading reasons for readmission. CONCLUSION: Prior studies that have reported only the readmissions back to index hospitals are likely underestimating the true 30-day readmission rate. GBM patients who were readmitted within 30 days had significantly shorter survival than nonreadmitted patients. Future studies that attempt to decrease readmissions and evaluate the impact of reducing readmissions on patient outcomes are needed. PMID- 24176956 TI - Cerebral microbleeds in patients with acute subarachnoid hemorrhage. AB - BACKGROUND: Cerebral microbleeds (CMBs) are commonly found after stroke but have not previously been studied in patients with subarachnoid hemorrhage (SAH). OBJECTIVE: To study the prevalence, radiographic patterns, predictors, and impact on outcome of CMBs in patients with SAH. METHODS: We analyzed retrospectively 39 consecutive patients who underwent T2*-weighted gradient-echo imaging within 7 days after onset of spontaneous SAH. We report the frequency and location of CMBs and show their association with demographics, vascular risk factors, the Hunt Hess grade, the modified Fisher Scale, the Acute Physiological and Chronic Health Evaluation II, magnetic resonance imaging findings including diffusion-weighted imaging lesions, and laboratory data, as well as data on rebleeding, global cerebral edema, delayed cerebral ischemia, seizures, the Telephone Interview for Cognitive Status, and the modified Rankin Scale. RESULTS: Eighteen patients (46%) had CMBs. Of these patients, 9 had multiple CMBs, and overall a total of 50 CMBs were identified. The most common locations of CMBs were lobar (n = 23), followed by deep (n = 15) and infratentorial (n = 12). After adjustment for age and history of hypertension, CMBs were related to the presence of diffusion-weighted imaging lesions (odds ratio, 5.24; 95% confidence interval, 1.14-24.00; P = .03). Three months after SAH, patients with CMBs had nonsignificantly higher modified Rankin Scale scores (odds ratio, 2.50; 95% confidence interval, 0.67-9.39; P = .18). CONCLUSION: This study suggests that CMBs are commonly observed and associated with diffusion-weighted imaging lesions in patients with SAH. Our findings may represent a new mechanism of tissue injury in SAH. Further studies are needed to investigate the clinical implications of CMBs. PMID- 24176954 TI - Fifty consecutive hemispherectomies: outcomes, evolution of technique, complications, and lessons learned. AB - BACKGROUND: Techniques for achieving hemispheric disconnection in patients with epilepsy continue to evolve. OBJECTIVE: To review the outcomes of the first 50 hemispherectomy surgeries performed by a single surgeon with an emphasis on outcomes, complications, and how these results led to changes in practice. METHODS: The first 50 hemispherectomy cases performed by the lead author were identified from a prospectively maintained database. Patient demographics, surgical details, clinical outcomes, and complications were critically reviewed. RESULTS: From 2004 to 2012, 50 patients underwent hemispherectomy surgery (mean follow-up time, 3.5 years). Modified lateral hemispherotomy became the preferred technique and was performed on 44 patients. Forty patients (80%) achieved complete seizure freedom (Engel I). Presurgical and postsurgical neuropsychological evaluations demonstrated cognitive stability. Two cases were performed for palliation only. Previous hemispherectomy surgery was associated with worsened seizure outcome (2 of 6 seizure free; P .005). The use of Avitene was associated with a higher incidence of postoperative hydrocephalus (56% vs 18%; P = .03). In modified lateral hemispherotomy patients without the use of Avitene, the incidence of hydrocephalus was 13%. Complications included infection (n = 3), incomplete disconnection requiring reoperation (n = 1), reversible ischemic neurological deficit (n = 1), and craniosynostosis (n = 1). There were no (unanticipated) permanent neurological deficits or deaths. Minor technique modifications were made in response to specific complications. CONCLUSION: The modified lateral hemispherotomy is effective and safe for both initial and revision hemispherectomy surgery. Avitene use appears to result in a greater incidence of postoperative hydrocephalus. PMID- 24176957 TI - Magnetic resonance imaging conditionally safe neurostimulation leads: investigation of the maximum safe lead tip temperature. AB - BACKGROUND: Magnetic resonance imaging (MRI) is preferred for imaging the central nervous system (CNS). An important hazard for neurostimulation patients is heating at the electrode interface induced, for example, by 64-MHz radiofrequency (RF) magnetic fields of a 1.5T scanner. OBJECTIVE: We performed studies to define the thermal dose (time and temperature) that would not cause symptomatic neurological injury. METHODS: Approaches included animal studies where leads with temperature probes were implanted in the brain or spine of sheep and exposed to RF-induced temperatures of 37 degrees C to 49 degrees C for 30 minutes. Histopathological examinations were performed 7 days after recovery. We also reviewed the threshold for RF lesions in the CNS, and for CNS injury from cancer hyperthermia. Cumulative equivalent minutes at 43 degrees C was used to normalize the data to exposure times and temperatures expected during MRI. RESULTS: Deep brain and spinal RF heating up to 43 degrees C for 30 minutes produced indistinguishable effects compared with 37 degrees C controls. Exposures greater than 43 degrees C for 30 minutes produced temperature dependent, localized thermal damage. These results are consistent with limits on hyperthermia exposure to 41.8 degrees C for 60 minutes in patients who have cancer and with the reversibility of low-temperature and short-duration trial heating during RF lesion procedures. CONCLUSION: A safe temperature for induced lead heating is 43 degrees C for 30 minutes. MRI-related RF heating above 43 degrees C or longer than 30 minutes may be associated with increased risk of clinically evident thermal damage to neural structures immediately surrounding implanted leads. The establishment of a thermal dose limit is a first step toward making specific neurostimulation systems conditionally safe during MRI procedures. PMID- 24176958 TI - Minocycline prevents focal neurological deterioration due to cerebral hyperperfusion after extracranial-intracranial bypass for moyamoya disease. AB - BACKGROUND: Cerebral hyperperfusion (CHP) is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD), and optimal postoperative management has not yet been established. Minocycline, a neuroprotective antibiotic agent, plays a role in blocking matrix metalloproteinase 9 (MMP-9), which contributes to edema formation and hemorrhagic conversion after cerebral ischemia-reperfusion. Patients with MMD have been shown to have increased serum MMP-9 levels. OBJECTIVE: To examine the effect of minocycline on the prevention of postoperative CHP after STA-MCA anastomosis for MMD. METHODS: N-isopropyl-p-[I]iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 109 hemispheres in 86 consecutive patients with MMD (ages, 9-69 years; mean, 37.2 years). Postoperative systolic blood pressure was strictly maintained at lower than 130 mm Hg in all 109 surgeries. The most 60 recent hemispheres were managed by the intraoperative and postoperative intravenous administration of minocycline hydrochloride (200 mg/d). The incidence of focal neurological deterioration (FND) due to CHP was then compared with that in 36 patients undergoing 49 surgeries managed without minocycline. RESULTS: FND due to CHP was observed in 4 operated hemispheres in patients treated without minocycline (4/49, 8.16%), and in none in the minocycline-treated group (0/60) (P = .0241). Multivariate analysis revealed that minocycline administration (P < .001), surgery on the left hemisphere (P = .031), and a smaller recipient artery diameter (P < .001) significantly correlated with FND due to CHP. CONCLUSION: The administration of minocycline with strict blood pressure control may represent secure and effective postoperative management to prevent symptomatic CHP after STA-MCA anastomosis for MMD. PMID- 24176959 TI - Technical concepts for vascular electromagnetic navigated interventions: aortic in situ fenestration and transjugular intrahepatic porto-systemic shunts. AB - This work presents concepts for complex endovascular procedures using electromagnetic navigation technology (EMT). Navigation software interfacing a standard commercially available navigation system was developed, featuring registration, electromagnetic field distortion correction, breathing motion detection and gating, and state-of-the-art 3D imaging post processing. Protocols for endovascularly placed, in-situ fenestrated abdominal aortic stent grafts and an EMT guided transjugular intrahepatic portosystemic shunt (TIPSS) creation have been designed. A dedicated set of interventional devices was developed for each of the procedures: For aortic in-situ fenestration a combination of high-porosity stentgrafts, steerable catheters and electromagnetically navigated guidewires was used, for TIPSS a dual-navigated (sheath and stylet) TIPSS-device was designed and manufactured. The developed devices underwent phantom testing, in preparation for animal experiments to prove the feasibility of the approach. Once established, these systems could aid in performing these challenging interventional radiology procedures, exploiting the unique characteristics of electromagnetic navigation and solving multiple of the problems associated with these interventions being performed under X-ray fluoroscopy, such as lacking real time 3D information or extensive exposure to ionizing radiation. PMID- 24176960 TI - Safety considerations for magnetic fields of 10 mT to 100 mT amplitude in the frequency range of 10 kHz to 100 kHz for magnetic particle imaging. AB - Magnetic particle imaging (MPI) is a new imaging modality using oscillating magnetic fields in the frequency range of 10 kHz to 100 kHz. The duration of data acquisition becomes smaller, and signal-to-noise ratio improves if the amplitude of these fields is increased - technically amplitudes of up to 100 mT might be feasible for human-sized systems. On the other hand, with increasing field strength, adverse health effects must be expected: oscillating magnetic fields can stimulate nerves and muscle and heat up tissue. Thresholds for stimulation with magnetic fields in this frequency range are not precisely known, neither is the local temperature rise following exposure. The ICNIRP guidelines define reference levels for magnetic field exposure for the general public that contain large safety factors - for medical diagnostics, they might be exceeded for a short time. In this article, research and guidelines in this field are briefly reviewed, and new results are presented in order to contribute to a future definition of safety limits for oscillating magnetic fields in MPI. PMID- 24176961 TI - Designs and performance of microprocessor-controlled knee joints. AB - In this comparative study, three transfemoral amputee subjects were fitted with four different microprocessor-controlled exoprosthetic knee joints (MPK): C-Leg, Orion, Plie2.0, and Rel-K. In a motion analysis laboratory, objective gait measures were acquired during level walking at different velocities. Subsequent technical analyses, which involved X-ray computed tomography, identified the functional mechanisms of each device and enabled corroboration of the performance in the gait laboratory by the engineering design of the MPK. Gait measures showed that the mean increase of the maximum knee flexion angle at different walking velocities was closest in value to the unaffected contralateral knee (6.2 degrees /m/s) with C-Leg (3.5 degrees /m/s; Rel-K 17.0 degrees /m/s, Orion 18.3 degrees /m/s, and Plie2.0 28.1 degrees /m/s). Technical analyses corroborated that only with Plie2.0 the flexion resistances were not regulated by microprocessor control at different walking velocities. The muscular effort for the initiation of the swing phase, measured by the minimum hip moment, was found to be lowest with C Leg (-82.1+/-14.1 Nm; Rel-K -83.59+/-17.8 Nm, Orion -88.0+/-16.3 Nm, and Plie2.0 91.6+/-16.5 Nm). Reaching the extension stop at the end of swing phase was reliably executed with both Plie2.0 and C-Leg. Abrupt terminal stance phase extension observed with Plie2.0 and Rel-K could be attributed to the absence of microprocessor control of extension resistance. PMID- 24176962 TI - First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia. AB - BACKGROUND: The aim of this study was to compare pregnancy-associated plasma protein A (PAPP-A) and the beta-subunit of human chorionic gonadotropin (hCGbeta) measured in maternal plasma at the first trimester screening, in women who later developed early or late pre-eclampsia (PE) to women with normal pregnancies. METHODS: In the study were included 161 cases with PE and 88 controls with uncomplicated pregnancies. Plasma PAPP-A and hCGbeta were measured between gestational age (GA) 8+2 and 14+0, and cases with early and late onset PE were compared with controls. RESULTS: Median of hCGbeta (MoM) was lower in women with early (p<0.05) and late PE (p<0.05) compared to healthy pregnant women. Median (range) of hCGbeta (MoM) for women with early onset PE, late onset PE, and women with healthy pregnancies, were 0.75 (0.30-1.21), 0.93 (0.26-3.18), and 0.97 (0.33 4.12), respectively. No significant difference in the median of PAPP-A (MoM) was found between the groups. CONCLUSIONS: hCGbeta was significantly lower in pregnancies that subsequently developed PE and might be of use in the effort of trying to find ways to predict PE. No significant difference was found for PAPP-A in our study. PMID- 24176964 TI - 5-years later - have faculty integrated medical genetics into nurse practitioner curriculum? AB - Abstract Many genetic/genomic educational opportunities are available to assist nursing faculty in their knowledge and understanding of genetic/genomics. This study was conducted to assess advance practice nursing faculty members' current knowledge of medical genetics/genomics, their integration of genetics/genomics content into advance practice nursing curricula, any prior formal training/education in genetics/genomics, and their comfort level in teaching genetics/genomic content. A secondary aim was to conduct a comparative analysis of the 2010 data to a previous study conducted in 2005, to determine changes that have taken place during that time period. During a national nurse practitioner faculty conference, 85 nurse practitioner faculty voluntarily completed surveys. Approximately 70% of the 2010 faculty felt comfortable teaching basic genetic/genomic concepts compared to 50% in 2005. However, there continue to be education gaps in the genetic/genomic content taught to advance practice nursing students. If nurses are going to be a crucial member of the health-care team, they must achieve the requisite competencies to deliver the increasingly complex care patients require. PMID- 24176963 TI - Cross allergic reactions in infants and toddlers with atopic dermatitis. AB - PURPOSE: Prevalence and clinical significance of cross sensitization in children up to 3 years old, diagnosed with atopic dermatitis. MATERIAL AND METHOD: The retrospective study included 69 children up to 3 years old with atopic dermatitis. Allergological diagnostics was performed based on skin tests, determination of total IgE concentration and allergen-specific IgE. RESULTS: Cross sensitization was found in 26% of children. Other patients were qualified to the control group. The sensitization to trees pollen and fruits as well as grass pollen and vegetables were the most frequent types of cross allergy. The patient's family history was positive with regard to atopy in 72% of children from the study group vs. 31% of children from the control group. The statistically higher prevalence of allergic rhinitis and bronchial asthma as well as co-existence of sensitization to house dust mite and animal dander were revealed in the study group. The total concentration of IgE, eosinophilia and SCORAD values were statistically higher in the study group. Children with cross sensitization required systemic steroid therapy more frequently. CONCLUSION: In children up to 3 years with atopic dermatitis and sensitization to plant pollen, the role of a pollen-food allergy syndrome must be taken into account in the pathogenesis of the disease. In children with cross sensitization, the course of atopic dermatitis is more severe; the symptoms from the respiratory and digestive system co-exist. The positive family history is a factor, predisposing to the development of cross sensitization in infants and toddlers. PMID- 24176965 TI - A novel electrochemical biosensor for sensitive detection of telomerase activity based on structure-switching DNA. AB - Telomerase has been considered to be an important tumor biomarker for early cancer diagnostics and a valuable target for therapy treatment. A novel electrochemical biosensor based on structure-switching DNA probe with ferrocene (Fc) as the electroactive reporter to detect telomerase activity was developed. The developed approach displayed desirable dynamic range from 10(2) to 6 * 10(4) Hela cells mL(-1) with a detection limit of 100 Hela cells mL(-1). This biosensor afforded good reproducibility, stability and simple operations. It provided a useful platform for practical use in quantitative telomerase activity assay for clinical applications. Telomerase inhibitor performance was also investigated and the results indicated the approach was suitable for telomerase inhibitor screening research. PMID- 24176966 TI - Use of cortical neuronal networks for in vitro material biocompatibility testing. AB - Neural interfaces aim to restore neurological function lost during disease or injury. Novel implantable neural interfaces increasingly capitalize on novel materials to achieve microscale coupling with the nervous system. Like any biomedical device, neural interfaces should consist of materials that exhibit biocompatibility in accordance with the international standard ISO10993-5, which describes in vitro testing involving fibroblasts where cytotoxicity serves as the main endpoint. In the present study, we examine the utility of living neuronal networks as functional assays for in vitro material biocompatibility, particularly for materials that comprise implantable neural interfaces. Embryonic mouse cortical tissue was cultured to form functional networks where spontaneous action potentials, or spikes, can be monitored non-invasively using a substrate integrated microelectrode array. Taking advantage of such a platform, we exposed established positive and negative control materials to the neuronal networks in a consistent method with ISO 10993-5 guidance. Exposure to the negative controls, gold and polyethylene, did not significantly change the neuronal activity whereas the positive controls, copper and polyvinyl chloride (PVC), resulted in reduction of network spike rate. We also compared the functional assay with an established cytotoxicity measure using L929 fibroblast cells. Our findings indicate that neuronal networks exhibit enhanced sensitivity to positive control materials. In addition, we assessed functional neurotoxicity of tungsten, a common microelectrode material, and two conducting polymer formulations that have been used to modify microelectrode properties for in vivo recording and stimulation. These data suggest that cultured neuronal networks are a useful platform for evaluating the functional toxicity of materials intended for implantation in the nervous system. PMID- 24176967 TI - Platinum porous nanoparticles hybrid with metal ions as probes for simultaneous detection of multiplex cancer biomarkers. AB - In this work, platinum porous nanoparticles (PtPNPs) absorbed metal ions as electrochemical signals were fabricated. Clean-surface PtPNPs were prepared by a surfactant-free method and decorated with amino groups via 2-aminoethanethiol. Amino capped PtPNPs complexation with Cd(2+) and Cu(2+) to form PtPNPs-Cd(2+) and PtPNPs-Cu(2+) hybrids, respectively. Anti-CEA and Anti-AFP separately labeled with PtPNPs-Cd(2+) and PtPNPs-Cu(2+) were used as distinguishable signal tags for capturing antigens. The metal ions were detected in a single run through differential pulse voltammetry (DPV) without acid dissolution, electric potentials and peak heights of which reflected the identity and concentrations of the corresponding antigen. Ionic liquid reduced graphene oxide (IL-rGO) modified glassy carbon electrode (GCE) was used as a substrate, which was rich in amino groups to immobilize antibodies by glutaraldehyde through cross-link between aldehyde groups and amino groups. Using the proposed probes and platform, a novel sandwich-type electrochemical immunosensor for simultaneous detecting carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) was successfully developed. This immunoassay possessed good linearity from 0.05 ng mL(-1) to 200 ng mL(-1) for both CEA and AFP. The detection limit of CEA was 0.002 ng mL(-1) and that of AFP was 0.05 ng mL(-1) (S/N=3). Furthermore, analysis of clinical serum samples using this immunosensor was well consistent with the data determined by the enzyme-linked immunosorbent assay (ELISA). It suggested that the proposed electrochemical immunoassay provided a potential application of clinical screening for early-stage cancers. PMID- 24176968 TI - An automatic enzyme immunoassay based on a chemiluminescent lateral flow immunosensor. AB - Microfluidic integrated enzyme immunosorbent assay (EIA) sensors are efficient systems for point-of-care testing (POCT). However, such systems are not only relatively expensive but also require a complicated manufacturing process. Therefore, additional fluidic control systems are required for the implementation of EIAs in a lateral flow immunosensor (LFI) strip sensor. In this study, we describe a novel LFI for EIA, the use of which does not require additional steps such as mechanical fluidic control, washing, or injecting. The key concept relies on a delayed-release effect of chemiluminescence substrates (luminol enhancer and hydrogen peroxide generator) by an asymmetric polysulfone membrane (ASPM). When the ASPM was placed between the nitrocellulose (NC) membrane and the substrate pad, substrates encapsulated in the substrate pad were released after 5.3 +/- 0.3 min. Using this delayed-release effect, we designed and implemented the chemiluminescent LFI-based automatic EIA system, which sequentially performed the immunoreaction, pH change, substrate release, hydrogen peroxide generation, and chemiluminescent reaction with only 1 sample injection. In a model study, implementation of the sensor was validated by measuring the high sensitivity C reactive protein (hs-CRP) level in human serum. PMID- 24176969 TI - Sequence-specific detection of DNA using functionalized graphene as an additive. AB - We developed a simple and sensitive method for sequence-specific DNA detection using functionalized graphene (FG) and methylene blue (MB). Target DNA with a specific sequence was identified by differential-pulse voltammetry, which produces a change in the redox currents of the incorporated MB. FG played a critical role in enhancing the sensitivity of DNA detection and reduced the concentration of MB substantially near the electrodes when the sequence of the target DNA was not complementary to that of the probe by adsorbing the single stranded DNA with the bound MB, and sinking. Our system could detect even single base-pair mismatches between the target and probe. Fabricating this system does not involve a laborious probe-immobilization process and is considerably simpler than fabricating graphene-electrode-based DNA sensors. PMID- 24176970 TI - An aptamer-based biosensor for sensitive thrombin detection with phthalocyanine@SiO2 mesoporous nanoparticles. AB - Silica nanoparticles, with entrapped hydrophobic photosensitizer tetra-alpha-(2, 4-di-tert-butylphenoxy)-phthalocyaninato zinc (ZnPc(OAr)4), were synthesized by hydrolyzing triethoxyvinylsilane (TEVS) and 3-amino propyl triethoxysilane (APTES). The as-prepared nanoparticles, which were highly monodispersed spheres (about 100 nm), exhibited strong Q-band absorption of ZnPc(OAr)4 centered at 701 nm. The aqueous solubility of ZnPc(OAr)4 encapsulated in silica nanoparticles was obviously improved. The nanoparticles efficiently generated singlet oxygen ((1)O2) both in organic and aqueous solutions after being irradiated at suitable wavelength. The resulting (1)O2 then initiated chemiluminescence (CL) by reacting with a methyl cypridina luciferin analog (MCLA). Based on the photoinduced CL, a sensitive aptamer-based sandwich-type sensor was presented to detect human thrombin. Thrombin was first attached to Pc@SiO2 via secondary aptamer, and then they were collected, for CL determination, by beads with primary aptamer. The proposed approach, which was highly selective with a low detection limit of 80 pmol/L, minimized the nonspecific adsorption. Such an aptamer-based biosensor is feasible in screening biomarkers in complex matrices at ultratrace levels. PMID- 24176971 TI - Biomolecule-based formaldehyde resin microspheres loaded with Au nanoparticles: a novel immunoassay for detection of tumor markers in human serum. AB - A surfactant-free and template-free method for the high-yield synthesis of biomolecule (serotonin)-based formaldehyde resin (BFR) microspheres is proposed for the first time. The colloidal microspheres loaded with Au nanoparticles (AuNPs) prepared by a convenient in-situ synthesis of AuNPs on BFR (AuNPs/BFR) microsphere surface show good stability. AuNPs/BFR microspheres not only favor the immobilization of antibody but also facilitate the electron transfer. It is found that the resultant AuNPs/BFR microspheres can be designed to act as a sensitive label-free electrochemical immunosensor for carcinoembryonic antigen (CEA) determination. The immunosensor is prepared by immobilizing capture anti CEA on AuNPs/BFR microspheres assembled on thionine (TH) modified glassy carbon electrode (GCE). TH acts as the redox probe. Under the optimized conditions, the linear range of the proposed immunosensor is estimated to be from 25 pg/mL to 2000 pg/mL (R=0.998) and the detection limit is estimated to be 3.5 pg/mL at a signal-to-noise ratio of 3. The prepared immunosensor for detection of CEA shows high sensitivity, reproducibility and stability. Our study demonstrates that the immunosensor can be used for the CEA detection in humans serum. PMID- 24176972 TI - Highly selective and sensitive adenosine aptasensor based on platinum nanoparticles as catalytical label for amplified detection of biorecognition events through H2O2 reduction. AB - Based on a combination of aptamer and platinum nanoparticles a new sensitive and selective adenosine aptasensor was fabricated. Functionalized thiol-terminated adenosine aptamer (5'-AGAGAACCTGGGGGAGTATTGCGGAGGAAGGT-SH-3') with Pt Nanoparticles (Pt-NPs) was employed as highly catalytic label for electrochemical detection of adenosine based on electrocatalytic activity of Pt-NPs toward H2O2 reduction. Multiwalled carbon nanotubes/ionic liquid/chitosan (MWCNTs/IL/CHIT) nanocomposite was applied as the interface for covalent attachment of 3'-amine terminated capture probe (3'-NH2-(CH2)6-TCTCTTGGACCC-5'). The presence of Pt nanoparticles improvement the conductivity and performance characteristics of the biosensor as well as incensement in the loading amount of the aptamer DNA sequence. The interaction of adenosine with the aptamer causes the releasing of aptamer with PtNPs into solution which resulted in a decreasing of hydrogen peroxide reduction peak current. Sensitive quantitative detection of adenosine was achieved by monitoring the decrease of voltammetric responses of H2O2 peak current. The peak current of H2O2 decreased with increase in the concentration of adenosine over a range of 1-750 nM with detection limit 1 nM. In addition the proposed aptasensor showed excellent selectivity toward adenosine in compared to some other nucleosides such as guanosine, cytidine and uridine. The proposed aptasensor was successfully used to detect adenosine in human serum samples. The elimination of enzymes or antibodies for the amplified detection of adenosine and the use of platinum nanoparticles as inorganic catalytic label, are the advantage of the proposed aptasensor. PMID- 24176973 TI - Magnetic resonance image reconstruction from undersampled measurements using a patch-based nonlocal operator. AB - Compressed sensing MRI (CS-MRI) has shown great potential in reducing data acquisition time in MRI. Sparsity or compressibility plays an important role to reduce the image reconstruction error. Conventional CS-MRI typically uses a pre defined sparsifying transform such as wavelet or finite difference, which sometimes does not lead to a sufficient sparse representation for the image to be reconstructed. In this paper, we design a patch-based nonlocal operator (PANO) to sparsify magnetic resonance images by making use of the similarity of image patches. The definition of PANO results in sparse representation for similar patches and allows us to establish a general formulation to trade the sparsity of these patches with the data consistency. It also provides feasibility to incorporate prior information learnt from undersampled data or another contrast image, which leads to optimized sparse representation of images to be reconstructed. Simulation results on in vivo data demonstrate that the proposed method achieves lower reconstruction error and higher visual quality than conventional CS-MRI methods. PMID- 24176974 TI - The immune responses triggered by CpG ODNs in shrimp Litopenaeus vannamei are associated with LvTolls. AB - CpG oligodeoxynucleotides (ODNs) represent a kind of pathogen-associated molecular patterns (PAMPs) as well as a novel adjuvant that activate the innate immune system through interaction with Toll-like receptor 9 (TLR9) in mammals. In the present study, the synthetic oligodeoxynucleotides, CpG ODN 2395, was employed to investigate the interactive mode of CpG ODNs with three known Tolls (LvToll1-3) from shrimp Litopenaeus vannamei. The mature peptides of extracellular domains of LvTolls (LvToll-ECDs) were recombinant expressed and their binding activities to CpG ODN 2395 were further examined by ELISA. rLvToll1 ECD and rLvToll3-ECD exhibited affinity to CpG ODN 2395 in a dose-dependent manner when their concentrations ranged from 0.25 to 2.00 MUmol/L, while rLvToll2 ECD did not show any binding activities to CpG ODN 2395 in tested concentrations. Additionally, after the stimulation of CpG ODN 2395, the luciferase activities of HEK293T cells transfected with LvToll1-mosaic or LvToll3-mosaic were significantly increased to 2.38-fold (p<0.01) and 1.56-fold (p<0.01), while that in the HEK293T cells transfected with LvToll2-mosaic declined to 0.41-fold. The TNF-alpha activities were significantly enhanced (p<0.01), and a significant increase (p<0.05) of the NO production was observed at 12h post CpG ODN 2395 stimulation. Moreover, the induced TNF-alpha activities and increased NO production triggered by CpG ODN 2395 were abolished after the treatment of chloroquine (CQ). The uptake of CpG ODN 2395 by shrimp haemocytes was investigated using the laser scanning confocal microscope, and CpG ODN 2395 was observed to be internalized by the haemocytes and distributed in the cytoplasm with aggregated signals around the nucleuses. It suggested that the interactions of CpG ODNs with LvToll1 and LvToll3 as well as the mature of endosomes in the haemocytes of shrimp L. vannamei were indispensable for the triggering of immune responses by CpG ODNs, and the results provided a foundation for the application of CpG ODNs as the novel immunostimulants in aquaculture. PMID- 24176975 TI - Costs of control: decreased motor cortex engagement during a Go/NoGo task in Tourette's syndrome. AB - Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by an impaired ability to inhibit unwanted behaviour. Although the presence of chronic motor and vocal tics defines Tourette's syndrome, other distinctive behavioural features like echo- and coprophenomena, and non-obscene socially inappropriate behaviour are also core features. We investigated neuronal activation during stimulus-driven execution and inhibition of prepared movements in Tourette's syndrome. To this end, we performed event-related functional magnetic resonance imaging and structural diffusion tensor imaging in 15 moderately affected uncomplicated patients with 'pure' Tourette's syndrome and 15 healthy control participants matched for age and gender. Subjects underwent functional magnetic resonance imaging during a Go/NoGo reaction time task. They had to withhold a prepared finger movement for a variable time until a stimulus instructed them to either execute (Go) or inhibit it (NoGo). Tics were monitored throughout the experiments, combining surface electromyogram, video recording, and clinical assessment in the scanner. Patients with Tourette's syndrome had longer reaction times than healthy controls in Go trials and made more errors in total. Their functional brain activation was decreased in left primary motor cortex and secondary motor areas during movement execution (Go trials) but not during response inhibition (NoGo trials) compared with healthy control subjects. Volume of interest analysis demonstrated less task-related activation in patients with Tourette's syndrome in primary and secondary motor cortex bilaterally, but not in the basal ganglia and cortical non-motor areas. They showed reduced co-activation between the left primary sensory-motor hand area and a network of contralateral sensory-motor areas and ipsilateral cerebellar regions. There were no between group differences in structural connectivity of the left primary sensory-motor cortex as measured by diffusion tensor imaging-based probabilistic tractography. Our results link reduced sensory-motor cortical activation during movement execution to a decreased co-activation between the sensory-motor cortex and other brain areas involved in motor processing. These functional changes in patients with Tourette's syndrome might result from adaptive reorganization in fronto parietal brain networks engaged in motor and behavioural control, possibly triggered by abnormal processing and presumably overactivity in cortico-striato cortical circuits. This might enable patients with Tourette's syndrome to better suppress unwanted movements but comes at a price of behavioural deficits in other domains. PMID- 24176976 TI - Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats. AB - A substantial proportion of cases with secondary progressive multiple sclerosis have extensive inflammation in the leptomeninges that is associated with increased subpial demyelination, neuronal loss and an exacerbated disease course. However, the mechanisms underlying this extensive subpial pathology are poorly understood. We hypothesize that pro-inflammatory cytokine production within the meninges may be a key to this process. Post-mortem cerebrospinal fluid and dissected cerebral leptomeningeal tissue from patients with multiple sclerosis were used to study the presence of tumour necrosis factor and interferon gamma protein and messenger RNA levels. A novel model of subpial cortical grey matter demyelination was set up in Dark Agouti rats and analysed using quantitative immunohistochemistry. Increased expression of the pro-inflammatory cytokines tumour necrosis factor and interferon gamma was found in the meninges of cases with secondary progressive multiple sclerosis exhibiting tertiary lymphoid-like structures. Injection of tumour necrosis factor and interferon gamma into the subarachnoid space of female Dark Agouti rats pre-immunized with a subclinical dose of myelin oligodendrocyte glycoprotein mimicked the pathology seen in multiple sclerosis, including infiltration of lymphocytes (CD4+ and CD8+ T cells and CD79+ B cells) into the meninges and extensive subpial demyelination. Extensive microglial/macrophage activation was present in a gradient from the pial surface to deeper cortical layers. Demyelination did not occur in control animals immunized with incomplete Freund's adjuvant and injected with cytokines. These results support the hypothesis that pro-inflammatory molecules produced in the meninges play a major role in cortical demyelination in multiple sclerosis, but also emphasize the involvement of an anti-myelin immune response. PMID- 24176977 TI - Ictal high frequency oscillations distinguish two types of seizure territories in humans. AB - High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80-150 Hz) amplitude, phase-locked to the low-frequency (1-25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1-25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and provide a practical, efficient method for using them to identify the small ictal core regions. Our observations suggest that it may be possible to reduce substantially the extent of cortical resections in epilepsy surgery procedures without compromising seizure control. PMID- 24176978 TI - SIL1 mutations and clinical spectrum in patients with Marinesco-Sjogren syndrome. AB - Marinesco-Sjogren syndrome is a rare autosomal recessive multisystem disorder featuring cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development. More recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum resident co-chaperone, were identified as the main cause of Marinesco-Sjogren syndrome. Here we describe the results of SIL1 mutation analysis in 62 patients presenting with early-onset ataxia, cataracts and myopathy or combinations of at least two of these. We obtained a mutation detection rate of 60% (15/25) among patients with the characteristic Marinesco-Sjogren syndrome triad (ataxia, cataracts, myopathy) whereas the detection rate in the group of patients with more variable phenotypic presentation was below 3% (1/37). We report 16 unrelated families with a total of 19 different SIL1 mutations. Among these mutations are 15 previously unreported changes, including single- and multi-exon deletions. Based on data from our screening cohort and data compiled from the literature we found that SIL1 mutations are invariably associated with the combination of a cerebellar syndrome and chronic myopathy. Cataracts were observed in all patients beyond the age of 7 years, but might be missing in infants. Six patients with SIL1 mutations had no intellectual disability, extending the known wide range of cognitive capabilities in Marinesco-Sjogren syndrome to include normal intelligence. Modestly constant features were somatic growth retardation, skeletal abnormalities and pyramidal tract signs. Examination of mutant SIL1 expression in cultured patient lymphoblasts suggested that SIL1 mutations result in severely reduced SIL1 protein levels irrespective of the type and position of mutations. Our data broaden the SIL1 mutation spectrum and confirm that SIL1 is the major Marinesco Sjogren syndrome gene. SIL1 patients usually present with the characteristic triad but cataracts might be missing in young children. As cognitive impairment is not obligatory, patients without intellectual disability but a Marinesco Sjogren syndrome-compatible phenotype should receive SIL1 mutation analysis. Despite allelic heterogeneity and many families with private mutations, the phenotype related to SIL1 mutations is relatively homogenous. Based on SIL1 expression studies we speculate that this may arise from a uniform effect of different mutations on protein expression. PMID- 24176979 TI - Identification of retinal ganglion cell neuroprotection conferred by platelet derived growth factor through analysis of the mesenchymal stem cell secretome. AB - The development of neuroprotective strategies to attenuate retinal ganglion cell death could lead to novel therapies for chronic optic neuropathies such as glaucoma. Intravitreal transplantation of mesenchymal stem cells slows retinal ganglion cell death in models of optic nerve injury, but the mechanism of action remains unclear. Here we characterized the neuroprotective effects of mesenchymal stem cells and mesenchymal stem cell-derived factors in organotypic retinal explant culture and an in vivo model of ocular hypertensive glaucoma. Co-culture of rat and human bone marrow-derived mesenchymal stem cells with retinal explants increased retinal ganglion cell survival, after 7 days ex vivo, by ~2-fold and was associated with reduced apoptosis and increased nerve fibre layer and inner plexiform layer thicknesses. These effects were not demonstrated by co-culture with human or mouse fibroblasts. Conditioned media from mesenchymal stem cells conferred neuroprotection, suggesting that the neuroprotection is mediated, at least partly, by secreted factors. We compared the concentrations of 29 factors in human mesenchymal stem cell and fibroblast conditioned media, and identified 11 enriched in the mesenchymal stem cell secretome. Treatment of retinal explants with a cocktail of these factors conferred retinal ganglion cell neuroprotection, with factors from the platelet-derived growth factor family being the most potent. Blockade of platelet-derived growth factor signalling with neutralizing antibody or with small molecule inhibitors of platelet-derived growth factor receptor kinase or downstream phosphatidylinositol 3 kinase eliminated retinal ganglion cell neuroprotection conferred by mesenchymal stem cell co-culture. Intravitreal injection of platelet-derived growth factor -AA or -AB led to profound optic nerve neuroprotection in vivo following experimental induction of elevated intraocular pressure. These data demonstrate that mesenchymal stem cells secrete a number of neuroprotective proteins and suggest that platelet-derived growth factor secretion in particular may play an important role in mesenchymal stem cell-mediated retinal ganglion cell neuroprotection. Furthermore, platelet derived growth factor may represent an independent target for achieving retinal ganglion cell neuroprotection. PMID- 24176980 TI - Intracranial electroencephalographic seizure-onset patterns: effect of underlying pathology. AB - Because seizures originate from different pathological substrates, the question arises of whether distinct or similar mechanisms underlie seizure generation across different pathologies. Better defining intracranial electroencephalographic morphological patterns at seizure-onset could improve the understanding of such mechanisms. To this end, we investigated intracranial electroencephalographic seizure-onset patterns associated with different epileptogenic lesions, and defined high-frequency oscillation correlates of each pattern. We analysed representative seizure types from 33 consecutive patients with drug-resistant focal epilepsy and a structural magnetic resonance imaging lesion (11 mesial temporal sclerosis, nine focal cortical dysplasia, six cortical atrophy, three periventricular nodular heterotopia, three polymicrogyria, and one tuberous sclerosis complex) who underwent depth-electrode electroencephalographic recordings (500 Hz filter, 2000 Hz sampling rate). Patients were included only if seizures arose from contacts located in lesional/peri-lesional tissue, and if clinical manifestations followed the electrographic onset. Seizure-onset patterns were defined independently by two reviewers blinded to clinical information, and consensus was reached after discussion. For each seizure, pre-ictal and ictal sections were selected for high-frequency oscillation analysis. Seven seizure onset patterns were identified across the 53 seizures sampled: low-voltage fast activity (43%); low-frequency high-amplitude periodic spikes (21%); sharp activity at <=13 Hz (15%); spike-and-wave activity (9%); burst of high-amplitude polyspikes (6%); burst suppression (4%); and delta brush (4%). Each pattern occurred across several pathologies, except for periodic spikes, only observed with mesial temporal sclerosis, and delta brush, exclusive to focal cortical dysplasia. However, mesial temporal sclerosis was not always associated with periodic spikes nor focal cortical dysplasia with delta brush. Compared to other patterns, low-voltage fast activity was associated with a larger seizure-onset zone (P = 0.04). Four patterns, sharp activity at <=13 Hz, low-voltage fast activity, spike-and-wave activity and periodic spikes, were also found in regions of seizure spread, with periodic spikes only emerging from mesial temporal sclerosis. Each of the seven patterns was accompanied by a significant increase in high-frequency oscillations upon seizure-onset. Overall, our data indicate that: (i) biologically-distinct epileptogenic lesions share intracranial electroencephalographic seizure-onset patterns, suggesting that different pathological substrates can affect similarly networks or mechanisms underlying seizure generation; (ii) certain pathologies are associated with intracranial electroencephalographic signatures at seizure-onset, e.g. periodic spikes which may reflect mechanisms specific to mesial temporal sclerosis; (iii) some seizure onset patterns, including periodic spikes, can also be found in regions of spread, which cautions against relying on the morphology of the initial discharge to define the epileptogenic zone; and (iv) high-frequency oscillations increase at seizure-onset, independently of the pattern. PMID- 24176981 TI - Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer's disease. AB - High amyloid has been associated with substantial episodic memory decline over 18 and 36 months in healthy older adults and individuals with mild cognitive impairment. However, the nature and magnitude of amyloid-related memory and non memory change from the preclinical to the clinical stages of Alzheimer's disease has not been evaluated over the same time interval. Healthy older adults (n = 320), individuals with mild cognitive impairment (n = 57) and individuals with Alzheimer's disease (n = 36) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent at least one positron emission tomography neuroimaging scan for amyloid. Cognitive assessments were conducted at baseline, and 18- and 36-month follow-up assessments. Compared with amyloid-negative healthy older adults, amyloid-positive healthy older adults, and amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease showed moderate and equivalent decline in verbal and visual episodic memory over 36 months (d's = 0.47-0.51). Relative to amyloid-negative healthy older adults, amyloid-positive healthy older adults showed no decline in non-memory functions, but amyloid positive individuals with mild cognitive impairment showed additional moderate decline in language, attention and visuospatial function (d's = 0.47-1.12), and amyloid-positive individuals with Alzheimer's disease showed large decline in all aspects of memory and non-memory function (d's = 0.73-2.28). Amyloid negative individuals with mild cognitive impairment did not show any cognitive decline over 36 months. When non-demented individuals (i.e. healthy older adults and adults with mild cognitive impairment) were further dichotomized, high amyloid positive non-demented individuals showed a greater rate of decline in episodic memory and language when compared with low amyloid positive non-demented individuals. Memory decline does not plateau with increasing disease severity, and decline in non-memory functions increases in amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease. The combined detection of amyloid positivity and objectively-defined decline in memory are reliable indicators of early Alzheimer's disease, and the detection of decline in non memory functions in amyloid-positive individuals with mild cognitive impairment may assist in determining the level of disease severity in these individuals. Further, these results suggest that grouping amyloid data into at least two categories of abnormality may be useful in determining the disease risk level in non-demented individuals. PMID- 24176982 TI - Inhibition of multidrug efflux as a strategy to prevent biofilm formation. AB - OBJECTIVES: We have recently shown that inactivation of any of the multidrug efflux systems of Salmonella results in loss of the ability to form a competent biofilm. The aim of this study was to determine the mechanism linking multidrug efflux and biofilm formation, and to determine whether inhibition of efflux is a viable antibiofilm strategy. METHODS: Mutants lacking components of the AcrAB TolC system in Salmonella enterica serovar Typhimurium were investigated for their ability to aggregate, produce biofilm matrix components and form a biofilm. The potential for export of a biofilm-relevant substrate via efflux pumps was investigated and expression of genes that regulate multidrug efflux and production of biofilm matrix components was measured. The ability of efflux inhibitors carbonyl cyanide m-chlorophenylhydrazone, chlorpromazine and phenyl arginine-beta-naphthylamide to prevent biofilm formation by Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus under static and flow conditions was assessed. RESULTS: Mutants of Salmonella Typhimurium that lack TolC or AcrB, but surprisingly not AcrA, were compromised in their ability to form biofilms. This defect was not related to changes in cellular hydrophobicity, aggregative ability or export of any biofilm-specific factor. The biofilm defect resulted from transcriptional repression of curli biosynthesis genes and consequent inhibition of production of curli. All three efflux inhibitors significantly reduced biofilm production in both static and flow biofilm assays, although different concentrations of each inhibitor were most active against each species. CONCLUSIONS: This work shows that both genetic inactivation and chemical inhibition of efflux pumps results in transcriptional repression of biofilm matrix components and a lack of biofilm formation. Therefore, inhibition of efflux is a promising antibiofilm strategy. PMID- 24176983 TI - An association between socioeconomic deprivation and primary care antibiotic prescribing in Scotland. AB - OBJECTIVE: To evaluate the association between socioeconomic deprivation and antibiotic prescribing in Scotland. PATIENTS AND METHODS: Data for dispensed antibiotic prescriptions written by general practitioners were obtained for all Scottish National Health Service boards from 2010 to 2012. Deprivation was assessed linking dispensing events to the Scottish Index of Multiple Deprivation (SIMD) score for the patient's datazone (neighbourhood area). The relationship between the deprivation area and antibiotic use (items per 1000 persons per day) was stratified according to the patient's age and sex and the antibiotic class dispensed. A multivariate Poisson regression model was used to formally test the associations. RESULTS: Approximately 12 million prescription items during 2010 2012 were assessed. Patients in the most deprived SIMD quintile had an overall prescription rate that was 36.5% higher than those in the least deprived quintile. The effect of deprivation upon prescription rates was most pronounced for women aged 40-59 years, and for penicillins and metronidazole. CONCLUSIONS: Deprivation was found to have a consistent association with increased rates of antibiotic prescribing in Scotland, which may have significant implications for antimicrobial stewardship and public health campaigns. PMID- 24176984 TI - Proteomic and genomic analysis of methicillin-resistant Staphylococcus aureus (MRSA) exposed to manuka honey in vitro demonstrated down-regulation of virulence markers. AB - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen. Its resistance to multiple antibiotics and its prevalence in healthcare establishments make it a serious threat to human health that requires novel interventions. Manuka honey is a broad-spectrum antimicrobial agent that is gaining acceptance in the topical treatment of wounds. Because its mode of action is only partially understood, proteomic and genomic analysis was used to investigate the effects of manuka honey on MRSA at a molecular level. METHODS: Two-dimensional gel electrophoresis with dual-channel imaging was combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry to determine the identities of differentially expressed proteins. The expression of the corresponding genes was investigated by quantitative PCR. Microarray analysis provided an overview of alterations in gene expression across the MRSA genome. RESULTS: Genes with increased expression following exposure to manuka honey were associated with glycolysis, transport and biosynthesis of amino acids, proteins and purines. Those with decreased expression were involved in the tricarboxylic acid cycle, cell division, quorum sensing and virulence. The greatest reductions were seen in genes conferring virulence (sec3, fnb, hlgA, lip and hla) and coincided with a down-regulation of global regulators, such as agr, sae and sarV. A model to illustrate these multiple effects was constructed and implicated glucose, which is one of the major sugars contained in honey. CONCLUSIONS: A decreased expression of virulence genes in MRSA will impact on its pathogenicity and needs to be investigated in vivo. PMID- 24176985 TI - ABCC3 as a marker for multidrug resistance in non-small cell lung cancer. AB - Multidrug resistance (MDR) contributes to the failure of chemotherapy and high mortality in non-small cell lung cancer (NSCLC). We aim to identify MDR genes that predict tumor response to chemotherapy. 199 NSCLC fresh tissue samples were tested for chemosensitivity by MTT assay. cDNA microarray was done with 5 samples with highest resistance and 6 samples with highest sensitivity. Expression of ABCC3 mRNA and protein was detected by real-time PCR and immunohistochemisty, respectively. The association between gene expression and overall survival (OS) was examined using Cox proportional hazard regression. 44 genes were upregulated and 168 downregulated in the chemotherapy-resistant group. ABCC3 was one of the most up-regulated genes in the resistant group. ABCC3-positive expression correlated with lymph node involvement, advanced TNM stage, more malignant histological type, multiple-resistance to anti-cancer drugs, and reduced OS. ABCC3 expression may serve as a marker for MDR and predictor for poor clinical outcome of NSCLC. PMID- 24176986 TI - It's a matter of trust: policing domestic violence in Hong Kong. AB - This article aims to examine the intervention approach of the police in handling domestic violence and the reasons behind the inactive response of police to domestic violence situations in Hong Kong. The study adopted a qualitative approach to data collection that included 20 in-depth interviews to survivors and 2 interviews to police officers. Findings of this study show that the police are likely to adopt a non-intervention or mediation approach rather than arrest approach because of their distrust of abused women. The police have different reactions in responding to domestic violence issues namely (1) stereotyping the victims, (2) cynical interpretation of women's motivation in reporting, and (3) disbelieve the problem is solvable. All these reactions are associated with the trust of the police that hold on domestic violence issues stems from the dominant patriarchy ideology. The beliefs of police are shaped by the male-dominated police occupational culture, which is characterized by sexism and suspicion. Such beliefs coupled with traditional family values and the dependency discourses prevalent in society have concealed the truth and reality of domestic violence. PMID- 24176987 TI - Interpersonal aggression victimization within casual sexual relationships and experiences. AB - The frequent occurrence of aggression within committed romantic relationships is well documented. However, little is known about experiences of interpersonal aggression within casual sexual relationships and experiences. This study aimed to describe the occurrence of emotional, physical, and sexual aggression victimization within committed romantic relationships, casual dating relationships, friends-with-benefit relationships, booty-calls, and one-night stands. College students (N = 172) provided data regarding the lifetime occurrence of emotional, physical, and sexual aggression across different forms of casual sexual relationships and experiences (friends-with-benefits, booty call, casual dating, one-night stands, committed relationships). Emotional, physical, and sexual subtypes of aggression were reported across all casual sexual relationships and experiences. While a higher percentage of individuals who had been involved in committed relationships reported experiencing at least one form of aggression (approximately 69%), prevalence of at least one form of aggression ranged from approximately 31% to 36% for the various casual sexual relationships/experiences. Across relationships/experiences, emotional and sexual aggression were more common than physical aggression. The findings from this study indicate that emotional, physical, and sexual aggression occur across types of relationships and experiences. Thus, the current study underscores the importance of considering casual dating, friends-with-benefits, booty-calls, and one-night stands when assessing interpersonal aggression. PMID- 24176988 TI - Sociodemographic characteristics of domestic violence in China: a population case control study. AB - A population case-control study of domestic violence in China was conducted to examine the relationship between individual- and household-level characteristics and violence perpetration and victimization. Demographic comparisons were conducted between perpetrators and victims (n = 624), perpetrators and matched controls (n = 628), and perpetrator households and control households (n = 620). A multivariate model of demographic risk was tested, integrating individual- and household-level correlates of violence perpetration. Compared with victims, perpetrators were more likely to be older, male, and have lower levels of education. In the final model, violence perpetration was more likely among individuals who earned more income, contributed a lower proportion of the household income, had a family member who was unemployed or lived in households with an authoritarian or independent power structure. PMID- 24176989 TI - Disease associations in alpha-1-antitrypsin deficiency. AB - INTRODUCTION: In addition to emphysema alpha-1-antitrypsin deficiency (AATD) has been shown to be associated with several inflammatory conditions, including bronchiectasis, vasculitis, (in particular Wegener's granulomatosis), and panniculitis, suggesting neutrophil proteinases also play a role in their pathophysiology. However, it remains unknown whether other inflammatory diseases are also more prevalent in AATD than the general population. The current study describes the prevalence of other co-morbidities in AATD with particular emphasis on inflammatory bowel disease. METHODS AND RESULTS: The case notes of 651 PiZZ or PiZnull patients attending the UK national centre for AATD between 1996 and 2011 were reviewed. The prevalence of inflammatory bowel disease (1.5%) was higher than that predicted in the UK (0.4%). Ten patients had a confirmed diagnosis of ulcerative colitis, and 1 had Crohn's disease. In 2 cases there was a family history of inflammatory bowel disease and all but 1 patient were ex or never smokers. There was also a higher prevalence of hypothyroidism in this patient group than expected for the UK population - 26 cases (7.2% of females and 1.3% of males). CONCLUSIONS: The current study of the UK cohort of patients with AATD confirmed a higher prevalence of ulcerative colitis than would be expected in the general population, providing further evidence of a potential link between these 2 conditions. In addition, the data suggested a potential link between hypothyroidism and AATD. PMID- 24176990 TI - The distribution of COPD in UK general practice using the new GOLD classification. AB - The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 document recommends a combined assessment of chronic obstructive pulmonary disease (COPD) based on current symptoms and future risk. A large database of primary-care COPD patients across the UK was used to determine COPD distribution and characteristics according to the new GOLD classification. 80 general practices provided patients with a Read code diagnosis of COPD. Electronic and hand searches of patient medical records were undertaken, optimising data capture. Data for 9219 COPD patients were collected. For the 6283 patients with both forced expiratory volume in 1 s (FEV1) and modified Medical Research Council scores (mean+/-sd age 69.2+/-10.6 years, body mass index 27.3+/-6.2 kg.m(-2)), GOLD 2011 group distributions were: A (low risk and fewer symptoms) 36.1%, B (low risk and more symptoms) 19.1%, C (high risk and fewer symptoms) 19.6% and D (high risk and more symptoms) 25.3%. This is in contrast with GOLD 2007 stage classification: I (mild) 17.1%, II (moderate) 52.2%, III (severe) 25.5% and IV (very severe) 5.2%. 20% of patients with FEV1 >=50% predicted had more than two exacerbations in the previous 12 months. 70% of patients with FEV1 <50% pred had fewer than two exacerbations in the previous 12 months. This database, representative of UK primary-care COPD patients, identified greater proportions of patients in the mildest and most severe categories upon comparing 2011 versus 2007 GOLD classifications. Discordance between airflow limitation severity and exacerbation risk was observed. PMID- 24176991 TI - Predictors of dyspnoea prevalence: results from the BOLD study. AB - Dyspnoea is a cardinal symptom for cardiorespiratory diseases. No study has assessed worldwide variation in dyspnoea prevalence or predictors of dyspnoea. We used cross-sectional data from population-based samples in 15 countries of the Burden of Obstructive Lung Disease (BOLD) study to estimate prevalence of dyspnoea in the full sample, as well as in an a priori defined low-risk group (few risk factors or dyspnoea-associated diseases). Dyspnoea was defined by the modified Medical Research Council questions. We used ordered logistic regression analysis to study the association of dyspnoea with site, sex, age, education, smoking habits, low/high body mass index, self-reported disease and spirometry results. Of the 9484 participants, 27% reported any dyspnoea. In the low-risk subsample (n=4329), 16% reported some dyspnoea. In multivariate analyses, all covariates were correlated to dyspnoea, but only 13% of dyspnoea variation was explained. Females reported more dyspnoea than males (odds ratio ~2.1). When forced vital capacity fell below 60% of predicted, dyspnoea was much more likely. There was considerable geographical variation in dyspnoea, even when we adjusted for known risk factors and spirometry results. We were only able to explain 13% of dyspnoea variation. PMID- 24176992 TI - Longitudinal relationship between physical activity and lung health in patients with cystic fibrosis. AB - Exercise is beneficial for patients with cystic fibrosis (CF) but long-term effects of physical activity on lung function evolution are unknown. We evaluated the longitudinal relationship between changes in habitual physical activity (HPA) and rate of decline in lung function in patients with CF. We tracked HPA using the Habitual Activity Estimation Scale, forced expiratory volume in 1 s (FEV1) and Stage I exercise tests in 212 patients with CF over a 9-year period. Adjusting for sex, baseline age and FEV1, mucoid Pseudomonas aeruginosa and CF related diabetes, mean +/- sd FEV1 % predicted decreased by 1.63 +/- 0.08% per year (p<0.0001) while mean +/- sd HPA increased by 0.28 +/- 0.03 h.day(-1) per year (p<0.0001) over the study period. A greater increase in HPA was associated with a slower rate of decline in FEV1 (r=0.19, p<0.0069). Dividing subjects into "high" and "low" activity (above or below the mean rate of change of activity, respectively), a steeper rate of FEV1 decline was observed for low (-1.90% per year) compared to high (-1.39% per year) (p=0.002). Increases in HPA are feasible despite progression of lung disease and are associated with a slower rate of decline in FEV1, highlighting the benefit of regular physical activity, and its positive impact on lung function in patients with CF. PMID- 24176993 TI - Disconnect between sputum neutrophils and other measures of airway inflammation in asthma. PMID- 24176994 TI - IDSA/ATS minor criteria aid pre-intensive care unit resuscitation in severe community-acquired pneumonia. AB - The effect of employing severity scores to identify severe community-acquired pneumonia (SCAP) cases for early aggressive resuscitation is unknown. Optimising pre-intensive care unit (ICU) care may improve outcomes in patients at risk of SCAP. We conducted a before-and-after study of patients classified into control and intervention groups (January 2004 to December 2007 and January 2008 to December 2010, respectively). Our intervention was two-pronged, using the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) minor criteria to identify SCAP for aggressive emergency department resuscitation. Patients with SCAP, defined as those with three or more IDSA/ATS minor criteria, were targeted. Differences in mortality, triage and compliance with emergency department resuscitation were compared between the groups. The hospital mortality rate was lower in the intervention versus the control group (5.7% versus 23.8%, p<0.001). On multivariate analysis, the intervention group was associated with lower mortality (OR 0.24, 95% CI 0.09-0.67). ICU admission rates decreased from 52.9% to 38.6% (p=0.008) and inappropriately delayed ICU admissions decreased from 32.0% to 14.8% (p<0.001). There was increased compliance with the aggressive resuscitation protocol after the intervention. A combined intervention, using a pneumonia score to identify those at risk of SCAP early and an aggressive pre-ICU resuscitation protocol may reduce mortality and ICU admissions. PMID- 24176995 TI - Processed meat consumption and lung function: modification by antioxidants and smoking. AB - Unhealthy dietary patterns are associated with poor lung function. It is not known whether this is due to low consumption of antioxidant-rich fruit and vegetables, or is a consequence of higher intakes of harmful dietary constituents, such as processed meat. We examined the individual and combined associations of processed meat, fruit and vegetable consumption and dietary total antioxidant capacity (TAC) with lung function among 1551 males and 1391 females in the UK in the Hertfordshire Cohort Study. Diet was assessed using a food frequency questionnaire. After controlling for confounders, processed meat consumption was negatively associated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio in males and females, while fruit and vegetable consumption and dietary TAC were positively associated with FEV1 and FVC, but not FEV1/FVC ratio. In males, the negative association between processed meat consumption and FEV1 was more marked in those who had low fruit and vegetable consumption (p=0.035 for interaction), and low dietary TAC (p=0.025 for interaction). The deficit in FEV1/FVC associated with processed meat consumption was larger in males who smoked (p=0.022 for interaction). Higher processed meat consumption is associated with poorer lung function, especially in males who have lower fruit and vegetable consumption or dietary TAC, and among current smokers. PMID- 24176996 TI - Real-life use of inhaled corticosteroids in COPD patients versus the GOLD proposals: a paradigm shift in GOLD 2011? PMID- 24176997 TI - Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study. AB - We evaluated the effect of QVA149, a dual bronchodilator combining indacaterol and glycopyrronium, on direct patient-reported dyspnoea in patients with moderate to-severe chronic obstructive pulmonary disease. In this multicentre, blinded, double-dummy, three-period crossover study, 247 patients were randomised to once daily QVA149 110/50 MUg, placebo or tiotropium 18 MUg. Superiority of QVA149 versus placebo (primary objective) and tiotropium (secondary objective) was assessed for improvement in dyspnoea via the self-administered computerised (SAC) version of the Baseline and Transition Dyspnoea Index after 6 weeks. Secondary end-points included lung function, rescue medication use and safety. After 6 weeks, the SAC Transition Dyspnoea Index total score was significantly higher with QVA149 versus placebo (least squares mean (LSM) treatment difference 1.37, p<0.001) and tiotropium (LSM treatment difference 0.49, p=0.021). QVA149 provided significant improvements in lung function, with higher forced expiratory volume in 1 s area under the curve from 0-4 h post-dose versus placebo and tiotropium at day 1 and week 6 (all p<0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p<0.001) and tiotropium (p=0.002). All treatments were well tolerated. Once-daily QVA149 provided superior improvements in patient reported dyspnoea and lung function versus placebo and tiotropium. These benefits were associated with improvements in other symptoms and reduced use of rescue medication. PMID- 24176999 TI - Molecular epidemiological analysis suggests cross-infection with Pseudomonas aeruginosa is rare in non-cystic fibrosis bronchiectasis. PMID- 24176998 TI - Acute exacerbation of idiopathic pulmonary fibrosis associated with air pollution exposure. AB - Acute exacerbations of idiopathic pulmonary fibrosis are associated with high mortality and are of unknown cause. The effect of air pollution on exacerbations of interstitial lung disease is unknown. This study aims to define the association of air pollution exposure with acute exacerbation of idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis and corresponding air pollution data were identified from a longitudinal cohort. Air pollution exposures were assigned to each patient for ozone, nitrogen dioxide, particulate matter, sulfur dioxide and carbon monoxide based on geo-coded residential addresses. Cox proportional hazards models were used to estimate the association of air pollution exposures and acute exacerbations. Acute exacerbation was significantly associated with antecedent 6-week increases in mean level, maximum level and number of exceedances above accepted standards of ozone (hazard ratio (HR) 1.57, 95% CI 1.09-2.24; HR 1.42, 95% CI 1.11-1.82; and HR 1.51, 95% CI 1.17 1.94, respectively) and nitrogen dioxide (HR 1.41, 95% CI 1.04-1.91; HR 1.27, 95% CI 1.01-1.59; and HR 1.20, 95% CI 1.10-1.31, respectively). Increased ozone and nitrogen dioxide exposure over the preceding 6 weeks was associated with an increased risk of acute exacerbation of idiopathic pulmonary fibrosis, suggesting that air pollution may contribute to the development of this clinically meaningful event. PMID- 24177000 TI - Serum bilirubin is associated with lung function in a Swiss general population sample. AB - Bilirubin is a strong antioxidant. Increased serum levels have been associated with lower respiratory disease and mortality risk. We studied the association of bilirubin with lung function in the Swiss study on Air Pollution and Lung Disease in adults (SAPALDIA) cohort. Associations between natural logarithmised bilirubin and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and mean forced expiratory flow between 25%-75% of FVC (FEF25-75%) were tested using multiple linear regression in the whole study population (n=4195) and strata of ever-smoking and high body mass index (BMI, defined by the highest distribution quartile). Associations were retested with single nucleotide polymorphism rs6742078, a genetic determinant of bilirubin. High bilirubin levels were significantly associated with higher FEV1/FVC and FEF25-75% overall. Upon stratification, significant associations persisted in ever-smokers, amounting to 1.1% (95% CI 0.1-2.2%) increase in FEV1/FVC, and 116.2 mL.s(-1) (95% CI -15.9 248.4 mL.s(-1)) in FEF25-75% per interquartile range of bilirubin exposure in smokers with high BMI. Associations were positive but nonsignificant in never smokers with high BMI. Similarly, rs6742078 genotype TT was associated with increased FEV1/FVC and FEF25-75%. Our results suggest a possible protective role of bilirubin on lung tissue, which could be important for prevention and therapy. PMID- 24177001 TI - Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. AB - We evaluated whether lysyl oxidase-like 2 (LOXL2), which promotes cross-linking of collagen in pathological stroma, was detectable in serum from idiopathic pulmonary fibrosis (IPF) patients, and assessed its relationship with IPF disease progression. Patients from the ARTEMIS-IPF (n=69) and the Genomic and Proteomic Analysis of Disease Progression in IPF (GAP) (n=104) studies were analysed. Baseline serum LOXL2 (sLOXL2) levels were compared with baseline clinical and physiological surrogates of disease severity, and the association with IPF disease progression was assessed using a classification and regression tree (CART) method. sLOXL2 correlated weakly with forced vital capacity and carbon monoxide diffusion capacity (r -0.24-0.05) in both cohorts. CART-determined thresholds were similar: ARTEMIS-IPF 800 pg.mL(-1) and GAP 700 pg.mL(-1). In ARTEMIS-IPF, higher sLOXL2 (>800 pg.mL(-1)) was associated with increased risk for disease progression (hazard ratio (HR) 5.41, 95% CI 1.65-17.73). Among GAP subjects with baseline spirometric data (n=70), higher sLOXL2 levels (>700 pg.mL( 1)) were associated with more disease progression events (HR 1.78, 95% CI 1.01 3.11). Among all GAP subjects, higher sLOXL2 levels were associated with increased risk for mortality (HR 2.28, 95% CI 1.18-4.38). These results suggest that higher sLOXL2 levels are associated with increased risk for IPF disease progression. However, due to multiple limitations, these results require validation. PMID- 24177002 TI - The 4-metre gait speed in COPD: responsiveness and minimal clinically important difference. AB - Usual gait speed is a consistent predictor of adverse outcomes in community dwelling elderly people. The reliability and validity of the 4-m gait speed (4MGS) has recently been demonstrated in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the responsiveness of the 4MGS and to estimate the minimal clinically important difference (MCID). In 301 COPD patients, 4MGS and incremental shuttle walk (ISW) were measured before and after pulmonary rehabilitation. 4MGS and ISW were also measured at baseline and 1 year later in a separate cohort of 162 COPD patients. The MCID of 4MGS was estimated using distribution and anchor-based methods. 4MGS improved significantly with pulmonary rehabilitation (mean change 0.08 m.s(-1), p<0.001). The minimal detectable change at 95% confidence was 0.11 m.s(-1). The MCID was estimated at 0.11 m.s(-1) (anchored against ISW) and 0.08 m.s(-1) (anchored against self-reported improvement). The effect size for 4MGS was greatest in frail individuals. After 12 months, mean 4MGS declined by 0.04 m.s( 1). When anchored against a decline of more than the MCID for ISW, change in 4MGS was -0.11 m.s(-1). The 4MGS is responsive to pulmonary rehabilitation and longitudinal change in COPD, and has potential as a simple functional assessment tool in COPD. The 4MGS may be particularly useful in frail individuals with COPD. PMID- 24177003 TI - Measuring central pulmonary pressures during exercise in COPD: how to cope with respiratory effects. AB - Respiratory influences are major confounders when evaluating central haemodynamics during exercise. We studied four different methods to assess mean pulmonary artery pressure (mPAP) and pulmonary capillary wedge pressure (PCWP) in cases of respiratory swings. Central haemodynamics were measured simultaneously with oesophageal pressure during exercise in 30 chronic obstructive pulmonary disease (COPD) patients. mPAP and PCWP were assessed at the end of expiration, averaged over the respiratory cycle and corrected for the right atrial pressure (RAP) waveform estimated intrathoracic pressure, and compared with the transmural pressures. Bland-Altman analyses showed the best agreement of mPAP averaged over the respiratory cycle (bias (limits of agreement) 2.5 (-6.0-11.8) mmHg) and when corrected with the nadir of RAP (-3.6 (-11.2-3.9) mmHg). Measuring mPAP at the end of expiration (10.3 (0.5-20.3) mmHg) and mPAP corrected for the RAP swing ( 9.3 (-19.8-2.1) mmHg) resulted in lower levels of agreement. The respiratory swings in mPAP and PCWP were similar (r(2)=0.82, slope +/- se 0.95 +/- 0.1). Central haemodynamics measured at the end of expiration leads to an overestimation of intravascular pressures in exercising COPD patients. Good measurement can be acquired even when oesopghageal pressure is omitted, by averaging pressures over the respiratory cycle or using the RAP waveform to correct for intrathoracic pressure. Assessment of the pulmonary gradient is unaffected by respiratory swings. PMID- 24177004 TI - Exceptional mobility of an advancing rhyolitic obsidian flow at Cordon Caulle volcano in Chile. AB - The emplacement mechanisms of rhyolitic lava flows are enigmatic and, despite high lava viscosities and low inferred effusion rates, can result in remarkably, laterally extensive (>30 km) flow fields. Here we present the first observations of an active, extensive rhyolitic lava flow field from the 2011-2012 eruption at Cordon Caulle, Chile. We combine high-resolution four-dimensional flow front models, created using automated photo reconstruction techniques, with sequential satellite imagery. Late-stage evolution greatly extended the compound lava flow field, with localized extrusion from stalled, ~35 m-thick flow margins creating >80 breakout lobes. In January 2013, flow front advance continued ~3.6 km from the vent, despite detectable lava supply ceasing 6-8 months earlier. This illustrates how efficient thermal insulation by the lava carapace promotes prolonged within-flow horizontal lava transport, boosting the extent of the flow. The unexpected similarities with compound basaltic lava flow fields point towards a unifying model of lava emplacement. PMID- 24177005 TI - Thermally robust and blinking suppressed core/graded-shell CdSe/CdSe1-xSx/CdS 'giant' multishell semiconductor nanocrystals. AB - We demonstrate that core/graded-shell CdSe/CdSe1-xSx/CdS giant semiconductor nanocrystals (g-NCs) have robust photoluminescence (PL) temperature response. At a size of 10.2 nm in diameter, these g-NCs undergo a PL drop of only 30% at 355 K relative to their PL intensity at 85 K. In comparison, the core/step-shell CdSe/CdS g-NCs at the same diameter exhibit 80% PL drop at 355 K. Spectral shifting and broadening were found to be, respectively, 5-10 times and 2-4 times smaller than those observed in standard CdSe core and CdSe/CdS core/shell NCs. These core/graded-shell g-NCs are largely blinking suppressed and have insignificant photoluminescence decay even after excitation at very high irradiance (44 kW cm(-2)) for over an hour. These types of g-NC have potential applications as the active medium for thermally robust laser devices (in the visible range) or as temperature-insensitive bioprobes for biomedical imaging. PMID- 24177007 TI - ER stress-mediated regulation of immune function under glucose-deprived condition in glial cells: up- and down-regulation of PGE2 + IFNgamma-induced IL-6 and iNOS expressions. AB - Glucose metabolism plays central role in maintaining brain function. Under ischemic condition, where glucose levels were reduced, glial cells induce pro inflammatory cytokine production. In the present study, we found prostaglandin (PG) E2+interferon (IFN) gamma-induced interleukin (IL)-6 production was enhanced under glucose-deprived condition in the primary cultured glial cells. On the other hand, to our surprise, we found that PGE2+IFNgamma-induced iNOS expression was attenuated under glucose-deprived condition. These dual effects would be mediated through endoplasmic reticulum (ER) stress, because we observed (1) up regulation of GRP78 and CHOP under glucose-deprived condition, which was inhibited by chemical chaperon TMAO, and (2) treatment with TMAO inhibited IL-6 production under glucose-deprived condition. By activating theses responses glial cells may protect neurons because we observed increased neuronal cell viability in the immune-activated glial cell conditioned medium. Overall, our results suggest a link between ER stress and immune reactions under glucose-deprived condition in the glial cells. PMID- 24177006 TI - Quality of life after lacunar stroke: the Secondary Prevention of Small Subcortical Strokes study. AB - BACKGROUND: We sought to describe the course and predictors of quality of life (QOL) after lacunar stroke. We hypothesized that there is a decline in QOL after recovery from lacunar stroke. METHODS: The Secondary Prevention of Small Subcortical Strokes is a clinical trial in lacunar stroke patients with annual assessments of QOL with the stroke-specific QOL score. The overall score was used and analyzed as a continuous variable (range 0-5). We fit linear mixed models to assess the trend in QOL over time, assuming linearity of time, and adjusted for demographics, medical risk factors, cognitive factors, and functional status in univariable and multivariable models. RESULTS: Among 2870 participants, mean age was 63.4 years (SD 10.7), 63% were men, 51% White, 32% Hispanic, 36% had college education, 36% had diabetes, 89% had hypertension, and 10% had prior stroke. Mean poststroke Barthel Index (BI) score was 95.4 (assessed on average 6 months after stroke). In the final multivariable model, there was an average increase in QOL of .6% per year, and factors associated with decline in QOL over time included age (-.0003 per year, P < .0001), any college education (-.0013 per year, .01), prior stroke (-.004 per year, P < .0001), and BI (-.0002 per year, P < .0001). CONCLUSIONS: In this clinical trial of lacunar stroke patients, there was a slight annual increase in QOL overall, and age, level of education, and prior stroke were associated with changes in QOL over time. Multiple strokes may cause decline in QOL over time in the absence of recurrent events. PMID- 24177008 TI - Atorvastatin inhibited Rho-associated kinase 1 (ROCK1) and focal adhesion kinase (FAK) mediated adhesion and differentiation of CD133+CD44+ prostate cancer stem cells. AB - Prostate cancer has become a global health concern and is one of the leading causes of cancer death of men after lung and gastric cancers. It has been suggested that the 3-hydroxy-3-methyl-glutarylcoenzyme-CoA (HMG-CoA) reductase inhibitor atorvastatin shows anticancer activity in prostate cancer cell lines. To this end, we analyzed the influence of atorvastatin on the cell adhesion and differentiation of CD133(+)CD44(+) cells derived from prostate cancer biopsies and peripheral blood. CD133(+)CD44(+) cells were treated with atorvastatin (16 64MUM) for different time periods. Cell adhesion to endothelial cell monolayers and differentiation into prostate cancer cells were evaluated. alpha1, beta1 and alpha2beta1 integrins adhesion receptors and the downstream target of atorvastatin Rho-dependent kinase (ROCK) and focal adhesion kinase (FAK) were analyzed by Western blot. Further blocking studies with the ROCK inhibitor H1152, anti-FAK antibody and anti-integrin alpha1 and beta1 antibodies were carried out. Atorvastatin treatment inhibited dose-dependently cell attachment to endothelium and differentiation. The inhibitory effect of atorvastatin on cell adhesion was associated with decreased expression of integrins alpha1 and beta1 and phosphorylated MYPT1 and FAK. Furthermore, atorvastatin strongly reduced ROCK1 and FAK mediated differentiation of CD133(+)CD44(+) cells, which was confirmed by antibody treatment. Atorvastatin modified the expression of cell adhesion molecules and differentiation markers. These beneficial effects of atorvastatin may be mediated by ROCK and FAK signaling pathway. The data presented may point to novel treatment options for prostate cancer. PMID- 24177009 TI - Environmental acidification triggers oxidative stress and enhances globin expression in zebrafish gills. AB - Animals in many aquatic ecosystems must cope with changing environmental parameters, such as temperature, oxygen availability or pH. We have investigated the molecular responses to acidification in the gills and body of zebrafish (Danio rerio) by means of quantitative real-time PCR. Expression levels of typical stress genes and genes for antioxidant defense were strongly enhanced in gills, and to lesser extents in the body, suggesting that acidification leads to oxidative stress. Surprisingly, the globins were found to be among the most prominent stress-responsive proteins in our study. Myoglobin showed the strongest response of all investigated genes in the gills, as confirmed by Western blotting. These findings agree with the role of globins in oxidative energy metabolism, but may also hint at a specific function in antioxidative defense. PMID- 24177010 TI - High chondroitin sulfate proteoglycan 4 expression correlates with poor outcome in patients with breast cancer. AB - Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified in melanoma cells, has been reported to be expressed in breast cancer cells. This study was performed to examine the expression and significance of CSPG4 in a cohort of breast cancer patients. Immunohistochemical analysis of CSPG4 was performed on tissue microarrays constructed from tissue specimens from 240 breast cancer patients. CSPG4 staining was correlated with clinical and pathological characteristics, overall survival (OS), and disease recurrence. Contradicting to a previous report, our results showed that high CSPG4 expression was not related to triple-negative status of breast cancer patients. The Kaplan-Meier method showed that high CSPG4 expression was significantly associated with shorter time to recurrence (TTR). Patients with high CSPG4 expression had poorer OS and shorter TTR in a multivariate survival analysis after adjustment for stage, tumor grade, expression of estrogen receptor and progesterone receptor, and HER2 overexpression. This study showed that high CSPG4 expression correlates with disease recurrence and OS in breast cancers. PMID- 24177011 TI - A novel calcium-dependent protein kinase gene from Populus euphratica, confers both drought and cold stress tolerance. AB - Populus species are the most important timber trees over the Northern hemisphere. Most of them are cold- and drought-sensitive except the Populus euphratica Oliv. Here, a calcium-dependent protein kinase (CDPK) gene cloned from P. euphratica, designated as PeCPK10, was rapidly induced by salt, cold, and drought stresses. The protein encoded by PeCPK10 was localized within the nucleus and cytosol, which may be important for its specific regulation in cellular functions. To elucidate the physiological functions of PeCPK10, we generated transgenic Arabidopsis plants overexpressing PeCPK10. The results showed that PeCPK10 transgenic lines experienced better growth than vector control plants when treated with drought. Stronger abscisic acid-induced promotion of stomatal closing has been showed in transgenic lines. Particularly, overexpression of PeCPK10 showed enhanced freezing tolerance. Constitutive expression of PeCPK10 enhanced the expression of several abscisic acid-responsive genes and multiple abiotic stress-responsive genes such as RD29B and COR15A. Accordingly, a positive regulator responsive to cold and drought stresses in P. euphratica is proposed. PMID- 24177012 TI - ICAM-3 endows anticancer drug resistance against microtubule-damaging agents via activation of the ICAM-3-AKT/ERK-CREB-2 pathway and blockage of apoptosis. AB - In a previous study, we showed that induction of ICAM-3 endows radioresistance in cervical cancer [1]. To ascertain whether ICAM-3 also promotes anticancer drug resistance, mock control (H1299/pcDNA3) or ICAM-3-expressing stable transfectants (H1299/ICAM-3) of the non-small cell lung cancer (NSCLC) cell line, NCI-H1299, were generated and treated with the microtubule-damaging agents, paclitaxel (TXL) and vincristine (VCS). TXL-/VCS-treated H1299/ICAM-3 cells showed significantly lower levels of apoptosis, activation of caspases-3, 8 or 9, and decrease in anti apoptotic protein levels, compared to H1299/pcDNA3 cells. Our data clearly indicate that ICAM-3 promotes drug resistance via inhibition of apoptosis. We additionally showed that Akt, ERK, and CREB-2 are located downstream of ICAM-3, and activation of the ICAM-3-Akt/ERK-CREB-2 pathway induces resistance against TXL and VCS. ICAM-3-expressing stable NCI-H460/ICAM-3 transfectant cells and radioresistant SiHa cells endogenously overexpressing ICAM-3 additionally showed drug resistance against TXL and VCS via activation of the ICAM-3-Akt/ERK-CREB-2 pathway. The finding that ICAM-3 endows drug resistance as well as radioresistance supports its potential utility as a major therapeutic target against cancer. PMID- 24177014 TI - Surface trafficking of NMDA receptors: gathering from a partner to another. AB - Understanding the molecular and cellular pathways by which neurons integrate signals from different neurotransmitter systems has been among the major challenges of modern neuroscience. The ionotropic glutamate NMDA receptor plays a key role in the maturation and plasticity of glutamate synapses, both in physiology and pathology. It recently appeared that the surface distribution of NMDA receptors is dynamically regulated through lateral diffusion, providing for instance a powerful way to rapidly affect the content and composition of synaptic receptors. The ability of various neuromodulators to regulate NMDA receptor signaling revealed that this receptor can also serve as a molecular integrator of the ambient neuronal environment. Although still in its infancy, we here review our current understanding of the cellular regulation of NMDA receptor surface dynamics. We specifically discuss the roles of well-known modulators, such as dopamine, and membrane interactors in these regulatory processes, exemplifying the recent evidence that the direct interaction between NMDAR and dopamine receptors regulates their surface diffusion and distribution. In addition to the well-established modulation of NMDA receptor signaling by intracellular pathways, the surface dynamics of the receptor is now emerging as the first level of regulation, opening new pathophysiological perspectives for innovative therapeutical strategies. PMID- 24177013 TI - Relevance of signaling molecules for apoptosis induction on influenza A virus replication. AB - Apoptosis is an important mechanism to maintain homeostasis in mammals, and disruption of the apoptosis regulation mechanism triggers a range of diseases, such as cancer, autoimmune diseases, and developmental disorders. The severity of influenza A virus (IAV) infection is also closely related to dysfunction of apoptosis regulation. In the virus infected cells, the functions of various host cellular molecules involved in regulation of induction of apoptosis are modulated by IAV proteins to enable effective virus replication. The modulation of the intracellular signaling pathway inducing apoptosis by the IAV infection also affects extracellular mechanisms controlling apoptosis, and triggers abnormal host responses related to the disease severity of IAV infections. This review focuses on apoptosis related molecules involved in IAV replication and pathogenicity, the strategy of the virus propagation through the regulation of apoptosis is also discussed. PMID- 24177015 TI - Characterization of two novel plasmids from Geobacillus sp. 610 and 1121 strains. AB - We describe two cryptic low molecular weight plasmids, pGTD7 (3279bp) and pGTG5 (1540bp), isolated from Geobacillus sp. 610 and 1121 strains, respectively. Homology analysis of the replication protein (Rep) sequences and detection of ssDNA indicate that both of them replicate via rolling circle mechanism. As revealed by sequence similarities of dso region and Rep protein, plasmid pGTD7 belongs to pC194/pUB110 plasmid family. The replicon of pGTD7 was proved to be functional in another Geobacillus host. For this purpose, a construct pUCK7, containing a replicon of the analyzed plasmid, was created and transferred to G. stearothermophilus NUB3621R strain by electroporation. Plasmid pGTG5, based on Rep protein sequence similarity, was found to be related mostly to some poorly characterized bacterial plasmids. Rep proteins encoded by these plasmids contain conservative motifs that are most similar to those of Microviridae phages. This feature suggests that pGTG5, together with other plasmids containing the same motifs, could constitute a new family of bacterial plasmids. To date, pGTG5 is the smallest plasmid identified in bacteria belonging to the genus Geobacillus. The two plasmids described in this study can be used for the construction of new vectors suitable for biotechnologically important bacteria of the genus Geobacillus. PMID- 24177016 TI - Injection synthesis of Ni-Cu@Au-Cu nanowires with tunable magnetic and plasmonic properties. AB - A facile nonaqueous injection method has been developed for the construction of one-dimensional nanostructure consisting of a magnetic alloy (Ni-Cu) core and a plasmonic alloy (Au-Cu) shell. The obtained Ni-Cu@Au-Cu nanowires exhibit tunable optical and magnetic properties. PMID- 24177017 TI - Cooperative gating between ion channels. AB - Cooperative gating between ion channels, i.e. the gating of one channel directly coupled to the gating of neighboring channels, has been observed in diverse channel types at the single-channel level. Positively coupled gating could enhance channel-mediated signaling while negative coupling may effectively reduce channel gating noise. Indeed, the physiological significance of cooperative channel gating in signal transduction has been recognized in several in vivo studies. Moreover, coupled gating of ion channels was reported to be associated with some human disease states. In this review, physiological roles for channel cooperativity and channel clustering observed in vitro and in vivo are introduced, and stimulation-induced channel clustering and direct channel cross linking are suggested as the physical mechanisms of channel assembly. Along with physical clustering, several molecular mechanisms proposed as the molecular basis for functional coupling of neighboring channels are covered: permeant ions as a channel coupling mediator, concerted channel activation through the membrane, and allosteric mechanisms. Also, single-channel analysis methods for cooperative gating such as the binomial analysis, the variance analysis, the conditional dwell time density analysis, and the maximum likelihood fitting analysis are reviewed and discussed. PMID- 24177018 TI - Adrenomedullin and the calcitonin receptor-like receptor system mRNA expressions in the rat heart and sensory ganglia in experimentally-induced long-term diabetes. AB - Both adrenomedullin and calcitonin gene-related peptide (CGRP) regulate vascular tone in the heart, being cardioprotective in hypoxia. Additionally, adrenomedullin exhibits antiproliferative and antiapoptotic functions in the myocardium, while CGRP exerts positive chronotropic effect. Their actions are mediated through the specific G protein-coupled receptor, CRLR, whose ligand affinity is determined by receptor activity modifying proteins RAMP1-3. CGRP binds to the complex formed by CRLR/RAMP1, whereas CRLR/RAMP2 and CRLR/RAMP3 serve as receptors for adrenomedullin. Here, we quantified expression of this signaling system in the rat heart and supplying sensory ganglia (dorsal root ganglia T1-T4 and vagal nodose ganglia) in streptozotocin-induced diabetes. In the course of diabetes, an increase of CRLR mRNA was noticed in the right ventricle 8 weeks and of RAMP3 mRNA in the left ventricle and right atrium 26 weeks after induction of diabetes. Relative expressions of other tested genes were not significantly altered. In the nodose vagal supplying specific cardiac afferents, but not in dorsal root ganglia which provide cardiac pain fibres, a small upregulation of CGRP expression was detected. In summary, the shifts observed in diabetes may favour a trend of a pronounced adrenomedullin signaling. These observations may provide a new possible therapeutic strategy for diabetic cardiomyopathy. PMID- 24177019 TI - Chronic consumption of three forms of palm oil diets alters glomerular filtration rate and renal plasma flow. AB - The effects of chronic consumption of three types of palm oil diets on glomerular filtration rate (GFR), renal plasma flow (RPF) and blood pressure were studied. Wistar rats were randomly assigned into four groups of ten rats each, respectively: control, fresh (FPO), photoxidized (PPO), thermoxidized (TPO) palm oil diet-fed rats. The control group was fed rat chow only, while experimental groups had different palm oil diets at 15% wt/wt for twelve weeks and tap water ad libitum. After the feeding period, GFR, RPF, systolic and diastolic blood pressures were measured. GFR and RPF of the TPO (0.07 +/- 0.01 ml/min and 1.50 +/ 0.24 ml/min) and PPO (0.14 +/- 0.01 and 2.54 +/- 0.11) groups were significantly (p < 0.001) reduced compared with control (0.77 +/- 0.04 and 5.3 +/- 0.30) and FPO (0.81 +/- 0.02 and 4.8 +/- 0.13) groups. The GFR and RPF of the TPO group was significantly (p < 0.05) higher than that of the PPO group. Systolic and diastolic blood pressures of the TPO group (140 +/- 3 mmHg and 106 +/- 4 mmHg) were significantly (p < 0.01) increased when compared with the control (112 +/- 6.4 and 78 +/- 5), FPO (118 +/- 5 and 81 +/- 6) and PPO (122 +/- 5 and 89 +/- 5) groups. These results suggest that chronic consumption of TPO and PPO caused a decrease in GFR and RPF, but increased blood pressure in rats, while FPO did not adversely affect blood pressure, GFR and RPF. PMID- 24177020 TI - Crystallization, solubility and thermodynamics of the highly thermostable glucose isomerase from Streptomyces sp. strain. AB - The crystallization behaviour of the highly thermostable glucose isomerase from the Streptomyces sp. strain isolated from Tunisian soil was investigated using ammonium sulfate as a precipitating agent. We established phase diagrams at different temperatures and protein concentrations. It was found that the solubility increased with increasing temperature and decreased with increasing salt concentration. The temperature-dependent solubility was used to characterize the thermodynamic parameters of crystallization such as enthalpy, entropy and free energy. PMID- 24177021 TI - Approximation of A1 adenosine receptor reserve appertaining to the direct negative inotropic effect of adenosine in hyperthyroid guinea pig left atria. AB - Hyperthyroidism elevates cardiovascular mortality by several mechanisms, including increased risk of ischemic heart disease. Therefore, therapeutic strategies, which enhance tolerance of heart to ischemia-reperfusion injury, may be particularly useful for hyperthyroid patients. One promising cardioprotective approach is use of agents that cause (directly or indirectly) A1 adenosine receptor (A1 receptor) activation, since A1 adenosinergic pathways initiate protective mechanisms such as ischemic preconditioning. However, previously we found great A1 receptor reserve for the direct negative inotropic effect of adenosine in isolated guinea pig atria. This phenomenon suggests that weakening of atria is a possible side effect of A1 adenosinergic stimulant agents. Thus, the goal of the present investigation was to explore this receptor reserve in hyperthyroidism. Our recently developed method was used that prevents the rapid intracellular elimination of adenosine, allowing sufficient time for exogenous adenosine administered for the generation of concentration-response curves to exert its effect. Our method also allowed correction for the bias caused by the consequent endogenous adenosine accumulation. Our results demonstrate that thyroxine treatment does not substantially affect the A1 receptor reserve for the direct negative inotropic effect of adenosine. Consequently, if an agent causing A1 receptor activation is administered for any indication, the most probable adverse effect affecting the heart may be a decrease of atrial contractility in both eu- and hyperthyroid conditions. PMID- 24177022 TI - Effect of Pb2+ ions on photosynthetic apparatus. AB - Using model lead compounds Pb(NO3)2 and Pb(CH3CHOO)2, the mechanism and the site of action of Pb2+ ions in the photosynthetic apparatus of spinach chloroplasts were studied. Both compounds inhibited photosynthetic electron transport (PET) through photosystem 1 (PS1) and photosystem 2 (PS2), while Pb(NO3)2 was found to be more effective PET inhibitor. Using EPR spectroscopy the following sites of Pb2+ action in the photosynthetic apparatus were determined: the water-splitting complex and the Z*/D* intermediates on the donor side of PS2 and probably also the ferredoxin on the acceptor side of PS1, because cyclic electron flow in chloroplasts was impaired by treatment with Pb2+ ions. Study of chlorophyll fluorescence in suspension of spinach chloroplasts in the presence of Pb2+ ions confirmed their site of action in PS2. Using fluorescence spectroscopy also formation of complexes between Pb2+ and amino acid residues in photosynthetic proteins was confirmed and constants of complex formation among Pb2+ and aromatic amino acids were calculated for both studied lead compounds. PMID- 24177023 TI - Single- and multiple-dose pharmacokinetics of arginase inhibitor Nomega-hydroxy nor-L-arginine, and its effect on plasma amino acids concentrations in Wistar rats. AB - Arginase inhibitor Nomega-hydroxy-nor-L-arginine (nor-NOHA) augments synthesis of nitric oxide (NO) exerting therapeutic effects in rodent models for cardiovascular and airway diseases. This study examined single- and multiple-dose pharmacokinetics and effects of nor-NOHA on plasma amino acids in Wistar rats. Animals were administered 30 mg/kg nor-NOHA in a single bolus intravenous (i.v.) or intraperitoneal (i.p.) injection, or five once-daily i.p. injections at the same dose, or vehicle. Nor-NOHA and amino acids were assayed in blood plasma by high-performance liquid chromatography. After a bolus i.v. injection, the elimination of nor-NOHA was rapid (the mean residence time was 12.5 min). The area under the concentration-time curve and maximum concentration were higher by 17% and 31%, respectively, after the fifth as compared to the first i.p. injection. A shift in arginine utilization towards the synthesis of NO was indicated by elevated citrulline-to-ornithine and citrulline-to-arginine ratios. No changes in plasma arginine were observed. Increased glutamine concentrations might indicate an alternative detoxification pathway for ammonia due to inhibition of hepatic arginase. In conclusion, pharmacokinetic data of the present study can guide rational dosing of nor-NOHA in future studies. Limitations of the strategy of NO modulation via arginase inhibition should be further explored. PMID- 24177024 TI - A new look at abnormal uterine bleeding. AB - New universal terminology, classifications, and definitions recommended by the International Federation of Gynecology and Obstetrics and supported by the American College of Obstetricians and Gynecologists to describe abnormal uterine bleeding abnormalities in reproductive women are presented. Identification and management of anovulatory and ovulatory uterine bleeding are explored. PMID- 24177025 TI - Hormonal contraception and headaches: what are the prescriber's options? AB - This article will review evidence-based hormonal contraception prescribing options in the primary care setting for reproductive age women who experience headaches. Safe prescribing of hormonal contraception requires the nurse practitioner to be able to differentiate between the common primary headache phenotypes, such as the migraine and the tension-type headache. PMID- 24177026 TI - Endogenous Serratia marcescens endophthalmitis: an atypical presentation. PMID- 24177028 TI - Translational repression of SLC26A3 by miR-494 in intestinal epithelial cells. AB - SLC26A3 [downregulated in adenoma (DRA)] is a Cl(-)/HCO3(-) exchanger involved in electroneutral NaCl absorption in the mammalian intestine. Altered DRA expression levels are associated with infectious and inflammatory diarrheal diseases. Therefore, it is critical to understand the regulation of DRA expression. MicroRNAs (miRNAs) are endogenous, small RNAs that regulate protein expression via blocking the translation and/or promoting mRNA degradation. To investigate potential modulation of DRA expression by miRNA, five different in silico algorithms were used to predict the miRNAs that target DRA. Of these miRNAs, miR 494 was shown to have a highly conserved putative binding site in the DRA 3' untranslated region (3'-UTR) compared with other DRA-targeting miRNAs in vertebrates. Transfection with pmirGLO dual luciferase vector containing DRA 3' UTR (pmirGLO-3'-UTR DRA) resulted in a significant decrease in relative luciferase activity compared with empty vector. Cotransfection of the DRA 3'-UTR luciferase vector with a miR-494 mimic further decreased luciferase activity compared with cells transfected with negative control. The transfection of a miR 494 mimic into Caco-2 and T-84 cells significantly increased the expression of miR-494 and concomitantly decreased the DRA protein expression. Mutation of the seed sequences for miR-494 in 3'-UTR of DRA abrogated the effect of miR-494 on 3' UTR. These data demonstrate a novel regulatory mechanism of DRA expression via miR-494 and indicate that targeting this microRNA may serve to be a potential therapeutic strategy for diarrheal diseases. PMID- 24177029 TI - Acute ethanol preexposure promotes liver regeneration after partial hepatectomy in mice by activating ALDH2. AB - It is known that chronic ethanol significantly impairs liver regeneration. However, the effect of acute ethanol exposure on liver regeneration remains largely unknown. To address this question, C57Bl6/J mice were exposed to acute ethanol (6 g/kg intragastrically) for 3 days, and partial hepatectomy (PHx) was performed 24 h after the last dose. Surprisingly, acute ethanol preexposure promoted liver regeneration. This effect of ethanol did not correlate with changes in expression of cell cycle regulatory genes (e.g., cyclin D1, p21, and p27) but did correlate with protection against the effect of PHx on indices of impaired lipid and carbohydrate metabolism. Ethanol preexposure protected against inhibition of the oxidant-sensitive mitochondrial enzyme, aconitase. The activity of aldehyde dehydrogenase 2 (ALDH2) was significantly increased by ethanol preexposure. The effect of ethanol was blocked by inhibiting (Daidzin) and was mimicked by activating (Alda-1) ALDH2. Lipid peroxides are also substrates for ALDH2; indeed, alcohol preexposure blunted the increase in lipid peroxidation (4OH-nonenal adducts) caused by PHx. Taken together, these data suggest that acute preoperative ethanol exposure "preconditions" the liver to respond more rapidly to regenerate after PHx by activating mitochondrial ALDH2, which prevents oxidative stress in this compartment. PMID- 24177027 TI - The mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK-M) and glucose homeostasis: has it been overlooked? AB - BACKGROUND: Plasma glucose levels are tightly regulated within a narrow physiologic range. Insulin-mediated glucose uptake by tissues must be balanced by the appearance of glucose from nutritional sources, glycogen stores, or gluconeogenesis. In this regard, a common pathway regulating both glucose clearance and appearance has not been described. The metabolism of glucose to produce ATP is generally considered to be the primary stimulus for insulin release from beta-cells. Similarly, gluconeogenesis from phosphoenolpyruvate (PEP) is believed to be the primarily pathway via the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C). These models cannot adequately explain the regulation of insulin secretion or gluconeogenesis. SCOPE OF REVIEW: A metabolic sensing pathway involving mitochondrial GTP (mtGTP) and PEP synthesis by the mitochondrial isoform of PEPCK (PEPCK-M) is associated with glucose stimulated insulin secretion from pancreatic beta-cells. Here we examine whether there is evidence for a similar mtGTP-dependent pathway involved in gluconeogenesis. In both islets and the liver, mtGTP is produced at the substrate level by the enzyme succinyl CoA synthetase (SCS-GTP) with a rate proportional to the TCA cycle. In the beta-cell PEPCK-M then hydrolyzes mtGTP in the production of PEP that, unlike mtGTP, can escape the mitochondria to generate a signal for insulin release. Similarly, PEPCK-M and mtGTP might also provide a significant source of PEP in gluconeogenic tissues for the production of glucose. This review will focus on the possibility that PEPCK-M, as a sensor for TCA cycle flux, is a key mechanism to regulate both insulin secretion and gluconeogenesis suggesting conservation of this biochemical mechanism in regulating multiple aspects of glucose homeostasis. Moreover, we propose that this mechanism may be important for regulating insulin secretion and gluconeogenesis compared to canonical nutrient sensing pathways. MAJOR CONCLUSIONS: PEPCK-M, initially believed to be absent in islets, carries a substantial metabolic flux in beta-cells. This flux is intimately involved with the coupling of glucose-stimulated insulin secretion. PEPCK-M activity may have been similarly underestimated in glucose producing tissues and could potentially be an unappreciated but important source of gluconeogenesis. GENERAL SIGNIFICANCE: The generation of PEP via PEPCK-M may occur via a metabolic sensing pathway important for regulating both insulin secretion and gluconeogenesis. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. PMID- 24177030 TI - Acute interactions between intestinal sugar and calcium transport in vitro. AB - Fructose consumption by Americans has increased markedly, whereas Ca(2+) intake has decreased below recommended levels. Because fructose metabolism decreases enterocyte ATP concentrations, we tested the hypothesis that luminal fructose acutely reduces active, diet-inducible Ca(2+) transport in the small intestine. We confirmed that the decrease in ATP concentrations was indeed greater in fructose- compared with glucose-incubated mucosal homogenates from wild-type and was prevented in fructose-incubated homogenates from ketohexokinase (KHK)(-/-) mice. We then induced active Ca(2+) transport by chronically feeding wild-type, fructose transporter glucose transporter 5 (GLUT5)(-/-), as well as KHK(-/-) mice a low Ca(2+) diet and measured transepithelial Ca(2+) transport in everted duodenal sacs incubated in solutions containing glucose, fructose, or their nonmetabolizable analogs. The diet-induced increase in active Ca(2+) transport was proportional to dramatic increases in expression of the Ca(2+)-selective channel transient receptor potential vanilloid family calcium channel 6 as well as of the Ca(2+)-binding protein 9k (CaBP9k) but not that of the voltage dependent L-type channel Ca(v)1.3. Crypt-villus distribution of CaBP9k seems heterogeneous, but low Ca(2+) diets induce expression in more cells. In contrast, KHK distribution is homogeneous, suggesting that fructose metabolism can occur in all enterocytes. Diet-induced Ca(2+) transport was not enhanced by addition of the enterocyte fuel glutamine and was always greater in sacs of wild-type, GLUT5( /-), and KHK(-/-) mice incubated with fructose or nonmetabolizable sugars than those incubated with glucose. Thus duodenal Ca(2+) transport is not affected by fructose and enterocyte ATP concentrations but instead may decrease with glucose metabolism, as Ca(2+) transport remains high with 3-O-methylglucose that is also transported by sodium-glucose cotransporter 1 but cannot be metabolized. PMID- 24177031 TI - FXR silencing in human colon cancer by DNA methylation and KRAS signaling. AB - Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol 4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ~12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer. PMID- 24177033 TI - Acanthamoeba keratitis - an increasing incidence. PMID- 24177034 TI - Distinguishing Obsessive-Compulsive Behavior From Stereotypy: A Preliminary Investigation. AB - The current project was an initial attempt to develop assessment procedures for distinguishing between obsessive-compulsive (OC) and stereotypic behavior and evaluate the impact of different treatments for these behaviors. Two individuals with autism, one with repetitive behavior characteristic of OC behavior and one with repetitive behavior not characteristic of OC behavior, participated in the study. In Experiment 1, given that individuals with Obsessive-Compulsive Disorder (OCD) report experiencing unpleasant urges that are relieved when they perform compulsive actions, an attempt was made to identify these experiences by measuring heart rate and affect when access to repetitive behavior was restricted and allowed. In Experiment 2, a multiple schedules treatment was conducted with each participant, and in Experiment 3, the participant with autism and OC behavior completed exposure and response prevention (ERP) treatment. The overall results across studies suggest that one potential way to discriminate between OC behavior and stereotypy in nonvocal children with autism is to consider the topography of repetitive behavior along with changes in physiology and affect. In addition, it may be worth considering the use of ERP, a traditional treatment for OCD, to treat repetitive behavior maintained by automatic reinforcement if treatments that provide access to repetitive behavior are not effective. PMID- 24177032 TI - Cholecystokinin and pancreatic cancer: the chicken or the egg? AB - The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, "CCK or the cancer." PMID- 24177036 TI - Objective sleep parameters in patients with postural tachycardia syndrome by actigraphy. PMID- 24177035 TI - Dysferlin and myoferlin regulate transverse tubule formation and glycerol sensitivity. AB - Dysferlin is a membrane-associated protein implicated in muscular dystrophy and vesicle movement and function in muscles. The precise role of dysferlin has been debated, partly because of the mild phenotype in dysferlin-null mice (Dysf). We bred Dysf mice to mice lacking myoferlin (MKO) to generate mice lacking both myoferlin and dysferlin (FER). FER animals displayed progressive muscle damage with myofiber necrosis, internalized nuclei, and, at older ages, chronic remodeling and increasing creatine kinase levels. These changes were most prominent in proximal limb and trunk muscles and were more severe than in Dysf mice. Consistently, FER animals had reduced ad libitum activity. Ultrastructural studies uncovered progressive dilation of the sarcoplasmic reticulum and ectopic and misaligned transverse tubules in FER skeletal muscle. FER muscle, and Dysf- and MKO-null muscle, exuded lipid, and serum glycerol levels were elevated in FER and Dysf mice. Glycerol injection into muscle is known to induce myopathy, and glycerol exposure promotes detachment of transverse tubules from the sarcoplasmic reticulum. Dysf, MKO, and FER muscles were highly susceptible to glycerol exposure in vitro, demonstrating a dysfunctional sarcotubule system, and in vivo glycerol exposure induced severe muscular dystrophy, especially in FER muscle. Together, these findings demonstrate the importance of dysferlin and myoferlin for transverse tubule function and in the genesis of muscular dystrophy. PMID- 24177037 TI - Magnetically tunable singlet-triplet spin qubit in a four-electron InGaAs coupled quantum dot. AB - A pair of self-assembled InGaAs quantum dots filled with two electrons can act as a singlet-triplet spin qubit that is robust against nuclear spin fluctuations as well as charge noise. This results in a T2* coherence time two orders of magnitude longer than that of a single electron, provided the qubit is operated at a particular "sweet spot" in gate voltage. However, at this fixed operating point the ground-state splitting can no longer be tuned into resonance with e.g. another qubit, limiting the options for coupling multiple qubits. Here, we propose using a four-electron coupled quantum dot to implement a singlet-triplet qubit that features a magnetically tunable level splitting. As a first step towards full experimental realization of this qubit design, we use optical spectroscopy to demonstrate the tunability of the four-electron singlet-triplet splitting in a moderate magnetic field. PMID- 24177038 TI - Brain circuitries of obsessive compulsive disorder: a systematic review and meta analysis of diffusion tensor imaging studies. AB - The potential role of white matter (WM) abnormalities in the pathophysiology of obsessive compulsive disorder (OCD) is substantially unexplored. Apart from alterations in the WM tracts within cortico-striato-thalamo-cortical circuitry, recent theorizations predict the existence of more widespread WM abnormalities. In this paper we systematically reviewed the current diffusion tensor imaging literature in OCD and purposely evaluated the prevalence and functional significance of specific WM tissue changes in the disorder. The relationship between clinical variables (medication status, symptom severity) and WM microstructural changes was also assessed. The reviewed studies are consistent with the existence of microstructural alterations in the fronto-basal pathways targeting the orbitofrontal cortex and the anterior cingulate cortex. Moreover, altered anatomical connectivity between lateral frontal and parietal regions and microstructural abnormalities in intra-hemispheric bundles linking distinctive areas of the prefrontal cortex to posterior parietal and occipital association cortices, are consistently reported. Finally, microstructural abnormalities in the corpus callosum, characterized by decreased connectivity in the rostrum and hyperconnectivity in the genu, are substantiated by a large body of evidence. PMID- 24177039 TI - Renal dysfunction does not affect the prognostic value of myocardial iodine-123 meta-iodobenzylguanidine imaging in heart failure. AB - PURPOSE: Iodine-123 meta-iodobenzylguanidine (I-mIBG) imaging has prognostic value in patients with heart failure (HF). Renal dysfunction is prevalent in HF patients. I-mIBG is excreted by the kidneys, and the effect of renal dysfunction on its myocardial uptake and established prognostic value in HF patients is unknown. MATERIALS AND METHODS: The data analysed are from patients with New York Heart Association (NYHA) class II or III HF enrolled in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study. Myocardial uptake and retention of I-mIBG were assessed by the early and late heart-to-mediastinal (HM) ratio. Effect of renal dysfunction on the prognostic value of I-mIBG was determined by multivariable-predicted survival analysis stratified by glomerular filtration rate (GFR) and late HM ratio. Cox proportional hazard models were used to determine the predictors of cardiac events (CEs, defined as death, HF progression or life-threatening arrhythmia). RESULTS: Complete data were available on 867 patients. The GFR range was 19-140 ml/min, and 344 (40%) patients had renal dysfunction (GFR<60 ml/min). A total of 523 (60%) and 689 (80%) patients had early and late HM ratios below the previously established prognostic cutoff of 1.6. There was no relationship between early or late HM ratios and GFR after controlling for HF severity (NYHA class and norepinephrine levels), indicating a lack of effect of renal dysfunction on the HM ratio. Significant independent predictors of CE were (hazard ratio, P), b-type natriuretic peptide level (1.4, <0.001), left ventricular ejection fraction (0.95, <0.001), BMI (1.04, 0.002), cardiac glycoside use (1.42, 0.019) and late HM ratio (7.04, 0.008). Neither GFR nor its interaction with late HM ratio was a significant predictor of CE. CONCLUSION: Renal dysfunction does not affect the HM ratios or the prognostic value of I-mIBG imaging in HF patients. PMID- 24177040 TI - Deficiencies in product labelling instructions and quality control directions for 99mTc radiopharmaceuticals. AB - OBJECTIVE: The aim of the study was to identify deficiencies in product labelling instructions for reconstitution and in the quality control directions detailed in the technical leaflets (TLs) or summary product characteristic (SPC) sheets of commonly used technetium labelling cold kits. MATERIALS AND METHODS: The reconstitution and quality control directions in 25 TLs/SPCs were evaluated to identify deficiencies, incompleteness, restrictions, errors, impracticability, and vagueness. In addition, their congruence with the statements given in the relative European Pharmacopoeia (Ph. Eur. VII ed.) monography and diagnostic reference levels of Directive 97/43/EURATOM was evaluated. RESULTS: Deficiencies in information were scored and classified into five categories: 1, absent or incomplete; 2, restrictive; 3, inconsistent or wrong; 4, impractical; and 5, vague. In the 25 documents analyzed a total of 141 deficiencies were found (corresponding to 40.2% of the total scores assigned), and more frequently they pertained to quality control procedures (70.9%), followed by those related to quantitative composition (14.9%), preparation (8.5%), and particle size (5.7%). Nearly 80% of these deficiencies were classified as type 1 - that is, absent or incomplete information. CONCLUSION: The indications in TLs and SPCs should provide useful information for maintaining the quality and purity of the radiopharmaceutical preparation and ensure the safety level and effectiveness required by law. However, the instructions are often suboptimal or even erroneous, and consequently there are countless failures or difficulties, which represent an impediment to good laboratory practice. We believe that a 'smart' review of radiopharmaceutical documentation would be beneficial in order to align these indications to the real needs of the operators involved in routine in-house nuclear medicine practice. PMID- 24177041 TI - Does lemon juice increase radioiodine reaccumulation within the parotid glands more than if lemon juice is not administered? AB - OBJECTIVE: The protective effect of sialagogues following I therapy became controversial after a study proposed that sialagogues increase the reaccumulation of I in the parotid glands (PGs) to a level higher than when sialagogues are not administered ('rebound effect'). The present study examined PG radiopharmacokinetics within 2-4 h after radioiodine administration to evaluate whether sialagogues cause a 'rebound effect'. PATIENTS AND METHODS: This prospective study was conducted at the Medstar Washington Hospital Center. The study patients had (i) differentiated thyroid cancer, (ii) no history of salivary gland disease or medications affecting the salivary glands, (iii) a clinical salivary scan (SS) with lemon juice (LJ) (SSwLJ) that was performed before I therapy, and (iv) a second SS performed without LJ (SSwoLJ) performed prior to I therapy after giving informed consent. Each PG was assessed for I uptake using time-activity curves (TACs) that were (i) corrected for background and decay, (ii) smoothed using a seven-point unweighted moving average, and (iii) normalized to the administered I activity. TACs of the SSwLJ and SSwoLJ were compared with activity at each time point over 120 min. Areas under the TACs for the PGs were calculated for each gland's SSwLJ and SSwoLJ, and the relative percentage change in potential radiation absorbed dose (PRAD) was calculated. RESULTS: A total of 2100 time points were analyzed in nine patients (18 PGs). I activity in the PGs on SSwLJ exceeded activity seen on the SSwoLJ at 134 time points (6.3%), and 98 (73%) of these were on the basis of spontaneous salivation during SSwoLJ. Mean percentage decrease in relative PRAD was 34.2+/-17.4% (range, 3.1-66.1%). CONCLUSION: During the time period studied, LJ administration did not result in a 'rebound effect' but resulted in mean relative decrease of 34.2% in PRAD to the PGs. PMID- 24177042 TI - The influence of SPECT reconstruction algorithms on image quality and diagnostic accuracy in phantom measurements and 99mTc-sestamibi parathyroid scintigraphy. AB - OBJECTIVE: The aim of the study was to determine the influence and clinical consequences of different tomographic reconstruction algorithms on the image quality and diagnostic accuracy of low count statistics single photon emission computed tomography (SPECT). METHODS: Phantom scans were used to assess the image quality (percentage of recovered contrast, relative noise level, and spatial resolution). The diagnostic accuracy of parathyroid SPECT performed in 60 patients with primary hyperparathyroidism was assessed. Phantom and patient SPECT scans were reconstructed by two different algorithms (ReSPECT and HOSEM). Two blinded nuclear medicine physicians interpreted the patient scans in random order, without knowledge of any clinical data. Subjective image quality and certainty of diagnosis were scored. RESULTS: Significantly lower relative noise levels (0.08 vs. 0.13, respectively; P=0.042) and higher image spatial resolution (6.6 vs. 17.1 mm full-width at half-maximum in the transaxial plane, respectively) were found in the phantom studies using ReSPECT as compared with HOSEM. In the clinical scans, the mean target-to-background ratio was higher for ReSPECT (4.53 vs. 2.97; P<0.001). There was no significant difference in region based sensitivity (73 vs. 68%; P=0.538) or specificity (93 vs. 92%; P=0.815) between ReSPECT and HOSEM. Subjective image quality as well as certainty of interpretation was higher for ReSPECT (P<0.001). CONCLUSION: There is a significant difference in image quality between commercially available algorithms for tomographic reconstruction of SPECT scans, which appears to have an impact on diagnostic accuracy and interpreter certainty. Therefore, we believe that a systematic comparison of different SPECT reconstruction algorithms should be made to ensure reproducible high image quality in clinical SPECT. PMID- 24177043 TI - Diagnostic value of 18F-FDG-PET or PET-CT in recurrent cervical cancer: a systematic review and meta-analysis. AB - OBJECTIVES: Accurate detection of recurrent cervical cancer remains a clinical difficulty. This study aims to assess the diagnostic value of PET or PET-computed tomography (PET-CT) using F-fluorodeoxyglucose (F-FDG) in recurrent cervical cancer using a meta-analysis. STUDY DESIGN: All published studies in English evaluating the diagnostic value of PET or PET-CT in detecting recurrent cervical cancer were collected. The methodological quality of the included studies was evaluated. Pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver-operating characteristic curves were obtained using statistical software. Twenty studies were included in the meta-analysis. RESULTS: The meta analysis showed that the pooled sensitivity and specificity of PET and PET-CT to detect distant metastasis in recurrent cervical cancer were 0.87 [95% confidence interval (CI): 0.80-0.92] and 0.97 (95% CI: 0.96-0.98), respectively. The pooled sensitivity and specificity for local regional recurrence were 0.82 (95% CI: 0.72 0.90) and 0.98 (95% CI: 0.96-0.99), respectively. CONCLUSION: F-FDG-PET and PET CT are valuable methods for the assessment of recurrent cervical cancer. PMID- 24177044 TI - PET/CT shows subjective pain in shoulder joints to be associated with uptake of (18)F-FDG. AB - OBJECTIVES: The aim of the study was to evaluate the capability of fluorine-18 fluorodeoxyglucose (F-FDG)-positron emission tomography (PET)/computed tomography (CT) in the screening of musculoskeletal inflammation and injury of the shoulder region. MATERIALS AND METHODS: The study included 122 participants (69 men and 53 women) who complained of shoulder pain at rest and 122 age-matched and sex matched controls who did not experience pain at rest. Standardized uptake values (SUVs) were calculated for both the left and right shoulders and compared using a four-point visual analog scale of subjective shoulder pain. Correlations between SUVs and uric acid and C-reactive proteins were also evaluated. RESULTS: SUVs for shoulder joints with rest and/or motion pain were significantly higher than those for pain-free shoulder joints. SUVs associated with mild and severe pain at rest were significantly higher than those associated with absence of pain at rest, and SUVs associated with moderate and severe pain on motion were significantly higher than those associated with absence of motion pain. Furthermore, SUVs were significantly correlated with uric acid in men (beta=0.21, P=0.02) and in all participants (beta=0.22, P<0.001). CONCLUSION: F-FDG-PET/CT may be useful for the screening of musculoskeletal inflammation and injury of the shoulder region. As shoulder pain is common, especially among elderly individuals, we should carefully consider the necessity of further examination when identifying the uptake of F-FDG in shoulder joints. PMID- 24177045 TI - Chronotropic and dromotropic responses to localized glutamate microinjections in the rat nucleus ambiguus. AB - The cardioinhibitory effects of cardiac vagal motoneurons (CVMs) are mediated by activation of postganglionic neurons in the epicardial ganglia which have been shown to exert functionally selective effects on heart rate and atrioventricular conduction in the rat. Here we investigate whether CVMs producing these responses may occupy different rostrocaudal positions within the nucleus ambiguus. Excitation of CVMs was attempted by microinjections of glutamate into the nucleus ambiguus of an arterially perfused preparation in a grid extending over 2mm in the rostrocaudal plane using the obex as a reference point. Microinjections were paired, one made during pacing to measure changes in atrioventricular conduction (P-R interval) independent of changes in heart rate and the other looking for changes in heart period (P-P interval) un-paced. Although evidence of a differential distribution was found in 7 cases, in the majority (13/20), sites producing maximal effects on both variables coincided. Maximal changes in atrioventricular conduction resulted from more rostral sites in 6 cases and from a more caudal site in only one. Overall, the ratio of the change in atrioventricular conduction to the change in heart rate for a given site was significantly greater 1mm rostral to the obex than at either end of the test grid. We conclude that while CVMs controlling atrioventricular conduction are distributed with a peak somewhat rostral to those controlling heart rate in a number of animals, there is a significant overlap and much greater variability in this distribution in the rat than in cats and dogs. PMID- 24177046 TI - Down-regulation of Nogo-A by collagen scaffolds impregnated with bone marrow stromal cell treatment after traumatic brain injury promotes axonal regeneration in rats. AB - Nogo-A is a major form of growth inhibitory molecule (growth-IM) which inhibits axonal regeneration and neurite regrowth after neural injury. Bone marrow stromal cells (MSCs) have been shown to inhibit Nogo-A expression in vitro and in cerebral ischemic animal models. The present study was designed to investigate the effects of treatment with human MSCs (hMSCs) impregnated into collagen scaffolds on the expression of Nogo-A and axonal plasticity after traumatic brain injury (TBI). Adult male Wistar rats were injured with controlled cortical impact and treated either with saline, hMSCs-alone or hMSCs impregnated into collagen scaffolds (scaffold+hMSC) transplanted into the lesion cavity 7 days after TBI. Rats were sacrificed 14 days after TBI and brain tissues were harvested for immunohistochemical studies, Western blot analysis, laser capture microdissections and qRT-PCR to evaluate axonal density and Nogo-A protein and gene expressions. Our data showed that treatment of TBI with scaffold+hMSC significantly decreased TBI-induced Nogo-A protein expression and increased axonal density compared to saline and hMSC-alone treatments. In addition, scaffold+hMSC transplantation decreased Nogo-A transcription in oligodendrocytes after TBI. Scaffold+hMSC treatment was superior to hMSC-alone treatment in suppressing Nogo-A expression and enhancing axonal regeneration after TBI. Our data suggest that transplanting hMSCs with scaffolds down-regulates Nogo-A transcription and protein expression which may partially contribute to the enhanced axonal regeneration after TBI. PMID- 24177048 TI - Structural and electrochemical characterization of a cerium(IV) hydroxamate complex: implications for the beneficiation of light rare earth ores. AB - Reaction of N-phenyl-pivalohydroxamic acid with Ce(III) precursors leads to a homoleptic hydroxamate complex: Ce(IV)[(t)BuC(O)N(O)Ph]4. Electrochemical experiments indicate a significant stabilization of the Ce(IV) cation at Ep,c = 1.20 V versus SCE in the hydroxamate ligand framework. The spontaneous oxidation of Ce(III) in a hydroxamate ligand field is discussed in the context of beneficiation of the light rare earths from the fluorocarbonate mineral bastnasite. PMID- 24177047 TI - A novel methylation PCR that offers standardized determination of FMR1 methylation and CGG repeat length without southern blot analysis. AB - Fragile X syndrome and associated disorders are characterized by the number of CGG repeats and methylation status of the FMR1 gene for which Southern blot (SB) historically has been required for analysis. This study describes a simple PCR only workflow (mPCR) to replace SB analysis, that incorporates novel procedural controls, treatment of the DNA in separate control and methylation-sensitive restriction endonuclease reactions, amplification with labeled primers, and two color amplicon sizing by capillary electrophoresis. mPCR was evaluated in two independent laboratories with 76 residual clinical samples that represented typical and challenging fragile X alleles in both males and females. mPCR enabled superior size resolution and analytical sensitivity for size and methylation mosaicism compared to SB. Full mutation mosaicism was detected down to 1% in a background of 99% normal allele with 50- to 100-fold less DNA than required for SB. A low level of full mutation mosaicism in one sample was detected using mPCR but not observed using SB. Overall, the sensitivity for detection of full mutation alleles was 100% (95% CI: 89%-100%) with an accuracy of 99% (95% CI: 93% 100%). mPCR analysis of DNA from individuals with Klinefelter and Turner syndromes, and DNA from sperm and blood, were consistent with SB. As such, mPCR enables accurate, sensitive, and standardized methods of FMR1 analysis that can harmonize results across different laboratories. PMID- 24177049 TI - Work schedule and client characteristics associated with workplace violence experience among nurses and midwives in sub-Saharan Africa. AB - Violence against health care workers perpetrated by clients and/or their friends and family (Type II) is a growing problem that can severely impact health care delivery. We examined the prevalence of Type II workplace violence among nurses and midwives in sub-Saharan Africa and its association with work status, schedule, and client characteristics. Nurses and midwives (n = 712) completed an anonymous survey while attending nursing meetings. Generalized estimating equation models, accounting for clustering within residing countries, were employed. Participants who were exposed to risky client characteristics (aOR = 1.39-1.78, p < .001), and those who worked more than 40 hours a week were more likely to have experienced Type II workplace violence (aOR = 1.72-2.15, p < .05). Findings will inform policy and organization level interventions needed to minimize nurses' and midwives' exposure to Type II workplace violence by identifying risky clients and addressing long work hours. PMID- 24177050 TI - Repression of Alzheimer's beta-secretase. PMID- 24177051 TI - Oral visual examination for early detection of potentially malignant mucosal disorders in an opportunistic population. PMID- 24177053 TI - Hemichordate neurulation and the origin of the neural tube. AB - The origin of the body plan of our own phylum, Chordata, is one of the most fascinating questions in evolutionary biology. Yet, after more than a century of debate, the evolutionary origins of the neural tube and notochord remain unclear. Here we examine the development of the collar nerve cord in the hemichordate Balanoglossus simodensis and find shared gene expression patterns between hemichordate and chordate neurulation. Moreover, we show that the dorsal endoderm of the buccal tube and the stomochord expresses Hedgehog RNA, and it seems likely that collar cord cells can receive the signal. Our data suggest that the endoderm functions as an organizer to pattern the overlying collar cord, similar to the relationship between the notochord and neural tube in chordates. We propose that the origin of the core genetic mechanisms for the development of the notochord and the neural tube date back to the last common deuterostome ancestor. PMID- 24177054 TI - Reduction in newborn screening metabolic false-positive results following a new collection protocol. AB - PURPOSE: Newborn screening includes testing for many metabolic diseases. False positive results are higher among neonatal intensive care unit infants, resulting in increased confirmatory testing and family stress. Amino acid administration as a component of total parenteral nutrition is commonly used in the neonatal intensive care unit and suggested as a factor increasing false-positive results. The purpose of this study was to investigate the impact of a new sample collection protocol on false-positive results. METHODS: This was a 2-year retrospective cohort study. Infants were grouped by birth year into pre- and postprotocol implementation and stratified by birth weight category. In 2010, newborn screening samples were collected from all infants regardless of total parenteral nutrition administration. In 2011, the protocol was changed, and total parenteral nutrition was replaced with 10% dextrose in water (D10W) for 3 h before sample collection. RESULTS: Data from 539 neonatal intensive care unit admissions were reviewed. The new protocol reduced false-positive results for each birth weight group by at least 50% and overall by 74% (P = 0.008). The odds of having a false-positive result preintervention were 3.87 times higher than postintervention. The protocol reduced estimated costs by >80%. CONCLUSION: A protocol interrupting total parenteral nutrition for 3 h before newborn screening collection resulted in a 74% reduction in false-positive results in a neonatal intensive care unit. PMID- 24177055 TI - A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors. AB - PURPOSE: To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound. METHODS: Patients referred for prenatal diagnosis due to ultrasound anomalies underwent analysis by array comparative genomic hybridization as the first-tier diagnostic test. RESULTS: A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization. Array analysis revealed causal imbalances in a total of 9.6% of patients (n = 37). Submicroscopic copy number variations were detected in 2.6% of patients (n = 10/37), and arrays added valuable information over conventional karyotyping in 3.9% of patients (n = 15/37). We highlight a novel advantage of arrays; a 500-kb paternal insertional translocation is the likely driver of a de novo unbalanced translocation, thus improving recurrence risk calculation in this family. Variants of uncertain significance were revealed in 1.6% of patients (n = 6/383). CONCLUSION: We demonstrate the added value of chromosomal microarrays for prenatal diagnosis in the presence of ultrasound anomalies. We advocate reporting back only copy-number variations with known pathogenic significance. Although this approach might be considered opposite to the ideal of full reproductive autonomy of the parents, we argue why providing all information to parents may result in a false sense of autonomy. PMID- 24177056 TI - Prenatal technologies and the sex ratio. PMID- 24177052 TI - Chemoprevention of head and neck squamous cell carcinoma through inhibition of NF kappaB signaling. AB - Nuclear factor-kappa B (NF-kappaB) transcription factors regulate cellular processes such as inflammation and cell survival. The NF-kappaB pathway is often activated with development and progression of head and neck squamous cell carcinoma (HNSCC). As such, NF-kappaB represents an attractive target for chemoprevention. HNSCC involves progression of lesions from premalignant to malignant, providing a window of opportunity for intervention with chemopreventive agents. Appropriate chemopreventive agents should be inexpensive, nontoxic, and target important pathways involved in the development of HNSCC. Several such agents that inhibit the NF-kappaB pathway have been investigated in HNSCC. Retinoids have been studied most extensively but have shown limited potential in human trials. Epidermal growth factor receptor inhibitors and PI3K mTOR inhibitors may benefit a subset of patients. Other agents such as green tea extract and curcumin are appealing because they are generally regarded as safe. In contrast, there is evidence that Vitamin E supplementation may actually increase mortality of cancer patients. Repurposed drugs such as cyclooxygenase (COX) inhibitors and antidiabetic drugs are an emerging area of interest. Future research to develop agents with lower toxicity and higher specificity for the NF kappaB pathway, and to target these therapies to individual patient genetic signatures should help to increase the utility of chemoprevention in HSNCC. PMID- 24177058 TI - Direct evidence for nuclear spin waves in Nd2CuO4 by high-resolution neutron spin-echo spectroscopy. AB - The possibility of coupling through the hyperfine interaction of nuclear spins with the electronic spin system has given rise to hope for potential novel applications in spintronics and quantum computations. We investigated the dispersion of nuclear spin waves in such a coupled system, Nd2CuO4, by using neutron-spin-echo spectroscopy at millikelvin temperatures. Our results show the existence of dispersion of nuclear spin waves in Nd2CuO4 at T D 40 mK. A fit of the dispersion data with the spin wave dispersion formula gave the Suhl-Nakamura interaction range to be of the order of 10 A degrees , which is much smaller than that expected theoretically. PMID- 24177057 TI - Impact of prenatal technologies on the sex ratio in India: an overview. AB - The fact that techniques of prenatal diagnosis are used in India and China to selectively eliminate females is widely known. It has been extensively reported in the international media and in scientific publications since the 1990s. The publication of the Census of India 2011 shows that the ratio of girls to boys below the age of 6 years continues to decline at an alarming rate. Following that publication, this topic has again received international attention. The aim of this article is to better inform the human genetics community of the magnitude of this practice and its consequences in India.In this overview, we examine the impact of prenatal technology on the sex ratio in India. We present facts and figures from the Census of India and other publications that show that the practice is wide spread throughout India, in urban and rural areas, among the rich and the poor, and among the educated and the illiterate. We also briefly discuss the possible causes, consequences, and solutions. PMID- 24177059 TI - Cantilever energy effects on bimodal AFM: phase and amplitude contrast of multicomponent samples. AB - Bimodal atomic force microscopy (AFM) is a recently developed technique of dynamic AFM where a higher eigenmode of the cantilever is simultaneously excited along with the fundamental eigenmode. The effects of different operating parameters while imaging an impact copolymer blend of polypropylene (PP) and ethylene-propylene (E-P) rubber in bimodal mode are explored through experiments and numerical simulations. The higher mode amplitude and phase contrasts between the two components of the sample reverse at different points as the free amplitude of the higher eigenmode is increased. Three different regimes are identified experimentally depending on the relative contrast between the PP and the E-P rubber. It is observed that the kinetic energy and free air drive input energy of the two cantilever eigenmodes play a role in determining the regimes of operation. Numerical simulations conducted with appropriate tip-sample interaction forces support the experimental results. An understanding of these regimes and the associated cantilever dynamics will guide a rational approach towards selecting appropriate operating parameters. PMID- 24177060 TI - Phosphodiesterase 5 as target for adipose tissue disorders. AB - INTRODUCTION: Adipose tissue as an endocrine organ is responsible for the release of multiple cytokines, which have the most diverse metabolic functions. Therefore, it is extremely important to preserve its physiological health in order to avoid local and systemic disorders. Experiments available in literature show the importance of the nitric oxide (NO)/guanosine 3'5' cyclic monophosphate (cGMP)/protein kinase G (PKG) pathway in adipocyte biology. Phosphodiesterase 5 (PDE5) is an enzyme responsible for cGMP inactivation, and the use of its inhibitors can be an alternative in the search of a more balanced adipose tissue. OBJECTIVE: This review aims to describe the PDE5 role and the possibility of using PDE5 inhibitors in adipocyte physiology derangements and their consequences. DESIGN AND METHODS: Studies published in the last 10years that related PDE5 and its inhibitors to adipose tissue were raised in major databases. RESULTS: PDE5 is present in adipocyte, and PDE5 inhibitors can promote adipogenesis, interfere with adipokines secretion, decrease inflammatory markers expression, and increase the thermogenic potential of white adipose tissue. CONCLUSIONS: PDE5 plays an important role in adipocyte physiology and the use of its inhibitors may prove a useful tool to combat adipose tissue disorders and its highest expression, metabolic syndrome. PMID- 24177061 TI - Modulating hemoglobin nitrite reductase activity through allostery: a mathematical model. AB - The production of nitric oxide by hemoglobin (Hb) has been proposed to play a major role in the control of blood flow. Because of the allosteric nature of hemoglobin, the nitrite reductase activity is a complex function of oxygen partial pressure PO2. We have previous developed a model to obtain the micro rate constants for nitrite reduction by R state (kR) and T state (kT) hemoglobin in terms of the experimental maximal macro rate constant kNmax and the corresponding oxygen concentration PO2max. However, because of the intrinsic difficulty in obtaining accurate macro rate constant kN, from available experiments, we have developed an alternative method to determine the micro reaction rate constants (kR and kT) by fitting the simulated macro reaction rate curve (kN versus PO2) to the experimental data. We then use our model to analyze the effect of pH (Bohr Effect) and blood ageing on the nitrite reductase activity, showing that the fall of bisphosphoglycerate (BPG) during red cell storage leads to increase NO production. Our model can have useful predictive and explanatory power. For example, the previously described enhanced nitrite reductase activity of ovine fetal Hb, in comparison to the adult protein, may be understood in terms of a weaker interaction with BPG and an increase in the value of kT from 0.0087M(-1)s( 1) to 0.083M(-1)s(-1). PMID- 24177062 TI - Osteoporosis: therapeutic guidelines. Guidelines for practice management of osteoporosis. AB - Therapeutic guidelines of osteoporosis are reviewed from North American Menopause Society, American Association of Clinical Endocrinologists, American College of Obstetrics and Gynecology, and the National Osteoporosis Foundation. The various guidelines are compared and discussed. PMID- 24177063 TI - Controversies in osteoporosis management: concerns about bisphosphonates and when are "drug holidays" required? AB - Bisphosphonates are effective treatments for osteoporosis. The pharmacology and observance of atypical femoral fractures in patients on long-term therapy raise questions about the need for intermittent discontinuation of treatment, a "drug holiday." Fracture protection benefits of bisphosphonate therapy far outweigh the risk of atypical fractures for the first 10 years of therapy. However, because the fracture probability of therapy abates slowly after stopping the treatment while the risk of atypical fracture appears to decrease quickly, a "drug holiday" of 1 to 2 years should be considered after 3 to 5 years of bisphosphonate therapy except in those patients who remain at very high fracture risk. PMID- 24177069 TI - Sub-four-cycle laser pulses directly from a high-repetition-rate optical parametric chirped-pulse amplifier at 3.4 MUm. AB - We generate sub-four-cycle pulses (41.6 fs) with 12 MUJ of pulse energy in the mid-infrared spectral range (center wavelength 3.4 MUm) from a high-repetition rate, collinear three-stage optical parametric chirped-pulse amplifier (OPCPA) operating at 50 kHz. Apodized aperiodically poled MgO:LiNbO3 crystals with a negative chirp rate are employed as gain media to achieve ultrabroadband phase matching while minimizing optical parametric generation. The seed pulses are obtained via a 1.56 MUm femtosecond fiber laser, which is spectrally broadened in a dispersion-shifted telecom fiber to support 1000 nm bandwidth idler pulses in the mid-infrared. PMID- 24177068 TI - Response characteristics of primary auditory cortex neurons underlying perceptual asymmetry of ramped and damped sounds. AB - Sound envelope plays a crucial role in perception: ramped sounds (slow attack and quick decay) are louder in strength and longer in subjective duration than damped sounds (quick attack and slow decay) even if they are equal in intensity and physical duration. To explain the asymmetrical perception, the perceptual constancy hypothesis supposes that the listener eliminates the slow decay of damped sounds from the judgment of perception, while the persistence of perception hypothesis supposes asymmetrical neural responses after the source has stopped. To understand neural mechanisms underlying the perceptual asymmetry, we explored response properties of the primary auditory cortex (A1) neurons during ramped and damped stimuli in awake cats. We found two distinct types of cells tuned to specific features of the sound envelope: edge cells sensitive to the temporal edge, such as quick attack and decay, while slope cells sensitive to slow attack and decay. The former needs a short (<2.5 ms) period of stimulus duration for evoking maximal peak responses, while the latter needs a long (20 ms) period, suggesting that the timescale of processing underlies differential sensitivity between the cell types. The findings suggest that perceptual constancy is not yet be executed at A1 because the specific cells distinguishing the direction of amplitude change (attack or decay) are lacking in A1. On the other hand, there is evidence of persistence of perception: overall response duration during ramped sound reached 1.4 times longer than that during damped sound, originating mainly from the response asymmetry of the edge cell (sensitive to the quick decay of ramped sounds but not to the slow decay of damped sounds), and neuronal persistence of excitation after the termination of ramped sounds was substantially longer than that of damped sounds, corresponding to the psychological evidence of persistence of perception. PMID- 24177070 TI - Guided wave microscopy: mastering the inverse problem. AB - Surface plasmon microscopy is widely recognized for its high sensitivity to nanoscale dielectric or metallic structures confined in a close neighborhood of a gold surface. Recently, its coupling to high-numerical-aperture objective lenses pushed its resolution down to the diffraction limit. Here, we show that the same microscope configuration can be used to excite standing guided waves in asymmetric slabs, which definitely extends the range of applications of this type of microscopy from nano- to microscale structure imaging. We demonstrate experimentally on PPMA films that the V(Z) response of a scanning surface plasmon microscope can be Fourier inverted in order to obtain the reflectivity curve R(nu). When the guided waves are excited, R(nu) shows a finite number of sharp peaks corresponding to quantified guiding modes from which one can extract both the refractive index (RI) and the thickness of the layer at the point focused by the microscope. This device can thus be used to reconstruct RI and thickness contours of dielectric samples with a high spatial resolution. PMID- 24177072 TI - Tunable comb filters and refractive index sensors based on fiber loop mirror with inline high birefringence microfiber. AB - Highly birefringent (Hi-Bi) microfiber-based fiber loop mirrors (FLMs) were studied for tunable comb filters and refractive index (RI) sensors. The use of two cascaded Hi-Bi microfibers instead of a single microfiber allows more flexibility in controlling the transmission/reflection characteristics of the FLM. The length of Hi-Bi microfibers is of the order of centimeters, one or even more than two orders of magnitude shorter than the conventional Hi-Bi fiber-based FLM devices. The transmission/reflection spectra are sensitive to the RI surrounding the microfibers, and RI sensitivity of 20,745 nm/RIU was experimentally demonstrated. PMID- 24177071 TI - Simultaneous and independent processing of multiple input WDM data signals using a tunable optical tapped delay line. AB - We demonstrate a tunable optical tapped delay line that can simultaneously and independently operate on multiple wavelength-division multiplexed (WDM) data signals. The system utilizes the wavelength-dependent speed of light, together with nonlinear wavelength conversion stages. A phase-preserving scheme enables coherent addition of the weighted taps. We reconfigured the system to perform separate simultaneous correlation (data pattern recognition), equalization, and modulation format conversion on four and eight WDM binary/quadrate phase-shift keyed channels at 26 and 20 Gbaud, respectively. The aggregate throughput of 416 Gb/s is achieved. PMID- 24177067 TI - Gene and protein therapies utilizing VEGF for ALS. AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is usually fatal within 2-5years. Unfortunately, the only treatment currently available is riluzole, which has a limited efficacy. As a redress, there is an expanding literature focusing on other potential treatments. One such potential treatment option utilizes the vascular endothelial growth factor (VEGF) family, which includes factors that are primarily associated with angiogenesis but are now increasingly recognized to have neurotrophic effects. Reduced expression of a member of this family, VEGF-A, in mice results in neurodegeneration similar to that of ALS, while treatment of animal models of ALS with either VEGF-A gene therapy or VEGF-A protein has yielded positive therapeutic outcomes. These basic research findings raise the potential for a VEGF therapy to be translated to the clinic for the treatment of ALS. This review covers the VEGF family, its receptors and neurotrophic effects as well as VEGF therapy in animal models of ALS and advances towards clinical trials. PMID- 24177073 TI - Frequency comb generation by a continuous-wave-pumped optical parametric oscillator based on cascading quadratic nonlinearities. AB - We report optical frequency comb generation by a continuous-wave pumped optical parametric oscillator (OPO) without any active modulation. The OPO is configured as singly resonant with an additional nonlinear crystal (periodically poled MgO:LiNbO3) placed inside the OPO for phase mismatched second harmonic generation (SHG) of the resonating signal beam. The phase mismatched SHG causes cascading chi(2) nonlinearities, which can substantially increase the effective chi(3) nonlinearity in MgO:LiNbO3, leading to spectral broadening of the OPO signal beam via self-phase modulation. The OPO generates a stable 4 THz wide (-30 dB) frequency comb centered at 1.56 MUm. PMID- 24177074 TI - Third-order intermodulation distortion elimination of microwave photonics link based on integrated dual-drive dual-parallel Mach-Zehnder modulator. AB - A method to realize a highly linear microwave photonics link is proposed based on the dual-drive dual-parallel Mach-Zehnder modulator (MZM). The scheme theoretically eliminates third-order intermodulation distortion (IMD3) completely by taking all the sidebands in the optical spectrum that cause IMD3 into consideration. Without digital linearization and other optical processors, the method utilizes simple electrical signal phase control. Microwave signals are symmetrically single sideband modulated in the two MZMs. IMD3 suppression of approximately 30 dB is experimentally demonstrated, and the spurious-free dynamic range is improved by 12 dB.Hz2/3. PMID- 24177075 TI - Twisted light in a nonlinear mirror. AB - Opposite directionality of the Poynting vector and the wave vector, an inherent property of negative index metamaterials (NIMs), was predicted to enable backward phase-matching condition for a second harmonic generation (SHG) process. As a result, such a nonlinear negative index slab acts as a nonlinear mirror. In this Letter, we predict that SHG with structured light carrying orbital angular momentum (OAM) and propagating in NIMs results in a possibility of generating a backward propagating beam with simultaneously doubled frequency, OAM, and reversed rotation direction of the wavefront. These results may find applications in high-dimensional communication systems, quantum information processing, and optical manipulation on a nanoscale. PMID- 24177076 TI - Continuous-wave laser damage of uniform and nanolaminate hafnia and titania optical coatings. AB - The laser-damage thresholds of single material and nanolaminate thin films were compared under continuous-wave (CW) illumination conditions. Nanolaminate films consist of uniform material interrupted by the periodic insertion of one or more atomic layers of an alternative material. Hafnia and titania were used as the base materials, and the films were deposited using atomic-layer deposition. The nanolaminates were less polycrystalline than the uniform films, as quantified using x-ray diffraction. It was found that the nanolaminate films had reduced laser-damage thresholds on smooth and patterned substrates as compared to uniform single-material films. This behavior is unusual as prior art indicates that amorphous (less polycrystalline) materials have higher laser-damage thresholds under short-pulse excitation. It is speculated that this may indicate that local thermal conduction affects breakdown more strongly under CW excitation than the dielectric properties that are important for short-pulse excitation. PMID- 24177077 TI - Phase difference in modulated signals of two orthogonally polarized outputs of a Nd:YAG microchip laser with anisotropic optical feedback. AB - We present an experimental observation of the output responses of a Nd:YAG microchip laser with an anisotropic external cavity under weak optical feedback. The feedback mirror is stationary during the experiments. A pair of acousto-optic modulators is used to produce a frequency shift in the feedback light with respect to the initial light. The laser output is a beat signal with 40 kHz modulation frequency and is separated into two orthogonal directions by a Wollaston prism. Phase differences between the two intensity curves are observed as the laser works in two orthogonal modes, and vary with the external birefringence element and the pump power. Theoretical analyses are given, and the simulated results are consistent with the experimental phenomena. PMID- 24177078 TI - Frequency agile microwave photonic notch filter with anomalously high stopband rejection. AB - We report a novel class microwave photonic (MWP) notch filter with a very narrow isolation bandwidth (10 MHz), an ultrahigh stopband rejection (>60 dB), a wide frequency tuning (1-30 GHz), and flexible bandwidth reconfigurability (10-65 MHz). This performance is enabled by a new concept of sideband amplitude and phase controls using an electro-optic modulator and an optical filter. This concept enables energy efficient operation in active MWP notch filters, and opens up a pathway toward enabling low-power nanophotonic devices as high-performance RF filters. PMID- 24177079 TI - Ultrahigh-Q microwave photonic filter with tunable Q value utilizing cascaded optical-electrical feedback loops. AB - A microwave photonic filter with the highest reported quality factor (Q) value of 4895.31 is proposed and experimentally demonstrated by using two cascaded infinite impulse response (IIR) filters. Each IIR filter comprises both optical and electronic signals in a feedback loop and thus the loop length can be reduced without the need to consider the light coherence length. The Vernier effect enables a significant improvement of the free spectral ranges and Q values of the cascaded filter. The Q value of the proposed microwave photonic filter can be changed when the loop lengths of two cascaded filters are carefully adjusted. In addition, for a fixed Q, the frequency response of the filter can also be tuned by adjusting the bias of the Mach-Zehnder modulator in each loop. PMID- 24177080 TI - Damage threshold influenced by the high absorption defect at the film-substrate interface under ultraviolet laser irradiation. AB - The laser-induced damage threshold (LIDT) of a single-layer coating at the nanosecond (ns) regime is obviously lower than an uncoated substrate or a high reflectivity coating coated by the same material. To elucidate this phenomenon, we demonstrate the LIDT of three types of samples at 355 nm with 8 ns. High absorption defects are found at the film-substrate interface by comparing their LIDTs and damage morphologies. These defects originate from the substrate and appear during the coating process. Simulation results show that these defects, coupled to the coating, are mainly responsible for decreasing the damage threshold. PMID- 24177081 TI - Simultaneous dual wavelength eye-tracked ultrahigh resolution retinal and choroidal optical coherence tomography. AB - We demonstrate an optical coherence tomography device that simultaneously combines different novel ultrabroad bandwidth light sources centered in the 800 and 1060 nm regions, operating at 66 kHz depth scan rate, and a confocal laser scanning ophthalmoscope-based eye tracker to permit motion-artifact-free, ultrahigh resolution and high contrast retinal and choroidal imaging. The two wavelengths of the device provide the complementary information needed for diagnosis of subtle retinal changes, while also increasing visibility of deeper lying layers to image pathologies that include opaque media in the anterior eye segment or eyes with increased choroidal thickness. PMID- 24177082 TI - Photonics-based microwave frequency measurement using a double-sideband suppressed-carrier modulation and an InP integrated ring-assisted Mach-Zehnder interferometer filter. AB - A photonic system capable of estimating the unknown frequency of a CW microwave tone is presented. The core of the system is a complementary optical filter monolithically integrated in InP, consisting of a ring-assisted Mach-Zehnder interferometer with a second-order elliptic response. By simultaneously measuring the different optical powers produced by a double-sideband suppressed-carrier modulation at the outputs of the photonic integrated circuit, an amplitude comparison function that depends on the input tone frequency is obtained. Using this technique, a frequency measurement range of 10 GHz (5-15 GHz) with a root mean square value of frequency error lower than 200 MHz is experimentally demonstrated. Moreover, simulations showing the impact of a residual optical carrier on system performance are also provided. PMID- 24177083 TI - Whispering gallery mode diamond resonator. AB - We demonstrate a nearly spherical diamond whispering gallery mode resonator with quality factor (Q factor) Q=2.4*10(7) limited by material loss approaching alpha=4*10(-3) cm(-1). The Q factor does not depend on the wavelength: it is approximately the same at 1319 and 1550 nm. Resonators with this range of Q (<10 MHz at 1550 nm wavelength) are attractive for laser locking and stabilization. Applications such as stable compact optical comb generators as well as Raman optical frequency shifters will be feasible with further improvement of the material. PMID- 24177084 TI - Nonlinear optical signal processing on multiwavelength sensitive materials. AB - Exploiting salient features in the photodynamics of specific types of light sensitive materials, a new approach is presented for realization of parallel nonlinear operations with optics. We briefly review the quantum structure and mathematical models offered for the photodynamics of two multiwavelength sensitive materials, doped crystals of lithium niobate and thick layers of bacteriorhodopsin. Next, a special mode of these dynamics in each material is investigated and a graphical design procedure is offered to produce highly nonlinear optical responses that can be dynamically reshaped via applying minimum changes in the optical setup. PMID- 24177085 TI - Coherence and shot-to-shot spectral fluctuations in noise-like ultrafast fiber lasers. AB - We report on experimental studies of coherence and fluctuations in noise-like pulse trains generated by ultrafast fiber oscillators. By measuring the degree of first-order coherence using a Young's-type interference experiment, we prove the lack of phase coherence across the seemingly regular array of pulses. We further quantify the pulse-to-pulse fluctuations by recording the single-shot spectra of the megahertz pulse train, and experimentally demonstrate the existence of spectral fluctuations that remain unresolved in conventional time-averaged ensemble measurements. Phase incoherence and spectral fluctuations are contrasted with quantified coherence and spectral stability when the laser is soliton mode locked. PMID- 24177086 TI - Multidimensional subwavelength position sensing using a semiconductor laser with optical feedback. AB - We demonstrate experimentally how to harness quasi-periodic dynamics in a semiconductor laser with dual optical feedback for measuring subwavelength changes in each arm of the cavity simultaneously. We exploit the multifrequency spectrum of quasi-periodic dynamics and show that independent frequency shifts are mapped uniquely to two-dimensional displacements of the arms in the external cavity. Considering a laser diode operating at telecommunication wavelength lambda~1550 nm, we achieve an average nanoscale resolution of approximately 9.8 nm (~lambda/160). PMID- 24177087 TI - Simple signal-to-signal beat interference cancellation receiver based on balanced detection for a single-sideband optical OFDM signal with a reduced guard band. AB - A simple signal-to-signal beat interference cancellation receiver based on balanced detection (ICRBD) with an interleaver, a 2*2 three-decibel optical coupler, and a balanced photodiode pair is proposed for a single-sideband optical orthogonal frequency division multiplexing (SSB-OOFDM) signal with a reduced guard band (GB). Simulation demonstration of the ICRBD for a 40 Gbit/s 16-QAM SSB OOFDM signal with a reduced GB was achieved successfully. PMID- 24177088 TI - Influence of the incident laser pulse energy on jitter time of GaAs photoconductive semiconductor switches. AB - We have experimentally investigated the jitter time of a GaAs photoconductive switch (PCSS) when it is triggered by a laser pulse with 30 ns pulse width and 1064 nm wavelength. It is found that the jitter time decreases as the incident laser pulse energy increases from 0.40 to 1.6 mJ. In addition, a theoretical analysis indicates that the jitter time is proportional to relative deviation of the laser pulse energy. This work provides a path to improve the performance of the PCSS, which is used in applications such as a high time precision synchronous control system and ultrawide-band radiation source. PMID- 24177089 TI - Greatly enhanced ultrabroadband light absorption by monolayer graphene. AB - We demonstrate greatly enhanced light absorption by monolayer graphene over a broad spectral range, from visible to near IR, based on the attenuated total reflection. In the experiment, graphene is sandwiched between two dielectric media referred to as superstrate and substrate. Based on numerical calculation and experimental results, the closer the refractive indices of the superstrate and the substrate are, the higher the absorption of graphene is. The light absorption of monolayer graphene up to 42.7% is experimentally achieved. PMID- 24177090 TI - Blue upconversion laser based on thulium-doped silica microcavity. AB - Whispering gallery mode optical resonant cavities fabricated from rare-earth doped silica glasses have demonstrated lasing from the visible through the near IR. However, achieving lasing in the blue has been elusive. In this Letter, thulium-doped silica films are synthesized and used to fabricate toroidal optical microcavities with quality factors in excess of 10 million. Despite the high phonon energy of silica, the high circulating optical intensities present in the microcavities enable upconversion of the thulium, resulting in emission in the blue and near-IR with microwatt threshold powers that scale linearly with the concentration of the thulium. PMID- 24177091 TI - Holographic spatial coherence analysis of a laser. AB - We show that the second-order coherent-mode representation of a stationary quasi monochromatic scalar light beam can be experimentally characterized by dual-mode holographic interference using an arbitrary basis. Analysis of the laser beam emitted from a stable spherical mirror cavity, using a mismatched Hermite Gaussian basis, recovered the profiles and powers of a set of cavity modes with the expected spot size, including a hybrid of frequency degenerate modes. Observed near- and far-field irradiance transverse profiles and associated M2 parameter measures confirmed the results. PMID- 24177092 TI - Pulse compression to subcycle field waveforms with split-dispersion cascaded hollow fibers. AB - Carefully dispersion- and nonlinearity-managed cascades of gas-filled hollow-core fibers enable, as our theoretical analysis shows, efficient pulse compression with ultrahigh compression ratios. With dispersion and nonlinearity of individual fibers in such cascades optimized toward distinctly different goal functions, millijoule picosecond laser pulses can be compressed to sub-100-GW subcycle field waveforms. PMID- 24177093 TI - Rashba-type plasmonic metasurface. AB - Observation of the plasmonic Rashba effect manifested by a polarization helicity degeneracy removal in a surface wave excitation via an inversion asymmetric metamaterial is reported. By designing the metasurface symmetry using anisotropic nanoantennas with space-variant orientations, we govern the light-matter interaction via the local field distribution arising in a wavelength and a photon spin control. The broken spatial inversion symmetry is experimentally manifested by a directional excitation of surface wave jets observed via a decoupling slit as well as by the quantum dot fluorescence. Rashba-type plasmonic metasurfaces provide a route for spin-based nanoscale devices controlled by the metamaterial symmetry and usher in a new era of light manipulation. PMID- 24177094 TI - All-optical tunable filters based on optomechanical effects in two-dimensional photonic crystal cavities. AB - All-optical tunable filters are basic elements for various micro-optical circuits. Obtaining all-optical tunability remains a challenge for micro-optical circuits. Optical forces with significant effects in nanophotonic systems provide new ways for wavelength tuning. In this Letter, the optomechanical effects in two dimensional photonic crystal cavities are investigated. Simulations based on the finite element method demonstrate that forces arise in single and coupled cavities with movable rods inside. The optical force controls the positions of the movable rods and, thus, the resonance wavelength of the cavity, based on which tunable filter is designed. The operating wavelength of the cavity or the filter for the signal can be tuned by a control light with a different frequency. The results have potential applications for various integrated circuits. PMID- 24177095 TI - Low-power spontaneous oscillations driven by band-filling effect. AB - We predict that self-sustained oscillations can be generated in a semiconductor nanocavity in which the dominant effect is band-filling dispersion. Linear stability analysis, validated through numerical integration of a mean-field model, leads us to envisage oscillations typically at tens of gigahertz, with onset at much lower input power (~100 MUW) compared with those driven by two photon absorption. PMID- 24177096 TI - Lifetime reduction due to photodarkening phenomenon in ytterbium-doped fibers and rate equation term. AB - In this Letter, the lifetime temporal reduction in ytterbium-doped aluminosilicate fibers due to pump-induced photodarkening (PD) has been reported. A linear correlation between lifetime reduction at equilibrium state and equilibrium losses due to the PD phenomenon was demonstrated. A squared-law dependence between lifetime reduction and dopant concentration (percent by weight) suggests a possible correction term for the rate equations system which allows improving its accuracy. Finally, a quenching effect was also observed for different pump power levels in order to find the corresponding lifetime value for different inversion levels. The quantitative analysis allows determination of the PD quenching term in the laser rate equations system to properly model a laser device that may be affected by this process. PMID- 24177097 TI - Path-length-multiplexed scattering-angle-diverse optical coherence tomography for retinal imaging. AB - A low-resolution path-length-multiplexed scattering angle diverse optical coherence tomography (PM-SAD-OCT) is constructed to investigate the scattering properties of the retinal nerve fiber layer (RNFL). Low-resolution PM-SAD-OCT retinal images acquired from a healthy human subject show the variation of RNFL scattering properties at retinal locations around the optic nerve head. The results are consistent with known retinal ganglion cell neural anatomy and principles of light scattering. Application of PM-SAD-OCT may provide potentially valuable diagnostic information for clinical retinal imaging. PMID- 24177098 TI - Optimization of cascaded regenerative links based on phase sensitive amplifiers. AB - We develop an analytical method for optimizing phase sensitive amplifiers for regeneration in multilevel phase encoded transmission systems. The model accurately predicts the optimum transfer function characteristics and identifies operating tolerances for different signal constellations and transmission scenarios. The results demonstrate the scalability of the scheme and show the significance of having simultaneous optimization of the transfer function and the signal alphabet. The model is general and can be applied to any regenerative system. PMID- 24177099 TI - Spectral engineering by flexible tunings of optical Tamm states and Fabry-Perot cavity resonance. AB - We present a design for spectral engineering in a metal dual distributed Bragg reflector (DBR)-based structure. Optical Tamm states and Fabry-Perot cavity mode, dual windows for light-matter interaction enhancement, can be excited simultaneously and tuned flexibly, including their respective bandwidth and resonant wavelength, due to the variable reflection phase from the outer DBR's internal surface. The design can find applications in solar cells for light trappings. Via calculations of overall absorptivity, the proposed simpler dual states-based scheme is demonstrated to be almost as effective as the coherent light-trapping scheme, owing to the dual-states-induced broader-band absorption enhancement. PMID- 24177100 TI - Multifrequency radio frequency sensing with photonics-assisted spectrum compression. AB - We propose and demonstrate a multifrequency radio frequency (RF) spectrum estimation technology. With photonic assistance, a multifrequency RF signal ranging from 0 to 1 GHz is highly spectrally compressed and sensed using a single analog-to-digital converter with analog bandwidth of 42.6 MHz. By calculating the cross correlation of pseudo random binary sequence and the encoded signal, up to 40 RF tones are precisely recognized without large computational load. The employment of optical mixing decreased the cost and increased the performance compared to its electrical counterpart. The theory and performance are also discussed. PMID- 24177101 TI - Photon-counting chirped amplitude modulation lidar using a smart premixing method. AB - We proposed a new premixing method for photon-counting chirped amplitude modulation lidar (PCCAML). Earlier studies used the counting results of the returned signal detected by a Geiger mode avalanche photodiode detector (Gm-APD) to mix with the reference signal, called the postmixing method. We use an alternative method known as the premixing method, in which the reference signal is used to directly modulate the sampling gate width of the Gm-APD, and the mixing of the returned signal and the reference signal is completed before the Gm APD. This premixing method is more flexible and may perform better than the postmixing method in terms of signal-to-noise ratio by cutting down a separated mixer commonly used in the postmixing lidar system. Furthermore, this premixing method lowers the demand for the sampling frequency of the Gm-APD. It allows the use of a much wider modulation bandwidth to improve the range accuracy and resolution. To the best of our knowledge, this is the first report to use the premixing method in the PCCAML system, which will benefit future lidar applications. PMID- 24177102 TI - Multifocus tomographic algorithm for measuring optically thick specimens. AB - A novel tomographic algorithm for reconstructing the two-dimensional refractive index fluctuations of an optically thick phase object from one-dimensional projections acquired at a multiplicity of focal positions and a multiplicity of angular orientations is described. The new method is validated by measurements of multicore and microstructured optical fibers using interference microscopy. The method will benefit other transverse fiber measurement technologies and is broadly applicable to any tomographic reconstruction problem in which the transverse dimension of the specimen is substantially larger than the depth-of field of the imaging system. PMID- 24177103 TI - Poled-fiber source of broadband polarization-entangled photon pairs. AB - We demonstrate broadband polarization-entangled photon pair generation in a poled fiber phase matched for Type II downconversion in the 1.5 MUm telecom band. Even with signal-idler separation greater than 100 nm, we observe fringe visibilities greater than 97% and tangle greater than 0.8. A Hong-Ou-Mandel interference experiment is also used to experimentally confirm the broadband nature of the entanglement. PMID- 24177104 TI - Cross-correlation frequency-resolved optical gating and dynamics of temporal solitons in silicon nanowire waveguides. AB - We demonstrate the evolution of picosecond pulses in silicon nanowire waveguides by sum frequency generation cross-correlation frequency-resolved optical gating (SFG-XFROG) and nonlinear Schrodinger equation (NLSE) modeling. Due to the unambiguous temporal direction and ultrahigh sensitivity of the SFG-XFROG, which enable observation of the pulse accelerations, the captured pulses' temporal and spectral characteristics showed remarkable agreement with NLSE predictions. The temporal intensity redistribution of the pulses through the silicon nanowire waveguide for various input pulse energies is analyzed experimentally and numerically to demonstrate the nonlinear contributions of self-phase modulation, two-photon absorption, and free carriers. It indicates that free carrier absorption dominates the pulse acceleration. The model for pulse evolution during propagation through arbitrary lengths of silicon nanowire waveguides is established by NLSE, in support of chip-scale optical interconnects and signal processing. PMID- 24177105 TI - Gain saturation in a Raman-assisted fiber optical parametric amplifier. AB - We investigate the gain saturation characteristics in a backward-pumped Raman assisted fiber optical parametric amplifier (FOPA). It is experimentally observed that the onset of saturation occurs at a higher input power as compared to the case of a conventional FOPA with the same unsaturated gain. The output power under strong saturation is also enhanced. Simulations are performed on the power profile of the parametric pump to explain the distinct saturation behaviors. The monotonic increase of the parametric pump power in the Raman-assisted FOPA results in highly efficient power transfer to the signal while it suppresses the signal conversion to high-order idlers in the saturation regime. PMID- 24177106 TI - Spectral analysis of bent fiber Bragg gratings: theory and experiment. AB - This Letter presents a simple mathematical model developed from coupled-mode theory to describe the relationship between Bragg transmission loss (BTL), grating length, coupling coefficients, and bending loss in a bent fiber Bragg grating. In our investigation, the finding indicates that the decrement of BTL can be attributed to the increasing bending loss and degradation of both dc and ac coupling coefficients as the bending radius decreases. Besides, the center wavelength shifts as a result of coupling coefficients degradation. The validity of the proposed model is supported by experimental result. PMID- 24177107 TI - Thermo-optomechanical oscillations in high-Q ZBLAN microspheres. AB - We report stable thermo-optomechanical oscillations in high-Q-spherical ZBLAN microcavities. The oscillations are manifested as a complex combination of fast and slow oscillation periods. This behavior appears to be a consequence of the interplay between the negative thermo-optic effect, thermal expansion, and the Kerr effect. We have characterized the oscillatory behavior and measured the corresponding frequencies as a function of input power, wavelength detuning, and loaded optical quality factor. Our analysis shows that, as a gas sensor in the mid-IR spectral region, this thermo-optomechanical oscillator is two orders of magnitude more sensitive than previously demonstrated hybrid microtoroidal oscillators operating in the near-IR spectral region. PMID- 24177108 TI - Light dynamics in materials with radially inhomogeneous thermal conductivity. AB - We study the properties of bright and vortex solitons in thermal media with nonuniform thermal conductivity and homogeneous refractive index, whereby the local modulation of the thermal conductivity strongly affects the entire refractive index distribution. While regions where the thermal conductivity is increased effectively expel light, self-trapping may occur in the regions with reduced thermal conductivity, even if such regions are located close to the material boundary. As a result, strongly asymmetric self-trapped beams may form inside a ring with reduced thermal conductivity and perform persistent rotary motion. Also, such rings are shown to support stable vortex solitons, which may feature strongly noncanonical shapes. PMID- 24177109 TI - Highly nonparaxial spin Hall effect and its enhancement by plasmonic structures. AB - We present a new way to obtain large spin Hall effect of light (SHEL) in nonparaxial situations. We use near field of dipoles which contain all plane waves, both homogeneous and evanescent. We base SHEL on dipole-dipole interaction initiated energy transfer (FRET), which we further enhance using plasmonic platforms. The spin-orbit coupling inherent in Maxwell equations is seen in the conversion of a sigma(+) photon to a sigma(-) photon. The FRET is mediated by the resonant surface plasmons (SPs), and hence we find very large SHEL. We present explicit results for SHEL on metal films. We also study how the splitting of the SP on a metal film affects the SHEL. PMID- 24177110 TI - Efficient dual-wavelength Nd:LuLiF4 laser. AB - We report an efficient continuous-wave (CW) and passively Q-switched dual wavelength Nd:LuLiF4 laser at 1314 and 1321 nm for the first time. Maximum CW output power of 6.08 W is obtained, giving an optical-to-optical conversion efficiency of 30.2% and a slope efficiency of 32.1%. Even using high doping V3+:YAG as the saturable absorber to passively Q-switch the laser, stable dual wavelength operation remains. Maximum pulse energy extracted from the resonator is 108.7 MUJ at 17.2 kHz pulse-repetition rate, and maximum peak power is 885 W. PMID- 24177111 TI - Detection of pH-induced aggregation of "smart" gold nanoparticles with photothermal optical coherence tomography. AB - We report the feasibility of a novel contrast agent, namely "smart" gold nanoparticles (AuNPs), in the detection of cancer cells with photothermal optical coherence tomography (PT-OCT). "Smart" AuNPs form aggregation in low pH condition, which is typical for cancer cells, and this aggregation results in a shift of their absorption spectrum. A PT-OCT system was developed to detect this pH-induced aggregation by combining an OCT light source and a laser with 660 nm in wavelength for photothermal excitation. Optical detection of pH-induced aggregation was tested with solution samples at two different pH conditions. An increase in optical path length (OPL) variation was measured at mild acidic condition, while there was not much change at neutral condition. Detection of cancer cells was tested with cultured cell samples. HeLa and fibroblast cells, as cancer and normal cells respectively, were incubated with "smart" gold nanoparticles and measured with PT-OCT. An elevated OPL variation signal was detected with the HeLa cells while not much of a signal was detected with the fibroblast cells. With the novel optical property of "smart" AuNPs and high sensitivity of PT-OCT, this technique is promising for cancer cell detection. PMID- 24177112 TI - Angle independent flow assessment with bidirectional Doppler optical coherence tomography. AB - Bidirectional Doppler optical coherence tomography is a stable and accurate method to extract the absolute velocity of vessels close to perpendicular to the optical axis by illuminating the sample under two different angles. However it requires knowledge of the vessel angle in the en face plane. In this Letter, we demonstrate that a direct calculation of the flow out of bidirectional Doppler cross sections perpendicular to the illumination plane is independent of that angle and of the Doppler angle, thereby improving the accuracy and flexibility of that technique. We validate our approach with an in vitro experiment and in vivo measurements of a human retinal vessel and discuss the practical limitations of this approach. The method yields accurate flow values for most vascular plexuses without precise knowledge of the vessel orientation. The precision gradually decreases for larger en face angles. PMID- 24177113 TI - Energy scaling of a nonlinear compression setup using passive coherent combining. AB - Passive spatial and temporal coherent combining schemes are implemented to scale the output energy of a nonlinear temporal compression setup. By generating 32 replicas of the incident femtosecond pulses, the output of a high-energy fiber chirped-pulse amplifier can be compressed using self-phase modulation in a large mode-area rod-type fiber at peak-power levels well beyond the self-focusing power. We demonstrate the generation of 71 fs 7.5 MUJ pulses at 100 kHz repetition rate, corresponding to a peak power of 86 MW. PMID- 24177114 TI - Experimental generation of ring-shaped beams with random sources. AB - We have experimentally reproduced ring-shaped beams from the scattered Laguerre Gaussian and Bessel-Gaussian beams. A rotating ground glass plate is used as a scattering medium, and a plano-convex lens collects the scattered light to generate ring-shaped beams at the Fourier plane. The obtained experimental results are supported with the numerical results and are in good agreement with the theoretical results proposed by Wang et al. [Opt. Express17, 22366 (2009)]. PMID- 24177115 TI - Standoff trace chemical sensing via manipulation of excited electronic state lifetimes. AB - We present a technique for standoff trace chemical sensing that is based on the dependence of excited electronic state lifetimes on the amount of internal vibrational energy. The feasibility of the technique is demonstrated using N,N dimethylisopropylamine (DMIPA). Time-resolved measurements show that the lifetime of the S1 state in DMIPA exponentially decreases with the amount of vibrational energy. This property is employed to acquire molecular spectral signatures. Two laser pulses are used: one ionizes the molecule through the S1 state; the other alters the S1 state lifetime by depositing energy into vibrations. Reduction of the S1 state lifetime decreases ionization efficiency that is observed by probing the laser-induced plasma with microwave radiation. PMID- 24177116 TI - Single-shot coherent Rayleigh-Brillouin scattering using a chirped optical lattice. AB - We present a method for obtaining coherent Rayleigh-Brillouin scattering (CRBS) spectra on timescales of hundreds of nanoseconds using rapidly chirped, pulsed, optical lattices. This enables us to transfer the spectral profile to a temporal profile which can be easily recorded on a single shot of an oscilloscope. These spectra are demonstrated to have sufficient signal-to-noise ratio to study CRBS models over a wide range of gas densities. PMID- 24177117 TI - Broadband and efficient plasmonic control in the near-infrared and visible via strong interference of surface plasmon polaritons. AB - Broadband and tunable control of surface plasmon polaritons in the near-infrared and visible spectrum is demonstrated theoretically and numerically with a pair of phased nanoslits. We establish, with simulations supported by a coupled wave model, that by dividing the incident power equally between two input channels, the maximum plasmon intensity deliverable to either side of the nanoslit pair is twice that for an isolated slit. For a broadband source, a compact device with nanoslit separation of the order of a tenth of the wavelength is shown to steer nearly all the generated plasmons to one side for the same phase delay, thereby achieving a broadband unidirectional plasmon launcher. The reported effect can be applied to the design of ultra-broadband and efficient tunable plasmonic devices. PMID- 24177118 TI - Widely tunable mid-infrared generation via frequency conversion in semiconductor waveguides. AB - Phase matching in a multilayer AlGaAs waveguide is used to generate mid-IR (7.5 8.5 MUm) light through difference frequency generation (DFG) between a 1550 nm pump and 1950 nm signal. This represents the longest wavelength generated through DFG in a 2D waveguide mode in a semiconductor waveguide. It was produced with an efficiency of 1.2*10(-4) %/W in a 1 mm long sample. The process is shown to be tunable across >2 MUm through appropriate tuning of the input pump and signal wavelengths and/or waveguide geometry, and is therefore a viable platform for monolithic, tunable, mid-IR sources. PMID- 24177119 TI - Noncollinear third-harmonic Maker fringes for the determination of third-order nonlinear optical susceptibilities. AB - We describe noncollinear third-harmonic Maker fringes for the determination of third-order optical nonlinearities. This method builds on the same principles as conventional Maker fringes experiments, but thanks to the limited interaction length of two intersecting beams, it allows to eliminate the requirement of taking into account the contribution of air to the third-harmonic signal. Thus, third-order susceptibilities can be accurately determined without the need for a vacuum chamber. We review the theoretical underpinnings of the method, and discuss the dependence of the coherence length for harmonic generation on the intersection angle between the beams and the sample orientation, and the effect this has on the Maker fringes pattern. PMID- 24177120 TI - Generation of microwave radiation by nonlinear interaction of a high-power, high repetition rate, 1064 nm laser in KTiOPO4 crystals. AB - We report measurements of microwave (RF) generation in the centimeter band accomplished by irradiating a nonlinear KTiOPO4 crystal with a home-made, infrared laser at 1064 nm as a result of optical rectification. The laser delivers pulse trains of duration up to 1 MUs. Each train consists of several high-intensity pulses at an adjustable repetition rate of approximately 4.6 GHz. The duration of the generated RF pulses is determined by that of the pulse trains. We have investigated both microwave- and second harmonic generation as a function of the laser intensity and of the orientation of the laser polarization with respect to the crystallographic axes of KTP. PMID- 24177121 TI - Simulation of optical caustics associated with the secondary rainbow of oblate droplets. AB - A vector-ray tracing (VRT) model is employed to simulate optical caustic structures [in terms of rainbow and hyperbolic umbilic (HU) fringes] in the secondary rainbow region of light scattering from oblate droplets. The changes of the rainbow fringe and HU fringe in response to shape deformation of oblate droplets are investigated and the curvature of the rainbow fringe is calculated. Then the location of cusp caustics is calculated from VRT simulations and compared with analytic solutions. PMID- 24177122 TI - Tunable phase-shifted fiber Bragg grating based on femtosecond laser fabricated in-grating bubble. AB - We present a type of phase-shifted fiber Bragg gratings based on an in-grating bubble fabricated by femtosecond (fs) laser ablation together with a fusion splicing technique. A microchannel vertically crossing the bubble is drilled by fs laser to allow liquid to flow in or out. By filling different refractive index (RI) liquid into the bubble, the phase-shift peak is found to experience a linear red shift with the increase of RI, while little contribution to the change of phase shift comes from the temperature and axial strain. Therefore, such a PS-FBG could be used to develop a promising tunable optical filter and sensor. PMID- 24177123 TI - Autocorrelation method for fractal analysis in nonrectangular image domains. AB - We report an autocorrelation-based approach that accurately measures fractal organization within arbitrarily shaped (nonrectangular) regions of interest of gray-scale images. It extends fractal analysis beyond what is possible using fast Fourier transforms and improves on a previous autocorrelation algorithm. We illustrate its use in detecting subtle changes in mitochondrial organization within murine fibroblasts expressing the human papillomavirus E7 oncogene. PMID- 24177124 TI - Mode shaping in semiconductor broad area lasers by monolithically integrated phase structures. AB - By broadening the stripe width of the active waveguide region, it is possible to extract high optical powers from semiconductor broad area lasers. However, a weak output beam quality, optical filamentation, and high peak power densities will result, which are invoked by the amplification of higher order modes. We show an approach to influence the optical field inside the resonator by integrating optical phase structures directly into the waveguide. Those elements offer the possibility to enlarge the active gain area for the desired fundamental laser mode, while additional diffraction losses for higher order modes are generated, thus achieving an improved beam quality. We report on considerations in designing those elements and demonstrate a first experimental realization. PMID- 24177125 TI - Adaptive holographic pumping of thin-film organic lasers. AB - In this Letter, we use a reconfigurable hologram to dynamically control the position of incidence of the pump beam onto a liquid-crystal dye-based laser. The results show that there is an increase in the stability of the laser output with time and the average power when compared with the output of the same laser when it is optically excited using a static pump beam. This technique also provides additional functionality, such as wavelength tuning and spatial shaping of the pump beam, both of which are demonstrated here. PMID- 24177126 TI - Photonic-assisted microwave frequency multiplication with a tunable multiplication factor. AB - Photonic-assisted microwave frequency multiplication with a tunable multiplication factor (MF) based on an optical comb generator and an embedded single-passband microwave photonic filter (MPF) is proposed and demonstrated. The optical comb is generated using two cascaded modulators which are driven by a microwave reference signal. By applying the optical comb to a photodetector, a fundamental frequency corresponding to the comb spacing and its harmonics is generated. Thanks to the embedded single-passband MPF, only one harmonic is selected by the single-passband MPF. Thus, a single-frequency frequency multiplied microwave signal is generated. In the proposed system, the embedded single-passband MPF is formed by using a sliced broadband optical source and a section of dispersion-compensating fiber (DCF). By tuning the central frequency of the passband at a frequency corresponding to that of a specific harmonic, a microwave signal at that specific frequency is generated. The proposed system is experimentally demonstrated. A frequency-multiplied microwave signal with an MF from 1 to 5 is generated. The phase noise and frequency tunability of the generated microwave signal are also investigated. PMID- 24177127 TI - Triangular pulse generation using a dual-parallel Mach-Zehnder modulator driven by a single-frequency radio frequency signal. AB - A simple scheme for the generation of full-duty-cycle triangular pulses is proposed and experimentally demonstrated using a dual-parallel Mach-Zehnder modulator driven by a single-frequency RF signal. By properly setting the bias voltages and the RF power, even-order harmonics in the optical intensity are suppressed, and the amplitude of the first-order harmonic is 9 times of that of the third-order harmonic. A periodical triangular pulse train is obtained in the time domain. 2.5, 5, and 10 GHz triangular pulse trains are experimentally generated, which verifies the feasibility of the proposed scheme. PMID- 24177128 TI - Experimental single qubit quantum secret sharing in a fiber network configuration. AB - We present a robust single-photon quantum secret sharing (QSS) scheme with phase encoding in three-party implementations and a design way of more parties over a 50 km single-mode fiber network using a single QSS protocol. This scheme automatically provides perfect compensation for birefringence. A high visibility of 99.4% is obtained over three hours in visibility and stability measurements without any system adjustments, showing good potential for practical systems. Furthermore, polarization-insensitive phase modulators are realized using this system. PMID- 24177129 TI - Ultrastrong plasmon-exciton coupling in metal nanoprisms with J-aggregates. AB - In this Letter, ultrastrong plasmon-exciton coupling in an Ag nanoprism-J aggregate hybrid nanostructure is reported. A localized surface plasmon wavelength of Ag nanoprisms is tunable starting from 400 to 1100 nm. Because of the large electric field localization at the corners of the nanoprisms, the observed Rabi splitting energy is higher than the previously reported Rabi splitting energies using metal nanoparticles. A giant Rabi splitting energy of more than 400 meV corresponding to ~19% of the j-band energy has been observed, thus indicating the ultrastrong coupling regime. The hybrid nanostructure of nanoprism-J-aggregate is easy to prepare in large quantities and it can be uniformly assembled on solid substrates. PMID- 24177130 TI - 6-GHz, Kerr-lens mode-locked Yb:Lu2O3 ceramic laser for comb-resolved broadband spectroscopy. AB - A laser diode (LD)-pumped, 6-GHz repetition rate, ytterbium (Yb)-doped Lu2O3 ceramic Kerr-lens mode-locked laser is described. A bow-tie ring cavity enabled the generation of femtosecond pulses centered at a wavelength of 1076 nm with an average power of 10 mW. The pulse duration after an amplifier was 161 fs whereas the transform-limited pulse duration directly from the oscillator was 148 fs. The repetition frequency was sufficiently high for each longitudinal mode to be spectrally resolved by a commercially available optical spectrum analyzer. The developed laser was successfully applied to the absorption spectroscopy of metastable helium4 and demonstrated the suitability of the system as a source for comb-resolved broadband spectroscopy. PMID- 24177131 TI - Vulnerability to chosen-plaintext attack of a general optical encryption model with the architecture of scrambling-then-double random phase encoding. AB - We demonstrate a new approach to chosen-plaintext attack on a general encryption model based on scrambling preprocessing operation and double random phase encoding (DRPE). With this attack, an opponent can access both the scrambling key and two random phase keys. We hope that our work motivates further security analysis of the optical encryption scheme combining the scrambling techniques and DRPE. PMID- 24177132 TI - Resolution and contrast enhancement in coherent anti-Stokes Raman-scattering microscopy. AB - We implement switching laser mode coherent anti-Stokes Raman-scattering (SLAM CARS) microscopy to enhance the spatial resolution and contrast in label-free vibrational microscopy. The method, based on the intensity difference between two images obtained with Gaussian and doughnut-shaped modes, does not depend on the specimen and relies on minimal modifications of the typical CARS setup. We demonstrate subdiffraction resolution imaging of myelin sheaths in a mouse brainstem. A lateral resolution of 0.36lambda(p) is achieved. PMID- 24177133 TI - Asymmetric double-clad fiber couplers for endoscopy. AB - We present an asymmetric double-clad fiber coupler (A-DCFC) exploiting a disparity in fiber etendues to exceed the equipartition limit (<=50% extraction of inner cladding multi-mode light). The A-DCFC is fabricated using two commercially available fibers and a custom fusion-tapering setup to achieve >70% extraction of multi-mode inner cladding light without affecting (>95% transmission) single-mode light propagation in the core. Imaging with the A-DCFC is demonstrated in a spectrally encoded imaging setup using a weakly backscattering biological sample. Other applications include the combination of optical coherence tomography with weak fluorescent or Raman scattering signals. PMID- 24177134 TI - How long wavelengths can one extract from silica-core fibers? AB - The generation of wavelengths above 3 MUm by nonlinear processes in short silica photonic crystal fibers is investigated numerically. It was found that wavelengths in the 3-3.5 MUm range may be generated quite efficiently in centimeter-long fiber pieces when pumping with femtosecond pulses in the 1.55-2 MUm range. Wavelengths in the range of 3.5-4 MUm can in principle be generated, but these require shorter fiber lengths for efficient extraction. The results indicate that useful 3 MUm sources may be fabricated with existing silica-based fiber technology. PMID- 24177135 TI - Influence of hydrogen-oxidizing bacteria on the corrosion of low carbon steel: Local electrochemical investigations. AB - Low carbon steel has been considered a suitable material for component of the multi-barrier system employed on the geological disposal of high-level radioactive waste (HLW). A non negligible amount of dihydrogen (H2) is expected to be produced over the years within the geological repository due to the anoxic corrosion of metallic materials and also to the water radiolysis. The influence of the activity of hydrogen-oxidizing bacteria (HOB) and iron-reducing bacteria (IRB) on carbon steel corrosion is considered in this study because of the high availability of energetic nutriments (H2, iron oxides and hydroxides) produced in anoxic disposal conditions. Local electrochemical techniques were used for investigating the activity of IRB as a promoter of local corrosion in the presence of H2 as electron donor. A local consumption of H2 by the bacteria has been evidenced and impedance measurements indicate the formation of a thick layer of corrosion products. PMID- 24177136 TI - Impact of microbial activity on the radioactive waste disposal: long term prediction of biocorrosion processes. AB - This study emphasizes different experimental approaches and provides perspectives to apprehend biocorrosion phenomena in the specific disposal environment by investigating microbial activity with regard to the modification of corrosion rate, which in turn can have an impact on the safety of radioactive waste geological disposal. It is found that iron-reducing bacteria are able to use corrosion products such as iron oxides and "dihydrogen" as new energy sources, especially in the disposal environment which contains low amounts of organic matter. Moreover, in the case of sulphate-reducing bacteria, the results show that mixed aerobic and anaerobic conditions are the most hazardous for stainless steel materials, a situation which is likely to occur in the early stage of a geological disposal. Finally, an integrated methodological approach is applied to validate the understanding of the complex processes and to design experiments aiming at the acquisition of kinetic data used in long term predictive modelling of biocorrosion processes. PMID- 24177137 TI - Effect of protein adsorption on the corrosion behavior of 70Cu-30Ni alloy in artificial seawater. AB - Copper alloys often used in cooling circuits of industrial plants can be affected by biocorrosion induced by biofilm formation. The objective of this work was to study the influence of protein adsorption, which is the first step in biofilm formation, on the electrochemical behavior of 70Cu-30Ni (wt.%) alloy in static artificial seawater and on the chemical composition of oxide layers. For that purpose, electrochemical measurements performed after 1h of immersion were combined to surface analyses. A model is proposed to analyze impedance data. In the presence of bovine serum albumin (BSA, model protein), the anodic charge transfer resistance deduced from EIS data at Ecorr is slightly higher, corresponding to lower corrosion current. Without BSA, two oxidized layers are shown by XPS and ToF-SIMS: an outer layer mainly composed of copper oxide (Cu2O redeposited layer) and an inner layer mainly composed of oxidized nickel, with a global thickness of ~30nm. The presence of BSA leads to a mixed oxide layer (CuO, Cu2O, Ni(OH)2) with a lower thickness (~10nm). Thus, the protein induces a decrease of the dissolution rate at Ecorr and hence a decrease of the amount of redeposited Cu2O and of the oxide layer thickness. PMID- 24177138 TI - Concordance between continuity of care reported by patients and measured from administrative data. AB - Continuity of care can be measured using patient survey or administrative data, though the degree of concordance between continuity of care reported by patients and measured from their actual utilization is not well understood. A cross sectional analysis of the 2010 Medicare Current Beneficiary Survey and linked 2009-2010 Medicare Carrier and outpatient claims data measured the concentration of ambulatory care visit patterns according to two commonly used metrics of continuity of care. Continuity of care measured from claims data did not align with patient reports of having a usual care provider. However, high levels of continuity for patients with a usual care provider were associated with a longer patient-provider relationship, greater patient-perceived provider knowledge of the patient's medical condition and history, and more confidence in the provider. Inferences about a patient's continuity of care must be placed in the context of the data source with which continuity is measured. PMID- 24177139 TI - Protective effects of fucoidan, a P- and L-selectin inhibitor, in murine acute pancreatitis. AB - OBJECTIVE: The objective of this study was to investigate the potential protective effects of fucoidan, an L- and P-selectin modulator, in 2 murine models of acute pancreatitis. METHODS: Acute pancreatitis was induced in mice either by the retrograde infusion of taurolithocholic acid sulfate into the pancreatic duct or by intraperitoneal injections of cerulein (50 MUg/kg per hour). The experimental groups received fucoidan (25 mg/kg, intravenously) before pancreatitis induction, whereas control groups received only saline. After 24 hours, serum amylase, lipase, interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and nitrite were measured. In addition, myeloperoxidase (MPO) activity (lung and pancreas) and histological assessment (pancreas) were determined. RESULTS: Serum amylase, lipase, nitrite, TNF-alpha, and IL-1beta, and pancreatic and lung MPO were increased in both taurolithocholic acid sulfate and cerulein acute pancreatitis compared with the respective control groups. Fucoidan significantly decreased the augmented levels of amylase, lipase, pancreatic and lung MPO, TNF-alpha, IL-1beta, and nitrite in both models. Pancreas histological changes observed in both acute pancreatitis models were significantly attenuated by fucoidan. CONCLUSIONS: Fucoidan reduced the severity of acute pancreatitis in mice by decreasing neutrophil infiltration and systemic inflammation, suggesting that modulation of selectins may constitute a promising therapeutic approach. PMID- 24177140 TI - Reported findings on endoscopic ultrasound examinations for chronic pancreatitis: toward establishing an endoscopic ultrasound quality benchmark. AB - OBJECTIVES: Endoscopic ultrasound (EUS) quality benchmarks for pancreatic disease previously focused on maintaining thresholds of diagnostic accuracy for fine needle aspiration and measuring complications. We aimed to evaluate quality indicators when performing EUS specifically for the diagnosis of chronic pancreatitis (CP). METHODS: Using a single-center EUS database, we identified patients who underwent an EUS since 2001 specifically for the indication of (1) suspected CP, (2) exclusion of CP, or (3) established CP. Each EUS report was evaluated for the number of parenchymal and ductal criteria as per minimal standards terminology criteria. RESULTS: Two hundred eighty-six EUS examinations performed by 4 endosonographers were included. The mean number of reported evaluated parenchymal criteria was 2.44 (median, 2), and that of ductal criteria was 2.41 (median, 2). There was a difference among endosonographers in terms of mean number of total criteria reported evaluated (P < 0.001): endosonographer 1 = 3.9 (n = 174 examinations), endosonographer 2 = 6.8 (n = 86 examinations), endosonographer 3 = 6.2 (n = 13 examinations), and endosonographer 4 = 2.5 (n = 11 examinations). However, there was no difference between endosonographers in the number of total (parenchymal and ductal) criteria found. CONCLUSIONS: There was a discrepancy among endosonographers when reporting which EUS findings were evaluated in patients undergoing EUS specifically to diagnose CP. PMID- 24177141 TI - Smoking and body mass index and survival in pancreatic cancer patients. AB - OBJECTIVE: The objective of this study was to provide further information on the role of personal characteristics and lifestyle factors, including obesity, diabetes, and tobacco smoking, on survival from pancreatic cancer. METHODS: We obtained follow-up data of pancreatic cancer patients enrolled in 2 Italian case control studies. Information on characteristics and habits up to the time of diagnosis was collected by trained interviewers. Vital status was ascertained through population registers and record linkage with health system databases. Hazard ratios (HRs) of all-cause mortality and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: Follow-up information was retrieved for 648 cancer patients. Compared with subjects with body mass index of less than 25 kg/m, the HRs were 1.14 (95% CI, 0.94-1.39) for overweight (ie, 25-29.9 kg/m) and 1.32 (95% CI, 0.98-1.79) for obese (ie, >=30 kg/m) patients (trend P = 0.046). The HRs were 1.37 (95% CI, 1.14-1.65) for ever, 1.30 (95% CI, 1.03-1.65) for ex-smokers, and 1.42 (95% CI, 1.16-1.73) for current versus never smokers. Increasing amount and duration of smoking were associated with reduced survival after pancreatic cancer. No association emerged with diabetes, alcohol consumption, and diet. CONCLUSIONS: Smoking and overweight before diagnosis may play a role in the prognosis of pancreatic cancer, besides its etiology. PMID- 24177142 TI - Anterior gradient 2 and mucin 4 expression mirrors tumor cell differentiation in pancreatic adenocarcinomas, but aberrant anterior gradient 2 expression predicts worse patient outcome in poorly differentiated tumors. AB - OBJECTIVES: This study aimed to determine anterior gradient 2 (AGR2) expression in biopsies from pancreatic ductal adenocarcinomas (PDACs) and to evaluate AGR2 as a potential independent prognostic factor. METHODS: Tissue sample sections from a cohort of 135 consecutive surgically resectable PDACs were subjected to semiquantitative immunohistochemical analysis of AGR2 and mucin 4 (MUC4) expression. RESULTS: Anterior gradient 2 was over-expressed in PDAC compared with normal ductal cells. Since tumor lesions of PDAC are heterogeneous and constitute structures with various differentiation states, expression of both AGR2 and MUC4 was evaluated in each separate component. Expression levels of both proteins reflected the degree of tumor differentiation. Generally, well differentiated regions of tumor lesions expressed high levels of both proteins, moderately differentiated regions showed less AGR2 and MUC4, and poorly differentiated structures showed only weak positivity or were entirely negative. Of particular interest were occasional cases of strong AGR2 expression in high-grade tumors, where elevated protein levels were associated with shorter patient survival. CONCLUSIONS: Anterior gradient 2 and MUC4 reflect the level of differentiation of PDACs. However, in less differentiated tumors, aberrantly elevated AGR2 expression predicts poor patient outcome. PMID- 24177143 TI - A newly discovered LGI1 mutation in Korean family with autosomal dominant lateral temporal lobe epilepsy. AB - PURPOSE: A new leucine-rich glioma-inactivated 1 gene (LGI1) mutation inducing an amino acid sequence substitution was found in a Korean family with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We report the clinical features and characteristics of this newly identified LGI1 mutation. METHODS: Clinical data were collected from a large ADLTE family. All exons and flanking regions of the LGI1 gene were directly sequenced. 243 healthy controls were screened for the putative mutation. The 'Sorting Tolerant From Intolerant' algorithm was employed for the prediction of mutated LGI1 protein stability. LGI1 protein secretion was confirmed in vitro by immunoblotting assay. RESULTS: The main clinical characteristics included a young age at onset (mean, 12.4 years), diverse phenotypic manifestations, the occurrence of generalized tonic-clonic seizures, and a favorable prognosis. The genetic analysis detected a nonsynonymous single nucleotide polymorphism of c.137G>T coding for p.C46F in the five affected family members. This variant was not found in the normal control population and one unaffected family member. All the amino acids substituted for cysteine at position 46 of the LGI1 protein were predicted to damage protein stability in in silico analysis. Mutated C46F protein was retained within the cell at the immunoblotting assay. CONCLUSION: We identified a new LGI1 mutation in a large Korean ADLTE family which appeared to be involved in the development of epilepsy through suppressing LGI1 protein secretion. PMID- 24177144 TI - 'Eventually you just get used to it': an interpretative phenomenological analysis of 10-16 year-old girls' experiences of the transition into temporary accommodation after exposure to domestic violence perpetrated by men against their mothers. AB - Moving suddenly into temporary accommodation with their mothers is a reality for many children who live with domestic violence. The experience of this transition is under-researched despite being considered a unique event for children alongside that of being exposed to domestic violence involving their mothers. This piece of qualitative research aimed to address the following question: 'How do girls aged 10-16 years old experience the transition into temporary accommodation following exposure to domestic violence'? Five girls aged 10-16 years who had moved into either refuge or 'bed and breakfast' accommodation with their mothers were interviewed. Interviews were analysed using interpretative phenomenological analysis. Three master themes emerged: (1) 'Out of their hands: The transition into a whole new world with loss and change', (2) 'The relentlessness of feeling unsafe and uncertain', (3) 'Coping with the transition: At the mercy of their environment and the actions of others'. All themes show how a lack of agency was experienced by the girls throughout the transition. Findings suggest that the environment of temporary accommodation may inhibit the child's capacity to emotionally process the transition. The role of others was central to either facilitating or constraining coping for the girls throughout this transition. PMID- 24177145 TI - Deriving comorbidities from medical records using natural language processing. AB - Extracting comorbidity information is crucial for phenotypic studies because of the confounding effect of comorbidities. We developed an automated method that accurately determines comorbidities from electronic medical records. Using a modified version of the Charlson comorbidity index (CCI), two physicians created a reference standard of comorbidities by manual review of 100 admission notes. We processed the notes using the MedLEE natural language processing system, and wrote queries to extract comorbidities automatically from its structured output. Interrater agreement for the reference set was very high (97.7%). Our method yielded an F1 score of 0.761 and the summed CCI score was not different from the reference standard (p=0.329, power 80.4%). In comparison, obtaining comorbidities from claims data yielded an F1 score of 0.741, due to lower sensitivity (66.1%). Because CCI has previously been validated as a predictor of mortality and readmission, our method could allow automated prediction of these outcomes. PMID- 24177146 TI - Internet-based cognitive bias modification of interpretations in patients with anxiety disorders: a randomised controlled trial. AB - BACKGROUND AND OBJECTIVES: Previous research suggests that negative interpretation biases stimulate anxiety. As patients with an anxiety disorder tend to interpret ambiguous information negatively, it was hypothesised that training more positive interpretations reduces negative interpretation biases and emotional problems. METHODS: In a randomised, double-blind placebo-controlled trial, patients with different anxiety disorders were trained online over eight days to either generate positive interpretations of ambiguous social scenarios (n = 18) or to generate 50% positive and 50% negative interpretations in the placebo control condition (n = 18) (Study 1). RESULTS: Positively trained patients made more positive interpretations and less negative ones than control patients. This training was followed by a decrease in anxiety, depression, and general psychological distress, but this effect was also observed in the control group. To get a better understanding of these unexpected results, we tested a 100% neutral placebo control group (Study 2, n = 19); now the scenarios described neutral, non-emotional situations and no valenced interpretations were generated. The results from this neutral group were comparable to the effects from the other control group. LIMITATIONS: An advantage, but potentially also a disadvantage of the study is that CBM-I training was performed online with less control over the procedures and setting. In addition, the scenarios were not matched to the specific concerns of each patient and the training sessions were performed in close proximity to one another. CONCLUSIONS: Compared to both control conditions, CBM-I had superior effects on interpretations, but not on emotions. The current findings showed the boundary conditions for CBM-I. PMID- 24177148 TI - Magnetic properties of ultrathin Ni81Fe19 films with Ta and Ru capping layers. AB - Magnetic properties of Ni81Fe19 (permalloy) ultrathin films with Ru and Ta capping layers (CLs) were investigated for applications to magnetic random access memory units (MRAM). The sample structure, which simulated an MRAM free layer, is Si- sub./SiO2/Ni81Fe19/Ru(Ta). The Ni81Fe19 thin films less than 3 nm thick with Ru CL show low coercive fields compared with the Ta capping layer. Both systems showed loss of momentum equivalent to magnetically dead layers of thickness (delta) ~0.6 nm for Ru cap layer and ~1.4 nm for Ta cap layer, respectively. Moreover, after annealing the thicknesses are slightly increased to an equivalent magnetic dead layer thickness of delta ~0:84 nm and ~1.80 nm for Ru and Ta CL, respectively. Our calculations showed that the presence of only 11% Ta concentration at the interface reduced the Ni momentum to zero, with the Ni-Ta coupling being anti-ferromagnetic; while 50% Ru intermixing at the interface reduced the Ni momentum to zero with the coupling between Ru and Ni being ferromagnetic. To find out more about the intermixing at the interface, the composition and chemical states were characterized by the x-ray photoelectron spectroscopy and peak decomposition technique. The result showed that the peak positions were different from the pure metallic case at the interface region, mainly because of the intermixing between two layers. In conclusion, the Ru capping layer might be important for MRAM use in terms of low coercive field and small delta layer thickness if compared with the Ta capping layer. PMID- 24177147 TI - Molecular diversity and body distribution of saponins in the sea star Asterias rubens by mass spectrometry. AB - Saponins are natural molecules that the common sea star Asterias rubens produces in the form of steroid glycosides bearing a sulfate group attached on the aglycone part. In order to highlight the inter-organ and inter-individual variability, the saponin contents of five distinct body components, namely the aboral body wall, the oral body wall, the stomach, the pyloric caeca and the gonads, from different individuals were separately analyzed by mass spectrometry. MALDI-ToF experiments were selected as the primary tool for a rapid screening of the saponin mixtures, whereas LC-MS and LC-MS/MS techniques were used to achieve chromatographic separation of isomers. First of all, our analyses demonstrated that the diversity of saponins is higher than previously reported. Indeed, nine new congeners were observed in addition to the 17 saponins already described in this species. On the basis of all the collected MS/MS data, we also identified collision-induced key-fragmentations that could be used to reconstruct the molecular structure of both known and unknown saponin ions. Secondly, the comparison of the saponin contents from the five different body components revealed that each organ is characterized by a specific mixture of saponins and that between animals there are also qualitative and quantitative variability of the saponin contents which could be linked to the sex or to the collecting season. Therefore, the observed high variability unambiguously confirms that saponins probably fulfill several biological functions in A. rubens. The current results will pave the way for our future studies that will be devoted to the clarification of the biological roles of saponins in A. rubens at a molecular level. PMID- 24177150 TI - Urinary cytidine as an adjunct biomarker to improve the diagnostic ratio for gastric cancer in Taiwanese patients. AB - BACKGROUND: Gastric cancer is a major public health concern as the fourth most common cancer, and it is of particular relevance as the second most common cause of cancer death worldwide. We caparisoned the urinary nucleoside concentrations between the gastric patients and healthy volunteers that try to evaluate the diagnostic value in the gastric cancer. METHOD: Urinary nucleosides from 49 gastric patients and 40 healthy volunteers were evaluated by high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (HPLC/ESI MS/MS) under optimized conditions as determined in our previous study. RESULTS: The mean concentrations of 5 urinary nucleosides, cytidine, 3-methylcytidine (m3C), 1-methyladenosine (m1A), adenosine, and inosine, were found to be elevated in cancer patients, but only cytidine showed a significant elevation. Moreover, cytidine concentrations were significantly elevated by an average of 1.42-fold in patients with late stage (S3+4) disease. Combining the determined concentrations of preoperative serum alpha-fetoprotein (AFP, cutoff of 20 MUg/l) or carbohydrate antigen 19-9 (CA19-9, cutoff of 37 U/ml) with the mean urinary cytidine concentration was shown to improve the diagnostic ratio (sensitivity) for gastric cancer from 16.3% (8/49 patients) to 38.8% (8+11/49 patients) or from 28.6% (14/49 patients) to 51.0% (14+11/49 patients), respectively. CONCLUSIONS: Urinary cytidine may be an important adjunct biomarker for gastric cancer. PMID- 24177151 TI - Catalytic reforming of nitrogen-containing volatiles evolved through pyrolysis of composted pig manure. AB - The pyrolysis of pig compost was performed in a two-stage fixed-bed reactor to determine the effects of decomposition temperatures and catalysts (i.e., transition-metal and non-transition-metal catalysts) on carbon and nitrogen conversions. The secondary decomposition was investigated at different temperatures from room temperature up to 750 degrees C. Then the effects of various catalysts were investigated at 650 degrees C. Approximately 60% of the carbon and 80% of the nitrogen in the pig compost were converted into volatiles during pyrolysis. Conversion of carbon and nitrogen species in tar into gas, and the evolution undesirable NH3 and HCN without catalyst increased with increasing decomposition temperature. Transition-metal catalysts showed excellent activity for conversion of condensable volatiles into gas and NH3 and HCN into N2. Although non-transition-metal catalysts had moderate activity for the conversion of volatiles into gas and negligible activity for the conversion of NH3 into N2, dolomite can provide liquid fuel with negligible amount of nitrogen species. PMID- 24177152 TI - Conversion of grass biomass into fermentable sugars and its utilization for medium chain length polyhydroxyalkanoate (mcl-PHA) production by Pseudomonas strains. AB - This study investigated the potential of grass biomass as a feedstock for mcl-PHA production. Pretreatments (2% NaOH at 120 degrees C or hot water at 120 degrees C) of perennial ryegrass were employed alone or in combination with sodium chlorite/acetic acid (SC/AA) delignification to evaluate the enzymatic digestibility and subsequent utilization of resultant sugars by Pseudomonas strains. NaOH pretreated sample had better digestibility than raw and hot water treated samples and this hydrolysate supported good growth of all tested strains with limited mcl-PHA (6-17% of cell dry mass (CDM)) accumulation. Digestibility of both untreated and pretreated samples was improved after SC/AA delignification and produced glucose (74-77%) rich hydrolysates. Tested strains accumulated 20 34% of CDM as PHA when these hydrolysates were used as sole carbon and energy source. CDM and PHA yields obtained for these strains when tested with laboratory grade sugars was similar to that achieved with grass derived sugars. PMID- 24177153 TI - Effect of enzyme secreting bacterial pretreatment on enhancement of aerobic digestion potential of waste activated sludge interceded through EDTA. AB - In this study, the effect of Ethylene diamine tetra acetic acid (EDTA) on Extracellular polymeric substance (EPS) removal tailed with bacterial enzymatic pretreatment on aerobic digestion of activated sludge was studied. In order to enhance the accessibility of sludge to the enzyme secreting bacteria; the extracellular polymeric substances were removed using EDTA. EDTA efficiently removed the EPS with limited cell lysis and enhanced the sludge enzyme activity at its lower concentration of 0.2 g/g SS. The sludge was then subjected to bacterial pretreatment to enhance the aerobic digestion. In aerobic digestion the best results in terms of Suspended solids (SS) reduction (48.5%) and COD (Chemical oxygen demand) solubilization (47.3%) was obtained in experimental reactor than in control. These results imply that aerobic digestion can be enhanced efficiently through bacterial pretreatment of EPS removed sludge. PMID- 24177154 TI - Overliming detoxification of pyrolytic sugar syrup for direct fermentation of levoglucosan to ethanol. AB - The application of pyrolytic sugars for biofuel production through fermentation is challenged by inhibitory contaminant compounds. Inhibition is so severe that only 0.25% sugar syrup can be used. In this study, overliming was tested as a simple detoxification method, using the Escherichia coli KO11+ lgk to directly convert levoglucosan into ethanol. After treatment with at least 14.8 g/L of Ca(OH)2, fermentation with 2% (w/v) pyrolytic sugar syrup was observed with no inhibition of ethanol production. Further investigation of treatment time and temperature showed that 8-16 h of treatment at 20 degrees C, and 1-4 h of treatment at 60 degrees C are necessary to obtain consistent ethanol production. The samples treated with 18.5 g/L Ca(OH)2 at 60 degrees C for 4 h showed no inhibition at 2.5%. Multiple contaminants removed by the overliming treatment were identified. This study demonstrates that overliming is a promising method for detoxification of pyrolytic sugars for fermentation. PMID- 24177155 TI - Harnessing the hydrolytic potential of phytopathogenic fungus Phoma exigua ITCC 2049 for saccharification of lignocellulosic biomass. AB - Phytopathogenic fungi develop unique systems for fast invasion by producing hydrolases, which may be explored as a source of hydrolytic enzymes for biofuel research. The present work deals with evaluation of a potato pathogen Phoma exigua ITCC 2049 for its potential to produce cellulase and xylanase enzyme. Taguchi methodology was applied to reveal the influence and contribution of five important factors (carbon source, organic and inorganic nitrogen source, surfactant, and pH) on hydrolytic enzyme production by Phoma. Cultivation of fungus under optimized condition produced endoglucanase (37.00 IU/ml), FPase (1.13 IU/ml), beta-glucosidase (2.67 IU/ml) and xylanase (24.92 IU/ml) within 8 days of submerged fermentation. Saccharification of biopretreated Parthenium and paddy straw with cocktail of Phoma secretome supplemented with commercial beta glucosidase resulted in the significantly higher reducing sugar yield (651.04 698.11 mg/gds). This study proves the potential of Phoma as an alternative source of enzymes for biomass saccharification. PMID- 24177156 TI - Changes of bacterial and fungal community compositions during vermicomposting of vegetable wastes by Eisenia foetida. AB - Changes of bacterial and fungal community during vermicomposting of vegetable wastes by hatchling, juvenile and adult Eisenia foetida were investigated through analysis of the extracted bacterial 16S rDNA and fungal 18S rDNA with quantitative polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and sequencing. After 60days of composting, significantly lower values of microbial activity and bacterial and fungal densities were revealed in the products of composting with earthworms than in the control (without earthworms). PCR-DGGE images showed vermicomposting significantly enhanced the diversities of bacterial and fungal communities. However, for their structures, sequencing results revealed that, compared to the control where the bacterial Firmicutes were predominant, in the composts with earthworms, the bacterial Bacteroidetes and Actinomycetes, and the fungal Sordariomycetes were found dominant. In addition, some beneficial species of bacteria and fungi against pathogens were also isolated from the vermicomposting products. PMID- 24177157 TI - Removal of metal from acid mine drainage using a hybrid system including a pipes inserted microalgae reactor. AB - In this study, the microalgae culture system to combined active treatment system and pipe inserted microalgae reactor (PIMR) was investigated. After pretreated AMD in active treatment system, the effluent load to PIMR in order to Nephroselmis sp. KGE 8 culture. In experiment, effect of iron on growth and lipid accumulation in microalgae were inspected. The 2nd pretreatment effluent was economic feasibility of microalgae culture and lipid accumulation. The growth kinetics of the microalgae are modeled using logistic growth model and the model is primarily parameterized from data obtained through an experimental study where PIMR were dosed with BBM, BBM added 10 mg L(-1) iron and 2nd pretreatment effluent. Moreover, the continuous of microalgae culture in PIMR can be available. Overall, this study indicated that the use of pretreated AMD is a viable method for culture microalgae and lipid accumulation. PMID- 24177158 TI - Thermophilic anaerobic digestion of coffee grounds with and without waste activated sludge as co-substrate using a submerged AnMBR: system amendments and membrane performance. AB - Coffee grounds are deemed to be difficult for degradation by thermophilic anaerobic process. In this research, a 7 L AnMBR accepting coffee grounds was operated for 82 days and failed with pH dropping to 6.6. The deficiency of micronutrients in the reactor was identified. The system was recovered by supplying micronutrient, pH adjustment and influent ceasing for 22 days. In the subsequent 160 days of co-digestion experiment, waste activated sludge (15% in the mixture) was mixed into coffee grounds. The COD conversion efficiency of 67.4% was achieved under OLR of 11.1 kg-COD/m(3) d and HRT of 20 days. Tannins was identified affecting protein degradation by a batch experiment. Quantitative supplements of NH4HCO3 (0.12 g-N/g-TSin) were effective to maintain alkalinity and pH. The solid concentration in the AnMBR reached 75 g/L, but it did not significantly affect membrane filtration under a flux of 5.1 L/m(2) h. Soluble carbohydrate, lipid and protein were partially retained by the membrane. PMID- 24177159 TI - Co-metabolic biodegradation of acetamiprid by Pseudoxanthomonas sp. AAP-7 isolated from a long-term acetamiprid-polluted soil. AB - An AAP-degrading bacterium, AAP-7, was isolated from AAP-polluted soil. AAP-7 was identified as Pseudoxanthomonas sp. on the basis of the comparative analysis of 16S rDNA sequences. The strain was able to transformate more than 80% AAP by means of co-metabolism and degraded AAP via hydrolysis or demethylation to form (E)-3-(((6-chloropyridin-3yl)methyl)(methyl)amino)acrylonitrile and N-((6 chloropyridin-3yl)methyl)-N-methylprop-1-en-2-amine, both of which transformed into ultimate product, which was 1-(6-chloropyridin-3yl)-N-methylmethanamine. A novel degradation pathway was proposed based on these metabolites. AAP could be transformed with a maximum specific degradation rate, half-saturation constant and inhibit constant of 1.775/36 h, 175.3 mg L(-1), and 396.5 mg L(-1), respectively, which proved that the degradation rate of AAP could be restrained at high AAP concentration. This paper highlights a significant potential use of co-metabolic cultures of microbial cells for the cleanup of AAP-contaminated soil. PMID- 24177160 TI - Fatty acid ethyl esters production in aqueous phase by the oleaginous yeast Rhodosporidium toruloides. AB - Fatty acid ethyl esters (FAEEs) are attractive biofuel molecules. Conventional FAEEs production process uses triglycerides and ethanol as feedstocks and is sensitive to water contents. In this work, we show that the oleaginous yeast Rhodosporidium toruloides cells are capable of converting lipids into FAEEs intracellularly in aqueous phase. Up to 73% of cellular neutral glycerides could be converted into FAEEs when lipid-rich cells were incubated for 84 h at 35 degrees C, pH 6.0 in a broth containing 10 vol% ethanol. It was found that neutral glycerides were first hydrolyzed to free fatty acids followed by esterification and that lipid droplets played important roles in the process. This new process provides a novel opportunity for integration of microbial lipid production technology with bioethanol fermentation for more efficient production of drop-in biofuels from renewable resources. PMID- 24177161 TI - Electrosorption driven by microbial fuel cells to remove phenol without external power supply. AB - This work studied the operating parameters (pH, electrolyte concentration, initial phenol concentration, MFCs connection numbers and mode), adsorption isotherms and kinetics of a novel electrosorption driven by microbial fuel cells (MFC-Sorption) to remove phenol without external electric grid energy supply. It proved that high electrolyte concentration and low solution pH promoted the performance of phenol removal. 3 MFCs connections in series achieved a adsorption capacity of 1.76 mmol/g, which was much higher than that in parallel connection (1.46 mmol/g). Well fitted with Langmuir isotherm, the maximum adsorption capacity by MFC-Sorption and electrosorption was observed 48% and 65% higher than that by conventional adsorption. The phenol removal by MFC-Sorption was supposed to be more suitable for a pseudo-second-order kinetics, and with the increase of initial phenol concentration from 20 mg/L to 300 mg/L, the initial adsorption rate increased 26.99-fold. It concluded that the MFC-Sorption system could cost effectively remove pollutant of phenol. PMID- 24177162 TI - Osmotic membrane bioreactor for wastewater treatment and the effect of salt accumulation on system performance and microbial community dynamics. AB - An osmotic membrane bioreactor was developed for wastewater treatment. The effects of salt accumulation on system performance and microbial community dynamics were investigated. Evident deterioration of biological activity, especially nitrification, was observed, which resulted in significant accumulation of organic matter and NH4(+)-N within the bioreactor. Arising from the elevation of salinity, almost all the dominant species was taken over by high salt-tolerant species. Significant succession among different species of Nitromonas was observed for ammonia-oxidizing bacteria. For nitrite-oxidizing bacteria, Nitrospira was not evidently affected, whereas Nitrobacter was eliminated from the system. Salt accumulation also caused significant shifts in denitrifying bacterial community from alpha- to gamma-Proteobacteria members. Overall, the microbial community adapted to the elevated salinity conditions and brought about a rapid recovery of the biological activity. Membrane fouling occurred but was insignificant. Biofouling and inorganic scaling coexisted, with magnesium/calcium phosphate/carbonate compounds identified as the inorganic foulants. PMID- 24177163 TI - Characterization of a new oxygen-insensitive azoreductase from Brevibacillus laterosporus TISTR1911: toward dye decolorization using a packed-bed metal affinity reactor. AB - This study reports the identification of a new bacterial azoreductase from Brevibacillus laterosporus TISTR1911, its heterologous production in Escherichia coli, the biochemical characterization and immobilization for use in dye biodegradation processes. The recombinant azoreductase (BrAzo) is a monomeric FMN oxygen-insensitive enzyme with a molecular mass of 23 kDa showing a broad specificity for the reduction of synthetic azo dyes. Double hexahistidine-tagged BrAzo was immobilized onto a nickel chelating column and methyl orange was used to assess its degradation potential using a packed-bed reactor. The dye degradation is described by an exponential model in a downstream batchwise continuous flow mode operated with recycling. The complete degradation of methyl orange (170 MUM at 600 mL/h) was achieved in 3 h and continued over 9 cycles. Coupling the immobilized BrAzo with glucose dehydrogenase for NADH regeneration yielded a shorter 1.5 h-degradation period that was maintained throughout 16 cycles. PMID- 24177164 TI - Simultaneous nitritation and p-nitrophenol removal using aerobic granular biomass in a continuous airlift reactor. AB - The chemical and petrochemical industries produce wastewaters containing ammonium and phenolic compounds. Biological treatment of these wastewaters could be problematic due to the possible inhibitory effects exerted by phenolic compounds. The feasibility of performing simultaneous nitritation and p-nitrophenol (PNP) biodegradation using a continuous aerobic granular reactor was evaluated. A nitrifying granular sludge was bioaugmented with a PNP-degrading floccular sludge, while PNP was progressively added to the feed containing a high ammonium concentration. Nitritation was sustained throughout the operational period with ca. 85% of ammonium oxidation and less than 0.3% of nitrate in the effluent. PNP biodegradation was unstable and the oxygen limiting condition was found to be the main explanation for this unsteadiness. An increase in dissolved oxygen concentration from 2.0 to 4.5 mg O2 L(-1) significantly enhanced PNP removal, achieving total elimination. Acinetobacter genus and ammonia-oxidising bacteria were the predominant bacteria species in the granular biomass. PMID- 24177165 TI - Bioaugmentation of biological contact oxidation reactor (BCOR) with phenol degrading bacteria for coal gasification wastewater (CGW) treatment. AB - This study was conducted to evaluate the performance of the biological contact oxidation reactor (BCOR) treating coal gasification wastewater (CGW) after augmented with phenol degrading bacteria (PDB). The PDB were isolated with phenol, 4-methyl phenol, 3,5-dimethyl phenol and resorcinol as carbon resources. Much of the refractory phenolic compounds were converted into easily biodegradable compounds in spite of low TOC removal. The bioaugmentation with PDB significantly enhanced the removal of COD, total phenols (TP) and NH3-N, with efficiencies from 58% to 78%, 66% to 80%, and 5% to 25%, respectively. In addition, the augmented BCOR exhibited strong recovery capability in TP and COD removal while recovery of NH3-N removal needed longer time. Microbial community analysis revealed that the PDB presented as dominant populations in the bacteria consortia, which in turn determined the overall performance of the system. PMID- 24177166 TI - Atomically perfect torn graphene edges and their reversible reconstruction. AB - The atomic structure of graphene edges is critical in determining the electrical, magnetic and chemical properties of truncated graphene structures, notably nanoribbons. Unfortunately, graphene edges are typically far from ideal and suffer from atomic-scale defects, structural distortion and unintended chemical functionalization, leading to unpredictable properties. Here we report that graphene edges fabricated by electron beam-initiated mechanical rupture or tearing in high vacuum are clean and largely atomically perfect, oriented in either the armchair or zigzag direction. We demonstrate, via aberration-corrected transmission electron microscopy, reversible and extended pentagon-heptagon (5-7) reconstruction at zigzag edges, and explore experimentally and theoretically the dynamics of the transitions between configuration states. Good theoretical experimental agreement is found for the flipping rates between 5-7 and 6-6 zigzag edge states. Our study demonstrates that simple ripping is remarkably effective in producing atomically clean, ideal terminations, thus providing a valuable tool for realizing atomically tailored graphene and facilitating meaningful experimental study. PMID- 24177167 TI - TAp63 regulates oncogenic miR-155 to mediate migration and tumour growth. AB - miR-155 is an oncogenic microRNA which is upregulated in many solid cancers. The targets of miR-155 are well established , with over 100 confirmed mRNA targets. However, the regulation of miR-155 and the basis of its upregulation in cancer is not well understood. We have previously shown that miR-155 is regulated by p63, and here we investigate the role of the major p63 isoforms TAp63 and DeltaNp63 in this regulation. When the TAp63 isoform was knocked down, or exogenously overexpressed, miR-155 levels were elevated in response to TAp63 knockdown or reduced in response to TAp63 overexpression. The DeltaNp63 isoform is shown to directly bind to the p63 response element on the miR-155 host gene, and this binding is enriched when TAp63 is knocked down. This could indicate that TAp63 prevents DeltaNp63 from binding to the miR-155 host gene. The knockdown of TAp63, and the subsequent elevation of miR-155, enhances migration and tumour growth similar to that seen when directly overexpressing miR-155. The migratory phenotype is abrogated when miR-155 is inhibited, indicating that miR-155 is responsible for the phenotypic effect of TAp63 knockdown. PMID- 24177168 TI - The GG genotype of the -1125G/T polymorphism in the EPO gene protects against the development of Graves' disease. PMID- 24177169 TI - Low gene expression levels of activating receptors of natural killer cells (NKG2E and CD94) in patients with fulminant type 1 diabetes. AB - Fulminant type 1 diabetes is an independent subtype of type 1 diabetes characterized by extremely rapid onset and absence of islet-related autoantibodies. However, detailed pathophysiology of this subtype is poorly understood. In this study, a comprehensive approach was applied to understand the pathogenesis of fulminant type 1 diabetes. We determined the genes that were differentially expressed in fulminant type 1 diabetes compared with type 1A diabetes and healthy control, using gene expression microarray in peripheral blood cells. Using volcano plot analysis, we found reduced expression of killer cell lectin-like receptor subfamily C, member 3 (KLRC3) which encodes NKG2E, a natural killer (NK) cell activating receptor, in fulminant type 1 diabetes, compared with healthy controls. This difference was confirmed by real-time RT-PCR among NK-enriched cells. The expression of KLRD1 (CD94), which forms heterodimer with NKG2E (KLRC3), was also reduced in NK-enriched cells in fulminant type 1 diabetes. Furthermore, flow cytometry showed significantly lower proportion of NK cells among peripheral blood mononuclear cells (PBMCs) in fulminant type 1 diabetes than in healthy controls. In patients with fulminant type 1 diabetes, the relative proportion of NK cells correlated significantly with the time period between onset of fever to the appearance of hyperglycemic-related symptoms. We conclude the presence of reduced NK activating receptor gene expression and low proportion of NK cells in fulminant type 1 diabetes. PMID- 24177171 TI - Nanoparticle amplification via photothermal unveiling of cryptic collagen binding sites. AB - The success of nanoparticle-based cancer therapies ultimately depends on their ability to selectively and efficiently accumulate in regions of disease. Outfitting nanoparticles to actively target tumor-specific markers has improved specificity, yet it remains a challenge to amass adequate therapy in a selective manner. To help address this challenge, we have developed a mechanism of nanoparticle amplification based on stigmergic (environment-modifying) signalling, in which a "Signalling" population of gold nanorods induces localized unveiling of cryptic collagen epitopes, which are in turn targeted by "Responding" nanoparticles bearing gelatin-binding fibronectin fragments. We demonstrate that this two-particle system results in significantly increased, selective recruitment of responding particles. Such amplification strategies have the potential to overcome limitations associated with single-particle targeting by leveraging the capacity of nanoparticles to interact with their environment to create abundant new binding motifs. PMID- 24177170 TI - The influence of four dual-cure resin cements and surface treatment selection to bond strength of fiber post. AB - In this study, we evaluate the influence of post surface pre-treatments on the bond strength of four different cements to glass fiber posts. Eighty extracted human maxillary central incisors and canines were endodontically treated and standardized post spaces were prepared. Four post pre-treatments were tested: (i) no pre-treatment (NS, control), (ii) sandblasting (SA), (iii) silanization (SI) and (iv) sandblasting followed by silanization (SS). Per pre-treatment, four dual cure resin cements were used for luting posts: DMG LUXACORE Smartmix Dual, Multilink Automix, RelyX Unicem and Panavia F2.0. All the specimens were subjected to micro push-out test. Two-way analysis of variance and Tukey post hoc tests were performed (alpha=0.05) to analyze the data. Bond strength was significantly affected by the type of resin cement, and bond strengths of RelyX Unicem and Panavia F2.0 to the fiber posts were significantly higher than the other cement groups. Sandblasting significantly increased the bond strength of DMG group to the fiber posts. PMID- 24177172 TI - Domain-confined catalytic soot combustion over Co3O4 anchored on a TiO2 nanotube array catalyst prepared by mercaptoacetic acid induced surface-grafting. AB - Herein, we introduce a specially designed domain-confined macroporous catalyst, namely, the Co3O4 nanocrystals anchored on a TiO2 nanotube array catalyst, which was synthesized by using the mercaptoacetic acid induced surface-grafting method. This catalyst exhibits much better performance for catalytic soot combustion than the conventional TiO2 powder supported one in gravitational contact mode (GMC). PMID- 24177173 TI - Contaminating levels of zinc found in commonly-used labware and buffers affect glycine receptor currents. AB - Zinc is an allosteric modulator of glycine receptor function, enhancing the effects of glycine at nM to low MUM concentrations, and inhibiting its effects at higher concentrations. Because of zinc's high potency at the glycine receptor, there exists a possibility that effects attributed solely to exogenously-applied glycine in fact contain an undetected contribution of zinc acting as an allosteric modulator. We found that glycine solutions made up in standard buffers and using deionized distilled water produced effects that could be decreased by the zinc chelator tricine. This phenomenon was observed in three different vials tested and persisted even if vials were extensively washed, suggesting the zinc was probably present in the buffer constituents. In addition, polystyrene, but not glass, pipets bore a contaminant that enhanced glycine receptor function and that could also be antagonized by tricine. Our findings suggest that without checking for this effect using a chelator such as tricine, one cannot assume that responses elicited by glycine applied alone are not necessarily also partially due to some level of allosteric modulation by zinc. PMID- 24177174 TI - Increase in Alzheimer's related markers preceeds memory disturbances: studies in vasopressin-deficient Brattleboro rat. AB - Alzheimer's disease (AD) is the most common form of dementia in the elderly. For more effective therapy early diagnostic markers could be beneficial. Therefore we compared one year old rats with adults and examined if changes in possible brain markers of AD preceeded memory decline. We also tested if vasopressin-deficient animals were useful model of AD as vasopressin has well known positive effect on memory and AD patient has decreased vasopressin production. We compared adult (3 month) and old (12 month), normal and vasopressin-deficient Brattleboro rats. To receive a comprehensive picture about their memory we examined their social discrimination, object discrimination and conditioned learning abilities (shuttle box). Amyloid precursor protein (APP), mitogen-activated protein kinase 1 (MAPK1), beta-actin and tryptophan 2,3-dioxygenase 2 (TDO2) mRNA levels was measured by quantitative PCR. There was no difference between the memory of adult and aged groups. The vasopressin-deficient rats at both ages showed a weaker performance in the course of social and object discrimination tests and a higher escape failure during the shuttle box experiment. The brain marker mRNAs of the elder animals were higher than the levels of the adults, but the absence of vasopressin had no influence on them. Thus, the one year old rats showed elevated levels of AD-related markers, but memory deficits were observable only in vasopressin deficient animals. Vasopressin does not seem to have pathogenic role in AD. Changes in the studied markers might predict later symptoms, although further studies are required for confirmation. PMID- 24177175 TI - Use of research questionnaires in the NHS Bowel Cancer Screening Programme in England: impact on screening uptake. AB - BACKGROUND: The NHS Bowel Cancer Screening Programme in England offers biennial screening to those aged 60-74 using a faecal occult blood test (FOBt) sent by post. Data from this national clinical programme can also be used for research. Awareness of the impact of such studies on screening participation is important. AIMS: To investigate the effect on screening uptake of adding a research questionnaire to the postal screening invitation. METHODS: People invited for screening in 2008-10 in two areas of England were randomized to receive or not to receive an additional research study questionnaire, consent form and study information, either with their test kit or 2-3 days later. Uptake of screening was examined in relation to study mailings. RESULTS: Among 11,579 people invited for screening by the Midlands and North West Bowel Cancer Screening Hub, screening uptake was significantly lower in those who received study documents with their FOBt kit than in those who did not (48.6% vs 53.5% respectively: p < 0.001). The reduction in uptake was similar in men and women, and was greater in people living in more deprived areas. Among a further 36,195 people invited for screening by the Midlands and North West and Southern Hubs, sending study documents by separate mailing 2-3 days after the FOBt kit did not affect screening uptake (uptake with and without additional study mailing: Midlands and North West, 56.7% and 56.2% respectively, p = 0.6; Southern, 52.0% and 51.4% respectively, p = 0.5). CONCLUSIONS: Researchers planning studies that include contact with potential participants within the NHS Bowel Cancer and similar screening programmes should be aware of the potential impact on uptake. PMID- 24177176 TI - Model-Driven Safety Analysis of Closed-Loop Medical Systems. AB - In modern hospitals, patients are treated using a wide array of medical devices that are increasingly interacting with each other over the network, thus offering a perfect example of a cyber-physical system. We study the safety of a medical device system for the physiologic closed-loop control of drug infusion. The main contribution of the paper is the verification approach for the safety properties of closed-loop medical device systems. We demonstrate, using a case study, that the approach can be applied to a system of clinical importance. Our method combines simulation-based analysis of a detailed model of the system that contains continuous patient dynamics with model checking of a more abstract timed automata model. We show that the relationship between the two models preserves the crucial aspect of the timing behavior that ensures the conservativeness of the safety analysis. We also describe system design that can provide open-loop safety under network failure. PMID- 24177177 TI - Loss of androgen receptor expression promotes a stem-like cell phenotype in prostate cancer through STAT3 signaling. AB - Androgen receptor (AR) signaling is important for prostate cancer progression. However, androgen-deprivation and/or AR targeting-based therapies often lead to resistance. Here, we demonstrate that loss of AR expression results in STAT3 activation in prostate cancer cells. AR downregulation further leads to development of prostate cancer stem-like cells (CSC), which requires STAT3. In human prostate tumor tissues, elevated cancer stem-like cell markers coincide with those cells exhibiting high STAT3 activity and low AR expression. AR downregulation-induced STAT3 activation is mediated through increased interleukin (IL)-6 expression. Treating mice with soluble IL-6 receptor fusion protein or silencing STAT3 in tumor cells significantly reduced prostate tumor growth and CSCs. Together, these findings indicate an opposing role of AR and STAT3 in prostate CSC development. PMID- 24177178 TI - Neuregulin autocrine signaling promotes self-renewal of breast tumor-initiating cells by triggering HER2/HER3 activation. AB - Currently, only patients with HER2-positive tumors are candidates for HER2 targeted therapies. However, recent clinical observations suggest that the survival of patients with HER2-low breast cancers, who lack HER2 amplification, may benefit from adjuvant therapy that targets HER2. In this study, we explored a mechanism through which these benefits may be obtained. Prompted by the hypothesis that HER2/HER3 signaling in breast tumor-initiating cells (TIC) promotes self-renewal and survival, we obtained evidence that neuregulin 1 (NRG1) produced by TICs promotes their proliferation and self-renewal in HER2-low tumors, including in triple-negative breast tumors. Pharmacologic inhibition of EGFR, HER2, or both receptors reduced breast TIC survival and self-renewal in vitro and in vivo and increased TIC sensitivity to ionizing radiation. Through a tissue microarray analysis, we found that NRG1 expression and associated HER2 activation occurred in a subset of HER2-low breast cancers. Our results offer an explanation for why HER2 inhibition blocks the growth of HER2-low breast tumors. Moreover, they argue that dual inhibition of EGFR and HER2 may offer a useful therapeutic strategy to target TICs in these tumors. In generating a mechanistic rationale to apply HER2-targeting therapies in patients with HER2-low tumors, this work shows why these therapies could benefit a considerably larger number of patients with breast cancer than they currently reach. PMID- 24177179 TI - HTLV-1 bZIP factor suppresses apoptosis by attenuating the function of FoxO3a and altering its localization. AB - As the infectious agent causing human adult T-cell leukemia (ATL), the human T cell leukemia virus type 1 (HTLV-1) virus spreads in vivo primarily by cell-to cell transmission. However, the factors that determine its transmission efficiency are not fully understood. The viral genome encodes the HTLV-1 bZIP factor (HBZ), which is expressed in all ATL cases and is known to promote T-cell proliferation. In this study, we investigated the hypothesis that HBZ also influences the survival of T cells. Through analyzing the transcriptional profile of HBZ-expressing cells, we learned that HBZ suppressed transcription of the proapoptotic gene Bim (Bcl2l11) and that HBZ-expressing cells were resistant to activation-induced apoptosis. Mechanistic investigations into how HBZ suppresses Bim expression revealed that HBZ perturbs the localization and function of FoxO3a, a critical transcriptional activator of the genes encoding Bim and also Fas ligand (FasL). By interacting with FoxO3a, HBZ not only attenuated DNA binding by FoxO3a but also sequestered the inactive form of FoxO3a in the nucleus. In a similar manner, HBZ also inhibited FasL transcription induced by T cell activation. Further study of ATL cells identified other Bim perturbations by HBZ, including at the level of epigenetic alteration, histone modification in the promoter region of the Bim gene. Collectively, our results indicated that HBZ impairs transcription of the Bim and FasL genes by disrupting FoxO3a function, broadening understanding of how HBZ acts to promote proliferation of HTLV-1 infected T cells by blocking their apoptosis. PMID- 24177180 TI - OX40 is a potent immune-stimulating target in late-stage cancer patients. AB - OX40 is a potent costimulatory receptor that can potentiate T-cell receptor signaling on the surface of T lymphocytes, leading to their activation by a specifically recognized antigen. In particular, OX40 engagement by ligands present on dendritic cells dramatically increases the proliferation, effector function, and survival of T cells. Preclinical studies have shown that OX40 agonists increase antitumor immunity and improve tumor-free survival. In this study, we performed a phase I clinical trial using a mouse monoclonal antibody (mAb) that agonizes human OX40 signaling in patients with advanced cancer. Patients treated with one course of the anti-OX40 mAb showed an acceptable toxicity profile and regression of at least one metastatic lesion in 12 of 30 patients. Mechanistically, this treatment increased T and B cell responses to reporter antigen immunizations, led to preferential upregulation of OX40 on CD4(+) FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, and increased the antitumor reactivity of T and B cells in patients with melanoma. Our findings clinically validate OX40 as a potent immune-stimulating target for treatment in patients with cancer, providing a generalizable tool to favorably influence the antitumor properties of circulating T cells, B cells, and intratumoral regulatory T cells. PMID- 24177183 TI - Out of Eurasia, a great primate evolutionary bottleneck? PMID- 24177181 TI - Genetic ancestry and risk of mortality among U.S. Latinas with breast cancer. AB - Multiple studies have reported that Latina women in the United States are diagnosed with breast cancer at more advanced stages and have poorer survival than non-Latina White women. However, Latinas are a heterogeneous group with individuals having different proportions of European, Indigenous American, and African genetic ancestry. In this study, we evaluated the association between genetic ancestry and survival after breast cancer diagnosis among 899 Latina women from the San Francisco Bay area. Genetic ancestry was estimated from single nucleotide polymorphisms from an Affymetrix 6.0 array and we used Cox proportional hazards models to evaluate the association between genetic ancestry and breast cancer-specific mortality (tests were two-sided). Women were followed for an average of 9 years during which 75 died from breast cancer. Our results showed that Individuals with higher Indigenous American ancestry had increased risk of breast cancer-specific mortality [HR: 1.57 per 25% increase in Indigenous American ancestry; 95% confidence interval (CI): 1.08-2.29]. Adjustment for demographic factors, tumor characteristics, and some treatment information did not explain the observed association (HR: 1.75; 95%CI, 1.12-2.74). In an analysis in which ancestry was dichotomized, the hazard of mortality showed a two-fold increase when comparing women with less than 50% Indigenous American ancestry to women with 50% or more [HR, 1.89, 95%CI, 1.10-3.24]. This was also reflected by Kaplan-Meier survival estimates (P for log-rank test of 0.003). Overall, results suggest that genetic factors and/or unmeasured differences in treatment or access to care should be further explored to understand and reduce ethnic disparities in breast cancer outcomes. PMID- 24177186 TI - Origin of anomalous magnetite properties in crystallographic matched heterostructures: Fe3O4(111)/MgAl2O4(111). AB - Magnetite films grown on crystallographically matched substrates such as MgAl2O4 are not expected to show anomalous properties such as negative magnetoresistance and high saturation fields. By atomic resolution imaging using scanning transmission electron microscopy we show direct evidence of anti-phase domain boundaries (APB) present in these heterostructures. Experimentally identified 1/4<101> shifts determine the atomic structure of the observed APBs. The dominant non-bulk superexchange interactions are between 180 degrees octahedral Fe/O/octahedral-Fe sites which provide strong antiferromagnetic coupling across the defect interface resulting in non-bulk magnetic and magnetotransport properties. PMID- 24177185 TI - Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa. AB - Bitter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. To better understand the genetic architecture and patterns of phenotypic variability of bitter taste perception, we sequenced a 996 bp region, encompassing the coding exon of TAS2R16, a bitter taste receptor gene, in 595 individuals from 74 African populations and in 94 non-Africans from 11 populations. We also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from Central and East Africa. In addition, we characterized TAS2R16 mutants in vitro to investigate the effects of polymorphic loci identified at this locus on receptor function. Here, we report striking signatures of positive selection, including significant Fay and Wu's H statistics predominantly in East Africa, indicating strong local adaptation and greater genetic structure among African populations than expected under neutrality. Furthermore, we observed a "star-like" phylogeny for haplotypes with the derived allele at polymorphic site 516 associated with increased bitter taste perception that is consistent with a model of selection for "high-sensitivity" variation. In contrast, haplotypes carrying the "low sensitivity" ancestral allele at site 516 showed evidence of strong purifying selection. We also demonstrated, for the first time, the functional effect of nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse Africans and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression in vitro, suggesting that one main polymorphism at TAS2R16 influences salicin recognition. Additionally, we detected geographic differences in levels of bitter taste perception in Africa not previously reported and infer an East African origin for high salicin sensitivity in human populations. PMID- 24177188 TI - Exploring cerebral networks in cluster headache: insights and perspectives. PMID- 24177187 TI - Phytosphingosine derivatives ameliorate skin inflammation by inhibiting NF-kappaB and JAK/STAT signaling in keratinocytes and mice. AB - Phytosphingosine is abundant in plants and fungi and is found in mammalian epidermis, including the stratum corneum. Phytosphingosine and its derivatives N acetyl phytosphingosine and tetraacetyl phytosphingosine are part of the natural defense system of the body. However, these molecules exhibit strong toxicities at high concentrations. We synthesized phytosphingosine derivatives, mYG-II-6 ((Z)-4 oxo-4-(((2S,3S,4R)-1,3,4-trihydroxyoctadecan-2-yl)amino)but-2-enoic acid) and fYG II-6 ((E)-4-oxo-4-(((2S,3S,4R)-1,3,4-trihydroxyoctadecan-2-yl)amino)but-2-enoic acid), to increase efficacy and decrease toxicity, and the biological activities of the derivatives in the inflammatory response were examined. Both YG-II-6 compounds effectively suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA) induced inflammatory skin damage and inflammatory response in a mouse model. In addition, topical application of fYG-II-6 suppressed ear swelling and psoriasiform dermatitis in the ears of IL-23-injected mice. Anti-inflammatory and antipsoriatic activities of the phytosphingosine derivatives inhibited NF-kappaB, JAK/signal transducer and activator of transcription (JAK/STAT), and mitogen activated protein kinase (MAPK) signaling. Finally, the YG-II-6 compounds induced programmed cell death in keratinocytes and mouse skin and were less toxic than phytosphingosine. Our study demonstrated that the phytosphingosine-derived YG-II 6 compounds have much stronger biological potencies than the lead compounds. The YG-II-6 compounds ameliorated inflammatory skin damage. Thus, YG-II-6 compounds are potential topical agents for treating chronic inflammatory skin diseases, such as psoriasis. PMID- 24177189 TI - Hyperreflective foci in outer retina predictive of photoreceptor damage and poor vision after vitrectomy for diabetic macular edema. AB - PURPOSE: To investigate the correlation between visual outcomes and preoperative hyperreflective foci in the outer retinal layers seen on spectral domain optical coherence tomography images in eyes that underwent vitrectomy for diabetic macular edema. METHODS: We retrospectively reviewed 32 consecutive eyes that underwent vitrectomy for diabetic macular edema. Ten eyes had accumulated or many hyperreflective foci in the outer retinal layers preoperatively; 22 eyes did not have the pathology. The logarithm of the minimum angle of resolution and the junction between inner and outer segments were studied in the groups. RESULTS: Logarithm of the minimum angle of resolution was significantly better in eyes without hyperreflective foci than in those with hyperreflective foci at 3 months and 6 months, and the last visit (P = 0.029, 0.010, and <0.001, respectively) compared with no differences at the baseline. Visual improvement was greater in eyes with no hyperreflective foci at the same time points. Seven eyes with hyperreflective foci had no junction between inner and outer segments at the final visit, whereas only 4 eyes with no foci had no junction between inner and outer segments (P = 0.004). However, the foveal thickness did not differ between the groups at any time. CONCLUSION: Preoperative hyperreflective foci in the outer retinal layers detected by spectral domain optical coherence tomography might predict the photoreceptor damage and a poorer prognosis after vitrectomy for diabetic macular edema. PMID- 24177190 TI - An improved optical coherence tomography-derived fundus projection image for drusen visualization. AB - PURPOSE: To develop and evaluate an improved method of generating en face fundus images from three-dimensional optical coherence tomography images which enhances the visualization of drusen. METHODS: We describe a novel approach, the restricted summed-voxel projection (RSVP), to generate en face projection images of the retinal surface combined with an image processing method to enhance drusen visualization. The RSVP approach is an automated method that restricts the projection to the retinal pigment epithelium layer neighborhood. Additionally, drusen visualization is improved through an image processing technique that fills drusen with bright pixels. The choroid layer is also excluded when creating the RSVP to eliminate bright pixels beneath drusen that could be confused with drusen when geographic atrophy is present. The RSVP method was evaluated in 46 patients and 3-dimensional optical coherence tomography data sets were obtained from 8 patients, for which 2 readers independently identified drusen as the gold standard. The mean drusen overlap ratio was used as the metric to determine the accuracy of visualization of the RSVP method when compared with the conventional summed-voxel projection technique. RESULTS: Comparative results demonstrate that the RSVP method was more effective than the conventional summed-voxel projection in displaying drusen and retinal vessels, and was more useful in detecting drusen. The mean drusen overlap ratios based on the conventional summed-voxel projection method and the RSVP method were 2.1% and 89.3%, respectively. CONCLUSION: The RSVP method was more effective for drusen visualization than the conventional summed-voxel projection method, and it may be useful for macular assessment in patients with nonexudative age-related macular degeneration. PMID- 24177191 TI - Synergy effects of herb extracts: pharmacokinetics and pharmacodynamic basis. AB - Herbal medicine, especially traditional Chinese medicine and Ayurvedic medicine have played and still play an important role in fighting against various diseases. Emerging clinical studies regarding traditional Chinese medicine have provided convincing evidence for the first time to gain credibility and reputation outside China. Although synergistic therapeutic actions of herbal ingredients have been frequently reported, few reports have offered clear underlying mechanisms. This might be the main reason for the conflicting views with respect to the therapeutic efficacy of medicinal herbs. Therefore, this paper reviews the herb synergisms reported in the recent literature and discusses thoroughly the mechanisms underlying synergistic actions of herbal ingredients. The authors conducted an electronic literature search to detect articles published mainly in the last five years. Articles were included if they pertained to synergy research of ethnomedicines or the active compounds derived from them, included verification of synergy effects using modern analytical tools and molecular-biological methods. Results have revealed that the multi-component nature of medicinal herbs makes them particularly suitable for treating complex diseases and offers great potential for exhibiting synergistic actions. The mechanisms underlying synergistic therapeutic actions of herb medicines are (1): different agents may regulate either the same or different target in various pathways, and therefore cooperate in an agonistic, synergistic way; (2): regulate the enzymes and transporters that are involved in hepatic and intestinal metabolism to improve oral drug bioavailability; (3): overcome the drug resistance mechanisms of microbial and cancer cells; and (4): eliminate the adverse effects and enhance pharmacological potency of agents by "processing" or by drug-drug interaction. The exploration of synergistic mechanisms of herbal ingredients will not only help researchers to discover new phytomedicines or drug combinations but also help to avoid the possible negative synergy. Further clinical research is required for verifying these reported drug combinations and discovered synergistic mechanisms. PMID- 24177193 TI - Bio-inspired in situ growth of monolayer silver nanoparticles on graphene oxide paper as multifunctional substrate. AB - In this study, we report a facile bio-inspired method for large-scale preparation of highly dispersed Ag nanoparticles (NPs) on the surface of flexible reduced graphene oxide (rGO) paper with using dopamine (DA) both as a reductant and a surface modifier. Through the self-polymerization of dopamine, free-standing GO paper can be simultaneously reduced and modified with following in situ growth of monolayer Ag NPs on such a substrate. The spherical Ag NPs with an average diameter of 80 nm have a narrow size distribution and tunable cover density. Such a flexible rGO/Ag hybrid paper presents enhanced antibacterial activity against E. coli and a high active and sensitive SERS response toward Rhodamine 6G (R6G) molecules. The detection signals can be obtained while the R6G concentration is as low as to 10(-8) M. This work provides a simple strategy for large-scale fabrication of monolayer Ag NPs on flexible rGO paper as a portable antibacterial substrate and a potential SERS substrate for molecular detection applications. PMID- 24177192 TI - HoxA9 regulated Bcl-2 expression mediates survival of myeloid progenitors and the severity of HoxA9-dependent leukemia. AB - Deregulated expression of Hox genes such as HoxA9 is associated with development of myeloproliferative disorders and leukemia and indicates a poor prognosis. To investigate the molecular mechanisms by which HoxA9 promotes immortalization of hematopoietic cells, we generated growth factor dependent myeloid cells in which HoxA9 expression is regulated by administration of 4-hydroxy-tamoxifen. Maintenance of HoxA9 overexpression is required for continued cell survival and proliferation, even in the presence of growth factors. We show for the first time that maintenance of Bcl-2 expression is critical for HoxA9-dependent immortalization and influences the latency of HoxA9-dependent leukemia. Hematopoietic cells lacking Bcl-2 were not immortalized by HoxA9 in vitro. Furthermore, deletion of Bcl-2 delayed the onset and reduced the severity of HoxA9/Meis1 and MLL-AF9 leukemias. This is the first description of a molecular link between HoxA9 and the regulation of Bcl-2 family members in acute myeloid leukemia. PMID- 24177194 TI - Muscle function and hydrodynamics limit power and speed in swimming frogs. AB - Studies of the muscle force-velocity relationship and its derived n-shaped power velocity curve offer important insights into muscular limits of performance. Given the power is maximal at 1/3 V(max), geometric scaling of muscle force coupled with fluid drag force implies that this optimal muscle-shortening velocity for power cannot be maintained across the natural body-size range. Instead, muscle velocity may decrease with increasing body size, conferring a similar n-shaped power curve with body size. Here we examine swimming speed and muscle function in the aquatic frog Xenopus laevis. Swimming speed shows an n shaped scaling relationship, peaking at 47.35 g. Further, in vitro muscle function of the ankle extensor plantaris longus also shows an optimal body mass for muscle power output (47.27 g), reflecting that of swimming speed. These findings suggest that in drag-based aquatic systems, muscle-environment interactions vary with body size, limiting both the muscle's potential to produce power and the swimming speed. PMID- 24177195 TI - Blood spot versus plasma chitotriosidase: a systematic clinical comparison. AB - OBJECTIVES: This study aimed to evaluate the agreement between blood spot and plasma chitotriosidase using the economic substrate 4-methylumbelliferyl-beta-D N,N',N"-triacetylchitotrioside, and to investigate the utility of the blood spot assay for the wide scale screening for lysosomal storage disorders among the clinically suspected. DESIGN AND METHODS: Blinded blood spot samples were compared with the corresponding plasma levels in 199 children (56 with confirmed diagnoses of ten different lysosomal storage disorders, 73 normal controls and 70 pathological controls). Several performance criteria (limit of detection, linearity, within-run and day-to-day precision and sample stability) were also evaluated. RESULTS: Plasma assay performed better by most criteria; however, blood spot performance was quite satisfactory. Quantitative values of the two methods can't be used interchangeably based on their 95% limits of agreement. Diagnostic sensitivity and specificity derived from ROC curves were 75.0 and 85.3% for the plasma assay and 71.4 and 79.0% for the blood spot assay, respectively. Cohen's kappa was 0.72 (95% CI: 0.616-0.821) denoting a good categorical agreement between the two methods. CONCLUSION: The clinical use of blood spot chitotriosidase for the screening of lysosomal storage disorders can be quite practical, provided proper cut-off values are determined for each lab. PMID- 24177196 TI - Analysis of synovial inflammatory markers to differ infectious from gouty arthritis. AB - OBJECTIVES: Septic and gouty arthritis show the same clinical symptoms, but septic arthritis is an orthopedic emergency and needs immediate surgical intervention, whereas a systemic drug therapy is needed in acute gouty arthritis. The aim of this study was to investigate which inflammatory markers allow an accurate differentiation of septic and gouty arthritis. DESIGN AND METHODS: This was a retrospective examination of serum markers (peripheral white blood cells, C reactive Protein and uric acid) and inflammatory markers in the synovial fluid (lactate, glucose, uric acid, lactate dehydrogenase, synovial fluid white blood cell count, total protein, and interleukin-6) in 53 patients with culture verified septic arthritis and 29 with gouty arthritis. Receiver-Operating Characteristic-curves with corresponding Area under the curve (AUC), sensitivity, specificity, likelihood-ratio and interval likelihood-ratios were calculated to define the diagnostic potential of the inflammatory markers. RESULTS: Synovial lactate showed the greatest diagnostic potential (AUC = 0.901, sensitivity = 89.5%, specificity = 77.3%, negative likelihood-ratio = 0.14) followed by synovial glucose (AUC=0.853) and synovial uric acid (AUC = 0.841). CONCLUSIONS: Lactate in the synovial fluid has excellent diagnostic potential to differ septic arthritis from gouty arthritis. Synovial lactate levels above 10 mmol/L almost proofed septic arthritis, lactate levels lower than 4.3 mmol/L make it very unlikely. PMID- 24177197 TI - Clinical use of novel urine and blood based prostate cancer biomarkers: a review. AB - In the era of upcoming techniques for molecular profiling, breakthroughs led to new discoveries in the field of prostate cancer (PCa) biomarkers. Since the early 1990s a tremendous increase in PCa incidence is seen, dedicated to the introduction of prostate specific antigen (PSA) testing. However, due to its lack of specificity many men undergo unnecessary biopsies, resulting in a rising incidence of clinically insignificant PCa. To overcome this drawback, cancer specific biomarkers are needed to identify patients who are at high risk of harbouring PCa and to distinguish patients with aggressive disease from patients with insignificant cancer. The most non-invasive, easy to obtain substrate for biomarker measurement is urine. The most promising markers to date are PCA3 and TMPRSS2-ERG. Both markers demonstrate to have a higher specificity and diagnostic accuracy for PCa outcome compared to serum PSA. This might better predict the presence of PCa and therefore reduce the number of unnecessary biopsies. Combining both markers in a panel might result in an even higher diagnostic accuracy, given the heterogeneity of the disease. In PCa management, circulating tumour cells (CTCs) detected in the blood seem a promising tool to predict treatment response and survival benefit. Although results appear to be encouraging, the biggest challenge about new markers in PCa is to validate them in large clinical trials and subsequently implement these markers into clinical practice. In this review we discuss the clinical usefulness of novel, non invasive tests in PCa management. PMID- 24177199 TI - Characterization of on-target generated tryptic peptides from Giberella zeae conidia spore proteins by means of matrix-assisted laser desorption/ionization mass spectrometry. AB - Traditionally characterization of microbial proteins is performed by a complex sequence of steps with the final step to be either Edman sequencing or mass spectrometry, which generally takes several weeks or months to be complete. In this work, we proposed a strategy for the characterization of tryptic peptides derived from Giberella zeae (anamorph: Fusarium graminearum) proteins in parallel to intact cell mass spectrometry (ICMS) in which no complicated and time consuming steps were needed. Experimentally, after a simple washing treatment of the spores, the aliquots of the intact G. zeae macro conidia spores solution, were deposited two times onto one MALDI (matrix-assisted laser desorption ionization) mass spectrometry (MS) target (two spots). One spot was used for ICMS and the second spot was subject to a brief on-target digestion with bead immobilized or non-immobilized trypsin. Subsequently, one spot was analyzed immediately by MALDI MS in the linear mode (ICMS) whereas the second spot containing the digested material was investigated by MALDI MS in the reflectron mode ("peptide mass fingerprint") followed by protonated peptide selection for MS/MS (post source decay (PSD) fragment ion) analysis. Based on the formed fragment ions of selected tryptic peptides a complete or partial amino acid sequence was generated by manual de novo sequencing. These sequence data were used for homology search for protein identification. Finally four different peptides of varying abundances have been identified successfully allowing the verification that our desorbed/ionized surface compounds were indeed derived from proteins. The presence of three different proteins could be found unambiguously. Interestingly, one of these proteins is belonging to the ribosomal superfamily which indicates that not only surface-associated proteins were digested. This strategy minimized the amount of time and labor required for obtaining deeper information on spore preparations within the nowadays widely used ICMS approach. PMID- 24177200 TI - De novo synthesis of 1-deoxythiosugars. AB - A short and efficient chemical synthesis of biologically potent and novel 1 deoxythiosugars is accomplished. Introduction of sulfur mediated by benzyltriethylammonium tetrathiomolybdate, as a sulfur transfer reagent through nucleophilic double displacement of tosylate in alpha,omega-di-O-tosyl aldonolactones in an intramolecular fashion is the key feature. The subsequent reduction of thiosugar lactones with borohydride exchange resin (BER) offers a number of deoxythiosugars in good overall yield. PMID- 24177201 TI - Combined Lewis acid and Bronsted acid-mediated reactivity of glycosyl trichloroacetimidate donors. AB - Biomimetic conditions for a synthetic glycosylation reaction, inspired by the highly conserved functionality of carbohydrate active enzymes, were explored. At the outset, we sought to generate proof of principle for this approach to developing catalytic systems for glycosylation. However, control reactions and subsequent kinetic studies showed that a stoichiometric, irreversible reaction of the catalyst and glycosyl donor was occurring, with a remarkable rate variance depending upon the structure of the carboxylic acid. It was subsequently found that a combination of Bronsted acid (carboxylic acid) and Lewis acid (MgBr2) was unique in catalyzing the desired glycosylation reaction. Thus, it was concluded that the two acids act synergistically to catalyze the desired transformation. The role of the catalytic components was tested with a number of control reactions and based on these studies a mechanism is proposed herein. PMID- 24177202 TI - Stereospecific generation and analysis of alpha- and beta-hemiacetals of monosaccharides in gas phase. AB - A series of Boc-protected 4-aminobutyl alpha- and beta-glycosides of commonly found neutral monosaccharides were synthesized. The sodium adducted ions of these individual molecules were used in producing corresponding alpha- and beta-anomers of hemiacetal species under collision-induced dissociation (CID) conditions. The Boc group was successfully removed under CID conditions producing 4-aminobutyl glycosides, which were then used as the precursors. An intramolecular attack of the aglyconic nitrogen atom onto C-1 position of aglycon assisted to leave hemiacetal ion species without affecting anomeric configurations. In this manner, stereospecific syntheses of sugar hemiacetals were first achieved in gas phase. The dissociation of sodium cation from a series of these hemiacetals was further studied according to energy-resolved mass spectrometry. In this study, it was found that all the sugar hemiacetals could be distinguished even if they have same m/z values. Furthermore, the order of affinity of Na(+) toward the hemiacetals was determined. PMID- 24177203 TI - Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. AB - BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is a common problem in patients with persistent dyspneic sarcoidosis. The objective of this study was to determine the effect of bosentan therapy on pulmonary arterial hemodynamics in patients with SAPH. METHODS: This 16-week study was a double blind, placebo-controlled trial of either bosentan or placebo in patients with SAPH confirmed by right-sided heart catheterization. Patients were enrolled from multiple academic centers specializing in sarcoidosis care. They were stable on sarcoidosis therapy and were receiving no therapy for pulmonary hypertension. The cohort was randomized two to one to receive bosentan at a maximal dose of 125 mg or placebo bid for 16 weeks. Pulmonary function studies, 6-min walk test, and right-sided heart hemodynamics, including pulmonary artery mean pressure and pulmonary vascular resistance (PVR), were performed before and after 16 weeks of therapy. RESULTS: Thirty-five patients completed 16 weeks of therapy (23 treated with bosentan, 12 with placebo). For those treated with bosentan, repeat hemodynamic studies at 16 weeks demonstrated a significant mean+/-SD fall in PA mean pressure (-4+/-6.6 mm Hg, P=.0105) and PVR (-1.7+/-2.75 Wood units, P=.0104). For the patients treated with placebo, there was no significant change in either PA mean pressure (1+/-3.7 mm Hg, P>.05) or PVR (0.1+/-1.42 Wood units, P>.05). There was no significant change in 6-min walk distance for either group. Two patients treated with bosentan required an increase of supplemental oxygen by >2 L after 16 weeks of therapy. CONCLUSIONS: This study demonstrated that bosentan significantly improved pulmonary hemodynamics in patients with SAPH. TRIAL REGISTRY: ClinicalTrials.gov; No: NCT00581607; URL: www.clinicaltrials.gov. PMID- 24177204 TI - Synthesis, characterization, DNA interaction, antioxidant and anticancer activity studies of ruthenium(II) polypyridyl complexes. AB - Two new Ru(II) polypyridyl complexes [Ru(phen)2(adppz)](ClO4)2 (1) and [Ru(dip)2(adppz)](ClO4)2 (2) have been synthesized and characterized. The DNA binding constants were determined to be 6.54 +/- 0.42 * 10(5) and 7.65 +/- 0.20 * 10(5)M(-1) for complexes 1 and 2. DNA binding experiments indicated that complexes 1 and 2 interact with DNA through intercalative mode. Antioxidant activity shows that the complexes have significant hydroxyl radical scavenging activity. Cytotoxic activities suggest that the complex 2 exhibits higher cytotoxic activity against BEL-7402, MG-63 and SKBR-3 cells than complex 1 under identical conditions. Complexes 1 and 2 can induce apoptosis of BEl-7402 cells. We have identified several cellular mechanisms induced by 1 and 2 in BEL-7402 cells, including the level detection of ROS, activation of procaspase 3, caspase 7, the expression of antiapoptotic proteins Bcl-x, Bcl-2, proapoptotic proteins Bad, Bax, Bid and cell cycle arrest. Thus, complexes 1 and 2 inhibit growth of BEL-7402 cells through induction of apoptotic cell death, enhancement of ROS levels and S-phase and G0/G1 cell cycle arrest. Further investigations have shown that complex 2 induces apoptosis by regulating the expression of Bcl-2 family proteins. PMID- 24177205 TI - The benzophenanthridine alkaloid chelerythrine binds to DNA by intercalation: photophysical aspects and thermodynamic results of iminium versus alkanolamine interaction. AB - The interaction of the natural benzophenanthridine alkaloid chelerythrine with DNA was studied by spectroscopy, viscometry and calorimetry techniques. The absorbance and fluorescence properties of the alkaloid were remarkably modified upon binding to DNA and the interaction was found to be cooperative. The mode of binding was principally by intercalation as revealed from viscosity studies and supported from fluorescence quenching, and polarization results. The binding remarkably stabilized the DNA structure against thermal strand separation. The binding induced conformational changes in the B-form structure of the DNA and the bound alkaloid molecule acquired induced circular dichroism. The binding affinity values obtained from spectroscopy, fluorescence polarization (and anisotropy) and calorimetry were in agreement with each other. The binding was exothermic, characterized by negative enthalpy and positive entropy change and exhibited enthalpy-entropy compensation phenomenon. The heat capacity changes of the binding revealed hydrophobic contribution to the binding. Molecular aspects of the interaction characterized by the involvement of multiple weak noncovalent forces are presented. PMID- 24177206 TI - Photobehavior and docking simulations of drug within macromolecules: binding of an antioxidative isoquinolindione to a serine protease and albumin proteins. AB - The principal intent of the present contribution is to decipher the binding domain and structural changes of trypsin (TPS), a proteolytic globular enzyme and two serum proteins, namely, bovine serum albumin (BSA), human serum albumin (HSA) association with a newly synthesized bioactive isoquinolindione derivative (ANAP) by employing steady state, time resolved fluorescence and circular dichroism (CD) techniques. Intramolecular charge transfer emission (ICT) of ANAP is found to be responsible for the commendable sensitivity of the probe as an extrinsic fluorescent marker to the protein environments. A sharp distinctive feature of determined micropolarities in proteinous media clearly demarcates the differential extent of hydrophobicity around the encapsulated ANAP. A proficient efficiency tunable fluorescence (Forster type) resonance energy transfer (FRET) from the excited tryptophan to ANAP reveals that ANAP binds in the close vicinity of the tryptophan residue in protein. Molecular modeling simulation has been exploited for evaluating the probable interaction site of ANAP in proteinous assembly which shows subdomain IIA are earmarked to possess affinity for ANAP in serum albumins whereas S1 binding pocket in TPS has been found potential binding region for ANAP. PMID- 24177207 TI - Relapsing optic neuritis: a multicentre study of 62 patients. AB - BACKGROUND: Optic neuritis (ON) may be the first symptom of a central nervous system demyelinating, systemic or infectious disease but few patients experience recurrent episodes and have a negative workup. OBJECTIVE: This disorder, named relapsing optic neuritis (RON), is poorly described in the literature and still presents a particular challenge in diagnosis and management. METHODS: We describe the clinical, laboratory, magnetic resonance imaging (MRI) and disability course of RON in a French cohort of 62 patients, based on a multicentre, retrospective, observational study. RESULTS: In our cohort, we identified two distinct groups of RON patients. The first is characterised by relapsing inflammatory optic neuritis (RION, 68%), which is non-progressive, whereas the second presented as a chronic relapsing inflammatory optic neuritis (CRION, 32%), which is progressive. We have noted more cases with steroid dependence in the CRION group than the RION group (42% vs 10%). The long-term visual prognosis was more severe in CRION patients and neuromyelitis optica-immunoglobulin G (NMO-IgG)-positive patients. CONCLUSION: RON is likely a separate entity corresponding to an autoimmune disease that differs from multiple sclerosis (MS), NMO and vasculitis. We provide a new classification system based on a better understanding of RON which could allow an improved management by early treatment of poor prognosis forms. PMID- 24177208 TI - Human bone marrow mesenchymal stem/stromal cells produce efficient localization in the brain and enhanced angiogenesis after intra-arterial delivery in rats with cerebral ischemia, but this is not translated to behavioral recovery. AB - Intravascular cell therapy is a promising approach for the treatment of stroke. However, high accumulation of cells to lungs and other filtering organs is a major concern after intravenous (i.v.) cell transplantation. This can be circumvented by intra-arterial (i.a.) cell infusion, which improves homing of cells to the injured brain. We studied the effect of i.a. delivery of human bone marrow-derived mesenchymal cells (BMMSCs) on behavioral and histological outcome in rats after middle cerebral artery occlusion (MCAO). Sixty male Wistar rats were subjected to transient MCAO (60 min) or sham-operation. BMMSCs (1*10(6)) were infused into the external carotid artery on postoperative day 2 or 7. Histology performed after a 42-day follow-up did not detect any human cells (MAB1281) in the ischemic brain. Endothelial cell staining with RECA-1 revealed a significant increase in the number of blood vessels in the perilesional cortex in MCAO rats treated with cells on postoperative day 7. Behavioral recovery as assessed in three tests, sticky label, cylinder and Montoya's staircase, was not improved by human BMMSCs during the follow-up. In conclusion, human BMMSCs did not improve functional recovery in MCAO rats despite effective initial homing to the ischemic hemisphere and enhanced angiogenesis, when strict behavioral tests not affected by repeated testing and compensation were utilized. PMID- 24177209 TI - Prenatal lipopolysaccharide exposure increases depression-like behaviors and reduces hippocampal neurogenesis in adult rats. AB - Major depression is one of the most prevalent mental disorders in the population. In addition to genetic influences, disturbances in fetal nervous system development might be a contributing factor. Maternal infection during pregnancy may affect fetal brain development and consequently lead to neurological and mental disorders. Previously, we used low-dose lipopolysaccharide (LPS) exposure on embryonic day 10.5 to mimic mild maternal infection in rats and found that dopaminergic and serotonergic neurons were reduced in the offspring. The offspring also showed more anxiety-like behavior and an enhanced stress response. In the present study we used forced swim test and chronic mild stress challenge to assess depression-like behaviors in the affected offspring and examined their adult hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) concentration. Our results showed that prenatally LPS-exposed rats (LPS rats) displayed more depression-like behaviors and had reduced adult neurogenesis and BDNF. The behavioral abnormalities and reduction in adult neurogenesis could be reversed by chronic fluoxetine (FLX) treatment. This study demonstrates that during the critical time of embryonic development LPS exposure can produce long term behavioral changes and reduction in adult neurogenesis. The findings of enhanced depression-like behaviors, reduced adult neurogenesis, and their responsiveness to chronic antidepressant treatment suggest that prenatal LPS exposure could serve as an animal model of depression. PMID- 24177210 TI - Blockade of Cav2.1-mediated NMDA receptor signaling disrupts conditioned fear extinction. AB - Although fear extinction requires N-methyl-d-aspartate (NMDA) receptor signaling, Cav2.1-regulated synaptic function in extinction remains unknown. This study examined whether Cav2.1-mediated signaling plays role in consolidation of extinction. Wild-type mice received intracerebroventricular injection of Cav2.1 blocker (omega-agatoxin IVA, 4.0 pg/side) showed impaired extinction behavior and increased expression of CREB-dependent gene Arc in medial prefrontal cortex (mPFC). Intra-mPFC injections of NMDA receptor antagonist (MK-801, 0.5 MUg/midline), which was ineffective in wild-type controls, blocked extinction in heterozygous rolling Nagoya (rol/+) mice carrying Cav2.1alpha1 gene mutation rol/+ mice. These results indicate that Cav2.1-mediated NMDA receptor signaling is functional pathway in mPFC-dependent fear extinction. Our results also indicate that the combination of pharmacological and genetic approaches can be used to study functional signaling pathways in neuronal circuits. PMID- 24177211 TI - Retinoids and rexinoids inhibit hepatitis C virus independently of retinoid receptor signaling. AB - Using a high-throughput screening system involving HCV JFH-1-Huh 7.5.1 cells, we determined that the ligands of class II nuclear receptors, retinoids and rexinoids inhibit HCV infection. Retinoids, ligands of retinoic acid receptor (RAR), and rexinoids, ligands of retinoid X receptor (RXR), reduced extracellular HCV RNA of HCV infected cells in a dose-dependent manner. The 50% effective concentrations were below 10 nM, and the 50% cytotoxic concentrations were over 10 MUM. Both agonists and antagonists demonstrated inhibition, which indicates that the effect is not dependent on retinoic acid signaling. These chemicals reduced HCV RNA and NS5A protein levels in cells harboring the subgenomic HCV replicon RNA, which suggests that the chemicals affect HCV RNA replication. These compounds were also effective against persistently infected cells, although the reduction in the intracellular HCV RNA was smaller than that of the extracellular HCV RNA, suggesting that viral post-replication step is also inhibited. In combination with interferon (IFN), retinoid exhibited a synergistic effect. Retinoids did not enhance expression of the IFN effector molecule PKR. These series of compounds warrant further investigation as new class of HCV drugs, for the clinical translation of our observation may lead to increased anti-HCV efficacy. PMID- 24177212 TI - Effects of low concentrations of the antiprogestin mifepristone (RU486) in adults and embryos of zebrafish (Danio rerio): 2. Gene expression analysis and in vitro activity. AB - Here, we analyzed the transcriptional effects of the antiprogestin mifepristone (MIF, RU486) and progesterone (P4) in zebrafish as well as their in vitro activities in yeast-based reporter gene assays. This study is associated with the reproduction study in adult zebrafish and embryos exposed for 21 days to 5, 39, 77 ng/L MIF, and 25 ng/L P4 (Bluthgen et al., 2013a). The in vitro activities of MIF and P4 were investigated using a series of recombinant yeast-based assays (YES, YAS, YPS) and compared to transcriptional alterations obtained in fish tissues and embryos from the exposure study. MIF elicited antiestrogenic, androgenic and progestogenic activities in recombinant yeast, similar to P4, and no antiprogestogenic activity in vitro. The transcriptional alterations of steroid hormone receptors were similar in adult males and females, and more pronounced in embryos. MIF tended to transcriptionally down-regulate the androgen (ar), progesterone (pgr) and glucocorticoid (gr) receptors in adult fish and embryos. Transcripts of the estrogen receptor (esr1) and vitellogenin (vtg1) were not significantly altered. A trend for down-regulation was observed for transcripts of genes belonging to steroidogenic enzymes including 17beta hydroxysteroid dehydrogenase type 3 (hsd17b3), 3 beta-hydroxysteroid dehydrogenase (hsd3b), P450 aromatase A (cyp19a) and 11beta-hydroxylase (cyp11b). P4 resulted in similar transcriptional alterations as MIF. The data indicate that gene expression changes (here and later gene expression is taken as synonym to gene transcription) and in vitro activities match only in part including the lack of antiprogestogenic activity of MIF. Additionally, effects on reproduction and gonad histology described in the associated report (Bluthgen et al., 2013a) can only partly be explained by gene expression data presented here. PMID- 24177213 TI - Interactive effects of copper and dissolved organic matter on sodium uptake, copper bioaccumulation, and oxidative stress in juvenile freshwater mussels (Lampsilis siliquoidea). AB - Freshwater mussels are exceptionally sensitive to many contaminants including metals, but the mechanisms of toxicity are not fully understood. Similarly, our understanding of the protective effects of dissolved organic matter (DOM) is also undergoing revision, since recent studies have found that DOM may also directly affect organism physiology, in addition to its well known capability in complexing and reducing bioavailability of metals. In the present study, these issues were investigated in juvenile (6-12 months old) freshwater mussels (Lampsilis siliquoidea) in moderately-hard reconstituted water (Ca(2+)=0.406 mmol/L; Mg(2+)=0.537 mmol/L; Na(+)=1.261 mmol/L;K(+)=0.077 mmol/L; hardness=80 100mg/L CaCO3; pH=8.02 and DOM=0.3 mgC/L). Mussels were acutely exposed (24 and 96 h) to Cu (0, 2 or 12 MUg Cu/L) combined with three concentrations (0, 3 or 6 mgC/L) of DOM of terrigenous origin (Luther Marsh). We analyzed unidirectional Na(+) influx, whole-body ion content (Na(+), K(+), Ca(2+) and Mg(2+)), enzyme (Na(+)/K(+)-ATPase, H(+)-ATPase and carbonic anhydrase) activities, copper bioaccumulation and oxidative stress-related parameters. Exposure to DOM alone caused a marked increase in the unidirectional Na(+) influx rate and a decrease in v-type H(+)-ATPase activity, suggesting that DOM alone can cause alterations in membrane transport functions and therefore, whole-body Na(+) metabolism. Unidirectional Na(+) influx rate and Na(+)K(+)-ATPase activity were inhibited when mussels were exposed to the higher Cu concentration tested (12 MUg Cu/L). The influx inhibition was ameliorated by the simultaneous presence of DOM. At this same Cu concentration, DOM also significantly protected mussels against whole-body Na(+) and K(+) losses associated with Cu exposure, as well as against Cu bioaccumulation. Oxidative stress parameters did not show clear trends across treatments. Overall, our results indicate that Cu is a potent ionoregulatory toxicant to freshwater mussels. They also demonstrate that natural DOM protects against both Cu bioaccumulation and ionoregulatory toxicity, and that at least part of this protection results from direct positive effects of DOM on Na(+) metabolism. PMID- 24177214 TI - Rapid adaptation of microalgae to bodies of water with extreme pollution from uranium mining: an explanation of how mesophilic organisms can rapidly colonise extremely toxic environments. AB - Extreme environments may support communities of microalgae living at the limits of their tolerance. It is usually assumed that these extreme environments are inhabited by extremophile species. However, global anthropogenic environmental changes are generating new extreme environments, such as mining-effluent pools of residual waters from uranium mining with high U levels, acidity and radioactivity in Salamanca (Spain). Certain microalgal species have rapidly adapted to these extreme waters (uranium mining in this area began in 1960). Experiments have demonstrated that physiological acclimatisation would be unable to achieve adaptation. In contrast, rapid genetic adaptation was observed in waters ostensibly lethal to microalgae by means of rare spontaneous mutations that occurred prior to the exposure to effluent waters from uranium mining. However, adaptation to the most extreme conditions was only possible after recombination through sexual mating because adaptation requires more than one mutation. Microalgae living in extreme environments could be the descendants of pre selective mutants that confer significant adaptive value to extreme contamination. These "lucky mutants" could allow for the evolutionary rescue of populations faced with rapid environmental change. PMID- 24177215 TI - Calcium-mediated responses and glutamine synthetase expression in greater duckweed (Spirodela polyrhiza L.) under diethyl phthalate-induced stress. AB - This study was carried out to assess the influence of diethyl phthalate (DEP) alone or associated with calcium chloride (CaCl2) on greater duckweed plants, emphasizing the implications of calcium in amelioration of DEP-induced stress on plant growth. Greater duckweed were treated with DEP in variable concentrations, as 0, 0.25, 0.5, 1.0 and 2.0mM for 7 days, or treated with the same concentration either 2mM DEP or 2mM DEP plus 10mM CaCl2.2H2O in different duration 0-7 days. Treatment with 2mM DEP resulted in increasing proline content, protease activity, and ammonia accumulation in duckweed tissues. NADH-glutamate dehydrogenase (NADH GDH; EC 1.4.1.2) and Delta(1)-pyrroline-5-carboxylate reductase (P5CR; EC 1.5.1.2), two key enzymes in the glutamate pathway of proline synthesis, showed increase in activity with DEP treatment and positively correlated with proline accumulation. No further increase in proline accumulation was observed with addition of calcium chloride to the DEP-treated cultures. However, supplementation of Ca(2+) can mitigate the adverse effect of DEP, at least in part to decrease the DEP-induced superoxide accumulation and increase in GDH activity for ammonia assimilation in duckweed fronds. In addition, effects of calcium on mitigation of DEP injury were also observed in glutamine synthetase (GS; EC 6.3.1.2) expression. Both GS1 and GS2 polypeptide accumulation and the level of total GS activity were nearly equivalent to the control. Exogenous proline protects GS2 from DEP-modulated redox damage in the chloroplast lysates but there is no remarkable protection effects on D1 (the 32kDa protein in photosystem II reaction center) degradation. In conclusion, the glutamate pathway of proline synthesis might be involved in mitigation of DEP-induced injury, and calcium plays an important role in increasing GDH, P5CR, and GS expression. PMID- 24177216 TI - Biomarker responses and morphological effects in juvenile tilapia Oreochromis mossambicus following sequential exposure to the organophosphate azinphos-methyl. AB - Pesticides are contaminants of aquatic environments. Such ecosystems in the Western Cape, South Africa are at risk as most organophosphates are highly toxic to fish and other aquatic organisms. The objective of this experimental study was firstly to determine the acute toxicity of azinphos-methyl (AZP) to juvenile fish (Oreochromis mossambicus) and, secondly, to investigate the effects of repeated exposure of fish to an array of sublethal concentrations on morphological parameters such as growth, condition factor and organ-somatic indices. Food consumption and feeding response time were investigated as ecologically relevant behavioral endpoints which could affect growth, reproduction and survival and subsequently causes impacts at the population and/or community level. Finally, acetylcholinesterase (AChE) was used as biomarker to investigate effects at sub organismal level following sequential exposure to AZP. The aim was to determine how sequential spraying procedures, using different exposure concentrations and intervals, affected fish as reflected by their responses at different organizational levels. A dose-dependent effect on feeding impairment was observed in the feeding response experiment. The correlation found between growth impairment, feeding activity and AChE inhibition therefore indicates that frequency of exposure can play an important role regarding the severity of impacts to non-target organisms. This study provides evidence that AZP has harmful effects on non-target aquatic organisms, such as fish which can be manifested in the early developmental stages. Sequential exposures showed that dosage and frequency of spraying and spraying interval could exacerbate harmful effects. AChE inhibition and organosomatic indices can be used effectively to measure effects. PMID- 24177217 TI - Molecular target sequence similarity as a basis for species extrapolation to assess the ecological risk of chemicals with known modes of action. AB - It is not feasible to conduct toxicity tests with all species that may be impacted by chemical exposures. Therefore, cross-species extrapolation is fundamental to environmental risk assessment. Recognition of the impracticality of generating empirical, whole organism, toxicity data for the extensive universe of chemicals in commerce has been an impetus driving the field of predictive toxicology. We describe a strategy that leverages expanding databases of molecular sequence information together with identification of specific molecular chemical targets whose perturbation can lead to adverse outcomes to support predictive species extrapolation. This approach can be used to predict which species may be more (or less) susceptible to effects following exposure to chemicals with known modes of action (e.g., pharmaceuticals, pesticides). Primary amino acid sequence alignments are combined with more detailed analyses of conserved functional domains to derive the predictions. This methodology employs bioinformatic approaches to automate, collate, and calculate quantitative metrics associated with cross-species sequence similarity of key molecular initiating events (MIEs). Case examples focused on the actions of (a) 17alpha-ethinyl estradiol on the human (Homo sapiens) estrogen receptor; (b) permethrin on the mosquito (Aedes aegypti) voltage-gated para-like sodium channel; and (c) 17beta trenbolone on the bovine (Bos taurus) androgen receptor are presented to demonstrate the potential predictive utility of this species extrapolation strategy. The examples compare empirical toxicity data to cross-species predictions of intrinsic susceptibility based on analyses of sequence similarity relevant to the MIEs of defined adverse outcome pathways. Through further refinement, and definition of appropriate domains of applicability, we envision practical and routine utility for the molecular target similarity-based predictive method in chemical risk assessment, particularly where testing resources are limited. PMID- 24177218 TI - Effects of triphenyltin on growth and development of the wood frog (Lithobates sylvaticus). AB - Exposure to contaminants in the environment has been suggested as a contributing cause of ongoing declines in populations of amphibians reported in certain locations around the world. In the current study, responses of the wood frog (Lithobates sylvaticus) to exposure to triphenyltin (TPT), a commonly used fungicide, during the larval period were characterized. Exposure of L. sylvaticus to 0.1, 1.0, or 5.0 MUg TPT/L significantly affected survival, growth, days to metamorphosis (DTM), and abundances of transcripts of genes of interest. After seven days of exposure there were no significant effects on survival, but masses and snout-ventral length (SVL) of larvae exposed to 5.0 MUg TPT/L were significantly lesser than controls. Mortality of larvae after exposure to 5.0 MUg TPT/L was 100% nine days after initiation of the experiment. Larvae exposed to 0.1 or 1.0 MUg TPT/L were allowed to grow for 100 days or until they reached metamorphic climax, whichever occurred earlier. Mortality of wood frogs exposed to 1.0 MUg TPT/L was 80%. The LC20 or LC50 after 100 days of exposure was 0.12 or 0.34 MUg TPT/L, respectively. However, DTM of larvae that survived exposure to 1.0MUgTPT/L was significantly less than that of controls. Abundances of transcripts of retinoid-X-receptor (rxr) and perixosomal proliferation receptor gamma (ppargamma) were significantly lesser in larvae exposed to either concentration of TPT for seven days. Also, abundances of transcripts of stearoyl CoA desaturase-1 (scd1), fatty acid synthase (fas), lipoprotein lipase (lpl), and beta-hydroxybutyrate dehydrogenase (beta-hb-m) were lesser in larvae exposed to 5.0 MUg TPT/L, which suggested that disruption of lipid metabolism might have affected survival in this exposure group. However, in larvae that survived to metamorphic climax during exposure to TPT for as long as 100 days, abundances of transcripts of perixosomal proliferation receptor alpha (pparalpha), ppargamma, cytochrome p4504B1 (cyp4b1), fas, and lpl were greater than in controls, suggesting that an up-regulation of processes related to metabolism of lipids might have been important for survival and development of these animals. Overall, concentrations of TPT that are found in the environment had a significant effect on the survival and development of L. sylvaticus, and this might have been due, in part, to effects on metabolism of lipids. PMID- 24177219 TI - Effects of bisphenol A on different trophic levels in a lotic experimental ecosystem. AB - Bisphenol A (BPA) is commonly used by manufacturers and can be found in many aquatic ecosystems. Data relative to BPA ecotoxicity are only available for studies in laboratory conditions on macro-invertebrates and fish. There is thus a lack of information for other trophic levels such as macrophytes. Moreover, the impacts of BPA within an ecosystem context, i.e. with populations from different trophic levels studied at long term in environmental conditions, have never been assessed. We carried out a long-term lotic mesocosm study in 20 m long channels under three exposure concentrations of BPA (nominal concentrations of 0, 1, 10 and 100 MUg/L) delivered continuously for 165 days. Three trophic levels were followed: macrophytes, macro-invertebrates (with a focus on Radix balthica) and fish (Gasterosteus aculeatus). Significant effects were shown at 100 MUg/L BPA on the three trophic levels. BPA had a direct impact on macrophyte community structure, direct and indirect impacts on macro-invertebrates and on fish population structure. Gonad morphology of fish was affected at 1 and 10 MUg/L of BPA, respectively for female and male sticklebacks. In addition to these ecotoxicity data, our results suggest that fish are good integrators of the responses of other communities (including macro-invertebrates and macrophytes) in mesocosm systems. PMID- 24177220 TI - Cocaine in high concentrations inhibits platelet aggregation in vitro. AB - Complications of cocaine administration are acute vascular occlusions such as myocardial infarction and stroke. We have studied the influence of cocaine on platelet function in vitro. For that purpose, citrated blood from healthy volunteers was incubated with cocaine concentrations of 0 (control), 10, 100, 1000, 2500, and 10'000 MUmol/l plasma. Platelet aggregation was measured in whole blood under high shear flow conditions with a platelet function analyzer PFA-100 using either epinephrine (EPI) or ADP as a platelet activator, as well as in non flowing blood measuring the change of impedance after the addition of either collagen or ADP (Chronolog-700 Aggregometer). In addition, platelet aggregation was measured by the change in light transmission in platelet rich plasma containing the same cocaine concentrations (Chronolog-700). Platelet aggregation in flowing whole blood (PFA-100) was not affected by cocaine up to 1000 MUmol/l, partially inhibited by 2500 MUmol/l and completely inhibited by 10'000 MUmol/l cocaine. In non-flowing blood, platelet aggregation was decreased already at cocaine concentrations of 1000 MUmol/l with ADP and 2500 MUmol/l with collagen as a platelet activator. In platelet-rich plasma, aggregation was partially inhibited by 1000 and 2500 MUmol/l and completely inhibited by 10'000 MUmol/l cocaine. We conclude that platelet aggregation is inhibited by cocaine in vitro. This occurs, however, at concentrations above those measurable in vivo. These observations make it very unlikely that a direct platelet activation plays a role in vascular events complicating cocaine consumption. PMID- 24177221 TI - Trends and challenges in United States neonatal intensive care units follow-up clinics. AB - OBJECTIVE: A mandate exists that all level III neonatal intensive care units (NICUs) provide a means to assess and follow their high-risk neonates after discharge. However, no standardized guidelines exist for the follow-up services provided. To determine trends of structure and care provided in NICU follow-up clinics in both the academic and private clinical setting. STUDY DESIGN: We sent an Internet survey to NICU follow-up clinic directors at both academically affiliated and private centers. This study received institutional review board exemption. RESULT: We received 89 surveys from academic institutions and 94 from private level III follow-up programs. These responses represent 55% of academic programs and 40% of private programs in the United States. Similar to academic institutions, 18% of private NICU follow-up clinics provide primary care services to patients. In both settings, the hospital supports 60% of the funding required for clinic activities. Forty-five percent of NICU graduates seen in both private and academic follow-up clinics have public aid as their primary insurance. Eighty five percent of NICUs in both settings have guidelines outlining requirements for referrals to the follow-up clinic. Academic programs find feeding difficulties the most difficult, whereas private programs find bronchopulmonary dysplasia and feeding difficulties equally as difficult. CONCLUSION: The care and struggles of NICU follow-up clinics are similar in both the academic affiliated and private settings. Similar referrals, clinical evaluation and medical care occur with varying struggles. PMID- 24177222 TI - STRUCTURAL CONNECTIVITY VIA THE TENSOR-BASED MORPHOMETRY. AB - The tensor-based morphometry (TBM) has been widely used in characterizing tissue volume difference between populations at voxel level. We present a novel computational framework for investigating the white matter connectivity using TBM. Unlike other diffusion tensor imaging (DTI) based white matter connectivity studies, we do not use DTI but only T1-weighted magnetic resonance imaging (MRI). To construct brain network graphs, we have developed a new data-driven approach called the epsilon-neighbor method that does not need any predetermined parcellation. The proposed pipeline is applied in detecting the topological alteration of the white matter connectivity in maltreated children. PMID- 24177223 TI - Significant interactions between maternal PAH exposure and haplotypes in candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking African American and Dominican mothers and newborns. AB - Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African American (n = 132) and Dominican (n = 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in gene-environment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P. PMID- 24177224 TI - ERK-dependent downregulation of Skp2 reduces Myc activity with HGF, leading to inhibition of cell proliferation through a decrease in Id1 expression. AB - Hepatocyte growth factor (HGF) has an inhibitory effect on human HepG2 hepatoma cell proliferation. Previously, it was shown that HGF treatment downregulated Id1 and upregulated p16(INK4a) in an ERK-dependent manner, leading to the inhibition of cellular proliferation. Here, new insight suggests that Skp2, an SCF complex component and potential prognosticator in cancer, is downregulated by injection of HGF into established HepG2 xenograft tumors. The downregulation was evident at both the mRNA and protein level and in an ERK-dependent manner. Critically, high expression of Skp2 restored HGF-inhibited cell proliferation, indicating that the inhibitory effect of HGF required the downregulation of Skp2. However, downregulation was not involved in the HGF-induced upregulation of a CDK inhibitor, p27(Kip1), a known SCF-Skp2 target. Instead, data revealed that Skp2 regulated Myc activity, which has oncogenic potential in the generation of hepatocellular carcinoma. Elevated expression of Skp2 or a mutant that is unable to associate with the SCF complex was capable of activating Myc, suggesting that Skp2 does not act on Myc as a component of the SCF complex, and thus functions as an activator of Myc independent of its role in ubiquitination. Furthermore, Skp2 regulated Id1 expression by regulating Myc activity, and the regulation of Skp2 is involved in the activity of p16 promoter through regulation of Id1 expression. Overall, these mechanistic findings provide the first evidence that ERK-dependent downregulation of Skp2 reduced Myc activity, leading to HGF-induced inhibition of cell proliferation through decreased Id1 expression. IMPLICATIONS: This study elucidates the molecular details of HGF-induced inhibition of cellular proliferation in liver cancer cells. PMID- 24177225 TI - Magnetism of TbPc2 SMMs on ferromagnetic electrodes used in organic spintronics. AB - Structural features and magnetic behaviour of TbPc2 thin films sublimated on LSMO and on cobalt surfaces have been investigated by synchrotron-based XNLD and XMCD techniques. Different orientation of the molecules is observed for the two substrates. No significant magnetic interaction with the ferromagnetic substrates is detected. PMID- 24177226 TI - Order/disorder phenomena in Zn1-xMnxGa2Se4 ordered vacancy compounds: high temperature neutron powder diffraction experiments. AB - We present a study of order-disorder phenomena in the series of tetrahedral ordered vacancy compounds Zn1-xMnxGa2Se4 by means of time-of-flight neutron diffraction at high temperature together with dc magnetic susceptibility, Raman spectroscopy, differential thermal analysis and optical absorption experiments. Samples of nominal composition x = 0, 0.24, 0.5, 0.77 and 1 have been studied. An order-disorder phase transition has been detected, with Tc ranging from 472 to 610 degrees C, which involves a structural change from a defect chalcopyrite phase, with I4 space group (s.g.) and three different cation sites, to a partially disordered defect stannite, in which Zn, Mn and half of the Ga ions share the 4d site in I42m s.g. Neither the vacancies nor the Ga ions occupying site 2a are involved in the phase transition. An additional ordering process is observed on approaching the phase transition from below, which is attributed to several factors: the activation of cation diffusion at ~300 degrees C, the partially disordered cation distribution exhibited by the as-grown single crystals and the preference of Mn atoms for the 2d crystallographic site in the I4 structure. The reversibility of the phase transition is analysed with the aid of magnetic, optical and Raman experiments. PMID- 24177227 TI - Covalent-organic framework as a template to assemble carbon nanotubes into a high density membrane: computational demonstration. AB - Carbon nanotube (CNT) membranes have a wide range of important technological applications; however, the fabrication of high-density CNT membranes is challenging. Using molecular simulation, we demonstrate that a covalent-organic framework (COF-8) can act as a template promoting (9, 9) CNTs to assemble into a homogeneous high-density membrane. Surprisingly, the templated assembly is unique for (9, 9) CNTs and not observed for smaller or larger CNTs. The microscopic analysis based on the potential of mean force reveals that the highly selective assembly of (9, 9) CNTs into COF-8 is thermodynamically favorable, in contrast to other CNTs. This proof-of-concept computational study proposes a bottom-up strategy to produce high-density CNT membranes, and has a significant implication in CNT applications. PMID- 24177228 TI - Quantum teleportation from a propagating photon to a solid-state spin qubit. AB - A quantum interface between a propagating photon used to transmit quantum information and a long-lived qubit used for storage is of central interest in quantum information science. A method for implementing such an interface between dissimilar qubits is quantum teleportation. Here we experimentally demonstrate transfer of quantum information carried by a photon to a semiconductor spin using quantum teleportation. In our experiment, a single photon in a superposition state is generated using resonant excitation of a neutral dot. To teleport this photonic qubit, we generate an entangled spin-photon state in a second dot located 5 m away and interfere the photons from the two dots in a Hong-Ou-Mandel set-up. Thanks to an unprecedented degree of photon-indistinguishability, a coincidence detection at the output of the interferometer heralds successful teleportation, which we verify by measuring the resulting spin state after prolonging its coherence time by optical spin-echo. PMID- 24177229 TI - Outcomes of a brief program, REORDER, to promote consumer recovery and family involvement in care. AB - OBJECTIVE: The Recovery-Oriented Decisions for Relatives' Support (REORDER) intervention is an innovative, manualized protocol utilizing shared decision making principles with persons who have serious mental illnesses to promote recovery and encourage consideration of family involvement in care. This study compared REORDER to enhanced treatment as usual in a randomized design. METHODS: Participants included 226 veterans with serious mental illness whose relatives had low rates of contact with treatment staff. REORDER involved up to three consumer sessions followed by up to three relative educational sessions if the consumer and relative consented. Individuals were assessed at baseline and six months later. RESULTS: Eighty-five percent of the 111 randomly assigned REORDER participants attended at least one REORDER consumer session; of those, 59% had at least one family session. REORDER participants had significantly reduced paranoid ideation and increased recovery at follow-up. CONCLUSIONS: Participation in REORDER led to marked increases in family participation and improved consumer outcomes. PMID- 24177230 TI - Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals. AB - Lipid content and composition in aquafeeds have changed rapidly as a result of the recent drive to replace ecologically limited marine ingredients, fishmeal and fish oil (FO). Terrestrial plant products are the most economic and sustainable alternative; however, plant meals and oils are devoid of physiologically important cholesterol and long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acids. Although replacement of dietary FO with vegetable oil (VO) has little effect on growth in Atlantic salmon (Salmo salar), several studies have shown major effects on the activity and expression of genes involved in lipid homeostasis. In vertebrates, sterols and LC-PUFA play crucial roles in lipid metabolism by direct interaction with lipid-sensing transcription factors (TFs) and consequent regulation of target genes. The primary aim of the present study was to elucidate the role of key TFs in the transcriptional regulation of lipid metabolism in fish by transfection and overexpression of TFs. The results show that the expression of genes of LC-PUFA biosynthesis (elovl and fads2) and cholesterol metabolism (abca1) are regulated by Lxr and Srebp TFs in salmon, indicating highly conserved regulatory mechanism across vertebrates. In addition, srebp1 and srebp2 mRNA respond to replacement of dietary FO with VO. Thus, Atlantic salmon adjust lipid metabolism in response to dietary lipid composition through the transcriptional regulation of gene expression. It may be possible to further increase efficient and effective use of sustainable alternatives to marine products in aquaculture by considering these important molecular interactions when formulating diets. PMID- 24177231 TI - The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: a pooled analysis of 41 sets of data from case-control studies. AB - Prostate cancer (PCa) is a malignant disease influencing numerous men worldwide every year. However, the exact pathogenesis and the genes, environment, and other factors involved have not been explained clearly. Some studies have proposed that cell signaling pathways might play a key role in the development and progression of PCa. According to our previous study, the RTK/ERK pathway containing nearly 40 genes was associated with PCa risk. On the basis of these genes, we conducted a meta-analysis with our own Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) study and available studies in the databases to describe the association between the pathway and PCa on the SNP level. The results suggested that rs4764695/IGF1 (recessive model: pooled OR=0.92, 95%CI=0.852-0.994, P=0.034; I(2)=0%, P=0.042; allele analysis: pooled OR=0.915, 95%CI=0.874-0.958, P=0; I(2)=0%, P=0.424; codominant model: OR=0.835, 95%CI=0.762-0.916, P=0; I(2)=0%, P=0.684) and rs1570360/VEGF (recessive model: OR=0.596, 95%CI=0.421-0.843, P=0.003; I(2)=23.9%, P=0.269; codominant model: OR=0.576, 95%CI=0.404-0.820, P=0.002; I(2)=49.1%, P=0.140) were significantly associated with PCa. In subgroup analysis, the relationship was also found in Caucasians for IGF1 (dominant model: OR=0.834, 95%CI=0.769-0.904, P=0; allele analysis: OR=0.908, 95%CI=0.863-0.955, P=0; AA vs CC: OR=0.829, 95%CI=0.750-0.916, P=0; AC vs CC: OR=0.837, 95%CI=0.768 0.912, P=0). In addition, in Asians (allele analysis: OR=0.21, 95%CI=0.168-0.262, P=0) and Caucasians (recessive model: OR=0.453, 95%CI: 0.240-0.855, P=0.015; codominant model: OR=0.464, 95%CI=0.240-0.898, P=0.023) for VEGF, the association was significant. The results indicated that rs4764695/IGF1 and rs1570360/VEGF might play a key role in the development and progression of PCa. On the SNP level, we suggest that the study gives us a new view of gene-pathway analysis and targeted therapy for PCa. PMID- 24177232 TI - Eight new mtDNA sequences of glass sponges reveal an extensive usage of +1 frameshifting in mitochondrial translation. AB - Three previously studied mitochondrial genomes of glass sponges (phylum Porifera, class Hexactinellida) contained single nucleotide insertions in protein coding genes inferred as sites of +1 translational frameshifting. To investigate the distribution and evolution of these sites and to help elucidate the mechanism of frameshifting, we determined eight new complete or nearly complete mtDNA sequences from glass sponges and examined individual mitochondrial genes from three others. We found nine new instances of single nucleotide insertions in these sequences and analyzed them both comparatively and phylogenetically. The base insertions appear to have been gained and lost repeatedly in hexactinellid mt protein genes, suggesting no functional significance for the frameshifting sites. A high degree of sequence conservation, the presence of unusual tRNAs, and a distinct pattern of codon usage suggest the "out-of-frame pairing" model of translational frameshifting. Additionally, we provide evidence that relaxed selection pressure on glass sponge mtDNA - possibly a result of their low growth rates and deep-water lifestyle - has allowed frameshift insertions to be tolerated for hundreds of millions of years. Our study provides the first example of a phylogenetically diverse and extensive usage of translational frameshifting in animal mitochondrial coding sequences. PMID- 24177233 TI - Cryopreservation of an artificial human oral mucosa stroma. A viability and rheological study. AB - The aim of this study was to evaluate the viability and biomechanical properties of artificial human oral mucosa stroma (HOMS) subjected to cryopreservation with different cryoprotectant solutions. Artificial HOMS based on a fibrin-agarose matrix with human gingival fibroblasts cultured 7 days in vitro were cryopreserved with three cryoprotectant solutions: (A) TC-199 Medium, DMSO 15%, albumin; (B) DMEM, FCS, DMSO 10%; (C) QC Medium, glycerol. As controls, artificial HOMS not subjected to cryopreservation (CF) and HOMS cryopreserved without cryoprotectant solution (CS) were used. Histological analysis by light microscopy showed that solutions A and B preserved a pattern of porosity similar to values in CF. Based on the number of intact cells in the fibrin-agarose matrix, substitutes preserved with solution B showed the best results. Cell proliferation detected with PCNA immunochemical methods showed that the cell proliferation index was highest in substitutes cryopreserved with solution B. The reculture method and cell viability analyses with Live & Dead((r)) revealed increased number of viable in cells preserved with solution B. Artificial stroma substitutes in CS control samples showed the greatest alterations in microstructure and cell proliferation. Analysis of the biomechanical properties showed that substitutes cryopreserved with different solutions had adequate rheological parameters (yield stress, elastic modulus and viscous modulus) and were therefore suitable for use in regenerative medicine. These results establish effective methods of cryopreservation for all experimental situations and suggest that solution B (DMEM, FCS, DMSO 10%) was the best cryoprotectant for the cryopreservation of an artificial oral human mucosa substitute based on a fibrin agarose matrix. PMID- 24177234 TI - Repeating a strongly masked stimulus increases priming and awareness. AB - Previous studies [Marcel, A. J. (1983). Conscious and unconscious perception: Experiments on visual masking and word recognition. Cognitive Psychology, 15(2), 197-237; Wentura, D., & Frings, C. (2005). Repeated masked category primes interfere with related exemplars: New evidence for negative semantic priming. Journal of Experimental Psychology: Learning, Memory, and Cognition, 31(1), 108 120] suggested that repeatedly presenting a masked stimulus improves priming without increasing perceptual awareness. However, neural theories of consciousness predict the opposite: Increasing bottom-up strength in such a paradigm should also result in increasing availability to awareness. Here, we tested this prediction by manipulating the number of repetitions of a strongly masked digit. Our results do not replicate the dissociation observed in previous studies and are instead suggestive that repeating an unconscious and attended masked stimulus enables the progressive emergence of perceptual awareness. PMID- 24177235 TI - Event-related potentials as brain correlates of item specific proportion congruent effects. AB - The item-specific proportion congruency (ISPC) effect is consistent with the idea that control processes can be applied rapidly in accord with previously experienced conflict for a particular category. An alternative account of this effect is that it reflects item-specific learning processes unrelated to control at the level of the category. The accounts predict the same behaviour but differ in terms of electrophysiological predictions. Two experiments examined the ISPC effect with a particular focus on neural correlates that might reveal whether, and how early in processing, high and low proportion congruent items are treated as distinct classes of stimuli. For both tasks, the proportion congruency category was distinguished prior to the congruence of the specific stimulus, as early as 100 ms post-stimulus onset for the global/local identification task (Experiment 1) and 150 ms for the Stroop task (Experiment 2). The results support an on-line control account of ISPC effects. PMID- 24177236 TI - Sense of identity in advanced Alzheimer's dementia: a cognitive dissociation between sameness and selfhood? AB - We looked at whether sense of identity persists in patients with Alzheimer's disease (AD) and if its profile remains the same between two examinations. A specifically designed protocol was administered to 16 AD patients in the mild to severe stages of dementia and to 16 matched healthy controls, both living in the same institution. We showed that sense of identity was broadly preserved in AD patients. The patterns of their responses were similar to those of controls, and remained consistent over a two-week period. However, some qualitative characteristics of sense of identity in AD patients differed significantly from those of controls, suggesting that AD patients may not be able to update their self-knowledge, probably because of their episodic memory deficit. These results are discussed in the light of both current models of the self and philosophical concepts such as sameness and selfhood. PMID- 24177237 TI - Performance reactivity in a continuous-performance task: implications for understanding post-error behavior. AB - Although there has been considerable interest in the effects of errors on subsequent performance, relatively few studies have considered the effects of non error events that contain some performance-relevant information, such as correct performance on critical trials. In the present article, we propose and assess a hypothesis of performance reactivity. In support of this hypothesis, we provide evidence of performance decrements following both incorrect and correct responses but not following performance-irrelevant events. More specifically, in a continuous response task (Sustained Attention to Response Task), we (1) replicate previous findings that errors of commission on rare NOGO trials produce decrements in subsequent performance, and (2) observe that correct withholds to NOGO trials produce decrements in subsequent accuracy relative to task-irrelevant tones. These results corroborate a hypothesis that some error-related effects on subsequent performance are not unique, but are instead a particularly salient version of a more general performance-reactivity effect. PMID- 24177238 TI - Catheter-related infections in patients on home parenteral nutrition. AB - Long-term parenteral nutrition in the community is a practice that is growing steadily in the UK. Catheter-related bloodstream infections (CRBSI) in these patients is one of the major causes of morbidity and re-hospitalisation. The prevention of CRBSI impacts the quality of life and outcomes of these patients. PMID- 24177239 TI - Nutrition and cancer: issues related to treatment and survivorship. AB - This paper reviews nutritional issues related to cancer treatment and further explores nutritional needs pertinent to cancer survivorship. It examines the major problems with nutrition when patients undergo the main cancer treatment modalities of chemotherapy, radiotherapy and surgery. Particular attention is paid to long-term dietary advice in acknowledgement of the improved effectiveness of cancer treatment and the chronic nature of the condition. PMID- 24177240 TI - Preventing malnutrition in home-dwelling elderly individuals. AB - The aim of this article is to provide an overview of the role of the nurse in the identification and prevention of malnutrition in home dwelling elderly individuals. It will examine the causes and prevalence of malnutrition outlining the factors that may place older home-dwelling people at risk of developing this serious nutritional disorder. The remainder of the article will provide an in depth focussed discussion on the role of the community nurse in the assessment and prevention of malnutrition, with recommendations for the improvement of clinical practice. PMID- 24177241 TI - Interview with Sean White. PMID- 24177242 TI - General practice: a vision for the future. PMID- 24177243 TI - Time to recognise dysphagia as a contributing factor to malnutrition. AB - Dysphagia is a term used to define an impairment of the ability to eat, drink or swallow (National Institute for Health and Care Excellence (NICE), 2006), and can be caused by a mechanical obstruction (a cancer, surgery or stricture of the oropharynx or upper gastrointestinal tract) or a neurological condition that affects the person's ability to swallow. This is a particular problem in the elderly population (Sura et al, 2012). PMID- 24177244 TI - Nasogastric feeding in the community: safe and effective practice. AB - A small percentage of patients receiving enteral tube feeding in the community receive feed via a nasogastric tube. There are risks associated with this method if the correct procedures for monitoring tube displacement are not in place. Guidance for checking tube position has been provided by the National Patient Safety Agency (NPSA). Nurses caring for patients with nasogastric tube feeds need to be aware of how NPSA alerts impact on practice and the advice and support they may need to offer patients. PMID- 24177246 TI - Sleep misperception, EEG characteristics and autonomic nervous system activity in primary insomnia: a retrospective study on polysomnographic data. AB - Misperception of Sleep Onset Latency, often found in Primary Insomnia, has been cited to be influenced by hyperarousal, reflected in EEG- and ECG-related indices. The aim of this retrospective study was to examine the association between Central Nervous System (i.e. EEG) and Autonomic Nervous System activity in the Sleep Onset Period and the first NREM sleep cycle in Primary Insomnia (n=17) and healthy controls (n=11). Furthermore, the study examined the influence of elevated EEG and Autonomic Nervous System activity on Stage2 sleep-protective mechanisms (K-complexes and sleep spindles). Confirming previous findings, the Primary Insomnia-group overestimated Sleep Onset Latency and this overestimation was correlated with elevated EEG activity. A higher amount of beta EEG activity during the Sleep Onset Period was correlated with the appearance of K-complexes immediately followed by a sleep spindle in the Primary Insomnia-group. This can be interpreted as an extra attempt to protect sleep continuity or as a failure of the sleep-protective role of the K-complex by fast EEG frequencies following within one second. The strong association found between K-alpha (K-complex within one second followed by 8-12 Hz EEG activity) in Stage2 sleep and a lower parasympathetic Autonomic Nervous System dominance (less high frequency HR) in Slow-wave sleep, further assumes a state of hyperarousal continuing through sleep in Primary Insomnia. PMID- 24177245 TI - "Ecstasy"-induced toxicity in SH-SY5Y differentiated cells: role of hyperthermia and metabolites. AB - 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a recreational hallucinogenic drug of abuse known to elicit neurotoxic properties. Hepatic formation of neurotoxic metabolites is thought to play a major role in MDMA related neurotoxicity, though the mechanisms involved are still unclear. Here, we studied the neurotoxicity mechanisms and stability of MDMA and 6 of its major human metabolites, namely alpha-methyldopamine (alpha-MeDA) and N-methyl-alpha methyldopamine (N-Me-alpha-MeDA) and their correspondent glutathione (GSH) and N acetyl-cysteine (NAC) conjugates, under normothermic (37 degrees C) or hyperthermic conditions (40 degrees C), using cultured SH-SY5Y differentiated cells. We showed that MDMA metabolites exhibited toxicity to SH-SY5Y differentiated cells, being the GSH and NAC conjugates more toxic than their catecholic precursors and MDMA. Furthermore, whereas the toxicity of the catechol metabolites was potentiated by hyperthermia, NAC-conjugated metabolites revealed higher toxicity under normothermia and GSH-conjugated metabolites-induced toxicity was temperature-independent. Moreover, a time-dependent decrease in extracellular concentration of MDMA metabolites was observed, which was potentiated by hyperthermia. The antioxidant NAC significantly protected against the neurotoxic effects of MDMA metabolites. MDMA metabolites increased intracellular glutathione levels, though depletion in thiol content was observed in MDMA-exposed cells. Finally, the neurotoxic effects induced by the MDMA metabolite N-Me-alpha-MeDA involved caspase 3 activation. In conclusion, this study evaluated the stability of MDMA metabolites in vitro, and demonstrated that the catechol MDMA metabolites and their GSH and NAC conjugates, rather than MDMA itself, exhibited neurotoxic actions in SH-SY5Y differentiated cells, which were differently affected by hyperthermia, thus highlighting a major role for reactive metabolites and hyperthermia in MDMA's neurotoxicity. PMID- 24177247 TI - Attentional disengagement is modulated by the offset of unpleasant pictures: a saccadic reaction time study. AB - We studied the influence of passively viewing a picture on saccade latencies to peripheral targets. Thirty-two volunteers were instructed to look at a central picture, wait for the onset of a peripheral target, and execute a saccade toward it as quickly as possible - saccadic reaction time (SRT). The central picture (neutral or unpleasant) could be turned off simultaneously with target onset (the no-gap condition) or 200ms prior to target onset (the gap-200 condition). We found that saccade latencies were influenced by emotional valence and condition. In the no-gap condition, SRTs were longer after viewing unpleasant pictures. In the gap-200 condition, the pattern was reversed, and unpleasant pictures induced shorter SRTs in relation to neutral pictures. Furthermore, the influence of unpleasant pictures gradually decreased when images were re-exposed to the participants - affective habituation. The results are discussed in terms of attentional avoidance and disengagement from unpleasant emotional pictures. PMID- 24177248 TI - Effects of orthostasis on endocrine responses to psychosocial stress. AB - Standardized psychological procedures have been designed to induce physiological stress responses. However, the impact of standing (orthostasis) on the physiological reaction after psychological stress remains unclear. The purpose of the current analysis was to examine and quantify the relative contribution of orthostasis to the physiological stress response by comparing a "standing with stress" to a "standing without stress" condition. We investigated the effect of standing with and without stress on responses of the sympathetic-adrenomedullary (SAM) system and the hypothalamic-pituitary-adrenal (HPA) axis using a standardized psychosocial stress protocol (Trier Social Stress Test) and a non stress condition in a repeated measures design. Subjects (N=30) were exposed to both conditions in randomized order and had to maintain a standing, upright position for 10minutes. In the "standing with stress" condition, significant increases in repeatedly assessed plasma norepinephrine (NE) and epinephrine (EP), as well as in saliva cortisol were found, while in the "standing without stress" condition, no significant changes in plasma epinephrine and saliva cortisol were observed. Calculations of the relative contribution of orthostasis to physiological stress responses revealed that 25.61% of the NE increase, 82.94% of the EP increase, and 68.91% of the cortisol increase, could be attributed to psychosocial stress adjusted for the effects of orthostasis and basal endocrine output. Although these results are indicative for a marked endocrine reaction that is caused by psychosocial stress alone, our findings show that the contribution of orthostasis must be taken into account when interpreting endocrine data collected in a psychosocial stress test. PMID- 24177249 TI - Proline induced disruption of the structure and dynamics of water. AB - We use quasi-elastic neutron scattering spectroscopy to study the diffusive motion of water molecules at ambient temperature as a function of the solute molar fraction of the amino acid, proline. We validate molecular dynamics simulations against experimental quasielastic neutron scattering data and then use the simulations to reveal, and understand, a strong dependence of the translational self-diffusion coefficient of water on the distance to the amino acid molecule. An analysis based on the juxtaposition of water molecules in the simulation shows that the rigidity of proline imposes itself on the local water structure, which disrupts the hydrogen-bond network of water leading to an increase in the mean lifetime of hydrogen bonds. The net effect is some distortion of the proline molecule and a slowing down of the water mobility. PMID- 24177250 TI - Characterization of ROP18 alleles in human toxoplasmosis. AB - The role of the virulent gene ROP18 polymorphisms is not known in human toxoplasmosis. A total of 320 clinical samples were analyzed. In samples positive for ROP18 gene, we determined by an allele specific PCR, if patients got the upstream insertion positive ROP18 sequence Toxoplasma strain (mouse avirulent strain) or the upstream insertion negative ROP18 sequence Toxoplasma strain (mouse virulent strain). We designed an ELISA assay for antibodies against ROP18 derived peptides from the three major clonal lineages of Toxoplasma. 20 clinical samples were of quality for ROP18 allele analysis. In patients with ocular toxoplasmosis, a higher inflammatory reaction on eye was associated to a PCR negative result for the upstream region of ROP18. 23.3%, 33% and 16.6% of serums from individuals with ocular toxoplasmosis were positive for type I, type II and type III ROP18 derived peptides, respectively but this assay was affected by cross reaction. The absence of Toxoplasma ROP18 promoter insertion sequence in ocular toxoplasmosis was correlated with severe ocular inflammatory response. Determination of antibodies against ROP18 protein was not useful for serotyping in human toxoplasmosis. PMID- 24177252 TI - Lymphocyte GH-axis hormones in immunity. AB - The production and utilization of common ligands and their receptors by cells of the immune and neuroendocrine systems constitutes a biochemical information circuit between and within the immune and neuroendocrine systems. The sharing of ligands and receptors allows the immune system to serve as the sixth sense notifying the nervous system of the presence of foreign entities. Within this framework, it is also clear that immune cell functions can be altered by neuroendocrine hormones and that cells of the immune system have the ability to produce neuroendocrine hormones. This review summarizes a part of this knowledge with particular emphasis on growth hormone (GH). The past two decades have uncovered a lot of detail about the actions of GH, acting through its receptor, at the molecular and cellular level and its influence on the immune system. The production and action of immune cell-derived GH is less well developed although its important role in immunity is also slowly emerging. Here we discuss the production of GH, GH-releasing hormone (GHRH) and insulin-like growth factor-1 (IGF-1) and their cognate receptors on cells of the immune system and their influence via endocrine/autocrine/paracrine and intracrine pathways on immune function. The intracellular mechanisms of action of immune cell-derived GH are still largely unexplored, and it is anticipated that further work in this particular area will establish an important role for this source of GH in normal physiology and in pathologic situations. PMID- 24177251 TI - Enhancement of antimycobacterial Th1-cell responses by a Mycobacterium bovis BCG prime-protein boost vaccination strategy. AB - Tuberculosis is a major global health problem, and the only available vaccine Bacille Calmette-Guerin (BCG) is not sufficiently effective against the disease. It is extremely urgent to develop novel vaccine approaches. Previous research demonstrated that there were several Regions of Difference (RD1-16) between the substrains of BCG and Mycobacterium tuberculosis or Mycobacterium bovis. The ORFs Rv1769 and Rv1772 are located in the RD14 deletions and have not been major targets of study. However, some studies have demonstrated that the two genes (Rv1769 and Rv1772) are excellent T cell antigens, which might induce an immune response. What kind of role these ORFs might play in anti-mycobacterial immunity, however, is still unknown. In our research we used the BCG prime-protein boost strategy to immunize BALB/c mice and evaluated its immunogenicity. Our data suggest that our novel BCG-P+PRO69 vaccine could elicit the most long-lasting and strongest Th1 type cellular immune responses. This response is characterized by a strong antibody response, the proliferation rate of splenocytes, a high percentage of CD4+ and CD8+ T cells and high levels of IFN-gamma in antigen stimulated splenocyte cultures. These results indicate that prime-boost is a potent strategy and the protein of gene Rv1769 is a potential antigen or subunit vaccine to TB for further study. PMID- 24177253 TI - Does an intraneural interface short-term implant for robotic hand control modulate sensorimotor cortical integration? An EEG-TMS co-registration study on a human amputee. AB - PURPOSE: Following limb amputation, central and peripheral nervous system relays partially maintain their functions and can be exploited for interfacing prostheses. The aim of this study is to investigate, for the first time by means of an EEG-TMS co-registration study, whether and how direct bidirectional connection between brain and hand prosthesis impacts on sensorimotor cortical topography. METHODS: Within an experimental protocol for robotic hand control, a 26 years-old, left-hand amputated male was selected to have implanted four intrafascicular electrodes (tf-LIFEs-4) in the median and ulnar nerves of the stump for 4 weeks. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subject's cortico-cortical excitability, connectivity and plasticity were tested via a neuronavigated EEG TMS experiment. RESULTS: The statistical analysis clearly demonstrated a significant modulation (with t-test p < 0.0001) of EEG activity between 30 and 100 ms post-stimulus for the stimulation of the right hemisphere. When studying individual latencies in that time range, a global amplitude modulation was found in most of the TMS-evoked potentials; particularly, the GEE analysis showed significant differences between T0 and T1 condition at 30 ms (p < 0.0404), 46 ms (p < 0.0001) and 60 ms (p < 0.007) latencies. Finally, also a clear local decrement in N46 amplitude over C4 was evident. No differences between conditions were observed for the stimulation of the left hemisphere. CONCLUSIONS: The results of this study confirm the hypothesis that bidirectional neural interface could redirect cortical areas -deprived of their original input/output functions- toward restorative neuroplasticity. This reorganization strongly involves bi hemispheric networks and intracortical and transcortical modulation of GABAergic inhibition. PMID- 24177254 TI - Clinical impact of 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-positron emission tomography (PET) on treatment choice in recurrent cancer of the cervix uteri. AB - OBJECTIVE: The superiority of positron emission tomography (PET) with 2-deoxy-2 [18F]fluoro-D-glucose (FDG) over computed tomography and magnetic resonance imaging in detecting recurrent cervical cancer and determining the extent of the disease has been demonstrated in several clinical trials. However, there is a lack of data concerning the clinical impact of the extra findings. We report here a prospective clinical study aimed at investigating the clinical impact of FDG PET findings on the treatment plans in recurrent cervical cancer. MATERIALS AND METHODS: Thirty-six patients with suspected recurrent cervical cancer underwent FDG-PET. Relapses were confirmed in 26 cases, and one case of primary lung cancer was found. The clinical impact of the FDG-PET results was assessed using a systematic scoring system with a 4-grade scale. Median follow-up time after FDG PET was 33.1 months (range, 5-83 months) for all patients and 22.4 months (range, 5-83 months) for patients with positive PET results. RESULTS: More sites of metastases were detected with FDG-PET in 56% of the patients compared to the findings by conventional imaging. The results of FDG-PET led to a change in treatment modality for 33% of the patients; and for 22%, a change in dose or deliverance of treatment was recorded. Treatment intention was changed in 30%, in all but one patient, from curative to palliative. In 48% of the patients, the initially planned treatment was reduced regarding dose or extent, or was withheld. CONCLUSION: In recurrent cervical cancer, FDG-PET provides clinically valuable information with a high impact on treatment decisions. PMID- 24177255 TI - Is there a place for sentinel technique in treatment of vaginal cancer?: feasibility, clinical experience, and results. AB - OBJECTIVE: To evaluate the clinical feasibility of sentinel lymph node (SLN) technique and the role of single-photon emission computed tomography with CT (SPECT/CT) compared to lymphoscintigraphy for detection of SLN in vaginal cancer. METHODS: The study was performed in a prospective, unicentric setting. Patients with vaginal carcinoma were scheduled for surgery and SLN labeling by peritumoral injection of 10-MBq technetium Tc 99m nanocolloid and patent blue. After 30 minutes, lymphoscintigraphy and SPECT/CT were carried out. We evaluated the number of SLNs in lymphoscintigraphy, SPECT/CT, and intraoperative histology of SLN and non-SLN as well as the impact of these results to therapeutic approach. RESULTS: Between January 2009 and December 2012, the SLN technique was used for 7 of 11 patients treated due to vaginal cancer. Detection rate was 100% (7/7). Lymphoscintigraphy and SPECT/CT showed at least one SLN in each patient. Lymphoscintigraphy detected 2.6 SLNs (range, 2-4 SLNs) per patient compared to 4.3 SLNs (range, 2-8 SLNs) in SPECT/CT (P = 0.053). Sentinel lymph nodes were detected in all patients during surgery with a mean number of 4.3 (range, 1-5). Pelvic SLNs were detected in all 6 patients with infiltration of middle or proximal vaginal third (100%). If the distal vaginal third was additional (3/7 patients) or exclusively (1/7 patients) infiltrated, the inguinal SLN detection rate was 33% and 100%, respectively. All patients with nodal metastases had at least one SLN positive for tumor. There were no false negatives. In 2 (29%) of 7 patients, treatment approach was modified owing to affected SLN. CONCLUSION: The SLN technique was favorably used in vaginal cancer in this series. It assists in identifying an inguinal and/or pelvic lymphatic drainage. When performed accurately (technetium Tc 99m nanocolloid, lymphoscintigraphy and/or SPECT/CT, blue dye), this technique predicts regional nodal status. This allows tumor stage adjusted therapy. Single photon emission computed tomography/CT improves preoperative planning and facilitates detection, thus enhancing the clinical value of the SLN technique and improving the oncologic safety of surgery. PMID- 24177256 TI - Detection of sentinel nodes for endometrial cancer with robotic assisted fluorescence imaging: cervical versus hysteroscopic injection. AB - OBJECTIVE: Sentinel lymph node (SLN) mapping with indocyanine green (ICG) detected by robotic near infrared (NIR) imaging is a feasible technique. The optimal site of injection (cervical or endometrial) for endometrial cancer has yet to be determined. We prospectively evaluated SLN mapping after cervical and endometrial injections of ICG to compare the detection rates and patterns of nodal distribution. METHODS: Twenty-nine subjects with endometrial cancer undergoing robotic hysterectomy with lymphadenectomy by a single surgeon received SLN mapping with robotic fluorescence imaging. Seventeen patients received cervical injections of 1 mg of ICG and 12 patients received hysteroscopic endometrial injections of 0.5-mg ICG. Detection rates between the 2 groups were compared using Fisher exact tests. Continuous variables such as operating room times and body mass index were compared using t tests. RESULTS: The SLN detection rate was 82% (14/17) for cervical and 33% (4/12) for hysteroscopic injection (P = 0.027). Sentinel lymph nodes were seen bilaterally in 57% (8/14) of the cervical injection group and 50% (2/4) of the hysteroscopic group. Para-aortic SLNs were seen in 71% (10/14) of patients who mapped after cervical injection and 75% (3/4) patients who mapped after hysteroscopic injection. There was 1 false-negative SLN in the cervical injection group. CONCLUSIONS: Cervical ICG injection achieves a higher SLN detection rate and a similar anatomic nodal distribution as hysteroscopic endometrial injection for SLN mapping in patients with endometrial cancer. PMID- 24177259 TI - A revised NOTCH1 mutation frequency still impacts survival while the allele burden predicts early progression in chronic lymphocytic leukemia. PMID- 24177260 TI - Electric and magnetic field effects on the excitonic properties of elliptic core multishell quantum wires. AB - The effect of eccentricity distortions of core-multishell quantum wires on their electron, hole and exciton states is theoretically investigated. Within the effective mass approximation, the Schrodinger equation is numerically solved for electrons and holes in systems with single and double radial heterostructures, and the exciton binding energy is calculated by means of a variational approach. We show that the energy spectrum of a core-multishell heterostructure with eccentricity distortions, as well as its magnetic field dependence, are very sensitive to the direction of an externally applied electric field, an effect that can be used to identify the eccentricity of the system. For a double heterostructure, the eccentricities of the inner and outer shells play an important role on the excitonic binding energy, especially in the presence of external magnetic fields, and lead to drastic modifications in the oscillator strength. PMID- 24177258 TI - International Myeloma Working Group recommendations for global myeloma care. AB - Recent developments have led to remarkable improvements in the assessment and treatment of patients with multiple myeloma (MM). New technologies have become available to precisely evaluate the biology and extent of the disease, including information about cytogenetics and genetic abnormalities, extramedullary manifestations and minimal residual disease. New, more effective drugs have been introduced into clinical practice, which enable clinicians to significantly improve the outcome of patients but also pose new challenges for the prevention and management of their specific side effects. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of patients, as access to the most sophisticated advances may vary depending on local circumstances. Here, we propose the minimal requirements and possible options for diagnosis, monitoring and treatment of patients with multiple myeloma. PMID- 24177261 TI - Endocrine disruption: fact or urban legend? AB - Endocrine disruptors (EDs) are substances that cause adverse health effects via endocrine-mediated mechanisms in an intact organism or its progeny or (sub) populations. Purported EDCs in personal care products include 4-MBC (UV filter) or parabens that showed oestrogenic activity in screening tests, although regulatory toxicity studies showed no adverse effects on reproductive endpoints. Hormonal potency is the key issue of the safety of EDCs. Oestrogen-based drugs, e.g. the contraceptive pill or the synthetic oestrogen DES, possess potencies up to 7 orders of magnitude higher than those of PCP ingredients; yet, in utero exposure to these drugs did not adversely affect fertility or sexual organ development of offspring unless exposed to extreme doses. Additive effects of EDs are unlikely due to the multitude of mechanisms how substances may produce a hormone-like activity; even after uptake of different substances with a similar mode of action, the possibility of additive effects is reduced by different absorption, metabolism and kinetics. This is supported by a number of studies on mixtures of chemical EDCs. Overall, despite of 20 years of research a human health risk from exposure to low concentrations of exogenous chemical substances with weak hormone-like activities remains an unproven and unlikely hypothesis. PMID- 24177257 TI - Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. AB - IMPORTANCE: The current recommendation is for at least 12 months of dual antiplatelet therapy after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown. OBJECTIVE: To assess the clinical noninferiority of 3 months (short-term) vs 12 months (long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) with zotarolimus eluting stents. DESIGN, SETTING, AND PATIENTS: The OPTIMIZE trial was an open label, active-controlled, 1:1 randomized noninferiority study including 3119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow up was performed at 1, 3, 6, and 12 months. Eligible patients were those with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing PCI with zotarolimus-eluting stents. INTERVENTIONS: After PCI with zotarolimus-eluting stents, patients were prescribed aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1563) or 12 months (n = 1556), unless contraindicated because of occurrence of an end point. MAIN OUTCOMES AND MEASURES: The primary end point was net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction [MI], stroke, or major bleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%. Secondary end points were major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization) and Academic Research Consortium definite or probable stent thrombosis. RESULTS: NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 [95% CI, -1.52 to 1.86]; P = .002 for noninferiority). Kaplan-Meier estimates demonstrated MACE rates at 1 year of 8.3% (128) in the short-term group and 7.4% (114) in the long-term group (HR, 1.12 [95% CI, 0.87-1.45]). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 [2.6%] vs 38 [2.6%] for the short- and long-term groups, respectively; HR, 1.03 [95% CI, 0.66-1.60]), MACE (78 [5.3%] vs 64 [4.3%]; HR, 1.22 [95% CI, 0.88-1.70]), or stent thrombosis (4 [0.3%] vs 1 [0.1%]; HR, 3.97 [95% CI, 0.44-35.49]). CONCLUSIONS AND RELEVANCE: In patients with stable coronary artery disease or low-risk ACS treated with zotarolimus eluting stents, 3 months of dual antiplatelet therapy was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01113372. PMID- 24177262 TI - Folic acid supplementation during pregnancy protects against lipopolysaccharide induced neural tube defects in mice. AB - Folic acid is a water-soluble B-complex vitamin. Increasing evidence demonstrates that physiological supply of folic acid during pregnancy prevents folic acid deficiency-related neural tube defects (NTDs). Previous studies showed that maternal lipopolysaccharide (LPS) exposure caused NTDs in rodents. The aim of this study was to investigate the effects of high-dose folic acid supplementation during pregnancy on LPS-induced NTDs. Pregnant mice were intraperitoneally injected with LPS (20 MUg/kg/d) from gestational day (GD) 8 to GD12. As expected, a five-day LPS injection resulted in 19.96% of fetuses with NTDs. Interestingly, supplementation with folic acid (3mg/kg/d) during pregnancy significantly alleviated LPS-induced NTDs. Additionally, folic acid significantly attenuated LPS-induced fetal growth restriction and skeletal malformations. Additional experiment showed that folic acid attenuated LPS-induced glutathione (GSH) depletion in maternal liver and placentas. Moreover, folic acid significantly attenuated LPS-induced expression of placental MyD88. Additionally, folic acid inhibited LPS-induced c-Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor kappa B (NF-kappaB) activation in placentas. Correspondingly, folic acid significantly attenuated LPS-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in placentas, maternal serum and amniotic fluid. In conclusion, supplementation with high-dose folic acid during pregnancy protects against LPS-induced NTDs through its anti-inflammatory and anti oxidative effects. PMID- 24177263 TI - Swap70b is required for convergent and extension cell movement during zebrafish gastrulation linking Wnt11 signalling and RhoA effector function. AB - Swap70 functions as a guanine nucleotide exchange factor for Rac and RhoA regulating F-actin cytoskeletal rearrangements and playing a crucial role in mammalian cell activation, migration, adhesion and invasion. Here we show that the zebrafish orthologue, Swap70b, is required for convergent and extension cell movement during gastrulation. Swap70b morphants exhibited broader and shorter body axis but cell fate specification appeared normal. While ectopic Swap70b expression robustly rescued Wnt11 morphants, RhoA overexpression was sufficient to rescue Swap70b morphants, establishing Swap70b as a novel member of the non canonical Wnt/PCP pathway downstream of Wnt11 and upstream of RhoA. This is distinct from the related Def6a protein that acts downstream of Wnt5b. Def6a/Swap70b morphants resemble Ppt/Slb double mutant embryos suggesting that Swap70b and Def6a delineate Wnt11 and Wnt5b signalling pathways. PMID- 24177264 TI - AGREEMENT BETWEEN THE WHITE MATTER CONNECTIVITY BASED ON THE TENSOR-BASED MORPHOMETRY AND THE VOLUMETRIC WHITE MATTER PARCELLATIONS BASED ON DIFFUSION TENSOR IMAGING. AB - We are interested in investigating white matter connectivity using a novel computational framework that does not use diffusion tensor imaging (DTI) but only uses T1-weighted magnetic resonance imaging. The proposed method relies on correlating Jacobian determinants across different voxels based on the tensor based morphometry (TBM) framework. In this paper, we show agreement between the TBM-based white matter connectivity and the DTI-based white matter atlas. As an application, altered white matter connectivity in a clinical population is determined. PMID- 24177265 TI - Endoscopic functional imaging of partial tendon tears--proof of concept and intraoperative feasibility. AB - The ability to quantify the biomechanical integrity of tendons could provide useful information for both clinical diagnostics and for clinical follow-up in tracking functional recovery of the injured tissue. This study develops and characterizes a functional endoscopy approach for intraoperative quantification of tendon tear severity using both ex vivo and in vivo experimental models. We first verified the accuracy of endoscopic strain (i.e., tissue stretch) imaging in an ex vivo tear model by comparing endoscopic measurements against gold standard measurements with research grade optics. We then tested in vivo feasibility by endoscopically quantifying altered tissue strain distributions in a rat supraspinatus model of partial tendon tear. The endoscopic method was able to achieve diagnostically relevant levels of accuracy compared to research grade optics (mean error = 26.2 +/- 19.1%), and tissue strain analysis could sensitively discern torn tendon subregions. Applying this approach to free-hand in vivo endoscopic strain measurements, we were similarly able to discern functional changes in partially torn tendons (average maximum principal strains surrounding the lesion: 5.1 +/- 2.9% versus intact controls: 1.9 +/- 1.4%; p = 0.023). These findings indicate that the functional endoscopic assessment of tendon mechanical integrity is not only possible but could potentially offer intraoperative arthroscopic guidance for management of tendon tears in man. PMID- 24177266 TI - Education and home based training for intermittent claudication: functional effects and quality of life. AB - BACKGROUND: Supervised exercise programs increase physical performance in patients with peripheral artery disease (PAD). However, there are a limited number of programs, and to date they have failed to provide evidence of long-term adherence to exercise or any meaningful effect on Quality of Life (QoL). We created a program of therapeutic education and a personalized program of reconditioning exercise for patients with PAD. METHODS: Patients with an ankle brachial index (ABI) below 0.9 in at least one limb, and an absolute claudication distance (ACD) <=500 meters, were included in the study. Quality of Life (QoL) as measured by SF-36, cardiovascular risk factors and functional parameters were evaluated at 0, 3, 6 and 12 months. RESULTS: Forty-six patients completed the program. Cardiovascular risks were controlled and stabilized over time. SF-36 scores improved significantly and remained stable. Initial and absolute claudication distance (ICD and ACD) as well as other functional parameters improved significantly (6 months: +138 m or +203% ICD and +139 m or +84% ACD). Ten patients (22%) did not show improvement in ICD or ACD within the first 3 months, but their SF-36 score did increase at subsequent visits. Interestingly, these patients had a significantly lower ACD at baseline. CONCLUSIONS: This study measured beneficial effects of an educational therapeutic program for patients with PAD. The results demonstrate a significant improvement in functional and QoL parameters during the first 3 months of coaching, and long-term persistence of the results even when patients were no longer coached. PMID- 24177267 TI - Presence of gallstones and the risk of cardiovascular diseases: The EPIC-Germany cohort study. AB - BACKGROUND: Gallstones are common disorders associated with several cardiovascular risk factors. Gallstone formation and atherosclerosis may share key pathways, but studies on putative associations between gallstones and the risk of cardiovascular disease are sparse and non-conclusive. We studied the relationship between gallstones and the risk of subsequent cardiovascular diseases in the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: The study comprises 46,468 participants from EPIC Potsdam and EPIC-Heidelberg aged 35-65 years, free of cardiovascular diseases and diabetes at baseline. Information about the gallstone status at baseline was ascertained via questionnaires. For all incident cases of myocardial infarction and stroke confirmation was obtained from the treating physician. Relative risks were estimated using Cox proportional hazards regression. RESULTS: During eight years of follow-up, 919 participants suffered a stroke or myocardial infarction. After multivariable adjustment for established risk factors, subjects with reported gallstones (n = 4828) had an increased risk of cardiovascular diseases (hazard rate ratio (HR) = 1.24, 95% confidence interval (CI): 1.02, 1.50). In individuals, who underwent a cholecystectomy before baseline a 1.32-fold increase in risk was observed (95%CI: 1.05, 1.65). HRs differed depending on the presence of selected established risk factors (e.g. HR for cardiovascular diseases regarding gallstones in smokers = 1.66, 95%CI: 1.20, 2.30, and non-smokers = 1.09, 95%CI: 0.86, 1.38). CONCLUSIONS: Our results indicate an increased cardiovascular risk for gallstone formers, which cannot be counteracted by gallbladder removal and opens up perspectives for individualized prevention strategies. PMID- 24177268 TI - Bipolar switching polarity reversal by electrolyte layer sequence in electrochemical metallization cells with dual-layer solid electrolytes. AB - Bipolar switching behaviours of electrochemical metallization (ECM) cells with dual-layer solid electrolytes (SiOx-Ge0.3Se0.7) were analyzed. Type 1 ECM cell, Pt (bottom electrode)/SiOx/Ge0.3Se0.7/Cu (top electrode), exhibited typical eightwise current-voltage (I-V) hysteresis of ECM cells whereas Type 2 ECM cell, Pt (bottom electrode)/Ge0.3Se0.7/SiOx/Cu(top electrode), showed counter-eightwise hysteresis. In addition, absolute off-switching voltage in Type 2 cell is lower than that in Type 1 cell while on-switching voltage in both cells is almost the same. An attempt to understand this electrolyte-stack-sequence-depending switching polarity reversal was made in terms of the ECM cell potential change upon the electrolyte stack sequence and the consequent change in Cu filament growth direction. Relevant experimental evidence for the hypothesis was obtained regarding the switching behaviours. Furthermore, given the switching polarity reversal, feasibility of serial complementary resistive switches was also demonstrated. PMID- 24177269 TI - Site specific carboxylation of abnormal anionic N-heterocyclic dicarbenes with CO2. AB - Herein, we report experimental and computational results for the carboxylation of abnormal anionic N-heterocyclic dicarbenes (NHDCs) with CO2. Under ambient dosing conditions, carbonyl addition occurs selectively at C4 without a second carboxylation event occurring at the C2 carbene center. PMID- 24177270 TI - Tick-borne encephalitis virus triggers inositol-requiring enzyme 1 (IRE1) and transcription factor 6 (ATF6) pathways of unfolded protein response. AB - Tick-borne encephalitis (TBE) is a serious human neurological disease caused by TBE virus (TBEV). However, the mechanisms of TBEV-caused pathogenesis remain unclear. The endoplasmic reticulum (ER) stress response, also defined as the unfolded protein response (UPR), is an important conserved molecular signaling pathway that modulates many biological functions including innate immunity and viral pathogenesis. Here, we investigated the effects of the two UPR signaling pathways upon TBEV infection in Vero E6 cells. We showed that the amount of heat shock protein 72 (Hsp72) increased in the course of TBEV infection. We then confirmed that TBEV infection activates the IRE1 pathway, leading to RNA and protein expression of the spliced X box binding protein 1 (sXBP1). Furthermore, we observed the translocation of ATF6 during TBEV infection and expression of cleaved transcription factor 6 (ATF6) which suggest activation of ATF6 pathway. Finally, we examined whether inhibition of the IRE1 pathway has an effect on TBEV infection. Cell treatment with 3,5-Dibromosalicylaldehyde (IRE1 inhibitor) and tauroursodeoxycholic acid (TUDCA) showed that TBEV replication was significantly limited. These findings provide the first evidence that TBEV infection activates the two UPR signaling pathways. Moreover, inhibition of TBEV replication by UPR inhibitors may provide a novel therapeutic strategy against TBE. PMID- 24177271 TI - Coxsackievirus B3-induced calpain activation facilitates the progeny virus replication via a likely mechanism related with both autophagy enhancement and apoptosis inhibition in the early phase of infection: an in vitro study in H9c2 cells. AB - Calpain is a family of neutral cysteine proteinase involved in many physiological and pathological processes including virus replication, autophagy and apoptosis. Previous study has indicated the involvement of calpain in pathogenesis of coxsackievirus B3 (CVB3)-induced myocarditis. Besides, many studies demonstrated that host cell autophagy and apoptosis mechanisms participate in virus life cycle. However, role of calpain in CVB3 replication via autophagy/apoptosis mechanisms has not been reported, which was discussed here in H9c2 cardiomyocytes. The data demonstrated that calpain was activated following CVB3 infection. Calpain inhibition decreased autophagy, indicating role of calpain in enhancing autophagy during CVB3 infection. Both calpain activity and autophagy were involved in facilitating CVB3 replication demonstrated by virus titer and CVB3 capsid protein VP1 expression alterations resulting from calpain inhibitor ALLN and autophagy inhibitor 3MA intervention. We also found that both calpain activity and autophagy suppressed caspase3 activity and host cell apoptosis 5-10h post-infection (p.i.). In summary, the present study shows that CVB3 infection of H9c2 cells hinders caspase3 activity provocation and cell apoptosis at least in the early phase of infection (5-10h p.i.) via calpain-induced autophagy enhancement, which might be a mechanism facilitating CVB3 replication in host cells. PMID- 24177272 TI - Efficient N-glycosylation at position 37, but not at position 146, in the street rabies virus glycoprotein reduces pathogenicity. AB - Most street rabies viruses have two N-glycosylation sites in their glycoproteins (G proteins), i.e., at Asn(37) and Asn(319), but Asn(37) is usually not core glycosylated in an efficient manner. Previously, we reported the possible roles of single additional N-glycosylations at Asn(194) or Asn(247) in the cell adaptation and reduced pathogenicity of a street rabies virus, which suggest that N-glycosylation is closely related to the evolution of rabies viruses. In this study, we characterized two novel N-glycosylation-modified variants, N5C#7 and N5C#8, which were cloned using the limiting dilution method after serial passaging of the street rabies virus strain 1088 in mouse neuroblastoma-derived NA cells. N5C#7 had an L38R mutation in the G protein, which led to efficient core glycosylation at Asn(37). On the other hand, N5C#8 had a D146N mutation in the G protein, which led to an additional N-glycosylation at position 146. Both variants replicated highly efficiently in NA cells compared with the parental strain. Like the parental strain, both variants caused lethal infections in adult mice after intracerebral inoculation. However, N5C#7 exhibited reduced pathogenicity after intramuscular inoculation, whereas N5C#8 displayed the same level of pathogenicity as the parental strain. In summary, the efficient core glycosylation at position 37 was related to cell adaptation and the reduced pathogenicity of the street rabies virus. By contrast, despite of being related to cell adaptation, the additional N-glycosylation at position 146 did not affect the pathogenicity, which is consistent with a report that street rabies virus strains with N-glycosylation sites at positions 37, 146, and 319 have been isolated from rabid animals. Thus, the results of the present study provide additional evidence that supports the relationship between G protein N glycosylation and rabies virus evolution. PMID- 24177274 TI - Stochastic switching of cantilever motion. AB - The cantilever is a prototype of a highly compliant mechanical system and has an instrumental role in nanotechnology, enabling surface microscopy, and ultrasensitive force and mass measurements. Here we report fluctuation-induced transitions between two stable states of a strongly driven microcantilever. Geometric nonlinearity gives rise to an amplitude-dependent resonance frequency and bifurcation occurs beyond a critical point. The cantilever response to a weak parametric modulation is amplified by white noise, resulting in an optimum signal to-noise ratio at finite noise intensity. This stochastic switching suggests new detection schemes for cantilever-based instrumentation, where the detection of weak signals is mediated by the fluctuating environment. For ultrafloppy, cantilevers with nanometer-scale dimensions operating at room temperature--a new transduction paradigm emerges that is based on probability distributions and mimics nature. PMID- 24177273 TI - The effects of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) on fuel stores and ion balance in a non-target fish, the rainbow trout (Oncorhynchus mykiss). AB - The pesticide 3-trifluoromethyl-4-nitrophenol (TFM) is used to control sea lamprey (Petromyzon marinus) populations in the Great Lakes through its application to nursery streams containing larval sea lampreys. TFM uncouples oxidative phosphorylation, impairing mitochondrial ATP production in sea lampreys and rainbow trout (Oncorhynchus mykiss). However, little else is known about its sub-lethal effects on non-target aquatic species. The present study tested the hypotheses that TFM exposure in hard water leads to (i) marked depletion of energy stores in metabolically active tissues (brain, muscle, kidney, liver) and (ii) disruption of active ion transport across the gill, adversely affecting electrolyte homeostasis in trout. Exposure of trout to 11.0mgl(-1) TFM (12-h LC50) led to increases in muscle TFM and TFM-glucuronide concentrations, peaking at 9h and 12h, respectively. Muscle and brain glycogen was reduced by 50%, while kidney and muscle lactate increased with TFM exposure. Kidney ATP and phosphocreatine decreased by 50% and 70%, respectively. TFM exposure caused no changes in whole body ion (Na(+), Cl(-), Ca(2+), K(+)) concentrations, gill Na(+)/K(+) ATPase activity, or unidirectional Na(+) movements across the gills. We conclude that TFM causes a mismatch between ATP supply and demand in trout, leading to increased reliance on glycolysis, but it does not have physiologically relevant effects on ion balance in hard water. PMID- 24177276 TI - Quantum state-resolved CH4 dissociation on Pt(111): coverage dependent barrier heights from experiment and density functional theory. AB - The dissociative chemisorption of CH4 on Pt(111) was studied using quantum state resolved methods at a surface temperature (T(s)) of 150 K where the nascent reaction products CH3(ads) and H(ads) are stable and accumulate on the surface. Most previous experimental studies of methane chemisorption on transition metal surfaces report only the initial sticking coefficients S0 on a clean surface. Reflection absorption infrared spectroscopy (RAIRS), used here for state resolved reactivity measurements, enables us to monitor the CH3(ads) uptake during molecular beam deposition as a function of incident translational energy (E(t)) and vibrational state (nu3 anti-symmetric C-H stretch of CH4) to obtain the initial sticking probability S0, the coverage dependence of the sticking probability S(theta) and the CH3(ads) saturation coverage theta(sat). We observe that both S0 and theta(sat) increase with increasing E(t) as well as upon nu3 excitation of the incident CH4 which indicates a coverage dependent dissociation barrier height for the dissociation of CH4 on Pt(111) at low surface temperature. This interpretation is supported by density functional calculations of barrier heights for dissociation, using large supercells containing one or more H and/or methyl adsorbates. We find a significant increase in the activation energies with coverage. These energies are used to construct simple models that reasonably reproduce the uptake data and the observed saturation coverages. PMID- 24177275 TI - APL-1, an altered peptide ligand derived from human heat-shock protein 60, selectively induces apoptosis in activated CD4+ CD25+ T cells from peripheral blood of rheumatoid arthritis patients. AB - Rheumatoid arthritis (RA) is a chronic T-cell mediated autoimmune disease that affects primarily the joints. The induction of immune tolerance through antigen specific therapies for the blockade of pathogenic CD4+ T cells constitutes a current focus of research. In this focus it is attempted to simultaneously activate multiple regulatory mechanisms, such as: apoptosis and regulatory T cells (Tregs). APL-1 is an altered peptide ligand derived from a novel CD4+ T cell epitope of human heat-shock protein of 60kDa, an autoantigen involved in the pathogenesis of RA. Previously, we have reported that APL-1 induces CD4+ CD25(high)Foxp3+ Tregs in several systems. Here, we investigated the ability of APL-1 in inducing apoptosis in PBMCs from RA patients, who were classified as active or inactive according to their DAS28 score. APL-1 decreased the viability of PBMCs from active but not from inactive patients. DNA fragmentation assays and typical morphological features clearly demonstrated that APL-1 induced apoptosis in these cells. Activated CD4+ CD25+ T cells but not resting CD4+ CD25- T cells were identified as targets of APL-1. Furthermore, CD4+ T-cell responses to APL-1 were found to be dependent on antigen presentation via the HLA-DR molecule. Thus, APL-1 is a regulatory CD4+ T cell epitope which might modulate inflammatory immune responses in PBMCs from RA patients by inducing CD4+ CD25(high)Foxp3+ Tregs and apoptosis in activated CD4+ T cells. These results support further investigation of this candidate drug for the treatment of RA. PMID- 24177277 TI - Scanning electron microscopy observations of osseointegration failures of dental implants that support mandibular overdentures. AB - AIM: : Investigating possible failure causes of mandibular implants after their immediate loading with an overdenture retained with bilateral bar attachments, using scanning electron microscope. PATIENTS AND METHODS: Twenty edentulous male patients were included in the present study. Each patient had 2 fixtures inserted in the canine and the first molar areas on each side of the mandible. After abutments screwing, the 2 fixtures on the same side were splinted with a bar, and immediately loaded with an overdenture. Implants mobility was assessed on weekly basis. Failed implants were removed, and examined by scanning electron microscope. RESULTS: The failed implants, removed after 4 weeks of treatment, showed an intimate contact of mineralized and osteoid tissues with dense collagen rich matrix in the apical third of implants. Furthermore, newly developed bone was observed at the same area in implants removed after 7 weeks. However, there was no evidence of such growth at the middle and/or cervical thirds in either case. CONCLUSION: Lack of osseointegration at the middle and cervical thirds of the root could be a possible cause of implant failure. Early loading by an overdenture retained with bilateral bars is considered a major contributing factor to incomplete osseointegration of the supporting implants. PMID- 24177278 TI - One-year survival rate outcomes of innovative dental implants: a prospective clinical study. AB - PURPOSE: The aim of this research was to evaluate an innovative implant design for different placement and loading protocols. The unique implant is a combination of tapered and cylindrical shape, which is aimed to enhance initial stability and long-term osseointegration. MATERIALS AND METHODS: Four hundred and sixty implants were placed in 141 patients under different placement and loading protocols in similarity to those encountered in a dental office. Implants were followed and evaluated for 1 year to assert the survival rate of the newly introduced implant. RESULTS: The results showed a total of 97.4% survival rate, ranging from 92% to 98.6% depending on the different protocols. There was no statistical difference between the different protocol groups. CONCLUSION: The new implant design showed good results for 1 year of follow-up, comparable with the literature, and could be a good choice for every implant-based procedure. PMID- 24177279 TI - Branemark system implant lengths in the pterygomaxillary region: a retrospective comparison. AB - PURPOSE: Implants that engage the cortical bone of the pterygomaxillary region help restore dentition to the posterior maxilla. However, proper implant length is required. The purpose of this study was to determine if there is a statistically significant difference in the survival rates between different sized implants placed in the pterygomaxillary region. MATERIALS AND METHODS: All Branemark System 4.0-mm-diameter implants delivered into the pterygomaxillary region in a single private practice were separated into 7- to 13-mm and 15- to 18 mm groups by retrospective patient chart review. Cumulative survival rates (CSR) were calculated. RESULTS: Of all implants delivered, 930 of the 992 osseointegrated for a CSR of 93.75%. Fifty-nine of the 67 implants in the 7- to 13-mm grouping and 871 of the 925 implants in the 15- to 18-mm grouping osseointegrated for CSRs of 88.06% and 94.16%, respectively. The results were statistically significant (P < 0.05). CONCLUSIONS: The results suggest that increased implant length in the pterygomaxillary region may result in higher osseointegration rates. The implant apex better engages the cortical bone between the medial and lateral pterygoid plates and therefore increases primary and secondary stability. PMID- 24177281 TI - Laboratory and clinical considerations on prosthetic zirconia infrastructures for implants. AB - Zirconia is a ceramic material that is used for constructing prosthetic infrastructures and implant abutments using CAD/CAM techniques. Although good initial mechanical properties are obtained with zirconia that is partially stabilized by yttrium, it may age in a moist environment, compromising such properties and, consequently, the longevity of the restorative work. To optimize the longevity of this material, it is essential that the clinician and laboratory technician understand its mechanical properties and limitations and take specific precautions needed to maintain its mechanical properties and ensure long-term performance especially in implant prosthetics. This article presents a clinical case where these precautions were taken, emphasizing the key surface treatments advocated for zirconia. PMID- 24177280 TI - Effects of hierarchical micro/nano-textured titanium surface features on osteoblast-specific gene expression. AB - PURPOSE: To investigate the influence of hierarchical hybrid micro/nano-textured titanium surface features on osteoblast differentiation. MATERIALS AND METHODS: In this study, 3 different implant discs were produced: a hierarchical hybrid micro-/nanostructured titanium surface topography was modified using electrolytic etching (EE) technique, and a sandblasted, acid-etched (SLA) group and a machined (M) group were used as control groups. MG-63 cells were cultured on discs for 1 day to 7 days. The osteoblast response to the hierarchical hybrid micro /nanostructured titanium surface was evaluated through the osteoblastic alkaline phosphatase (ALP) activity and gene (OCN, RUNX2, OPN, and Col-I) expression. RESULTS: On the first, third, fifth and seventh day, the ALP activity, OCN, RUNX2, OPN, and Col-I messenger RNA gene expression, levels of EE were higher in EE group than in M and SLA groups. CONCLUSION: Hierarchical hybrid micro /nanostructured titanium surface has a favorable biocompatibility, which can promote osteoblast differentiation. It could possibly accelerate bone growth, promote bone formation at early stage, and guarantee the immediate loading and early stage loading in clinical practice. PMID- 24177282 TI - The global scope of authors. PMID- 24177283 TI - Malnutrition coding 101: financial impact and more. AB - Recent articles have addressed the characteristics associated with adult malnutrition as published by the Academy of Nutrition and Dietetics (the Academy) and the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). This article describes a successful interdisciplinary program developed by the Department of Food and Nutrition at New York-Presbyterian Hospital to maintain and monitor clinical documentation, ensure accurate International Classification of Diseases 9th Edition (ICD-9) coding, and identify subsequent incremental revenue resulting from the early identification, documentation, and treatment of malnutrition in an adult inpatient population. The first step in the process requires registered dietitians to identify patients with malnutrition; then clear and specifically worded diagnostic statements that include the type and severity of malnutrition are documented in the medical record by the physician, nurse practitioner, or physician's assistant. This protocol allows the Heath Information Management/Coding department to accurately assign ICD-9 codes associated with protein-energy malnutrition. Once clinical coding is complete, a final diagnosis related group (DRG) is generated to ensure appropriate hospital reimbursement. Successful interdisciplinary programs such as this can drive optimal care and ensure appropriate reimbursement. PMID- 24177284 TI - The effect of parenteral lipid emulsions on pulmonary hemodynamics and eicosanoid metabolites in preterm infants: a pilot study. AB - BACKGROUND: Soy-based intravenous fat emulsion (IVFE) is known to cause a rise in pulmonary artery pressure in the preterm infant, thought to be mediated through eicosanoid metabolites of linoleic acid. We compared the effect of soy-based IVFE and an olive-oil-based IVFE containing less than half the content of linoleic acid on pulmonary artery pressure and eicosanoid metabolites in preterm infants receiving parenteral nutrition. METHODS: In this pilot study at a regional neonatal intensive care unit (ICU), infants received either a soy-based or olive oil-based IVFE as part of an otherwise identical feeding protocol. Pulmonary artery pressure and urinary thromboxane B2 and prostaglandin F1 alpha were measured at baseline and maximum lipid infusion. RESULTS: There was a greater fall in pulmonary artery pressure in the olive-oil-based IVFE group compared with the soy-based IVFE group. A decrease in urine thromboxane/prostaglandin F1 alpha ratio was seen only in the olive-oil-based IVFE group. CONCLUSIONS: In the parenterally fed preterm infant, an olive-oil-based IVFE may have a beneficial effect on pulmonary artery pressure when compared with soy-based IVFE. Effects on pulmonary vascular tone are likely to be mediated through alterations in eicosanoid metabolism. A randomized trial is warranted to compare the effects of different lipid emulsions. PMID- 24177285 TI - The Academy of Nutrition and Dietetics/the American Society for Parenteral and Enteral Nutrition consensus malnutrition characteristics: application in practice. AB - Malnutrition in adult hospitalized patients has been a significant issue for almost 40 years. Changes in 2007 to the diagnosis related groups reimbursement methodology, as outlined by the Center for Medicare and Medicaid Services, provided an impetus to improve the diagnosis and documentation of malnutrition in adult patients. Being able to accurately assess, diagnose, and document malnutrition has been challenged by the lack of a standard malnutrition definition. In 2012 a workgroup of the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition published a consensus paper outlining characteristics for the diagnosis of adult hospital malnutrition. Using the etiology approach for defining malnutrition as outlined by Jensen and colleagues, 6 general characteristics are outlined with specific thresholds to delineate severe and nonsevere malnutrition. The purpose of this article is to provide practical strategies for criteria implementation and to describe one institution's experience in implementing a broad-based "malnutrition program" within its healthcare system. PMID- 24177286 TI - Novel magnet-retained prosthetic system for facial reconstruction. AB - Traumatic facial defects negatively impact speech, mastication, deglutition, dental hygiene, and psychosocial well-being. Reconstruction must address restoration of function and aesthetics to provide quality of life. This report describes soft-tissue reconstruction using a novel magnet-retained facial prosthesis without osseointegrated abutments, performed in a patient after traumatic loss of the entire left lower part of the face, including lips, commissure, and mentum. This reconstructive technique successfully addressed the cosmetic defect while also restoring function with respect to speech and oral nutrition. For this reason, magnet-retained facial prosthesis should be added to free tissue transfer and regional flaps as a reasonable option in the reconstructive algorithm for complex soft-tissue defects of the lower face. PMID- 24177287 TI - Verapamil augments the neuroprotectant action of berberine in rat model of transient global cerebral ischemia. AB - Various potential molecules with putative positive role in stroke pathology have failed to confer neuro-protection in animal models due to their insufficient bioavailability in brain. Efflux of these molecules by P-glycoprotein (P-gp), on blood brain barrier (BBB) is one of the reasons of their poor bioavailability. Berberine, have anti-inflammatory, antioxidant, anti-apoptotic properties, but also having low oral bioavailabilty. Verapamil, which increased the central nervous system uptake of few drugs, when concomitantly administered with berberine was evaluated in this animal model. Wistar rats were subjected to bilateral common carotid artery occlusion to induce acute cerebral ischemia for 15 min followed by reperfusion resulting in transient global cerebral ischemia. For 19 days berberine (5, 10, 20mg/kg, p.o.) alone and in similar doses concomitantly with verapamil (2mg/kg, p.o.) was evaluated employing various neuro behavioral test, biochemical parameters and molecular estimations. The adjunction of berberine with verapamil improved the neurological outcome in a battery of behavioral paradigms, improved spatial memory in Morris water maze task, ameliorated the oxidative-nitrosative stress, increased acetylcholinesterase (AChE) activity, as well as improved mitochondrial complex (I, II, and IV) activity, reducing tumor necrosis factor-alpha, interleukin-1 beta and caspase-3 levels in brain tissues as compared to berberine alone group in ischemic rats. There is a strong possibility of improved brain bioavailabity of berberine when combined with verapamil. The findings suggested that the combination of berberine with verapamil, which could enhance its brain uptake, will surely provide a greater impact in neroprotection drug discovery for search of such combination. PMID- 24177288 TI - A novel selective androgen receptor modulator, NEP28, is efficacious in muscle and brain without serious side effects on prostate. AB - Age-related androgen depletion is known to be a risk factor for various diseases, such as osteoporosis and sarcopenia. Furthermore, recent studies have demonstrated that age-related androgen depletion results in accumulation of beta amyloid protein and thereby acts as a risk factor for the development of Alzheimer's disease. Supplemental androgen therapy has been shown to be efficacious in treating osteoporosis and sarcopenia. In addition, studies in animals have demonstrated that androgens can play a protective role against Alzheimer's disease. However, androgen therapy is not used routinely for these indications, because of side effects. Selective androgen receptor modulators (SARMs) are a new class of compounds. SARMs maintain the beneficial effects of androgens on bone and muscle while reducing unwanted side effects. NEP28 is a new SARM exhibiting high selectivity for androgen receptor. To investigate the pharmacological effects of NEP28, we compared the effects on muscle, prostate, and brain with mice that were androgen depleted by orchidectomy and then treated with either placebo, NEP28, dihydrotestosterone, or methyltestosterone. We demonstrated that NEP28 showed tissue-selective effect equivalent to or higher than existing SARMs. In addition, the administration of NEP28 increased the activity of neprilysin, a known Abeta-degrading enzyme. These results indicate that SARM is efficacious for the treatment of not only osteoporosis and sarcopenia, but also Alzheimer's disease. PMID- 24177289 TI - Magnetic field implementation in multiband k?p Hamiltonians of holes in semiconductor heterostructures. AB - We propose an implementation of external homogeneous magnetic fields in k?p Hamiltonians for holes in heterostructures, in which we make use of the minimal coupling prior to introducing the envelope function approximation. Illustrative calculations for holes in InGaAs quantum dot molecules show that the proposed Hamiltonian outperforms the standard Luttinger model (Luttinger 1956 Phys. Rev. 102 1030) describing the experimentally observed magnetic response. The present implementation culminates our previous proposal (Planelles et al 2010 Phys. Rev. B 82 155307). PMID- 24177290 TI - Production of highly potent recombinant siRNAs in Escherichia coli. AB - We recently invented a method to produce highly potent siRNAs in Escherichia coli, based on the serendipitous discovery that ectopic expression of p19, a plant viral siRNA-binding protein, stabilizes otherwise unstable bacterial siRNAs, which we named pro-siRNAs for prokaryotic siRNAs. We present a detailed protocol describing how to produce pro-siRNAs for efficiently knocking down any gene, beginning with the design of a pro-siRNA expression plasmid and ending with siRNA purification. This protocol uses one plasmid to co-express a recombinant His-tagged p19 protein and a long hairpin RNA containing sense and antisense sequences of the target gene. pro-siRNAs are isolated and purified using nickel beads and HPLC, using methods used to produce recombinant proteins. Once a pro siRNA plasmid is obtained, production of purified pro-siRNAs takes a few days. The pro-siRNA technique provides a reliable and renewable source of siRNAs, and it can be implemented in any laboratory whose members are skilled in routine molecular biology techniques. PMID- 24177291 TI - 13C-isotope-based protocol for prenyl lipid metabolic analysis in zebrafish embryos. AB - Metabolism has a decisive role in many fundamental biological processes, including organism development and tissue homeostasis. Here we describe a protocol for fast and reliable (13)C-isotope-based in vivo metabolic profiling. This protocol covers the loading of isotope precursor; extraction, preparation and quantification of the labeled lipid metabolites (e.g., the prenyl lipid CoQ10) by the means of HPLC-MS; and its analysis in zebrafish embryos. This protocol can be applied to different types of experimental settings, including tissue-specific metabolic analyses or dynamic metabolic changes that occur during vertebrate embryogenesis. The protocol takes 5-7 d to complete, requiring minimal equipment and analytical expertise, and it represents a unique alternative to the existing ex vivo (e.g., cell lines) isotope-based metabolic methods. This procedure represents a valuable approach for researchers interested in studying the effect of gene manipulation on lipid metabolism in zebrafish and in understanding the genetic conditions that result in metabolism dysfunction. PMID- 24177292 TI - Oxidative aliphatic C-H fluorination with manganese catalysts and fluoride ion. AB - Fluorination is a reaction that is useful in improving the chemical stability and changing the binding affinity of biologically active compounds. The protocol described here can be used to replace aliphatic, C(sp(3))-H hydrogen in small molecules with fluorine. Notably, isolated methylene groups and unactivated benzylic sites are accessible. The method uses readily available manganese porphyrin and manganese salen catalysts and various fluoride ion reagents, including silver fluoride (AgF), tetrabutylammonium fluoride and triethylamine trihydrofluoride (TREAT.HF), as the source of fluorine. Typically, the reactions afford 50-70% yield of mono-fluorinated products in one step. Two representative examples, the fragrance component celestolide and the nonsteroidal anti inflammatory drug ibuprofen, are described; they produced useful isolated quantities (250-300 mg, ~50% yield) of fluorinated material over periods of 1-8 h. The procedures are performed in a typical fume hood using ordinary laboratory glassware. No special precautions to rigorously exclude water are required. PMID- 24177293 TI - Generation of targeted mouse mutants by embryo microinjection of TALEN mRNA. AB - Genetically engineered mice are instrumental for the analysis of mammalian gene function in health and disease. As classical gene targeting, which is performed in embryonic stem (ES) cell cultures and generates chimeric mice, is a time consuming and labor-intensive procedure, we recently used transcription activator like (TAL) effector nucleases (TALENs) for mutagenesis of the mouse genome directly in one-cell embryos. Here we describe a stepwise protocol for the generation of knock-in and knockout mice, including the selection of TALEN binding sites, the design and construction of TALEN coding regions and of mutagenic oligodeoxynucleotides (ODNs) and targeting vectors, mRNA production, embryo microinjection and the identification of modified alleles in founder mutants and their progeny. After a setup time of 2-3 weeks of hands-on work for TALEN construction, investigators can obtain first founder mutants for genes of choice within 7 weeks after embryo microinjections. PMID- 24177295 TI - Zoonotic transmission of hepatitis E virus in industrialized countries. AB - Hepatitis E is an infectious viral disease with clinical and morphological features of acute hepatitis. The disease represents an important public health problem in developing countries, where it is often related to outbreaks mainly associated with consumption of contaminated water. During recent years, an increasing number of sporadic cases have also been described in industrialized countries. Besides humans, the hepatitis E virus (HEV) has also been identified in animals. In 1997, the virus was first detected in swine, and is now considered ubiquitous. Human and swine HEV strains from the same geographical region present a high level of nucleotide identity, and experimental infections have confirmed the cross-species transmission of swine strains to humans and of human strains to non-human primates. Studies on anti-HEV antibodies detection have demonstrated that people working in contact with swine or wild boar have a higher risk of infection than normal blood donors. In Japan and more recently in France, cases of hepatitis E have been associated with ingestion of uncooked meat from pigs, wild boar, or deer. The disease is currently considered an emerging zoonosis. PMID- 24177294 TI - Synthesis of a probe for monitoring HSV1-tk reporter gene expression using chemical exchange saturation transfer MRI. AB - In experiments involving transgenic animals or animals treated with transgenic cells, it is important to have a method to monitor the expression of the relevant genes longitudinally and noninvasively. An MRI-based reporter gene enables monitoring of gene expression in the deep tissues of living subjects. This information can be co-registered with detailed high-resolution anatomical and functional information. We describe here the synthesis of the reporter probe, 5 methyl-5,6-dihydrothymidine (5-MDHT), which can be used for imaging of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression in rodents by MRI. The protocol also includes data acquisition and data processing routines customized for chemical exchange saturation transfer (CEST) contrast mechanisms. The dihydropyrimidine 5-MDHT is synthesized through a catalytic hydrogenation of the 5,6-double bond of thymidine to yield 5,6-dihydrothymidine, which is methylated on the C-5 position of the resulting saturated pyrimidine ring. The synthesis of 5-MDHT can be completed within 5 d, and the compound is stable for more than 1 year. PMID- 24177296 TI - Phalangeal quantitative ultrasound: cheaper methods for screening and follow-up of bone pathologies in HIV-infected women? AB - This study estimated the prevalence of bone pathologies in a cohort of HIV infected women in comparison with a cohort of HIV-negative women. Bone mineral density was measured by phalangeal quantitative ultrasound (AD-SoS: amplitude- dependent speed of sound; UBPI: ultrasound bone profile index). Risk of fracture, expressed by UBPI, was considered for value <0.39. Comparisons between groups and multivariate analyses were carried out using an ANOVA model. Correlations were evaluated using the Pearson correlation coefficient. Osteopenia and osteoporosis were present in 34.4% and 2% of patients, respectively. UBPI was pathologic in 5.7%. In a multivariate linear regression model significant correlations were found between AD-SoS z-score, duration of HIV-infection and BMI value. We also compared our cohort with 499 HIV-negative women as a historical control group of healthy subjects. AdSoS (2100 versus 2070 m/s) and UBPI (0.89 versus 0.74) were lower in HIV-infected women (p<0.001). Significant differences were also found in T-score values (p = 0.0013). These data show a high prevalence of bone diseases in women with HIV infection, correlated with duration of HIV-infection and BMI values. This non-invasive technique opens up new interesting perspectives, suggesting a possible use for bone mass screening in HIV-infected women. PMID- 24177297 TI - Temporal trend and characteristics of recent HIV-1 infections: application of an algorithm for the identification of recently acquired HIV-1 infections among newly diagnosed individuals over a 10-year period. AB - Identification of recent infections (RI) may contribute to improve the quality of human immunodeficiency virus (HIV) surveillance, monitoring ongoing transmission and planning and evaluating prevention programs. Our study applied an algorithm combining clinical and serological information to identify RI in individuals newly diagnosed with HIV in Rome, during the years 1999-2008, in order to describe the trend and characteristics of recently infected individuals. RI were documented seroconverters, or people with an HIV avidity index (AI)<0.80. Individuals with advanced infection (CD4 count <200 cells/?L or AIDS-defining illness) or with AI ?0.80 were considered long-standing infections. Overall, we observed 2,563 new HIV diagnoses. The algorithm was applied in 2124/2563 (82.9%). Of these, 355 were RI (16.7%). RI was found independently associated with calendar year (adjusted odds ratio [aOR]= 1.06, 95% confidence intervals [CI]=[CI 1.02-1.11], for every year of increase), HIV-risk category (men having sex with men: aOR=1.44, [CI 1.04-1.98]; injecting drug users: aOR=1.58, [CI 1.03-2.42] vs. heterosexuals), country of origin (foreign-born: vs Italians: aOR=0.46, [CI 0.33 0.62]), and recruitment site (inpatient vs outpatient clinic: aOR=0.49, [CI 0.37 0.66]). By the application of our algorithm we could characterize the pattern of ongoing HIV transmission, identifying groups needing more urgent prevention programs. PMID- 24177298 TI - HCMV infection in renal transplant recipients: a retrospective cohort study. AB - Human Cytomegalovirus (HCMV) represents the most common viral complication affecting solid organ transplant recipients (SOTRs) and its management is still debated. This study analyzes the association between HCMV infection and renal transplant recipients' outcomes. From January 2008 through December 2009, 97 consecutive renal transplant recipients were retrospectively studied. HCMV disease prevention was pursued by pre-emptive therapy, reserving long-term prophylaxis for high-risk patients. A total of 32/97 patients (32.9%) developed HCMV positivity in blood for a cumulative estimated proportion at 3 months post transplantation of 0.21. HCMV disease developed in 7 patients (7.2%), while 25 patients had asymptomatic infection (25.7%). No patient died from HCMV. HCMV disease, older graft age and post-transplant renal dysfunction were independent predictors of rejection while HCMV infection without disease was associated with a higher number of other complications. The use of basiliximab was independently associated with a reduced hazard of HCMV infection/ disease. In renal transplant recipients HCMV infection still represents a major issue influencing the outcome, not only because of the potential to develop the disease and its link to graft rejection, but also in terms of higher number of complications. The choice of different immunosuppressive strategies might be associated with HCMV replication. PMID- 24177299 TI - Serratia marcescens in a neonatal intensive care unit: two long-term multiclone outbreaks in a 10-year observational study. AB - We investigated two consecutive Serratia marcescens (S. marcescens) outbreaks which occurred in a neonatal intensive care unit (NICU) of a tertiary level hospital in North Italy in a period of 10 years (January 2003-December 2012). Risk factors associated with S. marcescens acquisition were evaluated by a retrospective case-control study. A total of 21,011 clinical samples was examined: S. marcescens occurred in 127 neonates: 43 developed infection and 3 died. Seven clusters were recorded due to 12 unrelated clones which persisted for years in the ward, although no environmental source was found. The main epidemic clone A sustaining the first cluster in 2003 reappeared in 2010 as an extended spectrum ?-lactamase (ESBL)-producing strain and supporting the second epidemic. Birth weight, gestational age, use of invasive devices and length of stay in the ward were significantly related to S. marcescens acquisition. The opening of a new ward for non-intensive care-requiring neonates, strict adherence to alcoholic hand disinfection, the timely identification and isolation of infected and colonized neonates assisted in containing the epidemics. Genotyping was effective in tracing the evolution and dynamics of the clones demonstrating their long-term persistence in the ward. PMID- 24177300 TI - Phylogenetic analysis of multidrug-resistant Escherichia coli clones isolated from humans and poultry. AB - Chicken products represent a source for multidrug-resistant Escherichia coli causing extraintestinal infections (ExPEC) in humans. We applied phylogenetic analysis to a collection of E. coli strains from both hosts (poultry/humans) to improve our understanding of the origin and spread of ExPEC in humans. The dataset consisted of 58 sequences among 172 E. coli strains from human extraintestinal infections and avian species. Human phylogenetic tree analysis showed a major clade, within which ST clones belonging to groups A and B1 were largely intermixed, and two clusters, each exclusively including B2 or D clones. The avian tree exhibited greater heterogeneity between and within clades/clusters. In the Bayesian tree, consisting of sequences from both human and avian E. coli, the B2 and D human ST clones were clustered together separate from the avian strains, whereas B1 and A ST clones (frequently associated with multidrug resistance) were intermixed with avian strains. This study suggests that a subgroup of E. coli clones, A and B1, associated with multidrug resistance, is potentially exchangeable between poultry and humans. Such a subgroup may be of public health concern. On the contrary, E. coli clones included in B2 and D appeared clearly separate between human and avian sources, suggesting a minor zoonotic potential of these phylotypes. PMID- 24177301 TI - Sequence-based genotyping methods to assess the genetic diversity of Riemerella anatipestifer isolates from ducklings with tremor. AB - The aim of this study was to investigate sequence-based genotyping methods to distinguish 27 Riemerella anatipestifer isolates from ducklings in South Korea. The 16S rRNA sequences of the 27 R. anatipestifer isolates showed 99?100% similarities to each other and to reference sequences from Genbank (AY871822.2, AY871834.2, CP002562.1, EU715016.1, EU016548.1, EU715000.1, EU715008.1 and EU715011.1). In addition, the ompA gene sequences of 25 of the 27 R. anatipestifer isolates were 100% identical to each other, and these sequences were also 100% identical to reference sequences (CP002562.1, GQ415419.1, DQ059079, FJ765034.1, AY606207.1, AF104937.1, and FJ765033.1). Alternatively, four housekeeping genes (mdh, gdh, pgi, and rpoB) and three virulence-associated genes (prtC, hagA, and sspA) were used for a multi-locus sequence typing (MLST) and a single-locus sequence typing (SLST) among R. anatipestifer isolates. Compared to 16S rRNA and the ompA gene, seven genes showed higher genetic divergence patterns, and the isolates were separated into three distinct groups in phylogenetic trees. PMID- 24177302 TI - Clinical application of a molecular method based on real time RT-PCR for detection of influenza A(H1N1)v virus. AB - Given the new diagnostic need following the pandemic caused by the A(H1N1)v virus, we evaluated the performance characteristics of Xpert(r) Flu assay (Cepheid). The overall sensitivity and specificity were 65.6% and 92.8%, respectively. Sensitivity and specificity for A(H1N1)v virus were 85.7% and 94.9%, respectively, and therefore the Xpert(r) Flu assay is suitable for a rapid diagnosis in critically ill patients where diagnosis is crucial for clinical management and for an appropriate public health response. PMID- 24177303 TI - Identification of non-tuberculous mycobacteria from clinical samples. AB - Non-tuberculous mycobacterial infections cause morbidity worldwide. NTM are considered opportunistic pathogens, and several species have been associated with human disease which has typically pulmonary, skin and soft tissue, lymphatic or disseminated presentation. This study evaluated the distribution of non tuberculous mycobacteria in Sardinia. Mycobacterium avium, Mycobacterium gordonae and Mycobacterium xenopi were frequently found. Our results agreed with literature data both for the frequent isolation of M. avium, M. xenopi and M. gordonae, and the symptoms and radiological evidence of the patients analysed. PMID- 24177304 TI - RAPD discloses high molecular diversity of Mycobacterium tuberculosis from Michoacan, Mexico. AB - Random amplified polymorphism DNA (RAPD) is an easy, inexpensive technique for the characterization of pathogens in low-income countries. In this study we used RAPD to assess the genetic diversity of a small collection of isolates of mycobacteria from the Mexican state of Michoacan. In contrast with the low annual tuberculosis incidence in Michoacan relative to the national average, we found a high molecular diversity value suggesting high population diversity of M. tuberculosis in the studied region. Our findings justify further typing efforts with other molecular tools such as MIRU-VNTR and spoligotyping. PMID- 24177305 TI - Group A streptococcal meningitis: a case report. AB - Streptococcus pyogenes (Group A streptococcus, GAS) is a rare cause of bacterial meningitis, accounting for less than 1% of cases. GAS meningitis has rarely been reported in children, and is associated with a high (46%) rate of morbidity and a high (10-17%) case fatality rate. This paper describes a case of meningitis caused by GAS in a previously healthy child; M protein genotyping demonstrated an emm type 12. Although not common, GAS meningitis must be considered in children vaccinated for other invasive pathogens. Continuous monitoring of the molecular epidemiology of circulating invasive GAS strains is of crucial importance for planning intervention policies. PMID- 24177306 TI - Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient. A rare case report and literature review. AB - Sphingomonas paucimobilis occurs widely both in natural and nosocomial environments, including hospital water systems, respiratory therapy equipment, and laboratory instruments. It is an opportunistic pathogen that rarely causes infections in humans. Among S. paucimobilis nosocomial infections, osteomyelitis is particularly rare. Almost all infections occur in patients with comorbidities such as malignancy, immunosuppressant therapy, diabetes mellitus and acquired immunodeficiency syndrome. We present the first case of Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient and include updated literature concerning infections by this microorganism. PMID- 24177307 TI - Two rare cases of Acremonium acute endophthalmitis after cataract surgery in a tertiary care hospital. AB - This report describes two cases of Acremonium sp. endophthalmitis, occurring in two patients who underwent cataract surgery on the same day in the same operating room of our hospital ophthalmology clinic. Diagnosis of fungal endophthalmitis was established by the repeated isolation of the same fungal agent from vitreous washing, acqueous fluid and intraocular lens samples and by its identification on the basis of morphological and molecular features. The cases reported in this study emphasize the need for clinical microbiology laboratories to be prepared to face the diagnosis of uncommon infectious diseases such as exogenous fungal endophthalmitis by Acremonium, and to enhance the awareness of surgeons and clinicians of this occurrence. PMID- 24177308 TI - Virus investigation in ticks from migratory birds in Italy. AB - The role of migratory birds in circulation tick-borne viruses needs to be better defined. In order to assess the potential role of migratory birds in exotic virus spread, we conducted a study to identify ticks collected from migratory birds in the Central Region of Italy, and performed molecular investigation for Crimea Congo Hemorrhagic Fever (CCHFV), West Nile fever (WNFV) and Usutu (USUV) in the vectors. A total of 137 competent ticks were collected with predominance of Hyalomma species. Although, negative results were obtained for all viruses considered, the high proportion of Hyalomma ticks highlights the potential risk for the dissemination of tick-borne viruses through infested migratory birds. PMID- 24177309 TI - Analysis of facial and inspiratory muscles performance during breastfeeding. AB - BACKGROUND: Breastfeeding is a dynamic process in which the infant recruits several muscle groups in his face, head and throat. OBJECTIVE: The objective of this study was to explore the relative role of the submental muscle group, the orbicularis oris and the sternocleidomastoid muscles to breastfeeding process and to the relatively high intra-oral vacuum measured during this process. METHODS: Electromyography (EMG) measurements were conducted on 11 infants (mean age 1.91 +/- 1.0 days, mean weight 3364 +/- 328 g) using surface electrodes. The EMG data were filtered with a low pass filter to yield the linear envelopes (IEMG). The maximal and mean value and the area under each linear envelope curve were examined. RESULTS: During active suckling significantly higher activity (P< 0.05) of the submental muscle group were measured compared with the orbicularis oris and sternocleidomastoid muscles (mean +/- SE values of the maximal linear envelope were 24.4 +/- 1 MUV, 9.6 +/- 0.6 MUV and 14 +/- 0.7 MUV, respectively). CONCLUSION: These results confirmed that jaw movements have the primary role during breastfeeding, but also revealed that the inspiratory muscles have a substantial contribution to this process and probably have an important role in the generation of intra oral vacuum measured during breastfeeding. PMID- 24177310 TI - Deployment of an in-house designed training process in a quaternary care hospital. AB - BACKGROUND: Healthcare providers, such as doctors and nurses, have been famous for high resistance to change. A careful change management plan, particularly training process, is utmost necessary. A quaternary care hospital in India changed its system, from manual to Electronic Medical Record/Health Information System (EMR/HIS). The hospital management wanted to train its 4000 diverse end users on the EMR/HIS in two months' time. OBJECTIVE: This paper describes an in house designed training process and its deployment in the given healthcare organizational settings. METHODS: We designed a training process named DRIPDA. The training process was deployed to train 4000 end-users of EMR/HIS, in the quaternary care hospital. Various factors, such as methods and tools of training, constraints of trainees, trainers, and organization were considered while deploying the training process. The effectiveness of the DRIPDA was assessed using the Kirkpatrick model. RESULTS: End-users received training on the new system only in 25% of estimated time and 28% of the projected expense, without having any distraction in their usual workflow, or any productivity loss. CONCLUSION: We found that the DRIPDA training process could train all employees effectively and efficiently. A decent training process can help in managing the change, thereby reduce the training time and cost. PMID- 24177311 TI - Development of model for assessing the acceptance level of users in rural healthcare system of Tamilnadu, India. AB - BACKGROUND: HMIS will incorporate a paradigm shift in health such as removing manual records and transformation of data through the complex structure of health departments in Tamilnadu. Thus developing a model of technology acceptance in HMIS contest is important and necessary in order to promote usage of the HMIS in rural health care system. OBJECTIVE: The papers purpose is to formulate a model of technology acceptance of Health Management Information System (HMIS) by generating and validating a research model that best describes rural health care workers usage behavior and behavior intention. METHODS: This research proposes a theoretical framework which is comprised of key determinants that influence usage behavior of HMIS together with moderator. It has been tested through different parametric test and confirmatory factor analysis. RESULTS: Data analysis shows that health workers innovativeness and voluntariness have a direct and positive influence on Technology Acceptance level and that the basic TAM hypotheses are fulfilled. HMIS usage behavior and behavior intention can be increased with factors that are effecting the successful implementation of HMIS when it remains high. CONCLUSIONS: This research enables health departments to know which aspects of their HMIS components and variables to improve. This shows that HMIS usage and health workers/staffs acceptance level are key tools in the success of HMIS. This research has seemed to be done at the right time and in the right place to the best of its kind. PMID- 24177312 TI - A novel emulsion-type adjuvant containing CpG oligodeoxynucleotides enhances CD8+ T-cell-mediated anti-tumor immunity. AB - PELC is a novel emulsion-type adjuvant that contains the bioresorbable polymer poly (ethylene glycol)-block-poly (lactide-co-epsilon-caprolactone) (PEG-b PLACL), Span(r)85 and squalene. To investigate whether PELC is able to enhance CTL responses of antigens for treating tumor, peptides or protein antigens derived from HPV16 E7 were formulated with PELC nanoparticles and CpG oligodeoxynucleotide. We identified that PELC formulation could delay the release of antigens in vitro and in vivo. We assessed the immunogenicity of an H-2D(b) restricted CTL epitope RAHYNIVTF (RAH) formulated with PELC or PELC/CpG and investigated the ability of these formulations to promote tumor regression. Following a single-dose subcutaneous injection in mice, we found that the RAH peptide formulated with PELC/CpG (RAH/PELC/CpG) resulted in increased numbers of IFN-gamma-secreting cells and RAH-specific CD8(+) T cells and an enhanced cytotoxic T cell response compared with RAH formulated with PELC or CpG alone. The tumor-bearing mice received a single-dose injection of RAH/PELC/CpG, which induced complete tumor regression. These results demonstrated that peptide antigen formulated with PELC/CpG nanoparticles is feasible for cancer immunotherapy. PMID- 24177313 TI - Docetaxel-nicotinamide complex-loaded nanostructured lipid carriers for transdermal delivery. AB - Docetaxel (DTX) proved one of the most effective active pharmaceutical ingredients (APIs) for the treatment of cancers. However, in respect of its low solubility and high lipophilic property, nicotinamide (NCT) was chosen as the co former to form the docetaxel-nicotinamide complex to handle the drawbacks. As was analyzed by Fourier Transform Infrared spectrometer, thermal analysis and saturated solubility, the complex proved stable. Then, docetaxel-nicotinamide complex nanostructured lipid carriers (DN-NLCs) were prepared by emulsion evaporation at low temperature method. The average drug entrapment efficiency, particle size and drug loading of docetaxel-NLCs (D-NLCs) and DN-NLCs were 81.41 79.48%, 61.45-59.48nm and 1.60-1.63%, respectively. The physicochemical characteristics of nanoparticles were valued by transmission electron microscope and Powder X Ray Diffraction. The in vitro drug-release profile of nanoparticle formulations fitted the Weibull dynamic equation. The skin permeability test was performed by Vertical Franz-type diffusion cells. It demonstrated that DN-NLCs transported drugs more easily than D-NLCs. Confocal Laser Scanning Microscopy observation showed DN-NLCs permeated more effectively than D-NLCs. In vivo study demonstrated that DN-NLCs maintained most in the skin. These results suggest that the DN-NLCs can be a useful method to increase skin permeation of docetaxel. PMID- 24177314 TI - Characterization of alginate beads loaded with ibuprofen lysine salt and optimization of the preparation method. AB - The parameters influencing alginate ionotropic gelation and the production of alginate beads loaded with hydrosoluble ibuprofen lysine salt (IBU-L) were studied, as well as the optimization of the method for its attainment. A three factor and three-level factorial design (3(3)) was carried out to determine the influence of three experimental variables: polymer concentration, CaCl2 concentration, and curing time on the dependent variables drug load and encapsulation efficiency. The effect of the pH used in the preparation bath was also evaluated. Concentrations of CaCl2 and pH of gelling bath were seen to affect bead formation and stability as well as their ability to properly entrap the drug. In this work, IBU-L was used as a model of a non-steroidal anti inflammatory drug with good solubility in alginate solutions. IBU-L was successfully encapsulated in alginate beads obtained by the ionotropic gelation method. The obtained alginate matrixes are able to modify the release of the entrapped IBU-L and this occurs in a pH-sensitive way that can be correlated with the swelling behaviour of the alginate-produced beads. Morphological characteristics were evaluated by means of scanning electron microscopy. PMID- 24177315 TI - Approach-alcohol action tendencies can be inhibited by cognitive load. AB - RATIONALE: Dysregulated alcohol consumption has been attributed to an imbalance between an approach-alcohol action tendency and executive control processes. However, which specific executive control processes are involved is not known. One candidate executive process is interference suppression, which refers to the suppression of task-irrelevant information through the active maintenance of task relevant information or a cognitive load. OBJECTIVE: The present study aimed to (1) establish whether alcohol action tendency can be inhibited by interference suppression through the use of cognitive loads and (2) to assess whether individual differences in the degree of interference suppression from cognitive loads is related to individual differences in the ability to regulate alcohol consumption. METHOD: Two groups of social drinkers (total N = 58) who differed in their ability to regulate their alcohol consumption completed a novel cognitive load variant of the approach avoidance task (AAT) and an alcohol taste test. RESULTS: Results indicated that (1) there was a relationship between alcohol bias on the AAT and alcohol consumption under low load, but not high load, consistent with the hypothesis that the action tendency would be inhibited through interference suppression, and (2) this effect of load was not modified by drinking group, with both groups demonstrating equivalent ability to inhibit the action tendency. CONCLUSIONS: The present findings suggest that alcohol action tendency can be inhibited through interference suppression, and that this is effective even for those that have difficulty regulating their alcohol consumption. PMID- 24177317 TI - Using aggregated, de-identified electronic health record data for multivariate pharmacosurveillance: a case study of azathioprine. AB - OBJECTIVE: To demonstrate the use of aggregated and de-identified electronic health record (EHR) data for multivariate post-marketing pharmacosurveillance in a case study of azathioprine (AZA). METHODS: Using aggregated, standardized, normalized, and de-identified, population-level data from the Explore platform (Explorys, Inc.) we searched over 10 million individuals, of which 14,580 were prescribed AZA based on RxNorm drug orders. Based on logical observation identifiers names and codes (LOINC) and vital sign data, we examined the following side effects: anemia, cell lysis, fever, hepatotoxicity, hypertension, nephrotoxicity, neutropenia, and neutrophilia. Patients prescribed AZA were compared to patients prescribed one of 11 other anti-rheumatologic drugs to determine the relative risk of side effect pairs. RESULTS: Compared to AZA case report trends, hepatotoxicity (marked by elevated transaminases or elevated bilirubin) did not occur as an isolated event more frequently in patients prescribed AZA than other anti-rheumatic agents. While neutropenia occurred in 24% of patients (RR 1.15, 95% CI 1.07-1.23), neutrophilia was also frequent (45%) and increased in patients prescribed AZA (RR 1.28, 95% CI 1.22-1.34). After constructing a pairwise side effect network, neutropenia had no dependencies. A reduced risk of neutropenia was found in patients with co-existing elevations in total bilirubin or liver transaminases, supporting classic clinical knowledge that agranulocytosis is a largely unpredictable phenomenon. Rounding errors propagated in the statistically de-identified datasets for cohorts as small as 40 patients only contributed marginally to the calculated risk. CONCLUSION: Our work demonstrates that aggregated, standardized, normalized and de-identified population level EHR data can provide both sufficient insight and statistical power to detect potential patterns of medication side effect associations, serving as a multivariate and generalizable approach to post-marketing drug surveillance. PMID- 24177318 TI - An SVM-based high-quality article classifier for systematic reviews. AB - OBJECTIVE: To determine whether SVM-based classifiers, which are trained on a combination of inclusion and common exclusion articles, are useful to experts reviewing journal articles for inclusion during new systematic reviews. METHODS: Test collections were built using the annotated reference files from 19 procedure and 4 drug systematic reviews. The classifiers were trained by balanced data sets, which were sampled using random sampling. This approach compared two balanced data sets, one with a combination of included and commonly excluded articles and one with a combination of included and excluded articles. AUCs were used as evaluation metrics. RESULTS: The AUCs of the classifiers, which were trained on the balanced data set with included and commonly excluded articles, were significantly higher than those of the classifiers, which were trained on the balanced data set with included and excluded articles. CONCLUSION: Automatic, high-quality article classifiers using machine learning could reduce the workload of experts performing systematic reviews when topic-specific data are scarce. In particular, when used as training data, a combination of included and commonly excluded articles is more helpful than a combination of included and excluded articles. PMID- 24177319 TI - Pre-launch evaluation checklist for online health-promoting communities. AB - BACKGROUND: Despite the apparent potential of online health-promoting communities (OHPC), there is limited guidance available for developers on the basic design features that contribute to successful applications. The aim of this study was to develop a checklist for a pre-launch evaluation of OHPCs incorporating the perspectives of both the user and the health services communities. METHODS: The study was based on an action research design. Constructs previously applied to evaluate information system success were used as the basis for checklist development. The constructs were adapted for the OHPC context and formatively evaluated in a case study project. Evaluation data were collected from participatory observations and analyzed using qualitative methods. RESULTS: The initial OHPC checklist included the constructs information quality, service quality, and subjective norms. The contextual adaptation of the information quality construct resulted in items for content area, trust, and format; the adaptation of the service quality construct in items for staff competence, prompt service and empathy; and the adaptation of the subject norms construct in items for social facilitation, interconnectivity and communication. The formative evaluation demonstrated the critical need to balance the autonomy of the online community with the professional control of health services quality expressed in the information and service quality constructs. CONCLUSIONS: A pre-launch OHPC evaluation checklist has been designed for use in practical development of health promotion web resources. Research on instruments for OHPC evaluations is warranted. PMID- 24177320 TI - Automatic signal extraction, prioritizing and filtering approaches in detecting post-marketing cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS). AB - OBJECTIVE: Targeted drugs dramatically improve the treatment outcomes in cancer patients; however, these innovative drugs are often associated with unexpectedly high cardiovascular toxicity. Currently, cardiovascular safety represents both a challenging issue for drug developers, regulators, researchers, and clinicians and a concern for patients. While FDA drug labels have captured many of these events, spontaneous reporting systems are a main source for post-marketing drug safety surveillance in 'real-world' (outside of clinical trials) cancer patients. In this study, we present approaches to extracting, prioritizing, filtering, and confirming cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS). DATA AND METHODS: The dataset includes records of 4,285,097 patients from FAERS. We first extracted drug cardiovascular event (drug-CV) pairs from FAERS through named entity recognition and mapping processes. We then compared six ranking algorithms in prioritizing true positive signals among extracted pairs using known drug-CV pairs derived from FDA drug labels. We also developed three filtering algorithms to further improve precision. Finally, we manually validated extracted drug-CV pairs using 21 million published MEDLINE records. RESULTS: We extracted a total of 11,173 drug-CV pairs from FAERS. We showed that ranking by frequency is significantly more effective than by the five standard signal detection methods (246% improvement in precision for top-ranked pairs). The filtering algorithm we developed further improved overall precision by 91.3%. By manual curation using literature evidence, we show that about 51.9% of the 617 drug-CV pairs that appeared in both FAERS and MEDLINE sentences are true positives. In addition, 80.6% of these positive pairs have not been captured by FDA drug labeling. CONCLUSIONS: The unique drug-CV association dataset that we created based on FAERS could facilitate our understanding and prediction of cardiotoxic events associated with targeted cancer drugs. PMID- 24177321 TI - Design of hybrid multimodal poly(lactic-co-glycolic acid) polymer nanoparticles for neutrophil labeling, imaging and tracking. AB - Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) incorporating quantum dots (QDs), superparamagnetic iron oxide nanoparticles (SPIONs) and gold (Au) NPs for neutrophil labeling were fabricated via the w/o/w double emulsion method. QDs and SPIONs were entrapped in the PLGA core during emulsification while Au NPs were assembled on top of the PLGA NPs via electrostatic interactions. Transmission Electron Microscopy, Scanning Electron Microscopy and Confocal Scanning Laser Microscopy (CLSM) were applied to characterize the hybrid PLGA NPs. The uptake of the hybrid PLGA NPs by human neutrophils was studied by Flow Cytometry and confocal microscopy. In addition, the induction of reactive oxygen species (ROS) in neutrophils after incubation with the hybrid PLGA NPs was assessed. Magnetophoresis experiments showed that neutrophils with internalized hybrid PLGA NPs can be effectively laterally displaced towards the magnetic field. Magnetic Resonance Imaging of the hybrid PLGA NPs resulted in images with a contrast enhancement linearly dependent on the concentration of the hybrid PLGA NPs. Research reported in this work is relevant for imaging, tracking and manipulating neutrophils and has potential for in vivo applications, e.g., tumor visualization and localized photothermal treatment. PMID- 24177322 TI - Core-shell to yolk-shell nanostructure transformation by a novel sacrificial template-free strategy. AB - Au-conducting polymer core-shell nanostructures have been transformed into yolk shell nanostructures with enhanced catalytic activity through facile swelling evaporation processes without any sacrificial template. PMID- 24177324 TI - Modulation of protein C activation by histones, platelet factor 4, and heparinoids: new insights into activated protein C formation. AB - OBJECTIVE: Histones are detrimental in late sepsis. Both activated protein C (aPC) and heparin can reverse their effect. Here, we investigated whether histones can modulate aPC generation in a manner similar to another positively charged molecule, platelet factor 4, and how heparinoids (unfractionated heparin or oxygen-desulfated unfractionated heparin with marked decrease anticoagulant activity) may modulate this effect. APPROACH AND RESULTS: We measured in vitro and in vivo effects of histones, platelet factor 4, and heparinoids on aPC formation, activated partial thromboplastin time, and murine survival. In vitro, histones and platelet factor 4 both affect thrombin/thrombomodulin aPC generation following a bell-shaped curve, with a peak of >5-fold enhancement. Heparinoids shift these curves rightward. Murine aPC generation studies after infusions of histones, platelet factor 4, and heparinoids supported the in vitro data. Importantly, although unfractionated heparin and 2-O, 3-O desulfated heparin both reversed the lethality of high-dose histone infusions, only mice treated with 2 O, 3-O desulfated heparin demonstrated corrected activated partial thromboplastin times and had significant levels of aPC. CONCLUSIONS: Our data provide a new contextual model of how histones affect aPC generation, and how heparinoid therapy may be beneficial in sepsis. These studies provide new insights into the complex interactions controlling aPC formation and suggest a novel therapeutic interventional strategy. PMID- 24177323 TI - Proteasome proteolysis supports stimulated platelet function and thrombosis. AB - OBJECTIVE: Proteasome inhibitors used in the treatment of hematologic cancers also reduce thrombosis. Whether the proteasome participates in platelet activation or function is unclear because little is known of the proteasome in these terminally differentiated cells. APPROACH AND RESULTS: Platelets displayed all 3 primary proteasome protease activities, which MG132 and bortezomib (Velcade) inhibited. Proteasome substrates are marked by ubiquitin, and platelets contained a functional ubiquitination system that modified the proteome by monoubiquitination and polyubiquitination. Systemic MG132 strongly suppressed the formation of occlusive, platelet-rich thrombi in FeCl3-damaged carotid arteries. Transfusion of platelets treated ex vivo with MG132 and washed before transfusion into thrombocytopenic mice also reduced carotid artery thrombosis. Proteasome inhibition reduced platelet aggregation by low thrombin concentrations and ristocetin-stimulated agglutination through the glycoprotein Ib-IX-V complex. This receptor was not appropriately internalized after proteasome inhibition in stimulated platelets, and spreading and clot retraction after MG132 exposure also were decreased. The effects of proteasome inhibitors were not confined to a single receptor as MG132 suppressed thrombin-stimulated, ADP-stimulated, and lipopolysaccharide-stimulated microparticle shedding. Proteasome inhibition increased ubiquitin decoration of cytoplasmic proteins, including the cytoskeletal proteins Filamin A and Talin-1. Mass spectrometry revealed a single MG132-sensitive tryptic cleavage after R1745 in an extended Filamin A loop, which would separate its actin-binding domain from its carboxy terminal glycoprotein Ibalpha-binding domain. CONCLUSIONS: Platelets contain a ubiquitin/proteasome system that marks cytoskeletal proteins for proteolytic modification to promote productive platelet-platelet and platelet-wall interactions. PMID- 24177325 TI - MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus. AB - OBJECTIVE: Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice. APPROACH AND RESULTS: BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR 27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice. CONCLUSIONS: miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice. PMID- 24177326 TI - Positive feedback regulation of agonist-stimulated endothelial Ca2+ dynamics by KCa3.1 channels in mouse mesenteric arteries. AB - OBJECTIVE: Intermediate and small conductance KCa channels IK1 (KCa3.1) and SK3 (KCa2.3) are primary targets of endothelial Ca(2+) signals in the arterial vasculature, and their ablation results in increased arterial tone and hypertension. Activation of IK1 channels by local Ca(2+) transients from internal stores or plasma membrane channels promotes arterial hyperpolarization and vasodilation. Here, we assess arteries from genetically altered IK1 knockout mice (IK1(-/-)) to determine whether IK1 channels exert a positive feedback influence on endothelial Ca(2+) dynamics. APPROACH AND RESULTS: Using confocal imaging and custom data analysis software, we found that although the occurrence of basal endothelial Ca(2+) dynamics was not different between IK1(-/-) and wild-type mice (P>0.05), the frequency of acetylcholine-stimulated (2 MUmol/L) Ca(2+) dynamics was greatly decreased in IK1(-/-) endothelium (515+/-153 versus 1860+/-319 events; P<0.01). In IK1(-/-)/SK3(T/T) mice, ancillary suppression (+Dox) or overexpression (-Dox) of SK3 channels had little additional effect on the occurrence of events under basal or acetylcholine-stimulated conditions. However, SK3 overexpression did restore the decreased event amplitudes. Removal of extracellular Ca(2+) reduced acetylcholine-induced Ca(2+) dynamics to the same level in wild-type and IK1(-/-) arteries. Blockade of IK1 and SK3 with the combination of charybdotoxin (0.1 MUmol/L) and apamin (0.5 MUmol/L) or transient receptor potential vanilloid 4 channels with HC-067047 (1 MUmol/L) reduced acetylcholine Ca(2+) dynamics in wild-type arteries to the level of IK1(-/ )/SK3(T/T)+Dox arteries. These drug effects were not additive. CONCLUSIONS: IK1, and to some extent SK3, channels exert a substantial positive feedback influence on endothelial Ca(2+) dynamics. PMID- 24177327 TI - Role of soluble endothelial cell-selective adhesion molecule biomarker in albuminuria and kidney function changes in patients with coronary artery disease: the Heart and Soul Study. AB - OBJECTIVE: Endothelial dysfunction is a possible mechanism to explain the association between atherosclerosis and kidney disease. This study evaluated circulating soluble endothelial cell-selective adhesion molecule (sESAM), a marker of endothelial dysfunction, as a risk factor for kidney function decline and albuminuria. APPROACH AND RESULTS: In the Heart and Soul Study, we measured sESAM from baseline serum samples and defined elevated levels of sESAM by the highest quartile (quartile 4 [Q4]: >65.4 ng/mL). We evaluated the associations of high sESAM with baseline estimated glomerular filtration rate (eGFR) and ratio of urine albumin to creatinine (ACR), and with longitudinal changes in eGFR and ACR. Among 990 participants with sESAM measurements, median sESAM was 54.5 ng/mL (interquartile range, 45.3-65.8). After multivariable adjustment, elevated levels of sESAM were strongly and independently associated with baseline reduced eGFR <60 mL/min per 1.73 m(2) (odds ratio [OR], 11.44; P<0.0001) and ACR >=30 mg/g (OR, 5.23; P<0.0001). Associations of sESAM (Q4 versus quartile 1 [Q1]) with change in ACR (beta=54.47; P<0.0001) were also significant after full adjustment. The association with change in eGFR (1.56%; P=0.0049) was not statistically significant after application of the Bonferroni correction for multiple markers. In unadjusted models, sESAM was associated with rapid kidney function loss, defined as 3% annual eGFR decline (OR, 2.28; P=0.0003), although this was attenuated by adjustment (OR, 2.11; P=0.0095). CONCLUSIONS: sESAM is associated with albuminuria and reduced kidney function in both cross-sectional and longitudinal analyses. These findings implicate endothelial dysfunction as a potential contributor to the elevated kidney disease risk in persons with cardiovascular disease. PMID- 24177328 TI - Carotid atherosclerosis predicts future myocardial infarction but not venous thromboembolism: the Tromso study. AB - OBJECTIVE: Recent studies have suggested that arterial and venous thrombosis share common risk factors. Although carotid atherosclerosis is associated with arterial cardiovascular events, its role in venous thromboembolic disease is unclear. We wanted to investigate and compare the effect of carotid atherosclerosis on the risk of myocardial infarction (MI) and venous thromboembolism (VTE) in a general population, taking into account competing risks. APPROACH AND RESULTS: Mean intima-media thickness and total plaque area in the right carotid artery were measured with ultrasound in 6257 people aged 25 to 84 years who participated in a population-based health study, the Tromso Study, from 1994 to 1995. Incident MI and VTE events were registered from date of enrollment to end of follow-up on December 31, 2010. Cox proportional hazards regression models using age as time scale were used to estimate cause-specific hazard ratios with 95% confidence intervals for MI and VTE by increasing levels of intima-media thickness and total plaque area. There were 894 incident MI cases and 256 VTE events during a median of 15.4 years of follow-up. The risk of MI increased significantly across quartiles of mean intima-media thickness (P for trend <0.001) and with increasing total plaque area (P for trend <0.001), but neither intima-media thickness (P for trend=0.94) nor total plaque area (P for trend=0.45) was associated with VTE risk in multivariable-adjusted analysis. CONCLUSIONS: In this study, carotid atherosclerosis was strongly associated with future MI but not with VTE. Our findings suggest that carotid atherosclerosis does not represent a link between arterial and venous thrombosis. PMID- 24177330 TI - A correlated nickelate synaptic transistor. AB - Inspired by biological neural systems, neuromorphic devices may open up new computing paradigms to explore cognition, learning and limits of parallel computation. Here we report the demonstration of a synaptic transistor with SmNiO3, a correlated electron system with insulator-metal transition temperature at 130 degrees C in bulk form. Non-volatile resistance and synaptic multilevel analogue states are demonstrated by control over composition in ionic liquid gated devices on silicon platforms. The extent of the resistance modulation can be dramatically controlled by the film microstructure. By simulating the time difference between postneuron and preneuron spikes as the input parameter of a gate bias voltage pulse, synaptic spike-timing-dependent plasticity learning behaviour is realized. The extreme sensitivity of electrical properties to defects in correlated oxides may make them a particularly suitable class of materials to realize artificial biological circuits that can be operated at and above room temperature and seamlessly integrated into conventional electronic circuits. PMID- 24177331 TI - The development of surface-enhanced Raman scattering as a detection modality for portable in vitro diagnostics: progress and challenges. AB - This perspective provides an overview of the diverse surface-enhanced Raman scattering (SERS)-based sensor platforms that have been developed for in vitro diagnostic applications. To provide focus, protein and nucleic acid detection assays based on the principle of extrinsic SERS sensing are emphasized, as well as their potential for translation to fully integrated point-of-care (POC) test platforms. The development of intrinsic SERS sensors, which are predicated on the direct detection of analytes by laser excitation, entails unique opportunities and challenges deserving of their own attention. As the robust sensing of disease pathogens and cancers in both clinical facilities and limited resource settings is the targeted objective of many next-generation biosensors, the majority of the research progress summarized here centers on SERS sensors developed for the rapid, sensitive and selective detection of disease-causing pathogens and biomarkers. In our effort to communicate a realistic assessment of the progress that has been made and the challenges that lie ahead, we avoid an overtly optimistic appraisal of the current status of SERS diagnostics that does not tacitly acknowledge the difficulties inherent in aligning SERS-based technologies alongside ELISA and PCR technologies as a complementary method for bioanalyte detection possessing unique advantages. PMID- 24177329 TI - Age-related changes in aortic valve hemostatic protein regulation. AB - OBJECTIVE: Although valvular endothelial cells have unique responses compared with vascular endothelial cells, valvular regulation of hemostasis is not well understood. Heart valves remodel throughout a person's lifetime, resulting in changes in extracellular matrix composition and tissue mechanical properties that may affect valvular endothelial cell hemostatic function. This work assessed valvular endothelial cell regulation of hemostasis in situ and in vitro as a function of specimen age. APPROACH AND RESULTS: Porcine aortic valves were assigned to 1 of 3 age groups: Young (YNG) (6 weeks); Adult (ADT) (6 months); or Elderly (OLD) (2 years). Histological examination of valves showed that secreted thrombotic/antithrombotic proteins localize at the valve endothelium and tissue interior. Gene expression and immunostains for von Willebrand factor (VWF), tissue factor pathway inhibitor, and tissue plasminogen activator in YNG porcine aortic valve endothelial cells were higher than they were for OLD, whereas plasminogen activator inhibitor 1 levels in OLD were higher than those for YNG and ADT. Histamine-stimulated YNG porcine aortic valve endothelial cells released higher concentrations of VWF proteins than OLD, and the fractions of VWF-140 fragments was not different between age groups. A calcific aortic valve disease in vitro model using valvular interstitial cells confirmed that VWF in culture significantly increased valvular interstitial cell nodule formation and calcification. CONCLUSIONS: Hemostatic protein regulation in aortic valve tissues and in valvular endothelial cells changes with age. The presence of VWF and other potential hemostatic proteins increase valvular interstitial cell calcification in vitro. Therefore, the increased capacity of elderly valves to sequester the hemostatic proteins, together with age-associated loss of extracellular matrix organization, warrants investigation into potential role of these proteins in the formation of calcific nodules. PMID- 24177332 TI - Diagnosis and management of functional constipation in children. AB - Physician assistants (PAs) frequently manage children with constipation. A thorough history and physical examination usually is sufficient to diagnose functional constipation. Treatment consists of family education, disimpaction (via rectal or oral routes), and maintenance therapy. Osmotic laxatives such as polyethylene glycol are commonly used for disimpaction and maintenance therapy. PMID- 24177333 TI - Stay current with options for HIV prevention. AB - Conventional behavioral modification strategies have had limited effect on preventing the spread of HIV, and additional options are urgently needed. Antiretroviral drugs have been approved as preexposure prophylaxis, and vaccines and topical microbicides may provide additional options. This article reviews current HIV prevention options with a focus on biomedical prevention methods. PMID- 24177334 TI - Update on pharmacologic therapy for pulmonary embolism. AB - Warfarin, unfractionated heparin (UFH), and low-molecular-weight heparins are anticoagulants that have been used for treatment of pulmonary embolism. Currently approved drugs for treatment of venous thromboembolism include UFH, enoxaparin, dalteparin, fondaparinux, warfarin, and rivaroxaban. The advent of newer oral anticoagulants such as rivaroxaban, dabigatran, and apixaban has provided us with alternative therapeutic options for long-term anticoagulation. This article will give an overview of the various anticoagulant drugs, use in various clinical scenarios, data supporting their clinical use, and recommendations regarding duration of anticoagulant therapy. PMID- 24177335 TI - Inflammation and atherosclerosis--revisited. AB - Atherogenesis has been traditionally viewed as a metabolic disease representing arterial obstruction by fatty deposits in its wall. Today, it is believed that atherogenesis involves highly specific biochemical and molecular responses with constant interactions between various cellular players. Despite the presence of inflammatory reaction in each and every step of atherosclerosis from its inception to terminal manifestation, the cause--effect relationship of these 2 processes remains unclear. In this article, we have attempted to review the role of inflammation in the development of atherosclerosis and in its major complication--coronary heart disease. PMID- 24177336 TI - Myocardial protection provided by chronic skeletal muscle ischemia is not further enhanced by ischemic pre- or postconditioning: comparative effects on intracellular signaling. AB - Chronic skeletal muscle ischemia protects the ischemic heart by preserving coronary flow and inducing arterioangiogenesis. We sought to determine the effect and the underlying molecular mechanisms of preconditioning (PreC) and postconditioning (PostC), applied in a model of chronic skeletal muscle ischemia. Male rabbits were divided into 3 series. In each series, the animals were subjected either to severe hind limb (HL) ischemia, by excision of the femoral artery, or to sham operation (SHO). After 4 weeks, all the animals underwent 30 minutes of regional heart ischemia and 3 hours reperfusion. The animals of the first series received no further intervention (HL and SHO groups), those of the second series underwent PreC (HL + PreC and SHO + PreC), and of the third series PostC (HL + PostC and SHO + PostC). Infarct size (I) and risk zones (R) were determined, and their ratio was calculated in percentage. Three additional series of experiments were performed with respective interventions up to the 10th minute of reperfusion, where sample tissue was obtained for assessment of protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), glycogen synthase kinase 3beta (GSK3beta), p44/42, signal transducer and activator of transcription (STAT) 3, and STAT5. All groups demonstrated significantly smaller percentage of I/R compared with the SHO group (HL: 14.4% +/- 3.7%, HL + PreC: 13.1% +/- 1.0%, SHO + PreC: 21.3% +/- 1.6%, HL + PostC: 18.0% +/- 1.1%, and SHO + PostC: 24.3% +/- 1.7%, P < .05 vs 35.7% +/- 4.4% in SHO). The PreC and PostC did not further reduce the infarct size in HL groups. The Akt, eNOS, GSK3beta, p44/42, and STAT3 were activated in all PreC or PostC groups regardless of the infarct size reduction. The STAT5 was activated only in the HL groups compared with the SHO groups. In conclusion, chronic skeletal muscle ischemia results in effective cardioprotection, which is not further enhanced with application of PreC or PostC. The Akt, eNOS, GSK3beta, p44/42, and STAT3 may only be considered as indicators of the intracellular changes taking place during protection. Activation of STAT5 is possibly the end effector, which is responsible for infarct size reduction provided by chronic skeletal muscle ischemia. PMID- 24177337 TI - Magnetic anisotropy of FeO and CoO: the influence of gradient corrections on exchange and correlation. AB - We study the formation of local magnetic moments and the magnetic anisotropy of the antiferromagnetic transition-metal compounds FeO and CoO in the framework of the density functional theory. Exchange and correlation are described within two (semi-)local approximations, the local spin-density approximation (LDA) and the generalized gradient approximation (GGA), in order to investigate the role of gradient corrections. An additional on-site Coulomb interaction U is considered in an LDA+U/GGA+U approach and spin-orbit interaction is taken into account. We find that the orbital magnetization is strongly quenched in the GGA+U approach compared to LDA+U results and experimental findings. The quenching is explained in terms of an overestimated exchange enhancement for the partially filled 3d shells due to the gradient corrections inherent in GGA+U. PMID- 24177338 TI - Recombinant expression and biochemical characterisation of two alanyl aminopeptidases of Trypanosoma congolense. AB - Trypanosoma congolense is a haemoprotozoan parasite that causes African animal trypanosomosis, a wasting disease of cattle and small ruminants. Current control methods are unsatisfactory and no conventional vaccine exists due to antigenic variation. An anti-disease vaccine approach to control T. congolense has been proposed requiring the identification of parasitic factors that cause disease. Immunoprecipitation of T. congolense antigens using sera from infected trypanotolerant cattle allowed the identification of several immunogenic antigens including two M1 type aminopeptidases (APs). The two APs were cloned and expressed in Escherichia coli. As the APs were expressed as insoluble inclusion bodies it was necessary to develop a method for solubilisation and subsequent refolding to restore conformation and activity. The refolded APs both showed a distinct substrate preference for H-Ala-AMC, an optimum pH of 8.0, puromycin sensitivity, inhibition by bestatin and amastatin, and cytoplasmic localisation. The two APs are expressed in procyclic metacyclic and bloodstream form parasites. Down-regulation of both APs by RNAi resulted in a slightly reduced growth rate in procyclic parasites in vitro. PMID- 24177339 TI - Protease-activated-receptor-2 affects protease-activated-receptor-1-driven breast cancer. AB - Mammalian protease-activated-receptor-1 and -2 (PAR1 and PAR2) are activated by proteases found in the flexible microenvironment of a tumor and play a central role in breast cancer. We propose in the present study that PAR1 and PAR2 act together as a functional unit during malignant and physiological invasion processes. This notion is supported by assessing pro-tumor functions in the presence of short hairpin; shRNA knocked-down hPar2 or by the use of a truncated PAR2 devoid of the entire cytoplasmic tail. Silencing of hPar2 by shRNA attenuated thrombin induced PAR1 signaling as recapitulated by inhibiting the assembly of Etk/Bmx or Akt onto PAR1-C-tail, by thrombin-instigated colony formation and invasion. Strikingly, shRNA-hPar2 also inhibited the TFLLRN selective PAR1 pro-tumor functions. In addition, while evaluating the physiological invasion process of placenta extravillous trophoblast (EVT) organ culture, we observed inhibition of both thrombin or the selective PAR1 ligand; TFLLRNPNDK induced EVT invasion by shRNA-hPar2 but not by scrambled shRNA-hPar2. In parallel, when a truncated PAR2 was utilized in a xenograft mouse model, it inhibited PAR1-PAR2-driven tumor growth in vivo. Similarly, it also attenuated the interaction of Etk/Bmx with the PAR1-C-tail in vitro and decreased markedly selective PAR1-induced Matrigel invasion. Confocal images demonstrated co localization of PAR1 and PAR2 in HEK293T cells over-expressing YFP-hPar2 and HA hPar1. Co-immuno-precipitation analyses revealed PAR1-PAR2 complex formation but no PAR1-CXCR4 complex was formed. Taken together, our observations show that PAR1 and PAR2 act as a functional unit in tumor development and placenta-uterus interactions. This conclusion may have significant consequences on future breast cancer therapeutic modalities and improved late pregnancy outcome. PMID- 24177340 TI - Reconsidering ideas regarding the evolution of peroxisomes: the case for a mitochondrial connection. PMID- 24177341 TI - Precise anatomical study of rhinoplasty: description of a novel method and application to the lateral crural steal. AB - IMPORTANCE: The prediction of nasal tip position in terms of projection, rotation, and length is a major challenge in rhinoplasty. Studies using preoperative and postoperative photographs lack accuracy owing to variable position, and computer-simulated models lack clinical applicability. OBJECTIVES: (1) To describe an accurate and reproducible technique to study the effect of surgical manipulations on the nasal tip; and (2) to describe the effect on the nasal tip cartilages of the lateral crural steal (LCS). DESIGN, SETTING, AND PARTICIPANTS: Cadaveric study in a tertiary hospital center using 10 cadaveric specimens. INTERVENTIONS: Heads were placed in a Mayfield head holder, and a 12.2 megapixel camera was fixed on a tripod in a perfectly still position and focused on the surgical field during all surgical manipulations. An external rhinoplasty approach was performed for all specimens, and a 4-mm LCS was achieved. MAIN OUTCOMES AND MEASURES: Measures include tip projection, tip rotation, and nasal length using preoperative and postoperative photographs. RESULTS: Our method was successfully performed on all specimens: LCS resulted in a significant mean increase in projection using the Goode ratio (mean, 0.05; P = .005) and rotation (mean, 13.2 degrees ; P = .005). However, absolute tip projection variation was inconsistent, ranging from -1.0 mm to 0.6 mm. Nasal length was significantly shortened in all cases (mean, 1.3 mm, P = .005). CONCLUSIONS AND RELEVANCE: We describe the first technique for precise anatomical study of tip position in rhinoplasty on cadaveric specimens. This technique was successfully applied to 10 consecutive nasal tips. We have shown a significant increase in projection using the Goode ratio and rotation with LCS. However, the effect on absolute projection is inconsistent. LEVEL OF EVIDENCE: NA. PMID- 24177342 TI - The rapid identification and quantification of iso-alpha-acids and reduced iso alpha-acids in blood using UHPLC-MS/MS: validation of a novel marker for beer consumption. AB - A method for the detection of iso-alpha-acid (IAA) type ingredient congeners that are derived from the hop plant (Humulus lupulus L.) was developed to detect recent consumption of beer in blood. Three structurally similar but chemically altered IAA, also used as beer-specific ingredients, are known as "reduced IAA", consisting of the rho-, tetrahydro-, and hexahydro-IAA were also targeted. The use of a simple protein precipitation extraction and ultrahigh-performance liquid chromatography system coupled with a tandem mass spectrometer system enabled detection of these analytes in both antemortem and postmortem blood. Extracts were injected onto a C18 solid-core column under gradient elution to achieve separation of isobaric analogs and isomers within a 10-min run time. Electrospray ionization in negative multiple reaction monitoring mode was used to monitor three transitions for each of the analytes that were ultimately grouped together to form a calibration curve for quantification of each of the four IAA groups. The method was fully validated according to international guidelines that included extraction efficiency, matrix effects, process efficiency, ion suppression/enhancement of co-eluting analytes, selectivity, crosstalk, accuracy and precision, stabilities, and lower limits of quantification. Finally, applicability of the method described was demonstrated by the detection of IAA ingredient congeners in the blood of a volunteer following the consumption of a relatively small amount of beer in a pilot study. PMID- 24177343 TI - New insights into vestibular neuropharmacology: from bench to bedside. AB - Recent epidemiological investigations have highlighted the high prevalence of vestibular dysfunctions in the adult population and its association with aging. Despite a large and unmet medical need, the pharmaceutical options of targeted and efficient drugs to reduce the symptoms associated with vestibular deficits remains largely insufficient. This special issue of the Journal of Vestibular Research is devoted to the session: New insights on vestibular neuropharmacology: From bench to bedside, that was organized at the 2012 Midwinter Meeting of the Association of Research in Otolaryngology. This special issue intends 1. to emphasize the current state of the medical need for potent pharmacological treatments of vestibular deficits while highlighting questions regarding the molecular targets, the therapeutic window and the role of pharmacological treatment versus physiotherapy; 2. to give an overview of the fundamental mechanisms of vestibular system function and the mechanism of action of the drugs currently used in the treatment of vestibular disorders and 3. to present recent discoveries in basic research, that may lead to future drug identification to efficiently alleviate the vertigo crisis and protect the vestibule. This theme should target a broad audience ranging from ENT clinicians to scientists, including pharmacologists and pharmacists. PMID- 24177344 TI - Vestibular dysfunction: prevalence, impact and need for targeted treatment. PMID- 24177345 TI - Neuropharmacological basis of vestibular system disorder treatment. AB - This work reviews the neuropharmacology of the vestibular system, with an emphasis on the mechanism of action of drugs used in the treatment of vestibular disorders. Clinicians are confronted with a rapidly changing field in which advances in the knowledge of ionic channel function and synaptic transmission mechanisms have led to the development of new scientific models for the understanding of vestibular dysfunction and its management. In particular, there have been recent advances in our knowledge of the fundamental mechanisms of vestibular system function and of drug action. In this work, drugs acting on vestibular system have been grouped into two main categories according to their primary mechanisms of action: those with effects on neurotransmitters and neuromodulators dynamics and those that act on voltage-gated ion channels. Particular attention is given in this review to drugs that may provide additional insight into the pathophysiology of vestibular diseases. The critical analysis of the literature reveals that there is a significant lack of information defining the real utility of diverse drugs used in clinical practice. The development of basic studies addressing drug actions at the molecular, cellular and systems level, combined with reliable and well controlled clinical trials, would provide the scientific basis for new strategies for the treatment of vestibular disorders. PMID- 24177346 TI - Betahistine treatment in managing vertigo and improving vestibular compensation: clarification. AB - Betahistine dihydrochloride (betahistine) is currently used in the management of vertigo and vestibular pathologies with different aetiologies. The main goal of this review is to clarify the mechanisms of action of this drug, responsible for the symptomatic relief of vertigo and the improvement of vestibular compensation. The review starts with a brief summary recalling the role of histamine as a neuromodulator/neurotransmitter in the control of the vestibular functions, and the role of the histaminergic system in vestibular compensation. Then are presented data recorded in animal models demonstrating that betahistine efficacy can be explained by mechanisms targeting the histamine receptors (HRs) at three different levels: the vascular tree, with an increase of cochlear and vestibular blood flow involving the H1R; the central nervous system, with an increase of histamine turnover implicating the H3R, and the peripheral labyrinth, with a decrease of vestibular input implying the H3R/H4R. Clinical data from vestibular loss patients show the impact of betahistine treatment for the long-term control of vertigo, improvement of balance and quality of life that can be explained by these mechanisms of action. However, two conditions, at least, are required for reaching the betahistine therapeutic effect: the dose and the duration of treatment. Experimental and clinical data supporting these requirements are exposed in the last part of this review. PMID- 24177347 TI - Symptomatic treatment of vestibular deficits: therapeutic potential of histamine H4 receptors. AB - Vestibular disorders display high prevalence and can severely impact the daily life. However, pharmacological options that would efficiently relieve the vertigo symptoms without side effects are still lacking. In the present review we briefly review the common history of histamine receptor modulation and the pharmacological therapy of vestibular disorders. We also discuss the recent demonstration of Histamine H4 Receptor mRNAs expression in Scarpa's ganglion of mammal and the potential use of specific H4R antagonists as vestibulomodulators. Additional original data confirm the expression of H4R proteins in the rat vestibular primary neurons, the neuromodulatory properties of specific H4R antagonists in vitro (inhibition of vestibular neuron excitability) as well as their efficacy to decrease vestibular deficits induced in different in animal models. PMID- 24177348 TI - A review of synaptic mechanisms of vestibular efferent signaling in turtles: extrapolation to efferent actions in mammals. AB - The vestibular labyrinth of nearly every vertebrate class receives a prominent efferent innervation that originates in the brainstem and ends as bouton terminals on vestibular hair cells and afferents in each end organ. Although the functional significance of this centrifugal pathway is not well understood, it is clear that efferent neurons, when electrically stimulated under experimental conditions, profoundly impact vestibular afferent discharge. Effects range from chiefly excitation in fish and mammalian vestibular afferents to a more heterogeneous mixture of inhibition and/or excitation in amphibians, reptiles, and birds. What accounts for these diverse response properties? Recent cellular and pharmacological characterization of efferent synaptic mechanisms in turtle offers some insight. In the turtle posterior crista, vestibular efferent neurons are predominantly cholinergic and the effects of efferent stimulation on vestibular afferent discharge can be ascribed to three distinct signaling pathways: (1) Hyperpolarization of type II hair cells mediated by alpha9/alpha10 nAChRs and SK-potassium channels; (2) Depolarization of bouton and calyx afferents via alpha4beta2*-containing nAChRs; and (3) A slow excitation of calyx afferents attributed to muscarinic AChRs. In this review, we discuss the evidence for these pathways in turtle and speculate on their role in mammalian vestibular efferent actions where synaptic mechanisms are largely unknown. PMID- 24177349 TI - Ondansetron reduces lasting vestibular deficits in a model of severe peripheral excitotoxic injury. AB - Vestibular neuritis is a neuroinflammatory, peripheral vestibular pathology leading to chronic deficits and long-term disability. While current corticosteroid-based therapy does not appear to positively influence the long term outcome for the patient, a recent clinical pilot study suggested a functional vestibuloprotective effect of the anti-emetic ondansetron in the treatment of vestibular neuritis. We here demonstrate that systemic post-insult administration of ondansetron in a novel rat model of severe excitotoxic vestibular insult reproduces the clinically demonstrated functional benefits. This ondansetron-conferred reduction of functional deficits stems from the protection of synapses between sensory hair cells and primary neurons from excitotoxically induced lesion. PMID- 24177350 TI - Stepwise design of non-covalent wrapping of large diameter carbon nanotubes by peptides. AB - Single-walled carbon nanotube (SWCNT) is one of the most popular low-dimensional carbon materials in material science, nanomedicine, and nanoscale electronics. Yet the application of the SWCNTs was hindered by the self-aggregation. To purify and disperse the SWCNTs, non-covalent wrapping is one of the effective options to overcome such defects. In this work, two kinds of short peptides were designed to facilitate the modification of large-diameter SWCNT. The design of the peptide was carried out in a stepwise manner. The effective residues of helix-rich and sheet-rich proteins on SWCNT were studied at the first step, and then a coarse model peptide composed of the key adsorption residues above was built to investigate the adsorption dynamics on SWCNT. In the end, the residues include long alkyl side chain and that include aromatic rings were found to play key roles on the adsorption of protein/peptide on hydrophobic SWCNT. And two peptides rich in the long alkyl chain and aromatic rings were constructed respectively. The predominant adsorption capabilities of the two kinds of peptides were discerned by the adsorption details. PMID- 24177352 TI - Nanotechnology and drug resistance. PMID- 24177351 TI - Tumour-on-a-chip provides an optical window into nanoparticle tissue transport. AB - Nanomaterials are used for numerous biomedical applications, but the selection of optimal properties for maximum delivery remains challenging. Thus, there is a significant interest in elucidating the nano-bio interactions underlying tissue accumulation. To date, researchers have relied on cell culture or animal models to study nano-bio interactions. However, cell cultures lack the complexity of biological tissues and animal models are prohibitively slow and expensive. Here we report a tumour-on-a-chip system where incorporation of tumour-like spheroids into a microfluidic channel permits real-time analysis of nanoparticle (NP) accumulation at physiological flow conditions. We show that penetration of NPs into the tissue is limited by their diameter and that retention can be improved by receptor targeting. NP transport is predominantly diffusion-limited with convection improving accumulation mostly at the tissue perimeter. A murine tumour model confirms these findings and demonstrates that the tumour-on-a-chip can be useful for screening optimal NP designs prior to in vivo studies. PMID- 24177353 TI - Ethno-medicinal uses and screening of plants for antibacterial activity from Similipal Biosphere Reserve, Odisha, India. AB - ETHNOPHARAMCOLOGICAL RELEVANCE: The present study examined the variety and the extent of medicinal plants used in the health care system of tribal inhabitants of Similipal Biosphere Reserve. In addition to this, such plants were also screened for antibacterial properties against common pathogenic bacteria. MATERIAL AND METHODS: Semi-structured interview was carried out with 42 informants (mean age 42, 86% male, 14% female) at 24 locations in and around SBR, regarding the use of plants for the treatment of various human ailments. Antibacterial screening is adopted with the documented ethnomedicinal plants using methanol and aqueous extracts against eight bacterial strains. RESULTS: A total of 187 plant species belonging to 74 families were documented for frequent medicinal uses against common ailments such as stomach problems, fever, skin diseases, diarrhea and dysentery. Although all parts of plant are used, leaves and bark are most common. Tribals used the plant parts both in form of decoction (taken orally as in internal problems) and paste (external use). Out of 187 plant species, 120 plants recorded antibacterial activity against test bacterial strain. CONCLUSIONS: This study revealed that self care using medicinal plants is a common practice by the tribes of SBR. About 64% of the used plants have scientifically proved medicinal values with respect to the antibacterial properties. PMID- 24177354 TI - Transfection and structural properties of phytanyl substituted gemini surfactant based vectors for gene delivery. AB - In this study, the transfection ability and cytotoxicity of a series of phytanyl substituted gemini surfactants, rationally designed and synthesized in an attempt to create cationic surfactants that will improve transfection efficiencies of non viral vectors was evaluated in OVCAR-3 cells at the charge ratios (N(+)/P(-)) of 2:1, 5:1, and 10:1. Particle sizes, zeta potentials, and small angle X-ray scattering (SAXS) profiles were also determined. For each gemini surfactant complex, the transfection efficiency and cytotoxicity are observed to go through a more or less well-evidenced maximum, occurring at different values of the charge ratio (N(+)/P(-)), depending on the surfactant structure. Considering both results of in vitro transfection efficiency and cytotoxicity, the optimal charge ratio to formulate the complexes containing phy-3-m was found to be 5:1. The particle size decreased, while zeta potential increased with increasing N(+)/P( ). Comparing particle size and zeta potential with transfection efficiency, no correlation between size/zeta potential and transfection ability was observed. Analysis of SAXS profiles indicates that the ability of phy-3-m delivery system to adopt multiple phases correlated well with their higher transfection efficiency in OVCAR-3 cells. PMID- 24177355 TI - Comparative cost-effectiveness of bevacizumab-irinotecan-fluorouracil versus irinotecan-fluorouracil in first-line metastatic colorectal cancer. AB - PURPOSE: To evaluate the cost-effectiveness of the addition of bevacizumab to the irinotecan-fluorouracil (Douillard regimen-CPT-FUFA-) in first-line treatment of metastatic colorectal cancer in a single-institution population. METHODS: Controlled, nonrandomized retrospective observational study. Treatment-naive metastatic colorectal cancer patients received CPT-FUFA (January 2000-December 2003; control group) and bevacizumab_CPT-FUFA (January 2007-December 2010; study group). Variables related to: patient, clinical response (number of disease progression or death events, progression-free survival) and treatment (antineoplastic dose reduction, incremental cost/treated patient associated with the addition of bevacizumab). STATISTICAL ANALYSIS: median progression-free survival (Kaplan-Meier method), and hazard ratio (Cox regression). Survival curves were compared (Mantel-Haenszel test). RESULTS: In all, 69 patients were included: 32 (57.2 years -95%CI: 54.0-60.5-, 65.6% men) in CPT-FUFA group and 37 (68.1 years - 95%CI: 65.5-70.7-, 78.4% men) in bevacizumab_CPT-FUFA group. The disease progression or death events were 29 (90.6%) in CPT-FUFA group and 34 (91.9%) in bevacizumab_CPT-FUFA group. Median progression-free survival was 10.1 months (95%CI: 7.1-12.2) in CPT-FUFA and 11.0 months (95%CI: 7.6-12.6) in bevacizumab_CPT-FUFA (hazard ratio = 1.22; 95%CI: 0.7-2.1). Dose reductions: irinotecan and fluorouracil 11% (range: 4-20) in 5/32 (15.6%) CPT-FUFA patients and 25% (range: 8-35) in 18/37 (48.6%) bevacizumab_CPT-FUFA patients; Bevacizumab 30% (range: 4-50) in 20/37 (54.1%) bevacizumab_CPT-FUFA patients. The incremental cost associated with the addition of bevacizumab was 12,696.5 (IC95%:10,860.8 14,532.1) euros/patient. CONCLUSION: The addition of bevacizumab to the irinotecan-fluorouracil regimen, does not improve progression-free survival in our study population but increases costs per treated patient. These results potentially compromise the cost-effectiveness of the Bevacizumab_CPT-FUFA regimen. PMID- 24177356 TI - Retrospective review of vancomycin-induced nephrotoxicity in patients with leukemia. AB - BACKGROUND: The occurrence of nephrotoxicity with vancomycin is approximately 17%, but can increase to 35% when combined with other nephrotoxic agents. Patients with hematologic malignancies may be at greater risk for vancomycin induced nephrotoxicity due to nephrotoxic chemotherapy and tumor lysis syndrome. OBJECTIVE: The primary objective of this study was to determine the occurrence of nephrotoxicity in adult patients with leukemia receiving vancomycin. METHODS: A retrospective review approved by the Institutional Review Board was conducted on adult patients with leukemia who received at least one dose of vancomycin during hospital admission between 1 January 2009 and 30 April 2009. RESULTS: Forty patients had an occurrence of nephrotoxicity (16%) while 210 patients did not have an occurrence of nephrotoxicity. In multivariate analysis, variables significantly associated with development of nephrotoxicity included active disease status (odds ratio, 4.38 [95% CI 1.1-29.4], p = 0.0291), concomitant intravenous acyclovir administration (odds ratio, 3.83 [95% CI, 1.6-8.9]; p = 0.0022), and concomitant amphotericin administration (odds ratio, 4.26 [95% CI, 1.9-9.4]; p = 0.0004). CONCLUSION: The occurrence of nephrotoxicity in patients with leukemia treated with vancomycin was 16% in our study, similar to previously published reports. Active disease status and concomitant use of intravenous acyclovir and amphotericin were identified as significant risk factors for development of nephrotoxicity. The presence of risk factors for vancomycin nephrotoxicity should be evaluated prior to initiation of therapy to determine appropriateness of use. PMID- 24177357 TI - Synthesis, biological evaluation and molecular modeling studies of some novel thiazolidinediones with triazole ring. AB - A new series of thiazolidinedione derivatives were synthesized and evaluated for in vitro alpha-glucosidase inhibition and anticancer activities. Compounds 3d, 3e and 3j showed potential alpha-glucosidase inhibition with IC50 values ranging between 0.1 and 0.3 MUg/ml whereas compounds 3i, 3j and 3k have showed better anticancer activity towards human cancer cell lines IMR-32 (neuroblastoma), Hep G2 (hepatoma) and MCF-7 (breast). Molecular docking studies revealed compounds 3d, 3e and 3j are potent inhibitors of alpha-glucosidase and also showed compliance with standard parameters of drug likeness. PMID- 24177358 TI - Synthesis and evaluation of hexahydropyrimidines and diamines as novel hepatitis C virus inhibitors. AB - In order to identify novel anti-hepatitis C virus (HCV) agents we devised cell based strategies and screened phenotypically small molecule chemical libraries with infectious HCV particles, and identified a hit compound (1) containing a hexahydropyrimidine (HHP) core. During our cell-based SAR study, we observed a conversion of HHP 1 into a linear diamine (6), which is the active component in inhibiting HCV and exhibited comparable antiviral activity to the cyclic HHP 1. In addition, we engaged into the biological characterization of HHP and demonstrated that HHP does not interfere with HCV RNA replication, but with entry and release of viral particles. Here we report the results of the preliminary SAR and mechanism of action studies with HHP. PMID- 24177359 TI - Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides. AB - We herein report the application of the phosphorodiamidate phosphate prodrug approach to a series of thirteen nucleoside analogs with antiviral or anticancer activity. Twenty-five symmetrical phosphorodiamidates were synthesized, bearing esterified l-Alanine (and in one case d-Alanine) in the prodrug moiety, each as single stereoisomer. The presence of an achiral phosphorus represents a potential advantage over the phosphoramidate ProTide approach, where diastereoisomeric mixtures are routinely obtained, and different biological profiles may be expected from the diastereoisomers. Optimization of the synthetic pathway allowed us to identify two general methods depending on the particular nucleoside analogs. All the compounds were biologically evaluated in antiviral and anticancer assays and several showed improvement of activity compared to their parent nucleosides, as in the case of ddA, d4T, abacavir and acyclovir against HIV-1 and/or HIV-2. The biological results were supported by metabolism studies with carboxypeptidase Y monitored by (31)P NMR to investigate their bioactivation. This work further validates the phosphorodiamidate approach as a monophosphate prodrug motif with broad application in the antiviral and anticancer fields. PMID- 24177360 TI - Synthesis, anticonvulsant and anti-inflammatory studies of new 1,4-dihydropyridin 4-yl-phenoxyacetohydrazones. AB - The present work involves design and synthesis of new substituted 1,4 dihydropyridin-4-yl-phenoxyacetohydrazones (4a-s, 5a-h), starting from 4 hydroxybenzaldehyde. The final compounds were screened for their in vivo anticonvulsant activity by MES, scPTZ and 6 Hz methods, while their anti inflammatory screening was performed by Carrageenan induced Paw Edema method. The results indicated that compounds carrying electron donating groups are anticonvulsant active, while most of the tested compounds exhibited significant anti-inflammatory activity. Compounds 4k, l, 4p-s, and 5c showed rapid anti inflammatory activity within 30 min and appeared as lead compounds. Further, Neurotoxicity study revealed that all the tested compounds are non-toxic up to 300 mg/kg doses. Selected compounds were also subjected to analgesic screening following Tail immersion method and they exhibited good activity. PMID- 24177361 TI - Synthesis, biological evaluation and molecular modeling study of 5 trifluoromethyl-Delta2-pyrazoline and isomeric 5/3-trifluoromethylpyrazole derivatives as anti-inflammatory agents. AB - Searching for new anti-inflammatory agents, we have prepared a series of potential COX-2 inhibitors, 1-(4,6-dimethylpyrimidin-2-yl)-5-hydroxy-5 trifluoromethyl-Delta(2)-pyrazolines (3) and 1-(4,6-dimethylpyrimidin-2-yl)-3 trifluoromethylpyrazoles (4), by refluxing 2-hydrazino-4,6-dimethylpyrimidine (1) with a number of trifluoromethyl-beta-diketones (2) in ethanol. Further dehydration of compounds (3) to the corresponding 1-(4,6-dimethylpyrimidin-2-yl) 5-trifluoromethylpyrazoles (5) was also achieved. Fifteen of these compounds were screened for their anti-inflammatory activity using the carrageenan-induced rat paw edema assay. While all the compounds exhibited significant anti-inflammatory activity (47-76%) as compared to indomethacin (78%), 3-trifluoromethylpyrazoles (4) were found to be the most effective agents (62-76%). To rationalize this anti inflammatory activity, docking experiments molecular dynamics simulations were performed to study the ability of these compounds to bind into the active site of the COX-2 enzyme. PMID- 24177362 TI - Synthesis and anticancer potential of certain novel 2-oxo-N'-(2-oxoindolin-3 ylidene)-2H-chromene-3-carbohydrazides. AB - Treatment of ethyl 3-hydrazinyl-3-oxopropanoate (6) with indoline-2,3-dione derivatives 7a-g gave ethyl 3-oxo-3-(2-(2-oxoindolin-3 ylidene)hydrazinyl)propanoates 8a-g which were allowed to react with the appropriate salicyaldehyde 9a and/or 9b to furnish the chromene-based hydrazones 10a-i. Compounds 10a-i displayed a significant activity against HT-29 colon cancer cell line and a moderate activity against leukemia K562 cell line. Compound 10f emerged as the most active congener toward HT-29 colon cancer cell line with IC50 = 7.98 +/- 0.05 MUM whereas compound 10c exhibited the best antiproliferative activity against leukemia K562 cell line with IC50 = 9.44 +/- 0.02 MUM. Moreover, compound 1e showed 87.81 +/- 7% inhibition of side population (SP) HT-29 colon cancer stem cells. PMID- 24177363 TI - Two new neutral copper(II) complexes with dipicolinic acid and 3-amino-1H-1,2,4 triazole formed under different reaction conditions: synthesis, characterization, molecular structures and DNA-binding studies. AB - Two Cu(II) complexes, [Cu2(MU-atr)(pydc)2(H2O)4].5H2O (1) and [Cu(atr)(pydc) (H2O)].H2O (2), with pyridine-2,6-dicarboxylic acid (H2pydc) and 3-amino-1H-1,2,4 triazole (atr), have been synthesized and characterized. The interaction ability of the both complexes with native calf thymus DNA (CT-DNA) has been monitored as a function of the metal complex-DNA molar ratio. UV-vis spectrophotometry, circular dichroism (CD), thermal denaturation studies, cyclic voltammetry (CV) and viscosity measurements. The intrinsic binding constants K(b) of complexes 1 and 2, with CT-DNA obtained from UV-vis absorption studies were 4.7 (+/-0. 1) * 10(4) and 9.5 (+/-0. 1) * 10(4) M(-1), respectively. Further investigation of interaction mode was performed using viscosity, cyclic voltammetry and T(m) of CT DNA studies as well as CD study, indicating complexes bind to DNA via an intercalation mode. PMID- 24177364 TI - Novel camphane-based anti-tuberculosis agents with nanomolar activity. AB - A series of new amidoalcohols and amidodiols were designed on the base of the camphor scaffold and evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv and MDR strain 43. Some of the new compounds show 25 times higher activity than the classical anti-TB drug ethambutol. Small structural changes in the side chain shift the activity from micromolar to nanomolar inhibitory concentrations. Quantitative structure-activity relationship (QSAR) model is derived to guide the further lead optimization. Two hydrogen bond donors and up to three rings in the molecules are optimal for nanomolar activity. The camphane-based amides present novel promising scaffolds for antimycobacterial agents. PMID- 24177365 TI - Aziridines from alkenyl-beta-D-galactopyranoside derivatives: Stereoselective synthesis and in vitro selective anticancer activity. AB - A series of new aziridines beta-D-galactopyranoside derivatives were synthesized from alkenyl beta-D-galactopyranosides employing Sharpless conditions. The structures of the compounds were established by (1)H NMR, (13)C NMR, MS, HRMS and elemental analysis. The stereoselectivity of the reaction and the structural requirements of the alkenyl precursor for improving diastereoisomeric excesses of the direct aziridination reaction were also studied. The new compounds were subjected to a preliminary screening for cytotoxic activity against human lung cancer cells vs. human non-malignant lung cells. Terminal aziridine derivatives showed activity and, most notably, selectivity. One of the most active and selective compounds was also evaluated against breast cancer cells, melanoma cells, and non-malignant cells from the same origin. Its cytotoxic activity was similar to that of the positive controls, displaying a highly selective cytotoxic activity against both types of cancer cells. PMID- 24177366 TI - Novel toll-like receptor 4 (TLR4) antagonists identified by structure- and ligand based virtual screening. AB - Toll-like receptor 4 (TLR4) in complex with its accessory protein MD-2 represents an emerging target for the treatment of severe sepsis and neuropathic pain. We performed structure-based and ligand-based virtual screening targeting the TLR4 MD-2 interface. Three in silico hit compounds showed promising TLR4 antagonistic activities with micromolar IC50 values. These compounds also suppressed cytokine secretion by human peripheral blood mononuclear cells. The specific affinity of the most potent hit was confirmed by surface plasmon resonance direct-binding experiments. The results of our study represent a very promising starting point for the development of potent small-molecule antagonists of TLR4. PMID- 24177367 TI - Fragment-based approach to the design of 5-chlorouracil-linked-pyrazolo[1,5 a][1,3,5]triazines as thymidine phosphorylase inhibitors. AB - 5-Chlorouracil-linked-pyrazolo[1,5-a][1,3,5]triazines were designed as new thymidine phosphorylase inhibitors based on the fragment based drug design approach. Multiple-step convergent synthetic schemes were devised to generate the target compounds. The intermediate 5-chloro-6-chloromethyluracil was synthesized by a 4-step reaction. A series of the second bicyclic intermediates, namely pyrazolo[1,5-a][1,3,5]triazin-2-thioxo-4-one, was obtained from various substituted 3-aminopyrazoles. These two intermediates were coupled finally in the presence of sodium ethoxide and methanol to yield the desirable target compounds. The methylthio coupling spacer was found to be suitable in enabling the interaction of the two fragments at the active site and allosteric site of the enzyme. The best coupled compound (9q) inhibited the thymidine phosphorylase with an IC50 value as low as 0.36 +/- 0.1 MUM. In addition, 9q demonstrated a mixed type of enzyme inhibition kinetics, thus suggesting that it might indeed potentially bind at two different sites on the enzyme. PMID- 24177368 TI - Synthesis of 1,3-thiazine-2,4-diones with potential anticancer activity. AB - 2-Amino-1,3-thiazin-4-ones were subjected to acetylation followed by mild acid hydrolysis to give compounds containing the 1,3-thiazine-2,4-dione core. The potential of these S,N-containing heterocycles as antitumor agents against human cancer cell lines, among other types, was evaluated. The results show that phenyl and naphthyl-substituted thiazinediones presented selective antitumoral activity against leukemia cells. These compounds caused cell death with DNA fragmentation and the mechanism of action seems to involve caspase cascade activation, imbalance in intracellular Ca(2+) and mitochondrial metabolism, and/or endoplasmic reticulum stress. PMID- 24177369 TI - Course of quantitative ventricular fibrillation waveform measure and outcome following out-of-hospital cardiac arrest. AB - BACKGROUND: Quantitative measures of the ventricular fibrillation waveform at the outset of resuscitation are associated with survival. However, little is known about the course of these measures during resuscitation and how this course is related to outcome. OBJECTIVE: The purpose of this study was to determine how waveform measures change over the course of resuscitation and whether these changes might be used to guide resuscitation. METHODS: We evaluated 390 persons treated by emergency providers following out-of-hospital ventricular fibrillation arrest. We assessed the ventricular fibrillation waveform using the amplitude spectrum area (AMSA) from the defibrillator's continuous electrocardiogram measured before each of the first three shocks. We used logistic regression to evaluate the relationship of AMSA and the change in AMSA with favorable neurologic survival as determined by the Cerebral Performance Category at hospital discharge 1-2. RESULTS: Of the 390 patients who received an initial shock, 273 required a second shock and 210 required a third shock. The mean (standard deviation) for AMSA was 9.64 (0.52) for the 873 total shock cycles. AMSA1 measured before the first shock was strongly associated with favorable neurologic survival (odds ratio [OR] 3.40, 95% confidence interval [CI] [2.48, 4.66] for 1 SD change). We observed a similar relationship for second-shock AMSA2 (OR 3.53, 95% CI [2.42, 5.14]) and third-shock AMSA3 (OR 3.10, 95% CI [2.03, 4.73]). The median change in AMSA was 0.24 for DeltaAMSA1-2 and 0.21 for DeltaAMSA2-3. A positive median change in AMSA between shocks was associated with favorable neurologic survival (OR 1.44, 95% CI [1.16, 1.80] for DeltaAMSA1-2 and OR 1.31, 95% CI [1.01, 1.71] for DeltaAMSA2-3). CONCLUSION: Given their prognostic and dynamic qualities, quantitative waveform measures may provide an effective real-time strategy to guide individual treatment and improve survival. PMID- 24177370 TI - Initial impedance decrease as an indicator of good catheter contact: insights from radiofrequency ablation with force sensing catheters. AB - BACKGROUND: Good catheter-tissue contact force (CF) is critical for transmural and durable lesion formation during radiofrequency (RF) ablation but is difficult to assess in clinical practice. Tissue heating during RF application results in an impedance decrease at the catheter tip. OBJECTIVE: The purpose of this study was to correlate achieved CF and initial impedance decreases during atrial fibrillation (AF) ablation. METHODS: We correlated achieved CF and initial impedance decreases in patients undergoing ablation for AF with two novel open irrigated CF-sensing RF catheters (Biosense Webster SmartTouch, n = 647 RF applications; and Endosense TactiCath, n = 637 RF applications). We then compared those impedance decreases to 691 RF applications with a standard open-irrigated RF catheter (Biosense Webster ThermoCool). RESULTS: When RF applications with the CF-sensing catheters were analyzed according to an achieved average CF <5 g, 5-10 g, 10-20 g, and >20 g, the initial impedance decreases during ablation were larger with greater CF. Corresponding median values at 20 seconds were 5 Omega (interquartile range [IQR] 2-7), 8 Omega (4-11), 10 Omega (7-16), and 14 Omega (10-19) with the SmartTouch and n/a, 4 Omega (0-10), 8 Omega (5-12), and 13 Omega (8-18) with the TactiCath (P <.001 between categories for both catheters). When RF applications with the SmartTouch (CF-sensing catheter, median achieved CF 12 g) and ThermoCool (standard catheter) were compared, the initial impedance decrease was significantly greater in the CF-sensing group with median decreases of 10 Omega (6-14 Omega) vs 5 Omega (2-10 Omega) at 20 seconds (P <.001 between catheters). CONCLUSION: The initial impedance decrease during RF applications in AF ablations is larger when greater catheter contact is achieved. Monitoring of the initial impedance decrease is a widely available indicator of catheter contact and may help to improve formation of durable ablation lesions. PMID- 24177371 TI - How safe is ajmaline challenge in patients with suspected Brugada syndrome? PMID- 24177372 TI - Computer modeling and MRI-device safety: modeling, myths, and magical thinking. PMID- 24177374 TI - Synthesis of the double-shell anatase-rutile TiO2 hollow spheres with enhanced photocatalytic activity. AB - A novel double-shell TiO2 hollow sphere with an inner anatase shell and an outer rutile shell was synthesized by a simple sol-gel method and silica protected calcination process. The structure and formation mechanism was proposed based on characterization using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The double-shell spheres have a uniform diameter of 360 nm and a typical yolk-shell structure. Moreover, the double-shell TiO2 hollow spheres possess a large specific surface area (169 m(2) g(-1)). Due to the high surface area, multiple light reflection and beneficial electron conduction between the inner anatase and outer rutile shell of this special structure, the as-prepared double-shell TiO2 catalysts show remarkably enhanced photoactivity compared to the commercial P25 catalyst. In particular, rhodamine B molecules can be completely decomposed in the presence of the double-shell spheres after 60 minutes of irradiation with UV light. In addition, the high activity is retained after five cycles, indicating the stability and reusability of the double-shell catalyst. PMID- 24177373 TI - Gene expression and genetic variation in human atria. AB - BACKGROUND: The human left and right atria have different susceptibilities to develop atrial fibrillation (AF). However, the molecular events related to structural and functional changes that enhance AF susceptibility are still poorly understood. OBJECTIVE: The purpose of this study was to characterize gene expression and genetic variation in human atria. METHODS: We studied the gene expression profiles and genetic variations in 53 left atrial and 52 right atrial tissue samples collected from the Myocardial Applied Genomics Network (MAGNet) repository. The tissues were collected from heart failure patients undergoing transplantation and from unused organ donor hearts with normal ventricular function. Gene expression was profiled using the Affymetrix GeneChip Human Genome U133A Array. Genetic variation was profiled using the Affymetrix Genome-Wide Human SNP Array 6.0. RESULTS: We found that 109 genes were differentially expressed between left and right atrial tissues. A total of 187 and 259 significant cis-associations between transcript levels and genetic variants were identified in left and right atrial tissues, respectively. We also found that a single nucleotide polymorphism at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right atrial tissues. CONCLUSION: We found a distinct transcriptional profile between the right and left atrium and extensive cis-associations between atrial transcripts and common genetic variants. Our results implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF. PMID- 24177375 TI - Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn's disease. AB - BACKGROUND & AIMS: We assessed the accuracy of magnetic resonance enterography (MRE) in monitoring response to therapy in patients with Crohn's disease (CD) using ileocolonoscopy as a reference standard. METHODS: We performed a prospective multicenter study of 48 patients with active CD and ulcers in at least one ileocolonic segment. All patients underwent ileocolonoscopy and MRE at baseline and 12 weeks after completing treatment with corticosteroids (CS) or anti-tumor necrosis factor agents. Disease activity was quantified using Crohn's Disease Endoscopic Index of Severity (CDEIS) and Magnetic Resonance Index of Activity (MaRIA). The primary analysis was to determine the accuracy of MRE in identification of healing, defined as the disappearance of ulcers in endoscopy examination. Additional analyses established the accuracy of MRE in determining endoscopic remission (a CDEIS score <3.5) and change in severity based on consideration of all segments. RESULTS: MRE determined ulcer healing with 90% accuracy and endoscopic remission with 83% accuracy. The mean CDEIS and MaRIA scores significantly changed at week 12 in segments with ulcer healing, based on endoscopic examination (CDEIS: 21.28 +/- 9.10 at baseline vs 2.73 +/- 4.12 at 12 weeks; P < .001 and MaRIA: 18.86 +/- 9.50 at baseline vs 8.73 +/- 5.88 at 12 weeks; P < .001). The MaRIA score accurately detected changes in lesion severity (Guyatt score: 1.2 and standardized effect size: 1.07). MRE was as reliable as endoscopy in assessing healing; no significant changes in CDEIS or MaRIA scores were observed in segments with persistent ulcers, based on endoscopic examination (CDEIS: 26.43 +/- 9.06 at baseline vs 20.77 +/- 9.13 at 12 weeks; P = .18 and MaRIA: 22.13 +/- 8.42 at baseline vs 20.77 +/- 9.17 at 12 weeks; P = .42). The magnitude of change in CDEIS scores correlated with those in MaRIA scores (r = 0.51; P < .001). CONCLUSIONS: MRE evaluates ulcer healing with a high level of accuracy when ileocolonoscopy is used as the reference standard. The MaRIA is a valid, responsive, and reliable index assessing response to therapy in patients with CD. PMID- 24177376 TI - Boceprevir plus peginterferon alpha-2b/ribavirin in chronic hepatitis C genotype 1: impact of baseline viral load on sustained virologic response. AB - BACKGROUND: Baseline viral load is a predictor of treatment outcome in patients with hepatitis C virus (HCV) infection receiving peginterferon and ribavirin. The impact of baseline viral load on sustained virologic response (SVR) after boceprevir-based therapy is unknown. METHODS: This retrospective analysis included patients with chronic HCV genotype 1 infection who were previously untreated or were previous treatment failures. Virologic response was assessed according to baseline viral load (<=1 million IU/mL, >1 to <=5 million IU/mL, >5 to <=10 million IU/mL, and >10 million IU/mL). RESULTS: SVR was higher in patients receiving boceprevir plus peginterferon and ribavirin than in those receiving peginterferon and ribavirin alone, regardless of baseline viral load. Patients with a baseline viral load <=1 million IU/mL had the highest SVR (boceprevir plus peginterferon and ribavirin, 78% to 83%; peginterferon and ribavirin, 33% to 63%). Among patients with baseline viral load >1 million IU/mL, SVR rates were 57% to 68% in patients receiving boceprevir plus peginterferon and ribavirin, and 11% to 41% in patients receiving peginterferon and ribavirin. Relapse was higher in patients receiving peginterferon and ribavirin (previously untreated, 12% to 40%; previous treatment failures, 17% to 67%) than in those receiving boceprevir plus peginterferon and ribavirin (previously untreated, 3% to 12%; previous treatment failure, 9% to 16%), irrespective of baseline viral load. CONCLUSIONS: The efficacy of boceprevir plus peginterferon and ribavirin was unaffected by baseline viral loads >1 million IU/mL, whereas viral burden >1 million IU/mL was associated with lower SVR with peginterferon and ribavirin. Relapse rates were lower with boceprevir plus peginterferon and ribavirin than with peginterferon and ribavirin, and were unaffected by baseline viral load. PMID- 24177377 TI - Serum eosinophil cationic protein is superior to mast cell tryptase as marker for response to topical corticosteroid therapy in eosinophilic esophagitis. AB - GOALS: We evaluated the serum levels of eosinophil cationic protein (ECP) and mast cell tryptase (MCT) as surrogate markers for response to treatment in adults with eosinophilic esophagitis (EoE) under topical steroid therapy with fluticasone. BACKGROUND: EoE is a chronic disease characterized histologically by eosinophilic inflammation of the esophagus. Esophageal mastocytosis and mast cell activation have been implicated in EoE pathogenesis. STUDY: Fifteen patients with EoE completed this prospective observational study. Before and after 3 months of therapy with fluticasone, eosinophilic and mast cell counts were analyzed from histologic samples of the esophagus and were correlated with serum markers ECP and MCT. RESULTS: Fluticasone-therapy significantly decreased mean eosinophils [from 42.2 to 16.2 eosinophils/high-power field (hpf); P=0.004] and mast cells (from 13.9 to 5.1 mast cells/hpf; P=0.001) in the esophageal epithelium. There was a significant decrease of mean ECP (from 15.6 to 5.5 MUg/L; P=0.024) and MCT serum-values (from 4.7 to 3.8 MUg/L; P=0.029) under therapy. Serum-ECP correlated significantly with histologic eosinophilic counts after fluticasone-therapy (r=0.54; P=0.038) in contrast to serum-MCT. CONCLUSIONS: Serum-ECP but not serum MCT could be a promising noninvasive biomarker to assess response to topical corticosteroid therapy in EoE. These findings should be confirmed by larger studies; ClincialTrials.gov number, NCT01624129. PMID- 24177378 TI - A novel endoscopic papillectomy after a pancreatic stent placement above the pancreatic duct orifice: inside pancreatic stenting papillectomy. AB - BACKGROUND: Although pancreatic stenting is recommended for the prevention of postprocedure pancreatitis during endoscopic papillectomy (EP), in some patients it is technically difficult to perform postprocedure insertion of a pancreatic stent after endoscopic resection. GOALS: This study assessed the feasibility of a novel EP for the purpose of reliable post-EP pancreatic stenting. STUDY: We conducted a prospective pilot study involving 10 consecutive patients with tumor of the major duodenal papilla. We developed a novel pancreatic stent, which is attached to a suture, and devised a method by which the stent is first placed at an upstream migration into the major pancreatic duct above the orifice before resection and then placed at an appropriate location after endoscopic resection by pulling the suture attached to the stent [inside pancreatic stenting papillectomy (IPSP)]. RESULTS: The pancreatic stent was successfully placed at an upstream migration into the pancreatic duct above the orifice in 9 of the 10 patients. For the 9 patients with successful pancreatic stent placement, IPSP was performed. Although the suture was cut in 1 patient, pancreatic stents could be placed appropriately across the orifice by pulling the suture in all patients. Although bleeding occurred in 3 patients, there was no pos-procedure pancreatitis. CONCLUSIONS: IPSP is a practicable method allowing reliable post-EP pancreatic stenting and can contribute to pancreatitis prevention. However, larger studies need to be performed before its use can be recommended. PMID- 24177379 TI - A statistical model for QTL mapping in polysomic autotetraploids underlying double reduction. AB - As a group of economically important species, linkage mapping of polysomic autotetraploids, including potato, sugarcane and rose, is difficult to conduct due to their unique meiotic property of double reduction that allows sister chromatids to enter into the same gamete. We describe and assess a statistical model for mapping quantitative trait loci (QTLs) in polysomic autotetraploids. The model incorporates double reduction, built in the mixture model-based framework and implemented with the expectation-maximization algorithm. It allows the simultaneous estimation of QTL positions, QTL effects and the degree of double reduction as well as the assessment of the estimation precision of these parameters. We performed computer simulation to examine the statistical properties of the method and validate its use through analyzing real data in tetraploid switchgrass. PMID- 24177380 TI - Allotetraploid and autotetraploid models of linkage analysis. AB - As a group of important plant species in agriculture and biology, polyploids have been increasingly studied in terms of their genome structure and organization. There are two types of polyploids, allopolyploids and autopolyploids, each resulting from a different genetic origin, which undergo meiotic divisions of a distinct complexity. A set of statistical models has been developed for linkage analysis, respectively for each type, by taking into account their unique meiotic behavior, i.e. preferential pairing for allopolyploids and double reduction for autopolyploids. We synthesized these models and modified them to accommodate the linkage analysis of less informative dominant markers. By reanalysing a published data set of varying ploidy in Arabidopsis, we corrected the estimates of the meiotic recombination frequency aimed to study the significance of polyploidization. PMID- 24177382 TI - Slow magnetic relaxation in radical cation tetrathiafulvalene-based lanthanide(III) dinuclear complexes. AB - Lanthanide dinuclear complexes involving tetrathiafulvalene-based ligands in their radical cation form were synthesised and crystallised by a galvanostatic procedure. Dynamic magnetic measurements reveal an unprecedented slow magnetic relaxation for the Dy(III) analogue in this kind of molecular edifice. PMID- 24177383 TI - Changes in the structural organization of the surface membrane in malignant cell transformation. AB - Malignant transformation of normal cells resulting in agglutinability by the carbohydrate-binding protein Concanavalin A can be explained by three types of changes in the structural organization of sites on the surface membrane. There can be an exposure of cryptic sites, a concentration of exposed sites by a decrease in cell size, and a rearrangement of exposed sites without a decrease in cell size resulting in a clustering of sites. PMID- 24177384 TI - Location of amino acid and carbohydrate transport sites in the surface membrane of normal and transformed mammalian cells. AB - Amino acid and carbohydrate transport in normal and malignant transformed hamster cells was studied after binding of the protein Concanavalin A (Con. A) to the surface membrane. Experimental conditions were used so that a similar number of Con. A molecules were bound to both types of cells. The transport of amino acids was inhibited after Con. A binding in the transformed cells but not in normal cells. This was found with the metabolizable amino acidsL-leucine,L-arginine,L glutamic acid, andL-glutamine, and with the non-metabolizable amino acids cycloleucine and alpha-aminoisobutyric acid. Transport ofD-glucose andD-galactose was more inhibited by Con. A in transformed than in normal cells, and in both types of cellsD-glucose was inhibited more thanD-galactose. The inhibition by Con. A on transport was specific, since there was no effect on the transport ofL fucose in either normal or transformed cells. Con. A also did not effect the entry of 3-0-methyl-D-glucose.These observations can be used to locate amino acid and carbohydrate transport sites in the surface membrane in relation to the binding sites for Con. A. The results indicate that Con. A sites are associated in normal cells with transport sites forD-glucose and to a lesser extentD galactose, and in transformed cells with transport sites for amino acids and to a greater extent than in normal cells withD-glucose andD-galactose. Malignant transformation of normal cells therefore results in a change in the location of amino acid and carbohydrate transport sites in the surface membrane in relation to the binding sites for Con. A. PMID- 24177385 TI - Action of 1-fluoro-2,4-dinitrobenzene on passive ion permeability of the human red blood cell. AB - Dinitrofluorobenzene (DNFB) inhibits the penetration of anions such as sulfate, phosphate, succinate, and lactate, and facilitates the penetration of cations such as K(+) and Na(+). The phlorizin-glucose insensitive fraction of erythritol permeability is not affected by the agent. The effects of DNFB on ion permeability are similar to those of more specific amino reactive agents like trinitrobenzene sulfonate and 2-methoxy-5-nitrotropone.Anion permeability reacts more sensitively to DNFB than cation permeability. At a given concentration of DNFB in the medium, the inhibition of anion permeability develops faster than the facilitation of cation permeability. At a given time of exposure, lower concentrations of DNFB are required to produce a nearly maximal response of anion permeability than are necessary for maximal effect on cation permeability.The response of anion and cation permeability to DNFB is augmented by increasing the pH at which dinitrophenylation is allowed to take place.DNFB binding to the cell membrane is about one order of magnitude lower than DNFB binding to the whole cell. In the cell membrane, proteins as well as lipids are dinitrophenylated. Among the lipids, only phosphatidylethanolamine binds significant amounts of DNFB. Phosphatidylserine does not seem to react with the agent under the experimental conditions under which DNFB produces its effects on ion permeability.The experimental results are compatible with the assumption that removal of uncharged NH2-groups by dinitrophenylation of the membrane leads to a concomitant reduction of fixed NH 3 (+) -groups and hence of the positive membrane charge. This leads to an acceleration of cation movements and an inhibition of anion permeability while nonelectrolyte permeability remains unaffected. However, other explanations of our observations cannot be ruled out. PMID- 24177386 TI - Effects of pronase on passive ion permeability of the human red blood cell. AB - The effects of pronase fromStreptomyces griseus on sulfate, potassium, sodium, and erythritol permeability of human red blood cells were studied. It was found that the proteolytic enzyme reduces anion permeability, increases cation permeability and has no effect on the nonfacilitated component of the flux of the nonelectrolyte. These findings can be explained on the basis of the fixed charge hypothesis by the assumption that the enzyme exerts its effects by altering the density of positive fixed charges in the membrane.The effects of pronase are qualitatively similar to those of the amino reactive agent, dinitrofluorobenzene (DNFB). Therefore, attempts were made to discover if this similarity is due to alterations of the same membrane sites by the enzyme and the chemical modifier. It was found that the effects of pronase and DNFB were not additive. Hence, the enzyme and the amino reactive agent do not seem to act on two independent and parallel channels. A more detailed analysis of the data suggests that DNFB and pronase affect functionally identical sites.Proteolytic enzymes frequently exhibit some esterase activity. However, the amino-N content of lipid extracts of red cell membranes remained virtually unaltered after exposure of the cells to pronase. This finding indicates that the positive charge of the bulk of the lipid amino groups is not involved in the control of passive ion permeability. The carbohydrate amino groups of the red cell membrane are N-acylated and hence cannot contribute to the positive membrane charge. It seems reasonable to conclude that the effects of pronase on ion permeability are primarily due to alterations of the density of charged protein amino groups in the red cell membrane. PMID- 24177387 TI - The effect of anions on K(+)-binding in aHalobacterium species. AB - Trinitrocresolate (TNC) at a concentration of 2*10(-3) M brings about rapid loss of K from starvingHalobacterium cells. Higher concentrations of other anions such as salicylate, thiocyanate, and perchlorate produce a similar effect. The TNC induced K loss is not significantly reversed when TNC is removed from the ambient medium. The rate of K loss in the presence of 2*10(-3) M TNC is only slightly increased by the temperature in the ranges of 30 to 40 degrees C and 0 to 20 degrees C; between 20 and 30 degrees C, however, the rate increases 10-fold. The K loss was partly replaced by Na(+). These data are interpreted in terms of the hypothesis that K is retained in starvingHalobacterium sp. not by active transport, but rather by selective binding on loci which are modified by TNC. PMID- 24177388 TI - Non-equilibrium folding of individual DNA molecules recaptured up to 1000 times in a solid state nanopore. AB - We investigate translocation of linear and circular double-stranded DNA molecules through solid state nanopores where each molecule is recaptured and re translocated many times. Single molecules can be recaptured by switching voltage polarity for hundreds or even thousands of times. The large number of recapture events allows statistics on the translocation of individual molecules. Surprisingly, we observe that recaptured DNA molecules do not translocate in a linear head-to-tail fashion, but instead translocate as a folded blob where multiple parts of the DNA molecule simultaneously translocate through the pore in parallel. This folding is observed through the presence of up to 13 DNA double strands from the same molecule simultaneously inside the pore, as well as many smaller fold numbers occurring during the course of a translocation event. The strong folding is particularly prominent when the molecule is recaptured at short timescales, i.e. shorter than its characteristic time to relax to its equilibrium configuration. At longer recapture times, both the amount of folding and the mean duration of translocation approach the values observed in non-recapture experiments. The data shows that the translocation time of a molecule depends on the molecule's conformation at the start of the translocation process, with extended molecules having a longer translocation time. The observations can be attributed to a high-density non-equilibrium DNA configuration that arises in the close vicinity of the nanopore immediately after translocation, which dissipates on a timescale given by the Zimm relaxation time. PMID- 24177389 TI - Social identity management strategies used by workers with acquired hearing loss. AB - OBJECTIVES: There is a paucity of knowledge about social identity-management by persons with hearing loss. The objective of the study was to gain an understanding from the perspective of the participants, the ways in which workers with acquired hearing loss manage their identity in the workplace. PARTICIPANTS: Twelve persons with acquired hearing loss, who were gainfully employed in a variety of settings and occupations in three Canadian cities, participated in audio-recorded semi-structured interviews. METHODS: A secondary qualitative analysis was conducted on transcripts of interviews collected in a previous study on factors that influence disclosure of hearing loss in the workplace. A qualitative descriptive research paradigm was adopted and content analyses were used to extract pertinent information from verbatim transcripts. RESULTS: Participants described a range of identity-management strategies enacted in the workplace. Five recurrent themes emerged as important considerations in the Art of Identity Management in the workplace: 1. Managing the situation, 2. Having a buddy system, 3. Feeling comfortable, 4. Using personal resources, 5. It gets easier with time. CONCLUSIONS: Social identity-management is a complex process. Although persons with acquired hearing loss experience different challenges from other persons with invisible stigmas, similarities in the range of social identity-management strategies employed were evident in our findings. In addition, the social cognitive learning model of disclosure appears to be relevant to the experiences of our participants. The implications of the findings emphasize the importance of all stakeholders working collaboratively to address the issues of the growing population of workers with hearing loss. PMID- 24177390 TI - Rapid regional perturbations to the recent global geomagnetic decay revealed by a new Hawaiian record. AB - The dominant dipolar component of the Earth's magnetic field has been steadily weakening for at least the last 170 years. Prior to these direct measurements, archaeomagnetic records show short periods of significantly elevated geomagnetic intensity. These striking phenomena are not captured by current field models and their relationship to the recent dipole decay is highly unclear. Here we apply a novel multi-method archaeomagnetic approach to produce a new high-quality record of geomagnetic intensity variations for Hawaii, a crucial locality in the central Pacific. It reveals a short period of high intensity occurring ~1,000 years ago, qualitatively similar to behaviour observed 200 years earlier in Europe and 500 years later in Mesoamerica. We combine these records with one from Japan to produce a coherent picture that includes the dipole decaying steadily over the last millennium. Strong, regional, short-term intensity perturbations are superimposed on this global trend; their asynchronicity necessitates a highly non dipolar nature. PMID- 24177391 TI - Unified approach to partition functions of RNA secondary structures. AB - RNA secondary structure formation is a field of considerable biological interest as well as a model system for understanding generic properties of heteropolymer folding. This system is particularly attractive because the partition function and thus all thermodynamic properties of RNA secondary structure ensembles can be calculated numerically in polynomial time for arbitrary sequences and homopolymer models admit analytical solutions. Such solutions for many different aspects of the combinatorics of RNA secondary structure formation share the property that the final solution depends on differences of statistical weights rather than on the weights alone. Here, we present a unified approach to a large class of problems in the field of RNA secondary structure formation. We prove a generic theorem for the calculation of RNA folding partition functions. Then, we show that this approach can be applied to the study of the molten-native transition, denaturation of RNA molecules, as well as to studies of the glass phase of random RNA sequences. PMID- 24177392 TI - Our health: do we get what we pay for? PMID- 24177393 TI - Rubber dam. PMID- 24177394 TI - Authors' response. PMID- 24177395 TI - Fee schedules. PMID- 24177396 TI - Author's response. PMID- 24177397 TI - Resin-modified glass ionomer. PMID- 24177398 TI - Authors' response. PMID- 24177400 TI - Evidence-based outcomes of periodontal therapy: a legacy of Sigurd P. Ramfjord. 1987. PMID- 24177401 TI - Dental treatment intensity in frail older adults in the last year of life. AB - BACKGROUND: Palliative care focusing on pain and infection is recommended for patients who are terminally ill. It is difficult to implement this strategy in practice because of the lack of clear guidelines. The authors conducted a study to examine dental treatment provided to a group of long-term care (LTC) residents in the last year of life. METHODS: The authors retrospectively followed 197 LTC residents (60 years or older) in the last year of life to death. On the basis of the dental services patients received between the new patient examination and death, the authors categorized the patients into three groups: no care (NC), limited care (LC) and usual care (UC). The authors developed a multivariable continuation ratio logit model with shared regression coefficients across two logits to identify the factors associated with the end-of-life dental care pattern. RESULTS: The authors found that 50.8 percent of the patients received NC before death. Among those who received treatment, 62.9 percent received UC, and 60.7 percent of the patients in the UC group had completed their treatment in the last three months of life. A three-month increment in survival and having dental insurance resulted in 1.74 (95 percent confidence interval [CI], 1.32-2.30) and 2.59 (95 percent CI, 1.03-6.52) times greater odds, respectively, of receiving some dental treatment before death. Neither survival nor dental insurance, however, was associated with dental care intensity in the last year of life (that is, UC versus LC). CONCLUSIONS: While most of the patients who were in the last year of life received insufficient dental care, comprehensive treatment was provided commonly to frail patients at the end of life, raising questions about quality of care. PRACTICAL IMPLICATIONS: Palliative oral health management needs to be revisited to improve quality of care for frail older adults at the end of life. PMID- 24177402 TI - Pain catastrophizing in dental patients: implications for treatment management. AB - BACKGROUND: "Pain catastrophizing" refers to an exaggerated negative mental set brought to bear during an actual or anticipated painful experience. A patient's perception of a dental care experience as catastrophic can result not only in poor satisfaction with the therapy but also in avoidance of necessary treatments, resulting in the deterioration of oral health. METHODS: The author reviewed literature regarding pain catastrophizing regarding dental treatment as well as behavioral models related to catastrophizing. RESULTS: People who catastrophize show excessive attention to pain (rumination), exaggerate the threat value of pain (magnification) and feel unable to cope with their suffering (helplessness). During dental treatments, greater pain catastrophizing is associated with increased pain, dental anxiety and negative thoughts regarding pain and dental procedures. CONCLUSIONS: It is important that clinicians identify dental patients who catastrophize so as to plan and provide the best treatment for their needs. PRACTICAL IMPLICATIONS: To manage the care of patients who catastrophize, the clinician can actively probe patients' pain experience, help them reappraise threat, manipulate their attention to pain and improve dentist-patient communication. PMID- 24177403 TI - A case of small-bowel obstruction secondary to inadvertent ingestion of impression material. AB - BACKGROUND: Small-bowel obstruction (SBO) is responsible for approximately 12 to 16 percent of surgical hospital admissions and more than 300,000 operations annually in the United States. This has resulted in more than $2.3 billion in health care delivery per year. SBO is a serious complication, carrying a 10 percent risk of mortality. CASE DESCRIPTION: The authors report a case of SBO resulting from inadvertent ingestion of polysulfide impression material. A 74 year-old man visited the emergency department with diffuse, nonradiating, colicky periumbilical pain. The patient was admitted to the general surgery service of the hospital, and after four days of supportive therapy without evidence of progression of the foreign body, he underwent an exploratory laparotomy. The authors later identified the foreign body as polysulfide impression material. PRACTICAL IMPLICATIONS: SBO is a rare but significant complication that can result from a procedure that clinicians perform on a routine basis. Dentists should consider this complication whenever they are concerned that a high-risk patient may have ingested dental materials. PMID- 24177404 TI - Widespread red oral lesions. PMID- 24177405 TI - The effect of ceramic primer on shear bond strength of resin composite cement to zirconia: a function of water storage and thermal cycling. AB - OBJECTIVES: The authors investigated the use of ceramic primers combined with self-adhesive resin composite cements on the shear bond strength (SBS) to zirconia and compared them with one conventional resin composite cement. METHODS: The authors divided zirconia substrates (N = 550) into three groups: RelyX Unicem Aplicap self-adhesive universal resin composite cement (3M ESPE, St. Paul, Minn.) (group A) (n = 220); G-CEM Capsule self-adhesive resin composite cement (GC Europe, Leuven, Belgium) (group B) (n = 220); and Panavia 21 with Clearfil Porcelain Bond Activator and Clearfil SE Bond primer (n = 110) (Kuraray Dental, Tokyo) used as a standard comparison (SC). The authors examined the self-adhesive resin composite cements without (0) and with (1) the use of a ceramic primer. They measured SBS initially (37 degrees C for three hours), after water storage (37 degrees C for one, four, nine, 16 or 25 days) and after thermal cycling (5 degrees C and 55 degrees C for 1,500, 6,000, 13,500, 24,000 or 37,500 cycles). The authors analyzed data by using descriptive statistics, the Mann-Whitney test, the Kruskal-Wallis test and a chi(2) test. RESULTS: Application of a ceramic primer did not result in a negative impact on SBS. Specimens in the A1 group (that is, RelyX Unicem Aplicap with ceramic primer) exhibited significantly higher SBS before and after water storage and thermal cycling compared with specimens that were not treated with a primer. The self-adhesive resin composite cements combined with ceramic primer exhibited similar or higher SBS values compared with those in the SC group at each aging duration (that is, water storage and thermal cycling). With respect to G-CEM Capsule, the authors observed a significantly positive effect of the primer after nine and 16 days' water storage and after one and four days' thermal cycling. They observed predominantly adhesive failures. CONCLUSIONS: Ceramic primer in combination with self-adhesive resin composite cement demonstrated a positive effect on SBS to zirconia and should be used for cementation. PRACTICAL IMPLICATIONS: Long-term adhesion to ceramic plays an important role in the longevity of dental restorations. Therefore, the authors recommend that clinicians use a ceramic primer when cementing zirconia restorations. PMID- 24177406 TI - Reimbursement rates and policies for primary molar pit-and-fissure sealants across state Medicaid programs. AB - BACKGROUND: Little is known about Medicaid policies regarding reimbursement for placement of sealants on primary molars. The authors identified Medicaid programs that reimbursed dentists for placing primary molar sealants and hypothesized that these programs had higher reimbursement rates than did state programs that did not reimburse for primary molar sealants. METHODS: The authors obtained Medicaid reimbursement data from online fee schedules and determined whether each state Medicaid program reimbursed for primary molar sealants (no or yes). The outcome measure was the reimbursement rate for permanent tooth sealants (calculated in 2012 U.S. dollars). The authors compared mean reimbursement rates by using the t test (alpha = .05). RESULTS: Seventeen Medicaid programs reimbursed dentists for placing primary molar sealants (34 percent), and the mean reimbursement rate was $27.57 (range, $16.00 [Maine] to $49.68 [Alaska]). All 50 programs reimbursed dentists for placement of sealants on permanent teeth. The mean reimbursement for permanent tooth sealants was significantly higher in programs that reimbursed for primary molar sealants than in programs that did not ($28.51 and $23.67, respectively; P = .03). CONCLUSIONS: Most state Medicaid programs do not reimburse dentists for placing sealants on primary molars, but programs that do so have significantly higher reimbursement rates. PRACTICAL IMPLICATIONS: Medicaid reimbursement rates are related to dentists' participation in Medicaid and children's dental care use. Reimbursement for placement of sealants on primary molars is a proxy for Medicaid program generosity. PMID- 24177409 TI - Controlling your practice's image. PMID- 24177410 TI - What are the ethical obligations of an itinerant oral surgeon when he places implants in patients? PMID- 24177407 TI - Topical fluoride for caries prevention: executive summary of the updated clinical recommendations and supporting systematic review. AB - BACKGROUND: A panel of experts convened by the American Dental Association (ADA) Council on Scientific Affairs presents evidence-based clinical recommendations regarding professionally applied and prescription-strength, home-use topical fluoride agents for caries prevention. These recommendations are an update of the 2006 ADA recommendations regarding professionally applied topical fluoride and were developed by using a new process that includes conducting a systematic review of primary studies. TYPES OF STUDIES REVIEWED: The authors conducted a search of MEDLINE and the Cochrane Library for clinical trials of professionally applied and prescription-strength topical fluoride agents--including mouthrinses, varnishes, gels, foams and pastes--with caries increment outcomes published in English through October 2012. RESULTS: The panel included 71 trials from 82 articles in its review and assessed the efficacy of various topical fluoride caries-preventive agents. The panel makes recommendations for further research. PRACTICAL IMPLICATIONS: The panel recommends the following for people at risk of developing dental caries: 2.26 percent fluoride varnish or 1.23 percent fluoride (acidulated phosphate fluoride) gel, or a prescription-strength, home-use 0.05 percent fluoride gel or paste or 0.09 percent fluoride mouthrinse for patients 6 years or older. Only 2.26 percent fluoride varnish is recommended for children younger than 6 years. The strengths of the recommendations for the recommended products varied from "in favor" to "expert opinion for." As part of the evidence based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences. PMID- 24177411 TI - For the dental patient. Keeping your mouth healthy during pregnancy. PMID- 24177412 TI - Post-FESS middle meatal dressings: avoiding the inevitable? AB - HYPOTHESIS: Use of dressings in the middle meatus after functional endoscopic sinus surgery (FESS) improves clinically meaningful outcomes in patients with chronic rhinosinusitis (CRS). PMID- 24177413 TI - Rationale, design, and baseline characteristics of a community-based comparative effectiveness trial to prevent type 2 diabetes in economically disadvantaged adults: the RAPID Study. AB - Reaching Out and Preventing Increases in Diabetes (RAPID) is a community-based randomized trial evaluating the comparative costs and effectiveness of a group based adaption of the DPP lifestyle intervention developed and implemented in partnership with the YMCA. RAPID enrolled adult primary care patients, with BMI 24 kg/m(2) or higher and abnormal glucose metabolism (HbA1c 5.7-6.9% or fasting plasma glucose 100-125 mg/dL). 509 participants were enrolled and randomized to one of two groups: standard clinical advice plus free-of-charge access to a group based adaption of the DPP offered by the Y, versus standard clinical advice alone. Key outcomes for future analysis will include differences in body weight and other cardiovascular risk factors over a 24-month intervention period. At baseline, RAPID participants had a mean (SD) age of 51 +/- 12.1 years, weight of 225.1 +/- 56.2 lbs, and BMI of 36.9 +/- 8.6 kg/m(2). 70.7% were women, 57.2% were African American, 35.4% were non-Hispanic White, and 3.2% were Hispanic. Mean HbA1c was 6.05 +/- 0.34%. Additionally, 55.4% of participants had a baseline systolic blood pressure of >=130 mmHg, 33.1% had a total blood cholesterol exceeding 200mg/dL, and 74% reported a household income of <$25,000. The RAPID Study successfully randomized a large cohort of participants with a wide distribution of age, body weight, and race who are at high risk for developing type 2 diabetes. PMID- 24177414 TI - HNF4alpha contributes to glucose formation in aged rat hepatocytes. AB - Aging-dependent physiological conditions are attributed to parenchymal structural changes to cellular functions in aged organisms. Compared to the young animals, the primary hepatocytes from old rats showed a higher glucose output and a higher expression of the key gluconeogenesis-regulating enzyme, phosphoenol pyruvate carboxykinase (PEPCK). The primary hepatocytes from old rats showed a higher glucose output and a higher expression of the key gluconeogenesis-regulating enzyme, phosphoenol pyruvate carboxykinase (PEPCK), compared with those from the young animals. The in situ hybridization study showed increased PEPCK mRNA expression in the aged liver tissues. The livers from old rats showed loosened hexagonal hepatic lobular structures, increased collagen accumulation, and high expression of the hypoxia marker hypoxia-inducible factor 1alpha (HIF1alpha). Hypoxia increased the PEPCK mRNA and protein expression levels in accordance with the HIF1alpha expression. PEPCK promoter luciferase reporter assay showed that hypoxia increased PEPCK through transcriptional activation. Furthermore, the hepatocyte nuclear factor alpha (HNF4alpha) protein, but not the HNF4alpha mRNA level, increased in parallel with the PEPCK mRNA expression under hypoxic conditions. Glucose production increased under hypoxic conditions, but this increment diminished by HNF4alpha siRNA in young hepatocytes. Moreover, increased glucose production from old rat hepatocytes was reversed by the down-regulation of HNF4alpha through a specific siRNA. This study suggests that the mild hypoxic conditions in response to aging-dependent hepatic structural changes may contribute to the induction of the gluconeogenic enzyme PEPCK through HNF4alpha protein stabilization. PMID- 24177415 TI - Water-dispersable colloidal quantum dots for the detection of ionizing radiation. AB - Fluorescent CdSe-CdS-Cd0.5Zn0.5S-ZnS core-shell colloidal quantum dots (cQDs) dispersed in aqueous and organic solvents have been prepared and used as scintillators for detecting ionizing radiation. Results demonstrate a linear relationship between emitted luminescence and dose-activity. These results suggest that cQDs alone could be used as liquid scintillators for specific environmental and medical applications. PMID- 24177416 TI - Demographic and socio-cultural correlates of medical mistrust in two Australian States: Victoria and South Australia. AB - Studies on medical mistrust have mainly focused on depicting the association between medical mistrust and access/utilization of healthcare services. The effect of broader socio-demographic and psycho-social factors on medical mistrust remains poorly documented. The study examined the effect of broader socio demographic factors, acculturation, and discrimination on medical mistrust among 425 African migrants living in Victoria and South Australia, Australia. After adjusting for socio-demographic factors, low medical mistrust scores (i.e., more trusting of the system) were associated with refugee (beta=-4.27, p<0.01) and family reunion (beta=-4.01, p<0.01) migration statuses, being Christian (beta= 2.21, p<0.001), and living in rural or village areas prior to migration (beta= 2.09, p<0.05). Medical mistrust did not vary by the type of acculturation, but was positively related to perceived personal (beta=0.43, p<0.001) and societal (beta=0.38, p<0.001) discrimination. In order to reduce inequalities in healthcare access and utilisation and health outcomes, programs to enhance trust in the medical system among African migrants and to address discrimination within the community are needed. PMID- 24177417 TI - Perinatal health inequalities and accessibility of maternity services in a rural French region: closing maternity units in Burgundy. AB - Maternity unit closures in France have increased travel time for pregnant women in rural areas. We assessed the impact of travel time to the closest unit on perinatal outcomes and care in Burgundy using multilevel analyses of data on deliveries from 2000 to 2009. A travel time of 30min or more increased risks of fetal heart rate anomalies, meconium-stained amniotic fluid, out-of-hospital births, and pregnancy hospitalizations; a positive but non-significant gradient existed between travel time and perinatal mortality. The effects of long travel distances on perinatal outcomes and care should be factored into closure decisions. PMID- 24177418 TI - Spatial interactions between urban areas and cause-specific mortality differentials in France. AB - Spatial interactions constitute a challenging but promising approach for investigation of spatial mortality inequalities. Among spatial interactions measures, between-spatial unit migration differentials are a marker of socioeconomic imbalance, but also reflect discrepancies due to other factors. Specifically, this paper asks whether population exchange intensities measure differentials or similarities that are not captured by usual socioeconomic indicators. Urban areas were grouped pairwise by the intensity of connection estimated from a gravity model. The mortality differences for several causes of death were observed to be significantly smaller for strongly connected pairs than for weakly connected pairs even after adjustment on deprivation. PMID- 24177419 TI - Theories of how the school environment impacts on student health: systematic review and synthesis. AB - Public-health interventions informed by theory can be more effective but complex interventions often use insufficiently complex theories. We systematically reviewed theories of how school environments influence health. We included 37 reports drawing on 24 theories. Narrative synthesis summarised and categorised theories. We then produced an integrated theory of school environment influences on student health. This integrated theory could inform complex interventions such as health promoting schools programmes. Using systematic reviews to develop theories of change might be useful for other types of 'complex' public-health interventions addressing risks at the individual and community levels. PMID- 24177420 TI - Power to negotiate spatial barriers to breastfeeding in a western context: when motherhood meets poverty. AB - Although breastfeeding is beneficial to the health of babies born into poverty, rates have remained consistently low among this group. This paper presents findings from a study conducted with poor French Canadian women, who were exposed to breastfeeding promotion. Analysis of 31 qualitative interviews suggests that the 'good mother' imperative in context of poverty and the western hypersexualization of breasts acted as major deterrents to breastfeeding. Poor mothers, lacked access to the power required to negotiate these barriers in their social space. Public health should prioritize the transformation of social and public spaces when promoting breastfeeding to poor mothers. PMID- 24177421 TI - Retinoblastoma protein prevents enteric nervous system defects and intestinal pseudo-obstruction. AB - The retinoblastoma 1 (RB1) tumor suppressor is a critical regulator of cell cycle progression and development. To investigate the role of RB1 in neural crest derived melanocytes, we bred mice with a floxed Rb1 allele with mice expressing Cre from the tyrosinase (Tyr) promoter. TyrCre+;Rb1fl/fl mice exhibited no melanocyte defects but died unexpectedly early with intestinal obstruction, striking defects in the enteric nervous system (ENS), and abnormal intestinal motility. Cre-induced DNA recombination occurred in all enteric glia and most small bowel myenteric neurons, yet phenotypic effects of Rb1 loss were cell-type specific. Enteric glia were twice as abundant in mutant mice compared with those in control animals, while myenteric neuron number was normal. Most myenteric neurons also appeared normal in size, but NO-producing myenteric neurons developed very large nuclei as a result of DNA replication without cell division (i.e., endoreplication). Parallel studies in vitro found that exogenous NO and Rb1 shRNA increased ENS precursor DNA replication and nuclear size. The large, irregularly shaped nuclei in NO-producing neurons were remarkably similar to those in progeria, an early-onset aging disorder that has been linked to RB1 dysfunction. These findings reveal a role for RB1 in the ENS. PMID- 24177422 TI - Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis. AB - Aberrant blood vessel formation contributes to a wide variety of pathologies, and factors that regulate angiogenesis are attractive therapeutic targets. Endothelial and smooth muscle cell-derived neuropilin-like protein (ESDN) is a neuropilin-related transmembrane protein expressed in ECs; however, its potential effect on VEGF responses remains undefined. Here, we generated global and EC specific Esdn knockout mice and demonstrated that ESDN promotes VEGF-induced human and murine EC proliferation and migration. Deletion of Esdn in the mouse interfered with adult and developmental angiogenesis, and knockdown of the Esdn homolog (dcbld2) in zebrafish impaired normal vascular development. Loss of ESDN in ECs blunted VEGF responses in vivo and attenuated VEGF-induced VEGFR-2 signaling without altering VEGF receptor or neuropilin expression. Finally, we found that ESDN associates with VEGFR-2 and regulates its complex formation with negative regulators of VEGF signaling, protein tyrosine phosphatases PTP1B and TC PTP, and VE-cadherin. These findings establish ESDN as a regulator of VEGF responses in ECs that acts through a mechanism distinct from neuropilins. As such, ESDN may serve as a therapeutic target for angiogenesis regulation. PMID- 24177423 TI - Apelin is a positive regulator of ACE2 in failing hearts. AB - Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases. PMID- 24177424 TI - Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis. AB - Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen inducible POMC-cre system. These data demonstrate that serotonin 2C receptor expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control. PMID- 24177425 TI - Enhanced autophagy ameliorates cardiac proteinopathy. AB - Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryABR120G mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryABR120G hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryABR120G mice and the Atg7-crossed CryABR120G mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7 crossed CryABR120G cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions. PMID- 24177426 TI - The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging. AB - Anti-CD20 Ab therapy has proven successful for treating B cell malignancies and a number of autoimmune diseases. However, how anti-CD20 Abs operate in vivo to mediate B cell depletion is not fully understood. In particular, the anatomical location, the type of effector cells, and the mechanism underlying anti-CD20 therapy remain uncertain. Here, we found that the liver is a major site for B cell depletion and that recirculation accounts for the decrease in B cell numbers observed in secondary lymphoid organs. Using intravital imaging, we established that, upon anti-CD20 treatment, Kupffer cells (KCs) mediate the abrupt arrest and subsequent engulfment of B cells circulating in the liver sinusoids. KCs were also effective in depleting malignant B cells in a model of spontaneous lymphoma. Our results identify Ab-dependent cellular phagocytosis by KCs as a primary mechanism of anti-CD20 therapy and provide an experimental framework for optimizing the efficacy of therapeutic Abs. PMID- 24177429 TI - On the optical absorption of the anionic GFP chromophore in vacuum, solution, and protein. AB - In spite of the large number of experimental and theoretical studies, the optical absorption trend of the green fluorescent protein (GFP) chromophore in several environments has not been fully understood. We calculated at the same level of time dependent density functional theory the vertical excitation energy of the anionic GFP chromophore in the protein and in ethanol, dioxane, methanol and water solutions. As result, we reproduced for the first time the experimental trend of the absorption peaks with 0.015 eV as the standard deviation of the accuracy. This systematic error allowed us to analyze with confidence the relative weight of several solvation effects on the vertical excitation energy. Experimental trends not correlated with the solvent polarity were therefore explained with a fine balance of different steric and electronic effects on the photophysics of the chromophore. As an indirect and remarkable result, the present analysis confirms that the optical absorption of the chromophore in the gas phase is close to the value of 2.84 eV extrapolated by Dong et al. (J. Am. Chem. Soc., 2006, 128, 12038), and, as a consequence, that the protein environment induces a red shift of 0.23 eV. PMID- 24177427 TI - Insulin receptor substrate signaling suppresses neonatal autophagy in the heart. AB - The induction of autophagy in the mammalian heart during the perinatal period is an essential adaptation required to survive early neonatal starvation; however, the mechanisms that mediate autophagy suppression once feeding is established are not known. Insulin signaling in the heart is transduced via insulin and IGF-1 receptors (IGF-1Rs). We disrupted insulin and IGF-1R signaling by generating mice with combined cardiomyocyte-specific deletion of Irs1 and Irs2. Here we show that loss of IRS signaling prevented the physiological suppression of autophagy that normally parallels the postnatal increase in circulating insulin. This resulted in unrestrained autophagy in cardiomyocytes, which contributed to myocyte loss, heart failure, and premature death. This process was ameliorated either by activation of mTOR with aa supplementation or by genetic suppression of autophagic activation. Loss of IRS1 and IRS2 signaling also increased apoptosis and precipitated mitochondrial dysfunction, which were not reduced when autophagic flux was normalized. Together, these data indicate that in addition to prosurvival signaling, insulin action in early life mediates the physiological postnatal suppression of autophagy, thereby linking nutrient sensing to postnatal cardiac development. PMID- 24177430 TI - Optic perineuritis secondary to acute retinal necrosis. PMID- 24177428 TI - CX3CR1-dependent renal macrophage survival promotes Candida control and host survival. AB - Systemic Candida albicans infection causes high morbidity and mortality and is associated with neutropenia; however, the roles of other innate immune cells in pathogenesis are poorly defined. Here, using a mouse model of systemic candidiasis, we found that resident macrophages accumulated in the kidney, the main target organ of infection, and formed direct contacts with the fungus in vivo mainly within the first few hours after infection. Macrophage accumulation and contact with Candida were both markedly reduced in mice lacking chemokine receptor CX3CR1, which was found almost exclusively on resident macrophages in uninfected kidneys. Infected Cx3cr1-/- mice uniformly succumbed to Candida induced renal failure, but exhibited clearance of the fungus in all other organs tested. Renal macrophage deficiency in infected Cx3cr1-/- mice was due to reduced macrophage survival, not impaired proliferation, trafficking, or differentiation. In humans, the dysfunctional CX3CR1 allele CX3CR1-M280 was associated with increased risk of systemic candidiasis. Together, these data indicate that CX3CR1 mediated renal resident macrophage survival is a critical innate mechanism of early fungal control that influences host survival in systemic candidiasis. PMID- 24177433 TI - Physical and chemical activation of reduced graphene oxide for enhanced adsorption and catalytic oxidation. AB - Physical and chemical activation of reduced graphene oxide (RGO) using different reagents, CO2, ZnCl2 and CO2/ZnCl2, to obtain highly porous and metal-free carbonaceous materials was carried out and their adsorption and catalytic behavior were investigated. Physical activation using CO2 was proved to be much more effective than chemical ZnCl2 activation, and increased the specific surface area (SSA) of RGO from ~200 to higher than 600 m(2) g(-1). Methylene blue (MB) was then used to evaluate the adsorption and catalytic activity of the activated RGO (A-RGO) materials with peroxymonosulfate (PMS) as an oxidant. It was found that the SSA and oxygen containing groups are two important factors determining the adsorptive and catalytic performance of the A-RGO materials. RGO by physicochemical CO2/ZnCl2 activation presented the best adsorption and RGO by physical CO2 activation exhibited the highest catalytic degradation of MB. PMID- 24177435 TI - Immobilization and functional reconstitution of antibody Fab fragment by solid phase refolding. AB - In this study, we demonstrated the successful preparation of a Fab antibody immobilized hydrophilic polystyrene (phi-PS) plate via one- and two-step solid phase refolding methods. Both polystyrene-binding peptide (PS-tag)-fused Fd fragment of heavy chain (Fab H-PS) and full-length of light-chain (Fab L-PS) were individually produced in insoluble fractions of Escherichia coli cells, and they were highly purified in the presence of 8M of urea. Antigen-binding activities of Fab antibody immobilized were correctly recovered by the one-step solid-phase refolding method that a mixture of Fab H-PS and Fab L-PS was immobilized in the presence of 0.5-2M urea, followed by surface washing of the phi-PS plate with PBST. These results indicate that by genetic fusion of a PS-tag, a complex between Fab H and Fab L was efficiently immobilized on the surface of a phi-PS plate even in the presence of a low concentration of urea, and was then correctly refolded to retain its high antigen-binding activity via removal of the urea. A two-step solid-phase refolding method whereby Fab H-PS and Fab L-PS were successively refolded on the surface of a phi-PS plate also resulted in Fab antibody formation on the plate. Furthermore, both the binding affinity and the specificity of the Fab antibody produced by the two-step method were highly maintained, according to the results of sandwich ELISA and competitive ELISA using Fab antibody-immobilized plate via two-step solid-phase refolding. Thus, the solid-phase refolding method demonstrated in this study should be quite useful for the preparation of a Fab antibody-immobilized PS surface with high efficiency from individually produced Fab H-PS and Fab L-PS. This method will be applicable to the preparation of a large Fab antibody library on the surface of a PS plate for use in antibody screening. PMID- 24177434 TI - Dietary and inhalation exposure to polycyclic aromatic hydrocarbons and urinary excretion of monohydroxy metabolites--a controlled case study in Beijing, China. AB - Daily dietary and inhalation exposures to 16 parent polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 13 monohydroxy metabolites (OHPAHs) were monitored for 12 non-smoking university students in Beijing, China, during a controlled feeding experiment. The relationship between the urinary excretion of OHPAHs and the uptake of PAHs was investigated. The results suggest severe exposure of the subjects to PAHs via both dietary and inhalation pathways. Large increase of most urinary OHPAHs occurred after the ingestion of lamb kabob. Higher concentrations of OHPAHs were observed for female subjects, with the intakes of parent PAHs lower than those by males, likely due to the gender differences in metabolism. It appears that besides 1-PYR, metabolites of PHE could also be used as biomarkers to indicate the short-term dietary exposure to PAHs and urinary 3-BaA may serve as the biomarker for inhalation intake of high molecular weight PAHs. PMID- 24177436 TI - Genetic differentiation and spatial structure of Geosmithia morbida, the causal agent of thousand cankers disease in black walnut (Juglans nigra). AB - The main objectives of this study were to evaluate genetic composition of Geosmithia morbida populations in the native range of black walnut and provide a better understanding regarding demography of the pathogen. The fungus G. morbida, and the walnut twig beetle, Pityophthorus juglandis, have been associated with a disease complex of black walnut (Juglans nigra) known as thousand cankers disease (TCD). The disease is manifested as branch dieback and canopy loss, eventually resulting in tree death. In 2010, the disease was detected in black walnut in Tennessee, and subsequently in Virginia and Pennsylvania in 2011 and North Carolina in 2012. These were the first incidences of TCD east of Colorado, where the disease has been established for more than a decade on indigenous walnut species. A genetic diversity and population structure study of 62 G. morbida isolates from Tennessee, Pennsylvania, North Carolina and Oregon was completed using 15 polymorphic microsatellite loci. The results revealed high haploid genetic diversity among seven G. morbida populations with evidence of gene flow, and significant differentiation among two identified genetic clusters. There was a significant correlation between geographic and genetic distance. Understanding the genetic composition and demography of G. morbida can provide valuable insight into recognizing factors affecting the persistence and spread of an invasive pathogen, disease progression, and future infestation predictions. Overall, these data support the hypotheses of two separate, highly diverse pathogen introductions into the native range of black walnut. PMID- 24177437 TI - Double stimulus-induced stem cell aggregation during differentiation on a biopolymer hydrogel substrate. AB - A double stimulus-sensing platform based on a biopolymer hydrogel was developed for inducing stem cell aggregation and subsequent release. Our work will bring up a novel methodology to generate smart scaffolds with tailorable properties for biomedical applications. PMID- 24177438 TI - Nurse leaders' experiences of implementing regulatory changes in sexual health nursing practice in British Columbia, Canada. AB - Most research about regulatory policy change concerning expanded nursing activities has emphasized advanced practice roles and acute care settings. This study is a contribution to the small pool of research concerned with regulatory policy implementation for nurses undertaking expanded nursing practice activities in a public health context. Using the regulatory changes in certified nursing practice in one Canadian province as our starting point, we investigated the experiences of nurse leaders in implementing this change. Using a qualitative interpretive descriptive approach informed by tenets of complexity theory, we examined the experiences of 16 nurse leaders as situated within the larger public health care system in which nurses practice. Two interrelated themes, (a) preparing for certification and (b) the certification process, were identified to illustrate how competing and contrasting demands between health care and regulatory organizations created substantial barriers to policy change. Implications for health service delivery and future research are discussed. PMID- 24177440 TI - Nutritional quality of foods marketed to children in Honduras. AB - Evidence suggests that exposure to advertising of unhealthy foods may contribute to increased rates of obesity in children. This study examined the extent to which television stations marketed unhealthy foods to children during after school programming aired over one week in La Ceiba, Honduras. Content analysis was performed on four television stations, including one broadcast station and three cable networks. Eighty hours of programming were recorded and analyzed. Advertised products were categorized as food or non-food items, with food items further classified as healthy or unhealthy. Advertisements were coded as those aimed at children, adults, or both, and chi-square tests were used to compare the proportion of unhealthy advertisements by target audience. A total of 2271 advertisements aired during the observation period, with 1120 marketing products (49.3%). Of those, 397 (35.4%) promoted foods-30.2% were for healthy foods and 69.8% for unhealthy foods. The unhealthy foods were all advertised on cable networks and not the broadcast station. Children appeared to be targeted more than adults in advertisements for unhealthy foods (92.1%, p<0.001). Cable television programming during after-school hours advertised primarily unhealthy foods. Exposure to these advertisements may promote consumption of unhealthy foods by children, increasing their risk of obesity. PMID- 24177439 TI - Diurnal cortisol pattern, eating behaviors and overweight in low-income preschool aged children. AB - This study examined, among children, the associations among chaos in the home, diurnal cortisol patterns, eating behaviors and being overweight. Participants included 331 low-income children aged 3-4years. Mean salivary cortisol-intercept (representing morning peak, 60min since waking) and cortisol-slope (representing diurnal decline after peak) were calculated using mixed models from samples obtained across 3days. Parents reported chaos in the home by questionnaire and responded to the Children's Eating Behavior Questionnaire, generating subscales Food Responsiveness (FR), Emotional Overeating (EO), Enjoyment of Food (EF), and Satiety Responsiveness (SR). Body mass index was categorized as overweight vs. not. Path analysis evaluated associations among chaos, cortisol patterns, eating behaviors, and weight status. Children living in more chaotic homes had lower morning cortisol levels, consistent with "hypocortisolism" reported among individuals who have experienced significant allostatic load as a result of substantial early life chronic stress. Among girls, the hypocortisolism pattern predicted a higher likelihood of being overweight both directly and mediated through reduced Satiety Responsiveness; in boys, the association of the hypocortisolism pattern with being overweight was mediated entirely through Emotional Overeating. In summary, our results provide support for the conceptual model that psychosocial stress contributes to hypocortisolism, which contributes directly to a higher likelihood of being overweight in girls, and indirectly through reduced Satiety Responsiveness in girls and through increased Emotional Overeating in boys. PMID- 24177441 TI - Validation of the Dutch Eating Behavior Questionnaire (DEBQ) in a sample of Spanish women. AB - The Dutch Eating Behavior Questionnaire (DEBQ) was developed to measure eating styles that may contribute to or attenuate the development of overweight. It comprises three scales that measure emotional, external and restrained eating. The main goal of this study is to evaluate the internal structure of the Spanish version of the DEBQ using updated psychometric techniques in a sample of women. A sample of 647 Spanish females answered the questionnaire. Both exploratory structural equation modeling and confirmatory factor analysis were used to evaluate the factor structure of the DEBQ. Reliabilities were estimated with Cronbach's alpha. The relations between the subscales of the DEBQ and age, BMI, and scores on the Eating Attitude Test-26 (EAT) and the Restrained Scale-Revised (RS) were computed with Pearson correlations. Results showed that the internal structure was similar to the theoretical proposal, although items associated with boredom and idleness presented cross-loading problems. The reliability estimates were satisfactory. The Emotional and External Eating factors correlated with the BMI, and External Eating was negatively correlated with age. The Restraint factor of the DEBQ showed significant relationships with scales of the EAT-26 and RS. The dimensional validity of the DEBQ is reproduced in a Spanish sample, and the DEBQ seems to be an effective instrument for research in Spanish females. Minor modifications to the DEBQ are recommended. PMID- 24177442 TI - A tubular europium-organic framework exhibiting selective sensing of Fe3+ and Al3+ over mixed metal ions. AB - A luminescent europium-organic framework with tubular channels based on the H4BTMIPA ligand (H4BTMIPA = 5,5'-methylenebis(2,4,6-trimethylisophthalic acid)) was assembled and characterized. The [H2N(CH3)2](+) ions as counterions are located in the channels. The cation exchange between [H2N(CH3)2](+) and metal ions resulted in complex that can selectively sense Fe(3+) and Al(3+) ions through fluorescence quenching and enhancement, respectively. PMID- 24177443 TI - Cervical spinal cord injuries without radiographic evidence of trauma: the potential for recovery of upper extremity function. PMID- 24177444 TI - The membrane potential of Ehrlich ascites tumor cells microelectrode measurements and their critical evaluation. AB - Intracellular potentials were measured, using a piezoelectric electromechanical transducer to impale Ehrlich ascites tumor cells with capillary microelectrodes. In sodium Ringer's, the potential immediately after the penetration was -24+/-7 mV, and decayed to a stable value of about -8 mV within a few msec. The peak potentials disappeared in potassium Ringer's and reappeared immediately after resuspension in sodium. Ringer's, whereas the stable potentials were only slightly influenced by the change of medium. The peak potential is in good agreement with the Nernst potential for chloride. This is also the case when cell sodium and potassium have been changed by addition of ouabain. It is concluded that the peak potentials represent the membrane potential of the unperturbed cell, and that chloride is in electrochemical equilibrium across the cell membrane.The membrane potential of about -11 mV previously reported corresponds to the stable potential in this study, and is considered as a junction potential between damaged cells and their environment. Similar potential differences were recorded between a homogenate of cells and Ringer's.The apparent membrane resistance of Ehrlich cells was about 70 Omegacm(2). This is two orders of magnitude less than the value calculated from(36)Cl fluxes, and may, in part, represent a leak in the cell membrane.For comparison, the influence of an eventual leak on measurements in red cells and mitochondria is discussed. PMID- 24177445 TI - The molecular organization of nerve membranes : IV. The lipid composition of plasma membranes from squid retinal axons. AB - The lipid content and composition from an axolemma-rich preparation isolated from squid retinal axons was analyzed.The lipids, which accounted for 45.5% of the dry weight of this membrane, were composed of 22% cholesterol, 66.7% phospholipids and 5.2% free fatty acids. The negatively charged species phosphatidyl ethanolamine (37%), phosphatidyl serine (10%) and lysophosphatidyl ethanolamine (4%) made up 51% of the phospholipids. The amphoteric phosphatidyl choline and sphingomyelin accounted for 39% and 4%, respectively.The relative distribution of fatty acids in each of the isolated phospholipids was studied. The most remarkable feature of these phospholipids was the large proportion of long-chain polyunsaturated fatty acids. The 22?6 acyl chain accounted for 37% in phosphatidyl ethanolamine, 21.7% in phosphatidyl choline, 17.5% on phosphatidyl serine and 20.3% in sphingomyelin (all expressed as area %).The molar fraction of unsaturated fatty acids reached 65% in phosphatidyl ethanolamine and 42.0 and 44.8% in phosphatidyl choline and phosphatidyl serine, respectively. The double bond index in these species varied between 1.0 and 2.6.The lipid composition of the axolemma-rich preparation isolated from squid retinal axons appears to be similar to other excitable plasma membranes in two important features: (a) a low cholesterol/phospholipid molar ratio of 0.61; and (b) the polyunsaturated nature of the fatty acid of their phospholipids.This particular chemical composition may contribute a great deal to the molecular unstability of excitable membranes. PMID- 24177446 TI - The molecular organization of nerve membranes : V. Properties of mono- and bimolecular films formed with lipids isolated from an axolemma-rich preparation from squid retinal axons. AB - The formation and properties of mono- and bimolecular films of total lipids extracted from an axolemma-rich preparation from retinal axons of the squid are described.The bilayers formed with alpha-tocopherol showed resistance values of 10(7) Omega cm(2) indicating their low ionic permeability. These membranes were stable for 30 to 60 min and they behave as an ohmic resistance in the range of 120 to +120 mV.The films formed with these lipids did not discriminate between Na(+) and K(+) and showed a slight selectivity for Cl(-) as compared with cations, indicating a behavior as a rather neutral barrier.The pressure-area characteristics of monolayers built with the phospholipids fraction gave an area of 79 A(2)/molecule at a pressure of 10 dynes/cm. This expanded molecular area can be accounted for by the unsaturated fatty acid chains of polyenoic structure attached to these phospholipid molecules. The fraction containing 81% cholesterol presented an area of 29 A(2)/molecule at 10 dynes/cm.Monolayers of the total lipids displayed an area of 51.7 A(2)/molecule at a pressure of 10 dynes/cm. These findings indicate that the phospholipids, when mixed with cholesterol and free fatty acids, formed rather condensated films. Cholesterol might contribute significantly to increase the cohesive forces in the film and hence to its stability.The expanded films given by the phospholipids extracted from nerve membrane also indicate that they have a low transition temperature; their unusual unsaturated aliphatic chains might be in a special high mobile condition. Their behavior might be important for the position and order of polar groups in an excitable membrane. PMID- 24177447 TI - The membrane locus of Ca-stimulated K transport in energy depleted human red blood cells. AB - Energy depleted human red cells subsequently exposed to iodoacetate (IAA) develop, upon the addition of Ca, a marked increase in K permeability, while Na permeability is unaltered. The kinetic characteristics of this augmented K permeability indicate that the transport process is membrane mediated. Thus, the inward and outward rate constants for K increase as the concentration of external K is increased reaching maximum values between 2 to 5MM; further increases in external K results in a partial reduction of the rate constants. In addition, the Ca-stimulated K transport system displays counterflow of(42)K during its influx when a large gradient of(39)K exists (inside high, outside low). Furthermore, the Ca-induced K transport is inhibited by ouabain. The sensitivity of the Ca-induced system to ouabain parallels the action of ouabain on the Na-K pump. At least part of the increased K transport occurs through a preexisting pathway since ouabain bound to cells before exposure to Ca and IAA results in an inhibition of K outflux. Since ouabain does not alter the affinity of the cells for Ca, it is concluded that at least a portion of the increased K transport results from Ca acting to increase the turnover rate of the same system which serves as the Na-K pump in normal red cells. PMID- 24177448 TI - Ionic diffusion in membranes : I. A kinetic model for the squid axon conductances. AB - A fundamental approach to calculate the diffusion of ions through membranes is introduced. The membran eis considered as a heterogeneous structure with molecules that can have a selective affinity for a certain class of diffusing ions. To diffuse through a membrane an ion must become associated with, or dissolved into, at least one component of that membrane. Diffusion is produced by thermal jumps from one molecular site to another. It is assumed that the electric field can change the binding properties between ions and membrane molecules. The kinetics of the conductances are calculated from the chemical kinetic theory. The calculations are compared to the squid axon data and the unknown parameters are adjusted to fit the data curves. The results are very satisfactory. The calculated activation energies correspond to the measuredQ 10 in the squid axon. The calculated and measured action potentials are quite similar. PMID- 24177449 TI - Fine structure of ultrathin artificial membranes : I. Changes by acetylcholine addition in lipid proteolipid membranes. AB - A special technique for the electron-microscope study of the fine structure of ultrathin artificial membranes is described. Membranes made of total phospholipids of the cerebral cortex and cholesterol showed globular elements of 40 A embedded in a denser and diffuse matrix. These same elements were also seen organized in a periodic banded pattern. Identical patterns were observed with and without supporting films. Lipidic membranes containing small amounts of proteolipid fromElectrophorus showed a lower electron density, a finer and smoother texture and a decrease in electrical resistance.Lipidic membranes containing the cholinergic receptor proteolipid fromElectrophorus, upon addition of acetylcholine, showed a rapid and transient rise in conductance which was accompanied by changes in fine structure, consisting in a more uneven corrugated appearance of the membrane and the presence of dense spots of 20 A. These results are discussed in relation to the channel hypothesis of ion permeability. It is postulated that the binding of acetylcholine by the receptor proteolipid results in conformational changes in this protein that facilitate the translocation of ions through the membrane. PMID- 24177450 TI - Intercellular communication and tissue growth : V. A cancer cell strain that fails to make permeable membrane junctions with normal cells. AB - A method is described for testing communication between a normal and a cancerous cell in culture without inserting microprobes into either cell; microprobes are put into other normal cells coupled to the normal cell in question. It is shown with this method that a cell strain (class-A), of epithelial morphology, isolated from Morris' liver tumor (H-5123) fails to make communicative junctions with several types of normal cells; small inorganic ions and fluorescein do not pass from the normal cells to the class-A cells (they do pass from the normal cells to normal cells, even between normal cells of different type). The class-A cells also appear incapable of junctional communication among themselves. The cells of class-A are cancerous: they are not 'contact inhibited' by each other or by the normal cells and they form malignant tumors when injected into test animals. Another cell strain (class-B), of fibroblastic morphology, derived from the same liver tumor as class-A makes communicative junctions readily. This strain is 'contact inhibited' and does not produce tumors when injected into the animals. PMID- 24177451 TI - Synthesis of water-dispersible zinc oxide quantum dots with antibacterial activity and low cytotoxicity for cell labeling. AB - Typical photoluminescent semiconductor nanoparticles, called quantum dots (QDs), have potential applications in biological labeling. When used to label stem cells, QDs may impair the differentiation capacity of the stem cells. In this study, we synthesized zinc oxide (ZnO) QDs in methanol with an average size of ~2 nm. We then employed two different types of polyethylene glycol (PEG) molecules (SH-PEG-NH2 and NH2-PEG-NH2) to conjugate ZnO QDs and made them water dispersible. Fourier transform infrared spectroscopy spectra indicated the attachment of PEG molecules on ZnO QDs. No obvious size alteration was observed for ZnO QDs after PEG conjugation. The water-dispersible ZnO QDs still retained the antibacterial activity and fluorescence intensity. The cytotoxicity evaluation revealed that ZnO QDs at higher concentrations decreased cell viability but were generally safe at 30 ppm or below. Cell lines of hepatocytes (HepG2), osteoblasts (MC3T3-E1) and mesenchymal stem cells (MSCs) were successfully labeled by the water-dispersible ZnO QDs at 30 ppm. The ZnO QD labeled MSCs maintained their stemness and differentiation capacity. Therefore, we conclude that the water-dispersible ZnO QDs developed in this study have antibacterial activity, low cytotoxicity, and proper labeling efficiency, and can be used to label a variety of cells including stem cells. PMID- 24177452 TI - Pelvic pain and patient satisfaction after laparoscopic supracervical hysterectomy: prospective trial. AB - STUDY OBJECTIVE: To evaluate the occurrence and intensity of cyclic pelvic pain and patient satisfaction after laparoscopic supracervical hysterectomy and to explore the effect of the procedure on pelvic pain relief in women with perioperative detection of endometriosis and in women with histologic confirmation of adenomyosis. DESIGN: Prospective observational study with 12 month follow-up after laparoscopic supracervical hysterectomy (Canadian Task Force classification II-2). SETTING: University teaching hospital in Norway. PATIENTS: One hundred thirteen premenopausal women with preoperative cyclic pelvic pain treated via laparoscopic supracervical hysterectomy. INTERVENTIONS: Study participants underwent laparoscopic supracervical hysterectomy and were followed up at the outpatient clinic at 12 months after the procedure. MEASUREMENTS AND MAIN RESULTS: The main outcomes were occurrence, intensity, and reduction of cyclic pelvic pain and patient satisfaction measured using an ordinal and a visual analog scale at 12 months after the procedure. Of the 113 women included in the study, 8 were lost to follow-up. Consequently, 105 women (92.9%) were followed up at 12 months after surgery. All women had cyclic pelvic pain preoperatively, but only 34 (32.4%) experienced this pain at 12 months after the procedure. The intensity of pelvic pain was reduced from a mean (SD) of 5.5 (2.4) preoperatively to 0.7 (1.5) at 12 months after the procedure on a visual analog scale of 0 to 10 (p < .01). Endometriosis was diagnosed perioperatively in 14 women (12.4 %), and adenomyosis was confirmed at histologic analysis in 19 (18.1%). In women with perioperative detection of endometriosis or histologic confirmation of adenomyosis, there were no significant differences in main outcomes at 12 months after laparoscopic supracervical hysterectomy when compared with women without these diagnoses. CONCLUSION: Laparoscopic supracervical hysterectomy is associated with high patient satisfaction and reduces cyclic pelvic pain to a minimum by 12 months after the procedure. PMID- 24177453 TI - Re: endometrial ablation: is tubal ligation a risk factor for hysterectomy. PMID- 24177454 TI - The role of middle meatal dressings in endoscopic sinus surgery. PMID- 24177455 TI - Facial cutaneous metastasis of colorectal adenocarcinoma. AB - Facial cutaneous metastasis from carcinoma is a rare and late clinical finding that is associated with disseminated disease and a poor prognosis. Skin metastases predominantly originate from primary tumours of the lung and melanoma. Skin metastases from colon tumours occur in only 4-6.5% of cases of metastatic colorectal cancer. They are most often located on the abdominal skin. We present an unusual case in which a primary colorectal adenocarcinoma metastasised to the face. This cutaneous lesion occurred 4 years after diagnosis of the primary tumour. This case highlights the importance of prompt investigation of new or evolving skin lesions in patients with a history of malignancy. Early detection and initiation of treatment may prevent development of widespread skin metastases and extend life expectancy. PMID- 24177456 TI - C reactive protein may not be reliable as a marker of severe bacterial infection in patients receiving tocilizumab. AB - This is a case of a 65-year-old man with seropositive erosive rheumatoid arthritis (RA), well controlled on methotrexate, sulfasalazine, low-dose prednisolone and monthly infusions of tocilizumab. He presented with a 3-week history of pain and swelling in his left knee, gradually increasing in severity with an inability to bear weight. He was systemically well with normal vital signs. Examination confirmed an effusion and aspiration was turbid in appearance. C reactive protein (CRP) was normal. He was treated empirically with antibiotics. Synovial fluid and blood cultures confirmed Staphylococcus aureus infection. He completed a 6 weeks course of antibiotics with complete resolution of symptoms. Throughout the treatment his CRP remained normal which is likely to have been the result of prior treatment with tocilizumab. PMID- 24177457 TI - Eagle's syndrome presenting as a cervical mass. PMID- 24177458 TI - Postnatal pyomyoma: a diagnostic dilemma. AB - Pyomyoma is a rare, yet potentially fatal complication of uterine leiomyoma. Clinically difficult to diagnose as a result of non-specific symptoms, its presentation is commonly confused with fibroid degeneration. Late diagnosis has severe implications, with the mortality of the condition remaining high. Despite the availability of powerful antibiotics, surgical intervention is frequently required for the curative treatment of the critically ill patient. Here, we report a case of postpartum pyomyoma developing after a complicated antenatal course of placenta praevia resulting in recurrent antepartum haemorrhage, preterm prelabour rupture of membranes and eventual emergency caesarean section for cord prolapse. We highlight the diagnostic difficulty and delay in definitive surgical intervention. Using this case, we have emphasised the importance of strong clinical suspicion when faced with a triad of pain, sepsis without an obvious source and a known diagnosis of leiomyoma to prevent fatalities. PMID- 24177459 TI - Enterobius vermicularis infection of the ovary. AB - Enterobius vermicularis is an intestinal parasite, which may occasionally involve extraintestinal sites including the female genital tract. We report a rare case of ovarian involvement, which presented with chronic right iliac fossa pain in a 31-year-old woman. A transvaginal ultrasound scan was suggestive of a right adnexal dermoid cyst; however, histological examination of the subsequent salpingo-oophorectomy specimen showed an abscess containing viable E. vermicularis ova. E. vermicularis is the most prevalent human nematode worldwide. Its ova are ingested, larvae hatch and mature female worms journey to the perianal region where they lay eggs. Female worms may also migrate from the anus along the female genital tract. Although of low pathogenicity, complications such as infertility or peritonitis may arise. PMID- 24177460 TI - Rupture of the flexor digitorum superficialis muscle belly during isometric weight training. AB - Isometric weight training is a well-recognised technique used by fitness trainers to increase muscle strength. We report a case of a flexor digitorum superficialis muscle belly rupture that occurred during this form of muscle training. Rupture of the belly of the forearm flexor muscles is rare. When the muscle undergoes tractional force in isometric weight training, there is a potential for it to rupture and result in the formation of a haematoma. This can lead to raised intracompartmental pressures which would require treatment with urgent fasciotomy. An awareness of this potential injury mechanism will help with early recognition and appropriate treatment. PMID- 24177461 TI - Intermittent swelling in the chest; a case of spontaneous intermittent lung herniation. AB - Herniation of the lung is uncommon and occurs due to protrusion of the lung beyond the confines of the thoracic cavity through an abnormal opening in the chest wall. Any condition associated with raised intrathoracic pressure or that which weakens the thoracic wall may result in lung herniation. We present a case of spontaneous lung herniation which was managed successfully by minimally invasive thoracic surgery. PMID- 24177462 TI - Inactive cardiac sarcoidosis with characteristic findings on cardiac MRI. PMID- 24177463 TI - A conversation with John T. Potts Jr. Interview by Ushma S. Neill. PMID- 24177466 TI - Blood platelet kinetics and platelet transfusion. AB - The discovery of citrate anticoagulant in the 1920s and the development of plastic packs for blood collection in the 1960s laid the groundwork for platelet transfusion therapy on a scale not previously possible. A major limitation, however, was the finding that platelet concentrates prepared from blood anticoagulated with citrate were unsuitable for transfusion because of platelet clumping. We found that this could be prevented by simply reducing the pH of platelet-rich plasma to about 6.5 prior to centrifugation. We used this approach to characterize platelet kinetics and sites of platelet sequestration in normal and pathologic states and to define the influence of variables such as anticoagulant and ABO incompatibility on post-transfusion platelet recovery. The "acidification" approach enabled much wider use of platelet transfusion therapy until alternative means of producing concentrates suitable for transfusion became available. PMID- 24177467 TI - The perfect storm: challenges and opportunities for translational medicine. PMID- 24177464 TI - Deep brain stimulation (DBS) at the interface of neurology and psychiatry. AB - Deep brain stimulation (DBS) is an emerging interventional therapy for well screened patients with specific treatment-resistant neuropsychiatric diseases. Some neuropsychiatric conditions, such as Parkinson disease, have available and reasonable guideline and efficacy data, while other conditions, such as major depressive disorder and Tourette syndrome, have more limited, but promising results. This review summarizes both the efficacy and the neuroanatomical targets for DBS in four common neuropsychiatric conditions: Parkinson disease, Tourette syndrome, major depressive disorder, and obsessive-compulsive disorder. Based on emerging new research, we summarize novel approaches to optimization of stimulation for each neuropsychiatric disease and we review the potential positive and negative effects that may be observed following DBS. Finally, we summarize the likely future innovations in the field of electrical neural-network modulation. PMID- 24177465 TI - The genomics of schizophrenia: update and implications. AB - Schizophrenia is strongly familial yet rarely (if ever) exhibits classical Mendelian inheritance patterns. The advent of large-scale genotyping and sequencing projects has yielded large data sets with higher statistical power in an effort to uncover new associations with schizophrenia. Here, we review the challenges in dissecting the genetics of schizophrenia and provide an update of the current understanding of the underlying genomics. We discuss the breadth of susceptibility alleles, including those that may occur with low frequency and high disease risk, such as the 22q11.2 hemideletion, as well as alleles that may occur with greater frequency but convey a lower risk of schizophrenia, such as variants in genes encoding subunits of the voltage-gated L-type calcium channel. Finally, we provide an overview of the clinical implications for the diagnosis and treatment of schizophrenia based on progress in understanding the underlying genetic basis. PMID- 24177468 TI - Solutions to global health challenges: no more Band-Aids. PMID- 24177469 TI - Introduction of John T. Potts Jr. PMID- 24177470 TI - Acceptance remarks. PMID- 24177473 TI - Retraction: High-mobility group A1 inhibits p53 by cytoplasmic relocalization of its proapoptotic activator HIPK2. PMID- 24177477 TI - Secondary traumatic stress among mental health providers working with the military: prevalence and its work- and exposure-related correlates. AB - Our research assessed the prevalence of secondary traumatic stress (STS) among mental health providers working with military patients. We also investigated personal, work-related, and exposure-related correlates of STS. Finally, using meta-analysis, the mean level of STS symptoms in this population was compared with the mean level of these symptoms in other groups. Participants (N = 224) completed measures of indirect exposure to trauma (i.e., diversity, volume, frequency, ratio), appraisal of secondary exposure impact, direct exposure to trauma, STS, and work characteristics. The prevalence of STS was 19.2%. Personal history of trauma, complaints about having too many patients, and more negative appraisals of the impact caused by an indirect exposure to trauma were associated with higher frequency of STS symptoms. A meta-analysis showed that the severity of intrusion, avoidance, and arousal symptoms of STS was similar across various groups of professionals indirectly exposed to trauma (e.g., mental health providers, rescue workers, social workers). PMID- 24177478 TI - Drugs in context: a historical perspective on theories of psychopharmaceutical efficacy. AB - This article demonstrates that psychoanalysis and socially oriented psychiatry were crucial to the understanding and adoption of the first effective psychopharmaceuticals in North American psychiatry. In the 1950s and the early 1960s, psychoanalysts, socially oriented psychiatrists, and biologists collaborated, debated, and organized interdisciplinary conferences to situate the biochemistry of new psychopharmaceuticals, such as chlorpromazine, in the broader psychosocial context of patients' lives. Psychoanalytical and sociological perspectives not only helped American psychiatrists explain the mechanism of drug action in research but also established the professional authority of psychiatrists over the new pharmaceuticals. As modern pharmacology narrows its focus to microscopic targets in the body, I argue that this early drug research illustrates the present-day need for holistic and interdisciplinary approaches to drug response that acknowledge the psychosocial significance of psychiatric medication in the lives of individuals. PMID- 24177479 TI - Comorbid internet addiction in male clients of inpatient addiction rehabilitation centers: psychiatric symptoms and mental comorbidity. AB - Addictive Internet use has recently been proposed to be included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Still, little is known about its nosological features, including comorbidity with other mental disorders and disorder-specific psychopathological symptoms. To investigate whether Internet addiction (IA) is an issue in patients in addiction treatment, 1826 clients were surveyed in 15 inpatient rehabilitation centers. Male patients meeting criteria for comorbid IA (n = 71) were compared with a matched control group of male patients treated for alcohol addiction without addictive Internet use (n = 58). The SCL-90-R, the Patient Health Questionnaire, and the seven-item Generalized Anxiety Disorder were used to assess associated psychiatric symptoms and further comorbid disorders. Comorbid IA was associated with higher levels of psychosocial symptoms, especially depression, obsessive compulsive symptoms, and interpersonal sensitivity. Moreover, the patients with IA more frequently met criteria for additional mental disorders. They display higher rates of psychiatric symptoms, especially depression, and might be in need of additional therapeutic treatment. In rehabilitation centers, a regular screening for IA is recommended to identify patients with this (non-substance related) addiction and supply them with additional disorder-specific treatment. PMID- 24177480 TI - Testing a model of the relationship between childhood sexual abuse and psychosis in a first-episode psychosis group: the role of hallucinations and delusions, posttraumatic intrusions, and selective attention. AB - Several theories suggest that posttraumatic intrusive symptoms are central to the relationship between childhood trauma (CT) and hallucinations and delusions in psychosis. Biased selective attention has been implicated as a cognitive process underlying posttraumatic intrusions. The current study sought to test theories of the relationship between childhood sexual abuse (CSA), hallucinations and delusions, posttraumatic intrusions, and selective attention in first-episode psychosis (FEP). Twenty-eight people with FEP and 21 nonclinical controls were assessed for CT and psychotic and posttraumatic stress symptoms and completed an emotional Stroop test using CSA-related and other words. Those with FEP and CSA had more severe hallucinations and delusions than those with FEP and without CSA. They also reported posttraumatic intrusions at clinical levels and showed selective attention to CSA-related words. The results are consistent with the posttraumatic intrusions account of hallucinations and delusions in those with CSA and psychosis. PMID- 24177481 TI - Toxoplasma gondii infection and suicide attempts: a case-control study in psychiatric outpatients. AB - The association of Toxoplasma gondii infection with suicide attempts has been scarcely evaluated. Two hundred eighty-three psychiatric outpatients (156 patients with history of suicide attempt and 127 control patients without history of suicide attempt) were examined with enzyme-linked immunoassays for Toxoplasma immunoglobulin G (IgG) and IgM antibodies. Seroprevalences of Toxoplasma IgG and IgM in the cases and the controls were similar: 7 (4.5%) and 3 (1.9%) vs. 10 (7.9%) and 3 (2.4%) (p = 0.23 and p = 0.55), respectively. In contrast, the Toxoplasma IgG levels higher than 150 IU/ml were more frequently observed in the cases than in the controls (100% vs. 50%, respectively; p = 0.04). The seroprevalence of Toxoplasma infection increased with age and with the number of suicide attempts. Toxoplasma seropositivity was associated with reflex impairment, national trips, and snake meat consumption. Our results suggest that although seroprevalence of Toxoplasma infection is not associated with suicide attempts, a high anti-Toxoplasma antibody level is, therefore warranting further research. PMID- 24177483 TI - A test of the unique and interactive roles of anger experience and expression in suicidality: findings from a population-based study. AB - This study examined the unique and interactive roles of anger experience and expression in suicidality (suicidal ideation, plans, and attempts) in a large, nationally representative sample. Participants included 5692 adults from the National Comorbidity Survey-Replication, a nationally representative survey. Anger experience was assessed through a continuous measure, whereas anger expression problems were determined by the presence of an intermittent explosive disorder diagnosis. Tests of unique associations revealed that for the overall sample, anger experience and expression each predicted a unique variance in all outcomes of suicidality. Among the individuals reporting lifetime suicidal ideation, anger experience and expression were uniquely related to suicide attempts. Analyses also revealed anger experience and expression to interact in the prediction of suicidal ideation, suggesting that these have independent and additive effects on risk for suicide. The findings suggest that both anger experience and expression contribute to suicidality and the progression from suicidal ideation to plans and attempts. PMID- 24177482 TI - Correlates of irritability in college students with depressive symptoms. AB - Depression is a prevalent psychiatric disorder associated with significant personal and societal burden. There is accumulating evidence for the presence of a subtype of depression characterized by the presence of irritability that is associated with increased morbidity, risk for suicidal ideation, and functional impairments in adults. Little is known about the features of depressive symptoms with and without irritability among young adults in college. The primary aim of this study was to characterize the presentation of college students with depressive symptoms and irritability. Two-hundred eighty-seven undergraduate college students with depressive symptoms with and without irritability were compared across several psychiatric and functional outcome variables. Independent samples t-tests or logistic regressions were conducted for each outcome variable using the irritability item of the Beck Depression Inventory as a dichotomous grouping variable. Analyses were conducted separately for the men and the women. Both male and female students with depressive symptoms and severe irritability reported a greater severity of depressive symptoms compared with their peers with no or mild irritability. In the women, the presence of irritability was associated with greater symptoms of anxiety, whereas in the men, it was associated with increased likelihood of engaging in risky behaviors, including compulsive use of alcohol, illicit drugs, and prescription drugs. The male and female college students with depressive symptoms with and without irritability did not differ on severity of suicidal ideation, hopelessness, or cognitive functioning. The findings from this study suggest that depressive symptoms and irritability may characterize a subtype of college students who have a greater symptom burden and with the potential need for more aggressive and prompt treatment. PMID- 24177484 TI - The relation between family adversity and social anxiety among adolescents in Taiwan: effects of family function and self-esteem. AB - This study aimed to examine the relationship between three indicators of family adversity (domestic violence, family substance use, and broken parental marriage) and the severity of social anxiety among adolescents in Taiwan, as well as the mediating effects of perceived family function and self-esteem on that relationship, using structural equation modeling (SEM). A total of 5607 adolescents completed the social anxiety subscale of the Multidimensional Anxiety Scale for Children; the Family APGAR Index; the Rosenberg Self-Esteem Scale; and a questionnaire for domestic violence, family substance use, and broken parental marriage. The relation between family adversity and social anxiety, as well as the mediating effects of family function and self-esteem, was examined using SEM. SEM analysis revealed that all three indicators of family adversity reduced the level of family function, that decreased family function compromised the level of self-esteem, and that a low level of self-esteem further increased the severity of social anxiety. The results indicated that, along with intervening to change family adversity, evaluating and improving adolescents' self-esteem and family function are also important clinical issues when helping adolescents reduce their social anxiety. PMID- 24177485 TI - A brief inpatient measure of global psychiatric symptom severity: initial validation of the Brief Symptom Measure-25 for an adolescent inpatient sample. AB - Adolescent psychiatry is experiencing a growing need for brief yet psychometrically robust outcome measures for inpatient settings. Outcome measures currently available present limitations to clinicians and patients alike in terms of their excessive length, time of completion, difficulty to score, and focus on specific clusters of symptoms. The present study sought to validate the Brief Symptom Measure-25 (BSM-25) as a brief and easily administered measure of global psychiatric symptom severity in adolescent inpatient samples. This study evaluated the results from 154 adolescent inpatients who completed several self report measures at admission. The findings demonstrate that the instrument has good construct validity when compared with validated measures of psychological health and well-being, behavioral problems, and interpersonal distress. We also showed the sensitivity to change of the BSM-25 from admission to discharge, and we showed that this healthy change was paralleled in several measures (self reports and clinician ratings), using data from 75 adolescent psychiatric inpatients who were assessed at admission and also at discharge. Although this is only the first step in the validation of this measure for an adolescent inpatient setting, the BSM-25 shows promise as a brief outcome measure of global psychiatric symptom severity while maintaining validity and instrument sensitivity. PMID- 24177486 TI - The evaluation of a telephonic wellness coaching intervention for weight reduction and wellness improvement in a community-based cohort of persons with serious mental illness. AB - Obesity and metabolic disturbances frequently occur in individuals with psychiatric disorders. This study evaluates a telephonically delivered lifestyle coaching intervention aimed at weight reduction and wellness improvement in psychiatric outpatients. A cohort of 761 participants was prospectively followed up for a period of 12 months. Lifestyle coaching was administered telephonically on a weekly basis for the first 3 months and monthly thereafter. During the study period, there was a significant reduction in weight and waist circumference as well as a significant increase in general health in the completer group. A total of 46% of the participants lost 5% or more of their baseline weight. Significant predictors of attrition at baseline were the presence of metabolic syndrome, younger age, chronic illness, and the diagnosis of a mood disorder. Dropout was significantly less in those participants who received support from a nominated caregiver. Telephonic lifestyle coaching is feasible in this population. PMID- 24177487 TI - Suicide in medical doctors and nurses: an analysis of the Queensland Suicide Register. AB - This study aimed to estimate the risk for suicide among medical doctors and nurses compared with the education professions and the general population and to describe the characteristics of their suicides. Suicide cases and rates in the age group of 25 to 64 years were analyzed using the Queensland Suicide Register (QSR) during 1990 to 2007. The male medical doctors had lower suicide rates than those of the male education professionals and significantly lower rates than those of the general population. The female medical doctors had significantly higher rates than those of the education professionals, but the rates were similar to those of the general population. Among the nurses, both sexes had significantly higher rates than those of the education professionals; however, their rates were similar to those of the general population. Poisoning was used significantly more often by the medical professionals (59.3%) and the nurses (44.1%) than by the education professionals (23.5%) and others (18.8%). Depression was more common in suicide of the medical doctors than the nurses, the education professionals, and others. Work-related problems were most prevalent for the medical doctors (18.5%) followed by the education professionals (16.5%). PMID- 24177488 TI - Behavioral screening measures delivered with a smartphone app: psychometric properties and user preference. AB - The smartphone is an increasingly widespread technological vehicle for general health and psychological health promotion, evaluation, education, and sometimes intervention. However, the psychometric performance of behavioral health screening measures has not been commonly evaluated for the new, small-format, touch-screen medium. Before mobile-based applications for behavioral health screening can be disseminated confidently, the reliability and the validity of measures administered by the smartphone must be evaluated. We compared psychometric properties (i.e., internal consistency and test-retest reliability) of seven behavioral health measures completed on paper, a computer, and an iPhone by 45 army soldiers. The results showed the internal consistencies of the smartphone-delivered measures to be equivalent and very high across all three modalities and the test-retest reliability of the iPhone measures also to be very high. Furthermore, completion of the behavioral screening measures by the iPhone was highly preferred over the other modalities and was reported to be easy and convenient. Our findings help corroborate the use of smartphones and other small mobile devices for behavioral health screening. PMID- 24177489 TI - Hormonal therapy is associated with better self-esteem, mood, and quality of life in transsexuals. AB - Few studies have assessed the role of cross-sex hormones on psychological outcomes during the period of hormonal therapy preceding sex reassignment surgery in transsexuals. The objective of this study was to assess the relationship between hormonal therapy, self-esteem, depression, quality of life (QoL), and global functioning. This study incorporated a cross-sectional design. The inclusion criteria were diagnosis of gender identity disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) and inclusion in a standardized sex reassignment procedure. The outcome measures were self-esteem (Social Self-Esteem Inventory), mood (Beck Depression Inventory), QoL (Subjective Quality of Life Analysis), and global functioning (Global Assessment of Functioning). Sixty-seven consecutive individuals agreed to participate. Seventy-three percent received hormonal therapy. Hormonal therapy was an independent factor in greater self-esteem, less severe depression symptoms, and greater "psychological-like" dimensions of QoL. These findings should provide pertinent information for health care providers who consider this period as a crucial part of the global sex reassignment procedure. PMID- 24177490 TI - Number needed to harm can be clinically useful: a response to Safer and Zito. PMID- 24177491 TI - Number needed to harm. PMID- 24177492 TI - On the antitumor properties of novel cyclometalated benzimidazole Ru(II), Ir(III) and Rh(III) complexes. AB - Smart design and efficient synthesis of benzimidazole Ru, Ir and Rh cyclometalated complexes are reported with promising cytotoxic activity against HT29, T47D, A2780 and A2780cisR cancer cell lines. Their apoptosis, accumulation, cell cycle arrest, protein binding and DNA binding effects are also discussed. PMID- 24177493 TI - On the origin of mode- and bond-selectivity in vibrationally mediated reactions on surfaces. AB - The experimental observations of vibrational mode- and bond-selective chemistry at the gas-surface interface indicate that energy redistribution within the reaction complex is not statistical on the timescale of reaction. Such behavior is a key prerequisite for efforts to use selective vibrational excitation to control chemistry at the technologically important gas-surface interface. This paper outlines a framework for understanding the origin of non-statistical reactivity on surfaces. The model focuses on the kinetic competition between intramolecular vibrational energy redistribution (IVR) within the reaction complex, which in the long-time limit leads to statistical behavior, and quenching, scattering, or desorption processes that restrict the extent of IVR prior to reaction. Characteristic timescales for these processes drawn from studies of vibrational energy flow dynamics on surfaces and in the gas and condensed phases suggest that IVR is severely limited for important classes of surface reactions. Under these conditions, selective vibrational excitation can lead to preferential transition state access and result in mode- or bond selective chemistry, even at high collision energies above the barrier to reaction. In addition to providing a basis for understanding experimental observations, the model provides guidance for identifying other gas-surface reactions that may exhibit mode-selective behavior. PMID- 24177494 TI - Hypoxia-sensitive bis(2-(2'-benzothienyl)pyridinato-N,C(3'))iridium[poly(n-butyl cyanoacrylate]/chitosan nanoparticles and their phosphorescence tumor imaging in vitro and in vivo. AB - A new hypoxia-sensitive coordination compound, bis(2-(2'-benzothienyl)pyridinato N,C(3'))iridium[poly(n-butyl cyanoacrylate)], hereafter denoted as (btp)2Ir(PBCA), is synthesized and characterized by (13)C nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR). (btp)2Ir(PBCA)/chitosan [(btp)2Ir(PBCA)/CS] nanoparticles (NPs) with a core-shell structure are prepared by a two-step fabrication process. The size distributions of these NPs are measured with a Malvern size analyzer, and their morphology is observed by transmission electron microscopy (TEM). The functional groups on the surface are confirmed by FTIR. Phosphorescence spectra are obtained and lifetimes are determined with a spectrophotofluorometer and a time-correlated single photon counting (TCSPC) apparatus, respectively. HeLa and CT26 cell lines are used to examine the cytotoxicity by the MTT assay, as well as to determine the imaging capability of the samples in air and nitrogen atmospheres, respectively. Tumor bearing mouse models of colon adenocarcinoma are used for tumor imaging in vivo, and the imaging effect is evaluated with a Maestro 2 fluorescence imaging system. Compared with the hypoxia-associated probe bis(2-(2'-benzothienyl)pyridinato N,C(3'))iridium(acetylacetonate) (BTP), the phosphorescence lifetime of (btp)2Ir(PBCA)/CS NPs significantly decreases, but the hypoxia-sensitivity increases after preparation of NPs. Apart from the significantly lower cytotoxicity, (btp)2Ir(PBCA)/CS NPs also enhance the tumor imaging effect by more than 10 times, maintaining the phosphorescence signal in tumor tissue for over 24 h and significantly decreasing the phosphorescence signal in normal tissue in vivo compared with the BTP probe. PMID- 24177495 TI - Charge and spin transport in PEDOT:PSS nanoscale lateral devices. AB - The electrical transport of the highly conductive poly-(3,4 ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) is investigated with Ohmic and spin-polarized tunnel contacts at nanoscale lateral dimensions. Temperature-dependent charge transport measurements reveal that electrical conductivity scales non-linearly as a function of electrode spacing, which is attributed to the localization of carriers induced by the disorder introduced by the PSS polyelectrolyte. In addition, we demonstrate the integration of this conducting polymer in nanoscale lateral spin-valve devices by increasing the pH of the PEDOT:PSS solution. We present charge and magnetotransport measurement results of NiFe/AlOx/PEDOT:PSS/AlOx/NiFe lateral structures for various thicknesses of the alumina tunnel barriers. We discuss the absence of magnetoresistance of our spin valves within the framework of Valet-Fert theory, and estimate an upper limit for the spin lifetime of carriers in PEDOT:PSS to tausf <= 50 ns. PMID- 24177497 TI - Red cell hydrolases : II. Proteinase activities in human erythrocyte plasma membranes. AB - A 0.1% Triton X-100 extract of human erythrocyte plasma membranes contained high proteolytic activity as determined by a very sensitive assay utilizing(3)H acetylated hemoglobin (162 cpm/pmole) as a substrate. Two proteolytic enzymes having optimum activity at pH 3.4 and pH 7.4 were isolated from Sephadex G-100. The protease active at pH 3.4 was 75 times as active as the pH 7.4 enzyme and it was purified 182-fold over the original homogenate and characterized. A linear relationship for activity versus time and activity versus concentration of enzyme was found. The optimum temperature was 37 degrees C and theK m was 1*10(-5) M hemoglobin. No enzyme activation was observed with any cation studied and EDTA had no inhibitory effect; (10MM Fe(+3) and Hg(+2) were inhibitory). The pH 3.4 protease was stable indefinitely at -20 degrees C in 0.1% Triton X-100. Gel electrophoresis was performed on a sodium dodecylsulfate-mercaptoethanol enzyme preparation and two protein bands (mol. wt. 33,000 and 54,000) were evident for the Sephadex G-200 eluate containing the pH 3.4 protease. PMID- 24177498 TI - Multiple conductance states in single channels of variable resistance lipid bilayer membranes. AB - The properties of the cation-permeable excitability-inducing material (EIM) channels in lipid bilayer membranes have been investigated using membranes penetrated by only one to four active channel units. Under these conditions, individual channels may be observed to undergo on-off conductance transitions that may be correlated with the negative resistance characteristics of membranes having a large number of channels.In many lipid membrane systems, EIM channels have several conductance levels for each channel. Such channels may open or close with either a single, large conductance step or in several smaller jumps having a sum equivalent to the large jump. The conductance of the fully closed state in such channels is generally less than 2% of the open-state conductance, too low to be differentiated from membrane conductance in the absence of an EIM channel. This ratio is reflected in the current-voltage characteristics of membranes containing large numbers of channels, where ratios of maximum conductance to minimum conductance may range from 50 to 200.EIM channels in oxidized cholesterol bilayers are exceptional in showing only two conductance levels normally. The closed state in this system corresponds to a low intermediate state in the general channel.The conductance of each state apears to be linearly related to the activity of the electrolyte. PMID- 24177499 TI - Comparison of double layer potentials in lipid monolayers and lipid bilayer membranes. AB - It is shown that the Gouy-Chapman double layer analysis adequately describes the variation of the surface potential of monolayers of acidic natural lipids over a wide range of surface charge density and salt concentration. It is also shown that the potential which initially appears when an electrolyte gradient is rapidly imposed across a bilayer membrane is due to a difference in the double layer potentials on the two sides of the membrane. This conclusion follows from the fact that the observed bilayer potentials arise much more rapidly than can be accounted for by charge migration across the membrane and from the observation that the bilayer membrane concentration potentials, when measured immediately after establishment of a gradient, are equal to the surface potential change observed when the subphase concentration of a monolayer of the same lipid is changed by an amount equal to the gradient across the bilayer. The bilayer potential and monolayer potential changes, so measured, agree in a number of different electrolyte solutions over a wide range of electrolyte concentrations and surface charge densities. Because of this agreement and the applicability of the Gouy theory to monolayers, initial bilayer potentials may be calculated if the composition of the mixture used to form the membrane is known, provided that the pK's and areas of such components are available. In the absence of this information, membrane potentials may be calculated from electrophoretic data on the membrane lipid mixture; the conditions under which the latter approach is possible have been determined. The experimental results indicate that the composition of monolyers and bilayers spread from the same lipid mixture in decane are very similar, that the composition of the two types of film closely resembles the composition of the solution used to generate them, and that bilayer membranes are close-packed. The evidence further indicates that if any hydrocarbon solvent remains in these bilayers, it must be so situated that it contributes little, if anything, to the surface area. The steady state potential in the bilayer membrane system is frequently not identical with the initial potential which supports the hypothesis that in many cases only a fraction of the electrical conductance of unmodified membranes is caused by the ions which constitute the bulk electrolyte. An expression for the relationship between diffusion and double layer potentials has been derived which shows that, in the absence of any intrinsic selectivity of the hydrocarbon region of the membrane for hydrogen, hydroxyl, or impurity, the two potentials should be identical. PMID- 24177500 TI - Properties of lipid bilayer membranes separating two aqueous phases: The effects of Fe(+3) on electrical properties. AB - Ferric ion has been found to alter the electrical properties of lecithincholesterol-decane bilayer membranes. Within minutes after the addition of microgram quantities of FeCl3 to the ambient aqueous phase, the resistance of the membrane falls by a factor of 10(5) to 10(6). No change in capacitance is observed. The resistance change is obtained with membranes made from synthetic lecithin (fully saturated fatty acids) as well as by those formed from egg lecithin. The conductance of the modified membrane exhibits both time and voltage dependent behavior; the time dependence of the current is similar to that of an inductance, and the voltage dependence of the current is exponential. Concomitant with the resistance change, the modified membrane becomes permselective, passing chloride almost to the complete exclusion of sodium. Anion selectivity can be converted to cation selectivity by the subsequent addition of certain chelating agents. Area-conductance measurements show the resistance change occurs in the thin film. The addition of a reducing agent causes the effect of the ferric ion to be reversed, and the conductance returns to that characteristic of unmodified membranes. When ferric ion is added to only one side of the membrane, the system rectifies with current ratios of up to 20?1. It is concluded that the alteration of membrane properties owes its origin to the hydrolysis of membrane-bound ferric ion. The interaction of ferric ion with aqueous dispersions of lecithin has been investigated by several techniques, and evidence is presented that the dispersions bind charged species of iron and that this charge diminishes under conditions where iron hydrolysis occurs. PMID- 24177501 TI - Model approaches for evaluation of cell coupling in monolayers. AB - The electrical coupling of epithelial cells of the intestine of chick embryo cultured in monolayers was studied. This coupling can be evaluated by regarding the monolayer as a honeycomb structure of cells and the cells as equipotential spaces, as long as the cells are small (diameter <25MUm). With help of this discrete model it was found that for the non-junctional membrane the membrane resistance isrho m =250-2,000 Omega cm(2), and for the junctional membranerho m =5-50 Omega cm(2). In addition to this discrete model, a continuous model was also considered and good agreement between the two descriptions was found. With the aid of the continuous model, a value for the non-junctional membrane capacitance (C m ) was obtained: 5-50 MUF/cm(2). The electrical values are not corrected for membrane folding, microvilli and the like. Tentative corrections based on electron microscopy suggest: 1,000 73%) was obtained by the culture of large size somatic embryos or cotyledon-like structures on medium containing a combination of NAA/BAP/KIN or TDZ (10 MUM) alone, maltose (175 mM) and Phytagel (2.8 g/1). PMID- 24177544 TI - Microspore culture of radish (Raphanus sativus L.): influence of genotype and culture conditions on embryogenesis. AB - A number of factors influencing embryogenesis from isolated microspores of radish (Raphanus sativus) were examined. Of 11 genotypes evaluated, six produced embryos ranging from 8.3 embryos per 10(5) microspores for 'Chugoku-ao' to 0.2 for 'Tenshun', but five genotypes were not responsive. An initial culture period at elevated temperature before incubation at 25 degrees C was essential for induction of microspore embryogenesis. However, the optimum period of the treatment varied among genotypes and/or experiments. Bud size also influenced microspore embryogenesis. Though optimum bud size was different between genotypes, the microspore populations represented in these buds contained uninucleate and binucleate microspores. Selection of embryogenic microspores using percoll density gradient resulted in up to 1.3-fold increase of embryo yield. Though almost all embryos failed to develop directly into plantlets, plants were obtained by multiple subcultures. The regenerated plants had hyperploid chromosome numbers. PMID- 24177543 TI - Tissue-specific and ABA-regulated Maize GIN gene expression in transgenic tobacco. AB - To study the regulatory functions of the ON promoter region, a ppG1b1GUS construct, consisting of 1402 bp 5' flanking sequence ofGlbl, 1919 by GUS coding sequence, and 283 by 3' NOS terminator, was cloned into a binary vector and introduced into tobacco plants byAgrobacterium-mediated transformation. Histochemical GUS assays of To tobacco mature seeds indicate that theGlbl promoter drives GUS expression in ABA treated seeds. Further GUS assays of the T, seeds at different developmental stages revealed that without ABA treatment, theGibl promoter drives GUS expression in immature seeds. The results from both To and T1 tobacco plants indicated thatGlbl-driven GUS expression in tobacco is embryo specific. PMID- 24177545 TI - High regeneration rates in anther culture of interspecific sunflower hybrids. AB - Optimization of anther culture with regard to the induction of callus formation and direct embryogenesis was obtained for interspecific hybrids ofH. annuus withH. tuberosus, H. laetiflorus, andH. resinosus by investigating six different induction media and four regeneration media. One media combination (MS-13, MS-R3 and MS-R4) used under different culture conditions (30 degrees C / 35 degrees C and different dark treatments) gave up to 92.7% embryogenic anthers with an average of 8.5 embryos per anther. However, direct embryogenesis as well as callus formation showed a strong genotypec and treatment specific reaction. From 5,600 anthers of the four investigated genotypes more than 2,000 plants could be regenerated. Regenerants were characterized by morphological traits and isozyme analyses to prove their androgenetic origin. PMID- 24177546 TI - Expression of an environmentally friendly synthetic protein-based polymer gene in transgenic tobacco plants. AB - We report the expression of a protein-based polymer (Gly-Val-Gly-Val-Pro)121, i. e., (GVGVP)121 in transgenic tobacco (Nicotiana tabacum var. Kentucky 17) plants. The plant expression vector pBI121-XZ-120mer which contains the gene (GVGVP)121 with a prokaryotic preferred codon composition driven by the CaMV 35S promoter was introduced into tobacco plants byAgrobacterium-mediated transformation. Stable integration of the (GVGVP)121 polymer gene was confirmed by Southern blot analysis. Northern hybridization showed polymer transcripts in leaves of transgenic plants. The (GVGVP)121 polymer protein was detected in leaves of transgenic plants by Western blot. The (GVGVP)121 protein could be easily purified to a high degree of purity from leaves of transgenic plants by reversible phase transition as revealed by SDS-PAGE gels stained by CuCl2. Transgenic plants grew, flowered, and produced seeds normally. PMID- 24177547 TI - Canavanine synthesis in thein vitro propagated tissues ofCanavalia lineata. AB - Maximum shoot induction from stem explants ofCanavalia lineata was obtained with an agar-solidified PC medium containing 10 MUM benzylaminopurine and 1 MUM naphthaleneacetic acid. Rooting of thesein vitro produced shoots was achieved with hormone-free PC medium. Canavanine was produced almost exclusively in the leaves and was not detected in the roots ofin vitro propagatedC. lineata. To exclude the possibility of imminent translocation of canavanine from the root to leaf, adventitious roots were induced from leaf explants in PC medium supplemented with 1 MUM kinetin and 20 MUM indole-3-acetic acid and subcultured in medium lacking growth regulators, and the roots excised from germinated seedlings were cultured in hormone-free PC medium. All the roots were incapable of accumulation of canavanine. These results suggest that leaves ofC. lineata are the possible site of canavanine synthesis. PMID- 24177548 TI - Plant regeneration from somatic embryos ofTaxus brevifolia. AB - Taxusbrevifolia is the source of paclitaxel (Taxol(r)), an anticancer drug. A method for regeneration ofTaxus brevifolia from immature zygotic embryos via somatic embryogenesis is described. Embryogenic callus tissues were obtained by culturing immature zygotic embryos on Lloyd and McCown medium (MCM) supplemented with 160 MUM 2,4-dichlorophenoxyacetic acid (2,4-D) + 5 MUM benzylaminopurine (BA) + 5 MUM naphthaleneacetic acid (NAA) for 4 weeks. Putative embryoids were obtained following transfer of cultures to MCM medium supplemented with 4 MUM BA + 5 MUM kinetin + 1 MUM NAA for 6 to 8 weeks. Conversion of embryos was obtained on MCM medium supplemented with 40 MUM abscisic acid (ABA) + 1% activated charcoal. Development of bipolar structures with recognizable shoot and root apices was observed in somatic embryos. Five percent of somatic embryos were regenerated into plantlets on half-strength growth regulator-free MCM medium. PMID- 24177549 TI - A cell suspension ofLinum flavum (L.) in phosphate limited continuous culture. AB - A cell suspension ofLinum flavum was grown in phosphate limited continuous culture at two different growth rates. Energy metabolism (respiration), coniferin and lignin production and overall biomass composition were analysed, in order to establish the relations between growth, maintenance and secondary metabolism. The ATP turnover rate was higher in the faster growing cultures, corresponding with a higher energy requirement. The coniferin production was not directly correlated with the growth rate, indicating the possibility of high production at high growth rates. Steady states grown under identical conditions showed different characteristics that may have evolved during pre-culture time. PMID- 24177550 TI - Inhibition of somatic embryo maturation in Sitka spruce [Picea sitchensis (Bong.) Carr.] by butylated hydroxytoluene, a volatile antioxidant released by parafilm. AB - Head-space volatiles above embryogenicPicea sitchensis (Bong.) Carr. (Sitka spruce) tissues cultured in glass Petri dishes sealed with Parafilm M or cling film, were captured on Tenax adsorption traps and analysed by gas chromatography / mass spectrometry. Each sealing system released a single major compound into the head-space; butylated hydroxytoluene from Parafilm M and 2-ethyl-1-hexanol from cling-film. After two weeks sealed under Parafilm M butylated hydroxytoluene accumulated to 1.1 MUg g(-1) FW in tissues and subsequent somatic embryo maturation was prevented. When butylated hydroxytoluene was supplied via the head space (100 MUg/250 ml flask) 0.5 MUg g(-1) FW accumulated in tissues after two weeks and no somatic embryo maturation occurred. Potentially phytotoxic metabolites of butylated hydroxytoluene included a substituted stilbenequinone, butylated hydroxytoluene quinone methide and butylated hydroxytoluene dimer. PMID- 24177551 TI - Analysis of intra-specific somatic hybrids of potato (Solanum tuberosum) using simple sequence repeats. AB - We have utilised simple sequence repeat (SSR) polymorphism to analyse two sets of potential intra-specific hybrids of potato. Two primer pairs were used and both showed that one set of fusion products could not be true heterokaryons. In the other set, one of the primer pairs showed that unique bands in each of the parents were present in all of the hybrids, unambiguously demonstrating hybridity. This simple and robust, high-resolution assay can be used at the callus level and is amenable to automation, making it possible to reduce greatly the time required to screen a large number of potential somatic hybrids. PMID- 24177552 TI - Prolific shoot regeneration from immature embryo explants of sainfoin (Onobrychis viciifolia Scop.). AB - Immature cotyledons and embryo axes of sainfoin were cultured on Murashige and Skoog (MS) media supplemented with various concentrations of 6-benzylaminopurine (BAP) and a-naphthaleneacetic acid (NAA) to induce adventitious shoot regeneration. The highest frequency of shoot regeneration occurred following an initial callus growth on a MS medium containing 0.5 mg/l BAP and 2 mg/l NAA. Immature embryo axes showed higher regeneration capacity than immature cotyledons, however, shoot elongation was best achieved on immature cotyledons. Regenerated shoots were excised and rooted in half strength MS medium with 1 mg/l indole-butyric acid (IBA) or 1 mg/l NAA. The rooted plantlets were finally transferred to compost. PMID- 24177553 TI - High frequency adventitious shoot regeneration from excised leaves ofPaulownia spp. cultured in vitro. AB - High frequency, direct regeneration of shoots was induced in leaf cultures ofPaulownia tomentosa, P. fortunei x P. tomentosa andP. kawakamii. The optimum culture medium for the leaf explants derived from shoot cultures was Murashige Skoog (MS) medium supplemented with 10 MUM indole-3-acetic acid and 50 MUM benzyladenine. Up to 40 shoots were obtained over a 4 month culture period from each leaf explant. Rooting occurred spontaneously in the shoots that were about 1 cm tall when subcultured on phytohormone-free MS medium. The plantlets could be transplanted successfully. Some of the transplantedP. tomentosa plantlets flowered in the greenhouse one year after transplanting. The protocol is suitable not only for rapid multiplication of the various species ofPaulownia, but also for analytical studies associated with adventitious shoot regeneration. PMID- 24177554 TI - Somatic embryogenesis and plant regeneration from the immature cotyledonary tissues of cultivated tea (Camellia sinensis (L).O. Kuntze). AB - Embryogenic callus development, plant regeneration, and plant recovery were achieved from immature cotyledon explants of cultivated tea, when cultured on MS basal medium. The somatic embryo induction frequency was influenced when the medium was supplemented with 1 MUM auxin (NAA, NOA, 2,4-D, TPB, and PBOA) in combination with cytokinin (0.5 MUM BA, KIN) or 10% CM. The highest somatic embryo induction frequency was obtained using PBOA + BA or PBOA + KIN treatments. All auxins except 2,4-D stimulated rhizogenesis using 0.8% and l.5% agar concentrations, and differentiation of a characteristic swelling and friable callus from the exposed surface of the explant that remained nonembryogenic. Conversely, the novel auxins TPB and PBOA at 1 MUM concentration with 3% or 6% agar, produced somatic embryo induction, while at 0.8% and 1.5% produced nonembryogenic callus. Explants isolated proximal to the zygotic embryonal axis showed a greater somatic embryo induction frequency than did the distal explants. The embryogenic competence was maintained through repetitive embryogenesis for a period of over 18 months. The somatic embryos developed into plantlets when incubated on hormone-free medium. The conversion frequency was increased by 50% in MS medium containing 1 MUM Brassin and 0.8% agar. Concentration of agar at 3% and 6% decreased the conversion frequency and promoted anomalous plantlet development. The normal plantlets were treated with 1 MUM IAN, 1 MUM Brassin and 10 MU Phloroglucinol in liquid MS medium for 15 d, where profuse lateral roots were induced favoring a high rate of plant recovery. PMID- 24177555 TI - In vitro plant regeneration from leaf callus inPiper colubrinum Link. AB - Callus-mediated shoot regeneration from leaf explants ofPhytophthora resistant pepper (Piper colubrinum Link.) is described. The effect of basal media composition and growth regulators onin vitro response of explants was evaluated. Shoot buds were induced and elongated on half-strength MS medium containing 2.0 mg l(-1) BA and 0.5 mg l(-1) NAA , as well as 1.0 mg l(-1) BA and 0.5 mg l(-1) 2,4-D. The shoots were rooted in half-strength MS medium with or without IAA or IBA, and then were transferred to soil with 100% survival. PMID- 24177556 TI - A novel principle for selection of transgenic plant cells: positive selection. AB - A novel principle for selection of transgenic plant cells is presented. In contrast to traditional selection where the transgenic cells acquire the ability to survive on selective media while the non-transgenic cells are killed (negative selection), this selection method actively favours regeneration and growth of the transgenic cells while the non-transgenic cells are starved but not killed. Therefore, this selection strategy is termed 'positive selection'. TheE. coli beta-glucuronidase gene was used as selectable (as well as screenable) gene and a glucuronide derivative of the cytokinin benzyladenine as selective agent which is inactive as cytokinin but, upon hydrolysis by GUS, active cytokinin is released stimulating the transformed cells to regenerate. Selection ofAgrobacterium tumefaciens inoculated of tobacco leaf discs on benzyladenine N-3-glucuronide (7.5-15 mg/l) resulted in 1.7-2.9 fold higher transformation frequencies compared to kanamycin selection. A significant advantage of this selection procedure is the elimination of the need for herbicide and antibiotic resistance genes. PMID- 24177557 TI - Prevention of pink-pigmented methylotrophic bacteria (Methylohacterium mesophilicum) contamination of plant tissue cultures. AB - Pink-pigmented facultative methylotrophic bacteria (PPFMs) have been found on the surfaces of leaves of most plants tested. We found PPFMs on the leaf surfaces of all 40 plants (38 species) tested and on soybean pods by pressing onto AMS medium with methanol as the sole carbon source. The abundance ranged from 0.5 colony forming unit (cfu) /cm(2) to 69.4 cfu/cm(2) on the leaf surfaces. PPFMs were found in homogenized leaf tissues of only 4 of the species after surface disinfestation with 1.05% sodium hypochlorite and were rarely found in cultures initiated from surface disinfested Datura innoxia leaves or inside surface disinfested soybean pods. Of 20 antibiotics tested for PPFM growth inhibition, rifampicin was the most effective and of seven others which also inhibited PPFM growth, cefotaxime should be the most useful due to the expected low plant cell toxicity. These antibiotics could be used in concert with common surface sterilization procedures to prevent the introduction or to eliminate PPFM bacteria in tissue cultures. Thus, while PPFMs are present on the surfaces of most plant tissues, surface disinfestation alone can effectively remove them so that uncontaminated tissue cultures can be initiated in most cases. PMID- 24177558 TI - An improved and reliable chili pepper (Capsicum annuum L.) plant regeneration method. AB - In this work we report a new method forin vitro chili pepper (Capsicum annuum L.) plant regeneration based on shoot formation from wounded hypocotyls. Chili pepper seeds were surface sterilized and germinated on agar (0.8%) at 25 +/- 2 degrees C in the dark. Five factors that may influence shoot regeneration were studied: age of seedlings, hypocotyl wounding site, time elapsed between wounding the hypocotyls and decapitation of seedlings, culture media and cultivars. In order to study the influence of the first three factors on shoot regeneration, the apical, middle or basal hypocotyl regions of seedlings of cv. Mulato Bajio at different stages of development (9, 15, 16, 21 and 28 d old) were wounded with a syringe needle, and the seedlings were cultured on MS semisolid medium without growth regulators at 25 +/- 2 degrees C under a 16/8 h light/dark photoperiod (daylight fluorescent lamps; 35 MUmol m-(2) s-(-1)) until decapitation. The seedlings were decapitated (3 mm below the cotyledons) at different times after wounding (0, 2, 4, 10, 12 and 14 d), and each explant was evaluated for bud and shoot formation (>= 5 mm in length) at the wounded site after 30 d of incubation. In general, seedlings at the stage of curved hypocotyl (9 d old) wounded in the apical region of hypocotyl were the best explants for shoot regeneration when inoculated on culture medium without growth regulators. Decapitation after wounding also influenced the shoot regeneration efficiency, with 10-14 d being the best period. Up to 90% shoot regeneration in cv. Mulato Bajio was obtained under these conditions. Statistically significant differences were observed for shoot formation among 21 cultivars tested. Regeneration of whole plants was achieved by rooting the shoots with indole-3-butyric acid pulses of 60 mg L(-1) for 3 h and then subculturing on MS medium without growth regulators. PMID- 24177559 TI - Clonal propagation of Enset (Ensete superbum (Roxb.) Cheesman) through shoot tip cultures. AB - The morphogenetic potential of the shoot tip explants ofEnsete superbum (Roxb.) Cheesman, a wild relative of the cultivated bananas, was investigated and an effective clonal propagation method devised. Shoot tip explants grown in modified MS medium containing 1.5 mg l(-1) BAP and 1 mg l(-1) KIN developed corms which on transfer to medium containing 3 mg l(-1) IBA and 1.5 mg l(-1) BAP, regenerated a large number of shoots from the surface of the corm, the origin of which was traced to single hypodermal cells. Shoots were rooted on a half-strength MS medium salts containing 3 mg l(-1) IBA and 0.1 mg l(-1) BAP. The rooted plantlets were hardened and planted in the field where the plants looked normal. PMID- 24177560 TI - An examination of factors affecting the efficiency ofAgrobacterium-mediated transformation of tomato. AB - An improved protocol forAgrobacterium-mediated transformation of the tomato cultivar Moneymaker was developed by examining the effects of six different factors on the efficiency of transformation. Explant size, explant orientation, gelling agent and plate sealant were found to affect transformation efficiency. Two other factors, type of explant (hypocotyl or cotyledon) and frequency of transfer to fresh selective regeneration medium, did not have any effect on transformation efficiency. By combining the best treatments for each factor, an average transformation efficiency of 10.6% was obtained for Moneymaker. PMID- 24177561 TI - Inducer effect of Tween 20 permeabilization treatment used for release of stored tropane alkaloids inDatura innoxia Mill. hairy root cultures. AB - The effects of Tween 20 as permeabilizing agent on tropane alkaloids fromDatura innoxia Mill. hairy root cultures have been studied. The kinetics of the alkaloid release is detailed and shows three different stages: an initial rapid increase of the alkaloid level within the roots and in the culture medium, followed by a slower but higher increase of the alkaloid concentration in the medium. During this phase, the alkaloid concentration within the roots returned to a lower value. Finally, after a longer time, the quantity of hyoscyamine in the medium decreased significantly with a variable rate. According to the total alkaloid content per flask determinations under different conditions, it is clearly demonstrated that Tween treatment permeabilized the roots, but also acted as an inducer. PMID- 24177562 TI - EfficientAgrobacterium-mediated transformation and recovery of transgenic plants from pear (Pyrus communis L.). AB - An efficient and reproducible method was established for genetic transformation of one pear variety (Conference) usingAgrobacterium tumefaciens-mediated gene transfer. Wounded leaves of in vitro micropropagated plants were cocultivated with the disarmed strain EHA101 harbouring the binary vector pFAJ3000 carrying the chimaericnptII andgus genes. The protocol included a 3-6 month dark period on a regeneration medium solidified with gelrite, which contained 100 mg/l kanamycin. Up to 42% of inoculated leaves produced transformed buds or bud clusters. Expression, presence and integration of transgenes was confirmed by a histochemical test, polymerase chain reaction and Southern blot hybridisation, respectively. The transgenec plants could be successfully acclimatized in the glasshouse. This transformation procedure was also successfully applied to two other pear varieties, namely Doyenne du Cornice and Passe-Crassane, albeit at much lower transformation rates. PMID- 24177563 TI - Micropropagation ofBauhinia vahlii Wight & Arnott - a leguminous liana. AB - Anin vitro propagation protocol for a leguminous liana,Bauhinia vahlii, has been established. In the first experiment, cotyledonary nodes fromin-vitro-germinated seedlings were cultured on various basic media (Murashige and Skoog medium, Woody Plant medium, B5, and 1/2 Murashige and Skoog medium) containing 1.0MUM thidiazuron. Shoot proliferation (96.20%) and multiplication (5.55 shoots/explant) was best when cultured on Murashige and Skoog medium. The second experiment compared responses to benzylaminopurine, kinetin, zeatin and thidiazuron. Murashige and Skoog medium supplemented with 1.0MUM thidiazuron proved most effective for both shoot proliferation and shoot multiplication. The effect of cytokinin type and concentration and their interaction was found to be significant (P<0.001) for explant proliferation, shoot number and length. Subsequent rooting (55.14%) of the regenerated shoots was achieved on half strength Murashige and Skoog medium supplemented with IMUM 1- naphthaleneacetic acid. Successful transfer of regenerants to soil has been accomplished, and efforts are being made to gradually transfer them to field conditions. PMID- 24177564 TI - Synthesis of inosine 6-phosphate diesters via phosphitylation of the carbonyl oxygen. AB - Inosine derivatives bearing a phosphodiester group at the O(6)-position of the nucleobase were synthesized via phosphitylation of the carbonyl oxygen using phosphoramidites activated by non-nucleophilic acidic activators. PMID- 24177565 TI - Protective roles of Gadd45 and MDM2 in blueberry anthocyanins mediated DNA repair of fragmented and non-fragmented DNA damage in UV-irradiated HepG2 cells. AB - Growth Arrest and DNA Damage-inducible 45 (Gadd45) and MDM2 proteins, together with p21 and p53, play important roles in cell cycle checkpoints, DNA repair, and genome integrity maintenance. Gadd45 and MDM2 were activated and transcribed instantly by UV irradiation, whereas blueberry anthocyanins (BA) decreased the gene and protein expression levels in HepG2 cells for up to 24 h, and gradually restored the UV-induced fragmented and non-fragmented DNA damage of the nucleus at a time point of 12 h. Nevertheless, UV-irradiated HepG2 cell arrests occurred mainly in the G1 phase, which indicated G1 as a checkpoint. The proteins, p21 and p53, retain cellular integrity, suppressing the oncogenic transformation by interruption of the G1 phase of the cellular cycle, giving time for repairing the damage to DNA, or apoptosis induction if the damage is too severe to be repaired, while MDM2 and Gadd45 concomitantly ensure the presence of p53 and p21. Thus, we conclude that repair, together with Gadd45 and MDM2 genes, were involved in light and dark reaction mechanisms, however, BA could interfere and assist the repair through restoration, although further studies of the complex of the gene cascades triggered and responded to in BA-assisted DNA repair are needed. PMID- 24177566 TI - Imbalance between Th17 and regulatory T-Cells in sarcoidosis. AB - Sarcoidosis is a systemic granulomatous disease, which is thought to result from an aberrant immune response. CD4+ T lymphocytes play an important role in the development of granulomas. Previously, the immunopathogenesis of sarcoidosis was focused on Th1/Th2 disturbances. The aim of this study was to evaluate the balance between newer CD4+ T lymphocytes, i.e., Treg and Th17 cells. In our studies, a decrease in Treg cells and an increase in Th17 cells were observed in the peripheral blood and BALF of sarcoidosis patients. A significant increase in the Th17/Treg cell ratio was observed in sarcoidosis patients. After treatment with prednisone, the expression of Foxp3 mRNA was elevated in the peripheral blood, and expression of (ROR)gammat mRNA showed a downward trend. These findings suggest that sarcoidosis is associated with an imbalance between Th17 and Treg cells in peripheral blood and BALF. Therefore, targeting the cytokines that affect the Th17/Treg ratio could provide a new promising therapy for pulmonary sarcoidosis. PMID- 24177567 TI - Short-chain fatty acids inhibit growth hormone and prolactin gene transcription via cAMP/PKA/CREB signaling pathway in dairy cow anterior pituitary cells. AB - Short-chain fatty acids (SCFAs) play a key role in altering carbohydrate and lipid metabolism, influence endocrine pancreas activity, and as a precursor of ruminant milk fat. However, the effect and detailed mechanisms by which SCFAs mediate bovine growth hormone (GH) and prolactin (PRL) gene transcription remain unclear. In this study, we detected the effects of SCFAs (acetate, propionate, and butyrate) on the activity of the cAMP/PKA/CREB signaling pathway, GH, PRL, and Pit-1 gene transcription in dairy cow anterior pituitary cells (DCAPCs). The results showed that SCFAs decreased intracellular cAMP levels and a subsequent reduction in PKA activity. Inhibition of PKA activity decreased CREB phosphorylation, thereby inhibiting GH and PRL gene transcription. Furthermore, PTX blocked SCFAs- inhibited cAMP/PKA/CREB signaling pathway. These data showed that the inhibition of GH and PRL gene transcription induced by SCFAs is mediated by Gi activation and that propionate is more potent than acetate and butyrate in inhibiting GH and PRL gene transcription. In conclusion, this study identifies a biochemical mechanism for the regulation of SCFAs on bovine GH and PRL gene transcription in DCAPCs, which may serve as one of the factors that regulate pituitary function in accordance with dietary intake. PMID- 24177568 TI - NF-kappaB-targeted anti-inflammatory activity of Prunella vulgaris var. lilacina in macrophages RAW 264.7. AB - Prunella vulgaris var. lilacina, a herbal medicine, has long been used in Korea for the treatment of sore throat, and to alleviate fever and accelerate wound healing. Although the therapeutic effect of P. vulgaris var. lilacina is likely associated with anti-inflammatory activity, the precise underlying mechanisms are largely unknown. Here, we sought to elucidate the possible mechanisms of the anti inflammatory activity. We have investigated the anti-inflammatory activity of the various solvent fractions (hexane, butanol, chloroform and water) from the ethanol extract of P. vulgaris var. lilacina in activated macrophages. The hexane fraction exhibited higher anti-inflammatory activities, inducing inhibition of nitric oxide and prostaglandin E2 production as well as inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-alpha mRNA expression in response to lipopolysaccharide stimulation. Moreover, the hexane fraction from P. vulgaris var. lilacina significantly inhibited the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and the nuclear translocation of the NF-kappaB p50 and p65 subunits. These results indicate that P. vulgaris var. lilacina has an anti-inflammatory capacity in vitro, suggesting that it could be a potential source of natural anti inflammatory agents. PMID- 24177569 TI - Effects of polymorphisms in pepsinogen (PEP), amylase (AMY) and trypsin (TRY) genes on food habit domestication traits in mandarin fish. AB - Mandarin fish (Siniperca chuatsi) have a peculiar feeding habit of only accepting live fish prey and refusing dead prey and artificial diets. However, previous research has shown that some individuals accept dead prey after gradual domestication. Digestive enzymes are correlated with feeding habits in fish. In the current study, SNPs in the mandarin fish genes for pepsinogen (PEP), amylase (AMY), and trypsin (TRY) were evaluated for associations with feeding habits in domesticated mandarin fish by scanning their complete genomic sequence. In total, two SNPs were found in PEP, one was found in TRY, and none were found in AMY. The D1(CTCC) and D5(TTTT) diplotypes in the PEP gene tended to show strong effects on the feeding habits of domesticated fish (p < 0.01). The results indicate that PEP may be associated with the genetic mechanism for feeding habits in mandarin fish, and the D1(CTCC) and D5(TTTT) diplotypes in the PEP gene may be useful markers for selecting mandarin fish with appropriate feeding habits for domestication. PMID- 24177570 TI - Neuroprotective effects of liraglutide for stroke model of rats. AB - The number of diabetes mellitus (DM) patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1) are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson's test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF). The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation. PMID- 24177572 TI - Copper-indium-selenide quantum dot-sensitized solar cells. AB - We present a new synthetic process of near infrared (NIR)-absorbing copper-indium selenide (CISe) quantum dots (QDs) and their applications to efficient and completely heavy-metal-free QD-sensitized solar cells (QDSCs). Lewis acid-base reaction of metal iodides and selenocarbamate enabled us to produce chalcopyrite structured CISe QDs with controlled sizes and compositions. Furthermore, gram scale production of CISe QDs was achieved with a high reaction yield of ~73%, which is important for the commercialization of low-cost photovoltaic (PV) devices. By changing the size and composition, electronic band alignment of CISe QDs could be finely tuned to optimize the energetics of the effective light absorption and injection of electrons into the TiO2 conduction band (CB). These energy-band-engineered QDs were applied to QDSCs, and the quantum-confinement effect on the PV performances was clearly demonstrated. Our best cell yielded a conversion efficiency of 4.30% under AM1.5G one sun illumination, which is comparable to the performance of the best solar cells based on toxic lead chalcogenide or cadmium chalcogenide QDs. PMID- 24177573 TI - Probing water micro-solvation in proteins by water catalysed proton-transfer tautomerism. AB - Scientists have made tremendous efforts to gain understanding of the water molecules in proteins via indirect measurements such as molecular dynamic simulation and/or probing the polarity of the local environment. Here we present a tryptophan analogue that exhibits remarkable water catalysed proton-transfer properties. The resulting multiple emissions provide unique fingerprints that can be exploited for direct sensing of a site-specific water environment in a protein without disrupting its native structure. Replacing tryptophan with the newly developed tryptophan analogue we sense different water environments surrounding the five tryptophans in human thromboxane A2 synthase. This development may lead to future research to probe how water molecules affect the folding, structures and activities of proteins. PMID- 24177571 TI - Oxidative stress in diabetes: implications for vascular and other complications. AB - In recent decades, oxidative stress has become a focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence shows that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on these studies, an emerging concept is that oxidative stress is the "final common pathway" through which the risk factors for several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis; in particular, oxidative stress plays a key role in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes and its vascular complications, the leading cause of death in diabetic patients. PMID- 24177575 TI - Molecular characterization and possible biological roles of allatotropin in Rhodnius prolixus. AB - Allatotropins (ATs) are a family of neuropeptides that have been shown to stimulate the biosynthesis of juvenile hormone in certain insect species, and to have stimulatory activity on some visceral muscles. Here, we have examined the AT in Rhodnius prolixus. Molecular analysis revealed a cDNA fragment of 973 bp encoding one mature amidated AT (Rhopr-AT) with transcript levels observed in the central nervous system (CNS) and pool of fat body, trachea and associated peripheral nerves. AT-like immunoreactive neurons were found throughout the CNS and AT-like immunoreactive processes were present on some peripheral tissues. Bioassays based upon changes in hindgut and dorsal vessel contractions failed to demonstrate any myotropic effects of Rhopr-AT on these tissues; however Rhopr-AT stimulated contractions of muscles surrounding the salivary glands and secretion of saliva, as judged by the reduction in content of the cherry red saliva from the salivary glands. Serotonin stimulated an increase in peristaltic contractions of the gland though no secretion was observed. Co-application of Rhopr-AT and serotonin resulted in a more rapid secretion than either chemical alone. PMID- 24177574 TI - Evaluation of swallow function after tongue cancer treatment using real-time magnetic resonance imaging: a pilot study. AB - IMPORTANCE: Magnetic resonance imaging (MRI) has the advantage of imaging swallow function at any anatomical level without changing the position of patient, which can provide detailed information than modified barium swallow, by far the gold standard of swallow evaluation. OBJECTIVE: To investigate the use of real-time MRI in the evaluation of swallow function of patients with tongue cancer. DESIGN, SETTING, AND PARTICIPANTS: Real-time MRI experiments were performed on a Signa Excite HD 1.5-T scanner (GE Healthcare), with gradients capable of 40-mT/m (milli Tesla per meter) amplitudes and 150-mT/m/ms (mT/m per millisecond) slew rates. The sequence used was spiral fast gradient echo sequence. Four men with base of tongue or oral tongue squamous cell carcinoma and 3 age-matched healthy men with normal swallowing participated in the experiment. INTERVENTIONS: Real-time MRI of the midsagittal plane was collected during swallowing. Coronal planes between the oral tongue and base of tongue and through the middle of the larynx were collected from 1 of the patients. MAIN OUTCOMES AND MEASURES: Oral transit time, pharyngeal transit time, submental muscle length change, and the distance change between the hyoid bone and anterior boundary of the thyroid cartilage were measured frame by frame during swallowing. RESULTS: All the measurable oral transit and pharyngeal transit times of the patients with cancer were significantly longer than the ones of the healthy participants. The changes in submental muscle length and the distance between the hyoid bone and thyroid cartilage happened in concert for all 60 normal swallows; however, the pattern differed for each patient with cancer. To our knowledge, the coronal view of the tongue and larynx revealed information that has not been previously reported. CONCLUSIONS AND RELEVANCE: This study has demonstrated the potential of real-time MRI to reveal critical information beyond the capacity of traditional videofluoroscopy. Further investigation is needed to fully consider the technique, procedure, and standard scope of applying MRI to evaluate swallow function of patients with cancer in research and clinic practice. PMID- 24177576 TI - Glutamine-free condition inhibits lipopolysaccharide-induced invasion of BV2 microglial cells by suppressing of matrix metalloproteinase-9 expression. AB - Studies showing the mechanisms involved in glutamine (Gln) starvation and regulation of matrix metalloproteinase-9 (MMP-9) expression in microglia are rare, even though MMP-9 plays a crucial role in the proinflammatory microenvironment by degrading the blood-brain barrier. We investigated the effects of Gln on the expression of MMP-9 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Our findings showed that MMP-9 activity is significantly increased in response to LPS under Gln conditions. However, the Gln-free condition substantially inhibited LPS-induced MMP-9 activity and the expression of its corresponding gene. A matrigel invasion assay demonstrated that the Gln free condition attenuates LPS-induced invasion of BV2 microglial cells. In addition, our results showed that the Gln-free condition diminishes LPS-induced nuclear factor-kappa B (NF-kappaB) and activator protein (AP)-1 activity, which are transcription factors that potentially regulate the expression of the MMP-9 gene. Taken together, these data suggest that the Gln-free condition inhibits LPS induced invasion of BV2 microglial cells by suppressing MMP-9 expression, mainly via inhibition of the NF-kappaB and AP-1 pathway. PMID- 24177577 TI - Characterization and expression of cytochrome p450 cDNA (CYP9AT2) in Chironomus riparius fourth instar larvae exposed to multiple xenobiotics. AB - We identified and characterized a CYP9 family gene, CrCYP9AT2, from Chironomus riparius, an eco-toxicologically important model organism. The 1978 base pair (bp) length CrCYP9AT2 cDNA has an open reading frame of 1587 bp encoding a putative 528 amino acid protein. There was 267 bp 5' and 123 bp 3' untranslated region with a polyadenylation signal site (AATAAA). The putative heme-binding cysteine at position 471 and the typical p450 signature sequence of 463 FGIGPRNCIG-473 were also present. The CrCYP9AT2 transcript was present in all life stages with the highest expression in larvae. The modulation of CrCYP9AT2 was studied using real-time polymerase chain reaction after 24h exposure to cadmium chloride, benzo(a)pyrene; bisphenol A; nonylphenol; chlorpyrifos and ethinylestradiol. Significant up-regulation of CrCYP9AT2 gene was observed after exposure to Cd, B(a)P and CP. However, CrCYP9AT2 was significantly down-regulated after exposure to BPA, NP and EE. PMID- 24177578 TI - Exposure to the endocrine disruptor di(2-ethylhexyl)phthalate affects female reproductive features by altering pulsatile LH secretion. AB - The patterns of growth of preovulatory follicles and corpora lutea, as well as plasma concentrations of estradiol, progesterone and LH were evaluated in sheep exposed to DEHP. There were not found effects on the preovulatory follicular dynamics nor on the ovulatory efficiency between DEHP-exposed and control sheep. However, plasma estradiol concentration was significantly higher in the ewes exposed to DEHP than in the control females (P<0.001). Afterwards, DEHP-exposed ewes had significantly higher plasma progesterone concentration from Day 2 of the luteal phase (P<0.05), although there were no differences between groups in the macro- and microscopic features of the corpora lutea. Analysis of mean basal concentrations of LH showed lower values in DEHP-exposed than in control sheep (0.3 +/- 01 ng/mL vs. 0.7 +/- 0.1; P<0.05). Moreover, the frequency of LH pulses was 0.3 pulses/4 h, with amplitude of 0.6 ng/mL, in the control group; on the other hand, the pulsatile secretion of LH in the DEHP-exposed group was undetectable during the period of sampling. PMID- 24177579 TI - Effects of perchlorate on BDE-47-induced alteration thyroid hormone and gene expression of in the hypothalamus-pituitary-thyroid axis in zebrafish larvae. AB - To investigate the effects of perchlorate on thyroid hormone disturbances induced by 2,2',4',4-tetrabromodiphenyl ether (BDE-47) via thyroid hormone (TH)-mediated pathways, zebrafish embryos were exposed to a combination of BDE-47 and PER from the time of fertilisation to 14 d (dpf). The whole-body content of TH and the expression of genes and proteins related to the hypothalamic-pituitary-thyroid (HPT) axis were analysed. Co-exposure to BDE-47 and PER decreased the body weight and increased malformation rates relative to the effects of exposure to only BDE 47. Compared with the exposure to BDE-47 alone, the exposure to a combination of BDE-47 (10 MUg/L) and PER (3.5 mg/L) significantly up-regulated the expression of genes involved in TH synthesis (NIS and Nkx2.1a) and significantly down-regulated the expression of genes related to the regulation of the HPT axis (CRH and TSHbeta). The expression of TG at the gene and protein levels was significantly up-regulated, but the expression of TTR was significantly down-regulated in the co-exposures relative to BDE-47 treated alone. In addition, the larger reduction in the T4 level resulting from exposure to the mixture of BDE-47 and PER demonstrated that PER enhanced the thyroid-disruptive effects of BDE-47. These results help to elucidate the complicated chemical interactions and the molecular mechanism of action of these two TH disruptors. PMID- 24177580 TI - Hypervalent iodine-mediated oxidative cyclisation of p-hydroxy acetanilides to 1,2-dispirodienones. AB - 1,2-Dispirodienones were synthesized by hypervalent iodine-mediated phenolic oxidation of p-hydroxy acetanilides. The reaction is compatible with several substituted anilides and affords a new class of 1,2-dispirodienones that are remarkably stable under thermal or acidic conditions. PMID- 24177581 TI - A revised chromosome map of the fission yeast Schizosaccharomyces pombe. AB - The genetic map of the nuclear genome of the fission yeast Schizosaccharomyces pombe has been extended by mitotic and meiotic mapping data. A total of 158 markers are now assigned to the three linkage groups known in this organism, and 118 of them have been located on the corresponding chromosome map. Chromosome II and III each consist of one linkage group. There is some indication that the two large fragments which define chromosome I are meiotically linked, but the linkage observed is significant at the P = 0.05 level only. The length of the map is at least 1,700 map units, corresponding to an average of about 8 kilobases per map unit. The latter figure is comparable to the one obtained for intragenic recombination in the sup3 gene (Hofer et al. 1979). The basic frequency of gene conversion as measured for 21 genes varies according to a distribution of Poisson (with a modal value of 0.6% conversion per meiosis and per gene), in sharp contrast with Saccharomyces cerevisiae (Fogel et al. 1980) and Ascobolus immersus (Nicolas 1979). This may reflect the rarity of gene or region-specific rec alleles in S. pombe and may be related to the homothallism of this organism. PMID- 24177582 TI - Mapping of rRNA genes by integration of hybrid plasmids in Schizosaccharomyces pombe. AB - The major rRNA genes of the fission yeast Schizosaccharomyces pombe were mapped on chromosome III by plasmid integration. The integration vector YIp33 containing S. cerevisiae LEU2 gene was combined with the S. pombe rDNA. Since LEU2 complements S. pombe leu1 deficiency, it could be used as the genetic marker for integration. The 10.4 kb rDNA repeat contained ARS sequence, and therefore 2.4 kb and 0.7 kb subfragments not containing ARS were subcloned into YIp33 and transformed leu1 S. pombe cells to Leu(+). Genetic analyses of the transformants indicated that the integrated rDNA resides in the long arm of the shortest chromosome III, tightly linked to ade5 (1.4 cM). This result is consistent with our previous finding that the DAPI-stained smallest chromosomes were associated with the nucleolus (Umesono et al. 1983). PMID- 24177583 TI - Genetic studies of purine breakdown in the fission yeast Schizosaccharomyces pombe. AB - Purines such as hypoxanthine, xanthine, uric acid, allantoin and allantoic acid serve as sole nitrogen sources for the yeast Schizosaccharomyces pombe. A number of classes of mutants unable to use purines have been isolated and genetically analysed. Mutants in the urol gene lack uricase, all1 lack allantoinase, ala1 lack allantoicase whilst in ure1, ure2, ure3 and ure4 genes lack urease activity. Mutants in four hyp genes are unable to convert hypoxanthine to uric acid whilst mutation in xan1 results in impaired growth with xanthine. hyp5 strains are unable to convert both hypoxanthine and xanthine to uric acid. The mutations are recessive and none of the loci are linked to each other. The possible catalytic steps involved are discussed. PMID- 24177584 TI - Identification of regulatory genes of riboflavin permease and alpha-glucosidase in the yeast Pichia guilliermondii. AB - The method for a positive selection of Pichia guilliermondii yeast mutants which constitutively synthesize riboflavin (RF) permease has been developed. A genetic analysis revealed two regulatory genes of negative action (RFP80, RFP81) and one gene of positive action (RFP82); mutations in these loci determined the ability to synthesize RF permease in the medium without an inducer (alpha-glucosides). The constitutive mutants with cold-sensitive products of RFP80 and RFP81 genes were isolated. Interafelic complementation within RFP80 locus as well as restoration of the wild (inducible) phenotype in some hybrids between recessive rfp80 mutants and dominant RFP82 (c) mutants were observed. These data suggest a protein structure of products of identified regulatory loci and a direct interaction of the products of RFP80 and RFP82 genes.A meiotic segregants unable to synthesize RF permease in the inducer-containing media (genotype rfp82) were isolated by means of intragenic recombination in RFP82 locus. Epistasis hypostasis test showed that gene RFP82 acted after gene RFP80. RFP80, RFP81 and RFP82 loci are involved in regulation of biosynthesis of both RF permease and alpha-glucosidase. The model for action of RFP80 and RFP82 gene products in the expression of RF permease and alpha-glucosidase structural genes of P. gulliermondii is presented. PMID- 24177585 TI - Possible chromosomal location for the killer determinant in Torulopsis glabrata. AB - We have used cytoduction and protoplast fusion to characterise the killer trait in Torulopsis glabrata. Killer trait could not be transferred by cytoduction to a non-killer strain of T. glabrata suggesting that the determinant(s) is/are not present in the cytoplasm. Consistent with this interpretation is the observation that all fusion products, where chromosomes of both the parents are represented, are killers. Non-killer segregants could be isolated from fusion products after treatment with benlate suggesting that loss of the trait is associated with non disjunction and loss of a chromosome. PMID- 24177586 TI - Nuclear suppressors of mitochondrial chloramphenicol resistance in Baker's yeast: their use for the isolation of novel mutants. AB - Strains that are genotypically sensitive to chloramphenicol and also contain one of the nuclear suppressors of mitochondrial chloramphenicol resistance (Waxman et al. 1979) were constructed. A manganese mutagenesis on such a strain produced chloramphenicol resistant mutants, most of which resulted from mutations in nuclear genes. These mutants may be either dominant or recessive, and they probably do not code for membrane proteins. The few mitochondrial mutants fall into several classes, but all result from mutations in the 21S rRNA gene. The suppressor allele effectively prevents the appearance of the most common group of mitochondrial mutants (those that map at cap1), and thereby enhances the selection of novel mutants in the region. PMID- 24177587 TI - Ethidium bromide rejuvenation of senescent cultures of Podospora anserina : Loss of senescence-specific DNA and recovery of normal mitochondrial DNA. AB - The effect of ethidium bromide (EB) which is known to be able to "rejuvenate" senescent mycelia in Podospora anserina, has been investigated at the level of the mitochondrial DNA (mtDNA) by restriction analysis and molecular hybridization. While senescent mycelia display a very low growth ability and gross mtDNA modifications (tandem amplification of short sequences and disorganization of the mitochondrial chromosome: deletion of large sequences), the rejuvenated mycelia display a normal life span and contain a mtDNA in all respects identical to that of wild type mycelium (neither circular molecules nor amplified fragments could be detected). These results demonstrate a strict correlation between the senescent state and the presence of amplified mtDNA and suggest that EB rejuvenation could proceed by an efficient selection of intact mitochondrial chromosomes still present in senescent cultures. PMID- 24177588 TI - Biogenesis of Mitochondria: Genetic and molecular analysis of the oli2 region of mitochondrial DNA in Saccharomyces cerevisiae. AB - A genetic and molecular analysis of the oli2 region in mitochondrial DNA of Saccharomyces cerevisiae has been carried out. The oli2 gene codes for subunit 6 of the mitochondrial ATPase complex. We have isolated a series of 41 mit (-), temperature sensitive and oligomycin resistant mutants containing mutations located in the oli2 region. In addition the sequence in wild type mtDNA of 2820 nucleotides covering the oli2 gene and its flanking regions has been determined. A library of petite mutants which have various deletion end points in the oli2 region has been used to generate marker rescue data that allow the assignment of each mit (-), temperature sensitivity and oligomycin resistance mutation to one of seven uniquely ordered genetic groups. The following physical reference points allow the limits of the physical map positions of a number of the genetic groups to be established: DNA sequence data have been obtained for three of the petites so as to determine unambiguously their relevant deletion end points and the base substitution constituting the mtDNA sequence change in one oligomycin resistant mutant [oli2-23r] has been determined to lie at nucleotide +523 of the oli2 coding region. One group of mit (-) mutations (group N) are known to map within the aap1 gene that is found some 700 bases upstream of the oli2 gene, and which codes for subunit 8 of the mitochondrial ATPase complex. Mutations in the remaining six groups (A-F) map within (or very close to) the coding region of the oli2 gene. Various features of the DNA sequence in and around the oli2 gene are considered, including protein coding regions, sequence divergence in the A,T-rich spacer regions, properties of G,C-rich clusters, and potential ribosome binding sites. Consideration of the transcriptional map of this region of mtDNA suggests that an abundant 4,500 nucleotide transcript may represent the first defined example of a dicistronic messenger RNA in yeast mitochondria carrying distinct coding regions (aap1 and oli2) for two different proteins. PMID- 24177589 TI - Isolation, characterization, phosphorylation and site of synthesis of Spinacia chloroplast ribosomal proteins. AB - We have characterized the ribosomal proteins from Spinacia chloroplasts using two dimensional gel electrophoresis. The 30S and 50S subunits contain 23-25 and 36 ribosomal proteins, respectively. In contrast to prokaryotic ribosomes, chloroplast ribosomes contain at least one (and possibly two) phosphorylated ribosomal proteins. Isolated chloroplasts synthesize in the presence of ((35)S) labeled methionine and cysteine at least seven 30S and thirteen 50S ribosomal proteins which are assembled into (pre)ribosomes. This suggests that about one third of the chloroplast ribosomal proteins is encoded by the chloroplast DNA itself. The identity of several labeled proteins in the two-dimensional gel electrophoretic patterns which did not comigrate with stained chloroplast ribosomal proteins is discussed. PMID- 24177590 TI - 3D hierarchical architectures based on self-rolled-up silicon nitride membranes. AB - This study presents the superior structural versatility of strained silicon nitride (SiNx) membranes as a platform for three-dimensional (3D) hierarchical tubular architectures. The effects of compressive and tensile stressed SiNx layer thickness on the self-rolled-up tube curvature, the sacrificial layer etching anisotropy on rolling direction and chirality, and stress engineering by localized thickness control or thermal treatment, are explored systematically. Using strained SiNx membranes as an electrically insulating and optically transparent mechanical support, compact 3D hierarchical architectures involving carbon nanotube arrays and passive electronic components are demonstrated by releasing the functional structures deposited and patterned in 2D. These examples highlight the uniqueness of this platform that exploits 2D processing and self assembly to achieve highly functional 3D structures. PMID- 24177591 TI - High-energy transsyndesmotic ankle fracture dislocation--the "Logsplitter" injury. AB - OBJECTIVES: To describe and investigate the injury pattern and outcomes of high energy transsyndesmotic ankle fracture dislocations, or "Logsplitter" injuries, in which the talus is axially wedged into the tibiofibular joint. DESIGN: Prospective Cohort Study. SETTING: Level 1 trauma center. PATIENTS: Prospective evaluation of 23 high-energy transsyndesmotic ankle fracture dislocations (OTA 44 B). INTERVENTION: Operative fixation. MAIN OUTCOME MEASUREMENTS: Radiographs, clinical examination, American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Short Musculoskeletal Function Assessment. RESULTS: Fracture characteristics included 52% open fractures (all medial) and syndesmotic widening of 30.7 +/- 11.9 mm. The tibial plafond was involved in 11 (48%) of 23 injuries, with 5 (22%) Chaput, 5 (22%) posterior malleolar fragments, and 6 (26%) with articular impaction. A fibula fracture occurred in all but 1 patient, on average 64.2 +/- 40.0 mm above the distal tip. All patients had fixation of their fibular and medial malleolar fractures, 21 of 23 patients had syndesmotic screws, and 8 of 23 had tibial plafond fixation. Anatomic alignment (within <= 2 mm) was obtained in 21 (87%) of 23 injuries. Mean follow-up was 20.6 +/- 6.2 months. Sixteen (70%) of 23 patients had radiographic evidence of posttraumatic ankle arthritis. Dorsiflexion and plantarflexion at final follow-up were 6.9 +/- 9.6 and 35.6 +/- 12.1 degrees, respectively. Complications included a 17% infection and 17% nonunion rate. Average American Orthopaedic Foot and Ankle Society Ankle Hindfoot Scale score was 67.0 +/- 26.8, whereas Short Musculoskeletal Function Assessment Dysfunction index was 32.9 +/- 28.6 and Bother index 34.5 +/- 29.5. CONCLUSIONS: Transsyndesmotic ankle fracture dislocations, or "Logsplitter" injuries, represent an exceptional pattern of high-energy fractures with significant syndesmotic disruption, potential soft tissue compromise, and possible associated plafond injuries. Careful attention to radiographic findings can identify unique fracture characteristics relative to operative decision making. Outcomes are comparable to those of high-energy pilon fractures, thereby providing the treating surgeon with prognostic information. PMID- 24177592 TI - Firmicutes dominate the bacterial taxa within sugar-cane processing plants. AB - Sugar cane processing sites are characterised by high sugar/hemicellulose levels, available moisture and warm conditions, and are relatively unexplored unique microbial environments. The PhyloChip microarray was used to investigate bacterial diversity and community composition in three Australian sugar cane processing plants. These ecosystems were highly complex and dominated by four main Phyla, Firmicutes (the most dominant), followed by Proteobacteria, Bacteroidetes, and Chloroflexi. Significant variation (p < 0.05) in community structure occurred between samples collected from 'floor dump sediment', 'cooling tower water', and 'bagasse leachate'. Many bacterial Classes contributed to these differences, however most were of low numerical abundance. Separation in community composition was also linked to Classes of Firmicutes, particularly Bacillales, Lactobacillales and Clostridiales, whose dominance is likely to be linked to their physiology as 'lactic acid bacteria', capable of fermenting the sugars present. This process may help displace other bacterial taxa, providing a competitive advantage for Firmicutes bacteria. PMID- 24177594 TI - Molecular and morphological systematics of the sandfly Sergentomyia (Sintonius) clydei Sinton, 1928 and questions about its record in the Seychelles. AB - In the Phlebotomine sandflies, a few molecular studies related on the genus Sergentomyia have been published. The present study explored the genetic variability within Sergentomyia (Sintonius) clydei (Diptera, Psychodidae). The sampling included 15 populations originating from 12 countries. A morphological approach was coupled to the sequencing of two molecular markers (cytochrome b mtDNA and cacophony nuclear DNA). The most variable morphological characters resided in the cibarium of the females, especially (i) the pigment patch pattern and (ii) the number of cibarial teeth and denticles in the armature. However this morphological approach was unable to individualize any population within S. clydei. The NJ trees based on both molecular markers individualized the specimens from the Aldabra group of islands in the Seychelles. Surprisingly, cyt b variability was not compatible with the known data about the complete submersion of Aldabra occurring relatively recently some 125,000 years ago. The settlement of these islands by S. clydei from continental Africa, the Middle East or Asia, and the value of mtDNA markers are discussed. PMID- 24177593 TI - Breast cancer subtypes and previously established genetic risk factors: a bayesian approach. AB - BACKGROUND: Gene expression analyses indicate that breast cancer is a heterogeneous disease with at least five immunohistologic subtypes. Despite growing evidence that these subtypes are etiologically and prognostically distinct, few studies have investigated whether they have divergent genetic risk factors. To help fill in this gap in our understanding, we examined associations between breast cancer subtypes and previously established susceptibility loci among white and African-American women in the Carolina Breast Cancer Study. METHODS: We used Bayesian polytomous logistic regression to estimate ORs and 95% posterior intervals for the association between each of 78 single nucleotide polymorphisms (SNP) and five breast cancer subtypes. Subtypes were defined using five immunohistochemical markers: estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptors 1 and 2 (HER1/2), and cytokeratin (CK) 5/6. RESULTS: Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2-) or basal-like breast cancer (ER-, PR-, HER2-, HER1, or CK 5/6+), and one SNP (rs3104746) was associated with both. SNPs in FGFR2 were associated with luminal A, luminal B (ER/PR+, HER2+), or HER2+/ER- disease, but none were associated with basal-like disease. We also observed subtype differences in the effects of SNPs in 2q35, 4p, TLR1, MAP3K1, ESR1, CDKN2A/B, ANKRD16, and ZM1Z1. CONCLUSION AND IMPACT: We found evidence that genetic risk factors for breast cancer vary by subtype and further clarified the role of several key susceptibility genes. . PMID- 24177595 TI - Characterization of Vibrio cholerae from 1986 to 2012 in Yunnan Province, southwest China bordering Myanmar. AB - Vibrio cholerae is an important infectious pathogen causing serious human diarrhea. We analyzed 568 V. cholerae strains isolated from 1986 to 2012 in Yunnan province, southwest China bordering Myanmar. Polymerase chain reactions for detecting virulence genes, antibiotic susceptibility tests and pulse-field gel electrophoresis (PFGE) were performed. The results showed all the strains were El Tor biotype from 1986. The ctxB subunit sequence analysis for all strains have shown that cholera between 1986 and 1995 was associated with mixed infections with El Tor and El Tor variants, while infections after 1996 were all caused by El Tor variant strains. All of the strains were sensitive to aminoglycosides and quinolone antibiotics while resistant to beta-lactamase and carbapenem antibiotics increased gradually. 568 V. cholerae were divided into 218 PFGE-NotI patterns, and the isolates before 2001 and after 2011 were separated into two groups according to PFGE results. The strains isolated before 2001 were mainly referred to native cholera in Yunnan, and after 2011 were primarily referred to as imported strains from Myanmar, which showed the variation of V. cholerae in this area. The molecular characteristics of V. cholerae indicated regularity in bacterial variation and evolution in Yunnan province. PMID- 24177597 TI - One-pot rapid synthesis of core-shell structured NiO@TiO2 nanopowders and their excellent electrochemical properties as anode materials for lithium ion batteries. AB - Core-shell structured NiO@TiO2 nanopowders for application as anode materials for lithium ion batteries are prepared by one-pot flame spray pyrolysis from aqueous spray solution containing Ni and Ti components. A new formation mechanism of the core-shell structured nanopowders in the flame spray pyrolysis is proposed. Composite nanopowders are first formed by surface growth and coagulation from NiO and TiO2 vapors. A small amount of TiO2 in composite powders disturbs the crystallization of TiO2. Therefore, the TiO2 component moves out to the surface of the powders forming an amorphous shell during the formation of single crystalline NiO. The initial discharge and charge capacities of the NiO@TiO2 nanopowders at a current density of 300 mA g(-1) are 1302 and 937 mA h g(-1), respectively. The discharge capacities of the pure NiO and NiO@TiO2 nanopowders after 80 cycles are 542 and 970 mA h g(-1), respectively. The capacity retentions of the pure NiO and NiO@TiO2 nanopowders after 80 cycles measured after the first cycles are 75 and 108%, respectively. PMID- 24177596 TI - Prenatal dexamethasone augments the neurobehavioral teratology of chlorpyrifos: significance for maternal stress and preterm labor. AB - Glucocorticoids are the consensus treatment given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so human developmental coexposures to these two agents are common. This study explores how prenatal dexamethasone exposure modifies the neurobehavioral teratology of chlorpyrifos, one of the most widely used organophosphates. We administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. Dexamethasone did not alter brain chlorpyrifos concentrations, nor did either agent alone or in combination affect brain thyroxine levels. Assessments were carried out from adolescence through adulthood encompassing T-maze alternation, Figure 8 maze (locomotor activity, habituation), novelty-suppressed feeding and novel object recognition tests. For behaviors where chlorpyrifos or dexamethasone individually had small effects, the dual exposure produced larger, significant effects that reflected additivity (locomotor activity, novelty-suppressed feeding, novel object recognition). Where the individual effects were in opposite directions or were restricted to only one agent, we found enhancement of chlorpyrifos' effects by prenatal dexamethasone (habituation). Finally, for behaviors where controls displayed a normal sex difference in performance, the combined treatment either eliminated or reversed the difference (locomotor activity, novel object recognition). Combined exposure to dexamethasone and chlorpyrifos results in a worsened neurobehavioral outcome, providing a proof-of-principle that prenatal glucocorticoids can create a subpopulation with enhanced vulnerability to environmental toxicants. PMID- 24177598 TI - Biolistic transformation of elite genotypes of switchgrass (Panicum virgatum L.). AB - Transformation of elite switchgrass (Panicum virgatum L.) genotypes would facilitate the characterization of genes related to cell wall recalcitrance to saccharification. However, transformation of explants from switchgrass plants has remained difficult. Therefore, the objective of this study was to develop a biolistic transformation protocol for elite genotypes. Three switchgrass genotypes (ST1, ST2, and AL2) were previously selected for tissue culture responsiveness. One genotype, SA37, was selected for further use due to its improved formation of callus amenable to transformation. Various medium sets were compared and a previously published medium set provided cultures with >96 % embryogenic callus, and data on transient and stable gene expression of RFP were used to optimize biolistic parameters, and further validate the switchgrass (PvUbi1) promoter. SA37 proved to be the most transformable, whereas eight transgenic calli on average were recovered per bombardment of 20 calli (40 % efficiency) when using a three-day day preculture step, 0.6 M osmotic adjustment medium, 4,482 kPa rupture disks and 0.4 MUm gold particles which traveled 9 cm before hitting the target callus tissue. Regenerability was high, especially for ST2, for which it is possible to recover on average over 400 plants per half-gram callus tissue. It is now possible to routinely and efficiently engineer elite switchgrass genotypes using biolistic transformation. PMID- 24177599 TI - Stimulation of ANP by angiotensin-(1-9) via the angiotensin type 2 receptor. AB - AIMS: Angiotensin-(1-9) [Ang-(1-9)] and Ang-(1-7) are cleaved by Ang converting enzyme 2 forming Ang I and Ang II, respectively, and the truncated Angs play a role in regulating atrial natriuretic peptide (ANP) secretion. Previously, we found that Ang-(1-7) stimulates ANP secretion via the Mas receptor. However, the effect of Ang-(1-9) on ANP secretion is still unknown. The aim of the present study is to determine whether Ang-(1-9) stimulates ANP secretion and to characterize the signaling pathway involved in stimulating secretion. MAIN METHODS: We examined the effects of Ang-(1-9) on ANP secretion and atrial contractility with and without inhibitors in isolated perfused atria. KEY FINDINGS: Ang-(1-9) stimulated ANP secretion and concentration without change in atrial contractility. Ang-(1-9)-induced-ANP secretion was increased from 5% to 60% by 3 MUM Ang-(1-9) during the low-stretch state of the atrium. This stimulatory effect of Ang-(1-9) on ANP secretion was attenuated by pretreatment with an Ang II type 2 receptor (AT2R) antagonist but not by AT1R or Mas receptor antagonist. In addition, pretreatment with inhibitors of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), nitric oxide synthase (NOS) and soluble guanylyl cyclase (sGC) blocked Ang-(1-9)-induced ANP secretion. In the high stretch atrial state, Ang-(1-9)-induced ANP secretion was increased more than in the low-stretch state following addition of 1 MUM Ang-(1-9) (from 108% to 170%). In an in vivo experiment, acute infusion of Ang-(1-9) increased plasma ANP level without altering arterial blood pressure. This effect was attenuated by pretreatment with AT2R antagonist but not by Mas receptor antagonist. SIGNIFICANCE: These results suggest that Ang-(1-9) stimulates ANP secretion via the AT2R-PI3K-Akt-NO-cGMP pathway. PMID- 24177600 TI - Intra-arterial transplantation of human umbilical cord blood mononuclear cells in neonatal hypoxic-ischemic rats. AB - Based on preclinical findings, cellular therapy has become a promising therapeutic approach for neonatal hypoxia-ischemia (HI). However, before translation into the clinical setting, new and effective routes of cell delivery must be determined. Intra-arterial (IA) delivery is an attractive route of cellular administration but has never been used in neonatal HI rats. AIMS: In this study, we investigated the feasibility of IA transplantation of human umbilical cord blood (HUCB) mononuclear cells for the treatment of long-term behavior dysfunction and brain lesion after neonatal HI. MAIN METHODS: Seven-day old rats were subjected to a HI model and the animals received HUCB mononuclear cells into the left common carotid artery 24 h after HI insult. KEY FINDINGS: At 9 weeks post-HI, intra-arterially transplanted HUCB mononuclear cells significantly improved learning and long-term spatial memory impairments when evaluated by the Morris water maze paradigm. There was no effect of neonatal HI insult or IA procedure on body weight and on motor coordination and balance when evaluated by the accelerating rotarod test. Cellular transplantation by the IA route did not restore neonatal HI-induced brain damage according to stereological volume assessment. Furthermore, HUCB mononuclear cells were tracked in the injured brain and peripheral organs of HI transplanted-rats by nested polymerase chain reaction analysis at different time points. SIGNIFICANCE: Our findings contribute to the translational knowledge of cell based-therapy in neonatal HI and demonstrate for the first time that IA transplantation into rat pups is a feasible route for cellular delivery and prevents long-term cognitive deficits induced by experimental neonatal HI. PMID- 24177601 TI - Local thyroid renin-angiotensin system in experimental breast cancer. AB - An association between breast cancer and thyroid dysfunction exists although the underlying mechanisms remain to be elucidated. Numerous studies have characterized the role of thyroid hormones in controlling the synthesis and secretion of renin-angiotensin system (RAS) components, but little information is available on the putative role of the local RAS on thyroid function. AIMS: Here we analyze several soluble and membrane-bound RAS-regulating aminopeptidase activities in thyroid gland from rats with mammary tumors and the relationship with the circulating levels of thyroid stimulating hormone (TSH) and free thyroxin (fT4). MAIN METHODS: We analyze soluble and membrane-bound RAS regulating aminopeptidase activities fluorometrically using their corresponding aminoacyl-beta-naphthylamide as the substrate. KEY FINDINGS: We have found in rats with mammary tumors a concomitant change of thyroid RAS-regulating enzymes and thyroid hormone production. SIGNIFICANCE: We suggest that existence of alterations in the regulatory mechanisms mediated by the angiotensins of the local tissue RAS as a consequence of the carcinogenic process which could act alone or in combination with alterations at a higher level of regulation such as the hypothalamus-pituitary axis. PMID- 24177603 TI - Tits and tots of revising a manuscript. PMID- 24177602 TI - Liposomes as carriers of the lipid soluble antioxidant resveratrol: evaluation of amelioration of oxidative stress by additional antioxidant vitamin. AB - AIM: Resveratrol (RES) is a well-known antioxidant, yet in combination with other antioxidant vitamins, it was found to be more effective than any of these antioxidants alone. Present work aims to compare the antioxidant actions of resveratrol with and without vitamin C following delivery as liposomes tested using chemical and cellular antioxidative test systems. MAIN METHODS: Liposomes were prepared by the thin film hydration method and characterised for percent drug entrapment (PDE), Z-average mean size (nm), polydispersity index (PDI) and zeta potential. Antioxidative capacity was determined by studying the inhibition of AAPH induced luminol enhanced chemiluminescence and inhibition of ROS production in isolated blood leukocytes. Intracellular oxygen-derived radicals were measured using flow cytometry with buffy coats (BC) and human umbilical vein endothelial cells using H2DCF-DA dye. KEY FINDINGS: Particle size varied from 134.2 +/- 0.265 nm to 103.3 +/- 1.687 nm; PDI <= 0.3; zeta potential values were greater than -30 mV and PDE >= 80%. Radical scavenging effect was enhanced with liposomal systems; oxidative burst reaction in BC was inhibited by liposomal formulations, with the effect slightly enhanced in presence of vitamin C. Reduction in reactive oxygen species (ROS) production during spontaneous oxidative burst of BC and incubation of HUVECs with H2O2 further intensified the antioxidative effects of pure RES and liposomal formulations. SIGNIFICANCE: The present work clearly shows that the antioxidative effects of resveratrol loaded into liposomes are more pronounced when compared to pure resveratrol. Liposomal resveratrol is even active within the intracellular compartments as RES could effectively quench the intracellular accumulation of ROS. PMID- 24177604 TI - Toward more meaningful evaluation of contributions and journals across different specialties: introducing specialty impact factor. PMID- 24177605 TI - New insights in the pathogenesis of type 1 and type 2 lepra reaction. AB - In the current scenario of leprosy elimination, lepra reactions (LRs) remain a major persistent problem. Type 1 LR (T1LR) and type 2 LR (T2LR) are the major causes of nerve damage and permanent disabilities. The immunopathogenesis of LR have recently become an important field of research, since it may provide the relevant targets for the early detection and control of these episodes. Presently, there are no uniformly acceptable laboratory markers for LR. Genetic and serum markers in human host may predict susceptibility to reactions as well as progression of nerve damage in leprosy. Therefore, a deeper understanding of the molecular mechanisms involved in LR may provide a rational strategy for early diagnosis and prevention of the catastrophic consequences of LR. PMID- 24177606 TI - The role of vitamin D in melanogenesis with an emphasis on vitiligo. AB - Vitiligo is a common pigmentary disorder caused by the destruction of functional melanocytes. Vitamin D is an essential hormone synthesized in the skin and is responsible for skin pigmentation. Low levels of vitamin D have been observed in vitiligo patients and in patients with other autoimmune diseases. Therefore, the relationship between vitamin D and vitiligo needs to be investigated more thoroughly. We reviewed the literature to date regarding the role of vitamin D in skin pigmentation. Our review revealed that vitamin D deficiency has been identified in many conditions, including premature and dysmature birth, pigmented skin, obesity, advanced age, and malabsorption. Vitamin D increases melanogenesis and the tyrosinase content of cultured human melanocytes by its antiapoptotic effect. However, a few growth-inhibitory effects on melanocytes were also reported. Vitamin D regulates calcium and bone metabolism, controls cell proliferation and differentiation, and exerts immunoregulatory activities. Vitamin D exerts its effect via a nuclear hormone receptor for vitamin D. The topical application of vitamin D increased the number of L-3,4 dihydroxyphenylalanine-positive melanocytes. The topical application of vitamin D yields significant results when used in combination with phototherapy and ultraviolet exposure to treat vitiligo in humans. Vitamin D decreases the expression of various cytokines that cause vitiligo. In conclusion, application of vitamin D might help in preventing destruction of melanocytes thus causing vitiligo and other autoimmune disorders. The association between low vitamin D levels and the occurrence of vitiligo and other forms of autoimmunity is to be further evaluated. PMID- 24177607 TI - Acitretin in dermatology. AB - Acitretin, a synthetic retinoid has gradually replaced etretinate in today's dermatologic practice because of its more favorable pharmacokinetics. Acitretin over the past 20 years has proven useful in a number of difficult-to-treat hyperkeratotic and inflammatory dermatoses and nonmelanoma skin cancers. It is effective both as monotherapy and in combination with other drugs for hyperkeratotic disorders. It is considered to be an established second line treatment for psoriasis and exerts its effect mainly due to its antikeratinizing, antiinflammatory, and antiproliferative effect. Its antineoplastic properties make it a useful agent for cancer prophylaxis. Evidence-based efficacy, side effect profile, and approach to the use of acitretin would be discussed in this review. In addition to its approved uses, the various off label uses will also be highlighted in this section. Since its use is limited by its teratogenic potential and other adverse effects, including mucocutaneous effects and hepatotoxicity, this review would summarize the contraindications and precautions to be exercised before prescribing acitretin. PMID- 24177608 TI - Estimation of serum level of interleukin-17 and interleukin-4 in leprosy, towards more understanding of leprosy immunopathogenesis. AB - BACKGROUND: Combating Mycobacterium leprae is known to be via T-helper1 response. However, other T-helper effector cells; T-helper17 and T-helper2; play a role, particularly in the context of disease type. AIMS: We aimed to evaluate serum levels of interleukin (IL)-17 (T-helper17 cytokine) and IL-4 (T-helper2 cytokine) in untreated patients with different types of leprosy, compared to controls. METHODS: Using enzyme-linked immunosorbent assay, serum IL-17 and IL-4 levels were estimated in 43 leprotic patients and 43 controls. Patients were divided into six groups; tuberculoid, borderline cases, lepromatous, erythema nodosum leprosum (ENL), type 1 reactional leprosy, and pure neural leprosy. Patients were also categorized according to bacillary load and the presence or absence of reactions. RESULTS: Serum IL-17 was significantly lower in cases (4-61.5 pg/mL; median 19), compared to controls (26-55 pg/mL; median 36) (P < 0.001), and was significantly lower in each type of leprosy compared to controls, with the lowest level in lepromatous leprosy (4-61.5 pg/mL; median 12.5). Significantly elevated serum IL-4 was found in patients (1.31-122.4 pg/mL; median 2.31) compared to controls (1.45-5.72 pg/mL; median 2.02) (P = 0.008), with the highest level among lepromatous leprosy patients (2-87.2 pg/mL; median 28.9), and the lowest in type 1 reactional leprosy (1.4-2.5 pg/mL; median 1.87) (P = 0.006). CONCLUSION: Defective secretion of IL-17 is related to disease acquisition as well as progression toward lepromatous pole in leprosy patients. The overproduction of IL 4 in patients with lepromatous leprosy may infer their liability to develop ENL. Nevertheless, the small number of the studied population is a limitation. PMID- 24177609 TI - Prevalence and risk factors of onychomycosis in primary school children living in rural and urban areas in Central Anatolia of Turkey. AB - BACKGROUND: Onychomycosis is a world-wide public health concern in children, requiring epidemiological data for different regions for control and prevention. AIM: The aim of this study was to evaluate the predominant pathogens and risk factors for onychomycosis in school children living in Kayseri, Turkey. METHODS: This study included 8122 school children, aged 5-16 years, living in the rural and urban areas around Kayseri. Onychomycosis was clinically classified as distal and lateral subungual (DLSO), proximal subungual, superficial white, endonyx and totally dystrophic onychomycosis. Nail samples from children with clinically diagnosed onychomycosis were collected, examined by direct microscopy and inoculated for culture study. The demographic features and possible risk factors were recorded and assessed by logistic regression models. RESULTS: We clinically diagnosed onychomycosis in 152 out of 8,122 (0.18%) school children. DLSO was the most frequent clinical diagnosis (120/152, 78.9%). Culture-positive onychomycosis was detected in 27/152 (17.7%) children. The prevalence of culture-positive onychomycosis was determined as 0.33%. All culture-positive samples were only from toenails. The onychomycosis causative agents were dermatophytes in 17/27 cases (62.9%), including Trichophyton rubrum 12 (44.4%), Trichophyton mentagrophytes 1 (3.7%), Trichophyton tonsurans 1 (3.7%) and Trichophyton spp. 3 (11.1%) and yeasts in 10/27 cases (37.1%), including Candida glabrata 4 (14.8%), Candida parapsilosis 1 (3.7%), Trichosporon 2 (7.4%) and Rhodotorula 3 (11.1%). Age, father's occupation, number of siblings and rooms were statistically associated with the frequency of onychomycosis. CONCLUSIONS: Although to be prevalence of onychomycosis in school children in central Anatolia of Turkey seems very low degree, pediatric onychomycosis is a growing public health concern all over the world. Children having more siblings or unemployed fathers and children living in small house as well as older children should be examined carefully for onychomycosis. PMID- 24177610 TI - Clinical characteristics of adult-onset actinic prurigo in Asians: a case series. AB - BACKGROUND: Actinic prurigo (AP) is a chronic, pruritic skin condition caused by an abnormal reaction to sunlight. AIMS: The aim of this study is to determine the clinical characteristics of AP in patients attending the National Skin Centre, Singapore, from 1 st January 1999 to 30 th June 2008. METHODS: Cases of AP diagnosed from 1 st January 1999 to 30 th June 2008 were retrieved from the center's electronic medical records and analyzed. RESULTS: A total of 11 patients were diagnosed with AP. The mean age at diagnosis was 52 years. There were 9 (82%) Chinese and 2 (18%) Malay patients. Nine (82%) were male and 2 (18%) were female. The most commonly affected areas were the face, forearms, and hands (72%). Phototesting showed reduced minimal erythema dose (MED) to ultraviolet A (UVA) in 5 (46%) patients, both UVA and ultraviolet B (UVB) in 4 (36%) patients and UVB in 1 (9%) patient. Seven (64%) patients reported partial improvement after treatment with a combination of topical corticosteroids and sunscreens. Four (36%) patients received systemic therapy with partial response. CONCLUSION: Adult-onset AP is more common in the Asian population, with a male predominance. The face, forearms, and hands are the most commonly affected areas. The absence of mucosal involvement is also a distinguishing feature between the Asian and Caucasian population. Close to half of the patients have reduced MED to UVA on phototesting. The prognosis for AP is poor as it tends to run a chronic course with suboptimal response to treatment. PMID- 24177612 TI - Ichthyosiform sarcoidosis revisited. AB - Cutaneous manifestations of sarcoidosis are present in approximately one-third of the cases. Ichthyosiform lesion is one of the extremely rare cutaneous manifestations of sarcoidosis. It is a uncommon, but specific cutaneous manifestation of sarcoidosis that may precede or appear simultaneously with the diagnosis of systemic sarcoidosis. Approximately 20 cases of ichthyosiform sarcoidosis have been reported in the PubMed database. We report here a case of sarcoidosis with ichthyosiform skin lesions along with central nervous system (CNS) and pulmonary involvement for its rarity and interesting clinical presentation. PMID- 24177611 TI - Use of fine needle aspirate from peripheral nerves of pure-neural leprosy for cytology and PCR to confirm the diagnosis: a pilot study. AB - BACKGROUND: The diagnosis of pure neural leprosy (PNL) remained subjective because of over-dependence of clinical expertise and a lack of simple yet reliable diagnostic tool. The criteria for diagnosis, proposed by Jardim et al., are not routinely done by clinicians in developing country as it involves invasive nerve biopsy and sophisticated anti-PGL-1 detection. We conducted a study using fine needle aspiration cytology (FNAC) coupled with Ziehl Neelsen staining (ZN staining) and Multiplex-Polymerase Chain Reaction (PCR) specific for M. leprae for an objective diagnosis of pure neural leprosy (PNL), which may be simpler and yet reliable. AIM: The aim of the study is to couple FNAC with ZN staining and multiplex PCR to diagnose pure neural leprosy patients rapidly, in simpler and yet reliable way. METHODS: Thirteen patients of PNL as diagnosed by two independent consultants were included as case, and 5 patients other than PNL were taken as control in the study. Fine needle aspiration was done on the affected nerve, and aspirates were evaluated for cytology, ZN staining and multiplex-PCR. RESULTS: Out of the 13 cases where fine needle aspiration was done, M. leprae could be elicited in the nerve tissue aspirates in 5 cases (38.4%) with the help of conventional acid-fast staining and 11 cases (84.6%) with the help of multiplex PCR. On cytological examination of the aspirates, only 3 (23%) cases showed specific epithelioid cells, whereas 8 (61.5%) cases showed non-specific inflammation, and 2 (15.3%) cases had no inflammatory cells. CONCLUSION: Our study demonstrates that in the field of laboratory diagnosis of PNL cases, FNAC in combination with ZN staining for acid-fast bacilli (AFB) and Multiplex-PCR can provide a rapid and definitive diagnosis for the majority of PNL cases. FNAC is a less-invasive, outdoor-based and simpler technique than invasive nerve biopsy procedure. Thus, this study may enlighten the future path for easy and reliable diagnosis of PNL. PMID- 24177613 TI - Granulomatous cheilitis with granulomatous vulvitis: a rare association. AB - Granulomatous cheilitis and granulomatous vulvitis are rare disorders characterized by painless swelling of lips and vulva, respectively. Histopathology of both conditions show non-caseating epithelioid cell granulomas in the dermis. Both disorders have been associated with Crohn's disease rarely. Occurrence of the two conditions in the same patient is extremely infrequent. We hereby report, the association of granulomatous cheilitis with granulomatous vulvitis in a 30-year-old female. PMID- 24177614 TI - Follicular Dowling Degos disease: a rare variant of an evolving dermatosis. AB - Dowling Degos disease is a rare, reticulate pigmentary disorder with variable phenotypic expression that manifests as hyperpigmented macules and reticulate pigmentary anomaly of the flexures. Many variants of this condition and its overlap with other reticulate pigmentary disorders have been reported in the literature. We present here two cases of DDD with follicular localization, both clinically and histologically. It was associated with ichthyosis vulgaris in one case. Follicular DDD is an uncommon variant of this evolving dermatosis. Our report supports the possible role for disordered follicular keratinisation in its pathogenesis. PMID- 24177615 TI - Argyria an unrecognized cause of cutaneous pigmentation in Indian patients: a case series and review of the literature. AB - Argyria is an uncommon grey-blue pigmentation of skin and mucous membranes caused by prolonged silver exposure. The impetus behind this review is our experience with cases of generalized argyria resulting from a uniquely Indian socio-cultural practice and belief that it is under reported. Our objective is to increase the awareness for this esoteric entity through a review of the pertinent literature and to highlight clinical and histological features using our four well worked-up cases as examples. PMID- 24177616 TI - Idiopathic acquired true leukonychia: a few comments. PMID- 24177617 TI - Preliminary experience of patch testing at Srinagar, Kashmir. PMID- 24177618 TI - Syndromic management in the control of sexually transmitted infections: time for a relook. PMID- 24177619 TI - A simple and cost-effective device for mobile dermoscopy. PMID- 24177620 TI - Dermoscopic criteria for differentiating exogenous ochronosis from melasma. PMID- 24177621 TI - LEOPARD syndrome with Wolff-Parkinson-White syndrome on electrocardiography. PMID- 24177622 TI - Recurrent lymphocytic Sweet's syndrome. PMID- 24177623 TI - Functional esthetic rehabilitation of a 7-year-female patient with hereditary ectodermal dysplasia using flexible denture. PMID- 24177624 TI - Cutaneous metastasis of an advanced prostate cancer. PMID- 24177625 TI - Psoriatic plaques with leukotrichia: a novel observation. PMID- 24177626 TI - Cutaneous T-cell non Hodgkin lymphoma in a patient with idiopathic CD4+ lymphocytopenia. PMID- 24177627 TI - A case of linear immunoglobulin A disease with dapsone hypersensitivity and its management strategies. PMID- 24177628 TI - Patch testing in cutaneous adverse drug reactions: methodology, interpretation, and clinical relevance. PMID- 24177629 TI - Systemic skin whitening/lightening agents: what is the evidence? PMID- 24177630 TI - Painless dells on the cheek. PMID- 24177631 TI - Are dermatologists familiar with acronyms? PMID- 24177632 TI - Familial congenital generalized hypertrichosis. PMID- 24177633 TI - Eosinophilic panniculitis after subcutaneous administration of sodium heparin. PMID- 24177634 TI - De Sanctis-Cacchione syndrome. PMID- 24177636 TI - Editorial. PMID- 24177635 TI - Erythematous indurated plaque lesions on the breast. PMID- 24177637 TI - The effects of a cyclic polyether on the electrical properties of phospholipid bilayer membranes. AB - The cyclic polyether XXXII, a neutral, lipid soluble molecule, produces large increases in the conductance of bilayer membranes formed from a variety of lipids. The conductance increases linearly with the concentration of alkali metal cation but with the square, and at higher concentrations the cube, of the polyether concentration. This implies that two or three polyether molecules combine with a single cation to carry it across the membrane. In the presence of XXXII the bilayer is permeable solely to cations and the membrane potential is described by an equation of the Goldman-Hodgkin-Katz type. The permeability ratios determined from potential measurements are independent of salt concentration, decrease in the sequence Cs>Rb>K>NH4>Na>Li(1.0,0.25, 0.15, 0.075, 0.007, 0.0013) and are equal to the conductance ratios at low (e.g. 10(-3) M) salt concentration. At higher salt concentrations, the permeability and conductance ratios are not equal and maxima in the conductancevs. salt concentration curves are observed. Both these phenomena are postulated to be caused by the formation of relatively impermeant 1nu1 polyether cation complexes in the aqueous phase. The 1nu1 aqueous association constants deduced from bilayer measurements decrease in the sequence K>Rb>Na>NH4>Cs>Li (120, 34, 26, 19, 12, 4 liters per mole) and agree quantitatively with the literature values for the more water soluble polyether XXXI, which lacks only thet-butyl groups of XXXII. PMID- 24177638 TI - Chloride and potassium movements from frog's sartorius muscle in the presence of aromatic anions. AB - The efflux of(36)Cl and(42)K from frog's sartorius muscles equilibrated in Ringer's fluid with added KCl were measured in the absence and presence of salicylate, benzoate, and acetylsalicylate. The transmembrane potential and resistance were also measured in sartorii under similar conditions. Although the rate coefficient for loss of(42)K remained reasonably constant over extended experimental periods for untreated muscles, the rate coefficient for loss of(36)Cl fluctuated in many muscles giving rise to minima and maxima. The aromatic anions mentioned increased the efflux of chloride while having no detectable effect on the potassium efflux. The aromatic anion-stimulated chloride efflux was insensitive to alterations of external pH and was markedly reduced when nitrate replaced external chloride. No detectable changes in transmembrane potential or resistance were produced by salicylate, the most extensively studied aromatic anion. The results suggest that salicylate and the other aromatic anions stimulate an exchange diffusion mechanism for chloride. PMID- 24177639 TI - Permeability to water, dimension of surface, and structural changes during swelling in rat liver mitochondria. AB - Rates and amounts of water translocation across the mitochondrial membrane have been studied with a photometric technique. The process of water translocation can be described in terms of the diffusion equations, and the mitochondria behave as spherical bodies between 15 and 110 mosm. A permeability coefficient to water of 5.3*10(-3)cm sec(-1) has been calculated. The mitochondrial surface is about 1m(2)/g protein during incubation in 0.10M KCl, and increases to 30 m(2)/g protein during incubation in 0.005M KCl.The osmotic shrinkage of hypotonically swollen mitochondria has also been studied. Complete reversibility of hypotonic swelling occurs only after incubation of mitochondria in media below 60 to 90 mosm. The appearance of the reversibility is phenomenologically correlated with the rupture of the outer mitochondrial membrane., Below 30 mosm there is a change of the absorbance properties of the membrane. The change correlates with the complete unfolding of the cristae and is attributed to ultrastructural reorganization of the membrane following mechanical stretching. PMID- 24177640 TI - A quantitative correlation between the kinetics of solutes and water translocation in Liver Mitochondria. AB - A procedure is described for the calculation of solute fluxes in mitochondria from absorbance measurements. The procedure assumes that mitochondria behave as osmometers and that they are always at osmotic equilibrium.The rates and amounts of K(+) translocation have been calculated simultaneously, with the photometric procedure and electrometrically, during passive, K(+) efflux coupled to Ca(++) uptake and during active K(+) uptake and passive K(+) release coupled with anion translocation. Good agreement has been found between the two sets of measurements. The data are compatible with the concept that the energy-linked, ion translocation-coupled, mitochondrial swelling is osmotic in nature. It is concluded that the changes of absorbance are quantitatively related to changes in the inner volume and therefore the photometric procedure can be used to calculate, ion fluxes of osmotically active species under various circumstances. PMID- 24177642 TI - Errata. PMID- 24177641 TI - Studies on plasma membranes XVII. On the chemical composition of plasma membranes prepared from rat and mouse liver and hepatomas. AB - Plasma membranes were isolated under hypotonic conditions from rat and mouse livers and five hepatomas, i.e. one rather anaplastic rat hepatoma (and its subline) and three well-differentiated mouse hepatomas. All these membranes contained some 25% protein soluble in 0.15M NaCl. Evidence is presented that this protein is mainly, if not exclusively of nonmembranous origin. Protein/phospholipid P (P=phosphorus) ratios did not differ significantly for the various plasma membrane species except the rat-hepatoma subline, which showed a markedly lower ratio and was thus identified. Hepatoma membranes contained more P of a nonphospholipid nature than did liver membranes and to this increase contributed in all instances an increased RNA content and in some cases also an increased DNA content. The presence of DNA in these plasma membranes is artefactual, but that of RNA is more complicated. Artefactually, Ca(2+) associated RNA of low mol wt and soluble in 0.15M NaCl, and residual RNA (genuine?, in liver membranes less than 1% in respect of protein) have been demonstrated. The increase in hepatoma-membrane RNA is attributed to the ribosomal RNA of the few microsomal vesicles which are structurally connected with these plasma membranes. The sialic acid content and the percentage of neuraminidase-resistant sialic acid of hepatoma as compared with liver membranes was either similar or changed, depending on the hepatoma strain. Gelfiltration of trypsin-released peptides of liver plasma membranes showed hexosamine and hexose to be confined to the sialic acidcontaining fractions. In spite of quantitative differences among fractions, the relative contents of the three carbohydrates in the combined fractions were (about) similar to those in intact liver membranes. Similar experiments with the rat-hepatoma membranes showed a changed carbohydrate expression. PMID- 24177643 TI - Studies on plasma membranes : XVIII. lipid class composition of plasma membranes isolated from rat and mouse liver and hepatomas. AB - Plasma membranes were isolated from rat and mouse livers, one rat hepatoma (and its subline) and two mouse hepatomas, and their lipid class compositions were determined. Lipids accounted for 30 to 35% of the dry weight of the membranes of livers and mouse hepatomas, and for 45% in the case of rat hepatoma-subline. Of the total lipids of rat-liver plasma membranes, 60% consisted of phospholipids, the corresponding values for mouse-liver and rat-hepatoma plasma membranes amounting to 55% and for both mouse-hepatoma plasma membranes to about 50%. The free cholesterol and cholesteryl ester contents of all hepatoma plasma membranes were significantly increased as compared with normal. Evidence is presented that the increase of free cholesterol was not a preparative artefact. The major phospholipid classes in all plasma membranes were phosphatidyl choline, sphingomyelin, phosphatidyl ethanolamine and phosphatidyl serine. The relative proportions in each plasma membrane species could differ appreciably, the mouse- and rat-liver membranes showing the closest resemblance. Possible reasons for (a) the higher level of phosphatidyl serine as compared with published values, and (b) the wide divergencies which may be found among the phospholipid profiles of rat-liver plasma membranes reported by other authors, are presented. Cardiolipin was absent from liver plasma membranes, but some could be found in the hepatoma membranes due to mitochondrial contamination. No consistent phospholipid profile characterized hepatoma as distinct from liver plasma membranes, nor did the hepatoma data-including plasmalogens-resemble the few available data on other hepatomas. PMID- 24177644 TI - Water in biological membranes: Adsorption isotherms and circular dichroism as a function of hydration. AB - Adsorption isotherms of water on human red cell membranes have been measured and the results used to determine the Brunauer-Emmett-Teller monolayer coverage, saturation hydration, and relevant heats and entropies of hydration. The tightly bound monolayer corresponds to a complete covering of only one membrane surface and the saturation hydration is greater than values for globular proteins and phospholipids. A hysteresis loop is observed in the adsorption-desorption cycle.Circular dichroism spectra of membrane films have been measured as a function of hydration in the ultraviolet region of the spectrum. The spectra resemble those of membrane suspensions with reduced scattering. The circular dichroism did not change upon dehydration of the membrane films from 92 to 0% relative humidities, implying a stable membrane protein structure independent of both water content and lipid phase. PMID- 24177645 TI - Titration of mitochondrial buffer by accumulated anions. AB - Acidimetric titration of intact rat liver mitochondria discloses a buffer power of about 45 mEquiv per g between pH 7 and 8, the value rises to 60 mEquiv per g per pH unit after lysis using Triton X-100. The existence and properties of this buffer system have been related to mitochondrial anion accumulation. The uptake of permeant anions by mitochondria occurs to a charge-dependent extent and they are in electrochemical equilibrium with each other and the protons as in a Donnan system. Adding permeant anion causes the intramitochondrial anion content to rise towards a saturation level, the inside to outside concentration ratio falls and concomitantly the transmembrane proton gradient diminishes, making the interior less alkaline. The falling internal pH is associated with protonation of the internal buffer, thus providing a second method for measuring the buffer power, a method which also tests the arguments used in the calculations. The titration curve is constructed by relating the internal pH (deduced from the permeant anion ratio) to the total internal anion equivalents which in turn determines the ionization state of the buffer because the sum of the internal anion equivalents, including the buffer anion, equals the equivalents of internal cation. The buffer power so measured agrees with the acidimetric method applied to lysed mitochondria. The disparity between the acidimetric data from lysed and unlysed mitochondria follows theoretical predictions. PMID- 24177646 TI - Study of frog sartorius muscle acetylcholine receptor using the irreversible inhibitor TDF. AB - The response of normal and denervated frog sartorius muscles to several agonists differing in intrinsic activity was studied using the fluid electrode technique. The response to carbamylcholine could be irreversibly blocked by exposure of the muscles top-trimethylammoniumbenzenediazonium difluoroborate (TDF), but the response could be protected from blockage by agonists and antagonists indicating that both TDF and these ligands act at the acetylcholine binding site of the receptor. It is shown that specific reversible binding of the trimethylammonium group of TDF to the receptor plays little or no role in the irreversible reaction of TDF with the receptor, which accounts for the extremely low specificity of its reaction with the receptor. PMID- 24177647 TI - Orientation of the porphyrin ring in artificial chlorophyll membranes. AB - A sensitive photometric method is described by which the dichroism of lipid bilayer membranes in aqueous phase can be measured. The method is applied to black films with incorporated chlorophylla andb. With chlorophylla a relatively large dichroism is found in the Soret band and a much weaker dichroism in the red band. From the experimental data, the angles beta B and beta R between the "blue" and "red" transition moments and the membrane can be obtained. beta B and beta R are then used to calculate the angle gamma of the porphyrin ring with respect to the membrane surface. For chlorophylla and three different lipids, values of gamma between 44 and 49 degrees are found. PMID- 24177648 TI - Genes, enzymes and membrane proteins of the nitrate respiration system ofEscherichia coli. AB - A method was devised to isolate mutants carrying deletions through several genetic loci (chlD (+) andchlA (+)) which are involved in the membrane-bound nitrate respiratory complex ofEscherichia coli. Specific lambda transducing phages were used to reintroduce these genes. Comparisons of membrane fractions from these transduced strains showed five membrane proteins that are necessary for the formation of an active nitrate respiration system. Two particular bacterial genes (chlD (+) andchlA (+)) were shown to control these five membrane proteins.Three of the proteins specified bychlA (+), appear to be constitutively controlled and always present in the membrane ofE. coli irrespective of growth conditions, while the other two proteins, specified bychlD (+), appear to be induced byanaerobic growth in the presence of nitrate. PMID- 24177649 TI - The molecular organization of nerve membranes : VI. The separation of axolemma from schwann cell membranes of giant and retinal squid axons by density gradient centrifugation. AB - Plasma membranes were isolated from two types of squid nerves which have morphologically, different ratios of axolemma/Schwannlemma (A/S). These membranes were studied by means of differential and density gradient centrifugation.Thoroughly dissected giant axons were used as membrane source having low A/S ratio. Retinal fibers were used as membrane source with high A/S ratio. A similar procedure for the isolation of the plasma membranes was used for both types of squid axons.Differential centrifugation showed that at 1,500*g, the yield of membrane enzymes (Na, K-ATPase and NADH-ferricyanide oxidoreductase) from giant axon homogenates was 2 to 5 times greater than from retinal nerve homogenates, but at 105,000*g the opposite was the case, the yield from retinal axons being about two times greater. Thus, the major part of the membrane material from the retinal nerve seems to be less dense than the membrane material from giant axons.The behavior of the 105,000*g fraction from both types of fibers was studied by determining protein Na, K-ATPase, and NADH-oxidoreductase along a lineal sucrose gradient (10 to 40%; centrifuged at 40,600*g for 90 min). By any of the three measurements, retinal axons yielded a greater amount (2:1) of plasma membranes sedimenting at low sucrose concentration (16 to 25%) as compared to that observed at high sucrose concentration (35 to 38%). Giant axons, on the contrary, yielded a higher proportion of membranes (2.5:1) sedimenting at high sucrose concentrations (over 40%).The experimental data indicate that a different cellular origin can account for the behavior of nerve membranes along lineal gradient centrifugation. The membranes floating at low sucrose concentration ("light membranes") can be tentatively ascribed to the axolemma; the membranes found at high sucrose concentration ("heavy membranes") to the Schwannlemma and basement membranes.In accord with their high A/S morphological ratio, squid retinal axons yielded 5 times more light membranes (axolemma) than dissected giant axons. PMID- 24177650 TI - Opening of tight junctions in frog skin by hypertonic urea solutions. AB - The movements and distribution of lanthanum have been studied in frog skins treated on the outside with Ringer's solution to which 400MM urea had been added. Under these conditions,(140)La moved across the skin. This finding is in contrast with what is observed in control skins, which are impermeable to lanthanum. Examination with the electron-microscope of skins fixed during equilibration with outside hypertonic solutions plus lanthanum, showed penetration of the tracer from the outside into the intercellular spaces of all the inner layers of the epidermis. The occluding zonules (tight junctions) that normally prevent the inward movement of lanthanum beyond the outer border of the stratum granulosum (SG) are open. As a consequence, most intercellular spaces along the lateral cell surfaces of the SG were permeated by lanthanum throughout their extension. In skins treated with hypertonic solutions and then allowed to recover in normal Ringer's, the occluding zonules of the SG were impermeable to lanthanum, and(140)La did not move across the epidermis. These observations show that the increased skin permeability caused by outside hypertonic solutions results mainly from a reversible opening of tight junctions. PMID- 24177651 TI - Transport of ions of one kind through thin membranes : I. General and equilibrium considerations. AB - The general equation for movement of ions of one kind through planar membranes and its equilibrium solutions are reviewed. A simple procedure to obtain exact numerical solutions is presented, and results are displayed as profiles of potential, field and concentration across the membrane. Finally, useful approximations for very low and very high ionic concentrations are given, and the limits of applicability of the constant-field approximation are indicated. PMID- 24177652 TI - Electrical noise from synthetic membranes. AB - Voltage fluctuations were measured across collodion membranes acting as a constraint between two identical aqueous salt solutions, in the presence of an applied electrical potential difference. Membranes with d-c resistance between 1 and 20 MOmega cm(2) were studied, in solutions of KCl between 0.01 and 1.0 moles per liter.The steady-state d-c currents passed were between 1 and 1,000 namps/cm(2) of membrane. The noise was measured in the frequency range between 8 and 5,000 Hz. The spectral density of the noise power, in excess of that measured at equilibrium, was found to be proportional to the mean power being dissipated in the membrane, and inversely proportional to frequency. The d-c conductance of membrane, and the excess noise, are discussed in terms of the frictional interaction between the ions and the membrane. PMID- 24177653 TI - Failure of equilibrium dialysis to show selective monosaccharide binding by erythrocyte membranes. AB - Equilibrium dialysis has been reported to show stereoselective binding of the preferred sugar transport substrate,D-glucose, by NaI protein extracts of human erythrocyte membranes. However, we were unable to show any detectable differential binding ofD-glucose (as compared with the poorly transported analogue,L-sorbose) with NaI protein extracts. The basis for this decided dissonance is not clear. Extracts with nonionic detergents, various alcohols, and pyridine were also used, but the results with these were also negative. Our data indicate either that the transport sites are not thus extractable in a functional condition, or that only a very small number of binding sites (less than 100,000) are involved with the sugar translocation; and that this method cannot serve to measure the site population unless a far greater concentration of the binding material can be achieved than has so far been possible. PMID- 24177654 TI - Bi-ionic potentials across liquid anion exchanger membranes. AB - The bi-ionic potentials, B. I. P.'s, arising in cells of the type: A(+)L(-)c1| liquid anion exchanger membrane of extreme anionic selectivity| A(+)M(-)c1, are surveyed briefly but systematically. The membranes consisted of trioctyl-propyl ammonium salts dissolved ino-dichlorobenzene. As anticipated on the basis of previous theoretical and experimental work on porous membranes, the following regularities were observed. The B.I.P. arising with any pair of critical ions is essentially independent of the activity of the aqueous electrolytic solutions used, and is essentially independent of the degree of loading of the membrane with ion-exchanger compound. The B.I.P.'s are higher the farther apart the two critical anions under consideration, L(-) and M(-), are in the Hofmeister The B.I.P.'s, as shown in a series of 21 cells with seven different univalent critical ions are algebraically additive, in the sense that within the limits of the experimental error[Formula: see text] where L(-), M(-), and N(-) represent any arbitrary combination of the anions used. PMID- 24177655 TI - Different binding sites for glucose and sorbose at the erythrocyte membrane, studied by gel filtration and infrared spectroscopy. AB - Human red blood cell membranes were solubilized with sodium dodecylsulfate and incubated with various concentrations of(14)C-glucose and(14)C-sorbose. After gel filtration on Sephadex G-100, which separated lipoproteins of differing lipid content, it was observed that the radioactivity of the bound glucose coincided with the protein peak. Radioactivity of bound sorbose was found mainly before and after the protein peak. This distribution of bound sugars was confirmed by double labeling experiments in which(3)H-glucose and(14)C-sorbose were applied simultaneously. Infrared spectroscopy revealed differences between the membranes loaded with sorbose and glucose. Particularly, the band in the C-O-C and P=O region at 1,225 cm(-1) was intensified in the sorbose-loaded membranes. Compared to serum albumin, the erythrocyte membranes were found to bind 4 times as much(14)C-glucose per mg of protein. It is concluded from the results obtained by gel filtration that glucose and sorbose preferentially bind at different sites of the erythrocyte membrane. The results obtained by infrared spectroscopy correspond with this conclusion. PMID- 24177656 TI - The antagonistic effects of calcium and potassium on the time course of action of carbamylcholine at the neuromuscular junction. AB - The electrogenic action of carbamylcholine on the postjunctional membrane of muscle fibers disappears gradually over a period of several seconds even when this agent is applied by constant perfusion. This waning of drug action, termed "desensitization" by some investigators, occurs also at other cholinergic synapses. It has been found in earlier studies that increased amounts of calcium in the extracellular medium can cause the desensitization process to occur more rapidly and that potassium tends to oppose this action of calcium. In the present investigation, it is found that the relative effects of these ions can be expressed in terms of the quantity (Ca)/(K)(1.7). A simple ion-exchange mechanism is proposed in which one calcium ion or two potassium ions are able to combine with an anionic site near the cell surface. A general relation between the time course of conductance changes and the extracellular concentration of the ions is derived which appears to be consistent with the conductance measurements over a period of 60 seconds and in the range of calcium concentrations from 0.05 to 20 millimoles/liter and of potassium from 33 to 165 millimoles/liter. Further experiments are presented which suggest that the time course of conductance changes under these conditions is limited primarily by the rate of increase of the calcium concentration at the exchange site. PMID- 24177657 TI - Electrotonic spread of current in monolayer cultures of neonatal rat heart cells. AB - The passive electrical properties of neonatal rat heart cells grown in monolayer cultures were determined. Hyperpolarizing current pulses were injected through one microelectrode via an active bridge circuit. Membrane voltage displacements caused by the injected current pulses were measured at various distances from the first with a second microelectrode. Using a modified least-squares method the experimental results were fitted to a Bessel function, which is the steady-state solution of the differential equation describing the relation between membrane voltage caused by current injection and interelectrode distance in a very large and very thin plane cell. Best fit was obtained with a space constant of 360 MUm and an internal resistivity of 500 Omega cm. From these figures, specific membrane resistance was calculated to be 1,300 Omega cm(2), assuming all current to leave through the upper surface of the monolayer.The time constant of the membrane was measured from the time course of the current-induced membrane voltage displacements. From its value of 1.7 msec a membrane capacity of 1.3 MUF/cm(2) was calculated.From these results and some literature data on nexus distribution (A. W. Spira,J. Ultrastruct. Res. 34:409, 1971) specific nexus resistance was calculated to range between 0.25 and 1.25 Omega cm(2), depending on the amount of folding of the intercalated discs. The results suggest that spread of activation in monolayer cultures of heart cells by means of local circuit currents is very likely. PMID- 24177658 TI - The mechanism of action of DNP on phospholipid bilayer membranes. AB - The weak acid 2,4-dinitrophenol (DNP) acts as an uncoupler of oxidative phosphorylation in biological systems and, in consonance with the Mitchell hypothesis, also enhances the conductance of phospholipid bilayer membranes. Several models have been proposed in the literature to explain the molecular mechanism by which DNP exerts its electrical effects on the model membranes, none of which accounts for all of the data, and all of which ignore the possibility that the anion of DNP is also binding to the surface of the bilayer and modifying the charge density. Experimental evidence is presented in this report which suggests that when a bilayer membrane is formed from a neutral lipid, DNP does in fact adsorb to its surface and produce a substantial negative surface potential. When this phenomenon is taken into account, the model proposed by Lea and Croghan and by Finkelstein is capable of describing all of the effects of DNP on bilayer membranes. In this model, the permeant species is a negatively charged complex formed from the undissociated acid and its anion. PMID- 24177659 TI - Cation selectivity of the resting membrane of squid axon. AB - Permeability constant ratios among monovalent cations were studied in the resting membrane of a giant axon of a Pacific squid,Loligo opalescens, by observing the relationship between the membrane potential and the ion concentration.The average permeability ratios are: Tl, 1.8; K, 1.0; Rb, 0.72; Cs, 0.16; Na, <0.08; Li, <0.08. These permeability ratios suggest that neither valinomycin nor nonactin are adequate models for the sites producing the resting permeability in the axonal membrane.Cyclic polyetherbis(t-butyl cyclohexyl) 18-crown-6 does not increase the permeability ratioP Cs/P K except when applied at concentrations (5*10(-5) M) at which the surfactant properties of this molecule may become significant. PMID- 24177660 TI - The effects of maleic anhydride on the ionic permeability of red cells. AB - Maleic anhydride (MA) has been shown to react specifically and rapidly with amino groups of proteins; the maleyl amino groups are negatively charged and completely stable at neutral pH. Treatment of human red cells with this reagent results in a significant increase in K(+) permeability which is associated with a much smaller increase in Na(+) permeability. Opposite effects are observed on anion permeability, the SO 4 (--) and Cl(-) permeability being decreased to an approximately similar extent upon treatment with MA.Studies on the distribution of MA between membrane lipids and proteins shows that most of the membrane-bound MA is associated with membrane proteins. These results suggest that the observed effects of MA on the ion permeability of the red cell are caused by its combination with amino groups of cell membrane proteins. PMID- 24177662 TI - [Diseases of hair]. PMID- 24177663 TI - [Alopecia areata]. AB - The epidemiology of alopecia areata as well as murine models of this disease and genome-wide association studies support the concept of alopecia areata as an autoimmune disease. In addition, the genome-wide association studies have led to the identification of new potential therapeutic targets such as CTLA4; these results have already led to the initiation of clinical studies, for example, with abatacept. Currently topical and intralesional corticosteroids as well as immunotherapy with diphenylcyclopropenone are most common therapeutic approaches. PMID- 24177664 TI - [Androgenetic alopecia. Diagnosis and therapy- a current review]. AB - Androgenetic alopecia (AGA) is among the most frequent diagnoses in a hair clinic. Multiple studies prove that life quality is significantly impaired in affected individuals, independent of severity, age or gender. A thorough and standardized diagnostic approach to AGA in women, men and children is an essential step in developing a successful therapeutic concept. Treatment options range from topical and systemic medications to cosmetic products, nutricosmetics, hair transplantation and other aesthetic-corrective approaches. The physician and patient must decide together on the best suited individualized therapy, considering the expected results, practicality and compliance. Further interdisciplinary evaluation must be decided individually, as must the development of coping strategies and the decision to employ psychological support. A professional atmosphere and sensitive approach to an emotionally difficult situation help develop a trusting relationship between patient and physician, which in turn leads to greater satisfaction and compliance. The S1 guidelines for diagnosis and the S3 guidelines for treatment of AGA offer the treating physician important tools for the successful evidence-based management of patients. PMID- 24177666 TI - [Syphilis. Part 2: Laboratory diagnostics, therapy and prevention]. AB - Sexually transmitted infections and sexually transmitted diseases such as syphilis are a great problem for public health systems worldwide. Syphilis can be curatively treated with penicillin after early diagnosis, competent therapy and consistent monitoring. The fundamentals of syphilis diagnostics are direct and serological methods for pathogen detection. Prevention of syphilis includes exposition prophylaxis and in particular the routine use of condoms and the consistent education of affected persons and their sexual contacts. PMID- 24177667 TI - [New nomenclature for the vasculitides]. PMID- 24177665 TI - [Genetic hair diseases. An update]. AB - Patients suffering from hair loss or undesirable excessive hair growth are a challenge for dermatologists because the pathogenesis of most hair diseases is not well understood and therapeutic options are limited. This particularly holds true for genetic hair disorders, in which all current treatment attempts are unsuccessful. Furthermore, these diseases also pose a diagnostic challenge due to a broad range of clinical and genetic heterogeneity. However, the enormous progress in molecular biology over the past 20 years, in particular the availability of different new techniques such as whole exome and genome sequencing, has enabled us to elucidate the genetic basis of most monogenic hair disorders, given the availability of suitable index patients and families as well as adequate technical equipment and sufficient financial resources. In this review we provide an update on clinical and genetic aspects of selected monogenic and polygenic hair diseases manifesting with hypertrichosis and hypotrichosis. PMID- 24177668 TI - [Congratulations to Dr. Heinz Flegel on his 90th birthday]. PMID- 24177669 TI - Nanorings and rods interconnected by self-assembly mimicking an artificial network of neurons. AB - Molecular electronics based on structures ordered as neural networks emerges as the next evolutionary milestone in the construction of nanodevices with unprecedented applications. However, the straightforward formation of geometrically defined and interconnected nanostructures is crucial for the production of electronic circuitry nanoequivalents. Here we report on the molecularly fine-tuned self-assembly of tetrakis-Schiff base compounds into nanosized rings interconnected by unusually large nanorods providing a set of connections that mimic a biological network of neurons. The networks are produced through self-assembly resulting from the molecular conformation and noncovalent intermolecular interactions. These features can be easily generated on flat surfaces and in a polymeric matrix by casting from solution under ambient conditions. The structures can be used to guide the position of electron transporting agents such as carbon nanotubes on a surface or in a polymer matrix to create electrically conducting networks that can find direct use in constructing nanoelectronic circuits. PMID- 24177670 TI - Evidence of accelerated evolution and ectodermal-specific expression of presumptive BDS toxin cDNAs from Anemonia viridis. AB - Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging to the beta-defensin fold family and were initially described for their antihypertensive and antiviral activities. BDS-1 and BDS-2 are 43 amino acid peptides characterised by three disulfide bonds that act as neurotoxins affecting Kv3.1, Kv3.2 and Kv3.4 channel gating kinetics. In addition, BDS-1 inactivates the Nav1.7 and Nav1.3 channels. The development of a large dataset of A. viridis expressed sequence tags (ESTs) and the identification of 13 putative BDS-like cDNA sequences has attracted interest, especially as scientific and diagnostic tools. A comparison of BDS cDNA sequences showed that the untranslated regions are more conserved than the protein-coding regions. Moreover, the KA/KS ratios calculated for all pairwise comparisons showed values greater than 1, suggesting mechanisms of accelerated evolution. The structures of the BDS homologs were predicted by molecular modelling. All toxins possess similar 3D structures that consist of a triple stranded antiparallel beta-sheet and an additional small antiparallel beta-sheet located downstream of the cleavage/maturation site; however, the orientation of the triple-stranded beta-sheet appears to differ among the toxins. To characterise the spatial expression profile of the putative BDS cDNA sequences, tissue-specific cDNA libraries, enriched for BDS transcripts, were constructed. In addition, the proper amplification of ectodermal or endodermal markers ensured the tissue specificity of each library. Sequencing randomly selected clones from each library revealed ectodermal-specific expression of ten BDS transcripts, while transcripts of BDS-8, BDS-13, BDS-14 and BDS-15 failed to be retrieved, likely due to under-representation in our cDNA libraries. The calculation of the relative abundance of BDS transcripts in the cDNA libraries revealed that BDS-1, BDS-3, BDS-4, BDS-5 and BDS-6 are the most represented transcripts. PMID- 24177671 TI - Chemical diversity as a function of temperature in six northern diatom species. AB - In this study, we investigate how metabolic fingerprints are related to temperature. Six common northern temperate diatoms (Attheya longicornis, Chaetoceros socialis, Chaetoceros furcellatus, Porosira glacialis, Skeletonema marinoi, and Thalassiosira gravida) were cultivated at two different temperatures, 0.5 and 8.5 degrees C. To exclude metabolic variations due to differences in growth rates, the growth rates were kept similar by performing the experiments under light limited conditions but in exponential growth phase. Growth rates and maximum quantum yield of photosynthesis were measured and interpreted as physiological variables, and metabolic fingerprints were acquired by high-resolution mass spectrometry. The chemical diversity varied substantially between the two temperatures for the tested species, ranging from 31% similarity for C. furcellatus and P. glacialis to 81% similarity for A. longicornis. The chemical diversity was generally highest at the lowest temperature. PMID- 24177672 TI - LC-PUFA-enriched oil production by microalgae: accumulation of lipid and triacylglycerols containing n-3 LC-PUFA is triggered by nitrogen limitation and inorganic carbon availability in the marine haptophyte Pavlova lutheri. AB - In most microalgal species, triacyglycerols (TAG) contain mostly saturated and monounsaturated fatty acids, rather than PUFA, while PUFA-enriched oil is the form most desirable for dietary intake. The ability of some species to produce LC PUFA-enriched oil is currently of specific interest. In this work, we investigated the role of sodium bicarbonate availability on lipid accumulation and n-3 LC-PUFA partitioning into TAG during batch cultivation of Pavlova lutheri. Maximum growth and nitrate uptake exhibit an optimum concentration and threshold tolerance to bicarbonate addition (~9 mM) above which both parameters decreased. Nonetheless, the transient highest cellular lipid and TAG contents were obtained at 18 mM bicarbonate, immediately after combined alkaline pH stress and nitrate depletion (day nine), while oil body and TAG accumulation were highly repressed with low carbon supply (2 mM). Despite decreases in the proportions of EPA and DHA, maximum volumetric and cellular EPA and DHA contents were obtained at this stage due to accumulation of TAG containing EPA/DHA. TAG accounted for 74% of the total fatty acid per cell, containing 55% and 67% of the overall cellular EPA and DHA contents, respectively. These results clearly demonstrate that inorganic carbon availability and elevated pH represent two limiting factors for lipid and TAG accumulation, as well as n-3 LC-PUFA partitioning into TAG, under nutrient-depleted P. lutheri cultures. PMID- 24177673 TI - Cytotoxic effects of fucoidan nanoparticles against osteosarcoma. AB - In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of nanoparticle fucoidan was higher than native fucoidan. The higher bioactivity and superior bioavailability of nanoparticle fucoidan could potentially be utilized to develop novel therapies for osteosarcoma. PMID- 24177674 TI - Efficient screening of marine extracts for protease inhibitors by combining FRET based activity assays and surface plasmon resonance spectroscopy based binding assays. AB - The screening of extracts from marine organisms is a widely used strategy to discover new drug leads. A common problem in the screening process is the generation of false positive hits through unspecific effects from the complex chemical composition of the crude extracts. In this study, we explored a combination of a fluorescence resonance energy transfer (FRET) based activity assay and a surface plasmon resonance (SPR) based binding assay to avoid this problem. An aqueous extract was prepared from rest raw material of the Norwegian spring spawning herring, and further fractionated by methanol solubility and solid phase extraction. FRET based activity assays were used to determine the influence of each extract on the activity of different proteases. Several extracts showed more than 50% inhibition. The inhibition mechanisms were elucidated by SPR based competition experiments with known inhibitors. For the secreted aspartic proteases 1, 2, 3 and HIV-1 protease, the results indicated that some extracts contain inhibitors interacting specifically with the active site of the enzymes. The study shows that a combination of an activity assay and an SPR based binding assay is a powerful tool to identify potent inhibitors in marine extracts. Furthermore, the study shows that marine vertebrates offer an interesting source for new bioactive compounds, although they have rarely been explored for this purpose. PMID- 24177675 TI - Anxiolytic-like effect of a salmon phospholipopeptidic complex composed of polyunsaturated fatty acids and bioactive peptides. AB - A phospholipopeptidic complex obtained by the enzymatic hydrolysis of salmon heads in green conditions; exert anxiolytic-like effects in a time and dose dependent manner, with no affection of locomotor activity. This study focused on the physico-chemical properties of the lipidic and peptidic fractions from this natural product. The characterization of mineral composition, amino acid and fatty acids was carried out. Stability of nanoemulsions allowed us to realize a behavioral study conducted with four different tests on 80 mice. This work highlighted the dose dependent effects of the natural complex and its various fractions over a period of 14 days compared to a conventional anxiolytic. The intracellular redox status of neural cells was evaluated in order to determine the free radicals scavenging potential of these products in the central nervous system (CNS), after mice sacrifice. The complex peptidic fraction showed a strong scavenging property and similar results were found for the complex as well as its lipidic fraction. For the first time, the results of this study showed the anxiolytic-like and neuroprotective properties of a phospholipopeptidic complex extracted from salmon head. The applications on anxiety disorders might be relevant, depending on the doses, the fraction used and the chronicity of the supplementation. PMID- 24177676 TI - New diterpenoids from soft coral Sarcophyton ehrenbergi. AB - Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, in vitro tests show that compounds 1 and 2 displayed antiviral activity towards human cytomegalovirus, with EC50 of 20 and 8.0 ug/mL, respectively. PMID- 24177678 TI - Masculinities, work, and retirement among older men who experience depression. AB - The high incidence of depression among older men has been linked to numerous factors. In this qualitative descriptive study of 30 older, Canadian-based men who experienced depression, we explored the connections between participants' depression, masculinities, work, and retirement. Our analyses revealed three thematic findings. The recursive relationship between depression and work was reflected in depression impeding and emerging from paid work, whereby men's careers and work achievements were negatively impacted by depression amid assertions that unfulfilling work could also invoke depression. Lost or unrealized empires highlighted the centrality of wealth accumulation and negative impact of many participants' unfulfilled paid work aspirations. Retirement as loss and the therapeutic value of work reflected how masculine ideals influenced men to continue working to avoid the losses they associated with retirement. The findings confirm the need to support men's work-related transitions by affirming a diversity of masculine identities beyond traditional workman/breadwinner roles. PMID- 24177679 TI - Ten years on. PMID- 24177677 TI - Ultra-stable organic fluorophores for single-molecule research. AB - Fluorescence provides a mechanism for achieving contrast in biological imaging that enables investigations of molecular structure, dynamics, and function at high spatial and temporal resolution. Small-molecule organic fluorophores have proven essential for such efforts and are widely used in advanced applications such as single-molecule and super-resolution microscopy. Yet, organic fluorophores, like all fluorescent species, exhibit instabilities in their emission characteristics, including blinking and photobleaching that limit their utility and performance. Here, we review the photophysics and photochemistry of organic fluorophores as they pertain to mitigating such instabilities, with a specific focus on the development of stabilized fluorophores through derivatization. Self-healing organic fluorophores, wherein the triplet state is intramolecularly quenched by a covalently attached protective agent, exhibit markedly improved photostabilities. We discuss the potential for further enhancements towards the goal of developing "ultra-stable" fluorophores spanning the visible spectrum and how such fluorophores are likely to impact the future of single-molecule research. PMID- 24177680 TI - Diagnosis of chronic obstructive pulmonary disease earlier than current Global Initiative for Obstructive Lung Disease guidelines using a feasible spirometry parameter (maximal-mid expiratory flow/forced vital capacity). AB - Some patients suffer from clinical symptoms of chronic obstructive pulmonary disease (COPD) but their pulmonary function tests are in the normal range (at risk group). The objective of this study was to discover a practical test to distinguish these patients from non-COPD subjects. A total of 77 subjects including 40 COPD patients, 37 subjects at risk for developing COPD, and 32 control subjects were entered in this study. The accuracy of maximal-mid expiratory flow (MMEF)/forced vital capacity (FVC) for the diagnosis of COPD in at risk patients and its capability to differentiate from early COPD and normal patients were evaluated. Body plethysmography was used for measurement of lung volume as the Global Initiative for Obstructive Lung Disease standard. MMEF/FVC in the at risk group of COPD (0.73+/-0.19) was significantly lower than the normal control group (0.9+/-0.24, respectively), and also, it was significantly higher than the COPD group (0.31+/-0.17). There was significant correlation between the MMEF/FVC and amount of smoking measured by pack year (r2=0.112, p=0.005) and stages of COPD (Spearman's rho=0.82, p=0.0001). Early stage COPD (smoker subjects without spirometry derangement) can be diagnosed by MMEF/FVC. Using this tool we may be able to detect this highly preventable disease at an earlier stage. PMID- 24177681 TI - Patients admitted with an acute exacerbation of chronic obstructive pulmonary disease had positive experiences exercising from the beginning of their hospital stay: a qualitative analysis. AB - The aim of the study is to explore the experiences of inpatients with an acute exacerbation of chronic obstructive pulmonary disease, who participated in a very early exercise programme while acutely unwell. This qualitative study analysed responses from participant interviews as part of a mixed method trial whereby participants were randomly allocated into three groups: low intensity, moderate to high intensity aerobic and resistance exercises or a control group who received routine physiotherapy. Everyone allocated to the exercise groups were invited to participate in the qualitative study. Interviews were within a week post discharge and the results were analysed thematically. A total of 19 participants were interviewed and described their experience as positive and beneficial and reported an increased motivation towards exercising. These findings converged with the high levels of exercise adherence (83%) and within group improvements in walking capacity observed in both exercise groups. Participants also reported commencement of a home exercise programme after discharge but intention to participate in community pulmonary rehabilitation remained low. Participation in a very early exercise programme while acutely unwell can lead to positive attitude towards exercise. The results converge with the quantitative results that provided preliminary evidence of programme feasibility and within-group improvement in exercise tolerance. PMID- 24177682 TI - Directly measured physical activity as a predictor of hospitalizations in patients with chronic obstructive pulmonary disease. AB - Patients with clinically stable chronic obstructive pulmonary disease (COPD) are physically inactive, and this inactivity appears to be an independent predictor of hospitalizations. To explore this relationship further, we compared physical activity of COPD patients assessed in 2008 to subsequent hospitalizations and mortality. Sixty adults with a history of cigarette smoking, a diagnosis of COPD, a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <0.70, and no recent exacerbation were studied. Physical activity was measured using a triaxial accelerometerworn on the waist for seven consecutive days and the vector magnitude units (VMUs) that are the sum of movements in three planes over each minute were recorded. Those patients with mean VMU<170 (the median) were considered to be less physically active, and those with a 6-minute walk distance (6MWD) test of <350 m were considered to have lower functional exercise capacity. These two variables, along with age, gender, and a history of exacerbations in the preceding 12 months, FEV1, body mass index, and supplemental oxygen requirement, were related to subsequent all-cause and respiratory-related hospitalizations that occurred over the ensuing 53+/-2 months. The mean age was 68+/-11 years, 50% were male, and the FEV1 was 53+/-19%. All-cause and respiratory-related hospitalizations occurred in 58 and 35%, respectively. A 6MWD<350 m and VMU<170 each significantly predicted subsequent all-cause and respiratory-related hospitalizations in univariate Cox proportional hazards analyses after controlling for previous exacerbations. Both 6MWD<350 m and VMU<170 counts remained in a multivariate model predicting respiratory-related hospitalization. These results indicate that both directly measured physical activity and functional exercise capacity are important predictors of hospitalization in COPD. PMID- 24177683 TI - Impact of physiotherapy on patients with advanced lung cancer. AB - Patients with lung cancer have high mortality and high morbidity. Lung cancer related symptoms and problems such as dyspnea, fatigue, pain, and cachexia that begin in the early phase later result in poor physical functioning, psychosocial, and quality of life status. In addition, advancing age is associated with significant comorbidity. These patients may benefit from multidisciplinary therapy to reduce the perceived severity of dyspnea and fatigue and increase physical functioning and quality of life. Based on management of symptoms and problems such as dyspnea, physical inactivity, cancer-related fatigue, respiratory secretions, pain, and anxiety-depression of these patients, it is thought that physiotherapy techniques can be used on advanced lung cancer patients following a comprehensive evaluation. However, well-designed, prospective, and randomized-controlled trials are needed to prove the efficacy of physiotherapy and pulmonary rehabilitation in general for patients with advanced lung cancer. PMID- 24177684 TI - PRC1 marks the difference in plant PcG repression. AB - From mammals to plants, the Polycomb Group (PcG) machinery plays a crucial role in maintaining the repression of genes that are not required in a specific differentiation status. However, the mechanism by which PcG machinery mediates gene repression is still largely unknown in plants. Compared to animals, few PcG proteins have been identified in plants, not only because just some of these proteins are clearly conserved to their animal counterparts, but also because some PcG functions are carried out by plant-specific proteins, most of them as yet uncharacterized. For a long time, the apparent lack of Polycomb Repressive Complex (PRC)1 components in plants was interpreted according to the idea that plants, as sessile organisms, do not need a long-term repression, as they must be able to respond rapidly to environmental signals; however, some PRC1 components have been recently identified, indicating that this may not be the case. Furthermore, new data regarding the recruitment of PcG complexes and maintenance of PcG repression in plants have revealed important differences to what has been reported so far. This review highlights recent progress in plant PcG function, focusing on the role of the putative PRC1 components. PMID- 24177685 TI - Nanovesicles are secreted during pollen germination and pollen tube growth: a possible role in fertilization. PMID- 24177686 TI - The many faces of plant SWI/SNF complex. PMID- 24177687 TI - TRANSLUCENT GREEN, an ERF family transcription factor, controls water balance in Arabidopsis by activating the expression of aquaporin genes. AB - Water is the most abundant molecule in almost all living organisms. Aquaporins are channel proteins that play critical roles in controlling the water content of cells. Here, we report the identification of an AP2/EREBP family transcription factor in Arabidopsis thaliana, TRANSLUCENT GREEN (TG), whose overexpression in transgenic plants gave enhanced drought tolerance and vitrified leaves. TG protein is localized in the nucleus, binds DRE and GCC elements in vitro, and acts as a transcriptional activator in yeast cells. Microarray analysis revealed a total of 330 genes regulated by TG, among which five genes encode aquaporins. A transient expression assay showed that TG directly binds to the promoters of three aquaporin genes, such as AtTIP1;1, AtTIP2;3, and AtPIP2;2, indicating that TG directly regulates the expression of these genes. Moreover, overexpression of AtTIP1;1 resulted in vitrified phenotypes in transgenic Arabidopsis plants, similar to those observed in TG overexpression lines. Water injection into wild type leaves recapitulated the vitrified leaf phenotypes, which was reversed by cutting off the water supply from vascular bundles. Taken together, our data support that TG controls water balance in Arabidopsis through directly activating the expression of aquaporin genes. PMID- 24177688 TI - Distinct role of core promoter architecture in regulation of light-mediated responses in plant genes. AB - In the present study, we selected four distinct classes of light-regulated promoters. The light-regulated promoters can be distinctly grouped into either TATA-box-containing or TATA-less (initiator-containing) promoters. Further, using either native promoters or their swapped versions of core promoter elements, we established that TATA-box and Inr (Initiator) elements have distinct mechanisms which are involved in light-mediated regulation, and these elements are not swappable. We identified that mutations in either functional TATA-box or Inr elements lead to the formation of nucleosomal structure. The nucleotide diversity in either the TATA-box or Inr element in Arabidopsis ecotypes proposes that the nucleotide variation in core promoters can alter the gene expression. We show that motif overrepresentation in light-activated promoters encompasses different specific regulatory motifs present downstream of TSS (transcription start site), and this might serve as a key factor in regulating light promoters which are parallel with these elements. Finally, we conclude that the TATA-box or Inr element does not act in isolation, but our results clearly suggests the probable involvement of other distinct core promoter elements in concurrence with the TATA box or Inr element to impart selectivity to light-mediated transcription. PMID- 24177689 TI - Partitioning pulmonary vascular resistance using the reservoir-wave model. AB - The conventional determination of pulmonary vascular resistance does not indicate which vascular segments contribute to the total resistance of the pulmonary circulation. Using measurements of pressure and flow, the reservoir-wave model can be used to partition total pulmonary vascular resistance into arterial, microcirculation, and venous components. Changes to these resistance components are investigated during hypoxia and inhaled nitric oxide, volume loading, and positive end-expiratory pressure. The reservoir-wave model defines the pressure of a volume-related reservoir and the asymptotic pressure. The mean values of arterial and venous reservoir pressures and arterial and venous asymptotic pressures define a series of resistances between the main pulmonary artery and the pulmonary veins: the resistance of large and small arteries, the microcirculation, and veins. In 11 anaesthetized, open-chest dogs, pressure and flow were measured in the main pulmonary artery and a single pulmonary vein. Volume loading reduced each vascular resistance component, whereas positive end expiratory pressure only increased microcirculation resistance. Hypoxia increased the resistance of small arteries and veins, whereas nitric oxide only decreased small-artery resistance significantly. The reservoir-wave model provides a novel method to deconstruct total pulmonary vascular resistance. The results are consistent with the expected physiological responses of the pulmonary circulation and provide additional information regarding which segments of the pulmonary circulation react to hypoxia and nitric oxide. PMID- 24177690 TI - Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model. AB - Regular physical exercise is considered to be an integral component of cancer care strategies. However, the effect of exercise training on tumor microvascular oxygenation, hypoxia, and vascular function, all of which can affect the tumor microenvironment, remains unknown. Using an orthotopic preclinical model of prostate cancer, we tested the hypotheses that, after exercise training, in the tumor, there would be an enhanced microvascular Po2, increased number of patent vessels, and reduced hypoxia. We also investigated tumor resistance artery contractile properties. Dunning R-3327 AT-1 tumor cells (10(4)) were injected into the ventral prostate of 4-5-mo-old male Copenhagen or Nude rats, which were randomly assigned to tumor-bearing exercise trained (TB-Ex trained; n = 15; treadmill exercise for 5-7 wk) or sedentary groups (TB-Sedentary; n = 12). Phosphorescence quenching was used to measure tumor microvascular Po2, and Hoechst-33342 and EF-5 were used to measure patent vessels and tumor hypoxia, respectively. Tumor resistance artery function was assessed in vitro using the isolated microvessel technique. Compared with sedentary counterparts, tumor microvascular Po2 increased ~100% after exercise training (TB-Sedentary, 6.0 +/- 0.3 vs. TB-Ex Trained, 12.2 +/- 1.0 mmHg, P < 0.05). Exercise training did not affect the number of patent vessels but did significantly reduce tumor hypoxia in the conscious, resting condition from 39 +/- 12% of the tumor area in TB Sedentary to 4 +/- 1% in TB-Ex Trained. Exercise training did not affect vessel contractile function. These results demonstrate that after exercise training, there is a large increase in the driving force of O2 from the tumor microcirculation, which likely contributes to the considerable reduction in tumor hypoxia. These results suggest that exercise training can modulate the microenvironment of the tumor, such that a sustained reduction in tumor hypoxia occurs, which may lead to a less aggressive phenotype and improve patient prognosis. PMID- 24177691 TI - Microtrauma stimulates rat Achilles tendon healing via an early gene expression pattern similar to mechanical loading. AB - Mechanical loading increases the strength of healing tendons, but also induces small localized bleedings. Therefore, it is unclear if increased strength after loading is a response to mechanotransduction or microtrauma. We have previously found only five genes to be up-regulated 15 min after a single loading episode, of them four were transcription factors. These genes are followed by hundreds of genes after 3 h, many of them involved in inflammation. We now compared healing in mechanically unloaded tendons with or without added microtrauma induced by needling of the healing tissue. Nineteen rats received Botox into the calf muscle to reduce loading, and the Achilles tendon was transected. Ten rats were randomized to needling days 2-5. Mechanical testing on day 8 showed increased strength by 45% in the needling group. Next, another 24 rats were similarly unloaded, and 16 randomized to needling on day 5 after transection. Nineteen characteristic genes, known to be regulated by loading in this model, were analyzed by qRT-PCR. Four of these genes were regulated 15 min after needling. Three of them (Egr1, c-Fos, Rgs1) were among the five regulated genes after loading in a previous study. Sixteen of the 19 genes were regulated after 3 h, in the same way as after loading. In conclusion, needling increased strength, and there was a striking similarity between the gene expression response to needling and mechanical loading. This suggests that the response to loading in early tendon healing can, at least in part, be a response to microtrauma. PMID- 24177692 TI - A paradigm shift for local blood flow regulation. PMID- 24177694 TI - Engineering particle trajectories in microfluidic flows using particle shape. AB - Recent advances in microfluidic technologies have created a demand for techniques to control the motion of flowing microparticles. Here we consider how the shape and geometric confinement of a rigid microparticle can be tailored for 'self steering' under external flow. We find that an asymmetric particle, weakly confined in one direction and strongly confined in another, will align with the flow and focus to the channel centreline. Experimentally and theoretically, we isolate three viscous hydrodynamic mechanisms that contribute to particle dynamics. Through their combined effects, a particle is stably attracted to the channel centreline, effectively behaving as a damped oscillator. We demonstrate the use of self-steering particles for microfluidic device applications, eliminating the need for external forces or sheath flows. PMID- 24177693 TI - High inborn aerobic capacity does not protect the heart following myocardial infarction. AB - Maximal oxygen uptake (Vo2max) is a strong prognostic marker for morbidity and mortality, but the cardio-protective effect of high inborn Vo2max remains unresolved. We aimed to investigate whether rats with high inborn Vo2max yield cardio-protection after myocardial infarction (MI) compared with rats with low inborn Vo2max. Rats breed for high capacity of running (HCR) or low capacity of running (LCR) were randomized into HCR-SH (sham), HCR-MI, LCR-SH, and LCR-MI. Vo2max was lower in HCR-MI and LCR-MI compared with respective sham (P < 0.01), supported by a loss in global cardiac function, assessed by echocardiography. Fura 2-AM loaded cardiomyocyte experiments revealed that HCR-MI and LCR-MI decreased cardiomyocyte shortening (39%, and 34% reduction, respectively, both P < 0.01), lowered Ca(2+) transient amplitude (37%, P < 0.01, and 20% reduction, respectively), and reduced sarcoplasmic reticulum (SR) Ca(2+) content (both; 20%, P < 0.01) compared with respective sham. Diastolic Ca(2+) cycling was impaired in HCR-MI and LCR-MI evidenced by prolonged time to 50% Ca(2+) decay that was partly explained by the 47% (P < 0.01) and 44% (P < 0.05) decrease in SR Ca(2+)-ATPase Ca(2+) removal, respectively. SR Ca(2+) leak increased by 177% in HCR-MI (P < 0.01) and 67% in LCR-MI (P < 0.01), which was abolished by inhibition of Ca(2+)/calmodulin-dependent protein kinase II. This study demonstrates that the effect of MI in HCR rats was similar or even more pronounced on cardiac- and cardiomyocyte contractile function, as well as on Ca(2+) handling properties compared with observations in LCR. Thus our data do not support a cardio protective effect of higher inborn aerobic capacity. PMID- 24177695 TI - The novel [4,5-e][1,3]diazepine-4,8-dione and acyclic carbamoyl imino-ureido derivatives of imidazole: synthesis, anti-viral and anti-tumor Activity evaluations. AB - In the present paper, we report on the synthesis, and in vitro antiviral and cytostatic activities of a series of novel imidazole[4,5-e][1,3]diazepine-4,8 dione (compounds 9-11) and acyclic carbamoyl imino-ureido imidazole (compounds 12 and 13) derivatives. These new type of chemical entities showed no significant activity on the broad spectrum of DNA and RNA viruses. Results of antiproliferative assays performed on a panel of selected human tumor cell lines revealed that only compounds 1 and 5 showed moderate and selective cytostatic effect against HeLa cells (IC50 = 24 and 32 uM) with no concomitant cytotoxic effects on human normal fibroblasts (BJ). Importantly, an imidazole derivative containing a pyrrolidine moiety linked via an ethylenic spacer (3) showed a selective cytostatic effect toward cervical carcinoma (HeLa) cells (IC50 = 9.5 uM) with no apparent cytotoxicity on human normal fibroblasts (BJ). This compound can be therefore considered as a potential anti-tumor lead compound for further synthetic structure optimization. PMID- 24177696 TI - A piston-rotaxane with two potential stripes: force transitions and yield stresses. AB - We examine a rod piston-rotaxane system, where the positions of several mobile rings on the axle are controlled by an external force acting on one of the rings. This allows us to access the translational entropy of the rings. For a simple rotaxane molecule with an axle that has uniform ring-axle interactions along its length, the molecule behaves like a miniature piston filled with a one dimensional ideal gas. We then examine the effect of two stripes on the axle, having different ring-axle interactions with the mobile rings, so that one section is of high energy (repulsive) for the rings and another section is of lower energy (or attractive). This kind of rotaxane can exhibit rapid changes in displacement or force, and in particular, this molecule can exhibit a yield stress in which the piston suddenly compresses under a small increase in the applied force. PMID- 24177697 TI - NMR study on small proteins from Helicobacter pylori for antibiotic target discovery: a review. AB - Due to the widespread and increasing appearance of antibiotic resistance, a new strategy is needed for developing novel antibiotics. Especially, there are no specific antibiotics for Helicobacter pylori (H. pylori). H. pylori are bacteria that live in the stomach and are related to many serious gastric problems such as peptic ulcers, chronic gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Because of its importance as a human pathogen, it's worth studying the structure and function of the proteins from H. pylori. After the sequencing of the H. pylori strain 26695 in 1997, more than 1,600 genes were identified from H. pylori. Until now, the structures of 334 proteins from H. pylori have been determined. Among them, 309 structures were determined by X-ray crystallography and 25 structures by Nuclear Magnetic Resonance (NMR), respectively. Overall, the structures of large proteins were determined by X-ray crystallography and those of small proteins by NMR. In our lab, we have studied the structural and functional characteristics of small proteins from H. pylori. In this review, 25 NMR structures of H. pylori proteins will be introduced and their structure-function relationships will be discussed. PMID- 24177698 TI - One-pot chemoenzymatic multicomponent synthesis of thiazole derivatives. AB - A novel chemoenzymatic one-pot multicomponent synthesis of thiazole derivatives was developed. A series of thiazole derivatives were synthesized with high yields up to 94% under mild enzyme-catalyzed conditions. The blank and control experiments reveal that trypsin from porcine pancreas (PPT) displayed great catalytic activity to promote this reaction and showed a wide tolerance range towards different substrate amines. This trypsin-catalyzed multicomponent conversion method provides a novel strategy to synthesize thiazole derivatives and expands the application of enzymes in organic synthesis. PMID- 24177700 TI - Polyphenolic extracts of edible flowers incorporated onto atelocollagen matrices and their effect on cell viability. AB - The phenolic extract of chives flowers (Allium schoenoprasum, Liliaceae), introduced Sage (Salvia pratensis, Lamiaceae), European elderberry (Sambucus nigra, Caprifoliaceae) and common dandelion (Taraxacum officinale, Asteraceae) were characterised by High Performance Liquid Chromatography and incorporated in different concentrations onto atelocollagen thin films. In order to assess the biological impact of these phenolic compounds on cell viability, human immortalised non-tumorigenic keratinocyte cell line was seeded on the thin films and cell proliferation was determined by using an MTT assay. In addition, their antimicrobial activity was estimated by using an agar diffusion test. Data indicated the concomitance between cell viability and concentration of polyphenols. These findings suggest that these phenolic-endowed atelocollagen films might be suitable for tissue engineering applications, on account of the combined activity of polyphenols and collagen. PMID- 24177701 TI - Xanthene and xanthone derivatives as G-quadruplex stabilizing ligands. AB - Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene derivatives, as well as a dimeric "bridged" form. ESI and FRET measurements suggest that all the studied molecules are good G-quadruplex ligands, both at telomeres and on G-quadruplex forming sequences of oncogene promoters. The dimeric compound and the three-side chain xanthone derivative have been shown to represent the best compounds emerging from the different series of ligands presented here, having also high selectivity for G-quadruplex structures with respect to duplex DNA. Molecular modeling simulations are in broad agreement with the experimental data. PMID- 24177702 TI - (Pyridyl)benzoazole ruthenium(II) and ruthenium(III) complexes: role of heteroatom and ancillary phosphine ligand in the transfer hydrogenation of ketones. AB - The synthesis and structural characterization of ruthenium complexes supported by 2-(2-pyridyl)benzoazole ligands and their evaluation as catalysts in the transfer hydrogenation of ketones are reported. Reactions of 2-(2-pyridyl)benzoimidazole (L1), 2-(2-pyridyl)benzothiazole (L2) and 2-(2-pyridyl)benzoxazole (L3) with RuCl3.3H2O produced the corresponding complexes [RuCl3(L1)] (1), [RuCl3(L2)] (2) and [RuCl3(L3)] (3), respectively. Similarly, treatment of L1-L3 with RuCl2(PPh3)2 afforded the corresponding Ru(II) complexes [RuCl2(PPh3)2(L1)] (4), [RuCl2(PPh3)2(L2)] (5) and [RuCl2(PPh3)2(L3)] (6), respectively. Solid state structures of 1 and 2 confirmed the bidentate coordination mode of L1 and L2 to ruthenium. (31)P{(1)H} NMR spectroscopy revealed coordination of two PPh3 ligands trans to each other in an octahedral environment in 4-6 as confirmed by the solid state structure of 6. Complexes 1-6 produced active catalysts in the transfer hydrogenation of ketones in 2-propanol at 82 degrees C. Ruthenium(II) complexes 4-6, containing the PPh3 ligand, exhibited higher catalytic activities than the corresponding ruthenium(III) compounds 1-3. Complexes 1 and 4 of L1 were more active than the corresponding complexes of L2 and L3. Density functional theoretical calculations showed that dipole moments of 1-6 control their catalytic activities. PMID- 24177703 TI - The patellofemoral joint: do age and gender affect skeletal maturation of the osseous morphology in children? AB - BACKGROUND: The osseous morphology of the patellofemoral joint is an independent factor that affects the biomechanics of patellofemoral instability. OBJECTIVE: The purpose of this study is to determine age- and gender-related differences in the osseous morphology of the patellofemoral joint in children during skeletal maturation. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA-compliant. We included 97 children and young adults (age range 5-22 years; 51 girls and 46 boys, mean ages 14.3 years and 13.7 years, respectively). We studied 1.5-T knee MR exams, measuring the osseous morphology of the patellofemoral joint (lateral trochlear inclination, trochlear facet asymmetry, trochlear depth, patellar height ratio, tibial tubercle-trochlear groove distance, and lateral patellofemoral angle) for each MR exam. We compared measurements to published values for patellofemoral instability. Physeal patency (open or closing/closed) was determined on MR. We assessed the associations between MR osseous measurements and gender, age and physeal patency using Wilcoxon rank sum test and least square means regression models. RESULTS: The osseous patellofemoral joint morphology measurements were all within a normal range. There were no significant correlations between MR osseous measurements and age, gender or physeal patency. CONCLUSION: During skeletal maturation, age and gender do not affect the osseous morphology or congruency of the patellofemoral joint. PMID- 24177704 TI - Intranasal foreign body mimicking a fat-containing lesion. AB - We present a 21-month-old child with a foreign body (an intranasal almond) measuring fat attenuation on CT. To the best of our knowledge, this appearance has not been previously described and can be confused with other diagnoses resulting in inappropriate or delayed treatment. PMID- 24177705 TI - Social spiders of the genus Anelosimus occur in wetter, more productive environments than non-social species. AB - Latitude, rainfall, and productivity have been shown to influence social organisation and level of sociality in arthropods on large geographic scales. Social spiders form permanent group-living societies where they cooperate in brood care, web maintenance, and foraging. Sociality has evolved independently in a number of unrelated spider genera and may reflect convergent evolutionary responses to common environmental drivers. The genus Anelosimus contains a third of approximately 25 described permanently social spider species, eight to nine species that all occur in the Americas. To test for environmental correlates of sociality in Anelosimus across the Americas, we used logistic regression to detect effects of annual rainfall, productivity, and precipitation seasonality on the relative likelihood of occurrence of social and non-social Anelosimus spiders. Our analyses show that social species tend to occur at higher annual rainfall and productivity than non-social species, supporting the hypothesised effects of these environmental variables on the geographical distribution of social species. We did not find support for the hypothesis that permanently social species occur in areas with low precipitation seasonality. High annual precipitation and, to less extent, high productivity favour the occurrence of permanently group-living Anelosimus spiders relative to subsocial and solitary species. These results are partially consistent with previous findings for the Old World spider genus Stegodyphus, where a link between high habitat productivity and sociality was also found. Unlike Anelosimus, however, Stegodyphus typically occur in dry habitats negating a general importance of high precipitation for sociality. Sociality in spiders thus seems to be strongly linked to productivity, probably reflecting the need for relatively high availability of large prey to sustain social colonies. PMID- 24177706 TI - High-sensitivity accelerometer composed of ultra-long vertically aligned barium titanate nanowire arrays. AB - A configuration that shows great promise in sensing applications is vertically aligned piezoelectric nanowire arrays that allow facile interfacing with electrical interconnects. Nano-electromechanical systems developed using piezoelectric nanowires have gained interest primarily for their potential in energy harvesting applications, because they are able to convert several different sources of mechanical energy into useful electrical power. To date, no results have demonstrated the capability to use aligned piezoelectric nanowire arrays as a highly accurate nano-electromechanical system based dynamic sensor with a wide operating bandwidth and unity coherence. Here we report the growth of vertically aligned (~45 MUm long) barium titanate nanowire arrays, realized through a two-step hydrothermal synthesis approach, and demonstrate their use as an accurate accelerometer. High sensitivity of up to 50 mV g(-1) is observed from the sensor composed of vertically aligned barium titanate nanowire arrays, thus providing performance comparable to many of the commercial accelerometer systems. PMID- 24177707 TI - New ruthenium(II) arene complexes of anthracenyl-appended diazacycloalkanes: effect of ligand intercalation and hydrophobicity on DNA and protein binding and cleavage and cytotoxicity. AB - A series of half-sandwich Ru(II) arene complexes of the type [Ru(eta(6) arene)(L)Cl](PF6) 1-4, where arene is benzene (1, 2) or p-cymene (3, 4) and L is N-methylhomopiperazine (L1) or 1-(anthracen-10-ylmethyl)-4-methylhomopiperazine (L2), has been isolated and characterized by using spectral methods. The X-ray crystal structures of 2, 3 and 4 reveal that the compounds possess a pseudo octahedral "piano-stool" structure equipped with the arene ligand as the seat and the bidentate ligand and the chloride ion as the legs of the stool. The DNA binding affinity determined using absorption spectral titrations with CT DNA and competitive DNA binding studies varies as 4 > 2 > 3 > 1, depending upon both the arene and diazacycloalkane ligands. Complexes 2 and 4 with higher DNA binding affinities show strong hypochromism (56%) and a large red-shift (2, 10; 4, 11 nm), which reveals that the anthracenyl moiety of the ligand is stacked into the DNA base pairs and that the arene ligand hydrophobicity also dictates the DNA binding affinity. In contrast, the monocationic complexes 1 and 3 are involved in electrostatic binding in the minor groove of DNA. The enhancement in viscosities of CT DNA upon binding to 2 and 4 are higher than those for 1 and 3 supporting the DNA binding modes of interaction inferred. All the complexes cleave DNA effectively even in the absence of an external agent and the cleavage ability is enhanced in the presence of an activator like H2O2. Tryptophan quenching measurements suggest that the protein binding affinity of the complexes varies as 4 > 2 > 3 > 1, which is the same as that for DNA binding and that the fluorescence quenching of BSA occurs through a static mechanism. The positive DeltaH(0) and DeltaS(0) values for BSA binding of complexes indicate that the interaction between the complexes and BSA is mainly hydrophobic in nature and the energy transfer efficiency has been analysed according to the Forster non radiative energy transfer theory. The variation in the ability of complexes to cleave BSA in the presence of H2O2, namely, 4 > 2 > 3 > 1, as revealed from SDS PAGE is consistent with their strong hydrophobic interaction with the protein. The IC50 values of 1-4 (IC50: 1, 28.1; 2, 23.1; 3, 26.2; 4, 16.8 MUM at 24 h; IC50: 1, 19.0; 2, 15.9; 3, 18.1; 4, 9.7 MUM at 48 h) obtained for MCF 7 breast cancer cells indicate that they have the potency to kill cancer cells in a time dependent manner, which is similar to cisplatin. The anticancer activity of complexes has been studied by employing various biochemical methods involving different staining agents, AO/EB and Hoechst 33258, which reveal that complexes 1 4 establish a specific mode of cell death in MCF 7 breast cancer cells. The comet assay has been employed to determine the extent of DNA fragmentation in cancer cells. PMID- 24177708 TI - Red-koji fermented red ginseng ameliorates high fat diet-induced metabolic disorders in mice. AB - Fermentation of medicinal herbs improves their pharmacological efficacy. In this study, we investigated the effects of red-koji fermented red ginseng (fRG) on high-fat diet (HFD)-mediated metabolic disorders, and those effects were compared to those of non-fermented red ginseng (RG). fRG (500, 250 or 125 mg/kg), RG (250 mg/kg), simvastatin (10 mg/kg), silymarin (100 mg/kg) and metformin (250 mg/kg) were orally administered from 1 week after initiation of HFD supply for 84 days. The diameter of adipocytes in periovarian and abdominal fat pads and the thickness of the abdominal fat were significantly decreased by fRG treatment, while HFD-mediated weight gain was partly alleviated by fRG in a dose-dependent manner. Moreover, biochemical and histomorphometrical analyses clearly indicated that fRG significantly inhibited HFD-induced metabolic disorders such as hyperglycemia, hyperlipidemia, hepatopathy and nephropathy in a dose-dependent manner. More favorable pharmacological effects on HFD-mediated metabolic disorders were also observed with fRG compared to an equal dose of RG. This finding provides direct evidence that the pharmacological activities of RG were enhanced by red-koji fermentation, and fRG could be a neutraceutical resource for the alleviation of obesity-mediated metabolic disorders. PMID- 24177709 TI - The need for evidence based nutritional guidelines for pediatric acute lymphoblastic leukemia patients: acute and long-term following treatment. AB - High survival rates for pediatric leukemia are very promising. With regard to treatment, children tend to be able to withstand a more aggressive treatment protocol than adults. The differences in both treatment modalities and outcomes between children and adults make extrapolation of adult studies to children inappropriate. The higher success is associated with a significant number of children experiencing nutrition-related adverse effects both in the short and long term after treatment. Specific treatment protocols have been shown to deplete nutrient levels, in particular antioxidants. The optimal nutrition prescription during, after and long-term following cancer treatment is unknown. This review article will provide an overview of the known physiologic processes of pediatric leukemia and how they contribute to the complexity of performing nutritional assessment in this population. It will also discuss known nutrition related consequences, both short and long term in pediatric leukemia patients. Since specific antioxidants have been shown to be depleted as a consequence of therapy, the role of oxidative stress in the pediatric leukemia population will also be explored. More pediatric studies are needed to develop evidence based therapeutic interventions for nutritional complications of leukemia and its treatment. PMID- 24177710 TI - Suzuki-Miyaura cross-coupling of bulky anthracenyl carboxylates by using pincer nickel N-heterocyclic carbene complexes: an efficient protocol to access fluorescent anthracene derivatives. AB - A series of fluorescent (hetero)-aryl substituted anthracene derivatives were readily accessible from the corresponding bulky anthracen-9-yl carboxylates via Suzuki-Miyaura cross-coupling reactions by using pincer nickel N-heterocyclic carbene complex even at the catalyst loading as low as 0.1 mol% in the presence of catalytic amounts of PCy3. PMID- 24177711 TI - Effects of an aquatic therapy approach (Halliwick-Therapy) on functional mobility in subacute stroke patients: a randomized controlled trial. AB - OBJECTIVE: To evaluate the effects of an aquatic physiotherapy method (Halliwick Therapy) upon mobility in the post-acute phase of stroke rehabilitation. DESIGN: Randomized controlled trial. SETTING: Hospital for neurological rehabilitation. PARTICIPANTS: Adult patients after first-ever stroke in post-acute inpatient rehabilitation at least two weeks after the onset of stroke (n = 30). INTERVENTIONS: In the Halliwick-Therapy group (n = 14) the treatment over a period of two weeks included 45 minutes of aquatic therapy three times per week and a conventional physiotherapeutic treatment twice a week. Subjects in the control group (n = 16) received conventional physiotherapeutic treatment over a period of two weeks five times per week. OUTCOME MEASURES: The primary outcome variable was postural stability (Berg Balance Scale). Secondary outcome variables were functional reach, functional gait ability and basic functional mobility. RESULTS: Compared to the control group, significantly more subjects in the Halliwick-Therapy group (83.3% versus 46.7%) attained significant improvement of the Berg Balance Scale (P < 0.05). Improvement of the functional gait ability was significantly higher in the Halliwick-Therapy group (mean (SD) 1.25(0.86)) than in the control group (mean (SD) 0.73 (0.70)) (P < 0.1). The mean differences of improvements in functional reach and basic functional mobility were not statistically significant between groups. CONCLUSIONS: This study indicates that Halliwick-Therapy is safe and well tolerated in stroke patients in post-acute rehabilitation and has positive effects upon some aspects of mobility. PMID- 24177712 TI - Aquatic therapy improves pain, disability, quality of life, body composition and fitness in sedentary adults with chronic low back pain. A controlled clinical trial. AB - OBJECTIVE: To determine the effects of a two-month intensive aquatic therapy programme on back pain, disability, quality of life, body composition and health related fitness in sedentary adults with chronic low back pain. DESIGN: Controlled clinical trial. SETTING: Community. SUBJECTS: Forty-nine sedentary patients with chronic low back pain. INTERVENTIONS: Patients were allocated into active group (n = 24, two months, five times/week) or waiting list, control group (n = 25) according to space on the programme. MAIN MEASURES: Outcomes variables were pain (visual analogue scale), disability (Oswestry Disability Index), quality of life (Quality Short-Form Health Survey 36), body composition (weight, body mass index, body fat percentage and skeletal muscle mass) and health-related fitness (sit-and-reach, handgrip strength, curl-up, Rockport 1-mile test). RESULTS: The active group significantly improved low back pain (-3.83 +/- 0.35 mm on the visual analogue scale ), disability (-12.7 +/- 1.3 points for the Oswestry Disability Index) and the standardized physical component (10.3 +/- 1.4 points for the Quality Short-Form Health Survey 36) of quality-of-life domains (P < 0.001), with no significant changes on the standardized mental component (P = 0.114). In relation to body composition and fitness, the active group showed significant improvements (all P-values < 0.01). The control group presented no significant change in any parameter. CONCLUSIONS: A two-month intensive aquatic therapy programme of high-frequency (five times/week) decreases levels of back pain and disability, increases quality of life, and improves body composition and health-related fitness in sedentary adults with chronic low back pain. PMID- 24177713 TI - Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. AB - Recurrent miscarriage (RM) is defined as 3 or more miscarriages before 20 weeks' pregnancy. In recent years, interest has been focused on chronic endometritis (CE), a subtle inflammation thought to be associated with RM. We aimed to evaluate the relationships between CE and RM. The records of 360 women with unexplained RM were retrospectively analyzed. Data from hysteroscopy, endometrial histology, endometrial culture, and polymerase chain reaction for chlamydia, performed before and after antibiotic treatment for CE, were analyzed. The occurrence of successful pregnancies within 1 year after treatment was also evaluated. Results showed that 208 (57.8%) women with RM showed CE at hysteroscopy; 190 (91.3%), positive at hysteroscopy, were also positive at histology, and 142 (68.3%) had positive cultures. Common bacteria were found in 110 (77.5%) patients. Mycoplasma and Ureaplasma were found in 36 (25.3%) patients and Chlamydia in 18 patients (12.7%). In 102 (71%) women, antibiogram-based antibiotic treatment normalized hysteroscopy, histology, and cultures (group 1); while in 40 (28.2%) patients, CE was still present at hysteroscopy (group 2). In 16 of the 66 patients positive at hysteroscopy, but not at cultures, the hysteroscopy becomes normal (group 3) after a Centers for Disease Control and Prevention-based therapy; while in 50 women, CE was still present (group 4). One year after treatment, group 1 showed a significantly higher number of pregnancies (78.4%) compared to group 2 (17.5%; P < .001) and group 4 (15.3%; P = .005). The CE is frequent in women with RM. Antibiotic treatment seems to be associated with an improved reproductive outcome. PMID- 24177714 TI - First-trimester combined screening is effective for the detection of unbalanced chromosomal translocations at 11 to 12 weeks of gestation. AB - The first trimester combined screening, which analyzes fetal nuchal translucency and levels of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy associated plasma protein A (PAPP-A) in maternal serum, is routinely used to detect abnormal pregnancies associated with Down syndrome and other trisomy aneuploidies. Based on the hypothesis that major chromosomal translocations could lead to similar biochemical and developmental outcomes during early embryo development, we compared these markers among pregnancies with normal, balanced, or unbalanced fetal karyotypes. Among the parents, 71 (73%) carry balanced reciprocal translocation and 26 (27%) have Robertsonian translocation. Of the 97 pregnancies tested, 39 (40%), 37 (37%), and 22 (23%) fetuses had normal karyotype, balanced chromosomal translocations, and unbalanced chromosomal translocations, respectively. Importantly, we found that pregnancies with an unbalanced translocation had significantly higher free beta-hCG multiple of the median (MoM) and larger nuchal translucency thickness than those with normal karyotype or balanced translocations. Analysis showed that the area under a receiver operating characteristic curve (AUC) is 0.716, 0.820, and 0.936 for free beta-hCG MoM, PAPP-A MoM, and fetal nuchal translucency, respectively. When these 3 independent factors were combined, the AUC reached 0.976. In addition, logistic regression showed that the most optimal model for predicting an unbalanced chromosomal translocation is a combination of PAPP-A and nuchal translucency with an AUC of 0.980. Therefore, the first trimester combined screening is not only effective in the screening of Down syndrome and other trisomy abnormalities but also has high sensitivity for the detection of unbalanced chromosomal translocations in fetuses. PMID- 24177715 TI - NCS: incorporating positioning data to quantify nucleosome stability in yeast. AB - MOTIVATION: With the spreading technique of mass sequencing, nucleosome positions and scores for their intensity have become available through several previous studies in yeast, but relatively few studies have specifically aimed to determine the score of nucleosome stability. Based on mass sequencing data, we proposed a nucleosome center score (NCS) for quantifying nucleosome stability by measuring shifts of the nucleosome center, and then mapping NCS scores to nucleosome positions in Brogaard et al.'s study. RESULTS: We demonstrated the efficiency of NCS by known preference of A/T-based tracts for nucleosome formation, and showed that central nucleosomal DNA is more sensitive to A/T-based tracts than outer regions, which corresponds to the central histone tetramer-dominated region. We also found significant flanking preference around nucleosomal DNA for A/T-based dinucleotides, suggesting that neighboring sequences could affect nucleosome stability. Finally, the difference between results of NCS and Brogaard et al.'s scores was addressed and discussed. CONTACTS: jchiang@mail.ncku.edu.tw SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 24177716 TI - pyGCluster, a novel hierarchical clustering approach. AB - SUMMARY: pyGCluster is a clustering algorithm focusing on noise injection for subsequent cluster validation. The reproducibility of a large amount of clusters obtained with agglomerative hierarchical clustering is assessed. Furthermore, a multitude of different distance-linkage combinations are evaluated. Finally, highly reproducible clusters are meta-clustered into communities. Graphical illustration of the results as node and expression maps is implemented. AVAILABILITY AND IMPLEMENTATION: pyGCluster requires Python 2.7, it is freely available at http://pyGCluster.github.io and published under MIT license. Dependencies are NumPy, SciPy and optionally fastcluster and rpy2. CONTACT: christan@fufezan.net SUPPLEMENTARY INFORMATION: Supplementary data is available at Bioinformatics online and at http://pyGCluster.github.io. PMID- 24177717 TI - Prediction and early diagnosis of complex diseases by edge-network. AB - MOTIVATION: In this article, we develop a novel edge-based network i.e. edge network, to detect early signals of diseases by identifying the corresponding edge-biomarkers with their dynamical network biomarker score from dynamical network biomarkers. Specifically, we derive an edge-network based on the second order statistics representation of gene expression profiles, which is able to accurately represent the stochastic dynamics of the original biological system (with Gaussian distribution assumption) by combining with the traditional node network, which is based only on the first-order statistics representation of the noisy data. In other words, we show that the stochastic network of a biological system can be described by the integration of its node-network and its edge network in an accurate manner. RESULTS: By applying edge-network analysis to gene expressions of healthy adults within live influenza experiment sampling at time points before the appearance of infection symptoms, we identified the edge biomarkers (80 edges with 22 densely connected genes) discovered in edge-networks corresponding to symptomatic adults, which were used to predict the subsequent outcomes of influenza infection. In particular, we not only correctly predict the final infection outcome of each individual at an early time point before his/her clinic symptom but also reveal the key molecules during the disease progression. The prediction accuracy achieves ~90% under the leave-one-out cross-validation. Furthermore, we demonstrate the superiority of our method on disease classification and predication by comparing with the conventional node biomarkers. Our edge-network analysis not only opens a new way to understand pathogenesis at a network level due to the new representation for a stochastic network, but also provides a powerful tool to make the early diagnosis of diseases. CONTACT: lnchen@sibs.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 24177718 TI - EXPANDS: expanding ploidy and allele frequency on nested subpopulations. AB - MOTIVATION: Several cancer types consist of multiple genetically and phenotypically distinct subpopulations. The underlying mechanism for this intra tumoral heterogeneity can be explained by the clonal evolution model, whereby growth advantageous mutations cause the expansion of cancer cell subclones. The recurrent phenotype of many cancers may be a consequence of these coexisting subpopulations responding unequally to therapies. Methods to computationally infer tumor evolution and subpopulation diversity are emerging and they hold the promise to improve the understanding of genetic and molecular determinants of recurrence. RESULTS: To address cellular subpopulation dynamics within human tumors, we developed a bioinformatic method, EXPANDS. It estimates the proportion of cells harboring specific mutations in a tumor. By modeling cellular frequencies as probability distributions, EXPANDS predicts mutations that accumulate in a cell before its clonal expansion. We assessed the performance of EXPANDS on one whole genome sequenced breast cancer and performed SP analyses on 118 glioblastoma multiforme samples obtained from TCGA. Our results inform about the extent of subclonal diversity in primary glioblastoma, subpopulation dynamics during recurrence and provide a set of candidate genes mutated in the most well adapted subpopulations. In summary, EXPANDS predicts tumor purity and subclonal composition from sequencing data. AVAILABILITY AND IMPLEMENTATION: EXPANDS is available for download at http://code.google.com/p/expands (matlab version--used in this manuscript) and http://cran.r-project.org/web/packages/expands (R version). PMID- 24177719 TI - The functional therapeutic chemical classification system. AB - MOTIVATION: Drug repositioning is the discovery of new indications for compounds that have already been approved and used in a clinical setting. Recently, some computational approaches have been suggested to unveil new opportunities in a systematic fashion, by taking into consideration gene expression signatures or chemical features for instance. We present here a novel method based on knowledge integration using semantic technologies, to capture the functional role of approved chemical compounds. RESULTS: In order to computationally generate repositioning hypotheses, we used the Web Ontology Language to formally define the semantics of over 20 000 terms with axioms to correctly denote various modes of action (MoA). Based on an integration of public data, we have automatically assigned over a thousand of approved drugs into these MoA categories. The resulting new resource is called the Functional Therapeutic Chemical Classification System and was further evaluated against the content of the traditional Anatomical Therapeutic Chemical Classification System. We illustrate how the new classification can be used to generate drug repurposing hypotheses, using Alzheimers disease as a use-case. AVAILABILITY: https://www.ebi.ac.uk/chembl/ftc; https://github.com/loopasam/ftc. CONTACT: croset@ebi.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 24177720 TI - MetaboNetworks, an interactive Matlab-based toolbox for creating, customizing and exploring sub-networks from KEGG. AB - SUMMARY: MetaboNetworks is a tool to create custom sub-networks in Matlab using main reaction pairs as defined by the Kyoto Encyclopaedia of Genes and Genomes and can be used to explore transgenomic interactions, for example mammalian and bacterial associations. It calculates the shortest path between a set of metabolites (e.g. biomarkers from a metabonomic study) and plots the connectivity between metabolites as links in a network graph. The resulting graph can be edited and explored interactively. Furthermore, nodes and edges in the graph are linked to the Kyoto Encyclopaedia of Genes and Genomes compound and reaction pair web pages. AVAILABILITY AND IMPLEMENTATION: MetaboNetworks is available from http://www.mathworks.com/matlabcentral/fileexchange/42684. CONTACT: jmp111@ic.ac.uk or j.nicholson@imperial.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 24177721 TI - AnchorMS: a bioinformatics tool to derive structural information from the mass spectra of cross-linked protein complexes. AB - SUMMARY: Mass spectrometry is being increasingly used in the structural elucidation of mega-Dalton protein complexes in an approach termed MS3D, referring to the application of MS to the study of macromolecular structures. This involves the identification of cross-linked residues in the constituent proteins of chemically cross-linked multi-subunit complexes. AnchorMS was developed to simplify MS3D studies by identifying cross-linked peptides in complex peptide mixtures, and to determine the specific residues involved in each cross-link. When identifying cross-linked peptide pairs (CLPP), AnchorMS implements a mathematical model to exclude false positives by using a dynamic score threshold to estimate the number of false-positive peak matches expected in an MS/MS spectrum. This model was derived from CLPPs with randomly generated sequences. AnchorMS does not require specific sample labeling or pre-treatment, and AnchorMS is especially suited for discriminating between CLPPs that differ only in the cross-linked residue pairs. AVAILABILITY: AnchorMS was coded in Python, and is available as a free web service at cbio.ufs.ac.za/AnchorMS. PMID- 24177722 TI - [Interventional sonography of the liver and kidneys]. AB - CLINICAL/METHODICAL ISSUE: Optimization of ultrasound guided interventional procedures of the liver and kidneys using new imaging methods. STANDARD RADIOLOGICAL METHODS: Punctures, biopsies, drainage, intraoperative ultrasound, fusion, embolization in correlation with ultrasound and other imaging methods. METHODICAL INNOVATIONS: Real-time-sonography, contrast-enhanced ultrasound (CEUS) and fusion for planning, monitoring and postinterventional control. PERFORMANCE: The use of CEUS enables better detection, characterization and execution of interventional procedures. Fusion facilitates detection. ACHIEVEMENTS: The CEUS procedure is superior for detection and characterization of smaller lesions in comparison to the B scan. Fusion enables the performance of difficult interventional procedures. PRACTICAL RECOMMENDATIONS: The B scan is the standard imaging method but CEUS and fusion could be helpful for smaller lesions. PMID- 24177723 TI - [Image guiding techniques and navigation for TACE, SIRT and TIPS]. AB - CLINICAL/METHODICAL ISSUE: To avoid non-targeted embolization in liver tumors, arteries important for embolization must be detected. In transarterial chemoembolization (TACE) arteries for particle embolization have to be detected and in selective internal radiotherapy (SIRT) extrahepatic arteries which must be protected from embolization have to be detected. In transjugular intrahepatic portosystemic shunt (TIPS) the problem is to achieve an exactly targeted puncture of the portal vein. STANDARD RADIOLOGICAL METHODS: In TACE and SIRT detection of the vessels is performed from various angles by digital subtraction angiography (DSA). In TIPS puncture is guided by ultrasound or performed blindly. METHODICAL INNOVATIONS: Using cone beam CT (CBCT) very small vessels in the liver can be visualized and 2D-3D back projection is able to detect the exact position of the portal vein in TIPS. ACHIEVEMENTS: The use of CBCT and 2D-3D back projection significantly enhances navigation of vessels. PRACTICAL RECOMMENDATIONS: If flat detector technique is available CBCT should be used in TACE and SIRT and 2D-3D navigation needs hardware and software updates. PMID- 24177724 TI - Functionalization of the living diatom Thalassiosira weissflogii with thiol moieties. AB - Biomineralization processes identified within diatoms have inspired the design of synthetic silica structures in vitro using alkoxysilane precursors. Here we explore the use of the machinery within the living diatom to fabricate organo silica constructs using a combination of alkoxysilane and organoalkoxysilane precursors. We report on the incorporation of thiol moieties into the diatom during frustule synthesis. Formation of valves within the parent diatom is monitored using fluorescence microscopy, and the modification of the chemical composition of the diatom is confirmed using energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy and (29)Si-nuclear magnetic resonance spectroscopy. Chemical modification is achieved without loss of the nano-scale architectural features of the frustule. Extension of this work may allow the chemistry of the diatom to be tailored during synthesis. PMID- 24177725 TI - A theoretical study on supramolecularly-caged positively charged iridium(III) 2 pyridyl azolate derivatives as blue emitters for light-emitting electrochemical cells. AB - The photophysical and optical properties of a series of charged biscyclometalated [Ir(ppy(n))2(N^N(n))](+) complexes have been investigated with density functional theory, where ppy(0) = 2-phenylpyridine; ppy(1) = 2-(2,4-difluorophenyl)pyridine; N^N = 2-(1-phenyl-1H-pyrazol-3-yl)pyridine (1a, 1b); 2-(4-phenyl-1H-imidazol-2 yl)pyridine (2a, 2b); 2-(1,4-diphenyl-1H-imidazol-2-yl)pyridine (3a, 3b); 2-(2 phenyl-2H-1,2,3-triazol-4-yl)pyridine (4a, 4b); 2-(1-phenyl-1H-1,2,4-triazol-3 yl)pyridine (5a, 5b); 2-(3-(pyridin-2-yl)-1H-1,2,4-triazol-1-yl)pyridine (6a, 6b); 2-(1H-pyrazol-1-yl)pyridine (7a, 7b), respectively. The calculated results reveal that both the difluoro-substituent and the different 2-pyridyl azolate ancillary ligands have a large influence on tuning the emission energies and quantum yields of the studied complexes. On the basis of the results reported herein, we attempt to explain the experimental observation that the complexes 7a and 7b show high quantum phosphorescence efficiency (Phi(PL)) of 23% and 20% compared with 1a with Phi(PL) of 3%. To clarify this behavior, the metal-to ligand charge transfer contributions (MLCT%), the S1-T1 splitting energy (DeltaE(S1-T1)) and the transition dipole moment (MU(S1)) upon the S0->S1 transition were calculated. Drastically small DeltaE(S1-T1) and large MLCT% for 7a (0.06 eV and 28.2%, respectively) and 7b (0.08 eV and 24.6%, respectively) compared to those for 1a (0.60 eV and 19.5%, respectively) account for their relatively high Phi(PL) observed experimentally. Besides, the remarkably small DeltaE(S1-T1), large MLCT% and similar MU(S1) for 2a (0.04 eV, 29.1% and 0.026 D, respectively) compared with those for 2b (0.56 eV, 2.3% and 0.022 D, respectively) could be interpreted by the difluoro-substituent effects. Furthermore, 2a-4a and 4b-5b are considered to have relatively better physical properties with respect to the experimentally synthesized complexes 7a, 7b and 1a. Therefore, the newly designed complexes 2a-4a and 4b-5b are expected to be highly efficient sky-blue and blue-green emitters for LEC application. PMID- 24177726 TI - A new colorimetrically-calibrated automated video-imaging protocol for day-night fish counting at the OBSEA coastal cabled observatory. AB - Field measurements of the swimming activity rhythms of fishes are scant due to the difficulty of counting individuals at a high frequency over a long period of time. Cabled observatory video monitoring allows such a sampling at a high frequency over unlimited periods of time. Unfortunately, automation for the extraction of biological information (i.e., animals' visual counts per unit of time) is still a major bottleneck. In this study, we describe a new automated video-imaging protocol for the 24-h continuous counting of fishes in colorimetrically calibrated time-lapse photographic outputs, taken by a shallow water (20 m depth) cabled video-platform, the OBSEA. The spectral reflectance value for each patch was measured between 400 to 700 nm and then converted into standard RGB, used as a reference for all subsequent calibrations. All the images were acquired within a standardized Region Of Interest (ROI), represented by a 2 * 2 m methacrylate panel, endowed with a 9-colour calibration chart, and calibrated using the recently implemented "3D Thin-Plate Spline" warping approach in order to numerically define color by its coordinates in n-dimensional space. That operation was repeated on a subset of images, 500 images as a training set, manually selected since acquired under optimum visibility conditions. All images plus those for the training set were ordered together through Principal Component Analysis allowing the selection of 614 images (67.6%) out of 908 as a total corresponding to 18 days (at 30 min frequency). The Roberts operator (used in image processing and computer vision for edge detection) was used to highlights regions of high spatial colour gradient corresponding to fishes' bodies. Time series in manual and visual counts were compared together for efficiency evaluation. Periodogram and waveform analysis outputs provided very similar results, although quantified parameters in relation to the strength of respective rhythms were different. Results indicate that automation efficiency is limited by optimum visibility conditions. Data sets from manual counting present the larger day-night fluctuations in comparison to those derived from automation. This comparison indicates that the automation protocol subestimate fish numbers but it is anyway suitable for the study of community activity rhythms. PMID- 24177727 TI - Comparison of raw acceleration from the GENEA and ActiGraphTM GT3X+ activity monitors. AB - PURPOSE: To compare raw acceleration output of the ActiGraphTM GT3X+ and GENEA activity monitors. METHODS: A GT3X+ and GENEA were oscillated in an orbital shaker at frequencies ranging from 0.7 to 4.0 Hz (ten 2-min trials/frequency) on a fixed radius of 5.08 cm. Additionally, 10 participants (age = 23.8 +/- 5.4 years) wore the GT3X+ and GENEA on the dominant wrist and performed treadmill walking (2.0 and 3.5 mph) and running (5.5 and 7.5 mph) and simulated free-living activities (computer work, cleaning a room, vacuuming and throwing a ball) for 2 min each. A linear mixed model was used to compare the mean triaxial vector magnitude (VM) from the GT3X+ and GENEA at each oscillation frequency. For the human testing protocol, random forest machine-learning technique was used to develop two models using frequency domain (FD) and time domain (TD) features for each monitor. We compared activity type recognition accuracy between the GT3X+ and GENEA when the prediction model was fit using one monitor and then applied to the other. Z-statistics were used to compare the proportion of accurate predictions from the GT3X+ and GENEA for each model. RESULTS: GENEA produced significantly higher (p < 0.05, 3.5 to 6.2%) mean VM than GT3X+ at all frequencies during shaker testing. Training the model using TD input features on the GENEA and applied to GT3X+ data yielded significantly lower (p < 0.05) prediction accuracy. Prediction accuracy was not compromised when interchangeably using FD models between monitors. CONCLUSIONS: It may be inappropriate to apply a model developed on the GENEA to predict activity type using GT3X+ data when input features are TD attributes of raw acceleration. PMID- 24177728 TI - A Pt-doped TiO2 nanotube arrays sensor for detecting SF6 decomposition products. AB - The detection of partial discharge and analysis of SF6 gas components in gas insulated switchgear (GIS) is important for the diagnosis and operating state assessment of power equipment. The use of a Pt-doped TiO2 nanotube arrays sensor for detecting sulfur hexafluoride (SF6) decomposition products is proposed in this paper. The electrochemical pulse deposition method is employed to prepare the sensor array. The sensor's response to the main characteristic gaseous decomposition products of SF6 is evaluated. The gas sensing characteristic curves of the Pt-doped TiO2 nanotube sensor and intrinsic TiO2 nanotube arrays sensor are compared. The mechanism of the sensitive response is discussed. Test results showed that the Pt-doped nanoparticles not only change the gas sensing selectivity of the TiO2 nanotube arrays sensor with respect to the main characteristic SF6 decomposition products, but also reduce the operating temperature of the sensor. PMID- 24177729 TI - P(VDF-TrFE) polymer-based thin films deposited on stainless steel substrates treated using water dissociation for flexible tactile sensor development. AB - In this work, deionized (DI) water dissociation was used to treat and change the contact angle of the surface of stainless steel substrates followed by the spin coating of P(VDF-TrFE) material for the fabrication of tactile sensors. The contact angle of the stainless steel surface decreased 14 degrees at -30 V treatment; thus, the adhesion strength between the P(VDF-TrFE) thin film and the stainless steel substrate increased by 90%. Although the adhesion strength was increased at negative voltage treatment, it is observed that the crystallinity value of the P(VDF-TrFE) thin film declined to 37% at -60 V. In addition, the remanent polarization value of the P(VDF-TrFE) thin film declined from 5.6 mC/cm2 to 4.61 mC/cm2 for treatment voltages between -5 V and -60 V. A maximum value of approximately 1000 KV/cm of the coercive field value was obtained with the treatment at -15 V. The d33 value was approximately -10.7 pC/N for the substrate treated at 0 V and reached a minimum of -5 pC/N for treatment at -60 V. By using the P(VDF-TrFE) thin-film as the sensing material for tactile sensors, human pulse measurements were obtained from areas including the carotid, brachial, ankle, radial artery, and apical regions. In addition, the tactile sensor is suitable for monitoring the Cun, Guan, and Chi acupoints located at the radial artery region in Traditional Chinese Medicine (TCM). Waveform measurements of the Cun, Guan, and Chi acupoints are crucial because, in TCM, the various waveforms provided information regarding the health conditions of organs. PMID- 24177730 TI - Overview of thermostable DNA polymerases for classical PCR applications: from molecular and biochemical fundamentals to commercial systems. AB - During the genomics era, the use of thermostable DNA polymerases increased greatly. Many were identified and described-mainly of the genera Thermus, Thermococcus and Pyrococcus. Each polymerase has different features, resulting from origin and genetic modification. However, the rational choice of the adequate polymerase depends on the application itself. This review gives an overview of the most commonly used DNA polymerases used for PCR application: KOD, Pab (IsisTM), Pfu, Pst (Deep VentTM), Pwo, Taq, Tbr, Tca, Tfi, Tfl, Tfu, Tgo, Tli (VentTM), Tma (UITmaTM), Tne, Tth and others. PMID- 24177731 TI - A comparison of two 16S rRNA gene-based PCR primer sets in unraveling anammox bacteria from different environmental samples. AB - Two 16S rRNA gene-based PCR primer sets (Brod541F/Amx820R and A438f/A684r) for detecting anammox bacteria were compared using sediments from Mai Po wetlands (MP), the South China Sea (SCS), a freshwater reservoir (R2), and sludge granules from a wastewater treatment plant (A2). By comparing their ability in profiling anammox bacteria, the recovered diversity, community structure, and abundance of anammox bacteria among all these diverse samples indicated that A438f/A684r performed better than Brod541F/Amx820R in retrieving anammox bacteria from these different environmental samples. Five Scalindua subclusters (zhenghei-I, SCS-I, SCS-III, arabica, and brodae) dominated in SCS whereas two Scalindua subclusters (zhenghei-II and wagneri) and one cluster of Kuenenia dominated in MP. R2 showed a higher diversity of anammox bacteria with two new retrieved clusters (R2-New-1 and R2-New-2), which deserves further detailed study. The dominance of Brocadia in sample A2 was supported by both of the primer sets used. Results collectively indicate strongly niche-specific community structures of anammox bacteria in different environments, and A438f/A684r is highly recommended for screening anammox bacteria from various environments when dealing with a collection of samples with diverse physiochemical characteristics. PMID- 24177733 TI - Engineered P450pyr monooxygenase for asymmetric epoxidation of alkenes with unique and high enantioselectivity. AB - A triple mutant of P450pyr monooxygenase (P450pyrTM) catalysed the epoxidation of several para-substituted styrenes as the first enzyme showing high (R) enantioselectivity and high conversion, demonstrated a broad substrate range, and showed high enantioselectivity for the epoxidation of an unconjugated 1,1 disubstituted alkene, 2-methyl-3-phenyl-1-propene, and a cyclic alkene, N phenoxycarbonyl-1,2,5,6-tetrahydropyridine, respectively. PMID- 24177732 TI - omega3 fatty acid desaturases from microorganisms: structure, function, evolution, and biotechnological use. AB - The biosynthesis of very-long-chain polyunsaturated fatty acids involves an alternating process of fatty acid desaturation and elongation catalyzed by complex series of enzymes. omega3 desaturase plays an important role in converting omega6 fatty acids into omega3 fatty acids. Genes for this desaturase have been identified and characterized in a wide range of microorganisms, including cyanobacteria, yeasts, molds, and microalgae. Like all fatty acid desaturases, omega3 desaturase is structurally characterized by the presence of three highly conserved histidine-rich motifs; however, unlike some desaturases, it lacks a cytochrome b5-like domain. Understanding the structure, function, and evolution of omega3 desaturases, particularly their substrate specificities in the biosynthesis of very-long-chain polyunsaturated fatty acids, lays the foundation for potential production of various omega3 fatty acids in transgenic microorganisms. PMID- 24177734 TI - Cloning of a DNA fragment from Cephalosporium acremonium which functions as an autonomous replication sequence in yeast. AB - A fragment of DNA which functions as an autonomous replication sequence in yeast was cloned from Cephalosporium acremonium. Mitochondrial DNA (mtDNA) was isolated from an industrial strain of C. acremonium (08G-250-21) highly developed for the production of the antibiotic, cephalosporin C. Size, 27 kb, and restriction pattern indicated this DNA was identical to mtDNA previously isolated (Minuth et al. 1982) from an ancestral strain (ATTC 14553) which produces very low amounts of cephalosporin C. A 1.9 kb Pst1 fragment of the Cephalosporium mtDNA was inserted into a Pst1 site of the yeast integrative plasmid, Ylp5, to produce a 7.5 kb plasmid, designated pPS1. The structure of pPS1 was verified by restriction analysis and hybridization.PS1 transformed Saccharomyces cerevisiae (DBY-746) to uracil prototrophy at a frequency of 272 transformants/MUg DNA. Transformation frequencies of 715 transformants/MUg DNA and zero were obtained for the replicative plasmid, YRp7, and the integrative plasmid YIp5, respectively. Southern hybridization and transformation of E. coli by DNA from yeast transformed by pPS1 verified that pPS1 replicates autonomously in yeast.The uracil-independent pPS1-yeast transformants were mitotically unstable. The average retention of pPS1 after three days growth in selective and non-selective medium was 4.5% and 0.4%, respectively, compared to retentions of 4.6% and 0.5% for YRp7. The properties of pPS1 were compared to those of a related plasmid, pCP2. pCP2 was constructed (Tudzynski et al. 1982) by inserting the C. acremonium 1.9 kb Pst1 fragment into the yeast integrative plasmid, pDAM1. PMID- 24177736 TI - Structure and function of the TRP3 gene of Saccharomyces cerevisiae: Analysis of 3'- and 5'-deletions in vivo and in vitro. AB - Two sets of deletions, entering the TRP3 gene of Saccharomyces cerevisiae from the 3'- and the 5'-end were constructed. Complementation analysis with chromosomal trp3A, trp3B and trp3C mutations was done by introducing the 3'- and 5'-truncated gene on a multicopy 2 MUm-vector. The N-terminal glutamine amido transferase function is encoded by a DNA fragment of 600-700 bp, and the C terminal indole-3-glycerol-phosphate synthase function by a DNA fragment of about 900 bp, whereas both functions together are encoded by a contiguous DNA fragment of about 1,500 bp. The bi functional TRP3-peptide thus could be dissected into two catalytically independent peptides in vivo.For the indole-3-glycerol phosphate synthase activity, independent catalytic activity was also demonstrated in vitro: deletions entering the TRP3 gene from the 5'-end, and lacking large parts of the sequence coding for the glutamine amidotransferase function, still are able to ex press a peptide exhibiting functional indole-3-glycerol phosphate synthase activity in vitro. Deletion plasmids pME505.De1C102.2MUm and DelC10.2MUm exhibited shorter TRP3 transcripts according to the deleted DNA-fragments (150 and 426 by respectively) but yielded peptides of invariable Mr of 35,000 d. Transcription and translation of these peptides, which probably represent the independently folding indole-3-glycerol-phosphate synthase core are discussed. PMID- 24177735 TI - Structure and function of the TRP3 gene of Saccharomyces cerevisiae: Analysis of transcription, promoter sequence, and sequence coding for a glutamine amidotransferase. AB - The structure and function of the TRP3 gene of Saccharomyces cerevisiae were analyzed. Subcloning of an original 4.8 kb BamHI DNA fragment, carrying the yeast TRP3 gene, allowed for a localization of the gene on a 2.5 kb ClaI/BamHI fragment. Transcription was found to proceed from the ClaI site towards the BamHI site. Three major transcription start sites were determined at positions -92, 87, and -81 by S1-mapping. The synthesis of the TRP3 gene is regulated by the general control, and was found to take place- at the transcriptional level. The sequence of the 5'-noncoding region up to position -400 and part of the coding region to position 840 were determined. The 5'-noncoding region contains sequences common to most amino acid biosynthetic genes known so far, namely a presumptive ribosome binding site, "Goldberg-Hogness boxes", and a consensus sequence, possibly involved in the general control. For the coding region a single open reading frame was found. The deduced amino acid sequence was aligned with homologous amino acid sequences of Neurospora crassa, Pseudomonas putida and Escherichia coli. The exceptionally high homology (40-60%) between these sequences led us to postulate that the TRP3 gene product is of the structure NH2 glutamine amidotransferase-indole-3-glycerol-phosphate synthase-COOH. PMID- 24177737 TI - Temperature-dependent internuclear transfer of genetic material in heterokaryons of Candida albicans. AB - Heterokaryons (hets) of Candida albicans are produced by fusing protoplasts of complementing auxotrophic strains and can be propagated continuously on minimal medium despite their tendency to assort nuclei into monokaryotic blastospores. Most mono-karyons have parental-type nuclei, but some are nuclear hybrids with DNA contents between one and two times that of their parental strains. Evidence is presented that hybrids arise by transfer of a portion of the genetic material of one bet nucleus to another, and that the amount of material conveyed during transfer increases with increasing het growth temperatures over the range 25 degrees C to 41 degrees C. This partial hybridization is a general property of hets and is not determined by the wild-type strain backgrounds of their parental components or by the kinds of auxotrophies forcing heterokaryosis. Frequencies of mitotic recombinants induced in partial hybrids by ultraviolet radiation indicate that nuclei of C. albicans are naturally diploid. PMID- 24177738 TI - Conversion in gene b1 of Ascobolus: Polarity of 6:2 and inverted polarity of aberrant 4:4 segregations. AB - Thirteen mutations located in gene b1 of Ascobolus immersus were studied for their non-mendelian segregation patterns. All these motations yield post-meiotic segregations. The non-mendelian segregation frequencies are the highest for the left end mutations. From left to right, the frequency of aberrant 4:4 asci increases. The hybrid DNA formation and distribution pattern as deduced from this result is consistent with that previously found in gene b2, providing further support to the Aviemore model. The frequency of 6:2 asci decreases from left to right. This constitutes an entirely new observation, the meaning of which is discussed. PMID- 24177739 TI - Two tightly linked silent cassettes in the mating-type region of Schizosaccharomyces pombe. AB - Genetic evidence is presented for the presence of two silent cassettes mat2-P and mat3- M, which both map to the right of the expressible site mat1 of the mating type region in Schizosaccharomyces pombe. During a switch of mating type, the resident cassette at mat1 is replaced by a copy of opposite mating-type information from one of the silent loci. Usually the switch becomes effective in one of two daughter cells, thus allowing for efficient sister-cell conjugation. In swi mutants, mating-type switching can be observed as early as for the first division after spore germination, albeit at a lower frequency. Genetically the two silent cassettes are linked so tightly that no crossovers were observed between mat2 and mat3 at a resolution of 10(-3) cM. PMID- 24177740 TI - The pedigree pattern of mating-type switching in Schizosaccharomyces pombe. AB - The previous ovservation that in dividing sister cells of Schizosaccharomyces pombe only one of two parallel divisions can be accompanied by a switch of mating type, herein termed "Miyata's rule", has been confirmed in pedigrees of diploid cells heterozygous for the mat2-Pm-B102 allele. Moreover, this rule appears to operate at the level of individual chromosomes, since in diploid cells simultaneous single-switch events were frequently observed in both sister cells, albeit on different chromosomes. Assuming two successive precursory states for the smt switching signal to the right of mat1, a deterministic 3-step model coupled to the cell cycle has been fitted to the empirical frequency distribution of conjugation in "four-lined cells" (a minipedigree of dividing sister cells). The nature of the first intermediate is still unknown, while the ultimate precursor of a switching event is probably a double-strand cut at smt, which can be revealed by molecular analyses. PMID- 24177741 TI - Inhibition of thymidylate biosynthesis induces mitotic unequal sister chromatid recombination in Saccharomyces cerevisiae. AB - Inhibition of thymidylate biosynthesis has been found to induce deletion of a LEU2 insert from the ribosomal DNA gene cluster of haploid strains of Saccharomyces cerevisiae. Loss of the insert was detected phenotypically by the enhanced production of both sectored (leu(+)/leu(-)) and non-sectored (leu(-)) colonies. Hybridization patterns obtained by Southern blot analysis of DNA from the leu(+) and leu(-) sectors were consistent with the occurrence of unequal sister chromatid recombination. The induction of sectored colonies was prevented by the rad52-1 mutation but not by defects in RAD6. However, the formation of non sectored leu(-) colonies was induced by thymidylate depletion in both rad52-1 and rad6 strains. PMID- 24177742 TI - Strain specific differences in ribosomal DNA from the fungus Schizophyllum commune. AB - CsCl-bisbenzimide gradients were used to purify ribosomal DNA (rDNA) from Schizophyllum commune total DNA. Southern hybridizations demonstrate that this DNA codes for rRNA. Restriction mapping of the rDNA from four strains revealed strain variation with repeat lengths of 9.2-9.6 kbp. Specific differences in the length of the rDNA repeat in different strains are due to insertions of 0.2 or 0.4 kbp of DNA at a single site. Different strains also show restriction site polymorphisms. Our analysis demonstrates the caution that must be exercised when interpreting restriction data from genomes containing restriction polymorphisms. Restriction digests with MspI and HpaII indicate that the rDNA contains 5 methylcytosine and that the unit repeats are not methylated identically, but rather differentially. This is the first report of methylated rDNA in fungi. PMID- 24177743 TI - Transmission of chloroplast genes in crosses between Chlamydomonas reinhardtii diploids: Correlation with chloroplast nucleoid behavior in young zygotes. AB - In crosses between diploid strains of Chlamydomonas reinhardtii, the mode of chloroplast gene transmission was studied and correlated with the behavior of DAPI-stained chloroplast nucleoids in young tetraploid zygotes. Phenotypically plus (female) diploids with mating-type genotypes of mt (+)/mt (+) or mt (+)/0 (hemizygote) and phenotypically minus (male) diploids with genotypes of mt (+)/mt (-) or mt (-)/mt (-) or 0/mt (-) were obtained by either crosses or polyethylene glycol induced somatic fusions between haploid strains. When crosses were made between mt (+)/mt (+) or mt (+)/0 and mt (-)/mt (-) or 0/mt (-), the transmission of chloroplast genes occurred mostly from the female parent, indicating a typical maternal inheritance. In these cases the chloroplast nucleoids of one of the two parents disappeared within 2.5 h after mating. In contrast, when female diploids were crossed to mt (+)/mt (-) male diploids, the chloroplast genes from both parents were transmitted to the progeny at equal frequency. The chloroplast nucleoids derived from the two parents were conserved for at least 2.5 h after mating. It is concluded that the chloroplast genes derived from the heterozygous male (mt (+)/mt (-)) are protected from the degradation that takes place soon after zygote formation, by virtue of the presence of mt (+) gene although this allele is recessive with respect to the phenotypic expression of sexuality in diploids. PMID- 24177744 TI - Physical mapping, nucleotide sequencing and expression in E. coli minicells of the gene for the large subunit of ribulose bisphosphate carboxylase from Petunia hybrida. AB - The Petunia hybrida rbcL gene was identified and located on the physical map within the Sall S9 fragment of the Petunia hybrida cpDNA by heterologous hybridization with the cloned rbcL gene of spinach (pSoc3BE148). In E. coli minicells harbouring the S9 fragment inserted into pBR322, the rbcL polypeptide is synthesized as was shown by molecular weight determination, immunoprecipitation and proteolytic digestion. However, the size of the rbcL polypeptide synthesized in minicells appeared to be dependent on the orientation of the S9 fragment in pBR322. In minicells harbouring the S9 fragment inserted into pBR322 in the clockwise orientation the molecular weight of the rbcL polypeptide is approximately 53 kD, whereas in minicells harbouring the S9 fragment in the opposite orientation, the rbcL polypeptide synthesized has a molecular weight of 52 kD. The difference in molecular weight of the two rbcL polypeptides is the result of transcription and translation into the flanking pBR322 sequences. This is due to the absence of the terminal part (6 codons), including the translation stop codon, of the rbcL gene on the cloned S9 fragment as was determined by nucleotide sequencing. The observed expression of the cloned part of the rbcL gene of Petunia hybrida indicates that the E. coli minicell system can be used as a suitable and convenient system for the identification and physical mapping of chloroplast genes.Comparison of the sequence of the untranslated 3'-end of the rbcL gene of Petunia hybrida with that of Nicotiana tabacum revealed a striking similarity of the region in which stem and loop structures can be formed that are most likely involved in termination of transcription of the rbcL gene. This region appears to be highly conserved in the rbcL genes of P. hybrida, N. tabacum, S. oleracea and Z. mays. PMID- 24177745 TI - Biogenesis of mitochondria: genetic and molecular analysis of the oli2 region of mitochondrial DNA in Saccharomyces cerevisiae. PMID- 24177746 TI - Single-incision versus conventional laparoscopic distal pancreatectomy: a single institution case-control study. AB - PURPOSE: Laparoscopic distal pancreatectomy is becoming increasingly established at specialized surgical institutions worldwide. The purpose of this study was to compare single-incision laparoscopic distal pancreatectomy (panLESS) with conventional laparoscopic distal pancreatectomy (panLAP) to assess feasibility and 30-day morbidity. METHODS: Eight consecutive patients who underwent panLESS were matched with patients who underwent panLAP in the same time period. Matching criteria were age, body mass index, and American Society of Anesthesiologists score. Feasibility was based on tumor size, operative time, intraoperative bleeding, resection status, and hospital stay. Thirty-day morbidity was defined by the revised Accordion Classification system and the International Study Group on Pancreatic Fistula definition. RESULTS: Over a 19-month period, 8 and 16 patients were identified for panLESS and panLAP, respectively. There were no significant differences in tumor size, operative time, intraoperative bleeding, resection status, and hospital stay between the two groups. Surgical complications developed in four panLESS patients and five panLAP patients, and out of which, two patients from each group developed a postoperative pancreatic fistula (grade B). CONCLUSIONS: This study indicates that panLESS is comparable to panLAP in terms of feasibility. More experience is needed to define what role single-incision distal pancreatectomy should have in minimal invasive pancreatic surgery. PMID- 24177749 TI - Effects of high and low 17beta-estradiol doses on focal cerebral ischemia: negative results. AB - The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for the dichotomy. The current study aimed to test this hypothesis. Sixty ovariectomized female rats were randomized into three groups differing in 17beta-estradiol regimens, and transient focal cerebral ischemia was subsequently induced. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment. Infarct sizes did not differ between groups, however clear discrepancies were seen in body weight and feeding behavior. In comparison to sham-operated animals, ovariectomized rats rapidly increased in body weight, whereas the opposite was seen in rats receiving 17beta-estradiol. The weight gain in the ovariectomized rats was paralleled by an increased food intake. PMID- 24177748 TI - Sodium butyrate induces DRP1-mediated mitochondrial fusion and apoptosis in human colorectal cancer cells. AB - Sodium butyrate (NaBt) is the byproduct of anaerobic microbial fermentation inside the gastro-intestinal tract that could reach up to 20mM, and has been shown to inhibit the growth of various cancers. Herein, we evaluated its effect on mitochondrial fusion and associated induction of apoptosis in colorectal cancer cells (CRC). NaBt treatment at physiological (1-5mM) concentrations for 12 and 24h decreased the cell viability and induced G2-M phase cell cycle arrest in HCT116 (12h) and SW480 human CRC cells. This cell cycle arrest was associated with mitochondria-mediated apoptosis accompanied by a decrease in survivin and Bcl-2 expression, and generation of reactive oxygen species (ROS). Furthermore, NaBt treatment resulted in a significant decrease in the mitochondrial mass which is an indicator of mitochondrial fusion. Level of dynamin-related protein 1 (DRP1), a key regulator of mitochondrial fission and fusion where its up regulation correlates with fission, was found to be decreased in CRC cells. Further, at early treatment time, DRP1 down-regulation was noticed in mitochondria which later became drastically reduced in both mitochondria as well as cytosol. DRP1 is activated by cyclin B1-CDK1 complex by its ser616 phosphorylation in which both cyclin B1-CDK1 complex and phospho-DRP1 (ser616) were strongly reduced by NaBt treatment. DRP1 was observed to be regulated by apoptosis as pan-caspase inhibitor showing rescue from NaBt-induced apoptosis also caused the reversal of DRP1 to the normal level as in control proliferating cells. Together, these findings suggest that NaBt can modulate mitochondrial fission and fusion by regulating the level of DRP1 and induce cell cycle arrest and apoptosis in human CRC cells. PMID- 24177750 TI - Shadowing and mask opening effects during selective-area vapor-liquid-solid growth of InP nanowires by metalorganic molecular beam epitaxy. AB - Indium phosphide nanowires were grown by metalorganic molecular beam epitaxy using the selective-area vapor-liquid-solid method. We show experimentally and theoretically that the size of the annular opening around the nanowire has a major impact on nanowire growth rate. In addition, we observed a considerable reduction of the growth rate in dense two-dimensional arrays, in agreement with a calculation of the shadowing of the scattered precursors. Due to the impact of these effects on growth, they should be considered during selective-area vapor liquid-solid nanowire epitaxy. PMID- 24177747 TI - Tumor suppressor p53 and estrogen receptors in nuclear-mitochondrial communication. AB - Several gene transcription regulators considered solely localized within the nuclear compartment are being reported to be present in the mitochondria as well. There is growing interest in the role of mitochondria in regulating cellular metabolism in normal and disease states. Various findings demonstrate the importance of crosstalk between nuclear and mitochondrial genomes, transcriptomes, and proteomes in regulating cellular functions. Both tumor suppressor p53 and estrogen receptor (ER) were originally characterized as nuclear transcription factors. In addition to their individual roles as regulators of various genes, these two proteins interact resulting in major cellular consequences. In addition to its nuclear role, p53 has been localized to the mitochondria where it executes various transcription-independent functions. Likewise, ERs are reported to be present in mitochondria; however their functional roles remain to be clearly defined. In this review, we provide an integrated view of the current knowledge of nuclear and mitochondrial p53 and ERs and how it relates to normal and pathological physiology. PMID- 24177751 TI - Diffusion-weighted MRI for distinguishing non-neoplastic cysts from solid masses in the mediastinum: problem-solving in mediastinal masses of indeterminate internal characteristics on CT. AB - OBJECTIVES: To evaluate the usefulness of diffusion-weighted (DW) magnetic resonance images for distinguishing non-neoplastic cysts from solid masses of indeterminate internal characteristics on computed tomography (CT) in the mediastinum. METHODS: We enrolled 25 patients with pathologically proved mediastinal masses who underwent both thoracic CT and magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI). MRI was performed in patients with mediastinal masses of indeterminate internal characteristics on CT. Two thoracic radiologists evaluated the morphological features and quantitatively measured the net enhancement of the masses at CT. They also reviewed MR images including unenhanced T1- and T2-weighted images, gadolinium-enhanced images and DW images. RESULTS: The enrolled patients had 15 solid masses and ten non neoplastic cysts. Although the morphological features and the extent of enhancement on CT did not differ significantly between solid and cystic masses in the mediastinum (P > 0.05), non-neoplastic cysts were distinguishable from solid masses by showing signal suppression on high-b-value DW images or high apparent diffusion coefficient (ADC) values of more than 2.5 * 10(-3) mm(2)/s (P < 0.001). ADC values of non-neoplastic cysts (3.67 +/- 0.87 * 10(-3) mm(2)/s) were significantly higher than that of solid masses (1.46 +/- 0.50 * 10(-3) mm(2)/s) (P < 0.001). CONCLUSIONS: DWI can help differentiate solid and cystic masses in the mediastinum, even when CT findings are questionable. KEY POINTS: * Non invasive diagnosis of non-neoplastic cysts can save surgical biopsy or excision. * Conventional CT or MRI findings cannot always provide a confident diagnosis. * Mediastinal masses can be well-characterised with DWI. * Non-neoplastic mediastinal cysts show significantly higher ADC values than cystic tumours. * DWI is useful to determine treatment strategy. PMID- 24177752 TI - Amorphous V-O-C composite nanofibers electrospun from solution precursors as binder- and conductive additive-free electrodes for supercapacitors with outstanding performance. AB - Flexible V-O-C composite nanofibers were fabricated from solution precursors via electrospinning and were investigated as free-standing and additive-free film electrodes for supercapacitors. Specifically, composite nanofibers (V0, V5, V10 and V20) with different vanadyl acetylacetonate (VO(acac)2) contents of 0, 5, 10 and 20 wt% with respect to polyacrylonitrile (PAN) were prepared. The composite nanofibers were comparatively studied using XRD, Raman spectroscopy, XPS, N2 adsorption-desorption, FE-SEM, TEM and S-TEM. The vanadium element was found to be well-dispersed in the carbon nanofibers, free from the formation of an aggregated crystalline phase, even in the case of V20. A specific surface area of 587.9 m(2) g(-1) was reached for V10 after calcination, which is approximately twice that of the vanadium-free carbon nanofibers (V0, 300.9 m(2) g(-1)). To perform as an electrode for supercapacitors in an aqueous electrolyte, the V10 film delivered a specific capacitance of 463 F g(-1) at 1 A g(-1). V10 was also able to retain a specific capacitance of 380 F g(-1), even at a current density of 10 A g(-1). Additionally, very stable cycling stability was achieved, maintaining an outstanding specific capacitance of 400 F g(-1) at 5 A g(-1) after charge-discharge cycling 5000 times. Thus, V-O-C composite nanofibers are highly attractive electrode materials for flexible, high-power, thin film energy storage devices and applications. PMID- 24177753 TI - Analyzing gene expression data in mice with the Neuro Behavior Ontology. AB - We have applied the Neuro Behavior Ontology (NBO), an ontology for the annotation of behavioral gene functions and behavioral phenotypes, to the annotation of more than 1,000 genes in the mouse that are known to play a role in behavior. These annotations can be explored by researchers interested in genes involved in particular behaviors and used computationally to provide insights into the behavioral phenotypes resulting from differences in gene expression. We developed the OntoFUNC tool and have applied it to enrichment analyses over the NBO to provide high-level behavioral interpretations of gene expression datasets. The resulting increase in the number of gene annotations facilitates the identification of behavioral or neurologic processes by assisting the formulation of hypotheses about the relationships between gene, processes, and phenotypic manifestations resulting from behavioral observations. PMID- 24177754 TI - Structurally tailored graphene nanosheets as lithium ion battery anodes: an insight to yield exceptionally high lithium storage performance. AB - How to tune graphene nanosheets (GNSs) with various morphologies has been a significant challenge for lithium ion batteries (LIBs). In this study, three types of GNSs with varying size, edge sites, defects and layer numbers have been successfully achieved. It was demonstrated that controlling GNS morphology and microstructure has important effects on its cyclic performance and rate capability in LIBs. Diminished GNS layer number, decreased size, increased edge sites and increased defects in the GNS anode can be highly beneficial to lithium storage and result in increased electrochemical performance. Interestingly, GNSs treated with a hydrothermal approach delivered a high reversible discharge capacity of 1348 mA h g(-1). This study demonstrates that the controlled design of high performance GNS anodes is an important concept in LIB applications. PMID- 24177755 TI - RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial-mesenchymal transition. AB - S100A8/A9 proteins are members of EF-hand calcium-binding proteins secreted by neutrophils and activated monocytes. S100A8/A9 has cell growth-promoting activity at low concentrations by binding to the receptor for advanced glycation end products (RAGE). In this study, we report for the first time that S100A8/A9 promoted the invasion of breast cancer cells depending on RAGE. In addition, RAGE binding to S100A8/A9 promoted the phosphorylation of LIN-11, Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation is a critical step in cofilin recycling and actin polymerization. Interestingly, RAGE binding to S100A8/A9 enhanced cell mesenchymal properties and induced epithelial mesenchymal transition. Mechanistically, RAGE binding to S100A8/A9 stabilized Snail through the NF-kappaB signaling pathway. Based on these observations, RAGE expression in breast cancer cells was associated with lymph node and distant metastases in patients with invasive ductal carcinoma. Moreover, RAGE binding to S100A8/A9 promoted lung metastasis in vivo. In summary, our in vitro and in vivo results indicated that RAGE binding to S100A8/A9 played an important role in breast cancer invasion/metastasis. This study identified both RAGE and S100A8/A9 as potential anti-invasion targets for therapeutic intervention in breast cancer. PMID- 24177757 TI - Margin negative, breast conserving resection: adequate for benign phyllodes tumors, but inadequate therapy for borderline and malignant phyllodes tumors. PMID- 24177756 TI - Barriers to physical activity and healthy eating in young breast cancer survivors: modifiable risk factors and associations with body mass index. AB - Physical activity (PA) and healthy eating (HE) are important behaviors to encourage in breast cancer survivors (BCS). We examined associations between various factors and barriers to PA (BPA) and barriers to HE (BHE), as well as relationships between barriers and body mass index (BMI) in younger BCS. Self reported data from 162 BCS (mean age 48 years) were used. BPA were assessed with a 21-item scale and BHE with a 19-item scale. Participants were classified as high or low on each scale. Sociodemographic, medical, and psychosocial characteristics were compared by high/low barriers. Correlates of continuous BPA and BHE were assessed as were associations among BHE, BPA, and BMI. 61 % of participants were characterized as having low BHE and low BPA; 12 % were high for both. High BHE/high BPA participants had the least favorable scores for depression, perceived stress, social support, fatigue, bladder control, and weight problems. Factors associated with BHE were lower education, higher perceived stress, and more severe weight problems. Factors associated with BPA were more severe bladder control problems and lower physical well-being. Higher BHE and BPA were significantly and uniquely associated with higher BMI, controlling for covariates. Several biopsychosocial factors (e.g., depression, stress, and fatigue) characterize young BCS who experience barriers to both HE and PA. The correlates of BHE and BPA are distinct. Both BHE and BPA are associated with BMI. These results should be considered in designing interventions for younger women with breast cancer. PMID- 24177758 TI - Response to neoadjuvant chemotherapy in ductal compared to lobular carcinoma of the breast: a meta-analysis of published trials including 1,764 lobular breast cancer. AB - Infiltrating lobular carcinoma (ILC) of the breast is associated with greater oestrogen receptor expression and poorer response to neoadjuvant chemotherapy, when compared to infiltrating ductal carcinoma (IDC). In order to compare the pathological complete response rate (pCR) and breast conserving surgery (BCS) in patients with ILC versus IDC treated with neoadjuvant chemotherapy, we performed a systematic review and meta-analysis of all published studies. A search of PubMed, EMBASE, the Web of Science, SCOPUS and the Cochrane Central Register of Controlled Trials was performed to identify studies that investigated pCR, clinical response and BCS in patients with ILC that were treated with neoadjuvant chemotherapy. Random-effect models were adopted to estimate the summary odds ratio (OR), and the publication bias was evaluated using a funnel plot and Egger's regression asymmetry test. Seventeen studies were included (one randomized controlled trial, three prospective series and 13 retrospective trials), for a total of 12,645 IDCs and 1,764 ILCs to be compared. Ductal carcinoma of the breast was associated with a better pCR (from 5.9 to 16.7 %; OR = 3.1, 95 % CI 2.48-3.87, P < 0.00001) and rate of BCS (from 35.4 to 54.8 %; OR = 2.1, 95 % CI 1.8-2.45, P < 0.00001) compared to ILC. The overall pCR rates and BCS decreased in the ILCs compared with IDC when treated with neoadjuvant chemotherapy. PMID- 24177759 TI - Trends in the use of total ankle replacement and ankle arthrodesis in the United States Medicare population. AB - BACKGROUND: Total ankle replacement (TAR) has gained acceptance as an alternative to traditional ankle arthrodesis (AA) for end-stage ankle arthritis. Little is known about long-term trends in volume, utilization, and patient characteristics. The objective of this study was to use longitudinal data to examine temporal trends in TAR and AA. METHODS: We identified all United States fee-for-service Medicare beneficiaries who underwent TAR and AA between 1991 and 2010 (n = 5871 and 29 532, respectively). We examined changes in patient demographics and comorbidity, nationwide and hospital volume, per capita utilization, and length of stay (LOS). RESULTS: Between 1991 and 2010, both TAR and AA patients had modest shifts in characteristics, with higher rates of diabetes and obesity. Overall, TAR Medicare volume increased by more than 1000% from 72 procedures in 1991 to 888 in 2010, while per-capita standardized utilization increased 670.8% (P < .001). AA volume increased 35.8% from 1167 procedures in 1991 to 1585 in 2010, while per-capita standardized utilization declined 15.6% (P < .001). The percentage of all US hospitals performing TAR increased nearly 4-fold from 3.1% in 1991 to 12.6% in 2010, while the proportion performing AA remained relatively unchanged. LOS decreased dramatically from 8.7 days in 1991 to 2.3 days in 2010 in TAR and from 5.5 days to 3.2 days in AA (P < .001). CONCLUSION: Between 1991 and 2010, Medicare beneficiaries undergoing either TAR or AA became more medically complex. Both volume and per-capita utilization of TAR increased dramatically but remained nearly constant for AA. At the same time, mean hospital volume for both procedures remained low. Further research should be directed toward determining design, surgeon, and hospital variables that relate to optimal outcomes following TAR, which has become increasingly used for the treatment of ankle arthritis. LEVEL OF EVIDENCE: Level III, comparative series. PMID- 24177761 TI - Organization of a Solatium brevidens repetitive sequence related to the TGRI subtelomeric repeats of Lycopersicon esculentum. AB - A species-specific repetitive DNA fragment has been isolated from a genomic library of Solanum brevidens. Sequence analysis revealed a regular organization of three non-homologous subrepeats forming tandemly-arranged composite repetitive units. Interpretation of Southern hybridization patterns based on the known sequence data suggests that the isolated sequence element represents an abundant organization type, although the presence of simple tandem arrays of the subrepeats is also indicated. Seventy-four percent sequence similarity was found between one of the S. brevidens subrepeats (Sb4AX) and a satellite DNA (TGRI) localized as a subtelomeric repeat on almost all Lycopersicon esculentum chromosomes. Insitu hybridization indicated that, similarly to TGRI, the S. brevidens-specific repeats are located at the ends of the arms of several chromosomes. On the basis of the data obtained, a common ancestral sequence can be proposed for the tomato (TGRI) and the S. brevidens (Sb4AX) repeat however, the molecular organization of this element in these two species evolved in a basically different manner. PMID- 24177762 TI - Identification of a RAPD marker linked to sex determination in Pistacia vera using bulked segregant analysis. AB - The Random Amplified Polymorphic DNA (RAPD) technique was used to amplify DNA segments, with the objective of finding markers linked to sex determination in the dioecious species, Pistacia vera. Progenies from two female parents pollinated by a common male parent were studied. Two bulks of DNA were made in each cross, one from males and one from females, by pooling an equal weight of fresh leaves from each individual contributing to the bulk prior to DNA extraction. DNA was extracted from each bulked sample and from each of the contributing individuals. DNA was also extracted from 14 cultivars of P. vera and from 94 open-pollinated, fewweeks-old P. vera seedlings of unknown sex. Seven hundred different decamer oligonucleotide primers were used to perform DNA amplification, with 1 of these (OPO08) producing a 945 bp amplification band that was present only in the bulked female samples and absent in the bulked male samples of the two crosses. The relationship between band presence and female sex expression was conserved in every individual obtained from the two crosses and in the 14 cultivars unrelated to the crosses. We propose that this band is tightly linked to the gene(s) that control sex determination in pistachio. The OPO08945 RAPD marker could be used in a breeding program to screen the gender of pistachio plants long before they reach reproductive maturity, resulting in considerable savings of time and economic resources. In order to verify that assumption we screened 94 additional seedlings with the OPO08 primer and obtained results consistent with a 1?1 male:female ratio. PMID- 24177760 TI - High-risk human papillomavirus detection in oropharyngeal, nasopharyngeal, and oral cavity cancers: comparison of multiple methods. AB - IMPORTANCE: Human papillomaviruses are now recognized as an etiologic factor in a growing subset of head and neck cancers and have critical prognostic importance that affects therapeutic decision making. There is no universally accepted gold standard for high-risk HPV (hrHPV) assessment in formalin-fixed, paraffin embedded (FFPE) tissue specimens, nor is there a clear understanding of the frequency or role of hrHPV in sites other than oropharynx. OBJECTIVE: To determine the optimal assessment of hrHPV in FFPE head and neck tumor tissue specimens. DESIGN, SETTING, PARTICIPANTS: In the setting of a large Midwestern referral center, assessment of hrHPV by p16 immunohistochemical staining, in situ hybridization, and polymerase chain reaction (PCR)-MassArray (PCR-MA), with L1 PGMY-PCR and sequencing to resolve method discordance, was conducted for 338 FFPE oropharyngeal, nasopharyngeal, and oral cavity tumor tissue specimens. Relative sensitivity and specificity were compared to develop a standard optimal test protocol. Tissue specimens were collected from 338 patients with head and neck cancer treated during the period 2001 through 2011 in the departments of Otolaryngology, Radiation Oncology, and Medical Oncology. INTERVENTION: Patients received standard therapy. MAIN OUTCOMES AND MEASURES: Optimal hrHPV identification, detection, and activity in head and neck cancers. RESULTS: Using combined PCR-MA with L1 PGMY-PCR and sequencing for conclusive results, we found PCR-MA to have 99.5% sensitivity and 100% specificity, p16 to have 94.2% sensitivity and 85.5% specificity, and in situ hybridization to have 82.9% sensitivity and 81.0% specificity. Among HPV-positive tumors, HPV16 was most frequently detected, but 10 non-HPV16 types accounted for 6% to 50% of tumors, depending on the site. Overall, 86% of oropharynx, 50% of nasopharynx, and 26% of oral cavity tumors were positive for hrHPV. CONCLUSIONS AND RELEVANCE: PCR-MA has a low DNA (5 ng) requirement effective for testing small tissue samples; high throughput; and rapid identification of HPV types, with high sensitivity and specificity. PCR-MA together with p16INK4a provided accurate assessment of HPV presence, type, and activity and was determined to be the best approach for HPV testing in FFPE head and neck tumor tissue specimens. PMID- 24177763 TI - Classification of cultivated rices into indica and japonica types by the isozyme, RFLP and two milled-rice methods. AB - Four methods for classifying cultivated rices (Oryza sativa L.) (including IR varieties) into indica and japonica types - waxy gene product in endosperm starch, glutelin alpha3 molecular weight in milled rice, RFLP polymorphism at the Wx locus and Glaszmann's isozyme method - were compared. On the basis of the two endosperm traits and the RFLP method Glaszmann's group 1 (indica) was classified as mainly indica and intermediate groups 2, 3 and 4 as exclusively indica. However, the endosperm traits classified Glaszmann's group 5 as mainly indica, while the RFLP method classified it as japonica. The RFLP waxy gene probe was closest to the isozyme method in classifying group 6 as japonicas; the waxy gene product gave mainly indica reaction even in group 6, and the glutelin alpha3 method was intermediate. All IR rices were classified as being indica on the basis of Wx gene product and by Glaszmann's method, but a few were classified as japonica by the glutelin alpha3 method and by the RFLP waxy gene probe. PMID- 24177764 TI - Somatic hybrids with substitution type genomic configuration TCBB for the transfer of nuclear and organelle genes from Brassica tournefortii TT to allotetraploid oilseed crop B. carinata BBCC. AB - Oilseed crop Brassica carinata BBCC is a natural allotetraploid of diploid species B. nigra BB and B. oleracea CC. To transfer the nuclear and organelle genes in a concerted manner from an alien species, B. tournefortii TT, to B. carinata, we produced somatic hybrids with genomic configuration TCBB using B. nigra and B. oleracea stocks that carried selectable marker genes. B. tournefortii TT was sexually crossed with hygromycin-resistant B. oleracea CC. Protoplasts isolated from shoot cultures of hygromycin-resistant F1 hybrids of B. tournefortiixB. oleracea TC were fused with protoplasts of kanamycin-resistant B. nigra BB. In two different fusion experiments 80 colonies were obtained through selection on media containing both hygromycin and kanamycin. Of these, 39 colonies regenerated into plants. Analysis of 15 regenerants by random amplified polymorphic DNA (RAPD) markers showed the presence of all three genomes, thereby confirming these to be true hybrids. Restriction fragment length polymorphism (RFLP) analysis of organelle genomes with heterologous chloroplast (cp)and mitochondrial (mt) DNA probes showed that the chloroplast genome was inherited from either of the two parents while mitochondrial genomes predominantly showed novel configurations due to either rearrangements or intergenomic recombinations. We anticipate that the TCBB genomic configuration will provide a more conducive situation for recombination between the T and C genomes during meiosis than the TTCCBB or TCCBB type configurations that are usually produced for alien gene transfer. The agronomic aim of producing TCBB hybrids is to transfer mitochondrial genes conferring cytoplasmic male sterility and nuclear genes for fertility restoration from B. tournefortii to B. carinata. PMID- 24177765 TI - Phylogenetic analysis of Sorghum and related taxa using internal transcribed spacers of nuclear ribosomal DNA. AB - The phylogenetic relationships of the genus Sorghum and related genera were studied by sequencing the nuclear ribosomal DNA (rDNA) internal transcribed spacer region (ITS). DNA was extracted from 15 Sorghum accessions, including one accession from each of the sections Chaetosorghum and Heterosorghum, four accessions from Parasorghum, two accessions from Stiposorghum, and seven representatives from three species of the section Sorghum (one accession from each of S. propinquum and S. halepense, and five races of S. bicolor). The maize (Zea mays) line, H95, and an accession from Cleistachne sorghoides were also included in the study. Variable nucleotides were used to construct a strict consensus phylogenetic tree. The analyses indicate that S. propinquum, S. halepense and S. bicolor subsp. arundinaceum race aethiopicum may be the closest wild relatives of cultivated sorghum; Sorghum nitidum may be the closest 2n=10 relative to S. bicolor, the sections Chaetosorghum and Heterosorghum appear closely related to each other and more closely related to the section Sorghum than Parasorghum; and the section Parasorghum is not monophyletic. The results also indicate that the genus Sorghum is a very ancient and diverse group. PMID- 24177766 TI - Physical mapping of translocation breakpoints in rye by means of synaptonemal complex analysis. AB - A physical map including 40 translocation breakpoints has been constructed in rye by means of synaptonemal complex (SC) analysis of well-paired pachytene quadrivalents. The chromosome arms involved in such translocations were previously identified either from mitotic C-banding analysis or from the meiotic configurations observed in the progenies of crosses with a rye line having multiple chromosome rearrangements. The synaptonemal complexes formed by some translocation homozygotes were also analyzed, the relative pachytene SC length of their translocated chromosomes being compared to that observed in the corresponding translocation heterozygotes. In the translocations in which the position of the breakpoint could be well defined from mitotic C-banding analysis, a good correspondence between the relative position of the point showing partner exchange in the pachytene quadrivalents and the actual location of the breakpoint was established. It is concluded that the mapping of translocation breakpoints by SC analysis of pachytene quadrivalents provides a more accurate estimate of the position of the breakpoints than that obtained from mitotic C-banding analysis, due to the lack of evenly-distributed interstitial C-bands in most rye chromosomes. The distribution of the breakpoints along the chromosomes in relation to their spontaneous or induced origin is also discussed. PMID- 24177767 TI - Linkages among RFLP, RAPD, isozyme, disease-resistance, and morphological markers in narrow and wide crosses of cucumber. AB - A 58-point genetic map was constructed with RFLP, RAPD, isozyme, morphological, and disease-resistance markers spanning 766 cM on ten linkage groups for a cross within the cultivated cucumber (Cucumis sativus var. sativus). Relatively few DNA polymorphisms were detected, agreeing with previous studies documenting a narrow genetic base for cucumber. Most RFLPs within the cultivated cucumber appear to be changes at restriction-enzyme sites. Sixty-four percent of RAPD markers that fit expected ratios at P<0.001 were unlinked, possibly due to poor amplification and the inefficiency of dominant markers to detect linkage in an F2 family. A 70 point linkage map, spanning 480 cM on ten linkage groups, was constructed with RFLP, isozyme, morphological, and diseaseresistance markers for a cross between the cultivated cucumber and the wild or feral C. sativus var. hardwickii. Unlinked markers and more linkage groups than chromosome pairs indicated that both maps were not saturated. Twentyone markers doubly segregated in both families and regions of colinearity were identified. PMID- 24177768 TI - The semidwarf gene, sd-1, of rice (Oryza sativa L.). I. Linkage with the esterase locus, Estl-2. AB - The linkage relationship between the semidwarf gene (sd-1) and the isozyme locus EstI-2 was elucidated using segregating populations derived from crosses between several semidwarf testers and tall rice varieties. Bimodal distributions for culm length were observed in F2 populations of three cross combinations, including Shiokari/Shiokari (sd-1), Taichung 65 (A,Pn,Pau)/Taichung 65 (sd-1), and Milyang 23/Kasalath. Taking the valley of the distribution curves as the dividing point, two height classes were apparent with a segregation ratio of 3 tall?1 short, demonstrating this character to be under the control of a single recessive gene. An inheritance study of esterase isozymes, based on isoelectric focusing (IEF), showed that the EstI-2 locus had two active allozymes of monomeric structure and one null form, which were designated "a", "b", and "n", respectively (Eun et al. 1990). Semidwarf testers such as Shiokari (sd-1), Taichung 65 (sd-1) and Milyang 23 have an active allozyme designated as EstI-2(aa), while the tall parents, Shiokari and Taichung 65 (A,Pn,Pau), have the active allozyme, EstI-2(bb), and Kasalath has a null form of the allozyme, EstI-2(nn). By dividing F2 populations based on EstI-2 allozyme patterns, culmlength distributions exhibited trimodal curves. Most of the short plants had the homozygous EstI-2(aa) pattern of the short parents, most of the tall plants had the homozygous pattern, EstI-2(bb) or EstI-2(nn), and most of the intermediate plants had the heterozygous EstI-2(ab) or EstI-2(an) banding pattern. Einkage analysis indicated that sd-1 and EstI-2 were tightly linked. These findings were also confirmed by segregation analyses in F3 progenies. No recombinants among 171 F3 families from the Shiokari/Shiokari (sd-1) combination, five recombinants among 267 F3 families from Taichung 65 (A,Pn,Pau)/Taichung 65(sd-1), and only two recombinants out of 237 F3 families from Milyang 23/Kasalath, were found. The recombination values were 0, 1.87 and 0.8%, respectively. PMID- 24177769 TI - The semidwarf gene, sd-1, of rice (Oryza sativa L.). II. Molecular mapping and marker-assisted selection. AB - To establish the location of the semidwarf gene, sd-1, the anthocyanin activator (A), purple node (Pn), purple auricle (Pau), and the isozyme locus, EstI-2, in relation to DNA markers on the molecular linkage map of rice, 20 RFLP markers, previously mapped to the central region of chromosome 1 (McCouch et al. 1988), were mapped onto an F2 population derived from the cross Taichung 65 (A,Pn,Pau)/Taichung 65 (sd-1). sd-1 and EstI-2 were determined to be linked most tightly to RFLP markers RG 109 and RG 220, which cosegregated with each other. The distance between these RFLP markers and sd-1 was estimated to be 0.8 cM, based on an observed recombination value of 0.8%. The order of genes and markers in this region of chromosome 1 was determined to be sd-1 - (EstI-2 - RG220 - RG109) - RG381 - A - Pn - Pau. To test the efficacy of selection for sd-1 based on these linked markers, 50-day-old F2 seedlings derived from another cross, Milyang 23/Gihobyeo, were analyzed for marker genotype. At this age, the semidwarf character could not be clearly detected based on phenotype. In addition, plant height was normally distributed in this population, making it difficult to unambiguously identify plants carrying sd-1. Thirteen seedlings homozygous for the sd-1-associated allele at EstI-2, RG220 and RG109, and 13 seedlings homozygous for the Sd-1-associated allele at all three marker loci were selected for further genetic analysis. At 20 days after heading, the culm lengths of these 26 plants were measured and the expected phenotype was confirmed in every case. These 26 plants were then selfed for four generations and F6 lines were again evaluated to determine whether any recombination among the three molecular markers, or between these markers and the sd-1 gene, could be detected. No recombinants were identified, confirming the tight linkage of these loci and the usefulness of genotypic selection for this recessive semidwarf character prior to the time when it can be evaluated based on phenotype. PMID- 24177770 TI - Rye chromosome arm 3RS encodes a homodimeric inhibitor of insect alpha-amylase. AB - A new inhibitor of insect alpha-amylase, designated RDAI-1, has been purified from rye (Secale cereale L.) endosperm. RDAI-1 is homologous to wheat homodimeric inhibitors. This homology is supported by their similar N-terminal amino-acid sequences, inhibitory activities towards amylases from Tenebrio molitor (Coleoptera) and human saliva, and aggregative properties in gel-filtration chromatography. The gene encoding RDAI-1, IdhaR1, is located on the short arm of chromosome 3R, which is homoeologous with wheat chromosome arms 3BS and 3DS, where the genes for homodimeric inhibitors have been previously mapped. PMID- 24177771 TI - A low-copy-number Sorghum DNA sequence that detects hypervariable EcoRV fragments. AB - A sorghum genomic DNA clone that hybridized on Southern blots in simple but different patterns to fragments produced by digestion of DNA from the parents of an F2 mapping population was hybridized to EcoRV-digested DNA from 53 accessions. Forty-six different fragment patterns were observed, each comprised of from one to ten bands. Much less variability was detected in EcoRI than EcoRV digests of a selected subset of the accessions. Base-sequence analysis of the clone did not reveal a functional identity for the sequence and the clone does not contain repeated sequences often associated with hypervariable loci. Clones such as this will be especially useful in evaluating germplasm diversity and in identifying the potential parentage of hybrids. PMID- 24177772 TI - Identification of wheat-Agropyron cristatum monosomic addition lines by RFLP analysis using a set of assigned wheat DNA probes. AB - A non-radioactive digoxigenin-labelled DNA method was used successfully to identify RFLP markers in 54 Triticum aestivum cv 'Chinese Spring' - Agropyron cristatum (2n=28, genome PPPP) P-genome monosomic addition lines. Southern analysis using a set of 14 DNA probes identifying each homoeologous chromosome arm, combined with two restriction enzymes HindIII and EcoRI, indicated that six A. cristatum chromosomes (1P, 2P, 3P, 4P, 5P and 6P) and five A. cristatum chromosome arms (2PS, 2PL, 5PL, 6PS and 6PL) have been individually added to the wheat genome. The added chromosomes of three lines were Agropyron translocated chromosomes. It was also found that two addition plants possessed an Agropyron wheat translocation. These results showed that RFLP analysis using the set of assigned wheat probes was a powerful tool in detecting and establishing homoeology of alien A. cristatum chromosomes, or arms, added to wheat, as well as in screening the alien addition material. The creation of the monosomic addition lines should be useful for the transfer of disease-resistance genes from A. cristatum to wheat. PMID- 24177773 TI - Chromosomal localization and molecular-marker tagging of the powdery mildew resistance gene (Lv) in tomato. AB - We report the tagging of a powdery mildew [Leveillula taurica (Lev.) Arnaud.] resistance gene (Lv) in tomato using RAPD and RFLP markers. DNA from a resistant (cv Laurica) and a susceptible cultivar were screened with 300 random primers that were used to amplify DNA of resistant and susceptible plants. Four primers yielded fragments that were unique to the resistant line and linked to the resistance gene in an F2 population. One of these amplified fragments, OP248, with a molecular weight of 0.7 kb, was subsequently mapped to chromosome 12, 1 cM away from CT134. Using RFLP markers located on chromosome 12, it was shown that approximately one half of chromosome 12 (about 42 cM), in the resistant variety is comprised of foreign DNA, presumably introgressed with the resistance gene from the wild species L. chilense. Further analysis of a backcross population revealed that the Lv gene lies in the 5.5-cM interval between RFLP markers, CT211 and CT219. As a prelude to map-based cloning of the Lv gene, we are currently enriching the density of markers in this region by a combination of RAPD primers and other techniques. PMID- 24177774 TI - Random-amplified-polymorphic DNA markers in sorghum. AB - Conditions have been identified that allow reproducible amplification of RAPD markers in sorghum. High resolution of RAPD markers was accomplished by radiolabeling PCR-amplified DNAs followed by separation on denaturing 5% polyacrylamide gels. Reaction parameters including MgCl2 concentration and temperature significantly influenced yield and the type of amplification products synthesized. Unexplained amplified DNAs increased when more than 35 cycles of PCR amplification were used. Under standard conditions, approximately 80% of the primers tested amplified DNA, and most revealed 1-5 polymorphisms between BTx 623 and IS 3620C. Primers were used to amplify RAPDs in 32 genotypes of sorghum. In addition, 8 primers detected RAPDs in a population previously used to create an RFLP map for sorghum. These RAPDs were mapped successfully using a population of 50 F2 plants. PMID- 24177775 TI - Practical considerations for maintaining germplasm in maize. AB - The main goals of genetic resource management are to acquire, maintain, distribute, characterize, regenerate, preserve, evaluate, and utilize the genetic diversity of crops and their wild relatives. The objectives of this study for ex situ conservation of maize (Zea mays L.) are to review and describe: (1) practical regeneration methods that are based on population genetic theory; (2) practical problems encountered in choosing core subsets of a maize collection. Whenever possible, regeneration procedures should control the number of pollen parents (male gametes; through controlled hand pollination) and the number of female parent gametes (by harvesting equal numbers of kernels from each seed plant). When the number of pollen and seed parents are controlled during regeneration, the effective population size (Ne) is twice the size of the original population (N). Examples of practical methods for controlling the number of male and female parents are presented. The procedure involves random-paired plant crosses and taking equal numbers of seeds from each maize ear. To form a core subset, accessions of a maize race are subdivided through a stratified sampling procedure. Delineation of a core subset from a Tuxpeno racial collection is described as an example. PMID- 24177776 TI - Rapid mapping of two genes for resistance to downy mildew from Lactuca serriola to existing clusters of resistance genes. AB - Two resistances to downy mildew derived from Lactuca serriola were characterized genetically and mapped using molecular markers. Classical genetic analysis suggested monogenic inheritance; however, the presence of multiple, tightly linked genes in each case could not be eliminated. Therefore, they were designated resistance factors R17 and R18. Analysis with molecular markers known to be linked to clusters of resistance genes quickly revealed linkage of R18 to the major cluster of resistance genes and provided six linked markers, three RAPD (Random Amplified Polymorphic DNA) markers and three codominant SCAR (Sequence Characterized Amplified Region) markers. The mapping of R17 required the screening of arbitrary RAPD markers using bulked segregant analysis; this provided five linked markers, three of which segregated in the basic mapping population. This demonstrated loose linkage to a second cluster of resistance genes and provided additional linked markers. Two RAPD markers linked to R17 were converted into SCARs. The identification of reliable PCR-based markers flanking each gene will aid in selection and in combining these resistance genes with others. PMID- 24177777 TI - A population analysis of Robertsonian and Ag-NOR polymorphisms in brown trout (Salmo trutta). AB - An analysis of Robertsonian polymorphism and variation in the number of active NORs has been carried out in several populations of brown trout (Salmo trutta) from Northwestern Spain. The karyotype of this species appears to be soundly established, and essentially no variation has been found in chromosome number. Interindividual and interpopulation variation in arm number was detected, with figures ranging between 100 and 102 among individuals, and between 100.10 and 100.80 among populations. This variation in arm number is solely attributable to the polymorphism of the short arm of the main NOR-bearing pair 11, which can appear from acrocentric to metacentric in different individuals. Most populations analyzed showed the standard distribution of active NORs previously observed in this species. The Mino drainage basin, and specially the Chamoso population, showed a multi-chromosomal distribution of active NORs, with several new locations, always telomeric. In most cases no concordance was observed between previously detected rDNA sites in S. trutta and the new Ag-NOR locations. This fact suggests a transposition mechanism rather than an activation of silent rDNA sites to explain this multichromosomal NOR pattern. PMID- 24177778 TI - Correlation and path-coefficient analyses of seed-yield components in pearl millet x elephantgrass hybrids. AB - Correlation and path-coefficient analyses have been successful tools in developing selection criteria. Since increased seed yield is an important goal in our pearl millet x elephantgrass [Pennisetum glaucum (L.) R.Br. x P. purpureum Schum.] hexaploid breeding program, we used correlation and path-coefficient analyses on seed data. This study was conducted to develop appropriate selection criteria by determining the direct and indirect effects of seed-yield components on seed yield plant(-1). Number of tillers plant(-1), panicles tiller(-1), seeds panicle(-1), 100-seed weight, and seed yield plant(-1), were estimated for individual plants in seven families. Phenotypic (rp) and genetic correlations (rg) were calculated, and path analyses (phenotypic and genetic) were carried out according to predetermined causal relationships. Phenotypic and genetic correlations differed in several cases due to large environmental variance and covariance. Phenotypically, all components were positively and significantly associated with seed yield plant(-1). Genotypically, only seeds panicle(-1) and 100-seed weight were significantly correlated. These two components were also positively correlated (r p=0.55, r g=0.63), so simultaneous improvement for both components would be feasible. Panicles tiller(-1) and seeds panicle(-1) were negatively correlated (r g=-0.97). In the path analyses, all direct effects of the components on seed yield plant(-1) were positive. Phenotypic indirect effects were not as important as genetic indirect effects. The components seeds panicle( 1) and 100-seed weight influenced seed yield plant(-1) the greatest, both directly and indirectly. PMID- 24177779 TI - Variants within the 5'-flanking regions of bovine milk protein genes: I. kappa casein-encoding gene. AB - In order to identify DNA variants within the 5'-flanking region of the bovine kappa-casein (kappaCn)-encoding gene, this area of the gene from 13 cows belonging to seven breeds (Holstein Friesian, Brown Swiss, German Simmental, Jersey, Galloway, Scottish Highland and Ceylon Dwarf Zebu) was analysed. For each individual, about 1 kb of the 5'-flanking region including exon I was amplified by polymerase chain reaction (PCR). The biotinylated PCR product was immobilized on magnetic beads followed by direct bidirectional sequencing using an automated DNA sequencer. Fifteen DNA variants were identified, some of which are located within potential regulatory sites and possibly involved in the expression of the kappa-casein encoding gene. PMID- 24177780 TI - DNA variants within the 5'-flanking region of milk-protein-encoding genes II. The beta-lactoglobulin-encoding gene. AB - For the detection of polymorphisms within the 5'-flanking region of the beta lactoglobulin (-LG) -encoding gene a nucleotide sequence containing 795 bp of the promoter and 59 bp of exon I was cloned and sequenced. After comparing the sequence from the DNA of 11 diverse cows (different breeds and milk-protein yields), 14 singlebp substitutions were identified within the 5'-flanking region and two in the 5'-untranslated region (5'-UTR) of exon I. Some of the variants are located in potential binding sites for trans-acting factors or in the 5'-UTR. A PCR-based RFLP analysis was performed, and the genotypes of an additional 60 cows were identified at five variable 5'-flanking sites. The results reveal three frequent combinations between the A and B alleles of the protein-coding region and the novel 5'-flanking DNA variants. This finding may explain the differences of the protein-variant-dependent beta-LG synthesis (A>B) observed in vivo. A sequence comparison of the bovine and ovine promoters reveals an homology of 92.8% and shows a higher degree of conservation between positions -600 and -300. PMID- 24177781 TI - Variation among offspring of alloplasmic tobacco Nicotiana tabacum L. cv 'Zamojska 4' with the cytoplasm of N. knightiana Goodspeed. AB - Progeny obtained from single plants of cultivated tobacco Nicotiana tabacum cv 'Zamojska 4' and its isonuclear analogue with the cytoplasm of N. knightiana were compared for 16 agronomic traits. The alloplasmic strain showed reduced self fertility, increased 1 000-seed weight, lower plant height, lower leaf width, and reduced yield and money-value of cured leaves, most of which were fairly common effects of an alien cytoplasm. However, some of these parameters such as plant height, leaf width and length/width ratio, yield and money-value of the crop, and, less regularly, leaf number and fertility, underwent further reduction in the selfed offspring of the alloplasmic strain. Furthermore, among those offspring, especially in the S2-and S3-selfed generations, a significant progeny to-progeny variation was found for the majority of traits studied, the extent of which far exceeded that encountered in the selfed offspring of the autoplasmic paternal cultivar. PMID- 24177782 TI - Genetic control of androgenetic response in Lolium perenne L. AB - In a study of androgenesis in 90 Norwegian genotypes of perennial ryegrass (Lolium perenne L.), heritabilities ranged from h b (2) =0.46 to 0.80. Very high or completely positive genotypic correlations were found between most characters of androgenetic response (e.g. embryo-like structures per 100 anthers, plants per 100 embryo-like structures, albino plants per 100 anthers, green plants per 100 anthers). Three genotypes, 2 Norwegian (7-5 and 9-5) and 1 Danish (245), which had significantly different androgenetic responses were selected to study the genetic control of the processes. Genotypes 7-5 and 9-5 were highly embryogenie, 7-5 and 245 were relatively high producers of green plants, while 9-5 was unable to produce green plants. The six possible reciprocal crosses between these three genotypes were made, and 10 or 11 F1 plants from each cross were used for anther culture experiments. The cross 7-5 x 245 showed average superiority over both parents for total plant regeneration and green plant production, results not previously reported. The phenotypic correlations estimated among progenies from the crosses ranged from r=-0.99(***) to 0.81(***). These considerable changes, relative to the results of the screening experiment, are most likely the result of changed allele frequencies caused by the strong selection of parents in these crosses, and a relatively simple genetical control. This is also inferred from the large transgressive segregation observed. PMID- 24177783 TI - Colonic manometry and colonic scintigraphy as a diagnostic tool for children with severe constipation. AB - OBJECTIVE: In adults, colonic manometry and colonic scintigraphy are both valuable studies in discriminating normal and abnormal colonic motility. The objective of this study was to compare the diagnostic yield and tolerability of colonic manometry and colonic scintigraphy in children with severe constipation. METHODS: Twenty-six children (mean age 11.4 years, 77% boys) who had received colonic manometry and colonic scintigraphy as part of a colonic motility evaluation were included. Manometry was performed as per department protocol. After swallowing a methacrylate-coated capsule containing indium-111, images were taken at 4, 24, and 48 hours, and geometric centers were calculated. Results of both tests were categorized in 3 groups: normal, abnormal function in the distal part of the colon, and colonic inertia. Cohen kappa was used for the level of agreement. Patients and parents completed a questionnaire regarding their experience. RESULTS: Colonic scintigraphy showed normal transit time in 20%, delay in the distal colon in 48%, and colonic inertia in 32% of patients. Colonic manometry was normal in 40%, abnormal in the distal colon in 40%, and colonic inertia was diagnosed in 20%. The kappa score was 0.34. All 5 patients with colonic inertia during manometry had a similar result by scintigraphy. Eighty eight percent of patients preferred scintigraphy over manometry and 28% of parents preferred colonic manometry over scintigraphy. CONCLUSIONS: Colonic manometry and colonic scintigraphy have a fair agreement regarding the categorization of constipation. Scintigraphy is well tolerated in pediatric patients and may be a useful tool in the evaluation of children with severe constipation. PMID- 24177785 TI - Effect of operator experience and frequency of procedure performance on complication rate after ultrasound-guided percutaneous liver biopsies. AB - OBJECTIVE: The aim of the present study was to assess whether the complication rate after ultrasound-guided percutaneous liver biopsies in children is affected by how frequently the procedure is performed by the operator. METHODS: Medical charts and ultrasound descriptions of 311 ultrasound-guided percutaneous liver biopsy procedures performed by 18 radiologists at a single center from 2000 to 2011 were reviewed. Postbiopsy ultrasound the following day was performed after 97% of the procedures. RESULTS: There were no differences in the procedure associated rate of major bleeding incidents (2.2% vs 0.8%, P = 0.38), minor bleeding incidents (15.2% vs 10.2%, P = 0.31), or abdominal pain (13.0% vs 10.6%, P = 0.61) among operators who performed <=10 procedures and those who performed >10 procedures during the study period. A higher rate of minor bleeding incidents were recorded after liver biopsy when operators had performed <10 biopsies compared with operators who had performed >20 pediatric liver biopsies during the study period (odds ratio 3.4 [1.3-9.1], P = 0.02). No association between the number of biopsies performed by the operator during the 2 years preceding the date of the biopsy and complications was found. CONCLUSIONS: Major complications are infrequent after pediatric liver biopsies and no relation between operator experience and major complications was found. We found a significant, but minor, effect of operator procedure frequency on the rate of minor bleeding incidents after ultrasound-guided pediatric liver biopsies. PMID- 24177786 TI - Long-term outcomes of infants and children undergoing percutaneous endoscopy gastrostomy tube placement. AB - OBJECTIVES: Little is known about long-term outcomes of patients undergoing percutaneous endoscopic gastrostomy (PEG) placement. The purpose of this study was to examine tube-related major complications in pediatric patients undergoing PEG placement during a 10-year follow-up period. METHODS: A retrospective chart review of patients undergoing PEG placement from April 1999 through December 2000 at Boston Children's Hospital was performed. Cumulative incident rates of major complications (defined by additional hospitalization, surgical or interventional radiology procedures) as well as time between PEG placement and major complications were evaluated using Kaplan-Meier survival analysis. Time to elective tube removal and patient mortality was also assessed. RESULTS: One hundred thirty-eight patients (59% [n = 82] boys [median age 22.5 months] [interquartile range, IQR 9-72.5], weight 9.2 kg [IQR 6.1-15.8]), underwent PEG placement during the study period and were followed at our hospital for a median of 4.98 years (IQR 1.5-8.7) years. Median time to elective tube removal was 10.2 years, with approximately half of the patients estimated to still have an indwelling enteral tube 10 years after placement. Fifteen patients (11%) had at least 1 major complication related to their gastrostomy tubes during the examined time period. The cumulative incidence of patients having a major complication was 15% (95% confidence interval 8.9-24.5) by 5.4 years. CONCLUSIONS: Children undergoing PEG placement have a long-term high risk of morbidity related to enteral tubes. Major complications can occur many years after PEG placement. Larger prospective studies may be useful to assess risk factors for PEG-related complications in pediatrics. PMID- 24177784 TI - Estimation of fish and omega-3 fatty acid intake in pediatric nonalcoholic fatty liver disease. AB - AIMS: Fish and omega-3 fatty acids are reported to be beneficial in pediatric nonalcoholic fatty liver disease (NAFLD), but no studies have assessed their relation to histological severity. The objectives of this study were to evaluate the dietary intake of fish and omega-3 fatty acids in children with biopsy-proven NAFLD, and examine their association with serological and histological indicators of disease. METHODS: This was a cross-sectional analysis of 223 children (6-18 years) who participated in the Treatment of Nonalcoholic Fatty Liver Disease in Children trial or the NAFLD Database study conducted by the Nonalcoholic Steatohepatitis Clinical Research Network. The distribution of fish and omega-3 fatty acid intake was determined from responses to the Block Brief 2000 Food Frequency Questionnaire, and analyzed for associations with serum alanine aminotransferase, histological features of fatty liver disease, and diagnosis of steatohepatitis after adjusting for demographic, anthropometric, and dietary variables. RESULTS: The minority of subjects consumed the recommended 8 ounces of fish per week (22/223 [10%]) and 200 mg of long-chain omega-3 fatty acids per day (12/223 [5%]). Lack of fish and long-chain omega-3 fatty acid intake was associated with greater portal (P = 0.03 and P = 0.10, respectively) and lobular inflammation (P = 0.09 and P = 0.004, respectively) after controlling for potential confounders. CONCLUSIONS: Fish and omega-3 fatty acid intake was insufficient in children with NAFLD, which may increase susceptibility to hepatic inflammation. Patients with pediatric NAFLD should be encouraged to consume the recommended amount of fish per week. PMID- 24177787 TI - A practical guide for the diagnosis of primary enteric nervous system disorders. AB - OBJECTIVE: Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders. In addition, we provide further commentary on the continuing controversies in the field. RESULTS: Although the diagnostic criteria for Hirschsprung disease are well established, those for other forms of dysganglionosis remain ill-defined. Appropriate tissue sampling, handling, and expert interpretation are crucial to maximize diagnostic accuracy and reduce interobserver variability. The absence of validated age-related normal values for neuronal density, along with the lack of correlation between clinical and histological findings, result in significant diagnostic uncertainties while diagnosing quantitative aberrations such as hypoganglionosis or ultrashort Hirschsprung disease. Intestinal neuronal dysplasia remains a histological description of unclear significance. CONCLUSIONS: The evaluation of cellular quantitative or qualitative abnormalities of the ENS for clinical diagnosis remains complex. Such analysis should be carried out in laboratories that have the necessary expertise and access to their own validated reference values. PMID- 24177788 TI - A prospective comparative study of haemodynamic, electrolyte, and metabolic changes during percutaneous nephrolithotomy and minimally invasive percutaneous nephrolithotomy. AB - OBJECTIVES: To report the haemodynamic, electrolyte, and metabolic changes of a prospective clinical trial comparing minimally invasive percutaneous nephrolithotomy (MPCNL) with percutaneous nephrolithotomy (PCNL) for renal stones. METHODS: In all, 71 patients who had undergone MPCNL (37) or PCNL (34) were prospectively assessed. Heart rate and arterial blood pressure were monitored, and samples for electrolyte estimation and arterial blood gas analysis were drawn at the start, 30th, 60th, 90th, and 120th min of irrigation and 24 h later after both procedures. RESULTS: In the PCNL group, no significant changes occurred in heart rate, arterial blood pressure, electrolytes, and pH. In the MPCNL group, heart rate, arterial blood pressure, and serum sodium levels kept stably during and after irrigation; the decrease in potassium levels was found from the 30th to 120th min of irrigation and did not recovery until 24 h later after operation (P < 0.05), but the potassium levels was normal during the entire observation period; the increase in Cl(-) levels was noted at the 120th min of irrigation (P < 0.05); there was a decreasing trend of pH from the start to the 120th min of irrigation (P < 0.05) and 24 h later after operation this trend attenuated (P < 0.05); the changes in base excess levels were in accordance with those in pH levels. CONCLUSIONS: Although haemodynamic and electrolyte changes remains stable, a trend towards metabolic acidosis is obvious as the irrigation time goes by during MPCNL compared with PCNL. Therefore, arterial blood gases should be monitored during and after MPCNL in patients with prolonged irrigation time. PMID- 24177789 TI - Simple one-pot regioselective 6-O-phosphorylation of carbohydrates and trehalose desymmetrization. AB - Biologically essential carbohydrate 6-phosphates, especially trehalose 6 phosphate, can be synthesized easily in excellent overall yields in 2 steps involving minimum protecting group manipulations. We can cleave the diphenylphosphate group for further synthetic objectives. PMID- 24177790 TI - Contrasting the microbiomes from healthy volunteers and patients with chronic rhinosinusitis. AB - IMPORTANCE: Chronic rhinosinusitis (CRS) is the persistent inflammation of the sinus and nasal passages lasting over 3 months. The etiology of CRS is not well understood. OBJECTIVE: To obtain insights into the disease process, we contrasted the microbiome and immune response from patients with CRS and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: A case vs control design was used. Samples were collected in the operating room in an institutional hospital or clinic. Thirty patients with CRS and 12 healthy controls undergoing surgery were recruited. MAIN OUTCOMES AND MEASURES: The microbiome was analyzed by deep sequencing of the bacterial 16S and fungal 18S ribosomal RNA genes. Immune response was measured by quantification of 30 different cytokines by multiplexed enzyme-linked immunosorbent assay, and immune cells in the lavage were identified by flow cytometry. The immune response of peripheral blood leukocytes to the lavage microbiota was assessed by interleukin (IL)-5 enzyme-linked immunospot assay. RESULTS: While quantitative increase in most bacterial and fungal species was observed in patients with CRS relative to controls, the microbiomes of patients with CRS were qualitatively similar to the controls. Because these results indicated that bacteria and fungi are not triggering CRS, we undertook a more detailed characterization of the immune response. Patients with CRS had increased levels of the following cytokines: IL-4, IL-5, IL-8, and IL-13, along with increased levels of eosinophils and basophils in the lavage. Importantly, peripheral blood leukocytes isolated from patients with CRS responded to control lavage samples (ie, to commensals) to produce IL-5. In contrast, the same lavage sample evoked no IL-5 production in leukocytes from healthy controls. CONCLUSIONS AND RELEVANCE: These findings support the theory that in some cases CRS results from an immune hyperresponsiveness to commensal organisms. PMID- 24177791 TI - Suppressible alleles in a wide domain regulatory gene in Aspergillus nidulans. AB - The areA gene of Aspergillus nidulans is a one of the better studied eukaryotic wide domain regulatory genes, necessary for the expression of most structural genes involved in the utilization of a wide variety of nitrogen sources (Arst and Cove 1973; Arst 1983). Here we report the isolation and properties of areA alleles suppressible by translational suppressors (Roberts et al. 1979). Thus we show formally that the areA gene specifies a protein rather than an RNA product and we show that it is possible to generate by external suppression areA gene products with modified properties. PMID- 24177792 TI - Regulation of two alcohol dehydrogenases in Aspergillus nidulans. AB - In Aspergillus nidulans there are two alcohol dehydrogenases. In the presence of ethanol, alcohol dehydrogenase I (AHH I) is induced and alcohol dehydrogenase II (ADH II) is repressed. ADH I and ADH II have molecular weights of 39,000 and 36,000 respectively. At least ADH I is under the control of alcR, a transacting regulatory gene that is adjacent to alcA (the structural gene for ADH I, Pateman et al. 1983). Mutations in the alcR regulatory gene result in non inducibility of ADH I specific mRNA. Extreme alcA and alcR mutations result in derepressed levels of ADH II, and it is not clear whether alcR controls ADH II directly or through its control of ADH I synthesis. Both enzymes are subject to carbon catabolite repression. Induction of ADH I and ADH II operates at the level of synthesis or processing of mRNA. PMID- 24177793 TI - Photoregulation of carotenogenesis in Phycomyces. AB - Mutants of Phycomyces defective in carotene regulation were studied in relation with the photo carotenogenic response. Quantitative complementation analyses revealed that carC, carA and carS mutations are recessive and complement for this photoresponse in carC * carA and carC * carS heterokaryons. A scheme of the regulation of carotenogenesis by light is proposed. PMID- 24177794 TI - Cloning of a yeast dihydrofolate reductase gene in Escherichia coli. AB - The dihydrofolate reductase gene of Saccharomyces cerevisiae has been isolated by selection of trimethoprim resistant Escherichia coli transformed with a gene bank of yeast DNA in plasmid pBR322. From 9.2 kilobase pair BamHI DNA fragment this gene has been localized to a 1.76 kb fragment, the restriction map of which appears different from those reported for the E. coli and the mouse dihydrofolate reductase genes.The enzyme encoded by the chimeric plasmid was established as yeast dihydrofolate reductase by its sensitivity to antifolates in vivo through growth studies and in vitro by enzyme assay. Since, the expression of this gene occurs independent of its orientation within the chimeric plasmid, the 1.76 kb fragment may contain functional regulatory sequences in addition to the structural sequences for yeast dihydrofolate reductase. PMID- 24177795 TI - Isolation of a selective marker from Cephalosporium acremonium by complementation of an auxotrophic mutant of E. coli. AB - A Cephalosoporium acremonium gene library has been constructed using cosmid vector pYcl. After transformation of E. coli leuB strain JA221 with cosmids isolated from this gene library a cosmid (pCeleuB43) was isolated which complements the leucine auxotrophy of JA221. The same cosmid is also able to complement a leu2 strain of S. cerevisiae. The leuB and leu2 genes both code for beta-isopropylmalate dehydrogenase. The complementation of a leuB E. coli strain and a leu2 S. cerevisiae strain strongly suggests that the analogous gene from C. acremonium has been isolated. PMID- 24177796 TI - Effect of ochre nonsense mutations on yeast URA1 mRNA stability. AB - The genetic map of 27 mutants of the URA1 yeast gene has been established by meiotic recombination and 16 nonsense mutations characterized. The half life of URA1 mRNA was determined by two independent methods in the wild-type and in two ochre mutants localized at each extremity of the genetic map. A halflife of 15 min was found for the wild-type and for one of the ochre mutants. This half-life was radically reduced in the other ochre mutant whereas the instantaneous rate of its mRNA synthesis remained constant. After subcloning various endonucleolytic fragments the coding sequence of the URA1 gene was restricted to a 1.65 kb fragment within a 5.7 kb yeast DNA segment. Direct visualization of the URA1 mRNA by Northern hybridization of denatured RNA with a URA1 specific DNA probe revealed a length of 1.5 kb. PMID- 24177797 TI - Physical mapping of genes for chloroplast DNA encoded subunit polypeptides of the ATPsynthase complex from Petunia hybrida. AB - Escherichia coli minicells harbouring the cloned restriction fragment Sall S9 from P. hybrida chloroplast DNA synthesize the beta and epsilon polypeptide subunits of the CF1 component of the chloroplast ATPsynthase complex. The polypeptides were identified by molecular weight determination and immunoprecipitation. The position of the atpB and the atpE gene, encoding respectively the beta and epsilon subunit, on the Sall S9 fragment was determined in more detail by studying polypeptide synthesis directed by subclones of the S9 fragment in E. coli minicells. The atpB and atpE genes are located close to the rbcL gene, the distance between the rbcL gene and atpB gene being approximately 770 bp. Analysis of the expression of subclones of the S9 fragment in E. coli minicells also revealed that the atpE gene can be transcribed and translated independently of the expression of the atpB gene.The location of the genes coding for the alpha subunit (atpA gene) and the proteolipid subunit III of CF0 (atpH) of the ATPsynthase complex on the physical map of P. hybrida cpDNA was determined by hybridization of restriction enzyme digests of petunia cpDNA with cloned cpDNA fragments from Spirodela and wheat, containing internal parts of respectively the atpA and the atpH gene. The two genes map close together within a region of 5.2 kbp on the physical map of P. hybrida cpDNA. The distance between the atpA gene and the atpB and atpE genes is approximately 42 kbp. PMID- 24177798 TI - A restriction endonuclease map of the chloroplast genome of pearl millet. AB - Chloroplast DNA from pearl millet (Pennisetum americanum) was used to construct recombinant plasmids. These plasmids contained 97 kilobase pairs of unique DNA sequences. The chloroplast DNA fragments in these plasmids were mapped with the restriction endonucleases SalI, SphI, XhoI, BglI and HpaI. The technique of overlapping hybridization or chromosome walking was used to orient these DNA fragments on a restriction endonuclease map of the chloroplast genome. The size of the chloroplast DNA from pearl millet was estimated in this fashion to be 127 138 kilobase pairs. Twenty one kilobase pairs of the cloned DNA fragments were represented twice on the genome as inverted repeats. Thus, the recombinant plasmids which were isolated contained approximately 86-93% of the nucleotide sequences in the chloroplast genome of pearl millet. Previously characterized cloned chloroplast DNA sequences from other plants were used as hybridization probes to locate the genes for the large subunit of ribulose 1,5-bisphosphate carboxylase, the beta-coupling factor of ATPase and the 32 kilodalton polypeptide of photo system 11 on the restriction endonuclease map of the pearl millet chloroplast genome. PMID- 24177799 TI - The mitochondrial plasmid of Podospora anserina: A mobile intron of a mitochondrial gene. AB - In the ascomycete Podospora anserina strain ageing (senescence) is caused by a mitochondrial plasmid. In juvenile mycelia it is an integral part of the mtDNA and becomes liberated during ageing. The nucleotide sequence of this plasmid and of its flanking regions was determined. It consists of 2,539 by and contains an un identified reading frame (URF) originating in the adjacent mtDNA upstream of excision point 1. Within the URF a putative 48 by autonomously replicating sequence (ars) was identified. At both excision sites of the plasmid there are two short nonidentical interrupted palindromes and a few base pairs apart from these palindromes, both upstream and downstream, two short inverted repeats are localised. The experimental data make it evident that the mt plasmid is an intron of the cytochrome c oxidase gene (subunit I) which may be excised at the DNA level and thus become the mobile infective agent causing senescence. The concept of this mobile intron and current hypotheses concerning the relationship between introns and transposons are stressed. PMID- 24177801 TI - Molecular heterogeneity in mitochondrial and chloroplast DNAs from normal and male sterile cytoplasms in sugar beets. AB - Mitochondrial (mt) and chloroplast (ct) DNAs were prepared from normal (N) and male sterile (S) cytoplasmic lines of sugar beet. The DNAs were cleaved with BamHI, EcoRI, HindIII and SalI enzymes, and the resultant fragments were fractionated by agarose gel electrophoresis. The results showed that N and S cytoplasms contained distinct mtDNA. Although most of the DNA fragments were common to these two cytoplasms, each cytoplasm was readily characterized by bands specific to that cytoplasm. In addition, these distinctive cleavage patterns were invariant in different nuclear backgrounds. In contrast to the marked variation in mtDNA, restriction fragment analyses of ctDNA demonstrated little difference between both cytoplasms. Only HindIII digestion showed one band missing in the S genome. The data presented here provides circumstantial evidence for mitochondrial involvement in the inheritance of cytoplasmic male sterility in sugar beet. PMID- 24177800 TI - A maturase-like coding sequence downstream of the OXI2 gene of yeast mitochondrial DNA is interrupted by two GC clusters and a putative end-of messenger signal. AB - By completing and correcting the sequence of a 1.8 kb DNA segment downstream of the oxi2 gene of Saccharomyces cerevisiae, a long, potentially coding sequence ("RF2") has been identified. The sequence is rather closely related to the RF1 open reading frame, downstream of the oxil gene, and, further, to the major family of intronic open reading frames. The RF2 open reading frame is not continuous, however, for it is interrupted by two GC clusters, both of which ultimately result in a -1 frameshift. Comparison with RF1 reveals a third insertion. This is centered on an oligo nucleotide, AATAATATTCTTA, which is found (sometimes in a slightly modified form) downstream of ten proven or suspected protein coding genes, including RF1 and RF2, and is known to terminate the apocytochrome b messenger RNA. It is suggested from the known distribution of this putative "end-of-messenger" signal, that it could play an essential part in controlling the expression of several minor proteins, both intronic and non intronic. The possibility of the RF2 sequence being functional in spite of its interruptions is also discussed. PMID- 24177802 TI - Isolation and characterization of mitochondrial DNA of the oomycetous fungus Phytophthora infestans. AB - Mitochondrial DNA (mtDNA) of Phytophthora infestans has been isolated and preliminarily characterized. It has a low GC content of about 22.4% which is distinctly different from that of nuclear DNA (51 %). This property has been used to separate both DNA species in the presence of 4',6-diamidine-2-phenylindole (DAPI) in CsCl density gradients. The use of cetyl triammonium bromide (CTAB) for extraction of DNA significantly reduced its degradation. The base distribution of the mtDNA shows a limited intramolecular heterogeneity. The molecule contains 36.2 +/- 0.3 kb as revealed by endonuclease digestion and seems to be circular as shown by restriction mapping. No differences were found in restriction patterns between mtDNAs from various pathotypes. PMID- 24177803 TI - An improved fluorogenic NAD(P)+ detection method using 2-acetylbenzofuran: its origin and application. AB - We have developed a fluorogenic NAD(P)(+) detection method using 2 acetylbenzofuran. The reaction of NAD(P)(+) with 2-acetylbenzofuran produced a fluorescent product, allowing the highly-sensitive and quick detection of NAD(P)(+). This method was successfully applied to the detection of P450 substrates in the microtiter-plate format. PMID- 24177805 TI - The Journal of Clinical Immunology: an international journal for primary immunodeficiencies and related human immunologic diseases. PMID- 24177804 TI - Intermittent neutropenia as an early feature of mild mevalonate kinase deficiency. AB - A 15-month-old boy, born to Iranian consanguineous parents presented with intermittent neutropenia interspersed with episodes of fever and leukocytosis since early infancy. No ELA2 mutations were found and the bone marrow study was normal. At age 4 years he progressed to more typical attacks of periodic attacks of fever, abdominal pain, oral aphthous ulcers, cutaneous rash and leukocytosis. The clinical and laboratory features were compatible with the mild form of mevalonate kinase deficiency, usually named "Hyper-IgD and periodic fever syndrome" (HIDS). Genomic sequencing of the mevalonate kinase (MVK) gene revealed homozygous missense mutation (p.Val377Ile). On demand dexamethasone resulted in a rapid amelioration of febrile episodes. The presentation of intermittent neutropenia has not been reported in HIDS and deserves more attention in large patient cohorts. PMID- 24177806 TI - Piezoelectric properties of zinc oxide nanowires: an ab initio study. AB - Nanowires made of materials with non-centrosymmetric crystal structures are expected to be ideal building blocks for self-powered nanodevices due to their piezoelectric properties, yet a controversial explanation of the effective operational mechanisms and size effects still delays their real exploitation. To solve this controversy, we propose a methodology based on DFT calculations of the response of nanostructures to external deformations that allows us to distinguish between the different (bulk and surface) contributions: we apply this scheme to evaluate the piezoelectric properties of ZnO [0001] nanowires, with a diameter up to 2.3 nm. Our results reveal that, while surface and confinement effects are negligible, effective strain energies, and thus the nanowire mechanical response, are dependent on size. Our unified approach allows for a proper definition of piezoelectric coefficients for nanostructures, and explains in a rigorous way the reason why nanowires are found to be more sensitive to mechanical deformation than the corresponding bulk material. PMID- 24177807 TI - Visual field progression with frequency-doubling matrix perimetry and standard automated perimetry in patients with glaucoma and in healthy controls. AB - IMPORTANCE: A new analysis method called permutation of pointwise linear regression measures the significance of deterioration over time at each visual field location, combines the significance values into an overall statistic, and then determines the likelihood of change in the visual field. Because the outcome is a single P value, individualized to that specific visual field and independent of the scale of the original measurement, the method is well suited for comparing techniques with different stimuli and scales. OBJECTIVE: To test the hypothesis that frequency-doubling matrix perimetry (FDT2) is more sensitive than standard automated perimetry (SAP) in identifying visual field progression in glaucoma. DESIGN, SETTING, AND PARTICIPANTS: Patients with open-angle glaucoma and healthy controls were examined by FDT2 and SAP, both with the 24-2 test pattern, on the same day at 6-month intervals in a longitudinal prospective study conducted in a hospital-based setting. Only participants with at least 5 examinations were included. INTERVENTION: Data were analyzed with permutation of pointwise linear regression. MAIN OUTCOME AND MEASURE: Permutation of pointwise linear regression is individualized to each participant, in contrast to current analyses in which the statistical significance is inferred from population-based approaches. Analyses were performed with both total deviation and pattern deviation. RESULTS: Sixty-four patients and 36 controls were included in the study. The median age, SAP mean deviation, and follow-up period were 65 years, -2.6 dB, and 5.4 years, respectively, in patients and 62 years, +0.4 dB, and 5.2 years, respectively, in controls. Using total deviation analyses, statistically significant deterioration was identified in 17% of patients with FDT2, in 34% of patients with SAP, and in 14% of patients with both techniques; in controls these percentages were 8% with FDT2, 31% with SAP, and 8% with both. Using pattern deviation analyses, statistically significant deterioration was identified in 16% of patients with FDT2, in 17% of patients with SAP, and in 3% of patients with both techniques; in controls these values were 3% with FDT2 and none with SAP. CONCLUSIONS AND RELEVANCE: No evidence was found that FDT2 is more sensitive than SAP in identifying visual field deterioration. In about one-third of healthy controls, age-related deterioration with SAP reached statistical significance. PMID- 24177808 TI - Temporal-spatial heterogeneity in animal-environment contact: implications for the exposure and transmission of pathogens. AB - Contact structure, a critical driver of infectious disease transmission, is not completely understood and characterized for environmentally transmitted pathogens. In this study, we assessed the effects of temporal and spatial heterogeneity in animal contact structures on the dynamics of environmentally transmitted pathogens. We used real-time animal position data to describe contact between animals and specific environmental areas used for feeding and watering calves. The generated contact structure varied across days and among animals. We integrated animal and environmental heterogeneity into an agent-based simulation model for Escherichia coli O157 environmental transmission in cattle to simulate four different scenarios with different environmental bacteria concentrations at different areas. The simulation results suggest heterogeneity in environmental contact structure among cattle influences pathogen prevalence and exposure associated with each environment. Our findings suggest that interventions that target environmental areas, even relatively small areas, with high bacterial concentration can result in effective mitigation of environmentally transmitted pathogens. PMID- 24177809 TI - Feasibility and preliminary results of SPECT/CT arthrography of the wrist in comparison with MR arthrography in patients with suspected ulnocarpal impaction. AB - PURPOSE: To evaluate the feasibility and performance of SPECT/CT arthrography of the wrist in comparison with MR arthrography in patients with suspected ulnocarpal impaction. METHODS: This prospective study included 28 wrists of 27 patients evaluated with SPECT/CT arthrography and MR arthrography. Iodine contrast medium and gadolinium were injected into the distal radioulnar and midcarpal joints. Late-phase SPECT/CT was performed 3.5 h after intravenous injection of approximately 650 MBq (99m)Tc-DPD. MR and SPECT/CT images were separately reviewed in relation to bone marrow oedema, radionuclide uptake, and tears in the scapholunate (SL) and lunotriquetral (LT) ligaments and triangular fibrocartilage complex (TFCC), and an overall diagnosis of ulnar impaction. MR, CT and SPECT/CT imaging findings were compared with each other, with the surgical findings in 12 patients and with clinical follow-up. RESULTS: The quality of MR arthrography and SPECT/CT arthrography images was fully diagnostic in 23 of 28 wrists (82%) and 25 of 28 wrists (89%), respectively. SPECT/CT arthrography was not diagnostic for ligament lesions due to insufficient intraarticular contrast in one wrist. MR and SPECT/CT images showed concordant findings regarding TFCC lesions in 22 of 27 wrists (81%), SL ligament in 22 of 27 wrists (81%) and LT ligament in 23 of 27 wrists (85%). Bone marrow oedema on MR images and scintigraphic uptake were concordant in 21 of 28 wrists (75%). MR images showed partial TFCC defects in four patients with normal SPECT/CT images. MR images showed bone marrow oedema in 4 of 28 wrists (14%) without scintigraphic uptake, and scintigraphic uptake was present without MR bone marrow oedema in three wrists (11%). Regarding diagnosis of ulnar impaction the concordance rate between CT and SPECT/CT was 100% and reached 96% (27 of 28) between MR and SPECT/CT arthrography. The sensitivity and specificity of MR, CT and SPECT/CT arthrography were 93%, 100% and 100%, and 93%, 93% and 93%, respectively. CONCLUSION: SPECT/CT arthrography of the wrist is feasible. Regarding diagnosis of ulnar impaction we found a high concordance with MR arthrography. SPECT/CT arthrography of the wrist is an alternative to MR arthrography in patients with contraindications to MR imaging. PMID- 24177810 TI - Comparative evaluation of CT-based and respiratory-gated PET/CT-based planning target volume (PTV) in the definition of radiation treatment planning in lung cancer: preliminary results. AB - PURPOSE: The aim of this study was to compare planning target volume (PTV) defined on respiratory-gated positron emission tomography (PET)/CT (RG-PET/CT) to PTV based on ungated free-breathing CT and to evaluate if RG-PET/CT can be useful to personalize PTV by tailoring the target volume to the lesion motion in lung cancer patients. METHODS: Thirteen lung cancer patients (six men, mean age 70.0 years, 1 small cell lung cancer, 12 non-small cell lung cancer) who were candidates for radiation therapy were prospectively enrolled and submitted to RG PET/CT. Ungated free-breathing CT images obtained during a PET/CT study were visually contoured by the radiation oncologist to define standard clinical target volumes (CTV1). Standard PTV (PTV1) resulted from CTV1 with the addition of 1-cm expansion of margins in all directions. RG-PET/CT images were contoured by the nuclear medicine physician and radiation oncologist according to a standardized institutional protocol for contouring gated images. Each CT and PET image of the patient's respiratory cycle phases was contoured to obtain the RG-CT-based CTV (CTV2) and the RG-PET/CT-based CTV (CTV3), respectively. RG-CT-based and RG PET/CT-based PTV (PTV2 and PTV3, respectively) were then derived from gated CTVs with a margin expansion of 7-8 mm in head to feet direction and 5 mm in anterior to posterior and left to right direction. The portions of gated PTV2 and PTV3 geometrically not encompassed in PTV1 (PTV2 out PTV1 and PTV3 out PTV1) were also calculated. RESULTS: Mean +/- SD CTV1, CTV2 and CTV3 were 30.5 +/- 33.2, 43.1 +/- 43.2 and 44.8 +/- 45.2 ml, respectively. CTV1 was significantly smaller than CTV2 and CTV3 (p = 0.017 and 0.009 with Student's t test, respectively). No significant difference was found between CTV2 and CTV3. Mean +/- SD of PTV1, PTV2 and PTV3 were 118.7 +/- 94.1, 93.8 +/- 80.2 and 97.0 +/- 83.9 ml, respectively. PTV1 was significantly larger than PTV2 and PTV3 (p = 0.038 and 0.043 with Student's t test, respectively). No significant difference was found between PTV2 and PTV3. Mean +/- SD values of PTV2 out PTV1 and PTV3 out PTV1 were 12.8 +/- 25.4 and 14.3 +/- 25.9 ml, respectively. The percentage values of PTV2 out PTV1 and PTV3 out PTV1 were not lower than 10 % of PTV1 in 6/13 cases (46.2 %) and than 20 % in 3/13 cases (23.1 %). CONCLUSION: Our preliminary data showed that RG PET/CT in lung cancer can affect not only the volume of PTV but also its shape, as demonstrated by the assessment of gated PTVs outside standard PTV. The use of a gating technique is thus crucial for better delineating PTV by tailoring the target volume to the lesion motion in lung cancer patients. PMID- 24177811 TI - Cloning by genetic complementation and restriction mapping of the yeast HEM1 gene coding for 5-aminolevulinate synthase. AB - We have cloned the structural gene HEM1 for 5-aminolevulinate (ALA) synthase from Saccharomyces cerevisiae by transformation and complementation of a yeast hem1-5 mutant which was previously shown to lack ALA synthase activity (Urban-Grimal and Labbe Bois 1981) and had no immunodetectable ALA synthase protein when tested with yeast ALA synthase antiserum. The gene was selected from a recombinant cosmid pool which contained wild-type yeast genomic DNA fragments of an average size of 40 kb. The cloned gene was identified by the restauration.of growth on a non fermentable carbon source without addition of exogenous ALA. Sub cloning of partial Sau3A digests and functional analysis by transformation allowed us to isolate three independent plasmids, each carrying a 6 kb yeast DNA fragment inserted in either orientation into the single BamHI site of the vector pHCG3 and able to complement hem1-5 mutation. Analysis of the three plasmids by restriction endonucleases showed that HEM1 is contained within a 2.9 kb fragment. The three corresponding yeast trans formants present a 1, 2.5 and 16 fold increase in ALA synthase activity as compared to the wild-type strain. The gene product immunodetected in the transformant yeast cells has identical size as the wild type yeast ALA synthase and its amount correlates well with the increase in ALA synthase activity. PMID- 24177812 TI - Plasmid cloning and expression of the E. coli polA (+) gene in S. cerevisiae. AB - The E. coli polA (+) gene has been subcloned from a specialised lambda transducing phage onto a low copy number plasmid. Plasmid-encoded DNA polymerase I was synthesised at 2 to 3 times the wild-type E. coli level, and was biochemically indistinguishable from chromosomally-encoded protein. It was able to counteract the radio sensitivity of polA1, polAex1, polAex2 and polA12 mutants, but no complementation of polA107 mutants occurred, even though the plasmid polA(+) gene was expressed. S. cerevisiae ars-1 or 2 MU replicative sequences were introduced into the polA(+) plasmid. Transformation of yeast with these constructs increased total DNA polymerase levels 2-20 times, depending upon assay conditions. The additional activity was discriminated from yeast DNA polymerases by its ability to use low concentrations of substrate, by its resistance to chemical inhibition, and by co-electrophoresis with pure DNA polymerase I and its proteolytic fragments. The polA(+) gene was expressed in yeast without the aid of yeast promotor sequences. However, deletion of cloned DNA more than 99 base pairs in front of the structural gene prevented expression in yeast but not in E. coli, indicating that the two organisms use different sequences for expression of the plasmid polA(+) gene. PMID- 24177813 TI - Rapid genetic test for discrimination between haploid and polyploid transformants in Saccharomyces. AB - Spheroplast fusion induced by polyethylene glycol often occurs during transformation of yeast spheroplasts. It leads to the appearance of polyploid transformants. We have developed a method of discriminating between haploid and polyploid transformants, based on qualitative comparison of the frequency of mitotic homozygotization for a recessive marker, lys2, in diploid and polyploid hybrids of transformants crossed with a tester haploid bearing lys2.We have used this method to compare the frequency of appearance of polyploids during transformations of spheroplasts and of intact cells using lithium chloride in the strain DC5. Polyploids constitute from 15% to 74% of transformants after transformation of spheroplasts. In lithium chloride transformation polyploids arose in only one of four experiments and constituted 9% of transformants. PMID- 24177814 TI - Instability of Saccharomyces cerevisiae heterokaryons. AB - We have constructed heterokaryons of Saccharomyces cerevisiae by crossing kar1 - mutants incapable of nuclear fusion. Approximately 1% of the total zygotes from kar1 - crosses can form heterokaryotic clones. These are very small as compared to diploid colonies, and are composed mainly of a mixture of both types of heteroplasmons (cells which contain the cytoplasmic components of both parents, but the nuclear genotype of only one of them). This fact indicates that heterokaryons are unstable.This instability is already observed by pedigree analysis in the first zygotic divisions. We suggest that missegregation is the main factor in heterokaryon instability and results from an unequal nuclear transmission, which occurs when one of the mother nuclei divides and, although viable, does not migrate to the daughter bud. However, the proportion of inviable zygotes and buds found in the pedigree analysis, as well as the recovery of only one type of heteroplasmon, indicates the complete loss of one of the parental nuclei. Consequently nuclear inactivation is suggested as the second reason for heterokaryon instability. PMID- 24177815 TI - Hygromycin B resistance as dominant selectable marker in yeast. AB - Saccharomyces cerevisiae is normally sensitive to the drug hygromycin B; a hygromycin B concentration of 200 ug/ml in agar plates is sufficient to completely inhibit growth. We constructed yeast-E. coli bifunctional plasmids which confer hygromycin B resistance to Saccharomyces cerevisiae. Promoters and amino terminal coding regions of a heat shock gene, a heat shock cognate gene, and the phosphoglycerate kinase gene from yeast were fused to a bacterial hygromycin B resistance gene. In all three cases, yeast cells containing plasmids with the hybrid hygromycin B resistance gene were resistant to high levels of the drug. Yeast cells containing these plasmids can also be directly selected after transformation by using hygromycin B. The intact bacterial hygromycin B resistance gene and the kanamycin resistance gene from Tn903 were also tested in yeast for their ability to confer resistance to hygromycin B and G418. The intact bacterial genes were not effective in conferring drug resistance to yeast cells. PMID- 24177816 TI - The localization and orientation of specific genes in the chloroplast chromosome of Vicia faba. AB - The genes for six chloroplast polypeptides have been localized on the map of Vicia faba chloroplast DNA using heterologous probes. These include the three subunits (alpha, beta, epsilon) of CF1 of ATP synthase, subunit III of CF0 from ATP synthase, the 32 kilodalton thylakoidal membrane protein of photosystem II and cytochrome f of the electron transport chain. The direction of transcription has been determined for the three subunits of CF1 and the 32 kilodalton thylakoidal protein. The physical map of the chloroplast DNA has also been expanded to include Sma1 sites in addition to previously mapped restriction enzyme sites. Finally, the genetic arrangement of Vicia faba chloroplast DNA was compared to other known genetic maps. PMID- 24177817 TI - Mutations in a nuclear gene of Chlamydomonas cause the loss of two chloroplast ribosomal proteins, one synthesized in the chloroplast and the other in the cytoplasm. AB - The allelic nuclear mutations of Chlamydomonas reinhardtii, cr-6 and cr-7, result in the loss of two proteins from the large subunit of the chloroplast ribosome. One of these proteins, L-13, is synthesized in the chloroplast and the other, L29, is made in the cytoplasm. The loss of these two proteins is correlated with the inability of the large subunits of the chloroplast ribosomes to form monomers which incorporate labeled phenylalanine at normal rates in response to a polyuridylic acid template. Using antisera raised against L13 and L29, we found that protein L-13 was synthesized in appreciable amounts in pulse labeled cells of cr-6 and cr-7, but protein L-29 was not. We conclude that the inability to synthesize protein L29 is a primary defect in both cr-6 and cr-7 and that this protein is required for the stable assembly of protein L-13 into chloroplast ribosomes. The absence of one or both of these proteins from the large subunit of chloroplast ribosomes of the mutants interferes with the ability of the small and large subunits to associate properly into normal 70S monomers. PMID- 24177818 TI - Transfer RNAs and tRNA genes of Vicia faba chloroplasts. AB - Isolated chloroplasts from broad bean and common bean were found to contain a minimum of 31 and 32 tRNA species, respectively. These individual chloroplast tRNAs were (32)P-labeled in vitro and hybridized to DNA fragments obtained upon digestion of broad bean and common bean chloroplast DNAs with various restriction endonucleases. At least 30 tRNA genes were localized on the physical maps of the two chloroplast genomes. Comparison of the broad bean tRNA gene map to that of common bean revealed DNA sequence rearrangements, such as inversions, insertions/ deletions and duplications, within these two members of the Legu minosae family. PMID- 24177819 TI - Unstable cytoplasms in Hawaiian strains of Neurospora intermedia. AB - By subjecting a large sample of natural isolates of N. intermedia to prolonged serial subculturing, 26 cytoplasmic variants have been identified. These variants show senescence, and finally death at some strain-specific point in the subculture series. All senescent strains are from the Hawaiian archipelago, where their incidence in natural populations is high. Senescent cultures can be female fertile. Random ascospore analyses show that (i) senescence is maternally inherited; (ii) different stages of senescence give different proportions of senescent progeny; and (iii) ascospores from one cross show different degrees of senescence. These results indicate that senescence is determined by a genetic factor which re sides in the cytoplasm. This factor promotes instability of the cytoplasm, resulting initially in cytoplasmic heterogeneity shown by ascus and conidium sampling, and finally in death. Molecular studies to be published elsewhere show that the progression through senescence to death is correlated with the occurence of abnormalities in cytochrome content and mitochondrial DNA. The Hawaiian word kalilo (dying), symbolised [kal], is proposed to denote these cytoplasms. PMID- 24177820 TI - A RFLP linkage map of Sorghum bicolor (L.) Moench. AB - A RFLP linkage map of sorghum composed principally of markers detected with sorghum low-copy-number nuclear DNA clones has been constructed. The map spans 1789 cMs and consists of 190 loci grouped into 14 linkage groups. The 10 largest linkage groups consist of from 10 to 24 markers and from 103 to 237 cMs, and the other 4 linkage groups consist of from 2 to 5 markers and from 7 to 62 cMs. The map was derived in Sorghum bicolor ssp. bicolor by analysis of a F2 population composed of 50 plants derived from a cross of IS 3620C, a guinea line, and BTx 623, an agronomically important inbred line derived from a cross between a zera zera (a caudatum-like sorghum) and an established kafir line. The restriction fragment length polymorphism (RFLP) frequency detected in this population using polymerase chain reaction (PCR)-amplifiable low-copy-number sorghum clones and five restriction enzymes was 51%. A minimal estimate of the number of clones that detect duplicate sequences is 11 %. Null alleles occurred at 13% of the mapped RFLP loci. PMID- 24177821 TI - Inheritance of black sigatoka disease resistance in plantain-banana (Musa spp.) hybrids. AB - Black sigatoka (Mycosphaerella fijiensis Morelet), an airborne fungal leaf-spot disease, is a major constraint to plantain and banana (Musa spp.) production world-wide. Gaining further knowledge of the genetics of host-plant resistance will enhance the development of resistant cultivars, which is considered to be the most appropriate means to achieve stable production. Genetic analysis was conducted on 101 euploid (2x, 3x and 4x) progenies, obtained from crossing two susceptible triploid plantain cultivars with the resistant wild diploid banana 'Calcutta 4'. Segregating progenies, and a susceptible reference plantain cultivar, were evaluated over 2 consecutive years. Three distinct levels of host response to black sigatoka were defined as follows: susceptible (< 8 leaves without spots), less susceptible (8-10) and partially resistant (> 10). Segregation ratios for resistance at the 2x level fitted a genetic model having one major recessive resistance allele (bs 1) and two independent alleles with additive effects (bsr 2 and bsr 3). A similar model explains the results at the 4x level assuming that the favourable resistance alleles have a dosage effect when four copies of them are present in their respective loci (bs i (4) ). The proposed model was further validated by segregation data of S 1 progenies. Mechanisms of black sigatoka resistance are discussed in relation to the genetic model. PMID- 24177822 TI - Analysis of cytoplasmic and maternal effects I. A genetic model for diploid plant seeds and animals. AB - A genetic model for modified diallel crosses is proposed for estimating variance and covariance components of cytoplasmic, maternal additive and dominance effects, as well as direct additive and dominance effects. Monte Carlo simulations were conducted to compare the efficiencies of minimum norm quadratic unbiased estimation (MINQUE) methods. For both balanced and unbalanced mating designs, MINQUE (0/1), which has 0 for all the prior covariances and 1 for all the prior variances, has similar efficiency to MINQUE(theta), which has parameter values for the prior values. Unbiased estimates of variance and covariance components and their sampling variances could be obtained with MINQUE(0/1) and jackknifing. A t-test following jackknifing is applicable to test hypotheses for zero variance and covariance components. The genetic model is robust for estimating variance and covariance components under several situations of no specific effects. A MINQUE(0/1) procedure is suggested for unbiased estimation of covariance components between two traits with equal design matrices. Methods of unbiased prediction for random genetic effects are discussed. A linear unbiased prediction (LUP) method is shown to be efficient for the genetic model. An example is given for a demonstration of estimating variance and covariance components and predicting genetic effects. PMID- 24177823 TI - Analysis of cytoplasmic and maternal effects. II. Genetic models for triploid endosperms. AB - Genetic models for quantitative traits of triploid endosperms are proposed for the analysis of direct gene effects, cytoplasmic effects, and maternal gene effects. The maternal effect is partitioned into maternal additive and dominance components. In the full genetic model, the direct effect is partitioned into direct additive and dominance components and high-order dominance component, which are the cumulative effects of three-allele interactions. If the high-order dominance effects are of no importance, a reduced genetic model can be used. Monte Carlo simulations were conducted in this study for demonstrating unbiasedness of estimated variance and covariance components from the MINQUE (0/1) procedure, which is a minimum norm quadratic unbiased estimation (MINQUE) method setting 0 for all the prior covariances and 1 for all the prior variances. Robustness of estimating variance and covariance components for the genetic models was tested by simulations. Both full and reduced genetic models are shown to be robust for estimating variance and covariance components under several situations of no specific effects. Efficiency of predicting random genetic effects for the genetic models by the MINQUE (0/1) procedure was compared with the best linear unbiased prediction (BLUP). A worked example is given to illustrate the use of the reduced genetic model for kernel growth characteristics in corn (Zea mays L.). PMID- 24177824 TI - Molecular genetics of growth and development in Populus. III. A genetic linkage map of a hybrid poplar composed of RFLP, STS, and RAPD markers. AB - We have evaluated three DNA-based marker types for linkage map construction in Populus: RFLPs detected by Southern blot hybridization, STSs detected by a combination of PCR and RFLP analysis, and RAPDs. The mapping pedigree consists of three generations, with the F1 produced by interspecific hybridization between a P. trichocarpa female and a P. deltoides male. The F2 generation was made by inbreeding to the maximum degree permitted by the dioecious mating system of Populus. The applicability of STSs and RAPDs outside the mapping pedigree has been investigated, showing that these PCR-based marker systems are well-suited to breeding designs involving interspecific hybridization. A Populus genome map (343 markers) has been constructed from a combination of all three types. The length of the Populus genome is estimated to be 2400-2800 cM. PMID- 24177825 TI - Waxy protein deficiency and chromosomal location of coding genes in common wheat. AB - Deficiency of the wheat waxy (Wx) proteins (Wx-A1, Wx-B1 and Wx-D1) was studied in 1,960 cultivars derived from several countries. Gel electrophoretic analyses revealed that the null allele for the Wx-A1 protein occurred frequently in Korean, Japanese and Turkish wheats but was relatively rare in cultivars from other countries and regions. About 48% of the wheats deficient for the Wx-B1 protein were from Australia and India. One Chinese cultivar lacked the WxD1 protein. While 9 Japanese cultivars were deficient in both the Wx-A1 and Wx-B1 proteins, no cultivars lacked both the Wx-A1 and Wx-D1 proteins, both the Wx-B1 and Wx-D1 proteins or all three Wx proteins. Two-dimensional gel electrophoresis revealed polymorphisms of the three Wx proteins that varied according to isoelectric points or molecular weight. The Wx-A1 gene coding the Wx-A1 protein and the Wx-B1 gene coding the Wx-B1 protein were localized in the distal regions of chromosome arms 7AS and 4AL, respectively, by deletion mapping using the deletion lines developed in the common wheat cultivar 'Chinese Spring'. PMID- 24177826 TI - A diallel analysis of heterosis in elite hybrid rice based on RFLPs and microsatellites. AB - Hybrid rice has contributed significantly to the dramatic increase of rice production in the world. Despite this, little attention has been given to studying the genetic basis of heterosis in rice. In this paper, we report a diallel analysis of heterosis using two classes of molecular markers: restriction fragment length polymorphisms, (RFLPs) and microsatellites. Eight lines, which represent a significant portion of hybrid rice germ plasm, were crossed in all possible pairs, and the F1s were evaluated for yield and yield component traits in a replicated field trial. The parental lines were surveyed for polymorphisms with 117 RFLP probes and ten microsatellites, resulting in a total of 76 polymorphic markers well-spaced in the rice RFLP map. The results indicated that high level heterosis is common among these crosses: more than 100% midparent and 40% better-parent heterosis were observed in many F1s, including some crosses between maintainer lines. Heterosis was found to be much higher for yield than for yield component traits, which fits a multiplicative model almost perfectly. Between 16 and 30 marker loci (positive markers) detected highly significant effects on yield or its component traits. Heterozygosity was significantly correlated with several attributes of performance and heterosis. Correlations based on positive markers (specific heterozygosity) were large for midparent heterosis of yield and seeds/panicle and also for F1 kernel weight. These large correlations may have practical utility for predicting heterosis. PMID- 24177827 TI - Induced diploid gynogenesis and polyploidy in the ornamental (koi) carp, Cyprinus carpio L. : 4. Comparative study on the effects of high- and low-temperature shocks. AB - The effects of high- and low-temperature shock treatments, applied at different phases of the 2nd meiotic division within the limits of 0.05-0.60 tau0 (tau0 = relative unit of embryological age) in order to induce gynogenesis in the common carp, were studied. A remarkable difference in the effect of two temperature treatments applied at the same biological age after insemination (expressed in tau0) was revealed. The curves of embryo survival and diploid gynogenetic larva output showed a bimodal response in cold-shocked gynogenetic progenies, with the highest level of diploid larva output at the periods 0.05-0.10 tau0 and 0.30-0.40 tau0 (after insemination), separated by a period of high sensitivity to cold shock (0.15-0.25 tau0). In contrast to this, the curves of embryo survival and diploid gynogenetic larva output showed a single, narrow, peak corresponding to 0.15-0.25 tau0 in heat-shocked gynogenetic progenies. The results obtained are in general accord with those of previous experiments on induced gynogenesis and triploidy in common carp, in which either cold- or heat-shock was used. PMID- 24177828 TI - A simple derivation of the partitioning of genetic differentiation within subdivided populations. AB - The genetic differentiation [Formula: see text] within a subdivided population can be partitioned into two proportions, one due to differentiation within sub populations and the other due to differentiation among subpopulations. A simple mathematical derivation of this procedure, known as Nei's G ST -statistics, is presented. The significance of considering the differing relative sizes of subpopulations is stressed. Possible fields of applications for breeders and conservationists who are concerned with the establishment of genetically diverse populations are mentioned. PMID- 24177829 TI - Identification of self-incompatibility-related glycoproteins in styles of apple (Malus x domestica). AB - In this study, stylar proteins of apple (Malus x domestica) which correlate with known intervarietal incompatibility relationships and have similar characteristics to the S-glycoproteins of Japanese pear (Pyrus serotina) were surveyed by two-dimensional gel electrophoresis (2D-PAGE). Varietal differences were detected in a group of glycoproteins having Mrs and pIs similar to those of the S-glycoproteins of Japanese pear. 2D-PAGE profiles of these glycoproteins were correlated with intervarietal incompatibility relationships. These glycoproteins reacted with antiserum raised against the S (4)-glycoprotein of Japanese pear, a result suggesting that they may be the products of S-alleles in styles of apple. On the basis of the profiles of the putative S-glycoproteins, S genotypes were proposed for each of the apple cultivars examined. PMID- 24177830 TI - Inheritance of mitochondrial DNA in lentil (Lens culinaris Medik.). AB - Restriction fragment analysis was used to examine the inheritance of lentil mitochondrial DNA (mtDNA) in F1 and F5 progeny from intrasubspecific (Lens culinaris ssp. culinaris) crosses and in F1 progeny from intersubspecific (Lens culinaris ssp. orientalis x L. culinaris ssp. culinaris) crosses. Southern blots of digested parental and progeny DNA were hybridized to heterologous maize mtDNA probes specific to coxI and atp6 genes. Two restriction fragment polymorphisms separated L.c. ssp. culinaris 'Laird' and 'Eston' from L.c. ssp. culinaris 'ILL5588', and one restriction fragment polymorphism distinguished L.c. ssp. culinaris 'Laird' and 'Eston' from L.c. ssp. orientalis 'LO4'. Twelve of 13 f1 progeny and all F5 progeny from the intrasubspecific crosses, and all F1 progeny from intersubspecific crosses had only maternal mtDNA restriction fragments. One f1 plant from an 'Eston' x 'ILL5588' cross inherited mtDNA fragments from both parents. Nuclear DNA inheritance was biparental in all F1 progeny. PMID- 24177831 TI - Crossover distribution in barley analysed through RFLP linkage data. AB - The pattern of recombination in barley with regard to (1) the distribution of crossover points among whole gametes, (2) the distribution of crossover points among individual chromosomes and (3) the distribution of crossover points within chromosomes has been analysed using data sets underlying two recently published restriction fragment length polymorphism (RFLP) linkage maps representing male and female meiosis, respectively. The data indicated that the process of recombination had been random with no interference. The two data sets gave similar results, indicating that male and female meiosis in barley do no differ significantly. The possibility of using RFLP data in studies of crossover distribution is stressed. PMID- 24177832 TI - Characterization of a family of tandemly repeated DNA sequences in Triticeae. AB - The recombinant plasmid dpTa1 has an insert of relic wheat DNA that represents a family of tandemly organized DNA sequences with a monomeric length of approximately 340 bp. This insert was used to investigate the structural organization of this element in the genomes of 58 species within the tribe Triticeae and in 7 species representing other tribes of the Poaceae. The main characteristic of the genomic organization of dpTa1 is a classical ladder-type pattern which is typical for tandemly organized sequences. The dpTa1 sequence is present in all of the genomes of the Triticeae species examined and in 1 species from a closely related tribe (Bromus inermis, Bromeae). DNA from Hordelymus europaeus (Triticeae) did not hybridize under the standard conditions used in this study. Prolonged exposure was necessary to obtain a weak signal. Our data suggest that the dpTa1 family is quite old in evolutionary terms, probably more ancient than the tribe Triticeae. The dpTa1 sequence is more abundant in the D genome of wheat than in other genomes in Triticeae. DNA from several species also have bands in addition to the tandem repeats. The dpTa1 sequence contains short direct and inverted subrepeats and is homologous to a tandemly repeated DNA sequence from Hordeum chilense. PMID- 24177833 TI - An unusual polymorphic locus useful for tagging Rps1 resistance alleles in soybean. AB - The Phytophthora root and stem resistance locus Rps1 has been mapped to linkage group N of the USDA-ARS soybean molecular map, approximately 2 cM from locus A071 1. To determine if A071-1 polymorphisms exist that distinguish and tag different Rps1 alleles, germplasms containing the seven Rps1 alleles were screened with eight enzymes for pA071-detectable polymorphisms. Six enzymes revealed at least one polymorphic fragment. All six detected a polymorphism at A071-1 as determined by restriction fragment length polymorphism mapping, comparison to an EMBL3 clone containing locus A071-1, and Southern hybridization with probes specific for locus A071-1. Screening of the Rps1 donors and 24 Rps1-and 15 Rps1-containing U.S. soybean varieties showed that locus A071-1 exhibited three polymorphisms with each enzyme. The polymorphisms detected by one enyme did not always correlate with those detected by the other four, suggesting that multiple mutation events may be responsible for the different A071-1 polymorphisms. Although no combination of alleles distinguished Rps1-and Rps1-containing genotypes, polymorphism at A071-1 made it possible to distinguish five groups of soybean germplasms. Thus, the unusual polymorphism of locus A071-1 should useful for following Rps1 inheritance in many breeding programs. PMID- 24177834 TI - Comparisons of methods for introgressing exotic germ plasm into adapted sorghum. AB - The incorporation of exotic germ plasm into breeding populations can broaden and diversify the genetic base of adapted genotypes. To more effectively utilize the genetic resources existing in Sorghum bicolor (L.) Moench, a rapid and efficient method of incorporating exotic genotypes into adapted populations is needed. Therefore, this study was conducted to compare the effectiveness of backcrossing to a broad-based population versus backcrossing to an inbred line for developing improved lines from adapted x exotic crosses. A wild sorghum, a cultivated landrace, and a converted sorghum line were crossed to an inbred line (CK60) and a broad-based population (KP9B). After two generations of backcrossing to the respective adapted parent, 50 F2 lines were derived from each of the backcross generations of every mating and evaluated at three test environments. Backcrossing to an inbred line (CK60) gave fewer high-yielding segregates and generated less genetic variation than backcrossing to a population (KP9B). Also, the number of agronomically acceptable lines derived from each CK60 mating was fewer than that derived from the corresponding mating with KP9B. Overall, the use of a broad-based population as an adapted recurrent parent for introgressing exotic genotypes may provide good opportunities for developing suitable inbred lines from adapted x exotic backcrosses. PMID- 24177835 TI - Localization of translocation breakpoints in somatic metaphase chromosomes of barley. AB - Karyotype analyses based on staining by acetocarmine followed by Giemsa N-banding of somatic metaphase chromosomes of Hordeum vulgare L. were carried out on 61 reciprocal translocations induced by X-irradiation. By means of computer-based karyotype analyses all of the 122 breakpoints could be localized to defined sites or segments distributed over the seven barley chromosomes. The pre-definition of translocations with respect to their rearranged chromosome arms from other studies rendered it possible to define the break positions even in translocations having exchanged segments equal in size and the breakpoints located distally to any Giemsa band or other cytological marker. The breakpoints were found to be non randomly spaced along the chromosomes and their arms. All breaks but one occurred in interband regions of the chromosomes, and none of the breaks was located directly within a centromere. However, short and long chromosome arms recombined at random. An improved tester set of translocations depicting the known break positions of most distal location is presented. PMID- 24177836 TI - Genetic constitution of germ cells in intervarietal and interspecific chimeras of Brassica induced by in-vitro grafting. AB - The characteristics of intervarietal and interspecific chimeras synthesized by the graft-culture method were determined by morphology, anthocyanin pigmentation pattern, and crossing. In an intervarietal chimera between 'YR-ranpou' (green cabbage) and 'Ruby ball' (red cabbage) in Brassica oleracea, a segregation phenomenon was noted in which seeds giving rise to purple and green plants were both produced in a single capsule in F1 progeny from crosses of chimeras with YR ranpou, the anthocyanin-free graft partner type. The degrees of segregation varied, reflecting the structure of the chimeras. YR ranpou-dominant chimeras produced capsules in which seeds gave rise to green plants at a high frequency, while Ruby ball-dominant chimeras produced capsules in which seeds in one capsule gave rise to purple plants at a high frequency. Mixed chimeras produced capsules with green plants or purple plants more regularly than did other chimeral types. Furthermore, a chimeral type in which seeds gave rise to green and purple plants was found in 3.2% of the total crosses. Segregation patterns in the progenies corresponded with the chimeral types. Chlorophyll-deficient variation (resulting in variegation or the production of albino plants) was found at a frequency of 2.6%. These results show that chimeric tissues are actually in a mixed state and that either the ovary develops from more than two cells or else that variation occurs in the germ-cell layer. In interspecific chimeras between Ruby ball and Komatsuna (B. campestris) various types of chimeras generally showed low pollen fertility, few capsules, and low seed-setting. Progenies from selves (geitonogamy), open crosses and crosses with the two parental species produce a predominantly homogeneous genotype showing either the Ruby ball or the Komatsuna type. Only two crosses produced four interspecific hybrids which expressed variations in their morphological and isozymic characters. PMID- 24177837 TI - Determination of the frequency of wheat-rye chromosome pairing in wheat x rye hybrids with and without chromosome 5B. AB - Genomic in-situ hybridization (GISH) was used to determine the amount of wheat rye chromosome pairing in wheat (Triticum aestivum) x rye (Secale cereale) hybrids having chromosome 5B present, absent, or replaced by an extra dose of chromosome 5D. The levels of overall chromosome pairing were similar to those reported earlier but the levels of wheat-rye pairing were higher than earlier determinations using C-banding. Significant differences in chromosome pairing were found between the three genotypes studied. Both of the chromosome-5B deficient hybrid genotypes showed much higher pairing than the euploid wheat hybrid. However, the 5B-deficient hybrid carrying an extra chromosome 5D had significantly less wheat-rye pairing than the simple 5B-deficient genotype, indicating the presence of a suppressing factor on chromosome 5D. Non homologous/non-homoeologous chromosome pairing was observed in all three hybrid genotypes. The value of GISH for assessing the level of wheat-alien chromosome pairing in wheat/alien hybrids and the effectiveness of wheat genotypes that affect homoeologous chromosome pairing is demonstrated. PMID- 24177838 TI - Estimation of sampling variance of molecular marker data using the bootstrap procedure. AB - Knowledge of genetic relationships among genotypes is useful in a plant breeding program because it permits the organization of germplasm and provides for more efficient sampling. The genetic distance (GD) among genotypes can be estimated using random restriction fragment length polymorphisms (RFLPs) as molecular markers. Knowledge of the sampling variance associated with RFLP markers is needed to determine how many markers are required for a given level of precision in the estimate of GD. The sampling variance for GD among all pairs of 37 maize (Z. mays L.) inbred lines was estimated from 1202 RFLPs. The 1202 polymorphisms were generated from 251 enzyme-probe combinations (EPC). The sampling variance was used to determine how large a sample of RFLPs was required to provide a given level of precision. The coefficient of variation (CV) associated with GD has a nearly linear relationship between its expected standard deviation and mean. The magnitude of the decrease in the mean CV for GD with increasing numbers of bands was dependent upon the sampling unit; e.g., individual polymorphic bands vs EPC, and the degree of relatedness among the inbreds compared. The rate of reduction in mean CV with increasing sample size was the same regardless of the restriction enzyme used, BamHI, EcoRI or HindIII, when the bootstrap sampling units were individual polymorphic bands. In constrast, although the rate of reduction (slopes) was the same, the intercepts of the mean CVs were different when EPCs were used as the bootstrap sampling unit. This difference was due to the higher number of bands per EPC in BamHI (4.94) compared with EcoRI (4.83) and HindIII (4.63). PMID- 24177839 TI - A study of genetic variation and evolution of Phyllostachys (Bambusoideae: Poaceae) using nuclear restriction fragment length polymorphisms. AB - Phylogenetic and taxonomic difficulties are common within the woody bamboos, due to their unique life cycle, which severely limits the availability of floral characters. To addresss some of these problems, 20 species of woody bamboos in the genus Phyllostachys were analyzed using nuclear restriction fragment length polymorphisms (RFLPs). The RFLP data were used to generate genetic distances between all pairs of taxa and to examine the degree of genetic variation within and among bamboo species. The genetic distances were also used to create dendrograms of accessions and species. These trees supported the current division of the genus into two sections and provided some information on the thorny taxonomic problems in this group. We show that RFLPs can be used for species identification and the delineation of species limits. PMID- 24177840 TI - Molecular evidence for the hybrid origin of Paulownia Taiwaniana based on RAPD markers and RFLP of chloroplast DNA. AB - Genomic DNA of Paulownia fortunei, P. kawakamii and P. taiwaniana were amplified with 10-base primers of arbitrary sequences using the polymerase chain reaction (PCR). A total of 351 DNA fragments were amplified from 23 primers and of these 265 fragments (75.5%) were polymorphic. Almost all of the PCR-amplified products of P. taiwaniana were shared by either P. fortunei or P. kawakamii, or both, and the number of polymorphic fragments shared by P. taiwaniana and P. fortunei was about equivalent to those shared by P. taiwaniana and P. kawakamii. Restriction fragments of chloroplast DNA (cpDNA) purified from Paulownia species and from reciprocal crosses between P. fortunei and P. kawakamii were analyzed. Restriction enzyme SalI-digested cpDNA showed an identical pattern in both P. kawakamii and P. taiwaniana. These results further support the hypothesis that P. taiwaniana is the natural hybrid between P. fortunei and P. kawakamii and that the maternal parent of P. taiwaniana is P. kawakamii. PMID- 24177841 TI - Genetic control of amylose content in wheat endosperm starch and differential effects of three Wx genes. AB - The endosperm starch of the wheat grain is composed of amylose and amylopectin. Genetic manipulation of the ratio of amylose to amylopectin or the amylose content could bring about improved texture and quality of wheat flour. The chromosomal locations of genes affecting amylose content were investigated using a monosomic series of Chinese Spring (CS) and a set of Cheyenne (CNN) chromosome substitution lines in the CS genetic background. Trials over three seasons revealed that a decrease in amylose content occurred in monosomic 4A and an increase in monosomic 7B. Allelic variation between CS and CNN was suggested for the genes on chromosomes 4A and 7B. To examine the effects of three Waxy (Wx) genes which encode a granule-bound starch synthase (Wx protein), the Wx proteins from CS monosomics of interest were analyzed using SDS-PAGE. The amount of the Wx protein coded by the Wx-B1 gene on chromosome arm 4AL was reduced in monosomic 4A, and thus accounted for its decreased amylose content. The amounts of two other Wx proteins coded by the Wx-A1 and Wx-D1 genes on chromosome arms 7AS and 7DS, respectively, showed low levels of protein in the monosomics but no effect on amylose content. The effect of chromosome 7B on the level of amylose suggested the presence of a regulator gene which suppresses the activities of the Wx genes. PMID- 24177842 TI - Induced diploid gynogenesis and polyploidy in the ornamental (koi) carp Cyprinus carpio L. : 3. Optimization of heat-shock timing during the 2nd meiotic division and the 1st cleavage. AB - The results of a series of experiments conducted in our laboratory on the ornamental common carp (koi), aimed at optimizing heat-shock chromosome-set manipulation procedures, are described. The timing of heat-shock initiation was expressed in the relative unit of embryological age (tau0) in order to standardize this parameter, the absolute time for heat-shock initiation being calculated from duration of one tau0 at two different pre-treatment water temperatures. Heat shocks were applied within the periods of 0.05-0.60 tau0 and 1.20-2.20 tau0 which, respectively, cover the successive phases of the 2nd meiotic division and the 1st cleavage. The highest production of diploid gynogenetic offspring was observed when heat shocks were initiated at 0.15-0.25 tau0 and at 1.5 tau0, after insemination, corresponding to anaphase of meiosis II, and metaphase of the 1st cleavage, respectively. Similar results were obtained irrespective of the different pre-treatment water temperatures, thus confirming the possibility of standardizing heat-shock timing by tau0. PMID- 24177843 TI - Sister chromatid exchanges in cultured immature embryos of wheat species and regenerants. AB - Immature embryos of Triticum aestivum (ten cultivars and lines), T. durum, T. dicoccum and T. monococcum were cultured in vitro on MS medium supplemented with 1 or 2 mg/l of 2,4-D and 20 or 30 g/l of sucrose for 3 days and processed to score sister chromatid exchanges (SCEs) per chromosome. Media components affect DNA replication from the start of the culture. The SCE frequencies were dependent on the genotype and were not correlated with the degree of ploidy. They increased after doubling of the concentration of 2,4-D and/or sucrose, except in one cultivar of T. aestivum. The mean numbers were lower than observed in root meristems of T. aestivum (two cultivars) and T. dicoccum. Immature embryos of regenerants of T. aestivum (one cultivar) and T. durum demonstrated variable SCE frequencies, which may have been caused by mutations in the parental cell cultures. In the T. aestivum embryos the lowest frequencies were found in regenerants obtained from explants with the highest frequencies. PMID- 24177844 TI - Efficiency of early generation selections for yield and related characters in safflower (Carthamus tinctorius L.). AB - The efficiency of early generation selection for yield and related characters in safflower (Carthamus tinctorius L.) was studied in the F2, F3 and F4 generations. Twenty-five F2 progenies derived from various crosses were studied. In the F2 generation, number of capitula per plant (CNSP), number of seeds per capitulum (SPSP), test weight (SWSP), and seed yield (SYSP) were the criteria used for single plant selection. The analysis of variance showed significant differences for all of the characters in the F2, F3, and F4 generations. The analysis of variance in each of the selection classes showed highly significant genotypic differences. A large number of selections in the CNSP and SYSP classes showed greater yield than the check variety. In each class the mean for that particular character showed a positive shift. The observed F3 and F4 means for seed yield per plant was higher in SYSP, indicating the effectiveness of single plant selection for yield. Correlated response showed that selection for number of capitula per plant was effective for improvement of yield. PMID- 24177845 TI - Genetic mapping of the Gy4 and Gy5 glycinin genes in soybean and the analysis of a variant of Gy4. AB - The predominant storage protein of soybean [Glycine max (L.) Merr.] seed is a globulin called glycinin. Thus far five genes encoding glycinin subunits have been described, and these are denoted by the gene symbols Gy1 to Gy5. The objectives of this study were to map two of these genes, Gy4 and Gy5, and to conduct a genetic analysis of a subunit size-variant from an allele of Gy4. For this purpose a population was formed with an interspecific cross between PI 468916 (G. soja) and A81-356022 (G. max). The two size forms of G4, the subunit from Gy4, segregated codominantly in the mapping population, and were due to a short insertion in the hypervariable region of the mutant protein. The biochemical and molecular characteristics of the two subunits indicate that they are produced from alternate alleles of the same gene. The gene symbols Gy (a) and Gy (b) have been assigned to the normal and variant genes, respectively. When genomic DNA from the two parents was probed with a Gy4 cDNA, RFLPs were identified for both Gy4 and Gy5. Using these genetic markers, the Gy4 and Gy5 glycinin genes were mapped in linkage group "O" and "F" on the public soybean genomic map. PMID- 24177846 TI - Multiple regression for molecular-marker, quantitative trait data from large F2 populations. AB - Molecular marker-quantitative trait associations are important for breeders to recognize and understand to allow application in selection. This work was done to provide simple, intuitive explanations of trait-marker regression for large samples from an F2 and to examine the properties of the regression estimators. Beginning with a(- 1,0,1) coding of marker classes and expected frequencies in the F2, expected values, variances, and covariances of marker variables were calculated. Simple linear regression and regression of trait values on two markers were computed. The sum of coefficient estimates for the flanking-marker regression is asymptotically unbiased for an included additive effect with complete interference, and is only slightly biased with no interference and moderately close (15 cM) marker spacing. The variance of the sum of regression coefficients is much more stable for small recombination distances than variances of individual coefficients. Multiple regression of trait variables on coded marker variables can be interpreted as the product of the inverse of the marker correlation matrix R and the vector a of simple linear regression estimators for each marker. For no interference, elements of the correlation matrix R can be written as products of correlations between adjacent markers. The inverse of R is displayed and used to illustrate the solution vector. Only markers immediately flanking trait loci are expected to have non-zero values and, with at least two marker loci between each trait locus, the solution vector is expected to be the sum of solutions for each trait locus. Results of this work should allow breeders to test for intervals in which trait loci are located and to better interpret results of the trait-marker regression. PMID- 24177847 TI - Genetic analysis of tolerance for phosphorous deficiency in rice (Oryza sativa L.). AB - The inheritance of phosphorous (P) - deficiency tolerance in rice was investigated by a sevenparent diallel. The parent materials involved were four P efficient (IR20, IR54, IR28, and Mahsuri), one moderately P-efficient (TN1), and two P-inefficient (IR31406333-1 and IR34686-179-1-2-1), genotypes. Relative tilering ability (RTA) under P-deficient and P-supplemented soil conditions was the parameter used in determining the tolerance level of the different genotypes. Diallel graph analysis revealed that tolerant parents have an excess of recessive genes, while moderate and susceptible parents possess more dominant genes. Genetic-component analysis suggested that both additive and dominance gene effects are involved in the inheritance of P-deficiency tolerance in rice. The trait exhibited over doiminance as confirmed by the graphical analysis. Narrow sense heritability of the trait was moderate (0.50) and environmental effects were low. Both the general combining ability (GCA) and the specific combining ability (SCA) were significant, but GCA was more prevalent than SCA. Tolerant parents exhibited a high GCA whereas susceptibles have a very poor GCA, suggesting that tolerant parents were mostly enriched in additive genes and susceptible parents in non-additive genes. Crosses involving two high general combiners showed low SCA effects whereas crosses between poor general combiners manifested highly-significant SCA values. PMID- 24177848 TI - Prediction of the power of detection of marker-quantitative trait locus linkages using analysis of variance. AB - Analysis of variance can be used to detect the linkage of segregating quantitative trait loci (QTLs) to molecular markers in outbred populations. Using independent full-sib families and assuming linkage equilibrium, equations to predict the power of detection of a QTL are described. These equations are based on an hierarchical analysis of variance assuming either a completely random model or a mixed model, in which the QTL effect is fixed. A simple prediction of power from the mean squares is used that assumes a random model so that in the mixed model situation this is an approximation. Simulation is used to illustrate the failure of the random model to predict mean squares and, hence, the power. The mixed model is shown to provide accurate prediction of the mean squares and, using the approximation, of power. PMID- 24177849 TI - Relationships among genetic distance, forage yield and heterozygosity in isogenic diploid and tetraploid alfalfa populations. AB - Isogenic diploid and tetraploid alfalfa (Medicago sativa L.) was studied with molecular markers to help understand why diploid performance and breeding behavior does not always predict that of tetraploids. In a previous study of partially heterozygous alfalfa genotypes, we detected a low correlation between yields of isogenic diploid (2x) and tetraploid (4x) single-cross progenies, and genetic distances were more highly correlated with yields of tetraploids than diploids. These differences may be related to the level of RFLP heterozygosity expected among progenies derived from heterozygous parents at the two ploidy levels. The objectives of this study were to determine the relationships among genetic distance, forage yield and heterozygosity in isogenic 2 x and 4 x alfalfa populations. Four diploid genotypes were chromosome doubled to produce corresponding isogenic autotetraploids, and these genotypes were mated in 4 * 4 diallels to produce 6 single-cross families at each ploidy level for field evaluation. Allele compositions of parents were determined at 33 RFLP loci by monitoring segregation of homologous restriction fragments among individuals within progenies, and these were used to estimate RFLP heterozygosity levels for all single-cross progenies at both ploidy levels. RFLP heterozygosity rankings were identical between progenies of isogenic diploid and tetraploid parents; but significant associations (P < 0.05) between estimated heterozygosity levels and forage yield were detected only at the tetraploid level. Since tetraploid families were nearly 25% more heterozygous than the corresponding diploid families, inconsistencies in the association between molecular marker diversity and forage yields of isogenic 2 x and 4 x single crosses may be due to recessive alleles that are expressed in diploids but masked in tetraploids. The gene action involved in heterosis may be the same at both ploidy levels; however, tetraploids benefit from greater complementary gene interactions than are possible for equivalent diploids. PMID- 24177850 TI - Identification of homoeologous chromosomes in hexaploid oat (A. byzantina cv Kanota) using monosomics and RFLP analysis. AB - The use of RFLP markers, together with a partial set of monosomics available in Avena byzantina cv Kanota, has enabled us to identify putative homoeologous chromosome sets in hexaploid Avena species (2n = 6x = 42, AACCDD). We first identified probes producing distinct three-band patterns on Southern blots that possibly reflect orthologous loci of the three genomes present in the hexaploid. Using monosomic analysis, 51 different restriction fragments that hybridized to 26 probes were localized to 12 different chromosomes for which monosomic stocks were available. These DNA restriction fragments were localized to specific monosomics using image analysis to quantify band intensity relative to other bands in the same lane. From these data, we have tentatively identified two complete homoeologous sets of three chromosomes each and two partial sets of two of the three chromosomes. The results indicate that RFLP dosage analysis is useful in the characterization of homoeologous chromosomes in hexaploid oat where nullisomics for many of the chromosomes are not available.Mention of a trademark or proprietary product does not constitute a guarantee or warranty by the USDA ARS or the University of Minnesota and does not imply approval over other products that also may be suitable. PMID- 24177851 TI - The effect of population structure on the relationship between heterosis and heterozygosity at marker loci. AB - The relationship between heterozygosity at neutral marker loci and heterosis of F1 hybrids is investigated using a theoretical model. Results emphasize that linkage disequilibrium between the markers and the loci implicated in heterosis [quantitative trait loci (QTLs) that exhibit dominance effects] is a necessary condition to finding a correlation (rho mh ) between heterozygosity at marker loci and the heterosis. The effect of population structure, in which the parental inbred lines of the hybrids belong to different heterotic groups, is considered. rho mh is investigated for: (1) hybrids between lines that belong to the same heterotic group (within-group hybrids); (2) hybrids between lines that belong to different groups (between-group hybrids); and (3) all hybrids, both within and between-groups. Within a group, significant values of (rho mh ) may arise because of linkage disequilibrium generated by drift. At the between-group level, no correlation is expected since link-age disequilibrium should differ randomly from one group to the other, which is consistent with recent experimental results. Possible ways to achieve prediction of the heterosis in this situation are discussed. When all hybrids are considered simultaneously, divergence of allelic frequencies among groups for the markers and the QTLs produces a correlation between heterosis and heterozygosity at marker loci. This correlation increases with the number of markers that are considered. PMID- 24177852 TI - Chromosomal location of genes controlling short-term and long-term somatic embryogenesis in wheat revealed by immature embryo culture of aneuploid lines. AB - The expression of essential genes during somatic embryogenesis can be analysed by inducing aneuploid cells to undergo embryogenesis during immature embryo culture and then determining whether defects occur. Triticum aestivum disomic and aneuploid stocks, including 36 ditelosomics and 7 nullitetrasomic 'Chinese Spring' wheats, were compared for their ability to undergo somatic embryogenesis after 2 months of in vitro immature embryo culture. Their regeneration capacity was observed after 4 and 14 months of in vitro culture to determine which chromosome arms influence the process. The large range of variation found among the tested aneuploids suggested that genetic control of the somatic tissue culture ability is polygenic. Our results indicate that genes affecting somatic embryo-genesis and regeneration are located in all of the homoeologous chromosome groups. The lack of chromosome arms 1AL (DT 1AS) and 3DL (DT 3DS) practically suppresses somatic embryogenesis, demonstrating that major genes on wheat chromosome arms 1AL and 3DL control regeneration capacity. Results suggest that plants were mainly produced from somatic embryo development. Although the control of somatic embryogenesis and regeneration is polygenic, the genes located on the long arms of homoeologous group 3 chromosomes have a major effect. We also have evidence of chromosome arms that determine the time required for regeneration. PMID- 24177853 TI - Optimum spacing of genetic markers for determining linkage between marker loci and quantitative trait loci. AB - The cost of experiments aimed at determining linkage between marker loci and quantitative trait loci (QTL) was investigated as a function of marker spacing and number of individuals scored. It was found that for a variety of experimental designs, fairly wide marker spacings (ca. 50 cM) are optimum or close to optimum for initial studies of marker-QTL linkage, in the sense of minimizing overall cost of the experiment. Thus, even when large numbers of more or less evenly spaced markers are available, it will not always be cost effective to make full utilization of this capacity. This is particularly true when costs of rearing and trait evaluation per individual scored are low, as when marker data are obtained on individuals raised and evaluated for quantitative traits as part of existing programs. When costs of rearing and trait evaluation per individual scored are high, however, as in human family data collection carried out primarily for subsequent marker - QTL analyses, or when plants or animals are raised specifically for purposes of marker - QTL linkage experiments, optimum spacing may be rather narrow. It is noteworthy that when marginal costs of additional markers or individuals are constant, total resources allocated to a given experiment will determine total number of individuals sampled, but not the optimal marker spacing. PMID- 24177854 TI - Genotype x environment interaction in QTL analysis of an intervarietal almond cross by means of genetic markers. AB - Besides QTL location and the estimation of gene effects, QTL analysis based on genetic markers could be used to comprehensively investigate quantitative trait related phenomena such as pleiotropy, gene interactions, heterosis, and genotype by-environment interaction (G x E). Given that the G x E interaction is of great relevance in tree improvement, the objective of the research presented here was to study the effect of years on QTL detection for 15 quantitative traits by means of isozymatic markers in a large progeny group of an intervarietal cross of almond. At least 17 putative QTLs were detected, 3 of which had alleles with opposite effects to those predicted from the parental genotypes. Only 3 QTLs behaved homogeneously over the years. Three possible causes are discussed in relation to this lack of stability: the power of the test statistic being used, the low contribution of the QTL to the genetic variation of the trait, and a differential gene expression dependent on the year (G x E). Most cases showing lack of stability involved traits whose heritability estimates change drastically from year to year and/or whose correlation coefficients between years are low, suggesting the presence of G x E as the most likely cause. A marker-assisted selection scheme to improve late flowering and short flowering duration is suggested for an early and wide screening of the progeny. PMID- 24177855 TI - Production and analysis of asymmetric hybrid plants between monocotyledon (Oryza sativa L.) and dicotyledon (Daucus carota L.). AB - Asymmetric hybrid plants were obtained from fused protoplasts of a monocotyledon (Oryza sativa L.) and a dicotyledon (Daucus carota L.). X-ray-irradiated protoplasts isolated from a cytoplasmic malesterile (cms) carrot suspension culture were fused with iodoacetoamide-treated protoplasts isolated from a 5 methyltryptophan (5MT)-resistant rice suspension culture by electrofusion. The complementary recovered cells divided and formed colonies, which were then cultivated on regeneration medium supplemented with 25mg/l 5MT to eliminate any escaped carrot cells. Somatic hybrids were regenerated from 5 of the 5MT resistant colonies. The morphologies of most of the regenerated plants closely resembled that of the parental carrot plants. A cytological analysis of callus cultures induced from these plants indicated that most of the cells possessed 20 22 chromosomes and were resistant to 5MT. An isozyme analysis revealed that several regenerated plants had the peroxidase isozyme patterns of both parents. A Southern hybridization analysis with non-radioactively labelled DNA fragments of the rgp1 gene showed that regenerated plants had hybridizing bands from both rice and carrot. Chloroplast (cp) and mitochondrial (mt) DNAs were also analyzed by Southern hybridization by using several probes. CpDNA patterns of the regenerated plants were indistinguishable from those of the carrot parent. However 1 of the regenerated plants had a novel band pattern of mtDNA that was not detected in either of the parents, indicating a possible recombination of mitochondrial genomes. PMID- 24177856 TI - Chloroplast DNA differences between cultivated hop, Humulus lupulus and the related species H. japonicus. AB - Chloroplast DNA (cpDNA) of Humulus Lupulus and H. japonicus was examined by restriction endonuclease analysis with BamHI, BanI, BclI, BstEII, DraI, EcoRI, EcoRV, HindIII, KpnI, PaeR7I, PstI, PvuII, SalI and XhoI. The restriction fragment patterns showed that the cpDNAs shared a large number of restriction sites. However, the chloroplast genomes of the two species could be distinguished by differences in restriction site and restriction fragment patterns in the PstI, PvuII, BclI, EcoRV, DraI and HindIII digests. On the basis of the complexity of restriction enzyme patterns, the enzymes PstI, PvuII, SalI, KpnI and XhoI were selected for mapping the chloroplast genomes. Single and double restriction enzyme digests of cpDNA from the two species were hybridized to cpDNA probes of barley and tobacco. The data obtained from molecular hybridization experiments were used to construct the cleavage site maps. Except for the PstI digest, the arrangement of cpDNA restriction sites was found to be the same for both species. An extra PstI site was present in H. lupulus. Three small insertions/deletions of about 0.8 kbp each were detected in the chloroplast genomes of the two species. Two of these insertions/deletions were present in the large and one in the small singlecopy region of the chloroplast genome. The cpDNA of Humulus was found to be a circular molecule of approximately 148 kbp that contains two inverted repeat regions of 23 kbp each, a small and a large single -copy region of approximately 20 kbp and 81 kbp, respectively. The chloroplast genome of hop has the same physical and structural organization as that found in most angiosperms. PMID- 24177857 TI - Molecular analysis of the cms-inducing MAX1 cytoplasm in sunflower. AB - DNA from different male sterility-inducing sunflower cytoplasms was investigated in order to determine whether the cytoplasmic male sterility-inducing insertion of the PET1 mitochondrial DNA (mtDNA) is present in other cytoplasms. In one of these cytoplasms (MAX1) the mtDNA shows 93% sequence homology to the orfH522 of the PET1 mtDNA, which is probably responsible for cytoplasmic male sterility (cms) in the latter cytoplasm. In contrast to the situation in the PET1 mitochondrial genome, no transcription of the orfH522-related sequence could be detected in lines with the MAX1 cytoplasm. The organization of the MAX1 mtDNA and the mtDNA of a fertile line is shown to be widely different. In the study described here, homology to the mtDNA insertion was also detected in a fertile Helianthus maximiliani population, whereas DNA of four other H. maximiliani populations showed no hybridization signals. PMID- 24177858 TI - Light- and solvent-driven morphological transformations of self-assembled hydrogen-bonded nanostructures. AB - The morphology of aggregates formed by an E-azobenzene derivative possessing terminal phenylenebiuret hydrogen-bonding groups can be manipulated by the solvent composition and UV irradiation. PMID- 24177859 TI - Concentrations, distributions, sources, and risk assessment of organochlorine pesticides in surface water of the East Lake, China. AB - East Lake resides in the urban area of Wuhan City and is the largest urban lake in China. The concentrations of 16 organochlorine pesticides (OCPs) were analyzed in 108 surface water samples collected from the East Lake. The total concentrations of OCPs ranged from not detected to 120 ng L(-1) with predominance of delta-HCH, heptachlor, and alpha-HCH. The mean values of HCHs and DDTs were 7.40 and 5.70 ng L(-1), respectively, accounting for 40 and 31 % of the total OCPs. For the five lakelets in East Lake, Houhu Lake exhibited the highest concentrations of HCHs, DDTs, and total OCPs, which has been used actively for fisheries and surrounded by suburban rural areas and farmlands. Historical lindane or technical HCH input was probably the source of HCH, while technical DDTs might be the source of DDT in the East Lake. The ratio between heptachlor and its metabolic products indicated recent input of heptachlor. Although the combining ecological risks for all aquatic species in the East Lake calculated by species sensitivity distribution reached approximately 10(-5), the OCPs in the East Lake had slight effects on aquatic organisms. The carcinogenic risks and non carcinogenic hazard indices of DDTs and HCHs indicated that water in the East Lake was not suitable as water sources for human. However, the results indicated the water quality was safe for people to swim in the urban lake. PMID- 24177860 TI - Characteristics of a pressure sensitive touch sensor using a piezoelectric PVDF TrFE/MoS2 stack. AB - A new touch sensor device has been demonstrated with molybdenum disulfide (MoS2) field effect transistors stacked with a piezoelectric polymer, polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE). The performance of two device stack structures, metal/PVDF-TrFE/MoS2 (MPM) and metal/PVDF-TrFE/Al2O3/MoS2 (MPAM), were compared as a function of the thickness of PVDF-TrFE and Al2O3. The sensitivity of the touch sensor has been improved by two orders of magnitude by reducing the charge scattering and enhancing the passivation effects using a thin Al2O3 interfacial layer. Reliable switching behavior has been demonstrated up to 120 touch press cycles. PMID- 24177861 TI - Interaction of a copper (II) complex containing an artificial sweetener (aspartame) with calf thymus DNA. AB - A copper (II) complex containing aspartame (APM) as ligand, Cu(APM)2Cl2?2H2O, was synthesized and characterized. In vitro binding interaction of this complex with native calf thymus DNA (CT-DNA) was studied at physiological pH. The interaction was studied using different methods: spectrophotometric, spectrofluorometric, competition experiment, circular dichroism (CD) and viscosimetric techniques. Hyperchromicity was observed in UV absorption band of Cu(APM)2Cl2?2H2O. A strong fluorescence quenching reaction of DNA to Cu(APM)2Cl2?2H2O was observed and the binding constants (Kf) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters, enthalpy change (DeltaH) and entropy change (DeltaS) were calculated to be+89.3 kJ mol(-1) and+379.3 J mol(-1) K(-1) according to Van't Hoff equation which indicated that reaction is predominantly entropically driven. Experimental results from spectroscopic methods were comparable and further supported by viscosity measurements. We suggest that Cu(APM)2Cl2?2H2O interacts with calf thymus DNA via a groove interaction mode with an intrinsic binding constant of 8*10+4 M(-1). Binding of this copper complex to DNA was found to be stronger compared to aspartame which was studied recently. PMID- 24177862 TI - Fluorescence quenching and spectrophotometric methods for the determination of daunorubicin with meso-tera (4-sulphophenyl) porphyrin as probe. AB - In this work, a synthetic meso-tera (4-sulfophenyl) porphyrin (TPPS4) was used as a probe to determine daunorubicin (DNR) by fluorescence quenching and spectrophotometric methods. At pH 4.6 potassium acid phthalate-NaOH buffer solution, a 1:1 complex of DNR interacted with TPPS4 formed via the electrostatic attractions and hydrophobic interactions, thus resulted in TPPS4 fluorescence quenching and absorption spectra change. The maximum excitation wavelength (lambdaex) and the maximum emission wavelength (lambdaem) are 435 nm and 672 nm, respectively. The fluorescence quenching values (DeltaF) are the good linear relationship to the concentration of DNR in the range of 0.8-6.0 mgL(-1). The method exhibits high sensitivity with the detection limit (3sigma) being 27.0 ng mL(-1). Meanwhile, a decrease of absorbance is detected at 433 nm with the appearance of a new absorption peak at 420 nm. The optimum reaction conditions, influencing factors and the effect of coexisting substances have been investigated in our experiment. The results showed that the method had a good selectivity and could be applied to determine DNR in serum and urine samples. In addition, the combine ratio between DNR and TPPS4 was measured and the charge distribution before and after reaction was calculated by quantum chemistry calculation AM1 method. The type of fluorescence quenching was discussed by the absorption spectra change, Stern-Volmer plots and fluorescence lifetime determination. PMID- 24177863 TI - Non linear optical analyses of hexamine: phenol cocrystals based on hydrogen bonding: a comparative study. AB - Fourier-Transform Infrared (FT-IR) spectroscopy supported by Raman spectroscopy has been employed to explain the conventional and unconventional hydrogen bonding present in the 4,4'thiodiphenol: hexamine and 4,4'sulfonyldiphenol: hexamine cocrystals. The possible internal and external vibrational modes are predicted through factor group analysis. Influence of intra molecular charge transfer (ICT) interaction caused by the strong ionic ground state hydrogen bonding between charged species, giving rise to a non centro symmetric structure which is a criterion for second harmonic generation (SHG) efficiency has been discussed. Intense low wave number hydrogen bond vibrations in Raman which arise due to electron-phonon coupling are analyzed. Optical quality of adducts is identified through UV-Vis analysis. The second harmonic generation efficiency of both adducts is determined by Kurtz-Perry method. PMID- 24177864 TI - Synthesis, structural and optical properties of ZnO and Ni-doped ZnO hexagonal nanorods by Co-precipitation method. AB - Ni doped ZnO (Zn1-xNixO, x=0.0, 0.03, 0.06 and 0.09) nanorods have been synthesized by Co-precipitation method. Zinc acetate dehydrate [Zn(CH3COO)2?2H2O], nickel nitrate [Ni(NO3)3?6H2O], sodium hydroxide and poly (vinyl pyrrolidone) (PVP) were mixed together. The morphology, optical and microstructure were determined by X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy dispersive spectrum (EDS), atomic force microscopy (AFM), UV-DRS spectrum, photoluminescence spectra (PL) and Fourier transformer infrared spectroscopy (FT-IR). The presence of functional groups and chemical bonding is confirmed by FTIR. PL spectra of the Zn1-xNixO systems shows that the shift in near band edge (NBE) UV emission from 321 to 322 nm and a shift in red band (RB) emission from 620 to 631 nm which conforms the substitution of Ni into the ZnO lattice. The investigation conformed that the products were of the wurtzite structure of ZnO. The hexagonal nanorods have edge length 31 nm and thickness of 39 nm. EDS result showed that the amount of Ni in the product is about 9%, these Ni doped hexagonal nanorods exhibits a blue shifts and weak (UV) emission peak, compared with pure ZnO, which may be induced by the Ni-doping different concentrations 0.0, 0.3, 0.6 and 0.9 M. The growth mechanism of the doped hexagonal nanorods was also discussed. PMID- 24177865 TI - Computational studies of molecular charge transfer complexes of heterocyclic 4 methylepyridine-2-azomethine-p-benzene derivatives with picric acid and m dinitrobenzene. AB - Charge transfer complexes of substituted aryl Schiff bases as donors with picric acid and m-dinitrobenzene as acceptors were investigated by using computational analysis calculated by Configuration Interaction Singles Hartree-Fock (CIS-HF) at standard 6-31G* basis set and Time-Dependent Density-Functional Theory (TD-DFT) levels of theory at standard 6-31G** basis set, infrared spectra, visible and nuclear magnetic resonance spectra are investigated. The optimized geometries and vibrational frequencies were evaluated. The energy and oscillator strength were calculated by Configuration Interaction Singles Hartree-Fock method (CIS-HF) and the Time-Dependent Density-Functional Theory (TD-DFT) results. Electronic properties, such as HOMO and LUMO energies and band gaps of CTCs set, were studied by the Time-Dependent density functional theory with Becke-Lee-Young-Parr (B3LYP) composite exchange correlation functional and by Configuration Interaction Singles Hartree-Fock method (CIS-HF). The ionization potential Ip and electron affinity EA were calculated by PM3, HF and DFT methods. The columbic force was calculated theoretically by using (CIS-HF and TD-DFT) methods. This study confirms that the theoretical calculation of vibrational frequencies for (aryl Schiff bases--(m-dinitrobenzene and picric acid)) complexes are quite useful for the vibrational assignment and for predicting new vibrational frequencies. PMID- 24177866 TI - Synthesis, growth, thermal and optical studies on third order nonlinear optical material (E)-2-{3-[2-(4-chlorophenyl) vinyl]-5,5-dimethylcyclo-hex-2-en-1 ylidene}malononitrile for optoelectronic application. AB - A new polyene like organic molecule (E)-2-{3-[2-(4-chlorophenyl) vinyl]-5,5 dimethylcyclo-hex-2-en-1-ylidene}malononitrile (Cl1) was synthesized by knoevenagel condensation method. The Cl1 Single crystals were successfully grown by the slow evaporation method at a constant temperature 35 degrees C. Single crystal XRD confirms the Cl1 molecule belongs to monoclinic crystal system and space group P21/C with a=10.114, b=11.127, c=14.929 and V=1668.9 and Z=4. The grown Cl1 crystals were subjected to FTIR and 13C NMR studies to confirm the synthesized compound. The linear optical property of Cl1 crystal has been studied using UV-Vis-NIR spectroscopy in the wavelength range 190 nm-1100 nm. The thermal properties of Cl1 crystal were studied by using TG and DTA analysis. The refractive index of Cl1 crystal has measured using Abbe's refractometer and found to be 1.648. The third order nonlinear optical property of Cl1 crystal has been investigated using Z-scan technique with HeNe laser. Photoluminescence (PL) spectrum of Cl1 crystal was carried out using xenon lamp, which shows high intense emission peak at wavelength 614 nm. Laser optical damage threshold (LDT) of Cl1 crystal has studied using Nd-YAG laser (10 Hz, 420 mJ, 1064 nm). PMID- 24177867 TI - Triazole based ratiometric fluorescent probe for Zn2+ and its application in bioimaging. AB - An efficient fluorescent chemosensor 4-((2-hydroxynaphthalen-1-yl)methyleneamino) 3-phenyl-1H-1,2,4-triazole-5(4H)-thione, based on triazole has been designed by condensing 2-hydroxy-1-napthaldehyde with amine, appended to 1,2,4-triazole unit. The probe displays excellent selectivity and sensitivity in both absorbance and fluorescence detection of Zn2+ over other essential metal ions. The nature of fluorescence behavior of receptor upon addition of Zn2+ has been obtained from Density Functional Theory calculations. Imaging experiment indicates that probe works effectively for intracellular Zn2+ imaging with good cell permeability and biocompatibility. PMID- 24177868 TI - Synthesis and spectral properties of new fluorescent alkoxy-substituted thieno[3,2-b]indole derivatives. AB - The synthesis and optical properties of three new fluorescent alkoxy-substituted thieno[3,2-b]indole (TI) derivatives, including 7-methoxy thieno[3,2-b]indole (7 MeOTI), 6,7- methylenedioxythieno[3,2-b]indole (6,7-MDTI) and 6,7 dihexyloxythieno[3,2-b]indole, (6,7-DHTI), were investigated. Electronic absorption spectra, fluorescence excitation and emission spectra, fluorescence quantum yields (PhiF), lifetimes (tauF), and other photophysical parameters of the three TI derivatives were measured in DMSO solutions at room temperature. Theoretical electronic absorption and fluorescence spectra were also calculated by means of a molecular orbital (MO) method. For all three alkoxy-TI derivatives, the fluorescence emission maximum wavelength was significantly red shifted relative to un-substituted TI, which was attributed to delocalization of the fused hetero-aromatic ring pi electronic system by the electron-donating alkoxy group(s). PhiF values varied from 0.12 to 0.19, according to the compound. tauF were short, in the range 0.56-1.13 ns. PMID- 24177869 TI - Bi3+ sensitized Y2WO6:Ln3+ (Ln=Dy, Eu, and Sm) phosphors for solar spectral conversion. AB - The phosphors of Y2WO6:Bi3+, Ln3+ (Ln=Dy, Eu and Sm) were synthesized by solid state reaction in this study. The crystal structure, photoluminescence properties and energy transfer mechanism were investigated. By introducing Bi3+ ions, the excitation band of the phosphors was broadened to be 250-380 nm, which could be absorbed by the dye-sensitized solar cells (DSSCs). The overlap between excitation of W-O groups/Bi3+ and the emission of Ln3+ (Dy, Eu, and Sm) indicated that the probability of energy transfer from W-O groups and Bi3+ to Ln3+. The energy transfer efficiency from Bi3+ to Ln3+ (Ln=Dy, Eu and Sm) are calculated to be 16%, 20% and 58%. This work suggested that Y2WO6:Bi3+, Ln3+ (Ln=Dy, Eu and Sm) might be a promising ultraviolet-absorbing luminescent converter to enhance the photoelectrical conversion efficiency of dye-sensitized solar cells (DSSCs). PMID- 24177870 TI - Archaeometric study of black-coated pottery from Pompeii by different analytical techniques. AB - Complementary spectroscopic methods were used to characterize ceramic body and black coating of fine pottery found at Pompeii (Italy). This has enabled us to investigate local productions and to clarify the technological changes over the 4th-1st centuries BC. Two different groups of ceramics were originally distinguished on the basis of macroscopic observations. Optical microscopy (OM), X-ray diffraction (XRD) and X-ray fluorescence (XRF) seem to indicate the usage of the same raw materials for the production of black-coated ceramics at Pompeii for about three centuries. Raman microscopy (RM) and micro-analysis (SEM/EDS) suggest different production treatments for both raw material processing and firing practice (duration of the reducing step and the cooling rate). PMID- 24177871 TI - Development a novel approach of chemiluminescent probe array. AB - A new chemiluminescent (CL) probe array assay approach was first developed. The new CL probe array was based on Co3O4-SiO2 mesoporous nanocomposite material, which not only has an excellent catalytic effect on the luminol-H2O2 CL reaction in alkaline medium but also can be used for the immobilization of enzymes. As a model, the novel bifunctional CL probe array has been applied to the high throughput determination of glucose in human. The linear range of the glucose concentration was 3-90 MUM and the detection limit was 0.36 MUM. It breaks traditional development view in solid phase supports and provides new insights into the application of mesoporous material. PMID- 24177872 TI - Synthesis, spectral, thermal, optical and theoretical studies of (2E,6E)-2 benzylidene-6-(4-methoxybenzylidene)cyclohexanone. AB - Single crystals of (2E,6E)-2-benzylidine-6-(4-methoxybenzylidine)cyclohexanone are grown by slow evaporation of ethanolic solution at room temperature. The characteristic functional groups present in the molecule are confirmed by Fourier transform infrared and Fourier transform Raman analyses. The scanning electron microscopy study reveals the surface morphology of the material. Thermogravimetric/differential thermal analysis study reveals the purity of the material and the crystal is transparent in the visible region having a lower optical cut-off at ~487nm. The second harmonic generation efficiency of as-grown material is estimated by Kurtz and Perry technique. Optimized geometry has been derived using Hartree-Fock calculations performed at the level 6-31G (d,p) and the first-order molecular hyperpolarizability (beta) is estimated. The specimen is further characterized by nuclear magnetic resonance spectroscopy. PMID- 24177873 TI - Modification of chitosan by using samarium for potential use in drug delivery system. AB - In the presence of hydroxyl and amine groups, chitosan is highly reactive; therefore, it could be used as a carrier in drug delivery. For this study, chitosan-Sm complexes with different concentrations of samarium from 2.5 to 25 wt.% have been successfully synthesized by the impregnation method. Chitosan combined with Sm3+ ions produced a drug carrier material with fluorescence properties; thus, it could also be used as an indicator of drug release with ibuprofen (IBU) as a model drug. We evaluated the spectroscopic and interaction properties of chitosan and Sm3+ ions, the interaction of chitosan-Sm matrices with IBU as a model drug, and the effect of Sm3+ ions addition on the chitosan ability to adsorb the drug. The result showed that the hypersensitive fluorescence intensity of chitosan-Sm (2.5 wt.%) is higher than the others, even though the adsorption efficiency of chitosan-Sm 2.5wt.% is lower (29.75%) than that of chitosan-Sm 25 wt.% (33.04%). Chitosan-Sm 25 wt.% showed the highest efficiency of adsorption of ibuprofen (33.04%). In the release process of ibuprofen from the chitosan-Sm-IBU matrix, the intensity of orange fluorescent properties in the hypersensitive peak of 4G5/2->6H7/2 transition at 590 nm was observed. Fluorescent intensity increased with the cumulative amount of IBU released; therefore, the release of IBU from the Sm-modified chitosan complex can be monitored by the changes in fluorescent intensity. PMID- 24177874 TI - Characterization and electronic spectral studies of 2-(naphthalen-1-yl)-4,5 diphenyl-1H-imidazole bound Fe2O3 nanoparticles. AB - Multicomponent, one-pot, highly efficient, indium trifluoride (InF3) catalytic synthesis of 2-(naphthalen-1-yl)-4,5-diphenyl-1H-imidazole under solvent-free condition is reported. Characterization of imidazole has been carried out by spectral techniques. The synthesized phosphated imidazole (PI) and phosphated imidazole bound magnetic nanoparticles (PIBMN) were characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and powder X-ray diffraction (XRD). The photophysical characteristics of the synthesized phosphated imidazole and phosphated imidazole bound magnetic nanoparticles were investigated by steady state absorption and emission spectroscopy as well as time resolved fluorometry. From these experiments, the position of the spectral maxima (lambdaabs, lambdaexc and lambdaemi), and lifetime (tau) of the synthesized phosphated imidazole and phosphated imidazole bound magnetic nanoparticle have been determined. PMID- 24177875 TI - Cloud-point extraction, preconcentration and spectrophotometric determination of trace quantities of copper in food, water and biological samples. AB - A new, simple and sensitive cloud point extraction procedure was presented for the preconcentration and determination of copper(II) ion in food, water and biological samples. The analyte was complexed with a new synthesized reagent, 2 amino-4-(m-tolylazo)pyridine-3-ol (ATAP) as a new complexing agent and Triton X 114 as the surfactant. After centrifugation, dilution of the surfactant-rich phase with 0.4 mL of ethanol acidified with 1.0M HNO3 was performed after phase separation, and the copper contents were measured by spectrophotometry at lambdamax 608 nm. The influence of analytical parameters including concentration of complexing agent, Triton X-114, pH, equilibration temperature and time, centrifuge rate and time were optimized. The analytical characteristics of the method (e.g. linear range, molar absorptivity, Sandell sensitivity, optimum Ringbom concentration ranges limits of detection and quantification, preconcentration factor, and improvement factors) were obtained. Linearity was obeyed in the range of 4.0-115 ng mL(-1) of Cu(II) ion. The detection and quantification limits of the method were 1.20 and 3.94 ng mL(-1) of Cu(II) ion, respectively. The interference effect of some anions and cations was also tested. The method was applied for determination of copper in food, water and biological samples. PMID- 24177876 TI - Experimental FT-IR, Laser-Raman and DFT spectroscopic analysis of a potential chemotherapeutic agent 6-(2-methylpropyl)-4-oxo-2-sulfanylidene-1,2,3,4 tetrahydropyrimidine-5-carbonitrile. AB - In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential chemotherapeutic agent namely, 6-(2-methylpropyl)-4 oxo-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carbonitrile have been investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09 W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies and the other related molecular energy values have been calculated and depicted. PMID- 24177877 TI - Study on molecular structure, spectroscopic investigation (IR, Raman and NMR), vibrational assignments and HOMO-LUMO analysis of L-sodium folinate using DFT: a combined experimental and quantum chemical approach. AB - In the present work, an exhaustive conformational search of N-[4-[[(2-amino-5 formyl-(6S)-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L glutamic acid disodium salt (L-SF) has been preformed. The optimized structure of the molecule, vibrational frequencies and NMR spectra studies have been calculated by density functional theory (DFT) using B3LYP method with the 6 311++G (d, p) basis set. IR and FT-Raman spectra for L-SF have been recorded in the region of 400-4000 cm(-1) and 100-3500 cm(-1), respectively. 13C and 1H NMR spectra were recorded and 13C and 1H nuclear magnetic resonance chemical shifts of the molecule were calculated based on the gauge-independent atomic orbital (GIAO) method. Finally all of the calculation results were applied to simulate IR, Raman, 1H NMR and 13C NMR spectrum of the title compound which showed excellent agreement with observed spectrum. Furthermore, reliable vibrational assignments which have been made on the basis of potential energy distribution (PED) and characteristic vibratinonal absorption bands of the title compound in IR and Raman have been figured out. HOMO-LUMO energy and Mulliken atomic charges have been evaluated, either. PMID- 24177878 TI - Luminescence of solvate of boron difluoride dibenzoylmethanate with benzene: aggregates formation. AB - The concentration dependence of spectral-luminescence properties of solutions boron difluoride dibenzoylmethanate (DBMBF2) in benzene and chloroform has been studied through stationary and time-resolved emission spectroscopy methods. The formation of J-aggregates in the solution of DBMBF2 in chloroform has been revealed and a crystalline adduct of DBMBF2 with benzene has been obtained. A bright blue adduct luminescence is due only to the luminescence of J-aggregates, unlike the crystals of DBMBF2, for which the luminescence of excimers and J aggregates has been observed. The quantum chemistry simulation of geometric and electronic structure of the DBMBF2 S6N6 solvate has been performed, and the absorption spectra of DBMBF2 and it is adduct have been calculated. PMID- 24177879 TI - Quantum-chemical (DFT, MP2) and spectroscopic studies (FT-IR and UV) of monomeric and dimeric structures of 2(3H)-Benzothiazolone. AB - Molecular geometry and vibrational wavenumbers of 2(3H)-Benzothiazolone (C7H5NSO, HBT) was investigated using density functional (DFT/B3LYP) method with 6 311+G(d,p) basis set. The vibrational wavenumbers are found to be in good agreement with experimental FT-IR spectra. Hydrogen-bonded dimer of HBT, optimized by counterpoise correction, was studied by MP2 and DFT/B3LYP at the 6 311+G(d,p) level and the effects of molecular association through NH---O hydrogen bonding were discussed. A detailed analysis of the nature of the hydrogen bonding, using topological parameters, such as electronic charge density, Laplacian, kinetic and potential energy density evaluated at bond critical points (BCP) has also been presented. The UV absorption spectra of the compound dissolved in ethanol and chloroform solutions were recorded in the range of 200 600 nm. The UV-vis spectrum of the title molecule was also calculated using TD DFT method. The calculated energy and oscillator strength almost exactly reproduce the experimental data. Total and partial density of state (TDOS, PDOS) of the HBT in terms of HOMOs and LUMOs and molecular electrostatic potential (MEP) were calculated and analyzed. The electric dipole moment, polarizability and the first static hyper-polarizability values for HBT were calculated at the DFT/B3LYP with 6-311+G(d,p) basis set. The results also show that the HBT molecule may have nonlinear optical (NLO) comportment with non-zero values. Stability of the molecule arising from hyper-conjugative interactions and charge delocalization was analyzed using natural bond orbital (NBO) analysis. PMID- 24177880 TI - Synthesis, spectroscopic characterization and theoretical calculations of ClF2CC(O)NPCl3 ([chloro(difluor)acetyl]phosphorimidic trichloride). AB - The synthesis of [chloro(difluor)acetyl]phosphorimidic trichloride (ClF2CC(O)NPCl3), together with a tentative assignment of the vibrational, NMR and mass spectra, are reported. Quantum chemical calculations (MP2 and B3LYP methods with 6-311+G(d) and 6-311+G(2df,p) basis sets) predict three stable conformers in the gas phase (syn, gauche and anti, defined according to the rotation around both the ClCCN and the CCNP dihedral angles). However, only a single C1 symmetry conformer is observed in the liquid phase, possessing the CO double bond in synperiplanar orientation with respect to the PN double bond, and the ClC bond distorted from the plane defined by the CC(O)NP entity. A Natural Bond Orbital (NBO) analysis was carried out for the title compound and related molecules in order to provide an explanation about the electronic properties. PMID- 24177881 TI - Identification of structural and spectral features of synthesized cyano-stilbene dye derivatives: a comparative experimental and DFT study. AB - The synthesized three dye derivatives of cyano-stilbene monomer were identified by experimental spectroscopic techniques and density functional approach. The optimized geometrical structure, vibrational and electronic transitions along with the nonlinear optical (NLO) properties of those compounds were presented in this study. The vibrational spectra of investigated compounds were recorded in solid state with FT-IR and FT-Raman spectrometry in the range of 4000-400 cm(-1) and 3600-50 cm(-1), respectively. The theoretical ground state equilibrium conformations and vibrational wavenumbers were carried out by using density functional method with 6-311G(d,p) basis set. Assignments of the fundamental vibrational modes were examined on the basis of the measured data and total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanical (SQM) method. The UV absorption spectra of monomers were observed in the range of 200-600 nm in chloroform, acetonitrile and toluene, and time dependent DFT method was used to obtain the electronic properties. The linear polarizability and first hyperpolarizability of the studied molecules indicates that the title compounds can be used as a good nonlinear optical material. A detailed description of spectroscopic behaviors of compounds was given based on the comparison of experimental measurements and theoretical computations. PMID- 24177882 TI - Synthesis, spectral characterization, self-assembly and biological studies of N acyl-2-pyrazolines bearing long alkoxy side chains. AB - A series of new pyrazoline derivatives (1b-4c) bearing N-acyl arms and nine to twelve carbon long alkoxy side chains was synthesized and characterized on the basis of spectroscopic data and microanalysis. The nature of self-assembly to understand the interplay of alkoxy chain crystallization and various supramolecular interactions was investigated using single crystal X-ray diffraction studies. Interesting self-assembled supramolecular structures of 1b and 4c were observed in the crystal lattice owing to various CH?O, H?H, CH?pi, lonepair?pi and pi?pi interactions. Further, all the synthesized compounds (1b 4c) were screened for their in vitro antifungal and anti-inflammatory activities. Compounds 2b, 3b, 2c and 3c showed significant to moderate antifungal activity against Microsporum canis whereas most of the other compounds were found inactive against all the five tested fungal strains. Good anti-inflammatory activity was observed for compounds 1b with IC50 value 331 MUM compared to 273 MUM for Indomethacine, a standard reference drug. The bio-activity data demonstrates the relationship between lipophilicity, solubility and bioavailability. PMID- 24177883 TI - FT-IR, FT-Raman spectra and ab initio HF and DFT calculations of 7-chloro-5-(2 chlorophenyl)-3-hydroxy-2,3-dihydro-1H-1,4-benzodiazepin-2-one. AB - The Fourier Transform infrared and Fourier Transform Raman spectra of 7-chloro-5 (2-chlorophenyl)-3-hydroxy-2,3-dihydro-1H-1,4-benzodiazepin-2-one (7C3D4B) were recorded in the regions 4000-400 and 4000-100 cm(-1), respectively. The appropriate theoretical spectrograms for the IR and Raman spectra of the title molecule were also constructed. The calculated results show that the predicted geometry can well reproduce the structural parameters. Predicted vibrational frequencies have been assigned and compared with experimental IR spectra and they supported each other. Stability of the molecule arising from hyperconjugative interactions, charge delocalization and intramolecular hydrogen bond-like weak interaction has been analyzed using natural bond orbital (NBO) analysis by using B3LYP/6-31G(d,p) method. The results show that electron density (ED) in the sigma* and pi* antibonding orbitals and second-order delocalization energies E(2) confirm the occurrence of intramolecular charge transfer (ICT) within the molecule. The first order hyperpolarizability (betatotal) of this molecular system and related properties (beta, MU, and Deltaalpha) are calculated using HF/6-31G(d,p) and B3LYP/6-31G(d,p) methods based on the finite-field approach. PMID- 24177884 TI - Inheritance of qualitative and quantitative trypsin inhibitor variants in Pisum. AB - A trypsin inhibitor locus (Tri) has been mapped close to Vc-2 on Pisum (pea) linkage group 5 using recombinant inbred lines derived from crosses of genotypes showing qualitative variation in seed trypsin inhibitors. F2 seed populations derived from crosses between lines showing qualitative variation in trypsin inhibitors as well as quantitative variation in inhibitor activity showed an association between the segregation of the structural variation and relative activity levels. Clones complementary to Pisum trypsin inhibitor mRNA were used in hybridization analyses which showed that the segregation of protein polymorphisms reflected directly the segregation of polymorphisms associated with the structural genes. PMID- 24177885 TI - The effects of selection for gain in mice on the direct-maternal genetic correlation. AB - Components of genetic variation for postweaning growth traits were estimated for both control and growth stocks of mice. The effect of phenotypic selection for gain, which genetically combines selection for additive direct and maternal effects, on additive genetic variance components, heritability, and additive genetic correlationsis discussed. Quantitative genetic theory predicts that simultaneous selection for two metric traits in the same direction will cause the genetic correlation between the two traits to become more negative. The results presented in this paper conflict with this theory. The direct-maternal additive genetic correlation was more negative in the control line (with 356 mice) than in the growth-selected line (with 320 mice) for the three traits analyzed (0.310 vs 0.999 for 21-day weight, 0.316 vs 1.000 for 42-day weight, and 0.506 vs 1.000 for gain from 21-42 days). Estimates were obtained by restricted maximum likelihood (REML) computed under a derivative free algorithm (DFREML). PMID- 24177886 TI - Detection and inheritance of RFLPs in Eucalyptus nitens. AB - The level of polymorphism using genomic and cDNA probes with a number of restriction enzymes and the inheritance of the RFLP loci was investigated in E. nitens. The polymorphism detected with 366 genomic and cDNA probes and three to six restriction enzymes was analysed in three-generation outbred pedigrees. No difference in the level of polymorphism detected with genomic versus cDNA probes was observed. There was a difference in the efficiency of detection of polymorphism with six different restriction enzymes, with three of the enzymes (BglII, DraI and EcoRI) showing substantially more polymorphism than the others. There was no significant correlation between the size of the DNA fragments generated by the enzymes and the detection of polymorphism. Several cases of restriction-site mutations resulting in a polymorphism were observed. The inheritance of 69 loci was analysed in two pedigrees resulting from interpopulational crosses. The majority of the loci segregated according to expected ratios with distortion observed in only 3% of loci. Probes from the cDNA library detected a greater proportion of loci with more than two alleles than did probes from the genomic library. The high polymorphism, large number of alleles, and ease of interpretation of RFLPs in E. nitens means that they will be useful in a range of applications such as genetic linkage maps and paternity analysis. PMID- 24177887 TI - The incidence of mini- and micro-satellite repetitive DNA in the canine genome. AB - We have estimated the incidence of microand mini-satellites in the dog genome. A genomic phage library from canine liver, with an average insert size of 16 kb, was screened to detect potentially polymorphic microand mini-satellite sequences, which may be useful for the development of markers of inherited diseases, for fingerprinting, or for population genetics. Synthetic oligonucleotide probes were used to search for microsatellite sequences, and minisatellites were investigated with eight heterologous VNTR probes. (CA)n.(GT)n sequences were by far the most frequent, with a calculated average distance between consecutive loci of 42 kb. The average distance between loci of tri- or tetra-nucleotide repeats was about 330 kb. Mean inter-locus distances were 320 kb for (GGC)n, 205 kb for (GTG)n, 563 kb for (AGG)n, 320 kb for (TCG)n, 233 kb for (TTA)n, 384 kb for (CCTA)n, 368 kb for (CTGT)n, 122 kb for (TTCC)n, 565 kb for (TCTA)n, and 229 kb for (TAGG)n. Cross-hybridization with eight human minisatellite probes was found at average distances of 1400 kb; only one did not hybridize at all. We conclude that the di , tri and tetra-nucleotide short tandem repeats, as well as some minisatellite sequences, are potentially useful as genetic markers, for mapping of the canine genome, and also for paternity testing and the analysis of population characteristics. PMID- 24177888 TI - Identification of opaque-2 genotypes in segregating populations of Quality Protein Maize by analysis of restriction fragment length polymorphisms. AB - Quality Protein Maize (QPM) is a name given to genetically modified opaque-2 maize with hard endosperm. The opaque-2 mutation conditions a reduction in the amount of zein seed storage protein; zeins are deficient in the essential amino acids lysine and tryptophan, and mutant seed have a higher nutritional value. To utilize the potential of opaque-2 maize, elite inbreds can be converted to o2/o2 forms and subsequently to hard endosperm opaque-2. Since opaque-2 is recessive and endosperm specific, conventional backcross procedures to convert elite inbreds to opaque-2 forms are inefficient. To alleviate this problem, a marker assisted selection procedure was developed for the Texas A&M University Quality Protein Maize breeding program. Hybridization of an O2 cDNA probe to blots of DNA from plants carrying O2 and o2 alleles showed that restriction fragment length polymorphisms (RFLPs) exist between the W64A o2 allele and O2 alleles of Mo17 and TX5855 inbred lines. To identify the opaque2 genotypes in segregating populations, an RFLP marker assay combining the O2 cDNA probe and HindIII digestion of genomic DNA was developed. The effectiveness of the O2 RFLP marker assay was tested under field conditions using F2 and backcross populations of several hard endosperm opaque-2 lines. A comparison of the genotypes identified by RFLP analysis with the seed phenotypes of the next generation indicated that this procedure is accurate and can be used for identifying O2/O2, O2/o2, and o2/o2 genotypes of individual juvenile plants in breeding populations. PMID- 24177889 TI - Generation-means analysis and quantitative trait locus mapping of anthracnose stalk rot genes in maize. AB - A generation-means analysis was performed on two maize populations, each segregating for genes conferring resistance to anthracnose stalk rot (ASR). The populations were derived from a cross of DE811ASR x DE811 and of DE811ASR x LH132. The resistant parent, DE811ASR, was obtained through introgression with MP305 as the donor and DE811 as the recurrent parent. The analysis revealed significant additive effects in both populations and a significant additive x dominant effect in the DES11ASR x DES11 population. Quantitative trait locus (QTL) mapping, using restriction fragment length polymorphism (RFLP)-based molecular markers, indicated a significant QTL on linkage group 4 in both populations. The QTL analysis confirmed additive inheritance in both populations. This work demonstrates a close correspondence between generation-means analysis and discrete observations using molecular markers. Linkage of a genetic marker to genes conferring resistance to ASR will be useful for the introgression of resistance into elite germplasm. PMID- 24177890 TI - RFLP studies of genetic relationships among inbred lines of the cultivated sunflower, Helianthus annuus L.: evidence for distinct restorer and maintainer germplasm pools. AB - One-hundred-and-eighty-one nuclear DNA probes were used to examine restriction fragment length polymorphism in inbred lines of the cultivated sunflower (Helianthus annuus L.). The probes were from six libraries: two genomic libraries - one made with PstI and the other with HindIII, and four cDNA libraries - from etiolated plantlets, green leaves, ovaries, petals and anthers. Total DNA from 17 inbred lines representing an overview of the genetic stocks of sunflower, including restorer and maintainer lines of the classical cytoplasmic male sterility, was digested with four different restriction enzymes and probed in 331 probe-enzyme combinations. Of 181 clones analysed, 73 probes were found to be polymorphic. Genetic distances between inbreds were calculated from the resultant proportion of shared bands and submitted to principal component analysis and the UPGMA 'tree-making' method. The RFLP analysis allowed a clear differentiation between restorer and maintainer lines of the cytoplasmic male sterility, together with a grouping of some of the genotypes from the same origin. The analysis of the accuracy of distance estimation as a function of the number of probe-enzyme combinations used, indicates that 40-50 combinations ensure a confidence level of near 95%. Considering the inbreds as representatives of the range of cultivated inbreds, estimates of gene diversity, as well as estimates of average gene diversity between and within the sets of restorer and maintainer lines, were calculated. Estimation of gene diversity showed that the available genetic variability in cultivated sunflower, based on allelic frequencies, is lower than that of other plants (H=0.20). Moreover, we show that the proportion of genetic variability due to the difference between maintainer and restorer lines (Dm) is about 2%. PMID- 24177891 TI - Construction of a YAC library from a Beta vulgaris fragment addition and isolation of a major satellite DNA cluster linked to the beet cyst nematode resistance locus Hs1 (pat-1.). AB - A YAC library was constructed from the Beta vulgaris fragment addition AN5-203b. This monosomic fragment addition harbors an approximate 12-Mbp fragment of B.patellaris chromosome 1 accomodating the Hs1 (pat-1) conferring resistance to the beet cyst nematode (Heterodera schachtii). The YAC library consists of 20,000 YAC clones having an average size of 140 kb. Screening with organelle-specific probes showed that 12% of the clones contain chloroplast DNA while only 0.2% of the clones hybridizes with a mitochondrial specific probe. On the basis of a sugar beet haploid genome size of 750 Mbp this library represents 3.3 haploid genome equivalents. The addition fragment present in AN5-203b harbors a major satellite DNA cluster that is tightly linked to the Hs1 (pat-1) locus. The cluster is located on a single 250-kb EcoRI restriction fragment and consists of an estimated 700-800 copies of a 159-bp core sequence, most of which are arranged in tandem. Using this core sequence as a probe, we were able to isolate 1 YAC clone from the library that contains the entire 250-kb satellite DNA cluster. PMID- 24177892 TI - Molecular marker analysis of Helianthus annuus L. 1. Restriction fragment length polymorphism between inbred lines of cultivated sunflower. AB - cDNA and PstI genomic clones have been used to assess levels of restriction fragment length polymorphism (RFLP) in Helianthus annuus and to determine the inter-relationships between a diverse set of 24 inbred lines. Of the cDNA clones screened 45% were useful as RFLP probes, compared to less than 20% from the PstI library, which showed high levels of redundancy for high copy sequences. Fifty seven low-copy DNA probes (23 PstI and 34 cDNA clones) were used to fingerprint 12 maintainer (B) lines and 12 restorer (R) lines. The average number of RFLP variants per probe was found to be 3.2, with a mean polymorphic index of 0.49, indicating that high levels of nuclear DNA polymorphism are to be found in cultivated sunflower. Cluster and principal coordinate analysis of the fingerprinting data clearly separated the maintainer and restorer lines, but there was a degree of association between 2 unbranched R-lines and the B-line germ plasm pool. PMID- 24177893 TI - Use of random amplified polymorphic DNA (RAPD) markers in the discrimination and verification of genotypes in Eucalyptus. AB - We carried out four separate studies using random amplified polymorphic DNA (RAPD) markers to analyse samples of Eucalyptus supplied by several different organisations. The objective was to examine the reproducibility of the RAPD technique and its ability to discriminate between individual genotypes for verification of clonal identities. We found that RAPD profiles that are unique to a genotype can be generated reliably and simply and that even closely related genotypes can be distinguished. In addition, in each of the four studies, we detected cases where the plant material studied had been mis-sampled or mis labelled (i.e. the RAPD profiles were not consistent with the identification numbers): (1) ramets of a Eucalyptus grandis clone were found to be derived from 2 different clones; (2) ramets labelled as 2 different Eucalyptus hybrid clones were found to be the same clone, owing to a mis-planted clonal hedge; (3) samples supplied as a single progeny of a controlled E. nitens cross were derived from two crosses involving different pairs of parents; (4) mis-labelling was detected for ramets of 4 of a set of 10 clones of E. grandis and E. camaldulensis. For three of the four studies, the detection of genotype mis-identifications was unexpected, suggesting that labelling or sampling errors during the handling of plant material are a frequent occurrence, with potentially serious economic consequences. PMID- 24177894 TI - Molecular-marker-facilitated studies of morphological traits in maize. II: Determination of QTLs for grain yield and yield components. AB - Genetic factors controlling quantitative inheritance of grain yield and its components have not previously been investigated by using replicated lines of an elite maize (Zea mays L.) population. The present study was conducted to identify quantitative trait loci (QTLs) associated with grain yield and grain-yield components by using restriction fragment length polymorphism (RFLP) markers. A population of 150 random F2?3 lines was derived from the single cross of inbreds Mo17 and H99, which are considered to belong to the Lancaster heterotic group. Trait values were measured in a replicated trial near Ames, Iowa, in 1989. QTLs were located on a linkage map constructed with one morphological and 103 RFLP loci. QTLs were found for grain yield and all yield components. Partial dominance to overdominance was the primary mode of gene action. Only one QTL, accounting for 35% of the phenotypic variation, was identified for grain yield. Two to six QTLs were identified for the other traits. Several regions with pleiotropic or linked effects on several of the yield components were detected. PMID- 24177895 TI - Long-range organization of a satellite DNA family flanking the beet cyst nematode resistance locus (Hs1) on chromosome-1 of B. patellaris and B. procumbens. AB - New members of a satellite DNA family (Sat 121), specific for wild beets of the section Procumbentes of the genus Beta, were isolated. Sequence analysis showed that the members of Sat-121 fall into two distinct classes. The organization of Sat-121 in the vicinity of a beet cyst nematode (Heterodera schachtii Schm.) resistance locus (Hs1) in B. patellaris and B. procumbens was investigated by pulsed-field gel electrophoresis (PFGE) using DNA from a series of resistant monosomic fragment additions, each containing an extra chromosome fragment of B. patellaris chromosome-1 (pat-1) in B. vulgaris. In this way several clusters of Sat-121 flanking the Hs1 (pat-1) locus were identified. In nematode resistant diploid introgressions (2n=18), which contain small segments of B. procumbens chromosome-1 (pro-1) in B. vulgaris, only two major Sat-121 clusters were detected near the Hs1 (pro-1) locus. PMID- 24177896 TI - Resistance to powdery mildew (Oidium lycopersicum) in Lycopersicon hirsutum is controlled by an incompletely-dominant gene Ol-1 on chromosome 6. AB - The inheritance of resistance to powdery mildew (Oidium lycopersicum) in Lycopersicon hirsutum was investigated by disease tests in segregating populations obtained by hybridising tomato (L. esculentum) cv Moneymaker with the wild relative L. hirsutum G1.1560. One incompletely dominant gene Ol-1 was found to largely control resistance to the disease. To map Ol-1, DNA pools from seven resistant and ten susceptible F2 plants were analyzed for random amplified polymorphic DNA (RAPD). With 32 primers tested, one RAPD, primed with the sequence 5'-GACGTGGTGA-3', was observed between the susceptible and the resistant bulks, which cosegregated with resistance in the F2 population of L. esculentum * L. hirsutum G1.1560. This RAPD was mapped on chromosome 6 by using an F2 (L. esculentum * L. pennellii) already mapped for 49 RFLPs. RFLP analysis of the F2 from L. esculentum cv Moneymaker * L. hirsutum G1.1560 demonstrated that Ol-1 maps near the Aps-1 region on chromosome 6, in the vicinity of the resistance genes to Meloidogyne spp. (Mi) and to Cladosporium fulvum (Cf-2/Cf-5). PMID- 24177897 TI - Quantitative trait locus analysis of tuber dormancy in diploid potato (Solanum spp.). AB - Quantitative trait locus (QTL) analysis for tuber dormancy was performed in a diploid potato population (TRP133) consisting of 110 individuals. The female parent was a hybrid between haploid S. tuberosum (2x) and S. chacoense, while the male parent was a S. phureja clone. The population was characterized for ten isozyme loci, 44 restriction fragment length polymorphisms (RFLPs) and 63 random amplified polymorphic DNAs (RAPDs). Eighty-seven of these loci segregating from the female parent were utilized to develop a linkage map that comprised 10 of the 12 chromosomes in the genome. Dormancy, as measured by days-to-sprouting after harvest, ranged from 10 to 90 days, with a mean of 19 days. QTLs were mapped by conducting one-way analyses of variance for each marker locus by dormancy combination. Twenty-two markers had a significant association with dormancy, identifying six putative QTLs localized on each of chromosomes 2, 3, 4, 5, 7 and 8. The QTL with the strongest effect on dormancy was detected on chromosome 7. A multilocus model was developed using the locus with highest R(2) value in each QTL. This model explained 57.5% of the phenotypic variation for dormancy. Seven percent of possible epistatic interactions among significant markers were significant when tested through two-way analyses of variance. When these were included in the main-effects model, it explained 72.1% of the phenotypic variation for dormancy. QTL analysis in potato, the methodology to transfer traits and interactions into the 4x level, and QTLs of value for marker-assisted selection, are discussed. PMID- 24177898 TI - An RFLP-based genetic map of pearl millet (Pennisetum glaucum). AB - Analysis of a sample of diverse pearl millet genotypes with 200 genomic DNA probes revealed this crop species to be extremely polymorphic. Among these genotypes, 85% of probes detected polymorphism using only two restriction enzymes, with an average pair-wise polymorphism between all of the probe-enzyme combinations of 56%. Two crosses were employed to construct an RFLP-based genetic map. In an intervarietal F2 population, derived from a single F1 plant, 181 loci were placed on a linkage map. The total length of this map, which comprised seven linkage groups, was 303 cM and the average map distance between loci was about 2 cM, although a few intervals in excess of 10 cM were present at the ends of a few linkage groups. Very few clones, including those which hybridized to more than one copy, detected more than one locus in the pearl millet genome. The analysis was complicated initially because 83 of the 181 loci mapped to a single linkage group. Analysis of a second cross identified a probable translocation breakpoint in the middle of this large linkage group. PMID- 24177899 TI - The fate of recombinant chromosomes and genome interaction in Nicotiana asymmetric somatic hybrids and their sexual progeny. AB - Genomic in-situ hybridization (GISH) was used to monitor the behaviour of parental genomes, and the fate of intergenomic chromosome translocations, through meiosis of plants regenerated from asymmetric somatic hybrids between Nicotiana sylvestris and N. plumbaginifolia. Meiotic pairing in the regenerants was exclusively between chromosomes or chromosome segments derived from the same species. Translocation (recombinant) chromosomes contained chromosome segments from both parental species, and were detected at all stages of meiosis. They occasionally paired with respectively homologous segments of N. sylvestris or N. plumbaginifolia chromosomes. Within hybrid nuclei, the meiotic division of N. plumbaginifolia lagged behind that of N. sylvestris. However, normal and recombinant chromosomes were eventually incorporated into dyads and tetrads, and the regenerants were partially pollen fertile. Recombinant chromosomes were transmitted through either male or female gametes, and were detected by GISH in sexual progeny obtained on selfing or backcrossing the regenerants to N. sylvestris. A new recombinant chromosome in one plant of the first backcross generation provided evidence of further chromosome rearrangements occurring at, or following, meiosis in the original regenerants. This study demonstrates the stable incorporation of chromosome segments from one parental genome of an asymmetric somatic hybrid into another, via intergenomic translocation, and reveals their transmission to subsequent sexual progeny. PMID- 24177900 TI - The inheritance of host plant resistance and its effect on the relative infection efficiency of Magnaporthe grisea in rice cultivars. AB - The inheritance of host plant resistance and its effect on the relative infection efficiency for leaf blast was studied in the crosses 'IR36'/'CO39' (partially resistant * highly susceptible) and 'IR36'/'IR64' (both partially resistant). On the natural scale, gene action appeared multiplicative. After log transformation, additive effects described most of the genetic variation in the cross 'IR36'/'CO39', while additive and dominance effects were about equal in magnitude in the cross 'IR36'/'IR64'. Dominance was towards increased resistance. No transgressive segregation occurred in the cross 'IR36'/'CO39'. The number of genes that reduce lesion number was estimated to be zero in 'CO39' and five or more in 'IR36'. The cross 'IR36'/'IR64' showed transgressive segregation in both directions, and 'IR36' and 'IR64' each contain at least one gene that is not present in the other cultivar. The heritabilities (narrow sense) in the F2 were low (range 0.06-0.16), while narrow sense heritabilities based on F3 lines were much higher (range 0.41-0.68). Lesion numbers in F3 lines were reasonably correlated with those in F5 progenies derived from the same F2 plant (r was+/-0.6 in both crosses). Partial resistance can be effectively improved by selecting the most resistant plants from the most resistant F3 lines. PMID- 24177901 TI - Evaluation of the extent of genetic variation in mahoganies (Meliaceae) using RAPD markers. AB - Despite the economic importance of mahoganies (Meliaceae) little is known of the pattern of genetic variation within this family of tropical trees. We describe the application of a polymerase chain reaction (PCR)-based polymorphic DNA assay procedure random amplified polymorphic DNAs (RAPDs) to assess the extent of genetic variation between eight mahogany species from four genera. Pronounced genetic differentiation was found between the species and genera. There was a clear separation of Cedrela odorata from the other species, with 95% of the variable amplification products differing, whereas Lovoa trichilioides, Khaya spp. and Swietenia spp. were more closely grouped. These results are consistent with the current taxonomic viewpoint. A number of markers were found to be diagnostic for particular species, which could be of value in determining the status of putative hybrids. The application of RAPDs to the study of genetic variation in mahoganies is discussed in the context of developing genetic conservation and improvement strategies for these species. PMID- 24177902 TI - Polymorphisms in the alpha-amy1 gene of wild and cultivated barley revealed by the polymerase chain reaction. AB - alpha-Amylases are the key enzymes involved in the hydrolysis of starch in plants. The polymerase chain reaction (PCR) was used to detect polymorphisms in the length of amplified sequences between the annealing sites of two primers derived from published alpha-amy1 gene sequences in barley. These two primers (Bsw1 and Bsw7), flanking the promoter region and the first exon, amplified two PCR fragments in barley. One of the amplified products, with the expected length of 820 bp, appeared together with another shorter PCR band of around 750 bp. This 750-bp fragment seems to be derived from an alpha-amylase gene not reported previously. Both of the PCR products could be amplified from the two-rowed barley varieties tested, including cv Himalaya from which the sequence information was obtained. Five of the six-rowed barley varieties also have the two PCR fragments whereas another two have only the long fragment. These two fragments seem to be unique to barley, neither of them could be amplified from other cereals; for example, wheat, rye or sorghum. These two alpha-amylase fragments were mapped to the long arm of 6H, the location of the alpha-amy1 genes, using wheat-barley addition lines. Amplification of genomic DNA from wild barley accessions with primers Bsw1 and Bsw7 indicated that both of the fragments could be present, or the long and short fragments could be present alone. The results also demonstrated that the genes specifying these two fragments could be independent from each other in barley. The conserved banding pattern of these two fragments in the two-rowed barley varieties implies that artificial selection from these genes may have played an important role in the evolution of cultivated barley from wild barley. PMID- 24177903 TI - Ancient origin of the vacuolar H(+)-ATPase 69-kilodalton catalytic subunit superfamily. AB - Recently, two distinct cDNA clones encoding the catalytic subunit of the vacuolar H(+)-ATPase (V-ATPase) were isolated from the allotetraploid cotton species Gossypium hirsutum L. cv 'Acala SJ-2' (Wilkins 1992, 1993). Differences in the nucleotide sequence of these clones were used as molecular markers to explore the organization and structure of the V-ATPase catalytic subunit genes in the A and D genomes of diploid and allotetraploid cotton species. Nucleotide sequencing of polymerase chain reaction (PCR) products amplified from G. arboreum (A2, 2n=26), G. raimondii (D5, 2n=26), and G. hirsutum cv 'Acala SJ-2' [(AD)1, 2n=4x=52] revealed a V-ATPase catalytic subunit organization more complex than indicated hitherto in any species, including higher plants. In the genus Gossypium, the V ATPase catalytic subunit genes are organized as a superfamily comprising two diverse but closely related multigene families, designated as vat69A and vat69B, present in both diploid and allotetraploid species. As expected, each vat69 subfamily is correspondingly more complex in the allotetraploid species due to the presence of both A and D alloalleles. Because of this, about one-half of the complex organization of V-ATPase catalytic subunit genes predates polyploidization and speciation of New World tetraploid species. Comparison of plant and fungal V-ATPase catalytic subunit gene structure indicates that introns accrued in the plant homologs following the bifurcation of plant and fungi but prior to the gene duplication event that gave rise to the vat69A and vat69B genes approximately 45 million years ago. The structural complexity of plant V-ATPase catalytic subunit genes is highly conserved, indicating the presence of at least ten introns dispersed throughout the coding region. PMID- 24177904 TI - Regeneration of transgenic, microspore-derived, fertile barley. AB - We have developed a system for the biolistic transformation of barley using freshly-isolated microspores as the target tissue. Independent transformation events led, on average, to the recovery of one plant per 1*10(7) bombarded microspores. Putative transformants have been regenerated using phosphinothricin as a selective agent. R0 plants have been transferred to soil approximately 2 months after bombardment. Integration of the marker genes bar and uidA has been confirmed by Southern analysis. The marker genes are inherited in all progeny plants confirming the expected homozygous nature of the R0 plants. PMID- 24177905 TI - Erratum. PMID- 24177906 TI - Classifying married adults diagnosed with alpha-1 antitrypsin deficiency based on spousal communication patterns using latent class analysis: insights for intervention. AB - Married adults are increasingly exposed to test results that indicate an increased genetic risk for adult-onset conditions. For example, a SERPINA1 mutation, associated with alpha-1 antitrypsin deficiency (AATD), predisposes affected individuals to diseases such as chronic obstructive pulmonary disease (COPD) and cancer, which are often detected in adulthood. Married adults are likely to discuss genetic test results with their spouses, and interpersonal research suggests that spouses' communication patterns differ. Latent class analysis was used to identify subgroups of spousal communication patterns about AATD results from a sample of married adults in the Alpha-1 Research Registry (N = 130). A five-class model was identified, and the subgroups were consistent with existing spousal-communication typologies. This study also showed that genetic beliefs (e.g., genetic stigma), emotions, and experiences (e.g., insurance difficulties) covaried with membership in particular subgroups. Understanding these differences can serve as the foundation for the creation of effective, targeted communications interventions to address the specific needs and conversational patterns of different kinds of couples. PMID- 24177909 TI - Transmission and recombination of chloroplast genes in asexual crosses of Chlamydomonas reinhardii : I. Flagellar agglutination prior to fusion does not promote uniparental inheritance or affect recombinant frequencies. AB - Chlamydomonas reinhardii diploids homozygous for the plus mating-type (mt (+)) allele were constructed via polyethylene glycol (PEG)-induced cell fusion to investigate the transmission of chloroplast genes.We used two methods to determine whether the fusion products (PEG diploids) had inherited chloroplast markers uniparentally or biparentally. One method (multiple clone analysis) was found to markedly improve the detection of biparental transmission. With this method the frequency of biparental PEG-induced diploids was comparable to that seen in sexual diploids. Multiple clone analysis also demonstrated that fusion products which showed biparental inheritance were an extremely heterogeneous group.In some crosses, pre-treatment of one parent with isolated flagella from cells of the opposite mating type was used. This pre-treatment has been reported to promote chloroplast gene transmission from the mt (+) parent in diploids produced by PEG fusion (Adams 1982). In our crosses flagellar pretreatment had no significant effect on chloroplast gene transmission or recombination frequences. A significant bias was found for the date a cross was performed, but neither parent preferentially transmitted its alleles in all crosses. This indicates the necessity of comparing data from treated and control crosses done on the same day. We conclude from our data that separate hypotheses are not required to explain biparental inheritance in sexual versus PEG-induced diploids. The absence of biased parental allelic ratios with PEG-induced biparental diploid clones underscores their usefulness for the study of biparental gene transmission. PMID- 24177910 TI - ALG/alg: a single gene controlling the utilization of lactate in the presence of antimycin in the yeast Saccharomyces cerevisiae. AB - A strain dependent growth on lactate in the presence of antimycin A (AA) has been observed - the strain D261 can grow on lactate and AA, whereas in the strain K8/6C antimycin A prevents the utilization of lactate and the induction of LDH.Genetic analysis demonstrates that growth on lactate in the presence of AA segregates from D261 as a single nuclear factor which we indicate by ALG1 and alg1 in its dominant and recessive states. alg1 complements the gene(s) which give(s) rise to the same phenotype in K8/6C.The analysis of the regulation by lactate of LDH in the absence and presence of AA and in rho (-) cells shows that growth on lactate and antimycin A is not corretated with the induction by lactate of LDH. PMID- 24177907 TI - Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth. AB - Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti inflammatory effects. Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation. We here showed that abundance of omega-3 fatty acids reduced the incidence of preterm birth induced by LPS with fat-1 mice, capable of converting omega-6 to omega-3 fatty acids. We also indicated that the gene expression of IL-6 and IL-1beta in uteruses and the number of cervical infiltrating macrophages were reduced in fat-1 mice. The analyses of lipid metabolomics showed the high level of 18 hydroxyeicosapentaenoate in fat-1 mice, which was derived from EPA and was metabolized to anti-inflammatory product named resolvin E3 (RvE3). We finally showed that the administration of RvE3 to LPS-exposed pregnant wild type mice lowered the incidence of preterm birth. Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth. PMID- 24177911 TI - Physical and gene mapping of cauliflower (Brassica oleracea) mitochondrial DNA. AB - A physical map of the mitochondrial DNA isolated from B. oleracea (cauliflower) inflorescences was constructed with the restriction endonucleases Sall, Kpnl and Bgll. Physical mapping was made using the multi enzyme method with either unlabeled or labeled DNA fragments isolated by preparative electrophoresis and a clone bank prepared by inserting incomplete Sall restriction digests of mitochondrial DNA into a cosmid vector.The different mapping studies led to a circular map, about 217 kb in size, containing the entire sequence complexity of the genome. The 26S and 18S - 5S ribosomal RNA genes appeared to be separated by about 75 kb in this map. However, the particular cross-hybridization between several restriction fragments and the sequential diversity of some cosmids indicated that intra molecular recombination may occur naturally in higher plant mitochondria. Namely, one recombinational event resulted in the ribosomal RNA genes mapping closer together. PMID- 24177912 TI - Isolation and characterization of a methylammonium resistant mutant of Neurospora crassa. AB - A mutant of Neurospora crassa has been isolated which is resistant to methylammonium, a structural analog of ammonium. In contrast to wild type, this mutant, mea-1, has derepressed nitrate reductase and nitrite reductase activities in the presence of ammonium. However, glutamine still represses these nitrate assimilation enzymes in mea-1. The nit-2 mutant was epistatic to mea-1 since the mea-1; nit-2 double mutant has the nit-2 mutant phenotype. In addition, mea-1; nit-2 double mutants cannot utilize ammonium as a nitrogen source. We suggest therefore that nit-2 and mea-1 loci play a role in ammonia/methylamine uptake. PMID- 24177913 TI - Effect of erythromycin upon the protein pattern of heat shocked S. cerevisiae : Identification of new classes of heat-shock and heat-stroke products. AB - Conventional and two dimensional (2D) electrophoresis on ultrathin horizontal slab gels shows that heat shock proteins are synthesized and heat stroke proteins are curtailed after the transfer of Saccharomyces cerevisiae strain Z270 from 23 degrees C to 37 degrees C. Upon addition of the mitochondrial translation inhibitor erythromycin to cell cultures which incorporated labelled methionine at 23 degrees C, and after the transfer to 37 degrees C, we have shown that: a) in extracts of cells labelled at 23 degrees C, translational products sensitive to erythromycin could be observed on 2D gels; the synthesis of some of these proteins was enhanced, whereas the synthesis of some others declined when the labelling was carried out 20 min after the transfer to 37 degrees C; b) there are heat shock proteins whose induction at 37 degrees C was prevented by erythromycin; c) labelling of a number of proteins became weaker at 37 degrees C, but not at 23 degrees C, when this was done in the presence of erythromycin; d) two proteins were detectable only in samples labelled at 37 degrees C in the presence of erythromycin. PMID- 24177914 TI - Recombinational properties of the Saccharomyces cerevisiae FLP gene expressed in Escherichia coli. AB - The FLP gene from the 2-MUm DNA of Saccharomyces cerevisiae is shown to be functionally expressed in Escherichia coli leading to site-specific intramolecular as well as intermolecular recombination between IR sequences. The expression was achieved under control of a low expression as well as a high expression E. coli promoter. The FLP gene was found to complement in trans a Flp( ) plasmid and promote its interconversion.By the use of a low Flp expression plasmid, it could be shown that the rate of interconversion of a Flp(-) plasmid by complementation in trans, was lower than that of a Flp(+) plasmid, suggesting that in addition to the IR sequences another cis-acting function exists.Expression of the FLP gene fused to the lac promoter in an in vitro system yielded two polypeptides with apparent molecular weights of 44,000 and 37,000. The 37,000 dalton polypeptide can also be produced from Flp(-) plasmids and is generated from a translation start within the FLP gene. The 44,000 dalton polypeptide is considered to represent the FLP gene product. PMID- 24177915 TI - The mitochondrial DNA of the yeast Hansenula petersonii: genome organization and mosaic genes. AB - The mitochondrial genomes of yeasts are circular DNA molecules that vary greatly in size in different species. The mitochondrial DNA of the yeast H. petersonii is about 42 kbp in length, about one half the size of the corresponding genome in S. cerevisiae. Sequences homologous to protein-encoding genes from S. cerevisiae have been identified and localized on this genome by hybridization with DNA from petite mutants. The comparison between the mitochondrial genomes of H. petersonii and S. cerevisiae showed differences in the overall genome organization, but both include genes with mosaic organization. In fact, sequences homologous to the first intron of the S. cerevisiae cob short gene are found in (or adjacent to) the cob and cox1 genes present in the genome of H. petersonii. Moreover, an intron homologous to that present in the 21S rRNA gene of S. cerevisiae seems to have been conserved in the large ribosomal RNA gene of H. petersonii, in a similar position. PMID- 24177916 TI - RNA processing in yeast mitochondria: characterization of mit(-) mutants disturbed in the synthesis of subunit I of cytochrome c oxidase. AB - Mit(-) mutants disturbed in the synthesis of cytochrome c oxidase subunit I lack the mRNA for this protein and accumulate longer RNAs still containing intron sequences. We have analyzed the patterns of transcripts occurring in several such mutants in an attempt to define a pathway of processing events and to demarcate intron-sequences involved in RNA splicing. We find that processing does not follow a strictly ordered pathway and, in contrast to the situation for the cytochrome b gene, that a block in the processing of an intron does not necessarily lead to a block in the processing of introns downstream. Although in some cases, this may result from overlapping specificities of intronic-URF encoded RNA maturases, an internal start of translation on precursor RNAs seems more likely.M5-16, a mutant deleted for a large part of the central portion of the subunit I gene exhibits delayed processing and a highly simplified pattern of intermediates. The lengths of these indicate that maturation of the mRNA for subunit I involves processing, as well as splicing. PMID- 24177917 TI - Cloning and identification of a DNA fragment coding for the sup1 gene of Saccharomyces cerevisiae. AB - A plasmid, pYsup1-1, containing a DNA fragment able to suppress the recessive mutant phenotype of the suppressor locus sup1 (allele sup1-ts36) of Saccharomyces cerevisiae was isolated from a bank of yeast chromosomal DNA cloned in cosmid p3030. The complementing gene was localized on a 2.6 kb DNA fragment by further subcloning. Evidence is presented that the cloned DNA segment codes for the sup1 structural gene (chromosome IIR). PMID- 24177918 TI - Expression of the cloned endo-1,3-1,4-beta-glucanase gene of Bacillus subtilis in Saccharomyces cerevisiae. AB - A cloned endo-1,3-1,4-beta-glucanase gene from the Gram-positive bacterium B. subtilis has been located by deletion analysis on a 1.4 kb PvuI-ClaI DNA fragment. This gene has been sub-cloned in the yeast LEU2 vector pJDB207 to produce a hybrid plasmid designated pEHB9. pEHB9 has been transformed to S. cerevisiae and shown to direct the synthesis of an endo-1,3-1,4-beta-glucanase in yeast. The beta-glucanase activity was low and could only be detected in crude cell extracts of yeast harbouring pEHB9. PMID- 24177919 TI - A mutation in the extracellular domain of the alpha7 nAChR reduces calcium permeability. AB - The alpha7 neuronal nicotinic acetylcholine receptor (nAChR) displays the highest calcium permeability among the different subtypes of nAChRs expressed in the mammalian brain and can impact cellular events including neurotransmitter release, second messenger cascades, cell survival, and apoptosis. The selectivity for cations in nAChRs is thought to be achieved in part by anionic residues which are located on either side of the channel mouth and increase relative cationic concentration. Mutagenesis studies have improved our understanding of the role of the second transmembrane domain and the intracellular loop of the channel in ion selectivity. However, little is known about the influence that the extracellular domain (ECD) plays in ion permeation. In the alpha7 nAChR, it has been found that the ECD contains a ring of ten aspartates (two per subunit) that is believed to face the lumen of the pore and could attract cations for permeation. Using mutagenesis and a combination of electrophysiology and imaging techniques, we tested the possible involvement of these aspartate residues in the calcium permeability of the rat alpha7 nAChR. We found that one of these residues (the aspartate at position 44) appears to be essential since mutating it to alanine resulted in a decrease in amplitude for both whole cell and single-channel responses and in the complete disappearance of detectable calcium changes in most cells, which indicates that the ECD of the alpha7 nAChR plays a key role in calcium permeation. PMID- 24177921 TI - Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum. AB - IMPORTANCE: Microphthalmia, anophthalmia, and coloboma form an interrelated spectrum of congenital eye abnormalities. OBJECTIVE: To document the ocular and systemic findings and inheritance patterns in patients with microphthalmia, anophthalmia, and coloboma disease to gain insight into the underlying developmental etiologies. DESIGN, SETTING, AND PARTICIPANTS: This retrospective consecutive case series was conducted at a tertiary referral center. Included in the study were 141 patients with microphthalmia, anophthalmia, and coloboma disease without a recognized syndromic etiology who attended the Westmead Children's Hospital, Sydney, from 1981-2012. EXPOSURE: Cases were grouped on the basis of the presence or absence of an optic fissure closure defect (OFCD); those with OFCD were further subdivided into microphthalmic and nonmicrophthalmic cases. Anophthalmic cases were considered as a separate group. MAIN OUTCOMES AND MEASURES: Associated ocular and systemic abnormalities and inheritance patterns were assessed. RESULTS: Of 141 cases, 61 (43%) were microphthalmic non-OFCD (NOFCD), 34 (24%) microphthalmic OFCD, 32 (23%) nonmicrophthalmic coloboma (OFCD), 9 (6%) anophthalmic, and 5 (4%) were unclassified. Sixty-three (45%) had bilateral disease. Eighty-four patients (60%) had an associated ocular abnormality; of these, cataract (P < .001) and posterior segment anomalies (P < .001) were most common in the NOFCD group. Forty-eight (34%) had an associated systemic abnormality, most commonly neurological, musculoskeletal and facial, urological and genital, or cardiac. Neurological abnormalities were most common in the anophthalmic group (P = .003), while urological abnormalities were particularly seen in the OFCD groups (P = .009). Familial cases were identified in both the OFCD and NOFCD groups, with a likely autosomal dominant inheritance pattern in 9 of 10 families. CONCLUSIONS AND RELEVANCE: This series indicated that the OFCD/NOFCD distinction may be useful in guiding evaluation for ocular and systemic associations, as well as the direction and analysis of genetic investigation. PMID- 24177920 TI - G protein-coupled receptor signalling potentiates the osmo-mechanical activation of TRPC5 channels. AB - TRPC5 is an ion channel permeable to monovalent and divalent cations that is widely expressed in different tissues. Although implicated in the control of neurite extension and in the growth cone morphology of hippocampal neurons, as well as in fear-related behaviour, the mechanisms by which TRPC5 is activated remain poorly understood. TRPC5 is known to be activated downstream of Gq-coupled receptors and by membrane stretch, and since there is evidence that mechanical stress may directly activate Gq-coupled receptors, we examined the relationship between the activation of TRPC5 by the type 1 histamine receptor and osmotic stress. Using calcium imaging and patch clamp recordings, we found that a higher proportion of cells expressing TRPC5 respond to hypoosmotic solution when they co express H1R. This response is associated with a phospholipase C-dependent increase in the cells internal calcium concentration, which is abolished on depletion of calcium stores. We also found that the hypoosmotic stimulus that provokes mechanical stress drives the translocation of TRPC5 to the plasma membrane by a mechanism dependent on PI3K. This increase in TRPC5 at the plasma membrane augments the proportion of cells that respond to hypoosmotic stimulation. Together, these results suggest that hypoosmotic cell-swelling activates Gq-coupled receptors, which in turn enhance the activation of TRPC5 by regulating this channel membrane trafficking. Gq-coupled receptors and TPRC5 are co-expressed in several tissues such as those of the vascular system and in somatosensory neurons, suggesting that this mechanism of TRPC5 activation may have interesting and important implications in arterial pressure sensing and mechanotransduction. PMID- 24177922 TI - A modular LHC built on the DNA three-way junction. AB - A light-harvesting complex composed of a pi-stacked multichromophoric array in a DNA three-way junction is described. The modular design allows for a ready exchange of non-covalently attached energy acceptors. PMID- 24177923 TI - An Evaluation of IMPACT for the Treatment of Late-Life Depression in a Public Mental Health System. AB - IMPACT (Improving Mood--Promoting Access to Collaborative Treatment) has a large body of evidence demonstrating its effectiveness for treating late-life depression in clients enrolled in a clinical research study, but little is known about how well the collaborative care model translates into treatment provided in a public mental health setting. This evaluation examines the influence of clinical and demographic characteristics in 112 older adults treated for late life depression through publicly funded IMPACT in a large San Francisco Bay Area county. Depression severity decreased for 85% of clients between enrollment and treatments' end and 46% of clients realized a 50% reduction in symptom severity. Depression severity at enrollment, number of treatment sessions attended, ethnicity, and gender reliably predicted depression severity at the end of treatment. Men, clients attending more therapy sessions, and clients without substance abuse diagnoses had an increased likelihood of realizing a 50% reduction in symptoms. Results highlight the success of this evidence-based treatment program offered through the public mental health system but suggest that the demographic and clinical characteristics of the population being treated must be considered when adopting evidence-based practices. PMID- 24177924 TI - Advancing on the new frontier of behavioral health. PMID- 24177925 TI - Rice-straw-like structure of silicon nanowire arrays for a hydrogen gas sensor. AB - A rice-straw-like silicon nanowire (SiNW) array was developed for hydrogen gas sensing applications. The straight-aligned SiNW array sensor was first fabricated by the metal-assisted electroless etching (MAEE) technique. Rice-straw-like SiNW arrays were formed using a repeated MAEE technique. Hydrogen sensing characteristics were measured for gas concentrations from 20 to 1000 ppm at room temperature. The rice-straw-like SiNW-array-based hydrogen gas sensor performed with low noise and a high response (232.5%) for 1000 ppm hydrogen gas. It was found that the rice-straw-like SiNW-array hydrogen gas sensor had a much better response (approximately 2.5 times) than the straight-aligned SiNW-array sensor. The rice-straw-like SiNW-array structure effectively increased the surface area and the concentration of silicon oxide, which provided additional binding sites for gas molecules. Thus, the rice-straw-like SiNW-array-based hydrogen gas sensor possessed good sensing properties and has the potential for mass production of sensing devices. PMID- 24177926 TI - A new approach for mapping quantitative trait loci using complete genetic marker linkage maps. AB - A new approach based on nonlinear regression for the mapping of quantitative trait loci (QTLs) using complete genetic marker linkage maps is advanced in this paper. We call the approach joint mapping as it makes comprehensive use of the information from every marker locus on a chromosome. With this approach, both the detection of the existence of QTLs and the estimation of their positions, with corresponding confidence intervals, and effects can be realized simultaneously. This approach is widely applicable because only moments are used. It is simple and can save considerable computer time. It is especially useful when there are multiple QTLs and/or interactions between them on a chromosome. PMID- 24177927 TI - Intergeneric hybridization between Brassica napus and Sinapis pubescens, and the cytology and crossability of their progenies. AB - The cytological possibility of gene transfer from Sinapis pubescens to Brassica napus was investigated. Intergeneric hybrids between Brassica napus (2n = 38) and Sinapis pubescens (2n = 18) were produced through ovary culture. The F1 hybrids were dihaploid and the chromosome configurations were (0-1) III + (2-11) II + (5 24) I . One F2 plant with 38 chromosomes was obtained from open pollination of the F1 hybrid. Thirty-one seeds were obtained from the backcross of the F2 plant with B. napus. Five out of seven plants had 38 chromosomes, and the pollen stainability ranged from 0% to 81.4%. In the B2 plants obtained from the backcross of B1 plants with B. napus, 66.7% of the plants examined had 38 chromosomes. S. pubescens may become a gene source for the improvement of B. napus. PMID- 24177928 TI - Comparative performance of FDR and SDR progenies from reciprocal 4x-2x crosses in potato. AB - Numerically unreduced (2n) gametes from first division restitution (FDR) are considered to be superior to 2n-gametes from second division restitution (SDR) because they transfer a larger proportion of the total parental heterozygosity and epistasis intact to the tetraploid progeny. This supposed superiority was investigated by comparing 12 sets of reciprocal 4x-2x crosses. Each diploid parent used in a reciprocal set produced 2n-pollen by FDR and 2n-eggs by SDR. Six agronomic characters were investigated. FDR progenies (from 4x.2x) were found to have higher mean yields due to more and bigger tubers. With respect to underwater weight, the overall progeny mean of FDR progenies was significantly higher than that of SDR progenies (from 2x.4x). However, the absolute difference found between both overall progeny means was too small to be of practical significance. No differences between FDR and SDR progeny means were found for vine maturity and chip colour. In addition to the progeny mean, within-progeny variation is important in potato breeding. For vine maturity a higher within-progeny variation was detected in SDR progenies, whereas within-progeny variations for yield, underwater weight and chip colour were not different in FDR and SDR progenies. With regard to vine maturity, we conclude that SDR 2n-gametes are superior to FDR 2n-gametes because, with the same progeny means of FDR and SDR progenies, the within-progeny variation was higher in SDR progenies. Therefore the assumed superiority of FDR 2n-gametes was confirmed for yield but was not observed for vine maturity, underwater weight and chip colour. PMID- 24177929 TI - Molecular genetics of growth and development in Populus. II. Segregation distortion due to genetic load. AB - Distortion of expected Mendelian segregation ratios, commonly observed in many plant taxa, has been detected in an experimental three-generation inbred pedigree of Populus founded by interspecific hybridization between P. trichocarpa and P. deltoides. An RFLP linkage map was constructed around a single locus showing severe skewing of segregation ratio against F2 trees carrying the P. trichocarpa allele in homozygous form. Several hypotheses for the mechanism of segregation distortion at this locus were tested, including directional chromosome loss, segregation of a pollen lethal allele, conflicts between genetic factors that isolate the parental species, and inbreeding depression as a result of genetic load. Breeding experiments to produce inbred and outcrossed progenies were combined with PCR-based detection of RFLPs to follow the fate of the deficient allele throughout embryo and seedling development. A recessive lethal allele, lth, inherited from the P. trichocarpa parent, was found to be tightly linked to the RFLP marker locus POP1054 and to cause embryo and seedling mortality. Heterozygotes (lth/+) appear to be phenotypically normal as embryos, seedlings, and young trees. PMID- 24177930 TI - Durum wheat haploid production using maize wide-crossing. AB - While anther culture or pollinations with Hordeum bulbosum have provided suitable methods for haploid production in bread wheat, they have been largely unsuccessful in durum wheat. Pollinations with maize were used in an attempt to produce haploid seedlings and, from these, fertile doubled haploids of durum wheats. Moreover, the effect of various concentrations and combinations of a synthetic auxin, 2, 4-dichlorophenoxyacetic acid (2,4-D), kinetin, and an ethylene inhibitor, silver nitrate (AgNO3), on embryo recovery were also investigated. Haploid seedlings were recovered from Triticum turgidum ssp. turgidum cv 'Rampton Rivet' pollinated with maize following in-vivo treatment of ovaries with 2,4-D for 2 weeks and subsequent embryo culture. The recovery of haploid seedlings from T. turgidum ssp. durum cv. 'Wakona' pollinated with maize necessitated the addition of AgNO3, to the 2,4-D treatment. Overall, haploid seedlings were produced in 1.7% and 3.3% of pollinated florets for "Rampton Rivet" and "Wakona" respectively. The success of the present work represents a significant breakthrough for haploid production in durum wheats. Wide hybridization with maize followed by in-vivo treatment of ovaries with 2,4-D alone, or in combination with AgNO3, may provide a widely-applicable method of haploid production in tetraploid wheats. PMID- 24177931 TI - Chromosome characteristics and behavior differences in Allium fistulosum L., A. cepa L, their F1 hybrid, and selected backcross progeny. AB - Mitotic and meiotic studies were performed on Allium fistulosum, A. cepa, their F1 hybrid, and ten selected backcross (BC)1 plants [(A. fistulosum x A. cepa) x (A. cepa)]. Each BC1 plant had at least one A. cepa isozyme allele (Pgi, Idh, or Adh). Chromosome morphology and behavior differed among plants. Meiocytes were observed with one, two, or three bridges and/ or fragments, indicating at least three paracentric inversions between A. fistulosum and A. cepa. Unusual crossing over and multivalent associations suggest that the 5F subtelocentric chromosome of A. fistulosum is involved in at least one translocation. The number of bridges and fragments and multivalent associations varied between the F1 hybrid and BC1 progenies. The F1 hybrid and all BC1 progenies were either sterile or had very little seed set. Fertility was not restored in any of the selected BC1 plants. PMID- 24177932 TI - Unusual inheritance of the mitochondrial genome organization in the progeny of reciprocal crosses between alloplasmic hexaploid wheat regenerants. AB - The transmission of a structurally-hypervariable fraction of the mitochondrial genome has been studied in 42 F1 progenies obtained from reciprocal crosses between self-pollinated alloplasmic wheat plants regenerated after long-term somatic embryogenesis. This fraction of the genome is maternally and stoichiometrically inherited. In contrast, some additional restriction fragments specific to regenerated plants display a more complex mode of sexual transmission: one of the additional fragments was stoichiometrically and systematically inherited whereas two others were detected only in certain F1 hybrids. Assuming that the detection, by Southern analysis, of such a fragment in regenerated plants is due to the amplification of a pre-existing substoichiometric molecule generated by the activation of a rare recombination event, our results suggest that the probability of detecting a novel fragment in the F1 hybrids could be determined by the length of the repeated sequence at which recombination occurs. PMID- 24177933 TI - Transformation of protoplasts and intact cells from slowly growing embryogenic callus of wheat (Triticum aestivum L.). AB - A procedure for culturing protoplasts from slowly growing embryogenic calli of wheat was developed. The procedure was dependent on the ability to isolate large numbers of culturable protoplasts from slowly growing embryogenic callus. Approximately 68% of the isolated protoplasts divided, and 22% formed colonies; of the latter, 67% continued to proliferate. Plating efficiency was reduced when protoplasts were transformed by polythylene glycol, electroporation, and/or Agrobacterium. Intact cells were also directly transformed by electroporation. Direct electroporation of the Agrobacterium binary vector into intact cells resulted in a significant increase of GUS activity over the control. PMID- 24177934 TI - Genetic mapping of turnip mosaic virus resistance in Lactuca sativa. AB - Presence of the dominant Tu gene in Lactuca sativa is sufficient to confer resistance to infection by turnip mosaic virus (TuMV). In order to obtain an immunological assay for the presence of TuMV in inoculated plants, the TuMV coat protein (CP) gene was cloned by amplification of a cDNA corresponding to the viral genome using degenerate primers designed from conserved potyvirus CP sequences. The TuMV CP was overexpressed in Escherichia coli, and polyclonal antibodies were produced. To locate Tu on the L. sativa genetic map, F3 families from a cross between cvs "Cobbham Green" (resistant to TuMV) and "Calmar" (susceptible) were genotyped for Tu. Families known to be recombinant in the region containing Tu were infected with TuMV and tested by the indirect enzyme linked immunosorbent assay (ELISA) using the anti-CP serum. This assay placed Tu between two random amplified polymorphic DNA (RAPD) markers and 3.2 cM from Dm5/8 (which confers resistance to Bremia lactucae). Also, bulked segregant analysis was used to screen for additional RAPD markers tightly linked to the Tu locus. Five new markers linked to Tu were identified in this region, and their location on the genetic map was determined using informative recombinants in the region. Six markers were identified as being linked within 2.5 cM of Tu. PMID- 24177935 TI - Structure and organization of the B genome based on a linkage map in Brassica nigra. AB - We constructed a genetic map on Brassica nigra based on a segregating population of 83 F2 individuals. Three different types of molecular markers were used to build the map including isozymes, restriction fragment length polymorphisms (RFLP), and random amplified polymorphic DNA (RAPD). The final map contained 124 markers distributed in 11 linkage groups. The map covered a total distance of 677 cM with the markers distributed within a mean distance of 5.5cM. Of the sequences found in the B. nigra map, 40% were duplicated and organized into three different types of arrangements. They were either scattered throughout the genome, organized in tandem, or organized in blocks of duplicated loci conserved in more than 1 linkage group. PMID- 24177936 TI - Hybrids and backcross progenies between wheat (Triticum aestivum L.) and apomictic Australian wheatgrass [Elymus rectisetus (Nees in Lehm.) A. Love & Connor]: karyotypic and genomic analyses. AB - Wheat (Triticum aestivum L., 2n = 6x = 42, AABBDD) florets were emasculated and pollinated using two apomictic wheatgrass [Elymus rectisetus (Nees in Lehm.) A. Love & Connor, 2n = 6x = 42, SSYYWW] accessions, one of which produces 2n pollen. A 2n = 42 (BII) hybrid and four 2n = 63 (B III) hybrids were obtained. The spike morphology of the B II hybrid was intermediate to that of its parents. The pollen mother cells (PMCs) of this hybrid contained on average 38.361 and 1.62 II, which was consistent with its disparate genome composition (ABDSYW). Its pollen failed to stain and no BC1 progeny was obtained. The B III hybrids (reduced egg fertilized with unreduced sperm) were grasslike and had a full complement of E. rectisetus chromosomes, the synapsis of which was slightly impaired by wheat haplome and/or cytoplasm. Their PMCs contained on average 16.30 II, 25.72 I, and 1.54 multivalents (III plus IV). Pollen stainability in these hybrids was low (<1%), and when they were used as females, one 54- and 60-chromosome BC1 were obtained. A mean of 13.25 II was observed in PMCs of the 54-chromosome BC1 and pollen stainability was 10%. Pollen stainability in the 60-chromosome BC1 was only 5%. The use of 2n-pollen-producing E. rectisetus accession accelerated hybrid and BC1 formation and may accelerate the ultimate transfer of apomixis to wheat. PMID- 24177937 TI - Extension of the linkage map in Citrus using random amplified polymorphic DNA (RAPD) markers and RFLP mapping of cold-acclimation-responsive loci. AB - Genetic mapping with RAPD markers has been initiated in Citrus. Reproducible polymorphism of amplified DNA fragments was obtained with approximately half of the 140 random primers tested, revealing 266 segregating loci. These were tested for linkage using 60 BC1 progeny from an intergeneric cross of Citrus grandis (L.) Osb. x [Citrus grandis (L.) Osb. x Poncirus trifoliata (L.) Raf.]. A core linkage map was constructed that consists of nine linkage groups containing 109 RAPD markers and 51 previously-mapped RFLP and isozyme markers. A further 79 markers that could not be ordered unambiguously because of their allelic constitution were associated with individual linkage groups and are shown in relation to the core map. The core map has a total length of 1192 cM with an average distance of 7.5 cM between loci and is estimated to cover 70-80% of the genome. Loci with distorted segregation patterns clustered on several linkage groups. Individual clusters of loci were skewed in allelic composition toward one or the other parent, usually C. grandis. This relatively-saturated linkage map will eventually be used to identify quantitative trait loci for cold and salt tolerance in Citrus. As a beginning we have mapped three loci detected by a cold acclimation-responsive cDNA. PMID- 24177938 TI - RFLP mapping of Brassica napus using doubled haploid lines. AB - The combined use of doubled haploid lines and molecular markers can provide new genetic information for use in breeding programs. An F1-derived doubled haploid (DH) population of Brassica napus obtained from a cross between an annual canola cultivar ('Stellar') and a biennial rapeseed ('Major') was used to construct a linkage map of 132 restriction fragment length polymorphism loci. The marker loci were arranged into 22 linkage groups and six pairs of linked loci covering 1016 cM. The DH map was compared to a partial map constructed with a common set of markers for an F2 population derived from the same F1 plant, and the overall maps were not significantly different. Comparisons of maps in Brassica species suggest that less recombination occurs in B. napus (n = 19) than expected from the combined map distances of the two hypothesized diploid progenitors, B. oleracea (n = 9) and B. rapa (n=10). A high percentage (32%) of segregating marker loci were duplicated in the DH map, and conserved linkage arrangements of some duplicated loci indicated possible intergenome homoeology in the amphidiploid or intragenome duplications from the diploid progenitors. Deviation from Mendelian segregation ratios (P < 0.05) was observed for 30% of the marker loci in the DH population and for 24% in the F2 population. Deviation towards each parent occurred at equal frequencies in both populations and marker loci that showed deviation clustered in specific linkage groups. The DH lines and molecular marker map generated for this study can be used to map loci for agronomic traits segregating in this population. PMID- 24177939 TI - Cytogenetic investigation of Triticum timopheevii (Zhuk.) Zhuk. and related species using the C-banding technique. AB - Triticum timopheevii and related species T. militinae (2n=28, A(t)G) and T. zhukovskyi (2n=42, A(m)A(t)G), hybrids T. kiharae, T. miguschovae, the amphidiploid T. timopheevii x T. tauschii (all 2n=42, A(t)GD), T. fungicidum (ABA(t)G) and T. timonovum (2n=56, A(t)A(t)GG) were analyzed using the C-banding technique. Chromosomes of the A(m) and A(t) genomes in the karyotype of T. zhukovskyi differed in their C-banding pattern. Partial substitutions of A(t) genome chromosomes and a complete substitution of the G-genome chromosomes by homoeologous chromosomes of an unidentified tetraploid wheat species with an AB genome composition were found in the T. timonovum karyotype. A(t)- and G-genome chromosomes in the karyotypes of all studied species had similar C-banding patterns and were characterized by a low level of polymorphism. The comparative stability of the A(t) and G genomes is determined by the origin and specifity of cultivation of studied species. PMID- 24177940 TI - Evolution of genetic diversity during the domestication of common-bean (Phaseolus vulgaris L.). AB - M13 DNA fingerprinting was used to determine evolutionary changes that occurred in Latin American germ plasm and USA cultivars of commonbean (Phaseolus vulgaris L.) during domestication. Linkage mapping experiments showed that M13-related sequences in the common-bean genome were either located at the distal ends of linkage groups or that they were unlinked to each other or to any previously mapped markers. Levels of polymorphism observed by hybridization with M13 (1 probe-enzyme combination) were comparable to those observed by hybridization with single-copy random PstI genomic probes (36 enzyme-probe combinations) but were higher than those observed for isozymes (10 loci). Results indicated that the wild ancestor had diverged into two taxa, one distributed in Middle America (Mexico, Central America, and Colombia) and the other in the Andes (Peru and Argentina); they also suggested separate domestications in the two areas leading to two cultivated gene pools. Domestication in both areas led to pronounced reductions in diversity in cultivated descendants in Middle America and the Andes. The marked lack of polymorphism within commercial classes of USA cultivars suggests that the dispersal of cultivars from the centers of origin and subsequent breeding of improved cultivars led to high levels of genetic uniformity. To our knowledge, this is the first crop for which this reduction in diversity has been documented with a single type of marker in lineages that span the evolution between wild ancestor and advanced cultivars. PMID- 24177941 TI - Molecular markers shared by diverse apomictic Pennisetum species. AB - Two molecular markers, a RAPD (randomly amplified polymorphic DNA) and a RFLP/STS (restriction fragment length polymorphism/sequence-tagged site), previously were found associated with apomictic reproductive behavior in a backcross population produced to transfer apomixis from Pennisetum squamulatum to pearl millet. The occurrence of these molecular markers in a range of 29 accessions of Pennisetum comprising 11 apomictic and 8 sexual species was investigated. Both markers were specific for apomictic species in Pennisetum. The RFLP/STS marker, UGT 197, was found to be associated with all taxa that displayed apomictic reproductive behavior except those in section Brevivalvula. Neither UGT197 nor the cloned RAPD fragment OPC-04600 hybridized with any sexually reproducing representatives of the genus. The cloned C04600 was associated with 3 of the 11 apomictic species, P. ciliare, P. massaicum, and P. squamulatum. UGT197 was more consistently associated with apomictic reproductive behavior than OPC04600 or cloned C04600, thus it could be inferred that UGT197 is more closely linked to the gene(s) for apomixis than the cloned C04600. The successful use of these probes to survey other Pennisetum species indicates that apomixis is a trait that can be followed across species by using molecular means. This technique of surveying species within a genus will be useful in determining the relative importance of newly isolated markers and may facilitate the identification of the apomixis gene(s). PMID- 24177942 TI - An N-band marker for gene Lr18 for resistance to leaf rust in wheat. AB - The leaf rust resistance gene, Lr18, of common wheat cultivars has been derived from Triticum timopheevi and is located on chromosome arm 5BL. Chromosome banding (N-banding) analyses revealed that in the wheat cultivars carrying Lr18 that were examined, which had been bred in 6 different countries, chromosome arm 5BL possessed a specific terminal band not carried by their susceptible parental cultivars. It was suggested that this terminal N-band was introduced from T. timopheevi together with Lr18. N-banding analysis of a T. timopheevi strain showed that one of two timopheevi chromosomes had provided Japanese wheat lines containing Lr18 with the terminal band. PMID- 24177943 TI - Best Linear Unbiased Prediction (BLUP) for regional yield trials: a comparison to additive main effects and multiplicative interaction (AMMI) analysis. AB - Multilocation trials are often used to analyse the adaptability of genotypes in different environments and to find for each environment the genotype that is best adapted; i.e. that is highest yielding in that environment. For this purpose, it is of interest to obtain a reliable estimate of the mean yield of a cultivar in a given environment. This article compares two different statistical estimation procedures for this task: the Additive Main Effects and Multiplicative Interaction (AMMI) analysis and Best Linear Unbiased Prediction (BLUP). A modification of a cross validation procedure commonly used with AMMI is suggested for trials that are laid out as a randomized complete block design. The use of these procedure is exemplified using five faba bean datasets from German registration trails. BLUP was found to outperform AMMI in four of five faba bean datasets. PMID- 24177944 TI - Linkages between common wheat yields and climate in Morocco (1982-2008). AB - In Morocco, wheat production shows a high inter-annual variability due to uncertain rainfall. In view of the importance of this resource to the country's economy, it is important to gain a better understanding of the natural large scale climate oscillation governing this variability. In this study, we analyzed de-trended (1) time series of common wheat yields (1983-2008) from 11 agricultural provinces that account for 80% of national wheat production; (2) monthly rainfall and 10-day temperature from ten meteorological stations; (3) 10 day normalized difference vegetation index (NDVI) from the AVHRR sensor; (4) monthly atmospheric climate indices [North Atlantic Oscillation (NAO) and Scandinavian Pattern (SCA)] and monthly 500 hPa geopotentials fields; and (5) monthly sea surface temperature (SST) fields and indices (NINO3, Tropical North Atlantic and Tropical South Atlantic). The relationship between rainfall and temperature during tillering in early winter and grain filling in early spring and wheat yields already observed at the plot scale was also found to be significant at the provincial scale. The linkages between wheat yields and large scale climate have been analyzed for the first time over Morocco. In agreement with previous studies, results show a complex and competing influence of different climate phenomena. The NAO is found to be significantly related to yields during the early stage of wheat growth in December, whereas the SCA correlates with yields later in the season, in January and February. Interesting lagged correlations with higher lead time are also highlighted, with the leading modes of SST variability in the equatorial Atlantic during October (the "Atlantic Nino" mode) and in the North Atlantic (the "Atlantic tripole" mode) in February. Our conclusion is that regional climate indices and variables represent valuable information with which to increase lead time and skill regarding wheat yield predictions in Morocco. PMID- 24177945 TI - Frequency-doubling technology perimetry for detection of the development of visual field defects in glaucoma suspect eyes: a prospective study. AB - IMPORTANCE: While standard automated perimetry (SAP) remains the reference standard for evaluation of visual field (VF) defects in glaucoma, this study demonstrates that frequency-doubling technology (FDT) perimetry is effective in monitoring visual field progression and may detect the onset of visual field defects earlier than SAP. OBJECTIVES: To compare detection of the development of VF defects, rate of change of VF loss, and risk factors for progression between SAP and matrix FDT perimetry in glaucoma suspect and ocular hypertensive eyes. DESIGN, SETTING, AND PARTICIPANTS: A total of 113 glaucoma suspect and ocular hypertensive eyes from 76 patients with normal SAP and FDT perimetry results at baseline were prospectively followed up for SAP and FDT perimetry testing at approximately 4-month intervals for 30 months or longer. Patients were consecutively enrolled and followed up from January 2, 2008, to February 28, 2012, at the Hong Kong Eye Hospital, Chinese University of Hong Kong. Visual field progression was defined by the development of VF defects confirmed by 3 or more consecutive examinations at a cluster of 3 or more (less conservative) or 4 or more (more conservative) locations. The rates of change of mean deviation and pattern standard deviation were evaluated with linear mixed models and the risk factors for VF progression were computed with Cox proportional hazard models. RESULTS: During a median study period of 3.4 years, 8.0% of eyes developed VF defects detected by FDT perimetry, 6.2% by SAP, and 4.4% by both using the less conservative criteria. The detection dropped to 6.2%, 4.4%, and 2.7%, respectively, when the more-conservative criteria were applied. The rate of change of pattern standard deviation was significantly faster for FDT perimetry than SAP (P < .001). Baseline average retinal nerve fiber layer thickness and the number of clock hours of abnormal retinal nerve fiber layer measurement were associated with increased risk for VF progression for both SAP and FDT perimetry. CONCLUSIONS AND RELEVANCE: Frequency-doubling technology perimetry would be useful to monitor the onset of VF defects in glaucoma and may detect VF defects not evident in SAP. PMID- 24177946 TI - Structural and functional analysis of the origin of replication of mitochondrial DNA from Paramecium aurelia : I. Inverted complements form the terminal loop. AB - Initiation of replication of the linear mitochondrial DNA from Paramecium occurs at a unique cross-linked terminus of the monomer molecule. Dimer length molecules, containing head-to-head monomers, are replicative intermediates. Previous studies have been with cloned dimer initiation region fragments but here we have isolated and sequenced isomeric forms of restriction fragments located at the initiation end of the monomer. The sequence isomers are inverted complements of each other in the region identified as the single-stranded DNA terminal loop. The unusual electrophoretic behaviour of these terminal restriction fragments supports the sequence data result that the loop is single stranded. These structural features are discussed in regard to mechanisms for the processing of dimer to monomer molecules. PMID- 24177947 TI - Structural and functional analysis of the origin of replication of mitochondrial DNA from Paramecium aurelia : II. A-T rich repeat units serve as autonomously replicating sequences. AB - Replication of mitochondrial DNA in Paramecium aurelia involves the formation of a covalent crosslink at one end of this linear molecule and proceeds unidirectionally, producing a dimer consisting of two head to head monomers. The initiation regions within the dimer molecules have been sequenced and shown to be palindromic except for a central nonpalindromic A+T rich sequence, arranged in direct tandem repeats. This nonpalindromic region (see accompanying paper) has been identified as the cross-link which converts the initiation terminus into a continuous sequence. In this study, yeast transformation was used to assay the dimer initiation regions of P. aurelia mtDNA for the presence of autonomously replicating sequences. P. aurelia mtDNA fragments from species 1 and 4 were cloned into the yeast vector YIP5 and the hybrid plasmids (YPaM) were used to transform yeast. The dimer initiation regions from both species promoted high frequency transformation and extrachromosomal maintenance of YPaM plasmids. Subcloning analysis of the ARS-containing mtDNA fragments indicates, specifically, that the nonpalindrome, repetitive sequences are responsible for the autonomously replicating properties of YPaM plasmids. PMID- 24177948 TI - A mitochondrial reading frame which may code for a second form of ATPase subunit 9 in Aspergillus nidulans. AB - The nucleotide sequence of a 74 codon reading frame from the Aspergillus nidulans mitochondrial genome is presented. The derived amino acid sequence displays typical features of dicyclohexylcarbodiimide (DCCD) binding proteins and is 84% homologous with a mitochondrial reading frame that potentially encodes an ATPase subunit 9 polypeptide in Neurospora crassa. However, in A. nidulans, as in N. crassa, there is strong biochemical and genetic evidence that this subunit is in fact nuclearly-encoded. In both organisms the DCCD-binding protein found in the F0 complexes of mitochondria from actively-growing cultures is almost certainly the product of this nuclear gene, and definitely not that of the mitochondrial reading frame. The discovery of an intact open reading frame than can code for a DCCD-binding protein in the mitochondrial genome of a second species of filamentous fungus strenghthens the possibility that the presence of a mitochondrial version of this gene has some biological significance. PMID- 24177949 TI - Differential effect of the alkaloid lycorine on rho (+), mit (-), rho (-), and rho (o) strains of Saccharomyces cerevisiae. AB - The alkaloid lycorine inhibits growth of rho (+), mit (-), and rho (-) strains, whereas rho (0) strains (devoid of mitochondrial DNA) of Saccharomyces cerevisiae are resistant to high concentrations of the drug. The inhibitory effect of lycorine on the growth of rho (+) strains can be counteracted by the addition of ascorbic acid to the plating medium. Lycorine induces cytoplasmic respiratory deficient mutants upon growth in glucose complete medium containing the alkaloid. The minimal inhibitory concentration of lycorine in glucose complete medium is ten times higher than in glycerol complete medium, thus demonstrating its preferential action on mitochondrial functions. Total protein synthesis and mitochondrial protein synthesis are only slightly inhibited by lycorine. It has, however, an inhibitory effect on DNA and RNA synthesis. PMID- 24177950 TI - Comparison of the lignin-degrading white rot fungi Phanerochaete chrysosporium and Sporotrichum pulverulentum at the DNA level. AB - DNA-hybridisation studies showed a close relationship between Phanerochaete chrysosporium ME446, most used in lignin degradation studies, and Sporotrichum pulverulentum Novobranova, the other standard lignin degrading strain. Two other strains of P. chrysosporium were both less related. We show that P. chrysosporium ME446 and S. pulverulentum Novobranova both have a GC-content of 59% for chromosomal DNA with the rRNA genes present as an AT-rich satellite; the mitochondrial DNA has a GC-content of 33%. The genome size estimated for P. chrysosporium ME446 is about 4-5 * 10(7) bp. PMID- 24177951 TI - Isolation and characterization of an uncoupler-resistant mutant of Saccharomyces cerevisiae. AB - One mutant resistant to carbonylcyanide m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, was isolated in Saccharomyces cerevisiae.Genetic analysis showed that a single nuclear gene is responsible for increased resistance; this gene was dominant.The mutant showed cross-resistance or collateral sensitivity to several chemically-unrelated inhibitors (cycloheximide, dinitrophenol, tributhyltin chloride, chloramphenicol).The resistance of the mutant is related to a decreased uptake of CCCP which is not expressed in glucose-starved cells. It was shown that glucose induced a CCCP efflux which was more efficient in the mutant than in the wild-type cells. This effect was correlated to a greater acidification of the internal pH by glucose addition in the mutant cells.It was proposed that resistance was not due to a change of permeability of the plasmic membrane itself but to the change of internal pH which determines the extent of accumulation of weak acids or bases. PMID- 24177952 TI - The mitochondrial genome of the fission yeast Schizosaccharomyces pombe : 5. Characterization of mitochondrial deletion mutants. AB - The three mutator strains ana (r)-8, ana (r)-14, and diu (r)-301 were shown to produce respiratory deficient mutants at different rates. The frequency of respiratory deficient mutants in a culture could be increased by adding ethidium bromide. According to their cytochrome spectra and enzymatic activities they form three classes, namely mutants defective in cytochrome oxidase, in cytochrome b, and in both cytochromes. By restriction enzyme analysis of mitochondrial DNA from about 100 mutants, 22 deletion mutants were identified. The deletions, ranging from 50 to 1,500 base pairs were physically mapped. Deletions were localized in the genes coding for subunit 1 of cytochrome oxidase with its two introns, within the cytochrome b gene and its intron, and within the genes for subunits 2 and 3 of cytochrome oxidase. In several cases, where the physical mapping yielded ambiguous results, pairwise genetic crosses ruled out an overlap between two neighbouring deletions.Using these mitochondrial deletion mutants as tester strains, it was shown that only tetrad analysis and chemical haploidization, but not mitotic segregation analysis, allows a decision between chromosomal and mitochondrial inheritance of respiratory deficiency in Schizosaccharomyces pombe. PMID- 24177953 TI - Starch utilization by yeasts: mutants resistant of carbon catabolite repression. AB - Twenty-seven yeasts were screened for starch breakdown; the three with the highest rate were strains of Filobasidium capsuligenum, Lipomyces starkeyi and Schwanniomyces occidentalis. Of these, only the last gave mutants with diminished carbon catabolite repression and, hence, enhanced amylase activity. Unlike those yeasts previously reported to break down starch rapidly, these mutants had the commercially advantageous characteristic of growing only slowly on the products of starch break-down and gave rise to readily-inducible auxotrophs. Like hex1 mutants of Saccharomyces cerevisiae, these mutants of Schwanniomyces occidentalis (i) had diminished hexokinase activity, (ii) retained high levels of glucokinase and (iii) resisted carbon catabolite repression of invertase and alpha-D glucokinase. In one mutant, isomaltase was induced in the late exponential phase of growth on starch, and this isomaltase was also resistant to repression. PMID- 24177954 TI - Evidence for the control of a mutation in lysine catabolism by the mating type in Yarrowia lipolytica. AB - Reversions of a mutation lye 1.5 blocking the first step of the lysine catabolic pathway were isolated. These reversions mapped inside the LYC1 locus. They exhibited an alteration of the regulation of the lysine pool after nitrogen and phosphorus starvation. This phenomenon did not appear in sexual diploids homozygous for the reversion. Diploids homozygous for the mating type were constructed by protoplast fusion. They displayed a pattern similar to that of the haploids. We conclude that the expression of this mutation is under the control of the physiological state of the mating type. PMID- 24177955 TI - Synthesis of a dicyclohexylcarbodiimide-binding proteolipid by cucumber (Cucumis sativus L.) mitochondria. AB - When isolated cucumber (Cucumis sativus L.) mitochondria were treated with (14)C labelled dicyclohexylcarbodiimide (DCCD), a single polypeptide was predominantly labelled. This polypeptide was soluble in 1-butanol or chloroform: methanol (2: 1, v/v) and had an apparent molecular mass of approximately 7 kDa; it therefore had the characteristic properties of the DCCD-binding proteolipid subunit of the ATP synthase complexes of mitochondria, chloroplasts, and prokaryotes.When isolated cucumber mitochondria were allowed to synthesize protein in the presence of [(35)S]methionine and then extracted with 1-butanol or chloroform: methanol (2: l, v/v), a (35)S-labelled proteolipid that migrated more rapidly on SDS polyacrylamide gels than the pro-teolipid labelled by [(14)C]DCCD was solubilized. Treatment of mitochondria with unlabelled DCCD after they had been allowed to synthesize protein, specifically converted some of the [(35)S]methionine-labelled proteolipid to a form that comigrated with the [(14)C]DCCD-labelled proteolipid. We therefore conclude that a DCCD-binding proteolipid is synthesized by isolated cucumber mitochondria. PMID- 24177956 TI - Nucleotide sequence of the clustered genes for apocytochrome b6 and subunit 4 of the cytochrome b/f complex in the spinach plastid chromosome. AB - A 2.4 kilobase-pair segment of the spinach plastid chromosome carrying the genes for apocytochrome b6 and subunit 4 of the thylakoid membrane cytochrome b/f complex has been analysed by DNA sequencing and Northern blot analysis. The nucleotide sequence reveals two uninterrupted open reading frames of 211 and 139 triplets coding for two hydrophobic proteins of 23.7 kd (cytochrome b6) and 15.2 kd (subunit 4). The genes are located on the same strand and are separated from each other by 1018 untranslated base pairs. They map adjacent to the gene for the P680 chlorophyll alpha apoprotein of the photosystem II reaction center. The three genes appear to be under common transcriptional control and the transcripts post-transcriptionally modified. The deduced amino acid sequences of cytochrome b6 and subunit 4 both exhibit significant homology with published sequences from mitochondrial b cytochromes (42 kd) suggesting that these functionally equivalent polypeptides in photosynthetic and respiratory electron transport chains arose monophyletically. PMID- 24177957 TI - Nucleotide sequence of the gene for pre-apocytochrome f in the spinach plastid chromosome. AB - We have characterized a cloned fragment of the spinach plastid chromosome encoding the gene for apocytochrome f. Northern blot analysis and hybrid selection translation discloses that the gene is expressed. From the nucleotide sequence, we deduce that the protein contains 285 amino acids and an amino terminal signal sequence of 35 amino acid residues. The calculated molecular mass of pre-apocytochrome f is 35.3 kd. The clustering of hydrophobic residues indicates that the processed protein (31.3 kd) possesses only a single anchoring transmembrane domain close to the C terminus, and that 75% of the polypeptide chain including the heme-binding site protrudes into the thylakoid lumen. This topology resembles that reported for beef heart mitochondrial cytochrome c1. PMID- 24177958 TI - c-ABL tyrosine kinase modulates p53-dependent p21 induction and ensuing cell fate decision in response to DNA damage. AB - The c-ABL non-receptor tyrosine kinase and the p53 tumor suppressor protein are pivotal modulators of cellular responses to DNA damage. However, a comprehensive understanding of the role of c-ABL kinase in p53-dependent transcription of p21(CIP1/WAF1) and ensuing cell fate decision is still obscure. Here, we demonstrate that c-ABL tyrosine kinase regulates p53-dependent induction of p21. As a result, it modulates cell fate decision by p53 in response to DNA damage differently according to the extent of DNA damage. When human cancer cells were treated with DNA damaging agent, adriamycin (0.08 MUg/ml), p21 was induced following p53 induction. Owing largely to p21, a substantial fraction of cells treated with adriamycin were blocked at the G2 phase of the cell cycle and most cells eventually became senescent. When these cells were simultaneously treated with a c-ABL kinase inhibitor, STI571, or a c-ABL-specific siRNA along with adriamycin, the p53-dependent p21 induction was dramatically diminished, even though p53 is substantially induced. Accordingly, G2-arrest, and cellular senescence largely dependent on p21 were substantially abrogated. On the contrary, when cells were treated with a relatively high dose of adriamycin (0.4 MUg/ml) cells became apoptotic, and the simultaneous presence of a c-ABL kinase inhibitor STI571 augmented the extent of apoptosis. We speculate this is due to abrogation of p53-dependent p21 induction, which leads to elimination of anti apoptotic function of p21. In summary, c-ABL appears to promote senescence or inhibit apoptosis, depending on the extent of DNA damage. These findings suggest that the combined use of ABL kinase inhibitor and DNA damaging drug in chemotherapy against tumors retaining wild type p53 should be carefully designed. PMID- 24177959 TI - Helmet use among users of the Citi Bike bicycle-sharing program: a pilot study in New York City. AB - The use of bicycle helmets to prevent or reduce serious head injuries is well established. However, it is unclear how to effectively promote helmet use, particularly in the context of bicycle-sharing programs. The need to determine rates of helmet use specifically among users of bicycle-sharing programs and understand if certain characteristics, such as time of day, affect helmet use, is imperative if effective promotion and/or legislative efforts addressing helmet use are to be developed. We estimated the prevalence of helmet use among a sample of Citi Bike program users in New York City. A total of 1,054 cyclists were observed over 44 h and across the 22 busiest Citi Bike locations. Overall, 85.3% (95% CI 82.2, 88.4%) of the cyclists observed did not wear a helmet. Rates of helmet non-use were also consistent whether cyclists were entering or leaving the docking station, among cyclists using the Citi Bikes earlier versus later in the day, and among cyclists using the Citi Bikes on weekends versus weekdays. Improved understanding about factors that facilitate and hinder helmet use is needed to help reduce head injury risk among users of bicycle sharing programs. PMID- 24177960 TI - Purification and immunolocalization of an annexin-like protein in pea seedlings. AB - As part of a study to identify potential targets of calcium action in plant cells, a 35-kDa, annexin-like protein was purified from pea (Pisum sativum L.) plumules by a method used to purify animal annexins. This protein, called p35, binds to a phosphatidylserine affinity column in a calcium-dependent manner and binds (45)Ca(2+) in a dot-blot assay. Preliminary sequence data confirm a relationship for p35 with the annexin family of proteins. Polyclonal antibodies have been raised which recognize p35 in Western and dot blots. Immunofluorescence and immunogold techniques were used to study the distribution and subcellular localization of p35 in pea plumules and roots. The highest levels of immunostain were found in young developing vascular cells producing wall thickenings and in peripheral root-cap cells releasing slime. This localization in cells which are actively involved in secretion is of interest because one function suggested for the animal annexins is involvement in the mediation of exocytosis. PMID- 24177961 TI - Shoot elongation in Lathyrus odoratus L.: Gibberellin levels in light- and dark grown tall and dwarf seedlings. AB - The levels of gibberellin A1 (GA1), GA20, GA19, GA8, GA29 and GA81 (2-epiGA29) were measured in tall (L-) and dwarf (ll) sweet-pea plants grown in darkness and in light. In both environments the apical portions of dwarf plants contained less GA1; GA8 and GA19, but more GA20, GA29, and GA81 than did those of tall plants. It is concluded that the partial block in 3beta-hydroxylation of GA20 to GA1 is imposed by allele l in darkness as well as in the light. Furthermore, darkness does not appear to enhance elongation in sweet pea by increasing GA1 levels. The reduction of the pool size of GA19 in dwarf plants supports recent theories on the regulation of GA biosynthesis, formulated on the basis of observations in monocotyledonous species. Darkness results in decreased GA20, GA29, and GA81 levels in the apical portions of tall and dwarf plants and possible reasons for this are discussed. PMID- 24177962 TI - Compartmental distribution and redistribution of abscisic acid in intact leaves : I. Mathematical formulation. AB - Using experimental information obtained in earlier studies on the permeabilities of mesophyll and guard-cell membranes to abscisic acid (ABA), and on stress induced pH shifts in the apoplasm and in symplasmic compartments (Hartung et al., 1988, Plant Physiol. 86, 908-913; Hartung et al. 1990, BPGRG Monogr. 215-235), a mathematical model is presented which will permit computer analysis of the stress induced redistribution of ABA amongst different leaf cell types (mesophyll, epidermis, guard cells, phloem cells) and their compartments (cell wall, cytosol, chloroplast stroma, vacuole). Metabolism and conjugation of ABA and its transport in the xylem and the phloem are also taken into consideration. We ask whether the stressinduced redistribution of ABA is fast and intensive enough to induce stomatal closure within a few minutes. The model can be adapted to any other weak acid or base, e.g. to other phytohormones (auxins, gibberellins), which differ from ABA, e.g. by their membrane conductances, anion permeabilities and pKa values. Our wholeleaf model can predict the time course and the compartmentation of, for example, phytohormone concentrations as a function of changing source sink patterns (e.g. by compartmental pH shifts in the leaf lamina). An analysis of the present knowledge of the ABA physiology of leaves and studies on stress effects are presented in subsequent publications. In this communication we describe the whole-leaf model and present and discuss all necessary morphological (volumes, surfaces etc.) and physiological (pH, membrane conductances etc.) parameters of an unstressed leaf of Valerianella locusta L. We draw fundamental conclusions by comparing determined and calculated ABA concentrations in the leaf cell compartments. We found that the model predictions are close to measured data, and we conclude that in unstressed leaves ABA is close to flux equilibrium amongst the different tissues and compartments. PMID- 24177963 TI - Compartmental distribution and redistribution of abscisic acid in intact leaves : II. Model analysis. AB - A computer model written for whole leaves and described in the preceding publication (Slovik et al. 1992, this volume) has been developed for calculating the distribution and fluxes of weak acids or bases amongst different leaf tissues and their compartments, considering membrane transport, transpiration-driven mass transport, symplasmic and apoplasmic diffusion, and metabolic turnover rates in specified compartments. The model is used to analyse flux equilibria and the transport behaviour of the phytohormone abscisic acid (ABA) in unstressed and stressed leaves. We compare experimental data of unstressed Valerianella locusta L. leaves and expectations based on the detailed analysis of the data. (i) The mean daily influx of ABA into the leaf lamina via the xylem sap is about 10 nmol . m(-2) . day(-1). It is balanced by the sum of an export of ABA via the phloem sap (0.7%), possibly also by a basipetal ABA transport in the petiole parenchyma of young leaves (up to 18%), by an irreversible conjugation of ABA (0.4-4%) and by net degradation of ABA in the leaf lamina (80-95%). (ii) The estimated kinetic parameters of this net degradation are for the mesophyll apoplasm: apparent K m = 3.7 nM and V max = 12.9 nmol . m(-3) . s(-1), or for the mesophyll cytosol: apparent K m = 8.1 nM and V max = 32.3 nmol . m(-3) . s(-1). (iii) The dynamic ABA concentration in the phloem sap of Valerianella is 2.8 nM. This is only 5.5% of the static ABA equilibrium concentration in excised leaves or 70% of the ABA concentration in the mesophyll apoplasm, and it equilibrates within a few hours after source concentrations in the mesophyll apoplasm are changed under stress. Thus, the phloem sap is a flexible medium for transporting 'new phytohormone information' from the lamina to the shoot and roots, (iv) Measured compartmental ABA concentrations are close to calculated equilibrium concentrations in unstressed leaves. We conclude that model calculations are close to reality, (v) pH gradients within the apoplasm influence the apoplasmic distribution of ABA. Its concentration is maximally about twofold higher in guard-cell walls relative to the mesophyll apoplasm. (vi) Unexpectedly, all compartmental equilibrium concentrations of ABA in the leaf lamina depend on plasmalemma conductances for undissociated ABA and on the transport properties of the plasmodesmata. This is a consequence of the cyclic diffusion pathway: mesophyll cytosol - mesophyll plasmalemma - mesophyll apoplasm - epidermal apoplasm - epidermal plasmalemma - epidermal cytosol - plasmodesmata - mesophyll cytosol (in this direction), if there are different apoplasmic or cytosolic pH values in both tissues. The cyclisation rate is 42 fmol . s(-1) . m(-2) leaf area, which corresponds to a turnover time = 11.0 h for the total ABA content within the leaf lamina. A decrease of the epidermal plasmalemma conductance by 90% yields a threefold ABA concentration in the guard-cell free space, (vii) Compartmental relaxation-time coefficients are estimated and summarised for all leaf tissues and its major compartments. They range from 1.5 min for chloroplasts up to 3.3 d for mesophyll vacuoles, (viii) The highest ABA concentration, which can be expected in any leaf compartment, is 7 mM in the guard-cell cytoplasm of certain plant species, (ix) We employed circadian changes (equal day + night, 12 h each = equinoctium) of the stromal pH +/- 0.3 in C(3) plants, and for Crassulacean acid metabolism (CAM) plants, additionally, vacuolar pH +/- 2.5 changes, and calculated the consequences for ABA redistribution within the lamina. In plants of both photosynthesis types, the ABA concentration in guard-cell walls is only 1.5 times higher in the night relative to the day. We conclude that stomata may not be regulated by ABA in a night-day regime. The influence of the extreme vacuolar pH changes on ABA distribution is small in CAM plants for two reasons: the ABA content in CAM mesophyll vacuoles is low (maximum 2.7% of the total ABA mass per unit leaf area) and there is only a 6.5-fold increase of the mole fraction of undissociated ABA when the the vacuolar pH is lowered from 5.5 to 3.0 (importance of the absolute pKa = 4.75 of ABA). PMID- 24177964 TI - Compartmental distribution and redistribution of abscisic acid in intact leaves : III. Analysis of the stress-signal chain. AB - Using a computer model written for whole leaves (Slovik et al. 1992, Planta 187, 14-25) we present in this paper calculations of abscisic acid (ABA) redistribution among different leaf tissues and their compartments in relation to stomatal regulation under drought stress. The model calculations are based on experimental data and biophysical laws. They yield the following results and postulates: (i) Under stress, compartmental pH-shifts come about as a consequence of the inhibition of the pH component of proton-motive forces at the plasmalemma. There is a decrease of net proton fluxes by about 8.6 nmol . s(-1) . m(-2). (ii) Using stress-induced pH-shifts we demonstrate how 'stress intensities' can be quantified on a molecular basis. (iii) As the weak acid ABA is the only phytohormone which behaves in vivo and in vitro ideally according to the Henderson-Hasselbalch equation, pH-shifts induce a complicated redistribution amongst compartments in the model leaf. (iv) The final accumulation of ABA in guard-cell walls is intensive: up to 16.1-fold compared with only up to 3.4-fold in the guard-cell cytosol. We propose that the binding site of the guard-cell ABA receptor faces the apoplasm. (v) A twoto three-fold ABA accumulation in guard cell walls is sufficient to induce closure of stomata. (vi) The minimum time lag until stomata start to close is 1-5 min; it depends on the stress intensity and on the guard-cell sensitivity to ABA: the more moderate the stress is, the later stomata start to close or they do not close at all. (vii) In the short term, there is almost no influence of the velocity of pH-shifts on the velocity of the ABA redistribution, (viii) Six hours after the termination of stress there is still an ABA concentration 1.4-fold the initial level in the guard-cell cytosol (delay of ABA relaxation, 'aftereffect'), (ix) The observed 'induction' of net ABA synthesis after onset of stress may be explained by a decrease in cytosolic ABA degradation. About 1 h after onset of stress the model leaf would start to synthesise ABA (and its conjugates) automatically, (x) This ABA net synthesis serves to 'inform roots' via an increased ABA concentration in the phloem sap. The stress-induced ABA redistribution is per se not sufficient to feed the ploem sap with ABA. (xi) The primary target membrane of 'stress' is the plasmalemma, not thylakoids. (xii) The effective 'stress sensor', which induces the proposed signal chain finally leading to stomatal closure, is located in epidermal cells. Mesophyll cells are not capable of creating a significant ABA signal to guard cells if the epidermal plasmalemma conductance to undissociated molecular species of ABA (HABA) is indeed higher than the plasmalemma conductance of the mesophyll (plasmodesmata open), (xiii) All model conclusions which can be compared with independent experimental data quantitatively fit to them. We conclude that the basic experimental data of the model are consistent. A stress-induced ABA redistribution in the leaf lamina elicits stomatal closure. PMID- 24177965 TI - Nicotianamine and the distribution of iron into the apoplasm and symplasm of tomato (Lycopersicon esculentum Mill.) : I. Determination of the apoplasmic and symplasmic iron pools in roots and leaves of the cultivar Bonner Beste and its nicotianamine-less mutant chloronerva. AB - The apoplasmic and symplasmic iron pools were determined in roots and leaves of Lycopersicon esculentum Mill. cv. Bonner Beste and its mutant chloronerva. The mutant is auxotrophic for the ubiquitous plant constituent nicotianamine (NA) and exhibits an impaired iron metabolism. Formation of apoplasmic iron pools in roots was dependent on the iron source in the nutrient solution. With Fe ethylenediaminedi-(2-hydroxyphenylacetate) (FeEDDHA) only a very small apoplasmic iron pool was formed in the roots of both genotypes. Plants grown with FeEDTA increased their apoplasmic iron pool with increasing exogenous iron concentrations in the nutrient solution. The size of the apoplasmic pools in roots did not differ between the wild-type and the mutant (about 85 MUmol Fe . g( 1) DW). By contrast, the symplasmic iron concentrations in roots and leaves of the mutant were significantly higher when compared to the wild-type. An exogenous NA supply to the leaves of the mutant reduced the high symplasmic iron concentrations to the level of the wild-type. Mutant leaves exhibited a gradient of symplasmic iron concentrations depending on the developmental age of the leaves. The oldest leaves contained considerably more symplasmic iron than the youngest. The results demonstrate that the apparent iron deficiency of the mutant is not the consequence of an impaired iron transport from the apoplasm to the symplasm. Therefore, it is concluded that NA is not required for the transport of Fe(II) through the plasmalemma into the cell. PMID- 24177966 TI - Circadian rhythm and fast responses to blue light of photosynthesis in Ectocarpus (Phaeophyta, Ectocarpales) : I. Characterization of the rhythm and the blue-light response. AB - The photosynthetic oxygen production of Ectocarpus siliculosus (Dillwyn) Lyngb. under continuous high irradiances of red light displayed a circadian rhythm with maxima at about noon. Pulses of blue light induced rapid transient increases in the rate of photosynthesis. The increases started about 15 s after the beginning of blue light and reached their maxima after 3-4 min. This was followed by a gradual decrease. A second peak or shoulder about 20 min later indicated that at least two reactions were involved in the blue-light enhancement of photosynthesis. The magnitude of the response to blue light depended on the phase of the rhythm at which blue light was given. It was high when the red-light photosynthesis was at its troughs, and low at its peaks. Fluence-response curves indicated that the sensitivity to blue light at the peaks of the rhythm was identical to that at the troughs. In addition, blue light shifted the phase of the photosynthetic rhythm, where the essential trigger was the light-off signal. Red light had no specific influence on the circadian rhythm. After darkness, photosynthetic rates were different from those under steady-state conditions. Two different transient bursts in the rate of O2 evolution could be distinguished, an early non-rhythmical one that was probably caused by accumulation of inorganic carbon inside the cells, and a second later one that appeared at the peak activity phases of the ciradian rhythm or after blue light. Its origins are unclear. PMID- 24177967 TI - Circadian rhythm and fast responses to blue light of photosynthesis in Ectocarpus (Phaeophyta, Ectocarpales) : II. Light and CO2 dependence of photosynthesis. AB - Photosynthesis of Ectocarpus siliculosus (Dillwyn) Lyngb. under continuous saturating red irradiation follows a circadian rhythm. Blue-light pulses rapidly stimulate photosynthesis with high effectiveness in the troughs of this rhythm but the effectiveness of such pulses is much lower at its peaks. In an attempt to understand how blue light and the rhythm affected photosynthesis, the effects of inorganic carbon on photosynthetic light saturation curves were studied under different irradiation conditions. The circadian rhythm of photosynthesis was apparent only at irradiances which were not limiting for photosynthesis. The same was found for blue-light-stimulated photosynthesis, although stimulation was observed also under very low red-light irradiances after a period of adaptation, provided that the inorganic-carbon concentration was not in excess. Double reciprocal plots of light-saturated photosynthetic rates versus the concentration of total inorganic carbon (up to 10 mM total inorganic carbon) were linear and had a common constant for half-saturation (3.6 mM at pH 8) at both the troughs and the peaks of the rhythm and before and after blue-light pulses. Only at very low carbon concentrations was a clear deviation found from these lines for photosynthesis at the rhythm maxima (red and blue light), which indicated that the strong carbon limitation specifically affected photosynthesis at the peak phases of the rhythm. Very high inorganic carbon concentrations (20 mM) in the medium diminished the responses to blue light, although they did not fully abolish them. The kinetics of the stimulation indicate that the rate of photosynthesis is affected by two blue-light-dependent components with different time courses of induction and decay. The faster component seemed to be at least partially suppressed at red-light irradiances which were not saturating for photosynthesis. Lowering the pH of the medium had the same effects as an increase of the carbon concentration to levels of approx. 10 mM. This indicates that Ectocarpus takes up free CO2 only and not bicarbonate, although additional physiological mechanisms may enhance the availability of CO2. PMID- 24177968 TI - Control of mannose/galactose ratio during galactomannan formation in developing legume seeds. AB - Galactomannan deposition was investigated in developing endosperms of three leguminous species representative of taxonomic groups which have galactomannans with high, medium and low galactose content. These were fenugreek (Trigonella foenum-graecum L.; mannose/galactose (Man/Gal) = 1.1), guar (Cyamopsis tetragonoloba (L.) Taub.; Man/Gal = 1.6) and Senna occidentalis (L.) Link. (Man/Gal = 3.3), respectively. Endosperms were analysed at different stages of seed development for galactomannan content and the levels, in cell-free extracts, of a mannosyltransferase and a galactosyltransferase which have been shown to catalyse galactomannan biosynthesis in vitro (M. Edwards et al., 1989, Planta 178, 41-51). There was a close correlation in each case between the levels of the biosynthetic mannosyl- and galactosyltransferases and the deposition of galactomannan. The relative in vitro activities of the mannosyl- and galactosyltransferases in fenugreek and guar were similar, and almost constant throughout the period of galactomannan deposition. In Senna the ratio mannosyltransferase/galactosyltransferase was always higher than in the other two species, and it increased substantially throughout the period of galactomannan deposition. In fenugreek and guar the galactomannans present in the endosperms of seeds at different stages of development had the Man/Gal ratios characteristic of the mature seeds. By contrast the galactomannan present in Senna endosperms at the earliest stages of deposition had a Man/Gal ratio of about 2.3. During late deposition this ratio increased rapidly, stabilising at about 3.3, the ratio characteristic of the mature seed. The levels of alpha-galactosidase in the developing endosperms of fenugreek and guar were low and remained fairly constant throughout the deposition of the galactomannan. In Senna, alpha-galactosidase activity in the endosperm was low during early galactomannan deposition, but increased subsequently, peaking during late galactomannan deposition. The developmental patterns of the alpha-galactosidase activity and of the increase in Man/Gal ratio of the Senna galactomannan were closely similar, indicating a cause and-effect relationship. The endosperm alpha-galactosidase activity in Senna was capable, in vitro, of removing galactose from guar galactomannan without prior depolymerisation of the molecule. In fenugreek and in guar the genetic control of the Man/Gal ratio in galactomannan is not the result of a post-depositional modification, and must reside in the biosynthetic process. In Senna, the Man/Gal ratio of the primary biosynthetic galactomannan product is controlled by the biosynthetic process. Yet the final Man/Gal ratio of the galactomannan in the mature seed is, to an appreciable extent, the result of galactose removal from the primary biosynthetic product by an alpha-galactosidase activity which is present in the endosperm during late galactomannan deposition. PMID- 24177969 TI - Compartmental analysis of amino-acid release from attached and detached pea seed coats. AB - Using the empty-seed-coat technique, we have studied the release of amino acids from pea (Pisum sativum L. cv. Marzia) seed coats, either attached to or detached from the mother plant, at various stages of development. During an experimental period of 8 h, about 70% of the amino-acid content of the seed coat was released into the solution with which the seed-coat cup was filled. Major components of the released amino-acid mixture were glutamine (25%), alanine (20%) and threonine (15%). At the end of the experimental period (t>=6 h) the amino-acid efflux from attached seed coats was approx. 0.15 MUmol . h(-1).(seed coat)(-1) greater than that from detached seed coats. This difference may be attributed to the import of amino acids into attached seed coats. It is equivalent to approx. 0.3 MUmol N . h(-1) . (seed coat)(-1), whereas the nitrogen demand of the embryo amounted to 0.50 +/- 0.04 MUmol N . h(-1) . embryo(-1). The time course of the release from detached seed coats could be described by the sum of two exponentials with t1/2 = 0.4-0.7 h and t(1/2) = 3.3-6.9 h, respectively, which probably represent the emptying of the cytoplasmic and vacuolar compartments. During development the vacuolar amino-acid pool decreased considerably (from 6.2 to 1.4 MUmol . (seed coat)(-1)), whereas the cytoplasmic pool was much more constant (2.1-1.2 MUmol . (seed coat)(-1)). For attached seed coats it will be shown that the time course of the amino-acid release could be fully accounted for by the sum of two exponentials and a linear term, where the parameters of the exponentials were, within error, the same as for detached seed coats and the linear term represented the import of amino acids. The results will be discussed with reference to prevailing models of phloem unloading in the seed coat, and in relation to the flux of amino acids from seed coat to the developing embryo. PMID- 24177970 TI - Subcellular localization of luteolin glucuronides and related enzymes in rye mesophyll. AB - Vacuoles were isolated by osmotic rupture of mesophyll protoplasts from the primary leaves of 4-d- and 7-d-old plants of rye (Secale cereale L.). Their content of two flavones, luteolin 7-O-[beta-D-glucuronosyl-(1->2)beta-D glucuronide] (R2) and luteolin 7-O-[beta-D-glucuronosy 1 (1->2) beta-D glucuronide]-4'-O-beta-D-glucuronide (R1), as well as that of three specific flavone-glucuronosyltransferases involved in their biosynthesis and of a specific beta-glucuronidase was determined in comparison to the parent protoplasts. The two flavonoids were found to be entirely located in the vacuolar fraction, together with 70% of the activity of UDP-glucuronate: luteolin 7-O-diglucuronide 4'-O-glucuronosyl-transferase (LDT; EC 2.4.1.), the third enzyme of the sequence of three transferases in the anabolic pathway. The activities of the first and second anabolic enzymes, UDP-glucuronate: luteolin 7-O-glucuronosyltransferase (LGT; EC 2.4.1.) and UDP-glucuronate: luteolin 7-O-glucuronide glucuronosyltransferase (LMT; EC 2.4.1.) could not be found in the vacuolar fraction in appreciable amounts. The specific beta-glucuronidase (EC 3.2.1.), catalyzing the deglucuronidation of luteolin triglucuronide to luteolin diglucuronide, was present with 90% of its activity in the digestion medium after isolation of mesophyll protoplasts, indicating an apoplastic localization of this enzyme. The data presented indicate a directed anabolic and subsequent catabolic pathway for the luteolin glucuronides in the mesophyll cells of rye primary leaves. This includes two cytosolic and a last vacuolar step of glucuronidation of luteolin, and the vacuolar storage of the luteolin triglucuronide. We propose the transport of the latter into the cell wall, after which the triglucuronide is deglucuronidated, this being the first step for further turnover. PMID- 24177971 TI - Outer envelope membranes from chloroplasts are isolated as right-side-out vesicles. AB - Outer envelope membranes were isolated from purified chloroplasts of pea leaves. The sidedness of the vesicles was analyzed by (i) aqueous polymer-two phase partitioning, (ii) the effect of limited proteolysis on the outer-envelope proteins (OEP) 86 and OEP 7 in intact organelles and isolated membranes, (iii) fluorescence-microscopy and finally (iv) binding of precursor polypeptides to isolated outer-membrane vesicles. The results demonstrate that purified outer envelope membranes occur largely (>90%) as right-side-out vesicles. PMID- 24177972 TI - Compartmentation of soluble carbohydrates, of starch and of malate in motor organs (pulvini) and other parts of Phaseolus coccineus L. leaves. AB - Quantitative histochemistry was used to investigate the tissue-specific compartmentation of soluble carbohydrates (sucrose, glucose, fructose), starch and malate in the laminar pulvinus, leaf blade and petiole of Phaselous coccineus L. at day and night positions of diurnal leaf movement. Total carbohydrate levels measured in a series of cross sections along individual pulvini of 24-d-old plants showed only small differences between the day and night positions of the respective leaf. In contrast, the level of malate changed during diurnal leaf movement, especially in the central part of a pulvinus. The levels of glucose and fructose in the pulvinus increased towards the transition zones between the pulvinus and lamina, and pulvinus and petiole, and this trend was even more pronounced for starch. By contrast, sucrose levels were highest in the pulvinus proper. The transverse compartmentation of metabolites was studied in distinct, approx. 0.5-mm-thick tissue slices from the central part of a pulvinus. These were dissected further into up to 14 distinct subsamples (bundle, bundle sheath, motor tissues, flanks). Irrespective of the position of the leaf (day or night), the central vascular core and the surrounding bundle sheath had high levels of sucrose (up to 500 mmol-(kg DW)(-1)) and low levels of glucose and fructose (below 100 mmol-(kg DW)(-1)), while in the cortex the situation was reversed. In the night position the level of sucrose decreased by approx. 30% in the bundle sheath and the central vascular core but not in the other sections. We thus suggest that because of the relatively small diurnal changes in their cortical pools, soluble sugars are not involved in the osmotic processes resulting in leaf movement. In contrast, pulvini from 14-d-old plants showed an interesting diurnal change in starch and malate pools in the outermost layer of the extensor. Here starch increased at night while the malate pool was lowered nearly stoichiometrically. Inverse pool sizes were found in the day position of the respective leaves. Although less significant, the opposite diurnal variation occurred in samples taken from the flexor region. We thus were able to locate areas of different carbohydrate activities in the laminar pulvinus of P. coccineus. The central vascular core, including the bundle sheath, is involved in temporary storage of photoassimilates, and the cortical regions are responsible for osmotically driven leaf movement. The results are discussed with respect to guard-cell physiology. PMID- 24177973 TI - Enzymatic conversion of dihydroflavonols to flavan-3,4-diols using flower extracts of Dianthus caryophyllus L. (carnation). AB - Flavonoid analysis and supplementation experiments with dihydroflavonols and leucocyanidin on two cyanic, two acyanic and one white/red-variegated flowering strain of Dianthus caryophyllus (carnation) showed that in the acyanic strains recessive alleles (aa) of the gene A interrupt the anthocyanin pathway between dihydroflavonols and leucoanthocyanidins. The instability in the variegated strain involves the same step and is obviously caused by the multiple allele a (var) . In confirmation of these results, dihydroflavonol 4-reductase activity could be demonstrated in enzyme extracts from cyanic flowers and cyanic parts of variegated flowers but not in preparations from acyanic flowers or acyanic parts. The enzyme catalyzes the stereospecific reduction of (+)dihydrokaempferol to (+) 3,4-leucopelargonidin with NADPH as cofactor. A pH optimum around 7.0 and a temperature optimum at 30 degrees C was determined, but the reduction reaction also proceeded at low temperatures. (+)Dihydroquercetin and (+)dihydromyricetin were also reduced to the respective flavan-3,4-cis-diols by the enzyme preparations from carnation flowers, and were even better substrates than dihydrokaempferol. PMID- 24177974 TI - Mutations in loop six of the large subunit of ribulose-1,5-bisphosphate carboxylase affect substrate specificity. AB - Mutagenesis in vitro of the gene encoding the large subunit of ribulose-1,5 bisphosphate carboxylase/ oxygenase (EC 4.1.1.39) from Anacystis nidulans Synechococcus PCC 6301) was used to generate novel enzymes in Escherichia coli. Residues in C-terminal loop 6 of the beta/alpha barrel structure of the large subunit were changed. Replacement of valine 331 with alanine caused a 90% reduction in V max but did not alter the enzyme's relative specificity towards either of its gaseous substrates, CO2 and O2. However replacement of alanine 340 with glutamate decreased the enzyme's specificity for CO2 but had no significant effect on either the K m for ribulose-1,5-bisphosphate or CO2 or on V max. In contrast replacing a small cassette of residues 338-341 produced a small increase in the specificity factor. PMID- 24177975 TI - Reappearance of hydrolytic activities and tonoplast proteins in the regenerated vacuole of evacuolated protoplasts. AB - Mesophyll protoplasts of tobacco (Nicotiana tabacum L. cv. Xanthi) were evacuolated by centrifugation in a density gradient. Evacuolation resulted in the quantitative loss of vacuolar hydrolytic activities. The evacuolated miniprotoplasts were cultivated under different conditions, and the regeneration of the central vacuole was investigated by light and electron microscopy as well as by the determination of activities of vacuolar marker enzymes. Vacuoles and hydrolytic activities, as well as cell wall material reappeared faster when the cells were cultivated at low osmotic strength. A newly synthesized tonoplast polypeptide could be detected using a polyspecific serum raised against tonoplast proteins of barley (Hordeum vulgare L.). Both vacuolar proton pumps, the ATPase as well as the pyrophosphatase appear to be newly synthesized during the regeneration of the vacuole. PMID- 24177976 TI - Analysis of dark-relaxation kinetics of variable fluorescence in intact leaves. AB - The dark-relaxation kinetics of variable fluorescence, Fv, in intact green leaves of Pisum stativum L. and Dolichos lablab L. were analyzed using modulated fluorometers. Fast (t1/2 = 1 s) and slow (t1/2 = 7-8 s) phases in fv dark-decay kinetics were observed; the rate and the relative contribution of each phase in total relaxation depended upon the fluence rate of the actinic light and the point in the induction curve at which the actinic light was switched off. The rate of the slow phase was accelerated markedly by illumination with far-red light; the slow phase was abolished by methyl viologen. The halftime of the fast phase of Fv dark decay decreased from 250 ms in dark-adapted leaves to 12-15 ms upon adaptation to red light which is absorbed by PSII. The analysis of the effect of far-red light, which is absorbed mainly by PSI, on Fv dark decay indicates that the slow phase develops when a fraction of QA (-) (the primary stable electron acceptor of PSII) cannot transfer electrons to PSI because of limitation on the availability of P700(+) (the primary electron donor of PSI). After prolonged illumination of dark-adapted leaves in red (PSII-absorbed) light, a transient. Fv rise appears which is prevented by far-red (PSI-absorbed) light. This transient fv rise reflects the accumulation of QA (-) in the dark. The observation of this transient Fv rise even in the presence of the uncoupler carbonylcyanide m-chlorophenyl hydrazone (CCCP) indicates that a mechanism other than ATP-driven back-transfer of electrons to QA may be responsible for the phenomenon. It is suggested that the fast phase in Fv dark-decay kinetics represents the reoxidation of QA (-) by the electron-transport chain to PSI, whereas the slow phase is likely to be related to the interaction of QA (-) with the donor side of PSII. PMID- 24177977 TI - Long-term steady-state labelling of wheat plants by use of natural (13)CO 2/ (12)CO 2 mixtures in an open, rapidly turned-over system. AB - A photosynthate labelling method is presented which takes advantage of the natural difference in carbon-isotope composition (delta Carbon-isotope composition of a sample is conventionally presented as delta (0/00) = [(RP/RS) 1] . 1000, where RP and RS are the molar abundance ratios, (13)C/(12)C, of the sample and of the standard (PDB carbonate), respectively ) which exists between atmospheric CO2 (delta~-80/00) and commercially available compressed CO2. Carbon dioxide with delta-4.0 and -27.9%., respectively, has been used for labelling. A plant growth cabinet served as the labelling compartment. CO2-free air was continuously injected at a rate of up to 54m(3).h(-1). Dilution of cabinet CO2 by CO2-free air was counterbalanced by addition of CO2 with known constant delta. Since the labelling-cabinet atmosphere was continuously exchanged at a high rate, photosynthetic carbon-isotope discrimination was fully expressed. In order to study the distribution of carbon acquired by the plant during a defined growth period, the delta of CO2 was modified by replacing, for example, atmospheric CO2 by CO2 with delta -27.9%. and the weight and 5 of plant carbon pools was monitored over time. In such an experiment the delta change of CO2 was followed by a rapid change of the delta of sucrose in mature flag-leaf blades of wheat (Triticum aestivum L.). The 5 of sucrose stabilized near -51%., indicating complete exchange by current photosynthate. In contrast 83% of the total carbon in mature flag-leaf blades was not exchanged after 14 d continuous labelling. Differential labelling of pre- and post-anthesis photosynthate indicated that 13% of grain carbon originated from pre-anthesis photosynthesis. Carbon-isotope discrimination and its consideration in experimentation and labelling data evaluation are discussed in detail. Since the air supplied to the labelling cabinet is dry and free of CO2, carbon-isotope discrimination and carbon turnover and partitioning can be studied over a wide range of CO2 concentrations (0-2600 cm(3) . m(-3)) and vapor-pressure deficits. PMID- 24177978 TI - Fungal elicitors induce a transient release of active oxygen species from cultured spruce cells that is dependent on Ca(2+) and protein-kinase activity. AB - Cell-wall components from the ectomycorrhizal fungi Amanita muscaria and Hebeloma crustuliniforme and from the spruce pathogen Heterobasidion annosum elicited a transient release of active oxygen species from cultured spruce cells (Picea abies (L.) Karst.). Since the detection of active oxygen was suppressed by catalase, H2O2 was assumed to be the prevailing O2 species. On the other hand, superoxide dismutase enhanced the concentration of detectable H2O2 indicating that the superoxide anion was formed before dismutating to H2O2. The elicitors induced the formation of active oxygen in a dose-dependent manner. Interestingly, elicitors from mycorrhizal fungi had a lower H2O2-inducing activity than equal amounts of cell-wall preparations from the pathogen H. annosum. In Ca(2+) depleted medium the production of active oxygen by elicitor-treated spruce cells was suppressed. Additionally, the ionophore A 23187 induced active oxygen formation in a medium with Ca(2+) but not in a Ca(2+)-depleted medium. Furthermore, the protein-kinase inhibitor staurosporine inhibited the oxidative burst. At a concentration of 34 nM the effect was diminished to 50%. From these results it is suggested that the release of active oxygen species from cultured spruce cells triggered by cell-wall-derived fungal elicitors depends on external Ca(2+) and a protein-kinase activity. In these respects the effect shows similarities with the well-studied respiratory burst of mammalian neutrophils. PMID- 24177979 TI - Transgenic plants containing the phosphinothricin-N-acetyltransferase gene metabolize the herbicide L-phosphinothricin (glufosinate) differently from untransformed plants. AB - L-Phosphinothricin (L-Pt)-resistant plants were constructed by introducing a modified phosphinothricin-N-acetyl-transferase gene (pat) via Agrobacterium mediated gene transfer into tobacco (Nicotiana tabacum L), and via direct gene transfer into carrot (Daucus carota L). The metabolism of L-Pt was studied in these transgenic, Pt-resistant plants, as well as in the untransformed species. The degradation of L-Pt, (14)C-labeled specifically at different C-atoms, was analysed by measuring the release of (14)CO2 and by separating the labeled degradation products on thin-layer-chromatography plates. In untransformed tobacco and carrot plants, L-Pt was deaminated to form its corresponding oxo acid 4-methylphosphinico-2-oxo-butanoic acid (PPO), which subsequently was decarboxylated to form 3-methylphosphinico-propanoic acid (MPP). This compound was stable in plants. A third metabolite remained unidentified. The L-Pt was rapidly N-acetylated in herbicide-resistant tobacco and carrot plants, indicating that the degradation pathway of L-Pt into PPO and MPP was blocked. The N acetylated product, L-N-acetyl-Pt remained stable with regard to degradation, but was found to exist in a second modified form. In addition, there was a pH dependent, reversible change in the mobility of L-N-acetyl-Pt thin-layer during chromatography. PMID- 24177980 TI - Inorganic-carbon assimilation in the green seaweed Ulva rigida C.Ag. (Chlorophyta). AB - Mechanisms of carbon assimilation were investigated in thalli and protoplasts of Ulva rigida by measuring HCO 3 (-) -dependent O2 evolution at pH 6.5 and 8.6. In thalli, dextran-bound azetazolamide (DBAZ), a specific inhibitor of extracellular carbonic anhydrase (CA), inhibited the rate of O2 evolution at pH 8.6 when HCO 3 (-) was the only available form of inorganic carbon (Ci) in the medium. At pH 6.5 when CO2 is accessible, DBAZ did not affect photosynthetic O2 evolution. Inhibition of total CA activity (extracellular and intracellular) by ethoxyzolamide (EZ) inhibited photosynthesis at pH 6.5 and 8.6. During illumination of thalli the medium was alkalized at a rate which increased with increasing light. This alkalization decreased during inhibition of extracellular CA by DBAZ. Protoplasts at pH 6.5 exhibited a higher rate of O2 evolution than in pH 8.6. Addition of CA to protoplasts at pH 8.6 increased the rate of O2 evolution, whereas EZ was inhibitory at both pH 6.5 and 8.6, and DBAZ did not affect photosynthesis at either pH. We suggest that both extracellular and intracellular CA are present and that Ulva rigida assimilates HCO 3 (-) by an indirect mechanism. A theoretical scheme for carbon utilization is suggested. PMID- 24177981 TI - An unusual complete laryngo-tracheal separation in a suicidal hanging with a drop effect. PMID- 24177982 TI - Combining stress transfer and source directivity: the case of the 2012 Emilia seismic sequence. AB - The Emilia seismic sequence (Northern Italy) started on May 2012 and caused 17 casualties, severe damage to dwellings and forced the closure of several factories. The total number of events recorded in one month was about 2100, with local magnitude ranging between 1.0 and 5.9. We investigate potential mechanisms (static and dynamic triggering) that may describe the evolution of the sequence. We consider rupture directivity in the dynamic strain field and observe that, for each main earthquake, its aftershocks and the subsequent large event occurred in an area characterized by higher dynamic strains and corresponding to the dominant rupture direction. We find that static stress redistribution alone is not capable of explaining the locations of subsequent events. We conclude that dynamic triggering played a significant role in driving the sequence. This triggering was also associated with a variation in permeability and a pore pressure increase in an area characterized by a massive presence of fluids. PMID- 24177983 TI - Adsorbed emulsion droplets: capping agents for in situ heterogeneous engineering of particle surfaces. AB - It is found that emulsion droplets could adsorb onto particle (Cu2O) surfaces to form interfacial nanodroplets. The emulsion droplets capped domains on surfaces are protected, while the uncapped domains are exposed, thus allowing direct heterogeneous surface engineering in particle suspension. PMID- 24177984 TI - An EpCAM/CD3 bispecific antibody efficiently eliminates hepatocellular carcinoma cells with limited galectin-1 expression. AB - There have been several studies suggesting that cancer stem cells (CSCs) contribute to the high rates of recurrence and resistance to therapies observed in hepatocellular carcinoma (HCC). Epithelial cell adhesion molecule (EpCAM) has been demonstrated to be a biomarker of CSCs and a potential therapeutic target in HCC. Here, we prepared two anti-EpCAM monoclonal antibodies (1H8 and 2F2) and an anti-EpCAM bispecific T cell engager (BiTE) 1H8/CD3, which was derived from 1H8, and used them to treat HCC in vitro and in vivo. The results demonstrated that all of the developed anti-EpCAM antibodies specifically bound to EpCAM. Neither anti-EpCAM monoclonal antibody had obvious anti-HCC activities in vitro or in vivo. However, anti-EpCAM BiTE 1H8/CD3 induced strong peripheral blood mononuclear cell-dependent cellular cytotoxicity in Huh-7 and Hep3B cells but not EpCAM-negative SK-Hep-1 cells. Notably, 1H8/CD3 completely inhibited the growth of Huh-7 and Hep3B xenografts in vivo. Treatment of the Huh-7 HCC xenografts with 1H8/CD3 significantly suppressed tumor proliferation and reduced the expression of most CSC biomarkers. Intriguingly, galectin-1 (Gal-1) overexpression inhibited 1H8/CD3-induced lymphocytotoxicity in HCCs while knockdown of Gal-1 increased the lymphocytotoxicity. Collectively, these results indicate that anti-EpCAM BiTE 1H8/CD3 is a promising therapeutic agent for HCC treatment. Gal-1 may contribute to the resistance of HCC cells to 1H8/CD3-induced lysis. PMID- 24177985 TI - GPU accelerated segmentation and centerline extraction of tubular structures from medical images. AB - PURPOSE: To create a fast and generic method with sufficient quality for extracting tubular structures such as blood vessels and airways from different modalities (CT, MR and US) and organs (brain, lungs and liver) by utilizing the computational power of graphic processing units (GPUs). METHODS: A cropping algorithm is used to remove unnecessary data from the datasets on the GPU. A model-based tube detection filter combined with a new parallel centerline extraction algorithm and a parallelized region growing segmentation algorithm is used to extract the tubular structures completely on the GPU. Accuracy of the proposed GPU method and centerline algorithm is compared with the ridge traversal and skeletonization/thinning methods using synthetic vascular datasets. RESULTS: The implementation is tested on several datasets from three different modalities: airways from CT, blood vessels from MR, and 3D Doppler Ultrasound. The results show that the method is able to extract airways and vessels in 3-5 s on a modern GPU and is less sensitive to noise than other centerline extraction methods. CONCLUSIONS: Tubular structures such as blood vessels and airways can be extracted from various organs imaged by different modalities in a matter of seconds, even for large datasets. PMID- 24177986 TI - Effect of bariatric surgery on weight loss, inflammation, iron metabolism, and lipid profile. AB - BACKGROUND AND AIMS: Accumulating evidence indicates that a state of chronic inflammation has a crucial role in the pathogenesis of obesity-related metabolic dysfunction. This study aims to evaluate changes in inflammatory process, iron metabolism, erythropoiesis, and lipid profile associated with weight loss after gastric banding surgery. MATERIAL AND METHODS: A total of 46 patients were evaluated before and 3 months after gastric banding surgery. A survey was conducted to record demographic data, body mass index, and presence of comorbidities. Moreover, complete blood cell counts and serum levels of iron, ferritin, transferrin, high-sensitivity C-reactive protein, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides were performed. RESULTS: At a follow-up 3 months after surgery, our patients presented a significant decrease in weight and body mass index, associated with a decreased inflammatory process (decreased high-sensitivity C reactive protein, neutrophil counts, and neutrophil:lymphocyte ratio), increased iron availability (increased transferrin saturation and a trend to higher iron serum levels), and significant decreased triglycerides and triglycerides:high density lipoprotein-cholesterol ratio. CONCLUSIONS: Our results showed a significant decrease in the inflammation process 3 months after gastric banding surgery, associated with adipose tissue loss. This decrease in the inflammatory process is associated with more efficient iron absorption and increased iron availability for erythropoiesis. Moreover, we also found decreased triglyceride serum levels. These changes suggest benefits of weight loss, including decreased risk of cardiovascular disease. PMID- 24177987 TI - The frequency and outcome of breast cancer risk-reducing surgery in Finnish BRCA1 and BRCA2 mutation carriers. AB - BACKGROUND AND AIMS: Risk-reducing mastectomy of BRCA1 and BRCA2 gene mutation carriers is known to significantly reduce lifetime risk of breast cancer. Our aim was to study the frequency and outcome of risk-reducing mastectomies performed in Helsinki University Central Hospital during 1997-2010. MATERIAL AND METHODS: In testing for mutations in BRCA1 and BRCA2, 136 female carriers had been identified and followed up in Helsinki University Central Hospital. RESULTS: A total of 69 breasts in 52 women were operated on for risk-reduction, including 28 (54%) bilateral mastectomies at mean age of 43 years. Autologous tissue was used for reconstruction in 40 (50%) and implants in 31 (39%) of the breasts, respectively. In all, 8 patients (15%) chose to have no reconstruction. Minor or major complications were recorded in 21 (40%) patients. Five reconstructions failed and were corrected with re-reconstruction. CONCLUSIONS: In this series of Finnish BRCA1 and BRCA2 mutation carriers, a high percentage 52 (41%) chose risk-reducing breast surgery. Autologous tissue was favored in breast reconstructions. Immediate breast reconstructions were associated with a relatively high risk of complications in free flaps and in implant reconstructions, but not in latissimus dorsi reconstructions. It is mandatory that patients are informed about the risks associated with risk-reducing operations. PMID- 24177988 TI - Neural substrates of inhibitory control deficits in 22q11.2 deletion syndrome. AB - 22q11.2 deletion syndrome (22q11DS) is associated with elevated levels of impulsivity, inattention, and distractibility, which may be related to underlying neurobiological dysfunction due to haploinsufficiency for genes involved in dopaminergic neurotransmission (i.e. catechol-O-methyltransferase). The Stop signal task has been employed to probe the neural circuitry involved in response inhibition (RI); findings in healthy individuals indicate that a fronto-basal ganglia network underlies successful inhibition of a prepotent motor response. However, little is known about the neurobiological substrates of RI difficulties in 22q11DS. Here, we investigated this using functional magnetic resonance imaging while 45 adult participants (15 22q11DS patients, 30 matched controls) performed the Stop-signal task. Healthy controls showed significantly greater activation than 22q11DS patients within frontal cortical and basal ganglia regions during successful RI, whereas 22q11DS patients did not show increased neural activity relative to controls in any regions. Using the Barratt Impulsivity Scale, we also investigated whether neural dysfunction during RI was associated with cognitive impulsivity in 22q11DS patients. RI-related activity within left middle frontal gyrus and basal ganglia was associated with severity of self-reported cognitive impulsivity. These results suggest reduced engagement of RI-related brain regions in 22q11DS patients, which may be relevant to characteristic behavioral manifestations of the disorder. PMID- 24177989 TI - The role of the right temporoparietal junction in the control of imitation. AB - Controlling neural representations of the self and other people is fundamental to social cognition. Brain imaging studies have implicated the right temporoparietal junction (rTPJ) in this ability, but causal evidence for its role is lacking. A debate is also ongoing regarding whether the control of, or switching between, self and other representations is a specialized or domain-general process: the rTPJ's well-established role in reorienting attention supports a domain-general process, but a role specific to social cognition has also been proposed. Neuronavigated repetitive transcranial magnetic stimulation was used to target the rTPJ (and a control mid-occipital site) during a task requiring participants to switch between representations of others' actions on both a social and a nonsocial level, by manipulating imitative and spatial compatibility simultaneously and independently. Both imitative and spatial compatibility effects were apparent on response times; however, the effect of imitative compatibility was significantly stronger, indicating less control of imitation, during stimulation of the rTPJ relative to the control site. This suggests that the rTPJ is involved in switching between self and other representations, and further, that this process may not be entirely domain general. PMID- 24177990 TI - Ventral fronto-temporal pathway supporting cognitive control of episodic memory retrieval. AB - Achieving our goals often requires guiding access to relevant information from memory. Such goal-directed retrieval requires interactions between systems supporting cognitive control, including ventrolateral prefrontal cortex (VLPFC), and those supporting declarative memory, such as the medial temporal lobes (MTL). However, the pathways by which VLPFC interacts with MTL during retrieval are underspecified. Prior neuroanatomical evidence suggests that a polysynaptic ventral fronto-temporal pathway may support VLPFC-MTL interactions. To test this hypothesis, human participants were scanned using fMRI during performance of a source-monitoring task. The strength of source information was varied via repetition during encoding. Single encoding events should produce a weaker memory trace, thus recovering source information about these items should demand greater cognitive control. Results demonstrated that cortical targets along the ventral path--anterior VLPFC, temporal pole, anterior parahippocampus, and hippocampus- exhibited increases in univariate BOLD response correlated with increases in controlled retrieval demand, independent of factors related to response selection. Further, a functional connectivity analysis indicated that these regions functionally couple and are distinguishable from a dorsal pathway related to response selection demands. These data support a ventral retrieval pathway linking PFC and MTL. PMID- 24177993 TI - Abstracts of the 41st Annual Meeting of the Austrian Diabetes Society. November 21-23, 2013. Salzburg, Austria. PMID- 24177992 TI - Macrophages as potential targets for zoledronic acid outside the skeleton evidence from in vitro and in vivo models. AB - PURPOSE: Multiple cell types of the tumour microenvironment, including macrophages, contribute to the response to cancer therapy. The anti-resorptive agent zoledronic acid (ZOL) has anti-tumour effects in vitro and in vivo, but it is not known to what extent macrophages are affected by this agent. We have therefore investigated the effects of ZOL on macrophages using a combination of in vitro and in vivo models. METHODS: J774 macrophages were treated with ZOL in vitro, alone and in combination with doxorubicin (DOX), and the levels of apoptosis and necrosis determined. Uptake of zoledronic acid was assessed by detection of unprenylated Rap1a in J774 macrophages in vitro, in peritoneal macrophages and in macrophage populations isolated from subcutaneously implanted breast cancer xenografts following ZOL treatment in vivo. RESULTS: Exposure of J774 macrophages to 5 MUM ZOL for 24 h caused a significant increase in the levels of uRap1A, and higher doses/longer exposure induced apoptotic cell death. DOX (10 nM/24 h) and ZOL (10 MUM/4 h) given in sequence induced significantly increased levels of apoptotic cell death compared to single agents. Peritoneal macrophages and macrophage populations isolated from breast tumour xenografts had detectable levels of uRap1A 24 h following a single, clinically achievable dose of 100 MUg/kg ZOL in vivo. CONCLUSION: We demonstrate that macrophages are sensitive to sequential administration of DOX and ZOL, and that both peritoneal and breast tumour associated macrophages rapidly take up ZOL in vivo. Our data support that macrophages may contribute to the anti-tumour effect of ZOL. PMID- 24177991 TI - Role of quantitative and qualitative characteristics of free circulating DNA in the management of patients with non-small cell lung cancer. AB - BACKGROUND: The release of DNA into peripheral blood is a common event in cancer patients, occurring as a consequence of necrotic and apoptotic processes typical of tumor cells. However, free circulating DNA (fcDNA) is also present in patients with benign diseases and in healthy individuals. Both quantitative and qualitative aspects of fcDNA have been studied as potential biomarkers in a number of tumor types. In particular, quantitative analysis of fcDNA has been shown to play an important role in the diagnosis of non-small cell lung cancer (NSCLC), because of its ability to discriminate between healthy subjects and individuals with NSCLC. Additionally, fcDNA in cancer patients derives predominantly from tumor tissue and, as such, it can be used for the molecular characterization of the primary tumor. Targeted therapies in NSCLC have, in recent years, produced promising results, highlighting the importance of molecular profiling of the primary cancer lesions. Considering that little or no tumor material is available for at least some of the patients, the possibility of using fcDNA for molecular analysis becomes increasingly important. In the present review we evaluated several quantitative and qualitative aspects of fcDNA that could be instrumental for the differential diagnosis of lung disease. CONCLUSIONS: There is ample evidence in the literature to support the possible use of peripheral blood-derived fcDNA in the early diagnosis and molecular characterization of lung cancer. This non-invasive method may also turn out to be valuable in monitoring drug response and in identifying induced mechanisms of drug resistance. Before it can be implemented in routine clinical practice, however, additional efforts are needed to standardize the methodology. PMID- 24177994 TI - Cloning and integrative deletion of the RAD6 gene of Saccharomyces cerevisiae. AB - Three overlapping plasmids were isolated from a YEp24 library, which restore Rad+ functions to rad6-1 and rad6-3 mutants. Different subclones were made and shown to integrate by homologous recombination at the RAD6 site on chromosome VII, thus verifying the cloned DNA segments to be the RAD6 gene and not a suppressor. The gene resides in a 1.15 kb fragment, which restores Rad(+) levels of resistance to U.V., MMS and gamma-rays to both rad6-1 and rad6-3 strains. It also restores sporulation ability to rad6-1 diploids.Integrative deletion of the RAD6 gene was shown not to be completely lethal to the yeast. Our results suggest that the RAD6 gene has some cell cycle-specific function(s), probably during late S phase. PMID- 24177996 TI - Hybridization of Saccharomyces cerevisiae with Candida utilis through protoplast fusion. AB - Auxotrophic mutants of Saccharomyces cerevisiae and Candida utilis were hybridized through protoplast fusion. Spontaneous, UV- and FPA-induced mitotic segregation indicated that after cell fusion, exclusion of the S. cerevisiae nucleus or nuclear fusion followed by preferential loss of S. cerevisiae chromosomes can take place. Some of the hybrids were stable. One of them, expressed mating and sporulation functions of the S. cerevisiae parent. Thus, markers from both parents could be recovered as mitotic and meiotic segregants. PMID- 24177995 TI - A non-Mendelian factor, [eta(+)], causes lethality of yeast omnipotent-suppressor strains. AB - Omnipotent suppressors cause translational ambiguity and have been associated with poor growth and inviability. We now report that a non-Mendelian element, [eta(+)], causes this inviability. In [eta(-)] strains the suppressors are not inviable. The [eta(+)] genetic element segregates to about 70% of the meiotic progeny, although almost all of the spores probably have the [eta(+)] phenotype for the first few divisions. Growth on 5 mM guanidine hydrochloride efficiently causes [eta(+)] strains to become [eta(-)]. The [eta(+)] factor has many similarities with the previously described [psi(+)] factor (Cox 1965, 1971). However, [eta(+)] and [psi(+)] differ in their patterns of inheritance, and by the fact that [psi(+)] affects ochre specific and not omnipotent suppressors, while the converse is true of [eta(+)]. PMID- 24177997 TI - Biochemical characterization of the molybdenum cofactor mutants of Neurospora crassa: in vivo and in vitro reconstitution of NADPH-nitrate reductase activity. AB - Molybdenum cofactor (MoCo) mutants of Neurospora crassa lack both NADPH-nitrate reductase and xanthine dehydrogenase activity. In vivo and in vitro studies to further characterize these mutants are now reported. The MoCo mutants nit-9A and nit-9B are capable of growing, albeit poorly, with nitrate as the sole nitrogen source, provided high levels of molybdate are present. The MoCo mutants nit-9A, nit-9B and nit-9C, but not nit-1, nit-7 or nit-8, have significant levels of NADPH-nitrate reductase when grown in nitrate medium containing 30 mM molybdate. In vitro reconstitution experiments using cell free extracts of the N. crassa MoCo mutants and E. coli HB101 as a source of wild-type MoCo were performed. MoCo from E. coli was capable of reconstituting NADPH-nitrate reductase activity to nit-1, nit-7 and nit-8. Molybdate is required for the in vitro reconstitution of NADPH-nitrate reductase activity. It was not possible to in vitro reconstitute NADPH-nitrate reductase activity in the MoCo mutants nit-9A, nit-9B or nit-9C. PMID- 24177998 TI - Cloning and preliminary characterization of a molybdenum cofactor gene of Neurospora crassa. AB - A Neurospora crassa library, constructed in a derivative of the plasmid pBR322 (pRK9), was used to transform two E. coli ch1D molybdenum cofactor mutants (ch1D, ch1D::Mu). Subsequently, one transformant from each of three independent transformation experiments was restriction mapped. All three transformants had an identical N. crassa DNA insert (4.2 kb). Southern Blot analysis with one of the plasmids (pMoCo, 1:4) showed hybridization to a single band of N. crassa genomic DNA. When pMoCo plasmid (1:4) was used to transform various E. coli nitrate reductase mutants (ch1A, ch1B, ch1C, ch1D, ch1E, ch1G and ch1M), the pMoCo plasmid was capable of restoring E. coli nitrate reductase activity to only the ch1D mutant. In vitro reconstitution experiments using wild-type, ch1D and ch1D; pMoCo cell-free extracts as a source of molybdenum cofactor (MoCo) were performed with the N. crassa MoCo mutants nit-1, nit-7 and nit-8. MoCo from wild-type E. coli cell-free extracts was capable of reconstituting NADPH : nitrate reductase activity to all three N. crassa mutants. MoCo from ch1D; pMoCo cell-free extracts was capable of reconstituting more NADPH : nitrate reductase activity to the N. crassa mutants than cell-free extracts from the original ch1D mutant. PMID- 24178000 TI - Unusual organization and lack of recombination in the ribosomal RNA genes of Coprinus cinereus. AB - We find three interesting characteristics of the genes encoding the ribosomal RNA (rRNA) in the basidiomycete Coprinus cinereus. First, there are only 60 to 90 copies of the genes, fewer than in other fungi. Second, the genes are organized in an unusual arrangement. The 5S rRNA genes are located in the repeat unit which encodes the other rRNAs and all four rRNAs are transcribed in the same direction. Third, meiotic recombination is inhibited within the ribosomal DNA. PMID- 24177999 TI - Nucleotide sequence of the clustered genes for the 44 kd chlorophyll a apoprotein and the "32 kd"-like protein of the photosystem II reaction center in the spinach plastid chromosome. AB - A 2,900 base pair DNA segment of the spinach plastid chromosome which encodes the genes for the 44 kd chlorophyll a apoprotein and a "32 kd"-like protein of the photosystem II reaction center has been subjected to sequence and Northern blot analysis. The genes are located almost centrally in the large single-copy segment of the chromosome adjacent to the two genes for the P700 chlorophyll a apoproteins of the photosystem I reaction center. The DNA sequence reveals two uninterrupted protein-coding regions of 473 (44 kd chlorophyll a apoprotein) and 353 triplets ("32 kd"-like protein). The latter gene is strikingly similar to the gene for the herbicide-binding "32 kd" protein which maps some 30 kbp distant on the plastid chromosome. The two genes overlap by 50 base pairs but are read in different phases. They may be contranscribed and the RNA modified to give several discrete species ranging in size from 1.6 to 4.6 kb. A presumptive promoter site was only identified for the "32 kd"-like protein, while potential ribosome binding and transcription termination sites are found preceding and following both genes, respectively. The polypeptides possess a high content of hydrophobic amino acids, most of which appear to be clustered in transmembrane spans. The molecular weights of 51,785 (44 kd chlorophyll a apoprotein) and 39,465 ("32 kd" like protein) derived from the deduced amino acid sequences are higher than the experimentally determined protein sizes. Amino acid codon usage for both genes is highly selective. Comparison of the chlorophyll a apoproteins of spinach reveals regions of sequence homology. PMID- 24178001 TI - Plasmid-like DNAs in the commercially important mushroom genus Agaricus. AB - Two unique plasmid-like DNA components were localized in isolated mitochondria of the commercially important mushroom genus Agaricus: pEM (7.35 +/- 0.15 kilobases) and pMPJ (3.65 +/- 0.15 kilobases). These DNA moieties were linear; pEM possessed regions of terminal inverted repeated sequences. No homology was detected between pEM or pMPJ DNA and the nuclear or mitochondrial genomes. No homology existed between pEM and pMPJ. This suggests independent replication of pEM and pMPJ. Restriction endonuclease digests indicated that pEM consisted of two components (pEM1 and pEM2) with uniquely different restriction sites and copy number. PMID- 24178002 TI - Mitochondrial DNA of the filamentous ascomycete Cochliobolus heterostrophus : Characterization of the mitochondrial chromosome and population genetics of a restriction enzyme polymorphism. AB - The mitochondrial chromosome of Cochliobolus heterostrophus is a circle approximately 115 kb in circumference, among the largest known from fungi. A physical map of C. heterostrophus mtDNA was constructed using the restriction enzymes BamHI, EcoRI, and PvulI by DNA-DNA hybridizations with cloned or purified mtDNA BamHI fragments. The following sequences were located on the mtDNA map: (1) the large and small mitochondrial ribosomal RNA genes (identified by heterologous hybridization to cloned Neurospora crassa rRNA genes); (2) the sequence homologous to a mitochondrial plasmid present in one field isolate of C. heterostrophus; and (3) a 1.05 kb EcoRI fragment that functions as an autonomously replicating sequence in Saccharomyces cerevisiae. An examination of mtDNA from 23 isolates of C. heterostrophus collected worldwide revealed polymorphisms in restriction enzyme sites. One such polymorphism, coupled with data on a polymorphism in nuclear rDNA, suggests that there are two genetically distinct but geographically overlapping mating populations of C. heterostrophus in the world. PMID- 24178003 TI - The Euglena gracilis chloroplast genome: structural features of a DNA region possibly carrying the single origin of DNA replication. AB - We sequenced a Bg1II-HindIII DNA fragment of the Euglena gracilis chloroplast genome which most likely carries the single origin of DNA replication according to recent electronmicroscopic mapping studies (Koller and Delius 1982a; Ravel Chapuis et al. 1982). This DNA fragment contains a polymorphic region (Schlunegger et al. 1983) which is composed, as will be shown, of multiple tandem repeats (54 bp, 87% A+T). Furthermore we located on this DNA fragment a short inverted repeat element (96 positions) observed in the electronmicroscopic studies (Koller and Delius 1982b). Between the borders of the polymorphic region and the nearby inverted repeat (distance of 179 positions) we retrieved an exact copy of parts of the rDNA leader (105 positions) including 49 positions of the chloroplast trnW gene. A computer search for bacterial type Ori-regions did not reveal any significant sequence homology. However, the polymorphic region and its immediate vicinity have the capacity to form multiple stem and loop structures which may be involved in DNA replication initiation. PMID- 24178004 TI - Genetic analysis of nitrate reductase-deficient mutants in Chlamydomonas reinhardii. AB - Six mutants (305, 301, 203, 307, 104 and 102) of Chlamydomonas reinhardii, all defective in nitrate reductase (NR) activity, have been genetically analyzed. All except 102 carry single Mendelian mutations.Mutant 305, defective in diaphorase activity and mutant 301, defective in terminal enzyme activity, did not give rise to wild-type recombinants when crossed to each other or with the nit-1 mutant isolated from strain 137c (which is actually a double mutant nit-1 nit-2). Nit-1 was shown to lack both diaphorase and terminal activities. Whether the mutated sites in 305 and 301 are located in a unique cistron (nit-1) or in two adjacent cistrons (nit-1a and nit-1b) coding for a diaphorase subunit and a terminal subunit of NR is discussed in the light of previous biochemical findings.The 203 mutation affecting a regulatory gene did not recombine with nit-2, the other mutated locus present in strain 137c.Mutants 307, 104 and 102, all lacking molybdenum cofactor for both NR and xanthine dehydrogenase, where shown to be affected in different loci. The genes mutated in 307 and 104 have been designated nit-3 and nit-4, respectively. The 102 strain is mutated in two non-linked loci, nit-5 and nit-6, with both mutations required to confer the mutant phenotype. One of these cryptic mutations is present in the "wild" strain 21gr.The results indicate that at least six or seven loci are involved in the production of an active NR enzyme: one (nit-1) or two (nit-1a and nit-1b) cistrons to produce the NR apoproteins responsible for the partial activities diaphorase and terminal, one locus (nit-2) for the regulation of NR synthesis, and four loci (nit-3, nit 4, nit-5 and nit-6) to produce the molybdenum cofactor. The loci nit-1a and nit-2 seem to correspond to the nit-A and nit-B loci described by Nichols and Syrett (J Gen Microbiol 108:71-77, 1978). PMID- 24178006 TI - Gene flow between cultivated and wild sunflowers. AB - With the development of transgenic crops, concern has been expressed regarding the possible escape of genetically-engineered genes via hybridization with wild relatives. This is a potential hazard for sunflowers because wild sunflowers occur as weeds in fields where cultivated sunflowers are grown and hybridization between them has been reported. In order to quantify the potential for gene escape, two experimental stands of sunflower cultivars were planted at two sites with different rainfall and altitude profiles. Populations of wild plants were planted at different distances from each cultivar stand. An allele homozygous in the cultivar (6Pgd-3-a), but absent in the wild populations, was used as a molecular marker to document the incidence and rate of gene escape from the cultivar into the wild populations of sunflowers. Three-thousand achenes were surveyed to determine the amount of gene flow from the cultivated to the wild populations. The marginal wild populations (3 m from the cultivar) showed the highest percentage (27%) of gene flow. Gene flow was found to decrease with distance; however, gene flow occurred up to distances of 1000 m from the source population. These data suggest that physical distance alone will be unlikely to prevent gene flow between cultivated and wild populations of sunflowers. PMID- 24178005 TI - Efficient siRNA delivery and tumor accumulation mediated by ionically cross linked folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate nanoparticles: for the potential targeted ovarian cancer gene therapy. AB - For effective ovarian cancer gene therapy, systemic administrated tumor-targeting siRNA/folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate (FA-PEG COL) nanoparticles is vital for delivery to cancer site(s). siRNA/FA-PEG-COL nanoparticles were prepared by ionic gelation for effective FA receptor expressing ovarian cancer cells transfection and in vivo accumulation. The chemical structure of FA-PEG-COL conjugate was characterized by MALDI-TOF-MS, FT IR and (1)H NMR. The average size of siRNA/FA-PEG-COL nanoparticles was approximately 200 nm, and the surface charge was +8.4 mV compared to +30.5 mV with siRNA/COL nanoparticles. FA-PEG-COL nanoparticles demonstrated superior compatibility with erythrocytes in terms of degree of aggregation and haemolytic activity and also effects on cell viability was lower when compared with COL nanoparticles. FA grafting significantly facilitated the uptake of nanoparticles via receptor mediated endocytosis as demonstrated by flow cytometry. The in vitro transfection and gene knockdown efficiency of HIF-1alpha were superior to COL nanoparticles (76-62%, respectively) and was comparable to Lipofectamine 2000 (79%) as demonstrated by RT-qPCR and Western blot. Gene knockdown at the molecular level translated into effective inhibition of proliferation in vitro. Accumulation efficiency of FA-PEG-COL nanoparticles was investigated in BALB/c mice bearing OVK18 #2 tumor xenograft using in vivo imaging. The active targeting FA-PEG-COL nanoparticles showed significantly greater accumulation than the passive targeting COL nanoparticles. Based on the results obtained, siRNA/FA-PEG COL nanoparticles show much potential for effective ovarian cancer treatment via gene therapy. PMID- 24178007 TI - Identification of a codominant amplified polymorphic DNA marker linked to the verticillium wilt resistance gene in tomato. AB - Resistance to verticillium wilt, a vascular disease causing yield losses in many crops, is conferred in tomato by a single dominant allele, Ve. A population segregating for the Ve allele was generated using near-isogenic tomato lines. Analysis of the parental tomato DNA using the polymerase chain reaction and 400 random primers, each 10 deoxyribonucleotides in length, produced 1,880 amplified DNA fragments. Of the four polymorphisms observed between the resistant and susceptible parental genotypes, only one was linked to the Ve gene. No recombination was observed between this DNA marker and the Ve locus, indicating that the linkage is less than 3.5+/-2.7 cM. The marker detected both the susceptible and resistant alleles, producing amplified DNA fragments of approximately 1,300 and 1,350 bp, respectively. The sequence of the primer, determined from cloned amplified products, was 5' CTCACATGCA 3' instead of the expected 5' CTCACATGCC 3'. The marker will be of value to tomato breeding programs because of the tight linkage, Codominant nature, and analytical procedure utilized. PMID- 24178008 TI - RFLP inheritance and linkage in walnut. AB - Thirty-two low-copy-number genomic DNA clones from a walnut (Juglans sp.) Pst I genomic library were used to establish a molecular-marker linkage map for walnut. The clones were hybridized to restriction-endonuclease-digested DNA from parent walnut trees involved in an interspecific backcross of (J. hindsii x J. regia) x J. regia in order to identify parental polymorphism. Sixty-three backcross progeny were analyzed to determine the inheritance and linkage of 48 RFLP loci. Sixty-six percent of the walnut cloned sequences detected duplicated, but unlinked, loci. Twelve linkage groups were identified by 42 of the RFLP loci. A Poisson probability method for estimating genome size was utilized to calculate the approximate walnut genome length as 1660 cM and to estimate that 138 markers would be needed to cover 95% of the walnut genome within 20 cM of each marker. PMID- 24178009 TI - Molecular cloning of phenylalanine ammonia-lyase cDNA and classification of varieties and cultivars of tea plants (Camellia sinensis) using the tea PAL cDNA probe. AB - Tea (Camellia sinensis) phenylalanine ammonia-lyase (PAL) cDNA was cloned using labelled rice PAL cDNA as a probe. The PAL genes of the tea plant were investigated by restriction fragment length polymorphism (RFLP) analysis using tea PAL cDNA. PAL genetic variation in tea plants was much larger than predicted due to the presence of various hybridized fragments in the Assam hybrids, which are hybrids between C. sinensis var 'assamica' and var 'sinensis'. On the other hand, hybridized band patterns of Japanese green tea cultivars belonging to var 'sinensis' could be divided into five groups. Furthermore, a short-length PAL probe, about 280 bp including the 3' untranslated sequence, detected 3 DNA fragments of different lengths, which were named A, B and D. An experiment tracing the PAL gene heredity showed that A, B and D fragments were inherited according to the Mendelian monogenic ratio. Therefore, PAL genes identifiable by A, B and D fragments are multiple alleles, and the PAL gene is present as a single gene in the tea haploid genome. It was also clear that five groups of Japanese green tea cultivars were characterized by the composition of these PAL fragments. From RFLP analysis using tea PAL cDNA, we succeeded in distinguishing Assam hybrids and Japanese green tea cultivars with high and low catechin content, respectively, and in grouping Japanese green tea at the cultivar level. PMID- 24178010 TI - Genetic diversity among wild and cultivated barley as revealed by RFLP. AB - Genetic variability of cultivated and wild barley, Hordeum vulgare ssp. vulgare and spontaneum, respectively, was assessed by RFLP analysis. The material consisted of 13 European varietes, single-plant offspring lines of eight land races from Ethiopia and Nepal, and five accessions of ssp. spontaneum from Israel, Iran and Turkey. Seventeen out of twenty-one studied cDNA and gDNA probes distributed across all seven barley chromosomes revealed polymorphism when DNA was digested with one of four restriction enzymes. A tree based on genetic distances using frequencies of RFLP banding patterns was estimated and the barley lines clustered into five groups reflecting geographical origin. The geographical groups of land-race lines showed less intragroup variation than the geographical groups of spontaneum lines. The group of European varieties, representing large variation in agronomic traits, showed an intermediate level. The proportion of gene diversity residing among geographical groups (FST) varied from 0.19 to 0.94 (average 0.54) per RFLP pattern, indicating large diversification between geographical groups. PMID- 24178011 TI - Allelism of endosperm balance number (EBN) in Solanum acaule Bitt. and other wild potato species. AB - The inheritance of endosperm balance number (EBN), a genetic, dose-dependent crossability system functioning in tuber-bearing Solanum (potato) species, was investigated for certain wild potato species having an EBN equal to one half of their ploidy. The EBN of Solanum acaule, a disomic 4(2EBN) South American species, was investigated by producing F1 and F2 hybrids with artificial 4x(2EBN) S. commersonii. This allowed assessment of recombination among the two genomes of disomic S. acaule and that of S. commersonii. When crossability of the hybrids with 1EBN, 2EBN and 4EBN standards was tested, no variation for EBN was detected. The apparent lack of recombination and segregation for EBN in these hybrids indicates that the genomes of S. acaule and S. commersonii carry EBN in a genetically-similar way. Combined with previous reports, these data indicate that the inheritance of EBN is similar in widely-separated taxa from South America and Mexico. PMID- 24178012 TI - Effects of various breeding strategies on diploid drone frequency and quantitative traits in a honey bee population. AB - When selecting in a finite population of honeybees there is a conflict between gain in a quantitative trait and increasing homozygosity, and therefore the frequency of inviable diploid drones. The consequences when using different mating, import, and selection strategies on diploid drone frequency and genetic gain, was explored with Monte Carlo computer simulations.Within a closed population breeding structure, mass selection gave the highest genetic gain in the quantitative trait, but also the largest increase in percentage diploid drones and queens with unacceptably-low brood viability. Mass selection combined with truncation selection against queens having more than 15% diploid drones gave a comparable genetic gain and was the best strategy of the ones studied to avoid diploid drones. Within-family selection (one replacement per sib group) gave the least genetic gain, and a frequency of diploid drones comparable to random (no) selection. It was intermediate between mass selection and mass selection combined with viability selection concerning the frequency of diploid drones.Insemination with pooled and homogenized semen originating from all breeder queens (30), as compared to natural mating with 12 randomly-selected drones, had little effect on the genetic gain and on the overall frequency of diploid drones (10 to 15% by generation 20).The effect of opening the closed breeding population for the import of external queens every generation, by exchanging breeder queens of lowest performance with a corresponding number of new queens (5, 10and 15 out of 30), was also investigated. Under mass selection (natural mating as well as artificial insemination) the frequency of diploid drones and the proportion of queens discarded were reduced because of low brood viability. However, artificial insemination was superior to natural mating considering the latter criterion. If the imported queens were at the same genetic level for the quantitative trait under selection as the whole breeding population at that generation, or 10% better, the genetic gain was respectively slightly reduced and approximately maintained. If the imported queens were of inferior quality (equal to the initial population) the import of queens slowed genetic progress considerably. PMID- 24178013 TI - Predicting mean and variance of all possible lines and hybrids from designs with partially inbred progenies. AB - Two-factor mating designs at consecutive Sn and S(n+1) levels (S0 and S1 S1 and S2, or F2 and F3) allow estimation of all components of the variation among homozygous lines and F1 hybrids that can be derived from a given population. They also allow for the prediction of the mean of these lines and single-cross hybrids. Some tests for the presence of epistasis are possible at the levels of means and of variances. Such mating designs can be very useful for predicting the value of the best possible lines or the best possible F1 hybrids when it is difficult to produce, at an experimental level for exploratory purposes, either lines or hybrids. PMID- 24178014 TI - QTL analysis: a simple 'marker-regression' approach. AB - A method to locate quantitative trait loci (QTL) on a chromosome and to estimate their additive and dominance effects is described. It applies to generations derived from an F1 by selfing or backcrossing and to doubled haploid lines, given that marker genotype information (RFLP, RAPD, etc.) and quantitative trait data are available. The method involves regressing the additive difference between marker genotype means at a locus against a function of the recombination frequency between that locus and a putative QTL. A QTL is located, as by other regression methods, at that point where the residual mean square is minimised. The estimates of location and gene effects are consistent and as reliable as conventional flanking-marker methods. Further applications include the ability to test for the presence of two, or more, linked QTL and to compare different crosses for the presence of common QTL. Furthermore, the technique is straightforward and may be programmed using standard pc-based statistical software. PMID- 24178015 TI - Use of recombinant substitution lines in the construction of RFLP-based genetic maps of chromosomes 6A and 6B of tetraploid wheat (Triticum turgidum L.). AB - RFLP-based genetic maps of chromosomes 6A and 6B of Triticum turgidum have been constructed using data obtained by the study of Triticum turgidum var 'durum' cv 'Langdon'-T. t. var 'dicoccoides' recombinant substitution lines (RSLs) supplemented with data obtained from F3 families derived from 'Langdon' dicoccoides 6A and 6B disomic substitution lines. The average RFLP frequencies detected for the two chromosomes in a test of 45 DNA clones with six restriction enzymes were 56% and 53%, respectively, and a subset of 32 clones gave frequencies of 75% and 72%, respectively. Seventeen loci were mapped in 6A and 18 in 6B. With the possible exception of 5 loci in the centromeric region of 6A, all of the mapped 6A and 6B loci are located in the same arm as are homologous loci in hexaploid wheat, and the linear order of the loci is the same in the two chromosomes, except possibly close to the centromere. Major differences in genetic distances exist between homologous loci located in the proximal regions of the 6AL and 6BL linkage groups, however, the distances being much larger in the former than in the latter. The 6B maps that were constructed using data from both the RSL and the F2 populations and using data from the RSL population alone closely resemble one another, indicating that the 6B RSL population, composed of 85 lines, can be reliably used for genetic mapping. Additional studies must be conducted before the utility of the 6A RSL population, composed of 66 lines, can be adequately assessed. PMID- 24178016 TI - The utility of RAPD markers for the determination of genetic variation in oil palm (Elaeis guineensis). AB - The genetic variation among different accessions of oil-palm germplasm collected from Africa was estimated using random primers and the polymerase chain reaction. The present study revealed high levels of genetic variation in these accessions. Electrophoresis of the amplification products indicated that nine out of 20 primers were able to generate polymorphic products ranging in length from 0.2 kb to 2.3 kb. No individual palm or population-specific products were observed. Greatest diversity was seen in Zaire population 5 and the least in Zaire population 2. PMID- 24178017 TI - Variability of chloroplast DNA and nuclear ribosomal DNA in cassava (Manihot esculenta Crantz) and its wild relatives. AB - Chloroplast DNA (cp) and nuclear ribosomal DNA (rDNA) variation was investigated in 45 accessions of cultivated and wild Manihot species. Ten independent mutations, 8 point mutations and 2 length mutations were identified, using eight restriction enzymes and 12 heterologous cpDNA probes from mungbean. Restriction fragment length polymorphism analysis defined nine distinct chloroplast types, three of which were found among the cultivated accessions and six among the wild species. Cladistic analysis of the cpDNA data using parsimony yielded a hypothetical phylogeny of lineages among the cpDNAs of cassava and its wild relatives that is congruent with morphological evolutionary differentiation in the genus. The results of our survey of cpDNA, together with rDNA restriction site change at the intergenic spacer region and rDNA repeat unit length variation (using rDNA cloned fragments from taro as probe), suggest that cassava might have arisen from the domestication of wild tuberous accessions of some Manihot species, followed by intensive selection. M. esculenta subspp flabellifolia is probably a wild progenitor. Introgressive hybridization with wild forms and pressures to adapt to the widely varying climates and topography in which cassava is found might have enhanced the crop's present day variability. PMID- 24178018 TI - Sequence-tagged sites (STSs) as standard landmarkers in the rice genome. AB - Generating sequence-tagged sites (STSs) is a prerequisite to convert a genetic map to a physical map. With the help of sequence information from these STSs one can also isolate specific genes. For these purposes, we have designed PCR primer sets, of 20 bases each, by reference to sequences of restriction fragment length polymorphism (RFLP) landmarkers consisting of rice genomic clones. These markers were evenly distributed over the 12 chromosomes and were shown to be single copy by Southern-blot analysis. With improved PCR protocols, 63 standard STS landmarkers in the rice genome were generated. Similarity searches of all partial sequences of RFLP landmarkers by the FASTA algorithm showed that 2 of the 63 RFLP landmarkers, G357 and G385, contained part of the ORFs of aspartate aminotransferase and protein kinase, respectively. PMID- 24178019 TI - A partial genome assay for quantitative trait loci in wheat (Triticum aestivum) using different analytical techniques. AB - F1 plants between two intervarietal chromosome substitution lines of European spring wheat varieties, 'Sicco' ('Chinese Spring 5B') and 'Highbury' ('Chinese Spring 5B'), were used to produce 114 doubled haploid lines, 45 by the Hordeum bulbosum technique and 69 by anther culture. These two sets of lines were characterized for variation at a range of morphological, isozyme and RFLP marker loci, and genetic maps were developed with emphasis on chromosomes 6B, 7A, 7B and 7D. A subset of lines, scored for production traits in field trials in 1986 and 1987, were analysed for quantitative trait loci (QTL). The performance of the lines for the quantitative traits studied showed no overall differences due to the method of production of the lines. QTL were located on the linkage map for ear emergence time, height, tiller weight, yield and 50-grain weight using four analytical methods. Many of these effects showed genotype x year interaction. PMID- 24178020 TI - Somatic embryogenesis in white spruce (Picea glauca): genetic control in somatic embryos exposed to storage, maturation treatments, germination, and cryopreservation. AB - Genetic controls for growth of embryogenic cultures, storage, maturation treatments, germination and cryopreservation in white spruce somatic embryogenesis (SE) were examined. These SE processes were under genetic control but less strongly so than the initiation phase. For all the SE characters examined, variance due to clones within families was significant and often the largest genetic component of variance. This was further partitioned using an additive-dominance-epistasis model. A relatively-large proportion of the total genetic variance was due to epistatic variance in the maturation and germination of somatic embryos. Embryogenic lines were cryopreserved easily without a distinct genetic influence being noticed. PMID- 24178021 TI - Impact of mating design on selection response in Brassica rapa L. AB - The impact of four mating designs on selection response for leaf area was assessed at four different population sizes, using fast-cycling Brassica rapa L. Mating designs were either balanced (partial diallel or pair mating) or unbalanced (factorial mating designs with either one or two testers). When balanced, the mating designs required different numbers of crossings for the same number of parents: the partial diallel design, in the configuration retained here, required three times as many crossings as pair mating. Population sizes were 4, 8, 16, and 32. The percentage of selected individuals was kept constant at 25%. Despite an average estimated heritability around 0.4, the overall response to selection after five generations was fairly weak in all three replicates. For a given population size, selection response was larger under balanced mating designs than under unbalanced ones. There was no difference among balanced mating designs. Both results indicate that effective population size is more important than population size or the number of crossings in maintaining genetic gain. PMID- 24178022 TI - Inheritance of restriction fragment length polymorphisms and random amplified polymorphic DNAs in coastal Douglas-fir. AB - A total of 225 new genetic loci [151 restriction fragment length polymorphisms (RFLP) and 74 random amplified polymorphic DNAs (RAPD)] in coastal Douglas-fir [Pseudotsuga menziesii (Mirb.) Franco var. menziesii] have been identified using a three-generation outbred pedigree. The Mendelian inheritance of 16 RFLP loci and 29 RAPD loci was demonstrated based on single-locus segregation in a sample of F2 progeny. One RFLP locus, PtIFG2025, showed segregation distortion. Probe pPtIFG2025 is a loblolly pine cDNA probe encoding for rbcS. The 16 RFLP loci and 23 allozyme loci were also assayed in a sample of 16 Douglas-fir seed-orchard clones. Allelism was determined at 11 of the 16 RFLP loci. RFLPs were able to detect slightly more variation (4.0 alleles per locus) than allozymes (3.1 alleles per locus). The inheritance of an additional 80 RAPD loci was determined based on haploid segregation analysis of megagametophytes from parent tree 013-1. Once 200-300 markers are identified and placed on a genetic map, quantitative trait loci affecting bud phenology will be mapped. PMID- 24178023 TI - Genetic and amino-acid analysis of two maize threonine-overproducing, lysine insensitive aspartate kinase mutants. AB - The aspartate-derived amino-acid pathway leads to the production of the essential amino-acids lysine, methionine, threonine and isoleucine. Aspartate kinase (AK) is the first enzyme in this pathway and exists in isoforms that are feedback inhibited by lysine and threonine. Two maize (Zea mays L.) threonine overproducing, lysine-insensitive AK mutants (Ask1-LT19 and Ask2-LT20) were previously isolated. The present study was conducted to determine the map location of Ask2 and to examine the amino-acid profiles of the Ask mutants. The threonine-overproducing trait conferred by Ask2-LT20 was mapped to the long arm of chromosome 2. Both mutants exhibited increased free threonine concentrations (nmol/mg dry weight) over wild-type. The percent free threonine increased from approximately 2% in wild-type kernels to 37-54% of the total free amino-acid pool in homozygous mutant kernels. Free methionine concentrations also increased significantly in homozygous mutants. Free lysine concentrations were increased but to a much lesser extent than threonine or methionine. In contrast to previous studies, free aspartate concentrations were observed to decrease, indicating a possible limiting factor in threonine synthesis. Total (free plus protein-bound) amino-acid analyses demonstrated a consistent, significant increase in threonine, methionine and lysine concentrations in the homozygous mutants. Significant increases in protein-bound (total minus free) threonine, methionine and lysine were observed in the Ask mutants, indicating adequate protein sinks to incorporate the increased free amino-acid concentrations. Total amino-acid contents (nmol/kernel) were approximately the same for mutant and wild-type kernels. In five inbred lines both Ask mutations conferred the threonine overproducing phenotype, indicating high expressivity in different genetic backgrounds. These analyses are discussed in the context of the regulation of the aspartate-derived amino-acid pathway. PMID- 24178024 TI - Somatic hybrids between Solanum etuberosum and diploid, tuber bearing Solanum clones. AB - Electrofusion was used to obtain somatic hybrids between Solanum etuberosum (2n=2x=24) and two diploid potato lines. These hybridizations were conducted to determine if haploidxwild species hybrids are better fusion partners than conventional S. tuberosumGp. Tuberosum haploids. Restriction fragment length polymerase (RFLP) analyses of the putative somatic hybrids confirmed that each parental genome was present. The somatic hybrids between S. etuberosum and a haploid S. tuberosum clone, US-W730, were stunted and had curled, purple leaves. In contrast, somatic hybrids between S. etuberosum and a haploidxwild species hybrid (US-W 730 haploidx S. berthaultii), were vigorous and generally tuberized under field conditions. These hybrids were designated as E+BT somatic hybrids. Analyses of 23 E+BT somatic hybrids revealed a statistically significant bias towards the retention of S. etuberosum chloroplasts. Stylar incompatibilities were observed when the E+BT somatic hybrids were used as pollen donors in crosses with S. tuberosum cultivars. Reciprocal crosses did not show this incompatibility. The progeny were vigorous and had improved tuber traits when compared to the maternal E+BT parent. RFLP analyses of three sexual progeny lines confirmed the presence of all 12 S. etuberosum chromosomes. In two of these lines, RFLPs that marked each of the 24 chromosome arms of S. etuberosum were present. However, RFLP markers specific for regions on chromosomes 2, 7, and 11 were missing from the third clone. Because other markers for these chromosomes were present in the progeny line, these results indicated the likelihood of pairing and recombination between S. etuberosum and S. tuberosum chromosomes. PMID- 24178025 TI - Resistance to potato virus Y in somatic hybrids between Solanum etuberosum and S. tuberosum x S. berthaultii hybrid. AB - Somatic hybrids between a potato virus Y (PVY) resistant Solanum etuberosum clone and a susceptible diploid potato clone derived from a cross between S. tuberosum Gp. Tuberosum haploid US-W 730 and S. berthaultii were evaluated for resistance to PVY. All but one of the tested somatic hybrids were significantly more resistant than cultivars 'Atlantic' and 'Katahdin'. However, none was as resistant as the S. etuberosum parent. One hexaploid somatic hybrid, possibly the product of a triple-cell fusion involving one S. etuberosum protoplast and two haploid x S. berthaultii protoplasts, was as susceptible to PVY infection as the cultivars. Tetraploid progeny of the somatic hybrids, obtained from crosses with Gp. Tuberosum cultivars, were neither as resistant as the maternal somatic hybrid parent, nor as susceptible as the paternal cultivar parent. It appears that the introgression of PVY resistance from (1EBN) S. etuberosum into (4EBN) S. tuberosum (EBN-endosperm balance number) will be successful through the use of somatic hybridization and subsequent crosses of the somatic hybrids back to S. tuberosum. PMID- 24178026 TI - A monoclonal antibody chromosome marker analysis used to locate a loose smut resistance gene in wheat chromosome 6A. AB - Many genes have been located in wheat chromosomes, yet little is known about the location of genes for resistance to Ustilago tritici, which causes loose smut. Crosses were made between the loose smut susceptible alien substitution lines Cadet 6Ag(6A) and Rescue 6Ag(6A) (lines in which Agropyron chromosome 6 is substituted by wheat chromosome 6A) and four cultivars resistant to U. tritici race T19: 'Cadet', 'Kota', 'Thatcher' and 'TD18'. The segregating progeny were tested for reaction to race T19 and for the level of binding with a monoclonal antibody specific to a chromosome 6A-coded seed protein. The antibody, which does not bind to seed protein extracts in the absence of the 6A chromosome, was used as a chromosome marker. An association was established between resistance to race T19 and the presence of chromosome 6A for each of the cultivars tested, indicating that resistance to race T19 resides in chromosome 6A. Ustilago tritici race T19 resistance in 'Cadet' appears to be located in the short arm of chromosome 6A, based on the evaluation of the Cadet 6A long ditelosomic stock, which was susceptible, and the Cadet 6A-short: 6-Agropyron- short alien translocation stock, which was resistant. PMID- 24178027 TI - Location of a gene regulating drought-induced abscisic acid production on the long arm of chromosome 5A of wheat. AB - The accumulation of abscisic acid (ABA) by detached and partially dehydrated wheat leaves is known to be inherited in a quantitative manner. The location of genes having a major effect on drought-induced ABA accumulation in wheat was determined using a set of single chromosome substitution lines and populations derived from a cross between a high-ABA- and a low-ABA-producing genotype. Examination of a series of chromosome substitution lines of the high-ABA genotype 'Ciano 67' into the low-ABA recipient 'Chinese Spring' showed that chromosome 5A carries gene(s) that have a major influence on ABA accumulation in a drought test with detached and partially dehydrated leaves (DLT). A similar DLT was used to examine ABA accumulation in a population of F2 plants and doubled haploid (DH) lines derived from the cross between 'Chinese Spring' (low-ABA) and 'SQ1' (high ABA) in which the F2 population (139 plants) and DH lines (96 lines) were also mapped partially with molecular markers. Analysis of variance of ABA accumulation between and within marker allele classes in the F2 confirmed the location of a gene(s) regulating ABA accumulation on the long arm of chromosome 5A. MAPMAKERQTL showed the most likely position for the ABA quantitative trait locus (QTL) to be between the loci Xpsr575 and Xpsr426, about 8 cM from Xpsr426. A similar trend for high ABA accumulation was found in DH lines having the 'SQ1' allele at marker loci in the same region of chromosome 5AL, but the QTL effect was not significant. The function of the QTL is discussed. PMID- 24178028 TI - SubtiWiki-a database for the model organism Bacillus subtilis that links pathway, interaction and expression information. AB - Genome annotation and access to information from large-scale experimental approaches at the genome level are essential to improve our understanding of living cells and organisms. This is even more the case for model organisms that are the basis to study pathogens and technologically important species. We have generated SubtiWiki, a database for the Gram-positive model bacterium Bacillus subtilis (http://subtiwiki.uni-goettingen.de/). In addition to the established companion modules of SubtiWiki, SubtiPathways and SubtInteract, we have now created SubtiExpress, a third module, to visualize genome scale transcription data that are of unprecedented quality and density. Today, SubtiWiki is one of the most complete collections of knowledge on a living organism in one single resource. PMID- 24178029 TI - Stimulation of ribosomal frameshifting by RNA G-quadruplex structures. AB - Guanine-rich sequences can fold into four-stranded structures of stacked guanine tetrads, so-called G-quadruplexes (G4). These unique motifs have been extensively studied on the DNA level; however, exploration of the biological roles of G4s at the RNA level is just emerging. Here we show that G4 RNA when introduced within coding regions are capable of stimulating -1 ribosomal frameshifting (-1 FS) in vitro and in cultured cells. Systematic manipulation of the loop length between each G-tract revealed that the -1 FS efficiency positively correlates with G4 stability. Addition of a G4-stabilizing ligand, PhenDC3, resulted in higher -1 FS. Further, we demonstrated that the G4s can stimulate +1 FS and stop codon readthrough as well. These results suggest a potentially novel translational gene regulation mechanism mediated by G4 RNA. PMID- 24178030 TI - A meta-analysis revealed insights into the sources, conservation and impact of microRNA 5'-isoforms in four model species. AB - MicroRNA (miRNA) 5'-isoforms, or 5'-isomiRs, are small-RNA species that originate from the same genomic loci as the major miRNAs with their 5' ends shifted from the 5' ends of the miRNAs by a few nucleotides. Although 5'-isomiRs have been reported, their origins, properties and potential functions remain to be examined. We systematically studied 5'-isomiRs in human, mouse, fruitfly and worm by analysing a large collection of small non-coding RNA and mRNA profiling data. The results revealed a broad existence of 5'-isomiRs in the four species, many of which were conserved and could arise from genomic loci of canonical and non canonical miRNAs. The well-conserved 5'-isomiRs have several features, including a preference of the 3p over the 5p arms of hairpins of conserved mammalian miRNAs, altered 5'-isomiRs across species and across tissues, and association with structural variations of miRNA hairpins. Importantly, 5'-isomiRs and their major miRNAs may have different mRNA targets and thus potentially play distinct roles of gene regulation, as shown by an integrative analysis combining miRNA and mRNA profiling data from psoriatic and normal human skin and from murine miRNA knockout assays. Indeed, 18 5'-isomiRs had aberrant expression in psoriatic human skin, suggesting their potential function in psoriasis pathogenesis. The results of the current study deepened our understanding of the diversity and conservation of miRNAs, their plasticity in gene regulation and potential broad function in complex diseases. PMID- 24178031 TI - Vpr expression abolishes the capacity of HIV-1 infected cells to repair uracilated DNA. AB - The human immunodeficiency virus type 1 (HIV-1) Vpr protein binds to the cellular uracil-DNA glycosylase UNG2 and induces its degradation through the assembly with the DDB1-CUL4 ubiquitin ligase complex. This interaction counteracts the antiviral activity exerted by UNG2 on HIV-1 gene transcription, as previously reported by us. In this work, we show that Vpr expression in the context of HIV-1 infection markedly decreases UNG2 expression in transformed or primary CD4(+) T lymphocytes. We demonstrate for the first time that Vpr-UNG2 interaction significantly impairs the uracil excision activity of infected cells. The loss of uracil excision activity coincides with a significant accumulation of uracilated bases in the genome of infected cells without changes in cell division. Although UNG2 expression and uracil-DNA glycosylase activity are recovered after the peak of retroviral replication, the mutagenic effect of transient DNA uracilation in cycling cells should be taken into account. Therefore, the possible consequences of Vpr-mediated temporary depletion of endogenous nuclear UNG2 and subsequent alteration of the genomic integrity of infected cells need to be evaluated in the physiopathogenesis of HIV infection. PMID- 24178032 TI - A pathogenic non-coding RNA induces changes in dynamic DNA methylation of ribosomal RNA genes in host plants. AB - Viroids are plant-pathogenic non-coding RNAs able to interfere with as yet poorly known host-regulatory pathways and to cause alterations recognized as diseases. The way in which these RNAs coerce the host to express symptoms remains to be totally deciphered. In recent years, diverse studies have proposed a close interplay between viroid-induced pathogenesis and RNA silencing, supporting the belief that viroid-derived small RNAs mediate the post-transcriptional cleavage of endogenous mRNAs by acting as elicitors of symptoms expression. Although the evidence supporting the role of viroid-derived small RNAs in pathogenesis is robust, the possibility that this phenomenon can be a more complex process, also involving viroid-induced alterations in plant gene expression at transcriptional levels, has been considered. Here we show that plants infected with the 'Hop stunt viroid' accumulate high levels of sRNAs derived from ribosomal transcripts. This effect was correlated with an increase in the transcription of ribosomal RNA (rRNA) precursors during infection. We observed that the transcriptional reactivation of rRNA genes correlates with a modification of DNA methylation in their promoter region and revealed that some rRNA genes are demethylated and transcriptionally reactivated during infection. This study reports a previously unknown mechanism associated with viroid (or any other pathogenic RNA) infection in plants providing new insights into aspects of host alterations induced by the viroid infectious cycle. PMID- 24178033 TI - GPLEXUS: enabling genome-scale gene association network reconstruction and analysis for very large-scale expression data. AB - The accurate construction and interpretation of gene association networks (GANs) is challenging, but crucial, to the understanding of gene function, interaction and cellular behavior at the genome level. Most current state-of-the-art computational methods for genome-wide GAN reconstruction require high-performance computational resources. However, even high-performance computing cannot fully address the complexity involved with constructing GANs from very large-scale expression profile datasets, especially for the organisms with medium to large size of genomes, such as those of most plant species. Here, we present a new approach, GPLEXUS (http://plantgrn.noble.org/GPLEXUS/), which integrates a series of novel algorithms in a parallel-computing environment to construct and analyze genome-wide GANs. GPLEXUS adopts an ultra-fast estimation for pairwise mutual information computing that is similar in accuracy and sensitivity to the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE) method and runs ~1000 times faster. GPLEXUS integrates Markov Clustering Algorithm to effectively identify functional subnetworks. Furthermore, GPLEXUS includes a novel 'condition-removing' method to identify the major experimental conditions in which each subnetwork operates from very large-scale gene expression datasets across several experimental conditions, which allows users to annotate the various subnetworks with experiment-specific conditions. We demonstrate GPLEXUS's capabilities by construing global GANs and analyzing subnetworks related to defense against biotic and abiotic stress, cell cycle growth and division in Arabidopsis thaliana. PMID- 24178035 TI - Readability assessment of online ophthalmic patient information. AB - IMPORTANCE: Patients increasingly use the Internet to access information related to their disease, but poor health literacy is known to impact negatively on medical outcomes. Multiple agencies have recommended that patient-oriented literature be written at a fourth- to sixth-grade (9-12 years of age) reading level to assist understanding. The readability of online patient-oriented materials related to ophthalmic diagnoses is not yet known. OBJECTIVE: To assess the readability of online literature specifically for a range of ophthalmic conditions. DESIGN AND SETTING: Body text of the top 10 patient-oriented websites for 16 different ophthalmic diagnoses, covering the full range of ophthalmic subspecialties, was analyzed for readability, source (United Kingdom vs non United Kingdom, not for profit vs commercial), and appropriateness for sight impaired readers. MAIN OUTCOMES AND MEASURES: Four validated readability formulas were used: Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG), and Gunning Fog Index (GFOG). Data were compared with the Mann-Whitney test (for 2 groups) and Kruskal-Wallis test (for more than 2 groups) and correlation was assessed by the Spearman r. RESULTS: None of the 160 webpages had readability scores within published guidelines, with 83% assessed as being of "difficult" readability. Not-for-profit webpages were of significantly greater length than commercial webpages (P = .02) and UK-based webpages had slightly superior readability scores compared with those of non-UK webpages (P = .004 to P < .001, depending on the readability formula used). Of all webpages evaluated, only 34% included facility to adjust text size to assist visually impaired readers. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first study to assess readability of patient-focused webpages specifically for a range of ophthalmic diagnoses. In keeping with previous studies in other medical conditions, we determined that readability scores were inferior to those recommended, irrespective of the measure used. Although readability is only one aspect of how well a patient-oriented webpage may be comprehended, we recommend the use of readability scoring when producing such resources in the future. Minimum readability policies and inclusion of facilities within webpages to maximize viewing potential for visually impaired readers are important to ensure that online ophthalmic patient information is accessible to the broadest audience possible. PMID- 24178034 TI - IDEAL in 2014 illustrates interaction networks composed of intrinsically disordered proteins and their binding partners. AB - IDEAL (Intrinsically Disordered proteins with Extensive Annotations and Literature, http://www.ideal.force.cs.is.nagoya-u.ac.jp/IDEAL/) is a collection of intrinsically disordered proteins (IDPs) that cannot adopt stable globular structures under physiological conditions. Since its previous publication in 2012, the number of entries in IDEAL has almost tripled (120 to 340). In addition to the increase in quantity, the quality of IDEAL has been significantly improved. The new IDEAL incorporates the interactions of IDPs and their binding partners more explicitly, and illustrates the protein-protein interaction (PPI) networks and the structures of protein complexes. Redundant experimental data are arranged based on the clustering of Protein Data Bank entries, and similar sequences with the same binding mode are grouped. As a result, the new IDEAL presents more concise and informative experimental data. Nuclear magnetic resonance (NMR) disorder is annotated in a systematic manner, by identifying the regions with large deviations among the NMR models. The ordered/disordered and new domain predictions by DICHOT are available, as well as the domain assignments by HMMER. Some examples of the PPI networks and the highly deviated regions derived from NMR models will be described, together with other advances. These enhancements will facilitate deeper understanding of IDPs, in terms of their flexibility, plasticity and promiscuity. PMID- 24178036 TI - Solution and implementation of distributed lifespan models. AB - We consider a population where every individual has a unique lifespan. After expiring of its lifespan the individual has to leave the population. A realistic approach to describe these lifespans is by a continuous distribution. Such distributed lifespan models (DLSMs) were introduced earlier in the indirect response context and consist of the mathematical convolution operator to describe the rate of change. Therefore, DLSMs could not directly be implemented in standard PKPD software. In this work we present the solution representation of DLSMs with and without a precursor population and an implementation strategy for DLSMs in ADAPT , NONMEM and MATLAB . We fit hemoglobin measurements from literature and investigate computational properties. PMID- 24178037 TI - On the maintenance of hepatocyte intracellular pH 7.0 in the in-vitro metabolic stability assay. AB - The account of pH difference between hepatocytes (intracellular pH 7.0) and extracellular water (pH 7.4) leads to the novel equation for hepatic clearance (Berezhkovskiy, J Pharma Sci 100:1167-1683, 2011). The metabolic stability assay using hepatocytes is commonly performed in the incubation buffer of pH 7.4. If hepatocytes retain their physiological pH 7.0 in these conditions, then the assay would mimic the in vivo condition, that is pH 7.4 for plasma and extracellular water, and pH 7.0 in hepatocytes. In this case the rate of drug elimination, taken as proportional to unbound drug concentration in buffer, would correspond to the in vivo rate of drug elimination as proportional to the unbound drug concentration in the extracellular water. Consequently the commonly used PBPK equation for the rate of hepatic elimination, and the equation for hepatic clearance would be valid. However, the experiment designed to determine hepatocyte internal pH indicated that it was not maintained in the in vitro stability assay, so that hepatocytes acquire the same pH as the incubation buffer. Thus, the novel equations for hepatic clearance (that include an ionization factor) should be applied regardless if the intrinsic clearance was obtained either from microsomal or hepatocyte stability assay. PMID- 24178038 TI - Movement of elicitins, necrosis-inducing proteins secreted by Phytophthora sp., in tobacco. AB - In culture, Phytophthora fungi - except P. nicotianae - secrete proteins, called elicitins, which cause necrosis on the leaf of the non-host tobacco (Nicotiana tabacum L.) at a distance from the inoculation site, and are responsible for the incompatible reaction. Cryptogein and capsicein are elicitins secreted by P. cryptogea and P. capsici, respectively, and form part of a novel family of 10-kDa holoproteins. On tobacco, the necrotic activity of cryptogein is approx. 100-fold higher than that of capsicein. Using elicitins radioactively labelled in vivo, we have demonstrated that cryptogein and capsicein (i) move from a wound in the stem towards the leaves where they interact directly, (ii) reach their target without undergoing any molecular alteration, (iii) are carried in, and at the same rate as, the sap flow in the xylem, (iv) do not alter the rate of the xylem flow although they are able to provoke drastic damage to the lamina. Consequently, the remote necrotic activity of elicitins does not require any transportable secondary plant elicitor, so the differences in necrotic properties should be due to structural features involved in the interaction of elicitins with the leaf target cells. PMID- 24178039 TI - Evidence for a geranyl-diphosphate synthase located within the plastids of Vitis vinifera L. cultivated in vitro. AB - Intact plastids from cell suspensions of Vitis vinifera L. cv. Muscat de Frontignan, free of detectable contamination by other particles as judged by the distribution of organelle-specific marker enzymes and by electron microscopy, exhibit geranyl-diphosphate synthase activity (EC 2.5.1.1). This synthase activity remains stable after tryptic digestion of unlysed organelles and is enhanced by plastid disruption. We conclude that the enzyme is located within the organelle. The possibility of an isopentenyl diphosphate/dimethylallyl diphosphate translocating system which would play a major role in the regulation of monoterpene metabolism is discussed. PMID- 24178040 TI - A major stress-inducible Mr-42000 wall glycoprotein of French bean (Phaseolus vulgaris L.). AB - A major wall protein of suspension-cultured cells of French bean has been isolated and characterised. It can be prepared from walls or the culture filtrate and in composition it is particularly rich in proline, valine and glutamic acid/glutamine and contains appreciable amounts of hydroxyproline. The N-terminus shows some glycosylation, while following chemical deglycosylation the first 38 residues were found to be identical to those of proline-rich proteins from soybean. However, the composition of the highly purified Mr-42000 bean protein differs considerably from the soybean proteins and must contain its own specific domains. An antibody was raised and used to demonstrate the inducibility of the Mr-42000 bean protein in response to elicitor action. The protein was found to be mainly localised in the intercellular spaces of the cortical cells of bean hypocotyls and at the wall-plasmalemma interface of xylem vessels, another potentially accessible compartment for pathogens. Following wounding, the protein was found to be generally distributed in the wall of epidermal and cortical cells of the hypocotyls. The Mr-42000 protein is cross reactive with antibodies raised to glycoproteins of the Rhizobium infection thread and the chitin-binding hydroxyproline-rich glycoprotein, potato lectin. These common epitopes together with the previously demonstrated chitin-binding properties of the bean protein indicate a role in host-microbial interactions. Furthermore, the Mr-42000 protein itself bound to the growing hyphal tips of the bean pathogen, Colletotrichum lindemuthianum. PMID- 24178041 TI - Abscisic acid biosynthesis in roots : I. The identification of potential abscisic acid precursors, and other carotenoids. AB - The pathway of water-stress-induced abscisic acid (ABA) biosynthesis in etiolated and light-grown leaves has been elucidated (see A.D. Parry and R. Horgan, 1991, Physiol. Plant. 82, 320-326). Roots also have the ability to synthesise ABA in response to stress and it was therefore of interest to examine root extracts for the presence of carotenoids, including those known to be ABA precursors in leaves. All-trans- and 9'-cis-neoxanthin, all-trans- and 9-cis-violaxanthin, antheraxanthin (all potential ABA precursors), lutein and beta-carotene were identified on the basis of absorbance spectra, reactions with dilute acid, retention times upon high-performance liquid chromatography and by comparison with leaf carotenoids that had been analysed by mass spectrometry. The source of the extracted carotenoids was proved to be root tissue, and not contaminating compost or leaf material. The levels of total carotenoids in roots varied between 0.03-0.07% of the levels in light-grown leaves (Arabidopsis thaliana (L.) Heynh, Nicotiana plumbaginifolia Viv., Phaseolus vulgaris L. and Pisum sativum L.) up to 0.27% (Lycopersicon esculentum Mill.). The relative carotenoid composition was very different from that found in leaves, and varied much more between species. All-trans-neoxanthin and violaxanthin were the major carotenoids present (64-91 % of the total), but while Lycopersicon contained 67-80% all trans-neoxanthin, Phaseolus, Pisum and Zea mays L. contained 61-79% all-trans-violaxanthin. Carotenoid metabolism also varied between species, with most of the carotenoids in older roots of Phaseolus being esterified. Roots and leaves of the ABA deficient aba mutant of Arabidopsis had reduced epoxy-xanthophyll levels compared to the wild-type. PMID- 24178042 TI - Abscisic acid biosynthesis in roots : II. The effects of water-stress in wild type and abscisic-acid-deficient mutant (notabilis) plants of Lycopersicon esculentum Mill. AB - The ubiquity of the apo-carotenoid abscisic acid (ABA) biosynthetic pathway elucidated in water-stressed, etiolated leaves of Phaseolus vulgaris (see A.D. Parry and R. Horgan, 1991, Physiol. Plant. 82, 320-326), has been difficult to establish. Light-grown leaves contain very high carotenoid: ABA ratios, preventing correlative studies, and no etiolated leaves so far studied, other than those of Phaseolus, have been found capable of synthesising significant amounts of ABA in response to stress. Roots are known to synthesise ABA and contain low carotenoid levels; therefore ABA biosynthesis was investigated in soil- and hydroponically grown roots of Lycopersicon esculentum Mill. Hydroponically grown roots were stressed by immersion in 100 mM mannitol and soil grown roots by withholding water. In both cases stress led to an increase in ABA levels and a decrease in the levels of specific xanthophylls, namely all-trans- and 9'-cis-neoxanthin and all-trans-violaxanthin. In hydroponically grown roots, and soil-grown roots stressed after removal of the shoot, ratios of xanthophyll cleaved:ABA synthesised of approx. 1?1 were obtained. These findings are consistent with the operation of an apo-carotenoid pathway in roots, involving the conversion of all-trans-violaxanthin via all-trans-neoxanthin, to 9'-cis neoxanthin, and the specific cleavage of 9'-cis-neoxanthin to yield the C15 ABA precursor xanthosin. Similar experiments with roots of the "leaky", ABA-deficient mutant of Lycopersicon, notabilis, indicate that the mutation does not affect the perception or transduction of stress, or the ability of the plant to cleave carotenoids. Rather, it appears that notabilis possesses an enzyme with reduced substrate specificity which cleaves more all-trans-than 9'-cis-neoxanthin. PMID- 24178043 TI - Pyruvate-kinase isoenzymes from zygotic and microspore-derived embryos of Brassica napus : Developmental profiles and subunit composition. AB - Polyclonal antibodies against castor-oil seed cytosolic and leucoplastic pyruvate kinases (PKc and PKp, respectively; EC 2.7.1.40) were utilized to examine the subunit compositions and developmental profiles of canola (Brassica napus L. cv. Topas) PKc and PKp over 6 d of seed germination and 35 d of culture of microspore derived embryos. The PKc from germinating seeds appears to be composed of a single type of 56-kDa subunit, whereas the enzyme from cultured embryos contains equal proportions of immunologically related 57- and 56-kDa subunits. The PKp was immunologically undetectable in germinating seeds, while the enzyme from cultured embryos consisted of immunologically related 64- and 58-kDa subunits in a ratio of about 1?2, respectively. The large increase in PK activity that occurs between the second and fourth days of seed gemination is based upon de-novo synthesis of PKc. Between 7 and 14 d of culture of microspore-derived embryos, the levels of PKp and PK maximal activity increased approx. 3- and 2.5-fold, respectively. These increases were coincident with an approximately fourfold rise in the in vivo pyruvate: phosphoenolpyruvate concentration ratio. Conversely, PKc was not only far less abundant relative to PKp, but its level remained constant over 35 d of microspore-embryo culture. Developing non-zygotic (microspore-derived) embryos strongly resembled ripening zygotic (seed) embryos in terms of PK specific activity as well as relative amounts and subunit compositions of PKc and PKp. The results indicate that the synthesis of PK isoenzymes in B. napus seeds is highly regulated and that this regulation follows a preset developmental program. PMID- 24178044 TI - Expression of soybean-embryo lipoxygenase 2 in transgenic tobacco tissue. AB - To assess the role of lipoxygenase (LOX; EC 1.13.11.12) in plants, we increased the expression of LOX in the tissues of Nicotiana tabacum L. cv. 'KY 14' by over expression of the LOX2 gene from the soybean (Glycine max (L.) Merrill) embryo. The LOX2 cDNA was manipulated by replacing its 5'-untranslated sequence with the translational enhancer of the alfalfa mosaic virus (AMV), and subcloned into a plant expression vector, 3' to a duplicated cauliflower mosaic virus 35S promoter. The AMV-LOX2 construct was transferred into tobacco using Agrobacterium tumefaciens strain A281. The LOX2 was expressed in transgenic tobacco calli, leaves of transgenic plants, and their seed progeny at levels up to 0.1-0.2% of the total extracted protein. The introduced LOX2 affected fatty-acid oxidative metabolism as evidenced by a 50-529% increase in C6-aldehyde production. The impact on C6-aldehyde formation was greater than the effect on production of fatty-acid hydroperoxides. This is consistent with other studies indicating the greater propensity of soybean embryo LOX2 in generating C6-aldehydes than that of other well-characterized LOX isozymes. PMID- 24178045 TI - Growth at reduced turgor: irreversible and reversible cell-wall extension of maize coleoptiles and its implications for the theory of cell growth. AB - The relationship between steady-state elongation rate (G) and turgor pressure (P; G/P curve) was investigated using isolated segments of maize (Zea mays L.) coleoptiles incubated in osmotic solutions of a water potential range of 0 to -10 bar (polyethylene glycol 6000 as osmoticum). Short-term elongation measurements revealed curvilinear G/P curves with a steep slope at high turgor and a shallow slope at low turgor. Owing to a decrease of osmotic pressure and turgor, there was a tendency for straightening of the G/P curves during long-term elongation. An elongation rate of zero was adjusted by lowering the turgor by 4.5 bar at a constant osmotic pressure of 6.7 bar. Auxin increased - whereas abscisic acid decreased - the slope of the G/P curve but these hormones had no effect on the threshold turgor of growth (Y = 2.2 bar). It is concluded that extensibility of the growing cell walls represented by the 'yielding coefficient' of Lockhart's growth equation is turgor-dependent and therefore decreases to a very low value as the turgor approaches Y. When the turgor was kept at Y, a constant segment length was maintained over at least 6 h. However, separation of reversible (lrev) and irreversible (lirr) components of total (in vivo) length (ltot = lrev + lirr) W measuring segment length before and after freezing/thawing revealed that lirr increased continuously and lrev decreased continuously at constant ltot. After a step-down in turgor the segments grew in lirr although they shrank in ltot over the whole turgor range of 0ten years) survival rate and radiological results of the Duracon TKA. METHODS: Between 1992 and 1999 159 Duracon TKA were implanted at our institution. A Kaplan-Meier survival analysis for the endpoints exchange, addition or removal of any component for any reason, revision due to aseptic loosening and mechanical failure was performed. Radiological long-term (>ten years) follow-up (FU) analysis was performed according to the Knee Society Radiographic Evaluation and Scoring System. RESULTS: Mean age at surgery was 74.3 years, 28% were male, and 89% had primary osteoarthritis as diagnosis. Mean FU for survival analysis was 10.9 years (SD 4.2). A total of 58% of the patients died during follow-up. Three patients (2.1%) were lost to follow-up and five TKA (3.1%) were revised. After ten years the mean survival was 97.7%, 99.4% and 98.3% for the aforementioned endpoints, respectively. Mean radiological FU was 11.8 years (SD 2.3). We found no significant change in alignment of the components or axis over time. Progressive radiolucencies were found in nine TKA (17%), mainly around the tibial component (95%). CONCLUSION: The Duracon TKA showed excellent long-term survival comparable to data from national registers and to other successful designs. Radiological changes found on plain radiographs were scarce after almost 12 years of radiological follow-up indicating good implant stability. PMID- 24178065 TI - Perceptual adaptation to structure-from-motion depends on the size of adaptor and probe objects, but not on the similarity of their shapes. AB - Perceptual adaptation destabilizes the phenomenal appearance of multistable visual displays. Prolonged dominance of a perceptual state fatigues the associated neural population, lowering the likelihood of renewed perception of the same appearance (Nawrot & Blake in Perception & Psychophysics, 49, 230-44, 1991). Here, we used a selective adaptation paradigm to investigate perceptual adaptation for the illusory rotation of ambiguous structure-from-motion (SFM) displays. Specifically, we generated SFM objects with different three-dimensional shapes and presented them in random order, separating successive objects by brief blank periods, which included a mask. To assess the specificity of perceptual adaptation to the shape of SFM objects, we established the probability that a perceived direction of rotation persisted between successive objects of similar or dissimilar shape. We found that the strength of negative aftereffects depended on the volume, but not the shape, of adaptor and probe objects. More voluminous objects were both more effective as adaptor objects and more sensitive as probe objects. Surprisingly, we found these volume effects to be completely independent, since any relationship between two shapes (such as overlap between volumes, similarity of shape, or similarity of velocity profiles) failed to modulate the negative aftereffect. This pattern of results was the opposite of that observed for sensory memory of SFM objects, which reflects similarity between objects, but not volume of individual objects (Pastukhov et al. in Attention, Perception & Psychophysics, 75, 1215-1229, 2013). The disparate specificities of perceptual adaptation and sensory memory for identical SFM objects suggest that the two aftereffects engage distinct neural representations, consistent with recent brain imaging results (Schwiedrzik et al. in Cerebral Cortex, 2012). PMID- 24178064 TI - Genetic polymorphisms in pre-microRNAs and risk of ischemic stroke in a Chinese population. AB - Ischemic stroke is considered to be a complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. MicroRNAs participated in various physiopathological processes; common single nucleotide polymorphisms (SNPs) in pre-miRNAs have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of the hsa-mir-196-a2/rs11614913 T/C, hsa-mir-146a/rs2910164 C/G, and hsa-mir 499/rs3746444 A/G polymorphisms in pre-miRNAs with the risk of ischemic stroke in a Chinese population. The three polymorphisms were identified in 296 ischemic stroke patients and 391 healthy controls using polymerase chain reaction restriction fragment length polymorphism. The frequency of the allele G of hsa mir-499/rs3746444 A/G showed significant association with ischemic stroke when compared with controls (OR = 1.509, 95%CI = 1.151-1.978, P = 0.003). Increased ischemic stroke risks were associated with rs3746444 A/G genotypes in different genetic model (homozygote comparison: P = 0.045, OR = 2.084, 95%CI = 1.019-4.262; heterozygote comparison: P = 0.024, OR = 1.489, 95%CI = 1.063-2.087; dominant genetic model: P = 0.007, OR = 1.563, 95%CI = 1.135-2.153). Similar results were obtained by adjusted fully risk factors. However, we failed to find any association between the alleles and genotypes of rs2910164 C/G and rs11614913 T/C SNPs and ischemic stroke, respectively (p > 0.05). The present study provided evidence that hsa-mir-499/rs3746444 A/G polymorphism might be associated with a significantly increased risk of ischemic stroke in a Chinese population, indicating that the common genetic polymorphism in pre-microRNAs contributed to the pathogenesis of ischemic stroke. PMID- 24178066 TI - The role of the human microbiome in otolaryngology-head and neck surgery: a contemporary review. AB - OBJECTIVES/HYPOTHESIS: The human microbiome represents the collective genomes and gene products of microbes living within and on humans. The objective of this review is to provide a summary of the current microbiome literature pertaining to otolaryngology-head and neck surgery. DATA SOURCE: Ovid MEDLINE. METHODS: Scientific publications with clinical correlates. RESULTS: Human microbiome studies have been facilitated by culture-independent, high-throughput sequencing methods. Data from the Human Microbiome Project has shown that the composition of the human microbiome is specific to each body site and that each individual has a unique microbiome. Alterations in the human microbiome are associated with some disease states; thus, novel therapeutic strategies are being developed based on concepts and findings stemming from microbiome research. CONCLUSIONS: Although a growing body of research shows potential significance of the human microbiome for human health and disease, there is a paucity of microbiome studies in otolaryngology. More studies are required to increase our understanding of the indigenous microbiota and their effects on diseases of the head and neck. PMID- 24178067 TI - Elevated serum level of growth arrest-specific protein 6 (Gas6) in systemic lupus erythematosus patients is associated with nephritis and cutaneous vasculitis. AB - Growth arrest-specific protein 6 (Gas6) is a serum protein involved in granulocyte, platelet and endothelium interaction, and is implicated in both anti inflammatory response as well as platelet/leukocytes activation. We investigated serum Gas6 level in different clinical manifestations of systemic lupus erythematosus (SLE). Data were collected in 83 patients with SLE and 40 non-lupus controls. The Gas6 levels were detected by enzyme-linked immunosorbent assay. Our results demonstrated that the Gas6 level was higher in SLE patients as compared to the non-lupus control subjects (SLE vs. non-lupus control, median [inter quartile range (IQR)] 22.67 [19.40-28.60] vs. 18.97 [16.05-20.62] ng/mL, p < 0.01). Furthermore, Gas6 level was higher in patients with nephritis (nephritis vs. non-nephritis, median [IQR] 26.21 [21.17-31.61] vs. 22.22 [18.98-26.98] ng/mL, p = 0.03) and in patients with cutaneous vasculitis (vasculitis vs. non vasculitis, median [IQR] 27.89 [23.24-34.26] vs. 22.30 [19.32-27.16] ng/mL, p = 0.03). Our results indicate that the serum Gas6 level is increased in SLE patients with lupus nephritis or cutaneous vasculitis, implicating a potential to serve as a SLE disease activity marker. PMID- 24178068 TI - Chitinase and peroxidase in effective (fix(+)) and ineffective (fix (-)) soybean nodules. AB - Chitinase and peroxidase, two enzymes thought to be involved in the defense of plants against pathogens, were measured in soybean (Glycine max L. Merr.) roots and in nodules colonized by Bradyrhizobium japonicum strains differing in their symbiotic potential. Activities of both enzymes were higher in nodules than in roots. In "effective", nitrogen-fixing nodules, colonized by wild-type bacteria, chitinase and peroxidase activities had low levels in the central infected zone and were enhanced primarily in the nodule cortex. An ascorbate-specific peroxidase, possibly involved in radical scavenging, had similarly high activities in the infected zone and in the cortex. "Ineffective" nodules colonized by bacteria unable to fix nitrogen symbiotically showed a similar distribution of chitinase and peroxidase. In another type of "ineffective" nodule, colonized by a B. japonicum strain eliciting a hypersensitive response, activities of both enzymes were enhanced to a similar degree in the infected zone as well as in the cortex. Tissue prints using a direct assay for peroxidase and an antiserum against bean chitinase corroborated these results. The antiserum against bean chitinase cross-reacted with a nodule protein of Mr 32 000; it inhibited most of the chitinase activity in the nodules but barely affected the chitinase in uninfected roots. It is concluded that proteins characteristic of the defense reaction accumulate in the cortex of nodules independently of their ability to fix nitrogen, and in the entire body of hypersensitively reacting nodules. PMID- 24178069 TI - Complementary patterns of stiffness in stem and leaf sheaths of Triticale : Measurements of ultrasound velocity. AB - The variation in the stiffness of stem and leaf sheaths along the shoot axis of Triticale (Triticosecale W., cv. Jago) was examined, using an ultrasonic method, at two stages of development, (i) at the stage of high stem mechanical instability when upper internodes are forming (heading), and (ii) at milk maturity when development of strengthening tissues is completed (three weeks after anthesis). The squared velocity of low-frequency longitudinal pulse waves was used as a measure of the specific modulus of elasticity, averaged over the whole cross section of the structures and related to the unit density of the material. Structural material of varying effective stiffness was found to be utilized along leaf sheaths with a pattern complementary to that in growing stems. The stiffness increased basipetally along leaf sheaths in the direction of increasing flexibility of internodes. Maximum values of the specific modulus of elasticity in particular leaf sheaths were enhanced acropetally, ensuring the stronger mechanical protection of those meristematic zones which were actively elongating and were located at the upper internodes. The stiffest material present in leaf sheaths covered only those stem sections which could be the most critical for plant safety during stem elongation. This characteristic and very regular pattern of stiffness alteration along the shoot axis was structurally determined as it remained similar after air drying the specimens. It is concluded that adaptation of cereals to withstand environmental loads is realized not only on morphological and anatomical levels but is also reflected in a specific heterogeneity in the material properties of the cell walls which support the plant. PMID- 24178070 TI - Contrasting responses of sulphate and phosphate transport in barley (Hordeum vulgare L.) roots to protein-modifying reagents and inhibition of protein synthesis. AB - The uptake of sulphate into roots of barley seedlings is highly sensitive to phenylglyoxal (PhG), an arginine-binding reagent. Uptake was inhibited by >80% by a 1-h pre-treatment of roots with 0.45 mol . m(-3) PhG. Inhibition was maximal in pre-treatment solutions buffered between pH 4.5 and 6.5. Phosphate uptake, measured simultaneously by double-labelling uptake solutions with (32)P and (35)S, was less susceptible to inhibition by PhG, particularly at pH <6.5, and was completely insensitive to the less permeant reagent p-hydroxyphenylglyoxal (OH-PhG) administered at 1 mol . m(-3) at pH at 5.0 or 8.2; sulphate uptake was inhibited in -S plants by 90% by OH-PhG-treatment. Root respiration in young root segments was unaffected by OH-PhG pre-treatment for 1 h and inhibited by only 17% after 90 min pre-treatment. The uptake of both ions was inhibited by the dithiol specific reagent, phenylarsine oxide even after short exposures (0.5-5.0 min). Sulphate uptake was more severely inhibited than that of phosphate, but in both cases inhibition could be substantially reversed by 5 min washing of treated roots by 5 mol . m(-3) dithioerythritol. After longer pre-treatment (50 min) with phenylarsine oxide, inhibition of the ion fluxes was not relieved by washing with dithioerythritol. Inhibition of sulphate influx by PhG was completely reversed by washing the roots for 24 h with culture solution lacking the inhibitor. The reversal was dependent on protein synthesis; less than 20% recovery was seen in the presence of 50 mmol . m(-3) cycloheximide. Sulphate uptake declined rapidly when -S roots were treated with cycloheximide. In the same roots the phosphate influx was little affected, small significant inhibitions being seen only after 4 h of treatment. Respiration was depressed by only 20% in apical and by 31% in basal root segments by cycloheximide pre-treatment for 2 h. Similar rates of collapse of the sulphate uptake and insensitivity of phosphate uptake were seen when protein synthesis was inhibited by azetidine carboxylic acid, p fluorophenylalanine and puromycin. Considering the effects of all of the protein synthesis inhibitors together leads to the conclusion that the sulphate transporter itself, or some essential sub-component of the uptake system, turns over rapidly with a half-time of about 2.5 h. The turnover of the phosphate transporter is evidently much slower. The results are discussed in relation to strategies for identifying the transport proteins and to the regulation of transporter activity during nutrient stress. PMID- 24178071 TI - Increased sterol biosynthesis in tobacco calli resistant to a triazole herbicide which inhibits demethylation of 14alpha-methyl sterols. AB - The gamma-keto triazole derivative 4,4-dimethyl-1-(2-methoxyphenyl)-1-(1,2,4 triazol-1-yl)-1-penten-3-one is toxic to Nicotiana tabacum L. cv. Xanthi plants or cell cultures. Analysis of the sterol composition of treated wild-type plant material demonstrates that this herbicide is an inhibitor of the C-14alpha-methyl demethylation process in sterol biosynthesis. Selection experiments, consisting of screening large populations of microcalli derived from UV-mutagenized tobacco protoplasts for resistance to a lethal dose (1 mg . 1(-1)) of the gamma-keto triazole, have resulted in the recovery of two groups of resistant calli. In the first group, selected calli show a sterol composition in the absence or presence of the inhibitor very similar to that of wild-type sensitive calli, whereas in the second group the main feature of the selected calli is a new sterol profile. These calli present an overproduction of sterols with a concomitant esterification of overproduced metaolites, just as it was demonstrated for calli previously selected in our laboratory for resistance to LAB 170250F, a triazole fungicide (Maillot-Vernier et al., 1991, Mol. Gen. Genet. 231, 33-40). PMID- 24178072 TI - Ammonium-induced increase in NADH-glutamate dehydrogenase activity is caused by de-novo synthesis of the alpha-subunit. AB - When callus derived from shoot segments of Vitis vinifera L. was transferred to ammonium-containing medium the aminating activity of NAD(H)-glutamate dehydrogenase (GDH, EC 1.4.1.2) increased significantly. This increase in enzyme activity closely paralleled an increase in the protein of the GDH alpha-subunit (43.0 kDa), as detected by sodium dodecyl sulfate (SDS) gel electrophoresis and Western-blotting. A similar correlation was observed between the deaminating activity and the beta-subunit (42.5 kDa) which both decreased during this treatment. Using [(35)S]methionine and immunochemical detection it was shown that the rate of synthesis of the alpha-subunit increased considerably in the ammonium containing medium while there was no detectable synthesis of the beta-subunit. At the isoenzyme level, ammonium caused an increase in the de-novo synthesis and hence the activity staining of the more anodic isoenzymes, which are hexameric and consist mainly of alpha-subunits. The results indicate that the increase in NADH-GDH specific activity was due to de-novo synthesis of the alpha-subunit of GDH and the assembly of only the more anodic isoenzymes. PMID- 24178073 TI - Induction and purification of chitinase in Brassica napus L. ssp. oleifera infected with Phoma lingam. AB - A pathogen-induced chitinase (EC 3.2.1.14) was isolated from cotyledons of oilseed rape (Brassica napus cv. Bienvenu) 8 d after inoculation with Phoma lingam. The purified chitinase has a molecular weight of 30 kDa, and an isoelectric point of approx. 9.1. A partial amino-acid sequence obtained after tryptic digestion of the protein shows high sequence similarity to basic chitinases from bean, tobacco, potato, Arabidopsis, barley and rice, as well as to acidic chitinases from tobacco and petunia. A close serological relationship was found between the chitinase isoenzyme and an isoenzyme from sugar-beet (Beta vulgaris L.). When resistant and susceptible cultivars were inoculated with P. lingam there was a significant difference in the increase in chitinase activity during the early stage after inoculation. The resistant cultivars showed a rapid increase in chitinase activity, in contrast to susceptible cultivars where an increase in activity was delayed until 24 h after infection. By measuring the chitinase activity from the mycelium of P. lingam, it was concluded that the increase in chitinase activity found in infected plants was of plant origin. The chitinase activity was found to be restricted to the site of pathogen attack and was not systemically induced in other parts of the plant. PMID- 24178074 TI - Growth of cotton under continuous salinity stress: influence on allocation pattern, stomatal and non-stomatal components of photosynthesis and dissipation of excess light energy. AB - Cotton (Gossypium hirsutum L.) plants were grown in flowing-culture solutions containing 0%, 26% and 55% natural seawater under controlled and otherwise identical conditions. Leaf Na(+) content rose to 360 mM in 55% seawater, yet the K(+) content was maintained above 100 mM. The K(+)/Na(+) selectivity ratio was much greater in the saline plants than in the control plants. All plants were healthy and able to complete the life cycle but relative growth rate fell by 46% in 26% seawater and by 83% in 55% seawater. Much of this reduction in growth was caused by a decreased allocation of carbon to leaf growth versus root growth. The ratio of leaf area/plant dry weight fell by 32% in 26% seawater and by 50% in 55 % seawater while the rate of carbon gain per unit leaf area fell by only 20% in 26% seawater and by as much as 66% in 55% seawater. Partial stomatal closure accounted for nearly all of the fall in the photosynthesis rate in 26% seawater but in 55% seawater much of the fall also can be attributed to non-stomatal factors. As a result of the greater effect of salinity on stomatal conductance than on CO2-uptake rate, photosynthetic water-use efficiency was markedly improved by salinity. This was also confirmed by stablecarbon-isotope analyses of leaf sugar and of leaf cellulose and starch. - Although non-stomatal photosynthetic capacity at the growth light was reduced by as much as 42% in 55% seawater, no effects were detected on the intrinsic photon yield of photosynthesis nor on the efficiency of photosystem II photochemistry, chlorophyll a/b ratio, carotenoid composition or the operation of the xanthophyll cycle. Whereas salinity caused in increase in mesophyll thickness and content of chloroplast pigments it caused a decrease in total leaf nitrogen content. The results indicate that the salinity-induced reduction in non-stomatal photosynthetic capacity was not caused by any detrimental effect on the photosynthetic apparatus but reflects a decreased allocation to enzymes of carbon fixation. - Rates of energy dissipation via CO2 fixation and photorespiration, calculated from gas-exchange measurements, were insufficient to balance the rate of light-energy absorption at the growth light. Salinity therefore would have been expected to cause the excess excitation energy to rise, leading to an increased nonradiative dissipation in the pigment bed and resulting increases in non-photochemical fluorescence quenching and zeaxanthin formation. However, no such changes could be detected, implying that salinity may have increased energy dissipation via a yet unidentified energy-consuming process. This lack of a response to salinity stress is in contrast to the responses elicited by short term water stress which caused strong non-photochemical quenching and massive zeaxanthin formation. PMID- 24178075 TI - Plasmodesmatal distribution, structure and frequency in relation to assimilation in C3 and C 4 grasses in southern Africa. AB - This paper addresses plasmodesmatal distribution and frequency in the leaf-blade bundles of four southern African grasses - one C3, and one each of the NAPD-malic enzyme (ME), NAD-ME and phosphoenolpyruvate carboxykinase (PCK) C4 photosynthetic subtypes and, additionally, relates the calculated plasmodesmatal frequencies to the photosynthetic carbon-fixation rate. Plasmodesmata are, in all instances, constricted where they traverse suberin lamellae at the Kranz mesophyll-bundle sheath (KMS-BS), the bundle-sheath-vascular parenchyma (BS-VP), or the bundle sheath-mestome-sheath interfaces (BS-MS). Frequency studies clearly show that plasmodesmata are most numerous at the KMS-BS, BS-MS and BS-VP interfaces, (31.9 76.8% of the total) and that their numbers decrease rapidly with increasing proximity to both thin- and thickwalled sieve tubes. In Themeda triandra var. imberbis (Retz.) A. Camus and Bromus unioloides H.B.K. thickwalled sieve tubes have few connections with vascular parenchyma cells and are, to all intents and purposes, almost totally isolated from the rest of the vascular tissue, indicating that the loading pathways for these sieve tubes are predominantly apoplastic. Although decreasing plasmodesmatal frequencies indicate that loading of assimilate may become progressively more apoplastic with increasing proximity to the sieve tubes, a symplastic route to the thin-walled sieve tubes cannot be ruled out. Studies of net assimilation rate indicate a good correlation of photosynthetic rate with the photosynthetic type (C3, C4 NADP-ME, C4 PCK, and C4 NAD-ME); furthermore, the lowest plasmodesmatal frequencies were associated with C3, and the highest with C4 NAD-ME types. PMID- 24178076 TI - Quantification of symplastic continuity as visualised by plasmodesmograms: diagnostic value for phloem-loading pathways. AB - The use of plasmodesmatal frequency to correlate cell-cell symplastic transport capacity remains a contentious problem, as variation in cell shape, accurate determination of interface contact area between cell types, distribution (i.e. whether random or aggregated) and shape (i.e. whether single or branched), and state of permeability may confuse the issue. Additionally, variation in the methods used to determine the frequencies compounds the problem further. Data presented in this paper show that plasmodesmograms offer a means to visualise the potential transport pathway from mesophyll cells to sieve tubes. Furthermore, the results allow an instant appreciation of symplastic continuity or discontinuity and, accordingly, the potential symplastic and-or apoplastic stages involved in the overall loading process. PMID- 24178077 TI - The lipid-transfer protein C of Ricinus communis L.: isolation of two cDNA sequences which are strongly and exclusively expressed in cotyledons after germination. AB - Differential screening of cDNA libraries from Ricinus communis L. cotyledons at the day 4 of germination against those at day 2 led to the isolation of two cDNA sequences which code for type C of the "nonspecific lipid-transfer protein". The two clones are nearly identical in the coding region, which in each case starts with a sequence coding for a signal peptide. In the non-coding regions there is only 40% identity. Both clones are expressed only in the cotyledons and are strongly developmentally regulated, being exclusively expressed after the second day of germination with a maximum at days 4 and 5. No transcripts were found in the hypocotyls, roots or endosperm of seedlings and none in sink and source leaves of mature Ricinus plants. PMID- 24178078 TI - Fractionation of thylakoid membranes from Porphyridium purpureum using the detergent N-lauryl-beta-iminodipropionate : A study on the chlorophyll-protein and pigment composition of the membrane-intrinsic antenna complexes of a red alga. AB - Two green fractions, thought to represent the chlorophyll-antennae of photosystems I (PSI) and II (PSII), were isolated from the red alga Porphyridium purpureum by solubilisation of the thylakoid membranes using the detergent N lauryl-beta-iminodipropionate and subsequent sucrose-density-gradient centrifugation. No release of pigments from the pigment-protein complexes was detected during isolation. The fractions were analyzed with respect to their chlorophyll-protein pattern, spectral properties and pigment composition. The supposed PSII antenna fraction contained both the major carotenoids of P. purpureum, beta-carotene and zeaxanthin, and showed a long-wavelength absorption maximum at 672 nm and a low-temperature fluorescence maximum at 692-694 nm. Polypeptides of this fraction cross-reacted with antibodies raised against the PSII polypeptides D1, CP43 and CP47 from higher plants. The PSI fraction could perform P-700 photooxidation and showed a long-wavelength absorbance maximum at 679 nm and a low-temperature fluorescence maximum at 718 nm. It contained beta carotene as the only carotenoid. The fluorescence excitation spectrum of the fraction and measurements of the photochemical activity of a thylakoid preparation excited with light that is preferentially absorbed either by chlorophyll (433 nm) or by carotenoids (495 nm) indicate that beta-carotene serves as a very efficient antenna-pigment in PSI. In contrast, only a small amount of energy transfer from the carotenoids to chlorophyll could be observed with the supposed PSII fraction. PMID- 24178079 TI - Coaction of light, nitrate and a plastidic factor in controlling nitrite reductase gene expression in tobacco. AB - Nitrite reductase (NIR; EC 1.7.7.1) - a key enzyme of nitrate reduction - is known to be induced by nitrate and light. In the present study with tobacco (Nicotiana tabacum L.) seedlings the dependency of NIR gene expression on nitrate, light and a plastidic factor was investigated to establish the nature of the coaction between these controlling factors. A cDNA clone coding for tobacco plastidic NIR was available as a probe. The major results were as follows: (i) The light effect on the appearance of NIR occurred predominantly through phytochrome. However, a specific blue-light effect was also involved. (ii) There was no effect of light on NIR appearance in the absence of nitrate while light exerted a strong effect when nitrate was provided. (iii) Anion-exchange chromatography revealed only a single form of NIR. While experiments involving plastid photooxidation indicated that this NIR is plastidic, a small residual level could not be eliminated by photooxidation. (iv) Northern blot analysis of NIR-transcript levels indicated that a low transcript level existed in the absence of nitrate and light; however, this level appeared to be increased slightly by light (in the absence of nitrate) and by nitrate (in the absence of light). A high transcript level was detected only when light as well as nitrate were provided. A low level was found when the plastids were damaged by photooxidation. It is concluded that plastidic NIR gene expression in tobacco requires positive control by a plastidic factor. Moreover, a synergistic action of phytochrome and nitrate is required to bring about a high transcript level. As found previously with mustard and spinach seedlings, there is no quantitative relationship between the transcript level and the rate of enzyme synthesis. PMID- 24178080 TI - Sugar synthesis and phloem loading in Coleus blumei leaves. AB - Sugar-synthesis and -transport patterns were analyzed in Coleus blumei Benth. leaves to determine where galactinol, raffinose, and stachyose are made and whether phloem loading includes an apoplastic (extracellular) step or occurs entirely within the symplast (plasmodesmata-connected cytoplasm). To clarify the sequence of steps leading to stachyose synthesis, a pulse (15 s) of (14)CO2 was given to attached leaves followed by a 5-s to 20-min chase: sucrose was rapidly labeled while galactinol, raffinose and stachyose were labeled more slowly and, within the first few minutes, to approximately the same degree. Leaf tissue was exposed to either (14)CO2 or [(14)C]glucose to identify the sites of synthesis of the different sugars. A 2-min exposure of peeled leaf tissue to [(14)C]glucose resulted in preferential labeling of the minor veins, as opposed to the mesophyll; galactinol, raffinose and stachyose were more heavily labeled than sucrose in these preparations. In contrast, when leaf tissue was exposed to (14)CO2 for 2 min for preferential labeling of the mesophyll, sucrose was more heavily labeled than galactinol, raffinose or stachyose. We conclude that sucrose is synthesized in mesophyll cells while galactinol, raffinose and stachyose are made in the minorvein phloem. Competition experiments were performed to test the possibility that phloem loading involves monosaccharide uptake from the apoplast. Two saturable monosaccharide carriers were identified, one for glucose, galactose and 3-O-methyl glucose, and the other for fructose. Washing the apoplast of peeled leaf pieces with buffer or saturating levels of 3-O-methyl glucose, after providing a pulse of (14)CO2, did not inhibit vein loading or change the composition of labeled sugars, and less than 0.5% of the assimilated label was recovered in the incubation medium. These and previous results (Turgeon and Gowan, 1991, Plant Physiol. 94, 1244-1249) indicate that the phloem loading pathway in Coleus is probably symplastic. PMID- 24178081 TI - Manipulation of conditions for the culture of somatic embryos of white spruce for improved triacylglycerol biosynthesis and desiccation tolerance. AB - In order to enhance post-germinative vigour, somatic embryos of Picea glauca (Moench) Voss. were matured under in-vitro conditions that stimulated triacylglycerol (TAG) biosynthesis. In P. glauca seeds over 90% of the TAG was stored within the megagametophyte, and isolated zygotic embryos contained twice the amount of TAG of somatic embryos cultured for four weeks on basal medium containing 16 MUM abscisic acid (ABA). Polyethylene glycol-4000 (PEG) as a non permeating osmoticum with ABA promoted TAG biosynthesis by somatic embryos and sustained maturation throughout an eight-week culture period. Treatments that promoted TAG biosynthesis also prevented precocious germination and promoted desiccation tolerance. Thus, the optimal culture conditions for maturation, desiccation survival, and plantlet regeneration were 16-24 MUM ABA and 7.5% PEG for eight weeks, followed by desiccation. Under these conditions the levels of TAG per somatic embryo were raised ninefold to about five times the zygotic embryo level, and the TAG fatty-acid composition became similar to that of zygotic embryos. A study of sectioned material, using light and transmission electron microscopy, showed that the structure and distribution of lipid bodies within these somatic embryos and the degree of embryo development were similar to mature zygotic embryos. Up to 81% of the desiccated somatic embryos regenerated to plantlets during which time the TAG was utilised in a manner similar to zygotic seedlings. PMID- 24178082 TI - Improvements in immunostaining samples embedded in methacrylate: localization of microtubules and other antigens throughout developing organs in plants of diverse taxa. AB - Microtubules are important in plant growth and development. Localizing microtubules in sectioned material is advantageous because it allows any tissue of interest to be studied and it permits the positional relations of the cells within the organ to be known. We describe here a method that uses semi-thin (0.5 2 MUm) sections of material embedded in butyl-methylmethacrylate, to which 10 mM dithiothreitol was added. After removing the embedding material and using indirect immunofluorescence staining, we obtain clear images of microtubules, actin microfilaments, callose and pulse-fed bromodeoxyuridine. This method works on the root tissues of Arabidopsis thaliana(L.) Heynh, Pinus radiataD. Don, Zamia furfuraceaAit., Azolla pinnataR. Br. and on sporophytic tissues of Funaria hygrometricaHedw. In general, most of the cells in the organs studied are successfully stained. Using this method, we find that interphase meristematic cells in all of these species have microtubules not only in the usual cortical array but also throughout their cytoplasm. The presence of the calcium chelator ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid EGTA in fixation buffers led to some tissue damage, and did not enhance the preservation of microtubules. The common assumption that EGTA-containing buffers stabilize plant microtubules during fixation appears unwarranted. PMID- 24178083 TI - Identification and localisation of a nucleoporin-like protein component of the plant nuclear matrix. AB - Salt-detergent extraction of purified plant nuclei yields a fraction enriched in putative structural proteins known as the "nuclear matrix". Compared with mammalian nuclear matrices, which contain three major proteins, plant nuclear matrices are complex, containing at least 100 polypeptides. In order to characterise more fully the plant nuclear matrix we have used antibodies raised against both yeast (Saccharomyces cerevisiae) and mammalian (rat) nuclear pore proteins. We have shown that the nuclear matrix of carrot (Daucus carota L.) contains at least one nucleoporin-like protein of about 100 kDa which is immunologically related to both the yeast nuclear pore protein NSP1 and mammalian nucleoporins (p62). Antibody labelling of a variety of plant cells at the light microscope and electron-microscope levels confirms that this antigen is located at the nuclear pores. This, to our knowledge, is the first identification of a nuclear pore protein in plants. PMID- 24178084 TI - Induction by thidiazuron of somatic embryogenesis in intact seedlings of peanut. AB - In planta differentiation of somatic embryos was induced in seedlings of peanut (Arachis hypogaea L.) obtained from mature seeds germinated on a medium supplemented with thidiazuron (TDZ: N-phenyl-N(1)- (1,2,3 thiadiazol-yl)urea). At optimum levels of TDZ (10 MUM), all germinating seeds produced embryogenic seedlings, and somatic embryos developed in the apical region and on the surface of cotyledons and hypocotyls. These somatic embryos matured, germinated, and formed shoots which eventually developed into whole plants. Thidiazuron-induced direct embryogenesis from morphologically intact seedlings may provide an excellent experimental system for investigating somatic embryogenesis and the morphoregulatory role of TDZ. PMID- 24178085 TI - Antibiotic-associated complications following lower limb arthroplasty: a comparison of two prophylactic regimes. AB - INTRODUCTION: As part of a wider drive to reduce Clostridium difficile rates (CDAD), our trust switched from cefuroxime to gentamicin and flucloxacillin prophylaxis for joint replacement surgery. Anecdotal evidence suggested that we were seeing an increased incidence of acute kidney injury (AKI) following elective total hip replacement (THR) and total knee replacement (TKR) since this change. The aim of this study was to compare rates of AKI and post-operative infection between the two antibiotic regimes. METHODS: We carried out a single centre retrospective cohort study comparing 200 patients (100 THR and 100 TKR) who received cefuroxime with another age and procedure-matched group who received gentamicin and flucloxacillin (gentamicin 3 mg/kg and 5 g flucloxacillin in total). We compared rates of AKI, haemofiltration, CDAD, surgical site infection (SSI) and return to theatre for infection (RTT). RESULTS: Gentamicin was associated with a significant increase in AKI (1 vs. 8%, p < 0.01). More patients needed haemofiltration (0 vs. 1.5%) although this was not significant. Interestingly, when the groups were subdivided into THR and TKR, significantly more TKR patients receiving gentamicin developed AKI (0 vs. 11, p < 0.01). This difference was not significant following THR (2 vs. 5, p = 0.44). This may be related to tourniquet use in TKR. SSI and RTT were comparable. No patient developed CDAD. CONCLUSIONS: Gentamicin with flucloxacillin is comparable with cefuroxime in rates of SSI and RTT but is associated with a significant increase in AKI. AKI is associated with additional morbidity and mortality. This association should be considered when choosing a suitable prophylactic regime. PMID- 24178086 TI - Phylogenetic analysis of the genus Hordeum using repetitive DNA sequences. AB - A set of six cloned barley (Hordeum vulgare) repetitive DNA sequences was used for the analysis of phylogenetic relationships among 31 species (46 taxa) of the genus Hordeum, using molecular hybridization techniques. in situ hybridization experiments showed dispersed organization of the sequences over all chromosomes of H. vulgare and the wild barley species H. bulbosum, H. marinum and H. murinum. Southern blot hybridization revealed different levels of polymorphism among barley species and the RFLP data were used to generate a phylogenetic tree for the genus Hordeum. Our data are in a good agreement with the classification system which suggests the division of the genus into four major groups, containing the genomes I, X, Y, and H. However, our investigation also supports previous molecular studies of barley species where the unique position of H. bulbosum has been pointed out. In our experiments, H. bulbosum generally had hybridization patterns different from those of H. vulgare, although both carry the I genome. Based on our results we present a hypothesis concerning the possible origin and phylogeny of the polyploid barley species H. secalinum, H. depressum and the H. brachyantherum complex. PMID- 24178087 TI - Chromosome painting of Amigo wheat. AB - Chromosome painting using multicolor fluorescence in situ hybridization showed that, in addition to the T1AL.1RS translocation derived from rye, a segment from chromosome 3Ae#1 of Agropyron elongatum (2n=10x =70), is present in Amigo wheat. The Agropyron chromosome segment is located on the satellite of chromosome 1B and the translocation chromosome is designated as T1BL.1BS-3Ae#1L. T1BL.1BS-3Ae#1L was inherited from Teewon wheat and carries resistance genes to stem rust (Sr24) and leaf rust (Lr24). The Agropyron chromosome segments in different Sr24/Lr24 carrier wheat lines, including Agent, TAP 48, TAP 67, Teewon, and Amigo, showed a diagnostic C-band, and were derived from the same chromosome, 3Ae#1. PMID- 24178088 TI - Quantitative differences in sperm cells and organelles of tobacco (Nicotiana tabacum L.) grown under differing environmental conditions. AB - In flowers grown at warm temperatures in environmental chambers and at cooler temperatures in the greenhouse, eight parameters of the sperm-cell organization of Nicotiana tabacum were examined during sperm cell maturation using serial ultrathin sectioning, transmission electron microscopy and quantitative cytology. Despite employing the same seed source, and similar soil and nutrient conditions, the surface area and volume of the cell, the nucleus and the chondriome were larger in flowers grown in growth chambers under warmer controlled conditions, whereas the number of plastids appeared to be the same, or slightly higher, in flowers grown under cooler greenhouse conditions. These results suggest that environmental conditions may influence the quantity of cytoplasmic organelles, including mitochondria and plastids, thus potentially influencing the likelihood of male cytoplasmic inheritance. PMID- 24178089 TI - Inheritance of resistance to potyviruses in Phaseolus vulgaris L. III. Cosegregation of phenotypically similar dominant responses to nine potyviruses. AB - We have identified monogenic dominant resistance to azuki bean mosaic poty virus (AzMV), passionfruit woodiness potyvirus-K (PWV-K), zucchini yellow mosaic potyvirus (ZYMV), and a dominant factor that conditioned lethal necrosis to Thailand Passiflora potyvirus (ThPV), in Phaseolus vulgaris 'Black Turtle Soup 1'. Resistance to AzMV, PWV-K, ZYMV, watermelon mosaic potyvirus, cowpea aphid borne mosaic potyvirus, blackeye cowpea mosaic potyvirus, and lethal necrosis to soybean mosaic potyvirus and ThPV cosegregated as a unit with the I gene for resistance to bean common mosaic potyvirus. PMID- 24178090 TI - Inheritance in turnip of variable-number tandem-repeat genetic markers revealed with synthetic repetitive DNA probes. AB - Oligomers (16-26 mers) composed of short, tandemly repeated DNA sequences (3-10 bases) were used individually with their complementary oligomer in separate polymerase chain reactions (PCRs) that extended the number of repeats to make 15 different PCR synthetic tandem-repeat (STR) probes. These PCR-STR probes were used to examine the inheritance of variable-number tandem-repeat (VNTR) genetic markers from two parent plants of turnip (Brassica rapa L.) to 20 offspring. Following HinfI digestion and PCR-STR probing of Southern blots, interpretable variable parental and offspring band profiles were found with 9 of the 15 probes used. Each of these nine probes produced a unique set of fragments, and no cases of different probes revealing the same fragment were detected. Seventy-nine parental fragments were found and, of these, 65% (51) appeared to be heterozygous in one or both parents, with 52% (41) appearing to be heterozygous in one of the parents exclusively. That these fragments are transmitted as though heterozygous in the parents implies that they are derived from the nuclear complement of the genome. Chi-square analyses of the transmission of markers are, in general, consistent with Mendelian expectations, although three non-parental bands were found accounting for approximately 0.5% of these transmitted bands. For the fragments heterozygous in one of the parents exclusively, seven alleles exhibited complete linkage in three groups, 12 alleles were incompletely linked in six groups, and four allelic groups involving 11 alleles were identified. PCR-STR probes are relatively rapid to generate and apply (no cloning, clone screening, or sequencing steps are required), and have been shown to reveal VNTR genetic markers in a wide variety of plant species. These results add to the list of studies showing that VNTR genetic markers (and in this case, markers revealed by PCR-STR probes) are transmitted for the greater part in a Mendelian fashion. PMID- 24178091 TI - A linkage map of diploid Avena based on RFLP loci and a locus conferring resistance to nine isolates of Puccinia coronata var. 'avenae'. AB - An F2 oat population was produced by crossing the diploid (n=7) species Avena strigosa (CI 3815) with A. wiestii (CI 1994), resistant and susceptible, respectively, to 40 isolates of Puccinia coronata, the causal agent of crown rust. Eighty-eight F2 individuals were used to construct an RFLP linkage map representing the A genome of cultivated hexaploid oat. Two hundred and eight RFLP loci have been placed into 10 linkage groups. This map covers 2416 cM, with an average of 12 cM between RFLP loci. Eighty-eight F3 lines, derived from F2 individuals used to construct the map, were screened for resistance to 9 isolates of P. coronata. One locus, Pca, was found to confer a dominant resistance phenotype to isolates 203, 258, 263, 264B, 290, 298, 325A, and 345. Pca also conferred resistance to isolate 276; however, an unlinked second gene may also be involved. PMID- 24178092 TI - Genetics of Ustilago violacea. XXXII. Genetic evidence for transposable elements. AB - Crosses between Ustilago violacea mutant strains with different color phenotypes that were derived from the 1.A1 and 2.A2 laboratory strains yielded, as expected, bisectored teliospore colonies with the parental colors as well as the a-1 and the a-2 mating-types. Generally, wild teliospore collections usually produced sporidia of both mating-types, providing two-mating-type (TMT) strains. Occasionally, however, sporidia with only one mating-type allele, a-1 or a-2, were obtained from teliospores, providing one-mating-type (OMT) strains. Crosses between OMT and laboratory strains with different color phenotypes gave (1) bisectored teliospore colonies with the parental colors or colonies with a parental color and a nonparental color and (2) nonsectored colonies with the nonparental color or with the parental color. The frequencies for the occurrence of non-parental color ranged from 41% to 93%, depending on the strain. The yield of teliospore colonies was usually reduced for these crosses. In many of these teliospore colonies, morphologically-altered sporidia (MAS phenotype) were observed. The morphology and the size of the sporidia with the MAS phenotype differed from those of teliospore colonies of the crosses between the laboratory strains. In addition, these sporidia did not form conjugants. A cross involving the TMT strains C449 yielded the MAS phenotype as well as a high incidence of tetrad colonies with a nonparental color. The high degree of instability of the parental color phenotypes, and the high frequency of the appearance of nonparental color phenotypes as well as the appearance of the MAS phenotype, are in accord with the presence of active and inactive transposable elements in the OMT strains, TMT strains, and laboratory strains. PMID- 24178093 TI - Phylogeny analysis of 25 apple rootstocks using RAPD markers and tactical gene tagging. AB - RAPD (random amplified polymorphic DNA) markers were used to fingerprint eight commercially available apple rootstocks (Nertchinsk, Northern Spy, Osman, Heyer 12, M.1, M.9, M.26 and MM.106), 10 winter hardy offsprings derived from the cross of Nertchinsk x M.9, six winter hardy offsprings derived from the cross of Nertchinsk x M.26 and one winter hardy offspring derived from each of the two crosses between Osman x Heyer 12 and Northern Spy x M.1. Phylogeny analysis using parsimony allowed us to draw the genetic relationship between these lines using only RAPD markers data. The resulting cladogram was compared to the true genetic relationship between these lines in order to assess the efficiency of RAPD markers in determining accurately the phylogenetic relationship. We also developed a DNA fingerprinting system based on 13 informative RAPD loci amplified by five RAPD primers that allowed the rapid identification of apple rootstocks. PMID- 24178094 TI - A simple method to estimate the percentage of hybridity in canola (Brassica napus) F1 hybrids. AB - We have developed an efficient PCR-based system that uses RAPD markers for the certification of F1 hybrids of canola. These markers were selected by screening five parental lines used in three crosses X, Y and Z with 131, 131 and 322 primers respectively. Stable DNA fragments that were homozygous and specific to the male inbreds were used to certify F1 hybrid populations. The hybrid production system was based on self-incompatibility (SI) alleles that prevent self-pollination of the female parent. The efficiency of two S-alleles was compared under both field and greenhouse conditions. The percentage of hybridity was estimated in different F1 populations. We found a significant difference between the two alleles for their efficiency in controlling selfing; both alleles were stable under greenhouse conditions, one allele appeared less reliable under field conditions. PMID- 24178095 TI - Linkage localization of the starch branching enzyme I (Q-enzyme I) gene in rice. PMID- 24178096 TI - Application of the restriction landmark genomic scanning (RLGS) method to rice cultivars as a new fingerprinting technique. AB - The restriction landmark genomic scanning (RLGS) method was applied to rice, using two Japanese cultivars, 'Nipponbare' and 'Koshihikari', and a Chinese landrace, 'Liu'Zhou'Bao'Ya'Zao'. More than 3000 landmarks were detected as spots on the individual autoradiograms of each cultivar. 'Nipponbare' and 'Liu'Zhou' Bao'Ya'Zao' showed apparently different RLGS profiles, from which the genetic similarity (GS) between them was estimated as 0.344. Although the two Japanese cultivars, 'Nipponbare' and 'Koshihikari' showed quite similar RLGS profiles, they were easily distinguished on the basis of the presence or absence of specific spots; the GS value between them was calculated as 0.980. The RLGS method is shown to be a powerful fingerprinting technique, especially for the classification and identification of cultivars in rice and probably in other crops as well. PMID- 24178097 TI - Comparative RFLP mapping of Hordeum vulgare and Triticum tauschii. AB - Hordeum vulgare (barley) and Triticum tauschii are related, but sexually incompatible, species. This study was conducted to determine the extent of homology between the genomes of barley and T. tauschii using a common set of restriction fragment length polymorphism (RFLP) markers. Results showed that >95% of low-copy sequences are shared, but 42% of the conserved sequences showed copy number differences. Sixty-three loci were mapped in T. tauschii using RFLP markers previously mapped in barley. A comparison of RFLP marker order showed that, in general, barley and T. tauschii have conserved linkage groups, with markers in the same linear orders. However, six of the seven linkage groups of T. tauschii contained markers which mapped to unrelated (i.e., non-homoeologous) barley chromosomes. Additionally, four of the T. tauschii linkage groups contained markers that were switched in order with respect to barley. All the chromosome segments differing between T. tauschii and barley contained markers that were detected by multi-copy probes. The results suggest that the observed differences between the T. tauschii and barley genomes were brought about by duplications or deletions of segments in one or both species. The implications of these findings for genetic mapping, breeding, and plant genome evolution are discussed. PMID- 24178098 TI - Interaction between cytoplasmic composition and yield parameters in somatic hybrids of S. tuberosum L. AB - The nuclear and cytoplasmic composition of five different fusion combinations, consisting of up to 50 hybrid regenerants each, was characterized by RFLP analysis. Simultaneously, the hybrid clones of four fusion combinations were evaluated in field experiments for yield and starch content.Predominantly complete chloroplast segregation was found with a 1?1 ratio, in all but one fusion combination. Mitochondria, in contrast revealed up to 75% recombination, as proven by the partial addition of parental banding patterns and the altered assignment of the same genotypes with different probes. Newly occuring DNA bands were also indicative of rearrangements in the mitochondrial genome. Correlations between RFLP data and field parameters were calculated. Deviating RFLP patterns of the nuclear genome did not influence yield parameters. Also the assignment of hybrids to different chloroplast genotypes did not affect yield or starch content. However, mitochondrial types could be distinguished with respect to starch content and tuber yield. The more thorough analysis of mitochondrial composition, with different probes homologous to coding regions, revealed a relationship between the homogeneity of the mt genome and the yield level. PMID- 24178099 TI - Pto3 and Pto4: novel genes from Lycopersicon hirsutum var. glabratum that confer resistance to Pseudomonas syringae pv tomato. AB - Accessions of wild Lycopersicon germplasm were screened for resistance to Pseudomonas syringae pv tomato (P.s. tomato). Resistance to both race-0 and race 1 strains of P.s. tomato was identified in L. pimpinellifolium, L. peruvianum and L. hirsutum var. glabratum. Resistance to race-0 derived from L. hirsutum var. glabratum (Pto3) appeared to be inherited independently of Pto1 and Pto2. Filial and backcross generations derived from interspecific crosses between L. esculentum and L. hirsutum var. glabratum revealed that Pto3 resistance was inherited in a complex fashion and was incompletely dominant under conditions of high bacteria inocula. Resistance to P.s. tomato race-1 (Pto4) was also identified in L. hirsutum var. glabratum. Pto3 and Pto4 segregated independently of each other. PMID- 24178100 TI - Mapping of RFLP and qualitative trait loci in Brassica rapa and comparison to the linkage maps of B. napus, B. oleracea, and Arabidopsis thaliana. AB - A linkage map of restriction fragment length polymorphisms (RFLPs) was constructed for oilseed, Brassica rapa, using anonymous genomic DNA and cDNA clones from Brassica and cloned genes from the crucifer Arabidopsis thaliana. We also mapped genes controlling the simply inherited traits, yellow seeds, low seed erucic acid, and pubescence. The map included 139 RFLP loci organized into ten linkage groups (LGs) and one small group covering 1785 cM. Each of the three traits mapped to a single locus on three different LGs. Many of the RFLP loci were detected with the same set of probes used to construct maps in the diploid B. oleracea and the amphidiploid B. napus. Comparisons of the linkage arrangements between the diploid species B. rapa and B. oleracea revealed six LGs with at least two loci in common. Nine of the B. rapa LGs had conserved linkage arrangements with B. napus LGs. The majority of loci in common were in the same order among the three species, although the distances between loci were largest on the B. rapa map. We also compared the genome organization between B. rapa and A. thaliana using RFLP loci detected with 12 cloned genes in the two species and found some evidence for a conservation of the linkage arrangements. This B. rapa map will be used to test for associations between segregation of RFLPs, detected by cloned genes of known function, and traits of interest. PMID- 24178101 TI - Genetics of seed storage proteins in the love tree Cercis siliquastrum L. (Fabaceae). AB - The patterns of C. siliquastrum seed storage proteins ("cercins") are described using SDS-polyacrylamide gel electrophoresis. The polypeptides detected had very different molecular weights (ranging from 168 to 34 KDa) which, together with their high homogeneity, produced a very good resolution of bands. These proteins could be ascribed to five different loci. The analysis of seed sets of individual trees indicated that the love tree is almost completely autogamous with less than 5% of outcrosses. Although this mode of reproduction seems to produce a decrease in heterozygote frequency among the seeds of the population analysed, the levels of variability detected were very high for an autogamous plant: all of the loci were polymorphic, with a mean heterozygosity of 0.327 and a polymorphic index of 0.412. Protein segregation revealed a strong genetic linkage between three cercin loci (a, c and d) while the other two are independent. PMID- 24178102 TI - Genetic analysis of the components of winterhardiness in barley (Hordeum vulgare L.). AB - Winterhardiness in cereals is the consequence of a number of complex and interacting component characters: cold tolerance, vernalization requirement, and photoperiod sensitivity. An understanding of the genetic basis of these component traits should allow for more-effective selection. Genome map-based analyses hold considerable promise for dissecting complex phenotypes. A 74-point linkage map was developed from 100 doubled haploid lines derived from a winter x spring barley cross and used as the basis for quantitative trait locus (QTL) analyses to determine the chromosome location of genes controlling components of winterhardiness. Despite the greater genome coverage provided by the current map, a previously-reported interval on chromosome 7 remains the only region where significant QTL effects for winter survival were detected in this population. QTLs for growth habit and heading date, under 16 h and 24 h light, map to the same region. A QTL for heading date under these photoperiod regimes also maps to chromosome 2. Contrasting alleles at these loci interact in an epistatic fashion. A distinct set of QTLs mapping to chromosomes 1, 2, 3, and 5 determined heading date under 8 h of light. Under field conditions, all QTLs identified under controlled environment conditions were determinants of heading date. Patterns of differential QTL expression, coupled with additive and additive x additive QTL effects, underscore the complexity of winterhardiness. The presence of unique phenotype combinations in the mapping population suggests that coincident QTLs for heading date and winter survival represent the effects of linkage rather than pleiotropy. PMID- 24178103 TI - Heritabilities and genetic correlations for estimated growth curve parameters in maritime pine. AB - Height growth curves and several other characters were measured in five maritime pine (Pinus pinaster Ait) progeny tests aged from 18 to 27 years (about half the rotation age), with sample sizes of 272-1555 trees. These curves were fitted with a reparametrized Lundqvist-Matern sigmoidal growth function with global estimation of two of the four parameters. Each curve was characterized by two parameters: : the maximal growth rate (r), approximately proportional to the stem height at age 16 years, and essentially determined by the height increments around age 6 years. the asymptote (A), which is an extrapolation of growth after the measurement age. A is essentially determined by the latter growth period (around age 20 years), and is also related to the shape of the observed curve. The modelling framework appeared to be well suited to the characteristics of the data studied, and the estimation standard errors of the parameters were reasonably low. The heritabilities yielded for the growth curve parameters were high, similar to the heritabilities of cumulative heights. The genetic correlation between r and A was low, pointing to a poor juvenile-mature correlation. Discrepancies from one trial to another in heritabilities and in the correlation pattern were observed, they probably originated from environmental stresses. Maritime pine is actually selected using height and butt angle of lean at age 10 years as criteria. Improvements in the breeding program are suggested. PMID- 24178104 TI - Geographical cline of chloroplast DNA variation in Abies mariesii. AB - Where its populations are isolated in higher mountain regions, Abies mariesii is one of the more important conifers of Japan's alpine forest zone. In this study we tried to clarify the genetic variation of chloroplast DNA (cpDNA) in A. mariesii. Cones and fresh needles were collected from seven mountain regions. Total DNAs were extracted from individual seedlings, and these were digested by 15 restriction endonucleases. Southern hybridization was then done using cpDNA clones of Cryptomeria japonica and tobacco as probes. CpDNA variation was detected with enzyme-probe combinations: HindIII+pCS10 probe, HindIII+pCS7, and BglII+pCS7 in preliminary screening. These variations were considered to be caused by the same insertion, deletion or inversion. All populations surveyed for the combination HindIII+pCS10 resulted in only two frequency variations in each population. This indicates a gradual cline along latitude and longitude. PMID- 24178105 TI - Identification of RFLP markers linked to the cereal cyst nematode resistance gene (Cre) in wheat. AB - The cereal cyst nematode (CCN) (Heterodera avenae Woll.) is an economically damaging pest of wheat in many of the worlds cereal growing areas. The development of CCN-resistant cultivars may be accelerated by the use of molecular markers. The Cre gene of the wheat line "AUS 10894" confers resistance to CCN. Using a pair of near-isogenic lines (NILs) that should differ only in a small chromosome segment containing the Cre locus, we screened 58 group-2 probes and found two (Tag605 and CDO588) that detect polymorphism between the NILs. Nulli tetrasomic and ditelosomic lines confirmed that the restriction fragment length polymorphism (RFLP) markers identified were derived from the long arm of wheat chromosome 2. Crosses between "AUS 10894" and "Spear" and the NIL "AP" and its recurrent parent "Prins" were used to produce F2 populations that gave the expected 3?1 segregation ratio for the resistance gene. Linkage analysis identified two RFLP markers flanking the resistance gene. Xglk605 and Xcdo588 mapped 7.3 cM (LOD=6.0) and 8.4 cM (LOD=6.7), respectively, from the Cre locus. PMID- 24178106 TI - Mating system analysis in a natural population of Acacia nilotica subspecies leiocarpa. AB - The mating-system was investigated in a natural population of the tetraploid taxon Acacia nilotica ssp. leiocarpa using open-pollinated seeds from 15 families. Six-day-old germinated seeds were used for starch-gel electrophoresis. Three enzyme systems (ADH, EST-1, and 6PGD) were scored. Isozyme banding patterns and segregation of isozyme variants within families suggest that the species is an autotetraploid displaying tetrasomic inheritance. Estimates of single-locus (ts=0.358) and multilocus (tm=0.384) population outcrossing rates were homogeneous, and indicate substantial selfing in the population. Heterogeneity of outcrossing estimates among loci and families were marked, suggesting departure from the assumptions of the mixed-mating model. Implications of the result for the utilization of germplasm in tree-improvement programmes are noted. PMID- 24178107 TI - Implications of the variance effective population size on the genetic conservation of monoecious species. AB - The concept of variance effective population size [Ne(v)] and other expressions are reviewed and described for specific sampling steps in germplasm collection and regeneration of monoecious species. Special attention is given to procedures for computing the variance of the number of contributed gametes [V(k)] to the next generation. Drift, as it occurs between generations, was considered to contain a component due to the sampling of parents and a subsequent component due to the sampling of gametes. This demonstrates that drift, caused by reduction of seed viability, damages the genetic integrity of accessions stored in germplasm banks. The study shows how mating designs, such as plant-to-plant or chain crossings with additional female gametic control, can partially alleviate this problem. Optimal procedures for increasing Ne(v) when collecting germplasm in the field are also discussed. The effect of different female and male gametic control strategies on Ne(v) is considered under several situations. Practical examples illustrating the use of V(k) and Ne(v) expressions are given. PMID- 24178108 TI - Molecular markers and protein quantities as genetic descriptors in maize. I. Genetic diversity among 21 inbred lines. AB - Twenty-one maize (Zea mays L.) inbred lines were analysed using isozyme electrophoresis, restriction fragment length polymorphism (RFLP), and two dimensional electrophoresis of denatured proteins (2-D PAGE). Our goal was (1) to assess the genetic variability among these lines which are potential progenitors for the development of forage maize hybrids in Europe, and (2) to compare the relationship pattern revealed by the polymorphism at marker loci with the one derived from the amount of protein variability assessed by computer-assisted analysis of the 2-D electrophoregrams. Fourteen markers were obtained from isozyme polymorphism, 84 from the restriction fragment length polymorphism, and 70 from protein shifts revealed by 2-D PAGE. The Rogers' distance computed on the set of molecular markers was the most efficient to describe the pedigree relationships between lines. Quantitative protein data gave a picture of relationships between lines clearly different from the monogenic markers. When unrelated pairs of lines were considered, the Rogers' distance was weakly correlated to distances based on quantitative variations in the amount of protein which may be consistent with their polygenic control and the occurrence of gene interactions. PMID- 24178109 TI - Interaction of nuclear and mitochondrial genomes in the alteration of maize mitochondrial orf221 transcripts. AB - The interaction of nuclear and mitochondrial genomes in the alteration of maize (Zea mays L.) mitochondrial orf221 transcript patterns was examined. Northern analyses involving specific maize nuclear genotypes associated with N, C or S cytoplasms revealed considerable orf221 transcript heterogeneity. F1 progenies were developed from maize inbred-cytoplasm combinations that differed for orf221 transcript patterns. Northern analyses revealed that the presence or level of abundance of certain orf221 transcripts was dependent on nuclear genotype. The maize inbred B37(C) exhibits orf221 transcripts of 3500, 3200, 2800, and 1300 nt whereas the F1 of B37(C) x Ky21(N) does not exhibit a 2800-nt transcript but does give transcripts of 2100 and 1250 nt in addition to 3500-, 3200- and 1300-nt transcripts. Northern analyses also suggested that the size or the presence of certain orf221 transcripts was related to the mitochondrial genome configuration. Maize inbred A619 exhibits a 2300-nt orf221 transcript when associated with N cytoplasm and a 2100-nt orf221 transcript when associated with C and S cytoplasms. As a result of deletion of the gene T-urf13, the A188(T7) mitochondrial mutant exhibits only a 3100-nt orf221 transcript and not the very complex T-urf13/orf221 transcript pattern associated with A188(T). The genetic stock A188(T7) x W64A(N)(2) gives a highly abundant 2100-nt orf221 transcript not detected in A188(T7). Deletion of T-urf13 has enabled the nuclear genotype of W64A(N) to alter orf221 transcript patterns in a manner not detected in T cytoplasm. This observation suggests that alteration of the mitochondrial genomic configuration adjacent to orf221 results in a different response to nuclear gene products from that observed when or2f21 is present in the T mitochondrial genome configuration. PMID- 24178110 TI - Chromosome assortment in Saccharum. AB - Recent work has revealed random chromosome pairing and assortment in Saccharum spontaneum L., the most widely distributed, and morphologically and cytologically variable of the species of Saccharum. This conclusion was based on the analysis of a segregating population from across between S. spontaneum 'SES 208' and a spontaneously-doubled haploid of itself, derived from anther culture. To determine whether polysomic inheritance is common in Saccharum and whether it is observed in a typical biparental cross, we studied chromosome pairing and assortment in 44 progeny of a cross between euploid, meiotically regular, 2n=80 forms of Saccharum officinarum 'LA Purple' and Saccharum robustum ' Mol 5829'. Papuan 2n=80 forms of S. robustum have been suggested as the immediate progenitor species for cultivated sugarcane (S. officinarum). A total of 738 loci in LA Purple and 720 loci in Mol 5829 were amplified and typed in the progeny by arbitrarily primed PCR using 45 primers. Fifty and 33 single-dose polymorphisms were identified in the S. officinarum and S. robustum genomes, respectively (chi 2 at 98%). Linkage analysis of single-dose polymorphisms in both genomes revealed linkages in repulsion and coupling phases. In the S. officinarum genome, a map hypothesis gave 7 linkage groups with 17 linked and 33 unlinked markers. Four of 13 pairwise linkages were in repulsion phase and 9 were in coupling phase. In the S. robustum genome, a map hypothesis gave 5 linkage groups, defined by 12 markers, with 21 markers unlinked, and 2 of 9 pairwise linkages were in repulsion phase. Therefore, complete polysomic inheritance was not observed in either species, suggesting that chromosomal behavior is different from that observed by linkage analysis of over 500 markers in the S. spontaneum map. Implications of this finding for evolution and breeding are discussed. PMID- 24178111 TI - Association of a DNA marker with Hessian fly resistance gene H9 in wheat. AB - The Hessian fly [Mayetiola destructor (Say)] is a major pest of wheat (Triticum aestivum L.) and genetic resistance has been used effectively over the past 30 years to protect wheat against serious damage by the fly. To-date, 25 Hessian fly resistance genes, designated H1 to H25, have been identified in wheat. With near isogenic wheat lines differing for the presence of an individual Hessian fly resistance gene, in conjunction with random amplified polymorphic DNA (RAPD) analysis and denaturing gradient-gel electrophoresis (DGGE), we have identified a DNA marker associated with the H9 resistance gene. The H9 gene confers resistance against biotype L of the Hessian fly, the most virulent biotype. The RAPD marker cosegregates with resistance in a segregating F2 population, remains associated with H9 resistance in a number of different T. aestivum and T. durum L. genetic backgrounds, and is readily detected by either DGGE or DNA gel-blot hybridization. PMID- 24178112 TI - Length variation in the internal transcribed spacers of ribosomal DNA in Picea abies and related species. AB - The structure and variation of nuclear ribosomal DNA (rDNA) units of Picea abies, (L.) Karst. was studied by restriction mapping and Southern hybridization. Conspicuous length variation was found in the internal transcribed spacer (ITS) region of P. abies, although the length of this region is highly conserved both within and among most of the plant species. Two types of ITS variants (A and B), displaying a size difference of 0.5 kb in the ITS2 region, were present within individuals of P. abies from Sweden, Central Europe and Siberia. A preliminary survey of 14 additional Eurasian and North American species of Picea suggested that length variation in the ITS region is widespread in this genus. Alltogether three length variants (A, B and C) were identified. Within individuals of eight Picea species, two length variants were present within the genome (combinations of A and B variants in P. glehnii, P. maximowiczii, P. omorika, P. polita and P. sitchensis and variants B and C in P. jezoensis, P. likiangensis and P. spinulosa). Within individuals from five species, however only one rDNA variant was present in their genome (variant A in P. aurantiaca, P. engelmannii, P. glauca, P. koraiensis and P. koyamai; variant B in P. bicolor). The ITS length variation will be useful as a molecular marker in evolutionary studies of the Picea species complex, whose phylogeny is controversial. The presence of intraindividual variation in, and shared polymorphism of the, ITS length variants raises questions about the occurrence of interspecific hybridization during the evolutionary history of Picea. PMID- 24178113 TI - Diallel analysis to predict heterosis and combining ability for grain yield, yield components and bread-making quality in bread wheat (T. aestivum). AB - Combining ability for grain yield, yield components, and several agronomic and qualitative traits, was studied in a seven-parent diallel cross. The 21 F1 hybrids and the seven parental cultivars were grown in replicated plot trials sown at normal seed density in three locations in the years 1992 and 1993. The effects of general combining ability (gca) were highly significant for all the traits measured with the exception of seeds per spikelet, while the specific combining ability (sca) effects were statistically significant for grain yield, plant height, heading time, for all the yield components, and for the Chopin alveographic parameters P and P/L ratio. For the majority of the traits measured gca was greater than sca. Standard heterosis (sh) for grain yield, i.e., the superiority of the hybrids over the best pure line cultivar(cv Eridano), was only 3.3%, confirming previous finding which indicate sh effects in the range of 10%. The most interesting hybrid derived from the cross Maestra x Golia revealed a yield level approaching that of the highest yielding cv Eridano but appeared more interesting because of its reduced plant height and superior bread-making quality, signifying a selling price 30% higher. It was concluded, therefore, that the first generation of hybrids, likely to appear on the market in the next few years, will be characterized by a yield potential only slightly superior to that of the best standard cvs but associated with other desirable traits, such as bread-making quality. PMID- 24178114 TI - Study of androgenetic performance and molecular characterisation of a set of wheat-rye addition lines. AB - Rye chromosomes of wheat-rye addition lines were successfully identified by means of an RFLP analysis with 30 probes. Our results are in agreement with previous cytological data concerning the identity of lines F (+1R), D (+2R), C (+3R), A (+4R), E (+5R) and B (+7R). Two categories of chromosomal rearrangements have been distinguished, namely: (1) deletions: the current line D possesses a chromosome 2R deleted on its short arm and the line G a chromosome 3R deleted on its long arm; we have also noticed a deletion on the long arm of wheat chromosome 1A in line F61; and (2) evolutionary reciprocal translocations in rye relative to wheat which have been previously mentioned in the literature. The anther culture response of the different lines was studied. A significant difference between 'FEC 28' and the addition lines was observed for embryo production and plant regeneration. It appears that genes located on 'S 10' chromosome arm 3RL and on 'FEC 28' chromosome arm 1AL increase embryo frequency whereas gene(s) located on 'S 10' chromosome 5R reduce(s) it. Plant regeneration results suggest that genes increasing regeneration ability and green-plant frequency are located on 'S 10' chromosome 4R. The long arm of chromosome 1A seems to be involved positively in green-plant regeneration whereas chromosomes 1R and 3R limit plant regeneration. PMID- 24178115 TI - Comparison of marker systems and construction of a core collection in a pedigree of European spring barley. AB - Based on data in four publications describing European barley cultivars, similarities between pairs of cultivars were calculated using individual markers and combinations of markers. These markers included 19 isoenzyme patterns, Giemsa C-banding variants of each of the seven chromosomes, hordein polypeptide patterns, DDT susceptibility type, and three morphological descriptors. The rank correlation between the coefficients of parentage and marker-based similarities is low; the highest single marker correlation is with Est-1, 0.41, and the highest correlation with a combination of markers is 0.58. Giemsa C-banding patterns score rather high, as opposed to the three morphological characters that score very low. Selection of core collections using the effective-number-of origin-lines theory is successful. The average number of types found in a core collection of cultivars of given size is always considerably larger than a random set of the same size. The core collection approaches the maximum possible number of types. PMID- 24178116 TI - Amplification of DNA markers from evolutionarily diverse genomes using single primers of simple-sequence repeats. AB - The abundance and scattered distribution of simple-sequence repeats (SSR) in eukaryotic genomes prompted us to explore the use of SSR-based oligonucleotide primers in single primer amplification reactions. In a pilot experiment, 23 primers were used across a panel of evolutionarily diverse eukaryotic genomes, including grapes, lettuce, tomato, pine, maize, salmon, chicken, Holstein cows and humans. The primers were 16-20 bases in length and represented SSRs of di-, tri-, tetra-, and pentanucleotide repeats. The results showed that tetranucleotide repeat primers were most effective in amplifying polymorphic patterns. Of 11 such primers tested, 70% produced polymorphic patterns from the DNA of one or more species. Primers representing a combination of two tetranucleotide repeats, or compound microsatellites, were equally effective. The polymorphisms contained in such fingerprints were able to identify individuals of vertebrate species as well as lines or varieties of plants. Inheritance of the polymorphic bands was studied in a maize recombinant inbred population, DE811 x B73. Thirty-two polymorphic bands, derived from two amplification patterns, were mapped as dominant markers on an existing RFLP map of the same population. The bands were distributed across nine of the ten chromosomes. PMID- 24178117 TI - An RFLP linkage map of Lycopersicon peruvianum. AB - In order to map genes determining resistance to bacterial canker in tomato, backcrosses were made between a resistant and a susceptible Lycopersicon peruvianum accession. The linkage study with RFLP markers yielded a genetic map of L. Peruvianum. This map was compared to that derived from a L. esculentum x L. pennellii F2 population, based on 70 shared RFLP markers. The maps showed a good resemblance in both the order of markers and the length of the chromosomes, with the exception of just one relocated marker on chromosome 9. Because backcrosses were made with the F1, either as the pollen parent or as the pistil parent, linkage maps from male and female meioses could be estimated. It was concluded that recombination at male meiosis was reduced, and that gametophytic selection for parental genotypes at more than one locus per chromosome might be partly responsible for the reduction of the estimated male map length. PMID- 24178118 TI - CMS in rye: comparative RFLP and transcript analyses of mitochondria from fertile and male-sterile plants. AB - The mitochondrial (mt) genomes of rye (Secale cereale L.) lines with "normal" and cytoplasmic male sterility (CMS) inducing "Pampa" cytoplasm were compared by detailed restriction fragment length polymorphism (RFLP) and Northern analyses. RFLP analyses using several heterologous mt genes as probes revealed considerable differences in the overall structure of the two mt genomes. With cob and atpA, the data indicate intragenic recombination and/or different copy numbers of these genes in the two cytoplasms. In spite of this heterogeneity at DNA level, the transcriptional patterns of nine out of ten mitochondrial genes analysed are unaffected. The exception is in the "Pampa" cytoplasm which contains an additional cob-homologous transcript. Since this transcript is strongly reduced in the presence of restorer genes, it might causally be correlated to the CMS phenotype. PMID- 24178119 TI - Effective sizes of livestock populations to prevent a decline in fitness. AB - In livestock populations, fitness may decrease due to inbreeding depression or as a negatively correlated response to artificial selection. On the other hand, fitness may increase due to natural selection. In the absence of a correlated response due to artificial selection, the critical population size at which the increase due to natural selection and the decrease due to inbreeding depression balance each other is approximately D/2sigmawa (2), where D=the inbreeding depression of fitness with complete inbreeding, and sigmawa (2)=the additive genetic variance of fitness. This simple expression agrees well with results from transmission probability matrix methods. If fitness declines as a correlated negative response to artificial selection, then a large increase in the critical effective population size is needed. However, if the negative response is larger than the response to natural selection, a reduction in fitness cannot be prevented. From these results it is concluded that a negative correlation between artificial and natural selection should be avoided. Effective sizes to prevent a decline in fitness are usually larger than those which maximize genetic gain of overall efficiency, i.e., the former is a more stringent restriction on effective size. In the examples presented, effective sizes ranged from 31 to 250 animals per generation. PMID- 24178120 TI - The genetical basis of hybrid vigour in a highly heterotic cross of Nicotiana tabacum. AB - The genetical control of F1 heterosis, observed in a cross of desirable Nicotiana tabacum varieties, was investigated by analysing the data of the basic generations, triple test cross-families and random samples of doubled haploids (DH) and single-seed descent (SSD) lines. Analyses of the first-degree statistics revealed a complex control underlying the genetic variation, including the presence of epistasis, linkage, maternal effects and their interactions, in addition to the additive and dominance effects of the genes segregating in the cross. These analyses identified gene dispersion, directional dominance, and duplicate epistasis, as the main causes of heterosis. The triple test-cross analysis also confirmed the presence of non-allelic interactions and indicated that the dominance ratio, although inflated by epistasis, is consistently partial for all the traits. The extent of transgression in the recombinant inbred lines finally established unequivocally that, as in numerous other crosses, gene dispersion and unidirectional, but partial, dominance are the true causes of heterosis in this cross too. PMID- 24178121 TI - Quantitative-genetic analysis of reciprocal crosses between a winter and a spring cultivar of common wheat (Triticum aestivum L.). AB - The winter wheat cultivar Sakhalin (parent A) and the spring wheat cultivar Khush hal (parent B), assumed to be both nuclear-genetically and plasmotypically different, were reciprocally crossed and the F1 generation of the reciprocals backcrossed to either parent. The populations (AxB)F1, (AxB)F2, [(AxB)F1xA]F1 and [(AxB)F1xB]F1, and their reciprocals (BxA)F1, (BxA)F2, [(BxA)F1xA]F1 and [(BxA)F1xB]F1, assumed to have the plasmotypes of the parents A and B respectively, were spring sown in the same field from unvernalized (experiment #1) and vernalized (experiment #2) seeds. The results of the analyses of variance of the data recorded in the two experiments are fairly similar. In both the experiments the plasmotypically A populations have produced more heads and higher grain yields per plant than their plasmotypically B reciprocals. The components of the family means and of half the differences between the reciprocals within the families show that vernalization has not affected the efficiency of the nuclear genes of parent A but has reduced the efficiency of the nuclear genes of parent B in both the homozygous and the heterozygous states. This in turn has affected the components of family mean squares and those of the family x reciprocals interaction mean squares in the analysis of variance tables. PMID- 24178122 TI - RFLP markers associated with Sr22 and recombination between chromosome 7A of bread wheat and the diploid species Triticum boeoticum. AB - Analysis of the bread wheat variety Schomburgk, and related lines in its pedigree, identified RFLP markers associated with the segment of chromosome 7A carrying the Sr22 gene derived from the diploid species T. boeoticum. The distribution of the RFLP markers indicated that at least 50% of 7AS and 80% of 7AL in Schomburgk is of T. boeoticum origin. Evaluation of five sets of nearisogenic lines, backcross lines in 20 different genetic backgrounds and an F2 population segregating for Sr22 demonstrated a very low level of recombination between the 7A chromosomes of T. boeoticum and T. aestivum. Several recombinants carrying Sr22 but with a much reduced segment of T. boeoticum were identified and these may prove useful in the breeding of further varieties with Sr22. PMID- 24178123 TI - Quantitative genetics of growth and development in Populus. I. A three-generation comparison of tree architecture during the first 2 years of growth. AB - One approach to gain an insight into the genetics of tree architecture is to make use of morphologically divergent parents and study their segregating progeny in the F2 and backcross (B1) generations. This approach was chosen in the present study in which material of a three-generation pedigree growing side by side in a replicated plantation, was analyzed. The pedigree included Populus trichocarpa (T) and P. deltoides (D) parents, their F1 and F2 hybrids and their B1 hybrids to the D parent. The trees were grown in the environment of the T parent and measured for the first 2 years of growth. Nine quantitative traits were studied at the stem, branch and leaf levels of tree architecture, in which the original parents differed. Strong F1 hybrid vigor relative to the better parent (T) was expressed in growth and its components. Most quantitative traits in the F2 and B1 hybrids were intermediate between the T and D parents but displayed a wide range of variation due to segregation. The results from the analysis of variance indicated that all morphometric traits were significantly different among F2 and B1 clones, but the B1 hybrids were more sensitive to replicates than the F2. Broad-sense heritabilities (H (2)) based on clonal means ranged from moderately high to high (0.50-0.90) for the traits studied, with H (2) values varying over age. The H (2) estimates reflected greater environmental "noise" in the B1 than in the F2, presumably due to the greater proportion of maladaptive D alleles in those hybrids. In both families, sylleptic branch number and length, and leaf size on the terminal, showed strong genetic correlations with stem growth. The large divergence between the two original parents in the traits studied, combined with the high chromosome number in Populus (2n=38), makes this pedigree well suited for the estimation of the number of quantitative trait loci (QTLs) underlying quantitative variation by Wright's biometric method (1968). Variation in several traits was found to be under the control of surprisingly few major QTLs: 3-4 in 2nd-year height and diameter growth, a single QTL in stem diameter/height ratio. PMID- 24178124 TI - Optical imaging to map blood-brain barrier leakage. AB - Vascular leakage in the brain is a major complication associated with brain injuries and certain pathological conditions due to disruption of the blood-brain barrier (BBB). We have developed an optical imaging method, based on excitation and emission spectra of Evans Blue dye, that is >1000-fold more sensitive than conventional ultraviolet spectrophotometry. We used a rat thromboembolic stroke model to validate the usefulness of our method for vascular leakage. Optical imaging data show that vascular leakage varies in different areas of the post stroke brain and that administering tissue plasminogen activator causes further leakage. The new method is quantitative, simple to use, requires no tissue processing, and can map the degree of vascular leakage in different brain locations. The high sensitivity of our method could potentially provide new opportunities to study BBB leakage in different pathological conditions and to test the efficacy of various therapeutic strategies to protect the BBB. PMID- 24178125 TI - Ecological responses of a large shallow lake (Okeechobee, Florida) to climate change and potential future hydrologic regimes. AB - We considered how Lake Okeechobee, a large shallow lake in Florida, USA, might respond to altered hydrology associated with climate change scenarios in 2060. Water budgets and stage hydrographs were provided from the South Florida Water Management Model, a regional hydrologic model used to develop plans for Everglades restoration. Future scenarios include a 10% increase or decrease in rainfall (RF) and a calculated increase in evapotranspiration (ET), which is based on a 1.5 degrees C rise in temperature. Increasing RF and ET had counter balancing effects on the water budget and when changing concurrently did not affect hydrology. In contrast, when RF decreased while ET increased, this resulted in a large change in hydrology. The surface elevation of the lake dropped by more than 2 m under this scenario compared to a future base condition, and extreme low elevation persisted for multiple years. In this declining RF/increasing ET scenario, the littoral and near-shore zones, areas that support emergent and submerged plants, were dry 55% of the time compared to less than 4% of the time in the future base run. There also were times when elevation increased as much as 3 m after intense RF events. Overall, these changes in hydrologic conditions would dramatically alter ecosystem services. Uncertainty about responses is highest at the pelagic-littoral interface, in regard to whether an extremely shallow lake could support submerged vascular plants, which are critical to the recreational fishery and for migratory birds. Along with improved regional climate modeling, research in that interface zone is needed to guide the adaptive process of Everglades restoration. PMID- 24178126 TI - Forest biodiversity monitoring for REDD+: a case study of actors' views in Peru. AB - The climate change mitigation mechanism Reducing Emissions from Deforestation and Forest Degradation in developing countries (REDD+) is currently being negotiated under the United Nations Framework Convention on Climate Change (UNFCCC). Integrating biodiversity monitoring into REDD+ facilitates compliance with the safeguards stipulated by the UNFCCC to exclude environmental risks. Interviews with actors engaged in REDD+ implementation and biodiversity conservation at the national and sub-national level in Peru (n = 30) and a literature review (n = 58) were conducted to pinpoint constraints and opportunities for monitoring effects of REDD+ management interventions on biodiversity, and to identify relevant biodiversity data and indicators. It was found that particularly sub-national actors, who were frequently involved in REDD+ pilot projects, acknowledge the availability of biodiversity data. Actors at both the national and sub-national levels, however, criticized data gaps and data being scattered across biodiversity research organizations. Most of the literature reviewed (78 %) included indicators on the state of certain biodiversity aspects, especially mammals. Indicators for pressure on biodiversity, impacts on environmental functions, or policy responses to environmental threats were addressed less frequently (31, 21, and 10 %, respectively). Integrating biodiversity concerns in carbon monitoring schemes was considered to have potential, although few specific examples were identified. The involvement of biodiversity research organizations in sub-national REDD+ activities enhances monitoring capacities. It is discussed how improvements in collaboration among actors from the project to the national level could facilitate the evaluation of existing information at the national level. Monitoring changes in ecosystem services may increase the ecological and socioeconomic viability of REDD+. PMID- 24178127 TI - Aspirin use and aging macula disorder. PMID- 24178128 TI - Interpersonal and personal antecedents and consequences of peer victimization across middle childhood in Hong Kong. AB - Although much is known about peer victimization, the majority of the longitudinal research in this area has been restricted to Western settings. The main objective of this study was to examine the interpersonal (rejection) and personal (withdrawal, aggression) antecedents and consequences of victimization for Chinese children living in Hong Kong. A sample of 1,058 children (501 boys; M age = 9.5 years) in Hong Kong was followed longitudinally from the 3rd and 4th grades to the 7th and 8th grades. Consistent with a transactional framework, rejection and withdrawal contributed to, as well as resulted from, victimization. Although victimization predicted later aggression, aggression was unrelated to later victimization. These findings closely replicate past research conducted in North America and European settings, and suggest considerable correspondence in the links between maladaptive child characteristics and victimization across Western and Hong Kong schools. PMID- 24178129 TI - Design of aromatic heteropolycyclics containing borole frameworks. AB - The heteropolycyclic compounds containing borole units were theoretically designed. The presence of electron deficient boron atoms results in full electron delocalization and remarkably affects their aromaticity. While molecules 1 and 2a exhibit antiaromaticity for inner rings and non-aromaticity for outer rings, 2b and 2c are completely aromatic. PMID- 24178130 TI - Performing DISCO-SCA to search for distinctive and common information in linked data. AB - Behavioral researchers often obtain information about the same set of entities from different sources. A main challenge in the analysis of such data is to reveal, on the one hand, the mechanisms underlying all of the data blocks under study and, on the other hand, the mechanisms underlying a single data block or a few such blocks only (i.e., common and distinctive mechanisms, respectively). A method called DISCO-SCA has been proposed by which such mechanisms can be found. The goal of this article is to make the DISCO-SCA method more accessible, in particular for applied researchers. To this end, first we will illustrate the different steps in a DISCO-SCA analysis, with data stemming from the domain of psychiatric diagnosis. Second, we will present in this article the DISCO-SCA graphical user interface (GUI). The main benefits of the DISCO-SCA GUI are that it is easy to use, strongly facilitates the choice of model selection parameters (such as the number of mechanisms and their status as being common or distinctive), and is freely available. PMID- 24178132 TI - Model-based evaluation of the Canberra Hospital Acute Care Surgical Unit : acute care surgery: a case of one size fits all? AB - PURPOSE: Surgical services in Australia are under sustained and growing pressure. The global implementation of acute care surgery services has been shown to facilitate the timeliness of acute surgery. The question is: Do acute care surgical units fit major regional centers like ours? The current study coincides with the introduction of a Surgical Assessment and Planning Unit (SAPU) at the Canberra Hospital and compares patient outcomes before vs. after the introduction of the SAPU, using acute appendicitis as the model illness. METHODS: We reviewed patients presenting to the Canberra Hospital Emergency Department with a preliminary diagnosis of acute appendicitis before vs. after the introduction of an acute care surgical unit. RESULTS: The subjects were 150 patients, ranging in age from 16 to 97 years. The mean time from presentation at casualty to surgical review and the surgical review itself was reduced by 19 and 26 %, respectively (p < 0.05). Time to the operating table and the percentage of after-hours operations were reduced by 8 and 40 %, respectively. There was a significant reduction in the utilization of abdominal ultrasonography after the implementation of the SAPU. CONCLUSIONS: The implementation of a SAPU has benefited the management of patients with acute surgical conditions. Ultimately, patient care is enhanced, with patients being reviewed, admitted, and treated earlier. PMID- 24178131 TI - Mechanisms underlying odorant-induced and spontaneous calcium signals in olfactory receptor neurons of spiny lobsters, Panulirus argus. AB - We determined if a newly developed antennule slice preparation allows studying chemosensory properties of spiny lobster olfactory receptor neurons under in situ conditions with Ca(2+) imaging. We show that chemical stimuli reach the dendrites of olfactory receptor neurons but not their somata, and that odorant-induced Ca(2+) signals in the somata are sufficiently stable over time to allow stimulation with a substantial number of odorants. Pharmacological manipulations served to elucidate the source of odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons. Both Ca(2+) signals are primarily mediated by an influx of extracellular Ca(2+) through voltage-activated Ca(2+) channels that can be blocked by CoCl2 and the L type Ca(2+) channel blocker verapamil. Intracellular Ca(2+) stores contribute little to odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations. The odorant-induced Ca(2+) transients as well as the spontaneous Ca(2+) oscillations depend on action potentials mediated by Na(+) channels that are largely TTX-insensitive but blocked by the local anesthetics tetracaine and lidocaine. Collectively, these results corroborate the conclusion that odorant induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons closely reflect action potential activity associated with odorant-induced phasic-tonic responses and spontaneous bursting, respectively. Therefore, both types of Ca(2+) signals represent experimentally accessible proxies of spiking. PMID- 24178133 TI - Systematic suicide risk assessment for patients with schizophrenia: a national population-based study. AB - OBJECTIVES: Systematic suicide risk assessment is recommended for patients with schizophrenia; however, little is known about the implementation of suicide risk assessment in routine clinical practice. The study aimed to determine the use of systematic suicide risk assessment at discharge and predictors of suicide attempt among hospitalized patients with schizophrenia in Denmark. METHODS: A one-year follow-up study was conducted of 9,745 patients with schizophrenia who were discharged from psychiatric wards and registered in a national population-based schizophrenia registry between 2005 and 2009. RESULTS: The proportion of patients receiving suicide risk assessment at discharge from a psychiatric ward increased from 72% (95% confidence interval [CI]=71%-74%) in 2005, when the national monitoring began, to 89% (CI=89%-90%) in 2009. Within one year after discharge, 1% of all registered patients had died by suicide and 8% had attempted suicide. One out of three patients who died by suicide had no documented suicide risk assessment before discharge. CONCLUSIONS: The use of systematic suicide risk assessment at discharge among patients with schizophrenia increased in Denmark between 2005 and 2009, in accordance with recommendations in national clinical guidelines and monitoring in a national clinical registry. Additional efforts are warranted to ensure a lower risk of suicidal behavior after hospital discharge. PMID- 24178134 TI - The efficacy of religious service attendance in reducing depressive symptoms. AB - PURPOSE: To examine whether religiosity may help people ward off depression, we investigated the association between religious service attendance and depressive symptom scores in a community-based 30-year follow-up longitudinal study. METHODS: This study used data on 754 subjects followed over 30 years and evaluated at four time points. Linear mixed effects models were used to assess the association between religious service attendance and depressive symptoms development; frequency of attendance and age also were used as predictors. Demographic factors, life-time trauma, family socioeconomic status, and recent negative events were considered as control variables. RESULTS: Depressive symptom scores were reduced by an average of 0.518 units (95 % CI from -0.855 to -0.180, p < 0.005) each year in subjects who attended religious services as compared with subjects who did not. The more frequent the religious service attendance, the stronger the influence on depressive symptoms when compared with non-attendance. Yearly, monthly, and weekly religious service attendance reduced depression scores by 0.474 (95 % CI from -0.841 to -0.106, p < 0.01), 0.495 (95 % CI from 0.933 to -0.057, p < 0.05) and 0.634 (95 % CI from -1.056 to -0.212, p < 0.005) units on average, respectively, when compared with non-attendance after controlling for other covariates. CONCLUSION: Religious service attendance may reduce depressive symptoms significantly, with more frequent attendance having an increasingly greater impact on symptom reduction in this 30-year community-based longitudinal study. PMID- 24178135 TI - Characterization of the epidermis from barley primary leaves : I. Isolation of epidermal protoplasts. AB - A method is described for isolating epidermal protoplasts from the primary leaves of barley (Hordeum vulgare L.). Epidermal protoplasts are lighter than mesophyll protoplasts because of their smaller ratio of cytoplasm to vacuole, and can be separated from the latter by density-gradient centrifugation after complete digestion of the leaves. We have started a basic characterization of the epidermal protoplast fraction in comparison with mesophyll protoplasts. Epidermal protoplasts had a mean diameter of 63.5 MUm, whereas that of mesophyll protoplasts was 35.7 MUm. Their respiratory oxygen consumption was not influenced by light. They contained acid hydrolases and cytoplasmic enzymes in relative activities different from those of mesophyll protoplasts. Their polypeptide pattern as judged from two-dimensional separations was, in principle, similar to that of mesophyll cells after elimination of the plastids from the latter by the preparation of vacuoplasts. However, in addition, a considerable number of epidermis-specific polypeptides were observed. Isolated epidermal protoplasts were viable and efficiently incorporated [(35)S]methionine into newly synthesized proteins. The results show that epidermal protoplasts are suitable for the investigation of the physiological and molecular properties of epidermal cells in leaves. PMID- 24178136 TI - Characterization of the epidermis from barley primary leaves : II. The role of the epidermis in ion compartmentation. AB - The cation and anion distribution between the epidermis and mesophyll of primary leaves of 10-d-old barley (Hordeum vulgare L.) seedlings was studied in relation to growth conditions. A new method was employed to isolate epidermal protoplasts. The following observations were made: (i) Under standard hydroponic growth conditions, K(+) was the dominant cation and NO 3 (3-) the predominant anion, both in epidermal and mesophyll protoplasts. (ii) Levels of Cl(-) and particularly of Ca(2+) were specifically increased in the epidermis when growth conditions stimulated uptake of these ions into the plants. (iii) Epidermal PO 4 (3-) was maintained at a very low level even in the presence of 50 mM phosphate in the rooting medium, whereas the phosphate concentration in the mesophyll was high, with phosphate being accumulated in the mesophyll vacuoles. (iv) Sulphate and NO 3 (-) accumulated to a similar degree in the mesophyll and the epidermis when K2SO4 or KNO3 in the rooting medium caused salt stress to the plants. (v) Epidermal protoplasts took up (35)SO 4 (2-) and (36)Cl(-) from the surrounding medium. A comparison of the uptake rates indicates that specific ion deposition into the epidermis may partially be the consequence of differential uptake of ions from the transpiration stream. The results indicate an important function of the epidermis for ion compartmentation in barley leaves. PMID- 24178137 TI - Purification of iron superoxide dismutase from the cyanobacterium Anabaena cylindrica Lemm. and localization of the enzyme in heterocysts by immunogold labeling. AB - Iron superoxide dismutase (Fe-SOD; EC 1.15.1.1) was isolated from the nitrogen fixing cyanobacterium Anabaena cylindrica Lemm. Polyacrylamide gel electrophoresis separated the purified protein into three closely running, enzymatically active bands. The molecular weight of the enzyme was estimated by gel filtration to be about 40 kDa. Polyclonal antibodies were produced by immunization of rabbits with the isolated enzyme, and were purified on a column of protein A-Sepharose. The Fe-SOD antibody reacted with the purified Fe-SOD and also specifically recognized the protein in extracts of A. cylindrica. In the extracts, anti-Fe-SOD did not cross-react with Mn-SOD, an enzyme which belongs to an SOD class displaying high homology of primary and three-dimensional structure with respect to Fe-SOD. Iron superoxide dismutase was localized in heterocysts by immunogold labeling and transmission electron microscopy. These results are the first in-situ evidence for the presence of SOD in the cells specialized for nitrogenase activity. PMID- 24178138 TI - Morphology and monoterpene biosynthetic capabilities of secretory cell clusters isolated from glandular trichomes of peppermint (Mentha piperita L.). AB - Secretory cells were isolated from the monoterpene-producing glandular trichomes (peltate form) of peppermint as clusters of eight cells each. These isolated structures were shown to be non-specifically permeable to low-molecular-weight, water-soluble cofactors and substrates. Short incubation periods with the polar dye Lucifer yellow iodoacetamide (Mr=660) resulted in a uniform staining of the cytoplasm, with exclusion of the dye from the vacuole. The molecular-weight exclusion limit for this permeability was shown to be less than approx. 1800, based on exclusion of fluorescein-conjugated dextran (Mr ~ 1800). Intact secretory cell clusters very efficiently incorporated [(3)H]geranyl pyrophosphate into monoterpenes. The addition of exogenous cofactors and redox substrates affected the distribution of monoterpenes synthesized from [(3)H]geranyl pyrophosphate, demonstrating that the cell clusters were permeable to these compounds and that the levels of endogenous cofactors and redox substrates were depleted in the isolated cells. When provided with the appropriate cofactors, such as NADPH, NAD(+), ATP, ADP and coenzyme A, the isolated secretory cell clusters incorporated [(14)C]sucrose into monoterpenes, indicating that these structures are capable of the de-novo biosynthesis of monoterpenes from a primary carbon source, and that they maintain a high degree of metabolic competence in spite of their permeable nature. PMID- 24178139 TI - Calcium influx at the tip of growing root-hair cells of Arabidopsis thaliana. AB - The role of extracellular Ca(2+) in root-hair tip growth has been investigated in Arabidopsis thaliana (L.) Heynh. Root-hair length was found to be dependent on the concentration of Ca(2+) in the growth medium, with maximum length achieved at [Ca(2+)] of 0.3-3.0 mM. Using a non-intrusive calcium-specific vibrating microelectrode, an extracellular Ca(2+) gradient was detected at the tips of individual growing root-hair cells. The direction of the gradient indicated a net influx of Ca(2+) into root-hair cells. No gradient was detected near the sides of the root hairs or at the tips of non-growing root hairs. When root hairs were exposed to the Ca(2+)-channel blocker nifedipine, tip growth stopped and the extracellular Ca(2+) gradient was abolished. These results indicate that Ca(2+) influx through plasma-membrane Ca(2+) channels is required for normal root-hair tip growth. PMID- 24178140 TI - Phloem loading in Ricinus cotyledons: sucrose pathways via the mesophyll and the apoplasm. AB - Ricinus communis cv. Carmencita seedlings with their cotyledons incubated in sucrose solution and their hypocotyls cut to induce exudation of phloem sap, constitute a system of sucrose fluxes into and out of the cotyledons. This system was characterized with respect to quasi-steady-state conditions of sucrose uptake and export and then used to investigate the pathways of sucrose during phloem loading. The redistribution of (14)C-labelled internal sucrose between the three "compartments", cotyledons (mesophyll), exudate (sieve tubes) and incubation medium (cell-wall space), was measured in the presence or absence of external nonlabelled sucrose. It was found that mesophyll-derived labelled and external sucrose compete at uptake sites in the apoplasm. On the basis of the specific radioactivity of sucrose which reflects the proportionate intermixture of mesophyll-derived and external sucrose in the three "compartments", it was determined that about 50% of the sucrose exported is loaded directly from the apoplasm, while the other half takes the route via the mesophyll. It was confirmed that mesophyll-derived sucrose is released into the apoplasm, so that the existence of an indirect apoplasmic loading pathway is established. Calculations depending on the concentration gradients of labelled and non labelled sucrose in the cell-wall space are presented to quantify tentatively the proportions of direct and indirect apoplasmic as well as symplasmic loading. PMID- 24178141 TI - Association of particles that contain double-stranded RNAs with algal chloroplasts and mitochondria. AB - Linear dsRNAs (double-stranded RNAs) belonging to several distinct size classes were found to be localized in chloroplasts and mitochondria of Bryopsis spp., raising the possibility that these dsRNAs are prokaryotic in nature. The algal cytosol and nuclei did not contain dsRNAs. The amount of the dsRNAs in the organelles appeared constant, and there were about 500 copies per chloroplast. The four major dsRNAs from Bryopsis chloroplasts were about 2 kbp (kilobase pairs) in length and originated from discrete isometric particles of about 25 nm diameter. These virus-like particles were purified by CsCl density gradient centrifugation after extraction from isolated chloroplasts with chloroformbutanol and subsequent precipitation with polyethylene glycol. They had a buoyant density of about 1.40 g . cm(-3) and contained four major and three minor proteins. Mitochondrial dsRNAs were about 4.5 kbp in length and formed less-stable particles of about 40 nm in diameter with a buoyant density of 1.47 g . cm(-3). Some observations support the hypothesis that vertical transmission of the protein-coated, non-infectious dsRNAs occurs within cell organelles. Double stranded RNAs of various sizes were found in most green, red, and brown algae. The characteristics of the algal dsRNAs are compared with those of dsRNAs from higher plants and the biological significance of the dsRNAs in cell organelles is discussed. PMID- 24178142 TI - In-vitro morphogenesis of corn (Zea mays L.) : I. Differentiation of multiple shoot clumps and somatic embryos from shoot tips. AB - In-vitro methods have been developed to regenerate clumps of multiple shoots and somatic embryos at high frequency from shoot tips of aseptically-grown seedlings as well as from shoot apices of precociously-germinated immature zygotic embryos of corn (Zea mays L.). About 500 shoots were produced from a shoot tip after eight weeks of culture (primary culture and one subculture of four weeks) in darkness on Murashige and Skoog basal medium (MS) supplemented with 500 mg/L casein hydrolysate (CH) and 9 MUM N(6)-benzyladenine (BA). In this medium, shoots formed in shoot tips as tightly packed "multiple shoot clumps" (MSC), which were composed of some axillary shoots and many adventitious shoots. When the shoot tips were cultured on MS medium containing 500 mg/L CH, 9 MUM BA and 2.25 MUM 2,4 dichlorophenoxyacetic acid (2,4-D), most of the shoots in the clumps were adventitious in origin. Similar shoot tips cultured on MS medium containing 500 mg/L CH, 4.5 MUM BA and 2.25 MUM 2,4-D regenerated many somatic embryos within eight weeks of culture. Somatic embryos were produced either directly from the shoot apical meristems or from calli derived from the shoots apices. Both the MSC and the embryos produced normal shoots on MS medium containing 2.25 MUM BA and 1.8 MUM indole-3-butyric acid (IBA). These shoots were rooted on MS medium containing 3.6 MUM IBA, and fertile corn plants were grown in the greenhouse. The sweet-corn genotype, Honey N Pearl, was used for the experiments described above, but shoot-tip cultures from all of 19 other corn genotypes tested also formed MSC on MS medium containing 500 mg/L CH and 9 MUM BA. PMID- 24178143 TI - In-vitro morphogenesis of corn (Zea mays L.) : II. Differentiation of ear and tassel clusters from cultured shoot apices and immature inflorescences. AB - The objective of this research was to study the in-vitro morphogenetic pattern of corn (Zea mays L.) shoot tips excised from aseptically-grown seedlings, and of expiants of axillary shoot buds, immature tassels and ears (staminate and pistillate inflorescences) obtained from greenhouse-grown corn plants. The seedling shoot tips and immature ears first regenerated clumps of multiple shoots within four weeks of culture on Murashige and Skoog (MS) basal medium supplemented with 500 mg/L casein hydrolysate (CH) and 9.0 MUM N(6)-benzyladenine (BA). Multiple shoot clumps were also differentiated from spikelets of immature tassels cultured on MS medium containing 500 mg/L CH, 4.5 MUM BA and 0.45 MUM 2,4 dichlorophenoxy acetic acid (2,4-D). All these multiple shoot clumps in turn differentiated clusters of ears after further four subcultures at four-week intervals under light on MS medium supplemented with 500 mg/L CH and 2.25, 4.5, 9.0 or 18 MUM BA. Axillary shoot buds readily differentiated clusters of ears within four weeks of the initial culture on these media. Secondary and tertiary ear clusters were initiated following subculture of primary ears on MS medium containing 500 mg/L CH and 4.5 or 9.0 MUM BA. Most of the ear primordia developed into ears with well-developed ovaries and styles on subculture on MS medium containing 500 mg/L CH and 1.0 MUM BA. Corn kernels were obtained after pollination of in-vitro-formed ears with pollens collected from greenhouse-grown corn. These kernels germinated in vitro and developed into mature corn plants in the greenhouse. Clusters of tassels were also differentiated in darkness from the multiple shoot clumps after six months successive subcultures but the spikelet primordia of tassels failed to develop fully under the in-vitro conditions tested. Somatic embryos arose directly from spikelet primordia of young tassels or ears on MS medium containing 500 mg/L CH and 4.5 MUM 2,4-D, or indirectly from calli derived from spikelets of young tassels and ears on MS medium containing 500 mg/L CH and 9.0 MUM 2.4-D. PMID- 24178144 TI - Physical extensibility of maize coleoptile cell walls: apparent plastic extensibility is due to elastic hysteresis. AB - Segments of maize (Zea mays L.) coleoptiles demonstrate plastic cell-wall extensibility (Epl) as operationally defined by the amount of irreversible strain elicited by stretching living or frozen-thawed tissue under constant load in an extensiometer (creep test). Changes of Epl are correlated with auxin- and abscisic-acid-dependent growth responses and have therefore been causally related to hormone-controlled cell-wall loosening. Auxin induces an increase of Epl specifically in the outer epidermal wall of maize coleoptiles which is considered as the growth-limiting wall of the organ. However, detailed kinetic measurements of load-induced extension of frozen-thawed coleoptile segments necessitates a revision of the view that Epl represents a true plastic (irreversible) wall deformation. Segments demonstrate no significant irreversible extension when completely unloaded between loading cycles. Moreover, Epl can be demonstrated repeatedly if the same segment is subjected to repeated loading cycles in the extensiometer. It is shown that these phenomena result from the hysteresis behaviour of the cell wall. Stress-strain curves for loading and unloading form a closed hysteresis loop, the width of which represents Epl at a particular load. Auxin-treatment of segments leads to a deformation of the hysteresis loop, thereby giving rise to an increase of Epl. These results show that the creep test estimates the viscoelastic (retarded elastic) properties rather than the plastic properties of the wall. PMID- 24178145 TI - Kinetics of wound-induced hydraulic signals and variation potentials in wheat seedlings. AB - Displacement transducers were used to demonstrate that localised wounding causes a rapid and systemic increase in leaf thickness in seedlings of wheat (Triticum durum Desf. cv. Iva). These increases are interpreted as reflecting wound-induced hydraulic signals. The duration of the wound-induced increase was found to be about 1 h or more, and it was shown that repeated wounds could induce repeated responses. The increase occurred even when plants had no access to an external water supply. Change in leaf thickness was shown closely to reflect change in leaf water potential. The velocity and kinetics of the wound-induced hydraulic signal were measured using multiple transducers ranged along a single leaf. The front of the signal was shown to travel through the plant at rates of at least 10 cm . s(-1). Development of the increase in leaf thickness was found to be relatively faster furthest from the wound. Onset of the change in leaf thickness in leaves remote from the wound was shown to precede onset of changes in surface electrical potential (variation potential) which are also induced by wounding. In contrast to reports from other species, variation potentials in wheat were here shown to spread extremely rapidly, at rates similar to that of the hydraulic signal. These data support the view that wound-induced hydraulic signals are the trigger for variation potentials in wheat. PMID- 24178146 TI - Photosynthesis and photorespiration in a mutant of the cyanobacterium Synechocystis PCC 6803 lacking carboxysomes. AB - A mutant of the cyanobacterium Synechocystis PCC 6803 was obtained by replacing the gene of the carboxylation enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) with that of the photosynthetic bacterium Rhodospirillum rubrum. This mutant consequently lacks carboxysomes - the protein complexes in which the original enzyme is packed. It is incapable of growing at atmospheric CO2 levels and has an apparent photosynthetic affinity for inorganic carbon (Ci) which is 1000 times lower than that of the wild type, yet it accumulates more Ci than the wild type. The mutant appears to be defective in its ability to utilize the intracellular Ci pool for photosynthesis. Unlike the carboxysomal carboxylase activity of Rubisco, which is almost insensitive to inhibition by O2 in vitro, the soluble enzyme is competitively inhibited by O2. The photosynthetic rate and Ci compensation point of the wild type were hardly affected by low O2 levels. Above 100 MUM O2, however, both parameters became inhibited. The CO2 compensation point of the mutant was linearly dependent on O2 concentration. The higher sensitivity of the mutant to O2 inhibition than that expected from in-vitro kinetics parameters of Rubisco, indicates a low capacity to recycle photorespiratory metabolites to Calvin-cycle intermediates. PMID- 24178147 TI - Temporal organization of chilling resistance in cotton seedlings: effects of low temperature and relative humidity. AB - The effect of temperature and relative humidity (RH) on the time course of the rhythmic endogenous changes of chilling resistance was studied in cotton (Gossypium hirsutum L. cv. Deltapine 50) seedlings grown under light-dark cycles of 12:12 h. The resistant phase to 5 degrees C, 85% RH lasted during most of the dark period while to 5 degrees C, 100% RH it was longer and extended into the last half of the light period because a transient phase advance occurred when chilling started at the middle of the light period. Seedlings acclimated by low temperature were resistant throughout the light-dark cycle. A treatment with 100% RH before chilling to acclimated seedlings introduced a sensitive phase that corresponded to that of non-acclimated seedlings. In non-acclimated seedlings, this treatment decreased the resistance but the basic pattern of the rhythm was sustained. Changes in chilling resistance were analyzed under fluctuating temperatures and RHs, and explained taking into consideration the functioning of the circadian clock and environmental induction of resistance. PMID- 24178148 TI - Distribution of phytochrome and chlorophyll-a/b-binding-protein mRNAs in etiolated Avena seedlings. AB - In 4-d-old dark-grown oat (Avena sativa L.) seedlings, the majority of the type-I phytochrome (phyA) mRNA was found within 10 mm of the tip of the coleoptile sheath and in the mesocotyl node; almost none was detected in the enclosed primary leaf. In contrast, chlorophyll-a/b-binding-protein (cab) mRNAs were found almost exclusively in the enclosed primary leaf and were barely detectable in total-RNA samples from the coleoptile sheath or mesocotyl node of red-light treated etiolated seedlings. Separated, dark-grown primary leaves responded to a red-light treatment by increasing cab-mRNA abundance in the absence of the coleoptile sheath or mesocotyl node tissues. PMID- 24178149 TI - Nocturnal stachyose metabolism in leaf tissues of Xerosicyos danguyi H. Humb. AB - Leaf discs obtained from mature leaves of Xerosicyos danguyi were found to contain appreciable levels of stachyose throughout an 8-h nocturnal period during which this plant performs Crassulacean acid metabolism (CAM). In contrast, in mesophyll tissues obtained from paradermal sections of these same leaf discs and which were devoid of vascular tissues, stachyose pools were rapidly depleted during the nocturnal phase. The pattern of this depletion followed closely the depletion pattern observed for starch, indicating that mesophyll stachyose was possibly involved in nocturnal CAM processes and was not necessarily being used for export. Pulse-labelling of intact X. danguyi leaves prior to excision of leaf discs and mesophyll samples also indicated that, while labelled stachyose had turned-over completely in the mesophyll tissues by the end of the nocturnal period, substantial levels of labelled stachyose were always recovered from the leaf discs from which these mesophyll samples were derived. The data indicate the existence of two separate pools of stachyose in the X. danguyi leaf, one a mesophyll pool which turns over rapidly at night and which may be involved to a small extent in nocturnal CAM processes, and the other a pool associated with and possibly synthesized by the vascular tissues and which presumably represents the phloem-transport pool. PMID- 24178150 TI - An inositol 1,4,5-trisphosphate-6-kinase activity in pea roots. AB - A soluble extract from pea (Pisum sativum L.) roots, when incubated with ATP and inositol 1,4,5-trisphosphate, produced an inositol tetrakisphosphate. The chromatographic properties of this inositol tetrakisphosphate, and of the products formed by its chemical degradation, identify it as inositol 1,4,5,6 tetrakisphosphate. No evidence was obtained for a 3-phosphorylation of inositol 1,4,5-trisphosphate. The importance of these observations with respect to inositol phosphates and calcium signalling in higher plants, is discussed. PMID- 24178151 TI - Stomatal patchiness in Mediterranean evergreen sclerophylls : Phenomenology and consequences for the interpretation of the midday depression in photosynthesis and transpiration. AB - Midday depression of net photosynthesis and transpiration in the Mediterranean sclerophylls Arbutus unedo L. and Quercus suber L. occurs with a depression of mesophyll photosynthetic activity as indicated by calculated carboxylation efficiency (CE) and constant diurnal calculated leaf intercellular partial pressure of CO2 (Ci). This work examines the hypothesis that this midday depression can be explained by the distribution of patches of either wide-open or closed stomata on the leaf surface, independent of a coupling mechanism between stomata and mesophyll that results in a midday depression of photosynthetic activity of the mesophyll. Pressure infiltration of four liquids differing in their surface tension was used as a method to show the occurrence of stomatal patchiness and to determine the status of stomatal aperture within the patches. Liquids were selected such that the threshold leaf conductance necessary for infiltration through the stomatal pores covered the expected diurnal range of calculated leaf conductance (g) for these species. Infiltration experiments were carried out with leaves of potted plants under simulated Mediterranean summer conditions in a growth chamber. For all four liquids, leaves of both species were found to be fully infiltratable in the morning and in the late afternoon while during the periods leading up to and away from midday the leaves showed a pronounced patchy distribution of infiltratable and non-infiltratable areas. Similar linear relationships between the amount of liquid infiltrated and g (measured by porometry prior to detachment and infiltration) for all liquids clearly revealed the existence of pneumatically isolated patches containing only wide-open or closed stomata. The good correspondence between the midday depression of CE, calculated under the assumption of no stomatal patchiness, and the diurnal changes in non-infiltratable leaf area strongly indicates that the apparent reduction in mesophyll activity results from assuming no stomatal patchiness. It is suggested that simultaneous responses of stomata and mesophyll activity reported for other species may also be attributed to the occurrence of stomatal patchiness. In Quercus coccifera L., where the lack of constant diurnal calculated Ci and major depression of measured CE at noontime indicates different stomatal behavior, non-linear and dissimilar relationships between g and the infiltratable quantities of the four liquids were found. This indicates a wide distribution of stomatal aperture on the leaf surface rather than only wide-open or closed stomata. PMID- 24178152 TI - The mechanism of nitrate transport across the tonoplast of barley root cells. AB - Nitrate-selective microelectrodes were used to measure not only nitrate activity in the cytoplasm and vacuole of barley (Hordeum vulgare L.) root cells, but also the tonoplast electrical membrane potential. For epidermal cells, the mean cytoplasmic and vacuolar pNO3 (-log10 [NO3]) values were 2.3+/-0.04 (n=19) and 1.41+/-0.03 (n=35), respectively, while for cortical cells, the mean cytoplasmic and vacuolar nitrate values were 2.58+/-0.18 (n=4) and 1.17+/-0.06 (n=13), respectively. These results indicate that the accumulation of nitrate in the vacuole must be an active process. Proton-selective microelectrodes were used to measure the proton gradient across the tonoplast to assess the possibility that nitrate transport into the vacuole is mediated by an H(+)/NO 3 (-) antiport mechanism. For epidermal cells, the mean cytoplasmic and vacuolar pH values were 7.12+/-0.06 (n=10) and 4.93+/-0.11 (n=22), respectively, while for cortical cells, the mean cytoplasmic and vacuolar pH values were 7.24+/-0.07 (n=3) and 5.09+/-0.17 (n=7), respectively. Calculations of the energetics for this mechanism indicate that the observed gradient of nitrate across the tonoplast of both epidermal and cortical cells could be achieved by an H(+)/NO 3 (-) antiport with a 1?1 stoichiometry. PMID- 24178153 TI - Vesicoureteral reflux in a nonfunctioning kidney detected by 99mTc-DTPA study. AB - Vesicoureteral reflux (VUR) is a well-recognized condition in the pediatric population, but is less well described in the adult population, and its prevalence decreases with increasing age. We describe the case of a 53-year-old male with nonfunctional kidney in which accumulation of radioactivity was observed in the ureter and renal pelvis owing to VUR, which was detected by technetium-99m diethylenetriamine pentaacetic acid dynamic renal scintigraphy. PMID- 24178154 TI - Value of DW-MRI ADC quantification of colonic wall lesions in differentiation of inflammatory bowel disease and colorectal carcinoma. AB - PURPOSE: The purpose of our study was to assess the efficiency of diffusion weighted magnetic resonance imaging (DW-MRI) and the quantification of apparent diffusion coefficient (ADC) values in differentiating colorectal carcinoma from colonic inflammatory bowel disease (IBD) in cases with isolated colonic wall lesions and uncertain clinical and radiologic diagnostic criteria. METHODS: The study comprised 58 patients with segmental or focal isolated colonic wall thickening. All lacked satisfactory clinical-radiological findings for etiology determination. The mean ADC values of the thickened colonic walls were retrospectively compared with final histopathologic diagnoses. Receiver operating characteristic (ROC) curve analysis was used to determine the ADC cutoff value for differentiation. RESULTS: Mean ADC value in the colorectal carcinoma group was significantly lower than that in the IBD group: n = 27, 1.02 +/- 0.26 * 10( 3) mm(2)/s; and n = 31, 1.53 +/- 0.19 * 10(-3) mm(2)/s, respectively (P < 0.001). Cutoff ADC value for differentiating colorectal carcinoma from IBD was calculated as 1.39 * 10(-3) mm(2)/s, with 83.9 % sensitivity and 85.2 % specificity. CONCLUSION: ADC measurement of the involved colonic wall segments with DW-MRI has the potential to differentiate isolated colonic IBD from colorectal carcinoma in cases in which clinical-radiologic findings are insufficient for a definitive diagnosis. PMID- 24178155 TI - The effect of graphene substrate on osteoblast cell adhesion and proliferation. AB - Understanding the effect of graphene substrate on graphene-cell interaction is important for considering graphene as a potential candidate for biomedical applications. In this article, biocompatibility of few layers of graphene film transferred to different substrates was evaluated using osteoblasts. The substrates were oxidized silicon wafer (SiO2/Si stack), soda lime glass, and stainless steel. Chemical vapor deposition method was employed to synthesize graphene on copper substrate using methane and hydrogen as precursors. The quality and the thickness of graphene films on different substrates were estimated by Raman spectra, whereas the thickness of graphene film was confirmed by reflectance and transmittance spectroscopy. The study was also focused on cell attachment and morphology at two time points. The results show that graphene does not have any toxic effect on osteoblasts. The cell adhesion improves with graphene coated substrate than the substrate alone. It seems that graphene substrate properties play a dominant role in cell adhesion. The result of this study suggests that a layer of graphene on bone implants will be beneficial for osteoblast attachment and proliferation. PMID- 24178157 TI - Compliance with emergency obstetric care referrals among pregnant women in an urban informal settlement of Accra, Ghana. AB - This study examines the situation that women face when they require emergency obstetric care in urban Accra. The analysis clarifies the referral options available to women needing emergency obstetric care, assesses the constraints they face in accessing the obstetric referral system and identifies the drawbacks associated with the obstetric referral system for women living in informal settlements of a rapidly growing district in Ghana. This research was a descriptive cross-sectional study using structured questionnaires administered to antenatal care clinic attendees and in-depth interviews of principal healthcare personnel. Sixty-five women had referrals in their previous pregnancies of which 62 went to the referral centre at varying time intervals. Three respondents did not go due to lack of financial resources and preference for traditional services. With regard to adherence to referral advice, lack of finances was the major constraint (46.2%) followed by client complaints about the attitudes of nurses at the referral centres (10.8%), fear of surgery (7.7%) and concerns about the distance to referral centres (4.6%). Moreover, analysis identified a significant positive association between parity and time elapsed between service encounter and compliance with referral (p = 0.001). Major constraints are faced by women when they attempt to utilize referral healthcare services such as financial problems, perceived remoteness of care points, fear of surgical procedures and concerns about the discourteous attitude of nurses at the referral centres. Healthcare providers however, emphasized other elements of the climate of care such as their perceived need for increasing staff strength. PMID- 24178156 TI - Adverse childhood events and current depressive symptoms among women in Hawaii: 2010 BRFSS, Hawaii. AB - Research on the association between adverse childhood events (ACEs) and depression among women in Hawaii is scarce. ACEs have been linked to unfavorable health behaviors such as smoking and binge drinking which are more prevalent in the state compared to the US overall. The concomitant presence of ACEs with smoking or binge drinking may explain the excess depression prevalence in Hawaii compared to the national average. Using data of women residing in the state (2010 Hawaii Behavioral Risk Factor Surveillance System Survey), we examined the association between ACEs count or type (household dysfunction and physical, verbal and sexual abuse) and current depressive symptoms (CDS), in addition to modification by current smoking status (smoked >100 cigarettes in a lifetime and currently smoke) and binge drinking (consumed >=4 alcoholic beverage within the past month and in >=1 occasion(s)). Evaluation of ACEs before age 18 consisted of 11 indicators. Eight indicators of the Patient Health Questionnaire (PHQ-8) were used to assess CDS. All analyses utilized logistic regression taking into account sampling design. The odds ratio of having CDS between those with versus without ACEs increased per increasing number of ACEs (1 ACE: OR = 2.11, CI = 1.16-3.81; 2 ACEs: OR = 2.90, CI = 1.51-5.58; 3 or 4 ACEs: OR = 3.94, CI = 2.13-7.32; 5+ ACEs: OR = 4.04, CI = 2.26-7.22). Household dysfunction (OR = 2.10, CI = 1.37-3.23), physical abuse (OR = 1.67, CI = 1.08-2.59), verbal abuse (OR = 3.21, CI = 2.03 5.09) and sexual abuse (OR = 1.68, CI = 1.04-2.71) were all positively associated with CDS. Verbal abuse had the strongest magnitude of association. Neither current smoking status nor binge drinking modified the relationship between ACEs count (or type) and CDS. In conclusion, the presence of ACEs among women in Hawaii was indicative of CDS in adulthood, notably verbal abuse. Further, a dose response existed between the number of ACEs and the odds for CDS. The concomitant exposure to ACEs and current smoking status or binge drinking did not elevate odds for CDS. PMID- 24178158 TI - Prevention of secondary conditions in fetal alcohol spectrum disorders: identification of systems-level barriers. AB - Fetal alcohol spectrum disorders (FASD) impact 2-5% of the US population and are associated with life-long cognitive and behavioral impairments. Individuals with FASD have high rates of secondary conditions, including mental health problems, school disruptions, and trouble with the law. This study focuses on systems-level barriers that contribute to secondary conditions and interfere with prevention and treatment. Using a phenomenological methodology, semi-structured interviews and focus groups were conducted with parents of children with FASD and service providers. Data were analyzed using a framework approach. Participants emphasized the pervasive lack of knowledge of FASD throughout multiple systems. This lack of knowledge contributes to multi-system barriers including delayed diagnosis, unavailability of services, and difficulty qualifying for, implementing, and maintaining services. FASD is a major public health problem. Broad system changes using a public health approach are needed to increase awareness and understanding of FASD, improve access to diagnostic and therapeutic services, and create responsive institutional policies to prevent secondary conditions. These changes are essential to improve outcomes for individuals with FASD and their families and facilitate dissemination of empirically supported interventions. PMID- 24178159 TI - Transgenic plant production mediated by Agrobacterium in Indica rice. AB - A reproducible system has been developed for the production of transgenic plants in indica rice using Agrobacterium-mediated gene transfer. Three-week-old scutella calli served as an excellent starting material. These were infected with an Agrobacterium tumefaciens strain EHA101 carrying a plasmid pIG121Hm containing genes for beta-glucuronidase (GUS) and hygromycin resistnace (HygR). Hygromycin (50 mg/l) was used as a selectable agent. Inclusion of acetosyringone (50MUM) in the Agrobacterium suspension and co-culture media proved to be indispensable for successful transformation. Transformation efficiency of Basmati 370 was 22% which was as high as reported in japonica rice and dicots. A large number of morphologically normal, fertile transgenic plants were obtained. Integration of foreign genes into the genome of transgenic plants was confirmed by Southern blot analysis. GUS and HygR genes were inherited and expressed in R1 progeny. Mendelian segregation was observed in some R1 progeny. PMID- 24178160 TI - Effect of oxygen-enriched aeration on regeneration of rice (Oryza sativa L.) cell culture. AB - The effect of the oxygen concentration in the aeration gas on regeneration from rice cells in bioreactor cultures was investigated. The efficiency of regeneration in cultures aerated with over 40% oxygen was higher than that in a flask culture. In the case of a culture in which the dissolved oxygen(DO) was saturated by aeration with air, the efficiency of regeneration was less than the half that of cultures aerated with 40% oxygen. In cultures with the DO levels controlled at 8,10 and 12 mg/l, the efficiency of regeneration was highest at 12 mg/l. In the oxygenenriched cultures, although cell aggregation was observed and the color of plantlets was relatively pale, more than 90% of them grew into healthy plants. PMID- 24178161 TI - Plant regeneration from protoplasts of Japanese lawngrass. AB - Embryogenic callus of Japanese lawngrass (Zoysia japonica Steud.) was induced from sterile mature seeds on LS medium with 5 mg / l of 2,4-D. Embryogenic callus selected visually under microscope was proliferated in liquid N6 medium with amino acids (N6-AA medium). Protoplasts were isolated from suspension cells by the treatment of enzyme mixture containing pectolyase Y-23 and cultured in K8p medium with 2 mg / l of 2,4-D at the density of 10(6) / ml. Plants were regenerated by transferring the protoplasts derived callus to MS medium and incubating at 28 degrees C under light for two months. Plantlets were successfully transplanted in the soil. PMID- 24178162 TI - A regeneration protocol for sunflower (Helianthus annuus L.) protoplasts. AB - Hypocotyl protoplasts of four different Helianthus annuus genotypes were cultivated for 22-28 days in agarose droplets covered with liquid medium. In the first week, supplementation of the medium with plant growth regulators was at a 0.8/1 ratio of cytokinin and auxin followed by a high auxin concentration in the second week and a cytokinin to auxin ratio of 8/1 in the third and fourth week. Following transfer onto solid medium containing cytokinin and auxin in a proportion of 40/1 morphogenic callus started to form globular structures that developed into leaf primordia. Subsequent shoot elongation and rooting were obtained on hormone free medium after dipping the cut shoots into high auxin solution. Thirteen weeks after protoplast isolation, plantlets could be transferred to the greenhouse. Shoot regeneration was obtained for all four cultivars (Florom-328, Cerflor, Euroflor, Frankasol) at different rates reflecting their regenerative potential. PMID- 24178163 TI - Production of transgenic soybean lines expressing the bean pod mottle virus coat protein precursor gene. AB - Soybean (Glycine max. Merrill. cv. Fayette) cotyledonary nodes were transformed with bean pod mottle virus (BPMV) coat protein precursor (CP-P) gene via Agrobacterium-mediated transformation. The transformation rate was low, and only five primary transformants derived from five different cotyledons were obtained from 400 original cotyledons. Southern blot hybridization verified the integration of the BPMV CP-P gene. Inheritance and expression of this gene in R1 plants were also demonstrated. About 30% of R2 plants derived from one transgenic line showed complete resistance to BPMV infection, as assessed by symptomatology and ELISA, suggesting that homozygous, but not hemizygous, plants exhibit the resistant phenotype. PMID- 24178164 TI - High frequency plant regeneration via somatic embryogenesis in cell suspension cultures of coriander (Coriandrum sativum L.). AB - Hypocotyl segments and zygotic embryos of coriander formed embryogenic calli at frequencies of up to 75% when cultured on MS medium supplemented with 1 mgl(-1) 2,4-D. Calli were transferred to MS liquid medium with 1 mgl(-1) 2,4-D to initiate cell suspension cultures. Embryogenic cells became finely dispersible in the medium as the subculture proceeded. Cultures were transferred to a nitrogen compound enriched liquid MS medium containing 2% sucrose and 0.1 mgl(-1) 2,4-D, and cultured two weeks before plating on MS basal medium. Approximately 75% of cell aggregates (1 to two mm in diameter) underwent development into globular to cotyledonary somatic embryos after two weeks of plating. Most of the embryos were subsequently regenerated into plantlets. Regenerants were successfully transplanted to potting soil and grown to maturity in a phytotron. PMID- 24178165 TI - Plant regeneration via somatic embryogenesis from protoplasts of Uganda cherry orange (Citropsis schweinfurthii). AB - Protoplasts isolated from embryogenic callus of Citropsis schweinfurthii (Engl.) Swing. & M. Kell were cultured in MT (Murashige and Tucker 1969) basal medium containing 5% sucrose supplemented with 0.0, 0.001, 0.01, 0.1 or 1.0 mg l(-1) BA, 0, 300, 600 or 900 mg l(-1) malt extract and 0.6 M sorbitol. The highest plating efficiency was obtained on MT basal medium containing 5% sucrose supplemented with 0.01 mg l(-1) BA and 600 mg l(-1) malt extract. MT basal medium containing 5% sucrose and supplemented with 0.01 mg l(-1) kinetin was found to be a medium suitable for the development of globular somatic embryos derived from protoplasts into heart-shaped somatic embryos with cotyledon-like structures. The highest percentage of shoot formation was obtained using 0.1 mg l(-1) GA3. A complete protoplast to-plant system was developed for C. schweinfurthii, which could facilitate the transfer of nuclear and cytoplasmic genes from this species into cultivated Citrus through protoplast fusion. PMID- 24178166 TI - In situ gynogenetic haploid plants of chicory (Cichorium intybus L.) after intergeneric hybridization with Cicerbita alpina Walbr. AB - The possibility of obtaining haploid plants of chicory (Cichorium intybus L.) was investigated through intergeneric hybridization. Chicory plants (industrial chicory and Chioggia) were pollinated with pollen of Lactuca tatarica L. and Cicerbita alpina Walbr. Many achenes contained embryos which were rescued in vitro. Only a few embryos developed into plants which were then acclimatized in soil. Among them, three expressed a chicory phenorype and were haploid. PMID- 24178167 TI - Condensed tannin and anthocyanin production in Vitis vinifera cell suspension cultures. AB - Suspension cultures of Vitis vinifera were cultured in different media in order to establish a model system for promoting high levels of phenolic substances identical with those found in wine. These media were: a low sucrose maintenance medium (MM) and four high sucrose media (differing mainly in sucrose and mineral contents) which were shown to induce secondary metabolism. In MM medium, polyphenol accumulation in the cells was low, and concentrations of 0.1 mg/gfw for condensed tannins and 0.3 mg/gfw for anthocyanins were reached within two weeks of cultivation. Values of 1.4 and 6.4 mg/gfw, respectively, were obtained with a low nitrate and high sucrose medium (HM1), but cell proliferation was reduced. To obtain a maximal production of polyphenols, we investigated the most effective conditions for cell growth and polyphenol production (a high mineral and high sucrose medium, IM1; inoculum dilution of 1.25:10). Under these conditions, the cells produced mainly anthocyanins (1100 mg/l), proanthocyanidins (300 mg/l) and catechins (25 mg/l). PMID- 24178168 TI - Transformation of haploid, microspore-derived cell suspension protoplasts of rice (Oryza sativa L.). AB - We compared the transient activity of three cereal gene-derived promoter-gus fusions and the efficiency of selection mediated by three different selectable genes in a polyethylene glycol transformation system with haploid cell suspension protoplasts of rice. The maize ubiquitin promoter was found to be the most active in transformed protoplasts, and selection on ammonium glufosinate mediated by the bar gene was the most efficient for producing resistant calluses. Cotransformation of protoplasts with two separate plasmids carrying the gus and the bar genes, at either a 2?1 or 1?1 ratio, led to 0.8 * 10(-5) and 1.6 * 10(-5) resistant callus recovery frequencies and 59.7 and 37.9 cotransformation efficiencies respectively. No escapes were detected in dot blot analyses of 100 resistant calluses with a probe consisting of the bar coding region. Cotransformation efficiency, based on resistance to basta and beta-glucuronidase staining of the leaf tissue of 115 regenerated plants, was 47%. Resistance tests and Southern analysis of seed progenies of three diploid transgenic plants demonstrated homozygous integration of multiple copies of the transgene at one locus at least in the first plant, heterozygous integration at one locus in the second plant and heterozygous integration at two loci in the third plant. PMID- 24178170 TI - Erratum. PMID- 24178169 TI - Environmental scanning electron microscopy of the surface of normal and vitrified leaves of Gypsophila paniculata (Babies Breath) cultured in vitro. AB - Leaf surfaces of non-tissue-cultured, vitrified and non-vitrified plantlets of Gypsophila paniculata (Babies Breath) were examined using an environmental scanning electron microscope. Non-tissue-cultured plants had a complete epidermal surface, recessed stomata and wax present on the leaf surface. The surface of tissue-cultured plantlets appeared similar to non-tissue-cultured plants excepting stomata were slightly protruding and less wax appeared to be present. In both non-tissue-cultured and tissue-cultured plants stomata were found both opened and closed and were observed closing. In contrast vitrified plantlets had abnormal, malformed stomata which appeared non-functional. The ventral surfaces of leaves seemed more normal than the dorsal, this may be due to the former receiving more light. Additionally, discontinuities were found in the epidermis. Often epidermal holes were found in association with stomatal apertures. It is suggested that the main cause of desiccation of vitrified G. paniculata plantlets ex vitro is due to loss of water from the discontinuity in epidermis and not because of non-functional stomata. Liquid water could be seen through the epidermal holes indicating that at least some of the extra water in vitrified plantlets is contained in the intercellular spaces. PMID- 24178171 TI - Specific binding of a Verticillium dahliae phytotoxin to protoplasts of cotton, Gossypium hirsutum. AB - The occurrence of specific, high-affinity binding sites for a protein lipopolysaccharide (PLP) phytotoxin purified from culture filtrates of a virulent Vertidllium dahliae isolate has been demonstrated in cotton protoplasts. Binding of the (125)I-radiolabelled PLP-complex to protoplasts from cotyledon tissue was saturable and with an affinity (Kd = 17.3 nM) comparable with the concentration required for biological activity. A single class of binding site, accessible at the surface of the intact protoplasts, was found and the maximal number of binding sites were estimated as 2.41 * 10(-16) moles per protoplast. The binding affinity to protoplasts proved near identical to that found with purified plasma membrane fractions from roots. When cultivars exhibiting resistance or susceptibility towards the pathogen were compared, no significant differences were found in the affinity of binding, but five times as many binding sites per protoplast and sixteen times as many binding sites per mg membrane protein were found in the resistant cultivar. PMID- 24178172 TI - Ploidy of small individual embryo-like structures from maize anther cultures treated with chromosome doubling agents and calli derived from them. AB - In order to determine the ploidy of individual embryo-like structures (ELSs) following chromosome doubling treatments, a method was developed to determine the DNA content (ploidy level) of nuclei from single ELSs weighing as little as 1 mg using flow cytometry. About half (53%) of the ELSs which formed during anther culture of the maize inbred line used in control medium were haploid, 27% mixoploid and 20% diploid. Gibberellic acid (GA3) increased the diploid percentage to 52% without affecting the mixoploid frequency (26%). A four day treatment with the chromosome doubling agent colchicine (50MUM) increased chromosome doubling while oryzalin eliminated the diploidy and mixoploidy. When regenerable callus cultures were initiated from the ELSs none were found to be mixoploid but the haploid and diploid proportions were similar to that of the ELSs analyzed. Regenerable cultures could not be initiated from the colchicine treated ELSs, however. These studies show that with the genotype used here, GA3 and colchicine increased the amount of chromosome doubling of the ELSs while oryzalin and pronamide did not. The mixoploidy which existed in about 25% of the ELSs was never observed in calli apparently because these structures do not initiate callus or cells of only one ploidy level grew. PMID- 24178173 TI - Purification and characterization of an alcohol dehydrogenase from Lithospermum erythrorhizon cell cultures. AB - An NAD-dependent alcohol dehydrogenase has been purified to apparent homogeneity from cell suspension cultures of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae), using protamine sulphate and ammonium sulphate precipitation and chromatography on DEAE-Sephacel, Superdex 200, hydroxyapatite and HiTrap blue. The enzyme is a homodimer with a Mr of ca. 77,000. Each subunit with a Mr of 40,000 contains two zinc atoms. Its isoelectric point was found at pH 5.0. The best alcohol substrate of the enzyme is ethanol. The pH optimum for ethanol oxidation is at pH 8.7 and for acetaldehyde reduction at pH 4.6. The Michaelis constants for ethanol and NAD are 2.49 and 0.05 (pH 8.7), and for acetaldehyde and NADH 2.2 and 0.078 mM (pH 4.6), respectively. Partial amino acid sequences of the purified enzyme showed high homology to alcohol dehydrogenases from other plants. PMID- 24178174 TI - Responses to NaCl stress of cultivated and wild tomato species and their hybrids in callus cultures. AB - If in vitro culture is to be used for evaluating the salt tolerance of tomato hybrids and segregant populations in a breeding programme, it is previously necessary to get quick and reliable traits. In this work, growth and physiological responses to salinity of two interspecific hybrids between the cultivated tomato (Lycopersicon esculentum Mill) and its wild salt-tolerant species L pennellii are compared to those of their parents. The leaf callus of the first subculture was grown on media amended with 0, 35, 70, 105, 140, 175 and 210 mM NaCl for 40 days. Relative fresh weight growth of callus in response to increased salinity in the culture medium was much greater in L pennellii than in the tomato cultivars, and greater in the hybrids than in the wild species. Moreover, the different salt tolerance degree of hybrids was related to that of female parents. At high salt levels, only Cl(-) accumulation was higher in L pennellii than in tomato cultivars, whereas in the hybrids both Cl(-), and Na(+) accumulation were higher than in their parents. Proline increased with salinity in the callus of all genotypes; these increases were much higher in the tomato cultivars than in L pennellii, and the hybrids showed a similar response to that of the wild species. Salt-treated callus of the tomato cultivars showed significant increases in valine, isoleucine and leucine contents compared to control callus tissue. In contrast, these amino acids in callus tissues of the wild species and hybrids showed a tendency to decrease with increasing salinity. PMID- 24178175 TI - Organogenesis in vitro of Nothofagus alpina (P. et E.) Oerst, Fagaceae. AB - In vitro shoot and root regeneration of 2-year-old Nothofagus alpina plants was achieved from several types of expiants cultured in vitro on a modified Woody Plant Medium formulation. Multiple shoot formation was obtained from leaf expiants using 0.45-2.27 MUM thidiazuron and 0.0049-0.098 MUM indolebutyric acid. Excised axillary buds formed shoots and roots in the presence of 0.0049 MUM benzyladenine and 2.46 MUM indolebutyric acid, or in the absence of plant growth regulators. Nodal sections rooted when 2.46 MUM indolebutyric acid at was supplied in the medium. Subcultured shoots originating from nodal sections showed a high regeneration rate through multiple shoot and root formation. PMID- 24178176 TI - Organocatalysed decarboxylative protonation process from Meldrum's acid: enantioselective synthesis of isoxazolidinones. AB - An asymmetric organocatalysed decarboxylative protonation reaction allowed a straightforward synthesis of alpha-substituted isoxazolidin-5-ones from readily available 5-substituted Meldrum's acids. This process is initiated by an anionic formal (3+2) cycloaddition-fragmentation, generated in-situ from a sulfone-amide precursor which also served as a latent source of proton. PMID- 24178177 TI - Turning on fluorescence by plasmonic assembly with large tunable spacing: a new observation and its biosensing application. AB - Assembling nanoparticle-film metallic junctions with a spacing of up to tens of nanometers efficiently turned on fluorophores attached to the film from the quenching status to an intense surface plasmon-coupled emission. Benefiting from this new finding, a fluorescence biosensor was created based on the use of a biomolecule-linked plasmonic assembly as the trigger. PMID- 24178178 TI - CK-19 mRNA-positive cells in peripheral blood predict treatment efficacy and survival in small-cell lung cancer patients. AB - Small-cell lung caner (SCLC) is the most aggressive form of lung cancer. The aim of this study was to investigate whether the presence of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) predicts treatment response, progression-free survival (PFS), and overall survival (OS) in SCLC patients who received standard therapy. Fifty-five SCLC patients were enrolled in this single center prospective study. CK-19 mRNA-positive CTCs in blood samples were detected using real-time quantitative-PCR assay before the initiation of chemotherapy (B0) and after one chemotherapy cycle (B1) and three chemotherapy cycles (B3). The association with known prognostic factors and the effect of CK-19 mRNA-positive CTCs on patients' prognosis were analyzed. Patients with positivity for CK-19 mRNA-positive CTCs at B0, B1, and B3 time points had shorter PFS and OS compared with patients without (P = 0.014 and P = 0.01, respectively, at B0; P = 0.008 and P = 0.002, respectively, at B1; P = 0.003 and P = 0.001, respectively, at B3). Conversion of initial positivity for CK-19 mRNA-positive CTCs to negativity at B1 and B3 time points was associated with longer PFS and OS compared with patients with persistent positivity at three time points (P = 0.008 and P = 0.010, respectively). Multivariate analysis demonstrated that the presence of CK-19 mRNA positive CTCs at B0, B1, and B3 time points remained strong predictors of PFS and OS after adjustment for clinically significant factors. In conclusion, detection of CK-19 mRNA-positive CTCs before and during chemotherapy is an accurate indication of subsequent disease progression and mortality for SCLC patients. PMID- 24178179 TI - Clinical outcomes after unplanned extubation in a surgical intensive care population. AB - BACKGROUND: Clinical outcome after unplanned extubation (UE) in patients admitted to the surgical intensive care unit (SICU) has not been fully investigated. In this study we assessed in-hospital mortality of patients with UE and determined whether UE is a predictor of in-hospital mortality. Finally, we sought to identify predictors of reintubation after UE in mechanically ventilated patients in the SICU. METHODS: Medical charts of patients (n = 4,407) admitted to the SICU between October 2007 and December 2011 were reviewed retrospectively. RESULTS: Eighty-five episodes of UE occurred in 81 patients. Patients with UE required emergency surgery more frequently and had higher ICU and hospital mortality rates, reintubation rate, and APACHE II scores and longer mechanical ventilation (MV) and ICU stay than patients without UE (P < 0.05 for all associations). Multivariate analysis revealed that reintubation (odds ratio [95 % confidence interval]: 4.14 [2.58-6.67]; P < 0.001), APACHE II scores (1.14 [1.12-1.17]; P < 0.001), emergency surgery (1.73 [1.18-2.53]; P = 0.005), and chronic neurologic disease (2.11 [1.30-3.41]; P = 0.002) were associated with hospital mortality. Reintubation was necessary in 17 patients. On multivariate analysis, a score on the Richmond Agitation-Sedation Scale (RASS, 0.48 [0.31-0.76]; P = 0.001), PaO2/FiO2 ratio (0.99 [0.99-1.00]; P = 0.048), and MV duration before UE (1.46 [1.08-1.98]; P = 0.014) were independently associated with reintubation after UE. CONCLUSIONS: Our results indicated that although patients with UE had high in hospital mortality, UE was not directly associated with in-hospital mortality. Reintubation, chronic neurologic disease, emergency operation, and higher APACHE II score were related to increased in-hospital mortality. A low RASS score, a low PaO2/FiO2 ratio, and long MV duration before UE were related to reintubation after UE. PMID- 24178180 TI - Flow disruptions during trauma care. AB - BACKGROUND: Flow disruptions (FDs) are deviations from the progression of care that compromise safety or efficiency. The frequency and specific causes of FDs remain poorly documented in trauma care. We undertook this study to identify and quantify the rate of FDs during various phases of trauma care. METHODS: Seven trained observers studied a Level I trauma center over 2 months. Observers recorded details on FDs using a validated Tablet-PC data collection tool during various phases of care-trauma bay, imaging, operating room (OR)-and recorded work system variables including breakdowns in communication and coordination, environmental distractions, equipment issues, and patient factors. RESULTS: Researchers observed 86 trauma cases including 72 low-level and 14 high-level activations. Altogether, 1,759 FDs were recorded (20.4/case). High-level trauma comprised a significantly higher number (p = 0.0003) and rate of FDs (p = 0.0158) than low-level trauma. Across the three phases of trauma care, there was a significant effect on FD number (p < 0.0001) and FD rate (p = 0.0005), with the highest in the OR, followed by computed tomography. The highest rates of FD per case and per hour were related to breakdowns in coordination. CONCLUSIONS: This study is the largest direct observational study of the trauma process conducted to date. Complexities associated with the critical patient who arrives in the trauma bay lead to a high prevalence of disruptions related to breakdowns in coordination, communication, equipment issues, and environmental factors. Prospective observation allows individual hospitals to identify and analyze these systemic deficiencies. Appropriate interventions can then be evaluated to streamline the care provided to trauma patients. PMID- 24178181 TI - Inter-facility transfer of surgical emergencies in a developing country: effects on management and surgical outcomes. AB - OBJECTIVES: Outcomes of surgical emergencies are associated with promptness of the appropriate surgical intervention. However, delayed presentation of surgical patients is common in most developing countries. Delays commonly occur due to transfer of patients between facilities. The aim of the present study was to assess the effect of delays in treatment caused by inter-facility transfers of patients presenting with surgical emergencies as measured by objective and subjective parameters. METHODS: We prospectively collected data on all patients presenting with an acute surgical emergency at Aga Khan University Hospital (AKUH). Information regarding demographics, social class, reason and number of transfers, and distance traveled were collected. Patients were categorized into two groups, those transferred to AKUH from another facility (transferred) and direct arrivals (non-transfers). Differences between presenting physiological parameters, vital statistics, and management were tested between the two groups by the chi square and t tests. RESULTS: Ninety-nine patients were included, 49 (49.5 %) patients having been transferred from another facility. The most common reason for transfer was "lack of satisfactory surgical care." There were significant differences in presenting pulse, oxygen saturation, respiratory rate, fluid for resuscitation, glasgow coma scale, and revised trauma score (all p values <0.001) between transferred and non-transferred patients. In 56 patients there was a further delay in admission, and the most common reason was bed availability, followed by financial constraints. Three patients were shifted out of the hospital due to lack of ventilator, and 14 patients left against medical advice due to financial limitations. One patient died. CONCLUSIONS: Inter facility transfer of patients with surgical emergencies is common. These patients arrive with deranged physiology which requires complex and prolonged hospital care. Patients who cannot afford treatment are most vulnerable to transfers and delays. PMID- 24178182 TI - Long-term outcome of patients with acute cholecystitis receiving antibiotic treatment: a retrospective cohort study. AB - BACKGROUND: Few studies have followed patients who received antibiotic treatment for acute cholecystitis (AC). The present retrospective study investigated recurrence rates of AC and analyzed factors associated with recurrence after antibiotic treatment in adult AC patients. METHODS: We analyzed patients treated with antibiotics for AC between October 1, 2004, and November 30, 2010. A Cox proportional hazards model was used to identify factors associated with early recurrence. Generalized additive models were applied to detect the nonlinear effects of continuous covariates. RESULTS: The study included 226 patients (mean age: 62.2 years; 144 men [63.7 %]). The average duration of parenteral antibiotics was 8.0 days. Second-generation cephalosporins were administered to 199 patients (88.1 %). The Kaplan-Meier plot indicated that recurrences were more frequent within 100 days of AC; these were defined as early recurrences. The recurrence rate was 13.7 % (31/226) at a median follow-up of 308.5 days (early recurrences: 19/226 [8.4 %]). The duration of parenteral antibiotic use significantly correlated with early recurrence (hazard ratio: 0.83; 95 % confidence interval, 0.73-0.95; p = 0.005). Generalized additive models revealed that patients using parenteral antibiotics longer than 8 days were less likely to suffer from early recurrence. CONCLUSIONS: The rate of recurrence of AC in patients who received antibiotics alone was low. The recurrence rate was higher within 100 days of AC. Because of the inherent limitations of a retrospective study, further research is needed to identify factors associated with early recurrence. PMID- 24178183 TI - Influence of intraoperative radiotherapy (IORT) on perioperative outcome after surgical resection of rectal cancer. AB - BACKGROUND: Intraoperative radiotherapy (IORT) for locally advanced or recurrent rectal cancer as an integral part of multimodal treatment might be an option to reduce local cancer recurrence. The aim of the present study was to determine the influence of IORT on the postoperative outcome and complications rates in the treatment of patients with adenocarcinoma of the rectum in comparison to patients with rectum resection only. METHODS: A total of 162 patients underwent operation for International Union against Cancer stage III/IV rectal cancer or recurrent rectal cancer at our surgical department between 2004 and 2012. They were divided into two groups depending on whether they received IORT or not. General patient details, tumor, and operation details, as well as perioperative major and minor complications, were registered and compared. RESULTS: Of the 162 patients treated for stage III/IV rectal cancer, 52 underwent rectal resection followed by IORT. Complication rates were similar in the two groups. Operative time was significantly longer in the IORT group (248 +/- 84 vs 177 +/- 68 min; p < 0.001). No significant differences were found concerning anastomotic leakage rate, hospital stay, or wound infection rate. CONCLUSIONS: Intraoperative radiotherapy appears to be a safe treatment option in patients with locally advanced or recurrent rectal cancer with acceptable complication rates. The effect on local recurrence rate has to be estimated in long-term follow-up. PMID- 24178184 TI - Use of spiral computed tomography volumetry for determining the operative approach in patients with Graves' disease. AB - BACKGROUND: The purposes of the present study were to assess (1) the correlation between the weight of the postoperative thyroid specimen and the spiral computed tomography (CT) volumetry results of the thyroid gland in patients with Graves' disease, and (2) the utility of CT volumetry for determining the operative approach. METHODS: From 2009 to 2010, a total of 56 patients with Graves' disease underwent total or subtotal thyroidectomy. An enhanced spiral CT was taken in all patients prior to the operation. From 2.5 mm-thick slices of the thyroid gland, the surface area was calculated to measure the volume of the thyroid gland. The glandular volume was compared to the weight of the postoperative thyroid specimen. RESULTS: A total of 42 and 14 patients underwent total and subtotal thyroidectomy, respectively. The mean weight of the postoperative thyroid specimen was 43.9 +/- 33.4 g, and the mean volume obtained by CT volumetry was 44.2 +/- 32.8 mL. A good correlation was observed between the weight of the postoperative thyroid specimen and the volume calculated by CT (r = 0.98, p < 0.001). When 100 mL was set as the higher cut-off value of the thyroid volume for minimally invasive thyroid surgery, the estimated blood loss showed a significant difference between the >100 mL and the <=100 mL groups (608.3 +/- 540.8 vs. 119.7 +/- 110.4 mL; p = 0.036). CONCLUSIONS: Spiral CT volumetry may be used to measure the thyroid volume reliably in patients with Graves' disease. For cases in which surgery is indicated in patients with Graves' disease, CT volumetry provides useful information from which to determine the operative approach. One hundred milliliter or less of thyroid volume in CT volumetry is recommended to perform minimally invasive thyroid surgery. PMID- 24178185 TI - Perioperative immunonutrition in surgical cancer patients: a summary of a decade of research. AB - BACKGROUND: Immunonutrition is assumed to enhance immune system function. In surgical patients, it is supposed to reduce postoperative complications. However, results of recent clinical trials have been puzzling and have not supported this theory. AIM: The aim of our study was to evaluate the value of enteral and parenteral postoperative immunonutrition. METHODS: After initial evaluation of 969 patients, the intent-to-treat analysis included 776 patients (female 407, male 466, mean age 61.1 years) undergoing gastric or pancreatic resections between 2001 and 2009. All patients were randomly assigned after surgery to one of the following groups: standard enteral nutrition (SEN), immunomodulating enteral nutrition (IMEN), standard parenteral nutrition (SPN), or immunomodulating parenteral nutrition (IMPN). All malnourished patients received preoperative parenteral nutrition. Number and type of postoperative complications, length of hospitalization (length of stay [LOS]), and vital organ function were assessed. RESULTS: No statistically significant differences were observed in well-nourished patients, during either enteral or parenteral intervention, independent of the type of intervention (standard or immunomodulating). However, analysis of the malnourished group revealed the positive impact of enteral immunonutrition on reduction of postoperative complications (28.3 vs. 39.2 %, respectively; p = 0.043) and LOS (17.1 and 13.1 days, respectively; p < 0.05) compared with a standard enteral diet. The cross analysis of SEN, IMEN, SPN, and IMPN was insignificant. CONCLUSIONS: The type of postoperative nutrition was of no importance in well-nourished patients. However, in malnourished patients, enteral immunonutrition helped to improve treatment outcome. These findings suggest its use as a method of choice during the postoperative period. PMID- 24178186 TI - How allele frequency and study design affect association test statistics with misrepresentation errors. AB - We evaluate the effect of genotyping errors on the type-I error of a general association test based on genotypes, showing that, in the presence of errors in the case and control samples, the test statistic asymptotically follows a scaled non-central $?chi ^2$ distribution. We give explicit formulae for the scaling factor and non-centrality parameter for the symmetric allele-based genotyping error model and for additive and recessive disease models. They show how genotyping errors can lead to a significantly higher false-positive rate, growing with sample size, compared with the nominal significance levels. The strength of this effect depends very strongly on the population distribution of the genotype, with a pronounced effect in the case of rare alleles, and a great robustness against error in the case of large minor allele frequency. We also show how these results can be used to correct $p$-values. PMID- 24178187 TI - Joint modeling of ChIP-seq data via a Markov random field model. AB - Chromatin ImmunoPrecipitation-sequencing (ChIP-seq) experiments have now become routine in biology for the detection of protein-binding sites. In this paper, we present a Markov random field model for the joint analysis of multiple ChIP-seq experiments. The proposed model naturally accounts for spatial dependencies in the data, by assuming first-order Markov dependence and, for the large proportion of zero counts, by using zero-inflated mixture distributions. In contrast to all other available implementations, the model allows for the joint modeling of multiple experiments, by incorporating key aspects of the experimental design. In particular, the model uses the information about replicates and about the different antibodies used in the experiments. An extensive simulation study shows a lower false non-discovery rate for the proposed method, compared with existing methods, at the same false discovery rate. Finally, we present an analysis on real data for the detection of histone modifications of two chromatin modifiers from eight ChIP-seq experiments, including technical replicates with different IP efficiencies. PMID- 24178188 TI - Ingestion and absorption of particles derived from different macrophyta in the cockle Cerastoderma edule: effects of food ration. AB - We analyzed the capacity of the common cockle Cerastoderma edule to utilize detrital food particles obtained from three different macrophytes: the vascular plant Juncus maritimus and two green macroalgae (Ulva lactuca and Enteromorpha sp.). We measured feeding and digestive parameters at three concentrations of detritus (0.5, 1.0 and 3.0 mm(3) l(-1)), so that functional relationships between ingestive and digestive processes could be assessed. Increasing concentrations of detritus (food) resulted in a reduction in filtering activity (clearance rate l h(-1)), but an increase in ingestion rate. Consequently, gut content also increased with increasing food concentration, irrespective of food type. In contrast, the trend followed by absorption efficiency with increasing ingestion rate was determined by food type, being significantly reduced (from 0.63 to 0.11) with Juncus but remaining almost constant with the green macroalgae (0.58 +/- 0.07 with Ulva) or only minimally reduced (from 0.66 to 0.48 with Enteromorpha). This differential response had clear consequences for energy uptake: absorption rate increased with increasing particulate organic matter with Enteromorpha but decreased with Juncus. We discuss the possible role of digestive parameters such as digestibility, gut content and gut-residence time in the differential utilization of detrital matter from different vegetal origins by cockles. PMID- 24178189 TI - Development of universal influenza vaccines based on influenza virus M and NP genes. AB - PURPOSE: Vaccination is the safest and most effective measure against influenza virus infections. However, traditional influenza vaccines cannot respond effectively to an unforeseen epidemic or pandemic caused by a virus with antigenic drifts or antigenic shifts. Therefore, developing a universal influenza vaccine (UIV) that induces broad-spectrum and long-term immunity has become a major trend in influenza vaccine research and development. METHODS: This article reviews the development of UIVs based on these conserved influenza virus proteins. RESULTS AND CONCLUSION: The matrix protein (M1, M2) and nucleoprotein (NP) of influenza viruses have highly conserved sequences, and they become the major target antigens of current UIV studies. PMID- 24178190 TI - Influence of variation in the catechol-O-methyltransferase gene on the clinical outcome after lumbar spine surgery for one-level symptomatic disc disease: a report on 176 cases. AB - BACKGROUND: This study was aimed at the evaluation of the relationship between genetic polymorphisms of catechol-O-methyltransferase (COMT) (rs4680:A > G Val158Met, rs6269:A > G, rs4633:C > T, rs4818:C > G) and pain sensitivity after lumbar discectomy. METHODS: All patients had one-level symptomatic disc herniation from L3 to S1. The primary data recorded included visual analogue pain scales assessing back and leg pain, Oswestry Disability Questionnaire assessing quality of life and pain intensity, received/filled pre- and postoperatively. Each subject was genotyped for single-nucleotide polymorphism in the COMT gene. Clinical outcome was measured by difference between pre- and postoperative values and those results were analyzed with genetics findings. RESULTS: Pain intensity was associated with the COMT polymorphism. Carriers of rs6269 AA, rs4633 TT, rs4818 CC, and rs4680 AA genotypes were characterized by the lowest preoperative scores related to pain intensity and lower pain intensity at 1 year after the surgery. The rs4633 CC, rs4680 GG genotypes demonstrated significant clinical improvement in VASBACK score at 1 year after the surgery. Patients with COMT haplotype associated with low metabolic activity of enzyme (A_C_C_G) showed better clinical outcome measured by ODI score and VASBACK score 1 year after surgery. We did not observe any significant correlation between leg pain and single-nucleotide polymorphisms in the COMT gene. CONCLUSIONS: The results of our study indicate that polymorphism in the COMT gene may play an important role in the mechanism of pain perception, which may have a potential implication for clinical decision-making in the future. PMID- 24178192 TI - Role of external carbonic anhydrase in light-dependent alkalization by Fucus serratus L. and Laminaria saccharina (L.) Lamour. (Phaeophyta). AB - It has been proposed that many marine macroalgae are able to utilize HCO 3 (-) for photosynthesis and growth, and that energy-dependent ion pumping is involved in this process. We have therefore studied the light-dependent alkalization of the surrounding medium by two species of marine macroscopic brown algae, Fucus serratus L. and Laminaria saccharina (L.) Lamour. with the aim of investigating the role of extracellular carbonic anhydrase (EC 4.2.1.1.) in the assimilation of inorganic carbon from the seawater medium. In particular, the influence of membrane-impermeable or slowly permeable carbonic-anhydrase inhibitors on the rate of alkalization of the seawater has been investigated. Inhibition of the alkalization rate occurred in both species at an alkaline pH (pH 8.0) but no inhibition was observed at an acidic pH (pH 6.0). The alkalization was found to be light-dependent and inhibited by 3-(3',4'-dichlorophenyl)-1, 1-dimethylurea and, thus, correlated with photosynthesis. Alkalization by macroalgae has previously been shown to be proportional to inorganiccarbon uptake. We suggest that alkalization of the medium at alkaline pH in both of the species examined is mainly the consequence of an extracellular reaction. The reaction is catalyzed by extracellular carbonic anhydrase which converts HCO 3 (-) to OH(-) and CO2; CO2 is then taken up through the plasmalemma. However, we do not exclude the involvement of other mechanisms of inorganic-carbon uptake. PMID- 24178191 TI - Illness management and recovery: a review of the literature. AB - OBJECTIVE: Illness Management and Recovery (IMR) is a standardized psychosocial intervention that is designed to help people with severe mental illness manage their illness and achieve personal recovery goals. This literature review summarizes the research on consumer-level effects of IMR and articles describing its implementation. METHODS: In 2011, the authors conducted a literature search of Embase, MEDLINE, PsycINFO, CINAHL, and the Cochrane Library by using the key words "illness management and recovery," "wellness management and recovery," or "IMR" AND ("schizophrenia" OR "bipolar" OR "depression" OR "recovery" OR "mental health"). Publications that cited two seminal IMR articles also guided further exploration of sources. Articles that did not deal explicitly with IMR or a direct adaptation were excluded. RESULTS: Three randomized-controlled trials (RCTs), three quasi-controlled trials, and three pre-post trials have been conducted. The RCTs found that consumers receiving IMR reported significantly more improved scores on the IMR Scale (IMRS) than consumers who received treatment as usual. IMRS ratings by clinicians and ratings of psychiatric symptoms by independent observers were also more improved for the IMR consumers. Implementation studies (N=16) identified several important barriers to and facilitators of IMR, including supervision and agency support. Implementation outcomes, such as participation rates and fidelity, varied widely. CONCLUSIONS: IMR shows promise for improving some consumer-level outcomes. Important issues regarding implementation require additional study. Future research is needed to compare outcomes of IMR consumers and active control groups and to provide a more detailed understanding of how other services utilized by consumers may affect outcomes of IMR. PMID- 24178193 TI - Cloning and expression analysis of the plastidic fructose-1,6-bisphosphatase coding sequence from potato: circumstantial evidence for the import of hexoses into chloroplasts. AB - A copy DNA encoding the plastid-located isoform of the fructose-1,6 bisphosphatase (cp-FBPase) has been cloned from potato (Solanum tuberosum L.). Sequence analysis reveals a high degree of homology to cp-FBPases from wheat, spinach, and Arabidopsis. Analysis of RNA blots shows that the expression of the cp-FBPase is limited to green tissue such as leaf and stem, and is absent from photosynthetically inactive tissue such as roots, tubers and stolons. This provides additional evidence that hexoses or hexose phosphates are imported into amyloplasts of heterotrophic tissues. Incubation of detached leaves of potato in darkness in a sucrosecontaining medium leads to massive accumulation of both starch and transcripts encoding starch biosynthetic enzymes. However, no transcripts encoding the cp-FBPase are detectable under these conditions. PMID- 24178194 TI - Purification and characterization of an L-amino-acid oxidase from Chlamydomonas reinhardtii. AB - An L-amino-acid oxidase (EC 1.4.3.1) that catalyzes the oxidative deamination of twelve L-amino acids has been purified 21-fold and with 14% yield to electrophoretic homogeneity from Chlamydomonas reinhardtii cells by ammonium sulfate fractionation, gel filtration through Sephacryl and Superose, anion exchange chromatography and preparative electrophoresis in polyacrylamide gels. The native enzyme is a protein of 470 kDa and consists of eight identical or similarsized subunits of 60 kDa each. Optimum pH and temperature were 8.2 and 55 degrees C, respectively, with a Q10 (45-55 degrees C) of 1.7 and an activation energy of 45 kJ . mol(-1). Its absorption spectrum showed, in the visible region, maxima at 360 and 444 nm, characteristic of a flavoprotein with a calculated flavin content of 7.7 mol FAD per mol of native enzyme. Apparent K m values of the twelve L-amino acids which can act as substrates of L-amino-acid oxidase ranged between 31 MUM for phenylalanine and 176 MUM for methionine. The effect of several specific group reagents, chelating agents and bivalent cations on enzyme activity has also been studied. PMID- 24178195 TI - Components of chlorophyll biosynthesis in a barley albina mutant unable to synthesize delta-aminolevulinic acid by utilizing the transfer RNA for glutamic acid. AB - Components of chlorophyll biosynthesis were investigated in the plastid-ribosome deficient albostrians mutant of barley (Hordeum vulgare L.). Compared with green leaves, white leaves lacked chloroplast tRNA(Glu) and 16S ribosomal RNA, but contained a much higher level of the mRNA for glutamate 1-semialdehyde aminotransferase. Substantial amounts of protochlorophyllide were accumulated when the mutant was incubated in a solution of delta-aminolevulinic acid. The level of protochlorophyllide oxidoreductase mRNA (PCOR, EC 1.6.99.1.) in etiolated albostrians plants reached only about 50% of the level in wild-type plants. In addition the content of PCOR protein and the activity of chlorophyll synthetase were distinctly lower than in the wild-type. Mutant and wild-type barley seedlings which were grown under a daily light/dark regime and were therefore nonetiolated both possessed PCOR mRNA. The data presented may help explain the albino phenotype of this mutant. The results are discussed in relation to biosynthesis of tetrapyrrols in higher plants, regulation of chlorophyll biosynthesis and the action of a plastidderived signal involved in the expression of certain nuclear genes. PMID- 24178196 TI - Endogenous rhythms and chaos in crassulacean acid metabolism. AB - Endogenous free-running regular circadian oscillations of net CO2 exchange in the crassulacean-acidmetabolism (CAM) plant Kalanchoe daigremontiana Hamet et Perrier de la Bathie under constant external conditions in continuous light have been shown to change to irregular non-predictable (chaotic) time behaviour as irradiance or temperature are raised above a critical level. A model of CAM has been constructed with pools of major metabolites of varying concentrations, flows of metabolites leading to exchange between pools, metabolite transformations determined by chemical reactions, and feedback regulations. The model is described by a system of coupled non-linear differential equations. It shows stable rhythmicity in normal dark-light cycles and in continuous light and, like the K. daigremontiana leaves in the experiments, a change to chaos as irradiance is increased. The maintenance of endogenous oscillations in the model is brought about by a hysteresis switch or beat oscillator between two stable oscillation modes. In CAM these stable modes are vacuolar malate accumulation and remobilization. The model shows that the physical nature of the beat oscillator in the leaves can be explained by the balance between active and passive transport at the tonoplast. PMID- 24178197 TI - Light-regulated expression of the nitrate-reductase and nitrite-reductase genes in tomato and in the phytochrome-deficient aurea mutant of tomato. AB - The phytochrome-deficient aurea mutant of tomato (Lycopersicon esculentum (L.) Mill) was used to investigate if phytochrome plays a role in the regulation of nitrate-reductase (NR, EC 1.6.6.1) and nitrite-reductase (NiR, EC 1.7.7.1) gene expression. We show that the expression of the tomato NR and NiR genes is stimulated by light and that this light response is mediated by the photoreceptor phytochrome. The red-light response of the NR and NiR genes was reduced in etiolated aurea seedlings when compared to isogenic wild-type cotyledons. The relative levels of NR mRNA and NiR transcripts and their diurnal fluctuations were identical in mature white-light-grown leaves of the wild-type and of the aurea mutant. The transcript levels for cab and RbcS (genes for the chlorophyll a/b-binding protein of PSII and the small subunit of the enzyme ribulose-1,5 bisphosphate carboxylase/oxygenase, respectively) in aurea leaves grown in white light were indistinguishable from the respective transcript levels in the leaves of the wildtype grown under the same conditions. Despite a severe reduction in the chlorophyll content, the rate of net CO2 uptake by leaves of the aurea mutant was only slightly reduced when compared to the rate of net photosynthesis of wild type leaves. This difference in the photosynthetic performances of wild-type and aurea mutant plants disappeared during aging of the plants. The increase in zeaxanthin and the concomitant decrease in violaxanthin in leaves of the aurea mutant compared with the same pigment levels in leaves of the wild-type indicate that the activity of the xanthophyll cycle is increased in aurea leaves as a consequence of the reduced CO2-fixation capacity of the mutant leaves. PMID- 24178198 TI - Purification and characterization of isoforms of cinnamyl alcohol dehydrogenase from Eucalyptus xylem. AB - Two distinct isoforms of cinnamyl alcohol dehydrogenase, CAD 1 and CAD 2, have been purified to homogeneity from xylem-enriched fractions of Eucalyptus gunii Hook and partially characterized. They differ greatly in terms of both physical and biochemical properties, and can be separated by hydrophobic interaction chromatography on Phenyl Sepharose CL-4B. The native molecular weight of of CAD 1 is 38 kDa as determined by gel-filtration chromatography on Superose 6, and this isoform is likely to be a monomer since it yields a polypeptide of 35 kDa upon sodium dodecyl sulfatepolyacrylamide gel electrophoresis. It has a low substrate affinity for coniferyl and p-coumaryl alcohols and their corresponding aldehydes. No activity with sinapyl aldehyde and alcohol was detected. The more abundant isoform is CAD 2, which has a native molecular weight of 83 kDa and is a dinier composed of two subunits of slightly different molecular weights (42-43 kDa). These subunits show identical peptide patterns after digestion with N chlorosuccinimide. The isoform, CAD 2, has a high substrate affinity for all the substrates tested. The two isoforms are immunologically distinct as polyclonal antibodies raised against CAD 2 do not cross-react with CAD 1. The characterization of two forms of CAD exhibiting such marked differences indicates their involvement in specific pathways of monolignol utilisation. PMID- 24178199 TI - Calcium-dependent protein kinase in the green alga Chara. AB - Cytoplasmic streaming in the characean algae is inhibited by micromolar rises in the level of cytosolic free Ca(2+), but both the mechanism of action and the molecular components involved in this process are unknown. We have used monoclonal antibodies against soybean Ca(2+)-dependent protein kinase (CDPK), a kinase that is activated by micromolar Ca(2+) and co-localizes with actin filaments in higher-plant cells (Putnam-Evans et al., 1989, Cell Motil. Cytoskel. 12, 12-22) to identify and localize its characean homologue. Immunoblot analysis revealed that CDPK in Chara corralina Klein ex. Wild shares the same relative molecular mass (51-55 kDa) as the kinase purified from soybean, and after electrophoresis in denaturing gels is capable of phosphorylating histone III-S in a Ca(2+)-dependent manner. Immunofluorescence microscopy localized CDPK in Chara to the subcortical actin bundles and the surface of small organelles and other membrane components of the streaming endoplasm. The endoplasmic sites carrying CDPK were extracted from internodal cells by vacuolar perfusion with 1 mM ATP or 10(-4) M Ca(2+). Both the localization of CDPK and its extraction from internodal cells by perfusion with ATP or high Ca(2+) are properties similar to that reported for the heavy chain of myosin in Chara (Grolig et al., 1988, Eur. J. Cell Biol. 47, 22-31). Based on its endoplasmic location and inferred enzymatic properties, we suggest that CDPK may be a putative element of the signal transduction pathway that mediates the rapid Ca(2+)-induced inhibition of streaming that occurs in the characean algae. PMID- 24178200 TI - Vanadate-sensitive ATPase in the plasmalemma of Acetabularia: biochemical and kinetic characterization. AB - The electrogenic Cl(-)-pump in the plasmalemma of the marine alga Acetabularia acetabulum (L.) Silva has been suggested to be an unusual type of ATPase (Gradmann, 1989, Methods Enzymol. 174, 490). For a biochemical treatment of this issue, a plasmalemma-rich membrane fraction from Acetabularia has been prepared by phase-partitioning. About 80% of the ATPase activity in this material is inhibited by vanadate (K I50=1-2 MUM). The phosphohydrolytic properties of the corresponding enzyme were further investigated. Its primary substrate MgATP(2-) (K m about 270 MUM). Compared with other plasmalemma ATPases, it has an extremely alkaline pH optimum (pH 8-8.5), a weak sensitivity to diethyl-stilbestrol and to N,N'-dicyclohexylcarbodiimide, a strong selectivity for Mg(2+) over alternative divalent cations, and a weak selectivity for ATP over other phosphohydrolytic substrates. It is insensitive to KCl at concentrations up to 200 mM. Both ATP(4-) and Mg2ATP inhibit the ATPase, satisfying a relationship for competitive inhibition by 2ATP(4-) (K IATP=1.56 mM) and noncompetitive inhibition by Mg2ATP (K IMg2ATP=1.35 mM). Since no transport experiments are reported in this study, the ion species (H(+) or Cl(-)) that is transferred by this ATPase is not identified. PMID- 24178201 TI - Cytokinins and leaf development in sweet pepper (Capsicum annuum L.) : I. Spatial distribution of endogenous cytokinins in relation to leaf growth. AB - Immunoaffinity purification of zeatin, dihydrozeatin and isopentenyl-type cytokinins from expanding leaves of sweet pepper was accomplished using a single immobilized monoclonal antibody. Isopentenyl adenosine, zeatin, zeatin riboside and the N9-glucosides of zeatin and isopentenyl adenine were found to be the dominating endogenous cytokinins while the dihydrozeatin cytokinins were either absent or constituted a very minor group of cytokinin metabolites in pepper. Leaves were selected for analysis at an age where a range of developmental stages exist within a single leaf. The spatial distribution of endogenous cytokinins in rapidly expanding leaves at this stage was markedly different from the almost uniform distribution in expanded leaves. The distribution of zeatin and zeatin riboside in rapidly expanding leaves was found to be correlated with the rate of leaf expansion which is high (~40%/24 h) in the basal leaf tissue and low (~10%/24 h) near the leaf tip. Applied growtn factors supported a rate of expansion of excised discs comparable to the growth rates observed in situ, but did not affect the ability of the tissue to retain assimilated amino acids. The results are discussed in relation to sink-strength stimultation as a potential mode of cytokinin action in leaf development. PMID- 24178202 TI - Cytokinins and leaf development in sweet pepper (Capsicum annuum L.) : II. Sink metabolism in relation to cytokinin-promoted leaf expansion. AB - Stimulation of leaf expansion by an exogenous cytokinin was studied in isolated leaf discs of sweet pepper with emphasis on the assimilate utilization of the tissue. Leaf discs were floated on solutions containing sucrose and plant growth regulators. Benzyladenine (BA) promoted the area expansion rate of the leaf discs. Sucrose at 100 mM resulted in increased area expansion rate compared with 10 mM sucrose. However, the increased sucrose concentration had no influence on the effect of BA. Over a period of 24 h, treatment with BA did not result in any change of sucrose uptake nor of the partitioning of assimilated carbon in the leaf discs. Neither did BA treatment affect the activity of acid invertase (EC 3.2.1.26) or pyrophosphate-dependent phosphofructokinase (EC 2.7.1.90) in the leaf discs. We conclude that the observed promotion of leaf area expansion by exogenous BA is not mediated through the uptake of sucrose or the carbohydrate metabolism of the leaf tissue. PMID- 24178203 TI - Indole-3-acetic acid levels after phytochrome-mediated changes in the stem elongation rate of dark- and light-grown Pisum seedlings. AB - The effect of red (R) and far-red (FR) light on stem elongation and indole-3 acetic acid (IAA) levels was examined in dwarf and tall Pisum sativum L. seedlings. Red light reduced the extension-growth rate of etiolated seedlings by 70-90% after 3 h, and this inhibition was reversible by FR. Inhibition occurred throughout the growing zone. After 3 h of R, the level of extractable IAA in whole stem sections from the growing zone of etiolated plants either increased or showed no change. By contrast, extractable IAA from epidermal peels consistently decreased 3 h after R treatments. Decreases of 40% were observed for epidermal peels from the top 1 cm of tall plants receiving 3 h R. Brief R treatments resulted in smaller decreases in epidermal IAA levels and these decreases were not as great when FR followed R. In lightgrown plants, end-of-day FR stimulated growth during the following dark period in a photoreversible manner. The uppermost 1 cm of expanding third internodes was most responsive to the FR. Extractable IAA from epidermal peels from the upper 1 cm of third internodes increased by 30% or more 5 h after FR. When R followed the FR the increases were smaller. Levels of IAA in whole stem sections did not change and were twofold greater than in dark-grown plants. In both dark- and light-grown tall plants, IAA levels were lower in epidermal peels than in whole stem segments. These results provide evidence that IAA is compartmentalized at the tissue level within the growing stem and that phytochrome regulation of stem elongation rates may be partly based on modulating the level of IAA within the epidermis. PMID- 24178204 TI - A high-yield procedure for isolation of metaphase chromosomes from root tips of Vicia faba L. AB - A new method is described for the isolation of large quantities of Vicia faba metaphase chromosomes. Roots were treated with 2.5 mM hydroxyurea for 18 h to accumulate meristem tip cells at the G1/S interface. After release from the block, the cells re-entered the cell cycle with a high degree of synchrony. A treatment with 2.5 MUM amiprophos-methyl (APM) was used to accumulate mitotic cells in metaphase. The highest metaphase index (53.9%) was achieved when, 6 h after the release from the hydroxyurea block, the roots were exposed to APM for 4 h. The chromosomes were released from formaldehyde-fixed root tips by chopping with a scalpel in LB01 lysis buffer. Both the quality and the quantity of isolated chromosomes, examined microscopically and by flow cytometry, depended on the extent of the fixation. The best results were achieved after fixation with 6% formaldehyde for 30 min. Under these conditions, 1 . 10(6) chromosomes were routinely obtained from 30 root tips. The chromosomes were morphologically intact and suitable both for high-resolution chromosome studies and for flow-cytometric analysis and sorting. After the addition of hexylene glycol, the chromosome suspensions could be stored at 4 degrees C for six months without any signs of deterioration. PMID- 24178205 TI - Microtubule organization differs between acid and alkaline bands in internodal cells of Chara but bands can develop in the absence of microtubules. AB - We have studied the relationship between pH banding and the organization of cortical microtubules in the alga Chara corallina Klein ex Willd. Microtubules were visualized by immunofluorescence and also by imunogold-silver enhancement to allow immediate comparison of microtubule arrangement with visible structural cell features. In cells that are nearing growth completion, microtubule number and alignment change between acidic and alkaline bands over a distance of a few micrometres. Thus, it appears that the still unknown mechanisms for microtubule organization respond to the localized differences in membrane properties. Band formation was not prevented when microtubules were depolymerized with the herbicide oryzalin, demonstrating that microtubules are not necessary for pH bands to develop in these cells. PMID- 24178206 TI - Spectral-dependence of light-inhibited hypocotyl elongation in photomorphogenic mutants of Arabidopsis: evidence for a UV-A photosensor. AB - Photon fluence rate-response curves at different wavelengths were generated for the light-induced inhibition of hypocotyl elongation in seedlings of wildtype and photomorphogenic mutants of Arabidopsis thaliana. (L.) Heynh. Treatment of wild type seedlings with continuous low-fluence-rate light (< 1.0 MUmol photons . m( 2) . s(-1)) induced some inhibition of hypocotyl elongation at all wavelengths tested, with maximum inhibition in blue light. At higher fluence rates, inhibition reached a maximum of 70-80% in UV-A, blue, and far-red light. Fluence rate-response curves for seedlings of blu1, a blue light-response mutant, showed a specific reduction in their response to blue light, but their response to UV-A, red, and far-red light was similar to that in wild-type seedlings. In contrast, the phytochromedeficient mutant hy6 showed a loss of response to lowfluence-rate light at all wavelengths, as well as to highfluence-rate far-red light. However, hy6 seedlings retained sensitivity to high-fluence-rate blue and UV-A light. The data support the conclusion that blue-lightand phytochrome-dependent photosensory systems regulate hypocotyl elongation independently and in an additive manner. Furthermore, hypocotyl inhibition in wild-type, blul, hy6 and blul-hy6 double mutants was indistinguishable in UV-A light, whereas marked differences were observed at other wavelengths, indicating the involvement of a third photosensory system with an absorption maximum in the UV-A. PMID- 24178207 TI - Intracellular redistribution of phytochrome in etiolated soybean (Glycine max L.) seedlings. AB - The intracellular distribution of phytochrome in hypocotyl hooks of etiolated soybean (Glycine max L.) has been examined by immunofluorescence using a newly produced monoclonal antibody (Soy-1) directed to phytochrome purified from etiolated soybean shoots. Cortical cells in the hook region exhibit the strongest phytochrome-associated fluorescence, which is diffusely distributed throughout the cytosol in unirradiated, etiolated seedlings. A redistribution of immunocytochemically detectable hytochrome to discrete areas (sequestering) following irradiation with red light requires a few minutes at room temperature in soybean, whereas this redistribution is reversed rapidly following irradiation with far-red light. In contrast, sequestering in oat (Avena sativa L.) occurs within a few seconds (D. McCurdy and L. Pratt, 1986, Planta 167, 330-336) while its reversal by far-red light requires hours (J. M. Mackenzie Jr. et al., 1975, Proc. Natl. Acad. Sci. USA 72, 799-803). The time courses, however, of red-light enhanced phytochrome pelletability and sequestering are similar for soybean as they are for oat. Thus, while these observations made with a dicotyledon are consistent with the previous conclusion derived from work with oat, namely that sequestering and enhanced pelletability are different manifestations of the same intracellular event, they are inconsistent with the hypothesis that either is a primary step in the mode of action of phytochrome. PMID- 24178208 TI - Auxin autonomy in cultured tobacco teratoma tissues transformed by an auxin mutant strain of Agrobacterium tumefaciens. AB - We have studied the mechanism of auxin autonomy in tobacco (Nicotiana tabacum L.) crowngall tissues transformed by the auxin-mutant (tms (-)) A66 strain of Agrobacterium tumefaciens. Normally, tms (-) tobacco tumor tissues require the formation of shoots to exhibit auxin-independent growth in culture. We have isolated from tms (-) tobacco cells several stable variants that are fully hormone-independent and grow rapidly as friable, unorganized tissues, thus mimicking the growth and morphology of tms (+) tobacco cells that produce high levels of auxin. However, none of the variants contained the high levels of auxin found in tms (+) tumor cells. The variants could be divided into two classes with respect to their response to applied auxin. The first class was highly sensitive to applied auxin: low concentrations (1 MUM) of alpha-naphthaleneacetic acid (NAA) severely inhibited growth and markedly stimulated the accumulation of the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC). The second class of variants showed a low sensitivity to applied auxin: growth was promoted by concentrations of NAA up to 10 MUM, and growth inhibition and high ACC levels were observed only at high NAA concentrations (100 MUM). Unorganized variants with low auxin sensitivity were also isolated from a variant line with high auxin sensitivity. The isolation of tumor cells that exhibited the growth phenotype of tms (+) cells while retaining the low auxin content and low auxin sensitivity of tms (-) cells indicates that full hormone autonomy, characteristic of wild-type crown-gall tumors, can be achieved by a mechanism that is independent of changes in the auxin physiology of the cells. PMID- 24178209 TI - Ectomycorrhizins - symbiosis-specific or artitactual polypeptides from ectomycorrhizas? AB - Fungal mycelium of the fly agaric (Amanita muscaria [L. ex Fr.] Hooker), and inoculated or noninoculated seedlings of Norway spruce (Picea abies [L.] Karst.) were grown aseptically under controlled conditions. In order to detect symbiosis specific polypeptides ('ectomycorrhizins', see Hubert and Martin, 1988, New Phytol. 110, 339-346) the protein patterns of (i) fungal mycelium, (ii) mycorrhizal, and (iii) non-mycorrhizal root tips were compared by means of one- and twodimensional electrophoresis on a microscale. Because of the sensitivity of these micromethods (50 and 200 ng of protein, respectively), single mycorrhizal root tips and even the minute quantities of extramatrical mycelium growing between the roots of inoculated plants could be analysed. Differences in the protein patterns of root tips could be shown within the root system of an individual plant (mycorrhizal as well as non-mycorrhizal). In addition, the protein pattern of fungal mycelium grown on a complex medium (malt extract and casein hydrolysate) differed from that of extramatrical mycelium collected from the mycorrhiza culture (pure mineral medium). Such differences in protein patterns are obviously due to the composition of the media and/or different developmental stages. Consequently, conventional analyses which use extracts of a large number of root tips, are not suitable for differentiating between these effects and symbiosis-specific differences in protein patterns. In order to detect ectomycorrhizins, it is suggested that roots and mycelium from individual, inoculated plants should be analysed. This approach eliminates the influence of differing media, and at the same time allows a correct discrimination between developmental and symbiosisspecific changes. In our gels we could only detect changes in spot intensity but could not detect any ectomycorrhizins or the phenomenon of polypeptide 'cleansing', which both characterize the Eucalyptus Pisolithus symbiosis (Martin and Hubert, 1991, Experientia 47, 321-331). We thus suggest that these reported effects either are specific for the Eucalyptus Pisolithus symbiosis or simply represent artifacts. The latter point of view is strengthened by a comparison of the experimental approaches. PMID- 24178210 TI - Ectomycorrhizins - symbiosis-specific or artifactual polypeptides from ectomycorrhizas? AB - Fungal mycelium of the fly agaric (Amanita muscaria [L. ex Fr.] Hooker), and inoculated or noninoculated seedlings of Norway spruce (Picea abies [L.] Karst.) were grown aseptically under controlled conditions. In order to detect symbiosis specific polypeptides ('ectomycorrhizins', see Hubert and Martin, 1988, New Phytol.110, 339-346) the protein patterns of (i) fungal mycelium, (ii) mycorrhizal, and (iii) non-mycorrhizal root tips were compared by means of one- and twodimensional electrophoresis on a microscale. Because of the sensitivity of these micromethods (50 and 200 ng of protein, respectively), single mycorrhizal root tips and even the minute quantities of extramatrical mycelium growing between the roots of inoculated plants could be analysed. Differences in the protein patterns of root tips could be shown within the root system of an individual plant (mycorrhizal as well as non-mycorrhizal). In addition, the protein pattern of fungal mycelium grown on a complex medium (malt extract and casein hydrolysate) differed from that of extramatrical mycelium collected from the mycorrhiza culture (pure mineral medium). Such differences in protein patterns are obviously due to the composition of the media and/or different developmental stages. Consequently, conventional analyses which use extracts of a large number of root tips, are not suitable for differentiating between these effects and symbiosis-specific differences in protein patterns. In order to detect ectomycorrhizins, it is suggested that roots and mycelium from individual, inoculated plants should be analysed. This approach eliminates the influence of differing media, and at the same time allows a correct discrimination between developmental and symbiosisspecific changes. In our gels we could only detect changes in spot intensity but could not detect any ectomycorrhizins or the phenomenon of polypeptide 'cleansing', which both characterize theEucalyptus Pisolithus symbiosis (Martin and Hubert, 1991, Experientia47, 321-331). We thus suggest that these reported effects either are specific for theEucalyptus Pisolithus symbiosis or simply represent artifacts. The latter point of view is strengthened by a comparison of the experimental approaches. PMID- 24178211 TI - Transgenic plant production from leaf discs of Moricandia arvensis using Agrobacterium tumefaciens. AB - A high frequency shoot regeneration (80%) was developed from callus of leaf discs and stem internodes of Moricandia arvensis. Leaf discs were shown to be a preferable starting material for transformation experiments. Agrobacterium tumefaciens strain GV3101/pMP90 used in this study contained a binary vector with genes for kanamycin resistance, hygromycin resistance and beta-glucuronidase (GUS). Maximum transformation efficiency (10.3%) was achieved by using kanamycin at the rate of 200 mg/l as a selection agent. Presence of tobacco suspension culture during co-cultivation and a pre-selection period of seven days after co cultivation was essential for successful transformation. Transgenic plants grew to maturity and exhibited flowering in a glasshouse. GUS activity was evident in all parts of leaf and the presence of GUS gene in plant gemone was confirmed by PCR analysis. PMID- 24178212 TI - Screening for stable transformants and stability of beta-glucuronidase gene expression in suspension cultured cells of tall fescue (Festuca arundinacea). AB - By screening cell colonies derived from protoplasts of tall fescue (Festuca arundinacea), transformed with a rice actin-1-promoter-beta-glucuronidase gene construct, several beta-glucuronidase positive callus clones were obtained. Two callus clones with different GUS expression were derived from these. One was light blue after X-gluc staining, and expression of the beta-glucuronidase gene was stable over repeated subculture, while another stained intensely blue, and expression of the beta-glucuronidase gene was unstable. Southern blot analysis showed that only one copy of the beta-glucuronidase gene was integrated into the genome, and that these two clones appeared to have the same integration pattern. Treatment with 5-azacytidine maintained GUS expression in the unstable line but had no effect on reactivating expression of the GUS gene after expression had been lost. Following the screening procedure the callus clones would only regenerate albino plants. PMID- 24178213 TI - Transformation of cucumber (Cucumis sativus L.) plants using Agrobacterium tumefaciens and regeneration from hypocotyl explants. AB - Transgenic cucumber (Cucumis sativus L.) plants were successfully obtained from hypocotyl explants inoculated with Agrobacterium tumefaciens, which harbored a binary vector plasmid with NOS-nptII, CaMV 35S-I-gus and CaMV 35S-hph genes. Acetosyringone enhanced the efficiency of transformation at the cut surface cells of hypocotyl explants during five days of co-cultivation. Transformed cells were more effectively selected using 20-30 mg/l hygromycin B than using 50-100 mg/l kanamycin. Shoot regeneration occurred within 4-6 wks, and 12 of 21 regenerated plantlets displayed strong GUS expression in the very young leaves. All of 8 GUS positive R0 plants examined showed single or a few positive bands by Southern blot analysis. The expression of the CaMV 35S-I-gus gene was observed in various tissues and organs of R0 and R1 transgenic cucumber plants. PMID- 24178214 TI - DNA methylation and Dc8-GUS transgene expression in carrot (Daucus carota L.). AB - DNA methylation has been associated with gene activity in differentiating and developing plant tissues. The objective of this study was to determine the involvement of methylation in the expression of a gene transferred into carrot (Daucus carota L.) tissues by particle bombardment. Expression of the Dc8-GUS gene construct in response to treatments with 5-azacytidine (S-azaC) and to in vitro methylation by methylases was investigated by histochemical assay of GUS activity. The 5-azaC treatment increased the frequency of Dc8-driven GUS expression in both calli and somatic embryos. The increase occurred with treatment either to E. coli containing the plasmid insert or to the carrot tissues before bombardment. GUS expression, increased by the 5-azaC treatment, was enhanced by ABA treatment of both calli and somatic embryos and was more prominent in the latter. Increased digestion of the 5-azaC-treated plasmid DNA with EcoRII suggested that demethylation had occurred. In vitro methylation of Dc8-GUS by methylases generally resulted in a lower frequency of GUS expression. SssI methylase completely inhibited GUS expression. The level of GUS expression was correlated with the extent of methylation of the plasmid. PMID- 24178215 TI - Cannabis 25 (1), biotransformation of cannabidiol and cannabidiolic acid by Pinellia ternata tissue segments. AB - Two marihuana constituents, cannabidiol (1) and cannabidiolic acid (4) were each converted mainly to two metabolites using tissue segments of Pinellia ternata tuber. The structures of the metabolites formed from 1 were determined to be 1 Obeta-D-glucopyranoside and 1-Obeta-D-diglucopyranoside by (1)H nmr, (13)C nmr and fabms. Those from 4 were determined as 4-Obeta-D-glucopyranoside and 10' hydroxyl 4-Obeta-D-glucopyranoside. In time course experiments, 1 was absorbed rapidly by the tissues and glucosylated. Hydroxylation subsequent to the glucosylation occurred at the pentyl group in 4. PMID- 24178216 TI - Protoplasts from Phytolacca dodecandra L'Herit (endod) and P. americana L. (pokeweed). AB - Pokeweed (Phytolacca americana L.) and endod (P. dodecandra L'Herit) produce ribosome-inactivating proteins which are sequestered in leaf cell walls. These proteins display strong antiviral activity. To aid in studying the antiviral mechanism, we developed protocols to isolate protoplasts from suspension culture cells and leaves. Ninety-five percent of pokeweed or endod culture cells were converted to protoplasts using 2% cellulase, 0.25% pectinase, 0.2 M mannitol, 2% sucrose, 15 mM CaCl2 Murashige and Skoog salts, pH 5.7. Viability was >85% after 24 h. Culture-derived protoplasts were purified by centrifugation through a 15% sucrose pad. Protoplasts collected from the supernatant were then pelleted in 0.3 M mannitol. Pokeweed leaves provided respectable yields (4*10(6) protoplasts/g f w) of partially-purified viable protoplasts when digested in solution containing 1% cellulase, 0.2% Pectolyase, 0.4 M mannitol, CPW salts, 0.5 mM MES, pH 5.6. We were unable to completely separate cell debris from mesophyll protoplasts, which were small and easily damaged by centrifugation. Endod leaves were found to be resilient to several digestion enzymes tested. PMID- 24178217 TI - Androgenesis of the salt tolerant shrub Atriplex glauca. AB - Clusters of flowers, 4 to 5 days old, were successfully cultured on Nitsch and Nitsch (1969) medium in the presence of growth regulators. An average of 20 plants per explant were produced after 6 weeks. Organized growth was obtained only from flowers collected during spring or early summer. Microscopic observations during shoot regeneration indicated that shoot organogenesis took place directly from microspores to give rise to shrubby plants. Their subsequent transfer onto fresh medium in the presence of a different set of growth regulators resulted in the production of "haploid" and "diploid" lines in the proportion of 50?50. The presumed haploid plants were successfully rooted on Woody Plant Medium (Lloyd and McCown 1980) within a week. The significance of androgenic lines for the study of salt tolerance and the genetic improvement of Atriplex forage quality is discussed. PMID- 24178219 TI - Erratum. PMID- 24178218 TI - Ferricyanide reductase of rose plasma membranes is regulated by nitrogen supply. AB - The ability of suspension-cultured rose (Rosa damascena Mill. cv Gloire de Guilan) cells to reduce ferricyanide is decreased by 50% during an overnight incubation in a low-nutrient (1 mM CaCl2, 0.1 mM KCl) solution. This loss is not observed when nitrate and/or glutamate is added to the low-nutrient medium, but it occurs in medium containing all the components needed for normal growth except nitrate plus glutamate. Thus, the cells possess both constitutive and inducible enzymes for the reduction of ferricyanide, and nitrate or glutamate is both necessary and sufficient to stimulate the production of the inducible enzyme. PMID- 24178220 TI - Effect of promoter-leader sequences on transient expression of reporter gene chimeras biolistically transferred into sugarbeet (Beta vulgaris) suspension cells. AB - Chimeric constructs consisting of the gus coding region fused downstream of promoterun-translated leader sequences from the tobacco osmotin and PR-S genes, the potato proteinase inhibitor 2 gene (pin2), and the cauliflower mosaic virus (CaMV) 35S promoter were biolistically transferred into sugarbeet suspension cells. Each construct was expressed in recipient cells at 6 h after bombardment with maximum levels observed between 12 and 48 h. Expression of the PR-S construct mimicked the time-course expression of the constitutively expressed 35S construct but reached levels almost 50% higher. The pin2-promoter construct was ultimately expressed at levels similar to that of PR-S. Expression of the osmotin promoter-leader construct was highest, reaching levels approximately 2.5-fold higher than those of the 35S construct. PMID- 24178221 TI - Micropropagation of a fruit tree, Morus australis Poir. syn. M. acidosa Griff. AB - High frequency bud break and multiple shoots were induced in nodal explants collected between November to February from a 5 year old tree of Morus australis Poir syn. M. acidosa Griff. on Murashige and Skoog's medium supplemented with 6 benzylaminopurine (1.0 mg/1). Incorporation of gibberellic acid (0.3 mg/l) along with BAP (1.0 mg/l) not only induced faster bud break from nodal explants as well as from apical shoot buds, but it also enhanced the frequency of bud break. Nodal explants were more responsive than apical shoot buds. The shoots formed in vitro were multiplied further as nodal segments, and an average multiplication rate of 6-fold per subculture was established within 4-5 months. The shoots were successfully rooted on half-strength MS containing a combination of indole-3 acetic acid, indole-3-butyric acid and indole-3-propionic acid, each at 1.0 mg/1. The plantlets were successfully hardened off and established in natural soil. PMID- 24178222 TI - In vitro propagation of the medicinal herbs Ocimum americanum L. syn. O. canum Sims. (hoary basil) and Ocimum sanctum L. (holy basil). AB - A procedure is outlined for in vitro propagation of two medicinal herbs, Ocimum americanum L. syn. O. canum Sims (hoary basil) and Ocimum sanctum L. (holy basil), using axillary shoot buds. Multiple shoot formation was induced from shoot bud explants of both species on Murashige and Skoog medium (MS) supplemented with benzyladenine (BA). The optimum BA concentrations for shoot proliferation were 0.25 mg/l for O. americanum and 1.0 mg/l for O. sanctum. Incorporation of 0.5 mg/l gibberellic acid (GA3) along with BA in the culture medium resulted in a marked increase in the frequency of axillary branching as well as multiple shoot formation. Shoot buds collected between September through December were most responsive in culture. Shoots of O. americanum were rooted on half-strength MS supplemented with 1.0 mg/l indole-3-butyric acid (IBA), whereas O. sanctum rooted best on medium with 1.0 mg/l naphthaleneacetic acid (NAA). The plantlets were hardened off and successfully established in natural soil, where they grew and matured normally. PMID- 24178223 TI - Antiauxin enhanced microshoot initiation and plant regeneration from epicotyl originated thin-layer explants of sugarbeet (Beta vulgaris L.). AB - An in vitro method was developed for microshoot initiation from thin-layer explants prepared from the elongated epicotyls of sugarbeet (Beta vulgaris L.). Intact epicotyls of 14-day-old seedlings were excised from the hypocotyls above the cotyledons and allowed to elongate on De Greef and Jacobs (1979) medium supplemented with 0.2 mg/l 6-benzyladenine, 0.2 mg/l gibberellic acid and 0.1 mg/l indole-3-acetic acid in darkness. After a 21-day-incubation, the elongated epicotyls were halved to obtain apical and basal segments prior to removing the leaves and lateral buds. Subsequently, 5-8 mm long, 2-3 mm wide and 0.8-1.0 mm thick tangential sections were prepared longitudinally from the exterior parts of the halved epicotyls. These thin-layer explants were incubated on microshoot initiating media containing various growth regulators. The combination of 1.0 mg/l 6-benzyladenine and the antiauxin 2,3,5-triiodobenzoic acid (1.0 mg/l) resulted in maximum microshoot development (6.3+/-0.2 microshoots/thin-layer explant). The final efficiency of our tissue culture system was significantly increased by the NaCl (100 mg/l) initiated in vitro rooting of microshoot originated plantlets. PMID- 24178224 TI - Somatic embryogenesis and regeneration of triploid plants in endosperm cultures of Acacia nilotica. AB - Immature endosperm of Acacia nilotica formed a nodular callus on MS medium supplemented with 2,4-D, BAP and CH. In the third passage on this medium, in the dark, the callus differentiated somatic embryos. The embryos germinated on MS only after 15 d pre-treatment on modified MS medium in which major salts were replaced by those of major salts of B5 medium and supplemented with glutamine, CH and CW. Triploid nature of the somatic embryos was confirmed by Feulgen cytophotometry. PMID- 24178225 TI - Regeneration of plants from cryopreserved embryogenic cell suspension and callus cultures of cotton (Gossypium hirsutum L.). AB - Successful regeneration of cotton (Gossypium hirsutum L.) plants from cryopreserved embryogenic callus and cell suspension cultures is described. The cryoprotectant mixture consisting of a modified Murashige and Skoog (1962) medium with sucrose (5% w/v), DMSO (5% v/v) and glycerol (5% v/v) gave the highest survival rate (70%) from cell suspension cultures cryopreserved in liquid nitrogen after slow cooling (0.5 to 1.0 degrees C/min). A cooling rate of 0.5 degrees C/min provided a satisfactory recovery rate (30%) from cryopreserved embryogenic callus cultures and was superior to a cooling rate of 1 degrees C/min. Regenerated plants from cell suspension and embryogenic callus cultures cryopreserved for more than four years exhibited normal morphology, growth and boll set upon transfer to soil. PMID- 24178226 TI - Direct somatic embryogenesis and plant regeneration from single cell suspension cultures of Elymus giganteus Vahl. AB - A yellowish, nodular callus was induced from mature embryos of Elymus giganteus Vahl on MS medium containing 2.0 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.5 mg/l kinetin, from which a cell suspension culture was initiated in liquid MS medium supplemented with 0.5 mg/l 2,4-D, 1.0 mg/l kinetin and 0.2 mg/1 naphthaleneacetic acid (NAA). By filtering through a series of sieves with decreasing mesh sizes and collecting the resultant filtrate, a suspension culture composed mainly of single embryogenic cells was established. In a medium containing 0.3 mg/l 2,4-D, 1.0 mg/l 6-benzylaminopurine (6-BAP) and 500 mg/l casein hydrolysate (CH), the single cells underwent direct somatic embryogenesis resulting in the formation of proembryos. These proembryos developed into mature embryos when placed in a double-layer liquid overlay culture. Intact plants were developed from somatic embryos when they were transferred onto solidified MS medium without added growth regulators. PMID- 24178227 TI - Phenylacetic acid induced organogenesis in cultured leaf segments of Dianthus chinensis. AB - Shoot regeneration was achieved from leaf derived callus of Dianthus chinensis using Phenylacetic acid (PAA). Callus from basal leaf segments, raised on Murashige and Skoog's (MS) medium containing 2,4-dichlorophenoxyacetic acid (2,4 D) or 1-Naphthaleneacetic acid (NAA) in combination with 6-benzylamino purine (BAP), was subcultured on medium supplemented with BAP in combination with 2,4-D, NAA or PAA. Shoots were induced only when leaf derived callus was subcultured on medium containing BAP (2.0, 5.0 mg/l) in combination with PAA (0.5, 1.0 mg/l). No shoot regeneration was observed when 2,4-D, NAA or BAP were used in the medium either singly or in different combinations. These results demonstrate that PAA in combination with BAP was essential to trigger shoot regeneration from cultured leaf callus of D. chinensis. PMID- 24178228 TI - Cryopreservation of non-encapsulated embryogenic tissue of sweet potato (Ipomoea batatas). AB - Embryogenic tissue of the sweet potato (Ipomoea batatas (L) LAM) genotype TIB 10 was established from in vitro axillary shoot tips on Murashige and Skoog (1962) medium supplemented with 5 MUM 2,4-dichlorophenoxyacetic acid. Embryogenic aggregates of fresh mass 9.0-12 mg were subjected to a rapid freezing protocol in liquid nitrogen following sucrose preculture and varying degrees of dehydration. Up to 50% of embryogenic explants survived rapid freezing after preculture on 0.4 or 0.7M sucrose only. Dehydration with silica gel to moisture contents in the range 18-41% improved the survival after cryopreservation of embryogenic tissue. Tissue dehydrated for intermediate periods exhibited poor survival. Following freezing, embryogenic tissue appeared to develop normally, retaining its competence to produce mature embryos and plantlets. PMID- 24178229 TI - Occurrence and partitioning of phenolic endocrine-disrupting chemicals (EDCs) between surface water and suspended particulate matter in the north Tai Lake basin, eastern China. AB - Concentrations and distribution of octylphenol (OP), nonylphenol (NP), and bisphenol A (BPA) in surface water and suspended particulate matter (SPM) from the north Tai Lake basin, China were studied. Aqueous and particulate (dry weight) concentrations for OP, NP, and BPA varied from 10.5-1,175 ng/L to <1.52 5,365 ng/g, respectively. The spatial distribution of endocrine-disrupting chemicals (EDCs) in dissolved and particulate phases showed that the amount of EDCs in water that were adsorbed to SPM gradually increased from upstream to downstream. There were good correlations between particulate EDCs and particulate organic carbon, with correlation coefficients of 0.46-0.57. Regression analysis of in situ SPM-water partition coefficients (log K' oc) and log K ow for EDCs indicated that the hydrophobicity of chemicals greatly contributed to their SPM water partitioning. Strong positive correlations (r = 0.68-0.82) among in situ log K' oc of OP, NP, and BPA and flow velocity of water were observed, indicating the critical importance of riverine hydrodynamics on the sorption of these compounds. PMID- 24178230 TI - Determination and source identification of polycyclic aromatics hydrocarbons in Karaj River, Iran. AB - Sixteen priority polycyclic aromatic hydrocarbons (PAHs) were measured in six stations in Karaj River, which is the main resource of drinking water in Tehran. The single PAHs concentrations ranged from not detected to 2,327.8 ng L(-1), with a mean value of 31.5 ng L(-1). The total PAHs concentrations ranged from 25.6, in the spring, to 4,040.3 ng L(-1), in the summer. PAHs concentrations in different sampling stations were similar (p = 0.33-0.99), but strong relationships were detected between seasonal variations and total PAHs, BaP equivalent and carcinogen PAHs concentration (p = 0.010-0.037). Results showed that carcinogen PAHs comprised 7 %-92 % of detected PAHs in different sampling stations. The concentration of benzo(a)pyrene, as an indicator, was lower than the permissible limit of the World Health Organization; however, in some samples, carcinogen PAHs concentrations were higher than the permissible limits of the European Union and USA Environmental Protection Agency regulations for drinking water. PMID- 24178231 TI - Influence of atrazine on the scalation of Marcy's checkered gartersnake, Thamnophis m. marcianus (Baird and Girard, 1853). AB - Atrazine is one of the most commonly used herbicides in the United States. Despite the effectiveness of atrazine in eliminating broadleaf and grassy weeds, there has been growing concern over the potential impacts this chemical may have on non-target organisms. Little research has been conducted on the exposure of reptiles to this chemical. Our study examined the effects of environmentally relevant concentrations of atrazine on the scalation of Marcy's checkered gartersnake (Thamnophis m. marcianus). Our results indicate that atrazine exposure influences scalation, in particular, cranial scale counts. In addition, this alteration of morphology happens during embryological development as the result of the environment the mother was raised in. Further research on additional species and developmental exposure of atrazine and how it influences fitness of reptiles is required. PMID- 24178232 TI - Cationically rendered biopolymer surfaces for high protein affinity support matrices. AB - The use of cationic biopolymer surfaces for high protein binding affinity matrices is described. As model proteins, fluorescently labeled bovine serum albumins (FITC-BSA, TRITC-BSA) have been employed. The amount of proteins on such cationically rendered surfaces was quantified by QCM-D. In addition, flexible, transparent, patterned COP slides have been prepared and loaded with proteins ranging from 15 pM to 15 MUM TRITC-BSA. PMID- 24178234 TI - Sonographic determination of normal Conus Medullaris level and ascent in early infancy. AB - INTRODUCTION: Controversial reports exist in the literature regarding both the spinal level of the conus medullaris (CM) in normal infants and the age at which the CM achieves its adult level. Autopsy studies have demonstrated ascent continuing into early infancy while more recent imaging study series' suggest the adult conus level is attained by the 40th postmenstrual week. METHODS: The authors conducted a retrospective review of 1,273 screening lumbar ultrasound studies performed over 5 years at a pediatric tertiary referral center. All patients were infants referred for initial imaging to rule out the presence of a tethered spinal cord. Referral sources included urban academic, urban private practice, and rural private practice pediatricians. After excluding studies lacking sufficient documentation (n = 90) and those reported as abnormal (n = 106), 1,077 remained for review. The CM level and patient age in days were recorded from each study. Statistical analysis was performed using unpaired t testing and ANOVA for continuous variables; chi-square for categorical data. RESULTS: The mean CM level for infants in group I (ages 0-30 days) was compared to those in groups II (31-60 days) and group III (61-100 days). Group I had a mean CM level of 0.125 and 0.2 vertebral segments lower than groups II and III (p = 0.0005 and <0.0001, respectively). ANOVA comparison of all three groups confirmed a rostral migratory trend (p < 0.001). The prevalence of CM level caudal to L2 in group I was 13 %, group II 11.4 %, and group III 4.7 %; also indicating a significant rostral trend (p = 0.004). CONCLUSIONS: Rostral migration of CM level continues through the first few months of post-natal life, albeit of limited extent. Documentation of continued ascent in a neonate may obviate the need for magnetic resonance imaging. PMID- 24178233 TI - Stem cells for brain repair in neonatal hypoxia-ischemia. AB - Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain. PMID- 24178235 TI - Management of respiratory motion in extracorporeal high-intensity focused ultrasound treatment in upper abdominal organs: current status and perspectives. AB - Extracorporeal high-intensity focused ultrasound (HIFU) is a minimally invasive therapy considered with increased interest for the ablation of small tumors in deeply located organs while sparing surrounding critical tissues. A multitude of preclinical and clinical studies have showed the feasibility of the method; however, concurrently they showed several obstacles, among which the management of respiratory motion of abdominal organs is at the forefront. The aim of this review is to describe the different methods that have been proposed for managing respiratory motion and to identify their advantages and weaknesses. First, we specify the characteristics of respiratory motion for the liver, kidneys, and pancreas and the problems it causes during HIFU planning, treatment, and monitoring. Second, we make an inventory of the preclinical and clinical approaches used to overcome the problem of organ motion. Third, we analyze their respective benefits and drawbacks to identify the remaining physical, technological, and clinical challenges. We thereby consider the outlook of motion compensation techniques and those that would be the most suitable for clinical use, particularly under magnetic resonance thermometry monitoring. PMID- 24178236 TI - Pharmacokinetics of mirabegron, a beta3-adrenoceptor agonist for treatment of overactive bladder, in healthy Japanese male subjects: results from single- and multiple-dose studies. AB - BACKGROUND: Mirabegron is a human beta3-adrenoceptor agonist for the treatment of overactive bladder. The pharmacokinetic profile of mirabegron has been extensively characterized in healthy Caucasian subjects. OBJECTIVE: The objective of this study was to evaluate the pharmacokinetics, dose-proportionality, and tolerability of mirabegron following single and multiple oral doses in healthy Japanese male subjects. The results were compared with those reported in non Japanese (primarily Caucasian) subjects. METHODS: Two studies were conducted. In a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study (Study 1), mirabegron oral controlled absorption system (OCAS) tablets were administered at single doses of 50, 100, 200, 300, and 400 mg, with eight subjects (six active, two placebo) per dose group (Part I), and once daily for 7 days at 100 and 200 mg with 12 subjects (eight active, four placebo) per group (Part II). In an open-label, three-period, single-ascending dose study (Study 2), mirabegron OCAS was administered to 12 subjects at 25, 50, and 100 mg in an intra-subject dose-escalation design. Plasma and/or urine samples were collected up to 72 h after the first and last dose and analyzed for mirabegron. Pharmacokinetic parameters were determined using non-compartmental methods. Tolerability assessments included physical examinations, vital signs, 12 lead electrocardiogram, clinical laboratory tests (biochemistry, hematology, and urinalysis), and adverse event (AE) monitoring. RESULTS: Forty and 24 young male subjects completed Part I and II, respectively, of Study 1. Twelve young males completed Study 2. After single oral doses (25-400 mg), maximum plasma concentrations (C max) were reached at approximately 2.8-4.0 h postdose. Plasma exposure (C max and area under the plasma concentration-time curve) of mirabegron increased more than dose proportionally at single doses of 25-100 mg and approximately dose proportionally at high doses of 300 and 400 mg. A more than dose proportional increase in plasma exposure was noted in the body of the same individual. Mirabegron accumulated twofold upon once-daily dosing relative to single-dose data. Steady state was reached within 7 days. Mirabegron was generally well-tolerated at single doses up to 400 mg and multiple doses up to 200 mg. The AE with the highest incidence was increased pulse rate at 400 mg in Study 1. CONCLUSIONS: Mirabegron OCAS exhibits similar single- and multiple-dose pharmacokinetic characteristics and deviations from dose proportionality in healthy Japanese male subjects compared with those observed in non-Japanese (primarily Caucasian) subjects in previous studies. PMID- 24178237 TI - Comparison of algorithms for oral busulphan area under the concentration-time curve limited sampling estimate. AB - BACKGROUND AND OBJECTIVES: Therapeutic drug monitoring (TDM) of the first dose of busulphan during conditioning prior to allogeneic stem cell transplantation provides the possibility of improving the clinical outcome via dose adjustment of subsequent doses. The plasma area under the concentration-time curve (AUC) for busulphan is generally accepted as the parameter that gives the best exposure estimate; however, the sampling frequency needed for reliable AUC calculation remains controversial. The aim of the present investigation was to develop and evaluate a limited sampling model for oral busulphan. METHODS: We have compared models using three to four samples with standard WinNonlin((r)) adaptive compartment modeling based on eight samples as reference. The evaluated study population included both adult and pediatric patients, but the linear model was devised using analysis of only pediatric patient plasma concentrations. The present model was developed using data from 23 patients with a mean age of 38 years (range 13-59 years) and was evaluated in 20 pediatric patients with a mean age of 6 years (range 0.1-13 years) as well as 23 adult patients (mean age 43 years; range 18-67 years). RESULTS: In 23 patients, the mean AUC from a curve fitting model (Purves method) and a single compartment model had an intraclass correlation coefficient (ICC) of 0.947. From a log-log plot of AUC values it was evident that using this estimate of the AUC would affect dose adjustment decisions for very few of the patients. Applying the linear model using three samples resulted in an ICC of 0.932, mostly due to worse performance in the adult population. CONCLUSIONS: The present results support the use of limited sampling in clinical TDM for oral busulphan provided adequate algorithms and sampling times are used. Moreover, they also demonstrate the caution that is needed when transferring a pharmacokinetic model from a pediatric population to an adult population. PMID- 24178238 TI - Pharmacokinetics, safety and tolerability of rotigotine transdermal patch in healthy Japanese and Caucasian subjects. AB - BACKGROUND AND OBJECTIVES: Rotigotine is a dopamine receptor agonist with activity across the D1 through to D5 receptors as well as select serotonergic and adrenergic sites; continuous transdermal delivery of rotigotine with replacement of the patch once daily maintains stable plasma concentrations over 24 h. Rotigotine is indicated for the treatment of early and advanced-stage Parkinson's disease and moderate-to-severe idiopathic restless legs syndrome. The pharmacokinetics and pharmacodynamics of a drug may vary between subjects of different ethnic origin. This study evaluated the pharmacokinetics, safety, and tolerability of single-dose treatment with rotigotine transdermal patch in Japanese and Caucasian subjects. METHODS: In this open-label, parallel-group study, healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by sex, body mass index, and age. A single transdermal patch delivering 2 mg/24 h rotigotine (patch content 4.5 mg) was applied to the ventral/lateral abdomen for 24 h. The main outcome measures were the plasma concentrations of unconjugated and total rotigotine and its desalkyl metabolites and derived pharmacokinetic parameters (area under the concentration-time curve from time zero to last quantifiable concentration [AUClast], maximum plasma concentration [Cmax], and body weight- and dose-normalized values). RESULTS: The pharmacokinetic analysis included 48 subjects (24 Japanese, 24 Caucasian). The mean apparent dose of rotigotine was 2.0+/-0.5 mg for Japanese subjects and 2.08+/-0.58 mg for Caucasians. Plasma concentration-time profiles of unconjugated rotigotine and of the main metabolites were similar for both ethnic groups. Parameters of model-independent pharmacokinetics, Cmax, time to Cmax (tmax), and AUClast, for unconjugated rotigotine showed no statistically significant differences between Japanese and Caucasian subjects. Values of concentration dependent pharmacokinetic parameters were higher in female subjects; this difference was minimized after correction for body weight. A statistically significant difference between ethnic groups was observed for total rotigotine concentrations (total rotigotine=unconjugated rotigotine+conjugated rotigotine), with slightly lower values in Caucasians after correction for body weight and apparent dose. No relevant differences were observed between males and females. Inter-individual variability was high. The terminal half-life for unconjugated rotigotine was 5.3 h in Japanese subjects and 5.7 h in Caucasians; corresponding values for total rotigotine were 8.6 h and 9.6 h. Less than 0.1% of the apparent dose was renally excreted as the parent compound. Renal elimination of total rotigotine covers 11.7% of absorbed dose in Japanese subjects and 10.8% of the absorbed dose in Caucasians, whereas the renal elimination via total despropyl rotigotine was 8.2 and 7.1%, respectively. The corresponding values for total desthienylethyl rotigotine were 3.5% in Japanese subjects and 4.2% Caucasians. Most adverse events were mild in intensity and typical for dopamine agonists or for transdermal therapeutics. CONCLUSION: Administration of a single patch delivering 2 mg/24 h rotigotine resulted in comparable pharmacokinetic profiles in Japanese and Caucasian subjects. The rotigotine transdermal patch was generally well-tolerated. Our findings suggest similar dose requirements for Japanese and Caucasian populations. PMID- 24178239 TI - NF-kappaB-mediated miR-30b regulation in cardiomyocytes cell death by targeting Bcl-2. AB - Angiotensin II(Ang II)-stimulated cardiomyocytes hypertrophy and apoptosis are associated with nuclear factor-kappaB (NF-kappaB) activation. NF-kappaB, a redox sensitive transcription factor, contributes a critical role in cell death, but, Ang II-stimulated NF-kappaB-mediated cardiomyocytes apoptosis remains less understood. Recently, microRNAs (miRNAs) have been shown to be critical regulators in various cardiac remodeling processes; however, NF-kappaB-mediated miRNA's role in cardiomyocytes apoptosis remains undetermined. The miR-30b has been implicated in diverse cardiac remodeling; but, NF-kappaB-mediated miR-30b modulation in Ang II-induced cardiomyocytes death is currently unknown. In the present study, neonatal cardiomyocytes were pretreated with SN50, a selective cell permeable peptide inhibitor of NF-kappaB, or transfected with miR-30b mimetic and inhibitors separately, and then challenged with Ang II. The target gene, Bcl-2, and NF-kappaB transcriptional activity were analyzed. Our results demonstrated that NF-kappaB positively regulated miR-30b expression in Ang II induced cardiomyocytes apoptosis, and Bcl-2 was a direct target for miR-30b. NF kappaB further regulated the expression of Bcl-2 in the above setting. Furthermore, Ang II-induced cardiomyocytes apoptosis rescued by inhibiting either NF-kappaB or miR-30b provided an important role in cardiomyocytes cell death. We evaluated a critical role of NF-kappaB-mediated miR-30b modulation in Ang II stimulated cardiomyocytes targeting Bcl-2. Our data may provide a new insight of miR-30b's role in myocardial infarction or ischemia. PMID- 24178240 TI - ERK1/2 inhibition enhances apoptosis induced by JAK2 silencing in human gastric cancer SGC7901 cells. AB - Recent studies suggest JAK2 signaling may be a therapeutic target for treatment of gastric cancer (GC). However, the exact roles of JAK2 in gastric carcinogenesis are not very clear. Here, we have targeted JAK2 to be silenced by shRNA and investigated the biological functions and related mechanisms of JAK2 in GC cell SGC7901. In this study, JAK2 is commonly highly expressed in GC tissues as compared to their adjacent normal tissues (n = 75, p < 0.01). Specific down regulation of JAK2 suppressed cell proliferation and colony-forming units, induced G2/M arrest in SGC7901 cells, but had no significant effect on cell apoptosis in vitro or tumor growth inhibition in vivo. Interestingly, JAK2 silencing-induced activation of ERK1/2, and inactivation of ERK1/2 using the specific ERK inhibitor PD98059 markedly enhanced JAK2 shRNA-induced cell proliferation inhibition, cell cycle arrest and apoptosis. Ultimately, combination of PD98059 and JAK2 shRNA significantly inhibited tumor growth in nude mice. Our results implicate JAK2 silencing-induced cell proliferation inhibition, cell cycle arrest, and ERK1/2 inhibition could enhance apoptosis induced by JAK2 silencing in SGC7901 cells. PMID- 24178241 TI - Discovery of 4,6-substituted-(diaphenylamino)quinazolines as potent c-Src inhibitors. AB - A series of 4,6-substituted-(diaphenylamino)quinazolines as c-Src inhibitors have been prepared and their biological activity has also been evaluated. All the compounds displayed potential antiproliferation activities, with IC50 values ranging from 3.42 MUM to 118.81 MUM in five human tumor cell lines. Particularly, compound 15 exhibited higher cytotoxicity against the tested five tumor cell lines compared to the other small molecules. Generally, most of these compounds showed selectivity between the A549 cells and the other four cells, according to their corresponding IC50 values. The results obtained from the in vitro enzyme assay indicated compound 15 has remarkable inhibitory activity against c-Src kinase with an IC50 value of 27.3 nM, which is comparable to the control compounds. Furthermore, molecular docking and QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives. PMID- 24178244 TI - Facial emotion recognition is inversely correlated with tremor severity in essential tremor. AB - We here assess limbic and orbitofrontal control in 20 patients with essential tremor (ET) and 18 age-matched healthy controls using the Ekman Facial Emotion Recognition Task and the IOWA Gambling Task. Our results show an inverse relation between facial emotion recognition and tremor severity. ET patients also showed worse performance in joy and fear recognition, as well as subtle abnormalities in risk detection, but these differences did not reach significance after correction for multiple testing. PMID- 24178243 TI - Neuronal gap junction coupling as the primary determinant of the extent of glutamate-mediated excitotoxicity. AB - In the mammalian central nervous system (CNS), coupling of neurons by gap junctions (electrical synapses) increases during early postnatal development, then decreases, but increases in the mature CNS following neuronal injury, such as ischemia, traumatic brain injury and epilepsy. Glutamate-dependent neuronal death also occurs in the CNS during development and neuronal injury, i.e., at the time when neuronal gap junction coupling is increased. Here, we review our recent studies on regulation of neuronal gap junction coupling by glutamate in developing and injured neurons and on the role of gap junctions in neuronal cell death. A modified model of the mechanisms of glutamate-dependent neuronal death is discussed, which includes neuronal gap junction coupling as a critical part of these mechanisms. PMID- 24178245 TI - Expression of STAT3 and IGF2 in adrenocortical carcinoma and its relationship with angiogenesis. AB - OBJECTIVE: The aim of this study was to determine the correlation between human adrenocortical carcinoma and the proteins involved in tumor angiogenesis, and to evaluate the angiogenic status of adrenocortical carcinoma. METHODS: The expression of signal transducer and activator of transcription 3 and insulin-like growth factor 2 as well as microvessel density was measured in a series of tissue samples from 44 human sporadic adrenocortical tumors by immunohistochemistry. These specimens were classified as adenomas (n = 20) and carcinomas (n = 24) according to the histological criteria defined by Weiss. RESULTS: A total of 19 of 24 (79.17 %) malignant cases showed positive staining for signal transducer and activator of transcription 3 and 4 of 20 (20.00 %) benign cases showed positive, the difference of signal transducer and activator of transcription 3 expression between adrenocortical adenomas and adrenocortical carcinomas was statistically significant (P < 0.001). Similarly, insulin-like growth factor 2 staining was seen in 70.83 % (17/24) of the malignant cases versus 25.00 % (5/20) of the benign, the difference of insulin-like growth factor 2 expression among two groups was statistically significant (P = 0.002). Malignant cases showed higher microvessel density compared to benign tumors (84.70 +/- 12.44 vs 21.05 +/ 8.07, P < 0.001). Signal transducer and activator of transcription 3 and insulin like growth factor 2 expression were positively correlated with microvessel density in all specimens (r_s = 0.832, P < 0.001; r_s = 0.703, P = 0.001). CONCLUSIONS: This study has confirmed that adrenocortical carcinoma overexpress signal transducer and activator of transcription 3 and insulin-like growth factor 2; these results suggest that angiogenesis of human adrenocortical carcinoma may be mediated by these proteins and they could represent selective targets for the molecularly targeted treatments of adrenocortical carcinoma. PMID- 24178247 TI - HIV/hepatitis C virus-coinfected patients and cirrhosis: how to diagnose it and what to do next? AB - Liver disease, specifically cirrhosis, is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The diagnosis of early cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients may be challenging. The development of noninvasive methods for fibrosis assessment empowers the infectious disease specialist to diagnose advanced fibrosis or cirrhosis. Early diagnosis is essential to enroll patients in screening programs for esophageal varices and hepatocellular carcinoma. Cirrhosis may also modify decisions about treatment of both HIV and HCV, including vaccination, medications chosen, and referral for liver transplant. PMID- 24178246 TI - Escherichia coli dysbiosis correlates with gastrointestinal dysfunction in children with cystic fibrosis. AB - Cystic fibrosis gastrointestinal disease includes nutrient malabsorption and intestinal inflammation. We show that the abundances of Escherichia coli in fecal microbiota were significantly higher in young children with cystic fibrosis than in controls and correlated with fecal measures of nutrient malabsorption and inflammation, suggesting that E. coli could contribute to cystic fibrosis gastrointestinal dysfunction. PMID- 24178248 TI - Hypersensitivity reactions associated with fidaxomicin use. AB - We report hypersensitivity reactions associated with fidaxomicin, an antibacterial drug approved for the treatment of Clostridium difficile-associated diarrhea. These reactions are viewed as significant because of severity and unexpected because fidaxomicin is minimally absorbed. The fidaxomicin labeling was revised to include information about the possibility of hypersensitivity reactions. PMID- 24178249 TI - Progress in improving mental health services for racial-ethnic minority groups: a ten-year perspective. AB - OBJECTIVE: This study examined progress in making the mental health workforce more diverse and in better representing racial-ethnic minority groups in randomized intervention trials of common mental disorders since the publication of the U.S. Surgeon General's 2001 report Mental Health: Culture, Race, and Ethnicity. METHODS: Data on the mental health workforce were drawn from a work group comprising research staff from the American Psychiatric Association, American Psychological Association, and the National Association of Social Workers; representatives of professional psychiatric nursing; and staff from the National Institute of Mental Health. Additional data were pooled from clinical trials published between 2001 and 2010, which were examined for inclusion of racial-ethnic minority populations. Proquest, PubMed, and Google Scholar were searched for the terms "clinical trials" and "randomized trials." The search was constrained to trials of adults with bipolar disorder, schizophrenia, and major depression, along with trials of children and adults with attention-deficit hyperactivity disorder. RESULTS: Between 1999 and 2006, professionals from racial ethnic minority groups increased from 17.6% to 21.4% in psychiatry, from 8.2% to 12.9% in social work, and from 6.6% to 7.8% in psychology. Reporting race ethnicity in clinical trials has improved from 54% in 2001 to 89% in 75 studies of similar disorders published by 2010, although few ethnic-specific analyses are being conducted. CONCLUSIONS: Little progress has been made in developing a more diverse workforce; racial-ethnic minority groups remain highly underrepresented. There is more representation of racial-ethnic minority populations in randomized intervention trials, but their numbers often remain too small to analyze. Recommendations for improving both areas are considered. PMID- 24178250 TI - Distribution and accumulation of ultraviolet-radiation-absorbing compounds in leaves of tropical mangroves. AB - Ultraviolet (UV)-absorbing phenolic compounds that have been shown to be protective against the damaging: effects of UV-B radiation (Tevini et al., 1991, Photochem. Photobiol. 53, 329-333) were found in the leaf epidermis of tropical mangrove tree species. These UV-absorbing phenolic compounds and leaf succulence function as selective filters, removing short and energetic wavelengths. A field survey showed that the concentration of UV-absorbing compounds varied between species, between sites that would be experiencing similar levels of UV radiation, and between sun and shade leaves. Sun leaves have greater contents of phenolic compounds than shade leaves, and more saline sites have plants with greater levels in their leaves than less saline sites. In addition, increases in leaf nitrogen contents and quantum yields did not correlate with increasing levels of UV-absorbing compounds. It was concluded from these results that although UV absorbing compounds form a UV-screen in the epidermis of mangrove leaves, UV radiation may not be the only factor influencing the accumulation of phenolic compounds, thus an experiment which altered the level of UV radiation incident on mangrove species was done. Near ambient levels of UVA and UV-B radiation resulted in a greater content of UV-absorbing compounds in Bruguiera parviflora (Roxb.) Wight and Arn. ex Griff., but did not result in increases in B. gymnorrhiza (L.) Lamk or Rhizophora apiculata Blume. Total chlorophyll contents were lower in R. apiculata when it was grown under near-ambient levels of UV radiation than when it was grown under conditions of UV-A and UV-B depletion, but no differences were observed between the UV radiation treatments in the other two species. There was no difference in leaf morphology, carotenoid/chlorophyll ratios, or chlorophyll a/b ratios between UV treatments, although these varied among species; B. parviflora had the highest carotenoid/chlorophyll ratio and R. apiculata had the lowest. Thus it is proposed that differences in species response tu UV radiation may be influenced by their ability to dissipate excess visible solar radiation. PMID- 24178251 TI - High-pressure freezing of soybean nodules leads to an improved preservation of ultrastructure. AB - High-pressure freezing of chemically untreated nodules of soybean (Glycine max (L.) Merr.), in sharp contrast to chemical fixation and prefixation, appears to preserve the ultrastructure close to the native state. This is supported by the observation that the peribacteroid membrane of high-pressure-frozen samples is tightly wrapped around the bacteroids, a finding that is fully consistent with the current views on the physiology of oxygen and metabolite transport between plant cytosol and bacteroids. In soybean root nodules, the plant tissue and the enclosed bacteria are so dissimilar that conventional aldehyde-fixation procedures are unable to preserve the overall native ultrastructure. This was demonstrated by high-pressure freezing of nodules that had been pre-fixed in glutaraldehyde at various buffer molalities: no buffer strength tested preserved all ultrastructural aspects that could be seen after high-pressure freezing of chemically untreated nodules. PMID- 24178252 TI - Expression and localization of polygalacturonase during the outgrowth of lateral roots in Allium porrum L. AB - The presence of polygalacturonase and its correlation with the formation of lateral roots in leek (Allium porrum L.) seedlings have been investigated. During root growth, a steady increase in polygalacturonase activity was associated with that of the lateral root primordia. Fractionation of root extract by fast protein liquid chromatography resolved at least two polygalacturonase isoforms. One of the isoforms, a 75-kdalton protein, strongly reacted on Western blots probed with a polyclonal antibody raised against tomato polygalacturonase. It also reacted with both polyclonal and monoclonal antisera raised against Fusarium moniliforme polygalacturonase. In situ localization with these three antibodies showed that polygalacturonase was present over the meristems of lateral root primordia. Antibodies against pectins (Knox et al. 1990, Planta 181, 512-521) detected large amounts of pectic material filling the area between the apex of the primordium and the mother root tissues. We suggest that a polygalacturonase plays an important role in leek root morphogenesis, particularly during lateral root outgrowth. PMID- 24178253 TI - Light-grown plants of transgenic tobacco expressing an introduced oat phytochrome A gene under the control of a constitutive viral promoter exhibit persistent growth inhibition by far-red light. AB - A comparison of the photoregulation of development has been made for etiolated and light-grown plants of wild-type (WT) tobacco (Nicotiana tabacun L.) and an isogenic transgenic line which expresses an introduced oat phytochrome gene (phyA) under the control of a constitutive viral promoter. Etiolated seedlings of both the WT and transgenic line showed irradiance-dependent inhibition of hypocotyl growth under continuous far-red (FR) light; transgenic seedlings showed a greater level of inhibition under a given fluence rate and this is considered to be the result of the heterologous phytochrome protein (PhyA) functioning in a compatible manner with the native etiolated phytochrome. Deetiolation of WT seedlings resulted in a loss of responsiveness to prolonged FR. Light-grown transgenic seedlings, however, continued to respond in an irradiance-dependent manner to prolonged FR and it is proposed that this is a specific function of the constitutive PhyA. Mature green plants of the WT and transgenic lines showed a qualitatively similar growth promotion to a brief end-of-day FR-treatment but this response was abolished in the transgenic plants under prolonged irradiation by this same FR source. Growth inhibition (McCormac et al. 1991, Planta 185, 162 170) and enhanced levels of nitrate-reductase activity under irradiance of low red:far-red ratio, as achieved by the FR-supplementation of white light, emphasised that the introduced PhyA was eliciting an aberrant mode of photoresponse compared with the normal phytochrome population of light-grown plants. Total levels of the oat-encoded phytochrome in the etiolated transgenic tobacco were shown to be influenced by the wavelength of continuous irradiation in a manner which was qualitatively similar to that seen for the native, etiolated tobacco phytochrome, and distinct from that seen in etiolated oat tissues. These results are discussed in terms of the proposal that the constitutive oat-PhyA pool in the transgenic plants leads to a persistence of a mode of response normally restricted to the situation in etiolated plants. PMID- 24178254 TI - Immunoaffinity purification using monoclonal antibodies for the isolation of indole auxins from elongation zones of epicotyls of red-light-grown Alaska peas. AB - The endogenous indole auxins of red-light grown pea (Pisum sativum L.) epicotyls were investigated. Immunoaffinity purification of indole-3-acetic acid (IAA) and its methylester was achieved using two monoclonal antibodies. Antibodies against free IAA were raised against IAA-C5-BSA, a hapten-carrier-conjugate giving rise to highly specific antibodies for indole auxins with a free acetic-acid group at position 3. Immunoaffinity adsorbents prepared with these antibodies were used for single-step purification of extracts of Alaska pea epicotylar tissue prior to quantification by high-performance liquid chromatography (HPLC) with on-line fluorescence detection. Monoclonal antibodies against a hapten-carrier-conjugate with IAA linked to bovine serum albumin through the carboxyl group (IAA-C1'-BSA) were used for the isolation of IAA esters. Indol-3-acetic acid was identified in the elongation zone of the third internode of red-light-grown Alaska pea. 4 Chloro-indole-3-acetic acid, a constituent of immature pea seeds which is considered to be a very active auxin, was absent from the elongation zone. Several compounds were retained by the column based on antibodies against IAA-C1' BSA. Of these the methylester of IAA was identified by HPLC with on-line fluorescence detection, by co-migration in thin-layer chromatography and by gas chromatography-mass spectrometry. The methyl ester of IAA was very active in promoting elongation of pea third-internode segments. When fed to the epicotylar segments the IAA methylester was rapidly metabolized with IAA being the major metabolite. The methylester of IAA should therefore be classified as a labile auxin conjugate. PMID- 24178255 TI - Expression of the chlorophyll-a/b-protein multigene family in pea (Pisum sativum L.) : Evidence for distinct developmental responses. AB - To measure transcript levels for individual members of the Cab (chlorophyll a/b protein) multigene family in pea under a range of developmental situations, we developed a system using cDNA synthesis, the polymerase chain reaction (PCR), and chemiluminescence detection. In order to design gene-specific PCR primers for all genes, a partial genomic clone for a fifth, Type I LHCII (light-harvesting complex of photosystem II) gene, Cab-9 The Cab-9 sequence appears in the Genbank/EMBL databases under the accession number M86906 , was isolated and sequenced. All seven known Cab genes in pea are expressed in light-grown buds and leaves, including several genes previously known only from genomic clones. There appear to be at least two groups of Cab genes in pea which differ in their response to light and development. The first group (consisting of Cab-8, AB96, Cab-215 and Cab-315) includes Type I, Type II and Type III genes, shows a relatively strong response to red light, and has bud transcript levels similar to or slightly higher than leaves. The second group, consisting of the Type I genes Cab-9, AB80 and AB66, shows little or no transcript accumulation 24 h after a red light pulse, and has higher transcript levels in leaves than in buds. Transcript levels for genes in this second group appear to be lower than those of the first group in all developmental situations examined. These data indicate that there has been an evolutionary divergence of the responses to light and development among the Type I LHCII genes. PMID- 24178256 TI - Characterization of the plasma-membrane H(+)-ATPase from Vicia faba guard cells : Modulation by extracellular factors and seasonal changes. AB - Stomatal movement is controlled by external and internal signals such as light, phytohormones or cytoplasmic Ca(2+). Using Vicia faba L., we have studied the dose-dependent effect of auxins on the modulation of stomatal opening, mediated through the activity of the plasma-membrane H(+)-ATPase. The patch-clamp technique was used to elucidate the electrical properties of the H(+)-ATPase as effected by growth regulators and seasonal changes. The solute composition of cytoplasmic and extracellular media was selected to record pump currents directly with high resolution. Proton currents through the ATPase were characterized by a voltage-dependent increase in amplitude, positive to the resting potential, reaching a plateau at more depolarized values. Upon changes in extracellular pH, the resting potential of the cell shifted with a non-Nernst potential response (+/-21 mV), indicating the contribution of a depolarizing ionic conductance other than protons to the permeability of the plasma membrane. The use of selective inhibitors enabled us to identify the currents superimposing the H(+)-pump as carried by Ca(2+). Auxinstimulation of this electroenzyme resulted in a rise in the outwardly directed H(+) current and membrane hyperpolarization, indicating that modulation of the ATPase by the hormone may precede salt accumulation as well as volume and turgor increase. Annual cycles in pump activity (1.5-3.8 MUA . cm(-2)) were expressed by a minimum in pump current during January and February. Resting potentials of up to -260 mV and plasmamembrane surface area, on the other hand, did not exhibit seasonal changes. The pump activity per unit surface area was approximately 2- to 3-fold higher in guard cells than in mesophyll cells and thus correlates with their physiological demands. PMID- 24178257 TI - Triacylglycerol biosynthesis in developing seeds of Tropaeolum majus L. and Limnanthes douglasii R. Br. AB - Triacylglycerols of both Tropaeolum majus L. and Limnanthes douglasii R. Br. are predominantly esterified with very long-chain acyl groups at each position of the glycerol backbone. In order to elucidate whether these acyl groups are directly chanelled into the triacylglycerols via the stepwise acylation of glycerol-3 phosphate, seed oil formation has been investigated in developing embryos of both plant species. [1-(14)C]Acetate labelling experiments using embryos at different stages of development, as well as the determination of the properties of the microsomal acyl-CoA:sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15) and acyl-CoA:sn-1-acylglycerol-3-phosphate acyltransferase (EC 2.3.1.51), revealed differences between the two plant species, especially with respect to the incorporation of very longchain acyl groups into the C2 position of the triacylglycerols. In microsomal fractions of developing embryos of L. douglasii both a glycerol-3-phosphate and a 1-acylglycerol-3-phosphate acyltransferase were detected which utilize very long-chain acyl-CoA thioesters as substrates. Thus, in seeds of L. douglasii very long-chain acyl groups can enter not only the C1, but also the C2 position of the triacylglycerols in the course of de-novo biosynthesis. A comparison of the properties of the acyltransferases of developing embryos with those of the corresponding activities of leaves indicates an embryo specific expression of an erucoyl-CoA-dependent microsomal 1 acylglycerol-3-phosphate acyltransferase in L. douglasii. The microsomal glycerol 3-phosphate acyltransferase of developing embryos of T. majus displayed properties very similar to those of the corresponding activity of L. douglasii. On the other hand, the microsomal 1-acylglycerol-3-phosphate acyltransferases of the two plant species showed strikingly different substrate specificities. Irrespective of the acyl groups of 1-acylglycerol-3-phosphate and regardless of whether acyl-CoA thioesters were offered separately or in mixtures, the enzyme of T. majus, in contrast to that of L. douglasii, was inactive with erucoyl-CoA. These results of the enzyme studies correspond well with those of the [1 (14)C]acetate labelling experiments and thus indicate that T. majus has developed mechanisms different from those of L. douglasii for the incorporation of erucic acid into the C2 position of its triacylglycerols. PMID- 24178258 TI - Immunological comparison of the pyruvate dehydrogenase complexes from pea mitochondria and chloroplasts. AB - The pyruvate dehydrogenase complex (PDC) in pea (Pisum sativum L., cv. Little Marvel) was studied immunologically using antibodies to specific subunits of mammalian PDC. Pea mitochondria and chloroplasts were both found to contain PDC, but distinct differences were noted in the subunit relative molecular mass (Mr) values of the individual enzymes in the mitochondrial and chloroplast PDC complexes. In particular, the mitochondrial E3 enzyme (dihydrolipoamide dehydrogenase; EC 1.8.1.4) has a high subunit Mr value of 67 000, while the chloroplast E3 enzyme has a subunit Mr value of 52 000, similar in size to the prokaryotic, yeast ad mammalian E3 enzymes. In addition, component X (not previously noted in plant PDC) was also found to be present in two distinct forms in pea mitochondrial and chloroplast complexes. As in the case of E3, mitochondrial component X has a higher subunit Mr value (67 000) than component X from chloroplasts (48 000), which is similar in size to its mammalian counterpart. The subunit Mr value of E2 (dihydrolipoamide acetyltransferase; EC 2.3.1.12) in both mitochondria and chloroplasts (50 000) is lower than that of mammalian E2 (74 000) but similar to that of yeast E2 (58 000), and is consistent with the presence of only a single lipoyl domain. Neither mitochondria nor chloroplasts showed any appreciable cross-reactivity with antiserum to mammalian E1 (pyruvate dehydrogenase; EC 1.2.4.1). However, mitochondria cross-reacted strongly with antiserum to yeast E1, giving a single band (Mr 41 000) which is thought to be E1a. Chloroplasts showed no cross-reactivity with yeast E1, indicating that the mitochondrial E1a subunit and its chloroplast equivalent are antigenically distinct polypeptides. PMID- 24178259 TI - A comparative analysis of the effects of in-vivo and in-vitro abscisic-acid treatment on the surface electrical properties of barley chloroplast membranes. AB - The effects of in-vivo and in-vitro abscisic acid (ABA) treatments on the surface charge density (sigma) of barley (Hordeum vulgare L.) thylakoids were compared using 9-aminoacridine fluorescence. The estimated surface charge density of isolated thylakoid membranes from control (non-treated) barley leaves was-0.065 C . m(-2). The net negative surface charge density decreased after application of various concentrations of ABA (10(-6), 10(-5) M) for 7 d in-vivo, the more pronounced effect being observed at 10(-5) M ABA. When ABA was added to the suspension of isolated thylakoids the opposite effect was observed. The average charge density increased in in-vitro-treated thylakoids at 10(-5) M ABA to -0.081 C . m(-2). The results are discussed in terms of a specific ABA-induced influence of the composition and-or stoicheometry of charged protein complexes within the thylakoid membranes. PMID- 24178260 TI - Inorganic pyrophosphate content and metabolites in potato and tobacco plants expressing E. coli pyrophosphatase in their cytosol. AB - Metabolite levels and carbohydrates were investigated in the leaves of tobacco (Nicotiana tabacum L.) and leaves and tubers of potato (Solanum tuberosum L.) plants which had been transformed with pyrophosphatase from Escherichia coli. In tobacco the leaves contained two- to threefold less pyrophosphate than controls and showed a large increase in UDP-glucose, relative to hexose phosphate. There was a large accumulation of sucrose, hexoses and starch, but the soluble sugars increased more than starch. Growth of the stem and roots was inhibited and starch, sucrose and hexoses accumulated. In potato, the leaves contained two- to threefold less pyrophosphate and an increased UDP-glucose/ hexose-phosphate ratio. Sucrose increased and starch decreased. The plants produced a larger number of smaller tubers which contained more sucrose and less starch. The tubers contained threefold higher UDP-glucose, threefold lower hexose-phosphates, glycerate-3-phosphate and phosphoenolpyruvate, and up to sixfold more fructose 2,6-bisphosphatase than the wild-type tubers. It is concluded that removal of pyrophosphate from the cytosol inhibits plant growth. It is discussed how these results provide evidence that sucrose mobilisation via sucrose synthase provides one key site at which pyrophosphate is needed for plant growth, but is certainly not the only site at which pyrophosphate plays a crucial role. PMID- 24178261 TI - Effect of the growth retardant LAB 198 999, an acylcyclohexanedione compound, on epicotyl elongation and metabolism of gibberellins A1 and A 20 in cowpea. AB - The effect of LAB 198 999 [3,5-dioxo-4-butyryl-cyclohexane carboxylic acid ethyl ester; a new plant growth retardant which competitively inhibits 2-oxoglutarate dependent gibberellin (GA) dioxygenases] on elongation and in-vivo [(3)H]GA1 and [(3)H]GA20 metabolism in cowpea (Vigna sinensis L. cv Blackeye pea No. 5) epicotyls has been investigated. Gibberellins and LAB 198 999 were injected into the epicotyl at 25-30 mm from the apex. In intact seedlings, epicotyl elongation was inhibited by LAB 198 999 (25 MUg . epicotyl(-1)), and the inhibition was counteracted by GA1 but not by GA20. In contrast to intact seedlings, the inhibitor enhanced epicotyl elongation in de-bladed seedlings and expiants, in the latter case proportionally to the amount of inhibitor applied (up to 50 MUg . epicotyl(-1)), but not in explants made from paclobutrazol-treated seedlings. The inhibitor also enhanced dramatically the elongation induced in paclobutrazol treated expiants by GA1, but not by GA20. The promotive effect of LAB 198 999 was associated with increased contents of GA1 and GA8 in the growing region of the epicotyl, indicating a dependence on endogenous GAs. The effect of LAB 198999 decreased progressively with the age of the seedlings, probably as a consequence of a decreased level of GAs in the epicotyl. Gibberellin substrates and metabolites in the growing region of the epicotyl (upper 20 mm) were fractionated and identified tentatively by high-performance liquid chromatography and radiocounting using a homogeneous on-line radioactivity detector. The metabolism of [(3)H]GA1(t) (tentative) to [(3)H]GA8(t), and that of [(3)H]GA20(t) to [(3)H]GA1(t) and [(3)H]GA29(t) in the epicotyl were blocked by LAB 198 999, that of the former more efficiently than the latter. The results presented support the hypothesis that GA1 is the active GA controlling elongation of cowpea epicotyls. They also show that both the promotion of epicotyl elongation in explants and the enhancement of the effect of exogenous GA1 by LAB 198 999 are the result of the inhibitor blocking the in-vivo 2beta-hydroxylation of GA1. PMID- 24178262 TI - Gibberellin biosynthesis from gibberellin A12-aldehyde in a cell-free system from germinating barley (Hordeum vulgare L., cv. Himalaya) embryos. AB - Gibberellin (GA) metabolism from GA12-aldehyde was studied in cell-free systems from 2-d-old germinating embryos of barley. [(14)C]- or [17-(2)H2]Gibberellins were used as substrates and all products were identified by combined gas chromatography-mass spectrometry. Stepwise analysis demonstrated the conversion of GA12-aldehyde via the 13-deoxy pathway to GA51 and via the 13-hydroxylation pathway to GA29, GA1 and GA8. In addition, GA3 was formed from GA20 via GA5. We conclude that the embryo is capable of producing gibberellins that can induce alpha-amylase production in the aleurone layer. There was no evidence for 12beta- or 18-hydroxylation and GA4 was neither synthesised nor metabolised by the system. All metabolically obtained GAs, with the exception of GA3, were also found as endogenous components of the cell-free system in spite of ammonium sulfate precipitation and desalting steps. PMID- 24178263 TI - Tubulin-isotype analysis of two grass species-resistant to dinitroaniline herbicides. AB - Trifluralin-resistant biotypes of Eleusine indica (L.) Gaertn. (goosegrass) and Setaria viridis (L.) Beauv. (green foxtail) exhibit cross-resistance to other dinitroaniline herbicides. Since microtubules are considered the primary target site for dinitroaniline herbicides we investigated whether the differential sensitivity of resistant and susceptible biotypes of these species results from modified tubulin polypeptides. One-dimensional and two-dimensional polyacrylamide gel electrophoresis combined with immunoblotting using well-characterised anti tubulin monoclonal antibodies were used to display the family of tubulin isotypes in each species. Seedlings of E. indica exhibited four beta-tubulin isotypes and one alpha-tubulin isotype, whereas those of S. viridis exhibited two beta-tubulin and two alpha-tubulin isotypes. Comparison of the susceptible and resistant biotypes within each species revealed no differences in electrophoretic properties of the multiple tubulin isotypes. These results provide no evidence that resistance to dinitroaniline herbicides is associated with a modified tubulin polypeptide in these biotypes of E. indica or S. viridis. PMID- 24178264 TI - Hydration-state-responsive proteins link cold and drought stress in spinach. AB - Spinach (Spinacia oleracea L.) seedlings exposed to low nonfreezing temperatures (0-10 degrees C) that promote cold acclimation, synthesize a variety cold acclimation proteins and at the same time acquire a greater ability to withstand cellular dehydration imposed by the freezing of tissue water. Two of these proteins (160 and 85 kDa) become more abundant over time at low temperature. In addition, a small decline in tissue water status from a maximally hydrated state also appears to be associated with an initiation of the accumulation of these proteins at a noninductive temperature. Imposing a severe water stress on young seedlings grown at 25 degrees C by withholding water leads to substantial accumulation of the 160- and 85-kDa proteins, and maximal induction of freezing tolerance. This evidence implies that responses to cold acclimation and water stress involve common mechanisms, and further establishes the linkage of these two proteins with stresses having an osmotic component. PMID- 24178265 TI - Effects of the axr2 mutation of Arabidopsis on cell shape in hypocotyl and inflorescence. AB - The axr2 mutation of Arabidopsis thaliana (L.) Heynh. confers resistance to the plant growth hormones auxin, ethylene and abscisic acid. In addition, mutant plants have a pronounced dwarf phenotype and display defects in both shoot and root gravitopism. To further characterize this mutant we have determined the phenotype of both dark- and light-grown mutant seedlings. We find that the height of axr2 hypocotyls is reduced in dark conditions compared with wild-type seedlings and that both dark- and light-grown hypocotyls have a gravitropic defect. In addition, we have examined the cellular anatomy of a variety of wild type and axr2 tissues using light and scanning electron microscopy. Our results indicate that the axr2 mutation has a dramatic effect on cell length in both the inflorescence and the hypocotyl and a lesser effect on cell number in these tissues. The largest difference was observed in the epidermis of the inflorescence where axr2 cells were approximately eightfold shorter than wild type cells. We suggest that these reductions in cell length and number are sufficient to explain most aspects of the axr2 phenotype. In addition, we propose that a reduction in auxin-mediated cell elongation is responsible for the gravitropic defect in mutant roots, hypocotyls and floral stems. Finally, we have found that the reduction in epidermal cell size in the mutant inflorescence is accompanied by a fourfold increase in stoma density. The implications of this result for models of stoma development are discussed. PMID- 24178266 TI - Hygromycin resistance as an efficient selectable marker for wheat stable transformation. AB - A highly efficient method for stable wheat transformation using hygromycin resistance as a selectable marker is described. Young embryogenic calli growing from immature wheat embryos were transformed using a gunpowder-driven microparticle accelerator. Transgenic wheat plants were determined by PCR amplification of transgene fragments and confirmed by Southern hybridization, activity of the transgene expression and by analysis of the progeny. The hpt gene was as good as or a better selectable marker than the bar gene with an average efficiency (number of transgenic plants relative to the number of bombarded calli) of 5.5% compared with 2.6% for the bar gene. PMID- 24178267 TI - Plant regeneration in Kentucky bluegrass (Poa pratensis L.) via coleoptile tissue cultures. AB - Plant regeneration in Kentucky bluegrass (Poa pratensis L. cv. Touchdown) via culture of seedling tissues was investigated. When coleoptile, leaf, and stem sections of dark-germinated seedlings were cultured on Murashige and Skoog (MS) medium, different types of callus were produced, depending on the expiant source and growth regulator combinations. Only compact-friable callus (type 3) and moderately compact, friable callus (type 2) produced shoots upon subculture. The nonstructured watery callus (type 4) produced roots without shoots. Shoot differentiation from callus tissues was highest when the culture medium contained 0.2 mgL(-1) picloram + 0.01 mgL(-1) alpha-naphthaleneacetic acid (NAA). Calli grown from coleoptiles had higher shoot regeneration frequency (32%) than that obtained from either stem sections (12%) or young leaf tissues (2%) of the same seedlings. Some organogenic callus lines produced exclusively green plants, while others produced albino shoots or a mixture of green and albino shoots. The green plants were multiplied in a medium containing 0.1 mgL(-1) BAP plus either 0.2 mgL(-1) picloram or 0.1 mgL(-1) indole-3-acetic acid (IAA). Over 90% of the cultures in the shoot proliferation medium produced roots in 4 weeks. The rooted plants were successfully established in soil medium and grown in the greenhouse. PMID- 24178268 TI - Formation of terpenoid products in Ginkgo biloba L. cultivated cells. AB - Ginkgolides are diterpenes arising from the terpenoid precursor: geranylgeranyl pyrophosphate (GGPP). Incorporation of [1-(14)C] isopentenylpyrophosphate ([1 (14)C]IPP) into GGPP was monitored throughout the cultivation cycle of G. biloba L. cultivated cells. Because incorporation of [1-(14)C]IPP into GGPP had never been monitored in G. biloba, in either the whole plant or cultivated cell system, modifications to existing protocols were necessary. Modifications consisted of extracting the cells with an extraction buffer supplemented with Triton-X-100. Farnesylpyrophosphate (FPP) was the major product formed. The amount of GGPP detected was about one tenth that of FPP. PMID- 24178269 TI - Regeneration from Laminaria japonica Areschoug (Laminariales, Phaeophyceae) protoplasts isolated with bacterial alginase. AB - The conditions for effective isolation of viable protoplasts from Laminaria japonica with an alginase produced by marine bacterium Alteromonas sp. and a commercially available cellulase were investigated. The highest yields of viable protoplasts (7.9~10.4x10(6) cells g(-1) FW) were obtained with a hypertonic solution containing 50 % seawater, 25 mM MgCl2, 5 mM HEPES buffer system, and 0.5 M mannitol. Protoplasts were not obtained from thalli of L. japonica when an abalone alginase (abalone acetone powder; AAP: Sigma) was used instead of the bacterial alginase. The isolated protoplasts were cultured in an PESI medium at 5 degrees C. Complete cell wall formation was observed within 7 days, and dividing cells were first observed in a 9-day-old culture. Some protoplasts regenerated into sheet-shaped thalli and rhizoid structures were also observed on some thalli after 30 to 40 days in culture. This is the first report of protoplast regeneration into plantlets of L. japonica Areschoug (Laminariales, Phaeophyceae). PMID- 24178270 TI - Microcallus formation from leaf mesophyll protoplasts in the genus Actinidia Lindl. AB - Microcallus (more than 60 cells) formation was obtained from leaf mesophyll protoplasts of 6 species and varieties in the genus Actinidia Lindl. (kiwifruit). The best results were achieved by using liquid over agarose culture for A. arguta var. arguta, liquid and agarose disc type culture for A. arguta var. purpurea, agarose disc type culture for A. arguta cv. Issai and A. deliciosa and liquid agarose bead type- and disc type culture for A. kolomikta and A. polygama. Several factors influencing purification, browning, survival and sustained division of the protoplasts are briefly discussed. PMID- 24178271 TI - Somatic embryogenesis and plant regeneration in Sorghum bicolor (L.) Moench. AB - Callus induction, somatic embryogenesis and plant regeneration were obtained in two cultivars of Sorghum bicolor (L.) Moench. Transverse thin cell layers from roots/epicotyls of 15-day-old seedlings or of regenerated plantlets were used. Callus response depended on the genotype, the size of transverse thin cell layers, the level at which transverse thin cell layers were excised on the epicotyl, the composition of growth substances and the number of in vitro regeneration cycles undergone by the donor plant. Somatic embryos were differentiated under a defined dark/light sequence, from epidermised compact calluses (i.e having already differentiated an epidermis), obtained directly with dicamba or from friable callus initiated with kinetin and 2,4 dichlorophenoxyacetic acid. The importance of kinetin and dicamba on the induction of embryogenic potential is reported. PMID- 24178272 TI - Haploid plant regeneration from anther cultures of three north american cultivars of strawberry (Fragaria x ananassa Duch.). AB - A study was conducted to maximize plant regeneration frequencies from cultured anthers of 'Chandler', 'Honeoye', and 'Redchief' strawberries (Fragaria x ananassa Duch.). A comparison of auxins (IAA, NAA), cytokinins (BA, BPA, KIN) and carbohydrates (sucrose, glucose, maltose) in MS medium showed that the highest shoot regeneration across cultivars (8%) occurred when using a medium containing 2 mg/l IAA, 1 mg/l BA, and 0.2 M glucose. A comparison of MS, NN, and H1 inorganic medium (a new formulation based on the anther culture literature) solidified with either agar or gellan gum and containing IAA, BA, and glucose, showed the highest shoot regeneration across cultivars (19%) when using H1 and gellan gum. Lastly, media containing Fe-EDTA yielded more shoots than media containing Fe-Metalosate, and anthers cultured on Fe-EDTA media in darkness for 30d followed by 30d in white light produced more shoots (16% average regeneration) than those cultured on Fe-EDTA media under white or yellow light (16h photoperiod) for the initial 30d (0.3% and 5% respectively). Plants were acclimated ex vitro where they flowered and set fruit. Chromosome counts of root tip cells confirmed that haploid plants were obtained from all three cultivars. PMID- 24178273 TI - Production of ribosome-inactivating protein from hairy root cultures of Luffa cylindrica (L.) Roem. AB - Transformed root lines of Luffa cylindrica (L.) Roem. (Cucurbitaceae) were established by inoculation of in vitro grown plantlets with wild type Agrobacterium rhizogenes strain 1855. Cloned lines of hairy roots were tested for the presence of ribosome-inactivating proteins; crude extracts inhibited protein synthesis in a reaction mixture based on rabbit reticulocyte lysate. Inhibitory activity increased during culture period, reaching a maximum value in the stationary phase. No activity could be detected in the culture medium, nor in extracts from callus and/or suspension cultures. A ribosome-inactivating protein having specific activity of 62,100 U mg protein(-1) and a molecular mass of 26 28,000 Da was purified to homogeneity. The protein showed N-glycosidase activity on rat liver ribosomes. The results demonstrate that hairy root cultures can be successfully utilized for the in vitro production of ribosome-inactivating proteins. PMID- 24178274 TI - Regeneration of plant cell protoplasts under microgravity: Investigation of protein patterns by SDS-PAGE and immunoblotting. AB - As part of the D-2 Spacelab mission, tobacco (Nicotiana tabacum L.) protoplasts were cultured for 10 days in microgravity and successfully regenerated into microcalli, which, after further cultivation on the ground, gave rise to intact plants. Protein analysis was performed on samples taken during the initial microgravity period and compared to ground controls. Total protein content and protein patterns were monitored, as well as the cytoskeletal proteins tubulin and actin, a key enzyme of secondary metabolism, phenylalanine ammonia lyase, and the pathogenesis-related protein osmotin. None of the investigated proteins showed a gravity-dependent effect. Since relative changes due to culture age were detectable in the immunoblots as well as in the total protein pattern, an adaptation of the cells to microgravity without major modifications of their protein complement may be assumed. PMID- 24178275 TI - Somatic embryogenesis from immature leaves of in vitro grown tea shoots. AB - Immature leaves of in vitro grown shoots of tea were cultured on various levels of 2,4-D. Somatic embryos were induced directly on leaves or via embryogenic callus produced at the basal regions of the leaves. Induction of embryogenesis appeared to be correlated with the maturity of the leaf explants, with younger leaves responding better. The embryogenic response of leaf explants also was correlated with the period of culture in 2,4-D containing liquid medium. Embryogenic calli or repetitive somatic embryos maintained their regeneration capacity for more than 3 years. Histological observation revealed somatic embryos were formed on various regions of the leaf midrib. Somatic embryos germinated and developed into plantlets on agar medium containing BA and IBA. PMID- 24178276 TI - Transient and stable electrotransformations of intact black Mexican sweet maize cells are obtained after preplasmolysis. AB - When interested in plant cell transformation, the cell wall is often considered as a barrier to DNA transfer, which is only overcome by wounding or wall degrading enzymes. In this work, we demonstrate that cell plasmolysis before electropulsation is an efficient approach to DNA delivery into intact plant cells. Using such a method, transient expression (beta-glucuronidase and chloramphenicol acetyltransferase) and stable expression (phosphinotricin acetyltransferase) of exogenous genes are obtained in intact black Mexican sweet maize cells. PMID- 24178277 TI - Agrobacterium tumefaciens-mediated transformation of Artemisia annua L. and regeneration of transgenic plants. AB - A transformation system was developed for Artemisia annua L. plants. Leaf explants from in vitro grown plants developed callus and shoots on medium with 0.05 mg/L naphthaleneacetic acid and 0.5 mg/L N(6)-benzyladenine after transformation with the C58C1 Rif(R) (pGV2260) (pTJK136) Agrobacterium tumefaciens strain. A concentration of 20 mg/L kanamycin was added in order to select transformed tissue. Kanamycin resistant shoots were rooted on naphthaleneacetic acid 0.1 mg/L. Polymerase chain reactions and DNA sequencing of the amplification products revealed that 75% of the regenerants contained the foreign genes. 94% of the transgenic plants showed a beta-glucuronidase-positive response. PMID- 24178278 TI - Effect of media components on the gynogenic regeneration of onion (Allium cepa L.) cultivars and analysis of regenerants. AB - Two separate experiments were performed to analyze the effects of different media on gynogenic regeneration in four onion cultivars. In a two step flower/ovary culture procedure, 2,4-dichlorophenoxyacetic acid added to the induction medium was superior to phenylacetic acid in the highly regenerating cultivar, while the effect of thidiazuron in the regeneration medium was generally optimal in higher (2 mg/l) rather than in lower (0.2 mg/l) concentrations. Gellan-gum was compared to agar solidified media. A higher number of regenerants was achieved on the former, but an undesirable hyperhydricity of regenerants formed on gellan-gum solidified media greatly reduced the final survival of formed embryos. Analysis of the time interval needed for regeneration showed high variability (from 46 to 152 days after inoculation), which was particularly pronounced in genotypes with lower regeneration capacity. Simpler isozyme patterns of regenerants showed that all analysed regenerants of the cultivar with a high regeneration capacity were homozygous, while in the other three cultivars, a considerable percentage (11.1 to 36.4%) of heterozygous regenerants were also detected. Ploidy analysis of the regenerants with simpler isozyme patterns revealed that the majority of lines remain haploid. Identification of 2 homozygous triploid regenerants demonstrated that as in androgenesis, nuclear fusions can occur during gynogenic haploid regeneration. PMID- 24178279 TI - Synthesis of Ogura male sterile rapeseed (Brassica napus L.) with cold tolerance by protoplast fusion and effects of atrazine resistance on seed yield. AB - Twenty-one cold-tolerant, male sterile Brassica napus somatic hybrids were produced by protoplast fusion. The fusion partners were a coldsensitive, Ogura cytoplasmic male sterile cauliflower inbred (B. oleracea var. botrytis inbred NY7642A) and a cold-tolerant, fertile canola-type B. rapa cv. Candle. Hybridity was confirmed by morphology, isozyme expression, flow cytometry, and DNA hybridization. Organellar analyses revealed a very strong bias for Brassica over Raphanus chloroplasts. Cold tolerance was confirmed by cold chamber studies and chloroplast DNA analyses. Good female fertility with 21.4 +/- 3.1 seeds/pod was observed in the field using natural pollination vectors. Total seed yield was significantly greater for the atrazine-sensitive somatic hybrids produced in this study than for atrazine-resistant isolines. PMID- 24178280 TI - The role of Ca(2+) in elicitation of phytoalexin synthesis in cell culture of onion (Allium cepa L.). AB - Treatment of Allium cepa L. cellsuspension cultures with a biotic elicitor derived from the fungus Botrytis cinerea, resulted in phytoalexin synthesis. Two phytoalexins, 5-octylcyclopenta-1,3-dione and 5-hexyl-cyclopenta-1,3-dione, were accumulated in cultured onion cells. Removal of extracellular Ca(2+) by the calcium chelator ethylene glycol bis(b-aminoethyl ether) N,N'-tetraacetic acid abolished the elicitor-mediated phytoalexin synthesis. The calcium channel blockers, verapamil and 8-N,N-(dimethylamino)octyl-3,4,5-trimethoxybenzoate caused similar effects, whereas the addition of the Ca(2+) ionophore A23187 enhanced the accumulation of phytoalexins in the absence of the elicitor. Increase in the cytoplasmic Ca(2+) concentration in elicitor-treated onion cells was observed as monitored by the fluorescent calcium indicator indo-1. These observations suggest that Ca(2+) acts as a second messenger in the regulation of phytoalexin synthesis in cultured onion cells. PMID- 24178281 TI - Activation of the Ty1-copia group retrotransposons of potato (Solatium tuberosum) during protoplast isolation. AB - The potato (Solanum tuberosum) genome contains a highly heterogeneous population of Ty1-copia group retrotransposons. Here we identify the first such transposable element known to be transcribed in this species. The elements are transcriptionally activated during protoplast isolation. The majority of the activated Ty1-copia sequences are similar to elements which are transcriptionally induced under the same conditions in tobacco (Nicotiana tabacum). We also show that a previously identified potato element M166, which has no known equivalent in tobacco is also transcribed under these conditions. It appears that the control of transcription of this particular Ty1-copia group retrotransposons has been broadly conserved between these two species. PMID- 24178282 TI - Biologically-active soluble oligosaccharides from pea stem tissues. AB - Two active fractions of soluble oligosaccharides were isolated from pea (Pisum sativum L.) stem tissues. Both fractions are capable of affecting different phases of root development on buckwheat thin cell-layer explants (TCLs) and of inhibiting auxin-promoted growth of etiolated pea stem segments. The existence of non-wall bioactive oligosaccharides which may have a role in cell development in vivo is proposed. PMID- 24178283 TI - Transient expression of uidA constructs in in vitro onion (Allium cepa L.) cultures following particle bombardment and Agrobacterium-mediated DNA delivery. AB - Particle bombardment and Agrobacterium-mediated DNA delivery into immature embryos and microbulbs were used to investigate the expression of the uidA gene in in vitro onion cultures. Both methods were successful in delivering DNA and subsequent uidA expression was observed. Optimal transient beta-glucuronidase activity was observed in immature embryos that had been pre-cultured for three days and bombarded at a distance of 3 cm from the stopping plate, under 25 in Hg vacuum, using 900-1300 psi rupture discs. The CaMV35S-uidA gene construct gave five fold higher transient beta-glucuronidase activity than the uidA gene construct regulated by any of four other promoters initially chosen for high experession in monocotyledonous tissues. PMID- 24178284 TI - Optimization of biolistic method for transient gene expression and production of agronomically useful transgenic Basmati rice plants. AB - We have developed a reproducible biolistic procedure for the efficient transformation of embryogenic suspension cells of an improved aromatic Indica rice variety, Pusa Basmati 1. The beta-glucuronidase gene was used to assay transient transformation; other plasmids carrying either a potato protease inhibitor 2 (Pin2) gene, or a late embryogenesis-abundant protein (LEA3) gene from barley, were used for the optimization of biolistic process and transgenic plant production. After optimization of the procedure, over 600 transient transformants and at least five fertile plants showing integrative transformation were obtained per bombarded filter. At least 30% of the plants were derived from independent transformation events. The new improved procedure involves the use of a reporter gene or other useful genes driven by the strong rice actin 1 gene (Act1) promoter, osmotic pre-conditioning of cells for 24 h on medium supplemented with 0.25 M mannitol prior to bombardment, use of gold particles for DNA delivery, and use of plant regeneration medium with high (1.0%) agarose concentration. PMID- 24178285 TI - Photosynthetic electron transport in thylakoids from cotton cultivars (Gossypium sp.) differing in tolerance to prometryn. AB - A method to determine photosynthetic electron transport in thylakoid membranes is described for Gossypium barbadense (cv. Pima S-7) and G. hirsutum (cv. DP 5415). These cultivars differed markedly in tolerance to prometryn, a PS II inhibitor. The rates of photosynthetic electron transport obtained were 245 MUmole oxygen mg(-1) chl h(1). Plant age and leaf size influenced the activity of the thylakoid preparations. Thylakoids from leaves of plants 24 to 37 d and 50-70 mm in diameter had the highest activities; thylakoids from cotyledons, fully expanded leaves and young leaves had low activity. Thylakoids from both species had similar photosynthetic activities and I50's for prometryn, atrazine and diuron. Thus, tolerance to prometryn was not due to differential binding at D1 protein. PMID- 24178286 TI - Influence of BA and sucrose on the competence and determination of pepper (Capsicum annuum L. var. Sweet Banana) hypocotyl cultures during shoot formation. AB - The simultaneous presence of 6-benzyladenine (BA) and sucrose in a Murashige and Skoog medium (SIM) during the initial stages of shoot initiation have been found to be obligatory for high-frequency shoot formation in the Capsicum annuum L. var. 'Sweet Banana' upper hypocotyl explants. The explants are determined for shoot formation following a minimum of 8 days of culture on SIM. Deprivation of exogenous sucrose from day 6 to day 20 of culture had no effect on the shoot forming response of the explants. BA and sucrose appear to act independently on different aspects of the competence of explants to respond to SIM during shoot initiation. PMID- 24178287 TI - Genetic transformation of cotyledon explants of cowpea (Vigna unguiculata L. Walp) using Agrobacterium tumefaciens. AB - Mature de-embryonated cotyledons with intact proximal end of Vigna unguiculata were cultured on B5 basal medium containing varying concentrations of BAP. Thirty six percent of the explants produced shoots on B5 medium supplemented with 8* 10( 6) M BAP. Cotyledon explants were pre-incubated for 24 h, inoculated with A. tumefaciens pUCD2614 carrying pUCD2340, co-cultivated for 48 h and transferred to hygromycin-B (25 mg/l) containing shoot induction medium. Approximately 15-19% of the explants produced shoots on the selection medium. The elongated shoots were subsequently rooted on B5 basal medium containing hygromycin. The transgenic plants were later established in pots. The presence of hpt gene in the transgenic plants was confirmed by Southern blot hybridization. PMID- 24178288 TI - Bromodeoxy uridine combined with UV light and gamma irradiation promotes the production of asymmetric somatic hybrid calli. AB - The degree of gamma- or X-ray-induced donor chromosome elimination in asymmetric somatic hybrids is highly variable. Here the beneficial use of bromodeoxyuridine and UV light as additional chromosome destabilizing agents is described. Protoplasts of Nicotiana tabacum were fused with protoplasts of Nicotiana plumbaginifolia (Np) that carried the kanamycin-resistance and glucuronidase (GUS) genes on separate chromosomes. Prior to fusion, the Np donor protoplasts were pretreated with bromodeoxyuridine and then were inactivated by treatment with iodoacetate +/- UV light +/- 200 Gy gamma irradiation. Hybrids were selected on medium containing kanamycin. The elimination of Np DNA was assessed by scoring of the fraction of hybrid calli that expressed GUS and by dot-blot analysis using a Np-specific probe. Gamma irradiation alone resulted in elimination of 50% of Np DNA. Pretreatment with bromodeoxyuridine (10 MUM) followed by 2.5 to 5 min UV light resulted in the elimination of 35-45% of the donor genome, but incorporation of bromodeoxyuridine (10 MUM) followed by 2.5 to 5 min UV light and 200 Gy gamma irradiation resulted in 85 to 90% elimination of Np DNA. PMID- 24178289 TI - Regeneration of patchouli (Pogostemon cablin Benth.) plants from leaf and node callus, and evaluation after growth in the field. AB - Pogostemon cablin (Benth.) is commercially important for its aromatic patchouli oil. Plants were regenerated through callus culture from leaf and nodal segments. Highest callusing was obtained from leaf explants in Murashige and Skoog (MS) medium supplemented with 3% sucrose, 0.8% bacto agar and 2 mg/L NAA + 0.5 mg/L BA. Shoot formation frequency was maximum (83%) with BA at 1.0 mg/L. Regenerated plantlets were rooted on MS medium with auxins. Maximum (90%) rooting was obtained using 0.5 mg/L NAA. Plantlets were grown for 4 weeks in this medium and then transferred to pots containing sterile sand in a moisture saturated glass chamber under laboratory conditions. The established plants were grown in pots filled with a mixture of sand?soil?manure (2?1?1) under natural daylight conditions in the field. The total leaf yield was increased in the tissue culture derived plants. These plants were dwarf and had higher specific leaf weight (leaf thickness) and leaf area compared to control plants. PMID- 24178290 TI - A bizarre complication of shoulder arthroscopy. AB - A case is presented of an unusual complication of shoulder arthroscopy, which was caused by incorrect location of the posterior portal, inducing neurapraxia of both the axillary and radial nerves, with significant clinical and functional sequelae. A subsequent open surgical neurolysis was required to restore normal nerve function. This type of lesion has not been reported previously. Level of evidence V. PMID- 24178291 TI - Profiling cumulative proportional reporting ratios of drug-induced liver injury in the FDA Adverse Event Reporting System (FAERS) database. AB - BACKGROUND: Early prediction and accurate characterization of risk for serious liver injury associated with newly marketed drugs remains an important challenge for clinicians, the pharmaceutical industry, and regulators. To date, a biomarker that specifically indicates exposure to a drug as the etiologic cause of liver injury has not been identified. OBJECTIVES: Using cumulative proportional reporting ratios (PRRs), we investigated 'real-time' profiles of a set of pharmaceuticals, over the first 3 years of US marketing, for the signaling of clinically serious drug-induced liver injury (DILI) in a large spontaneous reporting database. METHODS: Using report counts of hepatic failure or clinically serious liver injury obtained from the FDA Adverse Events Reporting System (FAERS) database, PRRs of adverse drug event terms were calculated by division of counts of domestic reports of these events by counts of all serious adverse events for each of 13 selected drugs associated with a broad range of hepatotoxic risk (including three linked to only rare instances of clinically apparent liver injury) with reference to all other drugs in the database. Drug-specific cumulative PRRs were measured at successive intervals (calendar quarters) using cumulative tallies of FAERS reports to generate time-based profiles over the initial 3 years of US marketing. RESULTS: In the set of drugs analyzed, those with no known hepatotoxic risk demonstrated time-based cumulative PRR profiles that approximate the background rates of hepatic failure and serious liver injury reported in the entire FAERS database. In contrast, those that were removed from marketing or subjected to marketing restrictions due to their potential to cause liver injury were associated with profiles of rapidly rising cumulative PRRs that were greater than 5 within the first 10 million domestic prescriptions or the first four quarters of US marketing. The systematic tracking and identification of rising PRRs for DILI associated with newly marketed pharmaceutical and biological agents is a valuable tool for identification of safety signals within the FAERS database. LIMITATIONS: Disproportionality profiling of spontaneous reports in FAERS (e.g., cumulative PRR measurements), which signals an association between a recently marketed drug and liver injury, is not a method to quantitatively measure drug-related risk. Regulatory actions in response to emerging drug safety concerns often depend on an accurate assessment of risks using multiple sources of data and the consideration of overall benefits and risks of the agent. Causality must be determined through analysis of individual cases to exclude other etiologies of liver injury. CONCLUSION: The FAERS database can be used to advance empiric hepatotoxicity time-trending reporting levels for newly marketed agents in order to rapidly identify recently launched potential hepatotoxic agents and initiate further evaluation. PMID- 24178292 TI - Querying inter-disciplinary approaches. PMID- 24178293 TI - Inflammasome activation by altered proteostasis. AB - The association between altered proteostasis and inflammatory disorders has been increasingly recognized, but the underlying mechanisms are not well understood. In this study, we show that deficiency of either autophagy or sequestosome 1 (p62 or SQSTM) led to inflammasome hyperactivation in response to LPS and ATP in primary macrophages and in mice in vivo. Importantly, induction of protein misfolding by puromycin, thapsigargin, or geldanamycin resulted in inflammasome activation that was more pronounced in autophagy- or p62-deficient macrophages. Accumulation of misfolded proteins caused inflammasome activation by inducing generation of nonmitochondrial reactive oxygen species and lysosomal damage, leading to release of cathepsin B. Our results suggest that altered proteostasis results in inflammasome activation and thus provide mechanisms for the association of altered proteostasis with inflammatory disorders. PMID- 24178294 TI - Amino acid region 1000-1008 of factor V is a dynamic regulator for the emergence of procoagulant activity. AB - Single chain factor V (fV) circulates as an Mr 330,000 quiescent pro-cofactor. Removal of the B domain and generation of factor Va (fVa) are vital for procoagulant activity. We investigated the role of the basic amino acid region 1000-1008 within the B domain of fV by constructing a recombinant mutant fV molecule with all activation cleavage sites (Arg(709)/Arg(1018)/Arg(1545)) mutated to glutamine (fV(Q3)), a mutant fV molecule with region 1000-1008 deleted (fV(DeltaB9)), and a mutant fV molecule containing the same deletion with activation cleavage sites changed to glutamine (fV(DeltaB9/Q3)). The recombinant molecules along with wild type fV (fV(WT)) were transiently expressed in COS-7L cells, purified, and assessed for their ability to bind factor Xa (fXa) prior to and following incubation with thrombin. The data showed that fV(Q3) was severely impaired in its interaction with fXa before and after incubation with thrombin. In contrast, KD(app) values for fV(DeltaB9) (0.9 nM), fVa(DeltaB9) (0.4 nM), and fV(DeltaB9/Q3) (0.7 nM) were similar to the affinity of fVa(WT) for fXa (0.3 nM). Two-stage clotting assays revealed that although fV(Q3) was deficient in its clotting activity, fV(DeltaB9/Q3) had clotting activity comparable with fVa(WT). The kcat value of prothrombinase assembled with fV(DeltaB9/Q3) was minimally affected, whereas the Km value of the reaction was increased 57-fold compared with the Km value obtained with prothrombinase assembled with fVa(WT). These findings strongly suggest that amino acid region 1000-1008 of fV is a regulatory sequence protecting the organisms from spontaneous binding to fXa and unnecessary prothrombinase complex formation, which in turn results in catastrophic physiological consequences. PMID- 24178295 TI - Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor beta1a (TGFbeta1a). AB - Proprotein convertase subtilisin/kexin (PCSK) enzymes convert proproteins into bioactive end products. Although other PCSK enzymes are known to be essential for biological processes ranging from cholesterol metabolism to host defense, the in vivo importance of the evolutionarily ancient PCSK7 has remained enigmatic. Here, we quantified the expressions of all pcsk genes during the 1st week of fish development and in several tissues. pcsk7 expression was ubiquitous and evident already during the early development. To compare mammalian and zebrafish PCSK7, we prepared homology models, which demonstrated remarkable structural conservation. When the PCSK7 function in developing larvae was inhibited, we found that PCSK7-deficient fish have defects in various organs, including the brain, eye, and otic vesicle, and these result in mortality within 7 days postfertilization. A genome-wide analysis of PCSK7-dependent gene expression showed that, in addition to developmental processes, several immune system related pathways are also regulated by PCSK7. Specifically, the PCSK7 contributed to the mRNA expression and proteolytic cleavage of the cytokine TGFbeta1a. Consequently, tgfbeta1a morphant fish displayed phenotypical similarities with pcsk7 morphants, underscoring the importance of this cytokine in the zebrafish development. Targeting PCSK activity has emerged as a strategy for treating human diseases. Our results suggest that inhibiting PCSK7 might interfere with normal vertebrate development. PMID- 24178296 TI - Resveratrol induces a mitochondrial complex I-dependent increase in NADH oxidation responsible for sirtuin activation in liver cells. AB - Resveratrol (RSV) has been shown to be involved in the regulation of energetic metabolism, generating increasing interest in therapeutic use. SIRT1 has been described as the main target of RSV. However, recent reports have challenged the hypothesis of its direct activation by RSV, and the signaling pathways remain elusive. Here, the effects of RSV on mitochondrial metabolism are detailed both in vivo and in vitro using murine and cellular models and isolated enzymes. We demonstrate that low RSV doses (1-5 MUM) directly stimulate NADH dehydrogenases and, more specifically, mitochondrial complex I activity (EC50 ~1 MUM). In HepG2 cells, this complex I activation increases the mitochondrial NAD(+)/NADH ratio. This higher NAD(+) level initiates a SIRT3-dependent increase in the mitochondrial substrate supply pathways (i.e. the tricarboxylic acid cycle and fatty acid oxidation). This effect is also seen in liver mitochondria of RSV-fed animals (50 mg/kg/day). We conclude that the increase in NADH oxidation by complex I is a crucial event for SIRT3 activation by RSV. Our results open up new perspectives in the understanding of the RSV signaling pathway and highlight the critical importance of RSV doses used for future clinical trials. PMID- 24178297 TI - Trimeric transmembrane domain interactions in paramyxovirus fusion proteins: roles in protein folding, stability, and function. AB - Paramyxovirus fusion (F) proteins promote membrane fusion between the viral envelope and host cell membranes, a critical early step in viral infection. Although mutational analyses have indicated that transmembrane (TM) domain residues can affect folding or function of viral fusion proteins, direct analysis of TM-TM interactions has proved challenging. To directly assess TM interactions, the oligomeric state of purified chimeric proteins containing the Staphylococcal nuclease (SN) protein linked to the TM segments from three paramyxovirus F proteins was analyzed by sedimentation equilibrium analysis in detergent and buffer conditions that allowed density matching. A monomer-trimer equilibrium best fit was found for all three SN-TM constructs tested, and similar fits were obtained with peptides corresponding to just the TM region of two different paramyxovirus F proteins. These findings demonstrate for the first time that class I viral fusion protein TM domains can self-associate as trimeric complexes in the absence of the rest of the protein. Glycine residues have been implicated in TM helix interactions, so the effect of mutations at Hendra F Gly-508 was assessed in the context of the whole F protein. Mutations G508I or G508L resulted in decreased cell surface expression of the fusogenic form, consistent with decreased stability of the prefusion form of the protein. Sedimentation equilibrium analysis of TM domains containing these mutations gave higher relative association constants, suggesting altered TM-TM interactions. Overall, these results suggest that trimeric TM interactions are important driving forces for protein folding, stability and membrane fusion promotion. PMID- 24178298 TI - The orphan adhesion G protein-coupled receptor GPR97 regulates migration of lymphatic endothelial cells via the small GTPases RhoA and Cdc42. AB - The important role of the lymphatic vascular system in pathological conditions such as inflammation and cancer has been increasingly recognized, but its potential as a pharmacological target is poorly exploited. Our study aimed at the identification and molecular characterization of lymphatic-specific G protein coupled receptors (GPCRs) to assess new targets for pharmacological manipulation of the lymphatic vascular system. We used a TaqMan quantitative RT-PCR-based low density array to determine the GPCR expression profiles of ex vivo isolated intestinal mouse lymphatic (LECs) and blood vascular endothelial cells (BECs). GPR97, an orphan adhesion GPCR of unknown function, was the most highly and specifically expressed GPCR in mouse lymphatic endothelium. Using siRNA silencing, we found that GPR97-deficient primary human LECs displayed increased adhesion and collective cell migration, whereas single cell migration was decreased as compared with nontargeting siRNA-transfected control LECs. Loss of GPR97 shifted the ratio of active Cdc42 and RhoA and initiated cytoskeletal rearrangements, including F-actin redistribution, paxillin and PAK4 phosphorylation, and beta1-integrin activation. Our data suggest a possible role of GPR97 in lymphatic remodeling and furthermore provide the first insights into the biological functions of GPR97. PMID- 24178299 TI - The structural basis for endotoxin-induced allosteric regulation of the Toll-like receptor 4 (TLR4) innate immune receptor. AB - As part of the innate immune system, Toll-like receptor 4 (TLR4) recognizes bacterial cell surface lipopolysaccharide (LPS) by forming a complex with a lipid binding co-receptor, MD-2. In the presence of agonist, TLR4.MD-2 dimerizes to form an active receptor complex, leading to initiation of intracellular inflammatory signals. TLR4 is of great biomedical interest, but its pharmacological manipulation is complicated because even subtle variations in the structure of LPS can profoundly impact the resultant immunological response. Here, we use atomically detailed molecular simulations to gain insights into the nature of the molecular signaling mechanism. We first demonstrate that MD-2 is extraordinarily flexible. The "clamshell-like" motions of its beta-cup fold enable it to sensitively match the volume of its hydrophobic cavity to the size and shape of the bound lipid moiety. We show that MD-2 allosterically transmits this conformational plasticity, in a ligand-dependent manner, to a phenylalanine residue (Phe-126) at the cavity mouth previously implicated in TLR4 activation. Remarkably, within the receptor complex, we observe spontaneous transitions between active and inactive signaling states of Phe-126, and we confirm that Phe 126 is indeed the "molecular switch" in endotoxic signaling. PMID- 24178300 TI - Histone H4 promotes prothrombin autoactivation. AB - Recent studies have documented the ability of prothrombin to spontaneously convert to the mature protease thrombin when Arg-320 becomes exposed to solvent for proteolytic attack upon mutation of residues in the activation domain. Whether prothrombin autoactivation occurs in the wild-type under conditions relevant to physiology remains unknown. Here, we report that binding of histone H4 to prothrombin under physiological conditions generates thrombin by autoactivation. The effect is abrogated by mutation of the catalytic Ser-525 and requires the presence of the Gla domain. Fluorescence titrations document direct binding of histone H4 to prothrombin with an affinity in the low nm range. Stopped flow data and luminescence resonance energy transfer measurements indicate that the binding mechanism obeys conformational selection. Among the two conformations of prothrombin, collapsed and fully extended, histone H4 binds selectively to the collapsed form and induces a transition toward a new conformation where the distance between Ser-101 in kringle-1 and Ser-210 in kringle-2 increases by 13 A. These findings confirm the molecular plasticity of prothrombin emerged from recent structural studies and suggest that different conformations of the inter-kringle linker domain determine the functional behavior of prothrombin. The results also broaden our mechanistic understanding of the prothrombotic phenotype observed during cellular damage due to the release of histones in the blood stream. Prothrombin autoactivation induced by histone H4 emerges as a mechanism of pathophysiological relevance through which thrombin is generated independently of activation of the coagulation cascade. PMID- 24178301 TI - Impact of self-assembled monolayer films with specific chemical group on bFGF adsorption and endothelial cell growth on gold surface. AB - In this study, thiols ended with methyl, carboxyl, hydroxy, and amino groups are self-assembled on gold surfaces. The X-ray photoelectron spectroscopy test results show that chemical components on the self-assembled surface are similar to those in the theoretical calculations. The atomic force microscope test results show that the molecule assembled on the surface causes no significant variation in the surface roughness before and after the molecule assembly. The water surface contact angle increases with the increasing hydrophilicity of the end groups of the self-assembled monolayer. The surface zeta potential reveals that -COOH surface has the most electronegativity. The resulting substrates are then made to adsorb base fibroblast growth factor (bFGF). The quartz crystal microbalance test results show that the amounts of bFGF adsorbed onto different self-assembled surfaces are -COOH~-OH>-CH3 >-NH2. According to cell culture experiments, endothelial cells have different morphologies after adhering to different surfaces. Furthermore, endothelial cells achieve the quickest proliferation on the -COOH self-assembled surface and the slowest proliferation on the -CH3 self-assembled surface. PMID- 24178302 TI - A rare case of multiple skip segment Hirschsprung's disease in the ileum and colon. AB - As a rare form of Hirschsprung's disease, skip segment Hirschsprung's disease (SSHD) involves a "skip area" in normally ganglionated intestine, surrounded by aganglionosis. We report a case of multiple SSHD in the ileum and colon with total colonic aganglionosis. To our knowledge, this is the 27th case of SSHD, the third paper on multiple-segment SSHD, and the second patient with SSHD in the ileum to be reported in the English literature. PMID- 24178304 TI - 3D structure of a heparin mimetic analogue of a FGF-1 activator. A NMR and molecular modelling study. AB - The motional behaviour of heparin oligosaccharides in solution is best described as a top rotor having two perpendicular rotation axes. This prevents an accurate extraction of interprotonic distances by NOESY/ROESY based methods. In this paper, we describe the solution structure of the hexasaccharide 1 calculated from high exactitude distance data obtained from off-resonance ROESY combined with a long MD simulation of 500 ns. In previous studies, we have found that two synthetic hexasaccharides having the sulphate groups directed towards one side of its central plane have an opposite biological activity, while 1 is unable to activate the FGF-1 signalling pathway, the other (2) is even more active than the regular region derived hexasaccharide (3) that mimics the natural active compound, heparin. From the structural analysis it was concluded that 1 has similar three-dimensional characteristics to 2 or 3 and therefore the differences in the activity should be due to the arrangement of the sulphate groups within the hexasaccharidic sequence. PMID- 24178303 TI - Differential downregulation of Rbm5 and Rbm10 during skeletal and cardiac differentiation. AB - RBM5 and RBM10 play an important role in transformed cells. This role includes influencing the alternative splicing and/or expression of factors involved in apoptosis and cell cycle arrest. To date, all apoptosis studies relating to RBM5 and RBM10 have been performed in transformed cell lines, potentially confounding mechanistic interpretation because of the many mutations present in this population. The objective of this study was to identify a physiologically relevant non-transformed system in which to examine the expression of RBM5 and RBM10 for future mechanistic and target identification studies. Our system of choice was H9c2 myoblast differentiation. Expression of Rbm5, Rbm10, and selected splice variants was examined by end-point or real-time PCR and Western blot. We determined that all of the examined Rbm5 and Rbm10 variants were expressed in H9c2 myoblasts and throughout skeletal and cardiac myoblast differentiation. Furthermore, expression was differentially downregulated in a lineage-specific manner, suggesting lineage-specific regulation and roles. There was no correlation between mRNA and protein expression for Rbm5, Rbm10v1, and Rbm10v2, suggesting post-transcriptional and/or post-translational regulation. The differentiation expression profiles suggest the products encoded by Rbm5 and Rbm10 play a more important role in skeletal than cardiac myoblast differentiation and influence similar processes in non-tumor, differentiating cells as in transformed cells. The data also suggest that full-length Rbm5 and Rbm10 play a less important role than their alternative splice variants and/or shorter protein isoforms. This work establishes myoblast differentiation as a relevant model in which to conduct functional studies regarding Rbm5 and Rbm10. PMID- 24178305 TI - Horseshoe kidney: a review of anatomy and pathology. AB - Horseshoe kidney (HSK) is the most common renal fusion, which is characterized by three anatomic anomalies: ectopia, malrotation and vascular changes. Patients with HSK are prone to a variety of complications, genitourinary and non genitourinary. In this paper, the anatomy of HSK is delineated with a great emphasis on its blood supply. After reviewing the literature, the arterial supply patterns found by each author were categorized according to the classification system proposed by Graves. The majority of HSKs were found to be supplied by renal arteries derived from the abdominal aorta below the isthmus or by vessels originating from the common iliac arteries. In addition, the abnormalities associated with HSK are highlighted and classified in anatomical variations, congenital anomalies as well as in pathologic conditions related to HSK. PMID- 24178307 TI - Molecular variability of sugarcane streak mosaic virus in China based on an analysis of the P1 and CP protein coding regions. AB - Sequences of the protein 1 (P1) and coat protein (CP) coding regions of 22 sugarcane streak mosaic virus (SCSMV) isolates were determined. Phylogenetic analysis showed that SCSMV had at least three major lineages, and the lineages seemed to reflect geographical origin. The sudden expansions of the Chinese and Indian subpopulations were supported by calculations showing deviations from the neutral equilibrium model for the individual lineages with an overall lack of nucleotide diversity. Our study shows that Chinese and Indian SCSMV isolates are part of a distinct population, and the subpopulations probably reflect founder effects. PMID- 24178308 TI - In vitro RNA interference targeting the DNA polymerase gene inhibits orf virus replication in primary ovine fetal turbinate cells. AB - Orf, which is caused by orf virus (ORFV), is distributed worldwide and is endemic in most sheep- and/or goat-raising countries. RNA interference (RNAi) pathways have emerged as important regulators of virus-host cell interactions. In this study, the specific effect of RNAi on the replication of ORFV was explored. The application of RNA interference (RNAi) inhibited the replication of ORFV in cell culture by targeting the ORF025 gene of ORFV, which encodes the viral polymerase. Three small interfering RNA (siRNA) (named siRNA704, siRNA1017 and siRNA1388) were prepared by in vitro transcription. The siRNAs were evaluated for antiviral activity against the ORFV Jilin isolate by the observation of cytopathic effects (CPE), virus titration, and real-time PCR. After 48 h of infection, siRNA704, siRNA1017 and siRNA1388 reduced virus titers by 59- to 199-fold and reduced the level of viral replication by 73-89 %. These results suggest that these three siRNAs can efficiently inhibit ORFV genome replication and infectious virus production. RNAi targeting of the DNA polymerase gene is therefore potentially useful for studying the replication of ORFV and may have potential therapeutic applications. PMID- 24178309 TI - Etiological evaluation of adolescents with primary amenorrhea. AB - OBJECTIVES: To determine causes of amenorrhea in adolescents with primary amenorrhea and to emphasize general approach to primary amenorrhea. METHODS: Thirty-nine patients, evaluated between January 2007 and May 2011, were divided into normogonadotropic hypogonadism, hypergonadotropic hypogonadism and hypogonadotropic hypogonadism groups. Means of age, height, weight, body mass index and standard deviation scores, gonadotropin levels, and accompanying diseases were evaluated. RESULTS: Mean values of age, height, height standard deviation score, weight and, weight standard deviation score were 15.54 +/- 1.52 y. 152.0 +/- 1.1 cm, -1.37 +/- 1.3, 48.2 +/- 14.3 kg, 0.96 +/- 1.75, respectively. There were no statistical significances in the auxological parameters. Patients were distributed as 18 cases (46.1 %) with normogonadotropic hypogonadism, 12 cases (30.8 %) with hypergonadotropic hypogonadism, 9 cases (23.1 %) with hypogonadotropic hypogonadism. In the group of normogonadotropic hypogonadism, there were 6 patients with chronic diseases, 5 patients with insulin resistance, 4 patients with prolactinomas, 3 patients with mullerian agenesis. Of the hypergonadotropic hypogonadic patients, 3 were idiopathic primary ovarian failure, 3 were 46,XY disorders of sex development, 2 were Turner syndrome, 2 were ovarian insufficiency due to drug, one was 17 alpha-hydroxylase deficiency and one was autoimmune oophoritis. The group of hypogonadotropic hypogonadism included 5 patients with normosmic hypogonadism, 2 patients with constitutional delay of growth and puberty, 1 patient with panhypopituitarism and 1 patient with anosmic hypogonadism. CONCLUSIONS: Chronic diseases, prolactinoma, and insulin resistance may lead to hypogonadism without altering gonadotropin levels. Turner syndrome, primary ovarian failure, and autoimmune oophoritis should be investigated in cases with hypergonadotropic hypogonadism. 46, XY disorders of sex development also should be elucidated. Constitutional delay of growth and puberty should be distinguished from isolated hypogonadotropic hypogonadism. PMID- 24178310 TI - Use of health care services before and after a natural disaster among survivors with and without PTSD. AB - OBJECTIVE: This study used a questionnaire to identify individuals who met criteria for posttraumatic stress disorder (PTSD) ten months after surviving a disaster and compared their use of health care services before and after the disaster with that of survivors who did not meet criteria for PTSD. METHODS: Ten months after the December 26, 2004, Southeast Asian tsunami, Danish tourists who had been in areas exposed to the disaster were mailed a questionnaire asking about demographic characteristics and exposure to the tsunami. The questionnaire included the PTSD Checklist, which measures symptoms of posttraumatic stress. Individuals who met DSM-IV PTSD criterion A1--in this case, being caught, touched, or chased by the waves or having witnessed the death, serious injury, or suffering of others--were included in the analyses (N=635). The Danish National Health Service Register provided longitudinal data on annual number of contacts with health care services before (2002-2004) and after (2005-2007) the tsunami. RESULTS: Survivors with PTSD or partial PTSD used health care services more than survivors without PTSD before and after the tsunami. The severity of posttraumatic stress symptoms was positively correlated with postdisaster use of health care services. However, when adjusted for predisaster health care use, this association was not significant. CONCLUSIONS: Postdisaster health care service utilization was predicted by predisaster health care service utilization and was hardly affected by the onset of PTSD itself. Associations between PTSD and subsequent health problems must be interpreted with caution. PMID- 24178311 TI - Clinical effectiveness of cardiac resynchronization and implantable cardioverter defibrillator therapy in men and women with heart failure: findings from IMPROVE HF. AB - BACKGROUND: Many clinical trials have demonstrated a benefit for cardiac resynchronization (CRT) and implantable cardioverter-defibrillator (ICD) therapies in patients with heart failure and reduced ejection fraction, yet questions have been raised with regard to the benefit of ICDs for women. The purpose of this study was to determine the clinical effectiveness of CRT and ICD therapy as a function of sex in outpatients with heart failure and reduced ejection fraction (<=35%). METHODS AND RESULTS: Data from the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) were analyzed by device status and sex among guideline-eligible patients for vital status (alive/dead) at 24 months. Multivariate generalized estimating equation analyses were conducted adjusting for baseline patient and practice characteristics. In the ICD/CRT-defibrillator (CRT-D) eligible cohort (n=7748), there were 5485 (71%) men and 2261 (29%) women. In the CRT-pacemaker (CRT-P)/CRT-D eligible cohort (n=1188), there were 824 (69%) men and 364 (31%) women. The clinical benefit associated with ICD/CRT-D therapy was similar in both men and women (men adjusted odds ratio, 0.71; 95% confidence interval, 0.57-0.87; P=0.0012; and women adjusted odds ratio, 0.65; 95% confidence interval, 0.49 0.85; P=0.0019). For CRT-P/CRT-D, the associated benefits showed no significant heterogeneity (men adjusted odds ratio, 0.59; 95% confidence interval, 0.33-1.06; P=0.0793; and women adjusted odds ratio, 0.44; 95% confidence interval, 0.22 0.90; P=0.0243). The device-by-sex interactions were not significant (P=0.4441 for CRT-P/CRT-D and P=0.5966 for ICD/CRT-D). CONCLUSIONS: The use of guideline directed CRT and ICD therapy was associated with substantially reduced 24-month mortality in eligible men and women with heart failure and reduced ejection fraction. Device therapies should be offered to all eligible patients with heart failure, without modification based on sex. PMID- 24178312 TI - What is the optimum social marketing mix to market energy conservation behaviour: an empirical study. AB - This study attempts to identify the optimum social marketing mix for marketing energy conservation behaviour to students in Malaysian universities. A total of 2000 students from 5 major Malaysian universities were invited to provide their preferred social marketing mix. A choice-based conjoint analysis identified a mix of five social marketing attributes to promote energy conservation behaviour; the mix is comprised of the attributes of Product, Price, Place, Promotion, and Post purchase Maintenance. Each attribute of the mix is associated with a list of strategies. The Product and Post-purchase Maintenance attributes were identified by students as the highest priority attributes in the social marketing mix for energy conservation behaviour marketing, with shares of 27.12% and 27.02%, respectively. The least preferred attribute in the mix is Promotion, with a share of 11.59%. This study proposes an optimal social marketing mix to university management when making decisions about marketing energy conservation behaviour to students, who are the primary energy consumers in the campus. Additionally, this study will assist university management to efficiently allocate scarce resources in fulfilling its social responsibility and to overcome marketing shortcomings by selecting the right marketing mix. PMID- 24178313 TI - A modelling study of long term green roof retention performance. AB - This paper outlines the development of a conceptual hydrological flux model for the long term continuous simulation of runoff and drought risk for green roof systems. A green roof's retention capacity depends upon its physical configuration, but it is also strongly influenced by local climatic controls, including the rainfall characteristics and the restoration of retention capacity associated with evapotranspiration during dry weather periods. The model includes a function that links evapotranspiration rates to substrate moisture content, and is validated against observed runoff data. The model's application to typical extensive green roof configurations is demonstrated with reference to four UK locations characterised by contrasting climatic regimes, using 30-year rainfall time-series inputs at hourly simulation time steps. It is shown that retention performance is dependent upon local climatic conditions. Volumetric retention ranges from 0.19 (cool, wet climate) to 0.59 (warm, dry climate). Per event retention is also considered, and it is demonstrated that retention performance decreases significantly when high return period events are considered in isolation. For example, in Sheffield the median per-event retention is 1.00 (many small events), but the median retention for events exceeding a 1 in 1 yr return period threshold is only 0.10. The simulation tool also provides useful information about the likelihood of drought periods, for which irrigation may be required. A sensitivity study suggests that green roofs with reduced moisture holding capacity and/or low evapotranspiration rates will tend to offer reduced levels of retention, whilst high moisture-holding capacity and low evapotranspiration rates offer the strongest drought resistance. PMID- 24178314 TI - Soil amendment with olive mill wastes: impact on groundwater. AB - Two sets of soil lysimeters were amended with solid and liquid olive mill wastes and the composition of leachate was analysed. Five treatments were carried out using: olive mill wastewater (OMW) at two different rates (80 and 320 m(3)/ha); OMW pre-treated by catalytical digestion with MnO2; compost obtained by exhausted olive pomace; freshwater as the control. Electric conductivity, pH, potassium, total polyphenols and nitrates were monitored in the leachate as indexes of potential groundwater contamination. The study demonstrated that the impact of all the selected amendments on groundwater was the minimum. OMW was safely applied to soil even at four times the rate allowed by the Italian law, and pre treatment by catalytical digestion was not necessary to further reduce the impact on groundwater. The application of olive pomace compost was equally safe. PMID- 24178315 TI - Chitosan and alginate biopolymer membranes for remediation of contaminated water with herbicides. AB - This study investigated the adsorption behavior of the herbicides diquat, difenzoquat and clomazone on biopolymer membranes prepared with alginate and chitosan (pristine and multi-layer model) for contaminated water remediation applications. Herbicides, at concentrations ranging from 5 MUM to 200 MUM, were adsorbed in either pure alginate, pure chitosan or a bilayer membrane composed of chitosan/alginate. No adsorption of clomazone was observed on any of the membranes, probably due to lack of electrostatic interactions between the herbicide and the membranes. Diquat and difenzoquat were only adsorbed on the alginate and chitosan/alginate membranes, indicating that this adsorption takes place in the alginate layer. At a concentration of 50 MUM, diquat adsorption reaches ca. 95% after 120 min on both the alginate and chitosan/alginate membranes. The adsorption of difenzoquat, at the same concentration, reaches ca. 62% after 120 min on pure alginate membranes and ca. 12% on chitosan/alginate bilayer membranes. The adsorption isotherms for diquat and difenzoquat were further evaluated using the isotherm models proposed by Langmuir and by Freundlich, where the latter represented the best-fit model. Results indicate that adsorption occurs via coulombic interactions between the herbicides and alginate and is strongly related to the electrostatic charge, partition coefficients and dissociation constants of the herbicides. Biopolymer based membranes present novel systems for the removal of herbicides from contaminated water sources and hold great promise in the field of environmental science and engineering. PMID- 24178316 TI - Regulation of aplanospore germination in Vaucheria : Time-dependent responses to calcium modulators. AB - Germination of aplanospores in Vaucheria longicaulis Hoppaugh var. macounii Blum proceeds through three stages of development. Stage I begins with the initiation of germination and lasts approx. 2 h. During this stage germinating filaments grow at an accelerated rate (266 +/- 12 MUm . h(-1)). Stage II is characterized by a sharp decline in the growth rate of germinating filaments (96 +/- 4 MUm . h( 1)) and lasts 4 h. This is followed, during the next 4 h, by a recovery in the growth rate (168 +/- 8 MUm . h(-1)) of germinating filaments, stage III. Growth rates stabilize and remain unchanged during subsequent development (Oliveira and Fitch, 1988, J. Submicrosc. Cytol. Pathol. 20, 397-406). The Ca(2+)-influx modulators LaCl3, nifedipine and methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4 (2 trifluoromethylphenyl)-pyridine-5-carboxylate (Bay K-8644), the ionophore calcimycin (A23187), the intracellular Ca(2+)-release antagonist 8-N-N' (diethylamino)-octyl-3,4, 5-trimethoxybenzoate (TMB-8), the Ca(2+)-uptake inhibitor ruthenium red and the phosphoinositide-cycle modulators LiCl and myo inositol show that the events required for the initiation are distinct from those required for the completion of each stage of germination. These studies in conjunction with microinjection of germinating filaments with inositol 1,4,5 trisphosphate, the natural ligand for Ca(2+) release from Ca-storing organelles (endoplasmic reticulum, vacuole), and treatment with chlorotetracycline (CTC), to visualize the distribution of membrane-bound Ca(2+) reveal that both the initiation and completion of each stage of germination are controlled by Ca(2+) signals which are restricted to well-defined time intervals and are modulated by the origin (source) of Ca(2+). PMID- 24178317 TI - The defense-related STH-2 gene product of potato shows race-specific accumulation after inoculation with low concentrations of Phytophthora infestans zoospores. AB - The defense-related STH-2 gene is rapidly activated following infection or elicitor treatment of potato (Solanum tuberosum L.) tubers. However, its physiological or biochemical function is unknown. To study the STH-2 gene product and its accumulation during the defense response, we raised antibodies to a beta galactosidase-STH-2 fusion protein in Escherichia coli. The antiserum specifically recognized a protein of the predicted 17-kDa size in extracts of elicited tuber disks when analyzed by Western blot. In control extracts this band was not detected. The accumulation of STH-2 protein in response to incompatible and compatible zoospores of Phytophthora infestans (Mont.) de Bary depended on the inoculum density applied. Whereas a low concentration of spores induced accumulation of STH-2 protein faster in the incompatible than the compatible interaction, this difference in timing was less pronounced at higher inoculum densities. Inoculation with a high concentration of compatible spores also resulted in the disappearance of STH-2 protein late during the infection. In both control and induced tuber tissue the antibody strongly reacted with an unknown protein of 18 kDa. This protein was present constitutively in tubers, but in leaves its accumulation was stimulated by inoculation with P. infestans. PMID- 24178318 TI - Variation in free-radical damage in rice cell suspensions with different embryogenic potentials. AB - Levels of free-radical-mediated lipid peroxidation were monitored in cell suspension cultures of Oryza sativa L. possessing different embryogenic potentials. Oxidative stress was evaluated using assays which sequentially assessed the stages of lipid peroxidation (diene conjugation, peroxidation, and the formation of secondary lipid-peroxidation products). Lipid peroxidation was significantly higher in a cell line which had lost embryogenic ability compared with lines which still retained this capacity. Superoxide dismutase (EC 1.15.1.1) activity did not vary significantly between the embryogenic and previously embryogenic lines; however, catalase (EC 1.11.1.6) and peroxidase (EC 1.11.1.7) activities were significantly lower in the line which had lost embryogenic ability. Metabolic activity as estimated by reduction of triphenyl tetrazolium chloride decreased with diminishing embryogenic potential and was especially low in cell lines which never exhibited embryogenic capabilities. The possible involvement of free radicals in the loss of embryogenic potential of rice cells is discussed. PMID- 24178319 TI - The role of the plasma-membrane Ca(2+)-ATPase in Ca (2+) homeostasis in Sinapis alba root hairs. AB - The regulation of cytosolic Ca(2+) has been investigated in growing root-hair cells of Sinapis alba L. with special emphasis on the role of the plasmamembrane Ca(2+)-ATPase. For this purpose, erythrosin B was used to inhibit the Ca(2+) ATPase, and the Ca(2+) ionophore A23187 was applied to manipulate cytosolic free [Ca(2+)] which was then measured with Ca(2+)-selective microelectrodes. (i) At 0.01 MUM, A23187 had no effect on the membrane potential but enhanced the Ca(2+) permeability of the plasma membrane. Higher concentrations of this ionophore strongly depolarized the cells, also in the presence of cyanide. (ii) Unexpectedly, A23187 first caused a decrease in cytosolic Ca(2+) by 0.2 to 0.3 pCa units and a cytosolic acidification by about 0.5 pH units, (iii) The depletion of cytosolic free Ca(2+) spontaneously reversed and became an increase, a process which strongly depended on the external Ca(2+) concentration, (iv) Upon removal of A23187, the cytosolic free [Ca(2+)] returned to its steady-state level, a process which was inhibited by erythrosin B. We suggest that the first reaction to the intruding Ca(2+) is an activation of Ca(2+) transporters (e.g. ATPases at the endoplasmic reticulum and the plasma membrane) which rapidly remove Ca(2+) from the cytosol. The two observations that after the addition of A23187, (i) Ca(2+) gradients as steep as-600 mV could be maintained and (ii) the cytosolic pH rapidly and immediately decreased without recovery indicate that the Ca(2+)-exporting plasma-membrane ATPase is physiologically connected to the electrochemical pH gradient, and probably works as an nH(+)/Ca(2+)-ATPase. Based on the finding that the Ca(2+)-ATPase inhibitor erythrosin B had no effect on cytosolic Ca(2+), but caused a strong Ca(2+) increase after the addion of A23187 we conclude that these cells, at least in the short term, have enough metabolic energy to balance the loss in transport activity caused by inhibition of the primary Ca(2+)-pump. We further conclude that this ATPase is a major Ca(2+) regulator in stress situations where the cytosolic Ca(2+) has been shifted from its steady-state level, as may be the case during processes of signal transduction. PMID- 24178320 TI - Carbohydrate metabolism during postharvest ripening in kiwifruit. AB - Mature fruit (kiwifruit) of Actinidia deliciosa var. deliciosa (A. Chev.), (C.F.) Liang and Ferguson cv. Haywood (Chinese gooseberry) were harvested and allowed to ripen in the dark at 20 degrees C. Changes were recorded in metabolites, starch and sugars, adenine nucleotides, respiration, and sucrose and glycolytic enzymes during the initiation of starch degradation, net starch-to-sucrose conversion and the respiratory climacteric. The conversion of starch to sucrose was not accompanied by a consistent increase in hexose-phosphates, and UDP-glucose declined. The activity of sucrose phosphate synthase (SPS) measured with saturating substrate rose soon after harvesting and long before net sucrose synthesis commenced. The onset of sugar accumulation correlated with an increase in SPS activity measured with limiting substrates. Throughout ripening, until sucrose accumulation ceased, feeding [(14)C] glucose led to labelling of sucrose and fructose, providing evidence for a cycle of sucrose synthesis and degradation. It is suggested that activation of SPS, amplified by futile cycles, may regulate the conversion of starch to sugars. The respiratory climacteric was delayed, compared with net starchsugar interconversion, and was accompanied by a general decline of pyruvate and all the glycolytic intermediates except fructose 1,6-bisphosphate. The ATP/ ADP ratio was maintained or even increased. It is argued that the respiratory climacteric cannot be simply a consequence of increased availability of respiratory substrate during starch-sugar conversion, nor can it result from an increased demand for ATP during this process. PMID- 24178321 TI - Cell shape and localisation of ice in leaves of overwintering wheat during frost stress in the field. AB - Wheat leaf pieces were excised and freeze-fixed in the field, preparatory to low temperature scanning electron microscopy to study distribution of ice within leaf blades, and associated cell shapes, during natural frosts. Pieces of leaf blades from wheat plants (Triticum aestivum L. 7942H1-20-8) overwintering in Indiana, USA (January, 1991), were excised and immediately freeze-fixed by manually plunging in melting freon. Cells in controls were turgid and extracellular ice was absent. The leaves of the frost-stressed plants froze at about - 2.4 degrees C, and at that temperature extracellular ice was mainly located sub-epidermally, including in the substomatal cavity, and occupied about 14% of the fracture faces. The frequency of ice particles per unit leaf area in two specimens was 14 and 210 . mm(-2) (about 140 and 2100 . g(-1) leaf fresh-weight basis). At -9.0 degrees C, ice filled the extracellular spaces, occupying 61% of the fracture faces. Cells were somewhat collapsed at -2.4 degrees C and were much more collapsed at -9.0 degrees C. The epidermal cells were more collapsed than the mesophyll cells. Tissue structure (connections with adjacent cells), wall flexibility, and ice growth may all have influenced the shapes of the collapsing cells. The experiments demonstrate the feasibility of freeze-fixation in the field. The sub-epidermal location of most ice indicates that in the field either (i) ice is nucleated sub-epidermally (implying both the presence of nucleators and the presence of liquid water in the sub-epidermal spaces) or (ii) ice is nucleated on the leaf surface, then propagates into the leaf probably through stomata. PMID- 24178322 TI - Light dependence of protoplasmic streaming in Nitella flexilis L. as measured by means of laser-velocimetry. AB - Laser-velocimetry was applied in order to study the effect of light on the velocity of protoplasmic streaming (pps) in Characean cells. A change from dark to light (= 6 W . m(-2)) leads to an acceleration of streaming by about 15-30% with a time-constant of approx. 300 s. The transition from light to dark causes a transient decrease of velocity below the original dark level. This response occurs with a time constant of about 500 s. It returns to its initial value with a time-constant of about 2000 s. This may indicate that a control loop of cytosolic homeostasis takes a decrease in pCa more seriously than an increase. A possible involvement of temperature effects caused by illumination was excluded by measuring the influence of temperature. Steady-state velocity of streaming changed by 5% per 1 degrees C. Irradiation with infra-red light (lambda > 780 nm) did not cause a change in velocity. The absence of a light effect on streaming velocity in the presence of 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU) shows that photosynthesis and not phytochrome is involved. The role of light-induced changes of pCa is discussed, especially with respect to the hypothesis of Vanselow and Hansen (1989, J. Membr. Biol. 110, 175-187) that photosynthesis acts on the plasmalemma K(+)-channel via light-induced uptake of Ca(2+) into the chloroplasts. PMID- 24178323 TI - Cell-wall tension of the inner tissues of the maize coleoptile and its potential contribution to auxin-mediated organ growth. AB - Plant organs such as maize (Zea mays L.) coleoptiles are characterized by longitudinal tissue tension, i.e. bulk turgor pressure produces unequal amounts of cell-wall tension in the epidermis (essentially the outer epidermal wall) and in the inner tissues. The fractional amount of turgor borne by the epidermal wall of turgid maize coleoptile segments was indirectly estimated by determining the water potential psi(*) of an external medium which is needed to replace quantitatively the compressive force of the epidermal wall on the inner tissues. The fractional amount of turgor borne by the walls of the inner tissues was estimated from the difference between -psi(*) and the osmotic pressure of the cell sap (pii) which was assumed to represent the turgor of the fully turgid tissue. In segments incubated in water for 1 h, -psi(*) was 6.1-6.5 bar at a pii of 6.7 bar. Both -psi(*) and pii decreased during auxin-induced growth because of water uptake, but did not deviate significantly from each other. It is concluded that the turgor fraction utilized for the elastic extension of the inner tissue walls is less than 1 bar, i.e. less than 15% of bulk turgor, and that more than 85% of bulk turgor is utilized for counteracting the high compressive force of the outer epidermal wall which, in this way, is enabled to mechanically control elongation growth of the organ. This situation is maintained during auxin-induced growth. PMID- 24178324 TI - Purification and properties of pea (Pisum sativum L.) thioredoxin f, a plant thioredoxin with unique features in the activation of chloroplast fructose-1,6 bisphosphatase. AB - Thioredoxin (Td) f from pea (Pisum sativum L.) leaves was purified by a simple method, which provided a high yield of homogeneous Td f. Purified Td f had an isoelectric point of 5.4 and a relative molecular mass (Mr) of 12 kilodaltons (kDa) when determined by filtration through Superose 12, but an Mr of 15.8 kDa when determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified protein remained fully active for several months when conserved frozen at - 20 degrees C. The pea protein was able to activate fructose1,6 bisphosphatase (FBPase; EC 3.1.3.11), but in contrast to other higher-plant Td f proteins, was not functional in the modulation of NADP(+)-malate dehydrogenase activity. In spite of the absence of immunological cross-reactions of pea and spinach Td f proteins with the corresponding antibodies, pea Td f activated not only the homologous FBPase, but also the spinach enzyme. The saturation curves for pea FBPase, either with fructose-1,6-bisphosphate in the presence of different concentrations of homologous Td f, or with pea Td f in the presence of excess substrate, showed sigmoid kinetics; this can be explained on the basis of a random distribution of fructose-1,6-bisphosphate, and of the oxidized and reduced forms of the activator, among the four Td f- and substrate-binding sites of this tetrameric enzyme. From the saturation curves of pea and spinach Td f proteins against pea FBPase, a 4:1 stoichiometry was determined for the Td f enzyme binding. This is in contrast to the 2:1 stoichiometry found for the spinach FBPase. The UV spectrum of pea Td f had a maximum at 277 nm, which shifted to 281 nm after reduction with dithiothreitol (s at 280 nm for 15.8-kDa Mr = 6324 M(-1) . cm(-1)). The fluorescence emission spectrum after 280-nm excitation had a maximum at 334 nm, related to tyrosine residues; after denaturation with guanidine isothiocyanate an additional maximum appeared at 350 nm, which is concerned with tryptophan groups. Neither the native nor the denatured form showed a significant increase in fluorescence after reduction by dithiothreitol, which means that the tyrosine and tryptophan groups in the reduced Td f are similarly exposed. Pea Td f appears to have one cysteine residue more than the three cysteines earlier described for spinach and Scenedesmus Td f proteins. PMID- 24178325 TI - Localization of galactinol, raffinose, and stachyose synthesis in Cucurbita pepo leaves. AB - The biochemical pathway of stachyose synthesis was localized by immunocytochemical and (14)C-labeling techniques in mature Cucurbita pepo L. leaves. Galactinol synthase (GaS; EC 2.4.1.123), the first unique enzyme in this pathway, was immunolocalized within the intermediary cells of minor veins in conventionally fixed and cryo-fixed, resin-embedded sections using polyclonal anti-GaS antibodies and protein A-gold. Intermediary cells are specialized companion cells with extensive symplastic connections to the bundle sheath. Gold particles were not seen over the non-specialized companion cells of larger veins or over intermediary cells in young leaves prior to the sink-source transition. In another approach to localization, radiolabel was measured in isolated mesophyll tissue and whole tissue of leaves that were lyophilized following a 90 s exposure to (14)CO2. Mesophyll, obtained by abrasion of the leaf surface, contained labeled sucrose, galactinol, raffinose and stachyose. However, the latter three labeled compounds constituted a smaller proportion of the neutral fraction than in whole-tissue samples, which also contained minor veins. We conclude that synthesis of galactinol, raffinose, and stachyose occurs in both mesophyll and intermediary cells, predominantly the latter. PMID- 24178326 TI - Gibberellin-induced growth and regulation of the cell division cycle in deepwater rice. AB - Excised stem sections of deepwater rice (Oryza sativa L., cv. Pin Gaew 56) containing the highest internode were used to study induction of rapid internodal elongation by gibberellin. It has been shown previously that this growth response is based on an increased cell production rate in the intercalary meristem and on increased cell elongation. Our investigations were aimed at establishing the temporal sequence of these GA-regulated processes. Cell sizes were determined by scanning electron microscopy, the phases of the cell cycle by flow cytometry, and DNA synthesis by [(3)H]thymidine incorporation. The lag time for the onset of gibberellic acid (GA3)-induced growth was 40 min. Treatment with GA3 promoted cell elongation in the intercalary meristem within 2 h. After 4 h of treatment with GA3, the fraction of meristematic cells in the G2 phase had declined, indicating that cells in the G2 phase had entered mitosis. Subsequent activation of DNA replication led to an overall increase in the cell-production rate. This was evident from an increase in the percentage of cells in the S phase and from enhanced incorporation of [(3)H]thymidine into DNA between 4 and 7 h of GA3 treatment. An increase in the final cell length contributed to the growth response after 7 h of GA3 application. Our results are consistent with the hypothesis that gibberellin first promotes cell elongation in the intercalary meristem and that cell division is stimulated as a result of cell-growth. PMID- 24178327 TI - Effect of long-term photoinhibition on growth and photosynthesis of cold-hardened spring and winter wheat. AB - The effect of repeated exposure to high light (1200 MUmol . m(-2) . s(-1) photosynthetic photon flux density, PPFD) at 5 degrees C was examined in attached leaves of cold-grown spring (cv. Katepwa) and winter (cv. Kharkov) wheat (Triticum aestivum L.) over an eight-week period. Under these conditions, Kharkov winter wheat exhibited a daily reduction of 24% in FV/FM (the ratio of variable to maximal fluorescence in the dark-adapted state), in contrast to 41% for cold grown Katepwa spring wheat. Both cultivars were able to recover from this daily suppression of FV/FM such that the leaves exhibited an average morning FV/FM of 0.651 +/- 0.004. Fluorescence measurements made under steady-state conditions as a function of irradiance from 60 to 2000 MUmol . m(-2) . s(-1) indicated that the yield of photosystem II (PSII) electron transport under light-saturating conditions was the same for photoinhibited and control cold-grown plants, regardless of cultivar. Repeated daily exposure to high light at low temperature did not increase resistance to short-term photoinhibition, although zeaxanthin levels increased by three- to fourfold. In addition, both cultivars increased the rate of dry-matter accumulation, relative to control plants maintained at 5 degrees C and 250 MUmol . m(-2) . s(-1) PPFD (10% and 28% for Katepwa and Kharkov, respectively), despite exhibiting suppressed fv/fm and reduced photon yields for O2 evolution following daily high-light treatments. Thus, although photosynthetic efficiency is suppressed by a longterm, photoinhibitory treatment, light-saturated rates of photosynthesis are sufficiently high during the high light treatment to offset any reduction in photochemical efficiency of PSII. We suggest that in these cold-tolerant plants, photoinhibition of PSII may represent a longterm, stable, down-regulation of photochemistry to match the overall photosynthetic demand for ATP and reducing equivalents. PMID- 24178328 TI - Control of the appearance of alanine aminotransferase in the Scots pine (Pinus sylvestris L.) seedling. AB - In seedlings of the Scots pine (Pinus sylvestris L.), alanine aminotransferase (AlAT EC 2.6.1.2.) is present in the shoot and in the primary root but most activity is found in the cotyledons. During the experimental period (from 6 to 12 d after sowing), AlAT activity increased steadily. Anion exchange chromatography and native polyacrylamide gel electrophoresis were used to show that AlAT activity in extracts from cotyledons is associated with two isoforms of the enzyme. One isoform (AlAT 1) dominated in the cotyledons of lightgrown seedlings, but was absent from primary roots. Its accumulation was strongly increased by light, and both phytochrome and cryptochrome were shown to be involved in this effect. Results of experiments using dichromatic irradiation indicate that cryptochrome acts indirectly by establishing responsiveness towards phytochrome. When plastids were damaged by photooxidation, the accumulation of AlAT 1 decreased; however, AlAT 1 which had accumulated before the onset of photooxidative treatment seemed to remain undamaged. Therefore, and because of the absence of AlAT 1 from primary roots, it is suggested that this isoform is localized in leaf peroxisomes. The isoform AlAT 2 is the only one found in primary roots, and the predominant one in the cotyledons of dark-grown seedlings. It is unaffected by light. Upon photodestruction of plastids, a pronounced increase of its activity was found. This is taken as evidence that AlAT 2 is a cytosolic enzyme. Total AlAT activity in cotyledons was unaffected by feeding nitrate to the seedlings; supplying exogenous ammonium led to a considerably slower accumulation of AlAT compared with water controls. In contrast, AlAT accumulation in the primary roots was augmented by up to 45% if nitrogenous ions were supplied, ammonium being more effective than nitrate. PMID- 24178329 TI - Asparagine metabolism and nitrogen distribution during protein degradation in sugar-starved maize root tips. AB - Excised maize (Zea mays L.) root tips were used to monitor the effects of prolonged glucose starvation on nitrogen metabolism. Following root-tip excision, sugar content was rapidly exhausted, and protein content declined to 40 and 8% of its initial value after 96 and 192 h, respectively. During starvation the contents of free amino acids changed. Amino acids that belonged to the same "synthetic family" showed a similar pattern of changes, indicating that their content, during starvation, is controlled mainly at the level of their common biosynthetic steps. Asparagine, which is a good marker of protein and amino-acid degradation under stress conditions, accumulated considerably until 45 h of starvation and accounted for 50% of the nitrogen released by protein degradation at that time. After 45 h of starvation, nitrogen ceased to be stored in asparagine and was excreted from the cell, first as ammonia until 90-100 h and then, when starvation had become irreversible, as amino acids and aminated compounds. The study of asparagine metabolism and nitrogen-assimilation pathways throughout starvation showed that: (i) asparagine synthesis occurred via asparagine synthetase (EC 6.3.1.1) rather than asparagine aminotransferase (EC 2.6.1.14) or the beta-cyanoalanine pathway, and asparagine degradation occurred via asparaginase (EC 3.5.1.1); and (ii) the enzymic activities related to nitrogen reduction and assimilation and amino-acid synthesis decreased continuously, whereas glutamate dehydrogenase (EC 1.4.1.2-4) activities increased during the reversible period of starvation. Considered together, metabolite analysis and enzymic-activity measurements showed that starvation may be divided into three phases: (i) the acclimation phase (0 to 30-35 h) in which the root tips adapt to transient sugar deprivation and partly store the nitrogen released by protein degradation, (ii) the survival phase (30-35 to 90-100 h) in which the root tips expel the nitrogen released by protein degradation and starvation may be reversed by sugar addition and (iii) the cell-disorganization phase (beyond 100 h) in which all metabolites and enzymic activities decrease and the root tips die. PMID- 24178330 TI - Glutamine synthetase in Scots pine seedlings and its control by blue light and light absorbed by phytochrome. AB - The appearance of glutamine synthetase (GS. EC 6.3.1.2) in response to light and nitrogen (NO 3 (-) , NH 4 (+) ) was studied in the organs (roots, hypocotyl, cotyledonary whorl) of the Scots pine (Pinus sylvestris L.) seedling. Although GS activity was found to be mainly (> 80%) located in the whorl where it increased strongly in response to light, a significant GS synthesis was also detected in dark-grown seedlings. Anion-exchange chromatography was used to resolve two GS isoforms which appeared to be regulated differentially in the cotyledonary whorls. The isoform (presumably plastidic GS2) which eluted from the column at 90 mM KCl increased drastically in response to light. The other isoform (presumably cytosolic GS1), which eluted at 200 mM KCl, was not stimulated by light but tended to disappear during the experimental period (4 to 12 d after sowing). Immunoblotting of pine extract yielded a prominent band with a molecular weight of 43 kDa. The linear correlation between GS activity and immunodetectable GS protein could be extrapolated through zero, showing that any increase of GS2 activity is to be attributed to the de-novo synthesis of GS protein. Gelfiltration chromatography yielded a molecular mass for the GS holoenzyme of 340 kDa, a value which supports an octameric quarternary structure as previously suggested for angiosperms. While supplying seedlings with 10 mM NO 3 (-) stimulated GS synthesis in the whorl by 12%, 10 mM NH 4 (+) caused an incipient ammonium toxicity. Experiments using dischromatic light (simultaneous treatment with two light beams to vary the level of the physiologically active form of phytochrome, Pfr, in blue light) revealed that synthesis of GS2 was controlled by light in the same way as previously shown for ferredoxin-dependent glutamate synthase (Fd-GOGAT; EC 1.4.7.1). Up to 10 d after sowing the strong light effect could be attributed to phytochrome action whereas between 10 and 12 d after sowing phytochrome control of GS-synthesis failed if no blue/ultraviolet-A light was provided. The data show that blue light is required to maintain responsiveness of GS2 synthesis to phytochrome. Both enzymes, GS2 as well as Fd GOGAT, appear to be regulated coordinately to meet the demands of ammonium assimilation. PMID- 24178331 TI - Early events during the establishment of the Gunnera/Nostoc symbiosis. AB - The symbiosis between Gunnera and Nostoc was reconstituted using G. chilensis Lam. and G. manicata Linden, respectively, and three different Nostoc strains. Six stages characterised by specific modifications in both the cyanobiont and the host were recognised during the infection process. Mucilage-secreting stem glands developed on the Gunnera stems independent of the presence of cyanobacteria (Stage I). Soon after addition of the Nostoc isolates to the plant apices, an abundant differentiation of motile hormogonia commenced. The cyanobacteria accumulated in the mucilage on the surface of the gland (Stage II), and the hormogonia then proceeded into the stem tissue through intercellular channels (Stage III). At the channel bases, Nostoc was detected between the cell walls of small, densely cytoplasmic Gunnera cells and also in elaborate folds of these (Stage IV). The Gunnera cell walls subsequently dissolved adjacent to the cyanobacteria and Nostoc entered the host cells (Stage V). Once the intracellular association was formed, a high proportion of the vegetative Nostoc cells differentiated into heterocysts (Stage VI). Nostoc changed from being rich in inclusions (particularly cyanophycin) while on the gland surface into a comparatively "non-storing" form during penetration and the early intracellular stages. Bacteria were numerous on the gland surface, fewer in the channels, and were never detected within the Gunnera cells, indicating the existence of specific recognition mechanisms discriminating between conceivable microsymbionts. Mechanisms behind mutual adaptations and interactions between the two symbionts are discussed. PMID- 24178332 TI - Aluminum effects on the kinetics of calcium uptake into cells of the wheat root apex : Quantification of calcium fluxes using a calcium-selective vibrating microelectrode. AB - The effects of aluminum on the concentration-dependent kinetics of Ca(2+) uptake were studied in two winter wheat (Triticum aestivum L.) cultivars, Al-tolerant Atlas 66 and Al-sensitive Scout 66. Seedlings were grown in 100 MUM CaCl2 solution (pH 4.5) for 3 d. Subsequently, net Ca(2+) fluxes in intact roots were measured using a highly sensitive technique, employing a vibrating Ca(2+) selective microelectrode. The kinetics of Ca(2+) uptake into cells of the root apex, for external Ca(2+) concentrations from 20 to 300 MUM, were found to be quite similar for both cultivars in the absence of external Al; Ca(2+) transport could be described by Michaelis-Menten kinetics. When roots were exposed to solutions containing levels of Al that were toxic to Al-sensitive Scout 66 but not to Atlas 66 (5 to 20 MUM total Al), a strong correlation was observed between Al toxicity and Al-induced inhibition of Ca(2+) absorption by root apices. For Scout 66, exposure to Al immediately and dramatically inhibited Ca(2+) uptake over the entire Ca(2+) concentration range used for these experiments. Kinetic analyses of the Al-Ca interactions in Scout 66 roots were consistent with competitive inhibition of Ca(2+) uptake by Al. For example, exposure of Scout 66 roots to increasing Al levels (from 0 to 10 MUM) caused the K m for Ca(2+) uptake to increase with each rise in Al concentration, from approx. 100 MUM in the absence of Al to approx. 300 MUM in the presence of 10 MUM Al, while having no effect on the V max. The same Al exposures had little effect on the kinetics of Ca(2+) uptake into roots of Atlas 66. The results of this study indicate that Al disruption of Ca(2+) transport at the root apex may play an important role in the mechanisms of Al toxicity in Al-sensitive wheat cultivars, and that differential Al tolerance may be associated with the ability of Ca(2+)-transport systems in cells of the root apex to resist disruption by potentially toxic levels of Al in the soil solution. PMID- 24178333 TI - Mechanistic differences in photoinhibition of sun and shade plants. AB - Leaf discs of the shade plant Tradescantia albiflora Kunth grown at 50 MUmol . m( 2) . s(-1), and the facultative sun/shade plant Pisum sativum L. grown at 50 or 300 MUmol . m(-2), s(-1), were photoinhibited for 4 h in 1700 MUmol photons m(-2) . s(-1) at 22 degrees C. The effects of photoinhibition on the following parameters were studied: i) photosystem II (PSII) function; ii) amount of D1 protein in the PSII reaction centre; iii) dependence of photoinhibition and its recovery on chloroplast-encoded protein synthesis; and, iv) the sensitivity of photosynthesis to photoinhibition in the presence or absence of the carotenoid zeaxanthin. We show that: i) despite different sensitivities to photoinhibition, photoinhibition in all three plants occurred at the reaction centre of PSII; ii) there was no correlation between the extent of photoinhibition and the degradation of the D1 protein; iii) the susceptibility to photoinhibition by blockage of chloroplas-tencoded protein synthesis was much less in shade plants than in plants acclimated to higher light; and iv) inhibition of zeaxanthin formation increased the sensitivity to photoinhibition in pea, but not in the shade plant Tradescantia. We suggest that there are mechanistic differences in photoinhibition of sun and shade plants. In sun plants, an active repair cycle of PSII replaces photoinhibited reaction centres with photochemically active ones, thereby conferring partial protection against photoinhibition. However, in shade plants, this repair cycle is less important for protection against photoinhibition; instead, photoinhibited PSII reaction centres may confer, as they accumulate, increased protection of the remaining connected, functional PSII centres by controlled, nonphotochemical dissipation of excess excitation energy. PMID- 24178334 TI - cDNA cloning of an extracellular dermal glycoprotein of carrot and its expression in response to wounding. AB - Suspension-cultured cells of carrot (Daucus carota L.) synthesize and secrete a glycoprotein that is normally found only in dermal tissues (epidermis, endodermis and periderm). This protein, previously called GP57, is now referred to as EDGP (E xtracellular D ermal G lyco P rotein). We purified sufficient quantities of EDGP to obtain amino-acid sequences on two internal tryptic peptides and screened a cDNA library of young carrot roots with antiserum to EDGP and with oligonucleotides corresponding to the peptides. Here we report the derived amino acid sequence of EDGP. Sequence comparisons show that it has 40% amino-acid sequence identity with 7S basic globulin, a protein that is released when soybean seeds are soaked in hot water for a few hours. We suggest that these two proteins belong to a new family of dermal proteins. As far as we know, this is the first reported derived amino-acid sequence for protein that is specific to the epidermis and other dermal tissues. The level of EDGP mRNA is low in dry seeds, but increases rapidly in growing seedlings as they develop dermal tissues. The level of mRNA is low in storage roots, but increases rapidly in response to wounding. The presence of EDGP in dermal tissues and its up-regulation in response to wounding indicate a role in the response of plants to biotic and-or abiotic stresses. An unusual feature of the amino-acid sequence of EDGP is that it contains a short motif, which is present at the active site of aspartyl proteases such as pepsin and chymosin. PMID- 24178335 TI - Characterization of competent cells and early events of Agrobacterium-mediated genetic transformation in Arabidopsis thaliana. AB - The insertion of foreign DNA in plants occurs through a complex interaction between Agrobacteria and host plant cells. The marker gene beta-glucuronidase of Escherichia coli and cytological methods were used to characterize competent cells for Agrobacterium-mediated transformation, to study early cellular events of transformation, and to identify the potential host-cell barriers that limit transformation in Arabidopsis thaliana L. Heynh. In cotyledon and leaf explants, competent cells were mesophyll cells that were dedifferentiating, a process induced by wounding and-or phytohormones. The cells were located either at the cut surface or within the explant after phytohormone pretreatment. In root explants, competent cells were present in dedifferentiating pericycle, and were produced only after phytohormone pretreatment. Irrespective of their origin, the competent cells were small, isodiametric with thin primary cell walls, small and multiple vacuoles, prominent nuclei and dense cytoplasm. In both cotyledon and root explants, histological enumeration and beta-glucuronidase assays showed that the number of putatively competent cells was increased by preculture treatment, indicating that cell activation and cell division following wounding were insufficient for transformation without phytohormone treatment. Exposure of explants for 48 h to A. tumefaciens produced no characteristic stress response nor any gradual loss of viability nor cell death. However, in the competent cell, association between the polysaccharide of the host cell wall and that of the bacterial filament was frequently observed, indicating that transformation required polysaccharide-to-polysaccharide contact. Flow cytofluorometry and histological analysis showed that abundant transformation required not only cell activation (an early state exhibiting an increase in nuclear protein) but also cell proliferation (which in cotyledon tissue occurred at many ploidy levels). Noncompetent cells could be made competent with the appropriate phytohormone treatments before bacterial infection: this should aid analysis of critical steps in transformation procedures and should facilitate developing new strategies to transform recalcitrant plants. PMID- 24178336 TI - Role of prescribers in the level of patient satisfaction: a study in public health care settings. AB - AIMS: To assess the level of patient satisfaction with the various aspects of interaction of the health provider with the patient such as communication, examination and information regarding prescription in the allopathic public health facilities of Lucknow district. SETTINGS AND DESIGN: Public health facilities of Lucknow district, India. INTRODUCTION: Satisfaction in service provision is increasingly being used as a measure of health system performance. The satisfaction with the service provider i.e., the prescriber is a vital component of the whole process of consultation and largely determines the compliance of the patient to the treatment prescribed. Apart from this, satisfaction also varies according to the sociodemographic characteristics of the beneficiaries. We have therefore tried to study these factors in the present study. MATERIALS AND METHODS: Multistage stratified random sampling was used to select the health facilities while the patients were selected by systematic random sampling for the interview. STATISTICAL ANALYSIS: Number and percentages, mean and chi(2) test. RESULTS: The overall satisfaction regarding the doctor patient communication and certain aspects of examination was highest for the residents (75.4%) followed by the super specialists (71.5%) and specialists (69.1%). CONCLUSIONS: The findings of the study will help us educate the prescribers about the various neglected areas of the consultation which will go a long way to develop a consistent relationship between the providers and the beneficiaries for the attainment of the "Health for All". PMID- 24178337 TI - Clinical assessment of the autonomic nervous system in diabetes mellitus and its correlation with glycemic control. AB - AIM: Clinical assessment of the autonomic nervous system in Diabetes mellitus (DM) and its correlation with glycemic control. STUDY DESIGN: Cross sectional study of 50 adult diabetes patients. MATERIALS AND METHODS: Fifty patients with DM who were on regular treatment with either insulin and/or oral hypoglycemic agents were studied. Cardiovascular autonomic neuropathy (CAN) score was calculated using the clinical test variables. RESULTS: Of the 50 patients 30 had no CAN, 10 had early CAN and 10 had severe CAN. The mean of CAN score increased with duration of diabetes. The mean HbA(1C) was 7.73. The mean CAN score was higher in patients who had complication of diabetes as compared to patients without complications. The heart rate variability with respiration was found to be 15.84 +/- 7.02/min. The mean valsalva ratio was 1.31 +/- 0.23. The mean drop in BP on standing was 7.30 +/- 7.24 mmHg. The mean 30:15 ratio was 1.06 +/- 0.04. The mean rise in diastolic BP on sustained hand grip was 16.04 +/- 4.11 mmHg. CONCLUSIONS: The prevalence of autonomic neuropathy in DM as assessed by CAN score was 40%. The CAN score did not correlate with the duration of DM. The HbA(1C) had a significant correlation with the severity of autonomic neuropathy. Occurrence of CAN correlated with the presence of peripheral neuropathy but not with the presence of retinopathy or nephropathy. All individual tests in the battery of CAN score were significantly associated with the presence of autonomic neuropathy, except 30:15 ratio. PMID- 24178338 TI - A comparative study of computed radiography-based mammography using digital phosphor storage plate and full field digital mammography. AB - BACKGROUND: Two digital mammography systems, based on different physical concepts, have been introduced in the last few years namely the full-field digital mammography (FFDM) system and computed radiography-based mammography using digital storage phosphor plate (DSPM). AIMS: The objective of this study was to compare the image quality for DSPM and FFDM using a grading scale based on previously published articles. MATERIALS AND METHODS: This comparative diagnostic study was done for 5-month duration at the Breast Clinic. The system used was the Lorad Selenia FFDM system and the Mammomat 3000 Nova DSPM system. The craniocaudal and mediolateral oblique projections were done on both breast on 58 asymptomatic women using both DSPM and FFDM. The mammograms were evaluated for eight criteria of image quality: Tissue coverage, compression, exposure, contrast, resolution, noise, artifact, and sharpness by two independent radiologists. STATISTICAL ANALYSIS: Wilcoxon Signed Rank Test and Weighted Kappa. RESULTS: FFDM was rated significantly better (P < 0.05) for five aspects: Tissue coverage, compression, contrast, exposure, and resolution and equal to DSPM for sharpness, noise, and artifact. CONCLUSION: FFDM was superior in five aspects and equal to DSPM for three aspects of image quality. PMID- 24178339 TI - Vitamin D status and its association with antioxidant profiles in diabetic patients: A cross-sectional study in Iran. AB - BACKGROUND AND OBJECTIVES: There are increasing evidences about the relationship between vitamin D status and the control of diabetes. Several studies showed that vitamin D has an antioxidant property. In this study, we aimed to determine the relationship between serum levels of 25-hydroxy vitamin D (25-OH-D) and glycemic, antioxidant profile in diabetes compared to healthy groups. MATERIALS AND METHODS: This cross-sectional study was conducted in 100 patients with type 2 diabetes mellitus (T2DM) and 100 healthy controls. Fasting serum levels of 25-OH D, calcium, phosphorous, parathyroid hormone, glucose, HbA(1C), insulin, homeostasis model assessment of insulin resistance index, total antioxidant capacity (TAC), activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GSH-PX) were measured. RESULTS: Eighty-two percent of type 2 diabetic patients and 75% of healthy subjects were suffering from vitamin D deficiency or insufficiency. The activities of GR and GSH-PX were higher in diabetic patients compared to control. There was a negative relationship between 25-OH-D and activity of GR, GSH-PX. Also, 25-OH-D had a positive association with activity of SOD in diabetic patients. In the control group, 25-OH-D had an inverse relationship with SOD, GSH-PX, and positively with GR activities. INTERPRETATION AND CONCLUSIONS: Vitamin D deficiency has a high prevalence among Iranian adult population with and without type 2 diabetes. Our results showed that vitamin D may have a beneficial effect on the control of glycemic profiles and oxidative stress in T2DM patients. PMID- 24178340 TI - Assessment of bronchial responsiveness on exposure to isometric exercise during different phases of menstrual cycle: a pilot study. AB - OBJECTIVES: The present study was planned to assess the effects of gonadal steroids (estrogen and progesterone) on bronchial responsiveness, before and after handgrip exercise, during different phases of menstrual cycle. MATERIALS AND METHODS: In this study, 30 healthy (25-40 years), non-athletic, adult female volunteers were studied. The various pulmonary function parameters (FVC, FEV1, PEFR, FEF 25-75%) were recorded with a spirometer under resting conditions and then within five minutes of cessation of isometric exercise. Recordings were taken during the Menstrual phase (MP), Proliferative phase (PP), and Luteal phase (LP) of menstrual cycle and were confirmed by plasma levels of estrogen and progesterone. The oral temperature was recorded during each phase of the menstrual cycle. RESULTS: Under resting conditions, the above-mentioned parameters did not reveal significant differences during the three phases. A significant fall was observed only in the Peak Expiratory Flow Rate (PEFR) during all the phases after handgrip, but there was a non-significant decline in the other parameters. CONCLUSION: By this study we conclude that the physiological changes in hormone levels during the menstrual cycle are not in themselves associated with changes in airway responsiveness before and after the handgrip test. The general fall seen in the pulmonary parameters could be due to fatigue or psychic factors. PMID- 24178341 TI - Pregnancy in rudimentary horn of uterus. AB - A 20-year-old primigravida with 3 months amenorrhea presented with complaints of acute abdominal pain. Her vital systemic parameters were stable. On vaginal examination, the patient was provisionally diagnosed of right cornual ectopic pregnancy, which was confirmed sonographically, and taken up for surgery. There was moderate hemoperitoneum and rupture of right horn of uterus with products protruding. The rudimentary horn was excised. The patient was discharged and advised contraception and follow-up. PMID- 24178342 TI - Expression and purification of ecdysteroid-regulated protein from Chinese mitten crab Eriocheir sinensis in E. coli. AB - The glutathione S-transferase (GST) fusion protein system is widely used for high level expression and efficient purification of recombinant proteins from bacteria. The goal of this study was to clone, efficiently express and purify the ecdysteroid-regulated protein (ERP) in the form of a GST fusion protein. The mature peptide-coding cDNA fragment was extracted from Chinese mitten crap (Eriocheir sinensis), and then after using PCR to obtain the open reading frame, a recombinant plasmid designated pGEX-4T-1_ERP was successfully generated and showed to efficiently express the ERP fusion protein as determined by SDS-PAGE. The resulting expressed protein was successfully purified by a combination of affinity and conventional chromatographic methods. After purification, the recombinant protein showed the expected size of 41 kDa on SDS-PAGE gels which was further confirmed by mass spectrometry and western blotting. Purification of recombinant protein was achieved by fast protein liquid chromatography. About 2.4 mg/l recombinant protein with purity more than 80 % was obtained. PMID- 24178343 TI - Adiponectin decreases lipids deposition by p38 MAPK/ATF2 signaling pathway in muscle of broilers. AB - Adiponectin is an adipokine hormone that influences glucose utilization, insulin sensitivity and energy homeostasis. To investigate the effect of adiponectin on lipids deposition in broilers, rosiglitazone and dexamethasone were used to treat broilers. A total of 120 twenty-three-day-old male Cobb broilers were randomly divided into 3 groups for 3 weeks of drug treatment. Serum adiponectin level and fatty acid composition in muscles were measured. Adiponectin, adiponectin receptors (adipoR1, adipoR2) and lipid metabolism-related genes expression levels in muscles were measured using real-time PCR. Western blot was used to measure the expression levels of lipid metabolism-related proteins and the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK)/activating transcription factor 2 (ATF2) pathway marker proteins. Rosiglitazone increased serum adiponectin concentration and the expression levels of adiponectin and adipoR1 (P < 0.05), while dexamethasone had the opposite effect. Intramuscular fat content, total fatty acid, saturated fatty acid and monounsaturated fatty acid reduced in the rosiglitazone treatment group (P < 0.05). In the rosiglitazone treatment group, the expression levels of lipogenic genes and proteins decreased in the muscles, whereas the expression levels of lipolysis genes increased. Meanwhile, the phosphorylation levels of p38MAPK and ATF2 increased with supplementation of rosiglitazone and decreased in the dexamethasone treatment group (P < 0.01). These results indicated that rosiglitazone and dexamethasone could regulate adiponectin expression in muscle of broilers and adiponectin had an anti-lipogenic effect by p38 MAPK/ATF2 signaling pathway. PMID- 24178344 TI - Polymorphic microsatellite loci for two Atlantic oyster species: Crassostrea rhizophorae and C. gasar. AB - Using a CA/CAA enriched library screening procedure, we isolated and characterised a total of seventeen polymorphic microsatellite loci for two species of Crassostrea with recognised economic importance. Eleven microsatellite loci were developed for C. rhizophorae, a Western Atlantic species for which no microsatellites were previously known. Another six loci were developed for C. gasar, a species that occurs on both sides of the South Atlantic, adding to the ten loci previously described for the species. The levels of polymorphism were estimated using 24 C. rhizophorae from Southeast Brazil (Sao Paulo) and 23 C. gasar individuals from North Brazil (Maranhao). The number of alleles per polymorphic locus varied from 3 to 27, and the observed and expected heterozygosities ranged between 0.174 and 0.958 and between 0.237 and 0.972 in C. rhizophorae and C. gasar, respectively. No linkage disequilibrium was found between any locus pair, and four of them exhibited deviations from Hardy-Weinberg expectations. Of the 17 loci developed, 8 cross-amplified in C. gigas and 13 in C. virginica. These markers are useful for evolution and population genetics studies of Crassostrea species and may provide fundamental data for the future cultivation of native oysters in Western Atlantic. PMID- 24178345 TI - Overexpression of the anaphase-promoting complex (APC) genes in Nicotiana tabacum promotes increasing biomass accumulation. AB - The anaphase-promoting complex (APC) plays pivotal roles in cell cycle pathways related to plant development. In this study, we present evidence that overproduction of APC10 from Arabidopsis thaliana in tobacco (Nicotiana tabacum) plants promotes significant increases in biomass. Analyzes of plant's fresh and dried weight, root length, number of days to flower and number of seeds of plants overexpressing AtAPC10 verified an improved agronomic performance of the transgenic plants. Detailed analyzes of the leaf growth at the cellular level, and measurements of leaf cell number, showed that AtAPC10 also produce more cells, showing an enhancement of proliferation in these plants. In addition, crossing of plants overexpressing AtAPC10 and AtCDC27a resulted in a synergistic accumulation of biomass and these transgenic plants exhibited superior characteristics compared to the parental lines. The results of the present study suggest that transgenic plants expressing AtAPC10 and AtAPC10/AtCDC27a concomitantly are promising leads to develop plants with higher biomass. PMID- 24178347 TI - Transformation of barrel medic (Medicago truncatula Gaertn.) by Agrobacterium tumefaciens and regeneration via somatic embryogenesis of transgenic plants with the MtENOD12 nodulin promoter fused to the gus reporter gene. AB - Fertile and stable transgenic plants of the model legume Medicago truncatula Gaertn. were obtained through transformation of leaf tissue with the disarmed Agrobacterium tumefaciens strain LBA4404 and in vitro regeneration via somatic embryogenesis. An optimised transformation/regeneration protocol has been established for two genotypes of the cultivar Jemalong, including a previously described highly embryogenic line (Nolan et al. 1989, Plant Cell Rep. 8: 278 281). Using this protocol, transgenic plantlets were obtained within 4-10 months following cocultivation with Agrobacterium. We have introduced into M. truncatula a chimeric fusion between the early nodulin MtENOD12 promoter and the gus (beta glucuronidase) reporter gene, and shown that symbiosis-specific gene expression can be elicited in the roots of such transgenic plants following the addition of purified Rhizobium nodulation factors. PMID- 24178346 TI - Management of mantle cell lymphoma in the elderly: current and potential strategies. AB - Mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin lymphoma, accounting for 3-10 % of all non-Hodgkin lymphoma cases. The median age at diagnosis is nearly 70 years. The prognosis of patients is based on the Mantle Cell Lymphoma International Prognostic Index, which is calculated on the basis of four independent prognostic factors (age, performance status, serum lactate dehydrogenase and leukocyte count). Treatment of elderly patients with de novo untreated mantle cell lymphoma is based on rituximab combined with chemotherapy. The most commonly used regimen is the classical CHOP21 (cyclophosphamide, doxorubicin, vincristine and prednisone) regimen. Bendamustine is also an option, especially for patients with cardiac comorbidities. In elderly patients who are relatively young and fit, an approach based on treatment usually used for younger patients, with cytarabine-based induction followed by autologous stem cell transplantation, should be discussed. Treatment of relapsing patients is based on the use of newer effective drugs, including bortezomib, lenalidomide and thalidomide, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus. These drugs are often combined with rituximab and can be prescribed in combination with chemotherapy. Promising new drugs are Bruton tyrosine kinase inhibitors and other inhibitors of the phosphoinositide 3-kinase (PI3K)-mTOR protein kinase B (AKT) pathway. Despite these new advances, mantle cell lymphoma remains an incurable disease, and further basic and clinical research is warranted. PMID- 24178348 TI - Transgenic plantlets of 'Chancellor' grapevine (Vitis sp.) from biolistic transformation of embryogenic cell suspensions. AB - Transgenic plantlets of 'Chancellor' grapevine (Vitis L. complex interspecific hybrid) were produced via biolistic transformation. Embryogenic cell suspensions were bombarded with 1 MUm tungsten particles coated with pBI426 which encodes a fusion peptide between beta-glucuronidase (GUS) and neomycin phosphotransferase II (NPTII). The fusion peptide is under the control of a double 35S Cauliflower Mosaic Virus promoter and a leader sequence from Alfalfa Mosaic Virus. The cells were placed on kanamycin-containing media (10, 25 or 50 mg/l) 2 d after bombardment. Activated charcoal reduced cell browning. Embryos were first observed on selective media 14-29 weeks after bombardment. More than 1600 clusters of embryos were germinated and/or assayed for GUS. Of 621 embryos assayed for GUS expression, 182 (29.3%) were positive. PCR confirmed the presence of the NPTII gene in all 5 GUS-positive and 2 GUS-negative (bombarded) embryos tested. In germination experiments, 15% of the embryo clusters produced at least one plant with normal shoot growth. Of 164 normal plants assayed for GUS expression, 37 (22.6%) were positive. The NPTII gene was amplified by PCR in 1 (of 1) GUS-positive and 4 (of 5) GUS-negative bombarded plants, but not in non bombarded control plants. Southern blotting confirmed integration of the NPTII gene in all 3 of the GUS and PCR-NPTII positive plants tested. Biolistics is an efficient method for transformation of 'Chancellor' and should be applicable to other important grape cultivars. PMID- 24178349 TI - Transgenic fertile Scoparia dulcis L., a folk medicinal plant, conferred with a herbicide-resistant trait using an Ri binary vector. AB - Transgenic herbicide-resistant Scoparia dulcis plants were obtained by using an Ri binary vector system. The chimeric bar gene encoding phosphinothricin acetyltransferase flanked by the promoter for cauliflower mosaic virus 35S RNA and the terminal sequence for nopaline synthase was introduced in the plant genome by Agrobacterium-mediated transformation by means of scratching young plants. Hairy roots resistant to bialaphos were selected and plantlets (R0) were regenerated. Progenies (S1) were obtained by self-fertilization. The transgenic state was confirmed by DNA-blot hybridization and assaying of neomycin phosphotransferase II. Expression of the bar gene in the transgenic R0 and S1 progenies was indicated by the activity of phosphinothricin acetyltransferase. Transgenic plants accumulated scopadulcic acid B, a specific secondary metabolite of S. dulcis, in amounts of 15-60% compared with that in normal plants. The transgenic plants and progenies showed resistant trait towards bialaphos and phosphinothricin. These results suggest that an Ri binary system is one of the useful tools for the transformation of medicinal plants for which a regeneration protocol has not been established. PMID- 24178350 TI - Selection of large quantities of embryogenic calli from indica rice seeds for production of fertile transgenic plants using the biolistic method. AB - The microprojectile bombardment of immature embryos has proven to be effective in transforming many indica rice varieties. One of the drawbacks of using immature embryos is the requirement of a large number of high quality immature embryos, which itself is a tedious and laborious process. To circumvent these problems, we have developed a procedure, using indica variety TN1 as a model that generates highly homogenous populations of embryogenic subcultured calli by selectively propagating a small number of regeneration-proficient calli derived from seeds. Thousands of embryogenic calli were produced from 50 seeds within 10 weeks. Ten to 20 independent R0 transgenic lines were regenerated per 500 embryogenic calli bombarded. The convenience and reliability offered by this transformation system has made transformation of indica rice a routine procedure. PMID- 24178351 TI - Agrobacterium tumefaciens-mediated transformation of Vigna mungo (L.) Hepper. AB - Transformed Vigna mungo (blackgram) calli were obtained by cocultivating segments of primary leaves with Agrobacterium tumefaciens vir helper strains harbouring the binary vector pGA472 having kanamycin resistance gene as plant transformation marker. Transformed calli were selected on Murashige and Skoog medium supplemented with 50 mg/l kanamycin and 500 mg/l carbenicillin. Transformed calli were found to be resistant to kanamycin up to 900 mg/l concentration. Expression of kanamycin resistance gene in transformed calli was demonstrated by neomycin phosphotransferase assay. Stable integration of transferred DNA into V. mungo genome was confirmed by Southern blot analysis. PMID- 24178352 TI - Plant regeneration via somatic embryogenesis from protoplasts of six plant species related to Citrus. AB - Protoplasts isolated from embryogenic callus of Fortunella polyandra (Ridl.), Atalantia bilocularis (Pieree ex Guill.), Hesperethusa crenulata (Roxb.), Glycosmis pentaphylla (Retz.) Corr., Triphasia trifolia (Burm. f.) P. Wils. and Murraya koenigii (L.) Spreng. were cultured in MT (Murashige and Tucker 1969) basal medium containing 5% sucrose supplemented with 0.0, 0.001, 0.01, 0.1 or 1.0 mg l(-1) BA and 0.6 M sorbitol. The highest plating efficiencies for all species were obtained on MT basal medium containing 5% sucrose supplemented with 0.001 mg l(-1) BA. F. polyandra produced higher percentages of globular somatic embryo development, while A. bilocularis consistently showed a lower percentage of globular somatic embryo development in all 5 concentrations of BA. MT basal medium containing 5% sucrose and supplemented with 0.001 mg l(-1) BA was found to be a suitable medium for development of globular somatic embryos derived from protoplasts to form heart-shaped somatic embryos with cotyledon-like structures. The highest percentages of shoot formation for all 6 species were obtained using 0.1 mg l(-1) GA3. A complete protoplast-to-plant system was developed for F. polyandra, A. bilocularis and T. trifolia, which could facilitate the transfer of nuclear and cytoplasmic genes from these species into cultivated Citrus through protoplast fusion. PMID- 24178353 TI - RAPD and organelle specific PCR re-affirms taxonomic relationships within the genus Coffea. AB - The phenetic relationships between 18 Coffea accessions representing 11 of the most important Coffea species employed in current breeding programmes were examined using RAPD markers and chloroplast and mitochondrial genome specific sequence tagged sites (STS). Estimates of variability based on the number of shared RAPD amplification products placed the species into three distinct groups which were consistent with derived chloroplast DNA phenotypes, the geographical origins of the species and previous studies based on morphological characteristics and RFLPs. C. eugenioides (2n = 2x = 22) exhibited the greatest similarity to the cultivated C. arabica (2n = 4x = 44) and may represent its maternal progenitor. The results are discussed in the context of strategies for Coffea improvement. PMID- 24178354 TI - Cleavage polyembryos as explants for plant regeneration in wheat. AB - The increased efficiency of embryogenic callus formation and regeneration of plantlets was the result of using immature induced polyembryos of wheat rather than single embryos as primary explants. Plant regeneration was effected via embryogenesis, organogenesis, and a combined process beginning as embryogenesis and proceeding as organogenesis. PMID- 24178355 TI - Histological investigation of walnut cotyledon fragments for a better understanding of in vitro adventitious root initiation. AB - Rapid formation of adventitious roots by walnut cotyledon fragments in vitro was traced by light microscopy. It was shown that this plant model is characterized by two major developmental processes: a) confined elongation of the cotyledon petiole caused by a limited number of cell divisions and b) formation of a morphogenetic zone around each initially wounded vascular bundle within 36 h after detachment of the embryonic axis. During the first phase of development, granular storage protein bodies dissolved, and starch grains were deposited mainly in the distal portion of the cotyledon fragments. Rapidly, new globular protein bodies were formed, and phenolic inclusions accumulated in the vacuoles of epidermal and subepidermal cells and of individual cells close to the vascular bundles. Each adventitious root was found to be in continuity with a single vascular bundle of the cotyledon petiole. A short auxin treatment suppressed the formation of large roots and induced numerous tiny rootlets dispersed all over the surface of the cotyledons. PMID- 24178356 TI - Predictive correlates of shoot regeneration from potato protoplast culture. AB - Adaptation of protoplast regeneration systems for use on untested or recalcitrant potato genotypes can be a time-consuming exercise. Callus growth and xylogenesis were evaluated as early correlates of shooting potential to shorten this process. Callus growth was of limited value for predicting organogenesis but a linear relationship was observed between xylogenesis and shooting frequency. Increases in xylem content above a minimum threshold corresponded with increases in shooting frequency. The predictive value of the relationship was tested using a simple protocol modification (the culture of calli on a filter paper base). Calli on filter paper produced more xylem elements and shoots than those plated directly on medium. The potential of xylem content as a predictive test of shooting frequency is discussed. PMID- 24178357 TI - Direct somatic embroygenesis from immature embryos of rosewood (Dalbergia latifolia Roxb.). AB - Direct regeneration of somatic embryos was obtained from immature zygotic embryos of Dalbergia latifolia. Immature embryos dissected from green pods 90 d after flowering gave the highest frequency of somatic embryo formation. Preculture on high 2,4-D medium for 4 weeks induced direct somatic embryogenesis, which was expressed during the second culture phase in the presence of low 2,4-D along with a high sucrose concentration. Embryos were separated and transferred to the maturation medium containing MS + 0.5-1.0 mg/L BAP, where embryos developed into plantlets. Somatic embryos failed to convert into complete plants without BAP treatment. This method of direct regeneration of somatic embryos without a callus phase has direct application for genetic manipulation studies. PMID- 24178358 TI - Biosynthesis of the sesquiterpenic phytoalexin capsidiol in elicited root cultures of chili pepper (Capsicum annuum). AB - The biosynthesis of the sesquiterpenic phytoalexin capsidiol was investigated using in vitro root cultures of chili pepper (Capsicum annuum) elicited with cellulase. Optimal concentrations of cellulase and sucrose for capsidiol production were established. A simple spectrophotometric procedure to quantify capsidiol was improved. Monoclonal antibodies against a tobacco sesquiterpene cyclase were used to detect a similar protein in pepper root extracts. We found that capsidiol was secreted to the medium and the maximal production was achieved at 24 h after elicitation. In contrast, the maximal amount of the elicitor inducible sesquiterpene cyclase was found between 6 and 8 h. Addition of small amounts of polyvinylpyrrolidone was necessary for sesquiterpene cyclase enzyme activity assays. PMID- 24178359 TI - Rapid propagation of lemongrass (Cymbopogon flexuosus (Nees) Wats.) through somatic embryogenesis in vitro. AB - Somatic embryos induced from callus cultures of lemongrass [Cymbopogon flexuosus (Nees) Wats.] on Murashige and Skoog medium supplemented with 5 mg/l of 2,4-D, 0.1 mg/l of NAA and 0.5 mg/l of Kn developed into plantlets when plated on a medium supplemented with 3 mg/l of BA, 1 mg/l of GA3 and 0.1 mg/l of NAA. The regeneration potential of callus was retained for more than 2 years on the nutrient medium supplemented with comparatively lower levels of growth regulators (2,4-D at 2 mg/l, NAA at 0.1 mg/l and Kn at 0.25 mg/l). Approximately 30-35 plantlets were produced after two months of culture per 100 mg of callus inoculated. Regenerants were transplanted into soil and transferred to the field for assessment of various morphological and biochemical characteristics. The results of 1 year of field trials showed that plants derived from somatic embryoids were more uniform in all the characteristics examined when compared with the field performance of plants raised through slips by standard propagation procedures. Thus, a procedure has been developed for high frequency long term plant production of lemongrass through in vitro methods. PMID- 24178360 TI - Lanthanide ions are agonists of transient gene expression in rice protoplasts and act in synergy with ABA to increase Em gene expression. AB - Previous work has shown that in rice suspension cells, NaCl at 0.4 M can induce Em gene expression and act synergistically with ABA, possibly by potentiating the ABA response pathway through a rate-limiting intermediate (R.M. Bostock and R.S. Quatrano (1992) Plant Physiol., 98, 1356-1363). Since calcium is an intermediate in ABA regulation of stomatal closure, we tested the effect of calcium changes on ABA-inducible Em gene expression in transiently transformed rice protoplasts. We show that calcium is required for ABA-inducible Em-GUS expression and can act in synergy with ABA. The trivalent ions lanthanum, gadolinium, and aluminum, which are known to interact with calcium- and other signaling pathways, can act at sub millimolar concentrations to increase GUS reporter gene expression driven by several promoters in transiently transformed rice protoplasts. This effect is not specific for the ABA-inducible Em promoter, but is synergistic with ABA. The lanthanum synergy with ABA does not require calcium. In rice suspension cells, lanthanum alone does not induce Em gene expression, in contrast to transiently transformed protoplasts, yet can act synergistically with ABA to effectively increase the sensitivity to ABA greater than tenfold. Trivalent ions may be a useful tool to study the regulation of gene expression. The possible effects of trivalent ions on ABA signal transduction and gene expression are discussed. PMID- 24178361 TI - Plant regeneration through somatic embryogenesis from callus induced on immature embryos of Alstroemeria spp. L. AB - The plant regeneration ability of callus obtained from zygotic embryos of the monocot Alstroemeria spp. was studied. The best explants for somatic embryogenesis were immature zygotic embryos in half-ovules when the endosperm was still soft and white. For 2 genotypes embryogenic callus was induced on callus induction medium with a success rate of 54%. The best callus induction period was 10 weeks. The morphology of embryogenic callus was nodular. Somatic embryos were formed after transfer of the callus to regeneration medium. These somatic embryos revealed later on the typical features of zygotic Alstroemeria embryos. The total duration of the plant regeneration protocol, from inoculation till rooted plantlets ready for transfer to the greenhouse, was 28 weeks. PMID- 24178362 TI - Large scale screening of human sera for HCV RNA and GBV-C RNA. AB - North Carolina locates acute HIV cases by pooled nucleic acid testing of HIV antibody negative serum samples. Here, 224 pools of 80 HIV-negative samples (N = 17,920) were screened for viral RNA from HCV, GBV-C, and influenza A. No evidence of influenza A was found, but HCV and GBV-C were common (1.2% and 1.7% prevalence, respectively), demonstrating the utility of pooled testing in locating individuals that may remain undiagnosed otherwise. By sequencing positive pools, potential transmission clusters may be located as well. PMID- 24178363 TI - Chronic traumatic encephalopathy and risk of suicide in former athletes. AB - BACKGROUND: In the initial autopsy case studies of chronic traumatic encephalopathy (CTE), some researchers have concluded that the proteinopathy associated with CTE is the underlying cause of suicidality and completed suicide in former athletes. METHODS: A review of the literature on contact sports and risk of completed suicide revealed only one epidemiological study with direct relevant data. RESULTS: There are no published cross-sectional, epidemiological or prospective studies showing a relation between contact sports and risk of suicide. One published epidemiological study suggests that retired National Football League players have lower rates of death by suicide than the general population. Outside of sports, there is a mature body of evidence suggesting that the causes of suicide are complex, multifactorial and difficult to predict in individual cases. CONCLUSIONS: Future research might establish a clear causal connection between the proteinopathy of CTE and suicide. At present, however, there is insufficient scientific evidence to conclude that there is a strong causal relationship between the presence of these proteinopathies and suicide in former athletes. Additional research is needed to determine the extent to which the neuropathology of CTE is a possible mediator or moderator variable associated with suicide. PMID- 24178364 TI - Classification systems for reinjuries: a continuing challenge. PMID- 24178365 TI - Adipose tissue fatty acid composition and colon cancer: a case-control study. AB - PURPOSE: An increased dietary intake of fat, particularly polyunsaturated fatty acids (PUFAs), has been related to an increased risk of breast, prostate and colon cancers. Patients with and without colon cancer were tested for differences in their fatty stores composition. METHODS: The fatty acid levels were determined by gas-liquid chromatography in adipose tissue samples, subcutaneous and visceral, obtained intra-operatively from 52 colon cancer and 50 nonneoplastic abdominal disease patients. Statistical analysis was performed using one-way ANOVA, SNK test and Dunnet test. Differences in the composition of saturated, monounsaturated and polyunsaturated fatty acids, in visceral and in subcutaneous samples of colon cancer and nonneoplastic patients, were assessed. RESULTS: The sum of saturated and monounsaturated fatty acids, respectively, in visceral and in subcutaneous samples, was higher in neoplastic patients (p < 0.001). The sum of some n-6 polyunsaturated fatty acids (PUFAs), the dietary precursor linoleic acid (LA-18:2n-6), and their metabolites, gammalinolenic acid (GLA-18:3n-6) + dihomogammalinolenic acid (DGLA-20:3n-6) + arachidonic acid (AA-22:4n-6), was higher in subcutaneous fat of controls (p < 0.05). The samples from these patients had a fatty acid composition, both subcutaneous and visceral, with a higher content of alphalinolenic acid (ALA-18:3n-3) and stearidonic acid (SDA 18:4n-3) compared to neoplastic patients (p < 0.001). These had subcutaneous and visceral fat stores statistically higher in GLA, DGLA and AA (p < 0.001). Colon cancer patients had subcutaneous adipose stores higher in ALA and LA than visceral sites (p < 0.001). CONCLUSIONS: Fatty acids may be involved in colon carcinogenesis and there is a depot-specific impact on this process by visceral fat. PMID- 24178366 TI - Self-assembled rosette nanotubes and poly(2-hydroxyethyl methacrylate) hydrogels promote skin cell functions. AB - The next generation skin of wound healing materials should stimulate skin regeneration by actively promoting appropriate cellular adhesion and proliferation. As materials with novel self-assembling and solidification properties when transitioning from room to body temperatures, rosette nanotubes (RNTs) may be such a proactive material. RNTs resemble naturally occurring nanostructures in the skin (such as collagen and keratin) assembling with noncovalent forces in physiological environments. Presenting desirable bioactive properties, RNTs have been used for various tissue engineering applications including increasing in vivo bone and cartilage regeneration. The objective of the current in vitro study was, for the first time, to improve properties of a commonly used hydrogel (poly(2-hydroxyethyl methacrylate) or pHEMA) for skin regeneration by incorporating one type of novel self-assembled RNTs, called TBL. Results showed for the first time increased keratinocyte and fibroblast proliferation on hydrogels coated with TBLs compared to those not coated with TBL. In this manner, this study provides the first evidence that TBL RNTs are promising for wound healing applications due to their optimal cytocompatibility, solidification, and mechanical properties and, thus, should be further studied for such applications. PMID- 24178367 TI - Influence of thiourea application on some physiological and molecular criteria of sunflower (Helianthus annuus L.) plants under conditions of heat stress. AB - High temperature is a major factor limiting the growth of plant species during summer. Understanding the mechanisms of plant tolerance to high temperature would help in developing effective management practices and heat-tolerant cultivars through breeding or biotechnology. The present investigation was carried out to study the role of thiourea in enhancing the tolerance of sunflower plants to heat stress. Sunflower plants were subjected to temperature stress by exposing plants to 35 or 45 degrees C for 12 h. Two levels of thiourea (10 and 20 mM) were applied before sowing (seed treatment). The results indicated that the plants exposed to temperature stress exhibited a significant decline in growth parameters, chlorophylls, relative leaf water content, oil content, leaf nutrient status, and nitrate reductase activity. Treatment with thiourea, especially when applied at 10 mM, improved the above parameters and induced non-enzymatic and enzymatic antioxidants responsible for antioxidation. SDS-PAGE of protein revealed that high-temperature treatments alone or in combination with thiourea were associated with the disappearance of some bands or the appearance of unique ones. The result of RAPD analysis using five primers showed variable qualitative and quantitative changes. These findings confirm the effectiveness of applying thiourea on alleviating heat injuries in sunflower plants. PMID- 24178368 TI - A phase I, randomized, open-label study of the multiple-dose pharmacokinetics of vemurafenib in patients with BRAF V600E mutation-positive metastatic melanoma. AB - PURPOSE: This study characterized the multiple-dose pharmacokinetics of vemurafenib 240-960 mg twice daily (bid) in BRAF(V600E) mutation-positive metastatic melanoma patients, using the commercial formulation (240-mg microprecipitated bulk powder film-coated tablets). METHODS: Melanoma patients (N = 52) were randomly allocated to four vemurafenib dose cohorts (240, 480, 720, or 960 mg bid for 14 days). After the day 15 morning dose, doses were interrupted until day 22, at which point patients were restarted on vemurafenib. Serial pharmacokinetic samples were collected after the morning dose on days 1, 9, and 15; trough pharmacokinetic samples were collected on day 2. RESULTS: Vemurafenib concentration increased with multiple doses to steady state at day 15; C(max), AUC(0-8h), and AUC(0-168h) increased between 3.3- and 3.8-fold across the fourfold dose range tested. Statistical analysis indicated dose proportionality across the dose range of 240-960 mg bid. Day 15 mean accumulation ratios (ratio of AUC(0-8h) on day 15/AUC(0-8h) on day 1) ranged from ~19 to 25 across cohorts. At steady state, the peak-to-trough ratio for vemurafenib exhibited a relatively flat concentration-time profile throughout the bid dosing interval. During dose interruption (days 15-22), mean vemurafenib trough concentrations decreased to minimal levels; vemurafenib exhibited a mean terminal phase half-life of 31.5 38.4 h. CONCLUSIONS: Vemurafenib plasma concentration accumulates with multiple bid doses of 240 mg. Vemurafenib exposure (AUC and C(max)) is dose proportional over the 240- to 960-mg bid dose range and exhibits constant drug levels over the bid dosing interval. PMID- 24178370 TI - A colorimetric and fluorometric BODIPY probe for rapid, selective detection of H2S and its application in live cell imaging. AB - A BODIPY-azide based colorimetric and fluorescence turn-ON probe for rapid, selective and sensitive detection of H2S is reported. The probe displayed a fast response time (10 min in HEPES and 30 s in serum albumin), 28-fold fluorescence enhancement and low detection limit up to 259 nM. The application of the probe to the estimation of H2S in live cells was demonstrated. PMID- 24178369 TI - Braun gastrointestinal bypass surgery exerts similar hypoglycemic effects, with minimal operation time and earlier functional recovery, than Roux-en-Y bypass in type 2 diabetic rats. AB - BACKGROUND: Despite the beneficial hypoglycemic and potentially curative effects in type 2 diabetes, large stomach volume deficits caused by Roux-en-Y gastrointestinal bypass (RYGB) surgery increase complications. Hypoglycemic effects of Braun surgery and RYGB surgery, both modified to maximally preserve stomach volume, were compared in rat type 2 diabetes models. METHODS: Three-month old, male Goto-Kakizaki (GK) rats (n = 40) were randomly divided into equal groups and not treated (control) or treated with sham surgery (sham group), modified stomach-preserving Braun gastrointestinal bypass (Braun group), or modified RYGB (RYGB group). Pre- and postoperative body weight and water intake were recorded, along with operative and defecation times. Fasting blood glucose at 12 h, and blood glucose 180 min after intragastric glucose administration, were measured at weeks 1, 2, 3, 4, 10, and 11 along with glycosylated hemoglobin (preoperatively, week 11). RESULTS: Statistically similar (P > 0.05) increased body weight and decreased water intake, fasting blood glucose, blood glucose after intragastric glucose administration, and glycosylated hemoglobin were observed in Braun and RYGB groups compared with control and sham groups (P < 0.05). By week 1, RYGB and Braun groups exhibited sustained reductions in fasting blood glucose from 13.0 +/- 4.1 to 6.9 +/- 1.4 mmol/L and 12.4 +/- 4.4 to 7.3 +/- 0.9 mmol/L, respectively (P < 0.05); mean operative times were 139.1 +/- 4.9 and 81.6 +/- 6.4 min, respectively; and postoperative defecation times were 74.3 +/- 3.1 and 29.4 +/- 4.1 h, respectively (P < 0.05). CONCLUSIONS: Stomach volume preserving Braun gastrointestinal bypass surgery was faster and produced hypoglycemic effects similar to RYGB bypass surgery, potentially minimizing metabolic disruption. PMID- 24178371 TI - Advancing the recovery orientation of hospital care through staff engagement with former clients of inpatient units. AB - OBJECTIVES: This study was undertaken to assess the impact of consumer narratives on the recovery orientation and job satisfaction of service providers on inpatient wards that focus on the treatment of schizophrenia. It was developed to address the paucity of literature and service development tools that address advancing the recovery model of care in inpatient contexts. METHODS: A mixed methods design was used. Six inpatient units in a large urban psychiatric facility were paired on the basis of characteristic length of stay, and one unit from each pair was assigned to the intervention. The intervention was a series of talks (N=58) to inpatient staff by 12 former patients; the talks were provided approximately biweekly between May 2011 and May 2012. Self-report measures completed by staff before and after the intervention assessed knowledge and attitudes regarding the recovery model, the delivery of recovery-oriented care at a unit level, and job satisfaction. In addition, focus groups for unit staff and individual interviews with the speakers were conducted after the speaker series had ended. RESULTS: The hypothesis that the speaker series would have an impact on the attitudes and knowledge of staff with respect to the recovery model was supported. This finding was evident from both quantitative and qualitative data. No impact was observed for recovery orientation of care at the unit level or for job satisfaction. CONCLUSIONS: Although this engagement strategy demonstrated an impact, more substantial change in inpatient practices likely requires a broader set of strategies that address skill levels and accountability. PMID- 24178372 TI - A closer look at decision and analyst error by including nonlinearities in discrete choice models: implications on willingness-to-pay estimates derived from discrete choice data in healthcare. AB - BACKGROUND: Most researchers in health economics cite random utility theory (RUT) when analysing discrete choice experiments (DCEs). Under RUT, the error term is associated with the analyst's inability to properly capture the true choice processes of the respondent as well as the inconsistency or mistakes arising from the respondent themselves. Under such assumptions, it stands to reason that analysts should explore more complex nonlinear indirect utility functions, than currently used in healthcare, to strive for better estimates of preferences in healthcare. OBJECTIVE: To test whether complex indirect utility functions decrease error variance for models that either implicitly (i.e. the multinomial logit (MNL) model) or explicitly (i.e. entropy multinomial logit (EMNL) model) account for error variance in health(care)-related DCEs; and to determine the impact of complex indirect utility functions on willingness-to-pay (WTP) measures. METHODS: Using data from DCEs aimed at healthcare-related decisions, we empirically compared (1) complex and simple indirect utility specifications in terms of goodness of fit, (2) their impact on WTP measures, including confidence intervals (CIs) based on the Delta method, the Krinsky and Robb-procedure, and Bootstrapping, and (3) MNL and EMNL model results. RESULTS: Complex indirect utility functions had a better model fit than simple specifications (p < 0.05). WTP estimates were quite similar across alternative specifications. The Delta method produced the most narrow CIs. The EMNL model showed that respondents apply simplifying strategies when answering DCE questions. CONCLUSION: Complex indirect utility functions reduce error arisen from researchers, which can have important implications for measures in healthcare such as the WTP, whereas EMNL provides insights into the behaviour of respondents when answering DCEs. Understanding how respondents answer DCE questions may allow researchers to construct DCEs that minimise scale differences, so that the decision error made across respondents is more homogeneous and therefore taken out as additional noise in the data. Hence, better estimates of preferences in healthcare can be provided. PMID- 24178373 TI - The impact of the urban resident basic medical insurance on health services utilisation in China. AB - BACKGROUND: The Urban Resident Basic Medical Insurance (URBMI), launched in 2007 by the State Council, aims to cover around 420 million urban residents in China. OBJECTIVE: This study aimed to assess the impact of URBMI on health services access (especially inpatient utilisation) in urban China. METHODS: Data was drawn from the recent four-wave URBMI Survey (2008-2011). Probit and recursive bivariate probit models have been adopted to handle the possible endogeneity of medical insurance in the utilisation equations. RESULTS: Based on the preferred results from the unbalanced four-wave panel data, we found that the URBMI had significantly increased the likelihood of receiving inpatient treatment in the past year. However, the insurance effect on reducing the refused hospitalisation was insignificant. Finally, the URBMI had also increased the probability of using outpatient services in the past 2 weeks, although the insurance reimburses mainly against critical outpatient care. CONCLUSIONS: Given that it is still early days for the URBMI scheme, the positive effect on health services utilisation is appreciable. PMID- 24178375 TI - Stem elongation and changes in the levels of gibberellins in shoot tips induced by differential photoperiodic treatments in the long-day plant Silene armeria. AB - The effects of differential photoperiodic treatments applied to shoot tips and mature leaves of the long-day (LD) plant Silene armeria L. on growth and flowering responses, and on the levels of endogenous gibberellins (GAs), were investigated. Gibberellins were analyzed by gaschromatography-mass spectrometry and the use of internal standards. Exposure of mature leaves to LD, regardless of the photoperiodic conditions of the shoot tips, short days (SD), LD, or darkness, promoted elongation of the stems and of the immature leaves. Long-day treatment of the mature leaves modified the levels of endogenous GAs in shoot tips kept under LD, SD, or darkness. In shoot tips kept in LD or darkness the levels of GA53 were reduced, whereas the levels of GA19 and GA20 were increased. The contents of GA1 were increased in all three types of shoots: SD twofold, LD fivefold, and darkness eightfold. Dark treatment of the shoot tips on plants of which the mature leaves were grown in SD promoted elongation of the immature etiolated leaves and increased the GA1 content of the shoot tips threefold. However, this treatment did not cause stem elongation. The different photoperiodic treatments applied to the shoot tips did not change the levels of GAs in mature leaves. These results indicate that both LD and dark treatments result in an increase in GA1 in shoot tips. In addition, it is proposed that LD treatment induces the formation of a signal that is transmitted from mature leaves to shoot tips where it enhances the effect of GA on stem elongation. PMID- 24178374 TI - Disseminated infection due to Saksenaea vasiformis secondary to cutaneous mucormycosis. AB - Mucormycosis is an uncommon opportunistic fungal infection caused by Zygomycetes. It usually affects immunocompromised, diabetic and trauma patients with infected wounds. We report a case of disseminated infection secondary to facial cutaneous mucormycosis caused by Saksenaea vasiformis in a diabetic patient who had a farming accident causing him severe head injury. The patient was treated with a combination of surgical debridement and antifungal therapy with liposomal amphotericin B, but he had a slow and fatal outcome. In cases of tissue necrosis following trauma involving wound contact with soil (i.e., potential fungal contamination), testing for the presence of Zygomycetes fungi such as S. vasiformis in both immunocompetent and immunocompromised patients is crucial. The reason is that this infection usually has a rapid progression and may be fatal if appropriate treatment is not administered. PMID- 24178376 TI - Internode length in Pisum : A new, slender mutant with elevated levels of C19 gibberellins. AB - A new, elongated mutant of garden pea (Pisum sativum L.) is described, and shown to be conferred by a recessive allele of a new gene, sln. At the seedling stage, the mutant resembles the previously described slender type (genotype la cry (s) ), possessing markedly longer basal internodes than the wild-type. Furthermore, as for la cry (s) plants, application of gibberellin (GA)-biosynthesis inhibitors to the dry seeds (before sowing) did not markedly affect internode length in the mutant. However, the inheritance of the new slender phenotype is unusual, since in crosses between sln and Sln plants the mutant phenotype is absent in the F2 generation, reappearing in the F3. Young shoots possessing the new slender phenotype (sln) contained much higher levels of GA1, GA8, GA20 and GA29 than did wild-type shoots. Mature, near-dry seeds from slender plants contained very high levels of GA20, marginally more GA29, and very little (if any) GA29-catabolite, compared with seeds harvested from wild-type (Sln-) plants. It is suggested that sln may impair the catabolism of GA20 in maturing seeds. As a result, GA20 accumulates and on germination may move into the seedling where it is converted to GA1, promoting elongation growth. A model is proposed to explain the inheritance of the sln phenotype and its physiological implications are discussed. The new sln slender mutation has a different mode of action from the established la cry (s) slender gene combination. PMID- 24178377 TI - Photocontrol of thylakoid protein synthesis in Euglena: differential post transcriptional regulation depending on nutritional conditions. AB - The expression of three chloroplastic genes, psbA (the gene for the reaction center D1 protein of PSII), psbC (the gene for the P700 apoprotein of PSI) and psaB (the gene for the intermediate antema of PSII), and a nuclear gene, cab (the gene for the chlorophyll a/bbinding protein), has been investigated during chloroplast development in Euglena gracilis Klebs. The polysomal fraction, mRNA stability and protein turnover were analysed under different conditions of cell greening. The results indicate that the main regulatory step for the nuclear and chloroplastic genes was at the translational level when greening of cells took place on a resting medium. When cell greening took place on a medium with balanced phosphate, carbon and nitrogen sources (nutritional medium), the main regulation occurred posttranscriptionally by mobilization of the transcripts onto the polysomes. These results indicate that in E. gracilis, for a given gene, regulation operates at different levels, and that although light is the principal effector in the regulation of the genes involved in chloroplast development, the effect of metabolites should also be considered. Interestingly, it appears that these various regulation levels are similar for the chloroplastic and nucleocytoplasmic compartments. PMID- 24178378 TI - The effect of polyamines on ethylene synthesis during normal and pollination induced senescence of Petunia hybrida L. flowers. AB - Senescence of Petunia hybrida L. flowers is accompanied by a climacteric pattern in ethylene production and a rapid decline in the levels of putrescine and spermidine during the preclimacteric phase. The decrease in spermidine is caused by the decline in the availability of putrescine which is initially synthesized from L-arginine via agmatine and N-carbamoylputrescine. Inhibition of putrescine and polyamine synthesis resulted in a rapid drop in the levels of putrescine and spermidine without resulting in a concomitant increase in ethylene production. These results indicate that polyamine synthesis is not involved in the control of ethylene synthesis through its effect on the availability of S adenosylmethionine, and is confirmed by the results obtained with pollinated flowers. Treatment with polyamines may stimulate or suppress ethylene production in the corolla, depending on the concentrations applied. In unpollinated flowers the onset of the climacteric rise in ethylene production was accelerated after treatment with polyamines. However, in pollinated flowers this process was delayed as a result of treatment with low concentrations of polyamines. The effects of exogenous polyamines on ethylene production in both pollinated and unpollinated flowers indicate that ethylene synthesis in these flowers is not regulated by a feedback control mechanism. Although polyamines do not play a key role in the control of ethylene production during the early stages of senescence through their effect on the availability of S-adenosylmethionine, it appears that they play an important role in some of the other processes involved in senescence. PMID- 24178379 TI - Purification and properties of a glyphosate-tolerant 5-enolpyruvylshikimate 3 phosphate synthase from the cyanobacterium Anabaena variabilis. AB - 5-Enolpyruvylshikimate 3-phosphate (EPSP) synthase (3-phosphoshikimate 1 carboxyvinyltransferase; EC 2.5.1.9) from the glyphosate-tolerant cyanobacterium Anabaena variabilis (ATCC 29413) was purified to homogeneity. The enzyme had a similar relative molecular mass to other EPSP synthases and showed similar kinetic properties except for a greatly elevated K i for the herbicide glyphosate (approximately ten times higher than that of enzymes from other sources). With whole cells, the monoisopropylamine salt of glyphosate was more toxic than the free acid but the effects of the free acid and monoisopropylamine salt on purified EPSP synthase were identical. PMID- 24178380 TI - Effect of four classes of herbicides on growth and acetolactate-synthase activity in several variants of Arabidopsis thaliana. AB - We have isolated a triazolopyrimidine-resistant mutant csrl-2, of Arabidopsis thaliana (L.) Heynh. Here, we compare csrl-2 with the previously isolated mutants csrl and csr1-1, and with wild-type Arabidopsis for responses to members of four classes of herbicides, namely, sulfonylureas, triazolopyrimidines, imidazolinones, and pyrimidyl-oxy-benzoates. Two separable herbicide binding sites have been identified previously on the protein of acetolactate synthase (ALS). Here, the mutation giving rise to csrl, originating in a coding sequence towards the 5' end of the ALS gene, and that in csrl-2, affected the inhibitory action on growth and ALS activity of sulfonylurea and triazolopyrimidine herbicides but not that of the imidazolinones or pyrimidyl-oxybenzoates. The other mutation, in csrl-1, originating in a coding sequence towards the 3' end of the ALS gene, affected the inhibitory action of imidazolinones and pyrimidyl-oxy benzoates but not that of the sulfonylureas or triazolopyrimidines. Additional, stimulatory effects of some of these herbicides on growth of seedlings was unrelated to their effect on their primary target, ALS. The conclusion from these observations is that one of the two previously identified herbicide-binding sites may bind sulfonylureas and triazolopyrimidines while the other may bind imidazolinones and pyrimidyl-oxy-benzoates within a herbicide-binding domain on the ALS enzyme. Such a comparative study using near-isogenic mutants from the same species allows not only the further definition of the domain of herbicide binding on ALS but also could aid investigation of the relationship between herbicide-, substrate-, and allosteric-binding sites on this enzyme.This research was supported by an Operating Grant from the Natural Sciences and Engineering Research Council of Canada to J.K. PMID- 24178381 TI - Release of highly elicitor-active glucans by germinating zoospores of Phytophthora megasperma f. sp. glycinea. AB - An in-vitro culture system allowing the simultaneous germination of cysts was used to study the early host-independent release of phytoalexin elicitors by Phytophthora megasperma f. sp. glycinea, a soybean pathogen. Significant elicitor activity could be detected in the culture medium as early as 2 h after germination of P.m. f. sp. glycinea, race 1, cysts. The phytoalexin elicitor was heat-stable and heterogeneous in size. The apparent molecular mass ranged from 3 to 80 kDa. Anion exchange and lectin-affinity chromatography followed by sugar analysis confirmed that the elicitor activity resided primarily in glucans. The time course of elicitor release could then be accurately monitored by means of a competitive radioligand-displacement assay using the beta-glucan elicitor-binding sites of soybean (Glycine max (L.) Merr.) membranes. Linkage-composition analysis of the glucan elicitors showed that they were primarily (1 -> 3)beta-linked with (1 -> 6)-beta-branches, a composition similar to that of glucans obtained by heat release from mature mycelium but different from that of elicitors obtained by acid hydrolysis or from spontaneous autohydrolytic release by senescent cultures. The naturally released elicitors displayed a biological activity in soybean cotyledon bioassays higher than purified acid-hydrolysed glucan elicitor or than the hepta-(1 -> 3, 1 -> 6)-beta-glucoside, the smallest known carbohydrate elicitor for soybean. The present results demonstrate that elicitor release from the pathogen and perception by the potential host can take place in this system as early as during germ-tube formation and independent of the presence of host produced endoglucanases. PMID- 24178382 TI - Membrane binding sites for the human blood group H-type 2 determinant, an inducer of laminarinase activity in protoplasts of Rubus fruticosus L. AB - The human blood-group determinants H-type 1 (alpha-L-Fuc-(1 -> 2)-beta-D-Gal-(1 > 3)beta-D-GlcNAc), or type 2 (alpha-L-Fuc(1 -> 2)-beta-D-Gal(1 -> 4)-beta-D GlcNAc) and their mono- and disaccharidic precursors, have been reported to induce D-glycanase (laminarinase) activity in Rubus cells (Y. Lienart et al. 1990, Plant Science 68, 197-202) and protoplasts (Y. Lienart et al. 1991, Plant Science 77, 41-45). Using immunoadsorbent H-type 1 as a matrix for the affinity purification of membrane proteins, and the H-type 2 trisaccharide neoglycoprotein as ligand in kinetic-dependent enzyme-linked-immunosorbent assay for measuring binding, we were able to show that Rubus microsomes contain high-affinity binding sites for the laminarinase inducers. The N-acetyl glucosamine (GlcNAc) eluate was found to contain a saturable, high affinity binding activity for GlcNAc, compatible with the presence of a single class of binding sites Kd = 2 nM, Bmax = 400 pmol . (mg protein)(-1). In contrast, the Scatchard plot of proteins in the lactose eluate was nonlinear. In competition studies, the precursors of H-type 1 (GlcNAc-OCH3, beta-D-Gal-(1 -> 3)-beta-D-GlcNAc-OCH3) or of H-type 2 (GlcNAc, N acetyl lactosamine) trisaccharides inhibited the binding of the proteins in the GlcNAc eluate by H-type 2 neoglycoprotein with respective IC50 values of 0.6, 0.6 or 2, 0.4 nM. These data, and the binding of the H-type 2 trisaccharide by a protein of Mr 260 kDa in a ligand-blot process, are indicative of the general properties exhibited by receptors. PMID- 24178383 TI - Functional analysis of the eyespot in Chlamydomonas reinhardtii mutant ey 627, mt (-). AB - The function of the eyespot in phototaxis of the flagellate green alga Chlamydomonas reinhardtii Dangeard was studied using quantitative reflection confocal laser scanning microscopy and photoelectric measurements. The reflective properties of the eyespot and the photoreceptor current of the C. reinhardtii eyespot mutant ey 627, mt (-) were compared with those of Chlamydomonas strains possessing a well-developed eyespot. Under growth conditions in which strongly disorganized eyespots were observed in the mutant by electron microscopy, there was a significant reduction in the reflection intensity of the eyespot and in the amplitude ratio (500?440 nm) of photoreceptor currents induced by flashes of 500- and 440-nm light in non-oriented cells. Photoelectrical responses of pre-oriented cells revealed that the latter effect is caused by an altered directional sensitivity of the antenna complex, whereas the functional state of the photoreceptor pigment is not strongly affected in mutant cells. Both the reflection intensity and the amplitude ratio of photoreceptor currents increased to the level of reference strains under conditions supporting the development of a well-organized eyespot in the mutant. Furthermore, incubation of the mutant with high concentrations of all-trans-retinal (10 MUM), independent of whether carotenoid biosynthesis was inhibited or not, was found to increase the reflection intensity of the eyespot. An increase in the rate of photoorientation of the mutant occurred concomitant with the increase in the reflective properties of the mutant eyespot. These observations demonstrate the importance of an intact eyespot for interference reflection and absorption of phototactically active light, and thus for the directional sensitivity of the eyespot apparatus. PMID- 24178384 TI - Decreased ribulose-1,5-bisphosphate carboxylase-oxygenase in transgenic tobacco transformed with "antisense" rbcS : IV. Impact on photosynthesis in conditions of altered nitrogen supply. AB - The effect of nitrogen supply during growth on the contribution of ribulose-1,5 bisphosphate carboxylase-oxygenase (Rubisco; EC 4.1.1.39) to the control of photosynthesis was examined in tobacco (Nicotiana tabacum L.). Transgenic plants transformed with antisense rbcS to produce a series of plants with a progressive decrease in the amount of Rubisco were used to allow the calculation of the flux control coefficient of Rubisco for photosynthesis (CR). Several points emerged from the data: (i) The strength of Rubisco control of photosynthesis, as measured by CR, was altered by changes in the short-term environmental conditions. Generally, CR was increased in conditions of increased irradiance or decreased CO2. (ii) The amount of Rubisco in wild-type plants was reduced as the nitrogen supply during growth was reduced and this was associated with an increase in CR. This implied that there was a specific reduction in the amount of Rubisco compared with other components of the photosynthetic machinery. (iii) Plants grown with low nitrogen and which had genetically reduced levels of Rubisco had a higher chlorophyll content and a lower chlorophyll a/b ratio than wild-type plants. This indicated that the nitrogen made available by genetically reducing the amount of Rubisco had been re-allocated to other cellular components including light-harvesting and electron-transport proteins. It is argued that there is a "luxury" additional investment of nitrogen into Rubisco in tobacco plants grown in high nitrogen, and that Rubisco can also be considered a nitrogen store, all be it one where the opportunity cost of the nitrogen storage is higher than in a non-functional storage protein (i.e. it allows for a slightly higher water-use efficiency and for photosynthesis to respond to temporarily high irradiance). PMID- 24178385 TI - Periodic deposition of arabinogalactan epitopes in the cell wall of pollen tubes of Nicotiana tabacum L. AB - The monoclonal antibodies MAC 207 and JIM 8, recognizing arabinogalactan epitopes, were used to localize the corresponding antigenic sites in pollen tubes of Nicotiana tabacum L. grown in vitro or semi in vivo. The analysis of the immunofluorescence labelling was performed by means of confocal laser scanning microscopy. Most pollen tubes were labelled along their length, with the exception of the tip region, in a ring-like pattern with remarkable periodicity. The diameter of the rings was approx. 12 MUm and the distance between two rings was about 6 MUm. No labelling of the cytoplasm, the vegetative nucleus or the generative cell was observed. The presence of labelling in the non-apical tube wall after pectinase and cellulase digestion indicates that the epitopes for MAC 207 and JIM 8 are located in the inner callosic sheath of the pollen-tube wall. PMID- 24178386 TI - Active uptake of CO2 during photosynthesis in the green alga Eremosphaera viridis is mediated by a CO2-ATPase. AB - Mass spectrometry was used to investigate the uptake of CO2 in Eremosphaera viridis DeBary. Upon illumination, cells preincubated at pH 7.5 with 100 MUM dissolved inorganic carbon (DIC) rapidly depleted almost all the free CO2 from the medium. Rapid equilibrium between HCO 3 (-) and CO2 occurred upon addition of bovine carbonic anhydrase (CA) to the medium, showing that CO2 depletion resulted from a selective uptake of CO2 rather than an uptake of all inorganic carbon species. Glycolaldehyde (10 mM) completely inhibited CO2 fixation but had little effect on CO2 transport. Transfer of glycolaldehyde-treated cells to the dark caused a rapid efflux of CO2 from the unfixed intracellular DIC pool which was found to be at least threeto sixfold higher in concentration than that of the external medium. These results indicate that E. viridis actively transports CO2 against a concentration gradient. No external CA was detected in these cells either by potentiometric or mass-spectrometric assay. In the absence of external CA, the rate of photosynthetic O2 evolution in the pH range 7.5 to 8.0 did not exceed the calculated rate of CO2 supply, indicating a limited capacity for HCO2 uptake in these cells. Electrophysiological measurements indicate that CO2 uptake is electrically silent and thus is not a consequence of H(+)-CO2 symport activity. Microsomal membranes isolated from Eremosphaera showed ATPase activity which was enhanced by CO2. These results indicate that active CO2 uptake is mediated by an ATPase. PMID- 24178387 TI - Acquisition of competence for floral development in Nicotiana buds. AB - Grafting experiments were used to investigate the relative roles of strength of flowering signal(s) and competence of buds to respond to flowering signal(s) in the development of photoperiodic and day-neutral species of Nicotiana. At the time of commitment to floral development, a flowering signal (inhibitory or promotive) could reach a critical level or terminal buds could gain competence to perceive and-or respond to an existing signal. The latter hypothesis appears to be true for day-neutral N. tabacum L. cv. Wisconsin 38, while signal strength appears to be a more critical factor for long-day N. silvestris L. Nicotiana tabacum and N. silvestris differ in terms of signal intensity at anthesis of the terminal flower. Stocks of N. silvestris promote more rapid flowering in seedling scions of both genotypes. Terminal buds of seedlings of both genotypes have the same competence to respond to the signal affecting floral development. The competence of the terminal bud of both species to respond to this signal(s) changes as a function of age. PMID- 24178388 TI - Zygote formation in the homothallic green alga Chlamydomonas monoica Strehlow. AB - Mating between cells of opposite mating type within a clonal population of Chlamydomonas monoica results in thick-walled zygotes. Zygote formation was studied in cells from continuous cultures fed with culture medium containing nitrate concentrations sufficient or limiting for growth. The factors that were considered were cell density and nitrate content of the medium. The following results were obtained: (i) Zygotes were only formed by cells that had experienced a relatively low nitrogen level that did not limit cell division. (ii) Cells were competent to mate only during a limited period of time after their release from the mother cell wall. (iii) There was a correlation between zygote yields and the number of low-nitrogen cells that were able to execute a cell division under the conditions being tested. (iv) The zygote yield per cell division was independent of the cell density. These findings indicate that the strategy used by C. monoica cells to find a mate is not dependent on random encounters. A possible explanation is that at least a large proportion of zygotes is formed by matings between cells originating from the same mother cell (siblings). PMID- 24178389 TI - Intracellular transport and processing of a tobacco vacuolar beta-1,3-glucanase. AB - The class I beta-1,3-glucanases are basic, vacuolar enzymes implicated in the defense of plants against pathogen infection. The tobacco (Nicotiana tabacum L.) enzyme is synthesized as a preproprotein with an N-terminal signal peptide for targeting to the lumen of the endoplasmic reticulum and an N-glycosylated C terminal extension which is lost during protein maturation. The transport and processing of beta-1,3-glucanase in cellsuspension cultures of the tobacco cultivar Havana 425 was investigated by pulse-chase labelling and cell fractionation. We verified that mature beta-1,3-glucanase is localized in the vacuole of the suspension-cultured cells. Comparison of the time course of processing in homogenates, the soluble fraction, and membrane fractions indicates that proglucanase is transported from the endoplasmic reticulum via the Golgi compartment to the vacuole. Processing to the mature form occurs in the vacuole. Treatment of cells with tunicamycin, which inhibits N-glycosylation, and digestion of the (35)S-labelled processing intermediates with endoglycosidase H indicate that beta-1,3-glucanase has a single N-glycan attached to the C-terminal extension. Glycosylation is not required for proteolytic processing or correct targeting to the vacuole. PMID- 24178390 TI - Movement and metabolism of oligogalacturonide elicitors in tomato shoots. AB - We have studied the movement and metabolism of oligogalacturonides through shoots of tomato (Lycopersicon esculentum L. cv Rutgers). Oligomers of polygalacturonic acid were prepared by enzyme digestion and gel filtration. These were end-reduced with [(3)H]NaBH4, using an improved reaction method, to yield oligoalditols. The radiolabelled oligomer of degree of polymerisation 6 was supplied to tomato shoots through their transpiration stream. Analysis of the distribution of radiolabel in the plant, and TLC of radiolabelled material recovered from the plant revealed the following: a) material recovered from the plant could be identified as an oligogalacturonide from its behaviour on TLC and susceptibility to digestion with polygalacturonase; b) end-reduced oligogalacturonides moved freely through the plant and were not complexed to high-molecularweight compounds and immobilised; c) during passage through the plant, modifications to the oligogalacturonide occurred, presumably as a consequence of metabolism in the apoplastic space. We found evidence of i) esterification of the molecule, and ii) shortening of the oligogalacturonide chain. The results show that in the assay for protease-inhibitor-inducing factor using cut shoots, oligogalacturonide elicitors can move into the leaves and act directly on the cells producing protease inhibitor. PMID- 24178391 TI - Dynamics of tonoplast proton pumps and other tonoplast proteins of Mesembryanthemum crystallinum L. during the induction of Crassulacean acid metabolism. AB - In plants of Mesembryanthemum crystallinum the activities of the two proton pumps on the tonoplast, i.e. the ATPase and the pyrophosphatase, and the gelelectrophoretic pattern of the total tonoplast proteins were analyzed during the transition of the metabolic state from C3 photosynthesis to Crassulacean acid metabolism (CAM). In one series, CAM was induced by watering the plants with NaCl. In another series, the change of the metabolic state to CAM was a consequence of the aging of the plants. No significant differences in the specific activities of ATP hydrolysis were found in plants performing C3 photosynthesis and CAM, respectively. However, with both series the protein content of tonoplast preparations and, in parallel, the total ATP hydrolytic activity of the tonoplast ATPase were higher after the change to CAM. In contrast, the specific activity of pyrophosphate hydrolysis was maximum in the preparations of young plants and diminished after the induction of CAM in both series. Therefore the tonoplast ATPase seems to be the main enzyme responsible for the energization of malate accumulation in CAM. The tonoplast pyrophosphatase is important in the early stages of plant growth and plays a minor role in CAM. With M. crystallinum the change from C3 photosynthesis to CAM is accompanied by de-novo synthesis of tonoplast proteins. Several polypeptides with relative molecular masses (Mrs) of 55, 41, and 36 kDa were clearly more pronounced in the gel-electrophoretic pattern of the total tonoplast protein after CAM induction. These changes were independent of the CAM-inducing salt treatment or aging. Moreover, two subunits of the tonoplast ATPase with Mrs of about 27 and 31 kDa showed particularly high intensities only in the CAM state. It is assumed that the subunit composition of the tonoplast ATPase differs in the two metabolic states and that the two subunits induced modify the regulation of the ATPase in CAM. In addition, the reaction of the plants to the NaCl treatment per se was the induction at the tonoplast of a polypeptide with an Mr of 24 kDa. PMID- 24178392 TI - Levels of tropinone-reductase activities influence the spectrum of tropane esters found in transformed root cultures of Datura stramonium L. AB - The nortropane sulphur analogues 8-thiabicyclo[3.2.1] octan-3-one, 8 thiabicyclo[3.2.1]octan-3a-ol and 8-thiabicyclo[3.2.1]octan-3beta-ol have been found to have differential effects in vitro on the activities of tropinone reductase I and tropinone reductase II from Datura stramonium L. It has been demonstrated that only tropinone reductase I is able to metabolise 8 thiabicyclo[3.2.1]octan-3-one and that only this enzyme is inhibited by 8 thiabicyclo[3.2.1]octan-3alpha-ol and 8-thiabicyclo[3.2.1]octan-3beta-ol. A K m of 0.035 mM was determined for 8-thiabicyclo[3.2.1]octan-3-one and I50 values of 0.081 mM and 0.021 mM for 8-thiabicyclo[3.2.1]octan-3alpha-ol and 8 thiabicyclo[3.2.1]octan-3beta-ol, respectively. The influence that these differential interactions might have on metabolism was investigated in transformed root cultures of D. stramonium. It was found that when these cultures were grown in the presence of either 8-thiabicyclo[3.2.1]octan-3-one or 8 thiabicyclo[3.2.1]octan-3beta-ol the spectrum of alkaloids that accumulated was altered from that found in control roots in the manner predicted from the observed effects of these inhibitors on the isolated reductases. The effect could be mimicked by feeding pseudotropine, the product of tropinone reductase II. It is concluded that the relative levels of activity of the two tropinone reductases might play an important role in regulating the balance of tropan-3alpha-ols to tropan-3beta-ols seen in the spectrum of tropane-alkaloid-producing plants. PMID- 24178393 TI - Regulation of transcript level and synthesis of nitrate reductase by phytochrome and nitrate in turions of Spirodela polyrhiza (L.) Schleiden. AB - Control by light and nitrate of the appearance of nitrate reductase (NR; EC 1.6.6.1) in the turions of Spirodela polyrhiza (L.) Schieiden was investigated during the pre-germination phase, i.e. up to 120 h after the transfer from after ripening to germination conditions. Turions are particularily suited for this type of coaction study since control of nitrate uptake by light and long-distance transport of nitrate do not play a role. Control of NR gene expression was mainly studied between 72 and 120 h after transfer to germination conditions (phase II of the pre-germination process). It was found that the effect of light on NR appearance is exerted via phytochrome. The light effect on enzyme synthesis was only observed in the presence of nitrate. On the other hand, in darkness, the NR level decreased to almost zero even in the presence of an optimum supply of nitrate. It is concluded that in phase II a coaction of light (phytochrome) and nitrate is required to bring about NR synthesis. However, when nitrate was applied to turions - following a dark incubation without nitrate - the turions responded to nitrate even in darkness with strong NR synthesis. This response was augmented by light. The highest transcript levels were observed in the presence of both factors, light and nitrate. As a single factor, light was more effective in stimulating the transcript level than nitrate. However, no correlation between the transcript level and the rate of enzyme synthesis was observed. This is consistent with the previous conclusion (Schuster et al. 1988, Planta 174, 426 432) that in higher plants control at the transcript level is only coarse and does not determine quantitatively the output at the level of enzyme protein. PMID- 24178394 TI - Biosynthesis of p-hydroxybenzoic acid in elicitor-treated carrot cell cultures. AB - Carrot (Daucus carota L.) cells respond to treatment with fungal elicitors by synthesizing wallbound p-hydroxybenzoic acid (p-HBA). The biosynthetic pathway to p-HBA is still hypothetical. Tracer experiments with L-phenylalanine indicate the involvement of the general phenylpropanoid pathway. 3,4 (Methylenedioxy) innamic acid, an inhibitor of hydrocycinnamate CoA ligase, inhibits the accumulation of anthocyanins in carrot, while it does not interfere with p-HBA synthesis. Thus p HBA biosynthesis does not appear to involve CoA thioesters. In the present report the sequence of enzymic reactions leading to p-HBA was investigated in vitro using protein preparations from cells treated with a fungal elicitor from Pythium aphanidermatum (Edson) Fitzp. The side-chain degradation from p-coumaric acid to p-HBA is not analogous to the beta-oxidation of fatty acids and involves p hydroxybenzaldehyde as an intermediate. The final step from p-hydroxybenzaldehyde to p-HBA is catalyzed by an NAD-dependent p-hydroxybenzaldehyde dehydrogenase (EC 1.2.1.-). This reaction was characterized with regard to cofactor requirements, pH and temperature optima. The in-vitro formation of p-HBA from p-coumaric acid and the activity of the hydroxybenzaldehyde dehydrogenase are moderately elicitor induced but to a much lesser extent than phenylalanine ammonialyase, which is the starting enzyme of the general phenylpropanoid pathway. PMID- 24178395 TI - Use of an extracellular, ion-selective, vibrating microelectrode system for the quantification of K(+), H (+), and Ca (2+) fluxes in maize roots and maize suspension cells. AB - An ion-selective vibrating-microelectrode system, which was originally used to measure extracellular Ca(2+) gradients generated by Ca(2+) currents, was used to study K(+), H(+) and Ca(2+) transport in intact maize (Zea mays L.) roots and individual maize suspension cells. Comparisons were made between the vibrating ion-selective microelectrode, and a technique using stationary ion-selective microelectrodes to measure ionic gradients in the unstirred layer at the surface of plant roots. The vibrating-microelectrode system was shown to be a major improvement over stationary ion-selective microelectrodes, in terms of sensitivity and temporal resolution. With the vibrating ion microelectrode, it was easy to monitor K(+) influxes into maize roots in a background K(+) concentration of 10 mM or more, while stationary K(+) electrodes were limited to measurements in a background K(+) concentration of 0.3 mM or less. Also, with this system it was possible to conduct a detailed study of root Ca(2+) transport, which was previously not possible because of the small fluxes involved. For example, we were able to investigate the effect of the excision of maize roots on Ca(2+) influx. When an intact maize root was excised from the seedling at a position 3 cm from the site of measurement of Ca(2+) transport, a rapid fourfold stimulation of Ca(2+) influx was observed followed by dramatic oscillations in Ca(2+) flux, oscillating between Ca(2+) influx and efflux. These results clearly demonstrate that wound or perturbation responses of plant organs involve transient alterations in Ca(2+) transport, which had previously been inferred by demonstrations of touch-induced changes in cytoplasmic calcium. The sensitivity of this system allows for the measurement of ion fluxes in individual plant cells. Using vibrating K(+) and H(+)electrodes, it was possible to measure H(+)efflux and both K(+) influx and efflux in individual maize suspension cells under different conditions. The availability of this technique will greatly improve our ability to study ion transport at the cellular level, in intact plant tissues and organs, and in specialized cells, such as root hairs or guard cells. PMID- 24178396 TI - Effect of anoxia on starch breakdown in rice and wheat seeds. AB - The capabilities of rice (Oryza sativa L.) and wheat (Triticum aestivum L.) seeds (caryopses) to degrade starchy reserves present in the endosperm tissue were compared under anaerobic conditions. The results showed that rice, a species highly tolerant to anoxia, can readily break down starch under anaerobiosis concomitant with germination, while wheat does not germinate and fails to degrade starch present in the endosperm. This clearly distinct behavior is likely the consequence of the successful inducible formation of alpha-amylase (EC 3.2.1.1.) in rice under anoxia, whereas the enzyme is not produced in wheat seeds. We found that rice seeds possess a set of enzymes allowing starch and its degradative products to be utilized under anoxic conditions. Wheat seeds were shown to germinate even under anoxia if fed glucose or sucrose exogenously. The overall results indicate that induction of alpha-amylase appears to be one of the factors permiting rice seeds to germinate in totally anaerobic environments. PMID- 24178397 TI - Enhanced shape stability of Pd-Rh core-frame nanocubes at elevated temperature: in situ heating transmission electron microscopy. AB - Shape stability of Pd-Rh core-frame nanocubes was studied by in situ heating transmission electron microscopy. Pd-Rh nanocubes could maintain cubic shape at elevated temperature compared with pure Pd. The surface diffusion process of Rh onto {100} side surfaces is believed to postpone the degradation to higher temperature. PMID- 24178398 TI - Using a composite index of socioeconomic status to investigate health disparities while protecting the confidentiality of cancer registry data. AB - PURPOSE: The lack of individual socioeconomic status (SES) information in cancer registry data necessitates the use of area-based measures to investigate health disparities. Concerns about confidentiality, however, prohibit publishing patients' residential locations at the subcounty level. We developed a census tract-based composite SES index to be released in place of individual census tracts to minimize the risk of disclosure. METHODS: Two SES indices based on the measures identified in the literature were constructed using factor analysis. The analyses were repeated using the data from the 2000 decennial census and 2005 2009 American Community Survey to create the indices at two time points, which were linked to 2000-2009 Surveillance, Epidemiology, and End Results registry data to estimate incidence and survival rates. RESULTS: The two indices performed similarly in stratifying census tracts and detecting socioeconomic gradients in cancer incidence and survival. The gradient in the incidence is positive for breast and prostate, and negative for lung cancers, in all races, although the level varies. The positive gradient in survival is more salient for regional staged breast, colorectal, and lung cancers. CONCLUSIONS: The census tract-based SES index provides a valuable tool for monitoring the disparities in cancer burdens while avoiding potential identity disclosure. This index, divided into tertiles and quintiles, is now available to the researchers on request. PMID- 24178399 TI - How do cells optimize luminal environments of endosomes/lysosomes for efficient inflammatory responses? AB - The endosome/lysosome compartments play pivotal roles in immune cell functions as signalling platforms. These intracellular compartments can efficiently restrict the localization of signalling complexes and temporally regulate signalling events to produce qualitatively different outcomes. Immune cells also exploit the endosome/lysosome system for signal transduction and intercellular communication to elicit immune responses. Antigen-presenting cells such as dendritic cells and macrophages take up pathogens by endocytosis and prepare antigens via the endosome/lysosome system. At the same time, pathogen-derived DNA and RNA are recognized by immune sensors at the endosome/lysosome compartments, which transmit signals to induce immune responses. Recent studies revealed the importance of controlling the endosomal/lysosomal environment for eliciting efficient signalling events at the endosomes/lysosomes. Many factors including pH, membrane potential, amino acid concentrations and lipid composition are finely tuned at the endosome/lysosome compartments, and dysregulation of these factors greatly affect immune cell functions. Redox-related molecules and various types of transporters are involved in the control of endosomal/lysosomal environment and could be good therapeutic targets for treating autoimmune diseases. PMID- 24178400 TI - Results of diplopia and strabismus in patients with severe thyroid ophthalmopathy after orbital decompression. AB - PURPOSE: It has been frequently stated that the orbital decompression, in patients with thyroid ophthalmopathy, does not usually improve extraocular muscles function and that after the operation there is often a deterioration of these functions. The purpose of this article is evaluation of extraocular muscles function after applying personal method of 3 wall orbital decompression. MATERIALS AND METHODS: Retrospective review of case records of 119 patients with severe thyroid ophthalmopathy seen and treated by the author between December 1986 and December 2010. All patents underwent 3 wall orbital decompression combined with removal of the periorbital, intraorbital and retrobulbar fat. Correction of coexistent eyelid retraction and deformities were also performed. RESULTS: Comparison of preoperative and postoperative results was conducted in 65 patients three months after 3 wall decompression. All patients showed a significant reduction of exophthalmos [5-11 mm, 7.2 mm on average], reduction of intraocular pressure, marked improvement in ocular muscle function as well as considerable reduction in or disappearance of subjective symptoms. There were no cases of subsequent impairment of ocular motility. Strabismus surgery was performed in 6 patients with residual diplopia. There was an improvement in vision in 68% patients who had impaired vision before the operation. Less evident relapse of exophthalmos was recorded in 3 cases only and only one patient required unilateral reoperation. CONCLUSION: It can be concluded that this method of orbital decompression is logical, based on an understanding of the pathology, has less complication rates, is relatively easy to perform, gives very good functional and aesthetic long term results and allows rapid recovery. PMID- 24178401 TI - Not only pregnancy but also the number of fetuses in the uterus affects intraocular pressure. AB - AIM: To investigate whether, intraocular pressure (IOP) is affected when there is a second fetus in the uterus during pregnancy. MATERIALS AND METHODS: Eighty eyes of 40 twin pregnancies (TwPs), 80 eyes of 40 singleton pregnancies (SiPs) and 80 eyes of 40 non-pregnant females (NoPs) were included in the study. STATISTICAL ANALYSIS: Repeated measurements analysis of variance with two factors, one-way analysis of variance (ANOVA) and the Tukey's multiple comparison test were used. RESULTS: The mean IOP (MIOP) values in TwPs were 14.29 +/- 1.28, 11.48 +/- 1.20, and 9.81 +/- 1.36 mmHg and the MIOP values in SiPs were 14.42 +/- 0.95, 13.12 +/- 0.75, and 10.97 +/- 0.89 mmHg in subsequent trimesters. The MIOP values in NoPs were 14.77 +/- 1.18, 14.92 +/- 1.33, and 15.08 +/- 0.89 mmHg in subsequent 3 month measurements. The results show that the MIOP values for the TwPs group were significantly lower than the SiPs in all trimesters. CONCLUSIONS: During pregnancy, the number of fetuses in the uterus is an indirectly important factor that influences the decrease in IOP. We hypothesize that the increased ocular hypotensive effect of TwPs is most likely related to the presence of higher levels of hormones, particularly estrogen, progesterone and relaxin compared with SiPs. PMID- 24178403 TI - Clinical features and etiology of retinal vasculitis in Northern Thailand. AB - PURPOSE: To report on the clinical features and etiology of patients with retinal vasculitis (RV). MATERIALS AND METHODS: We reviewed medical records of 47 patients (75 affected eyes) diagnosed with RV. Clinical presentations, ocular complications, associated systemic diseases, and treatment regimens were registered. RESULTS: Etiology of RV included infectious causes in 10/47, (21%) while an association with systemic and/or ocular non-infectious disorders was noted in 22/47 (47%). Eales' disease and Behcet's disease represented the most common clinical entities in non-infectious group while tuberculosis-associated RV was diagnosed in 6/10 (60%) among those with infectious disorders. RV was bilateral in 28/47 (60%) patients. Retinal veins were most commonly affected (72%, 34/47). Involvement of arteries was present in 12/47 (25%) and was associated with viral infections and Behcet's disease. Ocular complications developed in 60/75 (80%) eyes. The most common complications were elevated intraocular pressure and/or glaucoma (33/75, 44%). Retinal detachment, vitreous hemorrhage, and cystoid macular edema developed in similar percentages (15%). CONCLUSIONS: RV in Thailand manifested mostly in male patients, was typically bilateral and involved mostly veins. Involvement of arteries was observed in patients with viral infections and Behcet's disease. Tuberculosis was the most common infectious cause. PMID- 24178402 TI - Successful treatment of Fusarium keratitis after photo refractive keratectomy. AB - A 39-year-old woman presented to our hospital with a history of photorefractive keratectomy (PRK), performed two weeks prior; slit-lamp examination revealed diffuse conjunctival congestion, corneal ulcer and stromal infiltration. After 5 days of antifungal and antibacteric treatment, the infiltrate progressively increased so that a therapeutic penetrating keratoplasty was necessary. The microbiological analyses revealed the presence of fungal filaments. Twenty days after surgery the patient had recurrent fungal infiltrate in the donor cornea with wound dehiscence. We performed a second penetrating keratoplasty. With the matrix-assisted-laser-desorption-ionization-time-of-flight analysis (MALDI-TOF) we identified a Fusarium solani. Intravenous amphothericine B, a combination of intracameral and intrastromal voriconazole and intracameral amphotericine B were administered. After 6 months from the last surgery the infection was eradicated. The management of fungal keratitis after PRK depends on many factors: In our experience, a prompt keratoplasty and the use of intracameral antifungal medication proved to be very effective. PMID- 24178404 TI - Dietary and lifestyle risk factors associated with age-related macular degeneration: a hospital based study. AB - AIM: To establish the frequency, associations and risk factors for age-related macular degeneration (AMD) in hospital population of South India. MATERIALS AND METHODS: In this cross-sectional hospital based study, 3549 subjects (2090 men and 1459 women) above 45 years of age were screened randomly for AMD. Participants underwent ocular evaluation and were interviewed for lifestyle variables and dietary intake of carotenoids by structured food frequency questionnaire. AMD was defined according to the international classifications and grading system. RESULTS: Either form of AMD was detected in 77 (2.2%) participants. Of which, early and late AMD was present in 63 (1.8%) and 14 (0.4%) subjects, respectively. Binary logistic analysis showed that the incidence of AMD was significantly higher with increasing age (Odds ratio [OR] 1.17; 95% CI 1.13 1.22) and diabetes (OR 3.97; 95% CI 2.11-7.46). However, AMD was significant among heavy cigarette smokers (OR 5.58; 95% CI 0.88-7.51) and alcoholics (OR 4.85; 95% CI 2.45-12.22). Dietary lutein/zeaxanthin (L/Z) and beta-carotene intake were associated (P < 0.001) with the reduction in risk for AMD, with an OR of 0.38 and 0.65, respectively. CONCLUSIONS: Higher dietary intake of carotenoids, especially L/Z, was associated with lower risk for AMD. Risk of AMD is higher with increasing age and was prevalent among subjects with diabetes. Cessation of smoking and alcohol may reduce the risk of AMD in this population. PMID- 24178405 TI - Repeated bevacizumab injections versus mitomycin C in rotational conjunctival flap for prevention of pterygium recurrence. AB - AIMS: To evaluate the efficacy of repeated bevacizumab injection in rotational conjunctival flap surgery versus rotational conjunctival flap with adjunctive mitomycin C (MMC) or rotational conjunctival flap alone. MATERIALS AND METHODS: Ninety eyes of 90 patients who underwent primary pterygium surgery with rotational flap were evaluated. Patients were randomly assigned to undergo conjunctival rotational flap alone (Group A) or conjunctival rotational flap with either 0.02% MMC application (Group B) or adjunctive subconjunctival 2.5 mg/0.1 ml bevacizumab injection (Group C). Each group consisted of 30 eyes. Recurrence rates at 9 months were evaluated. RESULTS: There were no statistically significant differences in mean size of the pterygium across the limbus in terms of length (P > 0.5). The recurrence rates at 9 months were 26.6% (n = 8) in Group A, 13.3% (n = 4) in Group B, and 10% (n = 3) in Group C. The recurrence rates in Group B and C were significantly lower than in Group A (P = 0.1806). The recurrence rates were similar in Group B and C (P > 0.05). CONCLUSIONS: Subconjunctival bevacizumab injection may decrease the recurrence rate of primary pterygium surgery with rotational conjunctival flap. Further studies with a larger population and longer follow-up period are needed to supplement this study. PMID- 24178406 TI - Clinical features and outcomes of vitrectomy in pediatric ocular injuries-eye injury vitrectomy study. AB - CONTEXT: Severe pediatric ocular injury remains a frequent and difficult problem. Vitrectomy is a major technique that has been used to manage severely damaged eyes. However, limited follow-up studies exist currently. AIMS: To evaluate the clinical features and predictive factors of visual and anatomic outcomes in Eye Injury Vitrectomy Study (EIVS). SETTINGS AND DESIGN: Retrospective, consecutive, interventional case series. MATERIALS AND METHODS: Reviewing and analyzing records of children, aged 15 years or younger, who had undergone vitrectomy for eye injuries in EIVS database between January 1997 and December 2009. STATISTICAL ANALYSIS USED: Descriptive analyses and multiple Logistic regressions were employed for all variables using SPSS software (version 17.0, SPSS Inc.). RESULTS: Eighty-seven children (89 eyes) with more than 6 months follow-up and complete records identified in EIVS were included in this study. Average follow up was 12.7 months. The mean age was 9.4 +/- 3.8 years. Seventy-seven eyes (86.5%) had open globe injuries, and 12 (13.5%) had closed globe injuries. Seventeen eyes (19.3%) presented with endophthalmitis. Seventy-five eyes (88.2%) presented with visual acuity of 4/200 or worse; however, 42 eyes (47.7%) achieved 4/200 or better vision with anatomical restoration after vitrectomy. Multiple analysis showed that choroidal damage, large scleral wound, and endophthalmitis were significantly associated with unfavorable outcome, the OR values were 16.7 (95% CI: 2.7-102.4, P = 0.002), 10.9 (95% CI: 1.7-71.6, P = 0.013), and 6.6 (95% CI: 1.0-42.4, P = 0.048), respectively. CONCLUSIONS: Vitrectomy intervention resulted in favorable visual and anatomic outcomes in almost half of the injured eyes. Choroidal damage, large scleral wound, and endophthalmitis were the prognostic indicators of unfavorable outcome. PMID- 24178407 TI - Step-by-step phacoemulsification training program for ophthalmology residents. AB - AIMS: The aim was to analyze the learning curve of phacoemulsification (phaco) performed by residents without experience in performing extra-capsular cataract extraction (ECCE) in a step-by-step training program (SBSTP). MATERIALS AND METHODS: Consecutive surgical records of phaco performed from March 2009 to Sept 2011 by four residents without previous ECCE experience were retrospectively reviewed. The completion rate of the first 30 procedures by each resident was calculated. The main intraoperative phaco parameter records for the first 30 surgeries by each resident were compared with those for their last 30 surgeries. Intraoperative complications in the residents' procedures were also recorded and analyzed. RESULTS: A total of 1013 surgeries were performed by residents. The completion rate for the first 30 phaco procedures was 79.2 MU 5.8%. The main reasons for halting the procedure were as follows: Anterior capsule tear, inability to crack the nucleus, and posterior capsular rupture during phaco or cortex removal. Cumulative dissipated energy of phaco power used during the surgeries was significantly less in the last 30 cases compared with the first 30 cases (30.10 MU 17.58 vs. 55.41 MU 37.59, P = 0.021). Posterior capsular rupture rate was 2.5 MU 1.2% in total (10.8 MU 4.2% in the first 30 cases and 1.7 MU 1.9% in the last 30 cases, P = 0.008; a statistically significant difference). CONCLUSION: The step-by-step training program might be a necessary process for a resident to transit from dependence to a self-supported operator. It is also an essential middle step between wet lab training to performing the entire phaco procedure on the patient both effectively and safely. PMID- 24178408 TI - Efficacy of combined intravitreal bevacizumab and triamcinolone for branch retinal vein occlusion. AB - PURPOSE: To evaluate the efficacy of combined treatment with intravitreal bevacizumab (IVB) and triamcinolone acetate (IVT) for patients with macular edema secondary to branch retinal vein occlusion (BRVO). MATERIALS AND METHODS: Retrospective analysis of 20 eyes injected with 1.25 mg IVB and 2 mg IVT for clinically identified BRVO within 8 weeks of onset. All patients lacked concomitant ocular pathology and completed 6 months' follow-up. Clinical examination including LogMAR visual acuity (VA) and central macular thickness (CMT) by spectralis optical coherence tomography (OCT) was performed preoperatively and at 1, 3 and 6 months post-operatively. RESULTS: Mean patient age was 61.3 years with a mean BRVO diagnosis time of 3 weeks at presentation. VA improved from logMAR 1.08 preoperatively to Mean logMAR VA of 0.55 +/- 0.17 at 1 month (P < 0.001), 0.56 +/- 0.21 at 3 months (P < 0.001), and 0.38 +/- 0.1 at 6 months (P < 0.001) Mean CMT improved from 482 +/- 107 MUm preoperatively to 319 +/- 53 MUm at 1 month (P < 0.001), 344 +/- 89 MUm at 3 months (P < 0.001), and 241 +/- 29 MUm at 6 months (P < 0.001). Mean IOP preoperatively was 16.5 mmHg, 21 mmHg at 1 month, and 15 mmHg at 6 months. Six out of 20 patients (30%) were re injected with IVB and IVT at 3 months. CONCLUSIONS: Early combined treatment with IVB and IVT is effective in improving anatomic and functional outcomes in patients with macular edema secondary to BRVO. PMID- 24178409 TI - The efficacy of sleeve technique in primary nasolacrimal duct obstruction with a high lacrimal sac. AB - PURPOSE: To evaluate the efficacy of a sleeve technique during endoscopic dacryocystorhinostomy (DCR) in primary nasolacrimal duct obstruction (NLDO) patients with a high lacrimal sac. MATERIALS AND METHODS: The medical records of 45 patients (49 cases) undergoing endoscopic DCR for primary NLDO with a high lacrimal sac were retrospectively reviewed. In 19 patients (21 cases), the thick maxilla covering the common canalicular opening was removed using a drill and a bicanalicular silicone tube was inserted (group 1). In 26 patients (28 cases), instead of removal of the thick maxilla, a sleeve was inserted into the bicanalicular silicone tube (group 2). At 6 months postoperatively, the success rate was evaluated and the size of the intranasal mucosal ostium was measured. RESULTS: The success rates in group 1 and 2 was 90.5% and 96.4%, respectively (P = 0.400). The intranasal mucosal ostium in group 1 and 2 measured 1.7 +/- 0.7 mm and 3.1 +/- 1.0 mm, respectively, and the difference was significant (P = 0.042). CONCLUSIONS: In primary NLDO patients with a high lacrimal sac, DCR inserting a silicone tube and a sleeve together had a satisfactory success rate without using a drill. In comparison with traditional surgical methods, it helped enlarge the size of the intranasal mucosal ostium. PMID- 24178410 TI - Poly-L-lactide acid-modified scaffolds for osteoinduction and osteoconduction. AB - Poly-L-lactide acid (PLLA) scaffold has been modified to enhance its osteoconductive and osteoinductive properties in view of a bone tissue engineering application. Two approaches have been followed: (i) coating with laminin or fibronectin and (ii) grafting with arginine-glycine-aspatic acid (RGD) or SIKVAV peptides. Moreover we have added a bioactive molecule 1,25-(OH)2 D3 into the scaffold that shows better cellular interaction to implement osteoinduction and osteogenesis. The two coatings promoted only cell adhesion in the very short term while even if grafted scaffolds had cell seeding efficiency similar to ungrafted PLLA, the grafted ones supported better the proliferation of seeded human osteoblast (hOB) and human mesenchymal stem cells (hMSCs) over 1 week of culture. Our data showed that in view of bone integration and bone regeneration, PLLA grafting with RGD can be considered a good substrate to induce hOB adhesion and proliferation but having no significant effect on the osteogenic induction, the scaffold has to be reinforced with osteoinductive molecules. It can be concluded from reverse transcriptase polymerase chain reaction results, alkaline phosphatase activity and mineralization assays that 1,25(OH)2 D3 reinforced RGD-PLLA keeps increased cell proliferation supported by an upregulation of the studied osteogenic markers and induced hMSCs differentiation into osteoblasts demonstrating osteoinductivity and osteoconductivity of the new formulated scaffold. These results can lead to a future application of RGD-D3 PLLA as an osteogenic material for bone replacement.. PMID- 24178411 TI - Racial and ethnic differences in receipt of antidepressants and psychotherapy by veterans with chronic depression. AB - OBJECTIVE: This study characterized racial-ethnic differences in treatment of veterans with chronic depression by examining antidepressant and psychotherapy use among non-Hispanic black, non-Hispanic white, Hispanic, Asian, and American Indian-Alaska Native (AI/AN) veterans. METHODS: Logistic regression models were estimated with data from the U.S. Department of Veterans Affairs (VA) medical records for a sample of 62,095 chronically depressed patients. Data (2009-2010) were from the VA External Peer Review Program. Three primary outcome measures were used: receipt of adequate antidepressant therapy (>=80% medications on hand), receipt of adequate psychotherapy (at least six sessions in six months), and receipt of guideline-concordant treatment (either of these treatments). RESULTS: Compared with whites, nearly all minority groups had lower odds of adequate antidepressant use and guideline-concordant care in unadjusted and adjusted models (antidepressant adjusted odds ratio [AOR] range=.53-.82, p<.05; guideline-concordant AOR range=.59-.83, p<.05). Although receipt of adequate psychotherapy was more common among veterans from minority groups in unadjusted analyses, differences between Hispanic, AI/AN, and white veterans were no longer significant after covariate adjustment. After adjustment for distance to the VA facility, the difference between black and white veterans was no longer significant. CONCLUSIONS: A better understanding of how patient preferences and provider and system factors interact to generate differences in depression care is needed to improve care for patients from racial-ethnic minority groups. It will become increasingly important to differentiate between health service use patterns that stem from genuine differences in patient preferences and those that signify inequitable quality of depression care. PMID- 24178413 TI - Rapid and repetitive plant regeneration in sweetpotato via somatic embryogenesis. AB - An efficient in vitro plant regeneration system characterized by rapid and continuous production of somatic embryos using leaf and petiole expiants has been developed in sweetpotato [Ipomoea batatas L. (Lam.)]. The optimal somatic embryogenic response was obtained in the genotype PI 318846-3 with a two-step protocol: (1) stage I-incubation of expiants in the dark for 2 weeks on Murashige Skoog (MS) medium containing 2,4-dichlorophenoxyacetic acid (2,4-D) (2.5 mg/l) and 6-benzylaminopurine (0.25 mg/l) and, (2) stage II-culture in the light on MS medium with abscisic acid (ABA) (2.5 mg/l). The addition of ABA was critical for enhanced production of somatic embryos. Secondary somatic embryos were produced from the primary embryos cultured on MS medium with 2,4-D at 0.2 mg/l. The somatic embryos were converted into normal plantlets when cultured on basal MS medium. Upon transfer to soil, plants grew well and appeared normal with no mortality. The system of somatic embryogenesis described here will facilitate tissue culture, germplasm conservation and gene transfer research of sweetpotato due to its rapidity (6 to 10 weeks), prolific plant production by direct embryogenesis, ease of secondary somatic embryo production and reproducibility. PMID- 24178412 TI - Making sense of the antisense transcripts in C9FTD/ALS. PMID- 24178414 TI - Histology and chimeral segregation reveal cell-specific differences in the competence for shoot regeneration and Agrobacterium-mediated transformation in Kohleria internode explants. AB - Internode explants of Kohleria sp. (Gesneriaceae) are capable of regenerating large numbers of adventitious shoots. Regeneration of green shoots from explants of an albino periclinal chimera with genetically green L1, as well as microsurgical removal of the epidermis revealed that shoots originate only from the epidermis. Histological studies further showed that shoots arise from a particular epidermal cell type, viz the basal cell of young glandular trichomes. On the other hand, cells competent for Agrobacterium-mediated transformation are mainly located in vascular tissues, as could be shown by histochemical localization of beta-glucuronidase (GUS) expression in explants that had been inoculated with A. tumefaciens strains carrying binary plasmids with GUS and kanamycin resistance (NPTII) genes. Only 3% of GUS expression events took place in the epidermis. Consequently, shoot regeneration in the presence of kanamycin was very poor. Moreover, most of those shoots proved GUS-negative and did not survive subcultivation on kanamycin-containing medium. Six regenerants, however, were most probably transgenic, as suggested by the ability to produce adventitious shoots in the presence of kanamycin and by polymerase chain reaction (PCR) analysis. To our knowledge, this is the first positive result towards genetic transformation in a taxon of the Gesneriaceae. PMID- 24178415 TI - Callus induction and plantlet formation through culture of isolated microspores of eggplant (Solanum melongena L.). AB - Morphogenic calli were obtained efficiently from ab initio cultures of isolated microspores in eggplant. Initial culture of freshly isolated microspores in sucrose-free medium at high temperature (35 degrees C) for 3 d was a prerequisite for callus induction. The microspores were re-cultured in modified NLN medium containing 2% sucrose and phytohormones (NAA 0.5 mg l(-1), BA 0.5 mg l(-1)) in the dark. After 4 weeks of re-culture, small calli derived from microspores were transferred to MS medium containing 4 mg l(-1) zeatin and 0.2 mg l(-1) IAA for shoot regeneration. The ploidy of 12 randomly selected regenerants was assessed by chromosome counts in root tips. Only one of the regenerants was haploid, 7 were diploid, 3 were triploid and one was tetraploid. The diploids set seeds after self-pollination and showed no segregation for morphological traits in the progeny, suggesting that they were spontaneously doubled haploids. PMID- 24178416 TI - Isolated microspore culture of Chinese flowering cabbage (Brassica campestris ssp. parachinensis). AB - Microspores of several genotypes of Brassica campestris ssp. parachinensis have been cultured in vitro and induced to undergo embryogenesis and plant formation. Conditions favourable for embryogenesis in this species include a bud size of 2 2.9 mm, NLN-13 culture medium (Nitsch and Nitsch 1967; Lichter 1981, 1982; Swanson 1990), and an induction through exposure to 32 degrees C for a period of 48 h. Longer periods of an elevated temperature for induction of embryogenesis resulted in embryo abortion at early developmental stages. With the protocol developed here, microspores of 60-80% of donor plants could be induced to produce embryos, although embryo yields were low, i.e. 2-5 embryos per 10 buds. Some genotypes responded to culture conditions with high numbers of embryo formation (100-150 embryos per 10 buds) but most of these subsequently failed to mature. The pattern of cell division and morphological changes of the microspores in culture were studied using various microscopic techniques. PMID- 24178417 TI - Effect of sugar type on the efficiency of plant regeneration from protoplasts isolated from shoot tip-derived meristematic nodular cell clumps of Lilium x formolongi hort. AB - Suspension cultures composed of meristematic nodular cell clumps of Lilium x formolongi hort were established from shoot tips placed on MS medium supplemented with 1 mg/l picloram and 30 g/l sucrose, glucose, fructose or sorbitol. Protoplasts isolated from these cultures were embedded in 1 g/l gellan gumsolidified 1/2MS medium with 1 mg/l picloram and the different kinds of sugars at 0.5 M, and cultured at 25 degrees C in the dark. The highest plating efficiency (13.7%) was obtained when the protoplasts were isolated from the cell clumps which had been subcultured in MS medium containing glucose and were likewise cultured in MS medium supplemented with 0.5 M glucose. Plants were regenerated from the protoplast-derived calli on 1/2MS medium containing 2.5-10 g/l sucrose or 5-10 g/l glucose. These results suggest that the kinds of sugar and concentration are important parameters affecting protoplast isolation, proliferation and plant regeneration in L. x formolomgi hort. PMID- 24178418 TI - Bacterial stimulation of adventitious rooting on in vitro cultured slash pine (Pinus elliottii Engelm.) seedling explants. AB - A bacterium has been isolated that initiates adventitious rooting when co cultured under in vitro conditions with seedling-produced hypocotylary explants of slash pine (Pinus elliottii). Rooting efficiencies produced through bacterial explant co-culture range from approximately 15% to greater than 90% over non treated controls. Explant exposure to the root inducing bacterium has produced no obvious pathology in the regenerated plantlets. Seedling explants rooted by bacterial-explant co-culture have been successfully transitioned to ambient greenhouse conditions. PMID- 24178419 TI - Two isoforms of acid phosphatase secreted by tobacco protoplasts: differential effect of brefeldin A on their secretion. AB - The effects of brefeldin A (BFA) on the secretion of acid phosphatase (APase) by tobacco protoplasts were investigated. Secretion of APase was inhibited by BFA in a dose-dependent manner, with a concomitant intracellular accumulation of the enzyme. The secreted APase was composed of two isoforms. BFA (10/ MUg/ml) inhibited the secretion of one of the isoforms without inhibiting that of the other, and this phenomenon explains the partial inhibition of APase secretion as a whole. The inhibition of APase secretion was accompanied by changes in the morphology of the Golgi apparatus and also by an increment in massdensity of cells. PMID- 24178420 TI - Agrobacterium T-DNA mutation causes the loss of GUS expression in transgenic tobacco. AB - A new freezer stock of an Agrobacterium tumefaciens clone of LBA4404/pBI121, designated 8999, was found to contain a mutation in the T-DNA region. GUS activity in Agrobacterium 8999 was reduced to levels in negative controls of LBA4404. Additionally, GUS activity in T1 seedlings from tobacco plants transformed with 8999 was reduced to that of untransformed plants. Southern and northern blotting showed that Agrobacterium clone 8999 transferred its T-DNA into the plant, that the correct sizes of 35S promoter and GUS coding region were integrated into the plant's genome in the correct orientation, but that no transcript was detectable after 24 h. Genomic DNA from a T1 seedling from 8999 transformation, digested with HpaII and MspI, indicated no methylation in the promoter region. We conclude from this data that Agrobacterium 8999 has a stable mutation that reduces expression at the mRNA level and is responsible for the lack of GUS expression in plants transformed with this Agrobacterium clone. Therefore, unselected genes within the T-DNA region may suffer mutations in Agrobacterium. PMID- 24178421 TI - Isolation of mesophyll and secretory cell protoplasts of the halophyte Ceratostigma plumbaginoides (L.): a comparison of ATPase concentration and activity. AB - A method is described for isolating mesophyll protoplasts from leaves and secretory cell protoplasts from salt glands of the facultative halophyte, Ceratostigma plumbaginoides (L.). Rates of ATP hydrolysis in both cell types were determined, and levels in secretory cell protoplast preparations were fourfold higher than those in mesophyll protoplast preparations, based on total protein. The rate of ATP hydrolysis was sensitive to azide and vanadate, and stimulated by Triton-X-100. Additionally, immunoblot procedures using an antibody to the plasma membrane H(+)/ATPase was used to compare ATPase levels of the mesophyll and secretory cell protoplasts. Results indicate that secretory cells have a higher concentration of H(+)/ATPase than mesophyll cells, consistent with their putative function in salt glands. PMID- 24178422 TI - Induction of high-frequency somatic embryogenesis in geranium (Pelargonium x hortorum Bailey cv Ringo Rose) cotyledonary cultures. AB - The cv Ringo Rose of hybrid seed geranium (Pelargonium x hortorum Bailey), previously shown to be recalcitrant in culture, produced somatic embryos when cotyledonary explants were cultured on regeneration medium containing thidiazuron (TDZ), forchlorfenuron (CPPU), or a combination of indole-3-acetic acid and N(6) benzylaminopurine (IAA+BAP). Amendment of the basal medium with TDZ (0.5 MUM) was the most effective treatment. Addition of amino acids to the medium promoted the growth of somatic embryos. Retention of the proximal region of the cotyledon was crucial for regeneration, but the removal of the distal 1/3 to 1/2 cotyledon had no significant effect on somatic embryogenesis. Cotyledonary explants formed somatic embryos in higher frequency and much earlier than hypocotyl explants cultured on the same medium. The somatic embryos induced on cotyledonary explants were germinated on basal medium. More than 70% of the somatic embryos were converted into plants and transferred to soil. PMID- 24178423 TI - Micropropagation of Hemidesmus indicus (L.) R. Br. through axillary bud culture. AB - A procedure for rapid in vitro propagation of the aromatic and medicinal plant Hemidesmus indicus (L.) R.Br. (Family Asclepiadaceae) from nodal explants is described. The highest shoot multiplication rate of 8.2 +/- 0.4 shoots/explant with a 95% frequency was achieved in S weeks culture period on Murashige and Skoog medium supplemented with 1.15 MUM kinetin and 0.054 MUM alpha naphthaleneacetic acid. Excised shoots were rooted on the same basal medium supplemented with 1.15 MUM kinetin and 7.35 MUM indole-3-butyric acid. Shoots derived from subcultures exhibited better rooting response than those from primary cultures. After a hardening phase of 2 weeks, there was a 70% transplantation success in the field. PMID- 24178424 TI - Stability and expression of amplified EPSPS genes in glyphosate resistant tobacco cells and plantlets. AB - The stability and expression of amplified 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) genes was examined in glyphosate resistant tobacco cells grown in glyphosate-free medium, and in plantlets regenerated from resistant cells. Amplified DNA was maintained in resistant cells grown in the absence of glyphosate for three years. Amplified EPSPS genes were retained in regenerated plantlets at levels comparable to those observed in the resistant cells, and EPSPS mRNA was overexpressed (compared to unselected plantlets). However, glyphosate resistance in cell lines grown in glyphosate-free medium declined 7 fold, and in regenerated plantlets approximately 20-fold, compared to resistant cells maintained under glyphosate selection. In plantlets, reduced resistance correlated with lower levels of EPSPS mRNA. Plantlets regenerated from resistant cells exhibited morphological variation, and had an approximate doubling of their nuclear genome size. PMID- 24178425 TI - Somatic embryogenesis in Encephalartos cycadifolius. AB - Callus cultures of Encephalartos cycadifolius were established from zygotic embryo explants on a modified B5 medium containing 1 mg l(-1) 2,4-D and 1 mg l( 1) kinetin. Callus was transferred to media containing various combinations of 2,4-D and kinetin for improvement of somatic embryogenesis. Somatic embryos were produced on media with several growth regulator combinations. The somatic embryos developed from proembryos, which developed long suspensors. A dicotyledonary embryo formed at the distal end of the suspensor. The embryos turned green in light. When transferred to a medium containing 1 mg l(-1) ABA the somatic embryos matured. The suspensors desiccated and these embryos rooted when transferred to a medium without phytohormones. PMID- 24178426 TI - Micropropagation of Melissa officinalis L. through proliferation of axillary shoots. AB - Multiple shoots were differentiated in cotyledonary nodes of 10 d old seedlings of Melissa officinalis, cultured on MS medium supplemented with BAP (0-4 mg/l). The production of shoots was further induced in subcultures of the original expiant, after the first harvest of shoots (stump), using similar conditions. The highest average number of shoots in the two inoculations was obtained with 2 mg/l of BAP: 24 axillary shoots per explant, 7 in the first inoculation and 17 in the second one. The maximum elongation of shoots was achieved with BAP at 0.2 mg/l, and higher concentrations of the hormone induced a decrease in their size. A range of BAP concentrations between 0.2-0.5 mg/l allowed the production of more shoots with a size suitable for rooting. Roots were induced in 30 d old shoots, transferred to MS medium individually supplemented with IBA or NAA (0-4 mg/l). Micropropagated plants were successfully transferred to soil. PMID- 24178427 TI - Regeneration of Ensete ventricosum through somatic embryogenesis and adventitious buds. AB - In southern and south-western Ethiopia, Ensete ventricosum is grown as an important starchy, staple food crop, supporting the diet of a quarter of the Ethiopian population. Due to difficulty in germinating seeds and the long vegetative period, breeding enset is extremely difficult. Adventitious buds and somatic embryos have been induced from callus derived from corm tissues and cultured on Murashige and Skoog's (MS) basal medium supplemented with benzylaminopurine (BAP) or 6 gamma-gamma-dimethylallylamino purine 2iP. Elongation of somatic embryos was achieved on the same medium and rooting was induced on half-strength MS basal medium supplemented with IBA. No phenotypic variation was observed among more than 200 potted regenerants. The possible implications for mutation breeding in this crop are discussed. PMID- 24178428 TI - Stimulatory effect of water stress on plant regeneration in aromatic Indica rice varieties. AB - Frequency of regeneration of fertile plants from cell suspensions was significantly increased using water stress treatments in two commercially cultivated Indian aromatic rice varieties, Basmati 385 and Pusa Basmati 1. The water stress treatments included the use of 1.0% (w/v) agarose instead of 0.5% (w/v) for medium solidification, inclusion of mannitol (0.1, 0.2 and 0.4 M) in regeneration medium, or 24 h partial desiccation of calli. When the agarose concentration of the regeneration medium was increased from 0.5% to 1.0% (w/v), the frequency of shoot formation in Pusa Basmati 1 from cell suspension-derived calli increased by over eightfold, to 86%. Mannitol, at 0.1 to 0.2 M concentration, stimulated the frequency of shoot regeneration in Pusa Basmati 1 by fivefold but had no effect in Basmati 385. Mannitol at 0.4 M concentration completely inhibited shoot regeneration but promoted embryogenesis. These calli regenerated shoots with greater frequencies when transferred to mannitol-free medium. Partial desiccation of rice calli resulted in an up to threefold increase in the shoot regeneration frequency. Best regeneration frequencies (54-98%) were obtained when 24 hdesiccated calli were grown on regeneration medium with 1.0% (w/v) agarose. A similar stimulatory effect of water stress on plant regeneration was observed in another Indica rice variety, IR43, and a Japonica rice variety, Taipei 309. PMID- 24178429 TI - Coeliac disease: A review of the causative agents and their possible mechanisms of action. AB - This review outlines the main theories for the aetiology of coeliac disease and presents in more detail the work carried out in an attempt to define the nature of the toxins in wheat gluten. This includes the results of work with synthetic peptides and a discussion of the various assays used.Evidence is presented for an enzyme deficiency in coeliac disease which leads to abnormally high concentrations of certain peptides in the small bowel. These peptides can bring about damage by direct toxic action and by immunological mechanisms.Investigations of activity of synthetic peptides based on the structure of Agliadin appear to be making good progress and point to certain regions of that molecule as being responsible for toxicity. Certain key sequences of amino acids appear to be of fundamental importance to these studies. PMID- 24178431 TI - Effects of taurine on GABA release from synaptosomes of rat olfactory bulb. AB - Superfusion of synaptosomes prepared from rat olfactory bulb revealed constant basal release of endogenous taurine (Tau), aspartate (Asp), glutamate (Glu) andgamma-aminobutyrate (GABA): their release rates were 110.4 +/- 13.0, 30.3 +/- 6.7, 93.7 +/- 13.1, and 53.3 +/- 8.8 pmol/min/mg protein, respectively. The depolarizing-stimulation with 30mM KCl evoked 1.17-, 2.18-, 2.55- and 1.53-fold increases, respectively. Tau release was calcium-independent. However, the perfusion of synaptosomes with Tau (10uM) inhibited the evoked increase in GABA release by 63% without changing basal release, although it did not affect release of Asp and Glu. Phaclofen (10uM, a GABAB receptor antagonist), but not bicuculline (10uM, a GABAA receptor antagonist), counteracted the Tau-induced reduction in GABA release. These data suggest that Tau may be abundantly released from nerve endings of rat olfactory bulb and that it may regulate GABA release through the activation of presynaptic GABAB autoreceptors. PMID- 24178432 TI - Effect of taurine on wound healing. AB - Taurine which has antioxidant effects is also known to have effects on cell proliferation, inflammation and collagenogenesis. The aim of this study was to investigate the effect of taurine on incisional skin wounds.The mice incised on the dorsal area were divided into control and experimental groups. Saline was injected intraperitoneally to half of the animals in the control group and locally applied to the other half. Fifty mM taurine solution was given intraperitoneally to the first half of the experimental animals and locally to the second half of the experimental group.After four days of treatment, malondialdehyde (MDA) and histamine levels as well as the tensile strength of the wound tissue were measured. Structural alterations in epidermis and dermis were histologically evaluated.The locally administreated taurine significantly increased wound tensile strength by decreasing the MDA and histamine levels and prevented the degranulation of the mast cells. These observations suggest that taurine may be useful on wound healing. PMID- 24178430 TI - L-Tryptophan: Biochemical, nutritional and pharmacological aspects. AB - Tryptophan is important both for protein synthesis and as a precursor of niacin, serotonin and other metabolites. Tryptophan is an unusual amino acid because of the complexity of its metabolism, the variety and importance of its metabolites, the number and diversity of the diseases it is involved in, and because of its use in purified form as a pharmacological agent. This review covers the metabolism of tryptophan, its presence in the diet, the disorders associated with low tryptophan levels due to low dietary intake, malabsorption, or high rates of metabolism, the therapeutic effects of tryptophan and the side effects of tryptophan when it is used as a drug including eosinophilia myalgia syndrome. PMID- 24178433 TI - Recognition of deficient nutrient intake in the brain of rat withL-lysine deficiency monitored by functional magnetic resonance imaging, electrophysiologically and behaviorally. AB - EachL-amino acid (AA) in plasma and brain remains unchanged all day long while normal diet is available. But once restriction ofL-lysine (Lys) was introduced, strong anorexia happened. When Lys deficient diet was offered to rats, their growth were decreased depending upon dietary Lys intake, and they ingested Lys solution in choice quantitatively and both appetite and growth normalized. The recognition site for the deficit in rat's brain was identified by brain oxygenation using a functional MRI that higher signals in the ventromedial hypothalamus and lateral hypothalamic area (LHA) appeared, at 30-50 minutes after Lys injection i.p. and then recovered. Degree of Lys hunger, assayed by bar pressing (50mg pellet of normal diet/30 presses), was suppressed by Lys micro injection into the LHA, similar to free Lys ingestion but any other AA never did, suggesting the LHA as recognition site for Lys deficit in rats with Lys deficiency due to AA homeostasis. PMID- 24178434 TI - Polyamine transport inEscherichia coli. AB - The polyamine content in cells is regulated by both polyamine biosynthesis and its transport. We recently obtained and characterized three clones of polyamine transport genes (pPT104, pPT79 and pPT71) inEscherichia coli. The system encoded by pPT104 was the spermidine-preferential uptake system and that encoded by pPT79 the putrescine-specific uptake system. Furthermore, these two systems were periplasmic transport systems consisting of four kinds of proteins: pPT104 clone encoded potA, -B,-C, and -D proteins and pPT79 clone encoded potF, -G, -H, and -I proteins, judging from the deduced amino acid sequences of the nucleotide sequences of these clones. PotD and -F proteins were periplasmic substrate binding proteins and potA and -G proteins membrane associated proteins having the nucleotide binding site. PotB and -C proteins, and potH and -I proteins were transmembrane proteins probably forming channels for spermidine and putrescine, respectively. Their amino acid sequences in the corresponding proteins were similar to each other. The functions of potA and -D proteins in the spermidine preferential uptake system encoded by pPT104 clone were studied in detail through a combined biochemical and genetic approach. In contrast, the putrescine transport system encoded by pPT71 consisted of one membrane protein (potE protein) haveing twelve transmembrane segments, and was active in both the uptake and excretion of putrescine. The uptake was dependent on membrane potential, and the excretion was due to the exchange reaction between putrescine and ornithine. PMID- 24178435 TI - Nighttime sleep, daytime napping, and labor outcomes in healthy pregnant women in Taiwan. AB - We prospectively examined the associations of nighttime and daytime sleep during the third trimester of pregnancy with labor duration and risk of cesarean deliveries in a convenience sample of 120 nulliparous women who completed sleep related questionnaires and wore wrist actigraphs for up to 7 days. Nap duration and 24-hour sleep duration were inversely associated with labor duration in women with vaginal delivery. Neither actigraphy-derived nor self-reported sleep variables were associated with type of delivery (e.g., vaginal, cesarean). Results showed a beneficial effect of sleep on labor duration and suggest that studies of sleep duration effects on labor and pregnancy outcomes require a consideration of the amount of both daytime and nighttime sleep. PMID- 24178436 TI - Lactobacillus reuteri in the treatment of Helicobacter pylori infection. AB - Probiotics have proven to be useful in the treatment of a number of gastrointestinal diseases. Probiotics may compete directly with Helicobacter pylori, possibly by interference with adherence or by the production of antimicrobial molecules. Lactobacillus reuteri has been shown to inhibit H. pylori in vitro and in vivo, and theoretically may play a role in eradication therapy. The aim of this study was to examine the efficacy of L. reuteri in H. pylori eradication therapy. This was an open label single center study. H. pylori infection was defined as positive gastric histopathology and (13)C-UBT. Intervention consisted of L. reuteri (DSM 17938) 10(8) cfu plus pantoprazole 20 mg twice a day for 8 weeks. Eradication was defined as a negative (13)C-UBT, 4-6 weeks post therapy. Compliance was considered good if at least 90% of the total number of the pills were taken. 21 of 22 subjects completed the study without protocol violation (mean age 52 years; 36% men). L. reuteri plus pantoprazole twice a day cured 13.6% (3/22; 95% CI 2.9-34.9%) of patients with H. pylori infection by ITT analysis and 14.2% (3/21; 95% CI 3.0-36%) by PP analysis. Overall urease activity assessed before and 4-6 weeks post therapy showed a significant reduction with a difference of mean of 38.8 vs. 25.4 by one-tailed test (P = 0.002). In conclusion, L. reuteri may have a potential role in H. pylori eradication therapy if the cure rate can be improved by changes in dose, dosing interval, or duration of therapy. PMID- 24178437 TI - Synthesis of diastereometrically pure cubane-like photodimers from 2,4 pentanediyl-bis-2-naphthoates. AB - Irradiation of (2R,4R)-(-)- and (2S,4S)-(+)-2,4-pentanediyl-bis-2-naphthoates (1R and 1S, respectively) in organic solutions exclusively results in cubane-like anti(HH) photodimers in 100% yield. Asymmetric induction with 100% diastereometric excess (de) has been achieved and the absolute configuration of the yielded diastereomers has been established. Moreover, irradiation of (2R,4S) 2,4-pentanediyl-bis-2-naphthoate (1M) gives cubane-like syn(HH) photodimers in 100% yield. PMID- 24178438 TI - Homologous SV40 RNA trans-splicing: a new mechanism for diversification of viral sequences and phenotypes. AB - Simian Virus 40 (SV40) is a polyomavirus found in both monkeys and humans, which causes cancer in some animal models. In humans, SV40 has been reported to be associated with cancers but causality has not been proven yet. The transforming activity of SV40 is mainly due to its 94-kD large T antigen, which binds to the retinoblastoma (pRb) and p53 tumor suppressor proteins, and thereby perturbs their functions. Here we describe a 100 kD super T antigen harboring a duplication of the pRB binding domain that was associated with unusual high cell transformation activity and that was generated by a novel mechanism involving homologous RNA trans-splicing of SV40 early transcripts in transformed rodent cells. Enhanced trans-splice activity was observed in clones carrying a single point mutation in the large T antigen 5' donor splice site (ss). This mutation impaired cis-splicing in favor of an alternative trans-splice reaction via a cryptic 5'ss within a second cis-spliced SV40 pre-mRNA molecule and enabled detectable gene expression. Next to the cryptic 5'ss we identified additional trans-splice helper functions, including putative dimerization domains and a splice enhancer sequence. Our findings suggest RNA trans-splicing as a SV40 intrinsic mechanism that supports the diversification of viral RNA and phenotypes. PMID- 24178439 TI - Study of chromosome 9q gain, Notch pathway regulators and Tenascin-C in ependymomas. AB - Ependymomas are relatively uncommon tumours of the central nervous system which arise from the ependymal lining of the ventricles and spinal canal. The molecular changes leading to ependymal oncogenesis are not completely understood. We examined chromosome 9q33-34 locus for gain, potential oncogenes at this locus (Notch-1 and Tenascin-C) and Notch pathway target genes (Hes-1, Hey-2 & C-myc) in ependymomas by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, to assess if they have any correlation with clinical characteristics. We analyzed 50 cases of ependymomas by FISH for 9q gain and by IHC for Notch-1 and its target gene proteins (Hes-1, Hey-2 and C-myc) expression. We also performed IHC for Tenascin-C to rule out any correlation with aggressiveness/grade of tumour. FISH study revealed significant chromosome 9q gain in ependymomas of adult onset (age > 18 years) and spinal cord origin. Notch 1 showed significantly more frequent immunohistochemical expression in supratentorial and anaplastic ependymomas. Tenascin-C (TN-C) expression was significant in intracranial, childhood (age <= 18 years) and anaplastic ependymomas. Of the three Notch pathway target gene proteins (Hes-1, Hey-2 and C myc), Hes-1 and C-myc expression showed significant correlation with anaplastic and adult onset ependymomas, respectively. Genetic alterations are independent prognostic markers in ependymomas. A clinicopathological correlation with various molecular signatures may be helpful in the development of new therapeutic targets. PMID- 24178440 TI - A meta-analysis of temozolomide versus radiotherapy in elderly glioblastoma patients. AB - Temozolomide (TMZ) alone has been proposed as a promising alternative to radiotherapy (RT) in elderly glioblastoma (GBM) patients. We report a meta analysis to systematically evaluate TMZ monotherapy in older GBM patients. A systematic literature search was performed using PubMed, EMBASE and the Cochrane database. Studies comparing TMZ versus RT in elderly patients (>= 65 years) with newly diagnosed GBM were eligible for inclusion. Two randomized clinical trials (RCTs) and three comparative studies were included in the analyses, which revealed an overall survival (OS) advantage for TMZ compared with RT (HR [hazard ratio] 0.86, 95 % CI [confidence interval] 0.74-1.00). However, a sensitivity analysis of 2 RCTs only supported its non-inferiority (HR 0.91, 95 % CI 0.66 1.27). Most elderly patients tolerated TMZ despite an increased risk of grade 3-4 (G3-4) toxicities, especially hematological toxicities. The quality of life was similar between the groups. In the MGMT analysis, methylated tumors were associated with a longer OS than unmethylated tumors among elderly patients receiving TMZ monotherapy (HR 0.50, 95 % CI 0.35-0.70). Moreover, in patients with methylated tumors, TMZ was more beneficial than RT alone in improving OS (TMZ vs. RT: HR 0.66, 95 % CI 0.47-0.93) whereas the opposite was true for those with unmethylated tumors (HR 1.32, 95 % CI 1.00-1.76). Although the meta-analysis demonstrated the non-inferiority to RT in improving OS, TMZ alone was not a straightforward solution for elderly GBM patients because of an increased risk of G3-4 toxicities, especially hematological toxicities. MGMT testing might be helpful for determining individualized treatment. PMID- 24178441 TI - Correlation between progression free survival and dynamic susceptibility contrast MRI perfusion in WHO grade III glioma subtypes. AB - The purpose of this study was to determine whether dynamic susceptibility contrast MR perfusion relative cerebral blood volume (rCBV) correlates with prognosis of World Health Organization (WHO) grade III glial tumors and their different subtypes. Retrospective evaluation of pre-treatment tumor rCBV derived from dynamic susceptibility contrast MR perfusion was performed in 34 patients with histopathologically diagnosed WHO grade III glial tumors (anaplastic astrocytomas (n = 20), oligodendrogliomas (n = 4), and oligoastrocytomas (n = 10)). Progression free survival was correlated with rCBV using Spearman rank analysis. ROC curve analysis was performed to determine the operating point for rCBV in patients with anaplastic astrocytomas dichotomized at the median progression free survival time. For all grade III tumors (n = 34) the mean rCBV was 2.51 with a progression free survival of 705.5 days. The mean rCBV of anaplastic astrocytomas was 2.47 with progression free survival 495.2 days. In contrast, the mean rCBV for oligodendroglial tumors was 2.56 with a progression free survival of 1005.6 days. Although there was no significant correlation between rCBV and progression free survival among all types of grade III gliomas (P = 0.12), among anaplastic astrocytomas there was a significant correlation between pretreatment rCBV and progression free survival with correlation coefficient of -0.51 (P = 0.02). The operating point for rCBV in patients with anaplastic astrocytomas dichotomized at the median progression free survival time (446.5 days) was 2.86 with 78 % accuracy and there was a significant difference between the survival of patients with anaplastic astrocytomas in the dichotomized groups (P = 0.0009). Pre-treatment rCBV may serve as a prognostic imaging biomarker for anaplastic astrocytomas, but not grade III oligodendroglioma tumors. PMID- 24178443 TI - Reaction of tetrachlorinated perylene bisimide in a strong base to form an asymmetric compound with charge transfer optical properties. AB - A novel perylene oxazine imide (POI) with donor-pi-bridge-acceptor (D-pi-A) asymmetric structure was synthesized from tetrachlorinated perylene bisimide (PBI) through transformation of one imide group to oxazine, which exhibits significant charge transfer optical properties in solutions. PMID- 24178442 TI - HMGB1 is involved in autophagy inhibition caused by SNCA/alpha-synuclein overexpression: a process modulated by the natural autophagy inducer corynoxine B. AB - SNCA/alpha-synuclein and its rare mutations are considered as the culprit proteins in Parkinson disease (PD). Wild-type (WT) SNCA has been shown to impair macroautophagy in mammalian cells and in transgenic mice. In this study, we monitored the dynamic changes in autophagy process and confirmed that overexpression of both WT and SNCA(A53T) inhibits autophagy in PC12 cells in a time-dependent manner. Furthermore, we showed that SNCA binds to both cytosolic and nuclear high mobility group box 1 (HMGB1), impairs the cytosolic translocation of HMGB1, blocks HMGB1-BECN1 binding, and strengthens BECN1-BCL2 binding. Deregulation of these molecular events by SNCA overexpression leads to autophagy inhibition. Overexpression of BECN1 restores autophagy and promotes the clearance of SNCA. siRNA knockdown of Hmgb1 inhibits basal autophagy and abolishes the inhibitory effect of SNCA on autophagy while overexpression of HMGB1 restores autophagy. Corynoxine B, a natural autophagy inducer, restores the deficient cytosolic translocation of HMGB1 and autophagy in cells overexpressing SNCA, which may be attributed to its ability to block SNCA-HMGB1 interaction. Based on these findings, we propose that SNCA-induced impairment of autophagy occurs, in part, through HMGB1, which may provide a potential therapeutic target for PD. PMID- 24178444 TI - Pulmonary embolism in young people. Trends in Germany from 2005 to 2011. AB - OBJECTIVES: There is an ongoing discussion about the impact of hormonal contraception on the incidence of venous thromboembolism (VTE) in young women. Specific data of the significance of this problem and its changes in recent years in Germany are not available. Thus, we analyzed the incidence of VTE in hospitalized young patients and looked for gender-specific differences. PATIENTS AND METHODS: Detailed lists of all pulmonary embolisms (PE) coded as I26 and deep vein thrombosis (DVT) coded as I80 in patients aged 10 to 39 years hospitalized in the years 2005 to 2011 were provided by the Federal Statistical Office. RESULTS: Beginning at the age of 12-13 years girls have higher numbers of PE and DVT documented as principal diagnosis, as compared to boys. This gender-specific difference disappears at the ages of 32-33 years. The difference in total numbers of PE (as principal diagnosis) between women and men within this 20-year time span increased from 318 in 2005 to 606 in 2010 and decreased to 505 in 2011. Stratifying the cases of PE according to presence or absence of cor pulmonale, the analysis showed a specific increase of PE in young women without cor pulmonale within the period of seven years between 2005 and 2011. Similar changes could not be shown for DVT as principal diagnosis. CONCLUSION: The presented data from the German DRG statistics show a disproportionally higher increase of young women hospitalised for pulmonary embolism as principal diagnosis in recent years. The possible impact of hormonal contraception on this increase has to be further elucidated. PMID- 24178445 TI - Renal cyclooxygenase products are higher and lipoxygenase products are lower in early disease in the pcy mouse model of adolescent nephronophthisis. AB - Nephronophthisis (NPHP) is a pediatric form of hereditary polycystic kidney disease (PKD), and is the leading cause of end stage renal disease in children. The pcy mouse is an orthologous model of human NPHP, with a mutation in the Nphp3 gene. Renal phospholipase A2, cyclooxygenase (COX) 1 and cyclic AMP are elevated in this model, suggesting that eicosanoid formation may be altered. In another type of PKD observed in the Han:SPRD-Cy rat, inhibition of eicosanoid production slows disease progression. If renal eicosanoids are similarly altered in NPHP, potential for pharmacologic intervention also may exist for this disorder. Therefore, renal fatty acids and eicosanoids were determined in pcy and normal mice at 15, 30 and 60 days of age by gas chromatography and HPLC-tandem mass spectrometry, respectively. Renal cysts in enlarged kidneys were observed in pcy mice by 15 days of age and increased over time. Renal phospholipid ARA levels were higher in pcy compared to normal mice at 15 and 30 days. Eicosanoid differences were observed starting at 30 days, when the COX products 6-keto prostaglandin (PG) F1alpha, thromboxane B2 and PGE2 were higher in pcy compared to normal kidneys. Overall, total COX products were elevated at 30 and 60 days. In contrast, the levels of the lipoxygenase (LOX) products were not altered until 60 days of age and these were lower in pcy kidneys compared to normal. These findings suggest that altered eicosanoids play a role in NPHP, and that manipulating these levels with pharmacologic agents may have therapeutic potential. PMID- 24178448 TI - Biochemical and quality of life responses to octreotide-LAR in acromegaly. AB - OBJECTIVES: AcroQoL is a questionnaire developed to assess quality of life in patients with acromegaly, covering physical and psychological dimensions. This study was designed to determine AcroQoL score changes and concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), before and after treatment with octreotide-LAR (oct-LAR) in acromegaly. METHODS: Retrospective observational study of 28 acromegalic patients with a mean age of 45 years (range 28-64), evaluated over a 4-year period, before and during treatment with oct-LAR in clinical practice conditions. RESULTS: Baseline AcroQoL score (53 +/- 15) improved after oct-LAR treatment (70 +/- 15) globally for the 28 patients (p < 0.001). Three patients in whom AcroQoL score did not improve over time had severe headaches, which did not disappear. In patients who normalized, both GH (<2.5 MUg/L) and IGF-1, AcroQoL score increased on average by 22 points (p = 0.003); when GH and IGF-1 improved, but did not normalize, AcroQol score increased on average by 16 points (p = 0.008). In 6 patients with discordant results, AcroQol score tended to improve if IGF-1 normalized (n = 4, p = 0.066), but not if IGF-1 remained high. CONCLUSION: Oct-LAR therapy in acromegaly improved quality of life scores in parallel to biochemical markers, except in patients with severe headaches. The AcroQoL questionnaire is an additional tool to establish therapeutic effectivity. PMID- 24178449 TI - A multitasking Argonaute: exploring the many facets of C. elegans CSR-1. AB - While initial studies of small RNA-mediated gene regulatory pathways focused on the cytoplasmic functions of such pathways, identifying roles for Argonaute/small RNA pathways in modulating chromatin and organizing the genome has become a topic of intense research in recent years. Nuclear regulatory mechanisms for Argonaute/small RNA pathways appear to be widespread, in organisms ranging from plants to fission yeast, Caenorhabditis elegans to humans. As the effectors of small RNA-mediated gene regulatory pathways, Argonaute proteins guide the chromatin-directed activities of these pathways. Of particular interest is the C. elegans Argonaute, chromosome segregation and RNAi deficient (CSR-1), which has been implicated in such diverse functions as organizing the holocentromeres of worm chromosomes, modulating germline chromatin, protecting the genome from foreign nucleic acid, regulating histone levels, executing RNAi, and inhibiting translation in conjunction with Pumilio proteins. CSR-1 interacts with small RNAs known as 22G-RNAs, which have complementarity to 25 % of the protein coding genes. This peculiar Argonaute is the only essential C. elegans Argonaute out of 24 family members in total. Here, we summarize the current understanding of CSR-1 functions in the worm, with emphasis on the chromatin-directed activities of this ever-intriguing Argonaute. PMID- 24178451 TI - Long-lasting in vivo and in vitro antibacterial ability of nanostructured titania coating incorporated with silver nanoparticles. AB - Although titanium (Ti) implants are widely used clinically, implant-associated bacterial infection is still one of the most serious complications in orthopedic surgery. Long-term antibacterial properties and the ability to inhibit biofilm formation are highly desirable to prevent implant associated infection. In this study, a controllable amount of silver (Ag) nanoparticles was incorporated into titanium oxide; or titanium, nanotubes (TiO2 -NTs). The reliable release and long term antibacterial function of Ag, in vivo and in vitro, and influence normal bone-implant integration from the Ag released from Ag-incorporated NTs in vivo have been studied to make them useable in clinical practice. In the current study, TiO2 -NTs loaded with Ag (NT-Ag) exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA, ATCC43300) in vitro for 30 days, and the ability to penetrate the protein layer well. In addition, X ray examination and 2-[(18)F]-fiuoro-2-deoxy-D-glucose positron emission tomography indicates that NT-Ag show extremely long antibacterial activity in vivo in a rat model. Furthermore, histomorphometric analysis demonstrated that satisfactory bio-integration can be expected. Our results indicate that NT-Ag has both simultaneous antimicrobial and excellent bio-integration properties, make it a promising therapeutic material for orthopedic application. PMID- 24178452 TI - Establishment of transformed root cultures of Perezia cuernavacana producing the sesquiterpene quinone perezone. AB - The sesquiterpene quinone currently known as perezone is abundantly produced by the roots of Perezia cuernavacana. This compound is of biotechnological interest since it may be used as a pigment and has several pharmacological properties. In this work we demonstrate that perezone is also produced in transformed root cultures of P. cuernavacana. Hairy roots were induced by inoculation of internodal segments of sterile plants of P. cuernavacana with Agrobacterium rhizogenes AR12 strain. The axenic liquid MS medium cultures of the hairy roots isolated from the internodes showed active growth in the absence of growth regulators. The transformed nature of the tissue was confirmed by genomic integration (PCR and slot blot hybridization) and expression (enzyme activity) of the marker gus-gene. The production of perezone by a transformed root culture was evidenced by IR spectroscopy. Our results offer an alternative for enhanced production of perezone and represent an advantage over its extraction from natural plant populations which present problems in their agronomic culture. PMID- 24178450 TI - Boosting transcription by transcription: enhancer-associated transcripts. AB - Enhancers are traditionally viewed as DNA sequences located some distance from a promoter that act in cis and in an orientation-independent fashion to increase utilization of specific promoters and thereby regulate gene expression. Much progress has been made over the last decade toward understanding how these distant elements interact with target promoters, but how transcription is enhanced remains an object of active inquiry. Recent reports convey the prevalence and diversity of enhancer transcription and transcripts and support both as key factors with mechanistically distinct, but not mutually exclusive roles in enhancer function. Decoupling the causes and effects of transcription on the local chromatin landscape and understanding the role of enhancer transcripts in the context of long-range interactions are challenges that require additional attention. In this review, we focus on the possible functions of enhancer transcription by highlighting several recent enhancer RNA papers and, within the context of other enhancer studies, speculate on the role of enhancer transcription in regulating differential gene expression. PMID- 24178453 TI - Transgenic papaya plants from Agrobacterium-mediated transformation of petioles of in vitro propagated multishoots. AB - In order to establish a model system for introduction of foreign genes into papaya (Carica papaya L.) plants by Agrobacterium-mediated transformation, petioles from multishoots were used as explant source and bacterial neomycin phosphotransferase II (NPT II) gene and beta-glucuronidase (GUS) gene were used as a selection marker and a reporter, respectively. Cross sections of papaya petioles obtained from multishoots micropropagated in vitro were infected with A. tumefaciens LBA4404 containing NPTII and GUS genes and co-cultured for 2 d. The putative transformed calluses were identified by growth on the selective medium containing kanamycin and carbenicillin, and consequently regenerated to plants via somatic embryogenesis. Thirteen putative transgenic lines were obtained from a total of 415 petiole fragments treated. Strong GUS activity was detected in the selected putative transgenic calli or plants by fluorogenic assay. Western blot analysis using GUS antiserum confirmed that the GUS protein was expressed in putative transformed papaya cells and transgenic plants. The presence of the GUS gene in the papaya tissues was detected by PCR amplification coupled with Southern blot. PMID- 24178454 TI - Regeneration of fertile transgenic indica (group 1) rice plants following microprojectile transformation of embryogenic suspension culture cells. AB - Regenerable embryogenic suspensions of elite Indica (group 1) rice varieties IR24, IR64, IR72 and an advanced Indica rice breeding line IR57311-95-2-3 were established within 6-8 weeks from 3-4 week old calli derived from mature seeds. Transgenic rice plants were obtained by introducing a plasmid carrying genes encoding hygromycin phosphotransferase (hph, conferring resistance to hygromycin B) and beta-glucuronidase (uidA), both driven by the CaMV 35S promoter, via particle bombardment of embryogenic suspensions. The effect of osmotic conditioning on transformation was evaluated. Regenerated plants were resistant to hygromycin B and expressed the uidA (GUS) gene. The growth of mother plants (R0) was normal and seeds were produced. Southern blot analysis of R0 and R1 plants showed that hygromycin resistant plants contained intact hph genes that were inherited in a Mendelian fashion. A protocol for a simple, efficient, repeatable, genotype- and environment-independent Indica rice transformation system is described. PMID- 24178455 TI - Production of dodecaploid plants of Japanese persimmon (Diospyros kaki L.) by colchicine treatment of protoplasts. AB - Dodecaploid plants of Japanese persimmon (Diospyros kaki L.) were obtained by colchicine treatment of protoplasts. Callus protoplasts of 'Jiro' (2n=90, x=15) were cultured in modified KM8p medium with 0.1% colchicine for 3-9 days. After colchicine treatment, they were cultured using agarose bead culture. Microcalli were recovered from the protoplasts after 3 months. Flow cytometric measurement showed that nine of 31 callus lines obtained from 6 days of colchicine treatment had twice the nuclear DNA content as non-treated controls. Plantlets were regenerated from the calli with twice the nuclear DNA content. Microscopic observation of root tip cells showed that their somatic chromosome number was 2n=180 (x=15). Compared with 'Jiro', dodecaploid plants had longer stomatal guard cells and lower stomatal densities, consistent with increased ploidy. PMID- 24178456 TI - The detection of somaclonal variants of beet using RAPD. AB - Plantlets were regenerated by adventitious shoot budding in tissue culture from leaf explants of a single genotype of sugar beet. DNA was extracted from the parental plant and from 120 regenerants. RAPD analysis was carried out using five decanucleotide primers; 4,557 RAPD marker bands were examined and two polymorphisms were observed. Thirty secondary regenerants were then derived, using the same tissue culture technique, from thirty of the primary regenerants. Again RAPD analysis was employed and a single band polymorphism was observed out of 1,050 bands examined. The overall frequency of detection of somaclonal polymorphisms using RAPD (3 in 5,607 = 0.05%) is similar to frequencies previously reported using isozyme and RFLP technologies. PMID- 24178457 TI - Tobacco (Nicotiana tobaccum) nuclear transgenics with high copy number can express NPTII driven by the chloroplast psbA promoter. AB - A chloroplast expression vector containing the NPTII gene under the control of apsbA promoter (psbA-NPTII) was constructed, and was biolistically delivered into both suspension cells and leaf strips of tobacco (Nicotiana tabaccum). Analyses of subsequently recovered kanamycin-resistant transgenic plants indicate that the psbA-NPTII gene was not located in the chloroplast, but was in the nucleus in very high copy number. This conclusion was based upon results from: (1) Southern hybridization analyses of chloroplast and nuclear DNAs using NPTII, chloroplast marker, and nuclear-marker probes; (2) pulse-field gel electrophoresis; and (3) kanamycin screening of sexual progenies. This study suggests that the nuclear expression of the NPTII gene may have been associated with many copies of the psbA-NPTII construction. Very high copy number in the nucleus might either allow NPTII expression from the otherwise inadequate psbA promoter, or might increase the chance of recombining with upstream tobacco regulatory sequences. PMID- 24178458 TI - In vitro flowering of Fortunella hindsii (Champ.). AB - Branch internodes of mature plants and stem internodes of seedlings of Fortunella hindsii flowered in vitro on half-strength MT (Murashige and Tucker 1969) basal medium supplemented with benzyladenine, adenine, 6-gamma-gamma dimethylallylaminopurine and kinetin. The highest percentage of flowering was achieved with explants originating from branch internodes of flowering plants close to the apex on half-strength MT basal medium containing 5% sucrose and 0.01 mg 1(-1) BA in light. Exposure to darkness for more than 3 weeks followed by re exposure to light reduced flowering. Flowering required a 4-day exposure to BA, but shoot formation could be initiated even without exposure to BA. First branch internode segments on MT basal medium containing 5% sucrose were prolific in flower (85%) production. The sucrose treatment affected the flower bud size distribution. There were about 13 flower buds per culture in the largest size category (>5 mm). PMID- 24178459 TI - Intron-mediated enhancement of gene expression in maize (Zea mays L.) and bluegrass (Poa pratensis L.). AB - We report a strength comparison of a large variety of monocot and dicot intron containing fragments inserted in the 5' untranslated leader, between the CaMV 35S promoter and the uidA gene (coding for the beta-glucuronidase: GUS). Relative strengths of the intron-containing fragments were evaluated by comparing transient GUS expression after particle bombardment in embryogenic maize and bluegrass suspension cultures. Our results confirm a dramatic dependence on the presence of an intron for chimeric gene expression in both species. On average, the maize first intron of ubi1 provided the highest enhancement of gene expression in maize and bluegrass (71- and 26-fold enhancement, respectively). Half of the introns tested affected gene expression differently in bluegrass and maize. This suggests that the intron-mediated enhancement of gene expression generally obtained with maize may not be fully applicable to all monocots. We also report enhancement of gene expression (92-fold) in a monocot species by a dicot intron (chsA intron). PMID- 24178460 TI - Polyamine biosynthesis during somatic embryogenesis in interior spruce (Picea glauca x Picea engelmannii complex). AB - Putrescine, spermidine, and spermine levels during somatic embryogenesis of interior spruce (Picea glauca x Picea engelmannii complex) were quantified On abscisic acid supplemented growth medium putrescine and spermidine levels increased two-fold coinciding with maturation of the early somatic embryos to globular embryos. Polyclonal antibodies raised against Escherichia coli arginine decarboxylase (ADC) and ornithine decarboxylase (ODC), following affinity purification specifically recognized spruce ADC and ODC, which corresponded to 85kD and 65kD bands on western blots of total protein extracts from embryogenic masses, Immunoassays using these antibodies showed increased ADC levels corresponding to embryo maturation while ODC levels remained the same. From these results it is concluded that polyamines are involved in the maturation of somatic embryos of interior spruce. PMID- 24178461 TI - Transformation of 12 different plasmids into soybean via particle bombardment. AB - Particle bombardment offers a simple method for the introduction of DNA into plant cells. Multiple DNA fragments may be introduced on a single plasmid or on separate plasmids (co-transformation). To investigate some of the properties and limits of co-transformation, 12 different plasmids were introduced into embryogenic suspension culture tissue of soybean [Glycine max (L.) Merrill] via particle bombardment. The DNAs used for co-transformation included 10 plasmids containing KFLP markers for maize and 2 plasmids separately encoding hygromycin resistance and beta-glucuronidase. Two weeks following bombardment with the 12 different plasmids, suspension culture tissue was placed under hygromycin selection. Hygromycin-resistant clones were isolated after an additional 5 to 6 weeks. Southern hybridization analysis of 26 hygromycin-resistant embryogenic clones verified the presence of introduced plasmid DNAs. All of the co transforming plasmids were present in most of the transgenic soybean clones and there was no preferential uptake and integration of any of the plasmids. The copy number of individual plasmids was approximately equal within clones but highly variable between clones. While some clones contained as few as zero to three copies of each plasmid, others clones contained as many as 10 to 15 copies of each of the 12 different plasmids. PMID- 24178462 TI - Inherited chilling tolerance in somatic hybrids of transgenic Hibiscus rosa sinensis x transgenic Lavatera thuringiaca selected by double-antibiotic resistance. AB - Improvement of Hibiscus rosa-sinensis for increased frost tolerance has been attempted through somatic hybridization with the frost tolerant Lavatera thuringiaca. Cell suspensions from Hibiscus and Lavatera were transformed with A. tumefaciens harboring plasmids containing selectable genes coding for kanamycin and hygromycin resistance, respectively. We provided evidence that H. rosa sinensis and L. thuringiaca were transformed by strong selection of transformed calluses in medium containing antibiotics, by GUS activity determination in protein extracts and by molecular confirmation of chromosomal integration and expression of the selectable genes. Protoplasts isolated from a kanamycinresistant Hibiscus callus and from a hygromycin-resistant Lavatera callus were fused and selected in medium containing both antibiotics. We determined unambiguously that the regenerated double-antibiotic resistant clones obtained are indeed somatic hybrids through analysis of acid phosphatase zymograms and nuclear DNA content. Plant regeneration through somatic embryogenesis was accomplished from both isolated protoplasts and transgenic calluses of L. thuringiaca. However, regeneration from the double-antibiotic resistant fusant calluses was unsuccessful. Analysis of the somatic hybrids at the callus level showed that chilling and freezing tolerance are governed by independent genetic components. The somatic hybrids displayed significant improvement for chilling tolerance at conditions lethal to H. rosa-sinensis, although frost tolerance was not expressed. PMID- 24178463 TI - Acetylsalicylic acid enhances and synchronizes thidiazuron-induced somatic embryogenesis in geranium (Pelargonium x hortorum Bailey) tissue cultures. AB - Thidiazuron (TDZ) effectively induced somatic embryogenesis in cultured hypocotyl explants of geranium (Pelargonium x hortorum Bailey) during only a 3-day period of induction. The presence of acetylsalicylic acid (ASA) during this period caused a two-fold increase in the number of somatic embryos and enhanced synchronization of embryo development compared to the TDZ treatment alone. Salicylic acid was ineffective in modulating similar embryogenic responses as ASA. The ASA-induced enhancement and synchronization of somatic embryogenesis could possibly be used as an experimental system to study the interplay of growth regulators in somatic embryogenesis. PMID- 24178464 TI - A reliable method for extraction of RNA from various conifer tissues. AB - A simple and efficient procedure suitable for extraction of high-quality RNA from cultured conifer tissues, somatic embryos, zygotic embryos, needles, stem and root tissues was developed. It produced from 100 MUg up to 700 MUg total RNA per gram tissue dependent on the types of tissues used. RNA quality was estimated by spectrophotometry, agarose gel electrophoresis, in vitro translation of mRNA, cDNA synthesis and Northern blot analysis. The method also worked well with Arabidopsis thaliana and tobacco tissues. PMID- 24178465 TI - Somatic embryogenesis and shoot regeneration from excised adventitious roots of the rootstock Rosa hybrida L. 'Moneyway'. AB - Plants were regenerated from excised adventitious roots of the rose rootstock 'Moneyway' via a three step procedure: callus induction, induction of somatic embryos and shoot development. Callus was induced on excised roots after incubation for 4 weeks in the dark on SH-medium (Schenk and Hildebrandt) containing 50 MUM 2,4-dichlorophenoxyacetic acid. For embryo induction, calluses were transferred to hormone-free SH-medium and incubated for 8 weeks. The use of Gelrite instead of agar during callus induction stimulated somatic embryogenesis (up to 16% of the explants formed organized structures), whereas the presence of 6-benzylaminopurine in this phase inhibited subsequent regeneration. Yellow solid calluses with embryo-like cotyledons or primordia and friable calluses with embryos were selected, and upon incubation in the light shoots developed. Shoot development was faster and more frequent on solid callus than on friable callus (64% and 21% of the calluses finally formed one or more shoots, respectively). Eleven out of thirteen regenerants developed similarly to control shoots. Finally this regeneration method is compared with other systems for somatic embryogenesis and opportunities for the production of transgenic rose rootstocks and rose cultivare are discussed. PMID- 24178466 TI - Embryogenic culture initiation and somatic embryo development in hybrid firs (Abies alba x Abies cephalonica, and Abies alba x Abies numidica). AB - Embryogenic cultures were established from silver fir (Abies alba Mill.) female megagametliophytes with developing embryos and from excised mature embryos after pollination with Abies cephalonica Lond. or Abies numidica DeLann pollea The frequency of embryogenic callus formation was dependent on genotype, collection time, medium and explants used. The embryogenic callus initiation potential of megagamethophytes with developing embryos in both hybrids was higher in early July and dropped as the zygotic embryos matured. Excised cotyledonary embryos were less suitable for induction of embryogenic cultures. SH medium supplemented with 1mg/l BAP was the most efficient for callus induction and maintenance. Cultures were composed of early somatic embryos with an embryonal mass formed of highly cytoplasmic cells, rich in cell organelles and a suspensor built up by vacuolated, strongly elongated cells. Maturation of embryos was detected with the formation of bipolar structures with shoot and root apices. Nutrition reserves were observed in cells of embryos cultured on DCR medium containing 1 or 10 mg/l ABA. Cotyledon formation, hypocotyl elongation and low frequency germination occured following transfer of the embryos to the same medium without ABA. PMID- 24178467 TI - Somatic embryogenesis and plant regeneration from leaf derived callus of winged bean [Psophocarpus tetragonolobus (L.) DC]. AB - Somatic embryos were obtained from callus cultures derived from leaf explants of the winged bean, Psophocarpus tetragonolobus (L.) DC. Initiation and development of the somatic embryos occurred with a two-step culture method. Callus cultures initiated on MS medium with NAA and BAP, upon transfer to a new medium with IAA and BAP, produced somatic embryos. Maximum embryogenesis of 60% was obtained on induction medium with 0.5 mg/l NAA plus 1.0 mg/l BAP followed by transfer to a secondary medium with 0.1 mg/l IAA and 2.0 mg/l BAP. Optimal embryo germination and plantlet development was achieved on MS medium with 0.2 mg/l BAP plus 0.1 mg/l IBA. The regenerated plants were successfully transferred to glasshouse conditions. PMID- 24178468 TI - Induction of direct somatic embryogenesis and plant regeneration in pepper (Capsicum annuum L.). AB - Pepper (cv. New Mexico - 6 and Rajur Hirapur) plants were regenerated from immature zygotic embryos via direct somatic embryogenesis. Somatic embryos were formed directly, without any intervening callus, on the zygotic embryo apex, embryo axis and cotyledons on Murashige and Skoog's (MS) medium containing 2,4-D (418 MUM), thidiazuron (10 MUM) and a high concentration of sucrose (6-10%). The best response was observed on MS medium containing 2,4-D (9 MUM), coconut water (10%) and high sucrose (8%). The entire process of induction and maturation of the embryos was completed on the same medium. Histological examination indicated that secondary embryogenesis also occurred directly from the primary somatic embryos. Differentiation of embryos was nonsynchronous, and some embryos were swollen and distorted with fasciation. More than 70% of the mature normal somatic embryos germinated readily on MS medium containing GA3 or TDZ, alone and in combination, and following transfer to pots developed into normal plants. PMID- 24178469 TI - Organogenesis in Camellia x williamsii: cytokinin requirement and susceptibility to antibiotics. AB - The genetic transformation of plants calls for efficient organogenetic methods. Both cytokinins and antibiotics were tested to evaluate shoot regeneration from internodes of in vitro plants of Camellia x williamsii cv Debbie. High regeneration rates were achieved by using thidiazuron, which turned out to be more effective than 6-benzylaminopurine. Up to 96% of explants regenerated when thidiazuron was used, whereas no more than 75% regenerated using 6 benzylaminopurine. The best average number of shoots per regenerant explant was 9.7 and 5.6 regarding respectively thidiazuron and 6-benzylaminopurine. Kanamycin, used in combination with the best performing thidiazuron concentration, completely blocked regeneration at 129 MUM. Cefotaxime at 524 MUM decreased the regeneration ability, especially when 2 day preculture was applied. The application of genetic transformation protocols as well as the main aims of genetic engineering in ornamental camellias are discussed. PMID- 24178470 TI - Shoot regeneration in long-term callus cultures derived from mature flowering plants of Cyclamen persicum Mill. AB - In long-term callus cultures of Cyclamen persicum Mill. two types of tissue could be distinguished. One type featured a brown suberised outer layer and was poorly organogenic. The other type was yellowish in appearance and gave rise to many shoot buds. Both types co-existed on the same callus, the former prevailing. Selection for organogenic tissue resulted in cultures yielding approximately three times more petioles than random subcultures. Callus-derived shoots could be rooted and established in the greenhouse. The method allowed for the production of thousands of plants but the regenerants often showed deviant phenotypes and genotypes. PMID- 24178471 TI - Agrobacterium-mediated transformation of apple (Malus x domestica Borkh.): an assessment of factors affecting regeneration of transgenic plants. AB - We have previously developed a protocol for efficient gene transfer and regeneration of transgenic calli following cocultivation of apple (cv. Jonagold) explants with Agrobacterium tumefaciens (De Bondt et al. 1994, Plant Cell Reports 13: 587-593). Now we report on the optimization of postcultivation conditions for efficient and reproducible regeneration of transgenic shoots from the apple cultivar Jonagold. Factors which were found to be essential for efficient shoot regeneration were the use of gelrite as a gelling agent and the use of the cytokinin-mimicing thidiazuron in the selective postcultivation medium. Improved transformation efficiencies were obtained by combining the hormones thidiazuron and zeatin and by using leaf explants from in vitro grown shoots not older than 4 weeks after multiplication. Attempts to use phosphinothricin acetyl transferase as a selectable marker were not successful. Using selection on kanamycin under optimal postcultivation conditions, about 2% of the leaf explants developed transgenic shoots or shoot clusters. The presence and expression of the transferred genes was verified by beta-glucuronidase assays and Southern analysis. The transformation procedure has also been succesfully applied to several other apple cultivars. PMID- 24178472 TI - Uncharged tRNA-phosphofructokinase interaction in amino acid deficiency. AB - When the tRNA of mammalian cells is incompletely charged due to amino acid deficiency or by analogs which cannot be activated, many metabolic events become limited. This rapid demise of cell function appears to be due to the inhibition of phosphofructokinase (PFK) by uncharged tRNA (FEBS Lett 302: 113 (1992)). Charged tRNA has been shown to be "sequestered within the protein synthetic machinery", (Negrutskii, B. S. and Deutscher, M. P. (1992) Proc Natl Acad Sci USA 89: 3601) and would therefore be removed from an inhibitory role. Besides the direct demonstration that tRNA inhibits PFK in an assay regarded as indicative of its control mechanism, several reports in the literature support this model. These include 1) The rapid onset of inhibition of glycolysis and glucose uptake by intact cells upon amino acid deficiency and the similar lesion at the 43S ribosomal subunit on glucose or amino acid deprivation. 2) The recognition that unusually high concentrations of cAMP required to stimulate protein synthesis in energy depleted or gel filtered lysates correlates with its action on PFK as an analog of the positive effector, adenosine-5'-monophosphate. 3) The often repeated observation that the product of PFK activity, fructose-1,6-diphosphate, is a stimulant of protein synthesis (see Jackson, R. J., et al. (1983) Eur J Biochem 131: 289). This diphosphate has been shown to be the proximate effector binding to eIF-2B, the guanine nucleotide exchange factor (Singh, L. P. Arror, A. R. and Wahba, A. J. (1994), FASEB J. 8: 279) which by releasing GDP bound to the inactive GDP: eIF-2 complex, permits the factor to initiate a new peptide chain. The above information supports the view that the block at the G1 restriction point in the cell cycle of normal cells brought about by amino acid deprivation is a result of inhibition of protein synthesis through the phosphofructokinase uncharged tRNA mechanism. This is consistent with observations in the literature that tumor and transformed cells, which are more resistant to this block (Pardee, A. B., Proc Natl Acad Sci USA 71: 1286-1291 (1974)) have a higher phosphofructokinase activity or higher levels of fructose-1,6-diphosphate. PMID- 24178473 TI - The polyamine-derived amino acid hypusine: its post-translational formation in eIF-5A and its role in cell proliferation. AB - The unusual amino acid hypusine [N (epsilon) -(4-amino-2-hydroxybutyl)lysine] is a unique component of one cellular protein, eukaryotic translation initiation factor 5A (eIF-5A, old terminology, eIF-4D). It is formed posttranslationally and exclusively in this protein in two consecutive enzymatic reactions, (i) modification of a single lysine residue of the eIF-5A precursor protein by the transfer of the 4-aminobutyl moiety of the polyamine spermidine to itsepsilon amino group to form the intermediate, deoxyhypusine [N (epsilon) -(4 aminobutyl)lysine] and (ii) subsequent hydroxylation of this intermediate to form hypusine. The amino acid sequences surrounding the hypusine residue are strictly conserved in all eukaryotic species examined, suggesting the fundamental importance of this amino acid throughout evolution. Hypusine is required for the activity of eIF-5Ain vitro. There is strong evidence that hypusine and eIF-5A are vital for eukaryotic cell proliferation. Inactivation of both of the eIF-5A genes is lethal in yeast and the hypusine modification appears to be a requirement for yeast survival (Schnier et al., 1991 [Mol Cell Biol 11: 3105-3114]; Wohl et al., 1993 [Mol Gen Genet 241: 305-311]). Furthermore, inhibitors of either of the hypusine biosynthetic enzymes, deoxyhypusine synthase or deoxyhypusine hydroxylase, exert strong anti-proliferative effects in mammalian cells, including many human cancer cell lines. These inhibitors hold potential as a new class of anticancer agents, targeting one specific eukaryotic cellular reaction, hypusine biosynthesis. PMID- 24178474 TI - Chronic administration of valproic acid induces a decrease in rat striatal glutamate and taurine levels. AB - The effect of acute and chronic (10 days) administration of 200 mg/kg (i.p.) of valproic acid (VPA) on endogenous levels of aspartate, glutamate, alanine, glycine and taurine in the cerebral frontal cortex and corpus striatum of rats was studied. Quantification of the amino acid levels was performed by HPLC.Valproic acid (VPA) did not either induce changes on these neurotransmitters contents in corpus striatum after acute treatment. After chronic administration we found a decrease on the endogenous levels of glutamic acid (24%, p < 0.05) which was related to an increase (250%, p < 0.02) of the in vitro KCl evoked release of glutamate. We found decrements in taurine endogenous levels (22%, p < 0.05) which was not associated with an increase of its release.In cerebral frontal cortex there was not found any change neither under the acute nor under the chronic condition.Thus, it may be conclude that chronic treatment with VPA produces decreases on the endogenous levels of glutamate and taurine. However the relevance of this effect concerning it therapeutic action remains unclear. PMID- 24178475 TI - MouseD-amino-acid oxidase gene: Restriction fragment length polymorphism among mouse strains. AB - Genomic DNA was extracted from mice of 15 strains (A/J, AKR, BALB/c, C3H/He, C57BL/6, CBA/J, CD-1, CF#1, DBA/2, ddY/DAO(+), ddY/DAO(-), ICR, NC, NZB and NZW) for the examination of the difference in the structure of theD-amino-acid oxidase gene among the mouse strains. The DNAs were digested with restriction endonucleases and analyzed by Southern hybridization usingD-amino-acid oxidase cDNA as a probe. The 15 strains showed the same hybridization patterns in theEcoRV,BamHI orBglII digestion. In theEcoRI digestion, the DBA/2 strain showed a different hybridization pattern from the other 14 strains. In thePvuII andXbaI digestion, C3H/He, CBA/J, ddY/DAO(+) and NC strains were different from the other 11 strains. In thePstI andHindIII digestion, restriction fragment length polymorphisms were observed, and the 15 strains were classified into four groups according to their hybridization patterns. These results indicate that the 15 strains of mice carry a structurally similarD-amino-acid oxidase gene, but there is a variation in its inside sequence among the groups of the strains. PMID- 24178476 TI - An unusual side chain C-C cleavage at the MeBmt amino acid in cyclosporin A. AB - The mixture of products obtained by alkaline treatment of cyclosporin A was analyzed by HPLC-continuous-flow-FAB/MS. The changes involve the atypical amino acid (4R)-4-((E)-2-butenyl)-4,N-dimethyl-L-threonine (MeBmt) without affecting the cyclic structure. The main degradation pathway is dehydration producing all four possible anhydro-MeBmt containing cyclosporins. A new cyclosporin, [Sar(1)]CS, resulting from the side chain cleavage of MeBmt has been isolated and characterized. PMID- 24178477 TI - Taurine depletion increases phosphorylation of a specific protein in the rat retina. AB - Partial depletion of the taurine content in the rat retina was accomplished for up to 22 weeks by introduction of 1.5% guanidinoethanesulfonate (GES) in the drinking water. Taurine levels decreased by 50% after 1 week of GES treatment and by 80% at 16 weeks. Replacement of GES by taurine to the GES-treated rats from week 16 to 22 returned their taurine content to the control value. Whereas addition of taurine (1.5%) to the drinking water of control rats from week 16 to 22 elevated the retinal taurine content to 118% of the control value, the administration of untreated water to GES-treated animals for the 16 to 22 week time period increased the retinal taurine content to only 76% of the control value.The amplitude of the electroretinogram (ERG) b-wave was decreased by 60% after GES-treatment for 16 weeks and maintained this reduced level for up to 22 weeks. Administration of taurine in the drinking water from week 16 to 22 returned the b-wave amplitude to a range not statistically different from the control values whereas the administration of untreated water produced less improvement.After 6 weeks of GES treatment when the retinal taurine content was reduced by 70% and the amplitude of the b-wave was reduced by 50% (extrapolated from Figure 1), phosphorylation of a specific protein with an approximate molecular weight of 20K was increased by 94%. The increased phosphorylation of the ~20K protein observed after GES treatment was reversed when the animals were treated with taurine (1 1/2%) in the drinking water for an additional 6 weeks. There was no change in the phosphorylation of the ~20K protein when animals were treated with taurine for 6 weeks. The data obtained support the theory that taurine may have a regulatory effect on retinal protein phosphorylation. PMID- 24178478 TI - Specific recognition of a tetrahedral phosphonamidate transition state analogue group by a recombinant antibody Fab fragment. AB - In order to obtain antibodies able to catalyse a peptide synthesis, a naive combinatorial library of human Fab antibody fragments was screened with the phosphonamidate transition state analogue of the reaction. Several Fab fragments were able to bind the analogue. Competitive binding studies performed with molecules containing representative parts of the hapten showed that two Fabs were able to recognize specifically the tetrahedral phosphorus present in the hapten. PMID- 24178479 TI - The biosynthesis of taurine fromN-acetyl-L-cysteine and other precursorsin vivo and in rat hepatocytes. AB - The synthesis of taurine fromN-acetylcysteine has been examined in ratsin vivo and in rat hepatocyte suspensionsin vitro. In ratsin vivo, administration ofN acetylcysteine significantly increased urinary taurine (3 fold) 24h after dosing and liver glutathione levels. Liver taurine was not increased significantly. In hepatocytes incubated in the presence ofN-acetylcysteine, glutathione concentration increased to a maximum after 1 hour but the increase was not dependent on the concentration ofN-acetylcysteine. In contrast, after an initial lag phase, taurine synthesis increased in relation to the concentration ofN acetylcysteine and continued for 3 hours. Glutathione synthesis seems to be preferential to taurine synthesis. Taurine synthesis from cysteine sulphinate was greater and from hypotaurine was greatest and maximal after 1 hour. Implications for the mechanism of protection byN-acetylcysteine are discussed. PMID- 24178480 TI - D-Aspartyl residue in a peptide can be liberated and metabolized by pig kidney enzymes. AB - The presence of an enzyme activity which hydrolyzes glycyl-D-aspartate was found in the homogenates of pig kidney cortex. The activity was inhibited by metal chelating agents and cilastatin, suggesting that the enzyme was a cilastatin sensitive metallo-peptidase. Of the two hydrolysis products,D-aspartate was found to be less accumulated than glycine. The fate ofD-aspartate was, therefore, examined and the amino acid was found to be converted toL-aspartate,L-alanine and pyruvate, in the presence ofL-glutamate. Experiments with enzyme inhibitors suggested that the conversion involvedD-aspartate oxidase, aspartate aminotransferase and alanine aminotransferase as well as decarboxylation of oxaloacetate produced fromD-aspartate. All the results indicate that the enzymes in the pig kidney can liberate theD-aspartyl residue in the peptide and convert it to the compounds readily utilizable. The finding suggests a probable metabolic pathway of theD-aspartate-containing peptide. PMID- 24178481 TI - Photophysical properties ofbeta-homo-tyrosine derivatives. AB - The observed monoexponential fluorescence decay of N-acetyl-beta-homo-tyrosine methylamide (Ac-betaHty-NHMe) (I) and N-acetyl-(O-methyl)-beta-homo-tyrosine methylamide (Ac-betaHty(OMe)-NHMe) (II) is supporting the rotamer population theory, according to which rotamers are responsible for heterogeneity of the fluorescence decay of N-acetyl-tyrosine amide or tyrosine incorporated within a peptide chain, in general. PMID- 24178482 TI - Evaluation of the outcomes of laparoscopic hysterectomy for normal and enlarged uterus (>280 g). AB - PURPOSE: The aim of this study was to evaluate intraoperative and postoperative outcomes of laparoscopic hysterectomy (LH) with routine intraoperative cystoscopy (CYS) for enlarged uterus (>280 g). METHODS: The patients, who underwent LH procedure in the Department of Obstetrics and Gynecology in Duzce University Faculty of Medicine between July 2012 and July 2013, were included in this study. Perioperative outcomes were compared between patients with and without enlarged uterus. RESULTS: Uterus weight of the operated patients ranges between 38 and 700 g. Mean uterus weight was 196.40 +/- 142.32 g. Although we found longer operation time (148.75 +/- 32.37 vs. 128.28 +/- 27.58) and higher delta hemoglobin (2.98 +/ 3.09 vs. 1.61 +/- 1.29) in patients with enlarged uterus undergoing LH, these findings were not statistically significant (p = 0.077 and 0.058). No significant difference was found between the two groups in terms of need for insertion of pelvic drainage (p = 0.664), duration of bladder catheterization (p = 0.673), time of first postoperative flatus (p = 0.509) and the duration of hospitalization (p = 0.844). None of the patients had postoperative fever. The two groups were not significantly different in terms of postoperative body temperature (p = 0.736). In normal uterus group, 1 patient developed ureterovaginal fistula and 1 patient required re-operation. No major complication was observed in large uterus group. CONCLUSIONS: In our study, we compared the outcomes of LH in patients with large uterus measuring up to 700 g. and patients with normal uterus, and we achieved successful results by making minor changes in the operation technique and performing diagnostic CYS at the end of the operation. PMID- 24178484 TI - Is vaginal hyaluronic acid as effective as vaginal estriol for vaginal dryness relief? AB - In a multicenter, randomized, controlled, open-label, parallel- group trial hyaluronic acid vaginal gel (Hyalofemme) was compared to estriol vaginal cream (Ovestin) in women with vaginal dryness due to various causes. A total of 144 supposedly postmenopausal women below age 70 years were randomized in a 1:1 ratio to either receive hyaluronic acid vaginal gel (5 g per application) or estriol vaginal cream (0.5 g cream per application = 0.5 mg estriol) every 3 days for a total of ten applications, respectively. Exclusion criteria included vaginal infections, conventional contraindications to estrogens, use of vaginal products other than the investigational compounds, being unmarried, pregnant, or breastfeeding. The aim of the study was to test for non-inferiority of hyaluronic acid vaginal gel compared to estriol vaginal cream. The primary efficacy end point was the percentage (%) improvement in vaginal dryness, with the secondary end points being the percentage (%) improvements in vaginal itching, burning, and dyspareunia. Efficacy was assessed by using a visual analog scale (VAS) (0-10; 0 = absent, 10 = intolerable) at baseline (V0), during telephone contact after the third administration (V1), and at the final visit after the tenth administration (V2). Safety parameters included vaginal pH, endometrial thickness, and a vaginal smear for vaginal microecosystem assessment. Adverse events were recorded according to international guidelines. 133 women completed the study. At baseline, participants' characteristics did not differ significantly. Mean age was 54 years, time since menopause was 5 years on average, and cause of menopause was mostly natural. However, mean menstrual cycle days were also reported, although according to inclusion criteria only postmenopausal women were eligible for the study. At V1, an improvement in vaginal dryness was reported by about 49 % of women using hyaluronic acid vaginal gel, and by 53 % of women using estriol vaginal cream (p = 0.31). At V2, the percentage improvement rates were 84 and 89 % (p = 0.13), respectively. Improvement rates for vaginal itching, burning, and dyspareunia at V2 were about 86, 85, and 57 % for hyaluronic acid vaginal gel, and 82, 87, and 62 % for estriol vaginal cream (p[0.05), respectively. After treatment, vaginal pH was significantly lower in estriol-treated women compared to those having received hyaluronic acid. Endometrial thickness did not differ between groups. In the majority of women, the vaginal microenvironment remained unaffected by treatment. However, the proportion of women whose abnormal vaginal microecological results became normal was higher in women using estriol vaginal cream. Adverse events (suspected to be) related to the investigational compounds were minor and included vaginal infection and genital itching. The authors concluded that hyaluronic acid vaginal gel was not inferior to estriol vaginal cream in women presenting with vaginal dryness. They suggest using hyaluronic acid vaginal gel not only as an alternative treatment to vaginal estrogens, but also to consider its general use in women presenting with vaginal dryness of any cause. PMID- 24178485 TI - Factors affecting the binding between fusicoccin and plasma membranes from maize roots. AB - Plasma membranes have been purified from roots of maize (Zea mays L.) using a two phase aqueous polymer system, dextran-polyethylene glycol. The plant material was homogenized in the presence of a mixture of natural protease inhibitors from potato (Solanum tuberosum L.); these inhibitors have been shown to be more effective than phenylmethylsulfonyl fluoride in suppressing the endogenous proteases in maize roots. Inhibition of proteolysis in the homogenization medium markedly increased (about tenfold) the number of lowaffinity binding sites for fusicoccin (FC). In addition, storage of plasma membranes at -20 degrees C decreased both the number of the low-affinity sites and their dissociation constant (KD); this effect was in all probability caused by lipid peroxidation. The presence of EDTA throughout isolation and storage of the plasma membranes stabilized the parameters of FC binding to the membranes. The kinetics of binding of [(3)H]dihydroFC and the competition between [(3)H]dihydroFC and FCs A, C, J, and H were determined for the low-affinity sites. It was found that (i) the rate constant of association between FC and the low-affinity binding sites is about two orders of magnitude lower than that for the high-affinity sites; (ii) different FCs can be arranged in the order of decreasing avidity for the low affinity FCbinding site: FC A>FC C>FC J>FC H. PMID- 24178486 TI - The effects of calcium deficiency on Cucurbita pepo L. hypocotyl cells: A (31)P nuclear-magnetic-resonance study. AB - Calcium deficiency in zucchini (Cucurbita pepo L.) is associated with reduced growth and a reduced ability to transport auxin (Allan and Rubery, 1991, Planta 183, 604-612). An investigation of the effects of calcium-deficiency on zucchini hypocotyl cells was made using weak-acid uptake and (31)P-nuclear magneticresonance ((31)P-NMR) spectroscopy in vivo and in tissue extracts. Calcium-deficient tissue had the same cytoplasmic and vacuolar pHs as normal tissue when extracellular pH was near neutral. At acidic external pH the vacuolar pH was lower in deficient tissue. Adenine nucleotides were present predominantly as ATP in both control and calcium-deficient tissues. Addition of calcium to calcium-deficient tissue, under conditions which cause recovery of auxin transport induced no changes in the (31)P-NMR spectra of deficient tissue. The content of mobile, phosphorylated metabolites was reduced in calcium-deficient tissue in comparison to control tissue. However, a substantial increase in the content of phosphorylcholine occurs in calcium-deficient tissues compared with controls; this may reflect changes in lipid turnover in calcium-stressed cells. PMID- 24178487 TI - Immunoaffinity co-purification of cytokinins and analysis by high-performance liquid chromatography with ultraviolet-spectrum detection. AB - A rapid methodology for the simultaneous analysis of a large number of cytokinins is presented. The cross-reactivity of a mixture of polyclonal antibodies against zeatin riboside and isopentenyladenosine was exploited in a protocol that can be used for immunoaffinity purification of 23 additional cytokinins. Ligands include the cytokinin bases zeatin, dihydrozeatin, isopentenyladenine, benzyl-adenine and kinetin, and their corresponding nucleoside, nucleoside-5'-monophosphate, and 9 glucoside derivatives, as well as cis-zeatin, cis-zeatin riboside, the 2 methylthiol derivatives of isopentenyladenosine and zeatin riboside, and benzyl adenine-3-glucoside. Mixtures of cytokinins could be retained with high recoveries of all the components. Immunoaffinity purification of extracts of Arabidopsis thaliana (L.) Heynh. and Solarium tuberosum L. gave fractions clean enough, as verified by gas chromatographymass spectrometry (GC-MS), to allow analysis of endogenous cytokinins using a single high-performance liquid chromatography (HPLC) step with on-line UV-spectrum detection. The detection limit was 4-6 pmol. The procedure described forms a routine assaying technique that is faster and simpler, yet yields better qualitative and quantitative information than the commonly used procedure of immunoassaying of HPLC fractions. PMID- 24178488 TI - Cell wall synthesis during growth and maturation of Nitella internodal cells. AB - An improved (13)C-density-labeling method was used to study cell wall synthesis in rapidly expanding, slowly expanding and recently mature internodes of Nitella translucens var axillaris (A.Br.) R.D.W. As cells matured, the rate of wall synthesis slowed and the deposition of cellulose microfibrils changed from a predominantly transverse direction in the primary wall of rapidly expanding internodes to a helicoidal array in the secondary wall of mature internodes. The secondary wall was characterized by relatively higher rates of cellulose synthesis and lower rates of pectin synthesis than the primary wall. The synthesis of xyloglucan also decreased markedly at the transition to secondary wall synthesis, while the synthesis of mannose-rich hemicellulose increased. Even though structural differences were striking between the primary and secondary walls of Nitella, compositional differences between the two types of wall were quantitative rather than qualitative. PMID- 24178489 TI - Sucrose synthase catalyses a readily reversible reaction in vivo in developing potato tubers and other plant tissues. AB - Experiments were carried out to investigate whether sucrose synthase (Susy) catalyses a readily reversible reaction in vivo in potato (Solanum tuberosum L.) tubers, Ricinus communis L. cotyledons, and heterotrophic Chenopodium rubrum L. cell-suspension cultures. (i) The contents of sucrose, fructose, UDP and UDP glucose were measured and the mass-action ratio compared with the theoretical equilibrium constant. In all three tissues the values were similar. (ii) Evidence for rapid turnover of label in the sucrose pool was obtained in pulse-chase experiments with potato discs and with intact tubers attached to the plant. The unidirectional rates of sucrose synthesis and degradation were considerably higher than the net flux through the sucrose pool in the tubers. (iii) Labelling of the glucosyl and fructosyl moieties of sucrose from [(14)C]glucose in the presence of unlabelled fructose provided evidence that Susy contributes to the movement of label into sucrose. Methods for estimating the contribution of sucrose-phosphate synthase and Susy are presented and it is shown that their relative contribution varies. For example, the contribution of Susy is high in developing tubers and is negligible in harvested tubers which contain low Susy activity. (iv) The absolute values of the forward (v(+1)) and backward (v(-1)) reaction direction of Susy are calculated from the kinetic labelling data. The estimated values of v(+1) and v(-1) are comparable, and much higher than the net flux through the sucrose pool. (v) The estimated concentrations of the substrates and products of Susy in tubers are comparable to the published K m values for potato-tuber Susy. (vi) It is concluded that Susy catalyses a readily reversible reaction in vivo and the relevance of this conclusion is discussed with respect to the regulation of sucrose breakdown and the role of Susy in phloem unloading. PMID- 24178490 TI - Biosynthesis of 12alpha-and 13-hydroxylated gibberellins in a cell-free system from Cucurbita maxima endosperm and the identification of new endogenous gibberellins. AB - Gibberellin (GA) biosynthesis in cell-free systems from Cucurbita maxima L. endosperm was reinvestigated using incubation conditions different from those employed in previous work. The metabolism of GA12 yielded GA13, GA43 and 12alpha hydroxyGA43 as major products, GA4, GA37, GA39, GA46 and four unidentified compounds as minor products. The intermediates GA15, GA24 and GA25 accumulated at low protein concentrations. The structure of the previously uncharacterised 12alpha-hydroxyGA43 was inferred from its mass spectrum and by its formation from both GA39 and GA43. Gibberellin A39 and 12alpha-hydroxyGA43 were formed by a soluble 12alpha-hydroxylase that had not been detected before. Gibberellin A12 aldehyde was metabolised to essentially the same products as GA12 but with less efficiency. A new 13-hydroxylation pathway was found. Gibberellin A53, formed from GA12 by a microsomal oxidase, was converted by soluble 2-oxoglutarate dependent oxidases to GA1 GA23, GA28, GA44, and putative 2beta-hydroxyGA28. Minor products were GA19, GA20, GA38 and three unidentified GAs. Microsomal 13 hydroxylation (the formation of GA53) was suppressed by the cofactors for 2 oxoglutarate-dependent enzymes. Reinvestigation of the endogenous GAs confirmed the significance of the new metabolic products. In addition to the endogenous GAs reported by Blechschmidt et al. (1984, Phytochemistry 23, 553-558), GA1, GA8, GA25, GA28, GA36, GA48 and 12alpha-hydroxyGA43 were identified by full-scan capillary gas chromatography-mass spectrometry and Kovats retention indices. Thus both the 12alpha-hydroxylation and the 13-hydroxylation pathways found in the cell-free system operate also in vivo, giving rise to 12alpha-hydroxyGA43 and GA1 (or GA8), respectively, as their end products. Evidence for endogenous GA20 and GA24 was also obtained but it was less conclusive due to interference. PMID- 24178491 TI - Gibberellin biosynthesis in cell-free extracts from developing Cucurbita maxima embryos and the identification of new endogenous gibberellins. AB - Gibberellin (GA) biosynthetic pathways from GA12-aldehyde, GA12 and GA53 were investigated in cell-free systems from developing embryos of Cucurbita maxima L. Gibberellin A12-aldehyde and GA12 were converted to GA25, putative 12alpha hydroxyGA25, GA13 and GA39 as main products. Minor products were GA4, GA34 and, when GA12 was the substrate, putative 12alpha-hydroxyGA12. The intermediates GA15 and GA24 accumulated at low protein concentrations. The influence of various factors on GA12 metabolism was examined. At low 2-oxoglutarate and ascorbate concentrations, or at acid pH, 3beta-hydroxylated products predominated, whereas with increasing 2-oxoglutarate and ascorbate concentrations, or at neutral pH, the yield of 12alpha-hydroxylated GAs increased. Gibberellin A53 was metabolised mainly to the C20-GAs GA44, GA19, GA17, GA23 and GA28, with the C19-GAs GA20, GA1 and GA8 as minor products. Only C19-GAs were 2beta-hydroxylated, which is a main characteristic of the embryo systems. In addition to GA13, GA25, GA39, GA43, GA49, GA58, GA74, 12alpha-hydroxyGA25 and GA39 3-isovalerate, which were known previously from embryos of C. maxima, GA1, GA4, GA17, GA28, GA37, GA38, GA48, GA85, 12alpha-hydroxyGA37 and putative 12alpha-hydroxyGA43 were identified as endogenous components by full-scan capillary gas chromatography-mass spectrometry and Kovats retention indices. Evidence for putative 2beta-hydroxyGA28 and GA23 was also obtained but it was less conclusive because of contamination. PMID- 24178492 TI - Photoinhibition of photosystem II in vivo is preceded by down-regulation through light-induced acidification of the lumen: Consequences for the mechanism of photoinhibition in vivo. AB - The mechanism of photoinhibition of photosystem II (PSII) was studied in intact leaf discs of Spinacia oleracea L. and detached leaves of Vigna unguiculata L. The leaf material was exposed to different photon flux densities (PFDs) for 100 min, while non-photochemical (qN) and photochemical quenching (qp) of chlorophyll fluorescence were monitored. The 'energy' and redox state of PSII were manipulated quite independently of the PFD by application of different temperatures (5-20 degrees C), [CO2] and [O2] at different PFDs. A linear or curvilinear relationship between qp and photoinhibition of PSII was observed. When [CO2] and [O2] were both low (30 MUl . l(-1) and 2%, respectively), PSII was less susceptible at a given qp than at ambient or higher [CO2] and photoinhibition became only substantial when qp decreased below 0.3. When high levels of energy-dependent quenching (qE) (between 0.6 and 0.8) were reached, a further increase of the PFD or a further decrease of the metabolic demand for ATP and NADPH led to a shift from qE to photoinhibitory quenching (qI). This shift indicated that photoinhibition was preceded by down-regulation through light induced acidification of the lumen. We propose that photoinhibition took place in the centers down-regulated by qE. The shift from qE to qI occurred concomitant with qP decreasing to zero. The results clearly show that photoinhibition does not primarily depend on the photon density in the antenna, but that photoinhibition depends on the energy state of the membrane in combination with the redox balance of PSII. The results are discussed with regard to the mechanism of photoinhibition of PSII, considering, in particular, effects of light-induced acidification on the donor side of PSII. Interestingly, cold-acclimation of spinach leaves did not significantly affect the relationship between qP, qE and photoinhibition of PSII at low temperature. PMID- 24178493 TI - Environmental effects on circadian rhythms in photosynthesis and stomatal opening. AB - Persistent circadian rhythms in photosynthesis and stomatal opening occurred in bean (Phaseolus vulgaris L.) plants transferred from a natural photoperiod to a variety of constant conditions. Photosynthesis, measured as carbon assimilation, and stomatal opening, as conductance to water vapor, oscillated with a freerunning period close to 24 h under constant moderate light, as well as under light-limiting and CO2-limiting conditions. The rhythms damped under constant conditions conducive to high photosynthetic rates, as did rates of carbon assimilation and stomatal conductance, and this damping correlated with the accumulation of carbohydrate. No rhythm in respiration occurred in plants transferred to constant darkness, and the rhythm in stomatal opening damped rapidly in constant darkness. Damping of rhythms also occurred in leaflets exposed to constant light and CO2-free air, demonstrating that active photosynthesis and not simply light was necessary for sustained expression of these rhythms. PMID- 24178494 TI - Proton efflux from oat coleoptile cells and exchange with wall calcium after IAA or fusicoccin treatment. AB - Elongation growth of plant cells occurs by stretching of cell walls under turgor pressure when intermolecular bonds in the walls are temporarily loosened. The acid-growth theory predicts that wall loosening is the result of wall acidification because treatments (including IAA and fusicoccin) that cause lowered wall pH cause elongation. However, conclusive evidence that IAA primarily reduces wall pH has been lacking. Calcium has been reported to stiffen the cell walls. We have used a microelectrode ion-flux measuring technique to observe directly, and non-invasively, the net fluxes of protons and calcium from split coleoptiles of oats (Avena sativa L.) in unbuffered solution. Normal net fluxes are 10 nmol . m(-2) . s(-1) proton efflux and zero calcium flux. The toxin fusicoccin (1 MUM) causes immediate efflux from tissue not only of protons, but also of calcium, about 110 nmol . m(-2) . s(-1) in each case. The data fit the "weak acid Donnan Manning" model for ion exchange in the cell wall. Thus we associate the known "acid-growth" effect of fusicoccin with the displacement of calcium from the wall by exchange for protons extruded from the cytoplasm. Application of 10 MUM IAA causes proton efflux to increase transiently by about 15 nmol . m(-2) . s(-1) with a lag of about 10 min. The calcium influx decreases immediately to an efflux of about 20 nmol . m(-2) . s(-1). It appears that auxin too causes an "acid-growth" effect, with extruded protons exchanging for calcium in the cell walls. PMID- 24178495 TI - Temporal and light regulation of the expression of three phytochromes in germinating seeds and young seedlings of Avena sativa L. AB - An oat (Avena sativa L.) plant contains at least three phytochromes, which have monomeric masses of 125, 124, and 123 kilodaltons (kDa) (Wang et al., 1991, Planta 184, 96-104). The 124-kDa phytochrome is most abundant in dark-grown seedlings, while the other two phytochromes predominate in light-grown seedlings. Using three monoclonal antibodies, each specific to one of the three phytochromes, we have monitored by immunoblot assay the expression of these three phytochromes in the 5 d following onset of imbibition of seeds. On a per-organism basis, each of these three phytochromes increased in abundance for the first 3 d in the light, or for the first 4 d in darkness, after which they each began to decrease in quantity. When 3-d-old dark-grown seedlings were transferred to the light, the abundance of each of these three phytochromes decreased both in absolute amount and relative to the phytochrome levels in control seedlings kept in darkness. In contrast, when 3-d-old light-grown seedlings were transferred to darkness, the abundance of the 124-kDa and 125-kDa phytochromes increased while that of 123-kDa phytochrome remained unchanged. In each case, the level of phytochrome was greater than that of control seedlings maintained in the light. Thus, in addition to temporal regulation, all three phytochromes exhibit photoregulated expression at the protein level, although the magnitude of this photoregulation varies substantially. PMID- 24178496 TI - Spatial distribution of three phytochromes in dark- and light-grown Avena sativa L. AB - We have addressed two issues regarding the spatial distribution of three phytochromes in 3-d-old oat (Avena sativa L.) seedlings. Three monoclonal antibodies, GO-4, GO-7 and Oat-22, were used as probes. Each antibody detects only one of the phytochromes. The first issue is whether any of the phytochromes might be membrane-bound. To address this issue the abundance of each phytochrome in extracts prepared with either a detergent-free or a detergent-containing buffer was compared by immunoblot assay. The detergent-free buffer was formulated to extract only soluble protein, while the detergent-containing buffer was intended to extract both soluble and membrane proteins. None of the data indicate that any of these three phytochromes is membrane-bound in either a dark- or a light-grown seedling. The second issue is whether these three phytochromes are distributed differentially in 3-d-old dark- and light-grown seedlings. When seedlings were dissected into shoots, scutellums, and roots, all three phytochromes were detected in all three fractions from both dark- and light-grown seedlings. Each of the three phytochromes was most abundant in the shoot and least abundant in the root, except that in light-grown seedlings type I, etiolated-tissue phytochrome was more abundant in the root than in either the shoot or the scutellum. When the equivalent fractions dissected from different seedlings were compared, those dissected from dark-grown seedlings contained a higher quantity of each of the three phytochromes than did those dissected from light-grown seedlings, except that green-tissue, type II phytochromes did not differ significantly in the roots. At this level of resolution, no evidence was obtained to indicate a substantive difference among the three phytochromes in their spatial distribution. PMID- 24178497 TI - Canatoxin-, concanavalin A- and canavalin-cross-reactive materials during maturation of Canavalia brasiliensis (Mart.) seeds. AB - The distribution of three cross-reactive materials (CRMs), a toxic protein analogous to canatoxin, CNTX-CRM, a lectin analogous to concanavalin A, Con A CRM, and a major storage protein, canavalin-CRM, was investigated during successive stages of maturation of Canavalia brasiliensis Mart. seeds. The data obtained by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunological analyses indicated that these proteins share extensive homology with the analogous proteins found in Canavalia ensiformis seeds. The changes in CNTX-CRM and Con A-CRM levels throughout the maturation process were assayed by rocket immunoelectrophoresis. Synthesis of Con A-CRM was detectable at 30 days post-anthesis (DPA) while its hemagglutinating activity appeared only at 35 DPA. The CNTX-CRM was detected as a biologically active protein from 30 DPA onwards. The behavior of CNTX-CRM during maturation of C. brasiliensis seeds was quite distinct from that of Con A-CRM, pointing to different biological roles of these proteins in the seed. PMID- 24178498 TI - Phenotypic changes in the fluidity of the tonoplast membrane of crassulacean-acid metabolism plants in response to temperature and salinity stress. AB - Electron paramagnetic resonance-spectroscopic studies on spin-labeled purified tonoplast membranes showed that in the obligate crassulacean-acid-metabolism (CAM) plant Kalanchoe daigremontiana Hamet et Perr. the fluidity of the tonoplast decreased during acclimation to higher temperatures. This phenotypic change in tonoplast fluidity was paralleled by a decrease in the mobilization of malic acid from the vacuoles during CAM in the light. The shift from the C3 to the CAM mode of photosynthesis in the facultative CAM plant Mesembryanthemum crystallinum L. also led to a decrease in the fluidity of the tonoplast membrane. The results are consistent with the hypothesis that the ability to store malic acid during CAM in the vacuoles depends largely on the actual fluidity of the tonoplast membrane. PMID- 24178499 TI - Comparison of K(+)-channel activation and deactivation in guard cells from a dicotyledon (Vicia faba L.) and a graminaceous monocotyledon (Zea mays). AB - We describe and compare inward and outward whole-cell K(+) currents across the plasma membrane surrounding guard-cell protoplasts from the dicotyledon, Vicia faba, and the graminaceous monocotyledon, Zea mays. Macrosopic whole-cell current is considered in terms of microscopic single-channel activity, which involves discrete steps between conducting (open) and nonconducting (closed) states of the channel protein. Kinetic equations are used to model the number of open and closed states for channels conducting K(+) influx (K(in)) and K(+) efflux (K(out)) in the two species, and to calculate the rate at which open-closed transitions occur. The opening and closure of K(in) channels in both Vicia and Zea follow single-exponential timecourses, indicating that K(in)-channel proteins in each species simply fluctuate between one open and one closed state. In both species, opening of K(in) channels is voltage-independent, but closure of K(in) channels is faster at more positive membrane potentials. In response to identical voltage stimuli, K(in) channels in Zea open and close approximately three times as fast as in Vicia. In contrast to K(in), K(out) channels in Zea open and close more slowly than in Vicia. The closure of K(out) channels follows a single exponential timecourse in each species, indicating one open state. The kinetics of K(out)-channel opening are more complicated and indicate the presence of at least two (Vicia) or three (Zea) closed states. PMID- 24178500 TI - On the relationship between isoprene emission and photosynthetic metabolites under different environmental conditions. AB - Isoprene emission is related to photosynthesis but the nature of the relationship is not yet known. To explore this relationship we have examined the rate of isoprene emission, photosynthesis, and the contents of photosynthetic metabolites in leaves of velvet bean (Mucuna deeringeniana L.) and red oak (Quercus rubra L.) in response to a light-to-dark transition and to changes in air composition. Isoprene emission fell when darkness was imposed and the drop was associated with reduced amounts of ribulose-1,5-bisphosphate and ATP. The rate of isoprene emission and ATP content were reduced to the same extent by exposure to low O2 or high CO2 partial pressures. Only when O2 and CO2 were simultaneously removed from the air did the rate of isoprene emission drop without a corresponding change in ATP. The results demonstrate that when carbon is not limiting, isoprene emission is highly correlated with ATP content. When synthesis of phosphoglyceric acid is inhibited, however, carbon availability may control isoprene production. PMID- 24178501 TI - Characterization of two acyl-acyl carrier protein thioesterases from developing Cuphea seeds specific for medium-chain- and oleoyl-acyl carrier protein. AB - Two acyl-acyl carrier protein (ACP) thioesterases were partially purified from developing seeds of Cuphea lanceolata Ait., a plant with decanoic acid-rich triacylglycerols. The two enzymes differ markedly in their substrate specificity. One is specific for medium-chain acyl-ACPs, the other one for oleoyl-ACP. In addition, these enzymes are distinct with regard to molecular weight, pH optimum and sensitivity to salt. The thioesterases could be separated by Mono Q chromatography or gel filtration. The medium-chain acyl-ACP thioesterase and oleoyl-ACP thioesterase were purified from a crude extract 29- and 180-fold, respectively. In Cuphea wrightii A. Gray, which predominantly contains decanoic a nd lauric acid in the seeds, two different thioesterases were also found with a similar substrate specificity as in Cuphea lanceolata. PMID- 24178502 TI - Evidence for loss of D1 protein during photoinhibition of Chenopodium rubrum L. culture cells. AB - The effects of high-light stress on chlorophyllfluorescence parameters, D1 protein turnover and the actual level of this protein were analysed in nitrogen deficient and nitrogen-replete cells of Chenopodium rubrum L. Changes in the number of atrazine-binding sites and in the D1-protein immunoblot signal indicated that a net loss of D1 protein occurred in high light and was partly reversible in low light. Nitrogen deficiency did not exacerbate these changes. The involvement of D1-protein turnover was shown in pulse-chase experiments with [(35)S]-methionine and by the application of a chloroplastic protein-synthesis inhibitor (chloramphenicol). The slowly reversible non-photochemical fluorescence quenching increased pronouncedly when D1 protein was lost at high irradiances, but its increase was only small when a net loss of D1 protein was produced at moderate irradiances by addition of chloramphenicol. The ratio of variable to maximum fluorescence, Fv/Fm, and the number of atrazine-binding sites were correlated but a proportionality between these parameters could not be observed. We conclude from these results that (i) degradation of D1 protein was not always coupled to its resynthesis, (ii) the actual level of D1 protein reflected the balance between degradation and resynthesis of D1 protein and (iii) changes in the level of D1 protein did not depend on a pronounced increase of the slowly reversible non-photochemical quenching. PMID- 24178503 TI - Response of a nitrite-reductase 3.1-kilobase upstream regulatory sequence from spinach to nitrate and light in transgenic tobacco. AB - In the present study the question was addressed of whether the nitrite-reductase (NIR-)promoter from spinach (Spinacia oleracea L.), fused to a reporter gene (bacterial beta-glucuronidase, GUS) and introduced into tobacco (Nicotiana tabacum L.) responds to nitrate and light in accordance with spinach (donor) or in accordance with tobacco (host). The data obtained at the GUS enzyme level as well as at the transcript level allow an unambiguous answer to this question: GUS gene expression under the control of the NIR-promoter from spinach responds to nitrate and light in accordance with the host (tobacco). Expression of the promoter-less GUS gene was not induced by any treatment. PMID- 24178504 TI - Studies on the behavior of organelles and their nucleoids in the root apical meristem of Arabidopsis thaliana (L.) Col. AB - The behavior of cell nuclei, mitochondrial nucleoids (mt-nucleoids) and plastid nucleoids (ptnucleoids) was studied in the root apical meristem of Arabidopsis thaliana. Samples were embedded in Technovit 7100 resin, cut into thin sections and stained with 4'-6-diamidino-2-phenylindole for light-microscopic autoradiography and microphotometry. Synthesis of cell nuclear DNA and cell division were both active in the root apical meristem between 0 MUm and 300 MUm from the central cells. It is estimated that the cells generated in the lower part of the root apical meristem enter the elongation zone after at least four divisions. Throughout the entire meristematic zone, individual cells had mitochondria which contained 1-5 mt-nucleoids. The number of mitochondria increased gradually from 65 to 200 in the meristem of the central cylinder. Therefore, throughout the meristem, individual mitochondria divided either once or twice per mitotic cycle. By contrast, based on the incorporation of [(3)H]thymidine into organelle nucleoids, syntheses of mitochondrial DNA (mtDNA) and plastid DNA (ptDNA) occurred independently of the mitotic cycle and mainly in a restricted region (i.e., the lower part of the root apical meristem). Fluorimetry, using a videointensified microscope photon-counting system, revealed that the amount of mtDNA per mt-nucleoid in the cells in the lower part of the meristem, where mtDNA synthesis was active, corresponded to more than 1 Mbp. By contrast, in the meristematic cells just below the elongation zone of the root tip, the amount of mtDNA per mt-nucleoid fell to approximately 170 kbp. These findings strongly indicate that the amount of mtDNA per mitochondrion, which has been synthesized in the lower part of the meristem, is gradually reduced as a result of continual mitochondrial divisions during low levels of mtDNA synthesis. This phenomenon would explain why differentiated cells in the elongation zone have mitochondria that contain only extremely small amounts of mtDNA. PMID- 24178505 TI - Caffeic acid and glycerol are constituents of the suberin layers in green cotton fibres. AB - The fibres of the green-lint mutant (Lg) of cotton (Gossypium hirsutum L.) are suberized and contain a large proportion of wax. The unidentified components of the wax were separated into a colourless fluorescent fraction and a yellow pigmented fraction. Using ultraviolet spectroscopy and nuclear-magneticresonance ((1)H-NMR) spectroscopy, esterified trans-caffeic acid was identified as the only phenolic component in the colourless fraction. This fraction was further purified and was shown to contain caffeic acid esterified to fatty acids (mainly omega hydroxy fatty acids), and glycerol in molar ratios of 4?5?5. When 2-aminoindan-2 phosphonic acid (AIP), an inhibitor of phenylalanine ammonia-lyase (EC 4. 3. 1. 5.) was added to ovules cultured in vitro, at the beginning of secondary wall formation, the fibres remained white and the colourless caffeic-acid derivative and the yellow compounds could no longer be detected by ultraviolet spectroscopy. Fibres grown in the presence of AIP were also examined in the electron microscope. Secondary cell walls were present in the treated fibres, but the electron-opaque suberin layers were replaced by apparently empty spaces. This result indicates that cinnamic-acid derivatives are covalently linked to suberin and have a structural role within the polymer or are involved in anchoring the polymer to the cellulosic secondary wall. Purified cell walls of green cotton fibres contained about 1% (of the dry weight) of bound glycerol, 0.9% of the glycerol being extractable with the wax fraction and 0.1% remaining in the cell wall residue. The corresponding values for white fibres were 0.03% (total), 0.02% (wax), and 0.01% (cell-wall residue). Fibres synthesizing their secondary walls in the presence of AIP contained about normal amounts of bound glycerol in the wax fraction, but glycerol accumulation in the cell-wall residue was inhibited by about 95%. These observations indicate that glycerol is an important constituent of cotton-fibre suberin. Considerable amounts of bound glycerol could also be determined in exhaustively extracted cell walls of the cork layer of potato periderm (1.2%) and smaller amounts in the outer epidermal cell wall of Agave americana L. leaf (0.1%) indicating that the presence of glycerol in suberins and possibly also in cutins may be more widespread than previously thought. PMID- 24178506 TI - Shift in carbon flow and stimulation of amino-acid turnover induced by nitrate and ammonium assimilation in Anacystis nidulans. AB - The influence of nitrate and ammonium assimilation on the flow of recently fixed carbon has been determined in intact Anacystis nidulans cells actively fixing CO2. Assimilation of nitrate or ammonium resulted in substantial increases in the incorporation of carbon into acid-soluble metabolites, the magnitude of the effect being dependent on the irradiance. The radiolabel in sugar phosphate was virtually unaffected by nitrogen assimilation, whereas that in organic acids and, in particular, in amino acids was markedly increased. Enhancement of carbon incorporation into amino acids induced by nitrogen assimilation was not accompanied by parallel increases in the size of the amino acid pools. This resulted in an appreciable increase of the specific radioactivity of most amino acids under conditions of nitrogen assimilation. The data indicate that nitrate and ammonium assimilation induce an enhancement of carbon flow through the glycolytic and the tricarboxylic-acid pathways to oxaloacetate and alpha ketoglutarate, as well as a stimulation of amino-acid turnover. These effects were more pronounced at saturating irradiance. PMID- 24178507 TI - Analysis of binding of biotinylated protoplast-release-inducing protein that induces release of gametic protoplasts in the Closterium peracerosum-strigosum littorale complex. AB - A protoplast-release-inducing protein (PR-IP) which is released from mating-type plus (mt(+)) cells and induces the release of gametic protoplasts from matingtype minus (mt(-)) cells of Closterium was biotinylated and then used to examine the interaction of this protein with mt(-) cells. The protoplast-release-inducing activity of PR-IP was not altered after the biotinylation. When mt(-) cells that had been pre-cultured for 24 h were incubated with biotinylated PR-IP for 6 h in nitrogen-deficient medium that contained 1% (w/v) bovine serum albumin, and then washed with the same medium, only a 19-kDa polypeptide, the smaller subunit of PR IP, was detected in cells by the avidin and biotinylated horseradish-peroxidase macromolecular complex system. The amount of bound 19-kDa polypeptide increased with increasing doses of PR-IP and reached a maximum at around 10 nM, reflecting the protoplast-release-inducing activity. From a Scatchard plot, the dissociation constant of the polypeptide was calculated to be 2.7 . 10(-8) M. The binding of the polypeptide proceeded only after an appropriate period of pre-culture in the light, and the polypeptide was competitively displaced by non-biotinylated PR-IP. From these results, it appears that the PR-IP induces the release of protoplasts from mt(-) cells by binding of a polypeptide of relative molecular mass 19000 to the receptor on the cell surface in a manner analogous to the binding of peptide hormones in animals. PMID- 24178508 TI - Warm-up and performance in competitive swimming. AB - Warm-up before physical activity is commonly accepted to be fundamental, and any priming practices are usually thought to optimize performance. However, specifically in swimming, studies on the effects of warm-up are scarce, which may be due to the swimming pool environment, which has a high temperature and humidity, and to the complexity of warm-up procedures. The purpose of this study is to review and summarize the different studies on how warming up affects swimming performance, and to develop recommendations for improving the efficiency of warm-up before competition. Most of the main proposed effects of warm-up, such as elevated core and muscular temperatures, increased blood flow and oxygen delivery to muscle cells and higher efficiency of muscle contractions, support the hypothesis that warm-up enhances performance. However, while many researchers have reported improvements in performance after warm-up, others have found no benefits to warm-up. This lack of consensus emphasizes the need to evaluate the real effects of warm-up and optimize its design. Little is known about the effectiveness of warm-up in competitive swimming, and the variety of warm-up methods and swimming events studied makes it difficult to compare the published conclusions about the role of warm-up in swimming. Recent findings have shown that warm-up has a positive effect on the swimmer's performance, especially for distances greater than 200 m. We recommend that swimmers warm-up for a relatively moderate distance (between 1,000 and 1,500 m) with a proper intensity (a brief approach to race pace velocity) and recovery time sufficient to prevent the early onset of fatigue and to allow the restoration of energy reserves (8-20 min). PMID- 24178509 TI - Early adolescent relationship predictors of emerging adult outcomes: youth with and without type 1 diabetes. AB - BACKGROUND: Emerging adulthood is a high-risk period for mental health problems and risk behaviors for youth generally and for physical health problems among those with type 1 diabetes. PURPOSE: The purpose of this study was to examine whether adolescents' relationships with parents and friends predict health and risk behaviors during emerging adulthood. METHOD: Youth with and without diabetes were enrolled at average age 12 and followed for 7 years. Parent and friend relationship variables, measured during adolescence, were used to predict emerging adulthood outcomes: depression, risk behavior, and, for those with diabetes, diabetes outcomes. RESULTS: Parent relationship quality predicted decreased depressive symptoms and, for those with diabetes, decreased alcohol use. Parent control predicted increased smoking, reduced college attendance, and, for control participants, increased depressive symptoms. For those with diabetes, parent control predicted decreased depressive symptoms and better self-care. Friend relationship variables predicted few outcomes. CONCLUSIONS: Adolescent parent relationships remain an important influence on emerging adults' lives. PMID- 24178510 TI - Extending the pharmacokinetic half-life of coagulation factors by fusion to recombinant albumin. AB - The prophylactic treatment of haemophilia B and the management of haemophilia A or B with inhibitors demand frequent administrations of coagulation factors due to the suboptimal half-lives of the products commercially available and currently in use, e.g. recombinant factor IX (rFIX) and recombinant factor VIIa (rFVIIa), respectively. The extension of the half-lives of rFIX and rFVIIa could allow for longer intervals between infusions and could thereby improve adherence and clinical outcomes and may improve quality of life. Albumin fusion is one of a number of different techniques currently being examined to prolong the half-life of rFIX and rFVIIa. Results from a phase I clinical trial demonstrated that the recombinant fusion protein linking FIX to albumin (rIX-FP) has a five-times longer half-life than rFIX, and preclinical studies with the recombinant fusion protein linking FVIIa to albumin (rVIIa-FP) suggest that rVIIa-FP possesses a significantly extended half-life versus rFVIIa. In this review, we describe albumin fusion technology and examine the recent progress in the development of rIX-FP and rVIIa-FP. PMID- 24178513 TI - Probing the carotenoid content of intact Cyclotella cells by resonance Raman spectroscopy. AB - In this study, we demonstrate the selective in vivo detection of diadinoxanthin (DD) and diatoxanthin (DT) in intact Cyclotella cells using resonance Raman spectroscopy. In these cells, we were able to assess both the content of DD and DT carotenoids relative to chlorophyll and their conformation. In addition, the sensitivity and selectivity of the technique allow us to discriminate between different pools of DD on a structural basis, and to follow their fate as a function of the illumination conditions. We report that the additional DD observed when cells are grown in high-light conditions adopts a more twisted conformation than the lower levels of DD present when the cells are grown in low light (LL) conditions. Thus, we conclude that this pool of DD is more tightly bound to a protein-binding site, which must differ from the one occupied by the DD present in LL conditions. PMID- 24178511 TI - Gene-centric association signals for haemostasis and thrombosis traits identified with the HumanCVD BeadChip. AB - Coagulation phenotypes show strong intercorrelations, affect cardiovascular disease risk and are influenced by genetic variants. The objective of this study was to search for novel genetic variants influencing the following coagulation phenotypes: factor VII levels, fibrinogen levels, plasma viscosity and platelet count. We genotyped the British Women's Heart and Health Study (n=3,445) and the Whitehall II study (n=5,059) using the Illumina HumanCVD BeadArray to investigate genetic associations and pleiotropy. In addition to previously reported associations (SH2B3, F7/F10, PROCR, GCKR, FGA/FGB/FGG, IL5), we identified novel associations at GRK5 (rs10128498, p=1.30x10(-6)), GCKR (rs1260326, p=1.63x10( 6)), ZNF259-APOA5 (rs651821, p=7.17x10(-6)) with plasma viscosity; and at CSF1 (rs333948, p=8.88x10(-6)) with platelet count. A pleiotropic effect was identified in GCKR which associated with factor VII (p=2.16x10(-7)) and plasma viscosity (p=1.63x10(-6)), and, to a lesser extent, ZNF259-APOA5 which also associated with factor VII and fibrinogen (p<1.00x10-2) and plasma viscosity (p<1.00x10(-5)). Triglyceride associated variants were overrepresented in factor VII and plasma viscosity associations. Adjusting for triglyceride levels resulted in attenuation of associations at the GCKR and ZNF259-APOA5 loci. In addition to confirming previously reported associations, we identified four single nucleotide polymorphisms (SNPs) associated with plasma viscosity and platelet count and found evidence of pleiotropic effects with SNPs in GCKR and ZNF259-APOA5. These triglyceride-associated, pleiotropic SNPs suggest a possible causal role for triglycerides in coagulation. PMID- 24178514 TI - Standardizing the initial evaluation for myelodysplastic syndromes. AB - The myelodysplastic syndromes (MDS) pose a unique diagnostic challenge for clinicians and pathologists due to the clinicopathologic heterogeneity of the disease and overlapping features with other benign and malignant disorders. Currently, the initial evaluation of a patient with suspected MDS centers around a detailed medical history, review of the peripheral blood and bone marrow by an expert hematopathologist and risk stratification using laboratory results, morphology and cytogenetics. More sophisticated technologies, including multi color flow cytometry, fluorescence in-situ hybridization (FISH), next-generation sequencing, and others are emerging and promise to offer significant refinements in diagnostic, prognostic and, hopefully, therapeutic information. With the incidence and prevalence of MDS increasing worldwide, it is critical for clinicians to optimize the initial evaluation of a patient with suspected disease, using a standard schema, to facilitate accurate diagnosis, risk stratification and treatment. PMID- 24178515 TI - Heparin modification of a biomimetic bone matrix for controlled release of VEGF. AB - Bone regeneration using tissue engineered constructs requires strategies to effectively stimulate vascularization within such a construct that is crucial for its supply and integration with the host tissue. In this work, porous scaffolds of a collagen/hydroxyapatite nanocomposite were modified with heparin to generate biomimetic bone matrices which are able to release angiogenic factors in a controlled manner. Heparin was either integrated during material synthesis (in situ) or added to the scaffolds after their fabrication (post). Both approaches resulted in stable incorporation of heparin into the matrix of mineralized collagen. Investigations of binding and release of the vascular endothelial growth factor (VEGF-A165) loaded onto the scaffolds revealed an enhanced binding capacity as well as a sustained and nearly constant delivery of VEGF as result of both heparin modification methods. The release rate could be controlled by varying the quantity of incorporated heparin and the modification method. Although the biological activity of VEGF released after 7 days from the unmodified scaffolds was reduced in comparison to control VEGF, it was maintained after release from post or even enhanced after release from in situ modified scaffolds. In conclusion, the heparin-modified scaffolds of mineralized collagen exhibited favorable growth factor binding and release properties and may be beneficial to stimulate vascularization. PMID- 24178516 TI - Detection of S100B in maternal blood before and after fetal death. AB - BACKGROUND: S100B is a brain damage biomarker. When measured immediately after birth, it reflects neonatal brain damage following asphyxia. In this study, we used feticide as a novel model of fetal brain damage. We examined whether such damage is reflected by a rise in S100B in maternal blood before delivery. METHODS: Eight pregnant women were recruited between January and July 2012. Maternal blood samples were drawn before and after feticide at predetermined time points (0, 15, 30, 60, 120, and 240 min). S100B, lactate dehydrogenase, creatine kinase, and creatinine concentrations were measured by standard human ELISA and chemical analyzer. RESULTS: No significant difference was noted between S100B levels before and after feticide, neither in non-specific cell death markers (lactate dehydrogenase and creatine kinase), which remained within normal range. S100B ranged between 0.015-0.04 ug/L through all the predetermined time points. CONCLUSION: No statistically significant differences were demonstrated in S100B levels before and after feticide. PMID- 24178517 TI - Traits of Panax ginseng hairy roots after cold storage and cryopreservation. AB - Panax ginseng hairy root cultures were established by infecting petiole segments with Agrobacterium rhizogenes strain 15834. Hairy root segments including root tips placed onto phytohormone-free 1/2 Murashige and Skoog solid medium and stored at 4 degrees C in the dark for 4 months, resumed elongation when the temperature was raised to 25 degrees C in the dark. For cryopreservation, a vitrification method was applied. Root tips precultured with 0.1 mg/l 2,4-D for 3 days and dehydrated with PVS2 solution for 8 minutes prior to immersion into liquid nitrogen had a survival rate of 60 % and could regenerate. The hairy roots regenerated from cryopreserved root tips grew well and showed the same ginsenoside productivity and patterns as those of the control hairy roots cultured continuously at 25 degrees C. The conservation of T-DNAs in the regenerated hairy roots was proved by PCR analysis. PMID- 24178518 TI - Stress-induced microspore embryogenesis in tobacco: an optimized system for molecular studies. AB - Specific stress treatments applied to isolated tobacco (Nicotiana tabacum L.) microspores efficiently induced haploid embryo formation in vitro. A heat shock at 33 or 37 degrees C in the presence of sugar, as well as sucrose-starvation at 25 degrees C, resulted in the formation of embryogenic microspores. A combination of both treatments had an additive effect. Under optimal induction conditions all viable microspores in the culture were embryogenic and developed subsequently into pollen embryos by culture at 25 degrees C in a sugar-containing medium, with induction frequencies of more than 70% with respect to the initial microspore population. A high fraction of the early pollen embryos continued their development in vitro, giving rise to haploid plants. In contrast to other available systems for microspore/pollen embryogenesis, the new protocol allows the production of homogeneous populations of embryogenic microspores and early globular embryos in large-scale cultures, without any purification step, and is therefore well suited for biochemical and molecular work. PMID- 24178519 TI - Highly efficient transformation and regeneration of aspen plants through shoot bud formation in root culture. AB - The natural capacity of aspen (Populus tremula L.) roots for direct shoot-bud regeneration was harnessed to establish a highly efficient transformation and regeneration procedure that does not require a pre-selection stage on antibiotics. Aspen stem segments were transformed using wildtype Agrobacterium rhizogenes (LBA9402) with the binary p35SGUSINT plasmid carrying the genes coding for beta-glucuronidase (GUS) and neomycin phosphotransferase II. High levels of transient GUS expression were found in the basal cut surface of 87% of the segments, and 98% of these formed well-developed adventitious roots. Proliferating root cultures were established in liquid culture, and GUS expression was found in 75% of the roots. Shoot-bud regeneration in root cultures was very high: 99% of the roots yielded shoot-buds (4.3 buds per root), of which 91% expressed GUS. Southern blot analysis and polymerase chain reaction confirmed the transgenic nature of the plants expressing GUS. Kanamycin resistance of transformants was tested with respect to callus growth and bud regeneration. Callus from transgenic plants exhibited a high growth rate in the presence of up to 100 MUg/MUl kanamycin, and bud regeneration from transformed roots occurred in the presence of up to 30 MUg/MUl kanamycin. Callus and buds from control (non transformed) plants failed to proliferate or regenerate, respectively, in the presence of kanamycin at concentrations above 10 MUg/MUl. Ninety-four independent clones from different transformation events were established, of which 52 were phenotypically true-to-type. PMID- 24178520 TI - Improvements in the transformation of Arabidopsis thaliana C24 leaf-discs by Agrobacterium tumefaciens. AB - We report here an efficient Arabidopsis leafdisc transformation protocol yielding an average transformation frequency of 1.6 transgenic shoots per leaf explant 4 weeks after the bacterial infection period. Subsequent cultivation in vitro is such that a high percentage (85-90%) of the primary transformants produces seeds with an average seed yield of 100-300 seeds per plant. This improved transformation protocol yields mainly (70%) transformants segregating for a single T-DNA locus of which 68% actually contain one T-DNA insert. The objective is to generate a pool of independent transformants harboring an activator T-DNA construct in a gene tagging approach to isolate genes involved in morphogenesis and auxin signal transduction. PMID- 24178521 TI - Adventitious shoot regeneration from leaf, stem and root explants of commercial cultivars of Gentiana. AB - Several culture conditions were examined for promoting efficient plant regeneration from explants of Gentiana. Adventitious shoot regeneration from leaf explants of cv. WSP-3 was very superior on MS medium, compared to B5 medium, supplemented with four cytokinins (TDZ, 4PU-30, BA and zeatin). An auxin / cytokinin combination was required for regeneration. TDZ was the most effective cytokinin, while NAA was more effective than IAA or 2,4-D. Optimum conditions for regeneration from explants (leaf, stem and root) of cv. WSP-3, evaluated in terms of regeneration frequency and number of regenerated shoots per explant, were TDZ and NAA in combination, 5-10 mg/l and 0.1 mg/l for leaf and stem explants, and 10 mg/l and 1 mg/l for root explants, respectively. Application of these conditions to eight other commercial cultivars resulted in 30-100% regeneration from leaf explants. The number of chromosomes in each of ten regenerated plants of each cultivar was diploid, 2n=26. Shoots regenerated in vitro were rooted in phytohormone-free medium and transferred to soil. PMID- 24178522 TI - Agrobacterium tumefaciens-mediated transformation of Solanum gilo Raddi as influenced by explant type. AB - An efficient system for Agrobacterium tumefaciens-mediated transformation of Solanum gilo was established. The marker genes for kanamycin resistance and beta glucuronidase expression were introduced. A comparison between cotyledon and hypocotyl explants showed that while regeneration was better from hypocotyl explants, cotyledon explants gave better transformation efficiency (46% vs. 32%). Four levels of kanamycin selection (100, 150, 200 and 250 mg/l) were tested for effect on transformation efficiency with each type of explant. Lower levels of kanamycin worked better using cotyledon explants, while higher levels of kanamycin worked better for hypocotyl explants. All nine t0 plants tested for expression of the kan (r) gene were positive. The progeny of three of these plants showed a pattern of classical Mendelian inheritance (3 to 1) for both the kan (r) and the beta-glucuronidase genes. PMID- 24178523 TI - Rapid and transient induction of calmodulin-encoding gene(s) of Brassica napus by a touch stimulus. AB - A cDNA clone for a calmodulin gene (bcm1) was isolated from Brassica napus. The clone encodes a peptide identical to the calmodulins encoded by the Arabidopsis ACaM-2, -3 and -5 cDNA clones and shows 92% nucleotide sequence identity to the ACaM-3 clone. Northern blot analysis shows that a single band of transcript is detected in all organs examined and most abundantly in the root with the 3' untranslated sequence probe. In addition, the transcript level increases rapidly (within 30 min) after wound or touch stimulation and starts to decline in 3 hr, suggesting that calmodulin may be involved in the responses to these stimuli in Brassica napus. The gene is a member of a multigene family in Brassica napus. PMID- 24178524 TI - Transformation of pickling cucumber with chitinase-encoding genes using Agrobacterium tumefaciens. AB - Transformation of cucumber cv. Endeavor was attempted using three Agrobacterium tumefaciens strains (a supervirulent leucinopine type, an octopine type and a nopaline type), each harbouring one of three binary vectors which contained an acidic chitinase gene from petunia, and basic chitinase genes from tobacco and bean, respectively, driven by the CaMV 35S promoter. Petiole explants were inoculated with a bacterial suspension (10(8) cells.ml(-1)), cocultivated for 48 96 h and placed on Murashige and Skoog (MS) medium with 5.0 MUM each of 2,4-D and BA, 50 mg.l(-1) kanamycin and 500 mg.l(-1) carbenicillin. The frequency of embryogenic callus formation ranged from 0 to 12%, depending on strains/vectors used and length of cocultivation, with the highest being obtained using the leucinopine strain with petunia acidic chitinase gene. The kanamycin-resistant embryogenic calli were used to initiate suspension cultures (in liquid MS medium with 1.0/1.0 MUM 2,4-D/BA, 50 mg.l(-1) kanamycin) for multiplication of embryogenic cell aggregates. Upon plating of cell aggregates onto solid MS medium with 1.0/1.0 MUM NAA/BA and 50 mg.l(-1) kanamycin, calli continued to grow and later differentiated into plantlets. Transformation by the leucinopine strain and all three vectors was confirmed by PCR amplification of the NPT II gene in transgenic calli and plants, in addition to Southern analysis. Expression of the acidic chitinase gene (from petunia) and both basic chitinase genes (from tobacco and bean) in different transgenic cucumber lines was confirmed by Western analyses. PMID- 24178525 TI - Effect of culture methods on the regeneration of albino rice (Oryza sativa L.) plantlets. AB - In our study, we investigated the effects of regeneration conditions on both green and albino rice plants (Oryza sativa L.). The regeneration frequency of an albino cell line was compared to a normal cell line obtained from mature seed under two kinds of culture conditions; namely, the static culture on semi-solid regeneration medium and the suspension culture in liquid regeneration medium. The albino cell line, from which only albino plantlets were regenerated, was induced from the albino leaf segments. There were no significant differences in the regeneration frequencies between normal and albino calli on the semisolid regeneration medium. On the other hand, the frequency of regeneration of albino calli was significantly lower than that of the control specifically in the liquid regeneration medium. PMID- 24178526 TI - Amyloplast formation in cultured tobacco cells; effects of plant hormones on multiplication, size, and starch content. AB - In BY-2 cultured tobacco cells (Nicotiana tabacum L.), depletion of 2,4 dichlorophenoxyacetic acid (2,4-D) and addition of benzyladenine (BA) caused amyloplast formation, a decrease in cell multiplication, and an increase in cell size. These changes were primarily triggered by the depletion of 2,4-D, and facilitated by the addition of BA. An increase in the starch content of BY-2 cells was always accompanied by a reduction in cell multiplication. However, when hormonal conditions were unsuitable for amyloplast formation, the starch content of the cells did not increase, even if cell multiplication was forcibly terminated by the addition of aphidicolin. This result indicates that the hormonal conditions themselves, and not the decrease in cell multiplication, induce amyloplast formation in BY-2 cultured tobacco cells. PMID- 24178527 TI - Genetic transformation of Begonia tuberhybrida by Ri rol genes. AB - We have developed an Agrobacterium -mediated transformation system for commercial Begonia species. The leaf explants of Begonia semperflorens, Begonia x hiemalis and B. tuberhybrida were inoculated with Agrobacterium tumefaciens LBA4404 harboring a binary vector pBI121 which contains rolA, B and C genes of an agropine type Ri plasmid (pRiA4b). Kanamycin resistant shoots of B. tuberhybrida were obtained on MS agar medium supplemented with 0.1 mg/l NAA, 0.5 mg/l BA, 500 mg/l claforan and 100 mg/l kanamycin. These shoots exhibited GUS activity and Southern analysis showed a single copy insertion into the genome. When the transgenic plants were transferred to soil, they displayed the phenotype specific to the transgenic plants by A. rhizogenes such as dwarfness, delay of flowering, and wrinkled leaves and petals. PMID- 24178528 TI - Increase of root induction in Pinus nigra explants using agrobacteria. AB - Wounding of explanted Pinus nigra primary explants followed by infection with Agrobacterium rhizogenes wild strains 8196, 15834, or with the pRiA4abc transconjugant strain of A. tumefaciens (C58 chromosomal background) resulted in adventitious root induction. Roots were formed in 60-97% of explants (1-3 roots/explant) but without a hairy root phenotype. The presence of T-DNA of pRi8196 or pRiA4abc in regenerated roots was confirmed by the opine (mannopinic acid) content. Transformation response was influenced by the bacterial strain, age of explant and period of co-cultivation. Both the aggregate state (liquid) of medium and the season of the year (spring) had a positive effect on the root induction and their development. Histological analysis of the transformed roots showed that complete elements of primary and secondary root structures were present but roots were always triarch or tetrarch in the central cylinder as opposed to the primary roots of the untransformed seedling wich are diarch. PMID- 24178529 TI - In vitro propagation of cashewnut. AB - In vitro plant propagation was developed for seedling shoot tips, leaf axils, and cotyledonary nodes of cashew, Anacardium occidentale. Factors affecting multiplication rate included age of explant source, explant type, medium composition, light requirements, and transfer frequency. Cotyledonary nodes produced more buds than other explant types. Nodes had a 90% viability when transferred daily to fresh medium containing activated charcoal for 7 d while exposed to continuous dark. Cultures were then exposed to low light illumination with weekly transfers. The phytohormone composition producing the most buds was 2.32 MUM kinetin, 9.12 MUM zeatin and 4.40 MUM BA. The highest frequency of rooted shoots was obtained by treating shoots with the bacterium, Agrobacterium rhizogenes. Plants also were recovered by induction of roots using auxin treatment on propagated shoots. PMID- 24178530 TI - Immunolocalization of lipoxygenase in pea (Pisum sativum L.) carpels. AB - Polyclonal antibodies against a part of pea (Pisum sativum L.) LOXG protein have been raised to study the pattern of distribution of related lipoxygenases in pea carpels. The antiserum recognized three lipoxygenase polypeptides in carpels. One of them became undetectable 24 hours after fruit development induction, suggesting that it may correspond to the protein derived from loxg cDNA. Immunolocalization experiments showed that lipoxygenase protein was present only in pod tissues: it was abundant in the mesocarp and, from the day of anthesis, in the endocarp layers. Lipoxygenase distribution is regulated throughout development. The association of lipoxygenase with cells in which processes of expansion and growth will potentially take place support a role in pod growth and development. PMID- 24178531 TI - Unilateral incompatibility as a major cause of skewed segregation in the cross between Lycopersicon esculentum and L. pennellii. AB - Skewed segregations are frequent events in segregating populations derived from different interspecific crosses in tomato. To determine a basis for skewed segregations in the progeny of the cross between Lycopersicon esculentum and L. pennellii, monogenic segregations of 16 isozyme loci were analyzed in an F2 and two backcross populations of this cross. In the F2, 9 loci mapping to chromosomes 1, 2, 4, 9, 10 and 12 exhibited skewed segregations and in all cases there was an excess of L. pennellii homozygotes. The genotypic frequencies at all but one locus were at Hardy-Weinberg equilibria. In the backcross populations, all except two loci exhibited normal Mendelian segregations. No post-zygotic selection model could statistically or biologically explain the observed segregation patterns in the F2 and backcross populations. A pre-zygotic selection model, assuming selective elimination of the male gametophytes during pollen function (i.e., from pollination to karyogamy), could adequately explain the observed segregations in all three populations. The direction of the skewed segregations in the F2 population was consistent with that expected based on the effects of unilateral incompatibility reactions between the two species. In addition, the chromosomal locations of 5 of the 9 markers that exhibited skewed segregations coincided with the locations of several known compatibility-related genes in tomato. Multigenic unilateral incompatibility reactions between L. esculentum pollen and the stigma or style of L. pennellii (or its hybrid derivatives) are suggested to be the major cause of the skewed segregations in the F2 progeny of this cross. PMID- 24178532 TI - A simple, accurate method for determining wet and dry weight concentrations of plant cell suspension cultures using microcentrifuge tubes. AB - A simple method using microcentrifuge tubes for determining fresh and dry weights, and collecting cell-free supernatant from plant suspension cultures is described. This method offers improvements in accuracy, precision, and time efficiency over traditional filtration methods. Using 4-day-old Nicotinia tabacum cultures, the centrifuge method was shown to remove 25% more of the interstitial water from cell aggregates compared to a suction filtration method, with significantly less variation in fresh weight data. PMID- 24178533 TI - Effect of jasmonates and exogenous polysaccharides on production of alkannin pigments in suspension cultures of Alkanna tinctoria. AB - The conditions for the efficient production of alkannin pigments by a suspension culture of Alkanna tinctoria were established. Pectin, polygalacturonic acid sodium salt and galactan increased the pigment production but not as much as agar did. A marked increase in the pigment content in cells and medium of suspension cultures after treatment with methyl jasmonate was observed. It was shown, applying a two-layer culture method, that mineral and olive oils intensified the pigment secretion from cells to the medium but did not enhance significantly their synthesis. Thin layer chromatography and high performance liquid chromatography methods showed that two main esters of alkannin are responsible for the characteristic colour of A. tinctoria suspension cultures. PMID- 24178534 TI - Shoot regeneration and Agrobacterium-mediated transformation of Fragaria vesca L. AB - An efficient and reliable method for shoot regeneration from leaf disks of Fragaria vesca L. has been developed. This protocol has been successfully employed to obtain transformed plants using Agrobacterium tumefaciens as gene vector. Murashige and Skoog basal medium supplemented with benzyladenine (4 mg/l) and indole-3-butyric acid (0.25 mg/l) induced the maximum percentage of shoot regeneration (98%) and the highest number of shoot colonies per explant (4.6) after 8 weeks of culture. Isolated shoots would elongate and proliferate when the benzyladenine concentration was lowered to 0.5 mg/l. The established protocol for shoot regeneration was employed to transform leaf disks using Agrobacterium tumefaciens carrying the plasmid pBI121. A 7.7% of the inoculated explants showed kanamycin resistance after 10 weeks of selection in a medium containing 25 mg/l of this antibiotic. The transgenic shoots obtained were rooted in the presence of 25 mg/ kanamycin and successfully acclimatized. The final percentage of transformation obtained based on beta-glucuronidase expression was 6.9%. PMID- 24178535 TI - Oligonucleotide fingerprinting and RAPD analysis of Achillea species: Characterization and long-term monitoring of micropropagated clones. AB - Two different DNA fingerprinting techniques were applied to a set of Achillea samples (Asteraceae), comprising ten taxa of the medicinally important A. millefolium group and six related species. Field-grown as well as in vitro micropropagated plants were individually screened for abundance and polymorphism of target sequences recognized by oligonucleotide fingerprinting with 13 different microsatellite-complementary probes. While most probes revealed a high level of intra- and interspecific variability, fingerprints proved to be somatically stable in vegetatively propagated plant material. Analysis of the same samples by polymerase chain reaction with arbitrary 10-mer primers yielded less polymorphic patterns. Because of its higher discriminatory ability, oligonucleotide fingerprinting offers itself as the method of choice for the identification and discrimination of A. asplenifolia and A. roseoalba clones, as well as for monitoring their stability during micropropagation. PMID- 24178537 TI - Plasma amino acids in four models of experimental liver injury in rats. AB - We studied the plasma amino acid profiles in four models of hepatic injury in rats. In partially hepatectomized rats (65% of liver was removed) we observed significant increase of aromatic amino acids (AAA; i.e. tyrosine and phenylalanine), taurine, aspartate, threonine, serine, asparagine, methionine, ornithine and histidine. Branched-chain amino acids (BCAA; i.e. valine, leucine and isoleucine) concentrations were unchanged. In ischemic and carbon tetrachloride acute liver damage we observed extreme elevation of most of amino acids (BCAA included) and very low concentration of arginine. In carbon tetrachloride induced liver cirrhosis we observed increased levels of AAA, aspartate, asparagine, methionine, ornithine and histidine and decrease of BCAA, threonine and cystine. BCAA/AAA ratio decreased significantly in partially hepatectomized and cirrhotic rats and was unchanged in ischemic and acute carbon tetrachloride liver damage. We conclude that a high increase of most of amino acids is characteristic of fulminant hepatic necrosis; decreased BCAA/AAA ratio is characteristic of liver cirrhosis; and decrease of BCAA/AAA ratio may not be used as an indicator of the severity of hepatic parenchymal damage. PMID- 24178538 TI - Analysis of cysteine residues in peptides and proteins alkylated with volatile reagents. AB - Conditions are described for the reduction and alkylation of cysteines in peptides and proteins with volatile reagents by use of triethylphosphine as reductant, bromopropane as alkylating reagent and triethylamine as base. Alkylated samples need only be vacuum dried prior to subsequent analysis steps. Alkylated samples have been acid hydrolyzed and analyzed on an amino acid analyzer with recoveries of cysteine within 10% of the expected value. Alkylated samples have been directly applied to a sequencer membrane, dried on the surface and cysteines identified by sequence analysis without additional wash steps. In addition proteins blotted onto PVDF have been alkylatedin situ and sequenced with identification of cysteines. On the analyzer and sequencer the S-propylcysteine derivative elutes at a unique position allowing for the unambiguous identification of cysteine. Cysteine residues are quantitativly alkylated under the conditions developed. The ease of this procedure allows the routine analysis of cysteine in peptides and proteins without additional, time consuming repurification or dialysis steps. PMID- 24178539 TI - An analysis of base frequencies in the anti-sense strands corresponding to the 180 human protein coding sequences. AB - Can the anti-sense chain of DNA encode for a protein? Such a problem has been explored by means of the codon-analyzing graph developed recently. PMID- 24178536 TI - Amino acid activation and polymerization at modular multienzymes in nonribosomal peptide biosynthesis. AB - The biosynthesis of microbial bioactive peptides is accomplished nonribosomally by large multifunctional enzymes consisting of linearly arranged building blocks of 1,000-1,500 amino acid residues. Each of these units acts as an independent enzyme which catalyzes the selection, activation, and in some cases modification (epimerization, N-methylation) of its cognate amino acid, as well as the elongation of the peptide product. The specific linkage of amino acid activating modules upon such polyenzymes defines the sequence of the peptide product. A series of functional domains could be identified upon an amino acid activating module which are involved in the sequential reactions in nonribosomal peptide biosynthesis. PMID- 24178540 TI - Cell growth in arginine- and ornithine-deprived medium and conversion of glutamate to ornithine and arginine in rat hepatoma cells. AB - A subline growing in medium without arginine and ornithine was established from a rat Reuber hepatoma cell line (R-Y121B.cho). The subline designated R-Y117B.cho was able to grow in glutamine, arginine and ornithine-free, glutamate supplemented medium. Arginine synthesis from glutamate requires four urea cycle enzymes and another two enzymes, glutamate semialdehyde dehydrogenase and ornithine aminotransferase. Since R-Y121B.cho cells have all the urea cycle enzymes, two other enzyme activities were determined. The activities of ornithine aminotransferase and glutamate semialdehyde dehydrogenase were similar in R Y117B.cho and its parental R-Y121B.cho cells, but R-Y117B.cho cells had higher conversion of glutamate to arginine than parental cells. PMID- 24178541 TI - An improved scheme of leucine derivative fragmentation in mass spectrometry. AB - This study illustrates the contribution of stable isotopes to amino acid mass spectrometry. The mass spectra of natural leucine and 1(13)C leucine were compared and the mass fragmentography pattern analysed. This analysis indicates that the position of the stable isotope in tracer molecules should be very dependent on the analytical procedure used for their determination. PMID- 24178542 TI - Correlation between nitric oxide synthase activity and reduced glutathione level in human and murine endothelial cells. AB - The synthesis of nitric oxide (NO), detected as citrulline production, in human (HUVEC) and murine (tEnd.1) endothelial cells correlated with intracellular GSH. tEnd.1, which exhibited an intracellular GSH level 2.5-fold higher than HUVEC, showed a citrulline production (basally and after ionomycin stimulation) 5-8 times higher than human cells. Ionomycinelicited citrulline synthesis in tEnd.1 cells increased 2.4-fold after loading with GSH, and decreased dose-dependently after GSH depletion. Cell loading with N-(2-mercaptopropionyl)-glycine neither significantly increased citrulline production nor relieved the effect of GSH depletion. PMID- 24178544 TI - Child psychiatry-whither goest thou? PMID- 24178543 TI - Hydroxyproline reaction with free radicals generated during benzoyl peroxide catalytic decomposition of carbon tetrachloride Structure of reaction products formed. AB - Benzoyl peroxide catalytic decomposition of carbon tetrachloride in a model system produces trichloromethyl and trichloromethylperoxyl free radicals. These radicals are also produced by CCl4 bioactivation in liver and are considered to be responsible for the deleterious effects of this hepatotoxin. In this study, it is attempted to learn about how the .CCl3 and CCl3O2. tend to react with hydroxyproline in a model system. Hydroxyproline was selected because of its role in collagen metabolism. During the interaction of both radicals with hydroxyproline a total of 16 reaction products were isolated and identified by gas chromatographic-mass spectrometric analysis. All of them were hydroxyproline analogs, no single one contained C from CCl4 and only three contained chlorine. Consequently, most adducts would be missed in experiments where formation of reaction products are studied by formation of(14)C or(36)Cl labeled adducts (e.g. covalent binding studies used by toxicologists). If similar hydroxyproline analog reaction products were observed during CCl4 intoxication it might be reasonably expected that they interfered with collagen metabolism and participate in cirrhogenic effects of CCl4 on the liver. PMID- 24178545 TI - The emergence of child psychiatry as an academic discipline. AB - Child psychiatry has come a long way since its tenuous beginnings fifty years ago. A few of the pioneers are still around to remind us of our short history. Its development has not by any means been linear and, from time to time over the years, it has wandered off into nonmedical fields and practices that have impeded its incorporation into the body of medicine. Within the past two decades, it has relinquished its purely guidance role and has been trying, although in a small way, to generate its own specific theory and research. However, it has still some way to go before it can get itself less ambivalently accepted in the medical schools. In making its approach to orthodox medicine, it should continue to remember its own history and not relinquish the many skills it acquired and is still acquiring from the behavioral sciences. PMID- 24178546 TI - Maternal perception of the neonate as related to development. AB - One hundred and twenty, full-term, normal, first-born infants were categorized at one month of age into a high-risk or low-risk group for possible development of emotional and developmental deviations. The predictions were based on measurements of the mother's perception of her infant as compared to the average. At age 4 1/2, the children were evaluated by two child psychiatrists who had no knowledge of the children's predictive risk rating. A statistically significant association was evident between prediction and outcome. This paper describes the methodology and discusses the implications of the findings. PMID- 24178547 TI - Child Psychiatry and Pediatrics in Medical School Medical Center settings. AB - The various ways in which Child Psychiatry can function in relation to Pediatrics in Medical School Medical Center settings are outlined and summarized; the author draws on his own experience and on those of others working in a number of different settings. While the precise details of teaching arrangements and clinical activities depend on the nature of individual settings, the general goals and approaches are common to all, as are the multiple functions of the child psychiatrist in his clinical and didactic teaching, his consultative, diagnostic and treatment activities. Although the greater part of his efforts are usually directed to the attending and resident pediatric staff, nurses and all of the other hospital staff involved in the care of the child patients are included to varying degrees in the teaching and consultative operations. His influence on the hospital administration is of highest importance. PMID- 24178548 TI - Hyperkinetic syndrome: The role of depression. AB - The hyperkinetic syndrome is one of many manifestations of minimal brain dysfunction and emotional distrubance. Both physical and psychologic factors can be seen in its etiology. Depression has often been found to be related to hyperkinesis. The children described in this study give ample support to the frequency of this relationship. Some preliminary hypotheses are also drawn about the dynamics of the relationship between depression and the hyperkinetic syndrome. PMID- 24178549 TI - Personality and attitudes of child care workers, psychotherapists, and parents of children in residential treatment. AB - The PARI, MMPI, F-Scale, and Dogmatism Scale were administered to (a) parents of child psychiatric patients, (b) psychotherapists, and (c) child care workers. Similarities and differences among these three groups were found on measures of hostility and control in child-rearing, general authoritarianism and dogmatism, anxiety, repression, dominance, and ego-strength. The findings have important implications for increased understanding of (a) interpersonal relations among adults collaborating in the treatment process, and (b) interactions between adults in these roles and children under their guidance. PMID- 24178550 TI - Student teachers as tutors for children in an inner city school. AB - A tutoring program for first grade inner city children, employing student teachers as tutors, was developed and evaluated. Tutoring had no discernible effects on performance on the Illinois Test of Psycholinguistic Ability. However, tutored children were placed in the highest reading group, and were rated by the regular classroom teacher as having completed the first grade reading series more often than controls. Tutors saw their children as becoming more responsive over time. Classroom teachers rated the tutored children as more competent in the classroom, more confident, and as viewing the classroom as more benevolent. In contrast to controls, student teachers maintained favorable attitudes toward teaching in the inner city, and they claimed to have benefited in practice teaching from their tutoring experience. However, relatively few actually took teaching positions in inner city schools after completing their training. PMID- 24178552 TI - Chromatin immunoprecipitation assay of Piwi in Drosophila. AB - The generation of high-resolution maps of the epigenome is crucial to research in epigenetics, developmental biology, and stem cell biology. In recent years, small RNA pathways have been implicated in epigenetic regulation. All small RNA pathways involve Argonaute proteins as their key biogenesis and effector components. In this chapter, we describe a chromatin immunoprecipitation method for whole-genome mapping of Drosophila Piwi, the defining member of the Argonaute protein family. This method should have general utility for mapping other chromatin-associated factors. PMID- 24178551 TI - Comparison of chirp versus click and tone pip stimulation for cervical vestibular evoked myogenic potentials. AB - The current study explored differences among cervical vestibular evoked myogenic potentials (cVEMP) that were evoked by CE-chirp and click and tone pip in healthy controls, and tried to explain the differences of cVEMP between the three of them. Thirty normal volunteers were used as subjects for CE-chirp and click and tone-pip (Blackman pip) stimuli. The latency of P1, N1, peak-to-peak P1-N1 amplitude, and cVEMP interaural difference were obtained and analyzed. The response rates of cVEMP were 93 % for click and 100 % for both Blackman pip and CE-chirp, respectively. The P1 and N1 latencies of cVEMP evoked by CE-chirp were the shortest, followed by click, with Blackman pip the longest (F = 6,686.852, P < 0.001). All indices of cVEMP evoked by the three stimuli showed no significant difference between the left and right ears or between genders. cVEMP responses were significantly different between the three stimuli. Compared with the currently used stimulus, CE-chirp can evoke cVEMP with shorter latencies and demonstrates increased speed and reliability. PMID- 24178553 TI - Drosophila germline stem cells for in vitro analyses of PIWI-mediated RNAi. AB - The Drosophila piwi gene has multiple functions in soma and germ cells. An in vitro system provides a powerful tool for elucidating PIWI function in each cell type using stable cell lines originating from germline stem cells (GSCs) and ovarian soma of adult ovaries. We have described methods for the maintenance and expansion of GSCs in an established cell line (fGS/OSS) and an in situ hybridization method for analyzing piwi. PMID- 24178554 TI - RNAi and overexpression of genes in ovarian somatic cells. AB - Emerging evidence indicates that PIWI proteins, in collaboration with PIWI interacting RNAs (piRNAs), play a critical role in retrotransposon silencing in Drosophila gonadal somatic and germ-line cells. The recent establishment of female germ-line stem cells/ovarian somatic sheet and its derivative cell line, ovarian somatic cells (OSCs), allows researchers to study the molecular functions of several protein factors involved in the primary piRNA pathway in Drosophila. Although transgene expression is difficult to achieve in gonad-derived cell lines, transfection of both expression vectors and knockdown reagents is highly effective in OSCs. Here, I focus on techniques that knockdown or overexpress genes of interest in OSCs. PMID- 24178555 TI - Making piRNAs in vitro. AB - Classical biochemical approaches have made great contribution to our current understanding of how small interfering RNA (siRNA) and microRNA (miRNA) are produced and function. However, it has been challenging to establish in vitro systems that can dissect the mechanism of PIWI-interacting RNAs (piRNAs), largely due to the lack of suitable cultured cell lines possessing the piRNA pathway endogenously. The silkworm ovary-derived BmN4 cell line is an emerging model for studying piRNAs, because this cell line harbors a fully functional germline piRNA pathway. We recently reported in vitro recapitulation of a part of piRNA biogenesis-loading of precursor piRNAs and 3'-end maturation-by using lysate prepared from BmN4 cells. Here we describe the methods for maintenance of BmN4 cells, preparation of cell lysate, and in vitro assays to dissect piRNA biogenesis. PMID- 24178556 TI - A framework for piRNA cluster manipulation. AB - Piwi proteins and their small-RNA partners, piwi-interacting (pi)RNA, form a natural mechanism that prevents the deleterious activity of transposable elements in the germ line of metazoan species. The piRNA pathway relies on extended noncoding genomic regions, dubbed piRNA clusters, to produce long precursor transcripts that are subsequently processed into mature piRNAs. The large size and repetitive nature of piRNA clusters provide significant challenges for their dissection using common genetic tools. Here we describe an effective approach for manipulation of piRNA clusters using a combination of BAC recombineering in E. coli and phiC31-mediated transgenesis in Drosophila. Although the described approach is instrumental for manipulating piRNA clusters, it can also be implemented for other problems in functional genomics. PMID- 24178557 TI - Biochemical and mass spectrometric analysis of 3'-end methylation of piRNAs. AB - Piwi-interacting RNAs (piRNA) are fully modified by 2'-O-methylation at their 3' termini. This terminal methylation is required to prevent 3'-nucleotide addition, which serves as a tag for destabilization. In this chapter, we describe biochemical and mass spectrometric analyses of 2'-O-methylation at 3'-termini of piRNAs. PMID- 24178558 TI - HITS-CLIP (CLIP-Seq) for mouse Piwi proteins. AB - Piwi proteins, such as Aubergine in Drosophila and Miwi and Mili in mice, form a major subclade of the Argonaute family, which comprise a distinct class of RNA binding proteins (RBPs) able to bind small RNAs. Small RNAs can target complementary RNAs. Piwis are essential for the animal germline and bind Piwi interacting RNAs (piRNAs) to form pi-RiboNucleoProteins (piRNPs). Although many piRNAs target retrotransposons for safeguarding genome integrity of the germ cell, whether piRNAs can target other mRNAs for regulatory purposes is still under investigation. Here we present the technical protocol for "High Throughput Sequencing after in vivo Crosslinking and Immunoprecipitation" (HITS-CLIP, CLIP Seq), adapted for mouse Piwi proteins Mili and Miwi. We also provide general recommendations for the application of this protocol for different RBPs and also for the bioinformatic analysis of the deep sequencing data. PMID- 24178559 TI - DNA methylation in mouse testes. AB - DNA methylation of retrotransposons and imprinted genes is accurately regulated in spermatogenesis. In particular, CpG methylation of long interspersed elements 1 (LINE1 or L1) and intracisternal A-particle (IAP) retrotransposons during spermatogenesis has been well characterized. CpG methylation of the regulatory regions of retrotransposons is acquired during embryonic testis development; however, reductions of DNA methylation in LINE1 and/or IAP and/or Rasgrf1, which is an imprinted gene, are observed in deficient mice of piRNA biogenesis concerning. Here, we describe two methods, bisulfite sequencing and Southern blotting using a methylation-sensitive restriction enzyme, for analysis of DNA methylation of LINE1, IAP, and imprinted genes in mouse testes. PMID- 24178560 TI - Analysis of small RNA-guided endonuclease activity in endogenous Piwi protein complexes from mouse testes. AB - Small RNAs associate with members of the Argonaute family to function in gene regulation, transposon control, and creation of silent chromatin domains. In this partnership, small RNAs act as guides for the bound Argonaute and other associated proteins. Complementary base pairing of small RNAs to target nucleic acid molecules allow specificity for the small RNA-mediated functions. One key activity of some Argonaute protein family members is their small RNA-guided endonuclease activity called Slicer action. Here we describe a protocol that can be used to probe slicer activity in endogenous Piwi complexes isolated from mouse testes. PMID- 24178561 TI - Small RNA library construction from minute biological samples. AB - Increasingly, the discovery and characterization of small regulatory RNAs from a variety of organisms have all required deep-sequencing methodologies. However, the crux to successful deep-sequencing analysis depends upon optimal construction of a cDNA library compatible for the high-throughput sequencing platform. Challenges to small RNA library constructions arise when dealing with minute tissue samples because certain structural RNA fragments can dominate and mask the desired characterization of regulatory small RNAs like microRNAs (miRNAs), endogenous small interfering RNAs (endo-siRNAs), and Piwi-interacting RNAs (piRNAs). Here, we describe methods that improve the chances of constructing a successful library from small RNAs isolated from minute tissues such as enriched follicle cells from the Drosophila ovarium. Because the ribosomal RNA (rRNA) fragments are frequently the major contaminants in small RNA preparations from minute amounts of tissue, we demonstrate the utility of antisense oligonucleotide depletion and an acryloylaminophenylboronic acid (APB) polyacrylamide gel system for separating the abundant 2S rRNA in Drosophila from endo-siRNAs and piRNAs. Finally, our methodology generates libraries amenable to multiplex sequencing on the Illumina Hi-Seq platform. PMID- 24178563 TI - Analyses of piRNA-mediated transcriptional transposon silencing in Drosophila: nuclear run-on assay on ovaries. AB - In the Drosophila germline, retrotransposons are silenced by the PIWI-interacting RNA (piRNA) pathway. piRNA pathway mutations lead to overexpression and mobilization of retrotransposons in the germline. In different organisms, small RNAs were shown to be implicated in the posttranscriptional degradation of mRNA and/or transcriptional repression of the homologous locus. In Drosophila, the mechanism of piRNA-mediated silencing is still far from being understood. Transcriptional silencing implies a piRNA-mediated formation of repressive chromatin which diminishes the transcriptional capacity of the target locus. Nuclear Run-On (NRO) assay allows a direct estimation of the density of transcribing polymerases at specific genomic regions. Here we describe the NRO protocol on Drosophila ovarian tissues which can be useful for investigation of the transcriptional silencing in the female germline. PMID- 24178562 TI - Analysis of sDMA modifications of PIWI proteins. AB - Arginine methylation is an important posttranslational protein modification that modulates protein function for a wide range of biological processes. PIWI proteins, a subclade of the Argonaute family proteins, contain evolutionarily conserved symmetrical dimethylarginines (sDMAs). It has become increasingly apparent that the sDMAs of PIWI proteins serve as binding elements for TUDOR domain-containing proteins and that sDMA-dependent protein interactions play crucial roles in the biogenesis and function of PIWI-interacting RNAs (piRNAs). We describe a method for detecting PIWI sDMAs and purifying PIWI/piRNA complexes using anti-sDMA antibodies. PMID- 24178564 TI - Combined RNA/DNA fluorescence in situ hybridization on whole-mount Drosophila ovaries. AB - DNA FISH (fluorescent in situ hybridization) analysis reveals the chromosomal location of the gene of interest. RNA in situ hybridization is used to examine the amounts and cell location of transcripts. This method is commonly used to describe the localization of processed transcripts in different tissues or cell lines. Gene activation studies are often aimed at determining the mechanism of this activation (transcriptional or posttranscriptional). Elucidation of the mechanism of piRNA-mediated silencing of genomic repeats is at the cutting edge of small RNA research. The RNA/DNA FISH technique is a powerful method for assessing transcriptional changes at any particular genomic locus. Colocalization of the RNA and DNA FISH signals allows a determination of the accumulation of nascent transcripts at the transcribed genomic locus. This would be suggest that this gene is activated at the transcriptional (or co-transcriptional) level. Moreover, this method allows for the identification of transcriptional derepression of a distinct copy (copies) among a genomic repeat family. Here, a RNA/DNA FISH protocol is presented for the simultaneous detection of RNA and DNA in situ on whole-mount Drosophila ovaries using tyramide signal amplification. With subsequent immunostaining of chromatin components, this protocol can be easily extended for studying the interdependence between chromatin changes at genomic loci and their transcriptional activity. PMID- 24178565 TI - Fast and accurate method to purify small noncoding RNAs from Drosophila ovaries. AB - The recent development of High Throughput Sequencing technology has boosted the study of small regulatory RNA populations. A critical step prior to cloning and sequencing is purification of small RNA populations. Here, we report the optimization of an anion-exchange chromatography procedure in order to purify small regulatory RNAs bound on proteins. We developed this procedure to make it less time-consuming since our improved method no longer requires specific equipment and can easily be performed at the bench. We believe that our procedure will increase the robustness and accuracy of small RNA libraries in the future. PMID- 24178566 TI - Isolation of zebrafish gonads for RNA isolation. AB - Piwi proteins and piRNAs are abundant in the gonads of various animal species. Gonads from different developmental stages provide us information regarding the function of piRNAs and the PIWI pathway during germline development. Here we describe methods for gonad and germ cell preparation from different developmental stages of zebrafish. We also describe how to use these gonads to purify and characterize piRNAs. PMID- 24178567 TI - Small RNA library construction for high-throughput sequencing. AB - Since their discovery about 20 years ago, small RNAs have been shown to play a critical role in a myriad of biological processes. The greater availability of high-throughput sequencing has been invaluable to furthering our understanding of small RNAs as regulatory molecules. In particular, these sequencing technologies have been crucial in understanding the role of small RNAs in reproductive tissues, where millions of individual sequences are generated. In this context, high-throughput sequencing provides the requisite level of resolution that other procedures, like northern blotting, would not be able to achieve. Here, we describe a protocol for the preparation of small RNA libraries for sequencing using the Solexa/Illumina technology. PMID- 24178568 TI - Analysis of Piwi-loaded small RNAs in Tetrahymena. AB - Scan RNAs (scnRNAs) are developmentally regulated siRNAs of ~26-32 nucleotides in length that are involved in programmed DNA elimination in Tetrahymena. scnRNAs are loaded onto the Piwi-related protein Twi1p and 2'-O-methylated at their 3' termini. We describe two alternative strategies for analyzing the Twi1p-loaded scnRNAs: preparation of loaded scnRNAs by immuno-purification of the Twi1p-scnRNA complex and exclusion of non-methylated scnRNAs during cDNA library construction using periodate oxidation. PMID- 24178569 TI - Effective gene knockdown in the Drosophila germline by artificial miRNA-mimicking siRNAs. AB - Gene knockdown using double-stranded RNA (dsRNA) is a powerful tool to characterize gene function in Drosophila. The Drosophila germline provides an elegant model to study the regulation of numerous processes, such as stem cell fate, gametogenesis, piRNA, and piRNA-related gene functions. However, for unknown reasons, traditional dsRNA gene knockdown has not been successful in the germline. Here, we establish a simple gene silencing method for the Drosophila germline by the generation of artificial miRNA-mimicking siRNAs. This method, which is different from that of classical dsRNA, mimics natural miRNA biogenesis and enables the analysis of gene functions specifically in the Drosophila germline. PMID- 24178570 TI - Isolation and bioinformatic analyses of small RNAs interacting with germ cell specific argonaute in rice. AB - The small noncoding RNAs in plants are categorized into two major classes, 21 nucleotides (nt) micro RNA (miRNA) and 21- or 24-nt small-interfering RNA (siRNA). ARGONAUTE (AGO) proteins associate with small RNAs and play central roles in transcriptional and posttranscriptional gene regulation. In plants, AGO1 miRNA complexes mainly regulate developmental processes, and AGO4-siRNA complexes suppress the activity of transposons and exogenous viral infections via RNA directed DNA methylation. In many animal species, the PIWI-subfamily AGOs interact with PIWI-interacting RNAs (piRNAs), which are most commonly 24-34 nt, and function to tame transposons and to regulate mRNA translation and stability in the germline. The rice protein MEIOSIS ARRESTED AT LEPTOTENE1 (MEL1) is a plant AGO member that has roles specific to development and maintenance of germ cells before meiosis. MEL1-binding small RNAs are mainly 21 nt, have a 5' terminal cytosine, and are distinct from animal piRNAs. In this chapter, we describe methods for RNA-immunoprecipitation (RNA-IP) using a specific antibody that recognizes MEL1 and subsequent purification of MEL1-associating small RNAs from the IP fraction. We also introduce the bioinformatic procedures including mapping, annotation, and identifying small RNA clusters on the rice genome. PMID- 24178571 TI - A review of animal models of nonneoplastic pancreatic diseases. AB - The nonneoplastic diseases of the human pancreas generally comprise the inflammatory and degenerative conditions that include acute and chronic pancreatitis, with cystic fibrosis being arguably one of the most important diseases that induce the condition. Both acute and chronic conditions vary in severity, but both can be life threatening; and because of this fact, the study of their progression, and their responsiveness to therapy, is largely conducted by indirect means using serum markers of damage and repair such as amylase and lipase activities that normally occur at very low levels in the circulation but can be significantly increased during inflammatory episodes. Progress in the understanding the pathogenesis of both conditions has therefore been largely due to time course studies in animal models of pancreatitis, and it is in this context that animal model development has been so significant. In general terms, the animal models can be divided into the invasive, surgical procedures, and those induced by the administration of chemical secretagogues that induce hypersecretion of the pancreatic enzymes. The former include ligation and/or cannulation of the biliopancreatic ducts with infusion of solutions of various kinds, or the formation of closed duodenal loops. Secretagogue administration includes administration of caerulein or l-arginine in various protocols. An additional model involves administration of dibutyltin dichloride, which induces a partial blockage of the pancreatic ducts to induce pancreatic disease through enzymic reflux into the gland. The models have been invaluable in generating testable hypotheses for the human diseases. These hypotheses for the production of cellular damage as the initiating events in the disease include (1) intracellular chemical activation, (2) pancreatic secretion reflux, (3) intracellular production of reactive oxygen species, and (4) intracellular production of free radicals. PMID- 24178572 TI - Gastric parietal cell atrophy and depletion after administration of a sphingosine 1-phosphate 1 inhibitor. AB - Sphingosine-1-phosphate (S1P) is a major bioactive phospholipid, which binds to and activates a family of five G-protein-coupled receptors designated as S1P 1 (S1P1) through S1P5. The S1P1 receptor subtype, expressed primarily on lymphocytes, is known to play a critical role in the regulation of lymphocyte trafficking. S1P1 inhibitors result in the inhibition of lymphoid cell trafficking and are of interest to treat various inflammatory conditions. In this study, we describe a gastric finding associated with oral gavage administration of a small molecule S1P1 inhibitor to Sprague-Dawley rats. Rats were administered an S1P1 inhibitor once daily for 4 weeks and necropsies were conducted at the end of the dosing phase, and clinical pathology and histopathologic examination were performed. Lymphopenia and changes in lymphoid tissues were noted and were consistent with the pharmacodynamic effects for S1P1 inhibitory action. Histopathologic examination of the stomach revealed atrophy and depletion of gastric parietal cells in the glandular portion of the stomach. There are no literature data to suggest that this gastric effect is related to S1P1 pharmacology. Therefore, the mechanism of the observed gastric lesion is likely chemotype mediated. PMID- 24178573 TI - Species- and dose-specific pancreatic responses and progression in single- and repeat-dose studies with GI181771X: a novel cholecystokinin 1 receptor agonist in mice, rats, and monkeys. AB - Compound-induced pancreatic injury is a serious liability in preclinical toxicity studies. However, its relevance to humans should be cautiously evaluated because of interspecies variations. To highlight such variations, we evaluated the species- and dose-specific pancreatic responses and progression caused by GI181771X, a novel cholecystokinin 1 receptor agonist investigated by GlaxoSmithKline for the treatment of obesity. Acute (up to 2,000 mg/kg GI181771X, as single dose) and repeat-dose studies in mice and/or rats (0.25-250 mg/kg/day for 7 days to 26 weeks) showed wide-ranging morphological changes in the pancreas that were dose and duration dependent, including necrotizing pancreatitis, acinar cell hypertrophy/atrophy, zymogen degranulation, focal acinar cell hyperplasia, and interstitial inflammation. In contrast to rodents, pancreatic changes were not observed in cynomolgus monkeys given GI181771X (1-500 mg/kg/day with higher systemic exposure than rats) for up to 52 weeks. Similarly, no GI181771X treatment-associated abnormalities in pancreatic structure were noted in a 24 week clinical trial with obese patients (body mass index >30 or >27 kg/m(2)) as assessed by abdominal ultrasound or by magnetic resonance imaging. Mechanisms for interspecies variations in the pancreatic response to CCK among rodents, monkeys, and humans and their relevance to human risk are discussed. PMID- 24178574 TI - Rodent intestinal epithelial carcinogenesis: pathology and preclinical models. AB - Colon cancer is a major human malignancy that afflicts millions of people throughout the world each year. Genetics and diet play large roles in colon carcinogenesis although chemicals may also contribute. For the past 40 years, scientists have studied experimentally induced intestinal carcinogenesis in rodents in order to elucidate the etiology and mechanisms involved. Comparative histopathology has revealed many similarities of rodent and human intestinal cancers. Comparative molecular pathology has also shown genetic similarities. More recently, genetically engineered mice and inflammatory colon cancer models have been used for investigating mechanisms and potential chemopreventive and treatment modalities. This review will focus on comparative histopathology and nonclinical models. PMID- 24178575 TI - (+)-Usnic acid-induced myocardial toxicity in rats. AB - (+)-Usnic acid (UA) has been known to be a strong uncoupler, and mitochondrial and endoplasmic reticulum (ER)-related stresses are suggested to be involved in the mechanism of hepatotoxicity. However, it has not been clarified whether UA causes toxicity in other mitochondria-rich organs such as the heart. We elucidated whether UA induces cardiotoxicity and its mechanism. UA was orally administered to rats for 14 days, and laboratory and histopathological examinations were performed in conjunction with toxicogenomic analysis. As a result, there was no alteration in blood chemistry, whereas cytoplasmic rarefaction of myocardium was observed microscopically. This finding corresponded to the swollen mitochondria observed ultrastructurally. Immunohistochemically, expression of prohibitin, indicating mitochondrial imbalance, increased in the sarcoplasmic area. Toxicogenomic analysis highlighted the upregulation of gene groups consisting of oxidative stress, ER stress, and amino acid limitation. Interestingly, the number of upregulated genes was larger in the amino acid limitation-related gene group than that in other groups, implying that amino acid limitation might be one of the sources of oxidative stress, not only mitochondria and ER-originated stresses. In conclusion, the heart was manifested to be one of the target organs of UA. Mitochondrial imbalance with complex stresses may be involved in the toxic mechanism. PMID- 24178576 TI - Incidental histopathological findings in hearts of control beagle dogs in toxicity studies. AB - In preclinical studies of pharmaceutical agents, the beagle dog is a commonly used model for the detection of cardiotoxicity. Incidental findings, postmortem changes, and artifacts must be distinguished histopathologically from test item related findings in the heart. In this retrospective analysis, cardiac sections from 88 control beagles (41 male, 47 female; ages 5-18 months) in preclinical studies were examined histopathologically. The most common finding was thickening of the tunica media of intramural coronary arteries, most likely a postmortem change. The second most common finding was the presence of vacuoles within Purkinje fibers. Dilated lymphatic and blood vessels at the insertion of chordae tendineae were noted more commonly in males than in females and were considered a normal anatomic feature. Mesothelial-lined papillary fronds along the epicardial surface of the atria were present in several dogs, as were small infiltrates of inflammatory cells usually within the myocardium. In summary, control beagles' hearts frequently have incidental findings that must be differentiated from test item-related pathologic changes. Historical control data can be useful for the interpretation of incidental and test item-related findings in the beagle heart. PMID- 24178578 TI - Targeting the protein-protein interaction between IRS1 and mutant p110alpha for cancer therapy. AB - Phosphoinositide-3-kinase, catalytic, alpha polypeptide, which encodes the catalytic p110alpha subunit of phosphatidylinositol 3-kinase alpha, is the most frequently mutated oncogene in human cancers. Targeting mutant p110alpha holds great promise for cancer therapy. However, it is challenging to develop p110alpha isoform-specific inhibitors. Most p110alpha mutations occur at two hot spot regions: an acidic cluster (E542, E545, and Q546) in the helical domain and a histidine residue (H1047) in the kinase domain. We recently discovered that p110alpha helical domain mutant proteins, but not the kinase domain mutant proteins, directly associate with insulin receptor substrate 1 (IRS1). Moreover, we demonstrated that disruption of protein-protein interaction between p110alpha helical domain mutant and IRS1 inhibits the growth of tumors with such mutations. The direct protein interaction between IRS1 and p110alpha helical domain mutants may provide a more accessible target for developing novel precision cancer therapy. PMID- 24178579 TI - Persistent hepatic structural alterations following nanoceria vascular infusion in the rat. AB - Understanding the long-term effects and possible toxicity of nanoceria, a widely utilized commercial metal oxide, is of particular importance as it is poised for development as a therapeutic agent based on its autocatalytic redox behavior. We show here evidence of acute and subacute adverse hepatic responses, after a single infusion of an aqueous dispersion of 85 mg/kg, 30 nm nanoceria into Sprague Dawley rats. Light and electron microscopic evidence of avid uptake of nanoceria by Kupffer cells was detected as early as 1 hr after infusion. Biopersistent nanoceria stimulated cluster of differentiation 3(+) lymphocyte proliferation that intermingled with nanoceria-containing Kupffer cells to form granulomata that were observed between days 30 and 90. Ultrastructural tracking of ceria nanoparticles revealed aggregated nanoceria in phagolysosomes. An increased formation of small nanoceria over time observed in the latter suggests possible dissolution and precipitation of nanoceria. However, the pathway for nanoceria metabolism/secretion remains unclear. Although frank hepatic necrosis was not observed, the retention of nanoceria increased hepatic apoptosis acutely, this persisted to day 90. These findings, together with our earlier reports of 5 nm ceria-induced liver toxicity, provide additional guidance for nanoceria development as a therapeutic agent and for its risk assessment. PMID- 24178580 TI - The study pathologist's role in GLP studies: a regulator's perspective. AB - Results of early nonclinical "General Toxicology" studies are used to set a safe starting dose for first-in-human (FIH) clinical trials. In FIH trials, the research subjects are typically healthy volunteers who have little to gain but much to lose if a trial goes wrong. With that in mind, good laboratory practice regulations require that a standardized system be used for the conduct, documentation, and retention of study-related materials. The study pathologist, working within that system of standards, documentation, and oversight, is key to the identification of potential target organs of toxicity and other toxicologically significant findings. PMID- 24178577 TI - Molecular alterations and biomarkers in colorectal cancer. AB - The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer (CRC) are leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing CRCs for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor. In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of CRC and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID- 24178581 TI - The role of the peer review pathologist in good laboratory practices studies: a sponsor perspective. AB - While the study pathologist (SP) signs the pathology report and is ultimately accountable for the data, the sponsor peer review pathologist (SPRP) generally signs a peer review (PR) statement indicating agreement with the overall pathology data and the associated interpretations. Additionally, the SPRP is often the initial contact to field internal and regulatory pathology data queries. Therefore, the SPRP should conduct as comprehensive a pathology PR as necessary to have complete confidence in the data and interpretations. Ideally, the SPRP should be involved at study design, as the study evolves, through completion of the overall study report. The SPRP should prepare as much as possible before the actual PR start date to include a review of all available data that may impact the PR. This review should focus on identifying findings not already identified in the draft pathology report that may need further interrogation. While all discrepancies between the SPRP and SP may be discussed for mutual learning, the emphasis should be on resolving issues that impact study interpretation. The final pathology report should reflect the consensus between the SP and SPRP and appropriately communicate the study findings. This article provides further background and example scenarios to illustrate these PR perspectives. PMID- 24178583 TI - STP position paper: interpreting the significance of increased alveolar macrophages in rodents following inhalation of pharmaceutical materials. AB - The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology (STP) appointed a working group to address risk assessment for increases in alveolar macrophages following inhalation of pharmaceutical materials. This position paper provides recommendations for inhalation study specific terminology and interpretation based on literature and information from marketed inhaled drugs. Based on a weight-of-the-evidence approach, and with appropriate consideration of the physical and pharmacological characteristics of the compound, uncomplicated increases in the size or number of alveolar macrophages in nonclinical species are interpreted as nonadverse. PMID- 24178582 TI - Pathogenesis of pancreatic cancer: lessons from animal models. AB - The past several decades have seen great effort devoted to mimicking the key features of pancreatic ductal adenocarcinoma (PDAC) in animals and have produced 2 robust models of this deadly cancer. Carcinogen-treated Syrian hamsters develop PDAC with genetic lesions, which reproduce those of human, including activation of the Kras oncogene, and early studies in this species validated nongenetic risk factors for PDAC including pancreatitis, obesity, and diabetes. More recently, PDAC research has been invigorated by the development of genetically engineered mouse models based on tissue-specific Kras activation and deletion of tumor suppressor genes. Surprisingly, mouse PDAC appears to arise from exocrine acinar rather than ductal cells, via a process of phenotypic reprogramming that is accelerated by inflammation. Studies in both models have uncovered molecular mechanisms by which inflammation promotes and sustains PDAC and identified targets for chemoprevention to suppress PDAC in high-risk individuals. The mouse model, in particular, has also been instrumental in developing new approaches to early detection as well as treatment of advanced disease. Together, animal models enable diverse approaches to basic and preclinical research on pancreatic cancer, the results of which will accelerate progress against this currently intractable cancer. PMID- 24178584 TI - Reducing aggression and impulsivity through school-based prevention programs: a gene by intervention interaction. AB - A variety of school-based, universal preventive interventions have been developed to address behavioral and mental health problems. Unfortunately, few have been evaluated within the context of randomized controlled trials with long-term follow-up. Even fewer still have examined the potential genetic factors that may drive differential impact of the intervention. In the present analysis, we examine the extent to which the longitudinal effects of two elementary school based interventions were moderated by the brain-derived neurotrophic factor (BDNF) gene, which has been linked with aggression and impulsive behaviors. The sample included 678 urban, primarily African American children who were randomly assigned along with their teachers to one of three first grade classroom conditions: classroom-centered (CC) intervention, Family School Partnership (FSP), or a control condition. The teacher ratings of the youth's aggressive and impulsive behavior were obtained at baseline and in grades 6-12. Single nucleotide polymorphisms (SNPs) from the BDNF gene were extracted from the genome wide data. Longitudinal latent trait-state-error models indicated a significant interaction between a particular profile of the BDNF SNP cluster (46 % of sample) and CC intervention on impulsivity (beta = -.27, p < .05). A similar interaction was observed for the BDNF SNP cluster and the CC intervention on aggression (beta = -.14, p < .05). The results suggest that the impacts of preventive interventions in early elementary school on late adolescent outcomes of impulsivity and aggression can be potentially modified by genetic factors, such as BDNF. However, replication of these results is necessary before firm conclusions can be drawn. PMID- 24178585 TI - Efficient chimeric plant promoters derived from plant infecting viral promoter sequences. AB - In the present study, we developed a set of three chimeric/hybrid promoters namely FSgt-PFlt, PFlt-UAS-2X and MSgt-PFlt incorporating different important domains of Figwort Mosaic Virus sub-genomic transcript promoter (FSgt, -270 to 60), Mirabilis Mosaic Virus sub-genomic transcript promoter (MSgt, -306 to -125) and Peanut Chlorotic Streak Caulimovirus full-length transcript promoter (PFlt-, 353 to +24 and PFlt-UAS, -353 to -49). We demonstrated that these chimeric/hybrid promoters can drive the expression of reporter genes in different plant species including tobacco, Arabidopsis, petunia, tomato and spinach. FSgt-PFlt, PFlt-UAS 2X and MSgt-PFlt promoters showed 4.2, 1.5 and 1.2 times stronger GUS activities compared to the activity of the CaMV35S promoter, respectively, in tobacco protoplasts. Protoplast-derived recombinant promoter driven GFP showed enhanced accumulation compared to that obtained under the CaMV35S promoter. FSgt-PFlt, PFlt-UAS-2X and MSgt-PFlt promoters showed 3.0, 1.3 and 1.0 times stronger activities than the activity of the CaMV35S2 (a modified version of the CaMV35S promoter with double enhancer domain) promoter, respectively, in tobacco (Nicotiana tabacum, var. Samsun NN). Alongside, we observed a fair correlation between recombinant promoter-driven GUS accumulation with the corresponding uidA mRNA level in transgenic tobacco. Histochemical (X-gluc) staining of whole transgenic seedlings and fluorescence images of ImaGene GreenTM treated floral parts expressing the GUS under the control of recombinant promoters also support above findings. Furthermore, we confirmed that these chimeric promoters are inducible in the presence of 150 MUM salicylic acid (SA) and abscisic acid (ABA). Taken altogether, we propose that SA/ABA inducible chimeric/recombinant promoters could be used for strong expression of gene(s) of interest in crop plants. PMID- 24178587 TI - Reply: To PMID 23996808. PMID- 24178588 TI - Editorial. PMID- 24178586 TI - Flower senescence: some molecular aspects. AB - Some molecular aspects of flower senescence have been reviewed. The isolation, identification and characterization of different genes from various flowers (mainly from petals) associated with senescence have been discussed. The isolated genes were divided into different groups. A large proportion of genes have been found to be upregulated during flower senescence while some genes were also found to be downregulated indicating that there exists a complex interplay between the expression patterns of various genes. The genes involved in petal expansion are found to be upregulated during normal flower development from anthesis to open flower stage, but XTH (Xyloglucan endotransglucosylase hydrolase) is found to be involved in petal expansion as well as abscission. Cysteine proteases or the genes encoding cysteine proteases (assigned a central role in protein degradation) have been identified from various flower systems, but no cysteine protease has been identified from senescing Mirabilis jalapa flowers. In addition to proteases, the genes encoding ubiquitin (exhibiting proteasomal degradation by 26S proteasomes) have also been identified suggesting the two alternate pathways for protein degradation. Genes encoding specific nucleases have also been identified, but they displayed an early increase in transcript abundance before the senescence symptoms become evident and characterize the involvement of PCD during flower senescence. A range of transcription factors are described and their possible role in flower senescence has been discussed. A detailed description of genes involved in ethylene synthesis and the components involved in ethylene signaling have been presented. PMID- 24178590 TI - Titania nanotubes dimensions-dependent protein adsorption and its effect on the growth of osteoblasts. AB - In this study, we report the influence of titania nanotubes (TiNTs) dimensions on the adsorption of collagen (COL) and fibronectin (FN), and its subsequent effect on the growth of osteoblasts. TiNTs with different diameters of around 30 and 100 nm were prepared with anodization. The adsorption profiles of proteins and cell behaviors were evaluated using spectrophotometric measurement, immunofluorescence staining, cell viability, and cytoskeleton morphology, respectively. The results showed that although the growth of osteoblasts was highly sensitive to the dimensions TiNTs, the preadsorbed COL and FN could reduce the difference. Molecular dynamics (MD) simulation results confirmed that the main driving force for protein adsorption was the physical adsorption. The TiNTs with bigger dimensions had higher interaction energies, and thus leading to higher proteins (COL and FN) adsorption and obvious influences on cell behaviors. MD simulation revealed that the orientation and conformation of proteins adsorbed onto surfaces of TiNTs was critical for cell integrins to recognize specific sites. When FN molecules adsorbed onto the surfaces of TiNTs, their RGD (Arg-Gly-Asp) sites were easily exposed to outside and more likely to bond with the fibronectin receptors, in turn regulating the cellular behaviors. PMID- 24178589 TI - Top 10 recent developments in health-related quality of life in patients with systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that has major implications for health-related quality of life (HRQoL). Improvements in the monitoring and management of SLE improves survival; however, improvement of HRQoL remains of paramount importance among these patients. Measurement of HRQoL has been recommended in clinical practice and research including drug development and testing in clinical trials. Both generic and disease specific instruments have been developed to ascertain HRQoL. In an increasingly global collaborative environment, the importance of assessing HRQoL across nations, acknowledgment of their confounders, and limitations of used instruments are critical. Here, we review selected major developments in the past 5 years highlighting: the importance of measuring HRQoL in SLE patients, the benefits and limitations of instruments that exist, and their application in research settings. PMID- 24178591 TI - Differential self assembly of amphiphilic helical peptides. AB - A series of amphiphilic, helical peptides was designed and synthesized to investigate the components necessary for formation of helical bundles with differing aggregation states. Minimalistic sequences were employed for the peptides which contained either four (Leu4), six (Leu6) or eight (Leu8) leucine residues within a sixteen amino acid sequence. All peptides were highly helical as evaluated by circular dichroism, and the helical content of each peptide exhibited a concentration dependence. Size exclusion chromatography confirmed aggregation states of dimer/trimer forLeu4, tetramer forLeu6, and hexamer octamer forLeu8. Disulfide crosslinking studies also confirmed that the dimer ofLeu4 favored a parallel orientation with respect to the helical dipole. This systematic study clearly defines the role of hydrophobicity in the self assembly of helical peptides; peptides with a small hydrophobic face favor small bundle sizes, whereas peptides containing larger hydrophobic faces form correspondingly larger helical bundles. PMID- 24178592 TI - Diagnosis and follow-up of inborn errors of amino acid metabolism: Use of proton magnetic resonance of biological fluids. AB - Proton magnetic resonance spectra of biological fluids such as urine, plasma and cerebro-spinal fluid can be used for multi-component analysis of highly concentrated species, thus providing information about the general metabolism of the patient. Hydrogen containing analytes in concentration higher than 10uM are indeed often detectable in biological fluid in 15 minutes by means of an unexpensive 200 MHz spectrometer essentially without sample manipulation. Amino acids, keton bodies, organic acids and other metabolites can be easily estimated by this approach; consequently this technique represents a powerful tool particularly in the diagnosis of inborn errors of amino acid metabolism, when improving the prognosis often depends on a very early diagnosis and on an effective method for monitoring the effects of therapy.In the present paper, several cases of inherited diseases related to amino acid impaired metabolism will be presented to illustrate the importance in the diagnosis. Phenylketonuria, tyrosinemia, cystinuria, ornithinemia, argininosuccinic aciduria, maple syrup urine disease (MSUD), alkaptonuria, lysinuria and other genetic pathologies were in fact unambiguously and rapidly diagnosed by means of the identification in the biological fluids of the relevant accumulating amino acids and/or of their metabolites. The proposed technique is suitable to become, in the future, a useful routine tool for a wide neonatal screening. PMID- 24178593 TI - Branched-chainalpha-amino acid chronic treatment: responses of plasmaalpha-keto related compounds and ammonia when used in physical exercise performance. AB - To examine the effects of acute branched-chainalpha-amino acids (BCAA) oral administration following chronic BCAA intake, a group of well trained young swimmers (n = 12) was submitted to a one month chronic BCAA treatment (0.2g/Kg body weight per die; Leu: Val: Ileu = 2:1:1) and a physical exercise test before and after this period of treatment was carried out. The exercise tests (60min swim) were performed in a high circulating BCAA level state which was obtained through oral BCAA administration (or placebo) just before the beginning of the exercise. The groups will be referred to as BCAA/before, BCAA/after, placebo/before, placebo/after. Blood and plasma (antecubital vein) samples were collected from the different groups at different times: on the morning of the day before the test (basal time, rest 0), the following day 30min after an acute administration (oral dose placebo or BCAA acute treatment: Leu 4.8g, Val 2.4g, Ileu 2.4g), just before the beginning of the exercise performance (time 0min, rest 1), at the end of the exercise (time 60min, EE) and during recovery (time 120min, Re). Plasma ammonia levels increased significantly from rest 1 to the end of the exercise in all subjects, but it was significantly higher in BCAA treated than in placebo subjects in both the before and after chronic treatment groups (BCAA/before: from 38 +/- 7 to 204 +/- 65mmol/l; placebo/before: from 36 +/- 10 to 93 +/- 29mmol/l; BCAA/after: from 36 +/- 9 to 171 +/- 43mmol/l; placebo/after: from 30 +/- 6 to 65 +/- 16mmol/l). Plasma ammonia level increments observed before a chronic one month BCAA treatment were significantly higher than after this treatment (p < 0.05). Plasma alanine was at all times of the test higher before the BCAA chronic treatment than after; this difference resulted significant at rest 0, rest 1 and recovery times (p < 0.05). After acute BCAA administration, plasma BCAA levels increased from 618 +/- 52mmol/l to 1893 +/- 284mmol/l (p < 0.05) from the onset of exercise and remained elevated throughout the test. Placebo and basal (rest 0) levels both before and after the chronic treatment did not demonstrate any significant differences. Plasma BCAA and BCKA levels, in the BCAA/before demonstrated significantly higher levels than placebo/before at rest 1 time (BCAA/before vs placebo/before: Leu 86 +/- 27 vs 620 +/- 97mmol/l; KIC 60 +/- 3 vs 87 +/- 5mmol/l, Ileu 51 +/- 19 vs 359 +/- 56mmol/l, KMV 26 +/- 1 vs 43 +/- 2mmol/l, Val 290 +/- 79 vs 915 +/- 133mmol/l, KIV 14 +/- 1 vs 24 +/- 2mmol/l). The levels after the chronic treatment maintained circa these differences in the two groups BCAA/after and placebo/after. The plasma BCAA as well as the BCKA levels of acutely treated athletes, in physical exercise, showed a different profile before and after the chronic treatment. The chronic treated BCAA/after group in fact depicted a decreasing BCKA level profile at the end of the exercise and during recovery; on the contrary, before the chronic treatments, acutely treated athletes demonstrated a tendency to increase these levels during recovery. These data seem to confirm that increased BCAA availability, before exercise, result in significantly greater plasma ammonia responses during exercise than does placebo administration; furthermore this increment is lower after chronic treatment. The interpretation of the ammonia data is difficult since the exercise type could have an influence on this phenomenon. The differences in the profile patterns of alanine, BCAA and BCKA levels seem to indicate that the chronic treatment brings about a state in which there is a better use of BCAA compounds as energy supply. PMID- 24178594 TI - Photoactive amino acid derivatives with long alkyl chains. AB - Azobenzene amphiphiles containingbeta-alanine, L-lysine orbeta-homolysine moieties were synthesized and characterised. Stable monomolecular layers at the air/water interface and LB multilayers has been obtained from some of them. One sample of azobenzenes synthesized has been shown to undergo a reversible trans/cis photoisomerization upon light irradiation in both solution and LB multilayer. PMID- 24178596 TI - Putative K(+) channel inSchizosaccharomyces pombe is regulated by H(+), K (+) and cAMP at transcriptional level. AB - Living cells control their electrical responsiveness by regulating the quality and quantity of channels expressed in the plasma membrane. Regulation of transcription of the voltage-gated ion channels is an important part of the molecular basis of cell energization. However, the factors which control the expression of channels are not well understood. We studied the effect on the transcription of the voltage-gated K(+) channel in the yeastSchizosaccharomyces pombe of cations, pH, and therapeutic spasmolytic and hypotensive agents with different mechanisms of action, including accumulation of intracellular cAMP. A highly specific 122 bp domain of the K(+) channel between S5 and H5 with a 55% homology with Dros shab and mbk3 was amplified by nested PCR from chromosomal DNAS. pombe. Northern blot revealed a 1.8kb transcript. mRNA dot-blot and RNase protected analysis revealed factors altering the K(+) channel transcription. PMID- 24178595 TI - Glycine modulates N-methyl-D-aspartic acid induced learning facilitation in rats. AB - Pretraining i.p. administration of N-methyl-D-aspartic acid (NMDA) at doses of 10 and 20mg/kg dose-dependently facilitated performance in a water T-maze learning task in rats. The effect of NMDA was inhibited by the competitive NMDA receptor antagonist CGP37849 [(DL)-E(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] (CGP) at a dose of 6mg/kg, and by the NMDA receptor complex glycine site antagonist 1-hydroxy-3-amino-2-pyrrolidone (HA-966) at a dose of 10mg/kg. The NMDA site antagonist, when given alone, did not impair learning. The glycine precursor milacemide (2-N-pentylaminoacetamide HCl), at doses of 5 and 10mg/kg accelearted learning acquisition and its effect was antagonized by HA-966. The learning rate was impaired following the administration of NMDA 10mg/kg together with milacemide 5mg/kg when compared with the effect of 10mg/kg NMDA alone.The administration of 5mg/kg NMDA was associated with an elevated tissue concentration of aspartate in the hippocampus, an effect which was antagonized by 6mg/kg of CGP. NMDA at doses of 10 and 20mg/kg elevated the concentration of glycine but decreased the concentration of aspartate, glutamate and glutamine in the cortex and aspartate in the hippocampus. The cortical effects of NMDA 10mg/kg were antagonized by 6mg/kg of CGP. Milacemide at the dose of 10mg/kg elevated glycine, aspartate, glutamate and taurine concentrations. The coadministration of 5 mg/kg NMDA with 5mg/kg milacemide elevated the concentrations of glycine, glutamate and glutamine in the cortex and taurine in the hippocampus. These amino acid levels were higher than after administration of 5mg/kg either agent alone. The results demonstrate a dose-dependent facilitation effect on learning performance by NMDA and glycine receptor agonists. Antagonists at the NMDA and glycine sites counteracted the learning improvement of NMDA, and the glycine site antagonist the effect of milacemide. PMID- 24178597 TI - Relationship between the level of serum L-tryptophan and its hepatic uptake and metabolism in rats with carbon tetrachloride-induced liver cirrhosis. AB - In the serum of rats with liver cirrhosis induced by 12-week intermittent carbon tetrachloride (CCl4) injection, free L-tryptophan (Trp) levels increased with decreases in total Trp, albumin-bound Trp, and albumin levels. In the serum of the cirrhotic rats, there were no changes in the ratio of albumin-bound Trp to albumin and the level of free fatty acids which are known to weaken the binding of Trp to albumin. In the liver of the cirrhotic rats, there were increases in protein and free Trp (i.e., non-protein Trp) contents and a decrease in total tryptophan 2,3-dioxygenase (TDO) activity. The decreased TDO activity was mainly due to the reduction of apo-TDO activity. When [(3)H]Trp was injected into the portal vein of the cirrhotic and control rats, radioactivity derived from the injected [(3)H]Trp in the liver was higher in the cirrhotic rats than in the control rats at 10min after the injection, while the radioactivity in the serum was lower in the former rats than in the latter rats. These results indicate that the increased Trp is easily taken up into the cirrhotic liver, and suggest that the Trp taken up into the cirrhotic liver could be utilized for the maintenance of synthesis of proteins in the tissue through the reduction of Trp metabolism due to reduced TDO activity in the tissue. PMID- 24178599 TI - Editorial. PMID- 24178598 TI - An insight in the mechanism of the aminoethylcysteine ketimine autoxidation. AB - Oxidation of aminoethylcysteine ketimine (AECK) is followed by the change of 296nm absorbance, by the O2 consumption and by the HPLC analysis of the oxidation products. The oxidation is strongly inhibited by the addition of superoxide dismutase (SOD) but not by hydroxyl radical scavengers or catalase. Addition of EDTA or o-phenanthroline (OPT) favours the oxidation, probably by keeping contaminating metals in solution at the pH studied. Addition of Fe(3+) ions strongly accelerates the oxidation in the presence of EDTA or OPT. AECK reacts stoichiometrically with OPT-Fe(3+) complex producing the Fe(2+) complex which is not reoxidised by bubbling O2. HPLC analyses of the final oxidation products reacting with 2,4-dinitrophenylhydrazine (DNPH) confirm the AECK sulfoxide as the main product of the slow spontaneous oxidation. The detection of other oxidation products when the reaction is speeded up by the addition of the OPT-Fe(3+) complex, suggests that the oxidation takes place essentially on the carbon portion of the AECK molecule in the side of the double bond. On the basis of the results presented here, a scheme of reactions is illustrated which starts with the transfer of one electron from AECK to a contaminating metal ion (possibly Fe(3+)) producing the radical AECK(*) as the initiator of a self propagating reaction. The radical AECK(*) reacting with O2 starts a series of reactions accounting for most of the products detected. PMID- 24178600 TI - Prevention in psychiatry -Problems and prospects. AB - Traditionally, psychiatry concerns itself with practice with the amelioration of behavioral and emotional symptoms. Since mental illness occupies more hospital beds than all other illnessess combined, its traditional role of treating mental illness is understandable. However, because of new methods of correlating genetic, intrauterine, environmental, and interactive factors, there seems to be what we might consider preventive modes, thereby establishing new therapeutic models. PMID- 24178601 TI - Family and peer relationships in children with paranoid delusions. PMID- 24178602 TI - Emotional reactions of children and adolescents to renal transplantation. AB - Coping defenses of children undergoing renal transplantation were taxed as the child progressed through the crucial phases of surgical procedures. Four of 12 children displayed serious disruption of defense mechanisms at some point during hospitalization with recovery of equilibrium when the stress was removed. Hemodialysis evoked a forceful emotional reaction. The most vulnerable period appeared to be immediately postoperative when ego resources could be depleted if surgical complications occurred. Profound depression or regression could be seen in a previously functional child. PMID- 24178603 TI - A "Rage-reduction" diagnostic technique with young children. AB - A rage-reduction diagnostic technique adapted for use with young children has been described and its potential delineated. This procedure has been effective with children, ages three to six, who present a confusing clinical picture in terms of speech development, intellectual status, parent-child relationships, degree of emotional disturbance, and possible brain syndrome. In addition, rage reduction provides an alternate method of evaluation when a child refuses to cooperate with traditional assessment methods, and may be the diagnostic technique of choice in selected cases.Rage-reduction is not proposed as a panacea for differential diagnosis, nor as a substitute for full-scale psychological or psychiatric workups. Itis proposed as a useful addition to diagnostic armamentarium. With omnipotent, controlling children, and in settings where time and staff allocation relative to heavy caseloads makes full clinical assessment of children the exception rather than the rule, the use of the technique can be a parsimonious approach to diagnosis. PMID- 24178604 TI - Production of fertile transgenic peanut (Arachis hypogaea L.) plants using Agrobacterium tumefaciens. AB - Fertile transgenic plants of peanut (Arachis hypogaea L. cv. New Mexico Valencia A) were produced using an Agrobacterium-mediated transformation system. Leaf section explants were inoculated with A. tumefaciens strain EHA105 harboring the binary vector pBI121 containing the genes for beta-glucuronidase (GUS) and neomycin phosphotransferase II (NPTII). Approximately 10% of the shoots regenerated on selection medium were GUS-positive. Five independent transformation events resulted in the production of 52 fertile transgenic peanut plants. On average, 240 d were required between seed germination for explant preparation and the production of mature t1 seed by T0 plants. Molecular analysis of transgenic plants confirmed the stable integration of the transgenes into the peanut genome. GUS expression segregated in a 3?1 Mendelian ratio in most T1 generation plants. PMID- 24178605 TI - In vitro regeneration of Alnus cremastogyne Burk from epicotyl explants. AB - Multiple shoots were grown from seedling explants of Alnus cremastogyne Burk by a two-stage culture procedure: initiation on WP medium supplemented with 2-8 MU M benzylammopurine(BAP) for 6 weeks, thereafter 3 weeks of subculture(shoot multiplication) on the same medium with 1 MU M BAP. A 5-9 fold multiplication rate was achieved. Type and concentration of sugar used in the multiplication medium were shown to be critical factors for both multiple shoot induction and bud elongation, the optima being 87.5mM glucose and 87.5mM sucrose respectively. After transfer to half-strength WP media either containing indolebutyric acid (IBA) or lacking plant growth regulator, almost all the shoots rooted. However, high rhizogenesis could be achieved only with shoots cultured in rooting medium containing 87.5mM sucrose or 175mM glucose, and shoots from multiplication media containing 87.5mM sucrose. Survival of the plantlets following transfer to vermiculite was 100%. PMID- 24178606 TI - Genetic diversity of potato determined by random amplified polymorphic DNA analysis. AB - The RAPD procedure was used to establish genetic diversity of 28 potato genotypes including siblings and genotypes with no immediate relationship. In addition amplified DNA from three parents and Solanum chacoense were compared with that from six progeny to determine the genetic relationships. Amplification of genomic DNA from the 28 genotypes using PCR and 12 decamer primers yielded 158 amplified DNA fragments, ranging in size from 490 to 3200 bp. A total of 128 unique RAPD fragments were observed among the 28 potato genotypes. Similarity measures and principal coordinate analysis generally reflected the expected trends in relationships of the full and half-sib potato genotypes. However there were important exceptions to this general trend and it appears that related varieties can be as genetically different as varieties with no immediate relationship. The data suggest that RAPD analysis used in conjunction with pedigree information can provide a superior measure of genetic divergence than analysis based solely on pedigree information. PMID- 24178607 TI - High frequency production of doubled haploid plants of Brassica napus cv. Topas derived from colchicine-induced microspore embryogenesis without heat shock. AB - This report describes a very high genome doubling efficiency of Brassica napus cv. Topas plants, derived from microspores induced to undergo embryogenesis with a colchicine treatment, without the use of a heat treatment. The plants showed normal growth and development, and 90% were fertile. In contrast, only 6% of the plants derived from heat-induced embryos were fertile diploids. All cytological analysis of the progeny of fertile plants showed 2n=38 chromosomes. These results show that colchicine can simultaneously induce microspore embryogenesis and double the ploidy level to produce doubled haploid plants. PMID- 24178608 TI - Further evidence of a cybridization requirement for plant regeneration from citrus leaf protoplasts following somatic fusion. AB - Somatic hybridization experiments in Citrus that involve the fusion of protoplasts of one parent isolated from either nucellus-derived embryogenic callus or suspension cultures with leaf-derived protoplasts of a second parent, often result in the regeneration of diploid plants that phenotypically resemble the leaf parent. In this study, plants of this type regenerated following somatic fusions of the following three parental combinations were analyzed to determine their genetic origin (nuclear and organelle): (embryogenic parent listed first, leaf parent second) (1) calamondin (C. microcarpa Bunge) + 'Keen' sour orange (C. aurantium L.), (2) Cleopatra mandarin (C. reticulata Blanco) + sour orange, and (3) 'Valencia' sweet orange (C. sinensis (L.) Osbeck) + 'Femminello' lemon (C. limon (L.) Burm. f.). Isozyme analyses of PGI, PGM, GOT, and IDH zymograms of putative cybrid plants, along with RFLP analyses using a nuclear genome-specific probe showed that these plants contained the nucleus of the leaf parent. RFLP analyses using mtDNA-specific probes showed that these plants contained the mitochondrial genome of the embryogenic callus donor, thereby confirming cybridization. RFLP analyses using cpDNA-specific probes revealed that the cybrid plants contained the chloroplast genome of either one or the other parent. These results support previous reports indicating that acquisition of the mitochondria of embryogenic protoplasts by leaf protoplasts is a prerequisite for recovering plants with the leaf parent phenotype via somatic embryogenesis following somatic fusion. PMID- 24178609 TI - Construction and rapid testing of synthetic and modified toxin gene sequences CryIA (b&c) by expression in maize endosperm culture. AB - The synthesis of two modified genes, Cry IA(b) and CryIA(c), each consisting of 1845 bp, is described in detail. The genes were synthesized using an improved PCR procedure based on recursive principles. The synthetic CryIA(c) gene was put under the control of a maize ubiquitin promoter. This construct was tested in a maize endosperm-derived suspension culture system. The use of maize endosperm culture as a quick and efficient system to test the activity of synthetic genes is described. PMID- 24178610 TI - Cell reabsorption in the Euphorbia dulcis endosperm. AB - Euphorbia dulcis endosperm is the site of controlled long lasting endocellular lysis involving segregation and autophagy of portions of the cytoplasm within the endoplasmic reticulum membrane. The lysis products may constitute a food source for the benefit of the early developing embryo. PMID- 24178611 TI - Synergistic effect of ethylene inhibitors and putrescine on shoot regeneration from hypocotyl explants of Chinese radish (Raphanus sativus L. var. longipinnatus Bailey) in vitro. AB - The role of ethylene and putrescine on shoot regeneration from hypocotyl explants of Chinese radish (Raphanus sativus L. var. longipinnatus Bailey cv. Red Coat) was investigated. Explants were recalcitrant in culture, but exogenous application of ethylene inhibitor [20-30 MUM aminoethoxyvinylglycine (AVG) or AgNO3] enhanced shoot regeneration of explants grown on medium supplemented with 2 mg/l N(6)-benzyladenine and 1 mg/l 1-naphthaleneacetic acid. The best regeneration occurred in the medium containing AgNO3 in combination with AVG. Culture medium solidified with agarose in the presence of AgNO3 but not AVG was also beneficial to shoot regeneration. Exogenous putrescine, 2 chloroethylphosphonic acid and 1-aminocyclopropane-1-carboxylate had no effect on shoot regeneration. However, regeneration was greatly promoted by 10-25 mM putrescine in combination with 30 MUM AgNO3 or AVG. Explants with high regenerability grown in the presence of AgNO3 or in combination with putrescine emanated high levels of ethylene throughout the 21-d culture period. By contrast, AVG or putrescine alone resulted in a decrease in ethylene production. For rooting of shoot cuttings, IAA and IBA at 1-5 mg/l were more effective than NAA. PMID- 24178612 TI - Forskolin synthesis in in vitro cultures of Coleus forskohlii Briq transformed with Agrobacterium tumefaciens. AB - Agrobacterium tumefaciens mediated tumor tissue and shooty teratomas of Coleus forskohlii were cultured in vitro. Forskolin was detected in tumorous callus (0.002%), rhizogenic callus (0.011%) and root cultures (0.014%), but not in shooty teratomas. Forskolin synthesis and accumulation in tumorous C. forskohlii cultures may permit the elucidation of diterpene metabolism in this species. PMID- 24178613 TI - The effects of proline, thioproline and methylglyoxal-bis-(guanylhydrazone) on shoot regeneration frequencies from stem explants of B. napus. AB - Internode segments from aseptic shoot cultures are the most prolific explants for the regeneration of Brassica shoots in vitro. These explants also have the advantage of not being subject to the genotypic variations in regeneration response observed in hypocotyl and cotyledon explants. Despite reports of 80-100% shoot regeneration from stem explants, observed frequencies are typically 50-60%. Three media additives, proline, thioproline and methylglyoxal-bis (guanylhydrazone) (MGBG), were tested for their efficacy in promoting shoot regeneration from stem explants of two B. napus varieties, Westar and Cobra. The effects of proline and thioproline on both varieties were neutral or deleterious. In Cobra the MGBG treatments caused a uniform reduction in explant regeneration. However, at low concentrations (0.35MUM) MGBG resulted in a 50% increase, to 92%, in regeneration from Westar. The potential of MGBG in promoting explant regeneration in B. napus is discussed in the light of its interaction with the explant genotype. PMID- 24178614 TI - Cryopreservation of somatic embryos and embryonic axes of Camellia japonica L. AB - Cryopreservation in liquid nitrogen was attempted with both somatic embryos and zygotic embryonic axes of the ornamental Camellia japonica L. Several protective measures were applied to somatic embryos (desiccation, chemical protectors, hardening by culture at low temperatures, encapsulation in alginate beads), but none allowed somatic embryos cultures to survive after 24 h in liquid nitrogen. Embryonic axes, however, were easily cryopreserved by means of the simplest technique: desiccation in a laminar flow hood and direct immersion in liquid nitrogen. Although the causes of the difference in cryopreservability between the two types of material are not known, one might be the difference between their degrees of differentiation and water content. PMID- 24178615 TI - Micropropagation of Sterculia urens Roxb. - an endangered tree species. AB - An in vitro procedure for large scale multiplication of Sterculia urens Roxb. (Gum Kadaya Tree) has been developed using cotyledonary node segments. An average of 4.0 shoots per node were obtained on Murashige and Skoog's (MS) medium containing 2.0 mgl(-1) 6-benzyl amino-purine (BAP) within 21 days of initial culture. Upon subsequent subculture 16 shoots/node could be harvested every three weeks and upto three times. Sixty per cent of the shoots were successfully rooted. Rooted plantlets were transferred to plastic pots containing soil under mist house conditions before they were finally exposed to an external environment. Fifty seven per cent of the plantlets survived in nursery sheds. PMID- 24178616 TI - A relationship between callose and ectodesmata in epidermal cells of Allium cepa L. AB - The outer wall of adaxial epidermal cells of onion bulb scales shows punctate callose deposits. The abundance of these callose deposits is highly variable, and seems to correlate with the distribution of ectodesmata. It is proposed that callose is involved in the regulation of ectodesmata as a waterflow regulator and/or molecular filter, thus influencing the cell-environment interaction. PMID- 24178617 TI - A simple and efficient procedure for cryopreservation of embryogenic cells of aromatic Indica rice varieties. AB - Embryogenic suspension cells of two commercially cultivated aromatic Indica rice varieties, Basmati 385 and Pusa Basmati 1, were cryopreserved using a simple one step freezing procedure that does not require a controlled-rate freezer. The procedure involves osmotic pre-conditioning of cells with mannitol, addition of a cryoprotectant solution consisting of sucrose, dimethyl sulfoxide, glycerol, proline, and modified R2 medium, cooling to -25 degrees C for 2 h in a freezer, and then storage in liquid nitrogen. After rapid thawing at 45 degrees C, these cultures showed post-thaw cell viability of 5.6 to 10.5% and formed actively dividing, readyto-use cell suspensions in 20-35 d when cultured directly into liquid medium. Plants were regenerated from cell clumps as well as from colonies formed by protoplasts that were isolated from suspension cells re-established from cryopreserved cells, with frequencies higher (54-98%) than, or comparable to, those obtained from three to four-month-old original non-frozen cell cultures. Cell viability and regeneration frequencies of post-thawed Pusa Basmati 1 cultures were similar to those obtained from the suspension cells cryopreserved using the conventional slow-freezing procedure which involves pre-freezing cells to -40 degrees C at the rate of -0.2 degrees C per min prior to immersion in liquid nitrogen. In Basmati 385, however, cells frozen at --25 degrees C showed lower post-thaw cell viability than those preserved using the slow-freezing procedure, but these cells produced cell suspensions that had greater shoot morphogenetic potential. The study indicates the beneficial effect of this simple freezing procedure, not only for preserving desirable cultured cells but also for an enrichment of embryogenic cells. PMID- 24178618 TI - Inhibition of mitochondrial respiration by the flavone aglycone isovitexin causes aberrant petal and leaf morphology in Silene latifolia. AB - The morphological mutant "isovitexin" in Silene latifolia (the white campion) has small and up-curled petals and leaves. In this mutant the aglycone isovitexin is the only flavone present in the vacuole. In the present study it is shown that isovitexin has a strong toxic effect on mitochondria that is to a large extent abolished by glycosylation. This effect can be used to explain the aberrant morphology. Isovitexin acts at the level of the ubiquinone pool; cytochrome c - cytochrome aa3 oxidase activity was unaffected, and with either reduced nicotinamide adenine dinucleotide or succinate as a respiratory substrate, effects on respiration were found in Silene leaves-, potato (Solanum tuberosum) tuber- and sweet potato (Ipomoea batata L.) tuber mitochondria. Since in sweet potato electron transport via the cyanide insensitive pathway was also inhibited, with the ubiquinone pool as the only component (besides the dehydrogenases) shared by these two pathways, the site of inhibition must be at this level. PMID- 24178619 TI - Plant regeneration from encapsulated embryoids and an embryogenic mass of pistachio, Pistacia vera L. AB - Pieces of an embryogenic mass (EMS) induced in culture from immature fruits of pistachio, Pistacia vera L., were encapsulated into calcium alginate beads. Somatic embryos were also encapsulated individually into calcium alginate beads to produce synthetic seeds. The viability of the encapsulated EMS and somatic embryos was investigated immediately following encapsulation, and after storage for 60 days at 4 degrees C. The encapsulated-stored EMS fragments recovered their original proliferative capacity after two months storage following two sub cultures, but non-encapsulated-stored EMS failed to recover. The conversion frequency of synthetic seeds to seedling plants was 14% after storage for 60 days at 4 degrees C, from which it may be concluded that encapsulation is a practical procedure for short-term storage of embryogenic pistachio tissue, and may be applicable to the preservation of desirable elite genotypes. PMID- 24178620 TI - Antitumoral activity of lenalidomide in in vitro and in vivo models of mantle cell lymphoma involves the destabilization of cyclin D1/p27KIP1 complexes. AB - PURPOSE: Clinical responses to the immmunomodulatory drug lenalidomide have been observed in patients with relapsed/refractory mantle cell lymphoma (MCL), although its mechanism of action remains partially unknown. We investigated whether the expression and subcellular localization of cyclin D1, a major cell cycle regulator overexpressed in MCL, and the cyclin-dependent kinase inhibitor p27(KIP1), could identify MCL cases sensitive to lenalidomide, and whether the compound could modulate cyclin D1/p27(KIP1) complexes in MCL cells. EXPERIMENTAL DESIGN: MCL primary samples and cell lines were analyzed for subcellular levels of cyclin D1/p27(KIP1) complexes by Western blot, immunohistochemistry, immunoprecipitation, and flow cytometry. Activity of lenalidomide in vitro and its effect on cyclin D1/p27(KIP1) complexes were evaluated by real-time PCR, immunoprecipitation, immunofluorescence, and Western blot. In vivo validation was carried out in a mouse xenograft model of human MCL. RESULTS: We found cyclin D1 and p27(KIP1) to be coordinately expressed in all the MCL samples tested. Immunoprecipitation analyses and siRNA assays suggested a direct role of cyclin D1 in the regulation of p27(KIP1) levels. The nuclear accumulation of both proteins correlated with MCL cell tumorigenicity in vivo, and sensitivity to lenalidomide activity in vitro and in vivo. Lenalidomide mechanism of action relied on cyclin D1 downregulation and disruption of cyclin D1/p27(KIP1) complexes, followed by cytosolic accumulation of p27(KIP1), cell proliferation arrest, apoptosis, and angiogenesis inhibition. CONCLUSIONS: These results highlight a mechanism of action of lenalidomide in MCL cases with increased tumorigenicity in vivo, which is mediated by the dissociation of cyclin D1/p27(KIP1) complexes, and subsequent proliferation blockade and apoptosis induction. PMID- 24178621 TI - Integrative genomic analysis of temozolomide resistance in diffuse large B-cell lymphoma. AB - PURPOSE: Despite advances, there is an urgent need for effective therapeutics for relapsed diffuse large B-cell lymphoma, particularly in elderly patients and primary central nervous system (CNS) lymphoma. Temozolomide (TMZ), an oral DNA alkylating agent routinely used in the therapy of glioblastoma multiforme, is active in patients with primary CNS lymphoma but the response rates are low. The mechanisms contributing to TMZ resistance are unknown. EXPERIMENTAL DESIGN: We undertook an unbiased and genome-wide approach to understand the genomic methylation and gene expression profiling differences associated with TMZ resistance in diffuse large B-cell lymphoma cell lines and identify mechanisms to overcome TMZ resistance. RESULTS: TMZ was cytotoxic in a subset of diffuse large B-cell lymphoma cell lines, independent of MGMT promoter methylation or protein expression. Using Connectivity Map (CMAP), we identified several compounds capable of reversing the gene expression signature associated with TMZ resistance. The demethylating agent decitabine (DAC) is identified by CMAP as capable of reprogramming gene expression to overcome TMZ resistance. Treatment with DAC led to increased expression of SMAD1, a transcription factor involved in TGF-beta/bone morphogenetic protein (BMP) signaling, previously shown to be epigenetically silenced in resistant diffuse large B-cell lymphoma. In vitro and in vivo treatment with a combination of DAC and TMZ had greater antilymphoma activity than either drug alone, with complete responses in TMZ-resistant diffuse large B-cell lymphoma murine xenograft models. CONCLUSIONS: Integrative genome wide methylation and gene expression analysis identified novel genes associated with TMZ resistance and demonstrate potent synergy between DAC and TMZ. The evidence from cell line and murine experiments supports prospective investigation of TMZ in combination with demethylating agents in diffuse large B-cell lymphoma. PMID- 24178623 TI - Homologous constitutive expression of Xyn III in Trichoderma reesei QM9414 and its characterization. AB - Xylanase III (Xyn III), a specific endoxylanase that belongs to family 10 of the glycoside hydrolases, was overexpressed in Trichoderma reesei QM9414 using a constitutive strong promoter of the gene encoding pyruvate decarboxylase (pdc). The maximum recombinant xylanase activity achieved was 817.2 +/- 65.2 U/mL in the transformant fermentation liquid. The productivities of Xyn III accounted for approximately 53% of the total protein secreted by the recombinant. The enzyme was optimally active at 60 degrees C and pH 6. The recombinant Xyn III was stable at pH 5-8. This is the first report on the homologous expression of xyn3 in T. reesei QM9414. The properties of Xyn III make it promising in a variety of industrial use. PMID- 24178624 TI - Synthesis of sulfonic acid-functionalized Fe3O4@C nanoparticles as magnetically recyclable solid acid catalysts for acetalization reaction. AB - The Fe3O4@C core-shell magnetic nanoparticles with an average size of about 190 nm were synthesized via a one-pot solvothermal process using ferrocene as a single reactant. The sulfonic acid-functionalized Fe3O4@C magnetic nanoparticles were obtained by grafting the sulfonic groups on the surface of Fe3O4@C nanoparticles to produce magnetically recyclable solid acid catalysts. The as prepared products were characterized by X-ray diffraction and transmission electron microscopy. The catalytic performance of the as-prepared catalysts was examined through the condensation reaction of benzaldehyde and ethylene glycol. The results showed that the catalysts exhibited high catalytic activity with a conversion rate of 88.3% under mild conditions. Furthermore, catalysts with a magnetization saturation of 53.5 emu g(-1) at room temperature were easily separated from the reaction mixture by using a 0.2 T permanent magnet and were reused 8 times without any significant decrease in catalytic activity. PMID- 24178622 TI - Phase II study of the oral MEK inhibitor selumetinib in advanced acute myelogenous leukemia: a University of Chicago phase II consortium trial. AB - PURPOSE: The clinical relevance of targeting the RAS/RAF/MEK/ERK pathway, activated in 70% to 80% of patients with acute myelogenous leukemia (AML), is unknown. EXPERIMENTAL DESIGN: Selumetinib is an oral small-molecule inhibitor of MAP-ERK kinase (MEK)-1/2. Forty-seven patients with relapsed/refractory AML or 60 years old or more with untreated AML were enrolled on a phase II study. Patients were stratified by FLT3 ITD mutation status. The primary endpoint was response rate (complete, partial, and minor). Leukemia cells were analyzed for extracellular signal-regulated kinase (ERK) and mTOR phosphorylation. RESULTS: Common drug-related toxicities were grade 1-2 diarrhea, fatigue, nausea, vomiting, and skin rash. In the FLT3 wild-type cohort, six of 36 (17%) patients had a response [one partial response, three minor responses, two unconfirmed minor responses (uMR)]. No patient with FLT3 ITD responded. NRAS and KRAS mutations were detected in 7% and 2% of patients, respectively. The sole patient with KRAS mutation had uMR with hematologic improvement in platelets. Baseline p ERK activation was observed in 85% of patients analyzed but did not correlate with a response. A single-nucleotide polymorphism (SNP) rs3733542 in exon 18 of the KIT gene was detected in significantly higher number of patients with response/stable disease compared with nonresponders (60% vs. 23%; P = 0.027). CONCLUSIONS: Selumetinib is associated with modest single-agent antileukemic activity in advanced AML. However, given its favorable toxicity profile, combination with drugs that target other signaling pathways in AML should be considered. The potential association of SNP rs3733542 in exon 18 of the KIT gene with antileukemic activity of selumetinib is intriguing, but will require validation in larger trials. PMID- 24178625 TI - OSA and coronary plaque characteristics. AB - BACKGROUND: Virtual histology intravascular ultrasound (VH-IVUS) is an intravascular imaging technique that enables the characterization of coronary plaques. We sought to determine the association between OSA and coronary plaque characteristics in patients presenting with coronary artery disease. METHODS: We prospectively recruited patients with angiographically proven coronary artery disease for a VH-IVUS examination and home-based sleep study. The total atheroma volume of the entire target coronary artery and the incidence of thin cap fibroatheroma of patients with no to mild and moderate to severe OSA were compared. RESULTS: One hundred eighteen patients were recruited from two university-affiliated centers. Among the 93 patients who completed the study, 32 (34.4%) had newly diagnosed moderate to severe OSA (apnea-hypopnea index > 15). Compared with patients with no to mild OSA, those with moderate to severe OSA had a larger total atheroma volume (461.3 +/- 250.4 mm3 vs 299.2 +/- 135.6 mm3, P < .001), and the association remained after adjustment for age, BMI, hypertension, diabetes mellitus, smoking, and hyperlipidemia (relative mean difference, 1.73; 95% CI, 1.38-2.15). In contrast, there were no significant differences between the patients with moderate to severe OSA and no to mild OSA regarding the prevalence of thin cap fibroatheroma in the culprit lesion (53.1% vs 54.2%, P = .919). CONCLUSIONS: In patients presenting with coronary artery disease, moderate to severe OSA was independently associated with a larger total atheroma volume in the target coronary artery. Further studies on the effects of CPAP on total atheroma volume are warranted. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01306526; URL: www.clinicaltrials.gov. PMID- 24178626 TI - Preparing to understand and use science in the real world: interdisciplinary study concentrations at the Technical University of Darmstadt. AB - In order to raise awareness of the ambiguous nature of scientific-technological progress, and of the challenging problems it raises, problems which are not easily addressed by courses in a single discipline and cannot be projected onto disciplinary curricula, Technical University of Darmstadt has established three interdisciplinary study concentrations: "Technology and International Development", "Environmental Sciences", and "Sustainable Shaping of Technology and Science". These three programmes seek to overcome the limitations of strictly disciplinary research and teaching by developing an integrated, problem-oriented approach. For example, one course considers fundamental nuclear dilemmas and uses role-playing techniques to address a controversy in the area of nuclear security. At the same time, incorporating interdisciplinary teaching into a university that is organized around mono- or multi-disciplinary faculties also poses a number of challenges. Recognition in disciplinary curricula, and appropriate organizational support and funding are examples of those challenges. It is expected that science and engineering students, empowered by such interdisciplinary study programmes, will be better prepared to act responsibly with regard to scientific and technological challenges. PMID- 24178627 TI - Student-driven courses on the social and ecological responsibilities of engineers : commentary on "student-inspired activities for the teaching and learning of engineering ethics". AB - A group of engineering students at the Technical University of Berlin, Germany, designed a course on engineering ethics. The core element of the developed Blue Engineering course are self-contained teaching-units, "building blocks". These building blocks typically cover one complex topic and make use of various teaching methods using moderators who lead discussions, rather than experts who lecture. Consequently, the students themselves started to offer the credited course to their fellow students who take an active role in further developing the course themselves. PMID- 24178628 TI - Neurocognitive function and dysfunction after hepatitis C therapy. PMID- 24178629 TI - Media multitasking and failures of attention in everyday life. AB - Using a series of online self-report measures, we examine media multitasking, a particularly pervasive form of multitasking, and its relations to three aspects of everyday attention: (1) failures of attention and cognitive errors (2) mind wandering, and (3) attentional control with an emphasis on attentional switching and distractibility. We observed a positive correlation between levels of media multitasking and self-reports of attentional failures, as well as with reports of both spontaneous and deliberate mind wandering. No correlation was observed between media multitasking and self-reported memory failures, lending credence to the hypothesis that media multitasking may be specifically related to problems of inattention, rather than cognitive errors in general. Furthermore, media multitasking was not related with self-reports of difficulties in attention switching or distractibility. We offer a plausible causal structural model assessing both direct and indirect effects among media multitasking, attentional failures, mind wandering, and cognitive errors, with the heuristic goal of constraining and motivating theories of the effects of media multitasking on inattention. PMID- 24178630 TI - Health-related quality of life among breast, prostate, and colorectal cancer patients with end-stage disease. AB - PURPOSE: To explore end-stage breast, prostate, and colorectal cancer patients' health-related quality of life (HRQoL); to compare results obtained by different HRQoL instruments; and to explore factors related to impaired HRQoL. METHODS: A cross-sectional observational study utilized two generic HRQoL instruments, the 15D and the EQ-5D, and a cancer-specific instrument, the EORTC QLQ-C30. Patients were recruited from the Helsinki University Hospital's Department of Oncology and from a local hospice. RESULTS: Of the 114 palliative care patients included in the analysis, 27 had breast cancer, 30 had prostate cancer, and 57 had colorectal cancer. Of these, 28 % died within 3 months after their response, while 32 % died within three to 6 months, and 39 % died more than 6 months after. Utility values varied widely by instrument: the 15D gave the highest utility values and VAS the lowest (15D: 0.74, EQ-5D: 0.59 and VAS: 55). Patients close to death had lower HRQoL scores independently from the instrument used. The EQ-5D showed a pronounced ceiling effect, with 13 % of patients reporting full health, whereas the corresponding figures for the 15D and VAS were 1 and 0 %, respectively. Fatigue was the most common symptom and also predicted impaired HRQoL most significantly. CONCLUSIONS: All instruments were applicable for the evaluation of HRQoL among end-stage cancer patients. Fatigue seemed to be the most significant deteriorating factor, whereas clinical and demographic factors had less of an effect on HRQoL. PMID- 24178631 TI - Comparison of face-to-face interview and telephone interview administration of COPD assessment test: a randomized study. AB - OBJECTIVE: To assess the measurement properties of the COPD assessment test (CAT) in a randomized trial comparing a face-to-face interview (FFI) with a telephone interview (TI). METHODS: A randomized study was conducted at two teaching hospitals in Fortaleza, Brazil. Patients were randomly assigned to answer the CAT questionnaire either in a FFI or by TI. The two groups were assessed for internal consistency reliability, cross-sectional validity and test-retest reliability. All patients performed spirometry and answered the modified medical research council dyspnea scale and the St. George's respiratory questionnaire (SGRQ). RESULTS: The total scores of the CAT questionnaire were similar for face-to-face and TI groups, 20.71 (95 % CI 18-23.4) versus 20.81 (95 % CI 19.31-21.7), respectively. For both mode of administration, we found good internal consistency reliability, the Cronbach's alpha ranged from 0.74 (95 % CI 0.61-0.84) to 0.89 (95 % CI 0.84-0.93) for the TI and FFI, respectively. In general, moderate-to high correlations of CAT with SGRQ were observed, independent of the administration format. For the test-retest reliability, the intraclass correlation coefficients were very similar for both FFI and TI group 0.96 (95 % CI 0.93-0.97) versus 0.98 (95 % CI 0.96-0.98), respectively. CONCLUSION: This study demonstrated that the CAT questionnaire administration either in a FFI or by TI presents moderate-to-high measurement properties. This provides support for the use of both modes of questionnaire administration. PMID- 24178632 TI - Application of an ampholine-functionalized hybrid organic-inorganic silica material for the SPE of aromatic amines. AB - An SPE cartridge based on an ampholine-functionalized hybrid organic-inorganic silica sorbent has been adopted for the analysis of aromatic amines including 4 aminobiphenyl, benzidine, 2-naphthylamine, p-chloroaniline, 2,4,5 trimethylaniline, and 3,3'-dichlorobenzidine. Crucial variables governing the extraction efficiency of the material such as the pH of sample, sample loading volume, solvent used for elution, and elution volume have been thoroughly optimized. The adsorption capacities for the six aromatic amines ranged from 0.17 to 1.82 MUg/mg. The recoveries of aromatic amines spiked in textile samples ranged from 78.9 to 103.0%, with RSDs of 1.1-11.9% (n = 3). Moreover, the extraction efficiency of the ampholine-functionalized hybrid organic-inorganic silica sorbent was at least comparable with that of Oasis WCX. PMID- 24178633 TI - Can assertive community treatment remedy patients dropping out of treatment due to fragmented services? AB - Previously, many patients with severe mental illness had difficulties to engage with fragmented mental health services, thus not receiving care. In a Dutch city, Assertive Community Treatment (ACT) was introduced to cater specifically for this group of patients. In a pre-post comparison, changes in mental health care consumption were examined. All mental health care contacts, ACT and non-ACT, of patients in the newly started ACT-teams were extracted from the regional Psychiatric Case Register. Analyses of mental health care usage were performed comparing the period before ACT introduction with the period thereafter. After the introduction of ACT, mental health care use increased in this group of patients, although not all patients remained under the care of ACT teams. ACT may succeed in delivering more mental health care to patients with severe mental illness and treatment needs who previously had difficulties engaging with fragmented mental health care services. PMID- 24178635 TI - Syntheses of fluorinated amino acids: from the classical to the modern concept. AB - A survey of the synthetic pathways leading to the fluorine-containing analogues of amino acids is given. From the great number of syntheses the typical examples are selected and divided into two groups: classical syntheses and the modern ones. The classical ammonolysis of halogeno acids and equivalent reactions are discussed as first, followed by a few examples of oxo -> amino group transformation. Conversion of the oxo compounds into amino acids richer by one carbon atom is realized by the Strecker and hydantoin syntheses. For the prolongation by two carbons, the Erlenmeyer azlactone method and alkylation of CH acidic esters are applied. The modern syntheses are represented by direct fluorination by elemental fluorine and other electrophilic fluorinating reagents. Further examples include the applications of the Yarovenko reagent, sulphur tetrafluoride and its derivative DAST. The use of trifluoropyruvates as the fluoro synthons is mentioned briefly. Finally, the examples of the amidocarboxylation method and the syntheses of diverseomega-fluorinated methionines are shown. PMID- 24178634 TI - Taurine: A therapeutic agent in experimental kidney disease. AB - Taurine is an abundant free amino acid in the plasma and cytosol. The kidney plays a pivotal role in maintaining taurine balance. Immunohistochemical studies reveal a unique localization pattern of the amino acid along the nephron. Taurine acts as an antioxidant in a variety ofin vitro andin vivo systems. It prevents lipid peroxidation of glomerular mesangial cells and renal tubular epithelial cells exposed to high glucose or hypoxic culture conditions. Dietary taurine supplementation ameliorates experimental renal disease including models of refractory nephrotic syndrome and diabetic nephropathy. The beneficial effects of taurine are mediated by its antioxidant action. It does not attenuate ischemic or nephrotoxic acute renal failure or chronic renal failure due to sub-total ablation of kidney mass. Additional work is required to fully explain the scope and mechanism of action of taurine as a renoprotective agent in experimental kidney disease. Clinical trials are warranted to determine the usefulness of this amino acid as an adjunctive treatment of progressive glomerular disease and diabetic nephropathy. PMID- 24178636 TI - Effects of branched-chain amino acids on plasma amino acids in amyotrophic lateral sclerosis. AB - Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, biological findings suggest that the excitatory amino acid glutamate contributes to the pathogenesis of ALS. In previous studies of ALS, the therapeutic effect of the branched-chain amino acids (BCAAs) leucine, valine and isoleucine has been evaluated. The present study aimed at investigating the acute effect of BCAAs on plasma glutamate levels in ALS patients. Following two oral doses of BCAAs, significantly increased plasma levels were seen for valine (500%), isoleucine (1,377%) and leucine (927%), however the plasma level of glutamate was not affected. The plasma level of several other amino acids (tryptophan, tyrosine, phenylalanine and methionine) were found decreased after oral BCAAs, which may indicate a diminution in the rate of degradation of muscle protein and/or an increase in tissue disposal of amino acids. PMID- 24178637 TI - Rabbit model simulating transient hyperglycinemia following transurethral prostatectomy. AB - Glycine was intravenously injected in rabbits and resulted in a dose dependent hyperglycinemia. A dose of 10mmol/kg was sufficient to achieve plasma levels of 10 to 16mM comparable to serum levels in patients at the end of a transurethral prostatectomy. The experiments documented that hyperglycinemia is associated with a significant increase of this substance in tissues outside the plasma compartment. Glycine loading resulted in a tenfold elevation of this amino acid in cerebrospinal fluid 10 minutes after injection. In retina and vitreous humor a five- to tenfold increase in glycine content was observed at 10 minutes post injection while in the anterior chamber fluid the maximum increase appeared at 30 minutes.Significant increases of the glycine content were found in different cerebral structures at 30 minutes post administration.The significant elevations of this neurotransmitter within the central nervous system are prerequisites for possible toxic side effects in the course of transurethral prostatectomy (TURP). Hyperglycinemia might be involved in the pathogenesis of visual disturbances following transurethral prostatectomy and the other neurological complications of TURP syndrome. Our observations add more evidence to this hypothesis. PMID- 24178638 TI - Influence of triiodothyronine and dexamethasone on renal amino acid handling in rats loaded with various amino acid mixtures. AB - In adult female rats, the influence of dexamethasone or triiodothyronine on renal amino acid handling was investigated in amino acid loaded animals. Amino acids were administered intravenously as two mixtures, each containing four amino acids to overload amino acid reabsorption capacity. Bolus injections of both mixtures were followed by temporary increase in fractional excretion of the administered amino acids as well of the amino acids which were not covered in the mixtures. The administration of the two mixtures was followed by different interactions between various amino acid carriers.After dexamethasone pretreatment (60ug/100g b.wt. for 3 days, once daily) a stimulation of the renal amino acid handling could be shown. Triiodothyronine (20ug/100g b.wt. for 3 days, once daily) did not increase tubular reabsorption capacity for amino acids. It even increased fractional amino acid excretion in amino acid loaded rats as a sign of enhanced amino acid metabolism in the kidney and/or increased amino acid uptake into the tubular cells from the luminal site. PMID- 24178639 TI - L-Arginine inhibits in vitro nonenzymatic glycation and advanced glycosylated end product formation of human serum albumin. AB - L-Arginine (Arg) has a structure similar to that of aminoguanidine (AG) and may inhibit glycation and advanced glycosylated end product (AGE) formation. Human serum albumin (HSA) (100mg/ml) was incubated for 2 weeks with glucose (200mM) at 37 degrees C or with glucose and equimolar concentrations of Arg, N-alpha-acetyl Arg, or AG with or without 25mM diethylenetriaminepentaacetic acid (DTPA). In the absence of DTPA, electrospray ionization mass spectrometry showed a 70% reduction of covalently bound glucose in the presence of Arg and a 30% reduction with AG. Digestibility by trypsin of HSA incubated with glucose and Arg was similar to that of HSA incubated alone. This suggests less covalent modification of HSA in the presence of Arg as compared with the absence of Arg. When incubations contained DTPA, autoradiography showed less(14)C labeling of HSA subunits in the presence of Arg and AG. When thealpha-amino group of Arg was blocked with an acetyl group, labeling was similar to that of HSA incubated with glucose, suggesting involvement of thealpha-amino group in the inhibition. Fluorescence of HSA at ex370 and em440 was reduced with Arg, but AG was more effective than Arg. These results suggest that Arg, like AG, can inhibit glycation and AGE formation. PMID- 24178640 TI - Tryptophanase-catalysed degradation of D-tryptophan in highly concentrated diammonium hydrogen phosphate solution. AB - Tryptophanase is and is perfectly inert to D-tryptophan under ordinary conditions. However, activity that can degrade D-tryptophan into indole is observed when tryptophanase is in highly concentrated diammoniumhydrogen phosphate solution. The reaction has been so far unknown in tryptophanase metabolic pathways. Here we report the characteristic of the reaction. We also discuss its significance in relation to selection of an amino acid optical isomer from a racemic mixture. PMID- 24178641 TI - Diet treatment of branched chain ketoaciduria studied by proton magnetic resonance spectroscopy. AB - A novel nuclear magnetic resonance method is proposed for the diagnosis and follow-up of patients affected by branched chain ketoaciduria. The method allows quantitation of the branched chain amino acids (BCAA's) such as leucine, isoleucine and valine and of related keto- and hydroxy acids by means of a single spectrum. The method implies short time of analysis, as opposed to the very long time required by the techniques currently in use (amino acid analyzer combined with gaschromatography/mass spectrometry of keto- and hydroxyacids), it is easy and suitable for adjustements of the dietary treatment even on a daily basis. The case of a 15 days old newborn child, presenting muscular hypertonicity was unambiguously diagnosed in few minutes by means of one single NMR spectrum of urine. More interestingly, NMR spectra of serum in the following days were suitable for quantitating amino-, and keto acids as well as other metabolites of relevance in the follow up of the dietary treatment of the disease. After a diet lacking of BCAA's, to eliminate keto acids, a low BCAA diet was introduced, that succeeded in keeping the serum levels of the three amino acids within the normal range, while dropping the related keto acids. PMID- 24178642 TI - Homocysteine and oxidative modification of plasma proteins. AB - The oxidative status of plasma proteins after incubation with elevated homocysteine levels has been examined in the presence and absence of transition metal ions. 200uM homocysteine alone does not provoke any loss of plasma thiols groups, but their oxidation significantly enhances as copper concentration increases. No plasma proteins carbonyl groups enhancement has been concurrently found.The physiological relevance of the study is discussed in relationship with the metal-catalyzed oxidation system increment connected with age and nutritional deficiences. PMID- 24178643 TI - Callus induction, regeneration of haploid plants and chromosome doubling in ovule cultures of pot gerbera (Gerbera jamesonii). AB - Gynogenetic plants of pot gerbera (Gerbera jamesonii) were successfully produced from cultures of unpollinated ovulesin vitro. Genotypic variations in the number of ovules that formed callus were found among the lines tested. One particularly responsive genotype was found among 17 genotypes tested where the frequency of callus-forming ovules was 17.5%. Four genotypes formed no callus at all. The frequency of shoot formation from the callus varied from 0-19.6% in nine genotypes. Ploidy was determined by flow cytometry, and 37 (80.4%) regenerants were haploid, seven (15.2%) were diploid, and two (4.3%) were mixoploid with both haploid and diploid cells. The doubling of chromosomes was achieved by treatment with 0.05% colchicine for 2-6 din vitro, and 24.2-34.1% of treated haploid plants were found to have been diploidized. PMID- 24178644 TI - Rapid transformation ofMedicago truncatula: regeneration via shoot organogenesis. AB - A rapid transformation and regeneration system has been developed forM. truncatula cv Jemalong (barrel medic) by which it is possible to obtain transgenic plants within 2.5 months. The procedure involvesAgrobacterium-mediated transformation of cotyledon explants coupled with the regeneration of transformed plants via direct organogenesis. To develop the procedure,M. truncatula explants were transformed with the binary plasmid pSLJ525 which carries thebar gene. Thebar gene encodes phosphinothricin acetyl transferase, and transformed plants were selected on media containing phosphinothricin (Ignite, AgrEvo). Transformed plants show phosphinothricin acetyl transferase activity and Southern blot analysis indicates that they carry thebar gene integrated into their genomes. The resistance to phosphinothricin is stable and is inherited by the R1 progeny as a single dominant Mendelian trait. The transgenic plants are highly resistant to the broad spectrum herbicide, Ignite and therefore may also have commercial applications. PMID- 24178645 TI - Accelerated production of transgenic wheat (Triticum aestivum L.) plants. AB - We have developed a method for the accelerated production of fertile transgenic wheat (Triticum aestivum L.) that yields rooted plants ready for transfer to soil in 8-9 weeks (56-66 days) after the initiation of cultures. This was made possible by improvements in the procedures used for culture, bombardment, and selection. Cultured immature embryos were given a 4-6 h pre-and 16 h post bombardment osmotic treatment. The most consistent and satisfactory results were obtained with 30 MUg of gold particles/bombardment. No clear correlation was found between the frequencies of transient expression and stable transformation. The highest rates of regeneration and transformation were obtained when callus formation after bombardment was limited to two weeks in the dark, with or without selection, followed by selection during regeneration under light. Selection with bialaphos, and not phosphinothricin, yielded more vigorously growing transformed plantlets. The elongation of dark green plantlets in the presence of 4-5 mg/l bialaphos was found to be reliable for identifying transformed plants. Eighty independent transgenic wheat lines were produced in this study. Under optimum conditions, 32 transformed wheat plants were obtained from 2100 immature embryos in 56-66 days, making it possible to obtain R3 homozygous plants in less than a year. PMID- 24178646 TI - Plant regeneration from mesophyll protoplasts ofDianthus superbus. AB - Leaf mesophyll protoplasts ofDianthus superbus were cultured at a density of 5 * 10(4) protoplasts/ml and divided at about 18% plating efficiency in MS liquid medium supplemented with 0.5 mg/L BAP, 2.0 mg/L NAA and 9% mannitol after 2 weeks. Protocolonies formed after 3 to 4 weeks of culture in the dark at 27 degrees C. These colonies were transferred to continuous illumination (21.5 MUE m(-2) sec(-1)) for 2 weeks where most of the colonies divided to form microcalli, about 2 mm in diameter. Subsequently, green microcalli were transferred to MS solidified medium with 2.0 mg/L 2,4-D that induced shoot-forming calli after 4 weeks. These calli were transferred onto N6-2 medium containing 0.1 mg/L 2,4-D, 0.1 mg/L NAA, 2.0 mg/L kinetin and 2.0 g/L casein hydrolysate and were cultured under light. After 5 weeks the calli gave rise to multiple shoots (10 to 15 per callus). Upon transfer to MS medium containing 2.0 mg/L NAA, individual shoots were rooted in 4 weeks. The regenerants were successfully transplanted into potting soil. PMID- 24178647 TI - Plant regeneration from protoplasts ofVicia narbonensis via somatic embryogenesis and shoot organogenesis. AB - Protoplasts ofVicia narbonensis isolated from epicotyls and shoot tips of etiolated seedlings were embedded in 1.4% sodium-alginate at a final density of 2.5*10(5) protoplasts/ml and cultivated in Kao and Michayluk-medium containing 0.5 mg/I of each of 2,4- dichlorophenoxyacetic acid, naphthylacetic acid and 6 benzylaminopurine. A division frequency of 36% and a plating efficiency of 0.40 0.5% were obtained. Six weeks after embedding, protoplast-derived calluses were transferred onto gelrite-solidified Murashige and Skoog-media containing various growth regulators. Regeneration of plants was achieved via two morphologically distinguishable pathways. A two step protocol (initially on medium with a high auxin concentration followed by a culture phase with lowered auxin amount) was used to regenerate somatic embryos, whereas cultivation on medium containing thidiazuron and naphthylacetic acid resulted in shoot morphogenesis. Mature plants were recovered from both somatic embryos as well as from thidiazuron induced shoots. PMID- 24178648 TI - Agrobacterium rhizogenes-mediated DNA transfer inPinus halepensis Mill. AB - Agrobacterium rhizogenes strain LBA9402 was used to transformPinus halepensis embryos, seedlings and shoots. Mature embryos exhibited susceptibility to the agrobacterium as monitored by beta-glucurortidase (GUS) expression, with more than 85% showing considerable transient GUS expression in the radicle. GUS expression was also observed in cotyledons, but at a lower rate of about 24% of the embryos (1-5 spots/embryo). Stable transformation was evidenced by the regeneration of GUS-expressing roots and calli from infectedP. halepensis seedlings. Inoculum injections into intact seedling hypocotyls induced callus and root formation at the wound sites in 64% of the seedlings. Dipping seedling cuttings in a bacterial suspension resulted in adventitious root formation in 7I% of the seedling cuttings, all of which expressed GUS activity. Adventitious shoots, that were induced on 2.5-year-old seedlings by pruning and spraying with 6-benzylaminopurine, were infected by injecting of bacterial suspension into their basal side. Two months later, adventitious roots and root primordia regenerated in 74% and 40% of 2- and 5-month-old shoots, respectively. Non transformed shoots, either without or with auxin application, failed to form roots. Polymerase chain reaction and Southern blot analyses confirmed theuidA transgenic nature of the root and callus, as well as the presence ofrolC androlB genes in roots from infectedP. halepensis seedlings. PMID- 24178649 TI - Efficient transgenic plant regeneration throughAgrobacterium-mediated transformation of Chickpea (Cicer arietinum L.). AB - Three genotypes of chickpea ICCV-1, ICCV-6 and a Desi (local) variety were tested for plant regeneration through multiple shoot production. The embryo axis was removed from mature seeds, the root meristem and the shoot apex were discarded. These explants were cultured on medium containing MS macro salts, 4X MS micro salts, I35 vitamins, 3.0 mg/1 BAP, 0.004 mg/1 NAA, 3% (w/v) sucrose and incubated at 26(0)C. The explants were transformed withAgrobacterium tumefaciens strain LBA4404 with binary vector pBI121 containing theuidA andnptIl genes. Multiple shoots were repeatedly selected with kanamycin. The selected kanamycin resistant shoots were rooted on MS medium supplemented with 0.05 mg/1 113A. The presumptive transformants histochemically stained positive for GUS. Additionally, nptll assay confirmed the expression ofnptII in kanamycin resistant plants. Transgenic plants were transferred to soil and grown in the green house. PMID- 24178650 TI - Genetic transformation ofRhododendron byAgrobacterium tumefaciens. AB - TransgenicRhododendron plants were obtained byAgrobacterium tumefaciens-mediated gene transfer.A. tumefaciens harboring a binary vector that contained the chimeric neomycin phosphotransferase II (NPTII) and (3-glucuronidase (GUS) genes was co-cultivated with stem and leaf segments fromRhododendron tissues culturedin vitro. Adventitious buds were fonned and shoots were regenerated on kanamycin selection medium 3-4 months after inoculation. Integration of the NPTII and the GUS genes was confirmed by polymerase chain reaction (PCR) and by Southern hybridization analyses. Histochemical GUS assay showed that the inserted gene was expressed in all tissues with the cauliflower mosaic virus (CaMV) 35S promoter. This transformation procedure has the potential to expand the range of genetic variation inRhododendron. PMID- 24178651 TI - Plant regeneration of eucalypts from rotating nodule cultures. AB - Nodule cultures were induced from shoot tips of aseptically grownEucalyptus botryoides in a vertically rotated incubator. N-(2-chloro-4-pyridyl)-N' phenylurea (4PU) was a very effective cytokinin for induction of nodules in liquid B5 basal medium supplemented with naphthalene acetic acid and 3% sucrose.The effective concentration of 4PU ranged from 0.2 to 0.5mg/l. The nodule had a very smooth surface and was composed of small meristematic cells outside and large vacuolated cells inside. Shoots were regenerated from these cultures on media supplemented with 6-benzyladenine at 0.2mg/l in place of 4PU. These regenerated shoots were successfully rooted and cultivated in the field. Nodule cultures were maintained for 3-4 years with monthly subcultures without losing proliferation and regeneration abilities. Nodules were also successfully induced from other eucalypts, namelyE. camaldulensis, E. deglupta andE.grandis with slightly modified media. Furthermore, nodule cultures were also induced from shoot tips of field-grown plants inE.camaldulensis. This system is beneficial for both mass propagation of selected elite clones and creation of genetically engineered plants. PMID- 24178652 TI - Effect of(12)C (+5) ion beam irradiation on cell viability and plant regeneration in callus, protoplasts and cell suspensions ofLavateva thuringiaca. AB - The biological effects of irradiation with(12)C(+5) ion beam on plant cells have been analyzed. Protoplasts and cell suspensions ofLavatera thuringiaca, and a somatic hybrid callus (Hibiscus rosa-sinensis +Lavatera thuringiaca), were irradiated with doses from 0.05 to 50 Gy, and the effects on cell growth, cell division, cell viability and embryogenesis rates were analyzed. Irradiation with(12)C(+5) ion beam at relatively very low doses (5.0 Gy) significantly inhibited cell division, yet the survival rate and regeneration capability of the cells through somatic embryogenesis were conserved in more than 70 and 50 %, respectively. These results indicate that cell division is the most sensitive parameter to irradiation, accounting for the inhibition of colony formation and callus growth. The potential use of the(12)C(+5) ion beam in asymmetric protoplast fusion experiments is discussed. PMID- 24178653 TI - Plantlet regeneration from mesophyll protoplasts ofBetula platyphylla var.japonica. AB - InBetula platyphylla var.japonica, colonies were induced efficiently from mesophyll protoplasts cultured in half strength MS (1/2MS) liquid medium containing 0.6 M mannitol, 0.09M sucrose and 1 MUM 4-PU and 1 MUM NAA at a cell density of 5 * 10(4)/ml. The colonies grew actively and developed into callus after 3 months of culture.Roots differentiated from the protoplast-derived white calluses cultured on the 1 /2MS solid media supplemented with 0.1-1 MUM 4-PU and 1 MUM NAA, and 10 MUM zeatin with no supplementation of NAA. Furthermore, the protoplast-derived green callus differentiated shoots with 1/2MS solid medium containing 1 MUM 4-PU or 10 MUM zeatin with no supplementation of NAA. When shoots obtained were cultured on the cytokinin-free MS solid medium with 2.5 MUM IBA and 0.1 MUM NAA, they rooted and developed into plantlets after one month of culture.The phenylurea-type cytokinin, 4-PU, was effective for plantlet regeneration from the mesophyll protoplasts ofB. platyphylla var.japonica. This suggests that there is potential for the use of 4-PU in the culture of protoplasts in many forest tree species. PMID- 24178654 TI - Expression of bacterial isochorismate synthase (EC 5.4.99.6) in transgenic root cultures ofRubia peregrina. AB - The gene coding for isochorismate synthase (EC 5.4.99.6) was amplified by the polymerase chain reaction fromEscherichia coli, cloned into a binary vector. and mobilised intoAgrobacterium rhizogenes LBA9402 which was used to transformRubia peregrina. Transgenic roots containing bacterial isochorismate synthase cDNA expressed twice as much isochorismate synthase activity (4.88 pkat/mg protein) as the control roots (2.45 pkat/mg protein) after 10 days in culture, and accumulatedca. 20% higher levels of total anthraquinones after 30 days in culture. Whilst the amount of total alizarin (free and bound) in the transgenic roots was 30% higher than in control roots, the level of free alizarin wasca. 85% higher. PMID- 24178655 TI - Relationship between endogenous auxin and cytokinin levels and morphogenic responses inActinidia deliciosa tissue cultures. AB - Thein vitro culture ofActinidia deliciosa petioles results in a decline of cytokinin content and an increase of auxin levels. The addition of plant growth regulators (PGRs) to the medium lead to recovery of the initial auxin content, and callus induction occurs at the basal end of the explants. Endogenous auxin/cytokinin ratio was higher at this side than in the apical one, due to unequal distribution of endogenous PGRs in the cultured petioles. Some of the induced calluses showed shoot formation when they were transferred to proliferation medium. Most important differences found in hormonal content between organogenic and non-organogenic callus concerned benzyladenine levels. In this paper the relationships between explant behaviour and their hormonal content is discussed. PMID- 24178656 TI - Growing tobacco cells respond to rapid medium changes with a transient increase in localized Ca(2+) activity. AB - A suspension of tobacco cells,Nicotiana tabacum L. BY-2, was subjected to a rapid change of medium, resulting in disturbance of growth. A subpopulation of growing cells responded to such a nutritional signal by establishing a transient, localized Ca(2+) accumulation, as judged by chlorotetracycline fluorescence. Residing near or at the plasma membrane, this initial Ca(2+) signal began to relax after 1 h to a value presumably corresponding to an equilibrium Ca(2+) level. This response was susceptible to treatment with brefeldin A, an agent impacting vesicular traffic, as indicated by a further increase in fluorescence. By contrast, undisturbed growing and non-growing cells did not display a Ca(2+) response, regardless of the presence of brefeldin A. PMID- 24178657 TI - Direct regenerationin vitro and transient GUS expression inMentha xpiperita. AB - Genetic transformation of peppermint is known to be very difficult essentially because of low efficiency regeneration. A regeneration protocol allowing 51% shooting frequency is proposed. Transient beta-glucuronidase expression and adjustment of selection pressure with kanamycin are also reported. The final retained method to attempt peppermint transformation is:Agrobacterium inoculation or biolistic treatment of the first apical leaves ofin vitro clones, regeneration in the dark with kanamycin (1 mg l(-1)) and 6-benzylaminopurine (2 mg l(-1)), followed by selection of regenerated shoots with 200 mg 1(-1) kanamycin. PMID- 24178658 TI - Transgenic sweet pepper plants fromAgrobacterium mediated transformation. AB - Fertile transgenic sweet pepper (Capsicum annuum var. grossum) plants were regenerated at relatively high rate from various explants that were cocultivated withAgrobacterium tumefaciens strain GV3111-SE harbouring a plasmid that contains the cucumber mosaic virus coat protein (CMV-CP) gene. The rate of plant regeneration was found to depend on the types of explants cultured and the media used. Young leaves were most effective for bud induction and subsequent plant elongation while hypocotyls were the most inefficient. Southern analysis of DNA isolated from putative transgenic plants revealed that 3 out of 5 R1 plant lines reacted positively with the CMV-CP gene. Western blot analysis of CMV-CP containing R1 plants showed that two of them accumulated significant levels of the foreign gene product while the other two expressed it only, to low levels. Thus, like many other dicotyledonous plant species, sweet pepper can be transformed byA. tumefaciens and regenerated into healthy, fertile plants that express foreign genes. PMID- 24178659 TI - Partial auxin deprivation affects endogenous cytokinins in an auxin-dependent, cytokinin-independent tobacco cell strain. AB - The dynamics of individual endogenous cytokinins within the growth cycle (subculture interval) of an auxin-dependent and cytokinin-independent cell suspension culture ofNicotiana tabacum L. (strain VBI-0) were determined using high performance liquid chromatography and radioimmunoassay. In cells grown at an optimum auxin concentration the transient maxima of N(6)-(Delta(2) isopentenyl)adenine and N(6)-(Delta(2)-isopentenyl)-adenosine correlated with the onset of cell division. Cultivation of the cells in a partially auxin-deprived medium resulted in ca. tenfold increase of all endogenous cytokinins. A very distinct maximum of N(6)-(Delta(2)-sopentenyl) adenine appeared at the beginning of subculture. This indicates that a lack of auxin induced an accumulation of cytokinins predominantly in the form of the free bases, which are physiologically more active than the corresponding ribosides. PMID- 24178660 TI - In vitro propagation ofMimosa tenuiflora (Willd.) Poiret, a Mexican medicinal tree. AB - Mimosa tenuiflora (Willd.) Poiret (Leguminosae) was micropropagated throughin vitro culture of axillary buds on Murashige and Skoog (MS) medium. Shoot formation was achieved when the media were supplemented with 0.1 mg.L(-1) IAA + 3 mg.L(-1) KN.In vitro rooting of regenerated shoots was achieved when 0.1 mg.L(-1) KN was combined with 1 mg.L(-1) IBA in the absence of IAA. Ninety-four percent of the rooted plants were succesfully adapted to field conditions and grown in the soil. A total of 180 trees grown under these conditions were obtained over a one year period. PMID- 24178661 TI - A highly efficientin vitro regeneration methodology for mature Chinese tallow tree (Sapium sebiferum Roxb.). AB - A highly efficientin vitro regeneration methodology for mature chutese tallow tree (Sapium sebiferum Roxb.) has been developed. Shoot segments cultured on MS medium supplemented with 7.5 uM NAA produced light green callus. Optimum shoot differentiation resulted when callus was transferred to MS medium with 1 uM BA and 0.25 uM NAA. Shoot forming ability of callus was higher on MS medium compared to B5, half-MS or WPM. A continuous shoot harvest system at four-week intervals was established. Shoot yield continued for six months without loss of vigour. Regenerated shoots were rooted by culturing on half strength agar-gelled MS medium containing 1 uM IBA. Rooted plantlets were transferred to 1:1 soil vermiculite mixture and acclimatized with 67 % survival rate. Fully acclimatized plants were planted in the field, and performance is being evaluated. PMID- 24178662 TI - Plant regeneration from protoplasts isolated from callus ofGentiana crassicaulis. AB - Fast growing calli induced from hypocotyl segments ofGentiana crassicaulis were used for preparation of protoplasts. High yields of viable protoplasts were produced in an enzyme solution containing 1-2% cellulase, I% pecfinase, and 0.5% Hemicellulase. Protoplasts were cultured in KM8P medium containing 1 mg/l 2,4-D, 0.5 mg/l 6BA, 500 mg/l LH, 0.5 M glucose and 0.1 M mannitol by the solid-liquid dual layer culture method. First division occurred within 4-5 days of culture at a frequency of 17.8%. Sustained divisions led to callus formation. Periodically diluting the cultures with freshly prepared liquid medium containing 1% glucose was critical for colony formation. Protocolonies about 2 mm in size were transferred onto MS medium supplemented with 3 mg/l ZT, 2 mg/l 6BA, 1 mg/l GA3, 1 mg/l NAA and 6% sucrose to obtain embryogenic calli. Plantlets were regenerated via somatic embryogenesis at high frequency on hormone-free MS Medium. PMID- 24178663 TI - Protoplast culture and plant regeneration ofPinellia ternata. AB - A study was undertaken to develop a protoplast regeneration system for pinellia. A yield of 19 29 x 10(5) protoplasts/g F. W. could be obtained from cell suspension cultures incubated in a digestion enzyme solution with 2% cellulase Onzuka R-10, 10% pectinase (Sigma), 0.01% pectolyase Y23. K8P and modified MS media were used to culture protoplasts in: a) liquid, b) liquid-solid double layer, or c) agarose embedded protoplast culture. The former two were conducive to colony formation from protoplast-derived cells. The frequency of cell division was about 8% after 3 days in culture. Gradually adding fresh medium of lower osmotic pressure into the medium for protoplast culture favored cell division. Calli (1-2 mm in diameter) formed after 30-40 days in culture. The calli transferred onto medium supplemented with KT (0.5 mg 1(-1)) and NAA (0.2 mg 1)( 1)) could regenerate plants after 40-50 days. Of 47 plantlets transplanted into plots, 29 flowered and were fertile. PMID- 24178664 TI - Oryzalin combined with adventitious regeneration for an efficient chromosome doubling of trihaploid kiwifruit. AB - Chromosome doubling of one parthenogenetic trihaploid from cultivar Hayward ofActinidia deliciosa was investigated. Two antimitotic agents, colchicine and oryzalin, appliedin vitro on shoots and leaves at different concentrations were compared with regard to their efficiency. Survival and regeneration rates were determined and ploidy level of regenerated plantlets was evaluated by flow cytometry. Differences were observed between the two antimitotic agents depending on whether shoots or leaves were treated. Hexaploid plantlets were obtained with highest efficiency by adventitious regeneration from leaves treated by oryzalin at 5 MUM, constituting an original and promising result which was corroborated for another trihaploid clone. Dodecaploid plantlets were also induced but only from oryzalin treated leaves. On the other hand, colchicine applied to leaves was very phytotoxic. This study demonstrates that oryzalin combined with adventitious regeneration is particularly efficient to induce chromosome doubling of trihaploid kiwifruit. PMID- 24178665 TI - Isozyme patterns in zygotic and somatic embryogenesis of carrot. AB - Isozyme patterns of carrot (Daucus carota L.) zygotic embryos between the torpedo stage up to 5-day-old seedlings have been compared with those of the similar stages from the embryogenic cell suspension culture to the late somatic plantlet. Somatic embryos blocked at the torpedo stage by beta-cyclodextrine have also been analyzed. All these stages have been analyzed with respect to seven different enzyme systems: arylesterase, glucosephosphate isomerase, phosphogluconate dehydrogenase, alcohol dehydrogenase, isocitrate dehydrogenase, aspartate aminotransferase and phosphoglucomutase (EC 2.7.5.1, PGM). The relationships between the different stages of both types of embryogenesis have been visualized using an unrooted tree. Generally, profiles of somatic embryos were different from those of zygotic embryos. Interestingly however, a typical zygotic embryo pattern was found in the cyclodextrine-blocked somatic embryos. Only aspartate aminotransferase patterns revealed a similarity between zygotic and somatic torpedo embryos. Both plantlet types showed close patterns with common isozymes. Moreover, similarities were evident between somatic plantlets and cell suspensions. A few isozymes appeared to be stage specific markers: esterase 10-11 were specific to achenes and early germination, phosphogluconate dehydrogenase 8 was specific to 4-5 day-old seedlings and phosphoglucomutase 1 and 7 and alcohol dehydrogenase 4 were markers for zygotic embryos. No somatic embryogenesis specific isozyme could be found. We show that patterns can be associated with particular tissue formation: mainly, aspartate aminotransferase 2 and 1, phosphoglucomutase 8 and 9 and phosphogluconate dehydrogenase 7 coincided with apical meristem initiation and phosphoglucomutase 4 and 5, zones "b" and "d" of esterase and zone "b" of phosphogluconate dehydrogenase coincided with vascular bundle formation. PMID- 24178666 TI - Improvements in rooting regenerated safflower (Carthamus tinctorius L.) shoots. AB - A continuing obstacle for regenerating safflower (Carthamus tinctorius L.) plants from cultured explants or callus has been a reliable method for rooting shoots. For shoots directly regenerated from primary explants, 76% of shoots rooted after a 7-d exposure to 10 mg/1 indole-3-butyric acid. Auxin source, concentration or exposure time did not greatly affect root formation or morphology, but strongly affected callus production. Shoots infected with Agrobacterium rhizogenes produced massive numbers of fibrous roots, but shoots did not elongate or survive transfer to soil. Shoot hyperhydricity symptoms were reduced by including 1 g/1 activated charcoal in rooting media. The optimal protocol for inducing root formation consisted of a 7-d exposure to 10 mg/l indole-3-butyric acid in root induction media, followed by incubation in media containing 15 g/l sucrose and 1 g/1 activated charcoal for 21 d. PMID- 24178667 TI - Induction of streptomycin-resistant plantlets inCapsicum annuum L. through mutagenesisin vitro. AB - Streptomycin resistant shoots were regenerated from mutagenised (ethylemethane sulphonate treated) cotyledon explants ofCapsicum annuum Cv G4. Streptomycin resistant shoots developed from green (unbleached) sectors of the cotyledons. Reciprocal crosses betweeen streptomycin resistant and sensitive plants have shown a non-mendelian transmission. Such mutant plants should be useful in designing biochemical selection schemes to recover somatic hybrids and cybrids ofC. annuum. PMID- 24178668 TI - Regeneration andAgrobacterium-mediated transformation ofForsythia xintermedia "Spring Glory". AB - Internode explants ofin vitro plants ofForsythia x intermedia "Spring Glory" were transformed with thegus andnpt II genes after inoculation with theA. tumefaciens strain EHA 101 harbouring the plasmid pFAJ3000. Shoot organogenesis took place from callused edges of explants. The first transformed buds were detected 4 to 6 weeks after transfer on regeneration medium, containing 25 mg/l kanamycin as selective agent. An average of 1% of explants regenerated transgenic shoots.beta glucuronidase assays and culture on kanamycin-containing medium provided the first indication of integration and expression of introduced genes in transformants. Southern blot and polymerase chain reaction amplification analyses gave molecular confirmation of genetic transformation. Transgenic plants were acclimatized in the greenhouse. Enzymatic assays on several organs of mature plants still showed beta-glucuronidase activity, thus confirming stable integration of T-DNA in the plant genome. PMID- 24178669 TI - Random amplified polymorphic DNA (RAPD) detection of dwarf off-types in micropropagated Cavendish (Musa spp. AAA) bananas. AB - A RAPD marker specific to the dwarf off-type (hereafter known as dwarf) from micropropagation of Cavendish banana (Musa spp. AAA) cultivars New Guinea Cavendish and Williams was identified following an analysis of 57 normal (true-to type) and 59 dwarf plants generated from several different micropropagation events. Sixty-six random decamer primers were used in the initial screen, of which 19 (28.8%) revealed polymorphisms between normal and dwarf plants. Primer OPJ-04 (5'-CCGAACACGG-3') was found to amplify an approx. 1.5 kb band which was consistently present in all normal but absent in all dwarf plants of both cultivars. Reliable detection of dwarf plants was achieved using this marker, providing the only available means ofin vitro detection of dwarfs. The use of this marker could facilitate early detection and elimination of dwarfs from batches of micropropagated bananas, and may be a useful tool in determining what factors in the tissue culture process lead to this off type production.Other micropropagation-induced RAPD polymorphisms were observed but were not associated with the dwarf trait. PMID- 24178670 TI - The analysis of temporal gene expression to estimate the age of forensically important blow fly pupae: results from three blind studies. AB - The estimation of the minimum postmortem interval can be implemented by age estimation of corpse-associated primary colonizers such as the blow flies (Diptera: Calliphoridae). In cases where pupae represent the oldest stages found on a body, their age must be added to the duration of prepupal development to estimate the minimum postmortem interval. Although methods to age blow fly larvae have been well established using morphology, length or weight and age estimation of pupae has proved challenging. In a previous work, we quantified the changes in mRNA levels of four differentially expressed genes during the metamorphosis of Calliphora vicina pupae, hence representing molecular markers for pupal age (i.e., time elapsed since pupariation). Here, we demonstrate how these data can be used to estimate pupal age with inverse prediction. We present three blind studies conducted under various conditions and show that age of C. vicina pupae can be well estimated based on gene expression data. As these data are quantitative and can be processed automatically, gene expression has the potential to outperform morphological analysis in age estimation of forensically relevant blow fly pupae. PMID- 24178671 TI - Influence of the examiner's qualification and sources of error during stage determination of the medial clavicular epiphysis by means of computed tomography. AB - Computed tomography (CT) of the medial clavicular epiphysis has been well established in forensic age estimations of living individuals undergoing criminal proceedings. The present study examines the influence of the examiner's qualification on the determination of the clavicular ossification stage. Additionally, the most frequent sources of error made during the stage assessment process should be uncovered. To this end, thin-slice CT scans of 1,420 clavicles were evaluated by one inexperienced and two experienced examiners. The latter did the evaluations in consensus. Two classification systems, a five-stage system and a substaging system for the main stages 2 and 3, were used. Prior to three of his six assessment sessions, the inexperienced examiner was specifically taught staging of clavicles. Comparison of the examiners' results revealed increasing inter- and intraobserver agreements with increasing state of qualification of the inexperienced examiner (from kappa= 0.494 to 0.674 and from kappa= 0.634 to 0.783, respectively). The attribution of a not-assessable anatomic shape variant to an ossification stage was identified as the most frequent error during stage determination (n= 349), followed by the overlooking of the epiphyseal scar defining stage 4 (n= 144). As to the clavicular substages, classifying substage 3a instead of 3b was found to be the most frequent error (n= 69). The data of this study indicate that kappa values must not be considered as objective measures for inter- and intraobserver agreements. Furthermore, a high degree of specific qualification, particularly the knowledge about the diversity of anatomic shape variants, appears to be mandatory and indispensable for reliable evaluation of the medial clavicular epiphysis. PMID- 24178672 TI - Ultrasound assessment of pulmonary embolism in patients receiving CT pulmonary angiography. AB - BACKGROUND: CT pulmonary angiography (CTPA) is considered the gold standard for the diagnosis of pulmonary embolism (PE) and is frequently performed in patients with cardiopulmonary complaints. However, indiscriminate use of CTPA results in significant exposure to ionizing radiation and contrast. We studied the accuracy of a bedside ultrasound protocol to predict the need for CTPA. METHODS: This was an observational study performed by pulmonary/critical care physicians trained in critical care ultrasonography. Screening ultrasonography was performed when a CTPA was ordered to rule out PE. The ultrasound examination consisted of a limited ECG, thoracic ultrasonography, and lower extremity deep venous compression study. We predicted that CTPA would not be needed if either DVT was found or clear evidence of an alternative diagnosis was established. CTPA parenchymal and pleural findings, and, when available, formal DVT and ECG results, were compared with our screening ultrasound findings. RESULTS: Of 96 subjects who underwent CTPA, 12 subjects (12.5%) were positive for PE. All 96 subjects had an ultrasound study; two subjects (2.1%) were positive for lower extremity DVT, and 54 subjects (56.2%) had an alternative diagnosis suggested by ultrasonography, such as alveolar consolidation consistent with pneumonia or pulmonary edema, which correlated with CTPA findings. In no patient did the CTPA add an additional diagnosis over the screening ultrasound study. CONCLUSIONS: We conclude that ultrasound examination indicated that CTPA was not needed in 56 of 96 patients (58.3%). A screening, point-of-care ultrasonography protocol may predict the need for CTPA. Furthermore, an alternative diagnosis can be established that correlates with CTPA. This study needs further verification, but it offers a possible approach to reduce the cost and radiation exposure that is associated with CTPA. PMID- 24178673 TI - Proteomics methods to study methionine oxidation. AB - The oxidation and consequent reduction of protein-bound methionine residues is of great interest in understanding different aspects of how oxidative stress affects protein functions and cellular signaling. To date, few technologies are available for the study of methionine sulfoxides. And, especially the absence of highly specific antibodies has impeded the field in understanding the exact role of methionine oxidation on a proteome-wide level. Nonetheless, the different models where the responsible enzymes for repair of the oxidized methionines have been studied show that there is an important role for this modification in a cellular context. We here review different mass spectrometry based and proteomics methods for characterizing in vivo methionine oxidation. PMID- 24178674 TI - Ru(III)(edta) mediated oxidation of azide in the presence of hydrogen peroxide. Azide versus peroxide activation. AB - The [Ru(III)(edta)(H2O)](-) (edta(4-) = ethylenediaminetetraacetate) complex catalyzes the oxidation of azide (N3(-)) with H2O2, mimicking the action of metallo-enzymes such as catalase and peroxidase in biochemistry. The kinetics of the catalytic oxidation process was studied by using stopped-flow and rapid-scan spectrophotometry as a function of [Ru(III)(edta)], [H2O2], [N3(-)] and pH. The catalytic activity of the different oxidizing species produced in the reaction of [Ru(III)(edta)(H2O)](-) with H2O2 for the oxidation of azide was compared to the oxidation of coordinated azide in [Ru(III)(edta)N3](2-) by H2O2. Detailed reaction mechanisms in agreement with the spectroscopic and kinetic data are presented for both reaction paths. PMID- 24178675 TI - CORR Insights (r): The effect of infrapatellar fat pad excision on complications after minimally invasive TKA: a randomized controlled trial. PMID- 24178676 TI - The relationship between gastric cancer and Helicobacter pylori in formaldehyde fixed paraffin embedded gastric tissues of gastric cancer patients-scorpion real time PCR assay findings. AB - Gastric cancer is the second leading cause of cancer-related deaths worldwide and it seems that environmental and lifestyle factors and infection with Helicobacter pylori (H. pylori) have had a major role in the etiology of gastric cancer. The aim of this study was to investigate the presence of H. pylori DNA in archival gastric tissues of patients with gastric cancer disease by rapid, sensitive and specific technique of Scorpion Realtime PCR. This retrospective cross-sectional study was performed on 285 paraffin embedded gastric specimens of patients who were pathologically proved for gastric cancer admitted in Bou-Ali, Shahid Rajaie and Dehkhoda hospitals and Bahar and Farzam private laboratory in Qazvin city in Iran during 2009 and 150 paraffin embedded pathological specimens of patients with other proved diagnosis other than gastric cancer. Results of our Scorpion Realtime PCR analysis showed that DNA of H. pylori DNA was present in 78.42% of our total specimens. Modified McMullen's Staining of paraffin embedded sections was positive in 210 patients. Also we were not able to finding significant relationship between demographic characteristics of our studied patients and presence of H. pylori DNA in their formaldehyde fixed paraffin embedded gastric tissues samples. Existence of H. pylori in gastric tissue samples of patients with gastric cancer is controversial and our results indicated that in our studied specimens prevalence of H. pylori was significantly more than recent published reports. PMID- 24178677 TI - Expression of cell cycle-related proteins, p16, p53 and p63 as important prognostic markers in gallbladder adenocarcinoma. AB - Gallbladder cancer, the most common biliary tract malignancy, is a highly malignant neoplasm. In the present work, we have analyzed the significance of cell cycle-related proteins to predict prognosis and to provide guidance for optimal therapeutic decision-making in patients with gallbladder adenocarcinoma. The expressions of p16, p21, p27, p53, p63, cyclin D1, bcl-2 and bcl-6 were examined in a tissue microarray constructed from 96 cases of gallbladder adenocarcinoma by immunohistochemistry and correlated with clinicopathologic prognostic factors. Expression of p16 was correlated with a low pT stage, adenoma background and good prognosis. Cases with p63 expression showed a higher T stage, more frequent perineural invasion and poor prognosis when compared to cases without p63 expression. Over-expression of p53 or loss of p53 was associated with poor tumor differentiation, frequent distant metastasis and low disease-specific survival rate. The expressions of p21, p27, bcl-2, bcl-6 and cyclin D1 were not significant prognostic factors for gallbladder adenocarcinoma. These results indicate that p16, p63 and p53 can be used as prognostic markers in gallbladder adenocarcinoma; especially p53 and p63 as poor prognostic markers and p16 as a favorable prognostic marker. PMID- 24178678 TI - A new model consists of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of prostate cancer. AB - The Prostate-specific antigen (PSA) level is largely used to diagnose prostate cancer (PCa) in last decades. However, its specificity is low in patients with a PSA level ranging from 4.0 to 10.0 ng/ml. This study aims to define the correlation between intravesical prostatic protrusion (IPP) and PSA and to establish a new model to predict PCa. A total of 339 patients order than 45 years examined between October 2010 and June 2012 were enrolled. Eligible patients were recommended for transrectal ultrasonography (TRUS)-guided prostate biopsies after measuring total prostate volume (TPV), tranzisional zone volume (TZV) and IPP. The levels of total PSA (tPSA), free PSA (fPSA) were analyzed by using Hybritech calibrated Access tPSA and fPSA assays. A new mathematical model, named IPP removed PCa predicting score (IRPPS), consists of tPSA, TZV and IPP was established. The predictive accuracy of IRPPS, PSA density (PSAD), %PSA and tPSA were compared using receiver-operator characteristic (ROC) analysis. Eighty-six patients had PSA levels of 4.0-10.0 ng/ml. Twenty of them were diagnosed as PCa. Using ROC curves, the areas under the curve for IRPPS, PSAD and %PSA and tPSA were 0.786, 0.768 and 0.664 and 0.585, respectively. We suggested IPP grade had a significant relationship with serum tPSA levels. The predictive accuracy of IRPPS was higher than the other 3 indictors. PMID- 24178679 TI - In contrast to many other mammals, cetaceans have relatively small hippocampi that appear to lack adult neurogenesis. AB - The hippocampus is essential for the formation and retrieval of memories and is a crucial neural structure sub-serving complex cognition. Adult hippocampal neurogenesis, the birth, migration and integration of new neurons, is thought to contribute to hippocampal circuit plasticity to augment function. We evaluated hippocampal volume in relation to brain volume in 375 mammal species and examined 71 mammal species for the presence of adult hippocampal neurogenesis using immunohistochemistry for doublecortin, an endogenous marker of immature neurons that can be used as a proxy marker for the presence of adult neurogenesis. We identified that the hippocampus in cetaceans (whales, dolphins and porpoises) is both absolutely and relatively small for their overall brain size, and found that the mammalian hippocampus scaled as an exponential function in relation to brain volume. In contrast, the amygdala was found to scale as a linear function of brain volume, but again, the relative size of the amygdala in cetaceans was small. The cetacean hippocampus lacks staining for doublecortin in the dentate gyrus and thus shows no clear signs of adult hippocampal neurogenesis. This lack of evidence of adult hippocampal neurogenesis, along with the small hippocampus, questions current assumptions regarding cognitive abilities associated with hippocampal function in the cetaceans. These anatomical features of the cetacean hippocampus may be related to the lack of postnatal sleep, causing a postnatal cessation of hippocampal neurogenesis. PMID- 24178680 TI - Comparative analysis of the serotonergic systems in the CNS of two lungfishes, Protopterus dolloi and Neoceratodus forsteri. AB - The organization of the serotonergic system, one of the most important neurotransmitter systems in the brain, has been carefully analyzed in most vertebrate groups, and major shared characteristics have been described, although traits particular to each vertebrate class have also been found. The present study is the first that provides a comprehensive and detailed map of the serotonergic structures in the brain of two representative species of lungfishes, the African lungfish (Protopterus dolloi) and the Australian lungfish (Neoceratodus forsteri), as revealed by immunohistochemistry against serotonin (5 HT). Lungfishes are currently considered the closest living relatives of tetrapods and represent an interesting group for the study of evolutionary traits in the transition from fishes to tetrapods. Distinct groups of serotonin immunoreactive cells were observed in the preoptic area, nucleus of the periventricular organ, pretectum, optic tectum and the long column of the raphe. Fiber labeling was widely distributed in all main brain subdivisions but was more abundant in regions such as the striatum, septum, amygdaloid complex, preoptic area, suprachiasmatic nucleus, lateral hypothalamic area, prethalamus, thalamus, mesencephalic tegmentum and rhombencephalic reticular formation. Comparison of these results with those from other classes of vertebrates highlights numerous common traits shared by most groups of fishes but also reveals that the serotonergic system in lungfishes largely resembles those of amphibians and other tetrapods. PMID- 24178681 TI - Meeting report on membrane transport and metabolism 4th International Congress on Amino Acids Vienna, Austria, August 7-11, 1995. AB - The session on Membrane Transport was a lively, interactive one with substantial audience participation in the discussion periods. Progress in this area of amino acid science is rapid as the genes encoding the transporter proteins are being cloned and characterized. The contributors to the platform session represented institutions from several countries giving the meeting a truly international flavor. Most of the participants contributed articles to this volume. The platform speakers were Dr. John McGivan (United Kingdom), Dr. Marcal Pastor Anglada (Spain), Dr. Bruce Stephens (USA), Dr. G. Gazzola and Dr. V. Dall'Asta (Italy), Dr. Carol MacLeod (USA), Miss Maria Rivera-Correa (Puerto Rico), Dr. Ellen Closs (Germany), Dr. Manuel Palacin (Spain), Dr. Ovidio Bussolati (Italy), Dr. Suresh Tate (USA), Dr. S. Nakamura (Japan). PMID- 24178682 TI - Regulation of amino acid transport in the renal epithelial cell line NBL-1. AB - The activities of the transport systems A, B degrees and XAG- are induced by various forms of stress in renal epithelial cells. Amino acid deprivation induces System A and XAG- in a protein-synthesis dependent process. In the case of System XAG- evidence is presented that induction of transport does not involve an increase in the amount of mRNA for the transporter or of the amount of transport protein. Preliminary evidence for the existence of a novel glycoprotein which is induced in parallel to the induction of these transport systems is presented. It is suggested that the induction of amino acid transport proteins and of some of the so-called stress proteins may be triggered by a common molecular mechanism. PMID- 24178683 TI - Emerging roles for sodium dependent amino acid transport in mesenchymal cells. AB - The functional aspects of sodium dependent amino acid transport in mesenchymal cells are the subject of this contribution. In a survey of the cross-talk existing among the various transport mechanisms, particular attention is devoted to the role played by substrates shared by several transport systems, such as L glutamine. Intracellular levels of glutamine are determined by the activity of System A, the main transducer of ion gradients built on by Na,K-ATPase into neutral amino acid gradients. Changes in the activity of the System are employed to regulate intracellular amino acid pool and, hence, cell volume. System A activity has been found increased in hypertonically shrunken cells and in proliferating cells. Under both these conditions cells have to increase their volume; therefore, System A can be employed as a convenient mechanism to increase cell volume both under hypertonic and isotonic conditions. Although less well characterized, the uptake of anionic amino acids performed by System X(-) AG may be involved in the maintenance of intracellular amino acid pool under conditions of limited availability of neutral amino acids substrates of System A. PMID- 24178684 TI - Long-term osmotic regulation of amino acid transport systems in mammalian cells. AB - Mammalian cells accumulate organic osmolytes, either to adapt to permanent osmotic changes or to mediate cell volume increase in cell cycle progression. Amino acids may serve as osmolytes in a great variety of cells. System A, a transport system for neutral amino acids, is induced after hypertonic shock by a mechanism which requires protein synthesis and gene transcription. Indirect evidence supports the view that system A activity increases due to the interaction of pre-existing A carriers with putative activating proteins. The intracellular accumulation of most neutral amino acids after hypertonic shock depends, exclusively, on the increase in system A activity. Long-term activation of system A is dependent on the integrity of cytoskeletal structures, but in a different way depending on whether cells are polarized or not. PMID- 24178685 TI - Parallel regulation of arginine transport and nitric oxide synthesis by angiotensin II in vascular smooth muscle cells role of protein kinase C. AB - Experiments were performed to characterize arginine transport in vascular smooth muscle cells (SMCs) and the effect of angiotensin II (Ang II) on this process. In addition, the role of arginine transport in the cytokineinduced nitric oxide (NO) production was assessed. Arginine transport takes place through Na(+)-independent (~60%) and Na(+)-dependent pathways (~40%). The Na(+)-independent arginine uptake appears to be mediated by system y(+) because of its sensitivity to cationic amino acids such as lysine, ornithine and homoarginine. The transport system was relatively insensitive to acidification of the extracellular medium. By contrast, the Na(+)-dependent pathway is consistent with system B(0,+) since it was inhibited by both cationic and neutral amino acids (i.e., glutamine, phenylalanine, and asparagine), and did not accept Li(+) as a Na(+) replacement. Treatment of SMCs with 100nM Ang II significantly inhibited the Na(+)-dependent arginine transport without affecting systems y(+), A, and L. This effect occurred in a dose-dependent manner (IC50 of 8.9 +/- 0.9nM) and is mediated by the AT-1 receptor subtype because it was blocked by DUP 753, a non-peptide antagonist of this receptor. The inhibition of system B(0,+) by Ang II is mediated by protein kinase C (PKC) because it was mimicked by phorbol esters (phorbol 12-myristate 13 acetate) and was inhibited by staurosporine. Ang II also inhibited the IL-1beta induced nitrite accumulation by SMCs. This action was also inhibited by staurosporine and reproduced with phorbol esters, suggesting a coupling between arginine uptake and NO synthesis through a PKC-dependent mechanism. However, arginine supplementation in the medium (10mM) failed to prevent the inhibitory action of Ang II on NO synthesis. These findings suggest that although Ang II inhibits concomitantly arginine transport and NO synthesis in SMCs, the reduction of NO synthesis is not associated with alterations in the cellular transport of arginine. PMID- 24178686 TI - Regulation of CAT: Cationic amino acid transporter gene expression. AB - The majority of mammalian cationic amino acid transport is mediated by the transport system y(+) which facilitates Na(+) independent cationic amino acid (arginine, lysine, & ornithine) transport and Na(+) dependent zwitterionic amino acid (glutamine & homoserine) transport. Other transport systems y(+)L, b(0,+) and B(0,+) also mediate cationic amino acid transport. Their broad substrate specificities and overlapping expression patterns confound biochemical analysis. The isolation of cDNA clones has permitted an analysis of their regulation and opens the opportunity to define the role of each protein in specific cell types. Two genes,Cat1 andCat2 encode transporters with properties similar to the y(+) transport system. Thecat2 gene from the mouse encodes two distinct proteins. mCAT2, and mCAT2A via alternate splicing; each protein has distinctly different transport properties. The regulation of mCAT1, mCAT2 and mCAT2A proteins are reviewed here. The implications of this gene specific regulation on cationic amino acid transport is discussed. PMID- 24178687 TI - CATs, a family of three distinct mammalian cationic amino acid transporters. AB - Three related mammalian carrier proteins that mediate the transport of cationic amino acids through the plasma membrane have been identified in murine and human cells (CAT for cationic amino acid transporter). Models of the CAT proteins in the membrane suggest they have 12 or 14 transmembrane domains connected by short hydrophilic loops and intracellular N- and C-termini. The transport activity of the CAT proteins is sensitive to trans-stimulation and independent of the presence of sodium ions. These features agree with the behaviour of carrier proteins mediating facilitated diffusion. The three CAT proteins, CAT-1, CAT-2A and CAT-2(B) are encoded by two different genes (CAT-1 and CAT-2). CAT-1 and CAT 2(B) exhibit transport properties consistent with system y(+), the principal mechanism for cellular uptake of cationic amino acids. In contrast, CAT-2A has tenfold lower substrate affinity, greater apparent maximal velocity and it is much less sensitive to trans-stimulation. In addition to structural and functional aspects, this review discusses the role of the CAT proteins for supplying substrate to NO synthases and the property of the rodent CAT-1 proteins to function as virus receptors. PMID- 24178688 TI - Evidence suggesting that the minimal functional unit of a renal cystine transporter is a heterodimer and its implications in cystinuria. AB - Cystinuria, one of the most common genetic disorders, is characterized by excessive excretion of cystine and basic amino acids in urine. The low solubility of cystine results in formation of kidney stones which can eventually lead to renal failure. Three types of cystinurias have been described. All involve defects in a high-affinity transport system for cystine in the brush border membranes of kidney and intestinal epithelial cells. The molecular properties of proteins involved in epithelial cystine transport are incompletely understood. A protein (NBAT, neutral and basic amino acid transporter), initially cloned by us from rat kidney and shown to be localized in the renal and intestinal brush border membranes, has been implicated in this transport, and mutations in human NBAT gene have been found in several cystinurics, making it a prime candidate for a cystinuria gene. However, mutations in NBAT were found only in Type I cystinurics and not in Types II and III suggesting that defects in other, as yet uncharacterized, genes may also be involved. NBAT has an unusual (for an amino acid transporter) membrane topology. We proposed that the protein contains four membrane-spanning domains, a model disputed by other investigators. We subsequently obtained experimental data consistent with a four membrane-spanning domain model. Furthermore, recently we showed that kidney and intestinal NBAT (85kDa) is associated with another brush border membrane protein (about 50kDa) and have proposed that the heterodimer represents the minimal functional unit of the high-affinity cystine transporter in these membranes. These findings raise the tantalizing possibilities that defects in the NBAT-associated protein might account for cystinurias in individuals with normal NBAT gene (such as the Types II and III cystinurics). PMID- 24178690 TI - Changes in neutral amino acid efflux and membrane potential associated with the expression of CFTR protein. AB - The expression of wild type CFTR facilitates the efflux of neutral amino acids (Rotoli et al., Biochem. Biophys. Res. Commun. 204: 653-658, 1994); as a result, after an extensive depletion of intracellular amino acid pool obtained through an incubation in saline solution, the intracellular leucine levels were lower in murine C127 cells transfected with the wild type CF gene (C127 CFTRw/t) than in cells transfected with either mutant CF (C127 CFTRDeltaF508 cells) or mock vector only. No change in amino acid efflux was detected when C127 CFTRw/t and C127 CFTRw/t and C127 CFTRDeltaF508 cells were studied under conditions known to activate protein kinase A. Upon an incubation in Cl(-) free medium, a permeant analogue of cAMP caused a marked cell depolarization of C127 CFTRw/t cells but not of C127 CFTRDeltaF508 cells, thus showing a functional expression of CFTR protein in the former cell line. However, we found that, upon a Cl(-) free incubation and in the absence of exogenous cAMP, C127 CFTRw/t cells developed a marked hyperpolarization that was not detected in C127 CFTRDeltaF508 cells. It is concluded that the expression of normal CFTR accelerates amino acid efflux and enhances cell hyperpolarization in Cl(-) free media; both these effects appear to be independent from PKA stimulation of CFTR. PMID- 24178689 TI - The molecular basis of cystinuria: the role of the rBAT gene. AB - The cDNAs of mammalian amino acid transporters already identified could be grouped into four families. One of these protein families is composed of the protein rBAT and the heavy chain of the cell surface antigen 4F2 (4F2hc). The cRNAs of rBAT and 4F2hc induce amino acid transport activity via systems b(0,+) like and y(+)L -like inXenopus oocytes respectively. Surprisingly, neither rBAT nor 4F2hc is very hydrophobic, and they seem to be unable to form a pore in the plasma membrane. This prompted the hypothesis that rBAT and 4F2hc are subunits or modulators of the corresponding amino acid transporters. The association of rBAT with a light subunit of ~40kDa has been suggested, and such an association has been demonstrated for 4F2hc.The b(0,+)-like system expressed in oocytes by rBAT cRNA transports L-cystine, L-dibasic and L-neutral amino acids with high affinity. This transport system shows exchange of amino acids through the plasma membrane ofXenopus oocytes, suggesting a tertiary active transport mechanism. The rBAT gene is mainly expressed in the outer stripe of the outer medulla of the kidney and in the mucosa of the small intestine. The protein localizes to the microvilli of the proximal straight tubules (S3 segment) of the nephron and the mucosa of the small intestine. All this suggested the participation of rBAT in a high-affinity reabsorption system of cystine and dibasic amino acids in kidney and intestine, and indicated rBAT (named SLC3A1 in Gene Data Bank) as a good candidate gene for cystinuria. This is an inherited aminoaciduria due to defective renal and intestinal reabsorption of cystine and dibasic amino acids. The poor solubility of cystine causes the formation of renal cystine calculi. Mutational analysis of the rBAT gene of patients with cystinuria is revealing a growing number (~20) of cystinuria-specific mutations, including missense, nonsense, deletions and insertions. Mutations M467T (substitution of methionine 467 residue for threonine) and R270X (stop codon at arginine residue 270) represent approximately half of the cystinuric chromosomes where mutations have been found. Mutation M467T reduces transport activity of rBAT in oocytes. All this demonstrates that mutations in the rBAT gene cause cystinuria.Three types of cystinuria (types, I, II and III) have been described on the basis of the genetic, biochemical and clinical manifestations of the disease. Type I cystinuria has a complete recessive inheritance; type I heterozygotes are totally silent. In contrast, type II and III heterozygotes show, respectively, high or moderate hyperaminoaciduria of cystine and dibasic amino acids. Type III homozygotes show moderate, if any, alteration of intestinal absorption of cystine and dibasic amino acids; type II homozygotes clearly show defective intestinal absorption of these amino acids. To date, all the rBAT cystinuria-specific mutations we have found are associated with type I cystinuria (~70% of the chromosomes studied) but not to types II or III. This strongly suggests genetic heterogeneity for cystinuria. Genetic linkage analysis with markers of the genomic region of rBAT in chromosome 2 (G band 2p16.3) and intragenic markers of rBAT have demonstrated genetic heterogeneity for cystinuria; the rBAT gene is linked to type I cystinuria, but not to type III. Biochemical, genetic and clinical studies are needed to identify the additional cystinuria genes; a low affinity cystine reabsortion system and the putative light subunit of rBAT are additional candidate genes for cystinuria. PMID- 24178691 TI - Changes in free amino acids and polyamine levels in Satsuma leaves in response to Asian citrus psyllid infestation and water stress. AB - The effects of biotic and abiotic stresses on changes in amino acids and polyamine levels in Satsuma orange (Citrus unshiu; cultivar Owari) leaves were investigated. Asian citrus psyllids Diaphorina citri (Kuwayama) (ACP) infestation was used to induce biotic stress while a water deficit was imposed to induce abiotic stress. Potted trees were infested by placing 50 psyllids on 3 citrus leaves enclosed in nylon mesh bags for 5 d. A parallel set of plants were kept water stressed by maintaining the soil at 20% water holding capacity for 5 d. Levels of total free amino acids were higher in water stressed and ACP infested leaves. Polyamine putrescine increased in infested leaves but not in water stressed leaves. Proline was the most abundant amino acid and its levels significantly increased by both biotic and abiotic stresses. Proline levels in infested leaves were significantly higher than the water stressed leaves. Histidine, methionine, asparagine, arginine, serine, and leucine levels also increased significantly in infested leaves, but in water stressed leaves only leucine, methionine, and threonine increased. Levels of amino acids, such as tyrosine, isoleucine, phenylalanine, glutamic acid, and alanine, declined in infested leaves. Under water stress asparagine, phenylalanine, serine, and histidine also declined compared to controls. This indicates that while proteolysis occurred under both stresses, metabolic conversion of amino acids was different under the two stresses. In ACP infested leaves some amino acids may be used as feeding material and/or converted into secondary metabolites for defense. PMID- 24178692 TI - Program change through mental health planning. AB - Planning for innovative program change is examined through references to selected experiences of the Massachusetts Mental Health Planning Project. The planning field was extremely complex and populated by a vast array of divergent forces. In the absence of an organization accepted as a neutral sanctioning body, the planning organism itself must develop some autonomy and positive sanction. It must develop credibility as a legitimate change system. Conscious mechanisms must be developed to insure interaction. Stressed factors are: open communication, two way participation, flexibility and clear objectives. Dissent to recommendations may be non-directed, or aimed at specific elements of the innovative change. Strategies of neutralization of conflict are necessary. The planning body must engage in a series of everchanging flexible coalitions. PMID- 24178693 TI - Evaluation and treatment of families at the Fort Logan Mental Health Center. AB - The evaluation and treatment of families at the Fort Logan Mental Health Center is described. There is considerable variation in the techniques used by the different treatment teams. The most widely used treatment technique is "multiple family group therapy" or "conjoint family group therapy." A number of trends are described: there is an increasing community orientation with many evaluations being done in homes, a wider extended family group being involved, and so on. There is an increasing tendency to view the locus of illness as being in the family rather than within the identified patient. PMID- 24178694 TI - An aid to needy children program: A study of types and responses to casework services. AB - In a study of an aid- to- needy-children program, a attempt was made to develop a typology and assess the effect of special services on personality, discontinuance and employment. The research design was experimental and sampling random for one part and purposive for another, as special services were available for one group and withheld from a control group. The techniques involved the California Psychological Inventory for the analysis of types and measure of personality change, and discontinuance and employment rates for the measure of the effect of the special services. Five types of clients were identified: apathetic, exploitative, transitory, manipulative, and disturbed. Experimental and control comparisons revealed no differences in the discontinuance or employment rates of the random sample, while personality showed some qualitative differences. Finally, the special services affected both the employment and discontinuance rates of the employable (purposive) sample. PMID- 24178695 TI - Systems analysis and mental health services. AB - Systems analysis, a method originating in engineering and planning areas, evaluates the costs and consequences of alternative approaches to a goal given a known set of constraints. Mental health services are badly in need of a more rational approach to planning, and this article shows how specific systems analysis techniques can be used to describe a mental health system and, at the same time, to evaluate consequences and costs of changing the system in different ways. The limitations of the approach are also considered. The authors' main aim is a general introduction to the systems approach for mental health practitioners. PMID- 24178696 TI - The mental health rehabilitation worker: A new member of the psychiatric team. AB - Changing treatment patterns have brought everincreasing numbers of the chronically mentally ill to a large municipal psychiatric department lacking personnel to meet their needs adequately. A new "inbetween" specialist in mental health rehabilitation has been created to provide certain useful services. Eight trainees are selected annually from among mature mothers seeking meaningful occupations after their children have become independent. Intensive theoretical and clinical training for one year leads to a certificate as a mental health rehabilitation worker. As a team member under professional supervision, this "in between" specialist works with socially disabled patients individually, in families, and in groups, in order to improve their functioning in daily living, social relationships, and work. PMID- 24178697 TI - The emerging role of the social worker in a psychiatric emergency service. AB - A unique round- the- clock service has evolved out of the need to provide extended emergency coverage in the Milwaukee County Mental Health Center despite the dearth of psychiatric personnel. Psychiatric social workers, who see themselves as specialists in social functioning, have developed a combined intake evaluation unit that sees all walkins, discusses prospective admissions, and considers alternatives to hospitalization. Using crisis intervention-psychiatric emergency criteria, they determine with applicants and referral sources the degree of disruption, the need for immediate action, and the most appropriate facility to handle the current situation. This is seen as a new extension of the traditional social work role, in the context of community mental health developments. PMID- 24178698 TI - Mental health roles of physicians in a Mexican-American community. AB - Family physicians who practice in a primarily Mexican-American community in Los Angeles were interviewed and answered questionnaires concerning their attitudes, opinions, and experiences in regard to mental illness and psychiatry. The results indicate that the physicians have a varied hut often high regard for psychiatry, a very diverse degree of sensitivity to and recognition of emotional disorders in office practice, and a desire in the majority for additional psychiatric education, consultation, and resources. Family physicians appear to serve as by far the most active and available mental health sustaining service in this particular low-income, ethnic community with its poverty of formal psychiatric facilities. PMID- 24178699 TI - Applicants for psychotherapy and the problem of early termination. AB - The current paper is essentially an evaluation and critique of a recent paper by Riess and Brandt (1965), pertaining to the general problem of dropouts in psychotherapy. These authors presented conclusions which were at variance with many of the previous findings in this area. In addition to evaluating the previous report in the light of other research, the present paper offers some possible explanations for apparent discrepancies in findings. Variation in findings may be due to a number of methodological considerations, including the definition of dropout and the adequacy and type of samples studied. Little data on significant patient variables were provided in the previous study. PMID- 24178700 TI - Intake policy as a community organization tool. AB - The intake policy of an agency is presented as an integral part of an agency's impact upon community organization and hence as crucial in the effectiveness and efficiency with which it carries out the mission of total community care. Three possible models for intake policy are elaborated: direct service, extended community management, and extensive community development. Under the latter model the judicious development, communication, and implementation of intake policy are evaluated in terms of impact in creating productive community ferment and thus fostering a community-wide examination of and involvement in the development of adequate services. PMID- 24178701 TI - Community involvement in mental health programs: The Wyandotte County Mental Health and Guidance Center. AB - In order to meet heavy service needs, and to extend preventative activities into the community as well, the Wyandotte County Mental Health and Guidance Center has developed a wide variety of methods and programs. Each of these programs has ties into the community, and derives assistance and collaboration from community agents. Included here is a description of the following programs: rapid evaluation procedures and short-term therapy methods for children and adults; suicide prevention telephone service; consulting and educative activities; prevention and early detection; research and evaluation; training; and a staff sensitivity group. PMID- 24178702 TI - A methodological report on household psychometric screening for retardation. AB - This report is a detailed description and analysis of the methods, problems, and results of mental testing carried out in the home as a phase of a community survey of mental retardation. A group of 409 individuals were tested, including a random sample of persons scoring in the lowest 10% of the developmental scales completed by the initial interviewers and a random sample of all persons in the interviewed households. Little testing of this type has been done in most other surveys of this nature; still fewer studies attempted testing in the home itself. The descriptive information on this successful project should be of value to other investigators who are interested in developing community-wide surveys. PMID- 24178703 TI - Publications received. PMID- 24178704 TI - Efficacy of infliximab in neuro-Behcet's disease presenting with isolated longitudinally extensive transverse myelitis. PMID- 24178705 TI - Heterogeneity and frequency of movement disorders in juvenile and adult-onset Niemann-Pick C disease. AB - Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults. PMID- 24178707 TI - Sporadic late-onset nemaline myopathy in a patient with systemic lupus erythematosus. PMID- 24178706 TI - Pallidal stimulation for primary generalised dystonia: effect on cognition, mood and quality of life. AB - We investigated the effect of pallidal deep brain stimulation (GPi-DBS) in dystonia on cognition, mood, and quality of life and also assessed if DYT1 gene status influenced cognitive outcome following GPi-DBS. Fourteen patients with primary generalized dystonia (PGD) were assessed, measuring their estimated premorbid and current IQ, memory for words and faces, and working memory, language, executive function, and sustained attention, one month before and one year or more after surgery. Changes in mood and behaviour and quality of life were also assessed. There was a significant improvement of dystonia with GPi-DBS (69 % improvement in Burke-Fahn-Marsden score, p < 0.0001). Performance on five cognitive tests either improved or declined at post-surgical follow-up. Calculation of a reliable change index suggested that deterioration in sustained attention on the PASAT was the only reliable change (worse after surgery) in cognition with GPi-DBS. DYT1 gene status did not influence cognitive outcome following GPi-DBS. Depression, anxiety and apathy were not significantly altered, and ratings of health status on the EQ5D remained unchanged. In our sample, GPi DBS was only associated with an isolated deficit on a test of sustained attention, confirming that GPi-DBS in PGD is clinically effective and safe, without adverse effects on the main domains of cognitive function. The dissociation between GPi-DBS improving dystonia, but not having a significant positive impact on the patients' QoL, warrants further investigation. PMID- 24178710 TI - Anion effects on the structures and magnetic properties of binuclear lanthanide single-molecule magnets. AB - Here we report the anion-induced changes of structures and magnetic properties in binuclear lanthanide compounds. Firstly, two Dy(3+)-based compounds, [Dy2(Mq)4(NO3)6] (1) and [Dy2(Mq)4Cl6](EtOH)2 (2) (Mq = 8-hydroxy-2 methylquinoline), were synthesized and characterized. They contain similar binuclear Dy2O2 cores, while the different peripheral anions lead to quite different coordination environments of the Dy(3+) ion. In compound 1, the Dy(3+) ion is nine-coordinated and characterized by a distorted 4,4,4-tricapped trigonal prism environment. In compound 2, the Dy(3+) ion has a highly distorted six coordinated octahedral environment. Their Gd(3+) analogues, [Gd2(Mq)4(NO3)6] (3) and [Gd2(Mq)4Cl6](EtOH)2 (4), were also studied to investigate the magnetic interaction between metal ions. Variable-temperature dc magnetic susceptibility measurements show that all the compounds are weakly antiferromagnetically coupled. Ac magnetic susceptibility measurements reveal that both compounds 1 and 2 exhibit single-molecule magnet (SMM) behaviour, while the thermal energy barrier of 2 is significantly higher than that of 1 (Delta/k(B) = 40.0 K for 1 and Delta/k(B) = 102.4 K for 2). PMID- 24178708 TI - Identification of carotenoids using mass spectrometry. AB - The present review compiles positive MS fragmentation data of selected carotenoids obtained using various ionization techniques and matrices. In addition, new experimental data from the analysis of carotenoids in transgenic maize and rice callus are provided. Several carotenes and oxygen-functionalized carotenoids containing epoxy, hydroxyl, and ketone groups were ionized by atmospheric pressure chemical ionization (APCI)-tandem mass spectrometry (MS/MS) in positive ion mode. Thus, on the basis of the information obtained from the literature and our own experiments, we identified characteristic carotenoid ions that can be associated to functional groups in the structures of these compounds. In addition, pigments with a very similar structure were differentiated through comparison of the intensities of their fragments. The data provide a basis for the structural elucidation of carotenoids by mass spectrometry (MS). PMID- 24178711 TI - Environmental risk assessment of GE plants under low-exposure conditions. AB - The requirement for environmental risk assessment (ERA) of genetically engineered (GE) plants prior to large scale or commercial introduction into the environment is well established in national laws and regulations, as well as in international agreements. Since the first introductions of GE plants in commercial agriculture in the 1990s, a nearly universal paradigm has emerged for conducting these assessments based on a few guiding principles. These include the concept of case by-case assessment, the use of comparative assessments, and a focus of the ERA on characteristics of the plant, the introduced trait, and the receiving environment as well as the intended use. In practice, however, ERAs for GE plants have frequently focused on achieving highly detailed characterizations of potential hazards at the expense of consideration of the relevant levels of exposure. This emphasis on exhaustive hazard characterization can lead to great difficulties when applied to ERA for GE plants under low-exposure conditions. This paper presents some relevant considerations for conducting an ERA for a GE plant in a low-exposure scenario in the context of the generalized ERA paradigm, building on discussions and case studies presented during a session at ISBGMO 12. PMID- 24178714 TI - Foreword. PMID- 24178712 TI - The innate immune playbook for restricting West Nile virus infection. AB - West Nile virus (WNV) is an emerging mosquito-borne flavivirus that causes annual epidemics of encephalitic disease throughout the world. Despite the ongoing risk to public health, no approved vaccines or therapies exist for use in humans to prevent or combat WNV infection. The innate immune response is critical for controlling WNV replication, limiting virus-induced pathology, and programming protective humoral and cell-mediated immunity to WNV infection. The RIG-I like receptors, Toll-like receptors, and Nod-like receptors detect and respond to WNV by inducing a potent antiviral defense program, characterized by production of type I IFN, IL-1beta and expression of antiviral effector genes. Recent research efforts have focused on uncovering the mechanisms of innate immune sensing, antiviral effector genes that inhibit WNV, and countermeasures employed by WNV to antagonize innate immune cellular defenses. In this review, we highlight the major research findings pertaining to innate immune regulation of WNV infection. PMID- 24178715 TI - Asymmetric catalysis of the Strecker amino acid synthesis by a cyclic dipeptide. AB - A novel cyclic dipeptide -cyclo[(S)-His-(S)-NorArg] - has been prepared which catalyzes an enantioselective version of the Strecker amino acid synthesis. The catalyst, when present in 2 mol % quantity in methanol solution, catalyzes the addition of hydrogen cyanide toN-alkylimines to affordalpha-amino nitriles in high yield and high enantiomeric excess. Furthermore, acid hydrolysis ofN benzhydryl-alpha-amino nitriles afforded the correspondingalpha-amino acids directly. This methodology affords a variety of arylglycines in exceptionally high enantiomeric excess, but aliphatic amino acids were obtained with low enantioselectivity. Current efforts are underway to expand the scope of this reaction, as well as to elucidate the mechanism of catalysis and the roles played by substrate and catalyst in determining the stereochemical outcome of the reaction. PMID- 24178716 TI - Synthesis of non-proteinogenic (D)- or (L)-amino acids by asymmetric hydrogenation. AB - Non-proteinogenic amino acids play an increasing role in oligopeptide chemistry. Their pharmacological and chemical properties, caused by D-configuration and "unnatural" residues, are more and more used for drug design. Different methods of asymmetric synthesis have been developed during the last decade to prepare "unusual" amino acids. One of them, the asymmetric hydrogenation of dehydroamino aids catalyzed by chiral rhodium (I) complexes, will be described. A series of examples, D- and L-configured, like naphthyl-, thienyl-, furyl-, and pyridylalanines, as well as phenylalanines substituted by chlorine, fluorine, p nitro, p-methyl, p-trifluoromethyl, p-isopropyl, and p-tert-butyl have been prepared and characterized. Some analytical data like melting points and values of optical rotation are summarized in tables. PMID- 24178713 TI - Involvement of eukaryotic small RNA pathways in host defense and viral pathogenesis. AB - Post-transcriptional gene regulation by small RNAs is now established as an important branch of the gene regulatory system. Many different classes of small RNAs have been discovered; among these are short interfering RNAs (siRNAs) and microRNA (miRNAs). Though differences in the processing and function of small RNAs exist between plants and animals, both groups utilize small RNA-mediated gene regulation in response to pathogens. Host encoded miRNAs and siRNAs are generated from viral RNA function in host defense and pathogenic resistance in plants. In animals, miRNAs are key regulators in both immune system development and in immune function. Pathogens, in particular viruses, have evolved mechanisms to usurp the host's small RNA-mediated regulatory system. Overall, small RNAs are a major component of host defense and immunity in eukaryotes. The goal of this review is to summarize our current knowledge of the involvement of eukaryotic small RNA pathways in host defense and viral pathogenesis. PMID- 24178717 TI - Synthesis ofgamma,delta-unsaturated amino acids via ester enolate Claisen rearrangement of chelated allylic esters. AB - Deprotonation ofN-protected amino acid allylic esters with LDA at -78 degrees C and subsequent addition of a metal salt presumably results in the formation of a chelated metal enolate which undergoes Claisen rearrangement upon warming up to room temperature, giving rise to unsaturated amino acid. Many different metal salts can be used for chelation, but in general the best results are obtained with zinc chloride. Due to the fixed enolate geometry, as a result of chelate formation, and a strong preference for thechair like transition state, the rearrangement proceeds with a high degree of diastereoselectivity. This methodology can be applied to acyclic as well as to cyclic substrates, and even to peptides, and allows for the synthesis of amino acids containing quaternary carbon centers. PMID- 24178718 TI - Stereoconservative and stereoselective syntheses of rare and non-naturalalpha amino acids from (S)-aspartic acid and (S)-malic acid. AB - A new strategy for stereoconservative and stereoselective syntheses of several types of amino acids starting fromalpha-functional carboxylic acids employing hexafluoroacetone as protecting and activating reagent is described. Outstanding features of this new method are the mild reaction conditions and the high yields for introduction and cleavage of the protective group allowing sensitive functional groups in the side chain to survive. Furthermore, the new concept results in saving of synthetic steps. PMID- 24178719 TI - beta,gamma-Alkynylalpha-amino acids: a synthetic challenge. AB - Ethynyl glycine is a naturally occurring unusualalpha-amino acid. Its known chemical and biological properties are summarized in the first part of this review. The second part is an overview on racemic syntheses of ethynyl glycine and otherbeta,gamma-alkynylalpha-amino acid derivatives, including patent data. These small polyfunctional compounds revealed as being very labile and the synthesis of mainly fully or partially protected forms seemed to have been actually performed. The last part deals with the approaches to the enantioselective synthesis ofbeta,gamma-alkynylalpha-amino acids derivatives, and details the only satisfactory strategy that has led to optically activebeta,gamma alkynylalpha-amino acids derivatives up to now. PMID- 24178720 TI - Synthesis of medicinally useful lipidicalpha-amino acids, 2-amino alcohols and diamines. AB - The lipidicalpha-amino acids (LAAs) are non-naturalalpha-amino acids with saturated or unsaturated long aliphatic side chains. LAAs and their derivatives (lipid mimetics) together with the lipidic peptides represent a class of compounds which combine structural features of lipids with those of amino acids and peptides. Racemic LAAs may be prepared by classical methods and resolved by chemical or enzymatic methods. LAA amides and esters with saturated or unsaturated long chain amines and alcohols respectively, as well as lipidic dipeptide derivatives inhibit both pancreatic and human platelet phospholipase A2. Lipophilic peptide derivatives are inhibitors of human neutrophil elastase. LAAs and their oligomers have been used as drug delivery system. A Lipid-Core Peptide system has been designed and used as a combined adjuvant-carrier-vaccine system. A variety of lipid mimetics such as lipidic 2-amino alcohols, lipidic 1,2 and 1,3-diamines have been prepared based upon LAAs. Some of them are potent inhibitors of phospholipase A2. A general approach to enantioselective synthesis of LAAs and lipid mimetics is based on the oxidative cleavage of 3-amino-1,2 diols obtained by the regioselective opening of enantiomerically enriched long chain 2,3-epoxy alcohols. PMID- 24178721 TI - Non-natural phenolic amino acids Synthesis and application in peptide chemistry. AB - Several non-natural phenolic amino acids have been synthesized.t-Butylated tyrosine and thyroxine derivatives, on one-electron oxidation, give persistent radicals which can be used as positional and/or spin labels for amino acids. Two electron oxidation ofN-protected tyrosines leads to spirolactones, useful active esters for peptide coupling. PMID- 24178722 TI - Utilization of some non coded amino acids as isosters of peptide building blocks. AB - In our study on non coded amino acids and their utilization in peptide chemistry we synthesized methylene-thio (CH2-S) and methyleneoxy (CH2-O) group containing amino acids and pseudodipeptides which could be used as building blocks for the construction of peptide hormone analogues. The (CH2-S) isoster of peptide bond exhibits increased flexibility, lipophility and resistance to proteolytic enzymes. This group exhibits similar properties as the isosteric disulfide bond in the side chain of cystine residue. The (CH2-O) isoster is moreover similar in its geometry to extended conformation of peptide bond. As a consequence, the changed profile of biological activities could be expected for peptide hormone analogues containing such isosteric moiety. The (CH2-S) isosters of the peptide bond were prepared by alkylation of thiolates of 2-mercaptocarboxylic acids, the disulfide bond by alkylation of cysteine or homocysteine. The (CH2-O) isosters were prepared by (AcO)4Rh2 catalyzed addition of carbenes of alkyl diazocarboxylates to N-protected aminoalcohols. Pseudodipeptides H-Leu-psi(CH2-S) Gly-NH2 and H-Leu-psi(CH2-O)-Gly-NH2 were introduced into the C-terminal part of the oxytocin molecule using solution methods of peptide chemistry. Both inserted isosteric bonds were resistant against proteolytic degradation, the first one was found to decrease an enzymic cleavage of the distant Tyr(2)-Ile(3) bond in the corresponding analogue, too. The (CH2-S) isosters of the disulfide bond containing an orthogonal protection of theiralpha-amino (Fmoc) andalpha-(OAll, OH) oromega-(OBu(+), OH) carboxylic groups were applied in the solid phase synthesis of the aminoterminal 1-deamino-15-pentadecapeptide of endothelin-I which represents a strong vasoactive agent. The solid phase synthesis was carried out by the step-wise protocol on the Rink or Merrifield type resin using orthogonally protected carba cystine building blocks. PMID- 24178723 TI - Reverse action of hydrolases in frozen aqueous solutions. AB - The reverse action of hydrolases provides an attractive alternative to the chemical synthesis of peptides, oligosaccharides and oligonucleotides. Freezing the reaction mixture has proved to suppress competitive reactions in enzyme catalysed peptide synthesis. After a short discussion of the influence of freezing on enzyme-catalysed reactions the current manuscript gives an overview of protease-catalysed peptide synthesis and the possible reasons of the yield enhancing effect of freezing. The application of glycosidases and ribonucleases for synthetic purposes in frozen reaction mixtures is summarized. PMID- 24178724 TI - Stereoselective synthesis ofbeta-amino acids via conjugate addition of nitrogen nucleophiles toalpha,beta-unsaturated esters - Recent advances. AB - The latest results concerning the asymmetric synthesis ofbeta-amino acids are reviewed, focussing on methodology involving 1,4-addition of nitrogen nucleophiles toalpha,beta-unsaturated esters. Approaches using both homochiral auxiliaries bound to the enoate and homochiral ammonia equivalents are included as well as alkylations and aldol reactions of enolates derived from homochiralbeta-amino acids. PMID- 24178725 TI - Syntheses ofgamma-fluoro-alpha-amino acids. AB - Methods for the synthesis of racemic and optically active title compounds are presented. Key step of these four-step procedures is the alkylation with 1-bromo 2-fluoroalkanes of glycine-ester-derived imines in anhydrous medium using lithium diisopropylamide as a base at low temperature or phase transfer catalyzed alkylation with 50% NaOH and triethylbenzylammoniumchloride as the phase transfer catalyst, respectively. Subsequent three-step deprotection gave the free acids in 13-33% overall yield. Deracemization ofgamma-fluoro-alpha-aminobutyric acid methyl and ethyl esters withalpha-chymotrypsin was shown to give the (-) enantiomers of the esters and (+)-gamma-fluoro-alpha-aminobutyric acid in >98% ee, while from thetert-butylester the opposite stereochemical result was observed giving the (-)-acid with 88% ee. Optically activegamma-fluoro-alpha-amino acids were synthesized alternatively by phase transfer catalysis with N-benzyl cinchonium chloride or using an auxiliary-directed asymmetric alkylation of the imine derived from (R)-(+)-camphor or (R)-(+)-2-hydroxypinan-3-one. These processes gave different enantiomers ofgamma-fluoro-alpha-aminobutyric acid via a monomeric lithium enolate in the first or a dimeric lithium enolate in the second case, respectively. The enantiomeric excess can be improved by lithium/magnesium exchange. PMID- 24178726 TI - Peptide modification by incorporation ofalpha-trifluoromethyl substituted amino acids. AB - Metabolic stabilization of pharmacologically active peptides can be achieved by incorporation of sterically hindered non-natural amino acids, e.g. C (alpha,alpha) -disubstituted amino acids.alpha-Trifluoromethyl substituted amino acids, a subclass of C (alpha,alpha) -disubstituted amino acids, also fulfil this requirement while featuring additional properties based on the electronic influence of the fluorine substituents.This review summarizes the results concerning the stability of peptides containingalpha-TFM amino acids towards proteolysis byalpha-chymotrypsin. Furthermore, configurational effects ofalpha TFMAla on the proteolytic stability of peptides are explained using empirical force field calculations. The influence ofalpha-TFMAla incorporation on the secondary structure of selected tripeptide amides is compared to the effects exerted by its fluorine-free analogue, aminoisobutyric acid.Finally, results on metabolic stabilization and biological activity of modified thyrotropin releasing hormone are interpreted. PMID- 24178727 TI - Pneumatic compression for embolic protection during upper extremity endovascular intervention. AB - Embolic protection devices are occasionally employed during endovascular interventions to prevent complications caused by embolic debris. However, these devices have imperfect efficacy, confer risk of endovascular trauma, and are expensive. We report a patient with giant cell arteritis and symptomatic axillary artery stenosis, with a perceived elevated risk of distal embolization during endovascular intervention. We describe a straightforward embolic protection technique of brachial pressure cuff inflation during endovascular intervention and aspiration of displaced thrombotic material from the static column of blood. This novel, effective, and cost-free technique could also be employed in other vascular beds during endovascular intervention. PMID- 24178728 TI - Review and update on new horizon in the management of venous ulcers. AB - Chronic venous ulcers (CVUs) contribute to functional deficits and are a source of significant morbidity among the affected population. In addition, they directly impact the quality of life of patients and are a significant economic burden on the health care system. In this review, we critically evaluate the current strategies for treating CVUs that have emerged within the last decade and outlined a suggested algorithm for treating patients with this difficult condition. PMID- 24178729 TI - The upside down Endurant iliac limb stent graft for treatment of a common iliac artery aneurysm. AB - Endovascular repair of the coverage from the common iliac artery to the external iliac artery after the internal iliac artery embolization has been proven to be a safe and effective treatment in isolated iliac artery aneurysms. But in cases in which the diameter of the proximal sealing zone is larger than that of the distal sealing zone, a reverse-tapered device is needed. We described the off-label use of the Endurant iliac limb stent graft in an upside down configuration to accommodate this diameter mismatch. PMID- 24178730 TI - New trick for removal of intravascular retained foreign body: a case report and review of literature. AB - A 54-year-old male presented to the vascular service for an urgent inpatient consultation. During an infusaport removal, the catheter was accidentally disconnected and lost intravascularly within the left subclavian vein, with the tip still in the right ventricle. We report on a novel technique for removing such intravascular foreign bodies (FBs), which will add a valuable technical option to our existing armamentarium regarding intracorporeal FB removal. PMID- 24178731 TI - True lumen stenting for a spontaneously dissected superior mesenteric artery may compromise major intestinal branches and aggravate bowel ischemia. AB - Optimal endovascular therapy for isolated superior mesenteric artery (SMA) dissection remains undetermined. Here, we report a 56-year-old male with ischemic bowel syndrome caused by such a serious vascular disease. He was treated with endovascular true lumen stenting yet got aggravated in bowel ischemia from unexpected jail of major intestinal branches perfused by the false lumen, requiring subsequent complex rewiring and dilatation procedures to resolve at the cost of excessive fluoroscopic and contrast medium exposure. Thus, when treating patients with isolated SMA dissection with a functioning false lumen, true lumen stenting may inadvertently compromise crucial intestinal branches and should not be indiscriminately considered as the prime therapeutic option. PMID- 24178732 TI - Decreased serum selenium levels are correlated with diminished coronary flow reserve among hemodialysis patients. AB - Cardiovascular diseases are the main reason of high mortality among hemodialysis patients. Decreased serum selenium levels may have a role in accelerated atherosclerosis in this patient group. The hypothesis of this study was to show a correlation between decreased serum selenium levels and coronary flow reserve as an indicator of endothelial dysfunction and atherosclerosis in HD patients. Seventy-one chronic hemodialysis patients and age 65 and sex-matched healthy controls were included in the study. Plasma selenium levels were measured by spectrophotometry, and coronary flow reserve was assessed by transthoracic Doppler echocardiography. Serum selenium levels (34.16 +/- 6.15 ng/ml vs. 52.4 +/ 5.51 ng/ml, P < 0.001) and coronary flow reserve values (1.73 +/- 0.11 vs. 2.32 +/- 0.28, P < 0.001) were significantly lower in hemodialysis patients compared with controls, respectively. There was a significant positive correlation between coronary flow reserve and serum levels of selenium (r = 0.676, P < 0.001). A linear regression analysis showed that serum levels of selenium were independently and positively correlated with coronary flow reserve (regression coefficient = 0.650, P < 0.05). This study was the first to show a positive and independent correlation between decreased selenium levels and diminished coronary flow reserve as an indicator of endothelial dysfunction and atherosclerosis in hemodialysis patients. Our data suggest that decreased serum selenium levels may facilitate the development of endothelial dysfunction and disruption of coronary flow reserve which occur before the development of overt atherosclerosis. PMID- 24178733 TI - Police as a community mental health resource. AB - In their pathways to the state mental hospital, almost 50% of mentally ill patients and their families from Baltimore utilize the police as a community resource. To better understand why so many people use the police for help with mental problems, a comparison was made between first admission patients who used the police (N=17) and those who used more conventional medical resources (N=35). The results indicate that families decide to call the police because other, more appropriate, resources are not as accessible and will not offer services to recalcitrant patients. Until community mental health facilities develop more active evaluation and treatment programs for reluctant patients, the police will continue to serve a needed role in the care of the mentally ill. PMID- 24178734 TI - Evaluation: A keystone of Comprehensive Health Planning. AB - This paper describes the implications for mental health programming of the emphasis on evaluation throughout the regulations for comprehensive health planning and health service development in the Partnership for Health legislation. PMID- 24178735 TI - Community psychiatry and the education of psychiatrists. AB - Opinions vary as to the place in psychiatric education of training for community psychiatry. The confusion is partly due to the assumption that community psychiatry represents a new subspecialty and that therefore training for community psychiatry should follow basic clinical education. With the exception of certain administrative and research aspects, the practices and the knowledge employed by community psychiatrists are becoming part of all effective contemporary psychiatric practice and should be part of the basic education of every psychiatrist. A three-year residency program which coordinates clinical and community psychiatric knowledge and experience is presented. The needs of participants in mental health programs, of teachers and of researchers in community psychiatry, can best be met by specific postgraduate instruction combined with simultaneous job experience. PMID- 24178736 TI - The assessment process in campus community mental health programs. AB - In developing campus community mental health programs, assessment is a more complicated and holistic process as compared with assessment within an individual therapeutic relationship. It includes a global assessment of the college as an ongoing social system, as well as an analysis of its present and past phases of evolution as an institution. Mental health staff must understand the way in which they affect others within the college community and the perceptions which others hold regarding the mental health program. They must also scrutinize their own dynamics as these affect their reactions to individual community members and to the core value orientations of the college. PMID- 24178737 TI - Missionaries or educators? Parent education for poverty families. AB - An adequately designed parent education program must provide answers to four central issues: (1) specification of the goals to be accomplished, (2) the message to be conveyed to the parents, (3) the most appropriate method to effect the desired change, and (4) some definitive evaluation of change related to parent participation. These four issues are considered with reference to a demonstration program of parent education for mothers of first-grade children in middle- and lower-class, white and Negro families. Implications for programs with poverty families are suggested. PMID- 24178738 TI - A developmental view of the comprehensive community mental health concept. AB - Apprehension and doubt about the Comprehensive Community Mental Health Center (CCMHC) service programs are felt by both mental health professionals and local and state government officials who have yet to see the comprehensive center operate independent of Federal financial support and consistent with the concept of total service. Critics and pessimists must recognize that the CCMHC must initially establish and maintain itself amid a network of local social and rehabilitation agencies before the goals spelled out as essential elements of service can be achieved. It is suggested that there are critical factors that affect the evolvement from Phase 1, in which the CCMHC directs attention to its own survival, to Phase 2, when the CCMHC can begin to deal effectively with the local problems of mental health. PMID- 24178739 TI - A mental health consultation-education program with group service agencies in a disadvantaged community. AB - The consultation-education program described here worked with about 20 community based group service agencies in a severely deprived urban area. The agencies included: (a) traditional neighborhood houses, (b) recreational and "character building" centers, (c) church-sponsored group programs, and (d) neighborhood service centers. The program involved: (a) a planning body of administrators of group service agencies, (b) a consultation service on problems of individuals or groups, and (c) training workshops for agency staff. The program was geared to both institutional changevia enhanced integration of services and promotion of new skills, and to attitude changeof individual psychosocial "caretakers". PMID- 24178740 TI - An experiment in police-community relations: A small group approach. AB - To study the effectiveness of group discussion in mitigating the rising hostility between police and residents of the urban ghetto, two 15-member groups of police and ghetto residents held weekly discussions, led and observed by university researchers, for 12 weeks. Attitude scales administered at the beginning and end of the study, as well as recorded logs of the meetings, reveal increased understanding and empathy between initially hostile and defensive participants by the end of the study. With increased awareness of each others' problems came an increased faith in the power of cooperation to solve problems. Police became more interested in attempting to affect the causes of problems than in serving merely as disciplinarians, and some of the community members began to attempt to instill in their neighbors a more friendly attitude toward the police. PMID- 24178741 TI - Mental retardation: A question of ethics for the consultant psychologist. AB - The consulting psychologist is frequently asked to make recommendations as to the institutionalization of a retarded child. This action is only too often undertaken without full consideration of all the factors involved. Available research data are not consonant with the assertion that institutional placement is likely to benefit the retardate or that it is necessitated by social circumstances, in preference to hospital or prison placement. The ethical implications of recommended institutionalization are discussed. PMID- 24178742 TI - Publications received. PMID- 24178743 TI - Film review. PMID- 24178744 TI - Synthesis and biological evaluation of glucagon-like peptide-1 receptor agonists. AB - In this study, a series of fused-heterocyclic derivatives were systematically designed and synthesized using an efficient route, and evaluated in terms of GLP 1R agonist activity. We employed short synthetic steps and reactions that are tolerant of the presence of various functional groups and suitable for parallel operations to enable the rapid generation of libraries of diverse and structurally complex small molecules. Of the compounds synthesized, 3-(8-chloro-6 (trifluoromethyl)imidazo[1,2-a] pyridin-2-yl)phenyl methanesulfonate (8e) was the most potent agonist with an EC50 of 7.89 MUM, and thus is the compound with the greatest potential for application. These findings represent a valuable starting point for the design and discovery of small-molecule GLP-1R agonists that can be administered orally. PMID- 24178745 TI - Therapeutic gene delivery using bioreducible polymers. AB - Bioreducible polymers, which can be degraded in reducing environment due to the cleavage of internal disulfide bonds, have been developed for gene delivery systems. They show high stability in extracellular physiological condition and cytoplasm-specific release of genetic materials, as well as decreased cytotoxicity because cytoplasm is a reducing environment containing high level of reducing molecules such as glutathione. Based on these advantages, recently, many bioreducible polymers have been further investigated with therapeutic genes for the treatment of diseases and demonstrated promising results. This review will focus on the therapeutic gene delivery using bioreducible polymers and the evaluation of therapeutic efficacy for cancer, myocardial infarction, diabetes and miscellaneous diseases. PMID- 24178746 TI - Morpho-functional characteristics of the scolex of Wardium chaunense (Cestoda: Aploparaksidae) penetrated into host intestine. AB - The scoleces of Wardium chaunense penetrated into the intestinal wall of a snipe (Gallinago gallinago) were examined by light and transmission electron microscopy for the first time. Naturally, the scolex is characterised by a shorter length in comparison with when it is removed from the host. Ultrastructural characteristics of the main parts of the scolex, such as suckers, rostellum and rostellar sac are reported. Partial degradation of the radial muscles of the suckers is clearly recognised; this can be the result of a deep penetration of the scolex into the mucosa and subsequent loss of attachment function by suckers. The muscular walls of the rostellum and rostellar sac have a structure of the same type: an outer longitudinal layer of muscles is separated from the inner circular one with a thin basal matrix, which, also, surrounds each muscular fibre of the circular layer. Circular fibres consist of mutually perpendicular myofibrils, connected with the basal matrix by hemidesmosomes. Microtriches, covering the tegument, vary in shape in different regions of the scolex. They are absent on the apical part of the rostellum, and are slightly curved and can be considered as belonging to the fixative type on the suckers. Special sensory endings with a dense central body and without cilia are situated at the distal cytoplasm of the tegument of the suckers. Two glands, having the same syncytial structure, are disposed inside the rostellum and rostellar sac. Erythroid granules produced by the glands are released during an apocrine process into the host-parasite contact zone. Secretions of the cestode tegument in the form of vesicles and bubbles of granular material were also observed. It is suggested that the scolex attachment method of W. chaunense has the tendency of 'anchoring', which is an irreversible attachment used by some cestode parasites of the snipe. PMID- 24178747 TI - Acaricidal activity of Cymbopogon winterianus, Vitex negundo and Withania somnifera against synthetic pyrethroid resistant Rhipicephalus (Boophilus) microplus. AB - Detection of resistance levels against cypermethrin and deltamethrin, the most commonly used synthetic pyrethroids (SPs) against Rhipicephalus (Boophilus) microplus collected from Moga, Punjab (India) was carried out using larval packet test. Results indicated the presence of resistance of level I and III against cypermethrin (resistance factors (RF) = 4.67) and deltamethrin (RF = 34.2), respectively. Adult immersion test was used to assess the acaricidal activity of aqueous and ethanolic extracts of leaves of Cymbopogon winterianus, Vitex negundo, and Withania somnifera along with roots of V. negundo against the SP resistant engorged females of R. (B.) microplus. The efficacy of various extracts was assessed by estimation of percent adult mortality, reproductive index (RI), percent inhibition of oviposition (%IO), and hatching rate. A concentration dependent increase in tick mortality was recorded which was more marked with various ethanolic extracts, and highest mortality was recorded in ticks treated with ethanolic extract of leaves of C. winterianus. The LC50 values were determined by applying regression equation analysis to the probit transformed data of mortality for various aqueous and ethanolic extracts. Acaricidal property was recorded to be higher in ethanolic extracts, and high activity was found with the ethanolic extract of leaves of C. winterianus with LC50 (95% CL) values of 0.46% (0.35-0.59%), followed by W. somnifera as 5.21% (4.45-6.09%) and V. negundo as 7.02% (4.58-10.74%). The egg mass weight of the live ticks treated with different concentrations of the various extract was significantly (p < 0.01) lower than that of control ticks; consequently, the RI and the %IO value of the treated ticks were reduced. Further, complete inhibition of hatching was recorded in eggs laid by ticks treated with ethanolic extracts of leaves of V. negundo and aqueous extracts of leaves of W. somnifera. The results of the current study indicate that extracts of C. winterianus, V. negundo, and W. somnifera can be used for the control of SP resistant ticks. PMID- 24178748 TI - A DTU-dependent blood parasitism and a DTU-independent tissue parasitism during mixed infection of Trypanosoma cruzi in immunosuppressed mice. AB - Trypanosoma cruzi (Tc) diversity is determined by different biological, genetic, and biochemical markers and has been grouped into six discrete typing units (DTUs) or taxonomic groups (TcI-TcVI). This variability, coupled with natural reinfection or the hosts' immunosuppression, may play an important role in the pathogenesis of Chagas disease. Therefore, we evaluated the blood and tissue parasitism and genetic profile of mice coinfected with the TcII (JG) strain and TcI AQ1-7 (AQ) or MUTUM (MT) strains during the acute and chronic phases of the disease and during immunosuppression. T. cruzi blood populations in mixed infections were clearly associated with the TcII strain during acute and chronic phases or during immunosuppression. However, in tissues, the parasite populations were distributed according to the strain and the stage of infection. TcII populations overlapped TcI strains during the acute phase; in contrast, during chronic phase, both TcI strains were more prevalent than the TcII strain. The immunosuppression induced selective exacerbation of parasite populations, leading to reactivation of the TcII strain when associated with the AQ, but not with MT strain. Thus, a differential distribution of T. cruzi populations in blood and tissues with overlapping according to the stage of infection and strain used was observed. Blood parasitism was associated with the DTU TcII and tissue parasitism with a specific parasite strain and not with DTUs. Finally, to our knowledge, this is the first study to analyze subpatent blood parasitism and to simultaneously identify different T. cruzi populations in tissues and blood. PMID- 24178749 TI - Sox2 promotes tamoxifen resistance in breast cancer cells. AB - Development of resistance to therapy continues to be a serious clinical problem in breast cancer management. Cancer stem/progenitor cells have been shown to play roles in resistance to chemo- and radiotherapy. Here, we examined their role in the development of resistance to the oestrogen receptor antagonist tamoxifen. Tamoxifen-resistant cells were enriched for stem/progenitors and expressed high levels of the stem cell marker Sox2. Silencing of the SOX2 gene reduced the size of the stem/progenitor cell population and restored sensitivity to tamoxifen. Conversely, ectopic expression of Sox2 reduced tamoxifen sensitivity in vitro and in vivo. Gene expression profiling revealed activation of the Wnt signalling pathway in Sox2-expressing cells, and inhibition of Wnt signalling sensitized resistant cells to tamoxifen. Examination of patient tumours indicated that Sox2 levels are higher in patients after endocrine therapy failure, and also in the primary tumours of these patients, compared to those of responders. Together, these results suggest that development of tamoxifen resistance is driven by Sox2 dependent activation of Wnt signalling in cancer stem/progenitor cells. PMID- 24178750 TI - Subcutaneous versus intravenous granulocyte colony stimulating factor for the treatment of neutropenia in hospitalized hemato-oncological patients: randomized controlled trial. AB - Intravenous (IV) granulocyte colony stimulating factor (G-CSF) might be safer and more convenient than subcutaneous (SC) administration to hospitalized hemato oncological patients receiving chemotherapy. To compare IV vs. SC G-CSF administration, we conducted a randomized, open-label trial. We included inpatients receiving chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma or multiple myeloma, and allogeneic or autologous hematopoietic cell transplantation (HCT). Patients were randomized to 5 mcg/kg single daily dose of IV bolus versus SC filgrastim given for its clinical indications. Patients were crossed-over to the alternate study arm on the subsequent chemotherapy course. The primary outcomes were time from initiation of filgrastim to recovery of stable neutrophil count of >500 cells/uL and a composite clinical outcome of infection or death assessed for the first course post-randomization. The study was stopped on the second interim analysis. Of 120 patients randomized, 118 were evaluated in the first treatment course. The mean time to neutropenia resolution was longer with IV G-CSF [7.9 days, 95% confidence interval (CI) 6.6-9.1] compared with SC G-CSF (5.4 days, 95% CI 4.6-6.2), log rank P = 0.001. Longer neutropenia duration was observed in all patient subgroups, except for patients undergoing autologous HCT. There was no significant difference between groups in the occurrence of infection or death, but more deaths were observed with IV (4/57, 7%) versus SC (1/61, 1.6%) G-CSF administration, P = 0.196. Similar results were observed when all 158 courses following cross-over were analyzed. Patients reported similar pain and satisfaction scores in both groups. Bolus IV administration of G-CSF results in longer neutropenia duration than SC administration, with no difference in clinical or quality-of-life measures. PMID- 24178751 TI - C5orf42 is the major gene responsible for OFD syndrome type VI. AB - Oral-facial-digital syndrome type VI (OFD VI) is a recessive ciliopathy defined by two diagnostic criteria: molar tooth sign (MTS) and one or more of the following: (1) tongue hamartoma (s) and/or additional frenula and/or upper lip notch; (2) mesoaxial polydactyly of one or more hands or feet; (3) hypothalamic hamartoma. Because of the MTS, OFD VI belongs to the "Joubert syndrome related disorders". Its genetic aetiology remains largely unknown although mutations in the TMEM216 gene, responsible for Joubert (JBS2) and Meckel-Gruber (MKS2) syndromes, have been reported in two OFD VI patients. To explore the molecular cause(s) of OFD VI syndrome, we used an exome sequencing strategy in six unrelated families followed by Sanger sequencing. We identified a total of 14 novel mutations in the C5orf42 gene in 9/11 families with positive OFD VI diagnostic criteria including a severe fetal case with microphthalmia, cerebellar hypoplasia, corpus callosum agenesis, polydactyly and skeletal dysplasia. C5orf42 mutations have already been reported in Joubert syndrome confirming that OFD VI and JBS are allelic disorders, thus enhancing our knowledge of the complex, highly heterogeneous nature of ciliopathies. PMID- 24178753 TI - Intensive hemodialysis compared to conventional hemodialysis: looking at recent evidence in an old debate. AB - Despite a significant research effort, the optimal dialysis regimen remains a topic of major controversy. There is a growing interest in intensive hemodialysis regimens as they have been associated with positive outcomes in several observational studies. However, recent evidence from a large cohort study casts doubts on the benefits of intensive hemodialysis. In this paper, we review the evidence on this topic and discuss the most recent results in the context of the existing literature to provide a global appraisal of the state of the evidence. PMID- 24178752 TI - Association of the HTR2A gene with alcohol and heroin abuse. AB - Positive genetic associations of rs6313 (102T/C at exon 1) and rs6311 (-1438A/G) on the 5-hydroxytryptamine (serotonin) 2A receptor gene (HTR2A or 5-HT2A) were reported for alcohol and drug abuse; however, other association studies failed to produce consistent results supporting the susceptibility of the two single nucleotide polymorphisms (SNPs). To clarify the associations of the HTR2A gene with substance use disorders, we performed a meta-analysis based on the genotypes from the available candidate gene association studies of the two SNPs with alcohol and drug abuse from multiple populations. Evidence of association was found for HTR2A rs6313 in all the combined studies (e.g., allelic P = 0.0048 and OR 0.86, 95 % CI 0.77-0.95) and also in the combined studies of alcohol dependence (abuse) (e.g., allelic P = 0.0001 and OR 0.71, 95 % CI 0.59-0.85). The same association trend was also observed in the Study of Addiction: Genetics and Environment datasets. The meta-analysis supports a contribution of the HTR2A gene to the susceptibility to substance use disorders, particularly alcohol dependence. PMID- 24178754 TI - Change in renal parenchymal volume in living kidney transplant donors. AB - PURPOSE: Uninephrectomy would induce compensatory hypertrophy in the remaining kidney. We investigated the relationship between changes in renal parenchymal volume (RPV) and renal function after nephrectomy in living kidney donors. METHODS: From July 2011 and January 2012, 45 kidney donors were enrolled in this study. Magnetic resonance scanning was performed before surgery, 3 and 7 days postoperatively, and RPV was calculated through disc summarize methods. Participants were followed up for 1 year. RESULTS: The RPV of the remaining kidney was 118.06 +/- 23.51 cm(3) and then increased by 21.23 % to 143.13 +/- 25.52 cm(3) at 3 days and by 24.17 % to 146.60 +/- 25.86 cm(3) at 7 days. Multivariate regression analysis showed that preoperative RPV is positively related to its initial function (p = 0.037); the RPV at 7 days is directly related to its initial, preoperative size (p < 0.001). With respect to change in postoperative RPV, there is bigger gain in size in smaller kidneys (p = 0.005). The kidneys that has >=20 % increase RPV after 7 days are more likely to show further increase in GFR at 1 year (p = 0.024). CONCLUSIONS: Uninephrectomy induced immediately increment in RPV of the remaining kidney. Donors with RPV increase of >=20 % at 1 week have a more favourable renal function adaptation at 1 year. PMID- 24178755 TI - Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection: a nationwide study in Sweden. AB - BACKGROUND: A few studies indicated that hepatitis C and hepatitis B virus (HCV/HBV) might be associated with pancreatic cancer risk. The aim of this nationwide cohort study was to examine this possible association. METHODS: Hepatitis C virus- and hepatitis B virus-infected individuals were identified from the national surveillance database from 1990 to 2006, and followed to the end of 2008. The pancreatic cancer risk in the study population was compared with the general population by calculation of Standardized Incidence Ratios (SIRs), and with a matched reference population using a Cox proportional hazards regression model to calculate hazard ratios (HRs). RESULTS: In total 340 819 person-years in the HCV cohort and 102 295 in the HBV cohort were accumulated, with 34 and 5 pancreatic cancers identified, respectively. The SIRHCV was 2.1 (95% confidence interval, CI: 1.4, 2.9) and the SIRHBV was 1.4 (0.5, 3.3). In the Cox model analysis, the HR for HCV infection was 1.9 (95% CI: 1.3, 2.7), diminishing to 1.6 (1.04, 2.4) after adjustment for potential confounders. CONCLUSION: Our results indicated that HCV infection might be associated with an increased risk of pancreatic cancer but further studies are needed to verify such association. The results in the HBV cohort indicated an excess risk, however, without statistical significance due to lack of power. PMID- 24178756 TI - Role of EIF5A2, a downstream target of Akt, in promoting melanoma cell invasion. AB - BACKGROUND: Cutaneous melanoma is a life-threatening skin cancer because of its poorly understood invasive nature and high metastatic potential. This study examines the importance of eukaryotic translation initiation factor 5A2 (EIF5A2) in melanoma pathogenesis. METHODS: We examined EIF5A2 expression in 459 melanocytic lesions using tissue microarray. In addition, melanoma cell lines were subjected to invasion and cell proliferation assays, zymography, FACS and real-time PCR to investigate the role of EIF5A2 in cancer progression. RESULTS: Positive EIF5A2 staining increased from dysplastic naevi to primary melanomas (PMs; P=0.001), and further increased in metastatic melanomas (P=0.044). Eukaryotic translation initiation factor 5A2 expression was correlated with melanoma thickness (P<0.001) and was inversely correlated with the 5-year survival of PM patients especially those with tumour <=2 mm thick. Strikingly, none of the latter died within 5 years in EIF5A2-negative staining group. Cox regression analysis revealed that EIF5A2 is an independent prognostic marker. Further, we found that EIF5A2 is a novel downstream target of phosphorylated Akt. Both melanoma cell invasion and MMP-2 activity increased and decreased with EIF5A2 overexpression and knockdown, respectively. CONCLUSION: We for the first time showed that EIF5A2, as a target of PI3K/Akt, promotes melanoma cell invasion and may serve as a promising prognostic marker and a potential therapeutic target for melanoma. PMID- 24178757 TI - Increased microvascular proliferation is negatively correlated to tumour blood flow and is associated with unfavourable outcome in endometrial carcinomas. AB - BACKGROUND: We aimed to study the angiogenic profile based on histomorphological markers in endometrial carcinomas in relation to imaging parameters obtained from preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) and to explore the potential value of these markers to identify patients with poor outcome. METHODS: In fifty-four surgically staged endometrial carcinoma patients, immunohistochemical staining with factor VIII and Ki67 allowed assessment of microvessel density (MVD) and microvascular proliferation reflecting tumour angiogenesis. In the same patients, preoperative pelvic DCE-MRI and DWI allowed the calculation of parameters describing tumour microvasculature and microstructure in vivo. RESULTS: Microvascular proliferation was negatively correlated to tumour blood flow (Fb) (r=-0.36, P=0.008), capillary permeability surface area product (PS) (r=-0.39, P=0.004) and transfer from the blood to extravascular extracellular space (EES) (Ktrans) (r=-0.40, P=0.003), and was positively correlated to tumour volume (r=0.34; P=0.004). High-tumour microvascular proliferation, low Fb and low Ktrans were all significantly associated with reduced progression/recurrence-free survival (P<0.05). CONCLUSION: Disorganised angiogenesis with coexisting microvascular proliferation and low tumour blood flow is a poor prognostic factor supporting that hypoxia is associated with progression and metastatic spread in endometrial carcinomas. PMID- 24178758 TI - Role of endoplasmic reticulum stress induction by the plant toxin, persin, in overcoming resistance to the apoptotic effects of tamoxifen in human breast cancer cells. AB - BACKGROUND: Persin is a plant toxin that displays synergistic cytotoxicity with tamoxifen in human breast cancer cell lines. Here, we examined the ability of persin to circumvent tamoxifen resistance and delineated the intracellular signalling pathways involved. METHODS: The induction of apoptosis in tamoxifen resistant and -sensitive breast cancer cells was measured by flow cytometry following treatment with persin+/-tamoxifen. Markers of endoplasmic reticulum stress (ERS) were analysed following treatment, and their causal role in mediating persin-induced apoptosis was determined using chemical inhibitors and RNA interference. RESULTS: Cells that were resistant to an apoptotic concentration of tamoxifen maintained an apoptotic response to persin. Persin induced apoptosis was associated with an increase in markers of ERS, that is, CHOP expression and XBP-1 splicing and was decreased by CHOP siRNA. The CASP-4 inhibitor Z-YVAD-FMK markedly inhibited persin-induced apoptosis in both tamoxifen-sensitive and -resistant cells. CONCLUSION: The cytotoxic effects of persin are CASP-4 dependent and mediated by CHOP-dependent and -independent ERS signalling cascades. Increased ERS signalling contributes to persin-induced reversal of tamoxifen resistance. PMID- 24178759 TI - Synergistic interaction of novel lactate dehydrogenase inhibitors with gemcitabine against pancreatic cancer cells in hypoxia. AB - BACKGROUND: Hypoxia is a driving force in pancreatic-ductal-adenocarcinoma (PDAC) growth, metastasis and chemoresistance. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis, ensuring supply of energy and anabolites in hypoxic-environments. Therefore, we investigated the molecular mechanisms underlying the pharmacological interaction of novel LDH-A inhibitors in combination with gemcitabine in PDAC cells. METHODS: Lactate dehydrogenase A levels were studied by quantitative RT-PCR, western blot, immunofluorescence and activity assays in 14 PDAC cells, including primary-cell-cultures and spheroids, in normoxic and hypoxic conditions. Cell proliferation, migration and key determinants of drug activity were evaluated by sulforhodamine-B-assay, wound-healing assay, PCR and LC-MS/MS. RESULTS: Lactate dehydrogenase A was significantly increased under hypoxic conditions (1% O2), where the novel LDH-A inhibitors proved to be particularly effective (e.g., with IC50 values of 0.9 vs 16.3 MUM for NHI-1 in LPC006 in hypoxia vs normoxia, respectively). These compounds induced apoptosis, affected invasiveness and spheroid-growth, reducing expression of metalloproteinases and cancer-stem-like-cells markers (CD133+). Their synergistic interaction with gemcitabine, with combination index values <0.4 in hypoxia, might also be attributed to modulation of gemcitabine metabolism, overcoming the reduced synthesis of phosphorylated metabolites. CONCLUSION: Lactate dehydrogenase A is a viable target in PDAC, and novel LDH-A inhibitors display synergistic cytotoxic activity with gemcitabine, offering an innovative tool in hypoxic tumours. PMID- 24178760 TI - Human fucosyltransferase 6 enables prostate cancer metastasis to bone. AB - BACKGROUND: The interaction between human prostate cancer (PCa) cells and bone marrow (BM) endothelium follows a rolling-and-adhesion cascade mediated by E selectin ligand (ESL): E-selectin. This adhesion is enabled by elevated expression of alpha-1,3-fucosyltransferases (FTs), enzymes responsible for ESL mediated bone metastasis in humans. In contrast, the incidence of bone metastasis in mice is rare. METHODS: FT 3, 6 and 7 were overexpressed in mouse PCa cells. The rolling cell number, cell-rolling velocity and transendothelial migration were characterised in vitro. Fucosyltransferases-transduced mouse PCa cells expressing luciferase were inoculated into mice via left ventricle to compare the capability of bone metastasis. Mass spectrometry and immunoprecipitation were utilised for identification of ESLs. RESULTS: Overexpression of FT3, FT6 or FT7 restored ESLs and enabled mouse PCa cells to roll and adhere in E-selectin functionalised microtubes, similar to trafficking of circulating PCa cells in BM vessels. Following intracardiac inoculation, FT6-transduced cells induced robust bone metastasis in mice. Inhibition of FT6 by a fucose mimetic significantly reduced bone metastasis. Importantly, comparison of FT3, FT6 and FT7 gene expression in existing clinical samples showed significant upregulation of FT6 in PCa-distant metastases. CONCLUSION: FT6 is a key mediator of PCa cells trafficking to the BM. It may serve as a viable drug target in preclinical tests of therapeutics for reduction of PCa bone metastasis. PMID- 24178761 TI - Recognition of cancer warning signs and anticipated delay in help-seeking in a population sample of adults in the UK. AB - BACKGROUND: Not recognising a symptom as suspicious is a common reason given by cancer patients for delayed help-seeking; but inevitably this is retrospective. We therefore investigated associations between recognition of warning signs for breast, colorectal and lung cancer and anticipated time to help-seeking for symptoms of each cancer. METHODS: Computer-assisted telephone interviews were conducted with a population-representative sample (N=6965) of UK adults age >= 50 years, using the Awareness and Beliefs about Cancer scale. Anticipated time to help-seeking for persistent cough, rectal bleeding and breast changes was categorised as >2 vs <= 2 weeks. Recognition of persistent cough, unexplained bleeding and unexplained lump as cancer warning signs was assessed (yes/no). Associations between recognition and help-seeking were examined for each symptom controlling for demographics and perceived ease of health-care access. RESULTS: For each symptom, the odds of waiting for >2 weeks were significantly increased in those who did not recognise the related warning sign: breast changes: OR=2.45, 95% CI 1.47-4.08; rectal bleeding: OR=1.77, 1.36-2.30; persistent cough: OR=1.30, 1.17-1.46, independent of demographics and health-care access. CONCLUSION: Recognition of warning signs was associated with anticipating faster help-seeking for potential symptoms of cancer. Strategies to improve recognition are likely to facilitate earlier diagnosis. PMID- 24178763 TI - Microreactors with integrated UV/Vis spectroscopic detection for online process analysis under segmented flow. AB - Combining reaction and detection in multiphase microfluidic flow is becoming increasingly important for accelerating process development in microreactors. We report the coupling of UV/Vis spectroscopy with microreactors for online process analysis under segmented flow conditions. Two integration schemes are presented: one uses a cross-type flow-through cell subsequent to a capillary microreactor for detection in the transmission mode; the other uses embedded waveguides on a microfluidic chip for detection in the evanescent wave field. Model experiments reveal the capabilities of the integrated systems in real-time concentration measurements and segmented flow characterization. The application of such integration for process analysis during gold nanoparticle synthesis is demonstrated, showing its great potential in process monitoring in microreactors operated under segmented flow. PMID- 24178762 TI - Identification of candidate circulating cisplatin-resistant biomarkers from epithelial ovarian carcinoma cell secretomes. AB - BACKGROUND: The majority of patients diagnosed with advanced epithelial ovarian carcinoma (EOC) relapse with resistant disease, and there are no biomarkers that possess clinical utility to identify or monitor these patients. This study aimed to identify secreted proteins ('secretome') collected from human EOC cell lines that differ in their inherent platinum sensitivity. METHODS: Secreted proteins collected from conditioned medium from ovarian cancer cell lines that vary in their sensitivity to cisplatin were digested with trypsin and analysed by liquid chromatography-tandem mass spectrometry for peptide identification. RESULTS: Of the 1688 proteins identified, 16 possessed significant differential abundances (P<0.05) between the platinum-resistant and -sensitive cell lines. A number of these were verified by immunoblot, including COL11A1, which was also found to be associated with worse progression-free survival (PFS; N=723) and overall survival (OS; N=1183) as assessed from publicly available transcript expression data from ovarian cancer tumour specimens. CONCLUSION: Secretome proteomics of EOC cells resulted in the identification of a novel candidate biomarker, COL11A1. The expression level of COL11A1 correlates to worse PFS and OS, and is predicted to reside in peripheral circulation making this an attractive candidate for validation in sera as a biomarker of cisplatin resistance and poor outcome. PMID- 24178764 TI - Assessment of chondrogenic differentiation potential of autologous activated peripheral blood stem cells on human early osteoarthritic cancellous tibial bone scaffold. AB - INTRODUCTION: Current therapeutic regimens in osteoarthritis (OA) address mainly pain but not the slow progressive degradation of the extracellular matrix (ECM) and the loss of a chondrogenic phenotype in articular cartilage. In the present study, using an early OA cancellous bone scaffold, we aimed to uncover evidence of the successful hyaline cartilage regenerative capacity of autologous human granulocyte colony-stimulating factor (hG-CSF)-activated peripheral blood stem cells (AAPBSC) with growth factor addition. MATERIALS AND METHODS: AAPBSC were harvested in ten patients (median age 58 years, 8 females), and flow cytometry was performed for cell surface markers. Arthroscopically obtained cancellous bone scaffold specimens were seeded with AAPBSC. In Group 1, the scaffold was seeded with AAPBSC only, in Group 2, AAPBSC plus hyaluronic acid (HA), and in Group 3, AAPBSC plus HA, hG-CSF, and double-centrifuged platelet-rich plasma (PRP). The specimens were analyzed for cell attachment and proliferation by the fluorometric quantification of cellular DNA assay and scanning electron microscopy. Chondrogenic gene expression was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) of Sox9, collagen type II (COL-2), and aggrecan. Histological sections of scaffold constructs for cartilaginous matrix formation were stained with toluidine blue (proteoglycan) and safranin O (sGAG) after 3 weeks. RESULTS: AAPBSC displayed especially high levels of CD29 and CD44 surface markers, as well as CD90, and CD105, while only a small proportion expressed CD34. Almost half of the seeded cells attached on the bone scaffolds in all three groups (not statistically significant), whereas the means of cell proliferation on day 7 compared to day 1 were statistically significant difference with the order of increase as group 3 > group 2 > group 1. RT-PCR showed statistically significant sequential increases in Sox9, COL-2, and Aggrecan all being highest in group 3. Histological analysis demonstrated cells in the cancellous bone scaffold with a round morphology, and ECM was positively stained by toluidine blue and safranin O indicating increased proteoglycan and glycosaminoglycan content, respectively, in the newly formed cartilage matrix. CONCLUSIONS: AAPBSC initiated chondrocyte differentiation on an autologous cancellous bone scaffold, and the addition of PRP and hG-CSF further stimulated cell proliferation toward a chondrocyte phenotype with potentiated Sox9 transcription resulting in sequential COL-2 and aggrecan mRNA increases that ultimately resulted in histologically confirmed increased proteoglycan and glucosaminoglycan content in newly formed hyaline cartilage. PMID- 24178765 TI - Effects of alcohol mixed with energy drink and alcohol alone on subjective intoxication. AB - Recent studies suggest that the combination of caffeine-containing drinks together with alcohol might reduce the subjective feelings of alcohol intoxication-the so-called "masking effect". In this study, we aimed to review the effects of alcohol in combination with caffeine or energy drink with special focus on the "masking effect". Fifty-two healthy male volunteers were analysed concerning breath alcohol concentration and subjective sensations of intoxication using a 18 item Visual Analogue Scale in a randomised, double-blinded, controlled, four treatments cross-over trial after consumption of (A) placebo, (B) alcohol (vodka 37.5% at a dose of 46.5 g ethanol), (C) alcohol in combination with caffeine at a dose of 80 mg (equivalent to one 250 ml can of energy drink) and (D) alcohol in combination with energy drink at a dose of 250 ml (one can). Primary variables were headache, weakness, salivation and motor coordination. Out of four primary variables, weakness and motor coordination showed a statistically significant difference between alcohol and non-alcohol group, out of 14 secondary variables, five more variables (dizziness, alterations in sight, alterations in walking, agitation and alterations in speech) also showed significant differences due mainly to contrasts with the non-alcohol group. In none of these end points, could a statistically significant effect be found for the additional ingestion of energy drink or caffeine on the subjective feelings of alcohol intoxication. This within-subjects study does not confirm the presence of a "masking effect" when combining caffeine or energy drink with alcohol. PMID- 24178766 TI - Protein homeostasis disorders of key enzymes of amino acids metabolism: mutation induced protein kinetic destabilization and new therapeutic strategies. AB - Many inborn errors of amino acids metabolism are caused by single point mutations affecting the ability of proteins to fold properly (i.e., protein homeostasis), thus leading to enzyme loss-of-function. Mutations may affect protein homeostasis by altering intrinsic physical properties of the polypeptide (folding thermodynamics, and rates of folding/unfolding/misfolding) as well as the interaction of partially folded states with elements of the protein homeostasis network (such as molecular chaperones and proteolytic machineries). Understanding these mutational effects on protein homeostasis is required to develop new therapeutic strategies aimed to target specific features of the mutant polypeptide. Here, I review recent work in three different diseases of protein homeostasis associated to inborn errors of amino acids metabolism: phenylketonuria, inherited homocystinuria and primary hyperoxaluria type I. These three different genetic disorders involve proteins operating in different cell organelles and displaying different structural complexities. Mutations often decrease protein kinetic stability of the native state (i.e., its half-life for irreversible denaturation), which can be studied using simple kinetic models amenable to biophysical and biochemical characterization. Natural ligands and pharmacological chaperones are shown to stabilize mutant enzymes, thus supporting their therapeutic application to overcome protein kinetic destabilization. The role of molecular chaperones in protein folding and misfolding is also discussed as well as their potential pharmacological modulation as promising new therapeutic approaches. Since current available treatments for these diseases are either burdening or only successful in a fraction of patients, alternative treatments must be considered covering studies from protein structure and biophysics to studies in animal models and patients. PMID- 24178767 TI - The link between vascular deterioration and branched chain amino acids in a population with high glycated haemoglobin: the SABPA study. AB - Globally the prevalence of non-communicable diseases, such as hypertension and type 2 diabetes, are escalating. Metabolomic studies indicated that circulating branched chain amino acids (BCAAs) are associated with insulin resistance, coronary artery disease and increased risk for cardiovascular events. We aimed to extend the current understanding of the cardiovascular risk associated with BCAAs. We explored whether BCAAs are related to markers of cardiovascular disease in a bi-ethnic population and whether this relationship was influenced by chronic hyperglycaemia. We included 200 African and 209 Caucasian participants, and determined their ambulatory blood pressure and carotid intima-media thickness (cIMT). We analysed blood samples for glycated haemoglobin (HbA1c) and BCAAs. Participants were stratified into two groups according to their HbA1c value using the median cut-off value of 5.6%. Ambulatory BP, cIMT and BCAAs were significantly higher (all p < 0.001) in the high HbA1c group. Single regression analyses indicated significant positive associations of ambulatory blood pressure and cIMT with BCAAs (all p < 0.05) in both the groups. These associations between ambulatory systolic blood pressure (SBP) (r = 0.16, p = 0.035) and cIMT (r = 0.22, p = 0.004) with BCAAs remained in the high HbA1c group after adjusting for age, gender, ethnicity and body mass index (BMI) and were confirmed in multiple regression analyses (ambulatory SBP: R (2) = 0.17, beta = 0.21, p = 0.005 and cIMT: R (2) = 0.30, beta = 0.19, p = 0.003). Our results demonstrate that BCAAs are independently related to ambulatory BP and cIMT in individuals with high HbA1c levels and suggest that potential cardiovascular deterioration accompany the rise in BCAAs in conditions of hyperglycaemia. PMID- 24178768 TI - Taurine chloramine modulates the expression of adipokines through inhibition of the STAT-3 signaling pathway in differentiated human adipocytes. AB - To examine the possible role of taurine chloramine (TauCl) in modulating the expression of adipokines in adipose tissue associated with obesity, we evaluated the effect of TauCl in human differentiated adipocytes in response to IL-1beta. To study the physiological effects of TauCl on adipokine expression, differentiated adipocytes were treated with IL-1beta in the presence or absence of TauCl at concentrations ranging from 200 to 600 MUM for 7 days. Cell culture supernatants and total RNA were analyzed by ELISA and real-time PCR, respectively, to determine protein and mRNA levels of adipokines, including adiponectin, leptin, IL-6, and IL-8. Levels of proteins involved in relevant signaling pathways were investigated by western blotting. Stimulation with IL 1beta significantly decreased levels of adiponectin and leptin in adipocytes, but increased levels of IL-6 and IL-8 in a dose-dependent manner. Treatment with TauCl significantly reversed the modulation of adipokine expression by inhibiting STAT-3 signaling in IL-1beta-stimulated adipocytes, independent of MAPK signaling. TauCl treatment more significantly modulated the expression of adipokines in adipocytes stimulated with IL-1beta than that of non-stimulated adipocytes, suggesting that TauCl plays a significant role in modulating the expression of adipokines under inflammatory conditions. In conclusion, TauCl and other taurine derivatives that inhibit the STAT-3 signaling pathway can modulate expression of adipokines and thus may be useful as therapeutic agents for obesity related diseases. PMID- 24178769 TI - Phosphorylation of cystic fibrosis transmembrane conductance regulator (CFTR) serine-511 by the combined action of tyrosine kinases and CK2: the implication of tyrosine-512 and phenylalanine-508. AB - The cystic fibrosis transmembrane conductance regulator (CFTR) harbors, close to Phe-508, whose deletion is the commonest cause of cystic fibrosis, a conserved potential CK2 phospho-acceptor site (Ser511), which however is not susceptible to phosphorylation by CK2. To shed light on this apparent paradox, a series of systematically substituted peptides encompassing Ser511 were assayed for their ability to be phosphorylated. The main outcomes of our study are the following: (a) Tyr512 plays a prominent role as a negative determinant as its replacement by Ala restores Ser511 phosphorylation by CK2; (b) an even more pronounced phosphorylation of Ser511 is promoted if Tyr512 is replaced by phospho-tyrosine instead of alanine; (c) Tyr512 and, to a lesser extent, Tyr515 are readily phosphorylated by Lyn, a protein tyrosine kinase of the Src family, in a manner which is enhanced by the concomitant Phe508 deletion. Collectively taken, our data, in conjunction with the notion that Tyr515 is phosphorylated in vivo, disclose the possibility that CFTR Ser511 can be phosphorylated by the combined action of tyrosine kinases and CK2 and disclose a new mechanism of hierarchical phosphorylation where the role of the priming kinase is that of removing negative determinant(s). PMID- 24178770 TI - The key jingler. AB - The key jingler is the staff person in any institution who uses his power in a manner that is debilitating to the inmates. He is a confidence man, bureaucrat, buck passer, someone putting up a front. Quite often it is the norms of the institution that impose this kind of behavior on the staff. The key jingling process then serves to place the inmate in a double bind, cool him out or institutionalize him into the system. The thoughts on the double bind process, cooling out process, and dysfunctional bureaucracy merge into one concept of key jingling. PMID- 24178771 TI - Planning for mental health. AB - This report is based on a study of comprehensive mental health state plans submitted to the National Institute of Mental Health in 1965, interviews with mental health planners in selected states, discussions with professionals and citizens involved in the planning, and a review of the pertinent literature. This study was made to bring together observations about the outcome of this massive planning effort, to comment on the current status of mental health planning, and to develop some directions for facilitating planning at the state level. PMID- 24178772 TI - A program leading to a master of science degree in community mental health. AB - Northern Illinois University now offers a master of science in community mental health degree program. This is a multidisciplinary program involving the Departments of Education, Psychology, Sociology, and Home Economics, with each department offering two or more relevant courses. This is a work-study program in which the student is required to work some 300 hours under supervision, in a variety of mental health agencies in a number of communities. He is finally qualified to serve as the linking agent between the patient and the various agencies and professional personnel. PMID- 24178773 TI - The day care neighbor service: An interventive experiment. AB - In the United States, more than one million children of working mothers are cared for in the homes of nonrelatives. An informal social system exists through which mothers and day care givers find each other, make, maintain, and dissolve their private arrangements, almost entirely without the intervention of any social agency. This paper describes the development of a new kind of day care service using consultation methods for preventive intervention at the neighborhood level. This "Day Care Neighbor Service" provides consultation to a network of women who perform an informal neighboring role in relation to family day care arrangements. The primary, secondary, and tertiary preventive potentials of this approach are discussed. PMID- 24178774 TI - Guidelines for community mental health plans and programs. AB - Planning is frequently compromised because clearly stated goals and objectives are not enunciated. Only by such statements is it possible to establish intermediate steps and assess progress toward the ultimate goals or to evaluate alternative paths. This paper outlines guiding principles which might serve as benchmarks for progress for community mental health and mental retardation programs. PMID- 24178776 TI - Community organization and the public interest. AB - The commitment to serve the "public interest"is often referred to by community organization and planning professionals. This idealized concept is examined and compared to the behavior of practitioners. The necessity for determining which publics, and whose interests, are to be served in order to find an appropriate approach are discussed. Whether the practitioners are to see themselves as technical expediters, change agents, or peacemakers, seems to be at issue. The past community organization commitment to a process as the ultimate guarantee of accomplishment is questioned and new directions are discussed. PMID- 24178775 TI - A cross-cultural format for national mental health program analysis. AB - With the growing interest in community mental health programs outside of the United States on the part of American mental health professionals, a cross cultural format has been developed to assist in making a comprehensive analysis of any national mental health program. The format itself, together with initial experiences with its utilization in the study of six different mental health programs, is presented. While continued revisions of the format can be expected, it has already proved useful in comparative analyses of a variety of mental health program components. PMID- 24178777 TI - New developments in the preparation of counselors. AB - Since World War II, the emphasis in clinical and counseling psychology has been on training people at the Ph.D. level. While some need for subdoctoral training has been expressed at national conferences, there has been comparatively little actual support for such programs. With the increasing social demand for mental health services, however, some new developments are apparent. Several such new attempts at innovative training programs are reviewed and their implications discussed. A trend is evident for such training to occur outside of universities, to emphasize practical training, and to focus on participatory learning. PMID- 24178778 TI - A research project in teaching in a women's prison. AB - The purpose of this project was to discover new goals and techniques for teaching commercial subjects to women inmates at the House of Detention for Women in New York City. Formerly, this program had been judged a failure, since almost none of the inmates went on to secretarial work after release. With long histories of recidivism, these women were generally out of touch with themselves and with reality; their behavior was evasive and manipulative both in and out of prison. A typewriter, however, cannot be manipulated; typing cannot be faked. The confrontation with the inflexible reality produced by the black symbol can thus be used by a well-trained teacher to impart new insights, encourage firmer reality orientation, and strengthen selfconcepts. The redirection must be from emphasis on the acquisition of technical skill to the understanding of behavior and the therapeutic value of autonomous achievement. PMID- 24178779 TI - Planning for Bellak's third revolution. AB - Traditional planning models which aim for comprehensiveness are examined and found to be misleading. Comprehensive planning is limited by the planner's knowledge and information sources, the influence of value premises, and the multiplicity of decision centers. Citizen participation is viewed as a further limitation upon rationality in the decision-making process. But citizen participation is also suggested as a means for adjudicating value conflicts and also as a purposeful method for overcoming the "politics" of community decision making. PMID- 24178780 TI - Publications received. PMID- 24178781 TI - Imaging mass spectrometry: a new tool for pathology in a molecular age. AB - Mass spectrometry (MS) provides unique advantages for the analysis of clinical specimens, and these capabilities have been critical to the advancement of diagnostic medicine. To date, LC-MS is the MS platform most commonly used for diagnostics; however, LC-MS based proteomics is very labor intensive and costly to implement for high volume assays. Furthermore, when analyzing tissue samples, additional laborious sample preparation steps must be employed (e.g. extraction methods or laser microdissection). The direct analysis of cells and tissues by MALDI imaging MS has developed significant momentum for applications that have diagnostic potential. MALDI imaging MS provides molecular information from specific cell types within tissue sections; however, this laser-based approach significantly reduces the analysis time for each location sampled. This Viewpoint discusses the technologies for direct analysis of tissues, the potential for diagnostic applications using MALDI imaging MS, and the challenges faced in the transfer of the technology to the clinical laboratory. PMID- 24178782 TI - Synthesis of solvent stable polymeric membranes via UV depth-curing. AB - Solvent stable polymeric membranes with morphologies ranging from highly porous to dense were prepared via UV curing using dedicatedly designed photopolymerizable compositions. To optimize the UV curing efficiency, various parameters including the photoinitiator type, cross-linker functionality, as well as membrane thickness were investigated. UV modified polysulfone membranes showed excellent solvent stability in addition to a 91% Rose Bengal (1017 Da) retention at a superior ethyl acetate permeance of 8 l m(-2) h(-1) bar(-1) in a typical solvent resistant nanofiltration (SRNF) experiment. PMID- 24178783 TI - The effect of a wellness program on adolescent females. AB - Guided by Bandura's Social Cognitive Theory, the purpose of this study was to examine the effect of a comprehensive wellness intervention on total wellness, physical fitness, and self-efficacy for health promoting behaviors in adolescent females, ages 14 to 19, enrolled in physical education (PE) classes in Grades 9 to 12. The intervention was administered in an experimental pre-test, post-test, two group design in rural east Texas. Participants (n = 153) were randomly assigned to a 12-week intervention or control group. Independent t-tests to determine differences between the intervention and control groups were nonsignificant for overall wellness and physical fitness. The Wellness Essential Self subscale score was significantly higher in the intervention group, t(64, 36) = 2.67, p = .005, d = .84. Self-Efficacy Health Promotion subscale scores for the intervention group were also significantly higher, t(20,28) = 2.60, p = .006, d = .74. The intervention has potential to improve overall wellness in adolescent females. PMID- 24178784 TI - Retinal ganglion cells in the Pacific redfin, Tribolodon brandtii dybowski, 1872: morphology and diversity. AB - We studied the morphology and diversity of retinal ganglion cells in the Pacific redfin, Tribolodon brandtii. These cells were retrogradely labeled with horseradish peroxidase and examined in retinal whole mounts. A sample of 203 cells was drawn with a camera lucida. A total of 19 structural parameters were estimated for each cell, and a variety of clustering algorithms were used to classify the cells. The optimal solution was determined by using silhouette analysis. It was based on three variables associated with dendritic field size and dendrite stratification in the retina. Kruskal-Wallis ANOVA-on-ranks with post hoc Mann-Whitney U tests showed significant pairwise between-cluster differences in two or more of the original variables. In total, eight cell types were discovered. The advantages and drawbacks of the methodology adopted are discussed. The present classification is compared with classifications proposed for other teleosts. PMID- 24178785 TI - Suppressive effects of dietary high fluorine on the intestinal development in broilers. AB - Fluoride (F) is a well-recognized hazardous substance. Ingested F initially acts locally on the intestines. The small intestine plays a critical role in the digestion, absorption, and defense. In this study, therefore, we investigated the effects of fluorine on the intestinal development by light microscopy, transmission electron microscopy, and histochemistry. A total of 280 one-day-old avian broilers were randomly divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine, 22.6 mg/kg) or the same basal diet supplemented with 400, 800, and 1,200 mg/kg fluorine (high fluorine groups I, II, and III) in the form of sodium fluoride for 42 days. The results showed that the intestinal gross, histological, and ultrastructural changes were observed in the high fluorine groups II and III. Meanwhile, the intestinal length, weight, viscera index, villus height, crypt depth, villus height to crypt depth ratio, diameter, muscle layer thickness, and goblet cell numbers were significantly lower (p < 0.01 or p < 0.05), and the intestinal diameter to villus height ratio was markedly higher (p < 0.01 or p < 0.05) in the high fluorine groups II and III than those in control group. In conclusion, dietary fluorine in the range of 800 1,200 mg/kg obviously altered the aforementioned parameters of the intestines, implying that the intestinal development was suppressed and the intestinal functions, such as digestion, absorption, defense, or osmoregulation were impaired in broilers. PMID- 24178786 TI - Mercury in scalp hair near the Mid-Atlantic Ridge (MAR) in relation to high fish consumption. AB - The aim of this study was to evaluate the potential risk of mercury contamination near the Mid-Atlantic Ridge relating total mercury (THg) concentrations in the human scalp hair (n = 110) and high fish consumption levels. THg was quantified in human scalp hair, and volunteers were questioned about age, gender, and smoking habits being subsequently grouped in categories based on the individual average intake of fish meals per week. THg concentrations ([THg]) in hair samples ranged from 0.05 to 2.24 MUg g(-1), and significant differences were found according to age (p < 0.05) and also among volunteers presenting different fish consumption rates (p < 0.001) being the highest [THg] observed on the adult population and also on volunteers that indicated consuming five or more meals of fish per week. Results indicate a pattern of increased mercury accumulation with increasing fish consumption. Despite mercury availability and a potential mercury intake of up to seven times, the WHO provisional tolerable weekly intake of mercury value, in consequence of high fish consumption, mercury concentrations in scalp hair are comparatively low regarding recommended levels by WHO. PMID- 24178787 TI - The effects of tesamorelin on phosphocreatine recovery in obese subjects with reduced GH. AB - CONTEXT: Few studies have assessed the relationship between GH and mitochondrial function. OBJECTIVE: The objective of this study was to determine the effects of improving IGF-I using a GHRH analog, tesamorelin, on mitochondrial function assessed by phosphocreatine (PCr) recovery using (31)P magnetic resonance spectroscopy in obese adults with reduced GH. DESIGN: A total of 39 obese men and women with reduced GH secretion as determined by GHRH-arginine stimulation tests underwent magnetic resonance spectroscopy as part of a 12-month, double-blind, randomized, placebo-controlled trial comparing tesamorelin vs placebo. PCr recovery after submaximal exercise was assessed at baseline and at 12 months. RESULTS: At baseline, there were no differences in age, sex, race/ethnicity, and GH or PCr parameters between tesamorelin and placebo. After 12 months, tesamorelin treatment led to a significantly greater increase in IGF-I than did placebo treatment (change, 102.9+/-31.8 MUg/L vs 22.8+/-8.9 MUg/L, tesamorelin vs placebo; P=.02). We demonstrated a significant positive relationship between increases in IGF-I and improvements in PCr recovery represented as ViPCr (R=0.56; P=.01). The association between IGF-I and PCr recovery was even stronger among subjects treated with tesamorelin only (ViPCr: R=0.71; P=.03). This association remained significant after controlling for age, sex, race, ethnicity, and parameters of body composition and insulin sensitivity (all P<.05). CONCLUSIONS: Increases in IGF-I from 12 months of treatment with tesamorelin were significantly associated with improvements in PCr recovery parameters in obese men and women with reduced GH secretion, suggestive of improvements in mitochondrial function. PMID- 24178788 TI - High prevalence of PROP1 defects in Lithuania: phenotypic findings in an ethnically homogenous cohort of patients with multiple pituitary hormone deficiency. AB - CONTEXT: PROP1 gene mutations cause multiple pituitary hormone deficiency (MPHD). OBJECTIVE: We sought to expand experience with PROP1 mutation carriers by studying a large cohort of Lithuanian patients. PATIENTS AND METHODS: Sixty-seven MPHD patients were tested for PROP1 defects. Perinatal and postnatal data were obtained from medical records. Hormonal investigations, pituitary imaging, and GH therapy were provided in a single center in Kaunas, Lithuania. RESULTS: A biallelic PROP1 gene mutation was found in 47 subjects (70.1%), of which 46 were homozygous for 296delGA. Positive finding rate among MPHD and population prevalence of PROP1 defects in Lithuania (15.8 per million) were the highest reported to date. Patients' birth lengths/weights were normal. Testicular retention was noted in 31% of boys. Median height SD scores declined over years 1 5: -1.56, -2.34, -3.43, -3.52, and -3.70. Mid-parental height predicted severity of growth retardation at diagnosis (r2=0.30; P=.0001). Deficiencies of GH, TSH, ACTH, and FSH/LH were diagnosed in 44/44, 44/44, 19/44, and 22/44 subjects at median age of 5.5, 5.6, 13.1, and 15.0 years, respectively. Pituitary height ranged from 16.6 mm (+20.2 SD) to 1.4 mm (-15.5 SD) and declined with age (r2=0.27, P=.001). GH replacement (dose 0.027 mg/kg/d) led to height velocities 12.2; 9.1; 6.9; 6.8; 6.7; 5.6; and 5.7 cm/y (medians) at years 1-7 and final height SD scores (17 patients) -0.98+/-1.77 (-1.04+/-1.41 below target height; P=.008 vs 0). CONCLUSIONS: High prevalence of PROP1 defects in Lithuania is due to 296delGA mutation, suggesting a founder effect. PMID- 24178789 TI - Fas and FasL expression in human adipose tissue is related to obesity, insulin resistance, and type 2 diabetes. AB - CONTEXT: Deletion of the death receptor Fas (CD95) in adipocytes of mice is associated with improved insulin sensitivity and reduced adipose tissue (AT) inflammation. OBJECTIVE: Here we investigate the relationship of AT Fas with human obesity. DESIGN AND METHODS: In paired samples of omental and sc AT from 256 lean and obese (including insulin-sensitive and insulin-resistant subgroups; n=60) participants, we investigated whether Fas and Fas-ligand (FasL) mRNA expression is fat depot-specific, altered in obesity, and related to measures of AT inflammation and insulin sensitivity. In addition, AT Fas mRNA expression was measured in 16 obese patients after significant weight loss of 45+/-6.3 kg in the context of a two-step bariatric surgery strategy. RESULTS: Fas and FasL are significantly higher expressed in omental (OM) compared to sc AT. Fas expression correlates with body mass index (OM, r2=0.44; sc, r2=0.14), AT macrophage infiltration (OM, r2=0.36; sc, r2=0.16), and glucose infusion rate in euglycemic hyperinsulinemic clamps (OM, r2=0.17; sc, r2=0.13) (P<.05 for all). FasL expression most strongly correlates with adipocyte size (OM, r2=0.32; sc, r2=0.17) and AT macrophage infiltration (OM, r2=0.46; sc, r2=0.02). Insulin sensitive obese individuals had significantly lower Fas and FasL expression than insulin-resistant obese individuals. Significant weight loss 12 months after gastric sleeve resection is associated with a significantly reduced Fas expression in OM and sc fat depots. CONCLUSIONS: Independently of body weight, increased Fas expression may contribute to impaired insulin sensitivity and AT dysfunction in obesity. Moreover, significant weight loss reduces Fas expression in OM and sc fat depots. PMID- 24178790 TI - Denosumab for management of parathyroid carcinoma-mediated hypercalcemia. AB - CONTEXT: Most of the morbidity and mortality from parathyroid cancer is due to PTH-mediated hypercalcemia. Classically, management mainly consists of surgical resection, chemotherapy, and alleviation of hypercalcemia using bisphosphonates and calcium receptor agonists. The use of denosumab in the treatment of parathyroid cancer-mediated hypercalcemia has not been reported. OBJECTIVE: The aim of this report is to describe the effect of denosumab on parathyroid cancer induced hypercalcemia. SUBJECT, MEASURES, AND RESULT: The patient is a 39-year old man with metastatic parathyroid cancer who presented at age 35. His calcium levels initially responded to surgery, bisphosphonates, calcium receptor agonist, and chemotherapy (dacarbazine). However, his disease progressed, and his hypercalcemia became refractory to these measures in the setting of rising PTH levels. The addition of denosumab, a humanized monoclonal antibody inhibiting receptor activator of nuclear factor kappaB ligand resulted in successful management of his hypercalcemia for an additional 16 months. CONCLUSIONS: Denosumab can be effective in the treatment of refractory hypercalcemia in parathyroid cancer. It may also be of potential use in settings of benign hyperparathyroid-related hypercalcemia such as parathyromatosis, where hypercalcemia is not amenable to surgery or medical therapy with bisphosphonates and calcium receptor agonists. PMID- 24178791 TI - Polycystic ovary syndrome: perceptions and attitudes of women and primary health care physicians on features of PCOS and renaming the syndrome. AB - CONTEXT: Polycystic ovary syndrome (PCOS) is an under-recognized, common, and complex endocrinopathy. The name PCOS is a misnomer, and there have been calls for a change to reflect the broader clinical syndrome. OBJECTIVE: The aim of the study was to determine perceptions held by women and primary health care physicians around key clinical features of PCOS and attitudes toward current and alternative names for the syndrome. DESIGN: We conducted a cross-sectional study utilizing a devised questionnaire. SETTING: Participants were recruited throughout Australia via professional associations, women's health organizations, and a PCOS support group. PARTICIPANTS: Fifty-seven women with PCOS and 105 primary care physicians participated in the study. MAIN OUTCOME MEASURES: Perceptions of key clinical PCOS features and attitudes toward current and alternative syndrome names were investigated. RESULTS: Irregular periods were identified as a key clinical feature of PCOS by 86% of the women with PCOS and 90% of the primary care physicians. In both groups, 60% also identified hormone imbalance as a key feature. Among women with PCOS, 47% incorrectly identified ovarian cysts as key, 48% felt the current name is confusing, and 51% supported a change. Most primary care physicians agreed that the name is confusing (74%) and needs changing (81%); however, opinions on specific alternative names were divided. CONCLUSIONS: The name "polycystic ovary syndrome" is perceived as confusing, and there is general support for a change to reflect the broader clinical syndrome. Engagement of primary health care physicians and consumers is strongly recommended to ensure that an alternative name enhances understanding and recognition of the syndrome and its complex features. PMID- 24178793 TI - Measurement of estradiol--challenges ahead. PMID- 24178792 TI - Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto's) thyroiditis: a randomized controlled clinical trial. AB - CONTEXT: Hashimoto's thyroiditis is less prevalent in tobacco smokers. Anatabine, an alkaloid found in Solanaceae plants including tobacco, has been reported to ameliorate a mouse model of Hashimoto's thyroiditis. OBJECTIVE: The effects of anatabine in patients with Hashimoto's thyroiditis were studied. DESIGN, SETTING, PATIENTS, AND INTERVENTION: This was a double-blind, randomized, placebo controlled multisite study. A total of 146 patients (70 treated with anatabine and 76 with placebo) completed the study. Approximately 50% of patients in each group were taking levothyroxine. Anatabine lozenges (9-24 mg/d) or placebo, each containing vitamins A and D3, were administered orally 3 times a day for 3 months. MAIN OUTCOME MEASURES: Serum thyroperoxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were assessed. Safety was assessed through adverse events, clinical laboratory evaluations, and vital sign measurements. RESULTS: Anatabine-treated patients had a significant reduction in absolute serum TgAb levels from baseline by study end relative to those receiving placebo (P=.027); however, there were no significant changes or differences in treatment group means for TPOAb or TgAb levels. Mean+/-SD TgAb values decreased by 46.2+/ 101.1 and 3.9+/-83.9 World Health Organization units for the anatabine and placebo groups, respectively. Significantly more patients had a >20% drop in TgAb levels in the anatabine than placebo group (P=.023). Overall, the anatabine supplement was safe and well tolerated, although significantly (P<.05) more patients in the anatabine group reported adverse events. CONCLUSIONS: These results demonstrate an immunological effect of anatabine on TgAb levels. Further studies are warranted to determine the longer-term effects and possible actions of anatabine on the course of Hashimoto's thyroiditis. PMID- 24178794 TI - Endurance exercise training up-regulates lipolytic proteins and reduces triglyceride content in skeletal muscle of obese subjects. AB - CONTEXT: Skeletal muscle lipase and intramyocellular triglyceride (IMTG) play a role in obesity-related metabolic disorders. OBJECTIVES: The aim of the present study was to investigate the impact of 8 weeks of endurance exercise training on IMTG content and lipolytic proteins in obese male subjects. DESIGN AND VOLUNTEERS: Ten obese subjects completed an 8-week supervised endurance exercise training intervention in which vastus lateralis muscle biopsy samples were collected before and after training. MAIN OUTCOME MEASURES: Clinical characteristics and ex vivo substrate oxidation rates were measured pre- and posttraining. Skeletal muscle lipid content and lipolytic protein expression were also investigated. RESULTS: Our data show that exercise training reduced IMTG content by 42% (P < .01) and increased skeletal muscle oxidative capacity, whereas no change in total diacylglycerol content and glucose oxidation was found. Exercise training up-regulated adipose triglyceride lipase, perilipin (PLIN) 3 protein, and PLIN5 protein contents in skeletal muscle despite no change in mRNA levels. Training also increased hormone sensitive-lipase Ser660 phosphorylation. No significant changes in comparative gene identification 58, G0/G1 switch gene 2, and PLIN2 protein and mRNA levels were observed in response to training. Interestingly, we noted a strong relationship between skeletal muscle comparative gene identification 58 and mitochondrial respiratory chain complex I protein contents at baseline (r = 0.87, P < .0001). CONCLUSIONS: Endurance exercise training coordinately up-regulates fat oxidative capacity and lipolytic protein expression in skeletal muscle of obese subjects. This physiological adaptation probably favors fat oxidation and may alleviate the lipotoxic lipid pressure in skeletal muscle. Enhancement of IMTG turnover may be required for the beneficial metabolic effects of exercise in obesity. PMID- 24178795 TI - Sclerostin is positively associated with bone mineral density in men and women and negatively associated with carotid calcified atherosclerotic plaque in men from the African American-Diabetes Heart Study. AB - CONTEXT: Bone mineral density (BMD) and calcified atherosclerotic plaque (CP) demonstrate inverse relationships. Sclerostin, an endogenous regulator of the Wnt pathway and bone formation, has been associated with impaired osteoblast activation and may play a role in vascular calcification. OBJECTIVE: Our objective was to assess the relationships between sclerostin, BMD, and CP. DESIGN: Generalized linear models were fitted to test for associations between sclerostin, volumetric BMD (vBMD), and CP. PARTICIPANTS: A targeted population of 450 unrelated African Americans (AAs) with type 2 diabetes (T2D) was 56% female with mean/SD/median age of 55.4/9.5/55.0 years and a diabetes duration of 10.3/8.2/8.0 years. MAIN OUTCOME MEASURES: Plasma sclerostin, computed tomography derived thoracic and lumbar vertebrae trabecular vBMD, coronary artery, carotid artery, and aortoiliac CP were measured. RESULTS: Plasma sclerostin was 1119/401/1040 pg/mL, thoracic vBMD was 206.3/52.4/204.8 mg/cm3, lumbar vBMD was 180.7/47.0/179.0 mg/cm3, coronary artery CP score was 284/648/13, carotid artery CP score was 46/132/0, and aortoiliac CP score was 1613/2910/282. Sclerostin levels were higher in men than women (P<.0001). Before and after adjusting for age, sex, body mass index, blood pressure, smoking, hemoglobin A1c, and low density lipoprotein-cholesterol, plasma sclerostin levels were positively associated with thoracic and lumbar vertebrae vBMD (P<.0001). Sex-stratified analyses verified significant relationships in both men and women (both P<.001). Sclerostin was not associated with CP except for an inverse relationship with carotid CP in men (fully adjusted model, P=.03). CONCLUSIONS: In this cross sectional study of AA men and women with T2D, circulating sclerostin was positively associated with vBMD in the spine in both sexes and inversely associated with carotid artery CP in men. Sclerostin may play a role in skeletal mineral metabolism in AA but fails to explain inverse relationships between BMD and CP. PMID- 24178797 TI - Penetrance of functioning and nonfunctioning pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 in the second decade of life. AB - CONTEXT: Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. A potential positive correlation between tumor size and malignancy (2-3 cm, 18%; >3 cm, 43%) has greatly influenced the management of MEN1 adults with NF-PETs. OBJECTIVE: The aim of the study was to estimate the penetrance of NF-PETs, insulinomas, and gastrinomas in young MEN1 carriers. DESIGN: The data were obtained from a screening program (1996-2012) involving 113 MEN1 patients in a tertiary academic reference center. PATIENTS: Nineteen MEN1 patients (aged 12-20 y; 16 patients aged 15-20 y and 3 patients aged 12-14 y) were screened for NF-PETs, insulinomas, and gastrinomas. METHODS: Magnetic resonance imaging/computed tomography and endoscopic ultrasound (EUS) were performed on 10 MEN1 carriers, magnetic resonance imaging/computed tomography was performed on five patients, and four other patients underwent an EUS. RESULTS: The overall penetrance of PETs during the second decade of life was 42% (8 of 19). All eight PET patients had NF-PETs, and half of those tumors were multicentric. One-fifth of the screened patients (21%; 4 of 19) harbored at least one large tumor (>2.0 cm). Insulinoma was detected in two NF-PET patients (11%) at the initial screening; gastrinoma was not present in any cases. Six of the 11 (54%) screened patients aged 15-20 years who underwent an EUS had NF-PETs. Potential false-positive EUS results were excluded based on EUS-guided biopsy results, the reproducibility of the NF-PET findings, or the observation of increased tumor size during follow-up. Distal pancreatectomy and the nodule enucleation of pancreatic head tumors were conducted on three patients with large tumors (>2.0 cm; T2N0M0) that were classified as grade 1 neuroendocrine tumors (Ki-67<2%). CONCLUSIONS: Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group. PMID- 24178798 TI - Highlight article: January-June 2013. PMID- 24178796 TI - Maternal antenatal vitamin D status and offspring muscle development: findings from the Southampton Women's Survey. AB - CONTEXT: Maternal 25-hydroxyvitamin D [25(OH)D] status in pregnancy has been associated with offspring bone development and adiposity. Vitamin D has also been implicated in postnatal muscle function, but little is known about a role for antenatal 25(OH)D exposure in programming muscle development. OBJECTIVE: We investigated the associations between maternal plasma 25(OH)D status at 34 weeks of gestation and offspring lean mass and muscle strength at 4 years of age. DESIGN AND SETTING: We studied a prospective UK population-based mother-offspring cohort: the Southampton Women's Survey (SWS). PARTICIPANTS: Initially, 12,583 nonpregnant women were recruited into the SWS, of whom 3159 had singleton pregnancies; 678 mother-child pairs were included in this analysis. MAIN OUTCOMES MEASURED: At 4 years of age, offspring assessments included hand grip strength and whole-body dual-energy x-ray absorptiometry, yielding lean mass and percent lean mass. Physical activity was assessed by 7-day accelerometry in a subset of children (n=326). RESULTS: The maternal serum 25(OH)D concentration in pregnancy was positively associated with offspring height-adjusted hand grip strength (beta=0.10 SD/SD, P=.013), which persisted after adjustment for maternal confounding factors, duration of breastfeeding, and child's physical activity at 4 years (beta=0.13 SD/SD, P=.014). Maternal 25(OH)D was also positively associated with offspring percent lean mass (beta=0.11 SD/SD, P=.006), but not total lean mass (beta=0.06 SD/SD, P=.15). However, this association did not persist after adjustment for confounding factors (beta=0.09 SD/SD, P=.11). CONCLUSIONS: This observational study suggests that intrauterine exposure to 25(OH)D during late pregnancy might influence offspring muscle development through an effect primarily on muscle strength rather than on muscle mass. PMID- 24178799 TI - The fifth vital sign. PMID- 24178800 TI - Subtalar distraction osteogenesis for old calcaneal fractures. PMID- 24178801 TI - Syndesmosis fixation using dual screws with tricortical and quadricortical purchase. PMID- 24178802 TI - Author response. PMID- 24178804 TI - Hypoxia enhances chondrogenic differentiation of human adipose tissue-derived stromal cells in scaffold-free and scaffold systems. AB - Human adipose-derived stromal cells (hASCs) possess the potential for chondrogenic differentiation. Recent studies imply that this differentiation process may be enhanced by culturing the cells in low oxygen tension in combination with three-dimensional (3D) scaffolds. We report the evaluation of the chondrogenic potential of hASC pellets in 5 and 21% O2 and as cell-scaffold constructs using a collagen I/III scaffold with chemical induction using TGF beta3. hASCs from four human donors were cultured both in a micromass pellet system and in 3D collagen I/III scaffolds in either 5 or 21% O2. Chondrogenesis was evaluated by quantitative gene expression analysis of aggrecan, SOX9, collagen I, II and X and histological evaluation with H&E and toluidine blue staining. Induced pellets cultured in 5% O2 showed increased peripheral cellularity and matrix deposition compared with 21% O2. Induced pellets cultured in 5% O2 had increased control-adjusted gene expression of aggrecan, SOX9 and collagen I and decreased collagen X compared with 21% O2 cultures. Induced pellets had higher gene expression of aggrecan, SOX9, collagen I, II and X and increased ratios of collagen II/I and collagen II/X compared with controls. As for pellets, scaffold cultures showed cellularity and matrix deposition organized in a zonal manner as a function of the oxygen tension, with a cartilage-like morphology and matrix deposition peripherally in the 5% O2 group and a more centrally located matrix in the 21% O2 group. There were no differences in histology and gene expressions between pellet and scaffold cultures. Five percent O2 in combination with chondrogenic culture medium stimulated chondrogenic differentiation of hASCs in vitro. We observed similar patterns of differentiation and matrix disposition in pellet and scaffold cultures. PMID- 24178805 TI - An alternative promoter of the human plakophilin-3 gene controls the expression of the new isoform PKP3b. AB - The plakophilin family (PKP1 to PKP3) is an essential component of the desmosomal adhesion complex with differentiation-dependent and partially overlapping expression and possible participation of the corresponding genes in malignant transformation. Here, we describe a new protein variant of the human PKP3 gene, namely PKP3b, which differs from the published PKP3a only at the amino-terminus by the splicing in of the newly identified exon 1b. Specific antibodies have demonstrated differential expression patterns of the two variants. Whereas PKP3a is broadly expressed among epithelial cells, PKP3b is abundant in the desmosomes of stratified epithelial cells, such as HaCaT but absent or heterogeneous in simple epithelial cells such as CaCo2 or MCF7. The differential expression of the PKP3 variants has been observed in a similar manner in selected normal human tissues and carcinomas derived thereof. Both variants are localized to the desmosomes of all cells of stratified tissues, whereas the new PKP3b is heterogeneously expressed in the colon and its tumors. Therefore, we assume that both variants are controlled by alternative promoters. Reporter gene assays have confirmed that a fragment upstream of exon 1b exhibits transcriptional activity only in HaCaT cells but not in CaCo2 cells and thus has been identified as an alternative promoter driving the expression of PKP3b. Finally, by using electromobility shift assays, we found a potential binding site in the PKP3b promoter for transcription factor C/EBP regulating keratinocyte differentiation and probably also PKP3b expression. We discuss the properties of the new variant PKP3b as a possible marker protein for the analyses of differentiation and malignant transformation. PMID- 24178806 TI - 3D nanocomposite architectures from carbon-nanotube-threaded nanocrystals for high-performance electrochemical energy storage. AB - Better electrode architecture: spherical assemblies of electrochemically active nanocrystals threaded with carbon nanotubes are made using a simple solvation induced-assembly process. This architecture provides the composites with mechanical robustness, effective ion- and electron-transport pathways, enabling the fabrication of electrodes with high rate, high capacity, and long cycling stability. PMID- 24178807 TI - Intravitreal triamcinolone injections in non-arteritic anterior ischemic optic neuropathy. AB - BACKGROUND: In non-arteritic anterior ischemic optic neuropathy (NA-AION), no treatments have demonstrated to be effective in recovering visual loss in randomized clinical trials. Oral steroids have been evaluated, and small series of intravitreal triamcinolone acetonide (IVTA) injection in NA-AION have been reported. The purpose of our study was to report the visual outcome and morphological changes in response to a single IVTA injection as a treatment for patients with NA-AION. PATIENTS AND METHODS: The charts of 36 patients with visual symptoms and optic disc swelling caused by NA-AION were evaluated. Twenty one patients had received 4 mg IVTA and were compared with 15 non-treated patients. Visual acuity (VA), retinal nerve fiber layer thickness and static visual field were evaluated after 6 months. RESULTS: VA improvement at 6 months is statistically better in the treated group than in the non-treated group (p = 0.0035). In the treated group, there was a significant inverse correlation between the delay of the injection and the visual acuity achieved at 6 months (p < 0.0083**, r = -0.56). A significant improvement of the visual field was noted in the injected group when compared with the non-treated group at 6 months (p < 0.0028). DISCUSSION: In this retrospective study, patients receiving IVTA in the acute phase of NA-AION have better improvement of VA and visual field during the follow-up period of 6 months. However, only a large randomized controlled trial may enable to evaluate the benefits of IVTA Injections on visual outcome in NA AION. PMID- 24178808 TI - Purification and characterization of a laccase from Coprinopsis cinerea in Pichia pastoris. AB - A modified laccase gene, CcLCC6, from Coprinopsis cinerea was chemically synthesized according to the yeast codon bias and expressed in Pichia pastoris. The main properties of laccase, effects of ions and inhibitors, and optimal condition for decolouring malachite green (MG) were investigated in this study. The optimal pH level and temperature of laccase are 3.0 and 40 degrees C, respectively. The metal ions Mn2+, Zn2+, Fe3+ and Al3+ could inhibit laccase activity, as well as 1 mM of sodium dodecyl sulphate and sodium thiosulphate. 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), as a mediator, was necessary in decolorizing MG. The optimal pH and temperature for MG decolorization were 3.0 and 50 degrees C, respectively. Approximately 0.02 MUM recombinant laccase could effectively decolour 0.05 mM of MG in 1 h. CcLCC6I could inhibit the toxicity of MG to P. pastoris. This is the first report on the successful expression in P. pastoris of CcLCC6I and its enzymatic property. Laccase can also be considered as a candidate for treating industrial effluent containing MG. PMID- 24178809 TI - Human cystatin C: a new biomarker of idiopathic pulmonary fibrosis? AB - PURPOSE: Human idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disorder with a poor prognosis. The identification of a new and specific biomarker in bronchoalveolar lavage fluids (BALFs) may assist in the diagnosis of the disease. EXPERIMENTAL DESIGN: Characterization of cysteine Cats and their endogenous inhibitor, cystatin C, was conducted by immunochemical analysis and measurement of endopeptidase activity of control (n = 11) and IPF (n = 25) BALFs (normalized conditions, 20 MUg protein/assay). RESULTS: Cathepsin (Cat) B was detected as proform and mature enzyme for both control and IPF samples, while Cats K, L, and S were found as zymogens with a strengthened staining in IPF BALFs. The overall endopeptidase activity related mainly to Cat B and did not vary significantly between control and IPF samples. Conversely a significant increase of immunoreactive cystatin C was measured in BALFs for each of three IPF grades. CONCLUSIONS AND CLINICAL RELEVANCE: An excessive deposition of extracellular matrix proteins is the hallmark of fibrotic disorders. Cats are potent collagenases and might be essential for lung homeostasis. Taken together, increase of cystatin C in IPF BALFs may reflect abnormal regulation of proteolytic activity of Cats in lung, which in turn can promote the development of fibrosis. PMID- 24178810 TI - A mechanistic role for polypeptide hormone receptor lateral mobility in signal transduction. AB - Lateral diffusion of membrane-integral receptors within the plane of the membrane has been postulated to be mechanistically important for signal transduction. Direct measurement of polypeptide hormone receptor lateral mobility using fluorescence photobleaching recovery techniques indicates that tyrosine kinase receptors are largely immobile at physiological temperatures. This is presumably due to their signal transduction mechanism which requires intermolecular autophosphorylation through receptor dimerization and thus immobilization for activation. In contrast, G-protein coupled receptors must interact with other membrane components to effect signal transduction, and consistent with this, the phospholipase C-activating vasopressin V1- and adenylate cyclase activating V2 receptors are highly laterally mobile at 37 degrees C. Modulation of the V2 receptor mobile fraction (f) has demonstrated a direct correlation between f and receptor-agonist-dependent maximal cAMP productionin vivo at 37 degrees C. This indicates that f is a key parameter in hormone signal transduction especially at physiological hormone concentrations, consistent with mobile receptors being required to effect V2-agonist-dependent activation of G-proteins. Measurements using a V2-specific antagonist show that antagonist-occupied receptors are highly mobile at 37 degrees C, indicating that receptor immobilization is not the basis of antagonism. In contrast to agonist-occupied receptor however, antagonistoccupied receptors are not immobilized prior to endocytosis and down regulation. Receptors may thus be freely mobile in the absence of agonistic ligand; stimulation by hormone agonist results in receptor association with other proteins, probably including cytoskeletal components, and immobilization. Receptor immobilization may be one of the important steps of desensitization subsequent to agonistic stimulation, through terminating receptor lateral movement which is instrumental in generating and amplifying the initial stimulatory signal within the plane of the membrane. PMID- 24178812 TI - Influence of the pH on the photodynamic effect in lysozyme A comparative kinetic study with the sensitized photooxidation of isolated amino acids. AB - The kinetics of the eosin-sensitized photooxidation ([O2((1)Deltag)]-mediated) of the protein lysozyme (Lyso) was investigated under two different pH conditions (pH 7 and pH 11). Rates of oxygen consumption and the fade in the protein fluorescence spectrum upon sensitized irradiation were monitored. Parallel studies on both denatured Lyso (absence of the four-S-S- bridges in the protein) and different mixtures of the photooxidizable amino acids of Lyso were also carried out. The mixtures maintained the same molar ratio as in the native protein, and were selected just in order to throw into relief the preferential amino acids that were being photooxidized at both pH values.Under work conditions Lyso was only photooxidizable at pH 7, whereas the opposite accounted for the denatured protein: only measurable oxygen consumption was detected at pH 11. Nevertheless, Lyso at pH 11, evidenced an important physical quenching of O2((1)Deltag) due to the Tyr and Trp residues.The results for the native protein were interpreted on the basis of a previously described dark complex Eosin-Lyso, which selectively favours the photooxidation of the bounded protein. The Trp residues were the main reactive entities in the native protein. The photodinamic effect in denatured Lyso was characterized by the prevalence of Tyr residues as photooxidizable targets.In the discussion of the results, a comparisson with the photooxidation kinetics of the mixtures of free amino acids was made. PMID- 24178813 TI - Study of the resolution of amino acids and aminoalcohols in organic solvents. AB - The enzymatic resolution of racemic phenylglycine, phenylglycinol and phenylalaninol has been studied in organic solvents under a variety of experimental conditions. Subtilisin in 3-methyl-3-pentanol was effective for the resolution of phenylglycine esters, via N-acylation with trifluoroethyl butyrate. Porcine pancreatic lipase in ethyl acetate gave satisfactory results in the resolution of phenylglycinol and phenylalaninol; thealpha orbeta position of the phenyl group was found to influence both the rate and the chemioselectivity of the reaction. PMID- 24178811 TI - Increase in cystathionine content in rat liver mitochondria after D,L propargylglycine administration. AB - Intraperitoneal administration of D,L-propargylglycine to rats resulted in an increase in the cystathionine content of whole liver and liver mitochondria. Cystathionine in mitochondria was identified by amino acid analysis, thin layer chromatography, high-voltage paper electrophoresis and liquid chromatography-mass spectrometry. The cystathionine content of whole liver was 5.37 +/- 1.59umol per g of fresh liver at 14 h after the administration of 50 mg of D,L propargylglycine per kg of body weight, while 0.07 +/- 0.02umol of cystathionine per g of fresh liver was detected in the control rats. The cystathionine content of liver mitochondria from both groups of rats was 9.40 +/- 1.20 and 0.19 +/- 0.04 nmol of cystathionine per mg of protein, respectively. The mitochondrial cystathionine increased dose-dependently with the increase of D,L propargylglycine administered. The increase was proportional to the time after the administration up to 12 h, and then decreased. The increase of cystathionine in the liver mitochondria was linearly proportional to that in the whole liver. These results suggest that cystathionine in liver mitochondria is in an equilibrium with that in the cytosol. PMID- 24178814 TI - Ketone bodies promote a rapid rise in glutamate efflux from the isolated perfused rat liver without altering the rate of glutamine production. AB - Livers of starved (48 hr) male Wistar rats were perfused in a non recirculating manner with a near physiological mix of ammonium, lactate, ornithine and pyruvate in Krebs buffer. The addition of ketone bodies (3-DL-hydroxybutyrate [B OHB] 2-30 mM or lithium-acetoacetate (15 mM) to the perfusate resulted in a rapid rise in the efflux of glutamate from the liver (five times above basal). This was not seen with control solutions (sodium chloride or lithium chloride). The increased efflux was sustained for the duration of the addition of the ketone bodies (7 min), was rapidly reversible and dose dependant. Glutamine export rates were not altered, suggesting that either the glutamate originated from cells not responsible for glutamine synthesis or that this glutamate was superfulous to the requirement of glutamine synthesis. There was no evidence that the lactate transporter was involved in the entry of lactate into perivenous hepatocytes for glutamine synthesis; lactate presumably entering the hepatocyte by an alternative pathway, probably nonionic diffusion. PMID- 24178816 TI - Amino acid determination in some edible Mexican insects. AB - The amino acid contents of edible insects from different provinces of Mexico and reference proteins were analysed by reversed-phase high-performance liquid chromatography and ion exchange chromatography. The insect amino acid contents were higher than the adult requirements indicated by the WHO/FAO pattern. PMID- 24178815 TI - Human branched-chain L-amino acid aminotransferase: Activity and subcellular localization in cultured skin fibroblasts. AB - Assay conditions for measurement of human skin fibroblast branched-chain L-amino acid aminotransferase activity were established and applied to studies on subcellular distribution and kinetic properties of the enzyme. Digitonin fractionation of cultured cells revealed that the aminotransferase activity was mainly (at least about 95%) associated with mitochondrial citrate synthase activity. As tested with L-leucine, activity of the enzyme against amino group acceptors (forward reaction) was in the order 2-oxoglutarate [Symbol: see text] branched-chain > straight-chain 2-oxo acids (C3-C8). With 4-methyl-2 oxopentanoate, activity against amino group donors (reverse reaction) was in the order L-glutamate [Symbol: see text] branched-chain > straight-chain (C2-C6) and other L-amino acids. The data suggest that, in human fibroblasts, isoenzyme type I resides within the mitochondrial space. Possible implications for the metabolism of branched-chain compounds are discussed. PMID- 24178817 TI - N-Acetyl-aspartylglutamate (NAAG) in human cerebrospinal fluid: Determination by high performance liquid chromatography, and influence of biological variables. AB - NAAG is one of the neuropeptides found in highest concentrations in the CNS. The presence of micromolar concentrations of NAAG in human CSF was demonstrated by using two different and complementary analytical approaches: 1) isocratic separation of endogenous NAAG by reverse-phase high performance liquid chromatography (HPLC) with dual wavelength detection and 2) derivatization of endogenous NAAG with acidic methanol and subsequent HPLC analysis of the derivative NAAG-trimethyl ester. The NAAG concentration was between 0.44umol/l and 7.16umol/l (mean of 2.19 +/- 1.53umol/l) in CSF samples from forty neuropsychiatric patients. Endogenous NAAG or [(3)H]NAAG added to CSF samples were not significantly degraded when the CSF was incubated at 37 degrees C during one hour, suggesting that the peptide is a highly stable metabolite in the subarachnoid space. In addition, evidence is provided that NAAG does not present a concentration gradient along the lower subarachnoid space. PMID- 24178818 TI - Facile synthesis of (R)N-2-hydroxyacyl-L-cysteine derivatives: (R)N-2-hydroxyacyl transfer from enzymatically-synthesized (R)S-2-hydroxyacylglutathione derivatives to L-cysteine. AB - N-(R)-2-Hydroxyacyl-L-cysteine derivatives were conveniently synthesized by the reaction of the corresponding S-(R)-2-hydroxyacyl-glutathione with cysteine. The (R)2-hydroxyacyl group was transferred from the S-glutathionyl moiety to S cysteinyl, forming the corresponding (R)S-2-hydroxyacylcysteine; this rearranged to the (R)N-hydroxyacylcysteine. These compounds have anti-proliferative activity associated with the inhibition ofde novo pyrimidine synthesis. PMID- 24178820 TI - Reflections on the changing scope of difficult airway management. PMID- 24178819 TI - Muscle strength and its relationship with skeletal muscle mass indices as determined by segmental bio-impedance analysis. AB - PURPOSE: Despite increasing interest in bio-impedance analysis (BIA) for estimation of segmental skeletal muscle mass (SMM), published results have not been entirely convincing. Furthermore, a better understanding of the relationship between muscle strength and SMM will be useful in interpreting outcomes of physical/training interventions particularly in groups with diverse body sizes (e.g. men vs women). This study aimed to measure SMM in the upper body (upper extremity and torso), to determine its correlation with muscle strength and to examine the effects of gender on muscle strength-muscle mass relationship. METHODS: Segmental (upper extremity and torso) SMM and muscle strength in five distinct shoulder planes (forward flexion, abduction in scapular plane, abduction in coronal plane, internal and external rotation) were measured in 45 healthy participants (22 males, 23 females) with mean age 30.3 years. Statistical analysis included independent t tests, Pearson correlation, and multiple regression analysis. RESULTS: Men and women differed significantly in body mass (BMI: 25.9 +/- 4.3 vs 23 +/- 3.6) and SMM (p < 0.01). A strong relationship correlation was found between the five shoulder strength measurements and upper extremity SMM (r = 0.66-0.80, p < 0.01), which was not affected by gender. There was a significant gender difference (p < 0.01) in absolute shoulder strength, but not after normalisation to the SMM. CONCLUSION: BIA-estimated SMM of upper extremity and torso was highly correlated with upper extremity (shoulder) strength independent of gender. SMM may, therefore, be useful for the normalisation of muscle strength allowing size-independent comparisons of muscle strength in individuals with diverse physical characteristics. PMID- 24178821 TI - The veterans administration and community mental health: New approaches in psychiatric rehabilitation. AB - The large government mental institution must become increasingly integrated with local community mental health programs. The Veterans Administration Hospital, Palo Alto, California, provides an example of how one such institution involves its programs with the community. The traditional hospital-based sheltered workshop, when operated as a nonprofit corporation, is especially well suited to the employment of mental patients in workshop-owned enterprises outside the hospital walls. The flexibility of the program is illustrated with case histories. Advantages to the client, the institution, and the community are discussed. PMID- 24178822 TI - Mental health consultation for school social workers: A conceptual model. AB - There are some very seriously disturbed children, families, and teachers who require individual casework or other individual therapeutic help. However, in the face of the mental health job to be done in the schools, mental health consultation is one very important way of utilizing the scarce talents of social workers in a more effective way for more children. A conceptual model of mental health consultation is presented and a special adaptation to mental health consultation in the school setting is illustrated. PMID- 24178823 TI - Placement of adult retardates from state institutions in community care facilities. AB - Results of a study evaluating the success of transfers of adult retardates from state institutions to public and private nursing homes indicate that most of the retardates adjusted well to the change, responded to program activities available in the nursing homes and nearby communities, and were visited more often by friends and relatives. Operators of the nursing homes, their staffs, the retardates, their families, and the other residents and their families accepted the placement program. By supporting social functioning at a lesser level of intervention than state institutions, nursing homes allow for greater exercise of even limited independence. PMID- 24178824 TI - Appalachian public health nursing: Mental health component in eastern Kentucky. AB - The Manchester Project, and its attendant public health nursing activity, is described as a unique mental health program in the commonwealth of Kentucky. It continues to operate within the existing framework of four local county health departments in eastern Kentucky, and utilizes much public health technique, personnel, and methodology. By focussing upon the intrinsic mental health component of public health work, the project demonstrates an effective way of meeting community mental health needs in rural, impoverished areas. PMID- 24178825 TI - The crisis of unwed motherhood: A consultation approach. AB - Unwed motherhood, particularly for the teenager, constitutes a series of subcrises: confrontation with the pregnancy, exclusion from school, physical changes, social isolation and interpersonal conflict, delivery, and caring for an infant. This paper describes the role which a mental health consultant can take in regard to interagency programs, research, and education. Specific consultation interventions, within the framework of crisis theory, are discussed for helping caregivers enable teenagers to cope with these subcrises. PMID- 24178826 TI - Patterns of adjustment of discharged psychiatric patients as measured by mailed questionnaires. AB - Mailed questionnaires were administered to 34 former psychiatric patients of a provincial mental institution and their relatives in order to assess frequency of psychopathological and social behavior, and to estimate validity and return rate of the forms. The sample reported few symptoms of mental illness, but a relatively low degree of social activity and leisure activities. The return rate was very high (88.9%). The questionnaires did not correlate significantly with a measure of vocational adjustment. PMID- 24178827 TI - The total demand for psychiatric service in an island community. AB - Data are given on the total demand for psychiatric service by the population of an island community where such service is promptly available, geographically accessible, and within the economic means of all. Without the existence of such circumstances, psychiatric patient counts are likely to be underestimates of the real demand. The data provided on admission rates by age, sex, and diagnosis may be useful in predicting the service demands of communities where new facilities are to be opened. PMID- 24178828 TI - Fragile egos. PMID- 24178829 TI - Publications received. PMID- 24178830 TI - Dithienocarbazole and isoindigo based amorphous low bandgap conjugated polymers for efficient polymer solar cells. AB - Three highly rigid and planar low-bandgap conjugated polymers comprising alternate isoindigo and dithienocarbazole groups are synthesized for the fabrication of high performance polymer solar cells. Power conversion efficiencies of up to 7.2% for conventional devices and 8.2% for inverted devices are demonstrated. PMID- 24178832 TI - Hydration of porphyrin and Mg-porphyrin: ab initio quantum mechanical charge field molecular dynamics simulations. AB - Ab initio QMCF-MD simulations were performed for porphyrin (POR) and magnesium porphyrin (Mg-POR) immersed in water to study their structural and dynamical properties. The observed hydration behaviour of these solutes representing biomimetic models is in fair agreement with structural and dynamical features of their biological analogues, protoporphyrin IX (PPIX) and chlorophyll (CHl). Structural data obtained from the radial, angular and spatial distribution functions as well as the angular-radial distributions have a consensus on possessing a contrasting hydration behaviour of POR and Mg-POR. Flexibility of the ring in both solutes described by the improper torsional distribution and root mean square fluctuation showed an influence on H-bond interactions between the nitrogen atoms and water molecules that are also reflected in the respective dynamics. An axial water molecule coordinated to the Mg(ii) ion indicates the penta-coordinated Mg-POR to be stable along the simulation. It was also shown that complexation of the Mg(ii) ion to the porphyrin influences the hydration patterns significantly compared to the porphyrin itself, which is further supported by the vibrational power spectra evaluated for both solutes. Free energy of binding and solvent accessible surface area calculations also confirmed that these two solutes have distinct hydration behaviour. Detailed knowledge of the individual hydration patterns is expected to be of particular benefit. PMID- 24178833 TI - Cordycepin, 3'-deoxyadenosine, prevents rat hearts from ischemia/reperfusion injury via activation of Akt/GSK-3beta/p70S6K signaling pathway and HO-1 expression. AB - Cordycepin (3'-deoxyadenosine) isolated from Cordyceps militaris, a species of the fungal genus Cordyceps, has been shown to exhibit many pharmacological functions, such as anticancer, anti-inflammatory, and antioxidant activities. In this study, we investigated the preventive role of cordycepin in ischemic/reperfusion (I/R) injury of isolated rat hearts and anesthetized rats. After Sprague-Dawley rats received cordycepin (3, 10, and 30 mg/kg) or control (0.5 % carboxyl methylcellulose) orally once a day for a week, hearts were isolated and mounted on Langendorff heart perfusion system. Isolated hearts were perfused with Krebs-Henseleit buffer for 15-min pre-ischemic stabilization period and subjected to 30-min global ischemia and 30-min reperfusion. Cordycepin administration (10 mg/kg, p.o.) significantly increased left ventricular developed pressure during the reperfusion period compared to that in the control group, but without any effect on coronary flow. Cordycepin (10 mg/kg, p.o.) significantly increased the phosphorylation of Akt/GSK-3beta/p70S6K pathways, which are known to modulate multiple survival pathways. In addition, cordycepin decreased Bax and cleaved caspase-3 expression while increasing Bcl-2 expression, Bcl-2/Bax ratio, and heme oxygenase (HO-1) expression in isolated rat hearts. In anesthetized rats subjected to 30 min occlusion of left anterior descending coronary artery/2.5-h reperfusion, cordycepin (1, 3, and 10 mg/kg, i.v.) administered 15 min before the onset of ischemia dose-dependently decreased the infarct size in left ventricle. In conclusion, cordycepin could be an attractive therapeutic candidate with oral activity against I/R-associated heart diseases such as myocardial infarction. PMID- 24178831 TI - Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice. AB - Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer's disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. Although DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3-7.5 months of age. Ts65Dn dams were maintained on a choline-supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; post weaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, and brains were sectioned and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75(NTR) ). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn-unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. PMID- 24178834 TI - Intra-specific variation in wild Brassica oleracea for aphid-induced plant responses and consequences for caterpillar-parasitoid interactions. AB - Herbivore-induced plant responses not only influence the initiating attackers, but also other herbivores feeding on the same host plant simultaneously or at a different time. Insects belonging to different feeding guilds are known to induce different responses in the host plant. Changes in a plant's phenotype not only affect its interactions with herbivores but also with organisms higher in the food chain. Previous work has shown that feeding by a phloem-feeding aphid on a cabbage cultivar facilitates the interaction with a chewing herbivore and its endoparasitoid. Here we study genetic variation in a plant's response to aphid feeding using plants originating from three wild Brassica oleracea populations that are known to differ in constitutive and inducible secondary chemistry. We compared the performance of two different chewing herbivore species, Plutella xylostella and M. brassicae, and their larval endoparasitoids Diadegma semiclausum and M. mediator, respectively, on plants that had been infested with aphids (Brevicoryne brassicae) for 1 week. Remarkably, early infestation with B. brassicae enhanced the performance of the specialist P. xylostella and its parasitoid D. semiclausum, but did not affect that of the generalist M. brassicae, nor its parasitoid M. mediator. Performance of the two herbivore parasitoid interactions also varied among the cabbage populations and the effect of aphid infestation marginally differed among the three populations. Thus, the effect of aphid infestation on the performance of subsequent attackers is species specific, which may have concomitant consequences for the assembly of insect communities that are naturally associated with these plants. PMID- 24178835 TI - Virus strains differentially induce plant susceptibility to aphid vectors and chewing herbivores. AB - Plants are frequently attacked by both pathogens and insects, and an attack from one can induce plant responses that affect resistance to the other. However, we currently lack a predictive framework for understanding how pathogens, their vectors, and other herbivores interact. To address this gap, we have investigated the effects of a viral infection in the host plant on both its aphid vector and non-vector herbivores. We tested whether the infection by three different strains of Potato virus Y (PVY(NTN), PVY(NO) and PVY(O)) on tomato plants affected: (1) the induced plant defense pathways; (2) the abundance and fecundity of the aphid vector (Macrosiphum euphorbiae); and (3) the performance of two non-vector species: a caterpillar (Trichoplusia ni) and a beetle (Leptinotarsa decemlineata). While infection by all three strains of PVY induced the salicylate pathway, PVY(NTN) induced a stronger and longer response. Fecundity and density of aphids increased on all PVY-infected plants, suggesting that the aphid response is not negatively associated with salicylate induction. In contrast, the performance of non-vector herbivores positively correlated with the strength of salicylate induction. PVY(NTN) infection decreased plant resistance to both non vector herbivores, increasing their growth rates. We also demonstrated that the impact of host plant viral infection on the caterpillar results from host plant responses and not the effects of aphid vector feeding. We propose that pathogens chemically mediate insect-plant interactions by activating the salicylate pathway and decreasing plant resistance to chewing insects, which has implications for both disease transmission and insect community structure. PMID- 24178836 TI - The significance of tryptophan in human nutrition. AB - Aside from its role as one of the limiting essential amino acids in protein metabolism, tryptophan (TRP) serves as precursor for the synthesis of the neurotransmitters serotonin and tryptamine as well as for the synthesis of the antipellagra vitamin nicotinic acid and the epiphyseal hormone melatonin.By involvement in so manifold pathways, TRP and its metabolites regulate neurobehavioral effects such as appetite, sleeping-waking-rhythm and pain perception. TRP is the only amino acid which binds to serum albumin to a high degree. Its transport through cell membranes is competetrvely inhibited by large neutral amino acids (NAA). The TRP/NAA ratio in plasma is essential for the TRP availability and thus for the serotonin synthesis in the brain.Due to its high TRP-concentration, human milk protein provides optimal conditions for the availability of the neurotransmitter serotonin. Low protein cow's milk-based infant formulas supplemented withalpha-lactalbumin - a whey protein fraction containing 5.8% TRP - present themselves as a new generation of formulas, with an amino acid pattern different from the currently used protein mixtures of adapted formulas, resembling that of human milk to a much higher degree. PMID- 24178837 TI - Free-GABA levels in the cerebrospinal fluid of patients suffering from several neurological diseases Its potential use for the diagnosis of diseases which course with inflammation and tissular necrosis. AB - Free GABA levels were measured in the cerebrospinal fluid (CSF) of 74 neurological patients suffering from cerebral cysticercosis (n = 9), Parkinson's disease (n = 5), multiple sclerosis (n = 6), epilepsy (n = 24), meningeal tuberculosis (n = 6), viral encephalitis (n = 3), cerebrovascular disease (n = 8) and several kinds of dystonia (n = 5). A statistical significant four-fold elevation in free GABA levels was found in patients with cerebral cysticercosis. A non statistical significant two-fold increase in free GABA levels was also encountered in the CSF of patients affected by cerebrovascular disease and viral encephalitis. No changes in CSF free GABA levels were found in patients suffering from any of the other disorders. It is suggested that free GABA levels may be elevated in the CSF of patients suffering from neurological diseases which course with inflammation and tissular necrosis such as cerebral cysticercosis. Much work is needed however to establishd whether CSF free GABA levels can be used as a diagnostic tool in at least some type of these patients. PMID- 24178838 TI - Modeling the solubility and activity of amino acids with the LCCI method. AB - The linear combinations of connectivity indices method (LCCI) is here employed to model the water solubility and activity of 19 natural amino acids. Starting with the molecular connectivity indices, reciprocal and supra molecular connectivity indices are designed to model the solubility and activity spaces of the natural amino acids. The reciprocal and supra molecular reciprocal connectivity indices have been obtained following the variability of the connectivity indices along solubility space of the natural amino acids. A linear combination of the reciprocals of the connectivity indices (LCRCI) showed a satisfactory modelling of the solubility and activity space while a model based on the LCRCI together with the introduction of supra reciprocal molecular connectivity indices for Pro, Ser and Arg achieved an optimal modelling of the solubility and activity space of the natural amino acids. PMID- 24178839 TI - Melanotropin-potentiating factor isolated from filtrate of uremic patients suffering from melanosis and carbohydrate intolerance. AB - Following the characterization of a hexadecapeptide,alpha-endorphin, melanotropin potentiating factor (MPF) was isolated from the filtrate of uremic patients suffering from melanosis and carbohydrate intolerance. The structure of MPF has been determined on the bases of chemical and physicochemical examinations which included HPLC, Edman sequence analysis combined analysis of the amino acid composition and FAB-MS analysis. An accumulation of MPF might be a cause of melanosis in uremic patients. PMID- 24178840 TI - A dual action of taurine on the delayed rectifier K(+) current in embryonic chick cardiomyocytes. AB - Effects of taurine on the delayed rectifier K(+) channel in isolated 10-day-old embryonic chick ventricular cardiomyocytes were examined at different intracellular Ca(2+) concentrations ([Ca]i), using whole-cell voltage and current clamp techniques. Experiments were performed at room temperature (22 degrees C). Test pulses were applied between -20 to +90m V from a holding potential of -40mV. When [Ca]i was pCa 7, addition of 10 and 20 mM taurine to the bath solution reduced the delayed rectifier K(+) current (IK) at +90mV by 17.4 +/- 2.8% (n = 5, P < 0.01) and 25.5 +/- 2.6% (n = 5, P < 0.001), respectively. In contrast, when [Ca]i was pCa 10, IK at +90 mV was enhanced by 19.1 +/- 3.1% (n = 7, P < 0.01) at 10mM taurine, and by 29.3 +/- 2.4% (n = 7, P < 0.001) at 20mM taurine. The voltage of half-maximum activation (V1/2) was shifted in a hyperpolarizing direction; at pCa 7, the value was +0.2 +/- 2.2mV (n = 5) in control and -10.6 +/ 1.8mV (n = 5) in 20mM taurine. At pCa 10, the V1/2 value was +18.5 +/- 4.6mV (n = 5) in control and +6.6 +/- 5.2mV (n = 5) in taurine (20mM). Taurine decreased the action potential duration (APD) at pCa 10, but at pCa 7 did not affect it. In addition, taurine enhanced the transient outward current in a concentration dependent manner. These results indicate that taurine modulates the delayed rectifier K(+) channel, an effect dependent on [Ca]i and capable of regulating APD. PMID- 24178841 TI - Visualization of the NMDA recognition site in rat and mouse spinal cord by [(3)H]CGS 19755in vitro autoradiography. AB - The possibility to visualize the NMDA recognition site with [(3)H]CGS 19755in vitro autoradiography was evaluated in rat brain and spinal cord sections and thereafter used to study the distribution of the NMDA recognition site in rat and mouse spinal cord. The [(3)H]CGS 19755 binding was concentrated to the dorsal horn, in particular to the substantia gelatinosa. Notable binding was also seen in the intermediate area and ventral horn, while some binding was observed in the funiculi. No major differences were seen in [(3)H]CGS 19755 binding at various levels of the rat or mouse spinal cord, although a more dense binding was seen in the mouse. A similar distribution of the [(3)H]CGS 19755 specific binding and the NMDA receptor associated ion-channel site, labeled with [(3)H]TCP, was found in the mouse spinal cord. Taken together, our data indicate that the NMDA recognition site can be visualized in rat and mouse spinal cord byin vitro [(3)H]CGS 19755 autoradiography. PMID- 24178842 TI - Glutamate excitatory effects on ampullar receptors of the frog. AB - The action of glutamate on frog ampullar receptors was investigated to assess the potential role of this excitatory amino acid as an afferent transmitter in the hair cell system. Intracellular recordings from single afferent units in the isolated labyrinth revealed that glutamate and the glutamate receptor agonists, N methyl-D-aspartic acid, quisqualic acid and kainic acid increase dose-dependently the frequency of the resting afferent discharge of EPSPs and spikes and produce long lasting depolarizations. After blocking synaptic transmission by using 5 mM Co(2+), the same compounds elicited only depolarizations of amplitude comparable to those observed in normal saline. Quisqualic acid and kainic acid were much more potent than N-methyl-D-aspartic acid in increasing the frequency of afferent discharge and in causing axonal depolarizations. The depolarization caused by glutamate was reduced dose-dependently by the competitive non-NMDA receptor antagonist 6-cyano-7-nitroquinaxoline-2,3 dione and disappeared almost completely in Na(+)-free Ringer solution. These results are consistent with the hypothesis that glutamate is the afferent transmitter in vestibular organs and indicate that receptors mainly of the non-NMDA type are present not only at postsynaptic level but also in hair cells. Presynaptic glutamate receptors may function as autoreceptors controlling by a positive feed-back mechanism the release of the afferent transmitter. PMID- 24178843 TI - Taurine: a preventive agent of the acute ethanol depletive action on the isolated human amniotic membrane. AB - The preventive effect of taurine towards the acute ethanol reduction action was studied on the ionic transfer through the isolated human amniotic membrane. Taurine increased 3 components of the ionic transfer expressed by the conductance measurements (Na(+) and K(+) paracellular conductances through the intercellular spaces and coupling cell factor between 2 adjacent epithelial cells, expressed by a voltage ratio). These components were decreased by ethanol. Electrophysiological studies (conductance and voltage measurements) indicated that the addition of taurine (0.1-1 mM) before ethanol (0.4 g/l) hindered the decrease action of ethanol on the Na(+) and K(+) paracellular conductances and on the coupling cell factor. These data indicated a common target between taurine and ethanol: the membraneous phospholipids, particularly the distribution of the external fixed charges. The preventive action of taurineversus ethanol, on the human amniotic membrane, was exerted on the polar groups of phospholipids, hindering the incorporation of ethanol molecules. PMID- 24178844 TI - Evidence for a functionally important histidine residue in human tyrosine hydroxylase. AB - Recombinant human tyrosine hydroxylase isozyme 1 (hTH1) shows a time- and concentration-dependent loss of catalytic activity when incubated with diethylpyrocarbonate (DEP) after reconstitution with Fe(II). The inactivation follows pseudo-first order kinetics with a second order rate constant of 300 M( 1) min(-1) at pH 6.8 and 20 degrees C and is partially reversed by hydroxylamine. The difference absorption spectrum of the DEP-modified vs native enzyme shows a peak at 244 nm, characteristic of mono-N-carbethoxy-histidine. Up to five histidine residues are modified per enzyme subunit by a five-fold excess of the reagent, and two of them are protected from inactivation by the active site inhibitor dopamine. However, derivatization of only one residue appears to be responsible for the inactivation. Thus, no inactivation by DEP was found when the apoenzyme was preincubated with this reagent prior to its reconstitution with Fe(II), modifying four histidine residues. PMID- 24178845 TI - Studies on the active sites ofBacillus cereus sphingomyelinase substitution of some amino acids by site-directed mutagenesis. AB - Chemical modifications suggested that acidic amino acids such as aspartic and glutamic acids are involved in the active sites ofBacillus cereus sphingomyelinase. Among aspartic acid residues in the conserved regions of this enzyme, Asp-126, Asp-156, Asp-233 and Asp-295 were converted to glycine by site directed mutagenesis. According to prediction on structural similarity to pancreatic DNase I, His-151 and His-296 were also converted to alanine. The Asp and His mutants, D126G, D156G, D233G, D295G, H151A and H296A, were produced inBacillus brevis 47, a protein-hyperproducing strain. The catalytic activities of D295G, H151A and H296A were completely abolished, and sphingomyelin hydrolyzing activity of D126G or D156G was reduced by more than 50%. The activity of D126G towardp-NPPC was comparable to that of the wild-type, while D156G catalyzed the hydrolysis of HNP andp-NPPC more efficiently than the wild-type. Hemolytic activities of the mutants were parallel to their sphingomyelin hydrolyzing activities. PMID- 24178846 TI - Development of proteome-wide binding reagents for research and diagnostics. AB - Alongside MS, antibodies and other specific protein-binding molecules have a special place in proteomics as affinity reagents in a toolbox of applications for determining protein location, quantitative distribution and function (affinity proteomics). The realisation that the range of research antibodies available, while apparently vast is nevertheless still very incomplete and frequently of uncertain quality, has stimulated projects with an objective of raising comprehensive, proteome-wide sets of protein binders. With progress in automation and throughput, a remarkable number of recent publications refer to the practical possibility of selecting binders to every protein encoded in the genome. Here we review the requirements of a pipeline of production of protein binders for the human proteome, including target prioritisation, antigen design, 'next generation' methods, databases and the approaches taken by ongoing projects in Europe and the USA. While the task of generating affinity reagents for all human proteins is complex and demanding, the benefits of well-characterised and quality controlled pan-proteome binder resources for biomedical research, industry and life sciences in general would be enormous and justify the effort. Given the technical, personnel and financial resources needed to fulfil this aim, expansion of current efforts may best be addressed through large-scale international collaboration. PMID- 24178847 TI - A neuromechanical simulation of insect walking and transition to turning of the cockroach Blaberus discoidalis. AB - A neuromechanical simulation of the cockroach Blaberus discoidalis was developed to explore changes in locomotion when the animal transitions from walking straight to turning. The simulation was based upon the biological data taken from three sources. Neural circuitry was adapted from the extensive literature primarily obtained from the studies of neural connections within thoracic ganglia of stick insect and adapted to cockroach. The 3D joint kinematic data on straight, forward walking for cockroach were taken from a paper that describes these movements in all joints simultaneously as the cockroach walked on an oiled plate tether (Bender et al. in PloS one 5(10):1-15, 2010b). Joint kinematics for turning were only available for some leg joints (Mu and Ritzmann in J Comp Physiol A Neuroethol Sens Neural Behav Physiol 191(11):1037-54, 2005) and thus had to be obtained using the methods that were applied for straight walking by Bender et al. (PloS one 5(10):1-15, 2010b). Once walking, inside turning, and outside turning were characterized, phase and amplitude changes for each joint of each leg were quantified. Apparent reflex reversals and joint activity changes were used to modify sensory coupling pathways between the CPG at each joint of the simulation. Oiled-plate experiments in simulation produced tarsus trajectories in stance similar to those seen in the animal. Simulations including forces that would be experienced if the insect was walking freely (i.e., weight support and friction) again produced similar results. These data were not considered during the design of the simulation, suggesting that the simulation captures some key underlying the principles of walking, turning, and transitioning in the cockroach. In addition, since the nervous system was modeled with realistic neuron models, biologically plausible reflex reversals are simulated, motivating future neurobiological research. PMID- 24178848 TI - Revealing instances of coordination among multiple cortical areas. AB - Cognitive functions must involve interactions between several (perhaps many) cortical regions. The instances of such interactions may not be tightly time locked to any external cue. Thus averaging over repeated trials of brain activity or its spectrograms may miss these instances. Here, coordinated activity among multiple cortical locations is revealed in ongoing activity with millisecond accuracy without the need for averaging over time or frequencies. This is based on reconstructions of the cortical current dipole amplitudes at multiple points from MEG recordings. In these current dipole traces, instances of brief activity undulations (BAUs) are automatically detected and used to reveal where and when cortical points interact. The article shows that these BAUs truly represent the reorganization of activity at the cortex and are strongly connected to behavior. PMID- 24178849 TI - Principles for the training of "new professionals" in mental health. AB - Experience with two of the recent programs for training mature women in "new professions" for mental health service has led the authors to develop a series of hypotheses concerning such new training programs. These hypotheses are presented as guidelines or principles of planning and training for developing new programs in nontraditional mental health roles. PMID- 24178850 TI - The mental health center as a community laboratory. AB - This discussion summarizes community-based research conducted by the Human Relations Service of Wellesley, Inc., during the first 15 years of its existence as a pilot mental health program. It suggests that the community mental health laboratory develop service and research as coordinated components. Service activities are viewed as vital parts of ongoing community research. A collaborative relationship between researcher and subjects is recommended. With flexibility and imaginative use of its unique characteristics, the community mental health laboratory provides observations not possible in other settings. PMID- 24178851 TI - Mental health in the job corps: An exploration of the role of the mental health worker in programs of education and training. AB - Recent years have seen the proliferation of programs of education and training. Mental health workers have become increasingly involved in such programs and have provided varied services. This paper reports the experience of psychiatrists, psychologists, and social workers in the Job Corps, the most intensive and only nationwide residential training program for disadvantaged youth. It is a report on the proceedings of the First Job Corps Mental Health Colloquium held in June, 1967. Moreover, the paper is an exploration of the role of the mental health worker in this and other similar programs. PMID- 24178852 TI - A survey of the nurse's role in psychiatric outpatient clinics in America. AB - This study proposed investigation of the duties of the registered nurse employed in psychiatric outpatient clinics, particularly those duties in which the nurse was involved in individual or group therapy. The method involved in this research was use of a questionnaire. A questionnaire concerning the duties of nurses was sent to the 187 psychiatric outpatient clinics in the United States thought to employ one or more nurses. The findings indicate that the majority of such nurses actively function in both individual and group psychotherapy, without additional educational preparation. PMID- 24178853 TI - The ex-addict as a member of the therapeutic team. AB - The utilization of the ex-addict as a member of the therapeutic team in the treatment and rehabilitation of narcotics addicts is a relatively new development. In the following article, the authors attempt to evaluate the ex addict's potential for success in this new role and how he is affected and affects the other members of the therapeutic team, particularly the psychiatric clinical nurse specialist. A description of the ex-addict's role is given, as well as the way in which he is utilized in New York City's Addiction Rehabilitation Program coordinated by Dr. Efren Ramirez. The central thesis is that there are certain functions which the ex-addict can perform more effectively than the professional. However, professional members of the team must recognize and accept the ex-addict if he is to successfully aid in treatment and rehabilitation. PMID- 24178854 TI - Social class and participation in outpatient care by schizophrenics. AB - Based on a random sample of male schizophrenics, the relationship between social class and involvement in outpatient treatment was investigated. It was found that the likelihood of utilizing outpatient facilities is significantly related to social class status, lower-class patients being less often involved. Participation in outpatient treatment was also assessed in relation to severity of pathology, marital status, and hospitalization. The results are discussed in terms of self selection and professional selectivity. PMID- 24178855 TI - An open-systems approach to the study of mental hospitals in transition. AB - In evaluating the functioning of a state mental hospital going through the transition of becoming a community mental health center, it is important to focus not only on the intraorganizational processes of the changing hospital but also on the exchanges and transactions between the hospital and the environment and the processes and structures through which parts of the environment are related to one another. This paper presents a framework for the study of the changing hospital organizational system and its relations to the community, based on the concepts of opensystems theory. PMID- 24178857 TI - Publications received. PMID- 24178856 TI - Film review. PMID- 24178858 TI - History, biology and chemistry of Mycobacterium ulcerans infections (Buruli ulcer disease). AB - Mycobacterium ulcerans infections (Buruli ulcer disease) have a long history that can be traced back 150 years. The successive discoveries of the mycobacteria in 1948 and of mycolactone A/B in 1999, the toxin responsible for this dramatic necrotic skin disease, resulted in a paradigm shift concerning the disease itself and in a broader sense, delineated an entirely new role for bioactive polyketides as virulence factors. The fascinating history, biology and chemistry of M. ulcerans infections are discussed in this review. PMID- 24178859 TI - Retrieval of impacted broken balloon by balloon inflation in guiding catheter. AB - Broken catheter fragment in a coronary artery during percutaneous coronary angioplasty is a rare complication. It can result in serious problems as a result of thrombus formation and embolization of broken fragment. We report an unusual complication of a broken balloon catheter during angioplasty, which was successfully retrieved by balloon inflation in guiding catheter technique. PMID- 24178861 TI - Aspartate-containing neurons of the brainstem and rostral spinal cord of the sea lamprey Petromyzon marinus: distribution and comparison with gamma-aminobutyric acid. AB - The amino acid L-aspartate (ASP) is one of the most abundant excitatory neurotransmitters in the mammalian brain, but its distribution in other vertebrates has not yet been well characterized. We investigated the distribution of ASP in the brainstem and rostral spinal cord of the adult sea lamprey by using ASP immunohistochemistry. Our results indicate that ASP is accumulated in specific neurons, but not in glia (tanycytes). ASP-immunoreactive neuronal populations were rather similar as the glutamatergic populations reported in the adult sea lamprey (Villar-Cervino et al. [2013] J Comp Neurol 521:522-557), although some important differences were noted. Characteristically, the largest reticular neurons of the lamprey brainstem (Muller cells) showed ASP immunoreactivity in perikarya and processes, in contrast to the absence or faint glutamate immunoreactivity reported in these perikarya. We also compared the distribution of ASP and gamma-aminobutyric acid (GABA) in brainstem neurons by using double immunofluorescence methods. In regions such as the midbrain tectum, dorsal isthmus, and motor nuclei, ASP and GABA immunoreactivity was mostly located in different neurons, whereas in other nuclei (torus semicircularis, octavolateralis area, parvocellular reticular formation), many of the ASP immunonegative neurons displayed colocalization with GABA. These results, together with those of our previous studies of colocalization of glutamate and GABA, suggest that some lamprey neurons may co-release both excitatory and inhibitory neurotransmitters. Further investigation is needed to elucidate the pathways of uptake and release of ASP by ASP-immunoreactive neurons. Our results indicate that ASP is a neurotransmitter in the central nervous system representative of agnathans, the earliest vertebrate group. PMID- 24178862 TI - Real-time image guidance in laparoscopic liver surgery: first clinical experience with a guidance system based on intraoperative CT imaging. AB - BACKGROUND: Laparoscopic liver surgery is particularly challenging owing to restricted access, risk of bleeding, and lack of haptic feedback. Navigation systems have the potential to improve information on the exact position of intrahepatic tumors, and thus facilitate oncological resection. This study aims to evaluate the feasibility of a commercially available augmented reality (AR) guidance system employing intraoperative robotic C-arm cone-beam computed tomography (CBCT) for laparoscopic liver surgery. METHODS: A human liver-like phantom with 16 target fiducials was used to evaluate the Syngo iPilot((r)) AR system. Subsequently, the system was used for the laparoscopic resection of a hepatocellular carcinoma in segment 7 of a 50-year-old male patient. RESULTS: In the phantom experiment, the AR system showed a mean target registration error of 0.96 +/- 0.52 mm, with a maximum error of 2.49 mm. The patient successfully underwent the operation and showed no postoperative complications. CONCLUSION: The use of intraoperative CBCT and AR for laparoscopic liver resection is feasible and could be considered an option for future liver surgery in complex cases. PMID- 24178863 TI - Risk of colon cancer after computed tomography-diagnosed acute diverticulitis: is routine colonoscopy necessary? AB - BACKGROUND: Current guidelines recommend computed tomography (CT) for diagnosing diverticulitis and for routine follow-up colonoscopy to rule out cancer. Scientific data to support routine colonoscopy after acute diverticulitis are scarce and conflicting. This study aimed to evaluate the risk of colon cancer mimicking diverticulitis, and hence the need for routine colonoscopy after CT diagnosed acute diverticulitis. METHODS: This study was a retrospective analysis of patients treated for acute diverticulitis in a single academic institution during 2006-2010. Data regarding age, sex, laboratory parameters, prior diverticulitis, surgical operations, pathology reports, and CT characteristics were collected. Risk factors for finding colon cancer after CT-diagnosed acute diverticulitis were identified by multivariate analysis. RESULTS: The study enrolled 633 patients with CT-diagnosed acute diverticulitis. Of these patients, 97 underwent emergency resection, whereas 536 were treated conservatively, 394 of whom underwent colonoscopy. The findings showed 17 cancers (2.7 %) in patients with an initial diagnosis of acute diverticulitis. As shown by CT, 16 cancer patients (94 %) had abscess, whereas one patient had pericolic extraluminal air but no abscess. Of the patients with abscess, 11.4 % had cancer mimicking acute diverticulitis. No cancer was found in the patients with uncomplicated diverticulitis. Besides abscess, other independent risk factors for cancer included suspicion of cancer by a radiologist, thickness of the bowel wall exceeding 15 mm, no diverticula observed, and previously undiagnosed metastases. CONCLUSIONS: Routine colonoscopy after CT-proven uncomplicated diverticulitis seems to be unnecessary, but colonoscopy should be performed for patients with a diagnosis of diverticular abscess. PMID- 24178860 TI - Pharmacotherapy of critical asthma syndrome: current and emerging therapies. AB - The critical asthma syndrome (CAS) encompasses the most severe, persistent, refractory asthma patients for the clinician to manage. Personalized pharmacotherapy is necessary to prevent the next acute severe asthma exacerbation, not just the control of symptoms. The 2007 National Asthma Education and Prevention Program Expert Panel 3 provides guidelines for the treatment of uncontrolled asthma. The patient's response to recommended pharmacotherapy is highly variable which risks poor asthma control leading to frequent exacerbations that can deteriorate into CAS. Controlling asthma symptoms and preventing acute exacerbations may be two separate clinical activities with their own unique demands. Clinicians must be prepared to use the entire spectrum of asthma medications available but must concurrently be aware of potential drug toxicities some of which can paradoxically worsen asthma control. Medications normally prescribed for COPD can potentially be useful in the CAS patient, particularly those with asthma-COPD overlap syndrome. Immunomodulation with drugs like omalizumab in IgE-mediated asthma syndromes is one important approach. New and emerging drugs address unique aspects of airway inflammation and biology but at a significant financial cost. The pharmacology and toxicities of the agents that may be used in the treatment of CAS to control asthma symptoms and prevent severe exacerbations are reviewed. PMID- 24178864 TI - Transanal endoscopic surgery using a single access port: a practical tool in the surgeon's toybox. AB - BACKGROUND: Large polyps and early carcinomas of the rectum may be excised with transanal endoscopic surgery (TES). Single-port techniques are emerging in the field of colorectal surgery and have been adapted to many colorectal procedures so far. In this article, we aimed to present our initial experience with TES using a single access port with its technical details. PATIENTS AND METHODS: Patients undergoing TES using a single access port between July 2010 and January 2013 were included in the study. Patient demographics, operative technique, and both operative and postoperative outcomes were evaluated and presented. RESULTS: A total of 12 patients (ten males) were included in our study. The median age was 63.5 years (50-84), median American Society of Anesthesiologists (ASA) score was 3 (2-4), and median body mass index was 28.8 kg/m(2) (17.4-55.6). Median operating time was 79 min (43-261). Histopathological diagnoses were as follows: tubulovillous adenoma (n = 6), tubular adenoma (n = 4), adenocarcinoma (n = 1), and neuroendocrine tumor (n = 1). Five patients were sent home on the day of surgery and the median postoperative hospital stay was 1 day (0-38). Median estimated blood loss was 22.5 ml (5-150). A transient urinary retention was developed in one patient postoperatively, and two patients had postoperative bleeding. The first of these patients with a long history of anticoagulant usage had rectal bleeding 13 days after surgery, which was successfully managed with medical treatment. The second patient was morbidly obese, had multiple comorbidities, and had rectal bleeding on postoperative day 7 which was managed with local epinephrine injection. He suffered unrelated cardiac death on postoperative day 38. CONCLUSIONS: TES is safe and feasible when using a single port and in the standard laparoscopic setting. The single-port technique may play a major role in the widespread utilization of TES as a treatment for large adenomas and early rectal cancers. PMID- 24178866 TI - CD44+/CD133+ immunophenotype and matrix metalloproteinase-9: Influence on prognosis in early-stage oral squamous cell carcinoma. AB - BACKGROUND: The purpose of this study was to investigate the expression of CD44 and/or CD133 immunophenotypes and the associated effects of matrix metalloproteinase-9 (MMP-9) in early-stage oral squamous cell carcinomas (SCC) to assess their influence on tumor prognosis. METHODS: The following data were derived from 150 patients: age, sex, primary anatomic site, smoking status, alcohol intake, recurrence, metastases, histological classification, treatment, disease-free survival (DFS), and overall survival (OS). Immunohistochemical study of CD44, CD133, and MMP-9 expression was performed on a tissue microarray of 150 paraffin blocks of oral SCCs. RESULTS: The predominant immunophenotype identified to exhibit a significant correlation with MMP-9 was the CD44+/CD133+. Multivariate analyses identified a significant correlation of OS with surgical treatment and with CD44+/CD133+ immunophenotype. CONCLUSION: This investigation demonstrated the prognostic importance of CD44/CD133 expression, which can help improve the prognostic value of surgical treatment for oral SCCs when diagnosed in early stages. PMID- 24178865 TI - Do colorectal cancer resections improve diabetes in long-term survivors? A case control study. AB - BACKGROUND: A clinical study was designed that aimed to analyze whether resection of the large bowel in cancer patients might benefit diabetes mellitus. METHODS: This prospective case-control study included retrospective information. Patients (n = 247) included diabetic and euglycemic groups with colorectal cancer operations (n = 60), cancer gastrectomy (n = 72), exclusive chemoradiotherapy for rectal cancer (n = 46), and noncancer clinical controls (n = 69). Follow-up periods were, respectively, 79.2 +/- 27.4, 86.8 +/- 25.1, 70.0 +/- 26.3, and 85.1 +/- 18.2 months (NS). Diabetes groups included patients with prediabetes. RESULTS: Diabetes remission, defined as conversion from diabetes to prediabetes or from this condition to normal, was documented in, respectively, 32.4 % (11 of 34), 41.2 % (14 of 34), 7.1 % (1 of 14), and 7.7 % (3 of 39) in the four cohorts (P = 0.004). Within the same period, progression of euglycemic participants to diabetes occurred in 30.8 % (8 of 26), 63.2 % (24 of 38), 25.0 (8 of 32), and 20.0 % (6 of 30) (P = 0.028). Diabetes amelioration was associated with weight loss in gastrectomy patients but not in the other groups. Dietary intake, estimated in the two surgical populations, did not predict outcome. CONCLUSIONS: Diabetes amelioration after colorectal interventions was demonstrated, but progression of euglycemic patients toward prediabetes was not changed in comparison with nonsurgical controls. It is speculated that reshaping of the bowel microbiome or hormone changes after colorectal interventions underlay the improvement in diabetes. Body weight fluctuations could not be incriminated in this investigation. PMID- 24178868 TI - Community mental health ideology, dogmatism, and political-economic conservatism. AB - The Community Mental Health Ideology (CMHI) Scale, an abridged version of Rokeach's Dogmatism (D) Scale, and the five-item form of the Political-Economic Conservatism (PEC) Scale were administered to 140 members of the Massachusetts Citizen Mental Health Area Boards. The results indicate that degree of adherence to community mental health ideology as measured by the CMHI Scale is significantly negatively correlated with dogmatism and political-economic conservatism. The sample of nonprofessional citizens scored higher on the CMHI Scale than did groups of mental health professionals who had been previously studied. They also obtained scores on the D Scale and PEC Scale indicating that these lay members of mental health area boards are less dogmatic and less conservative than the groups with which these scales were originally developed. PMID- 24178867 TI - Unilateral pulmonary agenesis: a report of four cases, two diagnosed antenatally and literature review. AB - Pulmonary agenesis is a rare congenital malformation of lung development defined as complete absence of lung tissues, bronchi, and pulmonary vessels; it may be uni- or bilateral. The right-sided form carries the poorest prognosis due to severity of co-existent anomalies. Its diagnostic circumstances are variables: first reported cases were diagnosed at autopsy, but early postnatal as well as fortuitous discovery have been reported. In recent years, progress in obstetrical imaging has made antenatal diagnosis possible so that fetal ultrasound and MRI allow early diagnosis and refinement by permitting the elimination of differential diagnoses (diaphragmatic hernia, cystic adenomatoid malformation of the lung, giant lobar emphysema, and situs inversus). This anomaly is compatible with normal life provided co-existent malformations are thoroughly investigated and managed in a multidisciplinary setting. We report four cases of lung agenesis two of which were diagnosed antenatally at 23rd and 30th weeks of gestation respectively. Our aim is to describe the circumstances having led to diagnosis and report both follow-up and outcome of our patients. PMID- 24178869 TI - Characteristics of community mental health center operations in small communities. AB - With increasing tempo, community mental health center programs are being developed in areas of low population density. Models created in urban areas will need modifications in philosophy and practice in order to flourish in this new environment. The distinctive characteristics of small community life must be taken into account. These characteristics may require alterations in the following selected areas of mental health center operations: type of personnel selected; method of program development; relationships with other professionals; approach to significant community "gatekeepers" and selection of program content. PMID- 24178870 TI - The psychiatric resident in the community. AB - A program in the state of Maryland which introduces psychiatric residents to community psychiatry is described. Since 1958, 80 senior psychiatric residents worked one day a week for a year as psychiatric consultants to Maryland county health departments. The program embodies the principle of inductive education, introduced into American medicine by Franklin Paine Mall and transplanted here to the developing field of education for community psychiatry. Supervision is more consultative and supportive than didactic, and residents and program directors engage in a mutual educational endeavor. This method can adequately prepare psychiatrists for work in the community. PMID- 24178871 TI - Problems of ethics in community mental health: A survey of community psychologists. AB - Psychologists in community mental health were surveyed to ascertain new ethical problems arising from their community activity. They were also asked what could be done about making psychologists more aware of these issues. Consultation, competence, confidentiality, and professional versus citizen's role were the important areas. Suggestions were made for early ethics education with examples in ethics handbooks of community activities. PMID- 24178872 TI - College mental health programs: A paradigm for Comprehensive Community Mental Health centers. AB - Some of the dilemmas confronting the Comprehensive Community Mental Health movement are reviewed. Existent paradigms to this movement or aspects of it are documented on various college campuses with special reference to the College Community Mental Health Program present at the University of Florida. The major content of the paper clarifies areas of applicable usefulness such community oriented College Mental Health Programs can serve in overcoming some of the dilemmas of the Comprehensive Community Mental Health movement. University of Florida utilization of the College Community Model for training of the psychiatric resident is outlined. PMID- 24178873 TI - Some diagnostic and psychotherapeutic implications of community awareness. AB - A state child diagnostic service, working with welfare departments and courts throughout Colorado in diagnosing and planning for emotionally disturbed children, moves from its traditional diagnostic function toward an increasing diagnostic-consultation service. This shift results from awareness of the rising importance of viewing pathology in its more complete context of child-family agency-community. This outlook is vital not only to better understand the nature and operation of the child's pathology, but also to be able to help the referring agency in its ongoing work with the family. Two case studies illustrate the family-community problematic interaction, as well as contrasting methods of working with this context. PMID- 24178874 TI - A modified team approach for the evaluation of children with moderate or greater mental retardation. AB - A modified diagnostic team approach was tried as a solution to increased service demands, staff shortage, and imbalance at a regional state diagnostic center. Departing from their usual diagnostic roles, psychologists and pediatricians did social history taking and related tasks. In this way, 100 moderate and severely retarded children and their families received diagnostic help over a year's time. Through care and responsibility and innovation in the planning and implementation of the project, and through cooperative staff functioning, problems involving staff shortage and imbalance and assumed urgent service demands were overcome. Pending an independent follow-up evaluation, the approach is recommended. PMID- 24178875 TI - "No-therapy": A method of helping persons with problems. AB - Groups, settings, and activities which are not labeled therapeutic but which are devoted to helping persons with problems seem to be quite effective. Persons involved in Alcoholics Anonymous, Synanon, and other similar groups are not therapists but yet attempt to deal with problems. "No-therapy" is proposed as a name for the activity which goes on. The relationship between therapist and patient and between "no-therapist" and person with a problem are quite different. "No-therapy" is particularly suited to help with problems of behavior and is not suited to help with problems of thought or emotion. PMID- 24178876 TI - Bereavement and the acceptance of professional service. AB - The results of a pilot study indicate that recently bereaved individuals are predisposed to accept an unsolicited offer of professional help. A conceptual orientation is presented, for the purpose of explaining why 90% of the family units accepted a psychiatric social work service, which suggests that survivors will accept an offer of professional assistance when they define the bereavement situation as a crisis in need of uncustomary sources of support. This definition is reached when the survivor considers lay customary support, e.g., close friends and relatives, as inadequate for relieving various problems associated with the death of a close person. PMID- 24178877 TI - Publications received. PMID- 24178878 TI - The total demand for psychiatric services in an island community. PMID- 24178880 TI - Synthesis of (E)-delta-hydroxy-beta,gamma-dehydroalpha-amino acids, a new class of vinylglycines by the rearrangement ofbeta acetoxyallylglycine derivatives. AB - The efficient synthesis ofdelta-hydroxy-beta,gamma-dehydroalpha-amino acids (1) was achieved by the hybrid process, in which the Pd(II)-assisted rear-rangement ofbeta-acetoxyallylglycine ester (6) afforded the corresponding (E)-delta acetoxyvinylglycine derivatives (7) in a moderate yield. The chemo- and stereo selective hydrolysis of7 was accomplished by the use of microbial lipase (Amano PS) to afford the allylic alcohol (8), which was transformed into1 in two step sequence. PMID- 24178879 TI - Metabolism of citrulline in man. AB - Citrulline is a non protein amino acid involved in three important metabolic pathways, the intrahepatic transformation of ammonia to urea, the de novo synthesis of arginine from glutamine in gut and kidney, the nitric oxide synthesis. The two first pathways use the same enzyme activities but are regulated in different way. This review describe these pathways and their regulation in different tissues. In the light of our knowledge we tried to explain the physiological and pathological (inherited or acquired) variations in man. PMID- 24178881 TI - Synthesis of symmetric disulfides as potential alternative substrates for trypanothione reductase and glutathione reductase: Part 1. AB - The synthesis of a series of symmetrical disulfides as potential substrates of trypanothione reductase and glutathione reductase was described. The key intermediate in the synthetic approach was the choice of S-(t)butylmercapto-L cysteine (1). The spermidine ring in the native substrate, trypanothione disulfide (TSST), was replaced with 3-dimethyl-aminopropylamine (DMAPA), while thegamma-Glu moiety was replaced by phenylalanyl or tryptophanyl residues. The same modifications in thegamma-Glu moiety of glutathione disulfide (GSSG) were applied. PMID- 24178882 TI - Synthesis of asymmetric disulfides as potential alternative substrates for trypanothione reductase and glutathione reductase: Part 2. AB - The synthesis of asymmetrical disulfides, based on Zervas' inter-mediate, monocarbobenzoxy-L-cystine, has been developed. A series of substrate analogues of trypanothione disulfide (TSST) and glutathione disulfide (GSSG) are described, where the spermidine ring of (TSST) has been replaced by 3 dimethylaminopropylamine (DMAPA). The free amino group in Zervas' product was condensed with phenylalanyl, tryptophanyl or glutamyl residues, while the carbobenzoxy group was unaffected under the reaction conditions employed. The same synthetic approach was applied in the design of analogues of glutathione disulfide (GSSG). PMID- 24178883 TI - Nuclear microanalysis of the monovalent ions distribution in the human amnion : II. Effect of taurine. AB - The effect of taurine on the Na(+), K(+), Cl(-) concentration and distribution in epithelial and compact layers of the human amniotic membrane had been investigated using the Bordeaux nuclear microprobe. Particle induced X-ray emission and Rutherford backscattering spectrometry techniques had been used to provice quantitative measurements. In physiological medium, the monovalent ions concentrations were identical in epithelial and compact layers. The addition of taurine in Hanks' physiological fluid had no effect on Na(+) concentration, but decreased K(+) and Cl(-) concentration in both layers. The quantitative results were related to electrophysiological observations on the effect of taurine on ionic exchanges through channels and paracellular pathways. PMID- 24178884 TI - Intramitochondrial localization of alanine aminotransferase in rat-liver mitochondria: comparison with glutaminase and aspartate aminotransferase. AB - The removal of the outer mitochondrial membrane and hence of constituents of the intermembrane space in rat-liver mitochondria using digitonin showed that phosphate-dependent glutaminase, alanine and aspartate aminotransferase were localized in the mitoplasts. Further fractionation of mitoplasts following their sonication resulted in 90% of glutaminase, 98% of alanine aminotransferase and 48% of aspartate aminotransferase being recovered in the soluble fraction while the remainder of each enzyme was recovered in the sonicated vesicles fraction. These results indicated that glutaminase and alanine aminotransferase were soluble matrix enzymes, the little of each enzyme recovered in the sonicated vesicles fraction being probably due to entrapment in the vesicles. Aspartate aminotransferase had dual localization, in the inner membrane and matrix with the high specific activity in sonicated vesicles confirming its association with the membrane. Activation experiments suggested that the membrane-bound enzyme was localized on the inner side of the inner mitochondrial membrane. PMID- 24178885 TI - Conformational studies of chemotactic HCO-Met-Leu-Phe-OMe analogues. AB - In order to investigate the proper peptide backbone conformation able to elicit a biological activity, HCO-Met-Pro-Phe-OMe, HCO-Met-Psi[COO]Leu-Phe-OMe, and HCO Met-OLeu-Phe-OMe, analogues of the prototypical chemotactic peptide HCO-Met-Leu Phe-OMe, were studied by CD and IR techniques. The results obtained comparing biological and conformational data evidence the critical presence of (i) the NH group at position 2, (ii) a rather flexible backbone, (iii) the chemical structure of the central residue which can affect the stability of a possible active conformer. PMID- 24178886 TI - Incorporation of nitrate nitrogen into amino acids during the anaerobic germination of rice. AB - Incorporation of(15)NO3-into amino acids was studied during the anaerobic germination of rice seeds. In treated coleoptiles, the label was incorporated into glutamine, glutamate, alanine,gamma-aminobutyric acid (Gaba), arginine, aspartate and methionine. These findings are consistent with a primary incorporation of nitrate nitrogen into glutamine, glutamate and aspartate, and their further conversion to alanine, Gaba, arginine and methionine. PMID- 24178887 TI - Neuroexcitatory amino acids: 4-methylene glutamic acid derivatives : Short Communication. AB - A short synthesis of 4-methylene glutamic acid was achieved. Under thermal conditions the corresponding anhydride reacted with 2,3 dimethylbutadiene to afford the corresponding DIELS-ALDER adduct in good yield. L-4-methylene glutamic acid essentially acts on glutamate metabotropic receptors and is as potent as L Glu in producing IPs. PMID- 24178888 TI - Human brain mercury levels related to exposure to amalgam fillings. AB - The safety of dental amalgam as the primary material in dental restoration treatments has been debated since its introduction. It is widely accepted that amalgam restorations continuously release elemental mercury (Hg) vapor, which is inhaled and absorbed by the body and distributed to tissues, including the brain. The aim of the present study was to investigate whether the presence of amalgam fillings is correlated with brain Hg level. The Hg levels in the parietal lobes of the brains of 32 cadavers were analyzed with an atomic absorption spectrometer with the mercury hydride system. A total of 32 brain samples were tested; of these, 10 were from cadavers with amalgam fillings, while 22 of them were amalgam free. Hg was detected in 60.0% (6 of 10) of the samples in the amalgam group and in 36.3% (8 of 22) in the amalgam-free group. The average Hg level of the amalgam group was 0.97 +/- 0.83 ug/g (minimum: 0.3 ug/g and maximum: 2.34 ug/g), and in the amalgam-free group, it was 1.06 +/- 0.57 ug/g (minimum: 0.17 ug/g and maximum: 1.76 ug/g). The results of the present study showed no correlation between the presence of amalgam fillings and brain Hg level. PMID- 24178889 TI - Paracrine factors of human mesenchymal stem cells increase wound closure and reduce reactive oxygen species production in a traumatic brain injury in vitro model. AB - Traumatic brain injury (TBI) consists of a primary and a secondary insult characterized by a biochemical cascade that plays a crucial role in cell death in the brain. Despite the major improvements in the acute care of head injury victims, no effective strategies exist for preventing the secondary injury cascade. This lack of success might be due to that most treatments are aimed at targeting neuronal population, even if studies show that astrocytes play a key role after a brain damage. In this work, we propose a new model of in vitro traumatic brain-like injury and use paracrine factors released by human mesenchymal stem cells (hMSCs) as a neuroprotective strategy. Our results demonstrate that hMSC-conditioned medium increased wound closure and proliferation at 12 h and reduced superoxide production to control conditions. This was accompanied by changes in cell morphology and polarity index, as both parameters reflect the ability of cells to migrate toward the wound. These findings indicate that hMSC is an important regulator of oxidative stress production, enhances cells migration, and shall be considered as a useful neuroprotective approach for brain recovery following injury. PMID- 24178890 TI - Manganese-impregnated mesoporous silica nanoparticles for signal enhancement in MRI cell labelling studies. AB - Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn(2+) is already implemented as a "positive" cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (~140 nm diam.) and high porosity (~60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(II) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn(2+) leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM(-1) s(-1) were measured at 60 MHz and 37 degrees C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because these Mn-labelled M48SNs express strong "positive" contrast media properties at low concentrations, they are potentially applicable for cell tracking and drug delivery methodologies. PMID- 24178891 TI - Impact of thyroid status and age on comprehensive geriatric assessment. AB - This study aimed to evaluate the prevalence of thyroid dysfunction in elderly subjects attending an outpatient clinic at a tertiary hospital and to assess whether subclinical hypothyroidism (SCH) or aging affected activities of daily living (ADLs), instrumental activities of daily living (IADLs), cognitive status, or depressive symptoms. This crosssectional study included 411 patients recruited in the outpatient geriatric setting. 48 subjects reported levothyroxine use and were evaluated separately. After excluding subjects with diseases or drugs which could influence thyroid status, the 284 subjects remaining were classified as having euthyroidism (n = 235, 82.8 %), subclinical hypothyroidism (n = 43, 15.1 %), subclinical hyperthyroidism (n = 4, 1.4 %), or overt hyperthyroidism (n = 2, 0.7 %). ADLs and IADLs were assessed using the Katz Index (ranging from 0 [independence] to 6 [dependence in all activities]) and Health Assessment Questionnaire (ranging from 0 to 3 [severely disabled]), respectively. Cognition was assessed using the mini mental state depressive symptoms that were assessed using the Geriatric depression scale or cornell scale for depression in dementia. SCH did not reduce performance in ADLs or IADLs in elderly subjects as a whole, but was an independent protective factor against dependence in ADLs (OR = 0.196 [0.045-0.853]; p = 0.003) and IADLs (OR = 0.060 [0.010-0.361]; p = 0.002) in subjects aged >=85 years. Very old subjects with SCH showed better performance in ADLs than did those with euthyroidism (Katz Index: 0.9 +/- 1.6 [median: 0.5] vs. 1.7 +/- 1.7 [1.0], p = 0.024; HAQ: 1.2 +/- 0.8 [0.9] vs. 1.8 +/- 1.0 [1.9], p = 0.015). This putative protective effect of SCH was not found in subjects aged <85 years. The number of falls, number of medications used, depressive symptoms, and cognitive impairment did not differ among thyroid status groups, regardless of age. In conclusion, SCH does not have impact functional performance in the elderly population as a whole, but was associated with better functional status in subjects aged >=85 years. PMID- 24178892 TI - Trigeminal intersubnuclear neurons: morphometry and input-dependent structural plasticity in adult rats. AB - Intersubnuclear neurons in the caudal division of the spinal trigeminal nucleus that project to the principal nucleus (Pr5) play an active role in shaping the receptive fields of other neurons, at different levels in the ascending sensory system that processes information originating from the vibrissae. By using retrograde labeling and digital reconstruction, we investigated the morphometry and topology of the dendritic trees of these neurons and the changes induced by long-term experience-dependent plasticity in adult male rats. Primary afferent input was either eliminated by transection of the right infraorbital nerve (IoN), or selectively altered by repeated whisker clipping on the right side. These neurons do not display asymmetries between sides in basic metric and topologic parameters (global number of trees, nodes, spines, or dendritic ends), although neurons on the left tend to have longer terminal segments. Ipsilaterally, both deafferentation (IoN transection) and deprivation (whisker trimming) reduced the density of spines, and the former also caused a global increase in total dendritic length and a relative increase in more complex arbors. Contralaterally, deafferentation reduced more complex dendritic trees, and caused a moderate decline in dendritic length and spatial reach, and a loss of spines in number and density. Deprivation caused a similar, but more profound, effect on spines. Our findings provide original quantitative descriptions of a scarcely known cell population, and show that denervation- or deprivation-derived plasticity is expressed not only by neurons at higher levels of the sensory pathways, but also by neurons in key subcortical circuits for sensory processing. PMID- 24178893 TI - Clinical and genetic features in autosomal recessive and X-linked Alport syndrome. AB - BACKGROUND: This study determined the family history and clinical features that suggested autosomal recessive rather than X-linked Alport syndrome. METHODS: All patients had the diagnosis of Alport syndrome and the mode of inheritance confirmed by genetic testing, and underwent examination at a single centre. RESULTS: Patients comprised 9 males and 6 females with autosomal recessive Alport syndrome, and 18 males and 22 females with X-linked disease. Fourteen (93 %) individuals with autosomal recessive Alport syndrome developed early end-stage renal failure, all 15 had hearing loss, and most had lenticonus (12, 80 %), and a central (13, 87 %) or peripheral (13, 87 %) retinopathy. These features occurred as often as in males with X-linked disease. Females with autosomal recessive inheritance were less likely to have an affected family member in another generation (p = 0.01) than females with X-linked disease. They were more likely to have renal failure (p = 0.003), hearing loss (p = 0.02) and lenticonus (p < 0.001). Fifty percent had a central retinopathy compared with 18 % with X-linked disease (p = 0.14), but peripheral retinopathy prevalence was not different (p = 0.64). Nonsense mutations accounted for 67 % (8/12) of these disease-causing mutations. CONCLUSIONS: Autosomal recessive inheritance is increased in females with Alport syndrome and early onset renal failure, hearing loss, lenticonus, and, possibly, central retinopathy. PMID- 24178894 TI - Lung ultrasound in pediatric pneumonia. The persistent need of chest X-rays. PMID- 24178895 TI - Exercise boosts hippocampal volume by preventing early age-related gray matter loss. AB - Recently, a larger hippocampus was found in exercising mice and men. Here we studied the morphological underpinnings in wheel running mice by longitudinal magnetic resonance imaging. Voxel-based morphometry revealed that running increases hippocampal volume by inhibiting an early age-related gray matter loss. Disruption of neurogenesis-related neuroplasticity by focalized irradiation is sufficient to block positive effects of exercise on macroscopic brain morphology. PMID- 24178896 TI - Sequence analysis of the ADRA2A coding region in children affected by attention deficit hyperactivity disorder. AB - Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral pathology characterized by distinct degrees of inattention, hyperactivity and impulsivity. Although ADHD etiology remains elusive, the ADRA2A candidate gene underlies a particular interest, since it participates in the prefrontal cortex regulation of executive function. Three SNPs located on 5' and 3'UTR regions of the gene have been extensively explored but none of them have been definitely validated as a predisposition or a causative sequence variation. In this study, in order to determine whether ADRA2A non-synonymous sequence variants, resulting in biochemical modifications of the protein, are a common cause of the disease we sequenced the complete ADRA2A coding region in a panel of ADHD children of Colombian origin. We identified the c.1138 C>A (p.Arg380Arg) silent substitution. We conclude that ADRA2A non-synonymous sequence variants do not cause ADHD in our sample population. We cannot formerly discard a potential role of this gene during ADHD pathogenesis since only the coding region was analysed. We hope that these results will encourage further researchers to sequence the promoter and coding regions of ADRA2A in large panels of ADHD patients from distinct ethnical origins. PMID- 24178898 TI - Revealing the nature of intermolecular interaction and configurational preference of the nonpolar molecular dimers (H2)2, (N2)2, and (H2)(N2). AB - Understanding the nature of noncovalent interactions between nonpolar small molecules is not only theoretically interesting but also important for practical purposes. The interaction mechanism of three prototype dimers (H2)2, (N2)2, and (H2)(N2) are investigated by state-of-the-art quantum chemistry calculations and energy decomposition analysis. It is shown that their configuration preferences are essentially controlled by the electrostatic component rather than the dispersion effect though the monomers have zero dipole moment. These configuration preferences can also be fairly well and conveniently interpreted by visually examining the electrostatic potential map. PMID- 24178897 TI - Cyclooxygenase-2 expression is associated with poor overall survival of patients with gastric cancer: a meta-analysis. AB - BACKGROUND: Cyclooxygenase-2 (COX-2) is believed to be involved in gastric carcinogenesis. However, it is still controversial whether COX-2 expression can be regarded as a prognostic factor for gastric cancer patients. AIM: To obtain a more accurate relationship between COX-2 overexpression and prognosis in gastric cancer by meta-analysis. METHOD: Relevant articles published up to May 2013 were searched by use of several keywords in electronic databases. Separate hazard ratio (HR) estimates and 95 % confidence intervals (95 % CI) for COX-2 overexpression and overall survival (OS) and disease-free survival (DFS) with gastric cancer were extracted. Combined HR with 95 % CI was calculated by use of Stata11.0 software to estimate the size of the effect. Publication bias testing and sensitivity analysis were also performed. RESULTS: A total of 27 studies which included 3,891 gastric cancer patients were combined in the final analysis. Combined results suggested that COX-2 overexpression was associated with an unfavorable OS (HR 1.58, 95 % CI 1.36-1.84) but not DFS (HR 1.15, 95 % CI 0.93 1.43) among patients with gastric cancer. Publication bias was absent. Sensitivity analysis suggested that the results of this meta-analysis were robust. CONCLUSIONS: The results of this meta-analysis suggest that high COX-2 expression may be an independent risk factor for poor OS of patients with gastric cancer. More large prospective studies are now needed to further clarify the prognostic value of COX-2 expression for DFS in gastric cancer. PMID- 24178899 TI - Role of chelation in the treatment of lead poisoning: discussion of the Treatment of Lead-Exposed Children Trial (TLC). AB - Lead exposure in children is one component leading to cognitive impairment. The Treatment of Lead-Exposed Children Trial (1994-2004) studied the effect of succimer in treating low levels of lead exposure (20-44 mcg/dL) in children 12 to 33 months old. While succimer was effective in reducing blood lead concentrations in the short term, treatment of blood lead levels did not result in any detectable improvement in a wide variety of measurements of cognitive or behavioral function. Furthermore, blood lead concentrations were not distinguishable between chelated and non-chelated individuals at 1 year. The most important treatment strategy is identification and termination of major sources of lead exposure. PMID- 24178900 TI - The role of chelation in the treatment of arsenic and mercury poisoning. AB - Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2 chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication. PMID- 24178901 TI - Editorial: Use and misuse of metal chelation therapy. PMID- 24178902 TI - The Toxicology Investigators Consortium Case Registry--the 2012 experience. AB - In 2010, the American College of Medical Toxicology (ACMT) established its Case Registry, the Toxicology Investigators Consortium (ToxIC). All cases are entered prospectively and include only suspected and confirmed toxic exposures cared for at the bedside by board-certified or board-eligible medical toxicologists at its participating sites. The primary aims of establishing this Registry include the development of a realtime toxico-surveillance system in order to identify and describe current or evolving trends in poisoning and to develop a research tool in toxicology. ToxIC allows for extraction of data from medical records from multiple sites across a national and international network. All cases seen by medical toxicologists at participating institutions were entered into the database. Information characterizing patients entered in 2012 was tabulated and data from the previous years including 2010 and 2011 were included so that cumulative numbers and trends could be described as well. The current report includes data through December 31st, 2012. During 2012, 38 sites with 68 specific institutions contributed a total of 7,269 cases to the Registry. The total number of cases entered into the Registry at the end of 2012 was 17,681. Emergency departments remained the most common source of consultation in 2012, accounting for 61 % of cases. The most common reason for consultation was for pharmaceutical overdose, which occurred in 52 % of patients including intentional (41 %) and unintentional (11 %) exposures. The most common classes of agents were sedative hypnotics (1,422 entries in 13 % of cases) non-opioid analgesics (1,295 entries in 12 % of cases), opioids (1,086 entries in 10 % of cases) and antidepressants (1,039 entries in 10 % of cases). N-acetylcysteine (NAC) was the most common antidote administered in 2012, as it was in previous years, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments were administered in 109 cases or 82 % of cases in which a snake envenomation occurred. There were 57 deaths reported in the Registry in 2012. The most common associated agent alone or in combination was the non-opioid analgesic acetaminophen, being reported in 10 different cases. Other common agents and agent classes involved in death cases included ethanol, opioids, the anti-diabetic agent metformin, sedatives-hypnotics and cardiovascular agents, in particular amlodipine. There were significant trends identified during 2012. Abuse of over-the-counter medications such as dextromethorphan remains prevalent. Cases involving dextromethorphan continued to be reported at frequencies higher than other commonly abused drugs including many stimulants, phencyclidine, synthetic cannabinoids and designer amphetamines such as bath salts. And, while cases involving synthetic cannabinoids and psychoactive bath salts remained relatively constant from 2011 to 2012 several designer amphetamines and novel psychoactive substances were first reported in the Registry in 2012 including the NBOME compounds or "N-bomb" agents. LSD cases also spiked dramatically in 2012 with an 18-fold increase from 2011 although many of these cases are thought to be ultra-potent designer amphetamines misrepresented as "synthetic" LSD. The 2012 Registry included over 400 Adverse Drug Reactions (ADRs) involving 4 % of all Registry cases with 106 agents causing at least 2 ADRs. Additional data including supportive cares, decontamination, and chelating agent use are also included in the 2012 annual report. The Registry remains a valuable toxico-surveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside care by a medical toxicologist. PMID- 24178903 TI - Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine. AB - INTRODUCTION: Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability. CASE REPORT: A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 MUg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes. DISCUSSION: Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension. PMID- 24178904 TI - TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer. AB - BACKGROUNDS AND OBJECTIVES: We previously examined the amplification status of 10 kinase genes (PIK3CA, EPHB3, TNK2, PTK7, EGFR, MET, ERBB2, HCK, SRC, and AURKA) in gastric cancer (GC). This study aimed to determine the prognostic significance of these gene amplifications in GC. METHODS: A survival analysis was performed for GC patients. Since TNK2 amplification was identified as a prognostic marker in the analysis, we also examined the functional effect of TNK2 overexpression on gastric cells. RESULTS: A Kaplan-Meier analysis showed that the prognosis of patients with GC exhibiting TNK2 or AURKA amplification was significantly poorer than the prognosis of patients with GC without TNK2 or AURKA amplification. A further multivariate analysis revealed that TNK2 amplification was an independent predictor of a poor survival outcome among patients with GC (hazard ratio, 3.668; 95% confidence interval, 1.513-7.968; P = 0.0056). TNK2-overexpressing GC cells showed an increase in cell migration and non-anchored cell growth. Finally, microarray and pathway analyses revealed the aberrant regulation of some cancer related pathways in TNK2-overexpressing GC cells. CONCLUSIONS: These results suggested that TNK2 amplification is an independent predictor of a poor prognosis in patients with GC and leads to an increase in the malignant potential of GC cells. PMID- 24178905 TI - A 129-kb deletion on chromosome 12 confers substantial protection against rheumatoid arthritis, implicating the gene SLC2A3. AB - We describe a copy-number variant (CNV) for which deletion alleles confer a protective affect against rheumatoid arthritis (RA). This CNV reflects net unit deletions and expansions to a normal two-unit tandem duplication located on human chr12p13.31, a region with conserved synteny to the rat RA susceptibility quantitative trait loci Oia2. Genotyping, using the paralogue ratio test and SNP intensity data, in Swedish samples (2,403 cases, 1,269 controls) showed that the frequency of deletion variants is significantly lower in cases (P = 0.0012, OR = 0.442 [95%CI 0.258-0.755]). Reduced frequencies of deletion variants were also seen in replication materials comprising 9,201 UK samples (1,846 cases, 7,355 controls) and 2,963 US samples (906 controls, 1,967 cases) (Mantel-Haenszel P = 0.036, OR = 0.559 [95%CI 0.323-0.966]). Combining the three datasets produces a Mantel-Haenszel OR of 0.497 (P < 0.0002). The deletion variant lacks 129-kb of DNA containing SLC2A3, NANOGP1, and SLC2A14. SLC2A3 encodes a high-affinity glucose transporter important in the immune response and chondrocyte metabolism, both key aspects of RA pathogenesis. The large effect size of this association, its potential relevance to other diseases in which SLC2A3 is implicated, and the possibility of targeting drugs to inhibit SLC2A3, argue for further examination of the genetics and the biology of this CNV. PMID- 24178906 TI - Increased rate of lung function decline in Australian adolescents with cystic fibrosis. AB - INTRODUCTION: Though baseline lung function as measured by spirometry in children with cystic fibrosis (CF) has improved, the annual rate of decline has not changed significantly during the critical period of adolescence. The aim of this study was to describe factors associated with longitudinal decline in lung function in a contemporary cohort of children with CF. METHODS: Best annual lung function data from children attending the CF service of the Royal Children's Hospital Melbourne were reviewed to determine rate of decline in FEV(1) up until time of transfer to an adult center. Mixed models were used to determine the influence of age, sex, genotype, newborn screening, respiratory hospitalization, CF related diabetes mellitus (CFRD), pancreatic insufficiency, Pseudomonas aeruginosa (PsA) infection, and body mass index (BMI) on lung function decline. RESULTS: Longitudinal lung function data (range 5-20 years) were obtained for 98 patients with CF (55 male). Overall, the annual rate of decline in FEV(1) % predicted for the entire cohort was 1.4% per annum though the greatest rate of FEV1 decline was seen during adolescence (2.6%). Increasing age, homozygous DeltaF508 genotype, CFRD, mucoid PsA infection, pancreatic insufficiency and respiratory hospitalizations were all significant predictors of FEV1 decline. CONCLUSION: FEV(1) declines at its sharpest rate during adolescence even in the presence of newborn screening. Genotype, increasing age, CFRD, PsA infection, pancreatic insufficiency and a greater number of respiratory hospitalizations are all associated with an increased rate of lung function decline in Australian children and adolescents with cystic fibrosis. PMID- 24178907 TI - Long-term effect of high-intensity laser therapy in the treatment of patients with chronic low back pain: a randomized blinded placebo-controlled trial. AB - The aim of this study was to compare the effect of high-intensity laser therapy (HILT), alone or combined with exercise, in the treatment of chronic low back pain (CLBP). A total of 72 male patients participated in this study, with a mean (SD) age of 32.81 (4.48) years. Patients were randomly assigned into three groups and treated with HILT plus exercise (HILT + EX), placebo laser plus exercise (PL + EX), and HILT alone in groups 1, 2, and 3, respectively. The outcomes measured were lumbar range of motion (ROM), pain level by visual analog scale (VAS), and functional disability by both the Roland Disability Questionnaire (RDQ) and the Modified Oswestry Disability Questionnaire (MODQ). Statistical analyses were performed to compare the differences between baseline and post-treatment measurements. The level of statistical significance was set as P < 0.05. ROM significantly increased after 4 weeks of treatment in all groups, then significantly decreased after 12 weeks of follow-up, but was still significantly more than the baseline value in groups 1 and 2. VAS, RDQ, and MODQ results showed significant decrease post-treatment in all groups, although the RDQ and MODQ results were not significantly different between groups 2 and 3. HILT combined with exercise appears to be more effective in patients with CLBP than either HLLT alone or placebo laser with exercise. PMID- 24178908 TI - Photodynamic antimicrobial chemotherapy (PACT) inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability. AB - The opportunistic fungal Candida albicans is able to produce both superficial and systemic infections in immunocompromised patients. Photodynamic antimicrobial chemotherapy (PACT) is a process that combines visible light and a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells and has been presented as a potential antimicrobial therapy. In this work, we study the effects of PACT, using toluidine blue (TB) as a photosensitizer drug, on ROS production and cell damage and the ability of C. albicans to form biofilm. A significant decrease was observed in the cell growth after PACT in a TB concentration-dependent manner. This effect was dependent on the incubation time after PACT. In addition, an increase in both the ROS production and cell permeability, after PACT, in a TB concentration-dependent manner was observed. PACT, using 0.1 mg/ml TB was able to reduce biofilm formation in 30, 50, and 62%, in cells submitted to incubation times of 1, 2, and 3 h, respectively. These results suggested that PACT, using TB, is able to decrease both growth and biofilm formation by C. albicans, possibly by a mechanism evolving both ROS production and the increase in the cell permeability. PMID- 24178909 TI - Regulation of onco and tumor suppressor MiRNAs by mTORC1 inhibitor PRP-1 in human chondrosarcoma. AB - Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. This study aimed to reveal the comparative analysis of miRNAs and their targets in human JJ012 chondrosarcoma cell line between control and experimental samples, treated with mTORC1 inhibitor, cytostatic antiproliferative proline-rich polypeptide (PRP-1). Examination of tumor-specific microRNA expression profiles has revealed widespread deregulation of these molecules in diverse cancers. It was reported that microRNAs can function as novel biomarkers for disease diagnostics and therapy, as well as a novel class of oncogenes and tumor suppressor genes. mTORC 1 inhibitor PRP-1 caused significant upregulation of tumor suppressors, such as miR20a, miR125b, and miR192; and downregulation of onco miRNAs, miR509-3p, miR589, miR490-3p, miR 550 in human chondrosarcoma JJ012 cell line. PMID- 24178910 TI - Genetic polymorphism of DNA methyltransferase 3B 149 C>T and risk of colorectal cancer: a meta-analysis. AB - Numerous studies have investigated the risk of colorectal cancer (CRC) associated with the polymorphism of DNA methyltransferase 3B (DNMT3B) 149 C>T, but results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of the association between this polymorphism and risk of CRC. A comprehensive search was conducted to identify all case-control studies of the 149C>T polymorphism of DNMT3B and CRC risk. A total of seven eligible studies, including 2,666 cases and 4,022 controls, relating the DNMT3B polymorphism of 149C>T to the risk of CRC were identified. It suggested no significant associations between -149C>T polymorphism of DNMT3B gene and the risk of developing CRC in the recessive, dominant, and co-dominant models (for CC versus TT: OR = 0.90, 95% CI = 0.90-1.25, P heterogeneity = 0.37; for recessive model: OR = 0.54, 95% CI = 0.28-1.04, P heterogeneity = 0.00001; for dominant model: OR = 1.07, 95% CI = 0.93-1.23, P heterogeneity = 0.83; and for C allele versus T allele: OR = 0.70, 95% CI = 0.43-1.13, P heterogeneity = 0.00001). In the subgroup analysis, there is no significant associations were also found in European populations (for CC versus TT: OR = 1.09, 95% CI = 0.92-1.30, P heterogeneity = 0.88; for recessive model: OR = 1.00, 95% CI = 0.88-1.13, P heterogeneity = 0.14; for dominant model: OR = 1.50, 95% CI = 0.89-2.54, P heterogeneity = 0.00001; and for C allele versus T allele: OR = 0.70, 95% CI = 0.38-1.28, P heterogeneity = 0.00001). In conclusion, no significant association was found between the -149C>T polymorphisms in DNMT3B and CRC susceptibility. PMID- 24178911 TI - Ocular vestibular evoked myogenic potentials in response to three test positions and two frequencies. AB - OBJECTIVES/HYPOTHESIS: To determine how eye closure, test positions, and stimulus frequencies influence ocular vestibular evoked myogenic potentials. STUDY DESIGN: This study used a within-subjects repeated measures design. METHODS: Twenty asymptomatic subjects were each tested on ocular vestibular evoked myogenic potentials in three head/eye conditions at 500 Hz and 1,000 Hz using air conducted sound: 1) sitting upright, head erect, eyes open, looking up; 2) lying supine, neck flexed 30 degrees , eyes open, looking up; and 3) lying supine, neck flexed 30 degrees , eyes closed, relaxed. The four dependent variables measured were n10, p16, amplitude, and threshold. RESULTS: Supine/eyes open was comparable to sitting/eyes open and better than supine/eyes closed. Eyes closed resulted in lower amplitude, higher threshold, and prolonged latency. Significantly fewer subjects provided responses with eyes closed than with eyes open. No significant differences were found between both eyes open conditions. Both n10 and p16 were lower at 1,000 Hz than at 500 Hz. Amplitude and threshold were higher at 1,000 Hz than at 500 Hz. CONCLUSIONS: Supine/eyes open is a reliable alternative to sitting/eyes open in patients who cannot maintain a seated position. Testing at 1,000 Hz provides a larger response with a faster onset that fatigues faster than at 500 Hz. The increased variability and decreased response in the eyes closed position suggest that the eyes closed position is not reliable. LEVEL OF EVIDENCE: 3b. PMID- 24178912 TI - Distinct patterns of genetic variations in potential functional elements in long noncoding RNAs. AB - Non-protein-coding RNAs have increasingly been shown to be an important class of regulatory RNAs having significant roles in regulation of gene expression. The long noncoding RNA (lncRNA) gene family presently constitutes a large number of noncoding RNA (ncRNA) loci almost equaling the number of protein-coding genes. Nevertheless, the biological roles and mechanisms of the majority of lncRNAs are poorly understood, with exceptions of a very few well-studied candidates. The availability of genome-scale variation datasets, and increasing number of variant loci from genome-wide association studies falling in lncRNA loci have motivated us to understand the patterns of genomic variations in lncRNA loci, their potential functional correlates, and selection in populations. In the present study, we have performed a comprehensive analysis of genomic variations in lncRNA loci. We analyzed for patterns and distributions of genomic variations with respect to potential functional domains in lncRNAs. The analysis reveals a distinct distribution of variations in subclasses of long ncRNAs and in potential functional domains of lncRNAs. We further examined signals of selections and allele frequencies of these prioritized set of lncRNAs. To the best of our knowledge, this is the first and comprehensive large-scale analysis of genetic variations in long ncRNAs. PMID- 24178913 TI - Spectrum of transient visual symptoms in a transient ischemic attack cohort. AB - BACKGROUND AND PURPOSE: Transient visual symptoms (TVS) are common complaints. They can be related to transient ischemic attacks, but the nature of the symptoms often remains uncertain, and data on prognosis are scarce. We studied the prevalence, presentation, and effect of different types of TVS, paying particular attention to the association with high-risk pathology of embolism. METHODS: A total of 2398 patients with suspected transient ischemic attack admitted to the SOS-TIA clinic between January 2003 and December 2008 underwent immediate evaluation and treatment. RESULTS: Eight hundred twenty-six (34.5%) patients had TVS, including 422 (17.6%) patients with isolated TVS. Transient monocular blindness was the most frequent TVS (36.3%), followed by diplopia (13.4%), homonymous lateral hemianopia (12.3%), bilateral positive visual phenomena (10.8%), and lone bilateral blindness (4.5%). Positive diffusion-weighted imaging was found in 11.8%, 8.1%, 8.1%, and 5.0% of patients with homonymous lateral hemianopia, diplopia, lone bilateral blindness, and transient monocular blindness, respectively. Among 1850 patients (595 patients with TVS) with definite/possible transient ischemic attack or minor stroke, a major source of embolism of cardiac or arterial origin was found less frequently in patients with isolated or nonisolated TVS than in patients without TVS (19.6%; 19.7% versus 28.1%, respectively; P<0.001). However, we found a higher rate of atrial fibrillation in patients with homonymous lateral hemianopia (23.2%) than in patients with other TVS (4.0%; adjusted odds ratio, 6.71; 95% confidence interval, 2.99-15.06) or nonvisual symptoms (9.1%; adjusted odds ratio, 4.39; 95% confidence interval, 2.26-8.50). CONCLUSIONS: Approximately 20% of patients with TVS had a major source of embolism detected, requiring urgent management. Atrial fibrillation was particularly frequent in patients with transient homonymous lateral hemianopia. PMID- 24178914 TI - Interrelationship among common medical complications after acute stroke: pneumonia plays an important role. AB - BACKGROUND AND PURPOSE: Medical complications are common among patients with stroke. However, little is known about the potential interrelationship among them. In the present study, we aimed to investigate the association between common in-hospital medical complications after acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH). METHODS: We analyzed patients enrolled in the China National Stroke Registry from 2007 to 2008. The occurrence of 11 common stroke-associated medical complications during acute hospitalization was prospectively registered. Multivariable analysis using generalized estimation equation was performed to assess association between medical complications in AIS and ICH cohort, respectively. RESULTS: A total of 14 702 patients with AIS and 5221 patients with ICH were enrolled. The median age was 65 years (interquartile range, 55-74 years), and 38.1% were female. The median length of hospital stay was 14 days (interquartile range, 10-20 days) for AIS and 18 days (interquartile range, 11-26 days) for ICH. Pneumonia was the most common medical complication after AIS (11.4%) and ICH (16.8%). In the AIS cohort, after adjusting for potential confounders, pneumonia was significantly associated with development of gastrointestinal bleeding (adjusted odds ratio [OR], 8.35; 95% confidence interval [CI], 6.27-11.1; P<0.001), decubitus ulcer (adjusted OR, 5.31; 95% CI, 3.39-8.31; P<0.001), deep vein thrombosis (adjusted OR, 4.27; 95% CI, 2.41-7.59; P<0.001), epileptic seizure (adjusted OR, 3.96; 95% CI, 2.67-5.88; P<0.001), urinary tract infection (adjusted OR, 3.34; 95% CI, 2.73-4.10; P<0.001), atrial fibrillation/flutter (adjusted OR, 3.17; 95% CI, 2.58-3.90; P<0.001), and recurrent stroke (adjusted OR, 2.65; 95% CI, 2.07-3.40; P<0.001). Similar significant association between pneumonia and development of several nonpneumonia medical complications was verified in ICH cohort as well. CONCLUSIONS: Pneumonia is closely associated with the development of several nonpneumonia medical complications after AIS and ICH. PMID- 24178915 TI - Meta-analysis of the efficacy of different training strategies in animal models of ischemic stroke. AB - BACKGROUND AND PURPOSE: Although several studies have shown beneficial effects of training in animal stroke models, the most effective training strategy and the optimal time to initiate training have not been identified. The present meta analysis was performed to compare the efficacy of different training strategies and to determine the optimal time window for training in animal stroke models. METHODS: We searched the literature for studies analyzing the efficacy of training in animal models of ischemic stroke. Training was categorized into forced physical training, voluntary physical training, constraint-induced movement therapy, and skilled reaching training. Two reviewers independently extracted data on study quality, infarct size, and neurological outcome. Data were pooled by means of a meta-analysis. RESULTS: Thirty-five studies with >880 animals were included. A meta-analysis of all treatments showed that training reduced the infarct volume by 14% (95% confidence interval, 2%-25%) and improved the cognitive function by 33% (95% confidence interval, 8%-50%), the neuroscore by 13.4% (95% confidence interval, 1.5%-25.3%), and the running function by 6.6% (95% confidence interval, 1.4%-11.9%). Forced physical training reduced the infarct volume and enhanced the running function most effectively, whereas skilled reaching training improved the limb function most effectively. A meta regression illustrated that training was particularly efficacious when initiated between 1 and 5 days after stroke onset. CONCLUSIONS: Our meta-analysis confirms that training reduces the infarct volume and improves the functional recovery in animal stroke models. Forced physical training and skilled reaching training were identified as particularly effective training strategies. The efficacy of training is time dependent. PMID- 24178916 TI - Bilateral priming accelerates recovery of upper limb function after stroke: a randomized controlled trial. AB - BACKGROUND AND PURPOSE: The ability to live independently after stroke depends on the recovery of upper limb function. We hypothesized that bilateral priming with active-passive movements before upper limb physiotherapy would promote rebalancing of corticomotor excitability and would accelerate upper limb recovery at the subacute stage. METHODS: A single-center randomized controlled trial of bilateral priming was conducted with 57 patients randomized at the subacute stage after first-ever ischemic stroke. The PRIMED group made device-assisted mirror symmetrical bimanual movements before upper limb physiotherapy, every weekday for 4 weeks. The CONTROL group was given intermittent cutaneous electric stimulation of the paretic forearm before physiotherapy. Assessments were made at baseline, 6, 12, and 26 weeks. The primary end point was the proportion of patients who reached their plateau for upper limb function at 12 weeks, measured with the Action Research Arm Test. RESULTS: Odds ratios indicated that PRIMED participants were 3* more likely than controls to reach their recovery plateau by 12 weeks. Intention-to-treat and per-protocol analyses showed a greater proportion of PRIMED participants achieved their plateau by 12 weeks (intention to treat, chi2=4.25; P=0.039 and per protocol, chi2=3.99; P=0.046). ANOVA of per-protocol data showed PRIMED participants had greater rebalancing of corticomotor excitability than controls at 12 and 26 weeks and interhemispheric inhibition at 26 weeks (all P<0.05). CONCLUSIONS: Bilateral priming accelerated recovery of upper limb function in the initial weeks after stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ANZCTR1260900046822. PMID- 24178917 TI - Cerebral microbleeds as a predictor of 1-year outcome of poststroke depression. AB - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are common in stroke survivors and community-dwelling elderly. The clinical significance of CMBs in the outcome of poststroke depression (PSD) is unknown. This study examined the association between the 1-year outcome of PSD and CMBs. METHODS: The study population comprised 774 Chinese patients with acute ischemic stroke who were admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong. Three and 15 months after the onset of the index stroke, a research assistant administered the locally validated 15-item Geriatric Depression Scale. PSD was defined as a Geriatric Depression Scale score of >=7. Of the 213 patients with PSD at the 3-month follow-up, 135 (63.4%) attended the 15-month follow-up, at which time 89 (65.9%) patients remained depressed (nonremitters), and 46 (34.1%) had recovered (remitters). The presence and location of CMBs were evaluated with magnetic resonance imaging. RESULTS: In comparison with the remitters, nonremitters were more likely to have lobar CMBs (18.4% versus 4.3%; P=0.024). Lobar CMBs remained an independent predictor of PSD in the multivariate analysis, with an odds ratio of 4.96 (P=0.039). CONCLUSIONS: The results suggest that lobar CMBs may influence the outcome of PSD. The importance of CMBs in the clinical course of depression in stroke survivors warrants further investigation. PMID- 24178918 TI - Evolution of computed tomography angiography spot sign is consistent with a site of active hemorrhage in acute intracerebral hemorrhage. AB - BACKGROUND AND PURPOSE: CT angiography spot sign predicts hematoma expansion in patients with acute intracerebral hemorrhage (ICH). The spot sign may represent a site of active extravasation, a locus of arrested hemorrhage forming fibrin globes, or represent associated epiphenomena such as hypertensive microaneurysms. We sought to describe the evolution of spot signs over 60 seconds in acute ICH using dynamic CT angiography and determine whether they grow and diffuse into the hematoma as would be expected with active extravasation. METHODS: We prospectively identified consecutive patients presenting with spontaneous ICH<6 hours from symptom onset that completed dynamic CT angiography imaging over a 60 second acquisition protocol. We determined spot positivity, quantified spot volumes, and then used repeated-measures ANOVA to assess changes in spot volume over time. RESULTS: We collected data on 35 patients; 13 of 35 (37%) patients were spot-positive. Spot-positive patients had larger median ICH volume compared with spot-negative patients (median 10.7 versus 49.2 mL; P=0.007). Maximal spot sign volumes ranged from 0.02 to 2.8 mL (median 0.17 mL). Spot sign volumes increased significantly with time (P<0.001) and seemed to disperse into the hematoma in all cases. Three of 13 (23%) spot-positive patients presented with 2 distinct spot signs, but the remaining patients either had only 1 spot sign or different contiguous components of an irregularly shaped spot sign. CONCLUSIONS: In this dynamic CT angiography study of ICH, spot signs evolve consistent with sites of active extravasation. PMID- 24178919 TI - Acquisition bias may have led to acceptance of the false null hypothesis that prevalence of scoliosis is the same in cystic fibrosis as the general population. PMID- 24178920 TI - beta-Shaped intracorporeal Roux-en-Y reconstruction after totally laparoscopic distal gastrectomy. AB - BACKGROUND: The use of laparoscopic gastrectomy for the treatment of gastric cancer has been increasing. Roux-en-Y (R-Y) reconstruction after laparoscopy assisted distal gastrectomy is now widely used to decrease leakage and prevent reflux. Owing to the need for a less invasive technique, we have developed a new technique for intracorporeal R-Y reconstruction (beta reconstruction) after totally laparoscopic distal gastrectomy (TLDG). METHODS: In this report, we describe the beta reconstruction technique and short-term outcomes of the initial 105 patients who underwent beta reconstruction from December 2008 to March 2012. RESULTS: The operative and beta reconstruction times were 330 +/- 61.3 and 29 +/- 5.6 min (mean +/- SD), respectively. Anastomotic leakage after gastrojejunostomy occurred in one patient (0.9 %), requiring reoperation. Four cases (3.8 %) of anastomotic stenosis required endoscopic balloon dilation. However, R-Y stasis was not noted. CONCLUSIONS: We have indicated a technical description as well as the usefulness of beta-shaped intracorporeal R-Y reconstruction after TLDG. PMID- 24178921 TI - Reconviction rates after suspended sentences: comparison of the effects of different types of suspended sentences on reconviction in the Netherlands. AB - Previous research has focused mainly on determining the effectiveness of suspended sentences compared with other sentences, and seldom on understanding to what extent the different types of suspended sentences reduce recidivism rates. This study examined reconviction rates of offenders (N = 1,258) who received fully or partly suspended prison sentences, with or without special conditions, in 2006 in two of the largest court districts in the Netherlands. Cox proportional hazard models revealed no difference in reconviction rates between fully and partly suspended prison sentences, with and without special conditions. However, suspended sentences without special conditions had significantly lower reconviction rates compared with special conditions that were solely control orientated. Although there are indications that certain types of suspended sentences reduced reconviction rates more than other types, more rigorous research is still required. PMID- 24178922 TI - Neutron-encoded protein quantification by peptide carbamylation. AB - We describe a chemical tag for duplex proteome quantification using neutron encoding (NeuCode). The method utilizes the straightforward, efficient, and inexpensive carbamylation reaction. We demonstrate the utility of NeuCode carbamylation by accurately measuring quantitative ratios from tagged yeast lysates mixed in known ratios and by applying this method to quantify differential protein expression in mice fed a either control or high-fat diet. PMID- 24178924 TI - Effect of prebiotic konjac mannanoligosaccharide on growth performances, intestinal microflora, and digestive enzyme activities in yellow catfish, Pelteobagrus fulvidraco. AB - In the present study, konjac mannanoligosaccharide (KMOS) was evaluated as a prebiotic in yellow catfish. The fish were fed with diets containing KMOS in four concentrations: 0 g kg(-1) (C), 1.0 g kg(-1) (KM1), 2.0 g kg(-1) (KM2), and 3.0 g kg(-1) (KM3) for 49 days, respectively. Another group fed with diets containing 3.0 g kg(-1) yeast cell wall mannanoligosaccharide (MOS) (M3) was set as positive control. The results indicated that fish receiving the diets supplemented with KMOS or MOS showed higher relative gain rate (RGR), specific growth rate (SGR), and lower feed conversion ratio (FCR) with significantly differences (P < 0.05) than those fed with the basal diets. Moreover, fish receiving the diets with 2.0 g kg(-1) KMOS inclusion showed higher RGR, SGR, and lower FCR (P < 0.05) than that feeding the diets supplemented with 3.0 g kg(-1) MOS. The quantities of Bifidobacterium spp. were significantly increased (P < 0.05). Meanwhile, Escherichia coli and Aeromonas spp. were significantly reduced (P < 0.05) in the fish-feeding diets with 2.0 g kg(-1) KMOS supplement. Compared with the control group, the significantly enhancement of protease and amylase activity (P < 0.05) in intestine and pancreas was observed in fish fed with diets containing KMOS or MOS. Collectively, an optimum level of KMOS inclusion in diets could modulate intestinal microflora, induce digestive enzyme activity, and improve the growth performance of yellow catfish significantly. PMID- 24178923 TI - The effects of dietary thiamin on oxidative damage and antioxidant defence of juvenile fish. AB - The present study explored the effects of thiamin on antioxidant capacity of juvenile Jian carp (Cyprinus carpio var. Jian). In a 60-day feeding trial, a total of 1,050 juvenile Jian carp (8.20 +/- 0.02 g) were fed graded levels of thiamin at 0.25, 0.48, 0.79, 1.06, 1.37, 1.63 and 2.65 mg thiamin kg(-1) diets. The results showed that malondialdehyde and protein carbonyl contents in serum, hepatopancreas, intestine and muscle were significantly decreased with increasing dietary thiamin levels (P < 0.05). Conversely, the anti-superoxide anion capacity and anti-hydroxyl radical capacity in serum, hepatopancreas, intestine and muscle were the lowest in fish fed the thiamin-unsupplemented diet. Meanwhile, the activities of catalase (CAT), glutathione peroxidase, glutathione S-transferase and glutathione reductase, and the contents of glutathione in serum, hepatopancreas, intestine and muscle were enhanced with increasing dietary thiamin levels (P < 0.05). Superoxide dismutase (SOD) activity in serum, hepatopancreas and intestine followed a similar trend as CAT (P < 0.05). However, SOD activity in muscle was not affected by dietary thiamin level (P > 0.05). The results indicated that thiamin could improve antioxidant defence and inhibit lipid peroxidation and protein oxidation of juvenile Jian carp. PMID- 24178925 TI - Differential DNA methylation between two wing phenotypes adults of Sogatella furcifera. AB - Sogatella furcifera is a major rice pest with wing dimorphism. DNA methylation is an important epigenetic modification that plays a role in gene regulation and phenotype variation in most organisms. The objective of the current research was to survey the frequencies and variation of cytosine methylation at CCGG sequences in macropterous female adults (MFA) and brachypterous female adults (BFA) of S. furcifera, and to determine the occurrence of methylation changes associated with wing phenotypes by using methylation-sensitive amplification polymorphism (MSAP). No differences were found in the average proportions of methylated CCGG sites between MFA and BFA, but there were significant differences for methylation patterns between MFA and BFA. The fully methylated ratio was 5.81% in BFA, much higher than 2.40% in MFA; while the hemi-methylated ratio was 4.35% in BFA, much lower than 8.35% in MFA. These results provide circumstantial evidence that DNA methylation might be related to wing phenotype variation in S. furcifera. We also cloned and got 14 satisfactory sequences, which displayed variable cytosine methylation patterns between MFA and BFA. All these data will facilitate the researches on the epigenetic mechanisms of insect wing polymorphism. PMID- 24178926 TI - Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles. AB - Although mitochondrial dysfunction is implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are not well established. We performed mitochondrial quantitative proteomic and whole transcriptome analysis followed by functional annotations within liver and skeletal muscles, using fasted and non-fasted 16- and 48-week-old high-fat diet (HFD)-fed and normal diet-fed (control group) wild-type C56BL/6J mice, and hyperphagic ob/ob and db/db obese mice. Our study identified 1,675 and 704 mitochondria-associated proteins with at least two peptides in liver and muscle, respectively. Of these, 221 liver and 44 muscle proteins were differentially expressed (adjusted p values <= 0.05) between control and all obese mice, while overnight fasting altered expression of 107 liver and 35 muscle proteins. In the liver, we distinguished a network of 27 proteins exhibiting opposite direction of expression changes in HFD-fed and hyperphagic mice when compared to control. The network centered on cytochromes P450 3a11 (Cyp3a11) and 4a14 (Cyp4a14), and fructose-bisphosphate aldolase B (Aldob) proteins which bridged proteins cluster involved in Metabolism of xenobiotics with proteins engaged in Fatty acid metabolism and PPAR signaling pathways. Functional annotations revealed that most of the hepatic molecular alterations, which characterized both obesity and fasting, related to different aspects of energy metabolism (such as Fatty acid metabolism, Peroxisome, and PPAR signaling); however, only a limited number of functional annotations could be selected from skeletal muscle data sets. Thus, our comprehensive molecular overview revealed that both obesity and fasting states induce more pronounced mitochondrial proteome changes in the liver than in the muscles. PMID- 24178927 TI - The utility of endoscopy and multichannel intraluminal impedance testing in children with cough and wheezing. AB - BACKGROUND: Gastroesophageal reflux (GER) has been implicated as a causal factor in respiratory disease but prior studies have focused on the role of acid alone in the genesis of symptoms. Prior studies have relied on pH probe testing but this is blind to non-acid reflux which has been implicated in the genesis of extraesophageal symptoms. The objective of this prospective, cross-sectional study is to determine the utility of gastroesophageal reflux testing, including multichannel intraluminal impedance with pH (pH-MII) and upper gastrointestinal endoscopy (EGD), in the child with intractable cough and wheezing. We hypothesize that there is a high rate of pathologic reflux testing in these patients. METHODS: Children ages 1-18 with chronic cough and wheezing who were undergoing bronchoscopy for the evaluation of cough and wheezing were recruited into this prospective, cross-sectional study. They underwent identical reflux testing with pH-MII and EGD at the time of bronchoscopy. Reflux burden, symptom association, and rates of esophageal pathology were determined. Results 58% of patients had abnormal reflux testing; 67% of patients had an abnormal pH-MII test and 32% of patients had abnormal esophageal biopsies. The most common pH-MII abnormality was an abnormal symptom association between cough and reflux and the most common endoscopic abnormality was reflux esophagitis. Seven percent of patients presenting only with cough were diagnosed with eosinophilic esophagitis. CONCLUSIONS: There is a high yield to reflux testing in children with chronic cough and wheezing. PMID- 24178928 TI - The ABCD of GOLD made clear. PMID- 24178929 TI - "The ABC of GOLD A-B-C-D". PMID- 24178930 TI - Learn from the past and create the future: the 2013 ATS/ERS statement on pulmonary rehabilitation. PMID- 24178931 TI - Last call for the flight simulation test? PMID- 24178932 TI - Follow-up after lung cancer resection: is intensified also justified? PMID- 24178933 TI - Lung adenocarcinoma expression profile: one more layer of heterogeneity. PMID- 24178934 TI - Pulmonologists and lung cancer: pivotal role in multidisciplinary approach. PMID- 24178935 TI - Use of household cleaning products, exhaled nitric oxide and lung function in children. PMID- 24178936 TI - Concurrent coxibs and anti-platelet therapy unmasks aspirin-exacerbated respiratory disease. PMID- 24178937 TI - The term "asthma" should be avoided in describing the chronic pulmonary disease of prematurity. PMID- 24178938 TI - From the authors. PMID- 24178942 TI - 50 years of inordinate fondness. PMID- 24178943 TI - C. elegans nuclear receptor NHR-6 functionally interacts with the jun-1 transcription factor during spermatheca development. AB - The NR4A nuclear receptor NHR-6 is an essential regulator of spermatheca organogenesis in C. elegans. In this study, we perform a focused, RNAi-based screen to identify modifiers of partial nhr-6 loss of function. Ninety-eight genes that encode signaling proteins expressed in the spermatheca were screened for enhancement of the nhr-6 RNAi phenotype. We identify the C. elegans gene jun 1, which encodes the homolog of the Jun transcription factor, as a strong enhancer of nhr-6 partial loss of function. We show that nhr-6 and jun-1 function together to regulate development of the spermatheca and are necessary for generating an organ with the normal number of cells. jun-1 is expressed in all cells of the developing spermatheca. We also provide evidence that NHR-6 and JUN 1 can physically interact in a yeast two-hybrid assay. Our results provide in vivo evidence that NR4A nuclear receptor and Jun transcription factor interactions are essential in regulating developmental processes in metazoans. PMID- 24178944 TI - Complex N-glycans: the story of the "yellow brick road". AB - The synthesis of complex asparagine-linked glycans (N-glycans) involves a multi step process that starts with a five mannose N-glycan structure: [Manalpha1 6(Manalpha1-3)Manalpha1-6][Manalpha1-3]-R where R = Manbeta1-4GlcNAcbeta1 4GlcNAcbeta1-Asn-protein. N-acetylglucosaminyltransferase I (GlcNAc-TI) first catalyzes addition of GlcNAc in beta1-2 linkage to the Manalpha1-3-R terminus of the five-mannose structure. Mannosidase II then removes two Man residues exposing the Manalpha1-6 terminus that serves as a substrate for GlcNAc-T II and addition of a second GlcNAcbeta1-2 residue. The resulting structure is the complex N glycan: GlcNAcbeta1-2Manalpha1-6(GlcNAcbeta1-2Manalpha1-3)-R. This structure is the precursor to a large assortment of branched complex N-glycans involving four more N-acetylglucosaminyltransferases. This short review describes the experiments (done in the early 1970s) that led to the discovery of GlcNAc-TI and II. PMID- 24178945 TI - Extralevator abdominoperineal excision of the rectum in patients with previous prostatectomy. PMID- 24178946 TI - Clostridium difficile: epidemiology, diagnostic and therapeutic possibilities-a systematic review. AB - This literature review looks at the epidemiology, clinical manifestations, diagnostics and current medical and surgical management of Clostridium difficile (C. difficile) infection. A literature search of PubMed and Cochrane database regarding C. difficile infection was performed. Information was extracted from 43 published articles from 2000 to the present day which met inclusion criteria. C. difficile is a gram-positive, anaerobic bacillus, which is widely found in the environment, especially in the soil. The occurrence of more resistant strains, which is mainly connected with the wide use of antibiotics, resulted in the rapid spread of the bacteria to different hospital departments. Particularly, elderly patients in surgical wards and intensive care units are at significant risk of developing C. difficile infection, which greatly increases morbidity and mortality. Symptoms of infection with C. difficile vary greatly. At one end of the spectrum, there are asymptomatic carriers, at the other patients with life threatening toxic megacolon. Metronidazole is considered to be the drug of choice, but recent guidelines recommend Vancomycin. Fulminant colitis and toxic megacolon warrant surgical intervention. The optimal time for surgery is within 48 h of initiating conservative treatment without seeing a response, the development of multiple organ failure or a bowel perforation. A factor that has become increasingly important and relevant is the escalating expense of treatment for patients with C. difficile infection. It is, therefore, highly recommended to consider reviewing all hospital antibiotic policies and clinical guidelines that may contribute to the prevention of the infection. PMID- 24178947 TI - Comments on Levic et al.: The outcome of rectal cancer after early salvage TME following TEM compared with primary TME: a case-matched study. PMID- 24178948 TI - Rectal ischaemia after stapled hemorrhoidopexy causing pain or bleeding: report of three cases. PMID- 24178949 TI - Heterogenous malignant presacral teratoma with a locally destructive benign intrasacral component. PMID- 24178950 TI - Update on common anorectal diseases. PMID- 24178951 TI - Inflammatory Pseudotumor Containing Kayexalate Crystals: A Case Report and Review of the Literature. AB - Kayexalate (sodium polystyrene sulfonate), a cation exchange resin often used to treat hyperkalemia, is known to produce gastrointestinal complications in a minority of patients. These complications range from mild gastrointestinal bleeding to perforation with acute abdomen. The typical histopathologic findings include mucosal ulceration, necrosis, and the presence of polygonal basophilic refractile crystals with a "fish scale" appearance. We present a unique case of Kayexalate crystals embedded in a perihepatic inflammatory pseudotumor, developing adjacent to a colostomy site in a 62-year-old woman following Kayexalate treatment. Microscopically, the lesion demonstrated a myofibroblastic proliferation rich in histiocytes and inflammation (lymphocytes, plasma cells, and eosinophils) as well as the presence of scattered typical Kayexalate crystals. This is the first report of extraintestinal Kayexalate identification in association with an inflammatory pseudotumor. PMID- 24178952 TI - Small bowel obstruction caused by a large B-cell lymphoma in a patient with multicentric Castleman's disease: An unusual occurrence. AB - Multicentric Castleman's disease is a rare condition of systemic nonclonal lymph node hyperplasia. Because of its strong association with human herpes virus 8 (HHV8), the multicentric, more aggressive, form may progress to Kaposi sarcoma or non-Hodgkin lymphoma. While surgery is curative in the treatment of localized Castleman's disease, operative treatment of the diffuse form has as yet been unsatisfactory. We report the case of a patient presenting with postprandial vomiting of 1 month duration consistent with partial small bowel obstruction secondary to terminal ileum intussusception. Resection of the small bowel showed a stenosing tumor triggering the intussusception. On pathological examination, the tumor was found to be composed of HHV8-positive plasmablastic lymphoma cells. To our knowledge, this represents the first case of a complication due to the progression of multicentric Castleman's disease requiring surgical intervention for intussusception. PMID- 24178953 TI - Analysis of serum insulin growth factor-1 concentrations in localized osteosarcoma: a children's oncology group study. AB - To investigate the role of insulin-like growth factor-1 (IGF-1), in localized osteosarcoma, serum levels of IGF-1, IGFBP-2, and IGFBP-3 were measured in 224 similarly treated, newly diagnosed patients. We demonstrated that younger patients had lower concentrations of IGF-1 and IGFBP-3 compared to older (P < 0.001) along with lower IGFBP-3:IGF-1 and IGFBP-2:IGF-1 ratios (P < 0.001). IGFBP 2 did not correlate with age (P = 0.16), yet IGFBP-2:IGF-1 ratios were higher in the younger population (P < 0.001). These findings show that older patients have higher concentrations of free IGF-1. None of IGF-1, IGFBP-2, nor IGFBP-3 concentrations were associated with event-free nor overall survival. PMID- 24178955 TI - Carrier-linked mutual prodrugs of biphenylacetic acid as a promising alternative to bioprecursor fenbufen: design, kinetics, and pharmacological studies. AB - Novel mutual prodrugs of biphenylacetic acid were designed as a promising gastro protective alternative to fenbufen. Biphenyacetic acid was covalently linked with two non-essential amino acids (D-phenylalanine and glycine) possessing wound healing, analgesic, and anti-inflammatory properties. The prodrugs exhibited good stability in stomach homogenates while hydrolytic release of biphenylacetic acid was observed in phosphate buffer, small intestinal homogenates, and 80% human plasma. In vivo behavior of prodrugs on oral administration to Wistar rats demonstrated 33-45% release of biphenylacetic acid in blood over a period of 24 h indicating passage of intact prodrugs to colon, colonic release of parent drug followed by its absorption through colonic mucosa into systemic circulation. Prodrugs were extensively evaluated for analgesic, anti-inflammatory, anti arthritic, and ulcerogenic activities. Biochemical, haemetological, histopathological, and radiological studies were also performed. Conversion of bioprecusor fenbufen into mutual carrier-linked prodrugs proved to be promising alternative in terms of reduced ulcerogenic propensity, longer duration of analgesia, enhanced/prolonged anti-inflammatory activity, and superior anti arthritic effect. These prodrugs could be developed further for chronotherapy of rheumatoid arthritis. PMID- 24178954 TI - Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. AB - Persistent pain affects nearly half of all people seeking medical care in the US alone, and accounts for at least $80 billion worth of lost productivity each year. Among all types of chronic pain, neuropathic pain stands out: this is pain resulting from damage or disease of the somatosensory nervous system, and remains largely untreatable. With few available treatment options, neuropathic pain represents an area of significant and growing unmet medical need. Current treatment of peripheral neuropathic pain involves several drug classes, including opioids, gabapentinoids, antidepressants, antiepileptic drugs, local anesthetics and capsaicin. Even so, less than half of patients achieve partial relief. This review discusses a novel approach to neuropathic pain management, based on knowledge of: the role of glia and mast cells in pain and neuroinflammation; the body's innate mechanisms to maintain cellular homeostasis when faced with external stressors provoking, for example, inflammation. The discovery that palmitoylethanolamide, a member of the N-acylethanolamine family which is produced from the lipid bilayer on-demand, is capable of exerting anti-allodynic and anti-hyperalgesic effects by down-modulating both microglial and mast cell activity has led to the application of this fatty acid amide in several clinical studies of neuropathic pain, with beneficial outcome and no indication of adverse effects at pharmacological doses. Collectively, the findings presented here propose that palmitoylethanolamide merits further consideration as a disease modifying agent for controlling inflammatory responses and related chronic and neuropathic pain. PMID- 24178956 TI - Comment on: Clinical significance of IgG deposition in the glomerular mesangial area in patients with IgA nephropathy. PMID- 24178957 TI - Increased urinary angiotensinogen is an effective marker of chronic renal impairment in very low birth weight children. AB - BACKGROUND: Recent advancements in perinatal and neonatal care have increased the survival of preterm infants with lower birth weight and very low birth weight (VLBW; < 1,500 g) infants. Such infants are exposed to a higher risk of renal insufficiency in later life due to congenitally fewer nephrons; however, urinalysis in order to detect renal insufficiency in those infants at school age has not yet been established. The aim of the study was to assess chronic renal impairment in VLBW infants during their childhood after discharge from the neonatal intensive care unit (NICU) until adolescence using urinary angiotensinogen (uAGT). METHODS: We compared serum levels of angiotensinogen (sAGT), creatinine, beta2-microglobulin (sbeta2MG) and cystatin C (sCysC), and urinary levels of uAGT, creatinine (uCre),beta2-microglobulin (ubeta2MG) and albumin between two infant groups-the VLBW group (50 children who were admitted to our NICU as infants), and a control group of 25 children who were born as full term infants with birth weight >=2,500 g. The median age of the VLBW group and control group infants was 60 months (range 7-135) and 57 months (range 5-144), respectively, at the time of evaluation. RESULTS: In the VLBW group, sCysC levels were high (p < 0.05) and estimated glomerular filtration rate (eGFR) was low (p < 0.05). There were no significant differences in the ratios of ubeta2MG to creatinine and urinary albumin to creatinine between the two groups. Although there were no differences in concentration of sAGT between the two groups (p = 0.062), the ratio of uAGT to creatinine was significantly higher in the VLBW group (p < 0.01). The examination of 19 VLBW infants (19/50) with eGFR <=90 ml/min/1.73 m(2) showed a positive correlation between uAGT/creatinine and urinary albumin/creatinine (r = 0.531, p < 0.05). Furthermore, the analysis of correlation between the ratio of uAGT to creatinine and eGFR showed a reverse correlation in 19 VLBW infants (19/50) with eGFR <=90 ml/min/1.73 m(2), 18 of whom had stage II chronic kidney disease and one who had stage III disease (r = 0.512, p <= 0.05). CONCLUSIONS: uAGT is an effective marker for predicting the progression of chronic renal impairment in preterm VLBW infants after their growth. uAGT measurement is easier to conduct, less invasive and more sensitive than conventional ubeta2MG or urinary albumin measurement. PMID- 24178958 TI - Ikaros: the enhancer makes the difference. PMID- 24178959 TI - Can CRd be a standard for refractory myeloma? PMID- 24178960 TI - Neutrophils: "neu players" in antibody therapy? PMID- 24178961 TI - Cutaneous EBV-associated lymphoma? PMID- 24178962 TI - Rac and Cdc42 team up for platelets. PMID- 24178963 TI - The EU's heath mandate after 20 years: the glass is half full. PMID- 24178964 TI - Glass half empty: the Eurozone and internal market overshadow the health effects of Maastricht. PMID- 24178965 TI - Endovascular procedures for the treatment of autonomic dysfunction. PMID- 24178967 TI - Eradication of non-Hodgkin lymphoma through the induction of tumor-specific T cell immunity by CD20-Flex BiFP. AB - Although monoclonal antibodies, including CD20 antibody rituximab, are standard therapeutics for several cancers, their efficacy remains variable and often modest. There is an urgent need to enhance the efficacy of the current generation of anticancer antibodies. Flt3 ligand, a soluble protein, has the ability to induce substantial expansion of dendritic cells (DCs). In this study, we constructed a bispecific immunoglobulin G-like bispecific fusion protein (BiFP) targeting both CD20 and Flt3 (CD20-Flex) by using CrossMab technology. We found that the BiFP exhibited stabilities that were comparable with the parental antibody rituximab and were able to bind to both targets with unaltered binding affinity. Notably, our data indicated that CD20-Flex BiFP could not only eliminate lymphoma temporarily but also potentiate tumor-specific T-cell immunity, which affords a long-lasting protection from tumor recurrence. The results showed that the expansion and infiltration of DCs into tumor tissues by CD20-Flex BiFP could be an effective way to generate protective immune responses against cancer, suggesting that the CD20-Flex BiFP could be a promising therapeutic agent against B-cell lymphomas. PMID- 24178966 TI - Fragment-based strategy for structural optimization in combination with 3D-QSAR. AB - Fragment-based drug design has emerged as an important methodology for lead discovery and drug design. Different with other studies focused on fragment library design and active fragment identification, a fragment-based strategy was developed in combination with three-dimensional quantitative structure-activity relationship (3D-QSAR) for structural optimization in this study. Based on a validated scaffold or fragment hit, a series of structural optimization was conducted to convert it to lead compounds, including 3D-QSAR modelling, active site analysis, fragment-based structural optimization and evaluation of new molecules. 3D-QSAR models and active site analysis provided sufficient information for confirming the SAR and pharmacophoric features for fragments. This strategy was evaluated through the structural optimization on a c-Met inhibitor scaffold 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one, which resulted in an c-Met inhibitor with high inhibitory activity. Our study suggested the effectiveness of this fragment-based strategy and the druggability of our newly explored active region. The reliability of this strategy indicated it could also be applied to facilitate lead optimization of other targets. PMID- 24178968 TI - Near-term prediction of sudden cardiac death in older hemodialysis patients using electronic health records. AB - BACKGROUND AND OBJECTIVES: Sudden cardiac death is the most common cause of death among individuals undergoing hemodialysis. The epidemiology of sudden cardiac death has been well studied, and efforts are shifting to risk assessment. This study aimed to test whether assessment of acute changes during hemodialysis that are captured in electronic health records improved risk assessment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were collected from all hemodialysis sessions of patients 66 years and older receiving hemodialysis from a large national dialysis provider between 2004 and 2008. The primary outcome of interest was sudden cardiac death the day of or day after a dialysis session. This study used data from 2004 to 2006 as the training set and data from 2007 to 2008 as the validation set. The machine learning algorithm, Random Forests, was used to derive the prediction model. RESULTS: In 22 million sessions, 898 people between 2004 and 2006 and 826 people between 2007 and 2008 died on the day of or day after a dialysis session that was serving as a training or test data session, respectively. A reasonably strong predictor was derived using just predialysis information (concordance statistic=0.782), which showed modest but significant improvement after inclusion of postdialysis information (concordance statistic=0.799, P<0.001). However, risk prediction decreased the farther out that it was forecasted (up to 1 year), and postdialytic information became less important. CONCLUSION: Subtle changes in the experience of hemodialysis aid in the assessment of sudden cardiac death and are captured by modern electronic health records. The collected data are better for the assessment of near-term risk as opposed to longer-term risk. PMID- 24178969 TI - Change in albuminuria and eGFR following insulin sensitization therapy versus insulin provision therapy in the BARI 2D study. AB - BACKGROUND AND OBJECTIVES: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial, glycemic control with insulin sensitization therapy was compared with insulin-provision therapy in patients with type 2 diabetes and coronary artery disease. This study examined differences in albumin excretion and renal function in the insulin-sensitization group versus the insulin-provision group over 5 years. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: In total, 1799 patients with measurements of creatinine and urine albumin/creatinine ratio at baseline and at least two follow-up visits were included. Management of BP, lipids, and lifestyle counseling was uniform. Progression of albuminuria was defined as doubling of baseline albumin/creatinine ratio to at least 100 mg/g or worsening of albumin/creatinine ratio status on two or more visits. Worsening renal function was defined as >25% decline in estimated GFR and annualized decline of >3 ml/min per 1.73 m(2) per year. RESULTS: By 6 months and thereafter, the mean glycated hemoglobin levels were lower in the insulin-sensitization group compared with the insulin-provision group (P<0.002 for each time point; absolute difference=0.4%). Albumin/creatinine ratio increased over time in the insulin-sensitization group (P value for trend<0.001) and was stable in the insulin-provision group. Risk for progression of albumin/creatinine ratio was higher in the insulin-sensitization group compared with the insulin-provision group (odds ratio, 1.59; 95% confidence interval, 1.25 to 2.02; P=0.02). Over 5 years, albumin/creatinine ratio increased from 11.5 (interquartile range=5.0-46.7) to 15.7 mg/g (interquartile range=6.2-55.4) in the insulin-sensitization group (P<0.001) and from 12.1 (interquartile range=5.3 41.3) to 12.4 mg/g (interquartile range=5.8-50.6) in the insulin-provision group (P=0.21). Estimated GFR declined from 75.0+/-20.6 to 66.3+/-22.6 ml/min per 1.73 m(2) in the insulin-sensitization group (P<0.001) and from 76.1+/-29.5 to 66.8+/ 22.1 ml/min per 1.73 m(2) in the insulin-provision group (P<0.001). CONCLUSION: Over 5 years, despite lower glycated hemoglobin levels, the insulin-sensitization treatment group had greater progression of albumin/creatinine ratio compared with the insulin-provision treatment group. Decline in estimated GFR was similar. PMID- 24178970 TI - Development and validation of a prediction rule using the Oxford classification in IgA nephropathy. AB - BACKGROUND AND OBJECTIVES: The risk assessment for developing ESRD remains limited in patients with IgA nephropathy (IgAN). The aim of this study was to develop and validate a prediction rule for estimating the individual risk of ESRD in patients with IgAN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 698 patients with IgAN diagnosed by renal biopsy at Kyushu University Hospital (derivation cohort) between 1982 and 2010 were retrospectively followed. The Oxford classification was used to evaluate the pathologic lesions. The risk factors for developing ESRD were evaluated using a Cox proportional hazard model with a stepwise backward elimination method. The prediction rule was verified using data from 702 patients diagnosed at Japanese Red Cross Fukuoka Hospital (validation cohort) between 1979 and 2002. RESULTS: In the derivation cohort, 73 patients developed ESRD during the median 4.7-year follow-up. The final prediction model included proteinuria (hazard ratio [HR], 1.30; 95% confidence interval [95% CI], 1.16 to 1.45, every 1 g/24 hours), estimated GFR (HR, 0.84; 95% CI, 0.74 to 0.96, every 10 ml/min per 1.73 m(2)), mesangial proliferation (HR, 1.85; 95% CI, 1.10 to 3.11), segmental sclerosis (HR, 3.21; 95% CI, 1.37 to 7.51), and interstitial fibrosis/tubular atrophy (T1: HR, 5.30; 95% CI, 2.63 to 10.7; T2: HR, 20.5; 95% CI, 9.05 to 46.5) as independent risk factors for developing ESRD. To create a prediction rule, the score for each variable was weighted by the regression coefficients calculated using the relevant Cox model. The incidence of ESRD increased linearly with increases in the total risk scores (P for trend <0.001). Furthermore, the prediction rule demonstrated good discrimination (c-statistic=0.89) and calibration (Hosmer-Lemeshow test, P=0.78) in the validation cohort. CONCLUSIONS: This study developed and validated a new prediction rule using clinical measures and the Oxford classification for developing ESRD in patients with IgAN. PMID- 24178971 TI - Incidence, outcomes, and comparisons across definitions of AKI in hospitalized individuals. AB - BACKGROUND AND OBJECTIVES: At least four definitions of AKI have recently been proposed. This study sought to characterize the epidemiology of AKI according to the most recent consensus definition proposed by the Kidney Disease Improving Global Outcomes (KDIGO) Work Group, and to compare it with three other definitions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective cohort study of 31,970 hospitalizations at an academic medical center in 2010. AKI was defined and staged according to KDIGO criteria, the Acute Dialysis Quality Initiative's RIFLE criteria, the Acute Kidney Injury Network (AKIN) criteria, and a definition based on a model of creatinine kinetics (CK). Outcomes of interest were incidence, in-hospital mortality, length of stay, costs, readmission rates, and posthospitalization disposition. RESULTS: AKI incidence was highest according to the KDIGO definition (18.3%) followed by the AKIN (16.6%), RIFLE (16.1%), and CK (7.0%) definitions. AKI incidence appeared markedly higher in those with low baseline serum creatinine according to the KDIGO, AKIN, and RIFLE definitions, in which AKI may be defined by a 50% increase over baseline. AKI according to all definitions was associated with a significantly higher risk of death and higher resource utilization. The adjusted odds ratios for in-hospital mortality in those with AKI were highest with the CK definition (5.2; 95% confidence interval [95% CI], 4.1 to 6.6), followed by the RIFLE (2.9; 95% CI, 2.2 to 3.6), KDIGO (2.8; 95% CI, 2.2 to 3.6), and AKIN (2.6; 95% CI, 2.0 to 3.3) definitions. Concordance in diagnosis and staging was high among the KDIGO, AKIN, and RIFLE definitions. CONCLUSIONS: The incidence of AKI in hospitalized individuals varies depending on the definition used. AKI according to all definitions is associated with higher in-hospital mortality and resource utilization. AKI may be inappropriately diagnosed in those with low baseline serum creatinine using definitions that incorporate percentage increases over baseline. PMID- 24178972 TI - Kidney function and prevalent and incident frailty. AB - BACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: CHS enrolled community-dwelling adults age >=65 years between 1989 1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity. RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) >=90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty. CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function. PMID- 24178973 TI - Principles of separation: indications and therapeutic targets for plasma exchange. AB - Extracorporeal "blood purification," mainly in the form of hemodialysis has been a major portion of the clinical activity of many nephrologists for the past 5 decades. A possibly older procedure, therapeutic plasma exchange, separates and then removes plasma as a method of removing pathogenic material from the patient. In contrast to hemodialysis, therapeutic plasma exchange preferentially removes biologic substances of high molecular weight such as autoantibodies or alloantibodies, antigen-antibody complexes, and Ig paraproteins. These molecular targets may be cleared through two alternative procedures: centrifugal separation and membrane separation. This review presents operational features of each procedure, with relevance to the nephrologist. Kinetics of removal of these plasma constituents are based on the principles of separation by the apheresis technique and by features specific to each molecular target, including their production and compartmentalization in the body. Molecular targets for common renal conditions requiring therapeutic plasma exchange are also discussed in detail. PMID- 24178974 TI - C3 glomerulopathy: clinicopathologic features and predictors of outcome. AB - BACKGROUND AND OBJECTIVES: The term C3 glomerulopathy describes renal disorders characterized by the presence of glomerular deposits composed of C3 in the absence of significant amounts of Ig. On the basis of electron microscopy appearance, subsets of C3 glomerulopathy include dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The full spectrum of histologic change observed in C3 glomerulopathy has yet to be defined and pathologic predictors of renal outcome within this patient population remain largely unknown. This study thus characterized a large C3 glomerulopathy cohort and identified clinicopathologic predictors of renal outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients with kidney biopsies fulfilling criteria for C3 glomerulopathy from two quaternary renal centers within the United Kingdom and Ireland between 1992 and 2012 were retrospectively reviewed. We recorded histologic, demographic, and clinical data and determined predictors of ESRD using the Cox proportional hazards model. RESULTS: Eighty patients with C3 glomerulopathy were identified: 21 with DDD and 59 with C3GN. Patients with DDD were younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN. Patients with C3GN were older and had more severe arteriolar sclerosis, glomerular sclerosis, and interstitial scarring than patients with DDD. Of 70 patients with available follow-up data, 20 (29%) progressed to ESRD after a median of 28 months. Age >16 years, DDD subtype, and crescentic GN were independent predictors of ESRD within the entire cohort. Renal impairment at presentation predicted ESRD only among patients with DDD. CONCLUSIONS: Although detailed serologic and genetic data are lacking, this study nevertheless identifies important clinicopathologic distinctions between patients with DDD and C3GN. These include independent predictors of renal outcome. If replicated in other cohorts, these predictors could be used to stratify patients, enabling application of emerging mechanism-based therapies to patients at high risk for poor renal outcome. PMID- 24178975 TI - IGF-1 and survival in ESRD. AB - BACKGROUND AND OBJECTIVES: IGF-1 deficiency links to malnutrition in CKD patients; however, it is not clear to what extent it associates with survival among these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Serum IGF-1 and other biochemical, clinical (subjective global assessment), and densitometric (dual energy x-ray absorptiometry) markers of nutritional status and mineral and bone metabolism were measured in a cohort of 365 Swedish clinically stable CKD stage 5 patients (median age of 53 years) initiating dialysis between 1994 and 2009; in 207 patients, measurements were also taken after 1 year of dialysis. Deaths were registered during a median follow-up of 5 years. Associations of mortality with baseline IGF-1 and changes of IGF-1 after 1 year of dialysis were evaluated by Cox models. RESULTS: At baseline, IGF-1 concentrations associated negatively with age, diabetes mellitus, cardiovascular disease, poor nutritional status, IL-6, and osteoprotegerin and positively with body fat mass, bone mineral density, serum phosphate, calcium, and fibroblast growth factor-23. At 1 year, IGF-1 had increased by 33%. In multivariate regression, low age, diabetes mellitus, and high serum phosphate and calcium associated with IGF-1 at baseline, and in a mixed model, these factors, together with high fat body mass, associated with changes of IGF-1 during the first 1 year of dialysis. Adjusting for calendar year of inclusion, age, sex, diabetes mellitus, cardiovascular disease, IL-6, and poor nutritional status, a 1 SD higher level of IGF-1 at baseline associated with lower mortality risk (hazard ratio, 0.57; 95% confidence interval, 0.32 to 0.98). Persistently low or decreasing IGF-1 levels during the first 1 year on dialysis predicted worse survival (adjusted hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.50). CONCLUSION: In incident dialysis patients, low serum IGF-1 associates with body composition and markers of mineral and bone metabolism, and it predicts increased mortality risk. PMID- 24178976 TI - Association between GFR estimated by multiple methods at dialysis commencement and patient survival. AB - BACKGROUND AND OBJECTIVES: The Initiating Dialysis Early and Late study showed that planned early or late initiation of dialysis, based on the Cockcroft and Gault estimation of GFR, was associated with identical clinical outcomes. This study examined the association of all-cause mortality with estimated GFR at dialysis commencement, which was determined using multiple formulas. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Initiating Dialysis Early and Late trial participants were stratified into tertiles according to the estimated GFR measured by Cockcroft and Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease-Epidemiology Collaboration formula at dialysis commencement. Patient survival was determined using multivariable Cox proportional hazards model regression. RESULTS: Only Initiating Dialysis Early and Late trial participants who commenced on dialysis were included in this study (n=768). A total of 275 patients died during the study. After adjustment for age, sex, racial origin, body mass index, diabetes, and cardiovascular disease, no significant differences in survival were observed between estimated GFR tertiles determined by Cockcroft and Gault (lowest tertile adjusted hazard ratio, 1.11; 95% confidence interval, 0.82 to 1.49; middle tertile hazard ratio, 1.29; 95% confidence interval, 0.96 to 1.74; highest tertile reference), Modification of Diet in Renal Disease (lowest tertile hazard ratio, 0.88; 95% confidence interval, 0.63 to 1.24; middle tertile hazard ratio, 1.20; 95% confidence interval, 0.90 to 1.61; highest tertile reference), and Chronic Kidney Disease Epidemiology Collaboration equations (lowest tertile hazard ratio, 0.93; 95% confidence interval, 0.67 to 1.27; middle tertile hazard ratio, 1.15; 95% confidence interval, 0.86 to 1.54; highest tertile reference). CONCLUSION: Estimated GFR at dialysis commencement was not significantly associated with patient survival, regardless of the formula used. However, a clinically important association cannot be excluded, because observed confidence intervals were wide. PMID- 24178978 TI - Dietary phthalates and low-grade albuminuria in US children and adolescents. AB - BACKGROUND: Low-grade albuminuria is an indicator of endothelial dysfunction and is associated with an increased risk of cardiovascular disease. A graded level of exposure to bisphenol A was recently identified to be associated with increased risk of low-grade albuminuria in children and adults. Because bisphenol A and phthalates coexist as dietary contaminants, this study investigated whether exposure to phthalates is also associated with low-grade albuminuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were examined from 667 children who participated in the 2009-2010 National Health and Nutrition Examination Survey and who had results for urinary phthalate metabolites and albumin excretion. Urinary albumin and creatinine concentrations were measured in a first morning specimen using a solid-phase fluorescent immunoassay and a Roche/Hitachi Modular P Chemistry Analyzer with an enzymatic method, respectively. Phthalate metabolites were analyzed in a separate spot urine sample from each participant, using high-performance liquid chromatography and tandem mass spectroscopy. RESULTS: For each (roughly) 3-fold increase in metabolites of di-2 ethylhexylphthalate (a high molecular weight phthalate commonly found in foods), a 0.55 mg/g increase in albumin/creatinine ratio (ACR) was identified (P=0.02), whereas a 1.30-fold odds of a higher ACR quartile was also identified for each (roughly) 3-fold increase (P=0.02). Higher ACR was not identified in relationship to metabolites of lower molecular phthalates commonly found in lotions or shampoos, suggesting specificity. CONCLUSIONS: Although reverse causation and unmeasured confounders represent alternative explanations, these findings, in conjunction with our earlier data on bisphenol A, indicate that a wide array of environmental toxins may adversely affect albuminuria and potentially increase the risk of cardiovascular disease. In view of the potential long-term health implications of ongoing exposure in this vulnerable subpopulation, our data support both further study and renewed regulatory efforts to limit exposure during childhood. PMID- 24178977 TI - Adult height in patients with advanced CKD requiring renal replacement therapy during childhood. AB - BACKGROUND AND OBJECTIVES: Growth and final height are of major concern in children with ESRD. This study sought to describe the distribution of adult height of patients who started renal replacement therapy (RRT) during childhood and to identify determinants of final height in a large cohort of RRT children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 1612 patients from 20 European countries who started RRT before 19 years of age and reached final height between 1990 and 2011 were included. Linear regression analyses were performed to calculate adjusted mean final height SD score (SDS) and to investigate its potential determinants. RESULTS: The median final height SDS was 1.65 (median of 168 cm in boys and 155 cm in girls). Fifty-five percent of patients attained an adult height within the normal range. Adjusted for age at start of RRT and primary renal diseases, final height increased significantly over time from -2.06 SDS in children who reached adulthood in 1990-1995 to -1.33 SDS among those reaching adulthood in 2006-2011. Older age at start of RRT, more recent period of start of RRT, cumulative percentage time on a functioning graft, and greater height SDS at initiation of RRT were independently associated with a higher final height SDS. Patients with congenital anomalies of the kidney and urinary tract and metabolic disorders had a lower final height than those with other primary renal diseases. CONCLUSIONS: Although final height remains suboptimal in children with ESRD, it has consistently improved over time. PMID- 24178979 TI - Recognition of CKD after the introduction of automated reporting of estimated GFR in the Veterans Health Administration. AB - BACKGROUND AND OBJECTIVES: Early detection of CKD is important for slowing progression to renal failure and preventing cardiovascular events. Automated laboratory reporting of estimated GFR (eGFR) has been introduced in many health systems to improve CKD recognition, but its effect in large, United States-based health systems remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using Veterans Affairs (VA) laboratory and administrative data, two nonoverlapping national cohorts of patients receiving care in VA medical centers before (n=66,323) and after (n=16,670) implementation of automated eGFR reporting between 2004 and 2010 were identified. Recognition was assessed by the presence of new CKD diagnostic codes, use of additional diagnostic testing, outpatient nephrology visits, or overall CKD recognition (receipt of at least one of these outcomes) for each patient during the 12-month period after their first eligible creatinine or eGFR laboratory result. Generalized estimating equations were used to assess change before and after automated eGFR reporting. RESULTS: Overall CKD recognition increased from 22.1% of veterans before eGFR reporting to 27.5% in the post-eGFR reporting period (odds ratio [OR], 1.19; 95% CI, 1.12 to 1.27; P<0.001). Higher overall CKD recognition was driven largely by increased documentation of CKD diagnosis codes in medical records (OR, 1.31; 95% CI, 1.21 to 1.41; P<0.001) and diagnostic testing for CKD (OR, 1.13; 95% CI, 1.03 to 1.24; P<0.01) rather than outpatient nephrology consultation. Automated eGFR reporting was not associated with greater CKD recognition among black or older patients (P=0.07). CONCLUSIONS: Automated eGFR laboratory reporting improved documentation of CKD diagnoses but had no effect on nephrology consultation. These findings suggest that to advance CKD care, further strategies are needed to ensure appropriate follow-up evaluation to confirm and effectively evaluate CKD. PMID- 24178981 TI - Responses of foliar antioxidative and photoprotective defence systems of trees to drought: a meta-analysis. AB - Current climate change predictions hint to more frequent extreme weather events, including extended droughts, making better understanding of the impacts of water stress on trees even more important. At the individual plant level, stomatal closure as a result of water deficit leads to reduced CO2 availability in the leaf, which can lead to photo-oxidative stress. Photorespiration and the Mehler reaction can maintain electron transport rates under low internal CO2, but result in production of reactive oxygen species (ROS). If electron consumption is decreased, upstream photochemical processes can be affected and light energy is absorbed in excess of photochemical requirements. Trees evolved to cope with excess energy and elevated concentration of ROS by activating photoprotective and antioxidative defence systems. The meta-analysis we present here assessed responses of these defence systems reported in 50 studies. We found responses to vary depending on stress intensity, foliage type and habitat, and on whether experiments were done in the field or in controlled environments. In general, drought increased concentrations of antioxidants and photoprotective pigments. However, severe stress caused degradation of antioxidant concentrations and oxidation of antioxidant pools. Evergreen trees seemed to preferentially reinforce membrane-bound protection systems zeaxanthin and tocopherol, whereas deciduous species showed greater responses in water-soluble antioxidants ascorbic acid and glutathione. Trees and shrubs from arid versus humid habitats vary in their antioxidative and photoprotective defence responses. In field experiments, drought had greater effects on some defence compounds than under controlled conditions. PMID- 24178980 TI - Metabolic subtypes and risk of mortality in normal weight, overweight, and obese individuals with CKD. AB - BACKGROUND AND OBJECTIVES: Higher body mass index (BMI) is paradoxically associated with lower mortality in persons with CKD, but whether cardiometabolic abnormalities modulate this association is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants with CKD from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study (n=4374) were analyzed. The harmonized criteria for metabolic syndrome were used to define metabolic health, and participants were categorized into one of six mutually exclusive categories defined by combined measures of metabolic health (metabolically healthy, <3 criteria for metabolic syndrome; metabolically unhealthy, >=3 criteria) and weight status (normal weight, BMI 18.5-24.9 kg/m(2); overweight, BMI 25-29.9 kg/m(2); obese, BMI >=30 kg/m(2)). Cox models were used to estimate the hazard ratio (HR) of death as a function of each category. RESULTS: A total of 683 deaths were observed over a mean 4.5 years of follow-up. In analyses adjusted for age, race, sex, and geographic region of residence, compared with metabolically healthy normal weight persons, the HRs of mortality in metabolically healthy overweight and obese persons were 0.68 (95% confidence interval [95% CI], 0.53 to 0.87) and 0.71 (95% CI, 0.51 to 0.98), respectively, whereas there were no statistically significant differences in survival among metabolically unhealthy overweight or obese individuals. After further adjustment for lifestyle, clinical and laboratory factors including markers of kidney function, the HR of mortality remained lower in metabolically healthy overweight individuals compared with metabolically healthy normal weight individuals (HR, 0.74; 95% CI, 0.57 to 0.96). CONCLUSIONS: Metabolic abnormalities may attenuate the magnitude and strength of survival benefits associated with higher BMI in individuals with CKD. PMID- 24178982 TI - Investigating the drought-stress response of hybrid poplar genotypes by metabolite profiling. AB - Drought stress is perhaps the most commonly encountered abiotic stress plants experience in the natural environment, and it is one of the most important factors limiting plant productivity. Here, we employed untargeted metabolite profiling to examine four drought-stressed hybrid poplar (Populus spp.) genotypes for their metabolite content, using gas chromatography coupled to mass spectrometry. The primary objective of these analyses was to characterize the metabolite profile of poplar trees to assess relative drought resistance and to investigate the underlying biochemical mechanisms employed by the genotypes to combat drought. Metabolite profiling identified key metabolites that increased or decreased in relative abundance upon exposure to drought stress. Overall, amino acids, the antioxidant phenolic compounds catechin and kaempferol, as well as the osmolytes raffinose and galactinol exhibited increased abundance under drought stress, whereas metabolites involved in photorespiration, redox regulation and carbon fixation showed decreased abundance under drought stress. One clone in particular, Okanese, displayed unique responses to the imposed drought conditions. This clone was found to have higher leaf water potential, but lower growth rate relative to the other clones tested. Okanese also had lower accumulation of osmolytes such as raffinose, galactinol and proline, but higher overall levels of antioxidants such as catechin and dehydroascorbic acid. As such, it was proposed that osmotic adjustment as a mechanism for drought avoidance in this clone is not as well developed in comparison with the other clones investigated in this study, and that a possible alternative mechanism for the enhanced drought avoidance displayed by Okanese may be due to differential allocation of resources or better retention of water. PMID- 24178983 TI - Evaluation of PHBHHx and PHBV/PLA fibers used as medical sutures. AB - Two types of fibers were prepared by using bio-based materials: a mono-filament made from poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a multi filament made from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and polylactic acid (PLA) blend. The two fibers were evaluated for mechanical properties, biocompatibility and degradability for the potential application as medical sutures. The PHBHHx fiber showed remarkable biocompatibility by H.E. Stainning, with very little impact to the surrounding tissues. The degradation of the fiber was observed by SEM after implantation for 36 weeks, and the major degradation product was detected after 96 weeks. Consistently, the PHBHHx fiber maintained more than half of the mechanical properties after 96 weeks. The other fiber was prepared by twisting PHBV/PLA blend strands to a bunch, and showed high biocompatibility and relatively high degradability. The bunched structure loosed after 36 weeks of implantation. These low-cost and easily prepared fibers have great potential in medical applications, since they could avoid the formation of fibrous capsule, reduce the size of scar, and degrade into non-toxic and even beneficial products. PMID- 24178984 TI - Effect of pore size and cross-linking of a novel collagen-elastin dermal substitute on wound healing. AB - Collagen-elastin (CE) scaffolds are frequently used for dermal replacement in the treatment of full-thickness skin defects such as burn wounds. But little is known about the optimal pore size and level of cross-linking. Different formulations of dermal substitutes with unidirectional pores were tested in porcine full thickness wounds in combination with autologous split skin mesh grafts (SSG). Effect on wound healing was evaluated both macro- and microscopically. CE scaffolds with a pore size of 80 or 100 MUm resulted in good wound healing after one-stage grafting. Application of scaffolds with a larger average pore size (120 MUm) resulted in more myofibroblasts and more foreign body giant cells (FBGC). Moderate crosslinking impaired wound healing as it resulted in more wound contraction, more FBGC and increased epidermal thickness compared to no cross linking. In addition, take rate and redness were negatively affected compared to SSG only. Vascularization and the number of myofibroblasts were not affected by cross-linking. Surprisingly, stability of cross-linked scaffolds was not increased in the wound environment, in contrast to in vitro results. Cross linking reduced the proliferation of fibroblasts in vitro, which might explain the reduced clinical outcome. The non-cross-linked CE substitute with unidirectional pores allowed one-stage grafting of SSG, resulting in good wound healing. In addition, only a very mild foreign body reaction was observed. Cross linking of CE scaffolds negatively affected wound healing on several important parameters. The optimal non-cross-linked CE substitute is a promising candidate for future clinical evaluation. PMID- 24178985 TI - Media-based effects on the hydrolytic degradation and crystallization of electrospun synthetic-biologic blends. AB - Tissue engineering scaffold degradation in aqueous environments is a widely recognized factor determining the fate of the associated anchorage-dependent cells. Electrospun blends of synthetic polycaprolactone (PCL) and a biological polymer, gelatin, of 25, 50, and 75 wt% were investigated for alterations in crystallinity, microstructure and morphology following widely used in vitro biological exposures. To our knowledge, the effects of these different aqueous based biological media compositions on the degradation of these blends have never been directly compared. X-ray diffraction (XRD) analysis exposed that differences in PCL crystallinity were observed following exposures to phosphate buffered solution (PBS), Dulbecco's modified eagle medium (DMEM) cell culture media, and DI water following 7 days of exposure at 37 degrees C. XRD data suggested that in vitro medium exposures aid in providing chain mobility and rearrangement due to hydrolytic degradation of the gelatin phase, allowing previously constrained, poorly crystalline PCL regions to achieve more intense reflections resulting in the presence of crystalline peaks. The dry, as-spun modulus of relatively soft 100 % PCL fibers was approximately 10 % of any gelatin-containing composition. Tensile testing results indicate that hydrated gelatin containing scaffolds on average had a fivefold increase in elongation compared to as-spun scaffolds. After 24-h of aqueous exposure, the elastic modulus decreased in proportion to increasing gelatin content. After 1 day of exposure, the 75 and 100 % gelatin compositions largely ceased to display measurable values of modulus, elongation or tensile strength due to considerable hydrolytic degradation. On a relative basis, common aqueous in vitro medium exposures (deionized water, PBS, and DMEM) resulted in significantly divergent amounts of crystalline PCL, overall microstructure and fiber morphology in the blended compositions, subsequently 'shielding' scaffolds from significant changes in mechanical properties after 24 h of exposure. Understanding electrospun PCL-gelatin scaffold dynamics in different aqueous-based cell culture medias enables the ability to tailor scaffold composition to 'tune' degradation rate, microstructure, and long-term mechanical stability for optimal cellular growth, proliferation, and maturation. PMID- 24178988 TI - Intact PIP implants do not need to be removed, European report confirms. PMID- 24178986 TI - Measuring liver triglyceride content in mice: non-invasive magnetic resonance methods as an alternative to histopathology. AB - OBJECT: Quantitative assessment of liver fat is highly relevant to preclinical liver research and should ideally be performed non-invasively. This study aimed to compare three non-invasive Magnetic Resonance (MR) and two histopathological methods against the reference standard of biochemically determined liver triglyceride content (LTC). MATERIALS AND METHODS: A total of 50 mice [21 C57Bl/6OlaHsd mice (C57Bl/6), nine low-density lipoprotein (LDL) receptor knock out -/- (LDL -/-) mice and 20 C57BL/6 mice] received either a high-fat, high-fat high-cholesterol or control diet, respectively. Mice were examined 4, 8 or 12 weeks into the diet using MR [(1)H-MR Spectroscopy, Proton Density Fat Fraction (PDFF), mDixon] and histopathological methods (visual scoring or digital image analysis (DIA) of Oil-Red-O (ORO) stained liver sections). Correlations [Pearson's coefficient (r)] were studied with respect to LTC. RESULTS: Microvesicular steatosis was seen in 42/50 mice. (1)H-MRS values showed normal to moderately elevated liver fat content. Visual scoring and DIA of ORO-sections correlated moderately with LTC at r = 0.59 and r = 0.49 (P < 0.001), respectively. (1)H-MRS, PDFF and mDixon correlated significantly better, at r = 0.74, r = 0.75 and r = 0.82, respectively. CONCLUSION: Non-invasively determined MR measures of normal to moderately elevated liver fat in mice had a higher correlation with LTC than invasive histopathological measures. Where available, MR is the preferred method for fat quantification. PMID- 24178990 TI - From the editors. PMID- 24178989 TI - HypoxiaDB: a database of hypoxia-regulated proteins. AB - There has been intense interest in the cellular response to hypoxia, and a large number of differentially expressed proteins have been identified through various high-throughput experiments. These valuable data are scattered, and there have been no systematic attempts to document the various proteins regulated by hypoxia. Compilation, curation and annotation of these data are important in deciphering their role in hypoxia and hypoxia-related disorders. Therefore, we have compiled HypoxiaDB, a database of hypoxia-regulated proteins. It is a comprehensive, manually-curated, non-redundant catalog of proteins whose expressions are shown experimentally to be altered at different levels and durations of hypoxia. The database currently contains 72 000 manually curated entries taken on 3500 proteins extracted from 73 peer-reviewed publications selected from PubMed. HypoxiaDB is distinctive from other generalized databases: (i) it compiles tissue-specific protein expression changes under different levels and duration of hypoxia. Also, it provides manually curated literature references to support the inclusion of the protein in the database and establish its association with hypoxia. (ii) For each protein, HypoxiaDB integrates data on gene ontology, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, protein protein interactions, protein family (Pfam), OMIM (Online Mendelian Inheritance in Man), PDB (Protein Data Bank) structures and homology to other sequenced genomes. (iii) It also provides pre-compiled information on hypoxia-proteins, which otherwise requires tedious computational analysis. This includes information like chromosomal location, identifiers like Entrez, HGNC, Unigene, Uniprot, Ensembl, Vega, GI numbers and Genbank accession numbers associated with the protein. These are further cross-linked to respective public databases augmenting HypoxiaDB to the external repositories. (iv) In addition, HypoxiaDB provides an online sequence-similarity search tool for users to compare their protein sequences with HypoxiaDB protein database. We hope that HypoxiaDB will enrich our knowledge about hypoxia-related biology and eventually will lead to the development of novel hypothesis and advancements in diagnostic and therapeutic activities. HypoxiaDB is freely accessible for academic and non profit users via http://www.hypoxiadb.com. PMID- 24178991 TI - Admission to medical school: International perspectives. AB - Admission to medical school is the goal of many students in many countries. The admission process varies from country to country. In some countries, students compete in an open market to gain a position in medical school. In other countries, "intake" is a more routine, planned beaureaucratic process. Where competition reigns, the interview is an important part of the selection process. The interview has been defined by Bingham and Moore [1] as:A serious conversation directed to a definite purpose other than satisfaction in the conversation itself ... We must recognize that not only spoken words, but other means of face-to-face communication also are used. Inflection, qualities of voice, facial expression, glint of the eye, posture, gestures, and general behavior supplement what is said. They all contribute to the purposeful exchange of meanings which is the interview.Faculty members in medical schools interview patients all the time. This type of interview, however, is different from the admission interview conducted for applicants to medical school. Patient interviews are highly patterned and structured to obtain specific information. Interviews of applicants, on the other hand, usually are more open-ended. The psychology of the two types of interviews differ also. Applicants to medical school, if accepted, will in time become colleagues with their interviewers and will have increasing levels of responsibility and respect. Patients, however, will always be dependent upon the physicians who treat them.In this article, we present basic facts, conclusions, and recommendations from a review of literature about the interview [2]. Results of a survey of admission interviews at Canadian and United Kingdom medical schools are presented for the first time, and comparisons with United States interview practices are drawn. Finally, descriptions of the selection process at several medical schools with problem based learning curricula are provided and comparisons are noted. PMID- 24178992 TI - Increased focus on the teaching of interactional skills to medical practitioners. AB - The interaction which occurs between the doctor and patient has been described as the cornerstone of medial care. Research has shown that interactional skills can have a substantial impact on patient outcomes in a number of areas. However, as practitioners do not necessarily acquire such skills through clinical practice, the introduction of formal training programmes for both under and postgraduate medical practitioners should be more closely examined. This paper outlines a number of issues which need to be considered in the formal instruction of medical practitioners in interactional skills. These issues include the teaching of skills within a clinical context that will reflect actual medical practice, the use of all medical disciplines to teach the skills and the inclusion of formal assessment strategies based on the same rigorous criteria as other components of the medical curriculum. PMID- 24178993 TI - Learning issues identified by students in tutorless problem-based tutorials. PMID- 24178994 TI - The assessment of professional competence: Developments, research and practical implications. PMID- 24178995 TI - Models of faculty development for problem-based learning. AB - Learning an innovative teaching method such as a problem-based learning is difficult for most faculty members because the method is based upon assumptions about learning that are often at variance with their beliefs. Faculty development can challenge assumptions about learning, provide experience with a new technique, and offer specific pedagogical skills that are needed to succeed as a tutor. A comprehensive approach to faculty development, derived from the literature in higher education, would include: instructional development, professional development, leadership development, and organizational development. Research on faculty development indicates positive results of such efforts. Faculty members who choose to learn about problem-based learning appear to progress through predictable stages of development that include: understanding and valuing the rationale for problem-based learning, acquiring general and content-specific tutor knowledge and skills, developing advanced skills in problem-based learning, and developing leadership and scholarship skills. Each of these steps, plus organizational vitality, are described along with recommendations for implementing such programs. Finally, five models of faculty development derived from medical schools with problem-based learning curricula are examined. PMID- 24178996 TI - Problem-based learning in medical education: Developing a research agenda. AB - While the use of problem-based learning (PBL) methods continues to increase in medical education, three literature reviews of PBL have appeared in the past several years which come to different opinions about their merits. This analysis summarizes the research evidence regarding PBL by examining how well it has met its originators' goals, what we know about how PBL works, and how PBL fares in a goal-free comparison with conventional curricula. A research agenda is suggested to refine our understanding of well-documented effects of PBL, to probe for other possible longer term PBL outcomes, and to examine if and how PBL affects knowledge acquisition and retention. Consistency of evidence from a variety of PBL implementations can help decide whether the effects seen can be attributed to PBL or are the results of other curricular features unique to one setting. PMID- 24178998 TI - Editorial. PMID- 24178997 TI - Sex differences in diabetes and risk of incident coronary artery disease in healthy young and middle-aged adults. AB - OBJECTIVE: Controversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated sex differences in CAD by diabetes status among healthy individuals with different underlying risks of heart disease. RESEARCH DESIGN AND METHODS: We examined subjects aged <60 years without CAD at enrollment in the high-risk GeneSTAR Study (n = 1,448; follow-up ~12 years), Multi-Ethnic Study of Atherosclerosis (MESA; n = 3,072; follow-up ~7 years), and National Health and Nutrition Examination Survey III (NHANES III) Mortality Follow-up Study (n = 6,997; follow-up ~15 years). Diabetes was defined by report, hypoglycemic use, and/or fasting glucose >=126 mg/dL. The outcome was any CAD event during follow-up (fatal CAD in NHANES). RESULTS: In the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, and 0.40/1,000 person-years, respectively) versus men (11.22, 5.64, and 0.88/1,000 person-years); log-rank P < 0.001 (GeneSTAR/MESA) and P = 0.07 (NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, and 2.37/1,000 person-years) versus men (12.86, 9.71, and 1.83/1,000 person-years); all log-rank P values > 0.05. Adjusting for demographics, diabetes was associated with a significant four to fivefold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for BMI, smoking, hypertension, HDL, and non-HDL cholesterol, antihypertensive and cholesterol lowering medication use, the hazard ratio of CAD in men versus women among nondiabetes was 2.43 (1.76-3.35) and diabetes was 0.89 (0.43-1.83); P = 0.013 interaction by diabetes status. CONCLUSIONS: Though young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by sex. Our findings support aggressive CAD prevention strategies in women with diabetes and at similar levels to those that exist in men. PMID- 24178999 TI - The answer key as a source of error in performance assessment. AB - OBJECTIVE: To determine the impact of variability in answer key construction (i.e., option weighting) on total errors of measurement and to compare several designs for reducing this effect. METHODS: A video-based format that assesses ability to interpret arteriograms is studied because it reproduces with high fidelity an important task faced by cardiologists. Responses given by highly qualified examinees are used to develop answer keys by the aggregate scoring method, and generalizability theory is applied to estimate the error variance in answer key construction. SAMPLE: Two hundred and two examinees who volunteered to participate in the study after taking their certifying examination in cardiovascular diseases. RESULTS: RESULTS show less scorer variability than case variability; however, several scorers make a sizeable reduction in measurement error. CONCLUSION: Although there is some error in the answer key construction process, its size is relatively small and it should not be a major impediment to the use of performance-based item formats. PMID- 24179000 TI - The association between reading time and students' performance in a surgery clerkship. AB - OBJECTIVE: Medical students are expected to acquire a large amount of knowledge in both the basic and clinical sciences by reading. The purpose of this study was to examine the relationship between reading time and students' performance on various objective and subjective evaluative measures. METHODS: The study examined the reading activities of 80 students in a third-year surgery clerkship. Students spent an average of 16 hours per week in reading activities. RESULTS: A modest but statistically significant correlation was found between the total amount of time spent in reading and students' performance on an objective standardized clinical examination, a standardized patient encounter, a subjective rating by faculty members, and the total objective grade. Reading time did not correlate with performance on objective measures such as quizzes or the National Board of Medical Examiners examination. CONCLUSION: Although achievement in the clerkship is associated to a minor degree with reading time, reading time alone is not a sufficient influence on achievement. PMID- 24179001 TI - The development of a 'Standardised Learner' in researching teaching behaviours. AB - Standardised patients are increasingly used in medical education and the reliability and validity of their use as an assessment method are supported by published research. This paper details the application of this methodology to the educational interaction between a teacher and a learner using a standardised learner.In contrast with standardised patients, a standardised learner must use a level of medical knowledge and experience appropriate for the role assumed. Some aspects of reliability and validity have been considered and appear supportive of this methodology.The feasibility and value of this method for researching actual teacher behaviour are discussed. PMID- 24179002 TI - The impact of early career specialization on licensing requirements and related educational implications. AB - PURPOSE: It was hypothesized that physicians who pursue early career specialization in their first year of graduate medical education after medical school are likely to experience a decline in their scores on the medical licensing examination. METHOD: A longitudinal prospective design was used in which 1,927 physicians who graduated from Jefferson Medical College between 1980 and 1991 were studied. Type of first-year graduate training program was the independent variable, and performance on a medical licensing examination (Part III examination of the National Board of Medical Examiners [NBME]) was the dependent variable. Scores on Parts I and II of the NBME taken in medical school, medical school class rank, and gender were the control variables. RESULTS: Findings showed significant differences on Part III scores among physicians in 12 different graduate programs despite statistical adjustments for baseline differences. Physicians in family medicine and emergency medicine programs obtained the highest adjusted Part III scores, followed by physicians in internal medicine and transitional programs. The next group consisted of physicians in pediatrics, obstetrics-gynecology, anesthesiology, and general surgery programs. The group with the lowest Part III scores included physicians in pathology, radiology, and psychiatry. IMPLICATIONS: These findings suggest that students who meet only the minimal standards in medical school should be advised to pursue a broad training program in the first year of graduate medical education to strengthen their general clinical competence as a means to increase their chances of passing licensing examinations. PMID- 24179003 TI - Comparative study of medical education as perceived by students at three Dutch universities. AB - Objective. The aim of the present study was to identify the differences that may exist in professional satisfaction and skills (clinical patient management and psychosocial skills) in students and graduates from two traditional medical schools and their counterparts from a problem-based medical school in the Netherlands. Also their satisfaction for their training was investigated. Method. Questionnaires were designed containing items reflecting the earlier mentioned differences between the students. Following an initial pilot study, the questionnaire used in this study was constructed accordingly. Sample. The questionnaires were sent to 180 near and recent graduates of these three schools. Results. A total of 127 questionnaires were returned (response rate of 70.5%). The students of the PBL curriculum felt better prepared in psychosocial and interpersonal skills. They felt more satisfied with their training, but were less enthusiastic with the profession. The results also suggest that in their own opinion students and graduates from the three schools do not differ in clinical patient management skills acquired in medical school. Conclusion. A limitation of this study lies in the fact that results are based on actual self-assessment of the students. One must be aware that self-assessment does not always provide for objective information. However, since this limitation applied equally to respondents of all three medical schools, the differences between the schools can be considered indicative of the effects resulting from the different curricula. PMID- 24179004 TI - Do professional attitudes change during medical education? AB - OBJECTIVE: The aim was to measure students' professional attitudes, in particular the level of humaneness. The quality of humaneness was defined in terms of both patient-centredness and psychosocial orientation towards disease. METHOD: Medical students completed a questionnaire designed to survey professional attitudes. Measuring instruments consisted of the Doctor-Patient Scale and the Social Context Scale, both containing statements of the Likert-type. Reliability and validity of the scales had to be established. SAMPLE: In total, 476 students from four different classes, both preclinical and clinical, were studied in a cross sectional design. RESULTS: The expectation that the attitudes of senior students would be less patient-centred and less psychosocially oriented due to a process of dehumanisation, was not supported by the results. Differences in the attitudes of male and female students were also examined. Generally, female students held more patientcentred and psychosocially oriented attitudes than their male counterparts. The possible influence of measurement and educational factors upon students' attitudes is also discussed. CONCLUSION: No decrease in humaneness during medical education was detected. Gender differences in professional attitudes were visible. More validation of the scales has to be done. PMID- 24179005 TI - Reflections. PMID- 24179006 TI - P B L farm. PMID- 24179007 TI - Obesity and CKD progression: hard facts on fat CKD patients. AB - Obesity is a worldwide epidemic and there is compelling evidence that excess fat is closely associated with chronic kidney disease (CKD) and end-stage kidney failure. In this review, we will describe some important mechanisms related with the pathogenesis and treatment of CKD in obesity by emphasizing the role of excess fat in renal haemodynamic and structural alterations. PMID- 24179008 TI - Association between the body mass index and chronic kidney disease in men and women. A population-based study from Israel. AB - BACKGROUND: Any association between the body mass index (BMI) and chronic kidney disease (CKD) has so far proved inconclusive. Most studies have estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. This has recently been replaced by the more accurate Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. METHODS: In a cross sectional study, data from a screening centre in Israel, n = 21880 (32% women) were used to assess the prevalence of CKD defined as eGFR < 60 mL/min/1.73 m(2) in relation to BMI categories. The CKD-EPI equation was used to assess the eGFR. RESULTS: CKD was found in 167 men and 45 women. Subjects with a BMI of 25-29.9 kg/m(2), compared with those with a BMI of <25 kg/m(2), had an odds ratio (OR; 95% confidence intervals) for CKD of 1.8 (1.2-2.7) and 3.4 (1.5-7.7) for men and women, respectively. Subjects with a BMI of 30-35 kg/m(2) had an OR of 2.5 (1.6 4.0) and 4.5 (1.7-11.7) for men and women, respectively. In comparable data, for subjects with a BMI > 35 kg/m(2) the OR was 2.7 (1.3-5.5) and 15.4 (6.4-36.7) for men and women, respectively. After multivariate adjustment for age, hypertension and diabetes mellitus, no association was found in men yet it persisted for women. This correlation in women, between the BMI and CKD, was attributed to the subcategory of severely obese women with a BMI of >35 kg/m(2). CONCLUSIONS: Our study is the first to suggest that morbid obesity may be an independent factor related to CKD in women. PMID- 24179010 TI - Prevalence of hypertension and decreased glomerular filtration rate in obese children: results of a population-based field study. AB - BACKGROUND: Obesity has risen considerably in the Western world and the trend is increasing in non-Western, developing countries, as well. Several school screening studies showed the relation between body mass index and hypertension. In adults, obesity is associated with an increased risk of development and progression of kidney disease. However, data at the epidemiological level are limited, both for children and adults. The aim of this study was to determine the prevalence of obesity and evaluate its association with hypertension and glomerular filtration rate (GFR) among children in Turkey. METHODS: A population based field study in which individuals were accessed by house visits throughout Turkey has been conducted. The study sample (3622 children; 5-18 years; 49.6% female, mean age 11.88 +/- 3.40 years) was selected to represent the Turkish population regarding geographical region, gender and age (5-18 years). Obesity was defined as the body mass index >=95th percentile for age and gender. The Schwartz formula was used to estimate GFR. Blood pressure (BP) percentile was determined according to age, gender and length. RESULTS: The prevalence of overweight, obesity and hypertension were 9.3, 8.9 and 6.1%, respectively. Logistic regression analysis revealed urban area (OR 1.50; 95% CI 1.15-1.96; P = 0.003) as an independent risk for obesity and age decreased (OR 0.921; 95% CI 0.890-0.924; P < 0.001) risk for obesity. Obese children had the highest rate of hypertension (11.4 versus 5.6%; P < 0.001; OR 2.17, 95% CI 1.49-3.17; P < 0.001) and stage II hypertension (3.8 versus 0.7%; OR 6.01, 95% CI 2.93-12.33; P < 0.001). Systolic and diastolic BP z-scores were significantly higher in obese children. The mean estimated (eGFR) was lower in obese children (122.7 +/- 21.6 versus 129.4 +/- 23.1, P < 0.001). The rates of children with eGFR < 90 and <75 mL/min/1.73 m(2) were higher in obese patients, but did not reach statistical significance. CONCLUSIONS: Our nation-wide population-based field study among children showed that the prevalence of obesity is increasing in Turkey. The prevalence of hypertension and stage II hypertension, BP z-scores and eGFR were associated with obesity. We suggest that obese children are future candidates for chronic kidney disease. Longitudinal research is necessary to better understand these associations. Strategies for the prevention and management of obesity are also important for emerging countries and for children. PMID- 24179009 TI - Adipokines protecting CKD. AB - Increasing incidence of chronic kidney disease (CKD) which leads to end-stage renal disease (ESRD) is one of the major health issues in the modern world and requires novel strategies for treatment. Adipose tissue has been recognized to have endocrine function and secretes a variety of hormones called adipokines. Several adipokines have been implicated in the pathogenesis of CKD and may have a strong impact as a risk factor for renal decline. The aim of this review is to provide an overview of the role of adipokines in the progression of CKD, with focus on recent experimental and clinical advances. PMID- 24179011 TI - Subclinical versus overt obesity in dialysis patients: more than meets the eye. AB - BACKGROUND: Obesity is an important problem in the epidemic of chronic kidney disease (CKD). Obesity is usually diagnosed by body mass index (BMI), but this metric has limitations as a measure of adiposity in CKD patients. Simple anthropometric tools, like skinfold thickness measurements, have been shown to be a better test to classify obesity among those with CKD. METHODS: The prevalence of obesity was estimated by BMI (>30 kg/m(2)) and by skinfold thickness-estimated body fat (>25% in men and 35% in women) in two cohorts comprising 284 incident dialysis and 209 prevalent haemodialysis (HD) patients from Sweden. Patient characteristics were compared among individuals with differing diagnosis. RESULTS: BMI obesity cut-offs misdiagnosed many patients (>50%) with excess adiposity. Obesity, estimated by BMI, was present in 9 and 10% of incident and prevalent dialysis patients, respectively. When estimated by percentage of body fat, the prevalence of obesity rose to 64 and 65%. In both cohorts, a large proportion of patients (55%) were obese in the context of a normal BMI (termed as subclinical obesity). These individuals were older, presented more co-morbidity and lower surrogates of muscle mass [handgrip strength, arm muscle circumference or insulin-growth factor (IGF)-1 levels] than those diagnosed by both methods (termed overt obesity). CONCLUSION: A BMI of <30 kg/m(2) does not exclude the presence of excess adiposity. Subclinical obesity is a frequent condition in dialysis patients, and the clinical consequences of this finding deserve further consideration. PMID- 24179012 TI - Obesity and atherosclerotic events in chronic hemodialysis patients: a prospective study. AB - BACKGROUND: Studies exploring the impact of overweight on mortality have reported controversial results in dialysis patients; some have found overweight to increase mortality, whereas others suggest that it offers a survival advantage. We conducted a prospective study to evaluate the impact of overweight on atherosclerotic events (AE) in dialysis patients with special respect to the malnutrition/inflammation complex syndrome (MICS). METHODS: Five hundred and forty-one hemodialysis patients from 11 dialysis centers in France were included. A number of baseline parameters including traditional and non-traditional cardiovascular (CV) risk factors were measured and the cohort was followed prospectively. RESULTS: Over a mean follow-up of 39 months, 207 patients (38.3%) experienced an AE. Overweight, defined by a body mass index greater than 25 kg/m(2), was associated with increased risk of AEs [RR: 1.68 (CI: 1.11-3.56)], and CV mortality [RR: 1.51 (CI: 1.07-2.13)]. The effect of overweight was different in patients with and without MICS. Age, diabetes, a previous history of CV disease, high serum levels of homocysteine and MICS were also associated with an increased risk of AEs. CONCLUSIONS: Similar to the general population, overweight contributes to an increased risk for AEs and CV mortality in hemodialysis patients. The presence or absence of MICS can modify the impact of overweight on development of AEs and mortality in this population. PMID- 24179013 TI - Impaired postprandial fibroblast growth factor (FGF)-19 response in patients with stage 5 chronic kidney diseases is ameliorated following antioxidative therapy. AB - BACKGROUND: While dysmetabolism is common in patients with chronic kidney disease (CKD) and associated with mortality, the mechanisms mediating these changes are unclear. New data implicate fibroblast growth factor (FGF)-19 as a possible entero-hepatic modulator of lipid metabolism. METHODS: Using samples previously gathered as part of a randomized placebo-controlled study of antioxidative therapy for postprandial dysmetabolism, we investigated short-term (4 h) postprandial changes in circulating FGF-19 (ELISA) and the relationship to metabolic markers in six haemodialysis (HD) patients and nine matched healthy subjects (HS), with each participant assessed on four separate occasions. RESULTS: The postprandial FGF-19 response was blunted in patients [maximum change +34.63 (0.24-186) pg/mL] versus controls [maximum change +150.3 (31.2-378.7) pg/mL; P < 0.0001], and the area under the curve (AUC; pg * min * mL(-1)) was also significantly lower 18 019 (12 513-44 387) versus 38 517 (19 775-72 816; P < 0.01). In patients, we found univariate correlations between AUC FGF-19 with AUC C-peptide (rho = 0.71; P = 0.001), AUC insulin (rho = 0.63; P = 0.001), but not with AUCs for triglycerides (TG) or glucose. Finally, treatment with the antioxidative compounds N-acetyl cysteine or MP865, but not with placebo, was associated with higher plasma FGF-19 (NAC and MP865 coefficients -0.28 and -0.23, P < 0.05, respectively). CONCLUSION: In advanced CKD, the postprandial FGF-19 response appears to be blunted, with partial normalization following antioxidative treatments. A blunted FGF-19 response was associated with impaired insulin and C-peptide signalling. PMID- 24179014 TI - A public health perspective on CKD and obesity. AB - End-stage renal disease (ESRD) is a growing health burden for global populations, which has generated keen interest in interventions to prevent or delay the progression of its antecedent chronic kidney disease (CKD). There are biologically plausible mechanisms that link increased adiposity to pathways of kidney injury, animal models of obesity-related kidney disease and specific glomerular disease that is observed in extremely obese humans. Further, individuals with progressive kidney disease and incident ESRD are more obese than their counterparts in the general population. These observations raise the consideration that population-based policies targeted at delaying progressive CKD should recommend interventions for treatment of obesity in these individuals. We examine this proposition first by describing the public health infrastructure that exists to translate CKD public health policy, illustrating it by examples familiar to the practicing nephrologist. Next, we suggest that, despite the evidence supporting an association between increased body weight and progressive CKD, it is premature to contemplate public health recommendations for weight reduction in CKD patients. This prematurity reflects the lack of strong evidence that reduction in body weight delays or prevents the progression of CKD and persistent uncertainty about the direction of the association between obesity and mortality in individuals with advanced kidney failure. We conclude by noting that this position is not that of therapeutic nihilism but rather a caution to approach weight management in CKD on an individual, patient-to-patient basis, and an emphasis for further randomized clinical trials to resolve these uncertainties. PMID- 24179015 TI - Body mass index and body fat distribution as renal risk factors: a focus on the role of renal haemodynamics. AB - Weight excess and/or central body fat distribution are associated with increased long-term renal risk, not only in subjects with renal disease or renal transplant recipients, but also in the general population. As the prevalence of weight excess is rising worldwide, this may become a main renal risk factor on a population basis, even more so because the risk extends to the overweight range. Understanding the mechanisms of this detrimental effect of weight excess on the kidneys is needed in order to design preventive treatment strategies. The increased risk associated with weight excess is partly attributed to associated comorbid conditions, such as hypertension, dyslipidaemia, insulin resistance and diabetes; however, current evidence supports a direct pathogenetic role for renal haemodynamics as well. Weight excess is associated with an altered renal haemodynamic profile, i.e. an increased glomerular filtration rate relative to effective renal plasma flow, resulting in an increased filtration fraction (FF). This renal haemodynamic profile is considered to reflect glomerular hyperfiltration and glomerular hypertension, resulting from a dysbalance between afferent and efferent arterial vasomotor balance. This unfavorable renal haemodynamic profile was found to be associated with renal outcome in experimental models and in human renal transplant recipients, and is associated with a blunted sodium excretion, and reversible by weight loss, renin-angiotensin aldosterone system blockade or by dietary sodium restriction. More recent evidence showed that a central body fat distribution is also associated with an increased FF, even independent of overall weight excess. In this review, we provide an overview on current literature on the impact of weight excess and central body fat distribution on the renal haemodynamic profile in humans, and its possible role in progressive renal damage. PMID- 24179016 TI - Adipokines promote chronic kidney disease. AB - The rapid growth in obesity worldwide contributes to an increase in metabolic syndrome and obesity-related kidney disease with an enhanced increased risk for chronic kidney disease, finally progressing to end-stage renal disease. Adipose tissue is a highly active endocrine organ secreting numerous factors that contribute to renal and cardiovascular complications. In renal damage, various adipokines are involved through mediating endothelial dysfunction, inducing oxidative stress and inflammation as well as stimulating renal sympathetic nervous activity, and it reduces cancellous bone but conversely increases cortical bone. Adipokines may also be involved in the development of renal anaemia. A balance exists between more protective adipokines (adiponectin) and factors mediating pathophysiological effects (angiotensin II, TNFalpha). Obesity may cause a disruption of this delicate balance, thereby inducing renal disease. Consequently, weight reduction and lifestyle changes affecting all components of the metabolic syndrome are essential to disrupt this vicious cycle. PMID- 24179017 TI - From the Editors: Research, theory and science in medical education. PMID- 24179018 TI - The fate of medical students with different levels of knowledge: Are the basic medical sciences relevant to physician competence? AB - Purpose - This study was designed to test the hypothesis that an early gap in knowledge of sciences basic to medicine could have a sustained negative effect throughout medical school and beyond.Method - A longitudinal prospective study of 4,437 students who entered Jefferson Medical College between 1972 and 1991 was conducted in which the students were divided into three groups. Group I consisted of 392 who failed at least one of the basic sciences courses in the first year of medical school, Group II was comprised of 398 who did not fail but had low first year grade-point averages; and 3,647 of the remaining sample were included in Group III. The groups were compared on retention and dismissal rates, medical school assessment measures, scores on medical licensing examinations, ratings of clinical competency in residency, board certification rates, and faculty appointments.Results - Significant differences were observed among the three groups confirming the hypothesis that students' level of knowledge in sciences basic to medicine early in medical school could predict later performance during medical school and beyond. Implications for early diagnosis of academic deficiencies, in better preparation of medical students, and in the assessment of clinical competency are discussed. PMID- 24179019 TI - Comparisons among three types of generalist physicians: Personal characteristics, medical school experiences, financial aid, and other factors influencing career choice. AB - A national survey of family physicians, general internists, and general pediatricians was conducted in the US to examine differences among the three groups of generalists physicians, with particular regard to the factors influencing their choice of generalist career. Family physicians were more likely to have made their career decision before medical school, and were more likely to have come from inner-city or rural areas. Personal values and early role models play a very important role in influencing their career choice. In comparison, a higher proportion of general internists had financial aid service obligations and their choice of the specialty was least influenced by personal values. General pediatricians had more clinical experiences either in primary care or with underserved populations, and they regarded medical school experiences as more important in influencing their specialty choice than did the other two groups. Admission committees may use these specialty-related factors to develop strategies to attract students into each type of generalist career. PMID- 24179020 TI - A large-scale study of the reliabilities of checklist scores and ratings of interpersonal and communication skills evaluated on a standardized-patient examination. AB - Checklists and rating scales are both used for assessing examinees in standardized-patient (SP) examinations. A common presumption, is that checklists are more objective than and hence superior to rating scales with respect to psychometric properties such as reliability. Recently, this presumption has been questioned and studies have been cited which support the clain that "objectified methods do not inherently provide more reliable scores." The purpose of this study was to further explore this issue, using a specially designed checklist/rating scale form for assessing interpersonal and communication skills. Methods. A 26-item checklist/rating scale form was developed, which consisted of five sections of 3 to 7 checklist items each, with a space provided at the end of each section for the SP to make a single global rating of the items in that section. Analyses were performed on data for 1,048 fourth-year medical students in the eight schools in the New York City Consortium, tested on the 7-case SP examination administered at The Morchand Center of Mount Sinai School of Medicine. Results/Conclusion. The intercase reliabilities for the checklist scores and ratings, respectively, were: 0.33 and 0.39 for eliciting information, 0.33 and 0.39 for non-verbal behavior, 0.55 and 0.52 for patient education, 0.48 and 0.45 for professional manner, and 0.49 and 0.52 for patient satisfaction. The correlations between the checklist scores and ratings for the five sections were 0.66, 0.60, 0.80, 0.69, and 0.75, respectively. The pattern of these results provides further support for the claim that "objectified" measures, like checklists, "do not inherently provide more reliable scores." PMID- 24179021 TI - The use of global ratings in OSCE station scores. AB - The Medical Council of Canada makes use of examiners' pass/borderline/fail judgments of candidates' performances in OSCE stations in defining cutting scores for these stations. This process assumes that there is consistency in the judgments of different examiners used in the same stations at different testing sites. This assumption was tested using the results of the fall 1994 administration of part 2 of the Medical Council of Canada Qualifying Examination. The Council anticipated using the examiner based global ratings as part of the OSCE station scores in the fall 1995 administration of the examination. In this study, the fall 1994 results were used to estimate to what extent test reliability would increase with the addition of the global ratings. PMID- 24179022 TI - Understanding and addressing cognitive bias in medical education. AB - Cognitive biases can impede the utilization of logical/statistical strategies in clinical decision-making. This paper reports on research and educational findings using the Inventory of Cognitive Biases in Medicine (ICBM). The ICBM was administered to groups of medical students before their clinical years and to practicing physicians to determine (a) the extent of cognitive bias in medical decision-making and whether experienced physicians differed from novices, (b) whether cognitive bias varied by medical speciality and (c) whether awareness of cognitive bias in medical decision-making could be taught. Preclinical medical students' mean score (41 %) was near the chance level (42%). While practicing physicians scored higher (49%), they also demonstrated considerable susceptibility to cognitive bias. Cognitive bias varied by medical speciality with internal medicine physicians (57%) scoring best on the ICBM. A controlled educational research study with preclinical medical students showed that learners exposed to a seminar on cognitive bias in medical decision-making scored better on the ICBM than their peers (55% vs. 41%, p < 0.001). Susceptibility to cognitive bias was found to be present substantially among both novices and experts in medicine, but carefully crafted educational strategies in both classroom and clinical settings may lessen the problem. PMID- 24179023 TI - The risks of thoroughness: Reliability and validity of global ratings and checklists in an OSCE. AB - OBJECTIVE: To compare checklists against global ratings for student performance on each station in an OSCE without the confounder of the global rating scorer having first filled in the checklist. METHOD: Subjects were 96 medical students completing their pre-clinical studies, who took an 8 station clinical OSCE. 39 students were assessed with detailed performance checklists; 57 students went through the same stations but were assessed using only a single global rating per station. A subset of 39 students were assessed by two independent raters. RESULTS: Inter-rater and inter-station reliability of the global rating was the same as for the checklist. Correlation with a concurrent multiple choice test was similar for both formats. CONCLUSION: The global rating was found to be as reliable as more traditional checklist scoring. A discussion of the validity of checklist and global scores suggests that global ratings may be superior. PMID- 24179024 TI - Reflections The problem based lecture course: An educational oxymoron? PMID- 24179025 TI - Toxicological assessment of refined naphthenic acids in a repeated dose/developmental toxicity screening test. AB - Naphthenic acids (NAs) are primarily cycloaliphatic carboxylic acids with 10 to 16 carbons. To characterize the potential of refined NAs (>70% purity) to cause reproductive and/or developmental effects, Sprague-Dawley rats (12/group) were given oral doses of 100, 300, or 900 mg/kg/d, beginning 14 days prior to mating, then an additional 14 days for males or through lactation day 3 for females (up to 53 days) in a repeated dose/reproductive toxicity test (Organization for Economic Cooperation and Development [OECD] 422). Potential mutagenic effects were assessed using Salmonella (OECD 471) and in in vivo micronucleus tests (OECD 474) using bone marrow taken from treated animals in the screening study described previously. Systemic effects included reduced terminal body weights, increased liver weights, and changes in a number of blood cell parameters. The overall no effect level for all target organ effects was 100 mg/kg/d. In the reproductive/developmental toxicity assessment, there were significant reductions in numbers of live born offspring in groups exposed to 300 and 900 mg/kg/d. The overall no effect level for developmental effects was 100 mg/kg/d. The data from the Salmonella and micronucleus tests provide evidence that refined NAs are not genotoxic. PMID- 24179026 TI - The toxicological properties of petroleum gases. AB - To characterize the toxicological hazards of petroleum gases, 90-day inhalation toxicity (Organization for Economic Cooperation and Development [OECD] 413) and developmental toxicity (OECD 414) tests were conducted with liquefied propane gas (LPG) at concentrations of 1000, 5000, or 10,000 ppm. A micronucleus test (OECD 474) of LPG was also conducted. No systemic or developmental effects were observed; the overall no observed adverse effect concentration (NOAEC) was 10,000 ppm. Further, there was no effect of LPG exposure at levels up to 10,000 ppm on micronucleus induction and no evidence of bone marrow toxicity. Other alkane gases (ethane, propane, n-butane, and isobutane) were then evaluated in combined repeated exposure studies with reproduction/development toxicity screening tests (OECD 422). There were no toxicologically important changes in parameters relating to systemic toxicity or neurotoxicity for any of these gases at concentrations ranging from 9000 to 16,000 ppm. There was no evidence of effects on developmental or reproductive toxicity in the studies of ethane, propane, or n butane at the highest concentrations tested. However, there was a reduction in mating in the high-exposure group (9000 ppm) of the isobutane study, which although not significantly different was outside the range previously observed in the testing laboratory. Assuming the reduction in mating to have been toxicologically significant, the NOAEC for the isobutane reproductive toxicity screening test was 3000 ppm (7125 mg/m(3)). A method is proposed by which the toxicity of any of the 106 complex petroleum gas streams can be estimated from its composition. PMID- 24179027 TI - Toxicological assessment of heavy straight run naphtha in a repeated dose/reproductive toxicity screening test. AB - Gasoline blending stocks (naphthas) are comprised of normal, iso- and cycloparaffins and aromatic hydrocarbons with carbon numbers ranging from C4 to C12. Heavy straight run naphtha (HSRN, CAS number 64741-41-9) was selected for toxicity screening because substances of this type contain relatively high levels (28%) of cycloparaffins by comparison to other naphtha streams and the data complement toxicity information on other gasoline blending streams. Rats were exposed by inhalation to wholly vaporized material at levels of approximately 100, 500, or 3000 parts per million (ppm) daily to screen the potential for systemic toxicity, neurotoxicity, reproductive toxicity, and developmental effects to postnatal day 4. All animals survived the treatment period. Principal effects of repeated exposure included increased liver weights in males and females, increased kidney weights in males, and histological changes in the thyroid, secondary to liver enzyme induction. These changes were not considered to be toxicologically meaningful and are not relevant to humans. There were no treatment-related effects in functional observation tests or motor activity; no significant reductions in fertility or changes in other reproductive parameters; and no evidence of developmental toxicity in offspring. The overall no observed adverse effect concentration was 3000 ppm (approximately 13, 600 mg/m(3)). In conclusion the HSRN effects on liver and kidney are consistent with the results of other studies of volatile fractions or other naphthas or formulated gasoline, and there were no HSRN effects on neurological developmental or reproductive parameters. PMID- 24179028 TI - Use of a statistical model to predict the potential for repeated dose and developmental toxicity of dermally administered crude oil and relation to reproductive toxicity. AB - Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general. PMID- 24179029 TI - The toxicological effects of heavy fuel oil category substances. AB - Heavy fuel oil (HFO) category substances are used to manufacture HFO, a product used in industrial boilers and marine diesel engines. Commercial HFOs and blending stream components are substances of complex and variable composition, composed of C20 to >C50 hydrocarbons, although lower molecular weight material may be added to reduce viscosity and improve flow characteristics. An HFO blending stream (catalytically cracked clarified oil [CCCO]) was tested for target organ and developmental toxicity in rats following repeated dermal administration at doses of 5, 25, or 50 mg/kg/d. In the repeated dose study, there was evidence of increased liver weights, reduced thymus weights, and reductions in hematological parameters with an overall no observed adverse effect level (NOAEL) of 5 mg/kg/d. In the developmental toxicity test, there were significant reductions in fetal survival, significant increases in resorption frequency, and significantly reduced fetal weights with an overall NOAEL of 5 mg/kg/d. These target organ and developmental effects are associated with the types and levels of aromatic constituents in these substances. Among HFO blending streams, CCCOs have the highest levels of aromatics and, because they produce the characteristic toxicological effects at the lowest levels, are considered as "reasonable worst-case examples" for this group of substances. Other HFO category members with lower levels of aromatics produce similar effects but have higher NOAELs. The potential for target organ and developmental effects of other HFO category members can be predicted from information on the types and levels of the aromatic constituents present in these substances. PMID- 24179030 TI - Characterization of the noncancer hazards of gas oils. AB - Gas oils, used to manufacture diesel fuel and residential heating oil, are complex hydrocarbon substances with carbon numbers of C9-C30 and boiling ranges of approximately 150 degrees C to 450 degrees C. Target organ (liver enlargement, reduced thymus weights, and reductions in hematological parameters) and developmental (reduced fetal viability, increased resorption frequency, and reduced fetal weights) effects are associated with aromatic constituents present in some gas oils. Two types of gas oils were tested for repeated-dose and developmental toxicity following repeated dermal administration. A blend of commercial diesel fuels containing 26% aromatics, primarily single-ring compounds, did not cause either target organ or developmental effects at levels up to 600 mg/kg/d. "Cracked" gas oils containing higher levels of aromatic constituents were also tested. Because of limited sample availability, 2 cracked gas oil samples were tested, one for systemic effects and the other for developmental toxicity. The sample tested in the repeated-dose toxicity study (81% aromatics including approximately 10% 3-ring compounds) produced increased liver weights, reduced thymus weights, and reductions in hematological parameters. The overall no observed adverse effect level (NOAEL) was 100 mg/kg/d. The sample tested for developmental toxicity (65% aromatics including approximately 5% 3-ring compounds) resulted in significant reductions in fetal survival, significant increases in resorption frequency, and significant reductions in fetal weights with an overall NOAEL of 100 mg/kg/d. In summary, gas oils may or may not cause target organ and/or developmental effects depending on the levels and types of aromatic constituents that they contain. PMID- 24179031 TI - Toxicological assessment of green petroleum coke. AB - Green petroleum coke is primarily inorganic carbon with some entrained volatile hydrocarbon material. As part of the petroleum industry response to the high production volume challenge program, the potential for reproductive effects was assessed in a subchronic toxicity/reproductive toxicity screening test in rats (OECD 421). The repeated-dose portion of the study provided evidence for dust accumulation and inflammatory responses in rats exposed to 100 and 300 mg/m(3) but there were no effects at 30 mg/m(3). In the reproductive toxicity screen, the frequency of successful matings was reduced in the high exposure group (300 mg/m(3)) and was not significantly different from control values but was outside the historical experience of the laboratory. The postnatal observations (external macroscopic examination, body weight, and survival) did not indicate any treatment-related differences. Additional tests conducted to assess the potential hazards to aquatic (fish, invertebrates, and algae) and soil dwelling organisms (earthworms and vascular plants) showed few effects at the maximum loading rates of 1000 mg coke/L in aquatic studies and 1000 mg coke/kg soil in terrestrial studies. The only statistically significant finding was an inhibition of algal growth measured as either biomass or growth rate. PMID- 24179032 TI - In vitro hydrolysis and transesterification of CDP323, an alpha4beta1/alpha4beta7 integrin antagonist ester prodrug. AB - We identified the enzyme(s) involved in the hydrolysis of the ethyl ester prodrug CDP323 (C28H29BrN403) and characterized its transesterification in the presence of ethanol with special emphasis on the risks of drug-drug interaction. The hydrolysis of CDP323 was evaluated in vitro using human liver and intestinal microsomes and recombinant human carboxylesterases (hCES1 and 2) and was shown to be approximately 20-fold higher in human liver microsomes when compared with human intestinal microsomes and in hCES1 when compared with hCES2. Nonspecific inhibitors of carboxylesterases significantly inhibited the hydrolysis of CDP323 (>80% inhibition) while specific inhibitors of CES2, acetylcholine esterase, arylesterase, and butyrylcholinesterase did not impair the hydrolysis reaction. The effect of ethanol on the kinetic parameters for hydrolysis was investigated, demonstrating that at high concentration (2%), Michaelis-Menten constant (Km), maximum velocity (Vmax), and intrinsic clearance (CLint) for the formation of the hydrolyzed product were decreased (~40%). The use of deuterated ethanol allowed more mechanistic investigations of the transesterification mechanism and showed that the intrinsic clearance based on parent loss was not impaired in the presence of alcohol. Overall, our data demonstrate that CDP323 is mainly hydrolyzed by hCES1 and is prone to transesterification in the presence of ethanol. Transesterification mechanisms compete with hydrolysis without impairing the overall clearance of the ester prodrug. Based on in vitro results, the risk of a clinically significant drug-drug interaction with ethanol is anticipated to be low. PMID- 24179033 TI - Restore the prominence of the medical ward round. PMID- 24179034 TI - Select the right medical students to be the next generation of generalists. PMID- 24179035 TI - Nominations open for The BMJ Awards 2014. PMID- 24179036 TI - Doctors should be encouraged to talk to colleagues who make errors, group says. PMID- 24179037 TI - Association between alcohol use and sexually transmitted infection incidence among kenyan women engaged in transactional sex. AB - Few prospective studies have evaluated the association between alcohol use and STI acquisition among African women. We examined the association between baseline drinking frequency and STIs in a cohort of Kenyan women reporting transactional sex. The association between alcohol use and STI differed significantly by HIV status. Among 139 HIV-positive women, STI acquisition was significantly associated with consuming 1-7 drinks/week and marginally associated with >=8 drinks/week in unadjusted analyses. However, no association between alcohol use and STIs was observed among 335 HIV-negative women. Addressing alcohol use within comprehensive HIV care may also reduce the burden of STIs among high-risk women. PMID- 24179038 TI - Nonomuraea guangzhouensis sp. nov., and Nonomuraea harbinensis sp. nov., two novel actinomycetes isolated from soil. AB - Two novel actinomycetes, designated strains NEAU-ZJ3(T) and NEAU-yn31(T), were isolated from soils in China and their taxonomic positions determined by a polyphasic approach. Key morphological and chemotaxonomic properties of the two strains were consistent with the description of the genus Nonomuraea. The G+C contents of strains NEAU-ZJ3(T) and NEAU-yn31(T) were determined to be 67.4 and 68.0 %, respectively. Phylogenetic analysis using 16S rRNA gene sequences indicated that the two strains should be classified in the genus Nonomuraea. The 16S rRNA gene sequence of strain NEAU-ZJ3(T) showed it to be most closely related to Nonomuraea salmonea DSM 43678(T) (98.27 %), Nonomuraea endophytica YIM 65601(T) (98.23 %) and Nonomuraea candida HMC10(T) (98.08 %), and that of strain NEAU-yn31(T) to Nonomuraea ferruginea IFO 14094(T) (99.08 %) and N. candida HMC10(T) (98.01 %). Furthermore, a combination of DNA-DNA hybridization results and some phenotypic characteristics indicated that the two strains can be distinguished from each other and their phylogenetically closest relatives. Thus, strains NEAU-ZJ3(T) and NEAU-yn31(T) represent two novel species of the genus Nonomuraea, for which the names Nonomuraea guangzhouensis sp. nov. and Nonomuraea harbinensis sp. nov. are proposed. The type strains are NEAU-ZJ3(T) (=CGMCC 4.7101(T) = DSM 45889(T)) and NEAU-yn31(T) (=CGMCC 4.7106(T) = DSM 45887(T)), respectively. PMID- 24179039 TI - Salinispora arenicola from temperate marine sediments: new intra-species variations and atypical distribution of secondary metabolic genes. AB - The obligate marine actinobacterium Salinispora arenicola was successfully cultured from temperate sediments of the Pacific Ocean (Tosa Bay, offshore Kochi Prefecture, Japan) with the highest latitude of 33 degrees N ever reported for this genus. Based on 16S rRNA gene sequence analysis, the Tosa Bay strains are of the same phylotype as the type strain S. arenicola NBRC105043. However, sequence analysis of their 16S-23S rRNA intergenic spacer (ITS) revealed novel sequence variations. In total, five new ITS sequences were discovered and further phylogenetic analyses using gyrase B and rifamycin ketosynthase (KS) domain sequences supported the phylogenetic diversity of the novel Salinispora isolates. Screening of secondary metabolite genes in these strains revealed the presence of KS1 domain sequences previously reported in S. arenicola strains isolated from the Sea of Cortez, the Bahamas and the Red Sea. Moreover, salinosporamide biosynthetic genes, which are highly homologous to those of Bahamas-endemic S. tropica, were detected in several Tosa Bay isolates, making this report the first detection of salinosporamide genes in S. arenicola. The results of this study provide evidence of a much wider geographical distribution and secondary metabolism diversity in this genus than previously projected. PMID- 24179040 TI - Diminazene aceturate (Berenil) modulates LPS induced pro-inflammatory cytokine production by inhibiting phosphorylation of MAPKs and STAT proteins. AB - Although diminazene aceturate (Berenil) is widely used as a trypanolytic agent in livestock, its mechanisms of action remain poorly understood. We previously showed that Berenil treatment suppresses pro-inflammatory cytokine production by splenic and liver macrophages leading to a concomitant reduction in serum cytokine levels in mice infected with Trypanosoma congolense or challenged with LPS. Here, we investigated the molecular mechanisms through which Berenil alters pro-inflammatory cytokine production by macrophages. We show that pre-treatment of macrophages with Berenil dramatically suppressed IL-6, IL-12 and TNF-alpha production following LPS, CpG and Poly I:C stimulation without altering the expression of TLRs. Instead, it significantly down-regulated phosphorylation of mitogen-activated protein kinases (p38, extracellular signal-regulated kinase and c-Jun N-terminal kinases), signal transducer and activator of transcription (STAT) proteins (STAT1 and STAT3) and NF-kB p65 activity both in vitro and in vivo. Interestingly, Berenil treatment up-regulated the phosphorylation of STAT5 and the expression of suppressor of cytokine signaling 1 (SOCS1) and SOCS3, which are negative regulators of innate immune responses, including MAPKs and STATs. Collectively, these results show that Berenil down-regulates macrophage pro inflammatory cytokine production by inhibiting key signaling pathways associated with cytokine production and suggest that this drug may be used to treat conditions caused by excessive production of inflammatory cytokines. PMID- 24179042 TI - A substantial tax on sugar sweetened drinks could help reduce obesity. PMID- 24179044 TI - Experience with pornography: Rapists, pedophiles, homosexuals, transsexuals, and controls. AB - An interview designed to assess a respondent's experience with erotic material in photographs, films, and books, during adolescence and adulthood, was administered to convicted male rapists, pedophiles, homosexuals, transsexuals, heavy pornography users, and two nondeviant contrast groups. One nondeviant group was composed of whites matched for the sex offender group; the other was composed of ghetto and middle-class blacks. Adolescent exposure to erotica was significantly less for all deviant and offender groups compared to the nondeviants. During adulthood, the sex offenders and transsexuals continued to report less exposure to erotic stimuli than controls. The homosexuals and users, however, both report greater exposure during adulthood. As adolescents, the control group, rapists, and heavy users were excited to masturbate by the erotic materials more than the other groups. As adults, the controls and rapists showed a sharp decrease in being excited to masturbate to erotica while the users' rate remained high and the homosexuals' rate rose. Less than a quarter of the respondents in any group imitated sexual behavior seen in the erotic material immediately or shortly after its viewing. The hypothesis that extent of exposure during adolescence to erotica is positively associated with the later emergence of sexual pathology is not borne out by this study. The nondeviant, non-sex-offender groups sampled had had significantly greater exposure to erotic materials during adolescence than the deviants, convicted sex offenders, or heavy adult users of pornography. PMID- 24179045 TI - The bisexual identity of transsexuals: Two case examples. AB - Clinical data from two cases of male transsexualism, a child and an adult, illustrate the nature of the bisexuality typical of such patients. The first, an 8-year-old boy whose desire to be a girl is seen in his constant dressing and acting like a girl, confirms in play therapy, story telling, and drawings his fantasies of being a female. However, these fantasies are never free of the knowledge that he has a penis and a male identity as well. That this bisexuality persists into the transsexual's adulthood is exemplified in the fantasy life of the second case, a 30-year-old operated male transsexual. The memory, "I was once a boy" never quite fades away; no matter how successfully the passing as a woman is managed, she cannot rid herself of the secret maleness. The belief in such patients that they are fundamentally female though possessed of an anatomically normal male body will persist through adulthood, unaltered by "sex change," by hormonal or surgical procedures, or by living successfully for years as a woman. This bisexuality is conscious, painful, and not assuaged by symptom formation, forgetting, or other defenses that would remove the conscious sense of having two sexes. In the child the unwanted sense of belonging to the male sex, which causes a disquieting undercurrent, can be used as the base upon which a more solid sense of masculinity can be built. Unfortunately, for the adult transsexual the balance of the "two-sexed" awareness cannot be tipped to a willingness to live as a man; despite treatment aimed at making them more manly, adult transsexuals retain their wish to be female-and their secret knowledge that, after all the operations and female hormones, a male part remains untouched within. PMID- 24179043 TI - Overall and income specific effect on prevalence of overweight and obesity of 20% sugar sweetened drink tax in UK: econometric and comparative risk assessment modelling study. AB - OBJECTIVE: To model the overall and income specific effect of a 20% tax on sugar sweetened drinks on the prevalence of overweight and obesity in the UK. DESIGN: Econometric and comparative risk assessment modelling study. SETTING: United Kingdom. POPULATION: Adults aged 16 and over. INTERVENTION: A 20% tax on sugar sweetened drinks. MAIN OUTCOME MEASURES: The primary outcomes were the overall and income specific changes in the number and percentage of overweight (body mass index >= 25) and obese (>= 30) adults in the UK following the implementation of the tax. Secondary outcomes were the effect by age group (16-29, 30-49, and >= 50 years) and by UK constituent country. The revenue generated from the tax and the income specific changes in weekly expenditure on drinks were also estimated. RESULTS: A 20% tax on sugar sweetened drinks was estimated to reduce the number of obese adults in the UK by 1.3% (95% credible interval 0.8% to 1.7%) or 180,000 (110,000 to 247,000) people and the number who are overweight by 0.9% (0.6% to 1.1%) or 285,000 (201,000 to 364,000) people. The predicted reductions in prevalence of obesity for income thirds 1 (lowest income), 2, and 3 (highest income) were 1.3% (0.3% to 2.0%), 0.9% (0.1% to 1.6%), and 2.1% (1.3% to 2.9%). The effect on obesity declined with age. Predicted annual revenue was L276m (L272m to L279m), with estimated increases in total expenditure on drinks for income thirds 1, 2, and 3 of 2.1% (1.4% to 3.0%), 1.7% (1.2% to 2.2%), and 0.8% (0.4% to 1.2%). CONCLUSIONS: A 20% tax on sugar sweetened drinks would lead to a reduction in the prevalence of obesity in the UK of 1.3% (around 180,000 people). The greatest effects may occur in young people, with no significant differences between income groups. Both effects warrant further exploration. Taxation of sugar sweetened drinks is a promising population measure to target population obesity, particularly among younger adults. PMID- 24179046 TI - Lower-class sexuality: Some emotional and social aspects in West German males and females. AB - Emotional and social aspects of lower-class sexuality in West Germany are examined on the basis of results of interviews with 150 male and 150 female, single, 20-21-year-old, unskilled or semi-skilled workers from six large cities. Particular attention was given to the relation between sexuality and love, the significance of fidelity and virginity, partner mobility, mutuality of sexual relations, attitudes to marriage and family, double standards and gender roles, emotional reactions to coitus, as well as the experience of orgasm in the female. A comparison between American and Scandinavian patterns of lower-class sexuality shows that the West German pattern is largely congruent with the Scandinavian pattern. PMID- 24179047 TI - Psychosexual development, maternalism, nonpromiscuity, and body image in 15 females with precocious puberty. AB - Fifteen females with a history of idiopathic sexual precocity were selected without known sampling bias. They had been followed for as long as 18 years. They showed various behavioral characteristics as a group, but were also individually unique. If the IQ permitted, they benefited socially from school acceleration. Left to their own devices, the majority preferred friends nearer to them in physique age rather than chronologic age. Play interests, though influenced by the age of playmates, showed no features unique to the precocious onset of hormonal puberty. About half of the girls had occasional moody or depressed spells and wanted to be left alone. Maternalistic interests were strongly represented; only one girl was a tomboy. Masturbation and sexual play in childhood were rarely confirmed, and in no instances were totally contrary to family or community mores. No consistent progression of erotic dream content was discerned. Dreams of having a baby were rare, but antedated intercourse dreams, which were also rarely reported and did not include sensations of climax. Whereas the youngest age of having a serious boyfriend was 8 years, and the youngest age of intercourse, 11, the majority of girls did not report romantic and sexual involvements before the middle teenage years or later. In the three instances of marriage, the youngest was at age 21. Motherhood has so far been achieved by only one patient. She delivered her first child at age 11. The visible appearance of early sexual development and early advanced statural growth created a problem in childhood human relationships for most of the girls, regardless of what they said, and regardless of their skill or ineptitude in handling it. They all benefited even from minimal counseling, as did their parents. Early appearance of physical sexual development does not automatically lead to premature engagement in erotic activity or promiscuous sexual behavior. Such activity and behavior require appropriate experience and facilitating knowledge of erotic opportunities. PMID- 24179049 TI - Hypersexuality, anti-androgens, and testicular function. PMID- 24179048 TI - The role of gonadal hormones in the sexual behavior of the rhesus monkey and human: A literature survey. AB - The importance of the gonads for the display of sexual behavior has been realized for hundreds of years, yet only within the last century has active research in this area been conducted. The present communication surveys the literature concerned with the role of gonadal hormones in the activation, maintenance, and control of sexual behavior in the rhesus monkey (Macaca mulatta)and human. To place this topic in perspective the survey begins with a description of the normative aspects of sexual behavior and the endocrine events which correlate with the cyclic behaviors of the female. Building on this base the survey then focuses on descriptions of the effects on sexual behavior of the removal of hormones in adulthood and of the replacement of these hormones with either heteroor homotypic hormones. PMID- 24179050 TI - Male transsexualism: An endocrine study. PMID- 24179051 TI - A statement of purpose. PMID- 24179052 TI - Prevalence and patterns of alcohol misuse in a community-dwelling elderly sample in Brazil. AB - OBJECTIVE: The aim of this study was to estimate prevalence and patterns of lifetime alcohol misuse. METHOD: This was a cross-sectional study of a representative sample of 1,078 individuals aged 60 or more. Structured interview included sociodemographic, lifestyle, health data, and the five alcohol misuse screening questions of the Self-Reporting Questionnaire. RESULTS: Prevalence of misuse was 6.5%. Men, aged 60 to 69, low educational level, separated/divorced, and tobacco smoking were independently associated with lifetime alcohol misuse. Odds ratios show increasing association with levels of alcohol misuse groups in males, low-educated, and tobacco users. Persons aged 60 to 69, 4 to 7 education years, and non-White ethnicity were significantly associated with the major alcohol misuse score. DISCUSSION: Younger elderly were more exposed to alcohol than previous cohorts. Thus, problems with alcohol in old age will possibly increase as they grow older. The results of this study call attention to a field of lacking evidence in alcohol-related problems of older persons. PMID- 24179054 TI - The establishment of core gender identity in normal girls. I. (a) introduction; (b) development of the ego capacity to differentiate. AB - There has been a gradual shift from Freud's point of view that there is no femininity until the phallic phase. Modification of Freud's view on the onset of femininity is furthered by establishing that differences between boys and girls are observable in the preoedipal period and by studying the origin of a girl's sense of femaleness, i.e., her core gender identity. It is not essential whether we call this early development of the girl's sense of her femaleness core gender identity, earliest gender identity,or precursors of gender identity.Several studies confirm it is an essential foundation on which subsequent gender identity is built, Its establishment is normally well under way and sometimes irreversible by age 3 and more firmly secured in the fourth and fifth years. Of the multiple factors-biological (including its expression as instinctual drive), genetic, and experiental-contributing to core gender identity, the ego capacity to differentiate is traced and stressed as a necessary condition. The psychoanalytic and relevant nonpsychoanalytic literature is reviewed. Cognitive functions play a more significant role in core gender identity formation than previously believed and probably are more universally contributory at this early age (before 3) than identification mechanisms, envy of the male genitals, or castration anxiety. Ascription of gender at birth followed by the environmental confirmation impinging on progressively maturating cognitive capacities in the child would then normally be the organizer of gender identity, although definitely not the sole forces molding it. PMID- 24179053 TI - Area deprivation, individual socioeconomic status and low vision in the EPIC Norfolk Eye Study. AB - BACKGROUND: Poor vision is associated with lower socioeconomic status, but less is known about its relationship to area deprivation. METHODS: The European Prospective Investigation into Cancer and Nutrition study Norfolk Eye Study was a cross-sectional study of 8563 participants with completed eye examinations. Logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was measured using standard protocols and low vision (LV) was defined as Snellen equivalent (VA) <=6/12 in the better eye. Uncorrected refractive error (URE) was defined as improvement of VA by 2 logarithm of the minimum angle of resolution lines with pinhole. The lowest 5% of index of multiple deprivation rank was used to define the most deprived areas. The index of multiple deprivation is a composite measure using routine data from seven domains of deprivation to identify the most disadvantaged areas in England. Logistic regression was used to examine univariable and multivariable associations with LV. RESULTS: Ninety-six participants with missing data were excluded, leaving 8467 for analysis (98.9%). The mean age of the study group was 68.7 years (SD=8.1, range=48-92), with 55.1% women. LV was present in 263 participants (3.1%, 95% CI 2.7 to 3.5%). LV was associated with deprivation after adjusting for age, sex, education, social class and cataract surgery (OR=1.7, 95% CI 1.1 to 2.6, p=0.03), but this effect was mitigated by additionally adjusting for URE (OR=1.5, 95% CI 1.0 to 2.4, p=0.09). CONCLUSIONS: People with LV are more likely to live in the most deprived areas; this association was independent of socioeconomic status and partly mediated by URE. Targeting URE in deprived areas may reduce health inequalities associated with LV. PMID- 24179055 TI - The establishment of core gender identity in normal girls. II. How meanings are conveyed between parent and child in the first 3 years. AB - Observations of a normal female child from birth to 3 years are selected to illustrate some of the ways early gender identity is established. These and observations of other normal children suggest that meanings conveyed by parents and identification processes contribute to the establishment of significant beginnings of gender identity before the phallic period and before penis envy, castration anxiety, and the oedipal complex contribute their main influence. PMID- 24179057 TI - Legal aspects of transsexualism. PMID- 24179056 TI - Fetal feminization and female gender identity in the testicular feminizing syndrome of androgen insensitivity. AB - Interview data on aspects of sex and eroticism from a sample of 10 chromosomally male (XY) patients with the complete testicular feminization (androgen insensitivity) syndrome and from a sample of 23 patients with the late-treated adrenogenital syndrome showed marked differences. Homosexual experiences and/or dreams were lacking in the androgen-insensitive group as compared with the adrenogenital group (p[Symbol: see text]0.01).The androgen-insensitive group reported lower frequency of sexual arousal from visual stimuli than did the adrenogenital group (p[Symbol: see text]0.05).Findings on different aspects of sexual behavior suggest a tendency for the androgen-insensitive patients as a group to have a lower sex drive, to be less keenly aware of their sex drive, to be less assertive in heterosexual relations, and to be less versatile in coitus than the adrenogenital patients. No case of exclusive lesbianism, transsexualism, or transvestism was reported from either patient group. Although the two groups differed in sexual and erotic behavior, both were within the range of what in our culture is accepted as feminine. Nonetheless, the androgen-insensitive patients conformed more closely to the conventional feminine stereotype. Regarding explicit satisfaction with female sex role and with cosmetic and clothing interests, the androgen-insensitive group was characteristically feminine. Findings on the Draw-a-Person Test and the Guilford-Zimmerman Temperament Survey are compatible with the results of normal females, but are in sharp contrast with those of normal males. Interview and psychometric data thus concur in showing the androgen-insensitive patients to be unmistakably feminine in behavior and outlook. Their femininity is best conceived of as a product of hormonal nonandrogenization, prenatally and later, in combination with the social experiences of rearing and development, after initial assignment as a girl. PMID- 24179058 TI - Indications for sex reassignment surgery. PMID- 24179059 TI - Prefatory remarks on outcome of sex reassignment in 24 cases of transexualism. PMID- 24179060 TI - Diagnosis and treatment of gender identity disorders during childhood. PMID- 24179061 TI - Maturational variables influencing sexual posturing in infant monkeys. PMID- 24179062 TI - Changes in the sexual behavior of adolescents of Czechoslovakia and Germany. PMID- 24179063 TI - Studies on neurogenic disorders of sexual function in 56 paraplegic men with complete irreversible injuries of the spinal cord or the cauda equina. PMID- 24179064 TI - Effect of calcium phosphate-based fillers on the structure and bonding strength of novel gelatin-alginate bioadhesives. AB - Interest in soft and hard tissue adhesives as alternatives for conventional wound closing and bone fixation applications has increased in recent decades as a result of numerous possible advantages such as better comfort and lower cost. A novel bioadhesive based on the natural polymers GA has recently been developed and studied in our laboratory. Hydroxyapatite and tricalcium phosphate are two bioactive ceramics known for their ability to enhance bone regeneration. In the current study, these two bioactive fillers were incorporated into the bioadhesive at concentrations of 0.125, 0.25 and 0.5% w/v, and their effects on the resulting adherence properties to soft and hard tissues were studied. Porcine skin and cortical portions of bovine femurs were used as soft and hard tissue specimens, respectively. The bonding strength was evaluated using an Instron universal testing machine in tensile mode, and the microstructure analysis was based on environmental scanning electron microscope observations. Both bioactive fillers were found to have a reinforcing effect on the adhesives, significantly improving their adhesion to soft tissues in certain concentrations. The best bonding strength results were obtained for 0.25% hydroxyapatite and 0.5% w/v tricalcium phosphate-18.1 +/- 4.0 and 15.2 +/- 2.6 kPa, respectively, compared with 8.4 +/- 2.3 kPa for adhesive with no fillers. The improved adherence is probably related to the stiffness of the insoluble hydroxyapatite and tricalcium phosphate particles which reinforce the adhesive. These particles can clearly be observed in the environmental scanning electron microscope analysis. The potential of these fillers to increase the bonding strength of the adhesive to hard tissues was also demonstrated. Hydroxyapatite and tricalcium phosphate thus improve our new gelatin-alginate bioadhesives, which can be used for both soft and hard tissue adhesive applications. PMID- 24179065 TI - Six homosexual siblings. AB - A family consisting of several homosexual siblings is reported. All ten of the siblings in this family were to some degree homosexually experienced. Six were homosexual or predominantly homosexual, and five had a homosexual identity. The sex composition of the family was three females and seven males. Of the three females, one was homosexual, one was bisexual, and one had had some homosexual experience. There was one set of male dizygotic twins concordant for homosexuality in the family. All ten siblings were exposed to relatively similar family dynamics. The father's behavior toward the children and his wife was characterized by hostility, violence, and alcoholism. He was eventually murdered when the youngest child was 6 years old. The mother demonstrated qualities that were essentially opposite those of the father. She was described as affectionate and loving toward all the children, and she did not display violent behavior. The male homosexual sibling who was interviewed displayed a strong identification with his mother via a feminine self-identification, the adoption of the housewife role in a homosexual marriage, and the adoption of the passive role in anal intercourse. Only one other multiple homosexual sibling family has been reported in the scientific literature. This family consisted of 14 siblings, 11 male and three female. The four homosexual siblings in this family were all male and consisted of two sets of dizygotic twins. The behavior of the parents of this family was quite similar to the behavior of the parents in this study-a hostile and violent father and an affectionate and loving mother. These two multiple homosexual sibling families provide support for theories that emphasize the importance of early family relationships in the development of a homosexual adaptation. It is held that multiple homosexual sibling families can be employed as strategic data in testing various etiological theories of homosexuality. PMID- 24179067 TI - Characterization of a self-designated transsexual population. AB - Since its founding, the Gender Identity Clinic of the Johns Hopkins Medical Institutions has been contacted by 1034 correspondents designating themselves as transsexuals and requesting sex conversion surgery. This group was surveyed using a simple screening questionnaire. Five hundred and ninety-nine respondents partially completed or completed the questionnaire and are characterized along demographic, medical, psychiatric, and personal parameters. PMID- 24179066 TI - Monoamines and ovarian hormone-linked sexual and emotional changes: A review. AB - Emotional upsets related to changes in ovarian hormones are highly prevalent and are responsible for psychiatric morbidity and mortality. Significant increases in acute psychiatric hospitalizations, suicidal activity, and other psychopathology occur during the premenstruum and during menstruation. This paper reviews evidence indicating that menstrual cycle psychopathology may be mediated by the effects of estrogen, progesterone, and possibly the renin-angiotensin-aldosterone system on the brain monoamines, norepinephrine, dopamine, and serotonin. During the menstrual cycle, psychopathology often begins with the onset of luteal estrogen-progesterone-angiotensin-aldosterone secretion and intensifies as these hormone levels later fall, prior to and during menstruation. Aldosterone is reported elevated in cases of premenstrual tension syndrome. There are numerous reports of affective upsets occurring with the use of estrogen-progestin oral contraceptives and following their withdrawal. Contraceptives stimulate the renin angiotensin-aldosterone system and are reported useful in alleviating premenstrual-menstrual emotional upsets and postpartum depressive episodes. Affective lability, prevalent at parturition, occurs when estrogen, progesterone, and aldosterone levels are first high and later falling. Exogenous estrogen and progesterone profoundly affect mating activity in castrated rhesus monkeys, and cyclic fluctuations in sexual activity in humans may occur during the menstrual cycle. Much information links manic and depressive reactions with alterations in brain monoamines. Lithium, monoamine oxidase inhibitors, and tricylic antidepressants, specifically used to treat affective disorders, are reported useful in treating ovarian hormone-linked upsets. Similarities exist between changes in animal behavior caused by drugs altering affective states and the effects of ovarian hormones. Like certain antidepressants, estrogen induces hyperactivity in rats. Like reserpine, progesterone exhibits sedative and soporific effects. Sexual behavior in female rats is reported linked to changes in brain monoamines. Agents increasing brain monoamine levels and availability decrease mating responses, and monoamine depletors, such as reserpine may be substituted for progesterone in activating mating behavior. Serotonin and dopamine appear to be important in the regulation of ovulation. Brain norepinephrine varies with the phases of the rat estrus cycle. Castration increases brain norepinephrine and decreases brain dopamine. Exogenous estrogen decreases rat brain norepinephrine content. The monoamine-destroying enzymes, monoamine oxidase, and catechol O-methyl transferase are affected by ovarian steroids and show fluctuating levels during the reproductive cycle. The effects of reserpine, monoamine oxidase inhibitors, tricyclic antidepressants, and lithium on monoamines in neurophysiological preparations have been used as evidence supporting theories linking monoamine changes with human affective disorders. Estrogen, progesterone, and angiotensin also exhibit effects on in vitromonoamine systems. Like the tricyclic antidepressants, uptake of norepinephrine and dopamine by nerve endings is inhibited in the presence of estrogen, progesterone, and angiotensin. As with reserpine, the flow of these monoamines from nerve endings is increased by progesterone. Estrogen slows the flow of norepinephrine from nerve endings and decreases the electrically induced release of serotonin and norepinephrine from brain slices. The above information provides clues that ovarian hormone-linked psychopathology, like affective disorders in general, may be related to alterations in brain monoamines. PMID- 24179068 TI - Dizygotic twin with XXYY chromosome aneuploidy and diffuse sexual orientation, with review of 30 XXYY cases. AB - A case of XXYY genotype with sexual psychopathology is described, and 30 previous cases are reviewed. Consideration of family history emphasizes a statistically high rate of twinning and firstborns. Review of the clinical appearance of the patients described indicates that obesity, tallness, and feminine features are more common in association with the XXYY karyotype but by no means pathognomonic of it. The incidence of other pathology, particularly cardiovascular and orthopedic conditions and hypogonadism, appears to be high in a group of XXYY patients. Psychometric evaluation of these patients suggests that low intelligence is a feature and that the incidence of EEG abnormalities may be high, but that personality, delinquency, aggression, and sex interest are not specific for this group. PMID- 24179070 TI - Interpersonal relationships of female patients with sexual disorders as assessed by Leary's test. PMID- 24179069 TI - Fetal hormones and the brain: Effect on sexual dimorphism of behavior-A review. AB - Experimental animal studies of the influence of prenatally or neonatally administered sex hormones on subsequent manifestations of sexual behavior implicate an organizing action of sex hormones and related substances on the brain, probably in the region of the hypothalamus. The rule would appear to be that female-male bipotentiality applies initially, prior to the influence of any sex hormone in the course of brain development. Bipotentiality would appear to persist when the early hormonal environment is feminine, so that either the feminine or the masculine component of mating behavior can be elicited in adulthood, dependent, among other things, on whether the eliciting hormone is estrogen or androgen. Bipotentiality is resolved in favor of unipolar masculinity of mating behavior if the early hormonal influence at the critical differentiating period is androgenic. The feminine component is then inhibited. Once this is accomplished, the feminine component will, in many, though perhaps not all species, be elicited only under special conditions, for example, direct brain stimulation, or not at all. In the course of normal differentiation, the initial completeness of inhibition of feminine potential varies across species. Thus, it is more complete in the rat than the hamster. In man it is probably not very complete, and is perhaps individually variable, as well. PMID- 24179071 TI - Sexual behavior and its development in pedophilic men. PMID- 24179072 TI - Clinical implications of new-onset left bundle branch block after transcatheter aortic valve replacement: analysis of the PARTNER experience. AB - AIMS: Cardiac conduction disturbances, including a left bundle branch block (LBBB), occur frequently following transcatheter aortic valve replacement (TAVR) and may be associated with adverse clinical events. This analysis examines the incidence and implications of new onset, persistent LBBB in patients undergoing TAVR with a balloon-expandable valve. METHODS AND RESULTS: Patients undergoing TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) trial and continued access registries with baseline and discharge/7-day electrocardiograms were included. Prior permanent pacemaker implantation (PPI) and baseline intraventricular conduction abnormalities were exclusion criteria. Predictors of new LBBB were identified and outcomes compared between patients with and without new LBBB. New LBBB occurred in 121 of 1151 (10.5%) patients and persisted in more than half at 6 months to 1 year. The only predictor of new LBBB was prior coronary artery bypass grafting. New LBBB was not associated with significant differences in 1-year mortality, cardiovascular mortality, repeat hospitalization, stroke, or myocardial infarction. However, it was associated with increased PPI during hospitalization (8.3 vs 2.8%, P = 0.005) and from discharge to 1 year (4.7 vs. 1.5%, P = 0.01). The ejection fraction failed to improve after TAVR in patients with new LBBB and remained lower at 6 months to 1 year (52.8 vs. 58.1%, P < 0.001). CONCLUSION: Persistent, new-onset LBBB occurred in 10.5% of patients without intraventricular baseline conduction who underwent TAVR in the PARTNER experience. New LBBB was not associated with death, repeat hospitalization, stroke, or myocardial infarction at 1 year, but was associated with a higher rate of PPI and failure of left ventricular ejection fraction to improve. PMID- 24179074 TI - Improving the interpretation of the athlete's electrocardiogram. PMID- 24179073 TI - Association between myocardial substrate, implantable cardioverter defibrillator shocks and mortality in MADIT-CRT. AB - OBJECTIVE: The aim of the present study was to assess a possible association between myocardial substrate, implantable cardioverter defibrillator (ICD) shocks, and subsequent mortality. METHODS: Within the multicentre automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) population (n = 1790), we investigated the association between myocardial substrate, ICD shocks and subsequent mortality using multivariate Cox regression analyses and landmark analyses at 1-year follow-up. RESULTS: The 4-year cumulative probability of ICD shocks was 13% for appropriate shock and 6% for inappropriate shock. Compared with patients who never received ICD therapy, patients who received appropriate shock had an increased risk of mortality [HR = 2.3 (1.47-3.54), P < 0.001], which remained increased after adjusting for echocardiographic remodelling at 1 year (HR = 2.8, P = 0.001). Appropriate anti tachycardia pacing (ATP) only was not associated with increased mortality (P = 0.42). We were not able to show an association between inappropriate shocks (P = 0.53), or inappropriate ATP (P = 0.10) and increased mortality. Advanced myocardial structural disease, i.e. higher baseline echocardiographic volumes and lack of remodelling at 1 year, was present in patients who received appropriate shocks but not in patients who received inappropriate shocks or no shocks. CONCLUSION: In the MADIT-CRT study, receiving appropriate ICD shocks was associated with an increased risk of subsequent mortality. This association was not evident for appropriate ATP only. These findings, along with advanced cardiac structural disease in the patients who received appropriate shocks, suggest that the compromised myocardium is a contributing factor to the increased mortality associated with appropriate ICD shock therapy. Clinical trials.gov identifier: NCT00180271. PMID- 24179075 TI - Advanced glycation endproducts and plaque instability: a link beyond diabetes. PMID- 24179076 TI - Participants in urban Mexican male homosexual encounters. AB - Preliminary data are presented on 53 urban Mexican males interviewed during 1970 1971 in a study of homosexual encounters in a large Mexican city. These data are compared with data from recent studies in the United States and England of male homosexual behavior. Although preliminary and limited, the Mexican data indicate that cultural factors are important determinants of life styles and sex practices of homosexual males. Forty-eight of the 53 (90%) preferred and usually practiced anal intercourse, four preferred oral contacts, and one preferred mutual masturbation. Interviewees were also grouped according to major type of sex activity during the first sustained year of homosexual activity after puberty. One intragroup comparison indicates significant differences between anal active and anal passive interviewees. For example, as children anal passive subjects had significantly more homosexual contacts with adults; they also considered themselves more effeminate and as children were more involved with female sex typed activities. Comparison of data from the English and United States studies with the present data suggests that preference for a particular sexual technique is not as developed in the former two countries; when there is a preference, it is not usually for anal intercourse. PMID- 24179077 TI - Mate selection among second generation kibbutz adolescents and adults: Incest avoidance and negative imprinting. AB - Premarital sexual behavior and marriage patterns were investigated in Israeli kibbutzim. All adolescents and adults of the second generation (N =65)in one kibbutz were studied. There were no cases of heterosexual activity between any two native adolescents of the same peer group and no cases of marriage between any two members of the same peer group. The avoidance was completely voluntary. Among 2769 marriages contracted by second generation adults in all kibbutzim, there were no cases of intra-peer group marriage. These findings could represent a case of negative imprinting whereby collective peer group education which includes an incessant exposure to peers from the first days of life and an unimpeded tactile relationship among the peers between ages 0-6 results in sexual avoidance and exogamy. PMID- 24179078 TI - The recording of physiological evidence of genital arousal in human males and females. AB - Eight methods for the recording of erections of men and women, chiefly during sleep, are described as an introduction to a series of publications about objective assessment of sexual behavior. Ohlmeyer et al. (1944 and 1947)performed kymographic recordings. Fisher et al. (1965)recorded objectively with an EEG apparatus and developed the phalloplethysmograph (a polyvinyl tube filled with water, twisted around the penis), a thermistor to record changes of penile skin temperature, and a mercury strain gauge (modified from Whitney, 1949). Johnson and Kitching (1968) used an open annealed metal ring, connected by four strain gauges with a Wheatstone bridge circuit. Jovanovic (1967) developed the phallograph for the recording of erections of men, the kolpograph to measure vaginal contractions for the recording of changes of the genital organs of women (Jovanovic, 1970), and the clitorograph (a thermistor similar to that of Fisher et al.,1965). PMID- 24179079 TI - Two monozygotic (identical) twin pairs discordant for gender identity. AB - Two pairs of monozygotic twins discordant for gender identity are described. The first set are 8-year-old males, one of whom enjoys doll play, cross-dressing, and taking the role of a female in fantasy games. His brother shows no feminine behavior, enjoys sports, and is more masculine in gestures and speech. The second set are 24-year-old females, one of whom wants to undergo sex-change surgery to male status. Her cotwin is a feminine woman desirous of marrying and bearing children. Differential childhood experiences are described for the cotwins. These highlight environmental influences, which may contribute to variances in masculinity and femininity, when genetic influences are held relatively constant. PMID- 24179080 TI - Delayed puberty, eroticism, and sense of smell: A psychological study of hypogonadotropinism, osmatic and anosmatic (Kallmann's syndrome). AB - In 13 male patients with a diagnosis of hypogonadotropic hypogonadism, associated in five cases with verified hyposmia (Kallmann's syndrome), social development and participation were delayed. The patients associated the lack of visible signs of male puberty with their delayed sociosexual maturation. However, the evidence of physical maturation after treatment did not have the ameliorative effect on their social behavior one would have liked to predict. Dating behavior was limited before and after treatment for all the patients, and sexual interest was low even for the three married ones. The experience of falling in love was notably absent in the relationships described. Two characteristic social reaction patterns were social introversion and hostile rejection of agemates. Intellectual functioning and the incidence of personality pathology were not diagnostically noteworthy. None of the patients had any problems with gender identity except for erotic apathy which extended to masturbation. There was an absence of homosexuality. Possibly hypogonadotropic patients have a primary defect of the hypothalamus, manifesting itself as a dysfunction of the behavioral concomitants of puberty as well as a failure of hormonal puberty. PMID- 24179081 TI - Failure of antiandrogen cyproterone acetate to modify sexual stimulation induced byp-Chlorophenylalanine and testosterone. PMID- 24179082 TI - The adolescent transvestite on a psychiatric service: Family patterns. AB - The symptom of transvestism is explored in a study of 18 adolescent boys who dressed in women's clothing and of their families. Twelve of this group who exhibit similar manifest behavior and family interaction are designated as transvestites. Their stated or apparent purpose in cross-dressing is to appear as a girl, with masturbation apparently of secondary importance. A sister is present in these families and is always the mother's preferred child. The mother-daughter relationship is characterized by relative absence of overt hostility. There is an intense interdependent interaction between the mother and the transvestite son; hostility is directed by the mother toward masculinity and specifically toward the son's masculine strivings. Dressing as a girl is openly or subtly encouraged by the mother. The father is present but relates to the son in a distant and passive manner. These observations are tentative, and further study is needed of the dynamics of transvestism. Direct observation of entire families may provide important information about the dynamics of many sexual deviations. PMID- 24179083 TI - The problem of the relationship between homosexuality and schizophrenia. PMID- 24179084 TI - Erratum. PMID- 24179085 TI - Sudden onset hair loss and colour change. PMID- 24179086 TI - Health inequalities are worsening across Europe, says WHO. PMID- 24179087 TI - Shortage of emergency department doctors needs urgent action, says watchdog. PMID- 24179088 TI - Obama seeks to quell furor over insurance cancellations. PMID- 24179089 TI - Study the biocatalyzing effect and mechanism of cellulose acetate immobilized redox mediators technology (CE-RM) on nitrite denitrification. AB - The biocatalyzing effect of a novel cellulose acetate immobilized redox mediators technology (CE-RM) on nitrite denitrification process was studied with anthraquinone, 1,8-dichloroanthraquinone, 1,5-dichloroanthraquinone and 1,4,5,8 tetrachloroanthraquinone. The results showed that the immobilized 1,4,5,8 tetrachloroanthraquinone presented the best biocatalyzed effect which increased nitrite denitrification rate to 2.3-fold with 12 mmol/L 1,4,5,8 tetrachloroanthraquinone. The unequal biocatalyzing effect was due to the quantity and position of -Cl substituent in anthraquinone-structure. Moreover, the nitrite denitrification rate was increased with the oxidation reduction potential (ORP) values becoming more negative during the biocatalyzing process. The stabilized ORP value with 12 mmol/L immobilized 1,4,5,8 tetrachloroanthraquinone were 81 mV lower than the control. At the same time, the more OH(-) was produced with the higher nitrite removal rate achieved in the nitrite denitrification process. In addition, a positive linear correlation was found between the nitrite removal reaction constants k [gNO2(-)-N/(gVSS d)] and immobilized 1,4,5,8-tetrachloroanthraquinone concentration (C1,4,5,8 tetrachloroanthraquinone), which was k = 1.8443 C1,4,5,8-tetrachloroanthraquinone + 33.75(R(2) = 0.9411). The initial nitrite concentration of 179 mgNO2(-)-N/L resulted in the maximum nitrite removal rate, which was 6.526[gNO2(-)-N/(gVSS d)]. These results show that the application of cellulose acetate immobilized redox mediators (CE-RM) can be valuable for increasing nitrite denitrification rate. PMID- 24179090 TI - In vitro comparative analysis of monocrotophos degrading potential of Aspergillus flavus, Fusarium pallidoroseum and Macrophomina sp. AB - Fungal degradation is emerging as a new powerful tool for the removal of potent neurotoxin pesticide, monocrotophos. Therefore, the present study is aimed at comparative characterization of monocrotophos degrading ability of three different fungal strains. Fungal strains were isolated from local agricultural soil by enrichment culture method, screened by gradient culture and identified as Aspergillus flavus, Fusarium pallidoroseum and Macrophomina sp. Growth kinetics revealed a direct positive influence of monocrotophos on the viability of fungal isolates. Fungal degradation was studied in phosphorus free liquid culture medium supplemented with 150 mg L(-1) concentration of monocrotophos for a period of 15 days under optimized culture conditions. Degradation of MCP followed first order kinetics with kdeg of 0.007, 0.002 and 0.005 day(-1) and half life (t1/2) of 4.21, 12.64 and 6.32 days for A. flavus, F. pallidoroseum and Macrophomina sp. respectively. To the best of our knowledge, it is the first report signifying the potential of monocrotophos degradation by Fusarium and Macrophomina sp. The results were further confirmed by HPTLC and FTIR which indicates disappearance of monocrotophos by hydrolytic cleavage of vinyl phosphate bond. Degradation of monocrotophos by fungal isolates was accompanied by the release of extracellular alkaline phosphatases, inorganic phosphates and ammonia. The overall comparative analysis followed the order of A. flavus > Macrophomina sp. > F. pallidoroseum. Therefore, it could be concluded from the study that these three different fungal strains could be effectively used as a potential candidate for the removal of monocrotophos from contaminated sites. PMID- 24179091 TI - Biodegradation of microcystin-LR and-RR by a novel microcystin-degrading bacterium isolated from Lake Taihu. AB - Microcystin-LR (MC-LR) and microcystin-RR (MC-RR) are the two most common microcystins (MCs) present in fresh water posing a direct threat to public health because of their hepatotoxicity. A novel MC-degrading bacterium designated MC LTH1 capable of degrading MC-LR and -RR was isolated, and the degradation rates and mechanisms of MC-LR and -RR for this bacterium were investigated. The bacterium was identified as Bordetella sp. and shown to possess a homologous mlrA gene responsible for degrading MCs. To the best of our knowledge, this is the first report of mlrA gene detection in Bordetella species. MC-LR and -RR were completely degraded separately at rates of 0.31 mg/(L h) and 0.17 mg/(L h). However, the degradation rates of MC-LR and -RR decreased surprisingly to 0.27 mg/(L h) and 0.12 mg/(L h), respectively, when both of them were simultaneously present. Degradation products were identified by high performance liquid chromatography coupled with time-of-flight mass spectrometry. Adda (m/z 332.2215, C20H29NO3) commonly known as a final product of MC degradation by isolated bacteria was detected as an intermediate in this study. Linearized MC-LR (m/z 1013.5638, C49H76N10O13), linearized MC-RR (m/z 1056.4970, C49H77N13O13), and tetrapeptide (m/z 615.3394, C32H46N4O8) were also detected as intermediates. These results indicate that the bacterial strain MC-LTH1 is quite efficient for the detoxification of MC-LR and MC-RR, and possesses significant bioremediation potential. PMID- 24179092 TI - Friend of GATA and GATA-6 modulate the transcriptional up-regulation of hepcidin in hepatocytes during inflammation. AB - Hepcidin is an antimicrobial peptide hormone that plays a central role in the metabolism of iron and its expression in the liver can be induced through two major pathways: the inflammatory pathway, mainly via IL-6; and the iron-sensing pathway, mediated by BMP-6. GATA-proteins are group of evolutionary conserved transcriptional regulators that bind to the consensus motif-WGATAR-in the promoter region. In hepatoma cells, GATA-proteins 4 and 6 in conjunction with the co-factor friend of GATA (FOG) were shown to modulate the transcription of HAMP. However, it is unclear as to which of the GATA-proteins drive the expression of HAMP in vivo. In this study, using in vitro and in vivo approaches, we investigated the relevance of GATA and FOG proteins in the expression of hepcidin following treatment with IL-6 and BMP-6. We found that treatment of Huh7 cells with either IL-6 or BMP-6 increased the HAMP promoter activity. The HAMP promoter activity following treatment with IL-6 or BMP-6 was further increased by co transfection of the promoter with GATA proteins 4 and 6. However, co-transfection of the HAMP promoter with FOG proteins 1 or 2 repressed the promoter response to treatments with either IL-6 or BMP-6. The effects of both GATA and FOG proteins on the promoter activity in response to IL-6 or BMP-6 treatment were abrogated by mutation of the GATA response element-TTATCT-in the HAMP promoter region -103/ 98. In vivo, treatment of mice with lipopolysaccharide led to a transient increase of Gata-6 expression in the liver that was positively correlated with the expression of hepcidin. Our results indicate that during inflammation GATA-6 is up-regulated in concert with hepcidin while GATA-4 and FOG (1 and 2) are repressed. PMID- 24179093 TI - Split-lobe resections versus lobectomy for lung carcinoma of the left upper lobe: a pair-matched case-control study of clinical and oncological outcomes. AB - OBJECTIVES: To compare left upper split-lobe procedures, being upper trisegmentectomy and resection of the lingula, with left upper lobectomy for surgical treatment of lung carcinoma originating from the left upper lobe. METHODS: A pair-matched control study comparing the clinical and oncological outcomes of 22 consecutive patients after left upper split-lobe resections with those of 44 pair-matched controls that received left upper lobectomy for non small-cell lung carcinomas. The control group was matched 1:2 for tumour diameter, histology, nodal status and patient age. In both groups, diagnosis and surgical treatment adhered to the principles of tissue-based preoperative mediastinal staging, intraoperative systematic nodal dissection, and gross surgical margins equal to the tumour diameter or at least 2 cm, a sufficient preoperative pulmonary function given. RESULTS: As intended by the study design, the split-lobe and lobectomy groups had similar median tumour diameters of 22.5 (range, 11-63) and 25 (range, 7-68) mm, respectively (P = 0.98), identical histologies (45.5% adenocarcinoma, 4.5% adenocarcinoma in situ, 45.5% squamous cell carcinoma and 4.5% neuroendocrine carcinoma) and identical pN stages (pN0 77.3%, pN1 9.1%, pN2 9.1% and ypN0 4.5%). In the split-lobe group, a lower preOP forced expiratory volume in one second (median 2.0 vs 2.3 l), a higher comorbidity (median Charlton score of 3 vs 2) and a preponderance of video assisted thoracoscopy procedures (63.6 vs 27.3%) were prevalent (all P < 0.05). There were no significant outcome differences detected, neither with regard to the postoperative clinical course assessed by intra- and postoperative complications, operation time, tissue margins, duration of drainage and hospital stay and 30-day mortality, nor with regard to 5-year overall (0.89 vs 0.81, P = 0.90). CONCLUSIONS: Left upper lobectomy might be an overtreatment for selected cases of lung carcinoma whose resection by a split-lobe procedure produces adequate margins and a complete lymphadenectomy. Tumour diameters exceeding 2 cm, nodal involvement and previous neoadjuvant treatment do not necessarily exclude this option for selected patients under the condition of a meticulous nodal dissection. In this context, we would like to suggest a translational research of the split-lobe concept to other large pulmonary lobes. PMID- 24179094 TI - Cervical partial oesophagectomy and trans-oral direct end-to-end anastomosis. AB - Many surgical procedures are used to restore the defect of the alimentary tract after cervical oesophagectomy. We present a case of a 69-year old woman, affected by a G2 squamous cell carcinoma of retro-cricodeal hypopharynx extend to the cervical oesopaghus. She underwent a direct reconstruction with a direct trans oral anastomosis by a mechanical device and without any interposition. No postoperative complication was observed and there was a good functional result at 24 months after surgery. In a few selected cases, this technique can be usefully performed, avoiding gastric or intestinal resection and improving the quality of life. PMID- 24179095 TI - The CEP family in land plants: evolutionary analyses, expression studies, and role in Arabidopsis shoot development. AB - In Arabidopsis, more than 1000 putative small signalling peptides have been predicted, but very few have been functionally characterized. One class of small post-translationally modified signalling peptides is the C-TERMINALLY ENCODED PEPTIDE (CEP) family, of which one member has been shown to be involved in regulating root architecture. This work applied a bioinformatics approach to identify more members of the CEP family. It identified 10 additional members and revealed that this family only emerged in flowering plants and was absent from extant members of more primitive plants. The data suggest that the CEP proteins form two subgroups according to the CEP domain. This study further provides an overview of specific CEP expression patterns that offers a comprehensive framework to study the role of the CEP signalling peptides in plant development. For example, expression patterns point to a role in aboveground tissues which was corroborated by the analysis of transgenic lines with perturbed CEP levels. These results form the basis for further exploration of the mechanisms underlying this family of peptides and suggest their putative roles in distinct developmental events of higher plants. PMID- 24179096 TI - CEP genes regulate root and shoot development in response to environmental cues and are specific to seed plants. AB - The manifestation of repetitive developmental programmes during plant growth can be adjusted in response to various environmental cues. During root development, this means being able to precisely control root growth and lateral root development. Small signalling peptides have been found to play roles in many aspects of root development. One member of the CEP (C-TERMINALLY ENCODED PEPTIDE) gene family has been shown to arrest root growth. Here we report that CEP genes are widespread among seed plants but are not present in land plants that lack true branching roots or root vasculature. We have identified 10 additional CEP genes in Arabidopsis. Expression analysis revealed that CEP genes are regulated by environmental cues such as nitrogen limitation, increased salt levels, increased osmotic strength, and increased CO2 levels in both roots and shoots. Analysis of synthetic CEP variants showed that both peptide sequence and modifications of key amino acids affect CEP biological activity. Analysis of several CEP over-expression lines revealed distinct roles for CEP genes in root and shoot development. A cep3 knockout mutant showed increased root and shoot growth under a range of abiotic stress, nutrient, and light conditions. We demonstrate that CEPs are negative regulators of root development, slowing primary root growth and reducing lateral root formation. We propose that CEPs are negative regulators that mediate environmental influences on plant development. PMID- 24179097 TI - Hybrid breeding in wheat: technologies to improve hybrid wheat seed production. AB - Global food security demands the development and delivery of new technologies to increase and secure cereal production on finite arable land without increasing water and fertilizer use. There are several options for boosting wheat yields, but most offer only small yield increases. Wheat is an inbred plant, and hybrids hold the potential to deliver a major lift in yield and will open a wide range of new breeding opportunities. A series of technological advances are needed as a base for hybrid wheat programmes. These start with major changes in floral development and architecture to separate the sexes and force outcrossing. Male sterility provides the best method to block self-fertilization, and modifying the flower structure will enhance pollen access. The recent explosion in genomic resources and technologies provides new opportunities to overcome these limitations. This review outlines the problems with existing hybrid wheat breeding systems and explores molecular-based technologies that could improve the hybrid production system to reduce hybrid seed production costs, a prerequisite for a commercial hybrid wheat system. PMID- 24179098 TI - Spatial expression of CLAVATA3 in the shoot apical meristem suggests it is not a stem cell marker in soybean. AB - CLAVATA3 (CLV3), a stem cell marker in Arabidopsis thaliana, encodes a secreted peptide that maintains the stem cell population within the shoot apical meristem. This work investigated the CLV3 orthologue in a major legume crop, soybean (GmCLV3). Instead of being expressed in the three outermost layers of the meristem as in Arabidopsis, GmCLV3 was expressed deeper in the central zone beneath the fourth layer (L4) of the meristem, overlapping with the expression of soybean WUSCHEL. Subsequent investigation using an alternative stem cell marker (GmLOG1) revealed its expression within layers L2-L4, indicating that GmCLV3 is not a stem cell marker. Overexpression studies of GmCLV3 in Arabidopsis and complementation of clv3-2 mutant suggest similar functional capacity to that of Arabidopsis CLV3. The expression of soybean CLV1, which encodes a receptor for CLV3 in Arabidopsis, was not detectable in the central zone of the meristem via reverse-transcription PCR analysis of amplified RNA from laser-microdissected samples or in situ, implicating a diverged pathway in soybean. This study also reports the novel expression of GmLOG1 in initials of axillary meristem in the boundary region between the SAM and developing leaf primordia, before the expression of GmWUS or GmCLV3, indicating cytokinin as one of the earliest signals in initiating and specifying the stem cell population. PMID- 24179099 TI - Ovarian function after allogeneic hematopoietic stem cell transplantation in childhood and adolescence. AB - OBJECTIVE: The aim of the study was to evaluate long-term ovarian function after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. SUBJECTS AND METHODS: Predictive factors for ovarian function were evaluated among 92 adult or pubertal female survivors transplanted at Huddinge and Helsinki University Hospital during 1978-2000, at a mean age of 9+/-4.3 years (range 1-19). At the time of the study a mean+/-s.d. of 13+/-5.5 years (range 6 27) had elapsed since the HSCT and the mean age of the participants was 22+/-6.3 years (range 9-41). RESULTS: Spontaneous puberty based on breast development occurred in 40 and menarche in 30 of the 70 girls who were prepubertal at transplantation. Six out of 20 girls who received HSCT after initiation of pubertal development recovered their ovarian function. Younger age at HSCT, conditioning without total body irradiation (TBI), and a non-leukemia diagnosis predicted the spontaneous menarche. The incidence of menarche was higher after fractioned vs single fraction TBI (P<0.05), cyclophosphamide (Cy) vs busulfan (Bu)-based conditioning (P<0.05), and among leukemia patients transplanted at first remission vs later remissions (P<0.01) and with no cranial irradiation (cranial radiotherapy, CRT) vs given CRT (14-24 Gy) (P<0.01). The majority of recipients conditioned with only Cy vs TBI (P<0.001) or vs Bu-based regimens (P<0.01) showed preserved ovarian function and required no estrogen replacement at their latest follow-up visit at a mean age of 23+/-6.3 years (range 15-41). Ten women became pregnant. CONCLUSIONS: Patients conditioned with TBI or Bu-based regimes are at high risk of ovarian failure. Intensive anti-leukemia therapy before HSCT including CRT especially among relapsed patients may further decrease the possibility of spontaneous menarche. PMID- 24179100 TI - Effects of smoking cessation on beta-cell function, insulin sensitivity, body weight, and appetite. AB - OBJECTIVE: To stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, beta-cell function, and appetite. SUBJECTS AND METHODS: Twenty-seven long-term smokers (n=27; nine females/18 males, 28+/-1 years, 22.9+/-0.6 kg/m(2)) attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B; n=14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and beta-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured. RESULTS: AFTER 3 MONTHS' SMOKING ABSTINENCE, BODY WEIGHT, AND FAT MASS WERE INCREASED (+4 AND +22% RESPECTIVELY, P0.05) AND FASTING INSULIN SENSITIVITY DETERIORATED (QUICKI: post, 0.37+/-0.02 vs baseline, 0.41+/-0.2; P<0.05), while OGIS remained unchanged throughout. IGI40 increased by 31% after >3 months' smoking abstinence (P<0.01). Carbohydrate ingestion increased after stopping smoking (P<0.05). NPY fasting levels were increased after >3 months (P<0.05), PYY, GLP1, leptin, ghrelin, and visfatin were unchanged. CONCLUSION: Smoking cessation is associated with transient metabolic changes including increased beta-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation. PMID- 24179101 TI - Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults. AB - OBJECTIVE: Senescent changes in body composition and muscle strength are accompanied by reduced production of GH and IGF1, but the causal relationship remains elusive. We speculate that serum bioactive IGF1, measured by the IGF1 kinase receptor activation assay, is closer related to human physiological ageing than total IGF1 measured by immunoassay. DESIGN: We conducted a cross-sectional study in 150 adult males and females, between 20 and 70 years. After an overnight fasting, serum levels of bioactive IGF1, total IGF1 and IGF-binding protein 1 (IGFBP1) and IGFBP3 were assessed. Furthermore, body composition and muscle strength was measured. RESULTS: Total IGF1 levels were higher in females (P=0.048). Bioactive IGF1 were identical in males and females (P=0.31), decreasing with age. Total IGF1 tended to decrease more with age compared with bioactive IGF1 (-1.48 vs -0.89 percent/year, P=0.052). Total body fat (TBF) was lower and BMI was higher in males (P<0.001 and P=0.005), and both increased with age. Knee extension and elbow flexion force were higher in males (P=0.001 and P=0.001), but decreased with age in both genders. Total but not bioactive IGF1 was positively correlated to TBF, knee extension and muscle function in males. In multiple linear regression, only age predicted total IGF1, whereas age and IGFBP1 predicted bioactive IGF1. CONCLUSIONS: Bioactive IGF1 tends to decrease to a lesser extent than total IGF1 with age and was not correlated with measures of body composition or muscle strength. Therefore, levels of circulating bioactive IGF1 does not appear to be a better biomarker of physiological ageing than total IGF1. PMID- 24179102 TI - Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas. PMID- 24179103 TI - Peritoneal ultrafiltration in refractory heart failure: a cohort study. AB - INTRODUCTION: Acutely decompensated heart failure (HF) in patients with diuretic resistance is often treated with extracorporeal ultrafiltration. Peritoneal ultrafiltration (PUF) has been proposed for the long-term management of severe HF after resolution of the acute episode. The aim of the present study was to evaluate the use of PUF in the treatment of chronic refractory HF in patients without end-stage renal disease. ? METHODS: This multicenter (10 nephrology departments throughout Italy) retrospective observational study included patients with severe HF refractory to maximized drug treatment. The patients were proposed for PUF because they had experienced at least 3 hospital admissions in the preceding year for acutely decompensated HF requiring extracorporeal ultrafiltration. ? RESULTS: Of the 48 study patients (39 men, 9 women; mean age 74 +/- 9 years), 30 received 1 nocturnal icodextrin exchange, 5 required 2 daily exchanges, and 13 received 2 - 4 sessions per week of automated peritoneal dialysis. During the first year, renal function remained stable (initial: 20.8 +/ 10.0 mL/min/1.73 m(2); end: 22.0 +/- 13.6 mL/min/1.73 m(2)), while pulmonary artery systolic pressure declined to 40 +/- 6.09 mmHg from 45.5 +/- 9.18 mmHg (p = 0.03), with a significant concomitant improvement in New York Heart Association functional status. Hospitalizations decreased to 11 +/- 17 days/patient-year from 43 +/- 33 days/patient-year before the start of PUF (p < 0.001). The incidence of peritonitis was 1 episode in 45 patient-months. Patient survival was 85% at 1 year and 56% at 2 years. ? CONCLUSIONS: This study confirms the satisfactory results of using PUF for chronic HF in elderly patients. PMID- 24179104 TI - Evaluation of a computer-guided curriculum using animation, visual images, and voice cues to train patients for peritoneal dialysis. AB - BACKGROUND: Training patients to perform peritoneal dialysis (PD) at home is key to good patient outcomes. Currently, no validated curriculum based on education concepts is available in the public domain, and training is not standardized. Few nurses are prepared to be effective trainers. The present study was designed to evaluate the efficiency and effectiveness of PD training using a new cycler designed with animation, visual images, and voice cues and provided by a qualified PD nurse with a standardized script to guide the trainer. ? METHODS: The study recruited 40 participants, including individuals naive to dialysis and current automated PD (APD) patients. Participants with visual, hearing, or touch impairments were purposely included to reflect the disabilities common to the general APD population. The participants encompassed a range of self-reported computer and technical experience and education levels. Experienced training nurses trained each participant, one on one, for 4 - 8 hours during a single day; the nurses followed the standardized script as the participants progressed through the cycler training curriculum. The pace of training was adjusted to meet individual abilities and needs. Participants were evaluated by the training nurse at the end of the training session for their proficiency in meeting the learning objectives. ? RESULTS: All 40 participants completed the 1-day training and successfully met all task objectives by the end of the day. Participant ages ranged from 23 to 73 years (mean: 53.8 +/- 11 years), with the women (50 +/- 12 years) being significantly younger than the men (57 +/- 9 years, p = 0.05). Among the participants, 90% had visual impairments; 40%, hearing impairments; and 45%, touch impairments. Twenty-nine participants (73%) had multiple impairments. Median training time was 7 +/- 0.13 hours, with a range of 5 - 8.25 hours. We found no correlation between the number of hours needed for successful training and age (r = 0.30). Training time did not differ significantly by sex, disability, computer or technical experience, or education level. The required training time was less for participants with previous PD experience (6.5 +/- 0.7 hours) than for those naive to dialysis (7 +/- 0.8 h), but at p = 0.056, the difference just missed being statistically significant. ? CONCLUSIONS: The most striking finding is that, despite a variety of barriers to learning, all 40 participants were able to meet all the stated objectives of the study with 4 - 8 hours of training. Ability to meet the study objectives was not less for participants with limited education or limited technical or computer experience than for those with more education or more advanced technical and computer skills. Thus, the highly technical aspect of the new cycler is able to promote learning for a wide range of learners. The cycler provides automated instruction using audio, video, and animation, and those features, combined with a qualified training nurse using a standardized script, appear to be both efficient and effective. PMID- 24179105 TI - Impact of hernias on peritoneal dialysis technique survival and residual renal function. AB - OBJECTIVE: We evaluated the effect of hernias and their surgical or conservative management on peritoneal dialysis (PD) technique survival and residual renal function. METHODS: This 10-year single-center retrospective case-control study (January 2001 - January 2011) compared patient survival, PD technique survival, and residual renal function in patients with a history of abdominal hernias and in a control cohort matched for age and PD vintage. RESULTS: Of 73 hernias identified in 63 patients (mean age: 55 years; 63% men), umbilical hernias were the most frequent (40%), followed by inguinal (33%), incisional, and epigastric hernias. Some hernias were surgically repaired before (n = 10) or at the time of PD catheter insertion (n = 11), but most (71%) were diagnosed and managed after initiation of PD. Overall, 49 of 73 (67%) hernias were treated surgically. In 53% of subjects, early postoperative dialysis was not needed; only 7 patients required temporary hemodialysis. The occurrence of a hernia and its treatment did not significantly affect residual renal function. After a hernia diagnosis or repair, 86% of patients were able to continue with PD. ? CONCLUSIONS: The incidence of abdominal hernia and hernia management in patients on PD do not significantly influence residual renal function or PD technique survival. Timely management of hernias is advisable and does not preclude continuation with PD as a dialysis modality. PMID- 24179106 TI - Peritoneal residual volume induces variability of ultrafiltration with icodextrin. AB - BACKGROUND: Icodextrin induces ultrafiltration (UF) during long-dwell exchanges by creating a difference in oncotic pressure between the peritoneal cavity and plasma; however, the mechanisms governing intra-patient and inter-patient variability in UF when icodextrin is used remain largely unexplained. In the present study, we show theoretically that differences in peritoneal residual volume (VR) have a more profound effect on UF with icodextrin use than with glucose use. This phenomenon is attributed to a differential effect of VR on oncotic, rather than osmotic, pressure between the peritoneal cavity and plasma. ? METHODS: The three-pore model was used to calculate the effect on UF of VR between 150 mL and 1200 mL when 7.5% icodextrin (ICO) or 3.86% glucose solution is used at the end of a 12-hour dwell in the four patient transport groups (that is, fast to slow). Oncotic (with ICO) and osmotic (with glucose) pressure differences averaged over the entire dwell were also calculated. ? RESULTS: As expected, at a nominal VR of 300 mL, UF with glucose differed substantially between the four patient transport groups (2 - 804 mL), whereas UF with ICO did not (556 - 573 mL). When VR was increased to 1200 mL from 150 mL, the concentrations of the oncotic and osmotic agents at the start of the dwell with an infusion volume of 2 L decreased to 4.9% from 7.0% with ICO and to 2.5% from 3.6% with glucose. The decrease in UF on average was greater with ICO [to 252 mL from 624 mL: that is, a reduction of 372 mL (60%)] than with glucose [to 292 mL from 398 mL: that is, a reduction of 106 mL (27%)]. Those trends agreed with the calculated reductions in the oncotic pressure difference with ICO [reduction of 12 mmHg (49%)] and the osmotic pressure difference with glucose [reduction of 19 mmHg (33%)]. ? CONCLUSIONS: When ICO is used, VR modifies the oncotic pressure difference between the peritoneal cavity and plasma to substantially alter UF. This modification suggests that potential causes of increased VR should be considered when UF with ICO is considerably less than expected. Prospective clinical studies evaluating the relationship between VR and UF with ICO are warranted to validate the theoretical predictions in this report. PMID- 24179107 TI - Serum concentrations of p-cresyl sulfate and indoxyl sulfate, but not inflammatory markers, increase in incident peritoneal dialysis patients in parallel with loss of residual renal function. AB - BACKGROUND: High serum concentrations of the protein-bound uremic retention solutes p-cresyl sulfate (PCS) and indoxyl sulfate (IndS) and inflammation are associated with increased cardiovascular morbidity and mortality in chronic kidney disease. Renal clearance contributes to up to 80% of the total clearance of PCS and IndS in peritoneal dialysis (PD) patients. Cross-sectional studies evaluating the impact of residual renal function (RRF) on serum concentrations of PCS, IndS, and circulating inflammatory markers have yielded conflicting results. ? METHODS: To clarify this issue, we carried out a prospective observational cohort study in incident PD patients (n = 35; 19 men; mean age: 55 +/- 17 years). Midday blood samples were collected and analyzed for total serum PCS, IndS, C reactive protein, and high-sensitivity interleukin 6. Peritoneal and renal clearances were calculated from urine and dialysate collections, and RRF was calculated as the mean of renal urea nitrogen and creatinine clearances. Patients were assessed 1, 6, 12, and 24 months after PD start. Differences between time points were analyzed using linear mixed models (LMMs). ? RESULTS: Residual renal function declined significantly over time (LMM p < 0.0001). Peritoneal clearances of both toxins tended to increase, but did not compensate for the declining renal clearances. Serum concentrations of PCS and IndS increased significantly over time (LMM p = 0.01; p = 0.0009). In contrast, total mass removal of both toxins remained stable. Circulating inflammatory markers did not change over time. ? CONCLUSIONS: Our data indicate that serum concentrations of PCS and IndS, but not inflammatory markers, increase in incident PD patients in parallel with loss of RRF. PMID- 24179108 TI - Hand hygiene in peritoneal dialysis patients: a comparison of two techniques. AB - INTRODUCTION AND OBJECTIVES: Hand hygiene is essential for preventing peritoneal dialysis (PD)-related infections. The present study compared the effectiveness of two hygiene techniques in reducing the number of colony-forming units (CFUs) on the hands of patients undergoing PD. METHODS: In this controlled clinical trial, 22 participants enrolled in the same PD program underwent a two-hand evaluation for microbiologic flora. Participants participated in two treatments: a) simple hand hygiene plus antiseptic hand hygiene, in which the patients washed their hands with water and glycerin soap for 1 minute and then rubbed and dried their hands with 70% ethyl alcohol gel; and b) antiseptic hand hygiene, in which the patients rubbed their hands with 70% ethyl alcohol gel until fully dry. To sample distal finger surfaces, we asked the participants to touch sheep blood agar plates directly. RESULTS: The CFU count for both hands was significantly higher in the regular hygiene group than in the gel-only group [69.0 (16.0 - 101.0) CFU vs 9.0 (2.2 - 55.5) CFU, p < 0.010]. Growth of coagulase-negative Staphylococcus colonies was significantly higher in right-hand cultures from the regular hygiene group than in those from the gel-only group [69.5 (26.25 - 101.0) CFU vs 9.5 (1.0 - 41.7) CFU; p < 0.050]. CONCLUSIONS: Among patients undergoing PD, using 70% ethyl alcohol gel to cleanse the hands may be more effective than following the regular hygiene recommendations in reducing bacterial populations. PMID- 24179109 TI - CCR5 expression is reduced in lymph nodes of HIV type 1-infected women, compared with men, but does not mediate sex-based differences in viral loads. AB - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-infected women have lower viral loads than men but similar rates of disease progression. We hypothesized that sex-based differences in CCR5 expression mediate viral load differences. METHODS: CCR5 was analyzed by flow cytometry in disaggregated lymph node cells from untreated HIV-1-infected women (n = 28) and men (n = 27). The frequencies of HIV-1 RNA-producing cells in the lymph node were determined by in situ hybridization. Linear and generalized linear regression models were used. RESULTS: The percentage of CCR5(+)CD3(+)CD4(+) cells was lower in women (mean, 12%) than men (mean, 16%; P = .034). Neither the percentage of CCR5(+)CD3(+)CD4(+) cells nor the CCR5 density predicted viral load or HIV-1 RNA producing lymph node cells (P >= .24), after adjusting for CD4(+) T-cell count, race, and age. Women had marginally fewer HIV-1 RNA-producing cells (mean, 0.21 cells/mm(2)) than men (mean, 0.44 cells/mm(2); P = .046). After adjusting for the frequency of HIV-1 RNA-producing cells and potential confounders, the viral load in women were 0.46 log10 copies/mL lower than that in men (P = .018). CONCLUSIONS: Reduced lymph node CCR5 expression in women did not account for the viral load difference between sexes. CCR5 expression did not predict viral load or frequencies of HIV-1 RNA-producing cells, indicating that physiologic levels of CCR5 do not limit HIV-1 replication in lymph node. Less plasma virus was associated with each HIV-1 RNA-producing cell in women as compared to men, suggesting that women may either produce fewer virions per productively infected cell or more effectively clear extracellular virus. PMID- 24179110 TI - No evidence for synergy between human papillomavirus genotypes for the risk of high-grade squamous intraepithelial lesions in a large population-based study. AB - BACKGROUND: Multiple human papillomavirus (HPV) genotypes may be independently or synergistically associated with risk of high-grade squamous intraepithelial lesions (HSILs). We evaluated the risk of HSIL in women concomitantly infected with multiple HPV genotypes. METHODS: A population-based stratified sample of 59 664 cervical cytology specimens from women residing in New Mexico were evaluated for cytologic abnormalities and HPV genotypes. We calculated the risk of HSIL in women infected with a single HPV genotype and the risk in those infected with multiple HPV genotypes. RESULTS: The highest risk of HSIL was observed for HPV-16 (0.036), followed by HPV-33 (0.028), HPV-58 (0.024), and HPV-18 (0.022). For most types, we observed a greater risk of HSIL in women infected with multiple carcinogenic HPV types. In contrast, the risk of HSIL was similar in women infected with HPV-16 and other types, compared with women infected with HPV-16 only. We observed an increased but plateauing risk of HSIL in women infected with multiple types, compared with those infected with a single type, with risk ratios of 1.5 (95% confidence interval [CI], 1.2-1.8), 1.7 (95% CI, 1.3-2.4), and 1.4 (95% CI, 0.83-2.5) for women infected with 2, 3, and >=4 genotypes, respectively. CONCLUSIONS: In the largest population-based study of HPV genotypes and cytologic outcomes so far, we did not see more than additive effects of HPV types on the risk of HSIL in women infected with multiple types. PMID- 24179111 TI - Distinct T-cell responses when BCG vaccination is delayed from birth to 6 weeks of age in Ugandan infants. AB - BACKGROUND: In Uganda, the tuberculosis vaccine BCG is administered on the first day of life. Infants delivered at home receive BCG vaccine at their first healthcare facility visit at 6 weeks of age. Our aim was to determine the effect of this delay in BCG vaccination on the induced immune response. METHODS: We assessed CD4(+) and CD8(+) T-cell responses with a 12-hour whole-blood intracellular cytokine/cytotoxic marker assay, and with a 6-day proliferation assay. RESULTS: We enrolled 92 infants: 50 had received BCG vaccine at birth and 42 at 6 weeks of age. Birth vaccination was associated with (1) greater induction of CD4(+) and CD8(+) T cells expressing either interferon gamma (IFN-gamma) alone or IFN-gamma together with perforin and (2) induction of proliferating cells that had greater capacity to produce IFN-gamma, tumor necrosis factor alpha (TNF alpha), and interleukin 2 together, compared with delayed vaccination. CONCLUSIONS: Distinct patterns of T-cell induction occurred when BCG vaccine was given at birth and at 6 weeks of age. We propose that this diversity might impact protection against tuberculosis. Our results differ from those of studies of delayed BCG vaccination in South Africa and the Gambia, suggesting that geographical and population heterogeneity may affect the BCG vaccine-induced T cell response. PMID- 24179113 TI - A changing landscape: traumatic brain injury in military combat and civilian athletics. PMID- 24179112 TI - Transplacental transfer of Azithromycin and its use for eradicating intra amniotic ureaplasma infection in a primate model. AB - BACKGROUND: Our goals were to describe azithromycin (AZI) pharmacokinetics in maternal plasma (MP), fetal plasma (FP), and amniotic fluid (AF) following intra amniotic infection (IAI) with Ureaplasma in pregnant rhesus monkeys and to explore concentration-response relationships. METHODS: Following intra-amniotic inoculation of Ureaplasma parvum, rhesus monkeys received AZI (12.5 mg/kg every 12 hours intravenously for 10 days; n = 10). Intensive pharmacokinetic sampling of MP, FP, and AF was scheduled following the first (ie, single) dose and the last (ie, multiple) dose. Noncompartmental and pharmacokinetic modeling methods were used. RESULTS: The AF area under the concentration-time curve at 12 hours was 0.22 ug*h/mL following a single dose and 6.3 ug*h/mL at day 10. MP and AF accumulation indices were 8.4 and 19, respectively. AZI AF half-life following the single dose and multiple dose were 156 and 129 hours, respectively. The median MP:FP ratio in concomitantly drawn samples was 3.2 (range, 1.3-9.6; n = 9). Eradication of U. parvum occurred at 6.6 days, with a 95% effective concentration (EC95) of 39 ng/mL for the maximum AZI AF concentration. CONCLUSIONS: Our study demonstrates that a maternal multiple-dose AZI regimen is effective in eradicating U. parvum IAI by virtue of intra-amniotic accumulation and suggests that antenatal therapy has the potential to mitigate complications associated with U. parvum infection in pregnancy, such as preterm labor and fetal sequelae. PMID- 24179114 TI - NIDCAP in preterm infants and the neurodevelopmental effect in the first 2 years. AB - This paper has been retracted because it contained errors in the data extraction and analyses that affect the results, figures and tables. Data from a study that had been published in two different journal articles were included twice in the analyses. There was an error in the description of the measures used for neurodevelopmental testing in the reporting of the results. PMID- 24179115 TI - Draft Genome Sequence of the Antibiotic-Producing Cystic Fibrosis Isolate Pantoea agglomerans Tx10. AB - Pantoea agglomerans is an enteric bacterium that is capable of causing both plant and human disease. Here, we report the genome sequence of a cystic fibrosis isolate, P. agglomerans Tx10, which produces an antibiotic that is effective against Staphylococcus aureus. PMID- 24179116 TI - Genome Sequence of a Strain of the Human Pathogenic Bacterium Pseudomonas alcaligenes That Caused Bloodstream Infection. AB - Pseudomonas alcaligenes, a Gram-negative aerobic bacterium, is a rare opportunistic human pathogen. Here, we report the whole-genome sequence of P. alcaligenes strain MRY13-0052, which was isolated from a bloodstream infection in a medical institution in Japan and is resistant to antimicrobial agents, including broad-spectrum cephalosporins and monobactams. PMID- 24179117 TI - Complete genome sequence of the last representative genotype of wild indigenous poliovirus type 1, which circulated in Brazil. AB - Polioviruses are the major etiological agents associated with acute flaccid paralysis (AFP). The complete genome sequence of a representative of the last wild poliovirus type 1 genotype isolated in Brazil from a paralytic poliomyelitis case is reported here. PMID- 24179118 TI - Whole-Genome Sequence of Streptococcus suis Serotype 3 Strain YB51. AB - We report here the second complete genome sequence of Streptococcus suis serotype 3 (strain YB51). The genome is 2,043,655 bp in length, which is 14,840 bp longer than the first reported genome of the same serotype, and it covers 2,012 coding sequences, 56 tRNAs, and 4 rRNA loci. PMID- 24179119 TI - Draft Genome Sequence of Pseudomonas azotifigens Strain DSM 17556T (6H33bT), a Nitrogen Fixer Strain Isolated from a Compost Pile. AB - Pseudomonas azotifigens strain 6H33b(T) is a nitrogen fixer isolated from a hyperthermal compost pile in 2005 by Hatayama and collaborators. Here we report the draft genome, which has an estimated size of 5.0 Mb, exhibits an average G+C content of 66.73%, and is predicted to encode 4,536 protein-coding genes and 100 RNA genes. PMID- 24179120 TI - Draft Genome Sequence of the Biosurfactant-Producing Bacterium Gordonia amicalis Strain CCMA-559, Isolated from Petroleum-Impacted Sediment. AB - Gordonia amicalis strain CCMA-559 was isolated from an oil-contaminated mangrove swamp and shown to produce biosurfactants. This strain is a strict aerobe that readily degrades an array of carbon sources, including N-acetylglucosamine, cellobiose, Tween 80, and 4-hydroxybenzoic acid, and, like other G. amicalis strains, likely desulfurizes dibenzothiophene. PMID- 24179121 TI - Complete Genome Sequence of Ralstonia pickettii DTP0602, a 2,4,6-Trichlorophenol Degrader. AB - Ralstonia pickettii strain DTP0602 utilizes 2,4,6-trichlorophenol as its sole carbon and energy source. Here, we report the complete genome sequence of strain DTP0602, which comprises three chromosomes and no plasmids. We also found that the two had gene clusters responsible for the degradation of 2,4,6 trichlorophenol are located on the 2.9-Mb chromosome 2. PMID- 24179122 TI - HFR1 sequesters PIF1 to govern the transcriptional network underlying light initiated seed germination in Arabidopsis. AB - Seed germination is the first step for seed plants to initiate a new life cycle. Light plays a predominant role in promoting seed germination, where the initial phase is mediated by photoreceptor phytochrome B (phyB). Previous studies showed that phytochrome-interacting factor1 (PIF1) represses seed germination downstream of phyB. Here, we identify a positive regulator of phyB-dependent seed germination, long hypocotyl in far-red1 (HFR1). HFR1 blocks PIF1 transcriptional activity by forming a heterodimer with PIF1 that prevents PIF1 from binding to DNA. Our whole-genomic analysis shows that HFR1 and PIF1 oppositely mediate the light-regulated transcriptome in imbibed seeds. Through the HFR1-PIF1 module, light regulates expression of numerous genes involved in cell wall loosening, cell division, and hormone pathways to initiate seed germination. The functionally antagonistic HFR1-PIF1 pair constructs a fail-safe mechanism for fine-tuning seed germination during low-level illumination, ensuring a rapid response to favorable environmental changes. This study identifies the HFR1-PIF1 pair as a central module directing the whole genomic transcriptional network to rapidly initiate light-induced seed germination. PMID- 24179123 TI - Disrupting autophagy restores peroxisome function to an Arabidopsis lon2 mutant and reveals a role for the LON2 protease in peroxisomal matrix protein degradation. AB - Peroxisomes house critical metabolic reactions that are essential for seedling development. As seedlings mature, metabolic requirements change, and peroxisomal contents are remodeled. The resident peroxisomal protease LON2 is positioned to degrade obsolete or damaged peroxisomal proteins, but data supporting such a role in plants have remained elusive. Arabidopsis thaliana lon2 mutants display defects in peroxisomal metabolism and matrix protein import but appear to degrade matrix proteins normally. To elucidate LON2 functions, we executed a forward genetic screen for lon2 suppressors, which revealed multiple mutations in key autophagy genes. Disabling core autophagy-related gene (ATG) products prevents autophagy, a process through which cytosolic constituents, including organelles, can be targeted for vacuolar degradation. We found that atg2, atg3, and atg7 mutations suppressed lon2 defects in auxin metabolism and matrix protein processing and rescued the abnormally large size and small number of lon2 peroxisomes. Moreover, analysis of lon2 atg mutants uncovered an apparent role for LON2 in matrix protein turnover. Our data suggest that LON2 facilitates matrix protein degradation during peroxisome content remodeling, provide evidence for the existence of pexophagy in plants, and indicate that peroxisome destruction via autophagy is enhanced when LON2 is absent. PMID- 24179124 TI - Translational landscape of photomorphogenic Arabidopsis. AB - Translational control plays a vital role in regulating gene expression. To decipher the molecular basis of translational regulation in photomorphogenic Arabidopsis thaliana, we adopted a ribosome profiling method to map the genome wide positions of translating ribosomes in Arabidopsis etiolated seedlings in the dark and after light exposure. We found that, in Arabidopsis, a translating ribosome protects an ~30-nucleotide region and moves in three-nucleotide periodicity, characteristics also observed in Saccharomyces cerevisiae and mammals. Light enhanced the translation of genes involved in the organization and function of chloroplasts. Upstream open reading frames initiated by ATG but not CTG mediated translational repression of the downstream main open reading frame. Also, we observed widespread translational repression of microRNA target genes in both light- and dark-grown Arabidopsis seedlings. This genome-wide characterization of transcripts undergoing translation at the nucleotide resolution level reveals that a combination of multiple translational mechanisms orchestrates and fine-tunes the translation of diverse transcripts in plants with environmental responsiveness. PMID- 24179126 TI - Crosstalk between the unfolded protein response and pathways that regulate pathogenic development in Ustilago maydis. AB - The unfolded protein response (UPR) is a conserved eukaryotic signaling pathway regulating endoplasmic reticulum (ER) homeostasis during ER stress, which results, for example, from an increased demand for protein secretion. Here, we characterize the homologs of the central UPR regulatory proteins Hac1 (for Homologous to ATF/CREB1) and Inositol Requiring Enzyme1 in the plant pathogenic fungus Ustilago maydis and demonstrate that the UPR is tightly interlinked with the b mating-type-dependent signaling pathway that regulates pathogenic development. Exact timing of UPR is required for virulence, since premature activation interferes with the b-dependent switch from budding to filamentous growth. In addition, we found crosstalk between UPR and the b target Clampless1 (Clp1), which is essential for cell cycle release and proliferation in planta. The unusual C-terminal extension of the U. maydis Hac1 homolog, Cib1 (for Clp1 interacting bZIP1), mediates direct interaction with Clp1. The interaction between Clp1 and Cib1 promotes stabilization of Clp1, resulting in enhanced ER stress tolerance that prevents deleterious UPR hyperactivation. Thus, the interaction between Cib1 and Clp1 constitutes a checkpoint to time developmental progression and increased secretion of effector proteins at the onset of biotrophic development. Crosstalk between UPR and the b mating-type regulated developmental program adapts ER homeostasis to the changing demands during biotrophy. PMID- 24179127 TI - ABI1 and PP2CA phosphatases are negative regulators of Snf1-related protein kinase1 signaling in Arabidopsis. AB - Plant survival under environmental stress requires the integration of multiple signaling pathways into a coordinated response, but the molecular mechanisms underlying this integration are poorly understood. Stress-derived energy deprivation activates the Snf1-related protein kinases1 (SnRK1s), triggering a vast transcriptional and metabolic reprogramming that restores homeostasis and promotes tolerance to adverse conditions. Here, we show that two clade A type 2C protein phosphatases (PP2Cs), established repressors of the abscisic acid (ABA) hormonal pathway, interact with the SnRK1 catalytic subunit causing its dephosphorylation and inactivation. Accordingly, SnRK1 repression is abrogated in double and quadruple pp2c knockout mutants, provoking, similarly to SnRK1 overexpression, sugar hypersensitivity during early seedling development. Reporter gene assays and SnRK1 target gene expression analyses further demonstrate that PP2C inhibition by ABA results in SnRK1 activation, promoting SnRK1 signaling during stress and once the energy deficit subsides. Consistent with this, SnRK1 and ABA induce largely overlapping transcriptional responses. Hence, the PP2C hub allows the coordinated activation of ABA and energy signaling, strengthening the stress response through the cooperation of two key and complementary pathways. PMID- 24179128 TI - The evolutionarily conserved iron-sulfur protein INDH is required for complex I assembly and mitochondrial translation in Arabidopsis [corrected]. AB - The assembly of respiratory complexes is a multistep process, requiring coordinate expression of mitochondrial and nuclear genes and cofactor biosynthesis. We functionally characterized the iron-sulfur protein required for NADH dehydrogenase (INDH) in the model plant Arabidopsis thaliana. An indh knockout mutant lacked complex I but had low levels of a 650-kD assembly intermediate, similar to mutations in the homologous NUBPL (nucleotide binding protein-like) in Homo sapiens. However, heterozygous indh/+ mutants displayed unusual phenotypes during gametogenesis and resembled mutants in mitochondrial translation more than mutants in complex I. Gradually increased expression of INDH in indh knockout plants revealed a significant delay in reassembly of complex I, suggesting an indirect role for INDH in the assembly process. Depletion of INDH protein was associated with decreased (35)S-Met labeling of translation products in isolated mitochondria, whereas the steady state levels of several mitochondrial transcripts were increased. Mitochondrially encoded proteins were differentially affected, with near normal levels of cytochrome c oxidase subunit2 and Nad7 but little Nad6 protein in the indh mutant. These data suggest that INDH has a primary role in mitochondrial translation that underlies its role in complex I assembly. PMID- 24179125 TI - Complexity of the alternative splicing landscape in plants. AB - Alternative splicing (AS) of precursor mRNAs (pre-mRNAs) from multiexon genes allows organisms to increase their coding potential and regulate gene expression through multiple mechanisms. Recent transcriptome-wide analysis of AS using RNA sequencing has revealed that AS is highly pervasive in plants. Pre-mRNAs from over 60% of intron-containing genes undergo AS to produce a vast repertoire of mRNA isoforms. The functions of most splice variants are unknown. However, emerging evidence indicates that splice variants increase the functional diversity of proteins. Furthermore, AS is coupled to transcript stability and translation through nonsense-mediated decay and microRNA-mediated gene regulation. Widespread changes in AS in response to developmental cues and stresses suggest a role for regulated splicing in plant development and stress responses. Here, we review recent progress in uncovering the extent and complexity of the AS landscape in plants, its regulation, and the roles of AS in gene regulation. The prevalence of AS in plants has raised many new questions that require additional studies. New tools based on recent technological advances are allowing genome-wide analysis of RNA elements in transcripts and of chromatin modifications that regulate AS. Application of these tools in plants will provide significant new insights into AS regulation and crosstalk between AS and other layers of gene regulation. PMID- 24179129 TI - Flower development under drought stress: morphological and transcriptomic analyses reveal acute responses and long-term acclimation in Arabidopsis. AB - Drought dramatically affects plant growth and crop yield, but previous studies primarily examined responses to drought during vegetative development. Here, to study responses to drought during reproductive development, we grew Arabidopsis thaliana plants with limited water, under conditions that allowed the plants to initiate and complete reproduction. Drought treatment from just after the onset of flowering to seed maturation caused an early arrest of floral development and sterility. After acclimation, plants showed reduced fertility that persisted throughout reproductive development. Floral defects included abnormal anther development, lower pollen viability, reduced filament elongation, ovule abortion, and failure of flowers to open. Drought also caused differential expression of 4153 genes, including flowering time genes flowering locus t, suppressor of overexpression of CO1, and leafy, genes regulating anther and pistil development, and stress-related transcription factors. Mutant phenotypes of hypersensitivity to drought and fewer differentially expressed genes suggest that dehydration response element B1A may have an important function in drought response in flowers. A more severe filament elongation defect under drought in myb21 plants demonstrated that appropriate stamen development requires MYB domain protein 21 under drought conditions. Our study reveals a regulatory cascade in reproductive responses and acclimation under drought. PMID- 24179130 TI - Mediation of clathrin-dependent trafficking during cytokinesis and cell expansion by Arabidopsis stomatal cytokinesis defective proteins. AB - Stomatal cytokinesis defective1 (SCD1) encodes a putative Rab guanine nucleotide exchange factor that functions in membrane trafficking and is required for cytokinesis and cell expansion in Arabidopsis thaliana. Here, we show that the loss of SCD2 function disrupts cytokinesis and cell expansion and impairs fertility, phenotypes similar to those observed for scd1 mutants. Genetic and biochemical analyses showed that SCD1 function is dependent upon SCD2 and that together these proteins are required for plasma membrane internalization. Further specifying the role of these proteins in membrane trafficking, SCD1 and SCD2 proteins were found to be associated with isolated clathrin-coated vesicles and to colocalize with clathrin light chain at putative sites of endocytosis at the plasma membrane. Together, these data suggest that SCD1 and SCD2 function in clathrin-mediated membrane transport, including plasma membrane endocytosis, required for cytokinesis and cell expansion. PMID- 24179131 TI - p-Hydroxybenzoyl-glucose is a zwitter donor for the biosynthesis of 7 polyacylated anthocyanin in Delphinium. AB - The blue color of delphinium (Delphinium grandiflorum) flowers is produced by two 7-polyacylated anthocyanins, violdelphin and cyanodelphin. Violdelphin is derived from the chromophore delphinidin that has been modified at the 7-position by Glc and p-hydroxybenzoic acid (pHBA) molecules. Modification of violdelphin by linear conjugation of Glc and pHBA molecules to a Glc moiety at the 7-position produces cyanodelphin. We recently showed that anthocyanin 7-O-glucosylation in delphinium is catalyzed by the acyl-Glc-dependent anthocyanin glucosyltransferase (AAGT). Here, we sought to answer the question of which enzyme activities are necessary for catalyzing the transfer of Glc and pHBA moieties to 7-glucosylated anthocyanin. We found that these transfers were catalyzed by enzymes that use p hydroxybenzoyl-Glc (pHBG) as a bifunctional acyl and glucosyl donor. In addition, we determined that violdelphin is synthesized via step-by-step enzymatic reactions catalyzed by two enzymes that use pHBG as an acyl or glucosyl donor. We also isolated a cDNA encoding a protein that has the potential for p hydroxybenzoylation activity and two AAGT cDNAs that encode a protein capable of adding Glc to delphinidin 3-O-rutinoside-7-O-(6-O-[p-hydroxybenzoyl]-glucoside) to form violdelphin. PMID- 24179133 TI - The plant cell reviews alternative splicing. PMID- 24179132 TI - Alternative splicing at the intersection of biological timing, development, and stress responses. AB - High-throughput sequencing for transcript profiling in plants has revealed that alternative splicing (AS) affects a much higher proportion of the transcriptome than was previously assumed. AS is involved in most plant processes and is particularly prevalent in plants exposed to environmental stress. The identification of mutations in predicted splicing factors and spliceosomal proteins that affect cell fate, the circadian clock, plant defense, and tolerance/sensitivity to abiotic stress all point to a fundamental role of splicing/AS in plant growth, development, and responses to external cues. Splicing factors affect the AS of multiple downstream target genes, thereby transferring signals to alter gene expression via splicing factor/AS networks. The last two to three years have seen an ever-increasing number of examples of functional AS. At a time when the identification of AS in individual genes and at a global level is exploding, this review aims to bring together such examples to illustrate the extent and importance of AS, which are not always obvious from individual publications. It also aims to ensure that plant scientists are aware that AS is likely to occur in the genes that they study and that dynamic changes in AS and its consequences need to be considered routinely. PMID- 24179134 TI - Characterization of the heterotrimeric G-protein complex and its regulator from the green alga Chara braunii expands the evolutionary breadth of plant G-protein signaling. AB - The lack of heterotrimeric G-protein homologs in the sequenced genomes of green algae has led to the hypothesis that, in plants, this signaling mechanism coevolved with the embryophytic life cycle and the acquisition of terrestrial habitat. Given the large evolutionary gap that exists between the chlorophyte green algae and most basal land plants, the bryophytes, we evaluated the presence of this signaling complex in a charophyte green alga, Chara braunii, proposed to be the closest living relative of land plants. The C. braunii genome encodes for the entire G-protein complex, the Galpha, Gbeta, and Ggamma subunits, and the REGULATOR OF G-PROTEIN SIGNALING (RGS) protein. The biochemical properties of these proteins and their cross-species functionality show that they are functional homologs of canonical G-proteins. The subunit-specific interactions between CbGalpha and CbGbeta, CbGbeta and CbGgamma, and CbGalpha and CbRGS are also conserved, establishing the existence of functional G-protein complex-based signaling mechanisms in green algae. PMID- 24179135 TI - Parallel recruitment of multiple genes into c4 photosynthesis. AB - During the diversification of living organisms, novel adaptive traits usually evolve through the co-option of preexisting genes. However, most enzymes are encoded by gene families, whose members vary in their expression and catalytic properties. Each may therefore differ in its suitability for recruitment into a novel function. In this work, we test for the presence of such a gene recruitment bias using the example of C4 photosynthesis, a complex trait that evolved recurrently in flowering plants as a response to atmospheric CO2 depletion. We combined the analysis of complete nuclear genomes and high-throughput transcriptome data for three grass species that evolved the C4 trait independently. For five of the seven enzymes analyzed, the same gene lineage was recruited across the independent C4 origins, despite the existence of multiple copies. The analysis of a closely related C3 grass confirmed that C4 expression patterns were not present in the C3 ancestors but were acquired during the evolutionary transition to C4 photosynthesis. The significant bias in gene recruitment indicates that some genes are more suitable for a novel function, probably because the mutations they accumulated brought them closer to the characteristics required for the new function. PMID- 24179136 TI - Models for the evolution of GC content in asexual fungi Candida albicans and C. dubliniensis. AB - Although guanine-cytosine (GC)-biased gene conversion (gBGC) following meiotic recombination seems the most probable mechanism accounting for large-scale variations in GC content for many eukaryotes, it cannot explain such variations for organisms belonging to ancient asexual lineages, such as the pathogenic fungi Candida albicans and C. dubliniensis. Analysis of the substitution patterns for these two species reveals a strong anticorrelation between the synonymous transition rates at third codon positions. I propose two models that can account for this observation. According to the first model, the evolution of GC content is driven by gBGC linked to mitotic recombination, either associated with parasexuality or with damage repair. Variations in the GC content thus reflect variations in the strength of gBGC, presumably variations in the mitotic recombination rate. According to the second model, the evolution of GC content is driven by misincorporation errors during the process of DNA replication in S phase. This model proposes that variations in GC content are due to variations in the proportions of dCTPs and dGTPs at the time when sequences are replicated. Experimental data regarding mitotic recombination rates or the variations of dCTPs and dGTPs during S phase are required to validate definitively one of the two models, but in any case, the fit of the models to the data suggests that C. albicans and C. dubliniensis constitute so far unique examples of GC content evolution driven either by mitotic recombination or replicative errors. PMID- 24179137 TI - Deconstructing formin-dependent actin cable assembly. PMID- 24179139 TI - The definition and application of Pilates exercise to treat people with chronic low back pain: a Delphi survey of Australian physical therapists. AB - BACKGROUND: Pilates exercise is recommended for people with chronic low back pain (CLBP). In the literature, however, Pilates exercise is described and applied differently to treat people with CLBP. These differences in the definition and application of Pilates exercise make it difficult to evaluate its effectiveness. OBJECTIVE: The aim of this study was to establish consensus regarding the definition and application of Pilates exercise to treat people with CLBP. METHODS: A panel of Australian physical therapists who are experienced in treating people with CLBP using Pilates exercise were surveyed using the Delphi technique. Three electronic questionnaires were used to collect the respondents' opinions. Answers to open-ended questions were analyzed thematically, combined with systematic literature review findings, and translated into statements about Pilates exercise for people with CLBP. Participants then rated their level of agreement with these statements using a 6-point Likert scale. Consensus was achieved when 70% of the panel members strongly agreed, agreed, or somewhat agreed (or strongly disagreed, disagreed, or somewhat disagreed) with an item. RESULTS: Thirty physical therapists completed all 3 questionnaires and reached consensus on the majority of items. Participants agreed that Pilates exercise requires body awareness, breathing, movement control, posture, and education. It was recommended that people with CLBP should undertake supervised sessions for 30 to 60 minutes, twice per week, for 3 to 6 months. Participants also suggested that people with CLBP would benefit from individualized assessment and exercise prescription, supervision and functional integration of exercises, and use of specialized equipment. LIMITATIONS: Item consensus does not guarantee the accuracy of findings. This survey reflects the opinion of only 30 physical therapists and requires validation in future trials. CONCLUSION: These findings contribute to a better understanding of Pilates exercise and how it is utilized by physical therapists to treat people with CLBP. This information provides direction for future research into Pilates exercise, but findings need to be interpreted within the context of study limitations. PMID- 24179140 TI - Determinants of guideline use in primary care physical therapy: a cross-sectional survey of attitudes, knowledge, and behavior. AB - BACKGROUND: Understanding of attitudes, knowledge, and behavior related to evidence-based practice (EBP) and use of evidence-based clinical practice guidelines in primary care physical therapy is limited. OBJECTIVES: The objectives of this study were: (1) to investigate self-reported attitudes, knowledge, behavior, prerequisites, and barriers related to EBP and guideline use among physical therapists in primary care and (2) to explore associations of self reported use of guidelines with these social cognitive factors along with demographic and workplace characteristics. DESIGN: This was a cross-sectional survey. METHODS: A web-based survey of 419 physical therapists in primary care in western Sweden was performed. Multiple logistic regression analysis was performed to examine factors associated with guideline use. RESULTS: The response rate was 64.7%. Most respondents had positive attitudes toward EBP and guidelines: 90% considered EBP necessary, and 96% considered guidelines important. Approximately two thirds reported confidence in finding and using evidence. One third reported being aware of guidelines. Thirteen percent knew where to find guidelines, and only 9% reported having easy access to guidelines. Fewer than half reported using guidelines frequently. The most important barriers to using guidelines were lack of time, poor availability, and limited access to guidelines. Young age and brief work experience were associated with positive attitudes toward EBP. A postgraduate degree was associated with higher application of EBP. Positive attitudes, awareness of guidelines, considering guidelines to facilitate practice, and knowing how to integrate patient preferences with guideline use were associated with frequent use of guidelines. LIMITATIONS: Data were self reported, which may have increased the risk of social desirability bias. CONCLUSIONS: Use of guidelines was not as frequent as could be expected in view of the positive attitudes toward EBP and guidelines among physical therapists. Awareness of and perceived access to guidelines were limited. The identified determinants can be addressed when developing guideline implementation strategies. PMID- 24179141 TI - Future directions in painful knee osteoarthritis: harnessing complexity in a heterogeneous population. AB - This perspective article proposes a conceptual model for the pain experience for individuals diagnosed with knee osteoarthritis (OA). Pain in knee OA is likely a heterogeneous, multifactorial phenomenon that involves not only the OA disease process but also elements specific to patient psychology and pain neurophysiology. The relevant contributions to the pain experience for any individual patient remain difficult, if not impossible, to definitively determine, and the rationale for many clinical treatment decisions arises primarily from a mechanistic understanding of OA pathophysiology. The Osteoarthritis Research Society International (OARSI) recently identified "phenotyping" of OA pain as a research priority to "better target pain therapies to individual patients." This perspective article proposes that contributions from 3 domains--knee pathology, psychological distress, and pain neurophysiology- should be considered equally important in future efforts to understand pain phenotypes in knee OA. Ultimately, characterization of pain phenotypes may aid in the understanding of the pain experience and the development of interventions specific to pain for individual patients. PMID- 24179142 TI - Highly efficient CRISPR/Cas9-mediated knock-in in zebrafish by homology independent DNA repair. AB - Sequence-specific nucleases like TALENs and the CRISPR/Cas9 system have greatly expanded the genome editing possibilities in model organisms such as zebrafish. Both systems have recently been used to create knock-out alleles with great efficiency, and TALENs have also been successfully employed in knock-in of DNA cassettes at defined loci via homologous recombination (HR). Here we report CRISPR/Cas9-mediated knock-in of DNA cassettes into the zebrafish genome at a very high rate by homology-independent double-strand break (DSB) repair pathways. After co-injection of a donor plasmid with a short guide RNA (sgRNA) and Cas9 nuclease mRNA, concurrent cleavage of donor plasmid DNA and the selected chromosomal integration site resulted in efficient targeted integration of donor DNA. We successfully employed this approach to convert eGFP into Gal4 transgenic lines, and the same plasmids and sgRNAs can be applied in any species where eGFP lines were generated as part of enhancer and gene trap screens. In addition, we show the possibility of easily targeting DNA integration at endogenous loci, thus greatly facilitating the creation of reporter and loss-of-function alleles. Due to its simplicity, flexibility, and very high efficiency, our method greatly expands the repertoire for genome editing in zebrafish and can be readily adapted to many other organisms. PMID- 24179143 TI - Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. AB - DNA methylation is crucial for a wide variety of biological processes, yet no technique suitable for the methylome analysis of DNA methylation at single-cell resolution is available. Here, we describe a methylome analysis technique that enables single-cell and single-base resolution DNA methylation analysis based on reduced representation bisulfite sequencing (scRRBS). The technique is highly sensitive and can detect the methylation status of up to 1.5 million CpG sites within the genome of an individual mouse embryonic stem cell (mESC). Moreover, we show that the technique can detect the methylation status of individual CpG sites in a haploid sperm cell in a digitized manner as either unmethylated or fully methylated. Furthermore, we show that the demethylation dynamics of maternal and paternal genomes after fertilization can be traced within the individual pronuclei of mouse zygotes. The demethylation process of the genic regions is faster than that of the intergenic regions in both male and female pronuclei. Our method paves the way for the exploration of the dynamic methylome landscapes of individual cells at single-base resolution during physiological processes such as embryonic development, or during pathological processes such as tumorigenesis. PMID- 24179144 TI - Counting efficiency of whole-body monitoring system using BOMAB and ANSI/IAEA thyroid phantom due to internal contamination of 131I. AB - In this study, the effect of Indian reference BOttle MAnnikin aBsorber (BOMAB) neck with axial cavity and American National Standards Institute (ANSI)/International Atomic Energy Agency (IAEA) thyroid phantom using pencil sources of (133)Ba ((131)I simulant) on counting efficiency (CE) is seen experimentally in static geometry for whole-body monitoring system comprising 10.16-cm diameter and 7.62-cm-thick NaI(Tl) detector. The CE estimated using the neck part of BOMAB phantom is 50.2% lower in comparison with ANSI phantom. In rest of the studies FLUKA code is used for Monte Carlo simulations using ANSI/IAEA thyroid phantom. The simulation results are validated in static geometries with experimental CE and the differences are within 1.3%. It is observed that CE for pencil source distribution is 3.97% higher for (133)Ba in comparison with CE of (131)I source. Simulated CE for pencil source distribution is 4.7% lower in comparison with uniform source distribution in the volume of thyroid for (131)I. Since the radiation workers are of different physique; overlying tissue thickness (OTT) and neck-to-detector distance play an important role in the calculation of activity in thyroid. The CE decreases with increase in OTT and is found to be 5.5% lower if OTT is changed from 1.1 to 2 cm. Finally, the simulations are carried out to estimate the variation in CE due to variation in the neck-to-detector distance. The CE is 6.2% higher if the neck surface-to detector distance is decreased from 21.4 to 20.4 cm and it goes on increasing up to 61.9% if the distance is decreased to 15.4 cm. In conclusion, the calibration of whole-body monitoring system for (131)I should be carried out with ANSI/IAEA thyroid phantom, the neck-to-detector distance controlled or the CE corrected for this, and the CE should be corrected for OTT. PMID- 24179145 TI - Determination of the response function for two personal neutron dosemeter designs based on PADC. AB - Since 1998 neutron dosimetry based on PADC (poly allyl diglycol carbonate) is done with a so-called original Paul Scherrer Institute (PSI) design at PSI. The original design (i.e. holder) was later changed. Both designs are optimised for use in workplaces around high-energy accelerators, where the neutron energy spectra are dominated by fast neutrons ranging up to some 100 MeV. In addition to the change of the dosemeter design a new evaluation method based on a microscope scanning technique has been introduced and the etching conditions have been optimised. In the present work, the responses obtained with the original and the new dosemeter designs are compared for fields of radionuclide sources and monoenergetic reference fields using the new evaluation method. The response curves in terms of the personal dose equivalent for normally incident neutrons were built as functions of the incident neutron energy. PMID- 24179146 TI - Editorial: Btk--friend or foe in autoimmune diseases? PMID- 24179147 TI - Editorial: New tricks for innate lymphoid cells. PMID- 24179148 TI - Psychosocial interventions for people with both severe mental illness and substance misuse. AB - Over 50% of people with a severe mental illness also use illicit drugs and/or alcohol at hazardous levels. This review is based on the findings of 32 randomized controlled trials which assessed the effectiveness of psychosocial interventions, offered either as one-off treatments or as an integrated or nonintegrated program, to reduce substance use by people with a severe mental illness. The findings showed that there was no consistent evidence to support any one psychosocial treatment over another. Differences across trials with regard to outcome measures, sample characteristics, type of mental illness and substance used, settings, levels of adherence to treatment guidelines, and standard care all made pooling results difficult. More quality trials are required that adhere to proper randomization methods; use clinically valuable, reliable, and validated measurement scales; and clearly report data, including retention in treatment, relapse, and abstinence rates. Future trials of this quality will allow a more thorough assessment of the efficacy of psychosocial interventions for reducing substance use in this challenging population. PMID- 24179149 TI - Endoplasmic reticulum stress impairs cholesterol efflux and synthesis in hepatic cells. AB - Metabolic disorders such as type 2 diabetes cause hepatic endoplasmic reticulum (ER) stress, which affects neutral lipid metabolism. However, the role of ER stress in cholesterol metabolism is incompletely understood. Here, we show that induction of acute ER stress in human hepatic HepG2 cells reduced ABCA1 expression and caused ABCA1 redistribution to tubular perinuclear compartments. Consequently, cholesterol efflux to apoA-I, a key step in nascent HDL formation, was diminished by 80%. Besides ABCA1, endogenous apoA-I expression was reduced upon ER stress induction, which contributed to reduced cholesterol efflux. Liver X receptor, a key regulator of ABCA1 in peripheral cells, was not involved in this process. Despite reduced cholesterol efflux, cellular cholesterol levels remained unchanged during ER stress. This was due to impaired de novo cholesterol synthesis by reduction of HMG-CoA reductase activity by 70%, although sterol response element-binding protein-2 activity was induced. In mice, ER stress induction led to a marked reduction of hepatic ABCA1 expression. However, HDL cholesterol levels were unaltered, presumably because of scavenger receptor class B, type I downregulation under ER stress. Taken together, our data suggest that ER stress in metabolic disorders reduces HDL biogenesis due to impaired hepatic ABCA1 function. PMID- 24179150 TI - In vivo generation of decidual natural killer cells from resident hematopoietic progenitors. AB - Decidual natural killer cells accumulate at the fetal-maternal interface and play a key role in a successful pregnancy. However, their origin is still unknown. Do they derive from peripheral natural killer cells recruited in decidua or do they represent a distinct population that originates in situ? Here, we identified natural killer precursors in decidua and uterus of pregnant mice. These precursors underwent rapid in situ differentiation and large proportions of proliferating immature natural killer cells were present in decidua and uterus as early as gestation day 4.5. Here, we investigated the origin of decidua- and uterus-natural killer cells by performing transfer experiments of peripheral mature natural killer cells or precursors from EGFP(+) mice. Results showed that mature natural killer cells did not migrate into decidua and uterus, while precursors were recruited in these organs and differentiated towards natural killer cells. Moreover, decidua- and uterus-natural killer cells displayed unique phenotypic and functional features. They expressed high levels of the activating Ly49D receptor in spite of their immature phenotype. In addition, decidua- and uterus-natural killer cells were poorly cytolytic and produced low amounts of IFN gamma, while they released factors (GM-CSF, VEGF, IP-10) involved in neo angiogenesis and tissue remodeling. Our data reveal in situ generation of decidual natural killer cells and provide an important correlation between mouse and human decidual natural killer cells, allowing further studies to be carried out on their role in pregnancy-related diseases. PMID- 24179153 TI - Transforming rural health care through information technology: an interventional study in China. AB - This article estimates the impacts of health information technology (HIT) on health-care delivery in the Wenchuan County of China, where the devastation of the 2008 Great Wenchuan Earthquake and the subsequent large-scale HIT implementation (the Healthy Wenchuan Program) offers a 'natural experiment' opportunity, enabling us to conduct a difference-in-difference evaluation of the potential benefits of HIT on accessibility, affordability and appropriateness of health-care services in the underdeveloped rural area. Based on data collected from two field surveys in township hospitals, we find that for both the inpatient and outpatient samples, the HIT system promotes access to medical care by increasing doctor referrals and encouraging within-county medical utilization, reduces patient financial burden in certain expenditure categories, and contributes to higher patient satisfaction on medical care quality. On the other hand, we also find that HIT leads to increased patient waiting time for hospital registration, reflecting the unique challenges in implementing HIT in the underdeveloped areas. Our study contributes to the growing body of literature on evaluating the impacts of HIT application in the developing regions, and provides implications on the potential role of HIT in China's national health system reforms. PMID- 24179152 TI - CHK1 and WEE1 inhibition combine synergistically to enhance therapeutic efficacy in acute myeloid leukemia ex vivo. AB - Novel combinations targeting new molecular vulnerabilities are needed to improve the outcome of patients with acute myeloid leukemia. We recently identified WEE1 kinase as a novel target in leukemias. To identify genes that are synthetically lethal with WEE1 inhibition, we performed a short interfering RNA screen directed against cell cycle and DNA repair genes during concurrent treatment with the WEE1 inhibitor MK1775. CHK1 and ATR, genes encoding two replication checkpoint kinases, were among the genes whose silencing enhanced the effects of WEE1 inhibition most, whereas CDK2 short interfering RNA antagonized MK1775 effects. Building on this observation, we examined the impact of combining MK1775 with selective small molecule inhibitors of CHK1, ATR and cyclin-dependent kinases. The CHK1 inhibitor MK8776 sensitized acute myeloid leukemia cell lines and primary leukemia specimens to MK1775 ex vivo, whereas smaller effects were observed with the MK1775/MK8776 combination in normal myeloid progenitors. The ATR inhibitor VE-821 likewise enhanced the antiproliferative effects of MK1775, whereas the cyclin-dependent kinase inhibitor roscovitine antagonized MK1775. Further studies showed that MK8776 enhanced MK1775-mediated activation of the ATR/CHK1 pathway in acute leukemia cell lines and ex vivo. These results indicate that combined cell cycle checkpoint interference with MK1775/MK8776 warrants further investigation as a potential treatment for acute myeloid leukemia. PMID- 24179154 TI - Detecting limited health literacy in Brazil: development of a multidimensional screening tool. AB - Screening questions have been proposed as practical tools for detecting limited functional health literacy, but have achieved only moderate accuracy in previous studies. We hypothesized that a combination of screening questions and demographic characteristics could better predict a patient's functional health literacy. Three hundred and twenty-two hospital users from Sao Paulo, Brazil, were interviewed for demographic information and answered questions about literacy habits and perceived difficulties. The Short Test of Functional Health Literacy in Adults was used to classify individuals as having adequate or limited functional health literacy. Of the 322 participants, 102 (31.7%) presented limited functional health literacy. The final logistic model included six predictors. The three demographic variables were educational attainment, mother's educational attainment and major lifetime occupation (manual or non-manual). The three questions concerned 'frequency of use of computers', 'difficulty with writing that have precluded the individual from getting a better job' and 'difficulty reading the subtitles while watching a foreign movie'. A simple score was derived to constitute a practical tool we named the Multidimensional Screener of Functional Health Literacy (MSFHL). The sensitivity of the MSFHL in detecting limited functional health literacy was 81.4% and the specificity was 87.7%, with an area under receiver operating characteristic (ROC) curve of 0.93 (95% CI 0.89 0.95). The MSFHL was better than educational attainment in accurately classifying functional health literacy status (p = 0.0018). We have developed a screening tool based on three demographic characteristics and three simple questions which provides an accurate prediction of a patient's functional health literacy level. PMID- 24179151 TI - Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma. AB - Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+) lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics. PMID- 24179155 TI - BTBD3 controls dendrite orientation toward active axons in mammalian neocortex. AB - Experience-dependent structural changes in the developing brain are fundamental for proper neural circuit formation. Here, we show that during the development of the sensory cortex, dendritic field orientation is controlled by the BTB/POZ domain-containing 3 (BTBD3). In developing mouse somatosensory cortex, endogenous Btbd3 translocated to the cell nucleus in response to neuronal activity and oriented primary dendrites toward active axons in the barrel hollow. Btbd3 also directed dendrites toward active axon terminals when ectopically expressed in mouse visual cortex or normally expressed in ferret visual cortex. BTBD3 regulation of dendrite orientation is conserved across species and cortical areas and shows how high-acuity sensory function may be achieved by the tuning of subcellular polarity to sources of high sensory activity. PMID- 24179156 TI - Oscillatory control of factors determining multipotency and fate in mouse neural progenitors. AB - The basic helix-loop-helix transcription factors Ascl1/Mash1, Hes1, and Olig2 regulate fate choice of neurons, astrocytes, and oligodendrocytes, respectively. These same factors are coexpressed by neural progenitor cells. Here, we found by time-lapse imaging that these factors are expressed in an oscillatory manner by mouse neural progenitor cells. In each differentiation lineage, one of the factors becomes dominant. We used optogenetics to control expression of Ascl1 and found that, although sustained Ascl1 expression promotes neuronal fate determination, oscillatory Ascl1 expression maintains proliferating neural progenitor cells. Thus, the multipotent state correlates with oscillatory expression of several fate-determination factors, whereas the differentiated state correlates with sustained expression of a single factor. PMID- 24179157 TI - Layer-resolved graphene transfer via engineered strain layers. AB - The performance of optimized graphene devices is ultimately determined by the quality of the graphene itself. Graphene grown on copper foils is often wrinkled, and the orientation of the graphene cannot be controlled. Graphene grown on SiC(0001) via the decomposition of the surface has a single orientation, but its thickness cannot be easily limited to one layer. We describe a method in which a graphene film of one or two monolayers grown on SiC is exfoliated via the stress induced with a Ni film and transferred to another substrate. The excess graphene is selectively removed with a second exfoliation process with a Au film, resulting in a monolayer graphene film that is continuous and single-oriented. PMID- 24179158 TI - The human language-associated gene SRPX2 regulates synapse formation and vocalization in mice. AB - Synapse formation in the developing brain depends on the coordinated activity of synaptogenic proteins, some of which have been implicated in a number of neurodevelopmental disorders. Here, we show that the sushi repeat-containing protein X-linked 2 (SRPX2) gene encodes a protein that promotes synaptogenesis in the cerebral cortex. In humans, SRPX2 is an epilepsy- and language-associated gene that is a target of the foxhead box protein P2 (FoxP2) transcription factor. We also show that FoxP2 modulates synapse formation through regulating SRPX2 levels and that SRPX2 reduction impairs development of ultrasonic vocalization in mice. Our results suggest FoxP2 modulates the development of neural circuits through regulating synaptogenesis and that SRPX2 is a synaptogenic factor that plays a role in the pathogenesis of language disorders. PMID- 24179159 TI - Crystal structure of a soluble cleaved HIV-1 envelope trimer. AB - HIV-1 entry into CD4(+) target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP.664 gp140 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the threefold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3, and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design. PMID- 24179161 TI - Prognostic implications of bleeding measured by Bleeding Academic Research Consortium (BARC) categorisation in patients undergoing primary percutaneous coronary intervention. AB - OBJECTIVE: To investigate the relationship between inhospital bleeding as defined by Bleeding Academic Research Consortium (BARC) consensus classification and short-term and long-term mortality in unselected patients admitted for primary percutaneous coronary intervention (PCI). METHODS: We analysed data of all consecutive patients with ST segment elevation myocardial infarction (STEMI) admitted for primary PCI, enrolled in a prospective registry of a high volume centre. The BARC-defined bleeding events were reconstructed from the detailed, prospectively collected clinical data. The primary outcome was mortality at 1 year. RESULTS: Of the 1808 patients with STEMI admitted for primary PCI, 115 (6.4%) experienced a BARC type >=2 bleeding. As the BARC bleeding severity worsened, there was a gradient of increasing rates of 1-year death. The 1-year mortality rate increased from 11.5% with BARC 0+1 type to 43.5% with BARC type 3b bleeding. After multivariable adjustment for demographic and clinical characteristics of patients, the independent predictors of 1-year death were BARC type 3a (HR 1.99; 95% CI 1.16 to 3.40, p=0.012) and BARC type 3b bleeding (HR 3.22; 95% CI 1.67 to 6.20, p<0.0001). CONCLUSIONS: The present study demonstrated that bleeding events defined according to the BARC classification hierarchically correlate with 1-year mortality after admission for primary PCI. The strongest predictor of 1-year mortality is the BARC type 3b bleeding. PMID- 24179160 TI - Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. AB - The HIV-1 envelope glycoprotein (Env) trimer contains the receptor binding sites and membrane fusion machinery that introduce the viral genome into the host cell. As the only target for broadly neutralizing antibodies (bnAbs), Env is a focus for rational vaccine design. We present a cryo-electron microscopy reconstruction and structural model of a cleaved, soluble Env trimer (termed BG505 SOSIP.664 gp140) in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 angstrom resolution. The structure reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1, and HR2 domains, as well as shielding glycans. The structure also provides insights into trimer assembly, gp120-gp41 interactions, and the CD4bs epitope cluster for bnAbs, which covers a more extensive area and defines a more complex site of vulnerability than previously described. PMID- 24179162 TI - A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ELAN-HF Score. AB - BACKGROUND: Models to stratify risk for patients hospitalised for acute decompensated heart failure (ADHF) do not include the change in N-terminal pro-B type natriuretic peptide (NT-proBNP) levels during hospitalisation. OBJECTIVE: The aim of our study was to develop a simple yet robust discharge prognostication score including NT-proBNP for this notorious high-risk population. DESIGN: Individual patient data meta-analyses of prospective cohort studies. SETTING: Seven prospective cohorts with in total 1301 patients. PATIENTS: Our study population was assembled from the seven studies by selecting those patients admitted because of clinically validated ADHF, discharged alive, and NT-proBNP measurements available at admission and at discharge. MAIN OUTCOME MEASURES: The endpoints studied were all-cause mortality and a composite of all-cause mortality and/or first readmission for cardiovascular reason within 180 days after discharge. RESULTS: The model that incorporated NT-proBNP levels at discharge as well as the changes in NT-proBNP during hospitalisation in addition to age >=75 years, peripheral oedema, systolic blood pressure <=115 mm Hg, hyponatremia at admission, serum urea of >=15 mmol/L and New York Heart Association (NYHA) class at discharge, yielded the best C-statistic (area under the curve, 0.78, 95% CI 0.74 to 0.82). The addition of NT-proBNP to a reference model significantly improved prediction of mortality as shown by the net reclassification improvement (62%, p<0.001). A simplified model was obtained from the final Cox regression model by assigning weights to individual risk markers proportional to their relative risks. The risk score we designed identified four clinically significant subgroups. The pattern of increasing event rates with increasing score was confirmed in the validation group (BOT-AcuteHF, n=325, p<0.001). CONCLUSIONS: In patients hospitalised for ADHF, the addition of the discharge NT-proBNP values as well as the change in NT-proBNP to known risk markers, generates a relatively simple yet robust discharge risk score that importantly improves the prediction of adverse events. PMID- 24179163 TI - Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort. AB - OBJECTIVE: Patients with repaired tetralogy of Fallot (TOF) experience increased rates of mortality and morbidity in adulthood. This study was designed to identify risk factors for death and ventricular tachycardia (VT) in a large contemporary cohort of patients with repaired TOF. METHODS: Subjects with repaired TOF from four large congenital heart centres in the USA, Canada and Europe were enrolled. Clinical, ECG, exercise, cardiac magnetic resonance (CMR) and outcome data were analysed. RESULTS: Of the 873 patients (median age 24.4 years), 32 (3.7%) reached the primary outcome (28 deaths, 4 sustained VT; median age at outcome 38 years; median time from CMR to outcome 1.9 years). Cox proportional-hazards regression identified RV mass-to-volume ratio >= 0.3 g/mL (HR, 5.04; 95% CI 2.3 to 11.0; p<0.001), LV EF z score<-2.0 (HR, 3.34; 95% CI 1.59 to 7.01; p=0.001), and history of atrial tachyarrhythmia (HR, 3.65; 95% CI 1.75 to 7.62; p=0.001) as outcome predictors. RV dysfunction was predictive of the outcome similar to LV dysfunction. In subgroup analysis of 315 subjects with echocardiographic assessment of RV systolic pressure, higher pressure (HR 1.39; 95% CI 1.19 to 1.62; p<0.001) was associated with death and sustained VT independent of RV hypertrophy and LV dysfunction. CONCLUSIONS: RV hypertrophy, ventricular dysfunction and atrial tachyarrhythmias are predictive of death and sustained VT in adults with repaired TOF. These findings may inform risk stratification and the design of future therapeutic trials. PMID- 24179164 TI - Pathogen-specific local immune fingerprints diagnose bacterial infection in peritoneal dialysis patients. AB - Accurate and timely diagnosis of bacterial infection is crucial for effective and targeted treatment, yet routine microbiological identification is inefficient and often delayed to an extent that makes it clinically unhelpful. The immune system is capable of a rapid, sensitive and specific detection of a broad spectrum of microbes, which has been optimized over millions of years of evolution. A patient's early immune response is therefore likely to provide far better insight into the true nature and severity of microbial infections than conventional tests. To assess the diagnostic potential of pathogen-specific immune responses, we characterized the local responses of 52 adult patients during episodes of acute peritoneal dialysis (PD)-associated peritonitis by multicolor flow cytometry and multiplex ELISA, and defined the immunologic signatures in relation to standard microbiological culture results and to clinical outcomes. We provide evidence that unique local "immune fingerprints" characteristic of individual organisms are evident in PD patients on the day of presentation with acute peritonitis and discriminate between culture-negative, Gram-positive, and Gram negative episodes of infection. Those humoral and cellular parameters with the most promise for defining disease-specific immune fingerprints include the local levels of IL-1beta, IL-10, IL-22, TNF-alpha, and CXCL10, as well as the frequency of local gammadelta T cells and the relative proportion of neutrophils and monocytes/macrophages among total peritoneal cells. Our data provide proof of concept for the feasibility of using immune fingerprints to inform the design of point-of-care tests that will allow rapid and accurate infection identification and facilitate targeted antibiotic prescription and improved patient management. PMID- 24179165 TI - C5a receptor (CD88) blockade protects against MPO-ANCA GN. AB - Necrotizing and crescentic GN (NCGN) with a paucity of glomerular immunoglobulin deposits is associated with ANCA. The most common ANCA target antigens are myeloperoxidase (MPO) and proteinase 3. In a manner that requires activation of the alternative complement pathway, passive transfer of antibodies to mouse MPO (anti-MPO) induces a mouse model of ANCA NCGN that closely mimics human disease. Here, we confirm the importance of C5aR/CD88 in the mediation of anti-MPO-induced NCGN and report that C6 is not required. We further demonstrate that deficiency of C5a-like receptor (C5L2) has the reverse effect of C5aR/CD88 deficiency and results in more severe disease, indicating that C5aR/CD88 engagement enhances inflammation and C5L2 engagement suppresses inflammation. Oral administration of CCX168, a small molecule antagonist of human C5aR/CD88, ameliorated anti-MPO induced NCGN in mice expressing human C5aR/CD88. These observations suggest that blockade of C5aR/CD88 might have therapeutic benefit in patients with ANCA associated vasculitis and GN. PMID- 24179167 TI - Antifibrotic therapy: is an antioxidative regimen the answer? PMID- 24179166 TI - New autophagy reporter mice reveal dynamics of proximal tubular autophagy. AB - The accumulation of autophagosomes in postischemic kidneys may be renoprotective, but whether this accumulation results from the induction of autophagy or from obstruction within the autophagic process is unknown. Utilizing the differential pH sensitivities of red fluorescent protein (RFP; pKa 4.5) and enhanced green fluorescent protein (EGFP; pKa 5.9), we generated CAG-RFP-EGFP-LC3 mice to distinguish early autophagic vacuoles from autolysosomes. In vitro and in vivo studies confirmed that in response to nutrient deprivation, renal epithelial cells in CAG-RFP-EGFP-LC3 mice produce autophagic vacuoles expressing RFP and EGFP puncta. EGFP fluorescence diminished substantially in the acidic environment of the autolysosomes, whereas bright RFP signals remained. Under normal conditions, nephrons expressed few EGFP and RFP puncta, but ischemia-reperfusion injury (IRI) led to dynamic changes in the proximal tubules, with increased numbers of RFP and EGFP puncta that peaked at 1 day after IRI. The number of EGFP puncta returned to control levels at 3 days after IRI, whereas the high levels of RFP puncta persisted, indicating autophagy initiation at day 1 and autophagosome clearance during renal recovery at day 3. Notably, proliferation decreased in cells containing RFP puncta, suggesting that autophagic cells are less likely to divide for tubular repair. Furthermore, 87% of proximal tubular cells with activated mechanistic target of rapamycin (mTOR), which prevents autophagy, contained no RFP puncta. Conversely, inhibition of mTOR complex 1 induced RFP and EGFP expression and decreased cell proliferation. In summary, our results highlight the dynamic regulation of autophagy in postischemic kidneys and suggest a role of mTOR in autophagy resolution during renal repair. PMID- 24179168 TI - Cloudy peritoneal dialysate: in search of a clear cause? PMID- 24179169 TI - Understanding the epigenetic syntax for the genetic alphabet in the kidney. AB - The cells in a human body have identical DNA sequences, yet the body has >200 cell types with different phenotypes. The basis for this nongenetic cellular memory, which records developmental and environmental cues, is epigenetics. The epigenome includes covalent modifications of the DNA and its associated proteins and defines DNA accessibility to the transcriptional machinery. Notably, the epigenome has emerged as an important mediator of the long-term programming effect of environmental exposure, and multiple lines of evidence point to the epigenome as an important missing link in our understanding of CKD development. For example, recent studies identified epigenetic differences in the enhancer regions of fibrosis-related genes in diseased human kidney samples. Furthermore, chromatin profiling and epigenome analysis are powerful tools for annotating gene regulatory regions that can be harnessed to interpret disease-causing polymorphisms for complex traits such as CKD. This review highlights the results of studies investigating the renal epigenome and discusses the significance of these findings and future directions in the context of novel diagnostic and treatment strategies for CKD. PMID- 24179170 TI - Sodium transport is modulated by p38 kinase-dependent cross-talk between ENaC and Na,K-ATPase in collecting duct principal cells. AB - In relation to dietary Na(+) intake and aldosterone levels, collecting duct principal cells are exposed to large variations in Na(+) transport. In these cells, Na(+) crosses the apical membrane via epithelial Na(+) channels (ENaC) and is extruded into the interstitium by Na,K-ATPase. The activity of ENaC and Na,K ATPase must be highly coordinated to accommodate variations in Na(+) transport and minimize fluctuations in intracellular Na(+) concentration. We hypothesized that, independent of hormonal stimulus, cross-talk between ENaC and Na,K-ATPase coordinates Na(+) transport across apical and basolateral membranes. By varying Na(+) intake in aldosterone-clamped rats and overexpressing gamma-ENaC or modulating apical Na(+) availability in cultured mouse collecting duct cells, enhanced apical Na(+) entry invariably led to increased basolateral Na,K-ATPase expression and activity. In cultured collecting duct cells, enhanced apical Na(+) entry increased the basolateral cell surface expression of Na,K-ATPase by inhibiting p38 kinase-mediated endocytosis of Na,K-ATPase. Our results reveal a new role for p38 kinase in mediating cross-talk between apical Na(+) entry via ENaC and its basolateral exit via Na,K-ATPase, which may allow principal cells to maintain intracellular Na(+) concentrations within narrow limits. PMID- 24179171 TI - Serum calcification propensity predicts all-cause mortality in predialysis CKD. AB - Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T50 tertile was more than two times the risk among patients in the highest T50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification. PMID- 24179172 TI - With complements from ANCA mice. PMID- 24179173 TI - Systems biology analysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA1. AB - DNA damage repair is implicated in neurodegenerative diseases; however, the relative contributions of various DNA repair systems to the pathology of these diseases have not been investigated systematically. In this study, we performed a systematic in vivo screen of all available Drosophila melanogaster homolog DNA repair genes, and we tested the effect of their overexpression on lifespan and developmental viability in Spinocerebellar Ataxia Type 1 (SCA1) Drosophila models expressing human mutant Ataxin-1 (Atxn1). We identified genes previously unknown to be involved in CAG-/polyQ-related pathogenesis that function in multiple DNA damage repair systems. Beyond the significance of each repair system, systems biology analyses unraveled the core networks connecting positive genes in the gene screen that could contribute to SCA1 pathology. In particular, RpA1, which had the largest effect on lifespan in the SCA1 fly model, was located at the hub position linked to such core repair systems, including homologous recombination (HR). We revealed that Atxn1 actually interacted with RpA1 and its essential partners BRCA1/2. Furthermore, mutant but not normal Atxn1 impaired the dynamics of RpA1 in the nucleus after DNA damage. Uptake of BrdU by Purkinje cells was observed in mutant Atxn1 knockin mice, suggesting their abnormal entry to the S phase. In addition, chemical and genetic inhibitions of Chk1 elongated lifespan and recovered eye degeneration. Collectively, we elucidated core networks for DNA damage repair in SCA1 that might include the aberrant usage of HR. PMID- 24179174 TI - Beta tubulin isoforms are not interchangeable for rescuing impaired radial migration due to Tubb3 knockdown. AB - Over the last years, the critical role of cytoskeletal proteins in cortical development including neuronal migration as well as in neuronal morphology has been well established. Inputs from genetic studies were provided through the identification of several mutated genes encoding either proteins associated with microtubules (DCX, LIS1, KIF2A, KIF5C, DYNC1H1) or tubulin subunits (TUBA1A, TUBB2B, TUBB5 and TUBG1), in malformations of cortical development (MCD). We also reported the identification of missense mutations in TUBB3, the postmitotic neuronal specific tubulin, in six different families presenting either polymicrogyria or gyral disorganization in combination with cerebellar and basal ganglial abnormalities. Here, we investigate further the association between TUBB3 mutations and MCDs by analyzing the consequences of Tubb3 knockdown on cortical development in mice. Using the in utero-electroporation approach, we demonstrate that Tubb3 knockdown leads to delayed bipolar morphology and radial migration with evidence, suggesting that the neuronal arrest is a transient phenomenon overcome after birth. Silenced blocked cells display a round-shape and decreased number of processes and a delay in the acquisition of the bipolar morphology. Also, more Tbr2 positive cells are observed, although less cells express the proliferation marker Ki67, suggesting that Tubb3 inactivation might have an indirect effect on intermediate progenitor proliferation. Furthermore, we show by rescue experiments the non-interchangeability of other beta-tubulins which are unable to rescue the phenotype. Our study highlights the critical and specific role of Tubb3 on the stereotyped morphological changes and polarization processes that are required for initiating radial migration to the cortical plate. PMID- 24179175 TI - Statin-induced changes in gene expression in EBV-transformed and native B-cells. AB - Human lymphoblastoid cell lines (LCLs), generated through Epstein-Barr Virus (EBV) transformation of B-lymphocytes (B-cells), are a commonly used model system for identifying genetic influences on human diseases and on drug responses. We have previously used LCLs to examine the cellular effects of genetic variants that modulate the efficacy of statins, the most prescribed class of cholesterol lowering drugs used for the prevention and treatment of cardiovascular disease. However, statin-induced gene expression differences observed in LCLs may be influenced by their transformation, and thus differ from those observed in native B-cells. To assess this possibility, we prepared LCLs and purified B-cells from the same donors, and compared mRNA profiles after 24 h incubation with simvastatin (2 um) or sham buffer. Genes involved in cholesterol metabolism were similarly regulated between the two cell types under both the statin and sham treated conditions, and the statin-induced changes were significantly correlated. Genes whose expression differed between the native and transformed cells were primarily implicated in cell cycle, apoptosis and alternative splicing. We found that ChIP-seq signals for MYC and EBNA2 (an EBV transcriptional co-activator) were significantly enriched in the promoters of genes up-regulated in the LCLs compared with the B-cells, and could be involved in the regulation of cell cycle and alternative splicing. Taken together, the results support the use of LCLs for the study of statin effects on cholesterol metabolism, but suggest that drug effects on cell cycle, apoptosis and alternative splicing may be affected by EBV transformation. This dataset is now uploaded to GEO at the accession number GSE51444. PMID- 24179176 TI - High-content screening identifies small molecules that remove nuclear foci, affect MBNL distribution and CELF1 protein levels via a PKC-independent pathway in myotonic dystrophy cell lines. AB - Myotonic dystrophy (DM) is a multi-system neuromuscular disorder for which there is no treatment. We have developed a medium throughput phenotypic assay, based on the identification of nuclear foci in DM patient cell lines using in situ hybridization and high-content imaging to screen for potentially useful therapeutic compounds. A series of further assays based on molecular features of DM have also been employed. Two compounds that reduce and/or remove nuclear foci have been identified, Ro 31-8220 and chromomycin A3. Ro 31-8220 is a PKC inhibitor, previously shown to affect the hyperphosphorylation of CELF1 and ameliorate the cardiac phenotype in a DM1 mouse model. We show that the same compound eliminates nuclear foci, reduces MBNL1 protein in the nucleus, affects ATP2A1 alternative splicing and reduces steady-state levels of CELF1 protein. We demonstrate that this effect is independent of PKC activity and conclude that this compound may be acting on alternative kinase targets within DM pathophysiology. Understanding the activity profile for this compound is key for the development of targeted therapeutics in the treatment of DM. PMID- 24179177 TI - Long-term results after aortic root replacement using self-assembled valve composite grafts in patients with small aortic annulus. AB - OBJECTIVES: The study was aimed to evaluate operative and long-term results after complete root replacement using self-assembled valve composite grafts in patients with a small aortic annulus. METHODS: Among 547 consecutive patients who received the Bentall procedure between 2000 and 2012, a total of 29 patients (61 +/- 10; range 42-79 years) had an annulus of <=20 mm (mean 19.0 +/- 0.9). Patients with a native aortic valve (22) suffered from stenosis, insufficiency or mixed defect in 10, 10 and 2 cases, respectively. Among the remaining 7 patients with an artificial aortic valve, there were 3 symptomatic prosthesis-patient mismatches, 3 valve prosthesis deteriorations (1 structural and 2 none-structural) and 1 paravalvular leak. Indication for aortic root replacement was true or false aneurysm, porcelain aorta and intraoperative aortic wall injury in 17, 6 and 6 patients, respectively. RESULTS: The composite graft for complete aortic root replacement was assembled using a mechanical (26) or biological (3) valve prosthesis placed inside a vascular graft with a median size of 24 (range 22-26) mm. The margin of the tube beneath the valve was anastomosed to the aortic annulus, and coronary ostia were implanted in the usual manner. The mean transvalvular gradient at discharge was 10.8 +/- 3.9 mmHg and remained virtually unchanged at the follow-up completed for all patients. Early mortality was 0. During the mean follow-up of 95.8 +/- 43.7 months, 2 patients died (54 and 146 months after surgery) due to pulmonary embolism and myocardial infarction, respectively. CONCLUSIONS: In patients with a small aortic annulus who need complete aortic root replacement, an oversizing of the valve can be easily achieved using modified, self-assembled composite grafts. Offering excellent haemodynamic characteristics, these grafts lead to prevention of prosthesis patient mismatch and result in very good and durable functional and clinical results. PMID- 24179178 TI - Microvirga vignae sp. nov., a root nodule symbiotic bacterium isolated from cowpea grown in semi-arid Brazil. AB - 16S rRNA gene sequence analysis of eight strains (BR 3299(T), BR 3296, BR 10192, BR 10193, BR 10194, BR 10195, BR 10196 and BR 10197) isolated from nodules of cowpea collected from a semi-arid region of Brazil showed 97 % similarity to sequences of recently described rhizobial species of the genus Microvirga. Phylogenetic analyses of four housekeeping genes (gyrB, recA, dnaK and rpoB), DNA DNA relatedness and AFLP further indicated that these strains belong to a novel species within the genus Microvirga. Our data support the hypothesis that genes related to nitrogen fixation were obtained via horizontal gene transfer, as sequences of nifH genes were very similar to those found in members of the genera Rhizobium and Mesorhizobium, which are not immediate relatives of the genus Microvirga, as shown by 16S rRNA gene sequence analysis. Phenotypic traits, such as host range and carbon utilization, differentiate the novel strains from the most closely related species, Microvirga lotononidis, Microvirga zambiensis and Microvirga lupini. Therefore, these symbiotic nitrogen-fixing bacteria are proposed to be representatives of a novel species, for which the name Microvirga vignae sp. nov. is suggested. The type strain is BR3299(T) ( = HAMBI 3457(T)). PMID- 24179179 TI - Hospital charges associated with motorcycle crash factors: a quantile regression analysis. AB - BACKGROUND: Previous studies of motorcycle crash (MC) related hospital charges use trauma registries and hospital records, and do not adjust for the number of motorcyclists not requiring medical attention. This may lead to conservative estimates of helmet use effectiveness. METHODS: MC records were probabilistically linked with emergency department and hospital records to obtain total hospital charges. Missing data were imputed. Multivariable quantile regression estimated reductions in hospital charges associated with helmet use and other crash factors. RESULTS: Motorcycle helmets were associated with reduced median hospital charges of $256 (42% reduction) and reduced 98th percentile of $32,390 (33% reduction). After adjusting for other factors, helmets were associated with reductions in charges in all upper percentiles studied. Quantile regression models described homogenous and heterogeneous associations between other crash factors and charges. CONCLUSIONS: Quantile regression comprehensively describes associations between crash factors and hospital charges. Helmet use among motorcyclists is associated with decreased hospital charges. PMID- 24179180 TI - Trachoma among children in community surveys from four African countries and implications of using school surveys for evaluating prevalence. AB - BACKGROUND: School surveys provide a convenient platform to obtain large child cohorts from multiple communities and are widely used as a proxy to determine community prevalence of neglected tropical diseases. The purpose of this study was to compare trachoma prevalence between preschool- and school-aged children and children who attend and do not attend school. METHODS: We analysed data from community-based trachoma surveys conducted from 2008-2011 in Ethiopia, Mali, Niger and Nigeria. The surveys utilised a cross-sectional, randomised cluster design. Individual-level data on school attendance was collected. RESULTS: Overall, 75 864 children aged 1-15 years from 2100 communities were included in the analysis. The prevalence of trachomatous inflammation follicular (TF) among these children in surveyed districts was 19.1% (95% CI 17.9-20.2%) in Ethiopia, 6.2% (95% CI 5.4-6.9%) in Niger, 4.6% (95% CI 4.2-4.9%) in Mali and 4.2% (95% CI 3.5-4.9%) in Nigeria. Controlling for age, sex and clustering, the OR of TF for school-attendees compared to non-attendees was 0.64 (95% CI 0.56-0.73) in Ethiopia, 0.67 (95% CI 0.56-0.80) in Mali, 1.03 (95% CI 0.81-1.16) in Niger and 1.06, (95% CI 0.65-1.73) in Nigeria. CONCLUSION: Estimating the prevalence of trachoma through examination of only school-going children risks underestimating the true prevalence. PMID- 24179181 TI - Bridging the science-to-service gap in schizophrenia care in the Netherlands: the Schizophrenia Quality Improvement Collaborative. AB - OBJECTIVE: Many patients with schizophrenia are not treated in line with evidence based guidelines. This study examines the large-scale implementation of the National Multidisciplinary Guideline for schizophrenia in the Netherlands. DESIGN: /st> Observational, prospective study, with repeated measurement. SETTING: Thirty mental healthcare teams in different regions of the Netherlands. PARTICIPANTS: Three hundred and fifty-nine clinicians with different professional backgrounds and 1489 patients suffering from schizophrenia. INTERVENTION(S): Six evidence-based interventions for schizophrenia were implemented, in the context of a quality improvement collaborative: assertive community treatment (ACT) or its adapted version functional assertive community treatment (FACT), cognitive behavioural therapy, psycho-education, family interventions, individual placement support and pharmacotherapy. MAIN OUTCOME MEASURE(S): Professional performance, social functioning and relapse rates. RESULTS: Improved professional performance, in line with guidelines. Availability of (F)ACT improved from 23 to 60%. Individual Placement Support improved from 20 to 53%. Complete care plans were composed for 38% of the patients and routine outcome monitoring was introduced in most teams. Social functioning improved slightly (HoNOS mean: from 6.2 to 5.6). Relapse rates did not improve during the course of the study. CONCLUSIONS: An intensive implementation programme can result in an improved delivery of evidence based care, increased continuity of care and slightly improved outcomes for individuals with schizophrenia. More rigorous research designs have to confirm these findings. PMID- 24179182 TI - NCRP report 160 and what it means for medical imaging and nuclear medicine. AB - The purpose of this paper is to briefly explain report 160 of the National Council on Radiation Protection and Measurement and the significance of the report to medical imaging as a whole and nuclear medicine specifically. The implications of the findings of report 160 have had repercussions and will continue to affect all of ionizing radiation medical imaging. The nuclear medicine community should have an understanding of why and how report 160 is important. After reading this article, the nuclear medicine technologist will be familiar with the main focus of report 160, the significant change that has occurred since the 1980s in the ionizing radiation exposure of people in the United States, the primary background source of ionizing radiation in the United States, the primary medical exposure to ionizing radiation in the United States, trends in nuclear medicine procedures and patient exposure, and a comparison of population doses between 2006 and the early 1980s as outlined in report 160. PMID- 24179183 TI - Relation of carotid artery 18F-FDG uptake to C-reactive protein and Framingham risk score in a large cohort of asymptomatic adults. AB - We investigated the relation of carotid (18)F-FDG uptake to high-sensitivity C reactive protein (hsCRP) and Framingham risk score (FRS) in a large cohort of asymptomatic adults. METHODS: Carotid artery (18)F-FDG uptake was measured on the PET/CT scans of 1,181 asymptomatic subjects, and maximum target-to-background ratio (M-TBR) and intima-media thickness (IMT) were compared with clinical risk factors and hsCRP. The estimated 10-y risk for general cardiovascular disease was calculated by FRS. RESULTS: FRS increased from 11.5% +/- 7.8% to 14.8% +/- 10.5% in subjects with an M-TBR >= 1.7, compared with < 1.7, and the odds ratio for an FRS >= 10% was 1.9 (95% confidence interval [CI], 1.4-2.5). Adjusting for age confirmed a significant association of M-TBR and IMT with FRS. Independent determinants of high M-TBR were abdominal fat (beta coefficient [B], 1.1040; P < 0.0001), low-density lipoprotein (LDL) (B, 0.0006; P < 0.05), and FRS (B, 0.0025; P < 0.05) for subjects < 50 y and abdominal fat (B, 0.9740; P < 0.0001), age (B, 0.0040; P = 0.0001), LDL (B, 0.0008; P = 0.0001), and IMT (B, 0.1097; P < 0.01) for subjects >= 50 y. Although hsCRP also stratified subjects for FRS-based risk, no correlation was found between hsCRP and M-TBR or IMT, suggesting that they may have different inferences. Importantly, in the low-hsCRP (14.2% +/- 9.7% vs. 11.3% +/- 7.4%) and high-hsCRP groups (18.8% +/- 14.3% vs. 13.3% +/- 10.2%), FRS was significantly greater for subjects with high M-TBR than for those with low M TBR. The odds ratio for FRS >= 10% between subjects with high and low M-TBR was 1.20 (95% CI, 0.90-1.60; P = 0.209) in the low-hsCRP group and 2.95 (95% CI, 1.48 5.86; P = 0.002) in the high-hsCRP group. CONCLUSION: High carotid (18)F-FDG uptake in asymptomatic adults is associated with increased clinical risk factors and FRS. Furthermore, it appears to reflect aspects of atherosclerotic inflammation distinct from hsCRP concentration and may offer incremental information regarding cardiovascular risk. PMID- 24179184 TI - 18F-FDG Imaging of carotid arteries for identifying the vulnerable patient: are we at the beginning of the end? PMID- 24179186 TI - Integrating mediation and moderation to advance theory development and testing. AB - OBJECTIVE: The concepts and associated analyses of mediation and moderation are important to the field of psychology. Although pediatric psychologists frequently incorporate mediation and moderation in their theories and empirical research, on few occasions have we integrated mediation and moderation. In this article, conceptual reasons for integrating mediation and moderation are offered. METHOD: We illustrate a model that integrates mediation and moderation. RESULTS: In our illustration, the strength of an indirect or a mediating effect varied as a function of a moderating variable. CONCLUSIONS: Clinical implications of the integration of mediation and moderation are discussed, as is the potential of integrated models to advance research programs in pediatric psychology. PMID- 24179185 TI - SPECT imaging of inflammatory response in ischemic-reperfused rat hearts using a 99mTc-labeled dual-domain cytokine ligand. AB - Soluble tumor necrosis factor (TNF) receptor-2 (TNFR2) and interleukin-1 receptor antagonist (IL-1ra) were fused to the Fc portion of IgG1 using recombinant DNA technology. The resulting dual-domain cytokine ligand, TNFR2-Fc-IL-1ra, specifically binds to TNF and to the type I IL-1 receptor (IL-1RI). This study was designed to characterize the kinetic profile of (99m)Tc-labeled TNFR2-Fc-IL 1ra (TFI) for imaging inflammatory response in an ischemic-reperfused (IR) rat heart model. METHODS: The IR model was created by ligating the left coronary artery for 45 min, followed by 2-h reperfusion. Cardiac SPECT images of TFI in the IR model (n = 6) were dynamically acquired for 3 h. Correlative data of myocardial TFI distribution versus microsphere-determined tissue blood flow were acquired in 3 extra IR hearts. Inflammation targeting affinity of TFI was compared with 2 individual cytokine radioligands, (99m)Tc-IL-1ra-Fc (IF) and (99m)Tc-TNFR2-Fc (TF) (n = 6 each group). Myocardial cytokine expression was evaluated by immunochemical assay. RESULTS: Increased TFI uptake was found in the ischemic area and correlated with the severity of ischemia. At 3 h after injection, the ratio of hot-spot accumulation in the ischemic area to a remote viable zone was 5.39 +/- 1.11 for TFI, which was greater than that for IF (3.28 +/- 0.81) and TF (3.29 +/- 0.75) (P < 0.05). The in vivo uptake profiles of TFI, TF, and IF were consistent with ex vivo radioactive measurements and correlated with upregulated IL-1 and TNF expression. CONCLUSION: The dual-domain TFI is promising for noninvasive detection of inflammatory reactions in IR myocardium because of its more potent affinity to the inflammatory sites compared with TF and IF. PMID- 24179188 TI - Seize the neuroscience moment. PMID- 24179187 TI - Combating human trafficking in the sex trade: can sex workers do it better? AB - BACKGROUND: The dominant anti-trafficking paradigm conflates trafficking and sex work, denying evidence that most sex workers choose their profession and justifying police actions that disrupt communities, drive sex workers underground and increase vulnerability. METHODS: We review an alternative response to combating human trafficking and child prostitution in the sex trade, the self regulatory board (SRB) developed by Durbar Mahila Samanwaya Committee (DMSC, Sonagachi). RESULTS: DMSC-led interventions to remove minors and unwilling women from sex work account for over 80% of successful 'rescues' reported in West Bengal. From 2009 through 2011, 2195 women and girls were screened by SRBs: 170 (7.7%) minors and 45 (2.1%) unwilling adult women were assisted and followed up. The remaining 90.2% received counselling, health care and the option to join savings schemes and other community programmes designed to reduce sex worker vulnerability. Between 1992 and 2011 the proportion of minors in sex work in Sonagachi declined from 25 to 2%. CONCLUSIONS: With its universal surveillance of sex workers entering the profession, attention to rapid and confidential intervention and case management, and primary prevention of trafficking-including microcredit and educational programmes for children of sex workers-the SRB approach stands as a new model of success in anti-trafficking work. PMID- 24179193 TI - Particle physics. New experiment torpedoes lightweight dark matter. PMID- 24179194 TI - Genetics. RNA helps resurrect ancient DNA. PMID- 24179195 TI - Marine biology. Industry lobbying derails trawling ban in Europe. PMID- 24179196 TI - Europe. French mathematician tapped to head key funding agency. PMID- 24179197 TI - Vaccines. Structural biology triumph offers hope against a childhood killer. PMID- 24179198 TI - HIV surface proteins finally caught going au naturel. PMID- 24179200 TI - Dark matter's dark horse. PMID- 24179199 TI - Short-circuiting depression. PMID- 24179201 TI - Health and obesity: a new normal? PMID- 24179202 TI - Health and obesity: not just skin deep. PMID- 24179203 TI - Emerging arsenic threat in Canada. PMID- 24179205 TI - Life in science. Zombiology. PMID- 24179206 TI - Economics. Doctoral students and U.S. immigration policy. PMID- 24179207 TI - Genetics. Our fallen genomes. PMID- 24179208 TI - Ecology. Dust unto dust. PMID- 24179209 TI - Plant science. A pathway to flowering--why staying cool matters. PMID- 24179210 TI - Applied physics. Storing quantum information in Schrodinger's cats. PMID- 24179211 TI - Physics. Quantized electronic heat flow. PMID- 24179212 TI - Physiology. Rhythmic respiration. PMID- 24179213 TI - Retrospective. David H. Hubel (1926-2013). PMID- 24179214 TI - Eppendorf. Space bats: multidimensional spatial representation in the bat. PMID- 24179215 TI - Eppendorf. Play it again, brain. PMID- 24179216 TI - Eppendorf. Brains don't play dice--or do they? PMID- 24179217 TI - The heavily connected brain. Connection, connection, connection... Introduction. PMID- 24179218 TI - Functional interactions as big data in the human brain. AB - Noninvasive studies of human brain function hold great potential to unlock mysteries of the human mind. The complexity of data generated by such studies, however, has prompted various simplifying assumptions during analysis. Although this has enabled considerable progress, our current understanding is partly contingent upon these assumptions. An emerging approach embraces the complexity, accounting for the fact that neural representations are widely distributed, neural processes involve interactions between regions, interactions vary by cognitive state, and the space of interactions is massive. Because what you see depends on how you look, such unbiased approaches provide the greatest flexibility for discovery. PMID- 24179219 TI - Predispositions and plasticity in music and speech learning: neural correlates and implications. AB - Speech and music are remarkable aspects of human cognition and sensory-motor processing. Cognitive neuroscience has focused on them to understand how brain function and structure are modified by learning. Recent evidence indicates that individual differences in anatomical and functional properties of the neural architecture also affect learning and performance in these domains. Here, neuroimaging findings are reviewed that reiterate evidence of experience dependent brain plasticity, but also point to the predictive validity of such data in relation to new learning in speech and music domains. Indices of neural sensitivity to certain stimulus features have been shown to predict individual rates of learning; individual network properties of brain activity are especially relevant in this regard, as they may reflect anatomical connectivity. Similarly, numerous studies have shown that anatomical features of auditory cortex and other structures, and their anatomical connectivity, are predictive of new sensory motor learning ability. Implications of this growing body of literature are discussed. PMID- 24179221 TI - Evolution of the magnetic field structure of the Crab pulsar. AB - Pulsars are highly magnetized rotating neutron stars and are well known for the stability of their signature pulse shapes, allowing high-precision studies of their rotation. However, during the past 22 years, the radio pulse profile of the Crab pulsar has shown a steady increase in the separation of the main pulse and interpulse components at 0.62 degrees +/- 0.03 degrees per century. There are also secular changes in the relative strengths of several components of the profile. The changing component separation indicates that the axis of the dipolar magnetic field, embedded in the neutron star, is moving toward the stellar equator. This evolution of the magnetic field could explain why the pulsar does not spin down as expected from simple braking by a rotating dipolar magnetic field. PMID- 24179220 TI - Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. AB - Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site O, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site O when exposed to extremes of pH, osmolality, and temperature. Six RSV F crystal structures provided atomic-level data on how introduced cysteine residues and filled hydrophobic cavities improved stability. Immunization with site O-stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold. PMID- 24179222 TI - Parameter space compression underlies emergent theories and predictive models. AB - The microscopically complicated real world exhibits behavior that often yields to simple yet quantitatively accurate descriptions. Predictions are possible despite large uncertainties in microscopic parameters, both in physics and in multiparameter models in other areas of science. We connect the two by analyzing parameter sensitivities in a prototypical continuum theory (diffusion) and at a self-similar critical point (the Ising model). We trace the emergence of an effective theory for long-scale observables to a compression of the parameter space quantified by the eigenvalues of the Fisher Information Matrix. A similar compression appears ubiquitously in models taken from diverse areas of science, suggesting that the parameter space structure underlying effective continuum and universal theories in physics also permits predictive modeling more generally. PMID- 24179223 TI - One-dimensional electrical contact to a two-dimensional material. AB - Heterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, depends critically on the ability to make high quality electrical contact. Here, we report a contact geometry in which we metalize only the 1D edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials. PMID- 24179224 TI - Pacific Ocean heat content during the past 10,000 years. AB - Observed increases in ocean heat content (OHC) and temperature are robust indicators of global warming during the past several decades. We used high resolution proxy records from sediment cores to extend these observations in the Pacific 10,000 years beyond the instrumental record. We show that water masses linked to North Pacific and Antarctic intermediate waters were warmer by 2.1 +/- 0.4 degrees C and 1.5 +/- 0.4 degrees C, respectively, during the middle Holocene Thermal Maximum than over the past century. Both water masses were ~0.9 degrees C warmer during the Medieval Warm period than during the Little Ice Age and ~0.65 degrees warmer than in recent decades. Although documented changes in global surface temperatures during the Holocene and Common era are relatively small, the concomitant changes in OHC are large. PMID- 24179225 TI - Reconstructing the microbial diversity and function of pre-agricultural tallgrass prairie soils in the United States. AB - Native tallgrass prairie once dominated much of the midwestern United States, but this biome and the soil microbial diversity that once sustained this highly productive system have been almost completely eradicated by decades of agricultural practices. We reconstructed the soil microbial diversity that once existed in this biome by analyzing relict prairie soils and found that the biogeographical patterns were largely driven by changes in the relative abundance of Verrucomicrobia, a poorly studied bacterial phylum that appears to dominate many prairie soils. Shotgun metagenomic data suggested that these spatial patterns were associated with strong shifts in carbon dynamics. We show that metagenomic approaches can be used to reconstruct below-ground biogeochemical and diversity gradients in endangered ecosystems; such information could be used to improve restoration efforts, given that even small changes in below-ground microbial diversity can have important impacts on ecosystem processes. PMID- 24179226 TI - Mosaic copy number variation in human neurons. AB - We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons. PMID- 24179227 TI - Resident neural stem cells restrict tissue damage and neuronal loss after spinal cord injury in mice. AB - Central nervous system injuries are accompanied by scar formation. It has been difficult to delineate the precise role of the scar, as it is made by several different cell types, which may limit the damage but also inhibit axonal regrowth. We show that scarring by neural stem cell-derived astrocytes is required to restrict secondary enlargement of the lesion and further axonal loss after spinal cord injury. Moreover, neural stem cell progeny exerts a neurotrophic effect required for survival of neurons adjacent to the lesion. One distinct component of the glial scar, deriving from resident neural stem cells, is required for maintaining the integrity of the injured spinal cord. PMID- 24179229 TI - Structural and functional brain networks: from connections to cognition. AB - How rich functionality emerges from the invariant structural architecture of the brain remains a major mystery in neuroscience. Recent applications of network theory and theoretical neuroscience to large-scale brain networks have started to dissolve this mystery. Network analyses suggest that hierarchical modular brain networks are particularly suited to facilitate local (segregated) neuronal operations and the global integration of segregated functions. Although functional networks are constrained by structural connections, context-sensitive integration during cognition tasks necessarily entails a divergence between structural and functional networks. This degenerate (many-to-one) function structure mapping is crucial for understanding the nature of brain networks. The emergence of dynamic functional networks from static structural connections calls for a formal (computational) approach to neuronal information processing that may resolve this dialectic between structure and function. PMID- 24179231 TI - Acta Radiologica: Special Pediatric Issue 2013. PMID- 24179230 TI - On and off retinal circuit assembly by divergent molecular mechanisms. AB - Direction-selective responses to motion can be to the onset (On) or cessation (Off) of illumination. Here, we show that the transmembrane protein semaphorin 6A and its receptor plexin A2 are critical for achieving radially symmetric arborization of On starburst amacrine cell (SAC) dendrites and normal SAC stratification in the mouse retina. Plexin A2 is expressed in both On and Off SACs; however, semaphorin 6A is expressed in On SACs. Specific On-Off bistratified direction-selective ganglion cells in semaphorin 6A(-/-) mutants exhibit decreased tuning of On directional motion responses. These results correlate the elaboration of symmetric SAC dendritic morphology and asymmetric responses to motion, shedding light on the development of visual pathways that use the same cell types for divergent outputs. PMID- 24179228 TI - Cortical high-density counterstream architectures. AB - Small-world networks provide an appealing description of cortical architecture owing to their capacity for integration and segregation combined with an economy of connectivity. Previous reports of low-density interareal graphs and apparent small-world properties are challenged by data that reveal high-density cortical graphs in which economy of connections is achieved by weight heterogeneity and distance-weight correlations. These properties define a model that predicts many binary and weighted features of the cortical network including a core-periphery, a typical feature of self-organizing information processing systems. Feedback and feedforward pathways between areas exhibit a dual counterstream organization, and their integration into local circuits constrains cortical computation. Here, we propose a bow-tie representation of interareal architecture derived from the hierarchical laminar weights of pathways between the high-efficiency dense core and periphery. PMID- 24179232 TI - Special issue: Pediatric imaging. PMID- 24179233 TI - Magnetic resonance imaging of the immature skeleton. AB - Magnetic resonance (MR) is unique in its ability to allow assessment of bone marrow, epiphyseal, physeal, and articular cartilage as well as tendons and ligaments. An understanding of skeletal maturation and the accompanying changes on MR is of utmost importance in pediatric radiology. In particular, it is important to recognize the normal spectrum related to ossification and marrow transformation. This review will include a brief description of main indications and common pitfalls in musculoskeletal MR in children. Also, we will focus on the MR appearance of the growing pediatric skeleton on the most commonly used sequences. PMID- 24179234 TI - Bone age assessment: automated techniques coming of age? AB - Bone age determination from hand radiographs is one of the oldest radiographic procedures. The first atlas was published by Poland in 1898, and to date the Greulich Pyle atlas, although it dates from 1959, is still the most commonly used method. Bone age rating is time-consuming, suffers from an unsatisfactorily high rater variability, and therefore already 25 years ago it was proposed to replace the manual rating by an automated, computerized method, a field nowadays referred to as computer-aided diagnosis (CAD). The pursuit of this goal reached a first stage of accomplishment in 1992-1996 with the presentation of several systems. However, they had limited clinical value, and efforts in CAD research were increasingly focused on lesion detection for cancer screening. It was only in 2008 that a fully-automated bone age method was presented, which appears to be clinically acceptable. In this paper we consider the requirements that should be met by an automated bone age method and review the state of the art. Integration in PACS and saving time are important factors for radiologists. But it is the validation of the methods which poses the greatest challenge, because there is no gold standard for bone age rating, and the direct comparison to manual rating is therefore not sufficient for demonstrating that manual rating can be replaced by automated rating. One needs additional studies assessing the precision of a method and its accuracy when used for adult height prediction, which serves as an objective. PMID- 24179236 TI - Nuisance parameter elimination for proportional likelihood ratio models with nonignorable missingness and random truncation. AB - We show that the proportional likelihood ratio model proposed recently by Luo & Tsai (2012) enjoys model-invariant properties under certain forms of nonignorable missing mechanisms and randomly double-truncated data, so that target parameters in the population can be estimated consistently from those biased samples. We also construct an alternative estimator for the target parameters by maximizing a pseudo-likelihood that eliminates a functional nuisance parameter in the model. The corresponding estimating equation has a U-statistic structure. As an added advantage of the proposed method, a simple score-type test is developed to test a null hypothesis on the regression coefficients. Simulations show that the proposed estimator has a small-sample efficiency similar to that of the nonparametric likelihood estimator and performs well for certain nonignorable missing data problems. PMID- 24179237 TI - The CVMA.....is it relevant? PMID- 24179238 TI - An ethicist's commentary on the food animal practitioner treating mange. PMID- 24179239 TI - Antimicrobial therapy of selected diseases in turkeys, laying hens, and minor poultry species in Canada. AB - This paper identifies common poultry diseases requiring antimicrobial therapy, antimicrobials deemed efficacious to treat these diseases, and antimicrobial resistance (AMR) in these commodity-pathogen combinations, and describes current residue issues and minor use minor species (MUMS) guidelines. Veterinarians with turkey/layer expertise and diagnosticians were surveyed to determine the bacterial and protozoal diseases diagnosed in the last 5 years. Avian pathogenic Escherichia coli, Staphylococcus aureus, and Ornithobacterium rhinotracheale were the 3 most frequently diagnosed pathogens of turkeys. In layers, E. coli peritonitis, and Clostridium perfringens/Eimeria spp. infections were the most common diagnoses. A literature review identified 32 antimicrobials as efficacious and/or recommended for treating these diseases. Surveillance and monitoring indicate the presence of enteric resistant organisms from some of these avian species (including resistance to antimicrobials of very high importance to human medicine). This paper highlights the need for surveillance of pathogen frequency, antimicrobial use (AMU), and AMR particularly in turkeys. PMID- 24179240 TI - Evaluation of environmental fecal culture for Mycobacterium avium subspecies paratuberculosis detection in dairy herds and association with apparent within herd prevalence. AB - This study evaluated test characteristics of environmental culture (EC) for the detection of Mycobacterium avium subspecies paratuberculosis (MAP) in 32 herds over a 2-year period. Individual fecal samples were collected every 6 mo and environmental samples every 3 mo. Individual fecal culture was performed on samples from positive pools. Samples were cultured in broth, with confirmatory polymerase chain reaction performed on positive fecal samples. Repeated measures were accounted for using GEE logistic models. Relative to a MAP herd-status based on all pooled fecal culture results collected during the study, sensitivity of a set of 6 EC-samples collected from prescribed locations within the herd environment (EC-6) was 71% [95% confidence interval (CI): 49% to 86%] and specificity was 99% (95% CI: 95% to 100%). Sensitivity of EC increased as apparent within-herd fecal culture prevalence (aWHP) increased. The estimated aWHP increased as the proportion of positive EC-samples within an EC-6 set increased. Environmental culture is an acceptable tool for herd diagnosis of MAP in low-prevalence herds. PMID- 24179241 TI - Comparison of wet-mount, Wright-Giemsa and Gram-stained urine sediment for predicting bacteriuria in dogs and cats. AB - This study assessed the standard urinalysis technique and sediment stain techniques as predictors of bacterial culture results for canine and feline urine. Canine (n = 111) and feline (n = 79) urine samples were evaluated using unstained wet-mount and air-dried Gram and Wright-Giemsa stained sediment; results were compared to aerobic bacterial culture. Eleven canine and 7 feline urine samples were culture positive. Unstained wet-mount and stained sediment had sensitivities of 89% and 83% and specificities of 91% and 99%, respectively. The specificity of using either stain was higher (P < 0.01) than wet-mount examination for detecting bacteriuria. There were significant differences among 3 technologists in detecting true positives (P < 0.01). Association of sediment and culture results used 112 canine and 81 feline samples. There was a negative association (P < 0.01) between lipid detection and wet-mount identification of bacteria. PMID- 24179242 TI - Comminuted fracture of the ulnar carpal bone in a Labrador retriever dog. AB - A 4-year-old male Labrador retriever dog was evaluated for acute lameness without weight-bearing in the right forelimb after an 8-meter fall. Radiographs revealed a comminuted fracture of the ulnar carpal bone that required removal of bone fragments. This appears to be the first report of such a condition. PMID- 24179243 TI - Ectopic spleen presenting with anemia and an abdominal mass in a dog. AB - An 11.5-year-old, neutered male, golden retriever dog that had previously had a splenectomy for benign disease 2 years prior to presentation was diagnosed with anemia and a large abdominal mass. Necropsy and histopathology identified the abdominal mass as ectopic splenic tissue. PMID- 24179244 TI - Primary diffuse leptomeningeal gliomatosis in 2 dogs. AB - Clinical, neuroimaging, and neuropathological findings of 2 cases of canine primary diffuse leptomeningeal gliomatosis are described. Magnetic resonance imaging and histopathological examination of the brain revealed diffuse leptomeningeal alterations with no parenchymal involvement. These cases share many similarities with the same disease in humans. PMID- 24179245 TI - Reduction of the abortion rate due to Toxoplasma in 3 goat herds following administration of sulfadimidine. AB - The efficacy of sulfadimidine (4 doses of 33 mg/kg body weight, IM, q48h) against Toxoplasma abortion was assessed in 3 dairy goat herds suffering from Toxoplasma abortions during the 4th month of gestation. This protocol was very effective for the control of Toxoplasma abortions (P < 0.01). PMID- 24179246 TI - Persistence of Mycobacterium avium subsp. paratuberculosis in soil, crops, and ensiled feed following manure spreading on infected dairy farms. AB - The goal of this study was to determine the persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in soil, crops, and ensiled feeds following manure spreading. This bacterium was often found in soil samples, but less frequently in harvested feeds and silage. Spreading of manure on fields used for crop harvest is preferred to spreading on grazing pastures. PMID- 24179247 TI - Is your examination fee costing you clients? PMID- 24179248 TI - Diagnostic ophthalmology. Corneal perforation with iris prolapse and anterior uveitis due to injury in a horse. PMID- 24179249 TI - Batteries used to Power Implantable Biomedical Devices. AB - Battery systems have been developed that provide years of service for implantable medical devices. The primary systems utilize lithium metal anodes with cathode systems including iodine, manganese oxide, carbon monofluoride, silver vanadium oxide and hybrid cathodes. Secondary lithium ion batteries have also been developed for medical applications where the batteries are charged while remaining implanted. While the specific performance requirements of the devices vary, some general requirements are common. These include high safety, reliability and volumetric energy density, long service life, and state of discharge indication. Successful development and implementation of these battery types has helped enable implanted biomedical devices and their treatment of human disease. PMID- 24179250 TI - Perceptions of environmental compensation in different scientific fields. AB - Environmental compensation is used worldwide, but remains a concept under development in many countries. The underlying idea is to maintain the overall quality of the environment in cases where environmental assets are damaged, for example, by residential or industrial development or by road construction. This study aimed to investigate how environmental compensation is perceived in a number of scientific fields and what the differences, if any, are between those fields. The results showed that the respondents took a positive view of environmental compensation in general, of the inclusion of social aspects and of the role of NGOs, but that they also (implicitly) questioned the mitigation hierarchy. The study also revealed several differences between the scientific disciplines, though mainly in the differing strengths of the groups' convictions. PMID- 24179251 TI - A novel multiblock immersed boundary method for large eddy simulation of complex arterial hemodynamics. AB - Computational fluid dynamics (CFD) simulations are becoming a reliable tool to understand hemodynamics, disease progression in pathological blood vessels and to predict medical device performance. Immersed boundary method (IBM) emerged as an attractive methodology because of its ability to efficiently handle complex moving and rotating geometries on structured grids. However, its application to study blood flow in complex, branching, patient-specific anatomies is scarce. This is because of the dominance of grid nodes in the exterior of the fluid domain over the useful grid nodes in the interior, rendering an inevitable memory and computational overhead. In order to alleviate this problem, we propose a novel multiblock based IBM that preserves the simplicity and effectiveness of the IBM on structured Cartesian meshes and enables handling of complex, anatomical geometries at a reduced memory overhead by minimizing the grid nodes in the exterior of the fluid domain. As pathological and medical device hemodynamics often involve complex, unsteady transitional or turbulent flow fields, a scale resolving turbulence model such as large eddy simulation (LES) is used in the present work. The proposed solver (here after referred as WenoHemo), is developed by enhancing an existing in-house high order incompressible flow solver that was previously validated for its numerics and several LES models by Shetty et al. [Journal of Computational Physics 2010; 229 (23), 8802-8822]. In the present work, WenoHemo is systematically validated for additional numerics introduced, such as IBM and the multiblock approach, by simulating laminar flow over a sphere and laminar flow over a backward facing step respectively. Then, we validate the entire solver methodology by simulating laminar and transitional flow in abdominal aortic aneurysm (AAA). Finally, we perform blood flow simulations in the challenging clinically relevant thoracic aortic aneurysm (TAA), to gain insights into the type of fluid flow patterns that exist in pathological blood vessels. Results obtained from the TAA simulations reveal complex vortical and unsteady flow fields that need to be considered in designing and implanting medical devices such as stent grafts. PMID- 24179252 TI - Equation of state for a coarse-grained DPPC monolayer at the air/water interface. AB - Pulmonary surfactant, a complex mixture of phospholipids and proteins, secreted by the type II epithelial cells in the lungs, is crucial to reducing the effort required for breathing. A lack of adequate amounts of pulmonary surfactant in underdeveloped lungs of premature infants results in infant respiratory distress syndrome (RDS). Surfactant replacement therapy (SRT) is the approved method of mitigating the effects of RDS. The development of new SRT regimens requires a fundamental understanding of the links between surfactant biochemistry and functionality. We use a coarse-grained (CG) model to predict the surface pressure surface concentration relationship (equation of state) for pure DPPC, which is a major component of endogenous and synthetic pulmonary surfactant mixtures. We show that the model can be efficiently used to predict the equation of state in excellent agreement with experimental results. We also study the structure of the monolayer as a function of the surface tension of the system. We show that a decrease in the applied surface tension results in an increase in order in the head group region and a decrease in order in the tail region of DPPC. This technique may be useful in the prediction of equations of state for surfactant replacements. PMID- 24179253 TI - A message from the editor. PMID- 24179254 TI - Surgeon general's perspectives. PMID- 24179255 TI - Fatalities of pedestrians, bicycle riders, and motorists due to distracted driving motor vehicle crashes in the U.S., 2005-2010. AB - OBJECTIVE: Distracted driving is an increasingly deadly threat to road safety. This study documents trends in and characteristics of pedestrian, bicycle rider, and other victim deaths caused by distracted drivers on U.S. public roads. METHODS: We obtained data from the Fatality Analysis Reporting System database from 2005 to 2010 on every crash that resulted in at least one fatality within 30 days occurring on public roads in the U.S. Following the definition used by the National Highway Traffic Safety Administration, we identified distracted driving based on whether police investigators determined that a driver had been using a technological device, including a cell phone, onboard navigation system, computer, fax machine, two-way radio, or head-up display, or had been engaged in inattentive or careless activities. RESULTS: The rate of fatalities per 10 billion vehicle miles traveled increased from 116.1 in 2005 to 168.6 in 2010 for pedestrians and from 18.7 in 2005 to 24.6 in 2010 for bicyclists. Pedestrian victims of distracted driving crashes were disproportionately male, 25-64 years of age, and non-Hispanic white. They were also more likely to die at nighttime, be struck by a distracted driver outside of a marked crosswalk, and be in a metro location. Bicycling victims of distracted crashes were disproportionately male, non-Hispanic white, and struck by a distracted driver outside of a crosswalk. Compared with pedestrians, bicyclists were less likely to be hit in early morning. CONCLUSIONS: Distracted drivers are the cause of an increasing share of fatalities found among pedestrians and bicycle riders. Policies are needed to protect pedestrians and bicycle riders as they cross intersections or travel on roadways. PMID- 24179256 TI - Leading causes of unintentional injury and suicide mortality in Canadian adults across the urban-rural continuum. AB - OBJECTIVE: We examined the leading causes of unintentional injury and suicide mortality in adults across the urban-rural continuum. METHODS: Injury mortality data were drawn from a representative cohort of 2,735,152 Canadians aged >= 25 years at baseline, who were followed for mortality from 1991 to 2001. We estimated hazard ratios and 95% confidence intervals for urban-rural continuum and cause-specific unintentional injury (i.e., motor vehicle, falls, poisoning, drowning, suffocation, and fire/burn) and suicide (i.e., hanging, poisoning, firearm, and jumping) mortality, adjusting for socioeconomic and demographic characteristics. RESULTS: Rates of unintentional injury mortality were elevated in less urbanized areas for both males and females. We found an urban-rural gradient for motor vehicle, drowning, and fire/burn deaths, but not for fall, poisoning, or suffocation deaths. Urban-rural differences in suicide risk were observed for males but not females. Declining urbanization was associated with higher risks of firearm suicides and lower risks of jumping suicides, but there was no apparent trend in hanging and poisoning suicides. CONCLUSION: Urban-rural gradients in adults were more pronounced for unintentional motor vehicle, drowning, and fire/burn deaths, as well as for firearm and jumping suicide deaths than for other causes of injury mortality. These results suggest that the degree of urbanization may be an important consideration in guiding prevention efforts for many causes of injury fatality. PMID- 24179257 TI - Lead and other heavy metals in dust fall from single-family housing demolition. AB - OBJECTIVE: We measured lead and other heavy metals in dust during older housing demolition and effectiveness of dust suppression. METHODS: We used American Public Housing Association Method 502 and U.S. Environmental Protection Agency Methods SW3050B and SW6020 at 97 single-family housing demolition events with intermittent (or no) use of water to suppress dust at perimeter, non-perimeter, and locations without demolition, with nested mixed modeling and tobit modeling with left censoring. RESULTS: The geometric mean (GM) lead dust fall during demolition was 6.01 micrograms of lead per square foot per hour (MUg Pb/ft(2)/hour). GM lead dust fall was 14.18 MUg Pb/ft(2)/hour without dust suppression, but declined to 5.48 MUg Pb/ft(2)/hour (p=0.057) when buildings and debris were wetted. Significant predictors included distance, wind direction, and main street location. At 400 feet, lead dust fall was not significantly different from background. GM lead concentration at demolition (2,406 parts per million [ppm]) was significantly greater than background (GM=579 ppm, p=0.05). Arsenic, chromium, copper, iron, and manganese demolition dust fall was significantly higher than background (p<0.001). Demolition of approximately 400 old housing units elsewhere with more dust suppression was only 0.25 MUg Pb/ft(2)/hour. CONCLUSIONS: Lead dust suppression is feasible and important in single-family housing demolition where distances between houses are smaller and community exposures are higher. Neighbor notification should be expanded to at least 400 feet away from single-family housing demolition, not just adjacent properties. Further research is needed on effects of distance, potential water contamination, occupational exposures, and water application. PMID- 24179258 TI - Health, chronic conditions, and behavioral risk disparities among U.S. immigrant children and adolescents. AB - OBJECTIVE: We examined differentials in the prevalence of 23 parent-reported health, chronic condition, and behavioral indicators among 91,532 children of immigrant and U.S.-born parents. METHODS: We used the 2007 National Survey of Children's Health to estimate health differentials among 10 ethnic-nativity groups. Logistic regression yielded adjusted differentials. RESULTS: Immigrant children in each racial/ethnic group had a lower prevalence of depression and behavioral problems than native-born children. The prevalence of autism varied from 0.3% among immigrant Asian children to 1.3%-1.4% among native-born non Hispanic white and Hispanic children. Immigrant children had a lower prevalence of asthma, attention deficit disorder/attention deficit hyperactivity disorder; developmental delay; learning disability; speech, hearing, and sleep problems; school absence; and >= 1 chronic condition than native-born children, with health risks increasing markedly in relation to mother's duration of residence in the U.S. Immigrant children had a substantially lower exposure to environmental tobacco smoke, with the odds of exposure being 60%-95% lower among immigrant non Hispanic black, Asian, and Hispanic children compared with native non-Hispanic white children. Obesity prevalence ranged from 7.7% for native-born Asian children to 24.9%-25.1% for immigrant Hispanic and native-born non-Hispanic black children. Immigrant children had higher physical inactivity levels than native born children; however, inactivity rates declined with each successive generation of immigrants. Immigrant Hispanic children were at increased risk of obesity and sedentary behaviors. Ethnic-nativity differentials in health and behavioral indicators remained marked after covariate adjustment. CONCLUSIONS: Immigrant patterns in child health and health-risk behaviors vary substantially by ethnicity, generational status, and length of time since immigration. Public health programs must target at-risk children of both immigrant and U.S.-born parents. PMID- 24179259 TI - Barriers to care and comorbidities along the U.S.-Mexico border. AB - OBJECTIVE: While limited access to care is associated with adverse health conditions, little research has investigated the association between barriers to care and having multiple health conditions (comorbidities). We compared the financial, structural, and cognitive barriers to care between Mexican-American border residents with and without comorbidities. METHODS: We conducted a stratified, two-stage, randomized, cross-sectional health survey in 2009-2010 among 1,002 Mexican-American households. Measures included demographic characteristics; financial, structural, and cognitive barriers to health care; and prevalence of health conditions. RESULTS: Comorbidities, most frequently cardiovascular and metabolic conditions, were reported by 37.7% of participants. Controlling for demographics, income, and health insurance, six financial barriers, including direct measures of inability to pay for medical costs, were associated with having comorbidities (odds ratios [ORs] ranged from 1.7 to 4.1, p<0.05). The structural barrier of transportation (OR=3.65, 95% confidence interval [CI] 1.91, 6.97, p<0.001) was also associated with higher odds of comorbidities, as were cognitive barriers of difficulty understanding medical information (OR=1.71, 95% CI 1.10, 2.66, p=0.017), being confused about arrangements (OR=1.82, 95% CI 1.04, 3.21, p=0.037), and not being treated with respect in medical settings (OR=1.63, 95% CI 1.05, 2.53, p=0.028). When restricting analyses to participants with at least one health condition (comparing one condition vs. having >= 2 comorbid conditions), associations were maintained for financial and transportation barriers but not for cognitive barriers. CONCLUSION: A substantial proportion of adults reported comorbidities. Given the greater burden of barriers to medical care among people with comorbidities, interventions addressing these barriers present an important avenue for research and practice among Mexican-American border residents. PMID- 24179260 TI - A systematic evaluation of different methods for calculating adolescent vaccination levels using immunization information system data. AB - OBJECTIVE: Immunization information systems (IISs) are valuable surveillance tools; however, population relocation may introduce bias when determining immunization coverage. We explored alternative methods for estimating the vaccine eligible population when calculating adolescent immunization levels using a statewide IIS. METHODS: We performed a retrospective analysis of the Michigan State Care Improvement Registry (MCIR) for all adolescents aged 11-18 years registered in the MCIR as of October 2010. We explored four methods for determining denominators: (1) including all adolescents with MCIR records, (2) excluding adolescents with out-of-state residence, (3) further excluding those without MCIR activity >= 10 years prior to the evaluation date, and (4) using a denominator based on U.S. Census data. We estimated state- and county-specific coverage levels for four adolescent vaccines. RESULTS: We found a 20% difference in estimated vaccination coverage between the most inclusive and restrictive denominator populations. Although there was some variability among the four methods in vaccination at the state level (2%-11%), greater variation occurred at the county level (up to 21%). This variation was substantial enough to potentially impact public health assessments of immunization programs. Generally, vaccines with higher coverage levels had greater absolute variation, as did counties with smaller populations. CONCLUSION: At the county level, using the four denominator calculation methods resulted in substantial differences in estimated adolescent immunization rates that were less apparent when aggregated at the state level. Further research is needed to ascertain the most appropriate method for estimating vaccine coverage levels using IIS data. PMID- 24179261 TI - Hepatitis B vaccination coverage among health-care personnel in the United States. AB - OBJECTIVES: We compared self-reported hepatitis B (HepB) vaccine coverage among health-care personnel (HCP) with HepB vaccine coverage among the general population and determined trends in vaccination coverage among HCP. METHODS: We used the 2010 National Health Interview Survey (NHIS) to determine the weighted proportion of self-reported >= 1- and >= 3-dose HepB vaccine coverage among HCP aged >= 18 years. We used logistic regression to determine independent predictors of vaccination and performed a trend analysis to determine changes in coverage from 2004 to 2010 using data from the 2004-2010 NHIS. RESULTS: Overall, 69.5% (95% confidence interval [CI] 67.2, 71.8) and 63.4% (95% CI 60.8, 65.9) of HCP reported receiving >= 1 and >= 3 doses of HepB vaccine, respectively, compared with 27.1% (95% CI 26.1, 28.1%) and 23.0% (95% CI 22.1, 24.0) among non-HCP. Among HCP with direct patient contact, 80.7% (95% CI 78.2, 83.1) and 74.0% (95% CI 71.2, 76.8) received >= 1 and >= 3 HepB vaccine doses, respectively. Independent predictors of vaccination included direct patient contact, having more than a high school education, influenza vaccination in the past year, and ever having been tested for HIV. There was no significant change in reported coverage from 2004 through 2010. CONCLUSION: The 2010 HepB vaccine coverage estimate among HCP remained well below the Healthy People 2010 goal of 90%. Efforts to target unvaccinated HCP for preexposure HepB protection should be encouraged. PMID- 24179262 TI - Enhanced chronic hepatitis C surveillance in New York City, April 2009-January 2011. AB - OBJECTIVE: We analyzed and evaluated enhanced chronic hepatitis C virus (HCV) surveillance in New York City (NYC), which involved detailed investigations on a sample of newly reported HCV patients. METHODS: Beginning in July 2009, we generated a simple random sample bimonthly from all patients newly reported with a positive HCV test. We administered questionnaires to clinicians and patients to collect clinical and epidemiological information on patients diagnosed from April 2009 to January 2011 and evaluated the staff resources required to conduct enhanced surveillance. RESULTS: Of 205 patients meeting inclusion criteria, 40 (19.5%) tested HCV ribonucleic acid (RNA) negative. For the remaining 165 patients, questionnaires were completed by 164 clinicians (99.4%) and 77 patients (46.7%). Many patients (54.0%) were born between 1945 and 1964, and most patients were Hispanic (32.7%) or non-Hispanic black (32.7%). Common risk factors were injection (43.0%) and intranasal (33.9%) drug use. One-third of patients were diagnosed in nontraditional medical settings including substance abuse/detoxification centers (25.0%), jail/prison (6.7%), and psychiatric facilities (1.8%). Of 98 patients with positive HCV RNA tests, 38.8% were immune to hepatitis A and 39.8% were immune to hepatitis B. Investigators required approximately 3.5 hours to complete each investigation and averaged 50 days from assignment to completion. CONCLUSIONS: Although conducting enhanced HCV surveillance requires significant resources, investigating a representative sample provides detailed information about NYC's HCV population. Surveillance data have been used to plan educational initiatives for clinicians and patients, which may have led to increased awareness of HCV status, improved patient support, and better overall care. PMID- 24179263 TI - Determinants of cervical cancer screening among women with intellectual disabilities: evidence from medical records. AB - OBJECTIVE: We examined receipt of cervical cancer screening and determinants of screening for women with intellectual disabilities in one Southeastern state. METHODS: Using medical records data from 2006 through 2010 for community-dwelling women with intellectual disabilities who were 18-65 years of age (n=163), we employed descriptive and bivariate statistics and a multivariate regression model to examine receipt of cervical cancer screening and the determinants of cervical cancer screening across women's sociodemographic and health-care provider characteristics. RESULTS: Of women 18-65 years of age with intellectual disabilities, 55% received a Papanicolaou (Pap) test during 2008-2010, markedly below the Healthy People 2020 targets or rates of Pap test receipt of women without intellectual disabilities. Women with intellectual disabilities who lived in residential facilities, those who lived in rural communities, and those who had an obstetrician/gynecologist had higher rates of receipt of care than other women with intellectual disabilities. CONCLUSIONS: Assertive measures are required to improve the receipt of cervical cancer screening among women with intellectual disabilities. Such measures could include education of women with intellectual disabilities, as well as their paid and family caregivers, and incentives for health-care providers who achieve screening targets. PMID- 24179264 TI - Assessing the validity and reliability of three indicators self-reported on the pregnancy risk assessment monitoring system survey. AB - OBJECTIVES: We investigated the reliability and validity of three self-reported indicators from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey. METHODS: We used 2008 PRAMS (n=15,646) data from 12 states that had implemented the 2003 revised U.S. Certificate of Live Birth. We estimated reliability by kappa coefficient and validity by sensitivity and specificity using the birth certificate data as the reference for the following: prenatal participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC); Medicaid payment for delivery; and breastfeeding initiation. These indicators were examined across several demographic subgroups. RESULTS: The reliability was high for all three measures: 0.81 for WIC participation, 0.67 for Medicaid payment of delivery, and 0.72 for breastfeeding initiation. The validity of PRAMS indicators was also high: WIC participation (sensitivity = 90.8%, specificity = 90.6%), Medicaid payment for delivery (sensitivity = 82.4%, specificity = 85.6%), and breastfeeding initiation (sensitivity = 94.3%, specificity = 76.0%). The prevalence estimates were higher on PRAMS than the birth certificate for each of the indicators except Medicaid-paid delivery among non-Hispanic black women. Kappa values within most subgroups remained in the moderate range (0.40-0.80). Sensitivity and specificity values were lower for Hispanic women who responded to the PRAMS survey in Spanish and for breastfeeding initiation among women who delivered very low birthweight and very preterm infants. CONCLUSION: The validity and reliability of the PRAMS data for measures assessed were high. Our findings support the use of PRAMS data for epidemiological surveillance, research, and planning. PMID- 24179265 TI - Vibrio infections and surveillance in Maryland, 2002-2008. AB - OBJECTIVE: Vibrio is a naturally occurring waterborne pathogen with potential occupational, recreational, and commercial impacts. During the last 15 years in the U.S. and in Maryland, the incidence of vibriosis has increased. Due to the increase in cases in Maryland, warming water temperatures, and public concern about human health effects resulting from exposure to the Chesapeake Bay, we reviewed cases of vibriosis and evaluated the Vibrio surveillance system in Maryland for timeliness and data quality, attributes necessary for successful outbreak investigation and illness prevention. METHODS: The evaluation included (1) informal qualitative surveys of state and local personnel who report and manage Vibrio cases and (2) a review of Vibrio surveillance data from 2002 through 2008 for data quality and timeliness of the system. RESULTS: From 2002 to 2008, 188 laboratory-confirmed cases of vibriosis were reported in Maryland with an annual average of 27 cases. The species of Vibrio that were most frequently responsible for infection, regardless of clinical presentation, were V. parahaemolyticus (43.6%), V. vulnificus (23.9%), V. alginolyticus (9.6%), and non toxigenic V. cholerae (9.0%). The case fatality rate fluctuated during the study period, but the number of cases increased. CONCLUSIONS: The surveillance system in Maryland is flexible and captures cases of vibriosis where specimens were collected for testing; however, the system may not adequately capture mild, self limiting infections. Better integration of data collection for clinical, laboratory, and environmental information and improved completion of variables for shellfish harvest or water exposure locations could improve the system. Quarterly meetings comprising surveillance, public health laboratory, and food control personnel could direct and ensure the success of improvement efforts. PMID- 24179266 TI - Electronic health information quality challenges and interventions to improve public health surveillance data and practice. AB - OBJECTIVE: We examined completeness, an attribute of data quality, in the context of electronic laboratory reporting (ELR) of notifiable disease information to public health agencies. METHODS: We extracted more than seven million ELR messages from multiple clinical information systems in two states. We calculated and compared the completeness of various data fields within the messages that were identified to be important to public health reporting processes. We compared unaltered, original messages from source systems with similar messages from another state as well as messages enriched by a health information exchange (HIE). Our analysis focused on calculating completeness (i.e., the number of nonmissing values) for fields deemed important for inclusion in notifiable disease case reports. RESULTS: The completeness of data fields for laboratory transactions varied across clinical information systems and jurisdictions. Fields identifying the patient and test results were usually complete (97%-100%). Fields containing patient demographics, patient contact information, and provider contact information were suboptimal (6%-89%). Transactions enhanced by the HIE were found to be more complete (increases ranged from 2% to 25%) than the original messages. CONCLUSION: ELR data from clinical information systems can be of suboptimal quality. Public health monitoring of data sources and augmentation of ELR message content using HIE services can improve data quality. PMID- 24179268 TI - The HIPAA Omnibus Rule: implications for public health policy and practice. PMID- 24179270 TI - Misperceptions of overweight: associations of weight misperception with health related quality of life among normal-weight college students. PMID- 24179271 TI - War or health? Assessing public health education and the potential for primary prevention. PMID- 24179272 TI - From theory to action: applying social determinants of health to public health practice. PMID- 24179273 TI - Integrating a social determinants of health approach into public health practice: a five-year perspective of actions implemented by CDC's national center for HIV/AIDS, viral hepatitis, STD, and TB prevention. PMID- 24179274 TI - What can public health programs do to improve health equity? PMID- 24179275 TI - School contexts as social determinants of child health: current practices and implications for future public health practice. PMID- 24179276 TI - Identifying the root causes of health inequities: reflections on the 2011 National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention health equity symposium. PMID- 24179277 TI - Improving occupational safety and health among Mexican immigrant workers: a binational collaboration. AB - Latino immigrants are 50% more likely than all workers in the United States to experience a fatal injury at work. Occupational safety and health (OSH) organizations often find that the approaches and networks they successfully use to promote OSH among U.S.-born workers are ineffective at reaching Latino immigrants. This article describes the collaboration between the National Institute for Occupational Safety and Health (NIOSH) and the Mexican Ministry of Foreign Affairs (Secretaria de Relaciones Exteriores) to promote OSH among Mexican immigrant workers. The Ministry of Foreign Affairs operates 50 consulates throughout the U.S. that provide four million discrete service contacts with Mexican citizens annually. The focus of this ongoing collaboration is to develop the internal capacity of Mexican institutions to promote OSH among Mexican immigrants while simultaneously developing NIOSH's internal capacity to create effective and sustainable initiatives to better document and reduce occupational health disparities for Mexican immigrants in the U.S. PMID- 24179278 TI - Protecting labor rights: roles for public health. AB - Federal, state, and local labor laws establish minimum standards for working conditions, including wages, work hours, occupational safety, and collective bargaining. The adoption and enforcement of labor laws protect and promote social, economic, and physical determinants of health, while incomplete compliance undermines these laws and contributes to health inequalities. Using existing legal authorities, some public health agencies may be able to contribute to the adoption, monitoring, and enforcement of labor laws. We describe how routine public health functions have been adapted in San Francisco, California, to support compliance with minimum wage and workers' compensation insurance standards. Based on these experiences, we consider the opportunities and obstacles for health agencies to defend and advance labor standards. Increasing coordinated action between health and labor agencies may be a promising approach to reducing health inequities and efficiently enforcing labor standards. PMID- 24179279 TI - Addressing the social determinants of health through the Alameda County, California, place matters policy initiative. AB - In Alameda County, California, significant health inequities by race/ethnicity, income, and place persist. Many of the county's low-income residents and residents of color live in communities that have faced historical and current disinvestment through public policies. This disinvestment affects community conditions such as access to economic opportunities, well-maintained and affordable housing, high-quality schools, healthy food, safe parks, and clean water and air. These community conditions greatly affect health. At the invitation of the Joint Center for Political and Economic Studies' national Place Matters initiative, Alameda County Supervisor Keith Carson's Office and the Alameda County Public Health Department launched Alameda County Place Matters, an initiative that addresses community conditions through local policy change. We describe the initiative's creation, activities, policy successes, and best practices. PMID- 24179280 TI - The role of effective partnerships in an Australian place-based intervention to reduce race-based discrimination. AB - Localities Embracing and Accepting Diversity (LEAD) is an ongoing place-based pilot program aimed at improving health outcomes among Aboriginal and migrant communities through increased social and economic participation. Specifically, LEAD works with mainstream organizations to prevent race-based discrimination from occurring. The partnership model of LEAD was designed to create a community intervention that was evidence-based, effective, and flexible enough to respond to local contexts and needs. LEAD's complex organizational and partnership model, in combination with an innovative approach to reducing race-based discrimination, has necessitated the use of new language and communication strategies to build genuinely collaborative partnerships. Allocating sufficient time to develop strategies aligned with this new way of doing business has been critical. However, preliminary data indicate that a varied set of partners has been integral to supporting the widespread influence of the emerging LEAD findings across partner networks in a number of different sectors. PMID- 24179281 TI - A community-academic partnership to address racial/ethnic health disparities through grant-making. AB - Because they focus on culturally and contextually specific health determinants, participatory approaches are well-recognized strategies to reduce health disparities. Yet, few models exist that use academic and community members equally in the grant funding process for programs aimed at reducing and eliminating these disparities. In 2008, the Communities IMPACT Diabetes Center in East Harlem, New York, developed a partnered process to award grants to community groups that target the social determinants of diabetes-related disparities. Community and academic representatives developed a novel strategy to solicit and review grants. This approach fostered equality in decision-making and sparked innovative mechanisms to award $500,000 in small grants. An evaluation of this process revealed that most reviewers perceived the review process to be fair; were able to voice their perspectives (and those perspectives were both listened to and respected); and felt that being reviewers made them better grant writers. Community-academic partnerships can capitalize on each group's strengths and knowledge base to increase the community's capacity to write and review grants for programs that reduce health disparities, providing a local context for addressing the social determinants of health. PMID- 24179282 TI - Synthesizing evidence-based strategies and community-engaged research: a model to address social determinants of health. AB - Addressing social determinants of health (SDH) requires multileveled intervention designs. Increasingly, organizations and coalitions face pressure to use evidence based strategies when seeking to address SDH. Evidence-based strategies, however, must be locally relevant and integrated into existing systems to function efficiently. We propose the incorporation of an effective rapid assessment technique, Rapid Assessment, Response, and Evaluation (RARE), with evidence-based strategies, findings, and recommendations embedded in community-engaged research to increase the likelihood of success in addressing SDH. Our RARE project--a partnership among a community health center, a nonprofit funding agency, and academic faculty researchers--resulted in community- and policy-level interventions for the prevention of childhood obesity in a Southwestern U.S. city. PMID- 24179283 TI - Using a Health in All Policies approach to address social determinants of sexually transmitted disease inequities in the context of community change and redevelopment. AB - OBJECTIVES: We used a Health in All Policies (HiAP) framework to determine what data, policy, and community efficacy opportunities exist for improving sexual health and reducing sexually transmitted diseases (STDs) in an area surrounding an Army base undergoing redevelopment in Atlanta, Georgia. METHODS: We conducted a literature review, consulted with experts, mapped social determinants in the community, conducted key informant interviews with community leaders to explore policy solutions, used Photovoice with community members to identify neighborhood assets, and shared data with all stakeholder groups to solicit engagement for next steps. RESULTS: We identified the following HiAP-relevant determinants of STD inequities in the literature: education, employment, male incarceration, drug and alcohol marketing, and social capital. Quantitative data confirmed challenges in education, employment, and male incarceration in the area. Interviews identified policy opportunities such as educational funding ratios, Community Hire Agreements, code and law enforcement, addiction and mental health resources, lighting for safety, and a nonemergency public safety number. Photovoice participants identified community assets to protect including family-owned businesses, green spaces, gathering places, public transportation resources, historical sites, and architectural elements. Stakeholder feedback provided numerous opportunities for next steps. CONCLUSIONS: This study contributes to the HiAP literature by providing an innovative mixed-methods design that locates social determinants of STDs within a geographic context, identifies policy solutions from local leaders, highlights community assets through the lens of place attachment, and engages stakeholders in identifying next steps. Findings from this study could inform other redevelopments, community-based studies of STDs, and HiAP efforts. PMID- 24179284 TI - Achieving a healthy zoning policy in Baltimore: results of a health impact assessment of the TransForm Baltimore zoning code rewrite. AB - OBJECTIVES: The social determinants of health (SDH) include factors apart from genes and biology that affect population health. Zoning is an urban planning tool that influences neighborhood built environments. We describe the methods and results of a health impact assessment (HIA) of a rezoning effort in Baltimore, Maryland, called TransForm Baltimore. We highlight findings specific to physical activity, violent crime, and obesity. METHODS: We conducted a multistage HIA of TransForm Baltimore using HIA practice guidelines. Key informant interviews identified focus areas for the quantitative assessment. A literature review and a zoning code analysis evaluated potential impacts on neighborhood factors including physical activity, violent crime, and obesity. We estimated potential impacts in high- and low-poverty neighborhoods. The findings resulted in recommendations to improve the health-promoting potential of TransForm Baltimore. RESULTS: Mixed-use and transit-oriented development were key goals of TransForm Baltimore. Health impacts identified by stakeholders included walkability and healthy communities. For Baltimore residents, we estimated that (1) the percentage of people living in districts allowing mixed-use and off-premise alcohol outlets would nearly triple, (2) 18% would live in transit-oriented development zones, and (3) all residents would live in districts with new lighting and landscaping guidelines. Limiting the concentration of off-premise alcohol outlets represented an opportunity to address health promotion. CONCLUSIONS: Changes to Baltimore's zoning code could improve population health including decreasing violent crime. HIAs are an important platform for applying SDH to public health practice. This HIA specifically linked municipal zoning policy with promoting healthier neighborhoods. PMID- 24179285 TI - Geo-epidemiologic and molecular characterization to identify social, cultural, and economic factors where targeted tuberculosis control activities can reduce incidence in Maryland, 2004-2010. AB - OBJECTIVES: Tuberculosis (TB) disproportionately affects members of socioeconomically disadvantaged and minority populations in the U.S. We describe the geospatial distribution of TB cases in Maryland, identify areas at high risk for TB, and compare the geospatial clustering of cases with genotype clustering and demographic, socioeconomic, and TB risk-factor information. METHODS: Addresses of culture-positive, genotyped TB cases reported to the Maryland Department of Health and Mental Hygiene from January 1, 2004, to December 31, 2010, were geocoded and aggregated to census tracts. Geospatial clusters with higher-than-expected case numbers were identified using Poisson spatial cluster analysis. Case distribution and geospatial clustering information were compared with (1) genotype clustering (spoligotypes and 12-locus MIRU-VNTR), (2) individual-level risk and demographic data, and (3) census tract-level demographic and socioeconomic data. RESULTS: We genotoyped 1,384 (98%) isolates from 1,409 culture-positive TB cases. Two geospatial clusters were found: one in Baltimore City and one in Montgomery and Prince George's counties. Cases in these geospatial clusters were equally or less likely to share genotypes than cases outside the geospatial clusters. The two geospatial clusters had poverty and crowding in common but differed significantly by risk populations and behaviors. CONCLUSIONS: Genotyping results indicated that recent transmission did not explain most geospatial clustering, suggesting that geospatial clustering is largely mitigated by social determinants. Analyses combining geospatial, genotyping, and epidemiologic data can help characterize populations most at risk for TB and inform the design of targeted interventions. PMID- 24179286 TI - Remediating Viking Origins: Genetic Code as Archival Memory of the Remote Past. AB - This article introduces some early data from the Leverhulme Trust-funded research programme, 'The Impact of the Diasporas on the Making of Britain: evidence, memories, inventions'. One of the interdisciplinary foci of the programme, which incorporates insights from genetics, history, archaeology, linguistics and social psychology, is to investigate how genetic evidence of ancestry is incorporated into identity narratives. In particular, we investigate how 'applied genetic history' shapes individual and familial narratives, which are then situated within macro-narratives of the nation and collective memories of immigration and indigenism. It is argued that the construction of genetic evidence as a 'gold standard' about 'where you really come from' involves a remediation of cultural and archival memory, in the construction of a 'usable past'. This article is based on initial questionnaire data from a preliminary study of those attending DNA collection sessions in northern England. It presents some early indicators of the perceived importance of being of Viking descent among participants, notes some emerging patterns and considers the implications for contemporary debates on migration, belonging and local and national identity. PMID- 24179287 TI - Interpretation of Ambiguity in Individuals with Obsessive-Compulsive Symptoms. AB - In two experiments we examined the psychometric properties of a new measure of interpretation bias in individuals with obsessive-compulsive symptoms (OCs). In Experiment 1, 38 individuals high in OC symptoms, 34 individuals high in anxiety and dysphoric symptoms, and 31 asymptomatic individuals completed the measure. Results revealed that the Word Sentence Association Test for OCD (WSAO) can differentiate those with OC symptoms from both a matched anxious/dysphoric group and a non-anxious/non-dysphoric group. In a second experiment, we tested the predictive validity of the WSAO using a performance-based behavioral approach test of contamination fears, and found that the WSAO was a better predictor of avoidance than an established measure of OC washing symptoms (Obsessive Compulsive Inventory-Revised, washing subscale). Our results provide preliminary evidence for the reliability and validity of the WSAO as well as its usefulness in predicting response to behavioral challenge above and beyond OC symptoms, depression, and anxiety. PMID- 24179288 TI - Rapid fixation and immunofluorescent staining of cultured cells using microwave irradiation. AB - Microwave irradiation during tissue fixation and immunostaining reduces the sample preparation time. Microwave irradiation also facilitates the penetration of fixatives and antibody solutions into the tissues, resulting in efficient fixation and reduction of non-specific antibody binding, respectively. Experimental procedures involving immunofluorescence microscopy are time consuming as this method relies on antigenantibody reaction. Here, we utilized a technique involving exposure of cultured cells and tissues to intermittent microwave irradiation and immunostaining of fixed samples. Intermittent microwave irradiation during fixation reduces the required incubation time with blocking and antibody solutions, and results in good preservation of the immunoreactivity of fixed cells. Microwave irradiation also reduces the non-specific binding of fluorescein-labeled antibodies. These microwave-assisted rapid immunofluorescence techniques are useful for analysis of molecular compositions in cultured cell systems. PMID- 24179289 TI - Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal? AB - OBJECTIVES: Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. DESIGN: Prospective cohort study. SETTING: Tertiary sleep disorders center. PARTICIPANTS: 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. MEASUREMENTS/RESULTS: Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). CONCLUSIONS: Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease. PMID- 24179290 TI - Longitudinal associations between objective sleep and lipids: the CARDIA study. AB - STUDY OBJECTIVE: To investigate the longitudinal relationships between actigraph derived sleep duration, fragmentation, and lipid levels. DESIGN AND SETTING: Longitudinal data from the Coronary Artery Risk Development in Young Adults Sleep Study (2003-05), an observational cohort at the Chicago site. PARTICIPANTS: There were 503 black and white adults, ages 32-51 years, with no prior history of cardiovascular disease. INTERVENTIONS: N/A. MEASUREMENT AND RESULTS: Sleep duration and fragmentation were measured using 6 days of wrist actigraphy. Sleep quality was measured with the Pittsburgh Sleep Quality Index. The outcome variables, measured at 3 examinations over 10 years (Baseline [2000-01], 5-year [2005-06], and 10-year follow-up [2010-11]), were total cholesterol (TC), high density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), and TC/HDL ratio. The associations between each sleep parameter and 10-year change in lipids were analyzed with generalized estimating equation models adjusting for relevant confounders. After adjustment, each hour increase in sleep duration was significantly associated with higher TC (5.2 mg/dL, 95%CI: 1.7, 8.6) and LDL (3.4 mg/dL, 95%CI: 0.2, 6.6) in the total sample, a 1.1 mg/dL increase in TG (95%CI: 1.0, 1.1) among men, and a borderline significant greater odds for a TC/HDL ratio >= 5 among men (OR: 1.37, 95%CI: 0.99, 1.90). Overall, sleep fragmentation and sleep quality scores were not associated with change in lipids. CONCLUSIONS: Beyond relevant covariates, over a 10-year follow-up, longer objective sleep duration was longitudinally and significantly associated with a poorer lipid profile. Greater objective sleep fragmentation and self-reported poor sleep quality were not related to a poorer lipid profile. PMID- 24179291 TI - Self-reported sleep correlates with prefrontal-amygdala functional connectivity and emotional functioning. AB - STUDY OBJECTIVES: Prior research suggests that sleep deprivation is associated with declines in some aspects of emotional intelligence and increased severity on indices of psychological disturbance. Sleep deprivation is also associated with reduced prefrontal-amygdala functional connectivity, potentially reflecting impaired top-down modulation of emotion. It remains unknown whether this modified connectivity may be observed in relation to more typical levels of sleep curtailment. We examined whether self-reported sleep duration the night before an assessment would be associated with these effects. DESIGN: Participants documented their hours of sleep from the previous night, completed the Bar-On Emotional Quotient Inventory (EQ-i), Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), and Personality Assessment Inventory (PAI), and underwent resting state functional magnetic resonance imaging (fMRI). SETTING: Outpatient neuroimaging center at a private psychiatric hospital. PARTICIPANTS: Sixty-five healthy adults (33 men, 32 women), ranging in age from 18-45 y. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Greater self-reported sleep the preceding night was associated with higher scores on all scales of the EQ-i but not the MSCEIT, and with lower symptom severity scores on half of the psychopathology scales of the PAI. Longer sleep was also associated with stronger negative functional connectivity between the right ventromedial prefrontal cortex and amygdala. Moreover, greater negative connectivity between these regions was associated with higher EQ-i and lower symptom severity on the PAI. CONCLUSIONS: Self-reported sleep duration from the preceding night was negatively correlated with prefrontal amygdala connectivity and the severity of subjective psychological distress, while positively correlated with higher perceived emotional intelligence. More sleep was associated with higher emotional and psychological strength. PMID- 24179292 TI - Daytime sleepiness is associated with decreased default mode network connectivity in both young and cognitively intact elderly subjects. AB - STUDY OBJECTIVES: Sleep deprivation and daytime somnolence impair numerous aspects of physical, cognitive, and memory performance. However, most studies examining the effect of somnolence on brain function focus on acute sleep restriction in young adults. We examine the relationship between chronic daytime somnolence and connectivity in six brain networks in both young and elderly subjects using stimulus-free resting-state functional magnetic resonance imaging. DESIGN: Cross-sectional. SETTING: Outpatient research at the Massachusetts General Hospital. PARTICIPANTS: Young (n = 27) and elderly (n = 84) healthy, cognitively normal volunteers. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Compared with young subjects, cognitively normal elderly adults report less daytime somnolence on the Epworth Sleepiness Scale (ESS) (P = 0.019) and display reduced default mode network (DMN) connectivity (P = 0.004). Across all subjects, increasing daytime sleepiness was associated with decreasing functional connectivity in the DMN (P = 0.003, partial r of ESS = -0.29). There was no difference in the slope of this relationship between young adults and elderly subjects. No other cortical networks were correlated with daytime sleepiness. Daytime sleepiness and DMN connectivity were not related to sex, brain structure, or body mass index. CONCLUSIONS: These findings suggest that daytime sleepiness is associated with impaired connectivity of the DMN in a manner that is distinct from the effects of aging. This association is important to consider in any study using DMN connectivity as a biomarker. Additionally, these results may help identify those subjects at risk for future memory decline. PMID- 24179293 TI - Combination of light and melatonin time cues for phase advancing the human circadian clock. AB - STUDY OBJECTIVES: Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. DESIGN: Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (~1.9 lux, ~0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (~3000 lux, ~7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. SETTING: Sleep and chronobiology laboratory environment free of time cues. PARTICIPANTS: Thirty-six healthy participants (18 females) aged 22 +/- 4 y (mean +/- SD). RESULTS: Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. CONCLUSION: Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep wakefulness disorders. PMID- 24179294 TI - Snoring during pregnancy and delivery outcomes: a cohort study. AB - STUDY OBJECTIVE: This cohort study examined the impact of maternal snoring on key delivery outcomes such as mode of delivery, infant birth centile, and small-for gestational age. DESIGN: Cohort study. SETTING: A large tertiary medical center. PATIENTS OR PARTICIPANTS: Pregnant women in their third trimester were recruited between March 2007 and December 2010. MEASUREMENTS AND RESULTS: Women were screened for habitual snoring, as a known marker for sleep disordered breathing. Outcome data were obtained from medical records following delivery and birth centiles were calculated. Of 1,673 women, a total of 35% reported habitual snoring (26% with pregnancy-onset snoring and 9% with chronic snoring). After adjusting for confounders, chronic snoring was associated with small forgestational age (OR 1.65, 95%CI 1.02-2.66, P = 0.041) and elective cesarean delivery (OR 2.25, 95%CI 1.22-4.18, P = 0.008). Pregnancy-onset snoring was associated with emergency cesarean delivery (OR 1.68, 95%CI 1.22-2.30, P = 0.001). CONCLUSION: Maternal snoring during pregnancy is a risk factor for adverse delivery outcomes including cesarean delivery and small-for-gestational age. Screening pregnant women for symptoms of SDB may provide an early opportunity to identify women at risk of poor delivery outcomes. CLINICAL TRIALS REGISTRATION: IDENTIFIER: NCT01030003. PMID- 24179295 TI - Obstructive sleep apnea, excessive daytime sleepiness, and morning plasma TNF alpha levels in Greek children. AB - BACKGROUND: Obstructive sleep apnea (OSA) has been associated with increased frequency of excessive daytime sleepiness (EDS). Increased plasma TNF-alpha levels may mediate this association in adults, but conflicting results have been reported in children. We hypothesized that: (i) the higher the OSA severity in childhood, the higher the frequency of EDS and morning plasma TNF-alpha levels; and (ii) high TNF-alpha levels predict presence of EDS. METHODS: Children without and with snoring underwent polysomnography. EDS was determined by parental response to specific questions, and plasma TNF-alpha levels were measured. RESULTS: Children with moderate-to-severe OSA (n = 24; 5.7 +/- 2 years; apnea hypopnea index [AHI] 11.5 +/- 5.1/h), but not participants with mild OSA (n = 22; 6 +/- 2.5 years; AHI 2.1 +/- 1/h) were at significantly higher risk for EDS than controls (n = 22; 6.8 +/- 2.1 years; AHI 0.5 +/- 0.3/h) (OR [95% CI] adjusted for age, gender, and obesity: 9.2 [1.7-50.2] and 3.8 [0.7-21.8], respectively). The 3 groups did not differ regarding TNF-alpha concentration (0.63 +/- 0.2 vs 0.65 +/- 0.18 vs 0.63 +/- 0.17 pg/mL; P > 0.05). TNF-alpha levels were associated significantly with body mass index z-score (P < 0.05) and not with polysomnography indices (P > 0.05). Subjects with high TNF-alpha levels (> 0.57 pg/mL) were not at higher risk for EDS than participants with low levels (OR [95% CI] adjusted for age, gender, and obesity: 1.7 [0.5-5.7]). CONCLUSIONS: Increasing severity of OSA is associated with increasing frequency of EDS, but not with elevated plasma TNF-alpha concentration. High TNF-alpha levels cannot be used as predictor for the presence of EDS in children with sleep apnea. PMID- 24179296 TI - Sleep disordered breathing in early childhood: quality of life for children and families. AB - OBJECTIVES: To characterize health-related quality of life (QOL) in preschool children with sleep disordered breathing (SDB) and their families compared with nonsnoring control patients in the community. It was hypothesized that children with SDB and their families would have poorer QOL than control children, that a relationship would be found between SDB severity and QOL, and that even children with mild SDB and their families would have reduced QOL. PARTICIPANTS AND METHODS: A clinical sample of preschool children (3-5 y) with SDB diagnosed by gold standard polysomnography (primary snoring, PS = 56, mild obstructive sleep apnea, OSA = 35, moderate/severe OSA = 24) and control children recruited from the community (n = 38) were studied. Parents completed health-related QOL and parenting stress questionnaires. RESULTS: Children and families in the PS and mild OSA groups had consistently poorer QOL than control children (both P < 0.05 0.001), based on parent ratings, and parents of children with PS had elevated stress ratings relative to control children (P < 0.05-0.001). The moderate/severe OSA group differed from the control group on select measures of parent and family QOL (worry, P < 0.001 and total family impact, P < 0.05). CONCLUSIONS: Our findings demonstrate that sleep disordered breathing is associated with reduced quality of life in preschool children and their families. These results support previous quality of life findings in older children and in samples with broader age ranges. Furthermore, clinically referred preschool children with mild forms of sleep disordered breathing may be at greatest risk. PMID- 24179297 TI - Increasing adherence to obstructive sleep apnea treatment with a group social cognitive therapy treatment intervention: a randomized trial. AB - OBJECTIVE: To examine whether a social cognitive therapy (SCT) intervention increases continuous positive airway pressure (CPAP) use compared to equivalent social interaction (SI) time. PARTICIPANTS: Individuals with obstructive sleep apnea (OSA) referred for CPAP therapy. INTERVENTION: Participants received a 30 min group education session regarding OSA and CPAP. Groups of three to four participants were then randomly assigned to an SCT session or social interaction. MEASUREMENTS: CPAP usage was assessed at 7 nights, then 1, 3, and 6 months. The two primary outcomes were adherence, usage >= 4 h per night at 6 months, and uptake of CPAP. Questionnaires were given pretreatment and posttreatment. RESULTS: Two hundred six individuals were randomized to SI (n = 97) or SCT (n = 109). CPAP uptake was not different between groups (82% in SI, 88% in SCT groups, P = 0.35). There were no differences between groups in adherence: 63-66% at 1 week, and at 6 months 55-47% (P = 0.36). Higher pretreatment apnea-hypopnea index, higher baseline self-efficacy, and use of CPAP (>= 4 h) at 1 week were independent predictors of CPAP adherence at 6 months. CPAP adherence increased by a factor of 1.8 (odds ratio = 1.8, 95% confidence interval 1.1-3.0) for every one unit increase in self-efficacy. There was no difference between groups postintervention in self-efficacy scores, sleepiness, mood, or sleep quality. CONCLUSIONS: In this randomized trial, a single SCT application did not increase adherence when compared with SI time. Although self-efficacy scores prior to CPAP predicted adherence, self-efficacy was not increased by the interventions. Increasing intensity and understanding of SCT interventions may be needed to improve CPAP adherence. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12607000424404. PMID- 24179298 TI - Motivational enhancement to improve adherence to positive airway pressure in patients with obstructive sleep apnea: a randomized controlled trial. AB - BACKGROUND: Obstructive sleep apnea (OSA) is associated with a variety of medical conditions. Positive airway pressure (PAP) is an effective treatment for improving sleep, yet adherence rates are low. The aim of the current study is to test two treatments versus standard care in improving adherence to PAP. METHOD: Two hundred twenty-seven patients with OSA were randomized to standard care (SC), education (ED) and motivational enhancement therapy (MET). Adherence was measured objectively and the first week of adherence (prior to the intervention) was used as an a priori moderator of the effect of the various interventions. Mediators of treatment response were also examined using theory-based measures of decisional balance and self-efficacy. RESULTS: Adherence declined over time for all three groups. There was a significant interaction between level of adherence during the first week of treatment and treatment group. Those who had moderate levels of adherence during their first week of PAP were more likely to adhere to treatment at follow-up if they had MET; those who had high levels of adherence during their first week of PAP were more likely to adhere to treatment at follow-up if they had ED. MET treatment increased the perception of the positive aspects of PAP, but ED did not. CONCLUSIONS: Initial adherence to positive airway pressure could help guide subsequent treatment plans. The results also support social cognitive theory in that educational approaches might be best suited for those who are ready for change whereas more motivational approaches might be best for those who are ambivalent about change. PMID- 24179299 TI - Inspiratory flow limitation in a normal population of adults in Sao Paulo, Brazil. AB - STUDY OBJECTIVES: Inspiratory flow limitation (IFL) during sleep occurs when airflow remains constant despite an increase in respiratory effort. This respiratory event has been recognized as an important parameter for identifying sleep breathing disorders. The purpose of this study was to investigate how much IFL normal individuals can present during sleep. DESIGN: Cross-sectional study derived from a general population sample. SETTING: A "normal" asymptomatic sample derived from the epidemiological cohort of Sao Paulo. PATIENTS AND PARTICIPANTS: This study was derived from a general population study involving questionnaires and nocturnal polysomnography of 1,042 individuals. A subgroup defined as a nonsymptomatic healthy group was used as the normal group. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All participants answered several questionnaires and underwent full nocturnal polysomnography. IFL was manually scored, and the percentage of IFL of total sleep time was considered for final analysis. The distribution of the percentage of IFL was analyzed, and associated factors (age, sex, and body mass index) were calculated. There were 95% of normal individuals who exhibited IFL during less than 30% of the total sleep time. Body mass index was positively associated with IFL. CONCLUSIONS: Inspiratory flow limitation can be observed in the polysomnography of normal individuals, with an influence of body weight on percentage of inspiratory flow limitation. However, only 5% of asymptomatic individuals will have more than 30% of total sleep time with inspiratory flow limitation. This suggests that only levels of inspiratory flow limitation > 30% be considered in the process of diagnosing obstructive sleep apnea in the absence of an apnea-hypopnea index > 5 and that < 30% of inspiratory flow limitation may be a normal finding in many patients. PMID- 24179300 TI - Sleep and quality of life in urban poverty: the effect of a slum housing upgrading program. AB - STUDY OBJECTIVES: To evaluate the effect of a housing transition on sleep quality and quality of life in slum dwellers, participating in a slum housing upgrading program. DESIGN: Observational before-and-after study with a convergent-parallel mixed method design. SETTING: Five slums located in the metropolitan area of Buenos Aires, Argentina. PARTICIPANTS: A total of 150 slum dwellers benefited by a housing program of the nonprofit organization TECHO (spanish word for "roof"). INTERVENTIONS: Participants moved from their very low-quality house to a basic prefabricated 18 m(2) modular house provided by TECHO. MEASUREMENTS AND RESULTS: The Pittsburgh Sleep Quality Index (PSQI) and World Health Organization Quality of Life brief scale (WHOQOL-BREF) were administered before and after housing upgrading. Data about housing conditions, income, education, sleeping conditions, and cardiovascular risk were also collected. Semistructured interviews were used to expand and nuance quantitative data obtained from a poorly educated sample. Results showed that sleep quality significantly increased after the housing program (z = -6.57, P < 0.001). Overall quality of life (z = -6.85, P < 0.001), physical health domain (z = -4.35, P < 0.001), psychological well-being domain (z = -3.72, P < 0.001) and environmental domain (z = -7.10, P < 0.001) of WHOQOL BREF were also improved. Interviews demonstrated the importance of serenity for improving quality of life. CONCLUSIONS: A minimal improvement in the quality of basic housing can significantly increase sleep quality and quality of life among slum dwellers. Understanding sleep and daily life conditions in informal urban settlements could help to define what kind of low-cost intervention may improve sleep quality, quality of life, and reduce existent sleep disparity. PMID- 24179301 TI - Lithium prevents REM sleep deprivation-induced impairments on memory consolidation. AB - BACKGROUND: Pre-training rapid eye movement sleep (REMS) deprivation affects memory acquisition and/or consolidation. It also produces major REMS rebound at the cost of waking and slow wave sleep (SWS). Given that both SWS and REMS appear to be important for memory processes, REMS rebound after training may disrupt the organization of sleep cycles, i.e., excessive amount of REMS and/or little SWS after training could be harmful for memory formation. OBJECTIVE: To examine whether lithium, a drug known to increase SWS and reduce REMS, could prevent the memory impairment induced by pre-training sleep deprivation. DESIGN: Animals were divided in 2 groups: cage control (CC) and REMS-deprived (REMSDep), and then subdivided into 4 subgroups, treated either with vehicle or 1 of 3 doses of lithium (50, 100, and 150 mg/kg) 2 h before training on the multiple trial inhibitory avoidance task. Animals were tested 48 h later to make sure that the drug had been already metabolized and eliminated. Another set of animals was implanted with electrodes and submitted to the same experimental protocol for assessment of drug-induced sleep-wake changes. SUBJECTS: Wistar male rats weighing 300-400 g. RESULTS: Sleep deprived rats required more trials to learn the task and still showed a performance deficit during test, except from those treated with 150 mg/kg of lithium, which also reduced the time spent in REM sleep during sleep recovery. CONCLUSION: Lithium reduced rapid eye movement sleep and prevented memory impairment induced by sleep deprivation. These results indicate that these phenomena may be related, but cause-effect relationship cannot be ascertained. PMID- 24179302 TI - Persistent sleep disturbance: a risk factor for recurrent depression in community dwelling older adults. AB - STUDY OBJECTIVES: The objective of this study was to examine the associations between the temporal and severity characteristics of sleep disturbance and subsequent depression in community-dwelling older adults. DESIGN: A prospective cohort study with assessment of sleep disturbance and depression at baseline and across 2 years of follow-up. SETTING: Three urban communities in the United States. PARTICIPANTS: Community-dwelling older adults in whom prior depression (n = 145), current depression (n = 68), or never mentally ill (n = 206) were diagnosed at the baseline assessment. MEASUREMENTS AND RESULTS: Major depression at year 2, defined by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. Among patients with either a depression history or current depression at baseline, persistent sleep disturbance throughout year 1 was associated with persistent or recurrent depression at year 2, after adjustment for group status, antidepressant and hypnotic sedative use, severity of depressive symptoms, chronic medical burden, and sociodemographic variables (adjusted odds ratio = 5.20, 95% confidence interval [CI] = 1.16 to 23.29). Among those who were not depressed at year 1, persistent sleep disturbance throughout year 1 predicted depression recurrence during year 2 (adjusted hazards ratio = 16.05, CI = 1.21 to 213.06), independent of the severity of sleep disturbance. None of the older adults who were never mentally ill developed a depression. CONCLUSIONS: Persistent sleep disturbance during a year-long period is associated with depression the following year. Among older adults with prior depression, identification of those with persistent sleep disturbance may optimize the efficacy of sleep related interventions to improve depression remission and/or prevent late-life depression. PMID- 24179303 TI - The role of sleep problems in the development of depression in those with persistent pain: a prospective cohort study. AB - STUDY OBJECTIVES: One theoretical model suggests a pathway between pain and the development of depression through sleep problems. Here, we prospectively test the hypothesis that incident sleep problems, in those with persistent pain, increase risk of new onset probable depression, and investigate the role of "pain that interferes with daily life" (pain interference) on this pathway. DESIGN: Prospective cohort study. SETTING: Community based population study within UK. PARTICIPANTS: Participants with persistent pain nested within a larger longitudinal community study. MEASUREMENTS: Participants were mailed health questionnaires at baseline (time 1) with follow-up at 3 years (time 2) and 6 years from baseline (time 3). Questionnaires at baseline and at follow up contained measures of sleep problems (Jenkins Sleep Questionnaire), depressive symptoms (Hospital Anxiety and Depressive Scale), and pain interference. RESULTS: In total, 2,622 participants returned health questionnaires at all time points and indicated the presence of pain at each time point. After adjustment for age, gender, marital status, employment status, alcohol intake, smoking status, and body mass index, having a new period of sleep problems at year 3 more than trebled the risk of a new period of probable depression at year 6 (relative risk 3.47, 95% CI 1.97 to 6.03). Mediation analysis showed that pain interference played a significant but relatively minor role in the pathway. CONCLUSION: Clinicians treating patients with persistent pain may wish to consider options that involve addressing the prevention or treatment of sleep problems, in addition to their primary focus of pain management. PMID- 24179304 TI - Cross-cultural comparison of maternal sleep. AB - BACKGROUND: To characterize cross-cultural sleep patterns and sleep problems in a large sample of mothers of children (ages birth to 6 years) in multiple predominantly Asian and predominantly Caucasian countries. METHODS: Mothers of 10,085 young children (predominantly Asian countries/regions: China, Hong Kong, India, Korea, Japan, Malaysia, Philippines, Singapore, Thailand; predominantly Caucasian countries: Australia, Canada, New Zealand, United Kingdom, United States) completed an internet-based expanded version of the Pittsburgh Sleep Quality Index. RESULTS: Mothers in predominantly Asian countries/regions had later bedtimes, decreased number and duration of night wakings, more nighttime sleep, and more total sleep than mothers from predominantly Caucasian countries, P < 0.001. More than half (54.7%) of mothers reported having poor sleep, ranging from 50.9% of mothers in Malaysia to 77.8% of mothers in Japan. Sleep disturbance symptoms were quite common, especially symptoms related to insomnia, and were more likely to be reported by mothers in predominantly Caucasian countries. However, psychosocial factors, including having children of a younger age, being unemployed, and having a lower education level were the best predictors of poor sleep, whereas culture was not a significant predictor. CONCLUSIONS: Overall, mothers in predominantly Asian countries/regions reported later bedtimes but sleeping better and longer than mothers from predominantly Caucasian countries, which is dissimilar to cross-cultural findings of young children. Psychosocial factors were found to be the best predictors of poor sleep, irrespective of culture. Further studies are needed to understand the impact of these findings. PMID- 24179305 TI - Respiratory and polysomnographic values in 3- to 5-year-old normal children at higher altitude. AB - STUDY OBJECTIVES: To determine polysomnographic parameter differences in children living at higher altitude to children living near sea level. DESIGN AND SETTING: Prospective study of non-snoring, normal children recruited from various communities around Denver, CO. In-lab, overnight polysomnograms were performed at a tertiary care children's hospital. All children required residence for greater than one year at an elevation around 1,600 meters. PARTICIPANTS: 45 children (62% female), aged 3-5 years, 88.9% non-Hispanic white with average BMI percentile for age of 47.8% +/- 30.7%. MEASUREMENTS AND RESULTS: Standard sleep indices were obtained and compared to previously published normative values in a similar population living near sea level (SLG). In the altitude group (AG), the apnea hypopnea index was 1.8 +/- 1.2 and the central apnea-hypopnea index was 1.7 +/- 1.1, as compared to 0.9 +/- 0.8 and 0.8 +/- 0.7, respectively, (P <= 0.005) in SLG. Mean end-tidal CO2 level in AG was 42.3 +/- 3.0 mm Hg and 40.6 +/- 4.6 mm Hg in SLG (P = 0.049). The >= 4% desaturation index was 3.9 +/- 2.0 in AG compared to 0.3 +/- 0.4 in SLG (P < 0.001). Mean periodic limb movement in series index was 10.1 +/- 12.3 in AG and 3.6 +/- 5.4 in SLG (P = 0.001). CONCLUSION: Comparison of altitude and sea level sleep studies in healthy children reveals significant differences in central apnea, apneahypopnea, desaturation, and periodic limb movement in series indices. Clinical providers should be aware of these differences when interpreting sleep studies and incorporate altitude adjusted normative values in therapeutic-decision making algorithms. PMID- 24179306 TI - Genetic and environmental contributions to sleep-wake behavior in 12-year-old twins. AB - STUDY OBJECTIVES: To examine the role of genetic and environmental factors on sleep behavior in 12-year-old twins matched for family environment. DESIGN: Population-based twin cohort. SETTING: Participants were assessed in their home environment. PATIENTS OR PARTICIPANTS: One hundred thirty-two adolescent twins comprising 25 monozygotic (MZ) and 41 dizygotic (DZ) twin pairs; aged 12.2 +/- 0.1 y (mean +/- standard deviation). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: For 2 weeks in their home environment, participants wore a wrist activity monitor and completed a daily sleep diary. Sleep diaries included reports of bedtime, wake time, and estimated sleep onset time. Mean timing, duration, and quality of sleep during the 2 weeks were calculated for each individual and compared within twin pairs. MZ twin correlations were higher than the DZ correlations for total sleep time (MZr = 0.64; DZr = 0.38) and sleep onset latency (MZr = 0.83; DZr = 0.53) and significantly higher for wake after sleep onset (MZr = 0.66; DZr = 0.04) and sleep efficiency (MZr = 0.82; DZr = 0.10). Univariate modeling showed additive genetic factors accounted for 65% of the variance in total sleep time, 83% in sleep onset latency, and 52% and 57% of the variance in wake after sleep onset and sleep efficiency, respectively. A predominant influence of shared environment was found on the timing of sleep (67% for sleep start time, 86% for sleep end time). CONCLUSIONS: There is a strong genetic influence on the sleep-wake patterns of 12-year-old adolescents. Genes have a greater influence on sleep initiation and sleep maintenance and a smaller role in sleep timing, likely to be influenced by family environment. PMID- 24179307 TI - Period-amplitude analysis reveals wake-dependent changes in the electroencephalogram during sleep deprivation. AB - STUDY OBJECTIVES: Electroencephalographic slow wave activity (SWA) during non rapid eye movement (NREM) sleep results from the synchronous oscillation of cortical neurons and is the standard measurement of sleep homeostasis. SWA is not a direct measure of sleep pressure accumulation, but rather a measure of the NREM sleep response to accumulated sleep pressure. Currently, no practical standard for the direct measurement of sleep pressure accumulation exists. Recently, it was demonstrated that rat cortical neurons undergo oscillations during wake that are similar to the cortical oscillations responsible for SWA. Furthermore, these oscillations increase in number as time awake increases. Here we hypothesize that period-amplitude analysis of the electroencephalogram (EEG), which treats the EEG as a series of discrete waves, can measure these cortical oscillations, and thus, is a measure of sleep-pressure accumulation during extended wake. DESIGN: Mice were sleep deprived for 24 h by confinement to a slowly rotating wheel in order to assess wake-dependent changes in EEG wave incidence. MEASUREMENTS AND RESULTS: Continuous period-amplitude analysis of the waking EEG across 24 h of sleep deprivation revealed that the incidence of 2 to 6 Hz waves increased exponentially over the deprivation period. This increase in wave incidence appeared to occur in two phases with exponential time constants of approximately 0.12 h and 3 h. Further analysis revealed that the changes in wave incidence were significantly correlated with two established markers of sleep pressure, SWA and NREM sleep latency. CONCLUSIONS: The data suggest that wave incidence is an effective method of measuring sleep homeostasis in the waking EEG that provides better temporal resolution than spectral power analysis. PMID- 24179308 TI - Snoring, daytime sleepiness, and incident cardiovascular disease in the health, aging, and body composition study. AB - OBJECTIVES: To examine the association between snoring and incident cardiovascular disease (CVD). DESIGN SETTINGS AND PARTICIPANTS: This is a prospective study in which community dwelling older adults were evaluated at baseline, and followed up for an average of 9.9 years. MEASUREMENTS: Data on snoring, daytime sleepiness, as well as demographic and clinical characteristics of study participants was collected at baseline, and participants were followed up every six months for an average of 9.9 years. Based on snoring and sleepiness status, 4 groups of participants were created: (1) No Snoring, No Sleepiness; (2) No Snoring, Sleepiness; (3) Snoring, No Sleepiness; (4) Snoring, Sleepiness. Incident CVD was defined as a diagnosis of myocardial infarction, angina pectoris, or congestive heart failure that resulted in overnight hospitalization during the follow-up period. Cox proportional hazard was used to estimate the risk of incident cardiovascular disease during follow-up by baseline snoring and sleepiness status. RESULTS: A total of 2,320 participants with a mean age of 73.6 (2.9) years at baseline were included in the analysis. Fifty-two percent were women, and 58% were white. A total of 543 participants developed CVD events during the follow-up period. Participants who reported snoring associated with daytime sleepiness had significantly increased hazard ratio for CVD events (HR = 1.46 [1.03-2.08], P = 0.035) after adjusting for demographic and clinical confounding factors. CONCLUSION: The results suggest that self-reported snoring and daytime sleepiness status are associated with an increased risk of future cardiovascular disease among older adults. PMID- 24179309 TI - Measuring sleep: accuracy, sensitivity, and specificity of wrist actigraphy compared to polysomnography. AB - OBJECTIVES: We validated actigraphy for detecting sleep and wakefulness versus polysomnography (PSG). DESIGN: Actigraphy and polysomnography were simultaneously collected during sleep laboratory admissions. All studies involved 8.5 h time in bed, except for sleep restriction studies. Epochs (30-sec; n = 232,849) were characterized for sensitivity (actigraphy = sleep when PSG = sleep), specificity (actigraphy = wake when PSG = wake), and accuracy (total proportion correct); the amount of wakefulness after sleep onset (WASO) was also assessed. A generalized estimating equation (GEE) model included age, gender, insomnia diagnosis, and daytime/nighttime sleep timing factors. SETTING: Controlled sleep laboratory conditions. PARTICIPANTS: Young and older adults, healthy or chronic primary insomniac (PI) patients, and daytime sleep of 23 night-workers (n = 77, age 35.0 +/- 12.5, 30F, mean nights = 3.2). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Overall, sensitivity (0.965) and accuracy (0.863) were high, whereas specificity (0.329) was low; each was only slightly modified by gender, insomnia, day/night sleep timing (magnitude of change < 0.04). Increasing age slightly reduced specificity. Mean WASO/night was 49.1 min by PSG compared to 36.8 min/night by actigraphy (beta = 0.81; CI = 0.42, 1.21), unbiased when WASO < 30 min/night, and overestimated when WASO > 30 min/night. CONCLUSIONS: This validation quantifies strengths and weaknesses of actigraphy as a tool measuring sleep in clinical and population studies. Overall, the participant-specific accuracy is relatively high, and for most participants, above 80%. We validate this finding across multiple nights and a variety of adults across much of the young to midlife years, in both men and women, in those with and without insomnia, and in 77 participants. We conclude that actigraphy is overall a useful and valid means for estimating total sleep time and wakefulness after sleep onset in field and workplace studies, with some limitations in specificity. PMID- 24179310 TI - Sleepwalking, amnesia, comorbid conditions and triggers: effects of recall and other methodological biases. PMID- 24179311 TI - A Multistate Life Table Analysis of Union Regimes in the United States: Trends and Racial Differentials, 1970-2002. AB - We estimate trends and racial differentials in marriage, cohabitation, union formation and dissolution (union regimes) for the period 1970-2002 in the United States. These estimates are based on an innovative application of multistate life table analysis to pooled survey data. Our analysis demonstrates (1) a dramatic increase in the lifetime proportions of transitions from never-married, divorced or widowed to cohabiting; (2) a substantial decrease in the stability of cohabiting unions; (3) a dramatic increase in mean ages at cohabiting after divorce and widowhood; (4) a substantial decrease in direct transition from never married to married; (5) a significant decrease in the overall lifetime proportion of ever marrying and re-marrying in the 1970s to 1980s but a relatively stable pattern in the 1990s to 2000-2002; and (6) a substantial decrease in the lifetime proportion of transition from cohabiting to marriage. We also present, for the first time, comparable evidence on differentials in union regimes between four racial groups. PMID- 24179312 TI - Ultra-trace analysis of 41Ca in urine by accelerator mass spectrometry: an inter laboratory comparison. AB - A 41Ca interlaboratory comparison between Lawrence Livermore National Laboratory (LLNL) and the Purdue Rare Isotope Laboratory (PRIME Lab) has been completed. Analysis of the ratios assayed by accelerator mass spectrometry (AMS) shows that there is no statistically significant difference in the ratios. Further, Bayesian analysis shows that the uncertainties reported by both facilities are correct with the possibility of a slight under-estimation by one laboratory. Finally, the chemistry procedures used by the two facilities to produce CaF2 for the cesium sputter ion source are robust and don't yield any significant differences in the final result. PMID- 24179313 TI - Cohort change and the diffusion of environmental concern: A cross-national analysis. AB - This study explores value change across cohorts for a multinational population sample. Employing a diffusion-of-innovations approach, we combine competing theories predicting the relationship between socio-economic status (SES) and environmentalism: post-materialism and affluence theories, and global environmentalism theory. The diffusion argument suggests that high-SES groups first adopt pro-environmental views, but as time passes by, environmentalism diffuses to lower-SES groups. We test the diffusion argument using a sample of 18 countries for two waves (years 1993 and 2000) from the International Social Survey Project (ISSP). Cross-classified multilevel modeling allows us to identify a non-linear interaction between cohort and education, our core measure of SES, in predicting environmental concern, while controlling for age and period. We find support for the diffusion argument and demonstrate that the positive effect of education on environmental concern first increases among older cohorts, then starts to level off until a bend-point is reached for individuals born around 1940 and becomes progressively weaker for younger cohorts. PMID- 24179314 TI - Scoring of prognostic parameters in patients with unresectable advanced or recurrent colorectal cancer undergoing chemotherapy. AB - BACKGROUND: Suitable chemotherapy is needed to prolong the survival of patients with unresectable advanced or recurrent colorectal cancer. We scored the periodical changes of several prognostic markers during chemotherapy in patients with this type of cancer to discern the effectiveness of chemotherapy. METHODS: Twenty consecutive patients with unresectable advanced or recurrent colorectal cancer were enrolled. All patients underwent combination chemotherapy with oxaliplatin or irinotecan plus 5-fluorouracil/leucovorin. Neutrophil/lymphocyte ratio (NLR), serum C-reactive protein (CRP), serum carcinoembryonic antigen (CEA) and serum albumin (ALB) were compared between the two periods (before chemotherapy and 3 months after it was started) in each patient. The scoring system was as follows: points are added when a patient shows a decrease of NLR, CRP and CEA and an increase of ALB at 3 months after the start of chemotherapy with a possible final score of +4. On the other hand, points are reduced if a patient shows an elevation of NLR, CRP and CEA and a decrease of ALB at 3 months after the start of chemotherapy with a possible final score of -4. RESULTS: At 3 months after the start of first line chemotherapy, 13 patients showed positive scores but 7 patients showed zero or minus scores. According to our scoring system, we found the mean survival time (MST) of the 13 patients with plus scores was 34 months and this was significantly better than that of the 7 patients who showed zero or minus scores (P = 0.0008). CONCLUSION: Our new scoring system is useful but when we find that first line chemotherapy is ineffective, we need to change it to second line chemotherapy as soon as possible. That may be the best treatment for patients with unresectable advanced or recurrent colorectal cancer. PMID- 24179315 TI - Perceived Burdensomeness in Older Adults and Perceptions of Burden on Spouses and Children. AB - Older adults are at high risk of suicide, and perceived burdensomeness is an important suicide risk factor in this population. Additionally, previous research indicates that older adults feel like a burden on their spouses most often, though perceptions of burden on younger generations were associated with greater overall perceived burdensomeness. The current study sought to clarify this complex pattern of results, and found that perceptions of burden on a spouse were linked to the most severe form of perceived burdensomeness-belief that others would be better off if one were gone-though perceptions of burden on a child were not significantly associated with this most severe form of perceived burdensomeness in the current sample. These results indicate that older adults' perceptions of burdensomeness on a spouse may be especially harmful. Clinical implications, including the need to assess not only whether older adults perceive themselves to be a burden on others, but also who is perceived to be burdened, and the importance of targeting perceived burdensomeness through cognitive restructuring, are discussed. PMID- 24179317 TI - Leading the young Saudi Generation Y dentists in the 21st century. PMID- 24179316 TI - Posttraumatic Stress Disorder and Co-Occurring Substance Use Disorders: Advances in Assessment and Treatment. AB - Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) are prevalent and frequently co-occur. Comorbid PTSD/SUD is associated with a more complex and costly clinical course when compared with either disorder alone, including increased chronic physical health problems, poorer social functioning, higher rates of suicide attempts, more legal problems, increased risk of violence, worse treatment adherence, and less improvement during treatment. In response, psychosocial treatment options have increased substantially over the past decade and integrated approaches - treatments that address symptoms of both PTSD and SUD concurrently -are fast becoming the preferred model for treatment. This paper reviews the prevalence, etiology and assessment practices as well as advances in the behavioral and pharmacologic treatment of comorbid PTSD and SUDs. PMID- 24179319 TI - Severity and causality of maxillofacial trauma in the Southern region of Saudi Arabia. AB - OBJECTIVE: The purpose of this study was to examine the causality and severity of maxillofacial trauma (MFT) among patients referred to a tertiary heath care center in the Southern Aseer region of Saudi Arabia. MATERIALS AND METHODS: The charts of all MFT patients referred to the tertiary care center from September 2010 to November 2011 were retrospectively reviewed. Pertinent data, including patient age, gender, and cause of injury, were obtained from 101 selected charts. RESULTS: Male patients comprised 91% of the 101 selected cases. The highest percentage of MFT cases (88.7%) were caused by road traffic accidents (RTAs) while physical altercations and sports injuries accounted for approximately 6% and 2.8% of MFT cases, respectively. A high fracture: patient ratio of 2.4:1 was observed, which was likely due to vehicular speeding (high energy trauma) involved in RTAs in the mountain regions. CONCLUSION: RTAs are a major cause of MFT in the southern region of Saudi. These accidents cause a heavy burden on the health care sector. PMID- 24179318 TI - Academic distress, perceived stress and coping strategies among dental students in Saudi Arabia. AB - OBJECTIVES: To evaluate the sources of stress among students in the dental school environment, their perceived levels of stress and effective coping strategies. METHODS: This study was conducted during the first semester of the academic year, 2009-10, at the College of Dentistry, King Saud University, Saudi Arabia. The eligible study group consisted of 556 undergraduate dental students from all five class years; they were surveyed with a detailed assessment tool. The validated and translated questionnaire comprised the modified version of the dental environmental stress (DES) survey, the perceived stress scale (PSS) and the brief coping scale (BCS). RESULTS: The overall findings substantiated with multiple regression indicate that, out of 20 factors of both DES and BC instruments, six factors were significantly and independently related to perceived stress scores (F = 34.638; p < 0.0001). Especially, the factors self-efficacy and workload of DES and the factors behavioral disengagement, denial, positive reframing and venting of BC were positively and independently related to perceived stress scores. CONCLUSIONS: Dental students displayed relatively high perceived stress scores. Female, advanced and married, compared with male, junior and single students reported more stress. Changes in certain environmental factors and coping strategies independently affected the perceived stress score. Strategies for stress management must be incorporated into dental education to ensure the output of effective dentists. PMID- 24179320 TI - Prevalence of oral mucosal lesions in patients of the Kuwait University Dental Center. AB - OBJECTIVES: The purpose of this study was to determine the number, types, and locations of oral mucosal lesions in patients who attended the Admission Clinic at the Kuwait University Dental Center to determine prevalence and risk factors for oral lesions. SUBJECTS AND METHODS: Intraoral soft tissue examination was performed on new patients seen between January 2009 and February 2011. The lesions were divided into six major groups: white, red, pigmented, ulcerative, exophytic, and miscellaneous. RESULTS: Five hundred thirty patients were screened, out of which 308 (58.1%) had one or more lesions. A total of 570 oral lesions and conditions were identified in this study, of which 272 (47.7%) were white, 25 (4.4%) were red, 114 (20.0%) were pigmented, 21 (3.7%) were ulcerative, 108 (18.9%) were exophytic, and 30 (5.3%) were in the miscellaneous group. Overall, Fordyce granules (n = 116; 20.4%) were the most frequently detected condition. A significantly higher (p < 0.001) percentage of older patients (21-40 years and ?41 years) had oral mucosal lesions than those in the ?20 years age group. A significantly higher (p < 0.01) percentage of smokers had oral mucosal lesions than did nonsmokers. Most of the lesions and conditions were found on the buccal mucosa and gingiva. CONCLUSIONS: White, pigmented, and exophytic lesions were the most common types of oral mucosal lesions found in this study. Although most of these lesions are innocuous, the dentist should be able to recognize and differentiate them from the worrisome lesions, and decide on the appropriate treatment. PMID- 24179321 TI - Knowledge of antibiotics among dentists in Riyadh private clinics. AB - INTRODUCTION: Dentists prescribe antibiotics for both therapeutic and prophylactic reasons to manage oral and dental infections. Antibiotic prescriptions can be associated with unfavorable side effects and the development of resistance. AIM OF THE STUDY: A survey was conducted among dental specialists (DSs) and general dental practitioners (GDPs) at private dental clinics in Riyadh, Saudi Arabia to assess their level of knowledge regarding the action of antibiotics, their use and misuse in oral conditions, systemic diseases and prophylaxis. SUBJECTS AND METHODS: A total of 380 identical surveys that contained 32 questions were completed by DSs and GDPs in a supervised setting. Descriptive statistics were calculated to assess the overall knowledge of both DSs and GDPs, and their knowledge within each category of questions. Independent t-tests were used to ascertain whether there were significant differences between DSs and GDPs. A scatterplot diagram was used to test for a correlation between the years of experience of practitioners and their knowledge level. RESULT: The response rate was 79.7%. An acceptable level of knowledge was attained by 85.5% of dentists and 42.2% just passed. The percentage of dentists with an acceptable level of knowledge regarding prophylaxis was 51%. The scores for overall information levels about antibiotics among both DSs and GDPs were close to 70%. The percentage of DSs with an acceptable level of knowledge on antibiotic actions was 69.2%, 90.7% for oral conditions and 66.7% for medical conditions, compared to 66.8%, 88.7% and 64.8%, respectively, for GDPs. No significant relationship was found between the experience and knowledge level. CONCLUSIONS: Our findings suggest that the overall knowledge level of dentists about antibiotics is acceptable, but more focus should be given to their ongoing training regarding the pharmacological aspects, pertinent medical conditions and prophylactic use of antibiotics. PMID- 24179322 TI - Aesthetic replacement of an anterior tooth using the natural tooth as a pontic; an innovative technique. AB - This article presents a novel technique for replacing an anterior tooth. A new modification to the clinical technique of direct fabrication of a resin-bonded bridge was employed, in which the patient's natural tooth was used as a pontic. Treatment with this modification led to overall improved aesthetics and reduced treatment cost. The natural tooth pontic was stabilized in the extraction socket with a resin-wire splint as a provisional restoration to maintain the gingival architecture while the permanent bridge was being constructed. PMID- 24179323 TI - Physical therapists drive thrust-manipulation research. PMID- 24179324 TI - Intra-rater reliability of an experienced physiotherapist in locating myofascial trigger points in upper trapezius muscle. AB - OBJECTIVES: Myofascial trigger points (MTrPs) are considered the principal clinical feature of myofascial pain syndrome (MPS). An MTrP consists of spot tenderness within a taut band of muscle fibers and its stimulation can produce both local and referred pain. The clinical diagnosis of MPS depends on correct history taking and a physical examination aimed at identifying the presence of MTrP. The purpose of this study was to investigate the intra-rater reliability of a palpation protocol used for locating an MTrP in the upper trapezius muscle. METHODS: Twenty-four subjects with MTrP in the upper trapezius muscle were examined by an experienced physiotherapist. During each of eight experimental sessions, subjects were examined twice in randomized order using a palpation protocol. An anatomical landmark system was defined and the MTrP location established using X and Y values. RESULTS: The intraclass correlation coefficient ICC(1,1) values were 0.62 (95% CI: 0.30-0.81) for X and 0.81 (95% CI: 0.61-0.91) for Y. The Bland-Altman plots for X and Y showed a mean of difference of 0.04 and -0.2 mm, respectively. Limits of agreement for X ranged from -26.3 to 26.2 mm and for Y from -27 to 26.4 mm. DISCUSSION: The ICC(1,1) for the observed values revealed a moderate to high correlation and the Bland-Altman analysis showed means of difference very close to zero with narrow limits of agreement. An experienced physiotherapist can reliably identify MTrP locations in upper trapezius muscle using a palpation protocol. PMID- 24179325 TI - Clinimetrics corner: the Global Rating of Change Score (GRoC) poorly correlates with functional measures and is not temporally stable. AB - The Global Rating of Change Score (GRoC) is a frequently used outcome measure that is used independently to measure improvements in a patient's condition or as an anchor for other outcomes measures. The tool has been criticized for recall bias, biases in administration, and for poor reliability over time. Our findings, captured from a sample of patients with shoulder impingement, suggest that all these concerns are of merit. Our results show poor correlation of the GRoC with functional measures after 2 and 3 weeks and decay of the associative stability of the GRoC from week to week. PMID- 24179326 TI - Automobilization intervention and exercise for temporomandibular joint open lock. AB - Temporomandibular joint disorders (TMDs) are common and may cause temporomandibular joint (TMJ) locking, pain, and disability. Evidence supports use of manual therapy and exercise for treatment of TMDs including disk displacement limiting full mouth opening, TMJ 'closed lock'. Only limited case studies describe management of TMJ 'open lock', a condition due to posterior disk displacement (PDD) or TMJ anterior dislocation (TMJ-AD). Reported treatment for open lock includes splinting and intraoral joint manipulation. This case report describes a novel extraoral automobilization using the mandibular elevator muscles to treat TMJ open lock in a 22-year-old male after intraoral joint mobilization failed. The exercise program used to restore neuromuscular control for post-reduction management is described. Short term results of automobilization were excellent with restored ability to swallow, speak normally, and achieve occlusion. Long term results at 14 months were good: the patient was pain-free, could swallow and speak normally, had no recurrence of TMJ locking, and minimal disability. Limited right lateral excursion range and left mandibular deviation during mouth opening indicated possible persistence of PDD. This case suggests that mandibular elevator automobilization and masticatory muscle exercise may be useful to treat TMJ open lock and should be considered to treat PDD and TMJ-AD. PMID- 24179327 TI - Short- and long-term clinical outcomes following a standardized protocol of orthopedic manual physical therapy and exercise in individuals with osteoarthritis of the hip: a case series. AB - OBJECTIVES: Describe short- and long-term outcomes observed in individuals with hip osteoarthritis (OA) treated with a pre-selected, standardized set of best evidence manual therapy and therapeutic exercise interventions. METHODS: Fifteen consecutive subjects (9 males, 6 females; mean age: 52+/-7.5 years) with unilateral hip OA received an identical protocol of manual therapy and therapeutic exercise interventions. Subjects attended 10 treatment sessions over an 8-week period for manual therapy interventions and performed the therapeutic exercise as a home program. RESULTS: Baseline to 8-week follow-up outcomes were as follows: Harris Hip Scale (HHS) scores improved from 60.3(+/-10.4) to 80.7(+/ 10.5), Numerical Pain Rating Scale (NPRS) scores improved from 4.3(+/-1.9) to 2.0(+/-1.9), hip flexion range of motion (ROM) improved from 99 degrees (+/-10.6) to 127 degrees (+/-6.3) and hip internal rotation ROM improved from 19 degrees (+/-9.1) to 31 degrees (+/-11.5). Improvements in HHS, NPRS, and hip ROM measures reached statistical significance (P<0.05) at 8-weeks and remained significant at the 29-week follow-up. Mean changes in NPRS and HHS scores exceeded the minimal clinically important difference (MCID) at 8-weeks and for the HHS scores alone at 29 weeks. The 8 and 29 week mean Global Rating of Change scores were 5.1(+/-1.4) and 2.1(+/-4.2), respectively. Improved outcomes observed following a pre selected, standardized treatment protocol were similar to those observed in previous studies involving impairment-based manual therapy and therapeutic exercise for hip OA. Future studies might directly compare the two approaches. PMID- 24179328 TI - Patient satisfaction with musculoskeletal physiotherapy care in Australia: an international comparison. AB - OBJECTIVES: (1) To attain a quantitative estimate of patient satisfaction with physiotherapy care for musculoskeletal conditions in Australia; (2) to compare the observed level of patient satisfaction with care in Australia with those from other countries; and (3) to compare factors contributing to patient satisfaction between Australia and the United States (US). METHODS: We conducted a prospective study of 274 patients presenting for physiotherapy treatment of a musculoskeletal disorder in Australian clinics. Patient satisfaction was measured using the 20 item MedRisk Instrument for Measuring Patient Satisfaction with Physical Therapy Care (MRPS) and satisfaction scores were compared with those from Northern Europe, North America, the United Kingdom, and Ireland. To investigate factors contributing to patient satisfaction between Australia and the US, we compared 20 item MRPS data from Australian and Spanish-speaking US cohorts. RESULTS: Mean Australian MRPS satisfaction score was 4.55 (95% confidence interval: 4.51-4.59) on a scale of 1 to 5, where 1 indicates high dissatisfaction and 5 indicates high satisfaction. This high level of patient satisfaction is consistent with international data. Australian respondents specifically valued interpersonal aspects of care, including advice and information about their condition and an explanation about self-management. The correlation between treatment outcomes and global patient satisfaction was low (r = -0.22). A comparison of data collected from Australia and the US showed that MRPS items regarding interpersonal aspects of care, such as the therapists' communication skills, correlated strongly with global satisfaction in both countries. However, there were other questionnaire items for which the correlation with global satisfaction was significantly different between Australia and the US. CONCLUSIONS: Patient satisfaction with musculoskeletal physiotherapy care in Australia is high and comparable with Northern Europe, North America, the United Kingdom and Ireland. Comparison of data between Australia and the US indicates that while some determinants of patient satisfaction are common, country-specific differences also exist. PMID- 24179329 TI - Contractile dysfunction of the shoulder (rotator cuff tendinopathy): an overview. AB - It is now over a decade since the features defining a contractile dysfunction of the shoulder were first reported. Since this time, some progress has been made to better understand this mechanical syndrome. In response to these developments, this narrative review will explore current understanding in relation to pathology, diagnosis, treatment, and prognosis of this syndrome with reference to literature specifically relating to contractile dysfunction but also literature relating to rotator cuff tendinopathy where necessary. The review not only identifies the strengths of the mechanical diagnosis and therapy approach with reference to a contractile dysfunction of the shoulder but also identifies where further progress needs to be made. PMID- 24179330 TI - Differential diagnosis of a patient referred to physical therapy with neck pain: a case study of a patient with an atypical presentation of angina. AB - BACKGROUND AND PURPOSE: A 64-year-old man with acute onset neck pain was referred to physical therapy by a neurosurgeon. The purpose of this case study is to examine the process of differential diagnosis in a patient with neck pain and to discuss common diagnostic errors that can occur in the outpatient setting. CASE DESCRIPTION: The patient had an 8-week history of neck pain, which was worse when running and lifting objects. He presented with imaging of the cervical spine demonstrating degenerative changes. During the examination, several differential diagnoses were considered. A thorough physical examination of the cervical spine and upper quarter failed to reproduce his symptoms. At that time, the physical therapist was suspicious that the origin of the patient's neck pain was non mechanical in nature. Additional testing during the examination included having the patient exercise briefly on gym equipment; this reproduced his symptoms. After additional positional and postural changes did not alleviate the symptoms, he stopped exercising, and his pain ceased. OUTCOMES: The patient was referred back to his primary care physician who ordered cardiovascular testing including an electrocardiogram and echocardiogram. These tests revealed significant cardiac abnormalities including multi-vessel blockage of the coronary arteries and evidence of infarction. He underwent a coronary artery bypass graft 4 days later. DISCUSSION: To make an appropriate differential diagnosis, physical therapists must use a patient-centered model of clinical reasoning and meta-cognition and have an awareness of diagnostic errors such that they can be avoided. The goal of the physical therapy examination, including differential diagnosis, is to efficiently classify the patient for treatment or to direct patients to the proper healthcare provider, thereby minimizing and preventing mortality and morbidity. PMID- 24179331 TI - Copper beta-trinitrocorrolates. AB - The beta-nitration reaction carried out on the corrole macrocycle has been shown to be extremely regioselective, although the reduced symmetry of the macrocycle could potentially lead to a huge number of possible regioisomers. We recently reported that the careful use of AgNO2/NaNO2 as a nitrating system enabled the achievement in good yields of mono- and dinitro-derivatives on both corrole free base and its copper complex, proving to be an efficient and cost-effective method. In this work, we present a detailed study of the scope of this method using TtBuCorrH3 as a model corrole. A further increase of the oxidant pushes the nitration up to the functionalization of three beta-pyrrolic positions, although concomitant decomposition of the macrocycle is also observed. The application of the proven nitration method with a five-fold excess of both silver and sodium nitrites with respect to corrole, afforded the 2,3,17-(NO2)3-TtBuPCorrCu as the main product, in 25% yield, together with traces of another compound identified by X-ray crystallographic analysis as the 3,8,17-(NO2)3-TtBuPCorrCu isomer. In light of these recent results, we also reinvestigated the characterization of the nitration products obtained from bis-substitution reactions, allowing among others the identification of the copper 3,8-(NO2)2 corrolate. PMID- 24179332 TI - Intravenous microemulsion of docetaxel containing an anti-tumor synergistic ingredient (Brucea javanica oil): formulation and pharmacokinetics. AB - The purpose of this study was to develop a docetaxel microemulsion containing an anti-tumor synergistic ingredient (Brucea javanica oil) and to investigate the characteristics of the microemulsion. Brucea javanica oil contains oleic acid and linoleic acids that have been shown by animal and human studies to inhibit tumor formation. The microemulsion containing Brucea javanica oil, medium-chain triglyceride, soybean lecithin, Solutol(r)HS 15, PEG 400, and water was developed for docetaxel intravenous administration. A formulation with higher drug content, lower viscosity, and smaller particle size was developed. The droplet size distribution of the dispersed phase of the optimized microemulsion was 13.5 nm, determined using a dynamic light scattering technique. The small droplet size enabled the microemulsion droplets to escape from uptake and phagocytosis by the reticuloendothelial system and increased the circulation time of the drug. The zeta potential was -41.3 mV. The optimized microemulsion was pale yellow, transparent, and non-opalescent in appearance. The value of the combination index was 0.58, showing that there was a synergistic effect when docetaxel was combined with Brucea javanica oil. After a single intravenous infusion dose (10 mg/kg) in male Sprague Dawley rats, the area under the curve of the microemulsion was higher and the half-time was longer compared with that of docetaxel solution alone, and showed superior pharmacokinetic characteristics. These results indicate that this preparation of docetaxel in emulsion is likely to provide an excellent prospect for clinical tumor treatment. PMID- 24179333 TI - Nanosilica coating for bonding improvements to zirconia. AB - Resin bonding to zirconia cannot be established from standard methods that are currently utilized in conventional silica-based dental ceramics. The solution gelatin (sol-gel) process is a well developed silica-coating technique used to modify the surface of nonsilica-based ceramics. Here, we use this technique to improve resin bonding to zirconia, which we compared to zirconia surfaces treated with alumina sandblasting and tribochemical silica coating. We used the shear bond strength test to examine the effect of the various coatings on the short term resin bonding of zirconia. Furthermore, we employed field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, and Fourier transform infrared spectroscopy to characterize the zirconia surfaces. Water-mist spraying was used to evaluate the durability of the coatings. To evaluate the biological safety of the experimental sol-gel silica coating, we conducted an in vitro Salmonella typhimurium reverse mutation assay (Ames mutagenicity test), cytotoxicity tests, and in vivo oral mucous membrane irritation tests. When compared to the conventional tribochemical silica coating, the experimental sol-gel silica coating provided the same shear bond strength, higher silicon contents, and better durability. Moreover, we observed no apparent mutagenicity, cytotoxicity, or irritation in this study. Therefore, the sol-gel technique represents a promising method for producing silica coatings on zirconia. PMID- 24179334 TI - Early intervention in the treatment of rheumatoid arthritis: focus on tocilizumab. AB - Tocilizumab is a fully humanized monoclonal antibody against interleukin-6 receptors that was approved for the treatment of patients with rheumatoid arthritis (RA). Several lines of evidence, obtained both from conventional disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor (TNF) inhibitors, have supported the concept of "window of opportunity" as showing that these therapies consistently work better in early disease as compared to established RA. This review addresses the question of whether a window of opportunity gained with conventional DMARDs and TNF inhibitors can also be achieved with tocilizumab. To this end, data regarding the use of tocilizumab in early RA patients are summarized. Currently available data suggest that the earlier the treatment with tocilizumab, the better the clinical outcome can be, which may have implications for various aspects of RA treatment strategies. PMID- 24179335 TI - Health claims database study of cyclosporine ophthalmic emulsion treatment patterns in dry eye patients. AB - BACKGROUND: Dry eye is a multifactorial, symptomatic disease associated with ocular surface inflammation and tear film hyperosmolarity. This study was designed to assess patterns of topical cyclosporine ophthalmic emulsion 0.05% (Restasis(r)) use in dry eye patients and determine if there were any differences in use based on whether dry eye is physician-coded as a primary or nonprimary diagnosis. METHODS: Records for adult patients with a diagnosis of dry eye at an outpatient visit from January 1, 2008 to December 31, 2009 were selected from Truven Health MarketScan(r) Research Databases. The primary endpoint was percentage of patients with at least one primary versus no primary dry eye diagnosis who filled a topical cyclosporine prescription. Data analyzed included utilization of topical corticosteroids, oral tetracyclines, and punctal plugs. RESULTS: The analysis included 576,416 patients, accounting for 875,692 dry eye outpatient visits: 74.7% were female, 64.2% were ages 40-69 years, and 84.4% had at least one primary dry eye diagnosis. During 2008-2009, 15.9% of dry eye patients with a primary diagnosis versus 6.5% with no primary diagnosis filled at least one cyclosporine prescription. For patients who filled at least one prescription, the mean months' supply of cyclosporine filled over 12 months was 4.44. Overall, 33.9% of dry eye patients filled a prescription for topical cyclosporine, topical corticosteroid, or oral tetracycline over 2 years. CONCLUSION: Patients with a primary dry eye diagnosis were more likely to fill a topical cyclosporine prescription. Although inflammation is key to the pathophysiology of dry eye, most patients seeing a physician for dry eye may not receive anti-inflammatory therapies. PMID- 24179336 TI - Introductory editorial. PMID- 24179337 TI - Rehabilitation following surgery for reconstruction of a foot defect. AB - BACKGROUND: This report illustrates the use of pressure for scar management to aid in foot re-shaping following a surgical intervention to repair an arterio venous (AV) malformation. METHODS: This report describes the rehabilitation of a 13-year-old girl after surgical reconstruction of a defect in her left foot following the removal of an AV malformation. Early surgical attempts to repair the problem resulted in complications that required the amputation of toes 2, 3, and 4, and the use of a split thickness skin graft to cover the plantar surface of the medial longitudinal arch on the left foot. Following surgery, the patient had an antalgic gait pattern with decreased weight bearing on the left. The graft obliterated the left medial longitudinal arch and the patient would only weight bear on the heel. The patient had decreased metatarsal joint mobility on the affected side and no movement in the remaining toes. Left talocrural joint active range-of-motion (AROM) was within normal limits and gross ankle muscle force production was assessed to have a grade of 3/5. RESULTS: Treatment included reshaping the left foot using a pressure garment and orthotic, followed by interventions to address range-of-motion and muscle force production deficiencies. All treatment objectives were achieved and all patient goals were achieved. CONCLUSIONS: Pressure was effective in re-shaping the foot to promote normal gait mechanics. PMID- 24179338 TI - Transradial approach superior to transfemoral approach for guide catheter engagement of right coronary artery. PMID- 24179339 TI - Pathological rupture of the spleen in uncomplicated myeloma. AB - Pathological rupture of the spleen in uncomplicated myeloma is extremely rare. We present a case of a splenic rupture which occurred in a 52 year old woman with uncomplicated multiple myeloma. The patient required an urgent splenectomy and had an uneventful recovery. Pathophysiological mechanisms leading to splenic rupture are discussed. Plasma cell leukaemias have been previously documented to present with splenic rupture. A subgroup of aggressive multiple myelomas such as in our case may have a similar tendency for splenic rupture. PMID- 24179340 TI - Pseudomonas aeruginosa in the Early Childhood: A Case Report. AB - Pseudomonas aeruginosa is an opportunistic bacterium that usually affects immunocompromised patients, causing infections whose signals and symptoms are related to the affected organ. The patient presented in this article was infected when he was 9 months old. Such condition led to certain alterations like dental improperly positioned teeth, retained deciduous teeth, hipodonty of permanent teeth, atrophy of the upper jaw and dental crowding. Therefore, the purpose of this article is to report the case of a patient affected by Pseudomonas aeruginosa infection in the early childhood and to describe the dental development disorders as consequence of this fact. PMID- 24179341 TI - Cerebral Sinus and Venous Thrombosis Associated with von Willebrand Factor, Independently of Factor VIII. AB - BACKGROUND AND PURPOSE: Previous studies have linked procoagulant factor VIII (F VIII) to an increased risk of venous thrombosis, whereas the relation between plasma von Willebrand factor (VWF) and venous thrombosis remains poorly understood. Elevated VWF levels are frequently found in patients with cerebral sinus and venous thrombosis (CSVT), always in association with high F VIII levels. We describe a patient with CSVT accompanied by elevated VWF levels without high F VIII levels. CASE DESCRIPTION: A 23-year-old healthy man who had headache noticed difficulty in moving the right hand. On the following day, he lost consciousness and had partial seizures of the right hand. After regaining consciousness, weakness of the right extremities developed. The cranial angiogram confirmed occlusion of the superior sagittal sinus. The levels of VWF and F VIII were 238% and 101.9 IU/dl, respectively. We performed balloon percutaneous transluminal angioplasty and mechanical thrombectomy, leading to successful recanalization of the intracranial sinuses. VWF levels were decreased along with radiographic improvement, independently of F VIII. CONCLUSION: VWF may contribute to CSVT and that inhibition of VWF activity potentially has a role in the future treatment of pathological conditions related to venous thrombosis. PMID- 24179342 TI - A Case of Hyper IgD and Periodic Fever Syndrome in Japan. AB - We report a four-year-old Japanese girl with hyper IgD and periodic fever syndrome. There is a first report of hyper IgD syndrome (HIDS) of which the genomic study was done in Japan. In this report a girl complained of periodic fever and abdominal symptoms accompanied with high levels of mevalonic acid in urine and serum. She has been well controlled by non-steroidal anti-inflammatory drugs (NSAIDs) for 3 years. PMID- 24179343 TI - Extremely low birthweight infant with wolf-hirschhorn syndrome: a dilemma in determination of the optimal timing of delivery. AB - Wolf-Hirschhorn syndrome (WHS) is characterized by multiple malformations as well as mental and developmental defects resulting from the absence of a distal segment of the short arm of chromosome 4. We experienced an extremely low birthweight infant with WHS. The male infant (birthweight 934 g) was born at 31 weeks' gestation by cesarean section due to intrauterine growth restriction and presented with the typical WHS phenotype. Chromosomal analysis showed a deletion: 46,XY,del(4)(p15.3 p16). Although the patient's respiratory distress syndrome resolved favourably and his subsequent condition was also stable, he had unusually severe retinopathy of prematurity and periventricular leukomalacia. We suppose that these severe complications were associated with not only prematurity but also with latent structural fragility due to WHS. Herein, we discuss the prenatal detection of WHS and the optimal timing of delivery. PMID- 24179344 TI - Monitoring gastric filling, satiety and gastric emptying in a patient with gastric balloon using functional magnetic resonance imaging-a feasibility report. AB - BACKGROUND: Intragastric balloons are used for short term weight loss therapy in obese. It is possible to monitor the ballon with sonography, however this method is sometimes insufficient in obese patients. Therefore MRI seems to be a potential therapy-monitoring option. PURPOSE: In this feasibility report we want to demonstrate the potential use of functional MRI in monitoring gastric filling, patient satiation and gastric emptying in a obese patient who previously received intragastric balloon placement. MATERIAL AND METHODS: We selected one patient (male, 178 cm, 127 kg, BMI = 40,5 kg/m(2)) who recently received a gastric balloon and visualized gastric motility in presence of the gastric balloon before and after food intake. Fast cross-sectional images in one breathhold spin echo or gradient echo sequences were aquired. Real-time gastric motion was performed with cine mode. RESULTS: MRI offers perfect visualisation of gastric balloons in obese patients. Gastric filling and emptying can be monitored in correlation to patient satiety sensation. MRI can visualize the gastric balloon with degree of filling and possible leakages. Cine mode sequences demonstrate gastric motility and gastric wall peristalsis. CONCLUSION: MR is a valuable imaging alternative for patients with intragastric balloons. PMID- 24179345 TI - The management of a patient with a cervical disc herniation: a case report. AB - PURPOSE: To present the management of a patient with a cervical disc herniation and illustrate the efficacy of cervical traction as a main form of treatment for cervical disc herniation in conjunction with a home exercise program. BACKGROUND: A 71-year-old white female diagnosed with cervical disc herniation at the levels of C5-6 and C6-7 presented to physical therapy with neck pain radiating into the left upper extremity down to the 5th digit of the left hand. TREATMENT: The patient reported to outpatient physical therapy for cervical disc herniation and radiculopathy. After initial evaluation she received intermittent cervical traction and was given a home exercise program consisting of cervical lateral flexion stretch, unilateral wall stretch for pectoralis muscles and to continue with her over the door cervical traction. CONCLUSION: Cervical traction and a good home exercise program have been shown to reduce cervical disc herniation and its subsequent symptoms. PMID- 24179346 TI - Non-autoimmune hemolytic anemia with clostridium ramosum bacteremia. PMID- 24179347 TI - Hepatocyte growth factor level in cerebrospinal fluid as an additional marker in patient with drug-resistant streptococcus pneumoniae meningitis treated with linezolid. AB - Hepatocyte growth factor (HGF) is a multifunctional cytokine that has well defined mitogenic, motogenic, and morphogenic functions on the epithelial cells. Strong increases of HGF concentrations in cerebrospinal fluid (CSF) are only present in patients with acute bacterial meningitis. We report a 15-year-old young man with drug resistant Streptococcus pneumoniae meningitis complicated with right 6th cranial nerve palsy. He presented with fever, headache and neck stiffness for 3 days and was treated with intravenous antimicrobial agents including linezolid and dexamethasone successfully. An association between CSF HGF concentrations and CSF proteins is observed (r = 0.897, p = 0.039. Pearson correlation test). This result showed that HGF level in CSF might act as an additional marker in patients with bacterial meningitis. PMID- 24179348 TI - Elongated styloid process and cervical spondylosis. AB - BACKGROUND: Dysphagia, is a significant sign of many different lesions in upper digestive system especially in proximal esophagus. Tumors, gastroesophageal reflux, achalasia and extrinsic compressions are the most common causes that may lead to dysphagia in geriatric population. Cervical osteophyte induced dysphagia, is one of the uncommon reasons of dysphagia, therefore other causes of dysphagia must be excluded to establish the exact diagnosis. Eagle syndrome is one of the considerable reason which may lead to misdiagnosis in patients with cervical osteophytes. In this case report, we represent four patients who had dysphagia due to anteriorly located cervical osteophytes and evaluate the patients with special reference to Eagle syndrome. MATERIAL AND METHODS: After a detailed anamnesis and ENT examination, cervical plain radiographs in four projections and Towne radiographs were obtained for every patient. After that, magnetic resonance imaging (MRI) of cervical spine and barium swallowing studies were performed to evaluate the presence of esophageal compression. RESULTS: Eagle syndrome was excluded due to absence of other symptoms and physical signs, eventhough unilateral or bilateral elongation of styloid processes was found in all of the patients. CONCLUSION: Cervical osteophytes induced dysphagia is a rare clinical entity, diagnosis should be done by a careful examination, intensive radiologic evaluation. Moreover, all the other causes like Eagle syndrome should be excluded during the diagnosis of cervical osteophyte induced dysphagia. PMID- 24179349 TI - Successful management of invasive pulmonary nocardiosis and aspergillosis in a patient with T-cell lymphoma: a case report. AB - In patients with malignant hematological disorders receiving immunosuppressive therapy, invasive pulmonary infections are serious complications that are associated with high morbidity and mortality. In immunocompromised hosts with impaired cellular immunity, two or more organisms may coexist leading to a wide range of clinical and radiological manifestations. Reported here is an old man who was diagnosed to have angioimmunoblastic T-cell lymphoma at King Faisal Specialist Hospital and Research Centre in Riyadh in December 2004. The lymphoma was treated with various immunosuppressive agents including alemtuzumab. In October 2006, the patient was admitted with severe bronchopneumonia caused by Nocardia asteroides and Aspergillus niger that was complicated by septic shock. The invasive pulmonary infections were successfully treated with trimethoprim sulphamethoxazole, amikacin and liposomal amphotericin-B (amBisome). PMID- 24179350 TI - Insufficiency fracture in the para-acetabulum, with features mimicking those of a malignant bone tumor. AB - Para-acetabular insufficiency fractures are rare and exceedingly difficult to diagnose without a high index of suspicion, since the images mimic those of bone tumors. We herein present the case of a 55-year-old woman who suffered from hip pain with subacute onset. She had undergone a hysterectomy-ovariectomy due to endometriosis when she was 41 years old. Her bone mineral density was normal due to supplemental treatment with female hormones. About 3 months after onset, she was referred to our institute with a diagnosis of pelvic bone tumor. Plain radiographs and computed tomography showed irregular osteosclerosis in the para acetabulum. Bone scintigraphy demonstrated uptake in the para-acetabulum. Magnetic resonance imaging showed abnormal signal with low-signal intensity on T1 weighted images and high-signal intensity on T2-weighted images throughout the entire hemipelvic bone. Since the pain continued for more than 3 months, open biopsy was undertaken and the lesion was found to be non-neoplastic. Six months after onset, the pain disappeared. The clinical course suggested a diagnosis of insufficiency fracture in the para-acetabulum. Para-acetabular insufficiency fractures should always be considered in cases of hip pain, even in patients with prolonged symptoms. PMID- 24179351 TI - A neurosurgical golf injury. PMID- 24179352 TI - Fulminant klebssiella pneumoniae pneumonia in immunocompetent non alcoholic patient. PMID- 24179353 TI - Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report. AB - We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment. PMID- 24179354 TI - Common variable immunodeficiency and peripheral lung nodule. PMID- 24179355 TI - Dissecting aneurysms of bilateral anterior cerebral artery complicated by subarachnoid hemorrhage after cerebral infarction: a case report. AB - INTRODUCTION: Intracranial dissecting aneurysms have been increased due to recent advancements in diagnostic imaging. However there have been little article with subarachnoid hemorrhage and cerebral infarction occurring almost at the same time. We performed the surgical treatment and obtained good result. CASE PRESENTATION: A 47-year-old male presented to our hospital with chief complaints of sudden headache and mild paralysis of the left lower extremity. Brain imaging at admission revealed cerebral infarction in the right frontal lobe and subarachnoid hemorrhage in the frontal convexy and anterior interhemispheric fissure. The left and right internal carotid angiography showed a bulging cerebral aneurysm at the left A1-A2 junction and stenosis and arterial dissections in the peripheral of the bilateral anterior cerebral artery. Wrapping was performed for the dissecting aneurysm of the left anterior cerebral artery. For the right anterior cerebral artery, trapping was performed at the A2 segment without vascular anastomosis. The patient's postoperative course was uneventful. CONCLUSION: A consensus has not been reached on the treatment for intracranial dissecting aneurysms. Proximal trapping without vascular reconstruction was performed for the right anterior cerebral artery without vascular anastomosis to prevent rebleeding. However no symptoms of neurological deficiency were observed. Proximal trapping of dissecting aneurysm seems to be a good option when patient's functional and life prognosis are taken into account in case that vascular reconstruction will be anticipated difficulty. PMID- 24179356 TI - Multiple complications in a sickle cell disease patient: a case report. AB - Summary This case report illustrates the multiple complications experienced by a sickle cell anaemia patient. Although he enjoyed fairly good health till age 16 years; he subsequently suffered grade four bilateral femoral head necrosis, cerebella infarct and cerebral atrophy from cumulative effect of repetitive vasoocclussion, recurrent overwhelming septicaemia, fixed flexion deformities and decubitous ulcer as a sequelae of earlier complications. He eventually became bed ridden. Financial constraint seriously compounded these problems. The determinants, of which type of the wide-ranging complications of SCD a particular patient will eventually develop, remain elusive. PMID- 24179357 TI - Successful management of multifactorial colitis in a recipient of hematopoietic stem cell transplant: a case report. AB - Recipients of allogeneic hematopoietic stem cell transplant can develop life threatening complications at any time following their transplants. These complications require repeated clinical assessment, appropriate and thorough screening as well as a comprehensive management approach. We report a young adult male who received a sibling allograft in the second complete remission of his acute lymphoblastic leukemia at King Faisal Specialist Hospital and Research Centre in Riyadh. The patient developed severe colitis which was caused by: acute exacerbation of chronic graft versus host disease of the lower gastrointestinal tract, cytomegalovirus disease of the colon and a superadded Salmonella infection caused by food poisoning. The multifactorial colitis was properly investigated and successfully managed. To our knowledge, this is the first case of multifactorial colitis in a recipient of hematopoietic stem cell transplant. PMID- 24179358 TI - Surgical anatomy of large retroperitoneal teratomas in infants: report of two cases. AB - We report on two infants of 11 and 12 months of age, respectively, with large solid-cystic retroperitoneal tumors. Complete resection was achieved, and both children are doing well over a follow-up of more than 17 months. The presented paper focuses on surgical anatomy of this very rare type of tumor. Teratomas were located mainly within the upper abdominal cavity, and both tumors displaced the pancreas in an anterior position. The following anatomical features were observed (1) displacement of surrounding organs, (2) deformation and elongation of large retroperitoneal vessels, (3) fibrous incorporation of large vessels by the tumor pseudocapsule, (4) wrapping of anterior aortic branches by lobes and fingers of the tumor. PMID- 24179359 TI - Nizatidine Improves Impaired Salivary Secretion in GERD. AB - During esophageal acid clearance, salivation plays an important role in defending the esophageal mucosa. Nizatidine, a histamine H2 receptor antagonist, inhibits acetylcholine esterase, with a resultant increase in acetylcholine. We experienced a patient with gastroesophageal reflux disease (GERD) and impaired salivary secretion who has been successfully treated with nizatidine. CASE REPORT: A 63-year-old female visited our hospital with complaints of heartburn and continuous laryngeal discomfort. Saliva scintigraphy was performed to evaluate the salivary function. Washout ratio was decreased to be 25%-40% in individual salivary gland. After the treatment with nizatidine, salivary scintigraphy demonstrated the increased washout ratios. The values of both parotid glands increased up to 90%, whereas those of submandibular glands improved to be around a normal range. GERD symptoms disappeared completely after treatment. In conclusion, nizatidine may be one of therapeutic options for low salivary excretion. PMID- 24179360 TI - Malignant myeloma in a patient after treatment for osteoporosis with teriparatide; a rare coincidence. AB - A breakthrough in understanding of mechanisms of bone structure regulation has brought about the introduction of the new synthetic recombinant human parathyroid hormone 1-34 (PTH1-34; Teriparatide) in the treatment of osteoporosis. These mechanisms, involving the RANKL, RANK, and osteoprotegerin system, are also known to be involved in malignant myeloma (MM) and tumor and bone metastasis development. We report a case in which MM was found after treatment of osteoporosis with teriparatide. We were unable to demonstrate any direct association between the MM and teriparatide treatment. However, it seemed intriguing that similar mechanisms are activated in the development of MM as those being working during teriparatide treatment. In the view of our case, we propose that MM by examination of serum protein fraction should be searched for prior to treatment with teriparatide as it is an exclusion criterion in teriparatide treatment of secondary osteoporosis. A search for other metastatic diseases prior to teriparatide treatment should eventually also be considered. The theoretical basis for our proposal is discussed. PMID- 24179361 TI - A rare embryologic variation: anterior communicating artery aneurysm associated with carotid-anterior cerebral artery anastomosis or infraoptic course of the anterior cerebral artery. AB - Aneurysms of the complex of the anterior cerebral artery are frequently associated with anatomic variations of the circle of Willis. We describe a case of aneurysmal rupture of the anterior communicating artery, a variant of the anterior cerebral artery. The aneurysm appeared to be situated on this vessel proximal to the infered site of the AcoA. Surgery was performed at the 6th day after hemorrhage. The anterior communicating artery aneurysm was clipped. The post operative course was unventful, with complete recovery. In our case, an extremely rare variation of the proximal tract of the anterior cerebral artery, i.e. an infraoptic course of the proximal precommunicating tract under the optic nerve, with the distal A1 tract anterior to the chiasm and positioned between the optic nerves, is presented. PMID- 24179362 TI - Diagnosis of paracardiac castleman disease by dynamic gadolinium-enhanced first pass perfusion magnetic resonance imaging. AB - Summary Castleman disease is an uncommon disorder affecting the lymphatic system and is characterised by atypical lymphocyte proliferation. The usual clinical presentation is of a solitary mass lesion, frequently within the thorax. A number of different imaging findings have been reported on CT and MRI. We present a case of paracardiac Castleman disease where the diagnosis was suggested by dramatic enhancement of the tumour mass during a dynamic MR perfusion sequence. To our knowledge this is the first report of the use of a first pass bolus tracking technique in the diagnosis of Castleman disease. PMID- 24179363 TI - A case report of hepatitis e infection leading to acute liver failure and transplantation. PMID- 24179364 TI - Photon-deficient Mass on FDG-PET Scan in Renal Cell Carcinoma: A Case Report. AB - F-18 Fluorodeoxyglucose Positron Emission Tomography imaging (F-18 FDG PET) detects malignancies depending on the uptake profile of glycolysis of tumors; however, the role of FDG PET is limited in the evaluation of primary renal malignancy because of low FDG uptake by renal cell carcinoma and also because normal urinary excretion of FDG seen in the images. A patient with renal cell carcinoma whose FDG PET imaging study incidentally shows a photon-deficient mass in the upper pole of the right kidney is present here. The diagnosis is also validated by the histopathological findings of tumor necrosis, hemorrhage, and scars. PMID- 24179365 TI - Bacteremia due to clostridium difficile: case report and review of the literature. AB - OBJECTIVE: The purpose of this study is to report a case of C. difficile bacteremia in a Crohn's disease patient and to review the literature on previously reported cases. METHODS: Searches of MEDLINE and PubMed databases were made. RESULTS: We report the first case of C. difficile bacteremia in a Crohn's disease patient. There are 15 other reported cases of C. difficile bacteremia reported in the literature. We found that the majority of patients (10 of 15 patients) had polymicrobial bacteremia and that the overall mortality rate is significant, with 6 of 15 reported patients dying. CONCLUSION: In conclusion, we find that C. difficile bacteremia is associated with a significant mortality rate and it would seem prudent to consider aggressive antibiotic therapy. PMID- 24179366 TI - Endobronchial Epstein-Barr Virus Associated Post-transplant Lymphoproliferative Disorder in Hematopoietic Stem Cell Transplantation. AB - The Epstein-Barr virus (EBV) associated Post-Transplant Lymphoproliferative Disorders (PTLD) are increasingly recognized as a fatal complication of hematological stem cell transplantation (HSCT). Thoracic involvement, that may be isolated or part of a disseminated disease, usually encompasses pulmonary nodules or masses and mediastinal lymph node enlargement. The current case study presents 2 patients who underwent HSCT, one allogenic and the other autologous, who developed an exceptional endobronchial EBV related PTLD. The first patient had a fleshy white endobronchial mass resulting in a right upper lobe atelectasis and the second had an extensive necrotising mucosa from trachea to both basal bronchi without any significant change of lung parenchyma on the CT scan. In both cases, the diagnosis was made by bronchial biopsies. Physicians should be aware of an endobronchial pattern of EBV associated PTLD after HSCT to permit quick diagnosis and therapeutic intervention. PMID- 24179367 TI - Acute autonomic, sensory and motor neuropathy associated with meningoencephalitis. AB - We report the first case of acute autonomic, motor and sensory neuropathy (AASMN) associated with meningoencephalitis. A 62-year-old man presented with fever, neck stiffness, and coma. Respiratory failure developed. Magnetic resonance images showed an abnormality in the medial temporal lobe. Cerebrospinal fluid analysis revealed pleocytosis with a high protein level. Intensive care gradually improved the consciousness level, but paralysis of the four extremities persisted. Nerve conduction studies revealed demyelinating sensory and motor polyneuropathy. Severe orthostatic hypotension, urinary retention, and constipation were also present. Clinical autonomic tests suggested both sympathetic and parasympathetic dysfunction. After intravenous immunoglobulin therapy, motor and sensory symptoms resolved rapidly; dysautonomia resolved gradually over the next 2 months. The response to immunological therapy and the presence of antecedent infection suggest that AASMN is a postinfectious, immune-mediated, autonomic, sensory and motor nervous system dysfunction. PMID- 24179368 TI - A case of large solitary fibrous tumor in the retroperitoneum. AB - Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm mainly originated in the pleural cavity. We report here an unusual case of a large SFT in the retroperitoneum. A 27-year-old female complaining of a palpable mass in the right flank with dull pain was admitted to our hospital with the diagnosis of right retroperitoneal tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large retroperitoneal tumor arising from latissimus dorsi muscle. Surgical findings revealed a partly encapsulated tumor and complete resection of tumor concomitantly with right kidney, 11th and 12th ribs, and diaphragm was performed. Pathological examination demonstrated the tumor to be composed of increased mitotic activity and cellularity of spindle cells with a collagenous matrix. Immunohistochemical staining was positive for CD34, vimentin, and basic fibroblast growth factor (bFGF) and negative for CD31, cytokeratin, desmin, S 100p, smooth muscle actin, Bcl-2, and insulin-like growth factor (IGF) with Ki-67 labeling index of 0.1%. Based on pathological features, diagnosis of SFT in the retroperitoneum was confirmed. To our knowledge, this is the first report of an SFT arising from latissimus dorsi muscle and it is important to include SFT in the differential diagnosis of retroperitoneal tumors that caused considerable diagnostic problems due to its unusual site of origin. PMID- 24179369 TI - A Case of Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome with High ASLO Titer. AB - Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disease and the pathogenesis is still unknown. We report a case of TINU syndrome with high ASLO titer. Uveitis improved and urine beta2-MG normalized with low dose systemic predonisolone and cyclosporin A. The high ASLO titer in early phase suggested that streptococcal infection might have triggered TINU syndrome. Lymphocyte phenotypes normalized after treatment with low dose systemic predonisolone and cyclosporin A. PMID- 24179370 TI - An Acute Leukaemia Masquerading as Immune Thrombocytopaenic Purpura (ITP)? A Case Report. AB - This is a case report of a 35 year old female with diagnosed Immune Thrombocytopaenic Purpura (ITP) that was strangely followed by acute myeloid leukaemia at 10 months post diagnosis of ITP. She was managed as ITP using prednisolone 45 mg daily for 10 months with good response. She also synchronously carried a pregnancy to term and safe delivery. Shortly after delivery, she represented with gingival bleeding and peripheral film review and subsequent bone marrow cytology was in keeping with AML-M4 subtype. She died shortly after diagnosis without being able to receive chemotherapy. PMID- 24179371 TI - Exophthalmos as a presenting manifestation of limited Wegener's granulomatosis in a patient with prior graves' disease. AB - Wegener's granulomatosis is a granulomatous necrotizing vasculitis characterized by its predilection to affect the upper and lower respiratory tracts and kidneys. Ocular manifestations such as keratitis, conjunctivitis, scleritis, episcleritis, nasolacrimal duct obstruction, uveitis, retroorbital pseudotumor with proptosis retinal vessel occlusion, and optic neuritis have all been described. We present a case of limited Wegener's granulomatosis presenting with proptosis. A 57 year old woman with a history of Graves' disease 20 yrs ago, presented to her ophthalmologist with new onset of exophthalmos of right eye. An MRI of the brain and orbits revealed a soft tissue mass behind the right orbit. The biopsy of the mass revealed transmural inflammation with fibrinoid necrosis consistent with necrotizing vasculitis. She was diagnosed with Wegener's granulomatosis limited to the eye and was treated with oral cyclophosphamide and prednisone followed by weekly methotrexate with good response. Though ocular manifestations of Wegener's granulomatosis are well described, a review of the literature revealed that exophthalmos as the lone presenting manifestation is quite rare. Only two cases have been reported in the English literature since 1977. This case illustrates the importance of considering a diagnosis of limited Wegener's granulomatosis presenting with proptosis of the orbit. PMID- 24179372 TI - Sarcomatoid carcinoma of the urinary bladder treated with adjuvant radiotherapy: a case report. AB - Sarcomatoid carcinoma is a rare tumor of the urinary bladder accounting for less than 0.5% of all primary urinary bladder tumors. Since the patients were presented with large tumor with extended stages, outcome was found to be poor. In order to improve local control, adjuvant local treatment may be practical. We report a rare case with sarcomatoid carcinoma of the urinary bladder diagnosed with immunuhistochemical (IHC) study and treated with 3D-conformal radiotherapy (3DCRT) post-operatively. A 55-year old female patient complained about painless hematuria for 2 months. Computed tomography of the pelvic region revealed tumor and wall thickening at the left posterolateral side of the bladder. Total cystectomy with lymph node dissection and total abdominal hysterectomy and bilateral salphingo-oopherectomy was performed and histopathological and immunohistochemical findings strongly correlate with sarcomatoid carcinoma. The patient was treated with 3D conformal radiotherapy (3DCRT) with a total dose of 59.4 Gy with 1.8 Gy fractional daily doses. Patient was alive without any local recurrence and distant metastasis 10 months after surgery. PMID- 24179373 TI - Methotrexate-induced acute leukemia: report of three cases and review of the literature. AB - For many years, methotrexate has been used in the treatment of certain chronic medical disorders e.g. rheumatoid arthritis and psoriasis as well as a number of malignant disorders e.g. acute lymphoblastic leukemia, certain types of lymphoma and breast carcinoma. Its use has been associated with various systemic toxicities and complications. The association between methotrexate therapy and the development of lymphoma and pseudolymphoma is well established. In patients treated with methotrexate, the development of leukemia has been attributed to either the primary disorder e.g. rheumatoid arthritis or to other drugs used concomitantly e.g. cyclophosphamide. Reported here are two patients with rheumatoid arthritis and one patient with psoriasis treated with low dose methotrexate for variable periods of time. Two of these patients developed acute myeloid leukemia on myelodysplastic syndrome background, while the third patient developed pre-B acute lymphoblastic leukemia that expressed few myeloid markers and had a positive philadelphia chromosome. To our knowledge, these are the first reported cases of methotrexate-induced acute leukemia. PMID- 24179374 TI - Asymmetrical weakness associated with central nervous system involvement in a patient with guillain-barre syndrome. AB - Guillain-Barre syndrome (GBS) is usually associated with symmetrical weakness, and therefore asymmetrical weakness may confuse diagnosis. We report on a patient with GBS subsequent to Campylobacter jejuni enteritis who had asymmetrical weakness with CNS involvement. The patient tested positive for anti-ganglioside antibodies, including anti-GM1 IgM, anti-GD1b IgG, and anti-GT1a IgG. Patients with GBS can manifest asymmetrical signs and symptoms attributable to CNS involvement. Prompt, accurate diagnosis and treatment of post-C. jejuni GBS is especially important because its prognosis is relatively poor. PMID- 24179375 TI - Metabolic complications of bypass surgery for morbid obesity. AB - Postoperative complications resulting from bariatric surgery can lead to severe vitamin-deficiency states. A patient who underwent bariatric bypass surgery and later developed Wernicke's encephalopathy prompted us to present her interesting case history for discussion. Although bariatric surgery is known to be a risk factor for Wernicke's encephalopathy, this diagnosis is only rarely evoked in the postoperative course. We recommend that the occurrence of digestive, psychiatric or neurological symptoms after bariatric surgery should suggest a thiamine deficiency that must be promptly assessed. Without waiting for the results, thiamine supplementation should be initiated. PMID- 24179376 TI - Dysfunction of Corticomotoneurons in Guillain-Barre Syndrome (GBS)? AB - Guillain-Barre syndrome (GBS) is characterized by acute and symmetric flaccid paraparesis and areflexia. Involvement of the central nervous system has been infrequently reported. In the current issue of Clinical Medicine: Case reports, an unusual case of GBS with asymmetric muscle weakness was reported. Corticomotoneuronal dysfunction was invoked as a possible cause for this neurological finding. Reversible blockade of voltage gated Na(+) channels resulting in conduction failure may be a possible pathophysiological mechanism. PMID- 24179377 TI - A Case of Fahr's Disease Presenting as Chorea Successfully Treated by the Use of Quetiapine. AB - We report a case of 30-year-old man presenting chorea in his legs. A brain computed tomography (CT) scan showed bilateral symmetric calcifications in the basal ganglia, thalamus, cerebellum and subcortical white matter. Laboratory studies showed no abnormalities of serum calcium, phosphate, PTH, lactic acid, pyruvic acid and cerebrospinal fluid. Under the diagnosis of Fahr's disease (FD), we treated with quetiapine (75 mg/day), which completely abolished his symptoms and he showed no other side effect. Our experience suggests that quetiapine is well tolerated in FD patients and effectively treats chorea without extrapyramidal movement. PMID- 24179378 TI - Common variable immunodeficiency associated with inflammatory bowel disease and type I diabetes. AB - Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency disorders characterized by defective antibody production, low levels of serum immunoglobulins and increased susceptibility to infection. The patient was a 39-year-old male who was admitted to the gastroenterology department with a two week history of diarrhea, blunt abdominal pain below the umbilicus, prolonged febrile state, loss of appetite and loss of body weight of 18 kg during the previous six months. Screening tests of serum immunoglobulins showed decreased concentrations of three types of immunoglobulins: IgA < 0.24 g/L, IgM < 0.18 g/L and IgG < 1.55 g/L. Lymphocytes immunophenotypisation revealed inversed CD4(+)/8(+) T cells ratio, 0.31 and absence of plasma cells (CD138 negative). Colonoscopy showed a rectal mucosa like cobblestones with multiple longitudinal and serpentinous ulceration, without involvement of other segments of the colon and the small intestine. Histopathology revealed aphtous ulcerative lesions, transmural inflammation with multiple lymphoid aggregates and benign lymphoid nodular hyperplasia of the small intestine. Plasma cells were absent from the lamina propria. Magnetic resonance imaging of a perianal fistula demonstrated a trans-sphicteric type. This case is specific because of the three illnesses associated and only one case of an association of diabetes mellitus type I and immunodeficiency reported thus far. PMID- 24179379 TI - Predicting cardiometabolic risk: waist-to-height ratio or BMI. A meta-analysis. AB - BACKGROUND AND OBJECTIVES: The identification of increased cardiometabolic risk among asymptomatic individuals remains a huge challenge. The aim of this meta analysis was to compare the association of body mass index (BMI), which is an index of general obesity, and waist-to-height ratio (WHtR), an index of abdominal obesity, with cardiometabolic risk in cross-sectional and prospective studies. METHODS: PubMed and Embase databases were searched for cross-sectional or prospective studies that evaluated the association of both BMI and WHtR with several cardiometabolic outcomes. The strength of relative risk (RR) with 95% confidence interval (CI) was calculated using the optimal cutoffs of BMI and WHtR in cross-sectional studies, while any available cutoff was used in prospective studies. The pooled estimate of the ratio of RRs (rRR [=RRBMI/RRWHtR]) with 95% CIs was used to compare the association of WHtR and BMI with cardiometabolic risk. Meta-regression was used to identify possible sources of heterogeneity between the studies. RESULTS: Twenty-four cross-sectional studies and ten prospective studies with a total number of 512,809 participants were identified as suitable for the purpose of this meta-analysis. WHtR was found to have a stronger association than BMI with diabetes mellitus (rRR: 0.71, 95% CI: 0.59 0.84) and metabolic syndrome (rRR: 0.92, 95% CI: 0.89-0.96) in cross-sectional studies. Also in prospective studies, WHtR appears to be superior to BMI in detecting several outcomes, including incident cardiovascular disease, cardiovascular disease mortality, and all-cause mortality. The usefulness of WHtR appears to be better in Asian than in non-Asian populations. BMI was not superior to WHtR in any of the outcomes that were evaluated. However, the results of the utilized approach should be interpreted cautiously because of a substantial heterogeneity between the results of the studies. Meta-regression analysis was performed to explain this heterogeneity, but none of the evaluated factors, ie, sex, origin (Asians, non-Asians), and optimal BMI or WHtR cutoffs were significantly related with rRR. CONCLUSION: The results of this meta-analysis support the use of WHtR in identifying adults at increased cardiometabolic risk. However, further evidence is warranted because of a substantial heterogeneity between the studies. PMID- 24179380 TI - Associations of demographic variables and the Health Belief Model constructs with Pap smear screening among urban women in Botswana. AB - PURPOSE: Papanicolaou (Pap) smear services are available in most urban areas in Botswana. Yet most women in such areas do not screen regularly for cancer of the cervix. The purpose of this article is to present findings on the associations of demographic variables and Health Belief Model constructs with Pap smear screening among urban women in Botswana. SAMPLE AND METHODS: The study included a convenience sample of 353 asymptomatic women aged 30 years and older who were living in Gaborone, Botswana. Data were collected using a demographic questionnaire and items of the Health Belief Model. Data analysis included descriptive statistics for demographic variables and bivariate and ordinal (logit) regression to determine the associations of demographic variables. RESULTS: Having health insurance and having a regular health care provider were significant predictors of whether or not women had a Pap smear. Women with health insurance were more likely to have had a Pap smear test than women without health insurance (91% vs 36%). Similarly, women who had a regular health care provider were more likely to have had a Pap smear test than women without a regular health care provider (94% vs 42%). Major barriers to screening included what was described as "laziness" for women who had ever had a Pap smear (57%) and limited information about Pap smear screening for women who had never had a Pap smear (44%). CONCLUSION: There is a need for more information about the importance of the Pap smear test and for increased access to screening services in Botswana. PMID- 24179382 TI - Promoter methylation in prostate cancer and its application for the early detection of prostate cancer using serum and urine samples. AB - Prostate cancer is the second most common cancer and the second leading cause of cancer death in men. However, prostate cancer can be effectively treated and cured, if it is diagnosed in its early stages when the tumor is still confined to the prostate. Combined with the digital rectal examination, the PSA test has been widely used to detect prostate cancer. But, the PSA screening method for early detection of prostate cancer is not reliable due to the high prevalence of false positive and false negative results. Epigenetic alterations including hypermethylation of gene promoters are believed to be the early events in neoplastic progression and thus these methylated genes can serve as biomarkers for the detection of cancer from clinical specimens. This review discusses DNA methylation of several gene promoters during prostate carcinogenesis and evaluates the usefulness of monitoring methylated DNA sequences, such as GSTP1, RASSF1A, RARbeta2 and galectin-3, for early detection of prostate cancer in tissue biopsies, serum and urine. PMID- 24179381 TI - Identification of gene expression signature in estrogen receptor positive breast carcinoma. AB - A significant group of patient with estrogen receptor (ER) alpha positive breast tumors fails to appreciably respond to endocrine therapy. An increased understanding of the molecular basis of estrogen-mediated signal transduction and resultant gene expression may lead to novel strategies for treating breast cancer. In this study, we sought to identify the dysregulated genes in breast tumors related to ERalpha status. Microarray analyses of 31 tumor samples showed 108 genes differentially expressed in ERalpha (+) and ERalpha (-) primary breast tumors. Further analyses of gene lists indicated that a significant number of dysregulated genes were involved in mRNA transcription and cellular differentiation. The majority of these genes were found to have promoter-binding sites for E74-like factor 5 (ELF5; 54.6% genes), E2F transcription factor 1 (E2F1; 22.2% genes), and nuclear transcription factor Y alpha (NFYA; 32.4% genes). Six candidate genes (NTN4, SLC7A8, MLPH, ENPP1, LAMB2, and PLAT) with differential expression were selected for further validation studies using RT qPCR (76 clinical specimen) and immunohistochemistry (48 clinical specimen). Our studies indicate significant over-expression of all the six genes in ERalpha (+) breast tumors as compared to ERalpha (-) breast tumors. In vitro studies using T 47D breast cancer cell line confirmed the estrogen dependant expression of four of the above six genes (SLC7A8, ENPP1, LAMB2, and PLAT). Collectively, our study provides further insights into the molecular basis of estrogen-dependent breast cancer and identifies "candidate biomarkers" that could be useful for predicting endocrine responsiveness. PMID- 24179383 TI - A novel strategy for mechanism based computational drug discovery. AB - Glioma, the common brain tumor, which arises from the glial cells, offers worse prognosis and therapy than any other tumors. Despite the genetic and pathological diversities of malignant gliomas, common signaling pathways that drive cellular proliferation, survival, invasion and angiogenesis have been identified. Very often, various tyrosine kinase receptors are inappropriately activated in human brain tumors and contribute to tumor malignancy. During such tumourous states where multiple pathways are involved, a few of them are responsbile for cell differentiation, proliferation and anti-apoptosis. Computational simulation studies of normal EGFR signaling in glioma together with the mutant EGFR mediated signaling and the MAPK signaling in glioma were carried out. There were no significant cross talks observed between the mutant EGFR and the MAPK pathways and thus from the simulation results, we propose a novel concept of 'multiple targeting' that combines EGFR and Ras targeted therapy thereby providing a better therapeutic value against glioma. Diallyl Disulfide (DADS) that has been commonly used for Ras inhibition in glioma was taken for analyses and the effect of inhibiting the EGFR downstream signaling protein with this DADS was analyzed using the simulation and docking studies. PMID- 24179384 TI - Identification of gene networks associated with acute myeloid leukemia by comparative molecular methylation and expression profiling. AB - Around 80% of acute myeloid leukemia (AML) patients achieve a complete remission, however many will relapse and ultimately die of their disease. The association between karyotype and prognosis has been studied extensively and identified patient cohorts as having favourable [e.g. t(8; 21), inv (16)/t(16; 16), t(15; 17)], intermediate [e.g. cytogenetically normal (NK-AML)] or adverse risk [e.g. complex karyotypes]. Previous studies have shown that gene expression profiling signatures can classify the sub-types of AML, although few reports have shown a similar feature by using methylation markers. The global methylation patterns in 19 diagnostic AML samples were investigated using the Methylated CpG Island Amplification Microarray (MCAM) method and CpG island microarrays containing 12,000 CpG sites. The first analysis, comparing favourable and intermediate cytogenetic risk groups, revealed significantly differentially methylated CpG sites (594 CpG islands) between the two subgroups. Mutations in the NPM1 gene occur at a high frequency (40%) within the NK-AML subgroup and are associated with a more favourable prognosis in these patients. A second analysis comparing the NPM1 mutant and wild-type research study subjects again identified distinct methylation profiles between these two subgroups. Network and pathway analysis revealed possible molecular mechanisms associated with the different risk and/or mutation sub-groups. This may result in a better classification of the risk groups, improved monitoring targets, or the identification of novel molecular therapies. PMID- 24179385 TI - EGFR and hTERT Expression as a Diagnostic Approach for Non-small Cell Lung Cancer in High Risk Groups. AB - OBJECTIVE: The early detection of NSCLC is of importance because it provides chances for better outcomes. The aim of the study was to explore the clinical utility of EGFR and hTERT mRNA expression as markers for diagnosis of NSCLC. METHODS: EGFR and hTERT mRNA were quantified by quantative reverse transcription real time polymerase chain reaction in plasma of 45 non-small cell lung cancer (NSCLC) and 40 chronic obstructive pulmonary disease (COPD) patients, selected by certain spirometric characteristics that made them at high risk of developing lung cancer in future. RESULTS: The gene expression level of each gene was calculated and given as a relative quantity-RQ. EGFR gene expression was found in all lung cancer patients. The mean level of expression was RQ = 29.39. hTERT mRNA could be detected in 88% of patients. The mean expression ratio in them was RQ = 17.31. Only 50% of the high risk patients turned to be positive for EGFR. The level of their expression was RQ = 2.09. The plasma levels of hTERT could be detected in 17 (42.5%) patients of the high risk COPD group. Their mean level of expression was RQ = 1.02. A statistically significant difference in EGFR and hTERT mRNA expression could be observed between the two groups of patients-p = 0.0001. CONCLUSION: EGFR and hTERT mRNA are potential markers for lung cancer diagnosis, whose clinical importance should be replicated in a larger cohort of patients. PMID- 24179386 TI - Circulating Natural IgM Antibodies Against Angiogenin in the Peripheral Blood Sera of Patients with Osteosarcoma as Candidate Biomarkers and Reporters of Tumorigenesis. AB - BACKGROUND: Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis. OBJECTIVES: To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers. METHODS: Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)-IgM directly in the peripheral blood sera of humans. RESULTS: Serum ANG-IgM levels are significantly higher in osteosarcoma patients than in healthy individuals (P < 0.005). Serum ANG-IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG IgM in the sera of 85% of newly diagnosed osteosarcoma patients and ANG-IgM levels were significantly higher in osteosarcoma patients compared to any other tumors (P < 0.001). CONCLUSIONS: These results demonstrated that the combined biomarker ANG-IgM has greater sensitivity and specificity in early diagnosis of osteosarcoma patients than the traditional biomarkers (ANG and vascular endothelial growth factor). Circulating ANG-IgM immune complexes can potentially serve as a biomarker for increased risk of osteosarcoma, because relatively high serum levels were also detected in otherwise healthy individuals with a first degree family history of osteosarcoma and in patients with a diagnosis of benign conditions. Immunological aspects of angiogenesis for managing osteosarcoma will have a practical value in early diagnosis, prognosis and monitoring response to antiangiogenic therapy. PMID- 24179388 TI - Serum YKL-40 Levels in Patients with Gastric Cancer. AB - AIMS AND BACKGROUND: YKL-40 is secreted by several types of tumors. Increased serum YKL-40 levels have been reported in prostate, glioblastoma, breast and colorectal cancers. Determination of YKL-40 levels may serve as a valuable biomarker for the diagnosis and treatment of gastric cancer. The purpose of this study was to determine the serum YKL-40 levels expressed in gastric carcinomas. METHODS: Between 2009 and 2011, we retrospectively reviewed 100 patients with gastric cancer and compared their serum samples to 75 healthy volunteers. YKL-40 levels were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: We found significantly higher serum levels of YKL-40 in patients with gastric cancer compared to the healthy population (P < 0.0001). We also found significant differences in serum YKL-40 levels between female and male patients with gastric cancer (P < 0.01). CONCLUSIONS: YKL-40 is over-expressed in gastric cancer, suggesting a more aggressive phenotype. YKL-40 may be a useful serum biomarker for gastric cancer identification, and future studies should focus on the role of YKL-40 in the tumorigenesis of gastric cancer and responsiveness toward treatment. PMID- 24179387 TI - Serum N-Terminal Propeptide of Collagen Type I is Associated with the Number of Bone Metastases in Breast and Prostate Cancer and Correlates to Other Bone Related Markers. AB - BACKGROUND: A number of biomarkers have been proven potentially useful for their ability to indicate bone metastases (BM) in cancer patients. The aim of this study was to investigate the relative utility of a newly developed N-terminal propeptide of collagen type I (PINP) human serum assay for the detection of BM in cancer patients. This assay has a corresponding rat PINP assay which in the future might help in translational science between rodent and human trials. METHODS: Participants were 161 prostate, lung and breast cancer patients stratified by number of BM (Soloway score). PINP was assessed and correlated to number of BM. Additionally, the PINP marker was correlated to bone resorption of young (ALPHA CTX-I)- and aged bone (BETA CTX-I); number of osteoclasts (Tartrate resistant acid phosphatase 5b, TRACP5B) and osteoclast activity (CTX-I/ TRACP5B). RESULTS: PINP was significantly elevated in breast- and prostate cancer patients +BM, compared to -BM (P < 0.001), however not in lung cancer patients. A strong linear association was seen between PINP and the number of BMs. Significant elevation of PINP was observed at Soloway scores 1-4 (<0 BM) compared with score 0 (0 BM) (P < 0.001). The correlation between bone resorption of young bone or aged bone and bone formation was highly significant in patients +BM and -BM (P < 0.0001). CONCLUSIONS: Data suggest that the present PINP potentially could determine skeletal involvement in patients with breast or prostate cancer. Correlations suggested that coupling between bone resorption and bone formation was maintained in breast- and prostate cancer patients. PMID- 24179389 TI - Organic Anion Transporting Polypeptide 5A1 (OATP5A1) in Small Cell Lung Cancer (SCLC) Cells: Possible Involvement in Chemoresistance to Satraplatin. AB - BACKGROUND: The role of organic anion transporting polypeptide 5A1 (OATP5A1) a member of a family of drug transporters that mediate cellular uptake of drugs has not been characterized so far. METHODS: Gene expression levels of OATP5A1 in small cell lung cancer (SCLC) cell lines were determined by real-time qPCR and chemosensitivity of HEK-293-SLCO5A1-transfected cells to satraplatin in MTT assays. RESULTS: Significant expression of this transporter was found at the mRNA level, primarily in drug-resistant SCLC cells, and SLCO5A1-transfected HEK-293 cells showed higher resistance to satraplatin. OATP5A1 is found preferentially in cytoplasmic membranes of tumor cells, including SCLC. CONCLUSIONS: OATP5A1 seems to effect intracellular transport of drugs and may participate in chemoresistance of SCLC by sequestration, rather than mediating cellular uptake. Since satraplatin failed to improve survival in SCLC patients, the relation of OATP5A1 expression to clinical drug resistance and its use as marker of chemoresistance should be further investigated. PMID- 24179390 TI - Clinical and Biological Significance of Cathepsin D Levels in Breast Cancer Cytosol in Women Over 70 years. AB - OBJECTIVE: To study cytosolic cathepsin D behavior and possible relationship with other clinical and biological parameters in women affected by breast invasive ductal carcinomas and older than 70 years (range: 71-88). MATERIAL AND METHODS: cytosolic levels of cathepsin D were determined by an Immunoradiometric Assay (IRMA-CIS France). Clinical and biological factors analyzed were: size, axillary lymph node involvement, distant metastasis, histological grade, ploidy, S phase cell, cytosolic estrogen receptor, progesterone receptor and pS2, and concentrations of epidermal growth factor receptor (EGFR) in cell membranes. RESULTS: Cathepsin D concentrations ranged between 13 and 1228 pmol/mg prot.. Median value of 41 was considered as threshold of positivity. Cathepsin D positive tumors showed higher S-phase values (P = 0.046) and were most often histological grade III (P = 0.047). However, the most important finding was the existence of a positive correlation (r = 0.51786) and statistically significant (P < 0.05) between S-phase values and cathepsin D in the overall group of tumors, and those ER+, but not in ER-. We determined cathepsin D concentrations in 131 women with invasive ductal breast carcinomas, but aged between 50 and 70 years (median 61) and we did not find differences based on those values in women >70 years. In addition, we found no correlation between S-phase values and Cathepsin D, both overall and in relation with hormone dependence (ER). CONCLUSIONS: THOSE RESULTS LED US TO THE FOLLOWING CONCLUSIONS: (1) cytosolic concentrations of cathepsin D in invasive infiltrating breast carcinomas in women over 70 are similar to those seen in women with the same type of tumor, but aged 50 to 70 years and are associated with increased cell proliferation measured by S phase, and histological grade III; (2) in women older than 70 years, cathepsin D concentrations are statistically significantly correlated with phase synthesis values in hormone-dependent tumors, but not in hormone-independent, fact not observed in infiltrating ductal breast carcinomas of women aged between 50 and 70. This could reflect a different mitogenic role of the aspartyl protease enzyme linked to hormone dependence as age function parameter. PMID- 24179391 TI - Urinary 1-hydroxypyrene as a biomarker to carcinogenic polycyclic aromatic hydrocarbon exposure. AB - In order to capture the extent of exposure to polycyclic aromatic hydrocarbons (PAHs), various biomarkers have been employed. The biomarkers employed for PAHs include PAHs genetoxic end points in lymphocytes, urinary metabolites, PAH-DNA adducts, and PAH-Protein adducts. Of these, excretory 1-hydroxypyene, a metabolite of pyrene, has been used extensively as a biological monitoring indicator of exposure to PAHs. This study attempts to assess the level of this biomarker in the body fluid of 68 exposed subjects using high performance liquid chromatography HPLC. The subjects screened included auto mechanics, drivers, and fuel attendants. 1-hydroxypyrene was extracted from the urine of the subjects using solid phase extraction method. The HPLC analysis was done in isocratic mode using water:methanol (12:88 v/v) mobile phase. The stationary phase was XBridge C18 (150 * 4.6 mm) 5 MUm column. The wavelength was 250 nm at a flow rate of 1.2 mL/min. The oven temperature was 30 oC and the injection volume was 20 MUL. The run time was 3 minutes. The level of urinary 1-hydroxypyrene detected varied for the different categories of occupation studied. About 27% of sampled fuel attendants and 22% of auto mechanics had detectable 1-hydroxypyrene in their urine samples. There was no detectable 1-hydroxypyene in the urine samples of commercial drivers or in the urine samples of students used as controls. The results of this study showed that fuel attendants and auto mechanics have significant exposures to PAHs. So far, there is no established benchmark for level of PAHs in urine, but our findings indicate the possibility of future cancer cases in this population as a result of their occupational exposure. The study was not able to link the level of 1-hydroxypyene with the smoking habits of the subjects. PMID- 24179393 TI - 1-hydroxypyrene levels in blood samples of rats after exposure to generator fumes. AB - Polynuclear Aromatic Hydrocarbons (PAHs) are a major component of fuel generator fumes. Carcinogenicity of these compounds has long been established. In this study, 37 Swiss albino rats were exposed to generator fumes at varied distances for 8 hours per day for a period of 42 days and the level of 1-hydroxypyrene in their blood was evaluated. This study also tried to correlate the level of blood 1-hyroxypyrene with the distance from the source of pollution. Plasma was collected by centrifuging the whole blood sample followed by complete hydrolysis of the conjugated 1-hydroxypyrene glucuronide to yield the analyte of interest, 1 hydroxypyrene, which was achieved using beta glucuronidase. High performance liquid chromatography (HPLC) with UV detector was used to determine the 1 hydroxypyrene concentrations in the blood samples. The mobile phase was water:methanol (12:88 v/v) isocratic run at the flow rate of 1.2 mL/min with CI8 stationary phase at 250 nm. After 42 days of exposure, blood concentration level of 1-hydroxypyrene ranged from 34 MUg/mL to 26.29 MUg/mL depending on the distance from source of exposure. The control group had no 1-hydroxypyrene in their blood. After the period of exposure, percentage of death correlated with the distance from the source of exposure. Percentage of death ranged from 56% to zero depending on the proximity to source of pollution. PMID- 24179392 TI - Potential biomarkers in the sera of breast cancer patients from bahawalpur, pakistan. AB - Most of the approximately 90,000 cases of Breast Cancer (BC) documented annually in Pakistan are not diagnosed properly because of lack of suitable markers. We performed serum proteome expression profiling of BC and benign breast disease (BBD) patients with the aim to identify biomarkers that can be helpful for diagnosis and prognosis of the disease. Sera of patients were analyzed by one dimensional SDS polyacrylamide gel electrophoresis (PAGE). Differentially expressed proteins were subjected to identification through LC-MS/MS analysis. In majority of the BC cases some acute phase proteins (APP) and some complement system components (C3 and C8) containing fractions were up-regulated with the exception of transthyretin (TTR) which was predominantly (68.75%) down-regulated (n = 33/48) in the sera of these patients. Varying expression patterns were observed in BBD patients and healthy controls. These differentially expressed proteins have the potential to serve as diagnostic biomarkers for BC as well as benign breast diseases. PMID- 24179394 TI - Use of Ber-EP4 and Epithelial Specific Antigen to Differentiate Clinical Simulators of Basal Cell Carcinoma. AB - EpCam is a transmembrane epithelial adhesion molecule present on all non-squamous epithelial cells. It is often overexpressed in certain carcinomas, such as breast and colon, and in dermatology, eg, basal cell carcinoma (BCC). Various monoclonal antibodies have been used to detect EpCam, including BerEP4 and epithelial specific antigen. We compared anti-EpCam clones, BerEP4, and epithelial specific antigen clone VU-1D9. One hundred and twelve lesions were stained with both antibodies. All basal cell carcinomas stained uniformly and strongly positive with both antibodies. Diffuse positive staining was also seen in all trichoepitheliomas and merkel cell carcinomas. Focal positive staining was seen in squamous cell carcinoma and benign sebaceous neoplasms. Clone VU-1D9 was more likely to produce focal positive staining as compared to BerEP4. This focal positive staining of sebaceous neoplasms and squamous cell carcinomas is a potential diagnostic pitfall. PMID- 24179396 TI - Circulating HER2 Extracellular Domain: A Specific and Quantitative Biomarker of Prognostic Value in all Breast Cancer Patients? AB - The HER2 oncoprotein has emerged as an essential biomarker in the treatment of breast cancer patients. Once the primary breast cancer is removed, there is an increasing need to detect breast cancer recurrence as early as possible with the hope that earlier intervention with new anti-HER2 therapies will improve quality of life and increase overall survival. Numerous publications have shown that increasing blood levels of circulating HER2 is an early indicator of progression, particularly in HER2-positive patients and that the rise and fall parallels the clinical course of disease and independent of therapy. Many studies show that the HER2 status of the primary tumor may not fully and accurately reflect the HER2 status of recurrent cancer. Thus, elevated serum HER2 levels may be an early signal of the emergence of a HER2-positive metastatic tumor and therefore alert the physician to re-assess HER2 status using a tissue test. PMID- 24179397 TI - Susceptibility to Cutaneous Squamous Cell Carcinoma in Renal Transplant Recipients Associates with Genes Regulating Melanogenesis Independent of their Role in Pigmentation. AB - The highly polymorphic melanocortin 1 receptor (MC1R) gene plays a crucial role in pigmentation. Variants of the gene have been implicated in risk of cutaneous squamous cell carcinoma (SCC) in the general population. In renal transplant (RT) recipients these cancers are more aggressive and very common. To evaluate the risk of SCC relative to MC1R and the pigmentation-associated genes ASIP, TYR, and TYRP1, a group of 217 RT recipients with and without SCC was genotyped. Associations with SCC risk were indicated in carriers of the red hair color associated MC1R variant p.Arg151Cys (OR = 1.99; 1.05-3.75), and in carriers of two of any of the MC1R variants disclosed (OR = 2.36; 1.08-5.15). These associations appeared independent of traditionally protective phenotypes, also supported by the stratifications from skin phototype and hair color. A tendency towards an increased SCC risk was observed for a specific ASIP haplotype (OR = 1.87; 0.91-3.83), while no such associations were observed for the TYR and TYRP1 variants. Thus, the risk of developing SCC in RT patients is modulated by MC1R variation irrespective of phenotypes considered to be protective. Heterozygous combinations of MC1R variants appear to be more relevant in assessing SCC risk than the effects of variants individually. PMID- 24179395 TI - The prognostic value of the apoptosis pathway in colorectal cancer: a review of the literature on biomarkers identified by immunohistochemistry. AB - Research towards biomarkers that predict patient outcome in colorectal cancer (CRC) is rapidly expanding. However, none of these biomarkers have been recommended by the American Association of Clinical Oncology or the European Group on Tumor Markers. Current staging criteria result in substantial under-and over-treatment of CRC patients. Evasion of apoptosis, a characteristic feature of tumorigenesis, is known to correlate with patient outcome. We reviewed the literature on immunohistochemistry-based studies between 1998 and 2011 describing biomarkers in this pathway in CRC and identified 26 markers. Most frequently described were p53, Bcl-2, survivin, and the Fas and TRAILR1 receptors and their ligands. None of the studies reviewed provided sufficient support for implementing a single marker into current clinical practice. This is likely due to the complex biology of this pathway. We suggest focusing on the combination of key markers within the apoptosis pathway that together represent an 'apoptotic tumor profile', which better reflects the status of this pathway in a tumor. PMID- 24179399 TI - Alternative agents to prevent fogging in head and neck endoscopy. AB - BACKGROUND: The essential factor for diagnosis and treatment of diseases in head and neck endoscopy is the visibility of the image. An anti-fogging agent can reduce this problem by minimizing surface tension to prevent the condensation of water in the form of small droplets on a surface. There is no report on the use of hibiscrub((r)) or baby shampoo to reduce fogging in the literature. The objective of this study was to compare the efficacy between commercial anti fogging agent, hibiscrub((r)) and baby shampoo to reduce fogging for the use in head and neck endoscopy. METHODS: The study was conducted at the Department of Otorhinolaryngology, Faculty of Medicine, Khon Kaen University in August 2010. Commercial anti-fogging agent, baby shampoo and hibiscrub((r)) were applied on rigid endoscope lens before putting them into a mist generator. The images were taken at baseline, 15 seconds, 30 seconds and 1 minute. The images' identifiers were removed before they were sent to two evaluators. A visual analogue scale (VAS) was used to rate the image quality from 0 to 10. RESULTS: The difference in mean VAS score between anti-fogging agent, baby shampoo and hibiscrub((r)) versus no agent were 5.46, 4.45 and 2.1 respectively. The commercial anti-fogging agent and baby shampoo had most protective benefit and performed significantly better than no agent (P = 0.05). CONCLUSIONS: Baby shampoo is an effective agent to prevent fogging during head and neck endoscopy and compares favourably with commercial anti-fogging agent. PMID- 24179400 TI - Nasopharyngeal cancer in Sudan: epidemiology, clinical and histological characteristics. AB - OBJECTIVES: To study the epidemiology, clinical features, staging, etiology and pathology of nasopharyngeal cancer in Sudan. STUDY DESIGN: This is a retrospective study. SETTING: Ear, Nose and Throat Department Khartoum Teaching Hospital, Khartoum City, Sudan. SUBJECTS AND METHODS: Patients suspected to have nasopharyngeal cancer were assessed during the period March 2004 to May 2010. Data from confirmed cases was obtained; it included clinical and epidemiological information. RESULTS: Three hundred and eighty five cases were studied. Bimodal age distribution of the disease was noted with two peaks, one at 15-19 years and one at 50-54 years. The male to female ratio was 2.6:1 and a distinct geographical distribution of the disease was noted, with clustering of cases in the towns of Dilling, Kadogli and the surrounding rural area of the Nuba Mountains. These areas in the Western States were reported to be of high background radiation due to naturally produced radioactive uranium. The Nuba tribe headed the list among other tribes, demonstrating a clear ethnic predilection. Sixty-eight cases presented at stage IV. There was a predominance of Type II (15.58%) and Type III (65.97%). Patients were treated by neoadjuvant chemoradiotherapy. CONCLUSIONS: NPC is an important form of cancer in Sudan. Some tribes are significantly more affected than others. Patients present with advanced disease. Environmental and genetic factors need further studies. Screening at risk populations that aim at early diagnosis and management of patients is recommended. PMID- 24179401 TI - Role of surgery in isolated concha bullosa. AB - OBJECTIVE: To study the benefit of surgery in different types of isolated concha bullosa. DESIGN: Prospective case series. SETTING: Academic Medical Center. PATIENTS: Forty seven symptomatic patients complaining of nasal congestion and block, headache and facial pain having concha bullosa without any other sinonasal finding. Their conchae bullosa were classified as lamellar, bulbous and extensive concha bullosa. They were subjected to endoscopic operation. MAIN OUTCOME MEASURES: Subjective evaluation of postoperative improvement of sinonasal symptoms and objective pre- and postoperative measurement of total nasal resistance by rhinomanometry. RESULTS: Two patients (25%) of lamellar type showed complete improvement, 5 patients (62.5%) showed partial improvement and 1 patient (12.5%) showed no improvement. Regarding bulbous type, 16 patients (72.72%) showed complete improvement, 6 patients (27.28%) showed partial improvement and no patient (0%) showed no improvement. Regarding extensive type, 15 (88.24%) patients showed complete improvement, 2 patients (11.76%) showed partial improvement and no patient (0%) showed no improvement. The total nasal resistance was 0.25 Pa/cm(3) per second postoperatively compared with 0.37 Pa/cm(3) per second preoperatively in patients having lamellar type; 0.28 Pa/cm(3) per second postoperatively compared with 0.71 Pa/cm(3) per second preoperatively in patients having bulbous type; and 0.27 Pa/cm(3) per second postoperatively compared with 0.67 Pa/cm(3) per second preoperatively in patients having extensive type. CONCLUSIONS: With proper patient selection, the operative management is of great value in relieving the sinonasal symptoms in patients having isolated Concha bullosa. This will be more obvious in certain types as bulbous and extensive types especially of large sizes. PMID- 24179398 TI - Can immunohistochemistry serve as an alternative to subjective histopathological diagnosis of oral epithelial dysplasia? AB - Many attempts have been made to identify objective molecular biomarkers to diagnose and prognosticate oral epithelial dysplasia (OED) because histopathological interpretation is subjective and lacks sensitivity. The majority of these efforts describe changes in gene expression at protein level in OED as determined by immunohistochemistry (IHC). However, the literature on these putative markers of oral cancer progression is vast and varied. The main purpose of this article is to review current knowledge on biomarkers of protein expression for OED by IHC approaches. We further discuss these findings in terms of the proposed essential hallmarks of cancer cells to better understand their role in oral oncogenesis. PMID- 24179402 TI - Management of the facial nerve in lateral skull base surgery analytic retrospective study. AB - BACKGROUND: Surgical approaches to the jugular foramen are often complex and lengthy procedures associated with significant morbidity based on the anatomic and tumor characteristics. In addition to the risk of intra-operative hemorrhage from vascular tumors, lower cranial nerves deficits are frequently increased after intra-operative manipulation. Accordingly, modifications in the surgical techniques have been developed to minimize these risks. Preoperative embolization and intra-operative ligation of the external carotid artery have decreased the intraoperative blood loss. Accurate identification and exposure of the cranial nerves extracranially allows for their preservation during tumor resection. The modification of facial nerve mobilization provides widened infratemporal exposure with less postoperative facial weakness. The ideal approach should enable complete, one stage tumor resection with excellent infratemporal and posterior fossa exposure and would not aggravate or cause neurologic deficit. The aim of this study is to present our experience in handling jugular foramen lesions (mainly glomus jugulare) without the need for anterior facial nerve transposition. METHODS: In this series we present our experience in Kasr ElEini University hospital (Cairo-Egypt) in handling 36 patients with jugular foramen lesions over a period of 20 years where the previously mentioned preoperative and operative rules were followed. The clinical status, operative technique and postoperative care and outcome are detailed and analyzed in relation to the outcome. RESULTS: Complete cure without complications was achieved in four cases of congenital cholesteatoma and four cases with class B glomus. In advanced cases of glomus jugulare (28 patients) (C and D stages) complete cure was achieved in 21 of them (75%). The operative complications were also related to this group of 28 patients, in the form of facial paralysis in 20 of them (55.6%) and symptomatic vagal paralysis in 18 of them (50%). CONCLUSIONS: Total anterior rerouting of the facial nerve carries a high risk of facial paralysis. So it should be reserved for cases where the lesion extends beyond the vertical ICA. Otherwise, for less extensive lesions and less aggressive pathologies, less aggressive approaches could be adopted with less hazards. PMID- 24179403 TI - Psychological status in patients seeking rhinoplasty. AB - BACKGROUND: Rhinoplasty is the most common operation performed by our facial plastic surgery unit. Recognition of patients with psychological problems which may result in an unfavourable post-operative outcome is essential. The objective of this study was to evaluate the psychological status of patients seeking rhinoplasty, compared with the general population. METHODS: We prospectively collected the data from patients who requested rhinoplasty in Srinagarind hospital, Thailand and controls. We used the general health questionnaire-28 (GHQ 28) for psychological problems detection. RESULTS: We included a total of 196 participants, 98 in study group and 98 in control group. The study group has a 5.5 times (95% CI 1.25 to 24.17, P = 0.01) higher risk for poor mental status more than control group. CONCLUSIONS: The patients seeking rhinoplasty group were more likely to have psychological problems when compared with the control group. Surgeons should be aware of the patient's psychological status before performing the operation. PMID- 24179405 TI - Cigarette smoking and alcohol ingestion as risk factors for laryngeal squamous cell carcinoma at kenyatta national hospital, kenya. AB - Laryngeal squamous cell carcinoma (SCC) is strongly linked to cigarette smoking. It is estimated to account for more than 70% of laryngeal SCCs and up to 89% in combination with alcohol. We wished to determine the prevalence of cigarette smoking and alcohol ingestion among patients with laryngeal squamous cell carcinoma and estimate risk attributed to cigarette smoking and alcohol ingestion. Fifty experimental group patients and fifty controls were recruited of matching age, sex and region of residence. History of smoking and alcohol intake was taken and analyzed to estimate the relative strengths of these exposures. Cessation of smoking was associated with reduced risk of SCC. Smokers had increased risk compared to controls. Those who smoked only had a higher glottic cancer risk. Those who smoked and drank alcohol had a higher supraglottic cancer risk. Being a current smoker and long duration of smoking were independent risk factors of laryngeal SCC. PMID- 24179404 TI - Treatment of recurrent metastatic head and neck cancer: focus on cetuximab. AB - EGFR belongs to the ErbB family of receptor tyrosine kinases and is associated with worse prognosis in head and neck squamous cell carcinoma (HNSCC). Cetuximab is a monoclonal antibody to the extracellular domain of EGFR and inhibits its downstream actions via multiple mechanisms. Besides its proven efficacy in locally advanced and incurable HNSCC, cetuximab has the distinct advantage of having a relatively tolerable side effect profile and not potentiating radiation toxicity. Though therapies for advanced HNSCC are evolving, locoregional recurrence and/or distant metastases occur in a large percentage of patients. Though some patients can be salvaged with surgery or radiation therapy, the majority are incurable, and are treated palliatively with systemic therapy. In the setting of first line therapy for recurrent/metastatic HNSCC, the EXTREME trial provided level 1 evidence that cetuximab improves overall survival when combined with cisplatinum and 5 FU. Following progression on first line chemotherapy, several phase II trials suggest that cetuximab monotherapy is a reasonable choice in this setting. Future studies should concentrate on clinical and molecular markers that may allow more personalized approaches to treating HNSCC, and combining EGFR inhibitors with other agents in a synergistic approach. PMID- 24179406 TI - Comparison of the Protective Effects of Radix Astragali, alpha-Lipoic Acid, and Vitamin E on Acute Acoustic Trauma. AB - OBJECTIVE: Oxidative damage is a critical role which involves hearing loss induced by impulse noise. That exogenous antioxidant agents reduce noise induced hearing loss (NIHL) has been well demonstrated in both animal studies and clinical practices. Choosing a stronger and more effective antioxidant is very important for treatment of NIHL. Vitamin E, alpha-lipoic acid, and radix astragali are the most commonly used anti-oxidants for cochlear oxidative damage from acoustic trauma. In this study, the protective effects of radix astragali, alpha-lipoic acid, and vitamin E on acute acoustic trauma are investigated. METHODS: Guinea pigs in the experimental groups were intragastrically administered vitamin E, alpha-lipoic acid, and radix astragali. Auditory thresholds were assessed by sound-evoked auditory brainstem response (ABR) at click and tone bursts of 8, 16 and 32 kHz, 24 hours before and 72 hours after exposure to impulse noise. Cochlear malondialdehyde (MDA) concentrations were detected. Hair cell damage was analyzed by scanning electron microscopy. RESULTS: Vitamin E, alpha-lipoic acid, and radix astragali significantly reduced ABR deficits, reduced hair cell damage, and decreased the concentrations of MDA. alpha-lipoic acid and radix astragali were better than vitamin E, and there were no significant differences between alpha-lipoic acid and radix astragali. CONCLUSIONS: alpha-lipoic acid or radix astragali are recommended for treatment of NIHL. PMID- 24179407 TI - Effect of recurrent otitis media on language profile in children with fragile x syndrome. AB - OBJECTIVE: Language is almost always affected in fragile X syndrome (FXS), and a delay in language acquisition is one of the first characteristics. The aim of this work was to study the effect of recurrent middle ear infections on the language profile in boys with FXS. STUDY DESIGN: Prospective case series. SETTING: Academic Medical Center. SUBJECTS AND METHODS: The present study was conducted on 30 males, ranging in age from 4-10 years. They were diagnosed as having a full mutation of DNA. The males were divided into two groups: Group A included 15 children with a history of recurrent middle ear infections more than four times per year during the first 4 years of life, and Group B did not have a history of recurrent middle ear infections during the first 4 years of life. Language assessments were done for all participants using the Standardized Arabic Language test. RESULTS: Results showed significant delays in language development in children with FXS. Relative strengths in semantics compared to syntax and pragmatics were observed in all boys. The recurrent ear infections of the boys played an important role in the language development delay. The mean of receptive, expressive, and total language age was better and higher among boys without a history of recurrent middle ear infections compared to boys with recurrent middle ear infections. CONCLUSION: Recurrent otitis media in boys with FXS exacerbates the language problems that exist in this syndrome. PMID- 24179408 TI - Magnetic resonance imaging versus computed tomography and different imaging modalities in evaluation of sinonasal neoplasms diagnosed by histopathology. AB - OBJECTIVE: The study purpose was to detect the value of magnetic resonance imaging (MRI) compared to computed tomography (CT) and different imaging modalities as conventional radiology in evaluation of sinonasal neoplasms diagnosed by Histopathology. METHODS: Thirty patients (16 males and 14 females) were complaining of symptoms related to sinonasal tract. After thorough clinical and local examination, the patients were subjected to the following: conventional radiography, CT, MRI, and histopathological examination. RESULTS: The nasal cavity was the most commonly involved site with sinonasal malignancies followed by the maxillary sinuses. The least commonly affected site was the frontal sinuses. Benign sinonasal tumors were present in 14 cases. The most common benign lesion was juvenile nasopharyngeal angiofibroma (6 cases), followed by inverted papilloma (3 cases). While malignant sinonasal tumors were present in 16 cases, squamous cell carcinoma was present in 5 cases, and undifferentiated carcinoma, in 3 cases. Lymphoepithelioma and non-Hodgkin lymphomas were present in 2 cases each, while adenocarcinoma, chondrosarcoma, adenoid cystic carcinoma, and rhabdomyosarcoma were present in 1 case each. CONCLUSION: MRI with its superior soft tissue contrast and multiplanar capability is superior to CT in pretreatment evaluation of primary malignant tumors of sinonasal cavity. PMID- 24179409 TI - Bilateral spontaneous hemotympanum secondary to chemotherapy-induced thrombocytopenia. AB - OBJECTIVE: To present a case of spontaneous, bilateral hemotympanum secondary to chemotherapy-induced thrombocytopenia. METHODS: Case report and review of the literature. RESULTS: Bilateral spontaneous hemotympanum is an exceedingly rare event. We present the first case of nontraumatic bilateral hemotympanum secondary to chemotherapy-induced thrombocytopenia in a patient with acute myelogenous leukemia. The patient presented with a 7-day history of progressive bilateral hearing loss and a platelet count of 10 * 10(9)/L after receiving his first dose of induction chemotherapy. A small, left-sided subdural hematoma was present in this patient though no extra-aural sources of bleeding to explain the bilateral hemotympanum were identified. CONCLUSION: Full resolution of symptoms was achieved with conservative management. PMID- 24179410 TI - Evaluation of temporal bone cholesteatoma and the correlation between high resolution computed tomography and surgical finding. AB - BACKGROUND: Acquired cholesteatomas are commonly seen in patients less than 30 years. There is a typical history of recurrent middle ear infections with tympanic membrane perforation. The diagnosis of cholesteatoma is usually made on otologic examination. OBJECTIVE: The aim of the work was to study the role of high resolution computed tomography (HRCT) in detecting, evaluating, and diagnosing middle ear cholesteatoma. PATIENTS AND METHODS: This was a prospective study that included 56 consecutive patients with chronic suppurative otitis media, unsafe type cholesteatomas. Each patient was subjected to full clinical evaluation, and HRCT examination. Intravenous contrast media was used in some patients with suspected intracranial complication. Preoperative radiological data were correlated with data related to surgical findings. RESULTS: The study showed that a high incidence of cholesteatoma in the third decade of life. The scutum and lateral attic wall were the most common bony erosions in the middle ear bony wall (64.3%), and the incus was the most eroded ossicle in the middle ear (88.2%). Sclerosing of mastoid air cells were encountered in 60.7% of patients and the lateral semicircular canal was affected in 9%, while facial canal erosion was found in 21.4%. Temporal bone complications are more common than intracranial complications. HRCT findings were compared with operative features; the comparative study included the accuracy and sensitivity of HRCT in detecting cholesteatoma (92.8%), its location and extension (96.4%), ossicular chain erosion (98%), labyrinthine fistula and intracranial complications (100%). CONCLUSION: The important role of HRCT scannig lies on the early detection of cholesteatoma, and more conservative surgical procedures can be used to eradicate the disease. PMID- 24179411 TI - Spinal osteosarcoma. AB - Although osteosarcoma represents the second most common primary bone tumor, spinal involvement is rare, accounting for 3%-5% of all osteosarcomas. The most frequent symptom of osteosarcoma is pain, which appears in almost all patients, whereas more than 70% exhibit neurologic deficit. At a molecular level, it is a tumor of great genetic complexity and several genetic disorders have been associated with its appearance. Early diagnosis and careful surgical staging are the most important factors in accomplishing sufficient management. Even though overall prognosis remains poor, en-block tumor removal combined with adjuvant radiotherapy and chemotherapy is currently the treatment of choice. This paper outlines histopathological classification, epidemiology, diagnostic procedures, and current concepts of management of spinal osteosarcoma. PMID- 24179412 TI - Current and emerging treatment options for patients with relapsed myeloma. AB - Multiple myeloma (MM) is a neoplastic disorder. It results from proliferation of clonal plasma cells in bone marrow with production of monoclonal proteins, which are detectable in serum or urine. MM is clinically characterized by destructive bone lesions, anemia, hypercalcemia and renal insufficiency. Its prognosis is severe, with a median survival after diagnosis of approximately 3 years due to frequent relapses. Treatments for patients with relapsed/refractory MM include hematopoietic cell transplantation, a rechallenge using a previous chemotherapy regimen or a trial of a new regimen. The introduction of new drugs such as thalidomide, lenalidomide and bortezomib has markedly improved MM outcomes. When relapse occurs, the clinician's challenge is to select the optimal treatment for each patient while balancing efficacy and toxicity. Patients with indolent relapse can be first treated with a 2-drug or a 3-drug combination. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Autologous stem cell transplantation should be considered as salvage therapy at first relapse for patients who have cryopreserved stem cells early in the disease course. The aim of this review is to provide an overview on the pharmacological and molecular action of treatments used for patients with relapsed/refractory multiple myeloma. PMID- 24179413 TI - Emerging options for the management of non-small cell lung cancer. AB - Lung cancer is one of the leading causes of death in industrialized and developing countries. Approximately 80% of patients are diagnosed with non-small cell histology. Although a multidisciplinary approach is necessary for the treatment of patients at early or locally-advanced stages of the disease, further successes in the treatment of patients with advanced disease will largely rely on improved systemic tumor control. Although therapies directed against the epidermal growth factor receptor (EGFR) have been incorporated into daily clinical practice, the value of other treatments remains to be elucidated. The current review highlights the most important driver mutations in non-small cell lung cancer (NSCLC) and describes recent study results and the status of EGFR directed therapy, anaplastic lymphoma kinase (ALK)-directed agents, antiangiogenic therapy, and mesenchymal-epithelial transition factor (MET) inhibitors. However, many other agents with different modes of action are being examined in clinical research. PMID- 24179414 TI - Metastatic castration-resistant prostate cancer: critical review of enzalutamide. AB - Enzalutamide, previously known as MDV300, is an oral, second-generation androgen receptor (AR) signaling inhibitor or antagonist that was approved by the Food and Drug Administration in 2012 for the treatment of metastatic castrate-resistant prostate cancer (mCRPC) postdocetaxel. Preclinical studies have demonstrated impressive affinity to the AR compared to the first-generation AR inhibitors. The landmark Phase III AFFIRM trial demonstrated improved overall survival benefit compared to placebo in addition to improvement in all tested parameters. Enzalutamide is currently being studied in several trials prechemotherapy and in earlier settings of prostate cancer. This review will discuss the mechanism of action of enzalutamide, its pharmacokinetics, the preclinical and clinical trials that led to its approval, the ongoing clinical trials, its safety and efficacy, as well as patterns of resistance, and discusses its place in therapy within the context of several recently approved agents for mCRPC. PMID- 24179415 TI - The importance of child car seats and current challenges with their use. PMID- 24179416 TI - The effect of surface and season on playground injury rates. AB - OBJECTIVE: To examine the effect of season on playground surface injury rates. METHODS: Injuries were identified through student incident report forms used in school districts in Calgary (Alberta) and the surrounding area. Playground surface exposure data were estimated based on school enrollment. RESULTS: A total of 539 injuries were reported during the 2007/2008 school year. Abrasions, bruises and inflammation were the most frequently reported injuries. The head, neck or face were most commonly injured. Injury rates per 1000 student days ranged between 0.018 (rubber crumb in spring) and 0.08 (poured-in-place and natural rock in the fall). Rubber crumb surfacing, compared with natural rock, had a significantly lower rate of injury in the spring, but no other season surface comparisons were statistically significant. CONCLUSIONS: Rates of injury were similar for natural rock, poured-in-place, and crushed rock in the fall and winter. There was some evidence of a lower rate of injury on rubber crumb surfaces in the spring. PMID- 24179417 TI - [Not Available]. AB - OBJECTIVE: To determine the opinion of medical students attending Laval University (Quebec, Quebec) regarding the controversial subject of corporal punishment in children. METHOD: For five consecutive years, from the 2006/2007 through to the 2010/2011 school year, an opinion poll was completed by the fourth year medical students at Laval University during a seminar concerning the maltreatment of children. RESULTS: Of the 712 students questioned, 91% were younger than 30 years of age and 74% were female. With respect to the use of corporal punishment on children, 22% of the respondents declared they were in favour of it. More men than women were in favour of this disciplinary practice, with 31% of the men in favour compared with 18% of the woman (adjusted RC 2.2 [95% CI 1.4 to 3.4]; P=0.0003). Approximately 36% of the students who had experienced corporal punishment were in favour of it, compared with only 4% of those who had not experienced this form of discipline (adjusted RC 16.5 [95%CI 8.6 to 31.4]; P<0.0001). Among those who stated that they had been victims of physical abuse, 25% declared themselves in favour of this practice, which was a similar proportion to those who had not been victims of physical abuse (21%) (P=0.52). CONCLUSION: While several medical organizations have declared opposition to the use of corporal punishment, greater than one in five future Quebec doctors are in favour of this disciplinary method and could influence the behaviour of parents in this regard. PMID- 24179418 TI - Burn injury from car seat in an 11-month-old infant. AB - Burns in young infants have long been recognized as a potential cause of nonaccidental injury. Accidental exposure to hot car seat parts resulting in significant burn injury is an unusual mimicker of child abuse. A case involving an 11-month-old child who presented with a significant contact burn injury related to the noncovered, heated, plastic part of a car seat, is described. The present case encourages physicians to maintain an unbiased approach to each referred case and to explore the differential diagnosis by detailed history and physical examination. It also serves as a reminder in caregiver education about the precautions to be taken during long-distance travel with young children and infants. PMID- 24179419 TI - Improper use of child restraint seats as a sleeping environment: Two cases of childhood death. AB - A child restraint seat (CRS) is designed to keep infants safe inside motor vehicles while in motion. However, there have been a growing number of reports of injuries sustained as a result of CRS use outside the vehicle. These injuries commonly result from a fall from an elevated surface or an overturning of the CRS. The incidence of death from these events, however, is not well documented. The present report retrospectively analyzed the British Columbia Coroner Service Database to identify deaths involving CRS use outside the vehicle. Two such fatalities were identified. In both instances, infants had been placed in a CRS overnight and, in both cases, the CRS was found overturned, resulting in asphyxiation. The history and pathological findings of both cases are summarized. PMID- 24179420 TI - Does decreasing the frequency of changing intravenous administration sets (>24 h) increase the incidence of sepsis in neonates receiving total parenteral nutrition? AB - BACKGROUND: The optimal timing for changing intravenous (IV) administration sets that contain total parenteral nutrition (TPN), with and without lipids, in neonates remains unknown. OBJECTIVE: To determine whether decreasing the frequency of changing IV administration sets (>24 h versus every 24 h) in neonates increases the incidence of sepsis within seven days of discontinuation of TPN and microbial contamination of the infusate. METHODS: The databases searched to identify studies that evaluated the frequency of IV administration sets on sepsis and microbial contamination of the infusate included MEDLINE, EMBASE, CINAHL, Cochrane Library, Scopus and Web of Science. The Evidence Evaluation Worksheet adapted from the American Heart Association's International Liaison Committee on Resuscitation was used to evaluate eligible studies for quality, level of evidence and direction of support. RESULTS: Two studies were reviewed; however, neither of the studies reported on the outcome of sepsis. One study reported that changing IV administration sets every 48 h did not increase the rate of infusate (amino acid or lipid) contamination compared with change every 24 h, while the other study reported an increase in the lipid infusate contamination rate when IV administration sets were changed every 72 h. CONCLUSIONS: There is insufficient evidence to support or refute routinely changing IV administration sets every 48 h or that decreasing the frequency of set changes increases the incidence of sepsis. PMID- 24179421 TI - Case 1: The formula dance. PMID- 24179422 TI - Case 2: An unusual case of delayed puberty. PMID- 24179423 TI - Letter to the editor. PMID- 24179424 TI - Bodychecking in youth ice hockey. AB - Hockey is one of the most popular sports for Canadian children and youth. While the health benefits of physical activity and sport participation are well recognized, there is increasing concern around the frequency and severity of hockey-related injuries, particularly concussion. Studies consistently identify bodychecking as the primary mechanism associated with youth hockey injuries, including concussion. Policy to delay bodychecking until bantam league play (when participants are 13 to 14 years of age) will reduce the risks of injury and concussion in young ice hockey players. Bodychecking should be eliminated from non-elite youth ice hockey. The age at which bodychecking is introduced in competitive hockey leagues must be reconsidered. Both initiatives require policy change in many provinces/territories, and must be re-evaluated prospectively in light of emerging research. PMID- 24179425 TI - Child and youth injury prevention: A public health approach. AB - The majority of child and youth injuries are preventable. This statement provides background, direction and a statement of commitment to the issue of child and youth injury prevention in Canada. It acts as a foundation to build upon by focusing first on definitions, scope and priorities for injury prevention. It also describes the burden and patterns of unintentional injury, and the principles of effective intervention for prevention. A list of resources for obtaining data and evidence-based information is included in the full-text version of this statement (www.cps.ca). This statement can also be used for broad based injury prevention advocacy. PMID- 24179426 TI - Preventing injuries from all-terrain vehicles. AB - All-terrain vehicles (ATVs) are widely used in Canada for recreation, transportation and occupations such as farming. As motorized vehicles, they can be especially dangerous when used by children and young adolescents who lack the knowledge, physical size, strength, and cognitive and motor skills to operate them safely. The magnitude of injury risk to young riders is reflected in explicit vehicle manual warnings and the warning labels on current models, and evidenced by the significant number of paediatric hospitalizations and deaths due to ATV-related trauma. However, helmet use is far from universal among youth operators, and unsafe riding behaviours, such as driving unsupervised and/or driving with passengers, remain common. Despite industry warnings and public education that emphasize the importance of safety behaviours and the risks of significant injury to children and youth, ATV-related injuries and fatalities continue to occur. Until measures are taken that clearly effect substantial reductions in these injuries, restricting ridership by young operators, especially those younger than 16 years of age, is critical to reducing the burden of ATV-related trauma in children and youth. This document replaces a previous Canadian Paediatric Society position statement published in 2004. PMID- 24179427 TI - Physiological referrals for paediatric musculoskeletal complaints: A costly problem that needs to be addressed. AB - BACKGROUND/OBJECTIVE: Referrals to paediatric orthopedists for physiologically normal conditions consume limited resources and delay care for patients. The goal of the present study was to formally define such referrals and determine their prevalence. METHODS: A retrospective review evaluated consecutive referrals to a single tertiary paediatric orthopedic centre over two eight-month periods. Referrals from family physicians and paediatricians were retained for analysis. Physiological referrals were defined as a final orthopedic diagnosis of 'within physiological norms'; and no scheduled follow up. RESULTS: Physiological conditions represented 22.5% of referrals. The type of referring physician did not determine referral quality. Flat foot, intoeing and genu varum/valgum exhibited physiological referral rates that exceeded 40%. CONCLUSION: Physiological referrals constitute a large portion of the outpatient paediatric orthopedic practice and represent a substantial unnecessary cost to the Canadian medical system. Future strategies to improve referral quality should target undergraduate and postgraduate musculoskeletal education. PMID- 24179428 TI - Nutritional differences in neurologically impaired children. AB - OBJECTIVES: To determine whether the recommended nutritional intake of moderately to severely neurologically impaired children is congruent with current growth parameter expectations. METHODS: Observational cross-sectional study at a children's hospice and a tertiary care children's hospital. Medically stable enterally fed children followed by the palliative care team underwent anthropometric assessment and chart review for diagnosis, intake and medications. Intakes, guidelines and recommendations were compared. RESULTS: Intakes were less than recommended. All children were <50th percentile weight-for-age, with many <3rd percentile. Fourteen of 15 were in higher percentiles for absolute and relative body fat. CONCLUSIONS: Recommended dietary intakes were not achieved by these children. Despite this, measures of body fat indicate adequate intake. Low weight values may reflect diagnosis-related growth stunting or decreased muscle mass and bone density from immobility. The Centers for Disease Control and Prevention (Georgia, USA) weight-for-age and body mass index are not suitable measures of adequate intake in this group of children. PMID- 24179430 TI - Effect of a novel stobadine derivative on isolated rat arteries. AB - The antioxidant and reactive-oxygen-species-scavenging activity of stobadine has been demonstrated in previous studies. Recently, chemical modification of this leading structure led to the synthesis of other pyridoindole derivatives with significantly increased intrinsic antioxidant efficacy. Further structural modifications of stobadine provided the opportunity to increase bioavailability and attenuate unwanted side effects, such as alpha-adrenolytic activity. The aim of the work was to evaluate the direct effect of a novel pyridoindole, SMe1EC2, on the vascular wall ex vivo. The vasomotor effect of SMe1EC2 (1*10(-8)-1*10(-4) mol/l) was measured on isolated and pressurized rat cerebral and coronary arterioles using video-microscopy. The effect of SMe1EC2 (1*10(-6) and 1*10(-5) mol/l) on high potassium-, phenylephrine- or serotonin-induced contraction or acetylcholine-induced relaxation was also determined in aortic rings. We found that SMe1EC2 (1*10(-8)-1*10(-4) mol/l) elicited significant dilatations in both cerebral and coronary arterioles (max dilatation: 25+/-8% and 18+/-5% respectively). Yet, SMe1EC2 (1*10(-6) and 1*10(-5) mol/l) did not influence the tone of aortic rings nor did it affect high potassium-, phenylephrine- or serotonin -induced contractions and acetylcholine-induced relaxation. Thus SMe1EC2 was able to dilate resistance arteries but did not affect aortic contractility. It is likely that SMe1EC2 does not possess alpha1-adrenolytic and anti-serotoninergic activity in the vascular wall. PMID- 24179431 TI - Acute toxicity of 31 different nanoparticles to zebrafish (Danio rerio) tested in adulthood and in early life stages - comparative study. AB - At present, nanoparticles are beginning to influence our lives in many ways and understanding the environmental health and safety aspect of nanomaterials has become a crucial issue. The aim of the work was to assess and compare the acute toxicity of 31 different nanomaterials to fish mature individuals Danio rerio with that to fish early life stages on using evaluation of the 48- and 96- hour LC50 values. A further aim was to evaluate teratogenicity of the nanoparticles tested to fish eggs. The nanoparticles tested were: 8 pure metals, 10 metal oxides, 5 other metal compounds and their mixtures, 2 silicon compounds, 3 calcium compounds, and 3 carbon compounds. Using 48-h and 96-h tests of acute toxicity (according to OECD 203), we evaluated mortality data, LC50 values, occurrence of malformations, as well as hatching time. In our study, 6 kinds of nanoparticles - calcium oxide, copper, copper in the form of oxide and CuZnFe4O4, magnesium oxide, and nickel - caused cumulative mortality. Two kinds of nanoparticles - copper and silver - were toxic for fish with LC50 values of approximately 3 mg/L. We did not observe marked differences between the 48-hour and 96-hour acute toxicity LC50 values, yet the possibility to evaluate hatching time in the 96-h acute fish toxicity test seems to be an advantage against that of the 48-hour toxicity. PMID- 24179429 TI - Lipophilic chemical exposure as a cause of cardiovascular disease. AB - Environmental chemical exposure has been linked to numerous diseases in humans. These diseases include cancers; neurological and neurodegenerative diseases; metabolic disorders including type 2 diabetes, metabolic syndrome and obesity; reproductive and developmental disorders; and endocrine disorders. Many studies have associated the link between exposures to environmental chemicals and cardiovascular disease (CVD). These chemicals include persistent organic pollutants (POPs); the plastic exudates bisphenol A and phthalates; low molecular weight hydrocarbons (LMWHCs); and poly nuclear aromatic hydrocarbons (PAHs). Here it is reported that though the chemicals reported on differ widely in chemical properties and known points of attack in humans, a common link exists between them. All are lipophilic species that are found in serum. Environmentally induced CVD is related to total lipophilic chemical load in the blood. Lipophiles serve to promote the absorption of otherwise not absorbed toxic hydrophilic species that promote CVD. PMID- 24179432 TI - Genotoxicity induced by iodine-131 in human cultured lymphocytes. AB - 131-radioiodine has been widely used as an effective radionuclide for treatment of patients with thyroid diseases. The purpose of this study was to investigate the genotoxic effects of iodine-131 in human cultured lymphocytes. Whole blood samples from human volunteers were incubated with iodine-131 (10, 50, 100 uCi/1.5ml) for 2 h. The lymphocytes were mitogenically stimulated to allow for evaluation of the number of micronuclei in cytokinesis-blocked binucleated cells. At the dose 100 uCi, iodine-131 induced genotoxicity by an 8.5 fold increase in the frequency of micronuclei in human lymphocytes compared with the control group. PMID- 24179433 TI - Assessment of genotoxic potential of the insecticide Dichlorvos using cytogenetic assay. AB - The possible genotoxic activity of Dichlorvos (2,2-Dichlorovinyl-O,O-dimethyl phosphate/DDVP, CAS No. 62-73-7), an organophosphorus insecticide was investigated employing three cytogenetic end points, i.e. micronucleus (MN) assay, mitotic indices (MI) and chromosome abberation (CA) analysis in vivo. The assays were carried out in hematopoietic bone marrow cells of Mus musculus at concentrations of 10, 20 and 30% of LD50 for intraperitoneal (ip) administration, corresponding to 0.06, 0.08 and 0.13 mg/kg Bwt, respectively. The normal control group received single ip dose of distilled water (2 ml/100 g Bwt), while animals of the positive group were injected with cyclophosphamide, a model mutagen (40 mg/kg Bwt) under identical conditions. The animals were sacrificed 24, 48 and 72 hrs post treatment. Under the present experimental conditions, there was no evidence of significant increase of MN frequencies at any dose or sampling time in polychromatic (PCE) and normochromatic (NCE) erythrocytes. The PCE/NCE ratio was not notably affected; however, a slight depression in prolonged exposure (48, 72 hr) intervals and a slight increase at the 24 hr interval were observed. Cells with various structural chromosome aberrations were noted but no significant (p<0.05; Man-Whitney U-test) differences in the frequencies of CA or mitotic indices (p<0.05; chi(2) test) were observed between Dichlorvos treated groups and the normal control group at doses or time intervals used. The results of the present investigation reflects a negative in vivo genotoxic potential of Dichlorvos at sublethal doses in bone marrow cells. Further studies are underway to confirm the presence or absence of genotoxic activity since compounds negative in genotoxic evaluation are susceptible of being carcinogens triggering cancer by genotoxic or non-genotoxic mechanisms. PMID- 24179435 TI - Arsenic toxicosis in sheep: The first report from Iran. AB - Arsenic contamination of groundwater has been previously reported in Ghopuz, a village located in the Northwest of Iran. Samples were taken from consuming and irrigation water and plants of the region for chemical analysis. A seven-year old ewe, which had lived in and fed a lifelong at the same place, with clinical signs such as weakness, wasting and inappropriate integument was necropsied. Grossly, buccal erosion, stomatitis, cutaneous ulcers and serous atrophy of fat deposits were observed. Rumen contents, wool and several tissue samples were obtained for toxicological and histopathological examinations. Mean arsenic concentration in the spring water, irrigation water and grass/algae were 70.11, 48.74 and 141.85 ppb (ug/kg), respectively. Arsenic levels were 486.73, 247.94, 127.92, 125.97 and 231.24 ppb in wool, skin, rumen contents, liver and kidney, respectively. Microscopic study revealed hyperemia and heavy parasitic infestation of the abomasal wall. Hyperemia and regeneration of renal tubule epithelia were observed in kidneys and hyperkeratosis, suppurative deep dermatitis and paniculitis were found in skin. Periacinar fibrosis and a poorly differentiated cholangiocarcinoma were seen in liver. In pancreas, reduced cell density of islands of Langerhans was noticeable. In the central nervous system, perineuronal and perivascular edema, ischemic changes in gray matter neurons, and microcavitation of white matter were present. Our findings confirmed chronic arsenic toxicosis in small ruminants in this region. It can be concluded that long-term consumption of arsenic contamined water and forage may be associated with chronic arsenic poisoning in domestic animals and human beings, with consequent neoplastic disease and induction of diabetes in this region. PMID- 24179434 TI - Lycopene supplementation prevents reactive oxygen species mediated apoptosis in Sertoli cells of adult albino rats exposed to polychlorinated biphenyls. AB - Sertoli cell proliferation is attenuated before attaining puberty and the number is fixed in adult testes. Sertoli cells determine both testis size and daily sperm production by providing physical and metabolic support to spermatogenic cells. Polychlorinated biphenyls (PCBs) exposure disrupts functions of Sertoli cells causing infertility with decreased sperm count. On the other hand, lycopene is improving sperm count and motility by reducing oxidative stress in humans and animals. Hence we hypothesized that PCBs-induced infertility might be due to Sertoli cell apoptosis mediated by oxidative stress and lycopene might prevent PCBs-induced apoptosis by acting against oxidative stress. To test this hypothesis, animals were treated with vehicle control, lycopene, PCBs and PCBs + lycopene for 30 days. After the experimental period, the testes and cauda epididymidis were removed for isolation of Sertoli cells and sperm, respectively. We observed increased levels of oxidative stress markers (H2O2 and LPO) levels, increased expression of apoptotic molecules (caspase-8, Bad, Bid, Bax, cytochrome C and caspase-3), decreased anti-apoptotic (Bcl2) molecule and elevated apoptotic marker activity (caspase-3) in Sertoli cells of PCBs-exposed animals. These results were associated with decreased sperm count and motility in PCBs exposed animals. On the other hand, lycopene prevented the elevation of Sertoli cellular apoptotic parameters and prevented the reduction of sperm parameters (count and motility). The data confirmed that lycopene as an antioxidant scavenged reactive oxygen substances, prevented apoptosis, maintained normal function in Sertoli cells and helped to provide physical and metabolic support for sperm production, thereby treating infertility in men. PMID- 24179436 TI - Assessment of surgical sutures POLYMED((r)) by intracutaneous irritation test in rabbits. AB - The aim of the present study was to evaluate local irritant effects to rabbit skin following a single application of test samples of non-sterile polyamide non absorbable surgical sutures POLYMED((r)). The polar and nonpolar extracts were prepared by using saline solution and olive oil, respectively, after sinking the materials tested (2.0 g) in 10 ml of the corresponding liquid. Incubation was carried out at the temperature of 37 degrees C for 72 h. The saline solution and pure olive oil, which had no contact with the materials tested, were used as negative control samples and were incubated under the same conditions as above. Assessments of the extracts from each material were conducted on 2 albino rabbits of the New Zealand breed. On the back of each animal, 5 intracutaneous injections of the extract tested and 5 injections of the control solution, each of 0.2 ml, were carried out. The degree of irritation was scored at 4, 24, 48, 72 hours after injection and no skin changes were found. The intracutaneous irritation index (III) was calculated and yielded 0.0. Hence it was concluded that under the experimental conditions the extracts of the material tested, i.e. non-sterile polyamide non-absorbable surgical sutures POLYMED((r)), were 'non-irritant' to the skin of rabbits when compared with the respective control groups. The experimental procedure was conducted according to ISO10993-10. PMID- 24179437 TI - Emission factors and particulate matter size distribution of polycyclic aromatic hydrocarbons from residential coal combustions in rural Northern China. AB - Coal consumption is one important contributor to energy production, and is regarded as one of the most important sources of air pollutants that have considerable impacts on human health and climate change. Emissions of polycyclic aromatic hydrocarbons (PAHs) from coal combustion were studied in a typical stove. Emission factors (EFs) of 16 EPA priority PAHs from tested coals ranged from 6.25 +/- 1.16 mg kg-1 (anthracite) to 253 +/- 170 mg kg-1 (bituminous), with NAP and PHE dominated in gaseous and particulate phases, respectively. Size distributions of particulate phase PAHs from tested coals showed that they were mostly associated with particulate matter (PM) with size either between 0.7 and 2.1 MUm or less than 0.4 MUm (PM0.4). In the latter category, not only were more PAHs present in PM0.4, but also contained higher fractions of high molecular weight PAHs. Generally, there were more than 89% of total particulate phase PAHs associated with PM2.5. Gas-particle partitioning of freshly emitted PAHs from residential coal combustions were thought to be mainly controlled by absorption rather than adsorption, which is similar to those from other sources. Besides, the influence of fuel properties and combustion conditions was further investigated by using stepwise regression analysis, which indicated that almost 57 +/- 10% of total variations in PAH EFs can be accounted for by moisture and volatile matter content of coal in residential combustion. PMID- 24179438 TI - Compatible solute engineering in plants for abiotic stress tolerance - role of glycine betaine. AB - Abiotic stresses collectively are responsible for crop losses worldwide. Among these, drought and salinity are the most destructive. Different strategies have been proposed for management of these stresses. Being a complex trait, conventional breeding approaches have resulted in less success. Biotechnology has emerged as an additional and novel tool for deciphering the mechanism behind these stresses. The role of compatible solutes in abiotic stress tolerance has been studied extensively. Osmotic adjustment, at the physiological level, is an adaptive mechanism involved in drought or salinity tolerance, which permits the maintenance of turgor under conditions of water deficit, as it can counteract the effects of a rapid decline in leaf water potential. Increasing evidence from a series of in vivo and in vitro studies of the physiology, biochemistry, genetics, and molecular biology of plants suggest strongly that Glycine Betaine (GB) performs an important function in plants subjected to environmental stresses. It plays an adaptive role in mediating osmotic adjustment and protecting the sub cellular structures in stressed plants, protection of the transcriptional and translational machineries and intervention as a molecular chaperone in the refolding of enzymes. Many important crops like rice do not accumulate glycinebetaine under stress conditions. Both the exogenous application of GB and the genetically engineered biosynthesis of GB in such crops is a promising strategy to increase stress tolerance. In this review we will discuss the importance of GB for abiotic stress tolerance in plants. Further, strategies like exogenic application and transgenic development of plants accumulating GB will be also be discussed. Work done on exogenic application and genetically engineered biosynthesis of GB will be listed and its advantages and limitations will be described. PMID- 24179439 TI - Epigenetics in ocular diseases. AB - Epigenetics pertains to heritable alterations in gene expression that do not involve modification of the underlying genomic DNA sequence. Historically, the study of epigenetic mechanisms has focused on DNA methylation and histone modifications, but the concept of epigenetics has been more recently extended to include microRNAs as well. Epigenetic patterning is modified by environmental exposures and may be a mechanistic link between environmental risk factors and the development of disease. Epigenetic dysregulation has been associated with a variety of human diseases, including cancer, neurological disorders, and autoimmune diseases. In this review, we consider the role of epigenetics in common ocular diseases, with a particular focus on DNA methylation and microRNAs. DNA methylation is a critical regulator of gene expression in the eye and is necessary for the proper development and postmitotic survival of retinal neurons. Aberrant methylation patterns have been associated with age-related macular degeneration, susceptibility to oxidative stress, cataract, pterygium, and retinoblastoma. Changes in histone modifications have also been observed in experimental models of diabetic retinopathy and glaucoma. The expression levels of specific microRNAs have also been found to be altered in the context of ocular inflammation, retinal degeneration, pathological angiogenesis, diabetic retinopathy, and ocular neoplasms. Although the complete spectrum of epigenetic modifications remains to be more fully explored, it is clear that epigenetic dysregulation is an important contributor to common ocular diseases and may be a relevant therapeutic target. PMID- 24179440 TI - Strand-Specific RNA-Seq Provides Greater Resolution of Transcriptome Profiling. AB - RNA-Seq is a recently developed sequencing technology, that through the analysis of cDNA allows for unique insights into the transcriptome of a cell. The data generated by RNA-Seq provides information on gene expression, alternative splicing events and the presence of non-coding RNAs. It has been realised non coding RNAs are more then just artefacts of erroneous transcription and play vital regulatory roles at the genomic, transcriptional and translational level. Transcription of the DNA sense strand produces antisense transcripts. This is known as antisense transcription and often results in the production of non coding RNAs that are complementary to their associated sense transcripts. Antisense tran-scription has been identified in bacteria, fungi, protozoa, plants, invertebrates and mammals. It seems that antisense tran-scriptional 'hot spots' are located around nucleosome-free regions such as those associated with promoters, indicating that it is likely that antisense transcripts carry out important regulatory functions. This underlines the importance of identifying the presence and understanding the function of these antisense non-coding RNAs. The information concerning strand ori-gin is often lost during conventional RNA-Seq; capturing this information would substantially increase the worth of any RNA-Seq experiment. By manipulating the input cDNA during the template preparation stage it is possible to retain this vital information. This forms the basis of strand specific RNA-Seq. With an ability to unlock immense portions of new in-formation surrounding the transcriptome, this cutting edge technology may hold the key to developing a greater under-standing of the transcriptome. PMID- 24179441 TI - Review: Alternative Splicing (AS) of Genes As An Approach for Generating Protein Complexity. AB - Prior to the completion of the human genome project, the human genome was thought to have a greater number of genes as it seemed structurally and functionally more complex than other simpler organisms. This along with the belief of "one gene, one protein", were demonstrated to be incorrect. The inequality in the ratio of gene to protein formation gave rise to the theory of alternative splicing (AS). AS is a mechanism by which one gene gives rise to multiple protein products. Numerous databases and online bioinformatic tools are available for the detection and analysis of AS. Bioinformatics provides an important approach to study mRNA and protein diversity by various tools such as expressed sequence tag (EST) sequences obtained from completely processed mRNA. Microarrays and deep sequencing approaches also aid in the detection of splicing events. Initially it was postulated that AS occurred only in about 5% of all genes but was later found to be more abundant. Using bioinformatic approaches, the level of AS in human genes was found to be fairly high with 35-59% of genes having at least one AS form. Our ability to determine and predict AS is important as disorders in splicing patterns may lead to abnormal splice variants resulting in genetic diseases. In addition, the diversity of proteins produced by AS poses a challenge for successful drug discovery and therefore a greater understanding of AS would be beneficial. PMID- 24179442 TI - Mitochondria and familial predisposition to breast cancer. AB - Mitochondrial genome and functional alterations are related to various diseases including cancer. In all cases, the role of these organelles is associated with defects in oxidative energy metabolism and control of tumor-induced oxidative stress. The present study examines the involvement of mitochondrial DNA in cancer and in particular in breast cancer. Furthermore, since mitochondrial DNA is maternally inherited, hereditary breast cancer has been focused on. PMID- 24179443 TI - Genomics of Chronic Obstructive Pulmonary Disease (COPD); Exploring the SNPs of Protease-Antiprotease Pathway. AB - The COPD has been an important respiratory condition that affects people worldwide and its incidence has been alarming. The increasing incidence of this disorder has been attributed to global industrialization and environmental pollution. Although the exposures to environmental pollutants and smoking have been important triggers, the genetic component of individuals has been shown to be important for development and progression of COPD. Recent literature reported that protease-antiprotease imbalance to be important in etiopathogenesis of COPD. The enzymes namely neutrophil elastase and matrix metalloprotienases are considered to be foremost proteolytic molecules released by neutrophils and macrophages during inflammatory events in COPD. Normally, the lungs remain protected from the destructive effect of these two antiproteases by alpha1 antitrypsin (alpha1AT) and tissue inhibitors of metalloproteinases (TIMPs) respectively. In this review, we are trying to highlight the work by various research groups in exploring the SNPs of various genes of inflammatory pathways and the protease-antiprotease pathway, which may have some degree of association with COPD. PMID- 24179444 TI - Phylogenetic Analysis of Brassica rapa MATH-Domain Proteins. AB - The MATH (meprin and TRAF-C homology) domain is a fold of seven anti-parallel beta-helices involved in protein-protein interaction. Here, we report the identification and characterization of 90 MATH-domain proteins from the Brassica rapa genome. By sequence analysis together with MATH-domain proteins from other species, the B. rapa MATH-domain proteins can be grouped into 6 classes. Class-I protein has one or several MATH domains without any other recognizable domain; Class-II protein contains a MATH domain together with a conserved BTB (Broad Complex, Tramtrack, and Bric-a-Brac ) domain; Class-III protein belongs to the MATH/Filament domain family; Class-IV protein contains a MATH domain frequently combined with some other domains; Class-V protein has a relative long sequence but contains only one MATH domain; Class-VI protein is characterized by the presence of Peptidase and UBQ (Ubiquitinylation) domains together with one MATH domain. As part of our study regarding seed development of B. rapa, six genes are screened by SSH (Suppression Subtractive Hybridization) and their expression levels are analyzed in combination with seed developmental stages, and expression patterns suggested that Bra001786, Bra03578 and Bra036572 may be seed development specific genes, while Bra001787, Bra020541 and Bra040904 may be involved in seed and flower organ development. This study provides the first characterization of the MATH domain proteins in B. rapa. PMID- 24179445 TI - Edward p. Buchanan. PMID- 24179446 TI - Pediatric plastic surgery-clefts. PMID- 24179448 TI - Contemporary concepts for the bilateral cleft lip and nasal repair. AB - The bilateral cleft lip and nasal deformity presents a complex challenge for repair. Surgical techniques continue to evolve and are focused on primary anatomic realignment of the tissues. This can be accomplished in a single-stage or two-stage repair early in infancy to provide a foundation for future growth of the lip and nasal tissue. Most cleft surgeons currently perform a single-stage repair for simplifying patient care. Certain institutions utilize presurgical orthopedics for alignment of the maxillary segments and nasal shaping. Methods for the bilateral cleft lip repair are combined with various open and closed rhinoplasty techniques to achieve improved correction of the primary nasal deformity. There is recent focus on shaping the nose for columellar and tip support, as well as alar contour and alar base position. The authors will present a new technique for closure of the nasal floor to prevent the alveolar cleft fistula. Although the alveolar fistula is closed, alveolar bone grafting is still required at the usual time in dental development to fuse the maxilla. It is paramount to try and minimize the stigmata of secondary deformities that historically have been characteristic of the repaired bilateral cleft lip. A properly planned and executed repair reduces the number of revisions and can spare a child from living with secondary deformities. PMID- 24179447 TI - Unilateral cleft lip: principles and practice of surgical management. AB - Management of cleft lip and palate requires a unique understanding of the various dimensions of care to optimize outcomes of surgery. The breadth of treatment spans multiple disciplines and the length of treatment spans infancy to adulthood. Although the focus of reconstruction is on form and function, changes occur with growth and development. This review focuses on the surgical management of the primary cleft lip and nasal deformity. In addition to surgical treatment, the anatomy, clinical spectrum, preoperative care, and postoperative care are discussed. Principles of surgery are emphasized and controversies are highlighted. PMID- 24179449 TI - Cleft palate. AB - Our understanding of cleft palates has come a long way over the last few decades. A better understanding of the long-term consequences of a cleft palate and its effect on speech development challenges surgeons to not only effectively repair the cleft, but to also restore function of the palate for adequate speech. Coordination with speech pathologists is integral for effective management of cleft palate patients, particularly as children begin to develop language. In this article, the authors review and summarize the various challenges and goals of cleft palate management. PMID- 24179450 TI - Velopharyngeal dysfunction. AB - Velopharyngeal dysfunction (VPD) is a generic term which describes a set of disorders resulting in the leakage of air into the nasal passages during speech production. As a result, speech samples can demonstrate hypernasality, nasal emissions, and poor intelligibility. The finding of VPD can be secondary to several causes: anatomic, musculoneuronal, or behavioral/mislearning. To identify the etiology of VPD, patients must undergo a thorough velopharyngeal assessment comprised of perceptual speech evaluation and functional imaging, including video nasendoscopy and speech videofluoroscopy. These studies are then evaluated by a multidisciplinary team of specialists, who can decide on an optimal course for patient management. A treatment plan is developed and may include speech therapy, use of a prosthetic device, and/or surgical intervention. Different surgical options are discussed, including posterior pharyngeal flap, sphincter pharyngoplasty, Furlow palatoplasty, palatal re-repair, and posterior pharyngeal wall augmentation. PMID- 24179451 TI - Alveolar bone grafting: past, present, and new horizons. AB - Alveolar bone grafting is an important part of the reconstructive journey for many cleft lip and palate patients. The reconstruction of the alveolar cleft can provide both aesthetic and functional benefits to the patient. To be able to effectively treat alveolar clefts, it is essential to possess an understanding of several aspects of the problem. Acquiring this knowledge will allow the provider to treat the different variants of the cleft alveolus. In this article, the author will discuss anatomy, history, techniques, controversies, and new technologies to provide the reader with new insight into treating this challenging condition. PMID- 24179452 TI - Cleft nasal deformity and rhinoplasty. AB - The cleft nasal deformity is a complex challenge in plastic surgery involving the skin, cartilage, mucosa, and skeletal platform. Ever since Blair and Brown first described the intricacies of the cleft pathology in 1931, the appropriate approach has been extensively debated in the literature with respect to timing, technique, and extent of surgical intervention. In this article, the authors review the literature and summarize the various modalities for achieving a successful rhinoplasty in the patient with a cleft nasal deformity. PMID- 24179453 TI - Efficient determination of protein-protein standard binding free energies from first principles. AB - Characterizing protein-protein association quantitatively has been a longstanding challenge for computer simulations. Here, a theoretical framework is put forth that addresses this challenge on the basis of detailed all-atom molecular dynamics simulations with explicit solvent. The proposed methodology relies upon independent potential of mean force (PMF) free-energy calculations carried out sequentially, wherein the biological objects are restrained in the conformation, position and orientation of the bound state, using adequately chosen biasing potentials. These restraints systematically narrow down the configurational entropy available to the system and effectively guarantee that the relevant network of interactions is properly sampled as the two proteins reversibly associate. Decomposition of the binding process into consecutive, well-delineated stages, for both the protein complex and the individual, unbound partners, offers a rigorous definition of the standard state, from which the absolute binding free energy can be determined. The method is applied to the difficult case of the extracellular ribonuclease barnase binding to its intracellular inhibitor barstar. The calculated binding free energy is -21.0 +/- 1.4 kcal/mol, which compares well with the experimental value of -19.0 +/- 0.2 kcal/mol. The relatively small statistical error reflects the precision and convergence afforded by the PMF-based simulation methodology. In addition to providing an accurate reproduction of the standard binding free energy, the proposed strategy offers a detailed picture of the protein-protein interface, illuminating the thermodynamic forces that underlie reversible association. The application of the present formal framework to barnase:barstar binding provides a foundation for tackling nearly any protein-protein complex. PMID- 24179454 TI - Does interprofessional collaboration between care levels improve following the creation of an integrated delivery organisation? The Bidasoa case in the Basque Country. AB - INTRODUCTION: This article explores the impact of the creation of a new integrated delivery organisation on the evolution of interprofessional collaboration between primary and secondary care levels. In particular, the case of the Bidasoa Integrated Healthcare Organisation is analysed. THEORY AND METHODS: The evolution of interprofessional collaboration is measured through a validated Spanish questionnaire, with 10 items and a 5-point Likert scale, based on the D'Amour's model of collaboration [20]. The final sample included 146 observations (doctors and nurses). RESULTS: The questionnaire identified a significant improvement on the mean scores for interprofessional collaboration of 0.57 points before and after the intervention. A significant improvement was also found in the two dimensions of the measure of interprofessional collaboration used, with the size of the change being higher for the dimension related to the organisational setting (0.63) than for interpersonal relationships (0.47). CONCLUSIONS: Before and after the creation of the Bidasoa Integrated Healthcare Organisation, an improvement in the perceived degree of interprofessional collaboration between primary and secondary care levels was observed. This finding supports the benefit of a multilevel and multidimensional approach to integration, as in the described Bidasoa case. DISCUSSION: Results on the two dimensions of the measure of interprofessional collaboration used seem to point to the longer time required for interpersonal relationships to change compared to the organisational setting. PMID- 24179455 TI - Community services' involvement in the discharge of older adults from hospital into the community. AB - BACKGROUND: Community services are playing an increasing role in supporting older adults who are discharged from hospital with ongoing non-acute care needs. However, there is a paucity of information regarding how community services are involved in the discharge process of older individuals from hospital into the community. METHODS: Twenty-nine databases were searched from 1980 to 2012 (inclusive) for relevant primary published research, of any study design, as well as relevant unpublished work (e.g. clinical guidelines) which investigated community services' involvement in the discharge of older individuals from hospital into the community. Data analysis and quality appraisal (using McMaster critical appraisal tools) were undertaken predominately by the lead author. Data was synthesised qualitatively. RESULTS: Twelve papers were eligible for inclusion (five randomised controlled trials, four before and after studies and three controlled trials), involving a total of 8440 older adults (>65 years). These papers reported on a range of interventions. During data synthesis, descriptors were assigned to four emergent discharge methods: Virtual Interface Model, In reach Interface Model, Out-reach Interface Model and Independent Interface Model. In each model, the findings were mixed in terms of health care and patient and carer outcomes. CONCLUSIONS: It is plausible that each model identified in this systematic review has a role to play in successfully discharging different cohorts of older adults from hospital. Further research is required to identify appropriate population groups for various discharge models and to select suitable outcome measures to determine the effectiveness of these models, considering all stakeholders' involved. PMID- 24179456 TI - An institutional ethnography inquiry of health care work in special education: a research protocol. AB - BACKGROUND: Special education for children with chronic health conditions or disabilities requires the integration of health care work with education. This phenomenon occurs in an understudied and challenging context for integrated care despite policies and protocols that outline work processes in this context. We are interested in an approach to inquiry that will allow us to address gaps in current literature and practices in integrated care, and move towards informing policy. STUDY DESIGN AND DATA COLLECTION METHODS: Institutional ethnography is an approach to inquiry that maps the actualities of what individuals do at an everyday local level, while examining this work activity in relation to the sociopolitical context. It has been used to change policy and local practice by highlighting disjunctures between policy and actuality. We are adopting institutional ethnography and its three common methods of data collection: document collection, interviews, and observation/shadowing. Informants to this inquiry are chosen from school-based teams, family-centred units and constellations of clinical professionals. METHODS OF ANALYSIS: We are following work processes, verbally and visually mapping what is done and by whom. It is important to note that work includes 'unofficial' work, including the work of families and others who may not be assigned an official work role in a policy or protocol. The mediating role of texts in work processes is also being mapped in order to link the local work to the high-level social coordinators. To begin, analysis focuses on local, or micro-level, work processes; next, analysis identifies and explains the macro-level coordination of the local work (i.e. social and political structures). CONCLUSION: A primary outcome of this study will be the creation of verbal and visual maps that demonstrate the social organisation of work processes occurring in the health care-special education interface. These maps will make invisible work visible, highlight disjunctures between policy and practice and identify opportunities for change. They will be useful for critical knowledge translation purposes, providing parents and professionals with an awareness of how their individual work fits in to the larger picture of integrating health care work in special education. PMID- 24179457 TI - Preferences of overweight and obese patients for weight loss programmes: a discrete-choice experiment. AB - INTRODUCTION: Obesity is associated with increased risk of morbidity and mortality and also appears to have an adverse effect on health-related quality of life. Though advances in obesity therapy and rehabilitation can be observed, the long-lasting outcome is dissatisfying to most of the patients and, therefore, the whole health care system. THEORY AND METHODOLOGY: The study aims to identify key attributes of coordinated weight loss programmes and elicit patients' preferences for overweight and obesity therapy in rehabilitation programmes. A self administered survey measuring attitudes and preferences was conducted in Germany in 2009. Discrete-choice experiment scenarios were developed using a fractional factorial design and results analysed using a random effects logit model. RESULTS: N=110 patients completed the questionnaire, 51.82% of these were male, the mean age was 53.05 years and mean body mass index was 33.54 kg/m2 (SD 7.73). A total of 823 choices could be included in the final estimation. The most important aspects for the respondents' selection were care coordination (coefficient 1.473; SE 0.185) and individual therapy (coefficient 1.446; SE 0.188). The aspect 'infrastructure of care' (coefficient 0.570; SE 0.175) was less relevant. All attributes led to significant coefficients. CONCLUSION: Patients value coordination of care and individual therapy most highly. So weight reduction therapy should enable patients to receive a structured, coordinated and interpersonal therapy that is tailored to their personal needs, behaviour and circumstances. Patients are willing to forego infrastructure quality in favour of better coordination and structure in their therapy. PMID- 24179458 TI - Transforming health care: an approach to system-wide implementation. AB - There are enormous financial, demographic, epidemiological and clinical safety pressures on health care systems around the world. These pressures are well known and are increasing every day. This perspective paper describes one possible way forward to meeting these pressures undertaken through the system-wide transformation of the health care system in the Basque Country to a population of over 2.3 million people. The overall goal has been to turn the health care system to become more proactive than reactive and more collaborative than fragmented. This ambitious plan started in 2009. PMID- 24179459 TI - How do you build programmes of integrated care? The need to broaden our conceptual and empirical understanding. PMID- 24179460 TI - Net community production and dark community respiration in a Karenia brevis (Davis) bloom in West Florida coastal waters, USA. AB - Oxygen-based productivity and respiration rates were determined in West Florida coastal waters to evaluate the proportion of community respiration demands met by autotrophic production within a harmful algal bloom dominated by Karenia brevis. The field program was adaptive in that sampling during the 2006 bloom occurred where surveys by the Florida Wildlife Research Institute indicated locations with high cell abundances. Net community production (NCP) rates from light-dark bottle incubations during the bloom ranged from 10 to 42 umole O2 L-1 day-1 with highest rates in bloom waters where abundances exceeded 105 cells L-1. Community dark respiration (R) rates in dark bottles ranged from <10 to 70 umole O2 L-1 day-1 over 24 h. Gross primary production derived from the sum of NCP and R varied from ca. 20 to 120 umole O2 L-1 day-1. The proportion of GPP attributed to NCP varied with the magnitude of R during day and night periods. Most surface communities exhibited net autotrophic production (NCP > R) over 24 h, although heterotrophy (NCP < R) characterized the densest sample where K. brevis cell densities exceed 106 cells L-1. PMID- 24179462 TI - NMDA Receptors in Glial Cells: Pending Questions. AB - Glutamate receptors of the N-methyl-D-aspartate (NMDA) type are involved in many cognitive processes, including behavior, learning and synaptic plasticity. For a long time NMDA receptors were thought to be the privileged domain of neurons; however, discoveries of the last 25 years have demonstrated their active role in glial cells as well. Despite the large number of studies in the field, there are many unresolved questions connected with NMDA receptors in glia that are still a matter of debate. The main objective of this review is to shed light on these controversies by summarizing results from all relevant works concerning astrocytes, oligodendrocytes and polydendrocytes (also known as NG2 glial cells) in experimental animals, further extended by studies performed on human glia. The results are divided according to the study approach to enable a better comparison of how findings obtained at the mRNA level correspond with protein expression or functionality. Furthermore, special attention is focused on the NMDA receptor subunits present in the particular glial cell types, which give them special characteristics different from those of neurons - for example, the absence of Mg(2+) block and decreased Ca(2+) permeability. Since glial cells are implicated in important physiological and pathophysiological roles in the central nervous system (CNS), the last part of this review provides an overview of glial NMDA receptors with respect to ischemic brain injury. PMID- 24179461 TI - Neurobiological consequences of sleep deprivation. AB - Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed. PMID- 24179463 TI - Cannabinoids, Neurogenesis and Antidepressant Drugs: Is there a Link? AB - Similar to clinically used antidepressants, cannabinoids can also regulate anxiety and depressive symptoms. Although the mechanisms of these effects are not completely understood, recent evidence suggests that changes in endocannabinoid system could be involved in some actions of antidepressants. Chronic antidepressant treatment modifies the expression of CB1 receptors and endocannabinoid (EC) content in brain regions related to mood and anxiety control. Moreover, both antidepressant and cannabinoids activate mitogen activated protein (MAP) kinase and phosphoinositide 3-kinase(PI3-K)/Akt or PKB signaling, intracellular pathways that regulate cell proliferation and neural cell survival. Facilitation of hippocampal neurogenesis is proposed as a common effect of chronic antidepressant treatment. Genetic or pharmacological manipulations of cannabinoid receptors (CB1 and CB2) or enzymes responsible for endocannabinoid-metabolism have also been shown to control proliferation and neurogenesis in the hippocampus. In the present paper we reviewed the studies that have investigated the potential contribution of cannabinoids and neurogenesisto antidepressant effects. Considering the widespread brain distribution of the EC system, a better understanding of this possible interaction could contribute to the development of therapeutic alternatives to mood and anxiety disorders. PMID- 24179464 TI - The changing landscape of voltage-gated calcium channels in neurovascular disorders and in neurodegenerative diseases. AB - It is a common belief that voltage-gated calcium channels (VGCC) cannot carry toxic amounts of Ca(2+) in neurons. Also, some of them as L-type channels are essential for Ca(2+)-dependent regulation of prosurvival gene-programs. However, a wealth of data show a beneficial effect of drugs acting on VGCCs in several neurodegenerative and neurovascular diseases. In the present review, we explore several mechanisms by which the "harmless" VGCCs may become "toxic" for neurons. These mechanisms could explain how, though usually required for neuronal survival, VGCCs may take part in neurodegeneration. We will present evidence showing that VGCCs can carry toxic Ca(2+) when: a) their density or activity increases because of aging, chronic hypoxia or exposure to beta-amyloid peptides or b) Ca(2+)-dependent action potentials carry high Ca(2+) loads in pacemaker neurons. Besides, we will examine conditions in which VGCCs promote neuronal cell death without carrying excess Ca(2+). This can happen, for instance, when they carry metal ions into the neuronal cytoplasm or when a pathological decrease in their activity weakens Ca(2+)-dependent prosurvival gene programs. Finally, we will explore the role of VGCCs in the control of nonneuronal cells that take part to neurodegeneration like those of the neurovascular unit or of microglia. PMID- 24179467 TI - Coping with hardship through friendship: the importance of peer social capital among children affected by HIV in Kenya. AB - Children living in households affected by HIV face numerous challenges as they take on significant household-sustaining and caregiving roles, often in conditions of poverty. To respond to their hardships, we must identify and understand the support systems they are already part of. For this reason, and to emphasise the agentic capabilities of children, this article explores how vulnerable children cope with hardship through peer social capital. The study draws on the perspectives of 48 HIV-affected and caregiving children who through PhotoVoice and draw-and-write exercises produced 184 photographs and 56 drawings, each accompanied with a written reflection. The themes emerging from the essays reveal that schools provide children with a useful platform to establish and draw on a mix of friendship structures. The children were found to strategically establish formalised friendship groups that have the explicit purpose of members supporting each other during times of hardship. The children also formed more natural friendship groups based on mutual attraction, with the implicit expectation that they will help each other out during times of hardship. In practice, the study found that children help each other through sharing (e.g. schools material and food) as well as through practical support (e.g. with domestic duties, securing food, and income-generation) - thus demonstrating that children are able to both accumulate and benefit from 'peer social capital.' The study concludes that a key coping strategy of HIV-affected and caregiving children is to mobilise and participate in friendship groups which are characterised by sharing and reciprocity of support. Development responses to support children affected by the HIV epidemic need to take heed of children's ability to draw on peer social capital. PMID- 24179466 TI - Acetylcholinesterase inhibitors: pharmacology and toxicology. AB - Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer's disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases. PMID- 24179468 TI - The effect of a commercial probiotic drink containing Lactobacillus casei strain Shirota on oral health in healthy dentate people. AB - BACKGROUND: In the past decade, the use of probiotic-containing products has been explored as a potential alternative in oral health therapy. A widely available probiotic drink, Yakult, was evaluated for oral health applications in this longitudinal study. Selected oral health parameters, such as levels and composition of salivary and tongue plaque microbiota and of malodorous gases, in dentate healthy individuals were investigated for changes. The persistence of the probiotic strain in the oral cavity was monitored throughout the study period. METHODS: A three-phase study (7 weeks) was designed to investigate simultaneously the effect of 4-week consumption of the probiotic-containing milk drink Yakult on the microbiota of saliva and dorsum tongue coating in healthy dentate people (n = 22) and levels of volatile sulphur compounds (VSCs) in morning breath. Study phases comprised one baseline visit, at which 'control' levels of oral parameters were obtained prior to the probiotic product consumption; a 4-week period of daily consumption of one 65 ml bottle of Yakult, each bottle containing a minimum of 6.5*10(9) viable cells of Lactobacillus casei strain Shirota (LcS); and a 2 week washout period. The microbial viability and composition of saliva and tongue dorsum coating were assessed using a range of solid media. The presence of LcS in the oral cavity was investigated using a novel selective medium, 'LcS Select'. Portable sulphur monitors Halimeter((r)) and OralChroma(TM) were used to measure levels of VSCs in morning breath. RESULTS: Utilization of the LcS Select medium revealed a significant (p < 0.05) but temporary and consumption-dependent presence of LcS in saliva and tongue plaque samples from healthy dentate individuals (n = 19) during the probiotic intervention phase. LcS was undetectable with culture after 2 weeks of ceasing its consumption. Morning breath scores measured with Halimeter and OralChroma were not significantly affected throughout the trial, except in a small number of individual cases where Halimeter scores were significantly reduced during the probiotic intervention period. Natural fluctuations in resident acidogenic populations, and numbers of Candida and anaerobic species, including malodourous Gram-negative anaerobes, were unaffected. CONCLUSION: While no broad ecological changes in the mouth were induced by consumption of Yakult in healthy dentate individuals, findings of this study confirm the temporary and intake-dependent presence of LcS. Future studies could focus on subjects at greater risk of oral infection, where ill-defined microbiota (e.g. an increased presence of periopathogens) or clinically diagnosed halitosis might be significantly affected by consumption of this probiotic. PMID- 24179465 TI - Nicotinic receptors in neurodegeneration. AB - Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (alpha2-alpha10) and 3 beta (beta2-beta4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer's disease (AD), Parkinson's disease (PD), schizophrenia, Tourette's syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment. PMID- 24179469 TI - Theoretical dietary modelling of Australian seafood species to meet long-chain omega 3 fatty acid dietary recommendations. AB - BACKGROUND: Several agencies recommend seafood to be consumed 2-3 times per week. In Australia, there is a lack of nutrient composition data for seafood species and it is not known whether including different seafood species in a diet would provide sufficient long-chain omega 3 fatty acids (LC n-3 PUFA) to meet various national recommendations. OBJECTIVE: To utilise recent nutrient composition data for major Australian seafood groups (n=24) with the addition of two tuna options (total n=26) to: (1) determine whether including these species into a diet based on the Australian Guide to Healthy Eating (AGHE) will achieve LC n-3 PUFA recommendations [Adequate Intake (AI: 160 mg/d men, 90 mg/d women)], Suggested Dietary Target (SDT), 500 mg/d Heart Foundation (HF) recommendation and (2) determine the weekly number of servings of seafood to meet recommendations using either lower fat (n=23, <10% total fat) or higher fat (n=3, >=10% total fat) seafood. DESIGN: Two simulation models incorporated all 26 species of seafood or only lower fat seafood into a diet based on the AGHE. Two further models identified the number of servings of lower or higher fat seafood required to meet recommendations. RESULTS: Including 2 and 3 servings/week of any seafood would enable 89% of women and 66% of men to meet the AI. Including only lower fat seafood would enable 83% of women and 47% of men to meet the AI. Half a serving/week of higher fat seafood would enable 100% of men and women to meet the AI. CONCLUSIONS: Including the recommended 2-3 servings of seafood/week requires at least some higher fat seafood to be consumed in order for most men and women to meet the AI. Further messages and nutrition resources are needed which provide options on how to increase intake of LC n-3 PUFA, specifically through consumption of the higher fat seafood. PMID- 24179470 TI - Hematopoietic growth factors in transfusion medicine and cellular therapy - part I. PMID- 24179471 TI - G-CSF in Healthy Allogeneic Stem Cell Donors. AB - Mobilization of peripheral blood stem cells (PBSC) in healthy volunteers with granulocyte colony-stimulating factor (G-CSF) is currently carried out at many institutions worldwide. This report presents the experience of the Dresden center regarding donor evaluation and mobilization schedule. Data regarding efficacy, short- and long-term safety of G-CSF treatment gained from 8290 PBSC collections in healthy donors are outlined. These results are discussed against the background of the available evidence from the literature. Although established as a standard procedure, G-CSF application to allogeneic donors will always be a very delicate procedure and requires the utmost commitment of all staff involved to ensure maximum donor safety. PMID- 24179472 TI - Physiology and pharmacology of plerixafor. AB - Autologous hematopoietic stem cell (HSC) transplantation is an important therapeutic option for patients with non-Hodgkin's lymphoma and multiple myeloma. The primary source of HSC is from the peripheral blood which requires mobilization from the bone marrow. Current mobilization regimens include cytokines such as G-CSF and/or chemotherapy. However not all patients mobilize enough HSC to proceed to transplant. The chemokine receptor CXCR4 and its ligand CXCL12 are an integral part of the mechanism of HSC retention in the bone marrow niche. The discovery of plerixafor, a selective inhibitor of CXCR4, has provided a new additional means of mobilizing HSC for autologous transplantation. Plerixafor consists of two cyclam rings with a phenylenebis(methylene) linker. It inhibits CXCL12 binding to CXCR4 and subsequent downstream events including chemotaxis. The molecular interactions of plerixafor have been defined indicating a unique binding mode to CXCR4. Plerixafor rapidly mobilizes HSC within hours compared with the multi-day treatment required by G-CSF in mouse, dog and non human primate. The mobilized cells once transplanted are capable of timely and endurable engraftment. Additionally CXCR4 has been implicated in the pathology of HIV, inflammatory disease and cancer and the pharmacology of plerixafor in various disease models is described. PMID- 24179473 TI - Successful mobilization, intra-apheresis recruitment, and harvest of hematopoietic progenitor cells by addition of plerixafor and subsequent large volume leukapheresis. AB - BACKGROUND: In patients failing successful conventional mobilization of hematopoietic progenitor cells (HPC) plerixafor (Mozobil((r))) seems to be an alternative. We report a series of 14 patients with multiple myeloma or NHL successfully mobilized and harvested by plerixafor together with large-volume leukaphereses (LVL). METHODS: In a first series (GI), 5 patients were mobilized with G-CSF and plerixafor. In the second series (GII), 9 patients were mobilized by chemotherapy, G-CSF, and plerixafor. RESULTS: In GI and GII, addition of plerixafor led to a significant (p < 0.01) increase of leukocytes and CD34+ cells in peripheral blood (PB). In GII, the median number of CD34+ cells in PB before and after addition of plerixafor was significantly (p = 0.019) higher compared to GI (9 vs. 5 and 50 vs. 24 cells/MUl, respectively). In GI and GII, a median number of three or one aphereses was performed. In GII, the median yield (6.7 * 10(6) CD34+ cells/kg) of the first apheresis and the median intra-apheresis recruitment of CD34+ cells were significantly (p < 0.05) higher compared to GI (2.94 * 10(6) CD34+ cells/kg). All patients transplanted, 5 in GI and 8 in GII, exhibited successful engraftment. CONCLUSIONS: Plerixafor and G-CSF mobilization or the addition of plerixafor during non-optimal chemotherapy and G-CSF mobilization together with LVL enabled, independent of leukocyte count and even without detectable CD34+ cells before addition of plerixafor, sufficient harvest of HPC numbers for transplantation. Addition of plerixafor during chemotherapy and G-CSF mobilization led to an increased intra-apheresis recruitment and a significantly higher yield of CD34+ cells compared to plerixafor and G-CSF steady state mobilized patients. PMID- 24179474 TI - Efficacy and side effects of granulocyte collection in healthy donors. AB - BACKGROUND: We report on the efficacy and side effects of granulocyte collection, which is comparatively infrequently performed in Germany. METHODS: Data from 378 healthy donors who underwent 914 granulocyte collections between 1999 and 2007 were retrospectively analyzed. Donors received G-CSF (lenograstim) at a median dose of 5.58 (3.25-7.36) MUg/kg body weight with (n = 243) or without (n = 57) 4 mg dexamethasone. Side effects were recorded by donor monitoring and interview (questionnaire). RESULTS: The median granulocyte yield in apheresis products was 8.47 * 10(10) (3.07-14.92 * 10(10)). Granulocyte yields correlated significantly with gender, baseline WBC, PMN and PLT counts, and nicotine consumption. Dexamethasone and lenograstim administration was more effective than lenograstim administration alone (p < 0.001). Side effects of granulocyte mobilization were generally mild: bone pain in 31.4%, headache in 19.6%, and fatigue in 15.7% of donors. During follow-up (4 weeks), pruritus and/or exanthema were reported in 17.6% of donors. CONCLUSIONS: Granulocyte mobilization with lenograstim with or without dexamethasone was a safe and effective regimen for granulocyte mobilization. Side effects were tolerable and milder than those seen in peripheral blood stem cell donors. Long-term monitoring of granulocyte donors is important to establish optimal standards for the procedure. PMID- 24179476 TI - Effect of fluorescent particle size on the modulation efficiency of ultrasound modulated fluorescence. AB - To investigate whether the size of fluorescent particles affects the modulation efficiency of ultrasound-modulated fluorescence (UMF), we measured UMF and DC (direct current) signals of the fluorescence emission from four different sized fluorescent particles: (1) three carboxylate-modified fluorescent microspheres (FM) with diameters of 20 nm, 200 nm, and 1.0 um and (2) streptavidin-conjugated Alexa Fluor 647 with a diameter of approximately 5 nm. The UMF and DC signals were simultaneously measured using a broadband lock-in amplifier and a narrowband amplifier, respectively. The ratio of the UMF strength to the DC signal strength is defined as the modulation efficiency. This modulation efficiency was then used to evaluate the effects of fluorophore size and concentration. Results show that the modulation efficiency was improved by approximately a factor of two when the size of the fluorescent particles is increased from 5 nm to 1 um. In addition, the linear relationship between the UMF strength and ultrasound pressure (observed in our previous study) were maintained regardless of the fluorescent particle sizes. PMID- 24179477 TI - Species-specific PCR to describe local-scale distributions of four cryptic species in the Penicillium chrysogenum complex. AB - Penicillium chrysogenum is a ubiquitous airborne fungus detected in every sampled region of the Earth. Owing to its role in Alexander Fleming's serendipitous discovery of Penicillin in 1928, the fungus has generated widespread scientific interest; however its natural history is not well understood. Research has demonstrated speciation within P. chrysogenum, describing the existence of four cryptic species. To discriminate the four species, we developed protocols for species-specific diagnostic PCR directly from fungal conidia. 430 Penicillium isolates were collected to apply our rapid diagnostic tool and explore the distribution of these fungi across the London Underground rail transport system revealing significant differences between Underground lines. Phylogenetic analysis of multiple type isolates confirms that the 'Fleming species' should be named Penicillium rubens and that divergence of the four 'Chrysogenum complex' fungi occurred about 0.75 million yr ago. Finally, the formal naming of two new species, Penicillium floreyi and Penicillium chainii, is performed. PMID- 24179478 TI - Using an 'action set' for the management of acute upper gastrointestinal bleeding. AB - BACKGROUND: We studied the management of patients with acute upper gastrointestinal (GI) bleeding (AUGIB) at the Royal Free Hospital. The aim was to compare our performance with the national standard and determine ways of improving the delivery of care in accordance with the recently published 'Scope for improvement' report. METHODS: We randomly selected patients who presented with haematemesis, melaena, or both, and had an oesophageogastroduodenoscopy (OGD) between April and October 2009. We developed local guidelines and presented our findings in various forums. We collaborated with the British Medical Journal's Evidence Centre and Cerner Millennium electronic patient record system to create an electronic 'Action Set' for the management of patients presenting with AUGIB. We re-audited using the same standard and target. RESULTS: With the action set, documentation of pre-OGD Rockall scores increased significantly (p <= 0.0001). The differences in the calculation and documentation of post-OGD full Rockall scores were also significant between the two audit loops (p = 0.007). Patients who inappropriately received proton-pump inhibitors (PPIs) before endoscopy were reduced from 73.8% to 33% (p = 0.02). Patients receiving PPIs after OGD were also reduced from 66% to 50% (p = 0.01). Discharges of patients whose full Rockall score was less than or equal to two increased from 40% to 100% (p = 0.43). CONCLUSION: The use of the Action Set improved calculation and documentation of risk scores and facilitated earlier hospital discharge for low risk patients. Significant improvements were also seen in inappropriate use of PPIs. Actions sets can improve guideline adherence and can potentially promote cost-cutting and improve health economics. PMID- 24179475 TI - West nile virus. PMID- 24179479 TI - Is side-viewing endoscope assisted balloon dilatation better for corrosive gastric outlet obstruction? AB - BACKGROUND: Endoscopic balloon dilatation (EBD) is an effective therapy for caustic-induced gastric outlet obstruction (GOO). Gaining access to the stricture site is the most important step. It is sometimes difficult to negotiate a balloon through the stricture with a front-viewing endoscope due to deformed anatomy of stomach. To overcome this technical difficulty, a side-viewing endoscope can be used. There is limited data regarding the use of side-viewing endoscopes in EBD. We here report on the short-term efficacy and safety of EBD in caustic-induced GOO. In technically difficult cases, a side-viewing endoscope was used for EBD and its efficacy and safety were assessed. METHODS: The study included 25 patients with caustic-induced GOO. Patients underwent EBD using a through-the scope balloon. Initial balloon dilatation was performed with a front-viewing endoscope. A side-viewing endoscope was used where negotiation across the stricture failed with a front-viewing endoscope. Dilatation was started at 8 mm diameter and was performed at 1-week intervals. The end point of dilatation was 15 mm diameter. RESULTS: In 18 patients successful balloon dilatation was possible with a front-viewing endoscope. A side-viewing endoscope was used in six patients as negotiation across the stricture was not possible with a front viewing endoscope. In all six patients negotiation across the stricture followed by successful dilatation was successful with a side-viewing endoscope. Of the 25 patients included in this study, 24 (96%) achieved procedural success (18 with a front-viewing endoscope and 6 with a side-viewing endoscope) in 3-9 sessions. CONCLUSION: Our results show that EBD is a safe and effective option for caustic induced GOO and in difficult cases a side-viewing endoscope can be used to achieve technical success. PMID- 24179480 TI - Screening colonoscopy bowel preparation: experience in an urban minority population. AB - METHODS: Suboptimal bowel preparation, present in over 20% of colonoscopies, can severely compromise the effectiveness of the colonoscopy procedure. We surveyed 93 primarily urban minority men and women who underwent asymptomatic 'screening' colonoscopy regarding their precolonoscopy bowel-preparation experience. RESULTS: Print materials alone (39.8%) and in-person verbal instructions alone (35.5%) were reportedly the most common modes of instruction from the gastroenterologists. Liquid-containing laxative (70.6%) was the most common laxative agent; a clear liquid diet (69.6%) the most common dietary restriction. Almost half of the participants mentioned 'getting the laxative down' as one of the hardest parts of the preparation; 40.9% mentioned dietary restrictions. The 24.7% who mentioned 'understanding the instructions' as one of the hardest parts were more likely to be non-US born and to have lower education and income. There was no relationship between difficulty in understanding instructions and mode of instruction or preparation protocol. One quarter suggested that a smaller volume and/or more palatable liquid would have made the preparation easier. Three quarters agreed that it would have been helpful to have someone to guide them through the preparation process. CONCLUSIONS: These findings suggest a variety of opportunities for both physician- and patient-directed educational interventions to promote higher rates of optimal colonoscopy bowel preparation. PMID- 24179481 TI - Treating hepatocellular carcinoma progression following first-line sorafenib: therapeutic options and clinical observations. AB - Despite the established efficacy of sorafenib in advanced hepatocellular carcinoma (HCC), a significant number of sorafenib-treated patients experience disease progression. Current guidelines recommend either best supportive care or clinical trial enrollment for this population. As such, there remains an unmet need for tolerable, life-prolonging strategies in the second-line setting. New information regarding the molecular pathogenesis of resistance to antiangiogenic therapy and positive post-progression experience with antiangiogenics in other tumor types has led to trials investigating the effect of continued use of sorafenib, alone or combined with other agents. Trials investigating the effect of switching from sorafenib to alternate antiangiogenic agents, phosphatidylinositol 3 kinase/AKT/mammalian target of rapamycin inhibitors, or cMet inhibitors are also underway. As these data emerge, clinicians may consider a new paradigm for managing advanced HCC. This article briefly reviews the mechanisms of disease resistance to antiangiogenic therapy as a vehicle for discussing clinical strategies to prolong survival in patients with advanced HCC that are currently employed at our institutions or are under investigation. Key ongoing trials investigating the use of molecularly targeted therapies in patients with progressive disease are also highlighted. PMID- 24179482 TI - Aflibercept in the treatment of patients with metastatic colorectal cancer: latest findings and interpretations. AB - Inhibition of angiogenesis is an established adjunct in the treatment of metastatic colorectal cancer. Bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF) A, improves clinical outcomes when added to standard chemotherapy for metastatic colorectal cancer. Unfortunately, the development of resistance is inevitable, and novel therapeutic strategies are needed. Aflibercept is an intravenously administered fusion protein of the human vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 extracellular domains. This antiangiogenic agent binds to VEGF A, VEGF B, and placental growth factor 1 (PlGF1) and PlGF2 with high affinity and inhibits downstream signaling. Common side effects of single agent aflibercept are similar to other antiangiogenic drugs and include hypertension, proteinuria, fatigue, and headache. Recent clinical data regarding the efficacy of aflibercept with standard chemotherapy for metastatic colorectal cancer, associated adverse events, and future areas of research are reviewed. PMID- 24179483 TI - Emerging therapies and latest development in the treatment of unresectable pancreatic neuroendocrine tumors: an update for clinicians. AB - Pancreatic neuroendocrine tumors (pNETs) differ in their clinical behavior, presentation and prognosis based on their initial histological features and disease stage. While small resectable tumors can be treated surgically, metastatic and locally advanced disease carries a significant mortality and treatment options have been limited in terms of their efficacy. Streptozocin based regimens were the only agents available before but recent advances have improved the armamentarium to treat pNETs. Newer chemotherapeutic agents such as temozolomide, somatostatin analogs and targeted therapies including everolimus and sunitinib are now available to treat these tumors. Several combination regimens with targeted therapies and newer agents such as pazopanib are being developed and tested in ongoing trials. PMID- 24179485 TI - Clinical characteristics of high-functioning youth with autism spectrum disorder and anxiety. AB - AIM & METHODS: Clinical characteristics were examined in 108 high-functioning youth (children with a full IQ scale of at least 70) with an autism spectrum disorder (ASD; aged 7-15 years) who were presenting for inclusion in one of four clinical trials examining the efficacy of cognitive behavioral therapy in youth with ASD and anxiety. RESULTS: We present baseline characteristics of this cohort, including prevalence rates of anxiety and comorbid disorders, and correlates of anxiety (e.g., comorbid diagnoses, impairment, anxiety severity and mental health services received) as a function of age and ASD diagnosis in treatment-seeking youth. Primary anxiety disorders were: 41.7% (n = 45) social phobia, 25.9% (n = 28) generalized anxiety disorder, 15.7% (n = 17) separation anxiety disorder, 12.0% (n = 13) obsessive-compulsive disorder and 4.6% (n = 5) specific phobia. Overall, 91.6% of participants (n = 99) met criteria for two or more anxiety disorders. Parents reported considerable functional impairment as measured by the Columbia Impairment Scale and anxiety severity as measured by the Pediatric Anxiety Rating Scale; this did not statistically differ as a function of ASD diagnosis or age. Anxiety severity, the number of comorbid anxiety diagnoses and total comorbid diagnoses were directly associated with parent reported child impairment. Youth with ASD and anxiety present as a heterogeneous cohort with significant impairments and complex diagnostic presentations. CONCLUSION: These data provide information about the nature of anxiety in youth with ASD, which may foster the development of tailored treatment protocols. PMID- 24179486 TI - Early palliative care in cancer treatment: rationale, evidence and clinical implications. AB - Patients with advanced cancer often experience symptoms of disease and treatment that contribute to distress and diminish their quality of life (QOL). Care that is aimed at control of these symptoms, whether or not the patient is undergoing ongoing disease-directed therapy to control the cancer, is thus a key feature of high-quality patient-centered care. In standard oncology practice, it is easy for focus on this type of care to be obscured by discussions and management of anticancer therapy and adequate attention to QOL, patient preferences, and goals of care often occur only days to weeks from the patient's death. The initiation of palliative care and discussion of the patients' goals and preferences earlier in the course of disease can lead to improved symptom control, reduced distress throughout the disease-directed therapy, and care delivery that matches the patients' preferences. This review discusses the evolving evidence for early initiation of palliative care in patients with advanced cancer and ongoing barriers to care in this setting. We highlight challenges for research and care delivery and the potential for broader awareness of the demonstrated benefits of palliative care to help translate known benefits into improved outcomes for patients facing advanced cancer. PMID- 24179487 TI - Vascular endothelial growth factor receptor tyrosine kinase inhibitors in metastatic renal cell cancer: latest results and clinical implications. AB - Metastatic renal cell cancer (mRCC) accounts for 25-30% of patients with renal cell cancer at presentation. In addition to this, a significant proportion of patients with localized disease at presentation will develop metastatic disease. With the introduction of tyrosine kinase inhibitors (TKIs), the treatment of mRCC has been radically altered. Several newer generation vascular endothelial growth factor receptor TKIs have been tested in the clinical setting over recent years, resulting in the availability of more drugs. We review the latest results from clinical trials and the implications these have on the management of patients with mRCC. PMID- 24179488 TI - Which patients with metastatic breast cancer benefit from subsequent lines of treatment? An update for clinicians. AB - The outcome of patients with metastatic breast cancer (MBC) has clearly improved over the past decades and the proportion of women living with their disease for several years is increasing. However, the usefulness of multiple lines of treatment is still debated and under evaluation. The available data from both randomized trials and large retrospective series are reviewed and discussed in order to analyze management practices, with emphasis on potential prognostic and predictive factors for clinical outcome. At present, evidence-based medicine provides some support for the use of second-line and to a lesser degree and in selected cases, third-line chemotherapy in human epidermal growth factor receptor 2 (HER2) negative MBC. Beyond third-line treatment, messages from recently reported retrospective studies also suggest a clear potential gain for women receiving further therapies after disease progression, since each line can contribute to a longer survival. In HER2-positive disease, the data from observational and retrospective studies support a clinical benefit from the use of trastuzumab beyond disease progression and emerging evidences from randomized controlled trials are leading to the introduction of newer HER2-targeted therapies in multiple lines. The question 'How many lines of treatment should we give patients?' clearly needs further research through prospective, high-quality clinical trials, aiming for a better definition of factors with prognostic and predictive role. In the meantime, the 'optimal' treatment strategy should probably be to use as many therapeutic options as possible, either in sequence or combination, to keep the best efficacy/toxicity balance, considering MBC as a chronic disease. PMID- 24179489 TI - Toward an understanding of the pathophysiology of clear cell carcinoma of the ovary (Review). AB - Endometriosis-associated ovarian cancers demonstrate substantial morphological and genetic diversity. The transcription factor, hepatocyte nuclear factor (HNF) 1beta, may be one of several key genes involved in the identity of ovarian clear cell carcinoma (CCC). The present study reviews a considerably expanded set of HNF-1beta-associated genes and proteins that determine the pathophysiology of CCC. The current literature was reviewed by searching MEDLINE/PubMed. Functional interpretations of gene expression profiling in CCC are provided. Several important CCC-related genes overlap with those known to be regulated by the upregulation of HNF-1beta expression, along with a lack of estrogen receptor (ER) expression. Furthermore, the genetic expression pattern in CCC resembles that of the Arias-Stella reaction, decidualization and placentation. HNF-1beta regulates a subset of progesterone target genes. HNF-1beta may also act as a modulator of female reproduction, playing a role in endometrial regeneration, differentiation, decidualization, glycogen synthesis, detoxification, cell cycle regulation, implantation, uterine receptivity and a successful pregnancy. In conclusion, the present study focused on reviewing the aberrant expression of CCC-specific genes and provided an update on the pathological implications and molecular functions of well-characterized CCC-specific genes. PMID- 24179491 TI - Prognostic value of molecular markers and cytogenetic alterations that characterize breast cancer precursor lesions (Review). AB - The understanding of the molecular mechanisms that underlie all stages of tumor progression in breast cancer (BC) represents an important goal in the biomedical research of this disease, particularly for the identification of more specific targeted therapies. In this context, BC preinvasive and precursor lesions represent a major dilemma. These lesions are well characterized under the phenotypic and genotypic profile, but it is not clear if they represent obligatory passages of a multistep process determining breast cancer evolution. In fact, the numerous cytogenetic and molecular alterations identified are not always representative of the progression into invasive phenotypes. PMID- 24179492 TI - Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review). AB - Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study. PMID- 24179490 TI - A new perspective of vasculogenic mimicry: EMT and cancer stem cells (Review). AB - Vasculogenic mimicry (VM), a new pattern of tumor microcirculation, is important for the growth and progression of tumors. Epithelial-mesenchymal transition (EMT) is pivotal in malignant tumor progression and VM formation. With increasing knowledge of cancer stem cell (CSC) phenotypes and functions, increasing evidence suggests that CSCs are involved in VM formation. Recent studies have indicated that EMT is relevant to the acquisition and maintenance of stem cell-like characteristics. Thus, in this review we discuss the correlation between CSCs, EMT and VM formation. PMID- 24179493 TI - Clinical necessity of the immunohistochemical reassessment of para-aortic lymph nodes in resected pancreatic ductal adenocarcinoma. AB - Para-aortic lymph node (PALN) metastasis is widely regarded as a systemic disease in cancer. Undetected PALN micrometastases during routine hematoxylin and eosin (HE) staining may be a cause of poor prognosis following a potentially curative pancreatectomy for pancreatic cancer. In the present study, paraffin-embedded PALN tissue blocks from 99 patients who underwent a pancreatectomy were re evaluated by immunohistochemical staining using cytokeratin (CK)-19. Patients with PALN metastasis were summarized according to the clinicopathological data. A total of 484 PALNs (median, 4.9 nodes per patient; range, 1-19) were evaluated. PALN metastases were revealed in eight patients (8.1%) by routine HE staining of frozen section biopsies and in one patient (1.0%) by HE staining of a permanent section. Only one patient (1.0%) demonstrated micrometastasis by IHC; this patient did not display any adverse pathological characteristics and had a relatively favorable survival period of 41 months. The present study concluded that an additional reassessment for micrometastasis in PALNs using CK-19 immunohistochemistry (IHC) is not a viable method for determining the survival outcome. A careful examination of a frozen section biopsy is sufficient for attempting curative surgery. PMID- 24179494 TI - Expression of Foxp3, CD25 and IL-2 in the B16F10 cancer cell line and melanoma is correlated with tumor growth in mice. AB - The forkhead box P3 (Foxp3) transcription factor is one of the most studied markers used to identify CD4+CD25+ regulatory T cells (Tregs), and has been identified as a key regulator in the development and function of Tregs. Foxp3 expression has been reported in a variety of solid human tumors, including melanoma. The aims of the present study were to analyze Foxp3 expression in B16F10 melanoma cells in vitro, to determine whether this expression was affected during tumor growth in a murine melanoma model and to correlate Foxp3 expression with CD25 expression, interleukin (IL)-2 production and tumor weight. Foxp3 expression was analyzed with quantitative (q)PCR, flow cytometry and confocal microscopy. CD25 expression was analyzed by flow cytometry, and cytokine production was measured by ELISA [IL-2, interferon (IFN)-gamma, transforming growth factor (TGF)-beta and IL-10] and flow cytometry (IL-2, IFN-gamma, IL-4 and IL-5). Foxp3 and CD25 expression was detected in the B16F10 cells in culture and in the intratumoral B16F10 cells. An increase in Foxp3 and CD25 expression was observed in a time-dependent manner during tumor growth at 7, 14 and 21 days. The production of the IL-2, IL-10, IFN-gamma and TGF-beta cytokines was observed in the B16F10 cells and also detected in the tumoral microenvironment during tumor growth (7, 14 and 21 days). An increase in IL-2 and IL-10 production was observed, whereas IFN-gamma production decreased in a time-dependent manner. The production of tumor necrosis factor (TNF)-alpha was not observed in culture, but was detected during tumor growth, whereas the production of IL-4 and IL-5 was not detected. These data showed a positive correlation between the expression of Foxp3, CD25 and IL-2 and tumor weight in murine melanoma. From these data, it may be suggested that Foxp3 participates in melanoma growth, the modulation of the IL 2, IFN-gamma and TNF-alpha cytokines and CD25 expression, and that it also plays a possible role in immunosuppression. PMID- 24179495 TI - Notch signaling induces EMT in OSCC cell lines in a hypoxic environment. AB - Epithelial-mesenchymal transition (EMT) is an early step in the acquisition of invasiveness by malignant tumors. It has been clarified that the tumor microenvironment affects malignancy in a number of different carcinomas, in particular, that a hypoxic environment induces EMT. Activation of Notch signaling induces EMT, but it remains unclear how the Notch pathway is involved in oral squamous cell carcinoma (OSCC) under hypoxia. Three OSCC cell lines were cultured for examination under hypoxic (1% O2) and normoxic (21% O2) conditions. Expression of E-cadherin was investigated as a hallmark of EMT by immunohistochemical examination. Cell motility and invasion were examined by wound-healing and invasion assays, respectively. The expression of Notch pathway molecules was analyzed by qPCR. Hypoxia increased the mRNA expression of Notch receptors, ligands and target genes, and Snail. Hypoxia decreased the expression of E-cadherin, and increased the motility and invasiveness of OSCC cell lines. gamma-secretase inhibitor, a Notch-specific inhibitor, prevented these effects caused by h-ypoxia. These findings suggest that hypoxia induces EMT in OSCC cell lines via activation of Notch signaling, and inhibition of the Notch signaling pathway to suppress EMT may be a useful approach for the treatment of OSCC. PMID- 24179496 TI - Differences in EGFR and KRAS mutation spectra in lung adenocarcinoma of never and heavy smokers. AB - Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinomas of never smokers, while KRAS mutations are more frequent among heavy smokers. Different clinicopathological and biological characteristics may, therefore, exist in lung adenocarcinoma according to smoking status. In the present study, a retrospective review was performed using 521 patients with surgically resected lung adenocarcinomas. The clinicopathological factors of age, gender, pathological tumor size, nodal status, lymphatic permeation and blood vessel invasion and the EGFR and KRAS mutation spectra were compared between never and heavy smokers. EGFR mutations were detected in 233 (45%) patients, while KRAS mutations were detected in 56 (11%) patients. EGFR-mutated adenocarcinomas had a higher prevalence of females in the never smokers compared with the heavy smokers (P<0.001). KRAS-mutated adenocarcinomas had a higher prevalence of females (P<0.001) and showed less frequent vascular invasion (P=0.018) in the never smokers compared with the heavy smokers. Minor EGFR mutations, excluding exon 21 L858R and exon 19 deletions, were more common in heavy smokers than never smokers (P=0.055). KRAS G to A transition was more common in never smokers, while KRAS G to T and G to C transversions were more common in heavy smokers (P=0.036). The clinicopathological characteristics and the spectra of the EGFR and KRAS mutations in lung adenocarcinoma were different between the never and heavy smokers. Further large-scale studies are required to evaluate the efficacy of molecular targeting agents with consideration to specific EGFR and KRAS mutations. PMID- 24179497 TI - Prognostic factors in patients with hepatitis B virus-related hepatocellular carcinoma undergoing nucleoside analog antiviral therapy. AB - In the present era of entecavir (ETV) use for chronic hepatitis B (CHB), the prognostic factors in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. The aims of the present study were to investigate the prognostic factors in patients with HBV-related HCC treated with ETV who underwent curative therapy. A total of 74 HBV-related HCC patients treated with ETV who underwent curative therapy were analyzed. Predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) were examined using univariate and multivariate analysis. Our study population included 49 males and 25 females with a median age of 62 years. The median observation period was 3.4 years (range, 0.2-11.5 years). The 1-, 3- and 5-year cumulative OS rates were 100, 89.8 and 89.8%, respectively. The corresponding RFS rates were 82.8, 52.1 and 25.6%, respectively. In this study, 73 patients (98.6%) achieved an HBV DNA level of <400 copies/ml during the follow-up period. No viral breakthrough hepatitis, as defined by 1 log increase from nadir, was observed during ETV therapy. According to multivariate analysis, only hepatitis B e antigen (HBeAg) positivity was significantly associated with OS [hazard ratio (HR), 0.058; 95% confidence interval (CI), 0.005-0.645; P=0.020)], whereas HCC stage (HR, 0.359; 95% CI, 0.150-0.859; P=0.021), HBeAg positivity (HR, 0.202; 95% CI, 0.088-0.463; P<0.001) and gamma-glutamyl transpeptidase >=50 IU/l (HR, 0.340; 95% CI, 0.152 0.760; P=0.009) were significant predictive factors linked to RFS. In conclusion, HBeAg positivity was significantly associated with OS and RFS in HBV-related HCC patients treated with ETV who underwent curative therapy. In such patients, close observation is required, even after curative therapy for HCC. PMID- 24179498 TI - Endometrioid adenocarcinoma concurrent with a blue nevus of the endometrium and uterine cervix: A case report. AB - A blue nevus is a benign melanocytic lesion that is composed of spindle-shaped pigmented melanocytes. Although the uterine cervix is believed to be the most common extracutaneous location of blue nevi, the occurrence of these lesions in the endometrial stroma has been reported, albeit rarely. The present study describes a case of endometrioid adenocarcinoma concurrent with a blue nevus of the endometrium and uterine cervix. A 58-year-old female presented with abnormal vaginal bleeding. A biopsy from the endometrium revealed an endometrioid adenocarcinoma and subsequently, a total hysterectomy was performed. Histopathological study revealed the proliferation of columnar cells that formed irregularly-shaped tubular and cribriform glands. The neoplastic columnar cells had large, round to oval nuclei containing a single small nucleolus. Focal squamous differentiation was noted. In the stroma of the non-neoplastic endometrium, single or small aggregates of short spindle-shaped cells containing melanin without atypia were observed. These melanocytes were also present in the endocervix. Therefore, the final diagnosis was of endometrioid adenocarcinoma concurrent with a blue nevus of the endometrium and cervix. This is the first documented case of a blue nevus of the endometrium and endocervix. The pathogenesis of blue nevi of the genital tract is not yet completely understood. Possible origins of these cells include Schwann cells or perineural cells of the peripheral nerve fiber or the abnormal migration of neural crest-derived cells. PMID- 24179499 TI - Screening for novel protein targets of indomethacin in HCT116 human colon cancer cells using proteomics. AB - Non-steroidal anti-inflammatory drugs, such as indomethacin (IN), inhibit colorectal cancer (CRC) growth through cyclooxygenase (COX)-independent mechanisms, however, the precise biological mechanisms are not completely understood. The aim of the present study was to investigate new molecular factors potentially associated with IN in HCT116 human CRC cells, which do not express COX, using a proteomic approach. The total proteins from the IN-treated and untreated groups were separated by immobilized pH gradient-based two-dimensional gel electrophoresis. The differentially-expressed proteins were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time of flight mass spectrometry. The PMF maps were searched in the SWISS-PROT/TrEMBL database using the PeptIdent software. Between the IN-treated and untreated groups, a total of 45 differential protein spots were detected and 15 differentially-expressed proteins were identified by PMF. IN downregulated Wnt1-inducible signaling pathway protein 1, Bcl-2-related protein A1 and mitogen-activated protein kinase, inhibited HCT116 cell growth and induced apoptosis. In conclusion, IN may exert its effects on CRC to induce HCT116 cell apoptosis and suppress growth through COX-independent pathways. PMID- 24179500 TI - Effect of the new synthetic vitamin E derivative ETS-GS on radiation enterocolitis symptoms in a rat model. AB - Radiation enterocolitis is a severe adverse event that occurs after radiotherapy for malignant abdominal tumors. In this study, the therapeutic effects of ETS-GS, a novel vitamin E derivative with antioxidative and anti-inflammatory abilities, were examined in a rat model of radiation enterocolitis. The radiation enterocolitis model was created by irradiation of male rats with a single dose of 10 Gy. ETS-GS was administered subcutaneously (10 mg/kg/day) for five consecutive days from two days prior to irradiation. The animals were sacrificed three days after irradiation; following which, ileal tissue samples were analyzed for macroscopic and histological findings, presence of apoptosis, degree of oxidative stress and inflammation. In the irradiated group, severe erosion was observed in the small intestine in addition to necrosis of the mucosal layer, swelling and invasion of inflammatory cells of the submucosal layer, and shortening of the crypts. In irradiated rats that received ETS-GS, mucosal injury in the small intestine was milder compared with that of irradiated rats that received no ETS GS. In addition, ETS-GS decreased apoptosis in the small intestine and reduced the activity of myeloperoxidase and malondialdehyde, which are markers for inflammation and oxidative stress. ETS-GS with antioxidant activity has a therapeutic effect on the symptoms of radiation enterocolitis in a rat model. PMID- 24179501 TI - Effect of AKT inhibition on epithelial-mesenchymal transition and ZEB1 potentiated radiotherapy in nasopharyngeal carcinoma. AB - Radiotherapy is a major treatment regime for nasopharyngeal carcinoma (NPC), and although initial responses to a complete course of radiation are good, recurrence and metastasis are frequent events. A number of previous studies have observed that ionizing radiation (IR) may enhance the migratory and invasive properties of cancer cells through epithelial-mesenchymal transition (EMT). In the present study, a tumor cohort of 22 NPC and 7 normal cases (chronic inflammation only) were investigated and the expression of AKT was demonstrated to positively correlate with the expression of ZEB1. Following treatment with IR, 7/10 patients suffered recurrence and metastasis, in addition to high expression levels of phosphorylated AKT (S473) and ZEB1. The AKT inhibitor, GSK690693, inhibited AKT, blocked the expression of ZEB1 and vimentin and restored the expression of E cadherin following IR, thus preventing the migration and EMT of the tumor cells. In addition, the inhibition of AKT via GSK690693 was shown to markedly increase the sensitivity of tumor cells to IR in vitro and in vivo. These observations indicate that GSK690693 may aid in the prevention of recurrence and metastasis following IR therapy in NPC patients. PMID- 24179502 TI - Recurrence of a carcinoid tumor of the ovary 13 years after the primary surgery: A case report. AB - The current study presents the case of a patient with a recurrent carcinoid tumor of the ovary, 13-years after the primary surgery. The primary surgery consisted of a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a left ovarian tumor at 54 years old. Pathologically, the tumor was diagnosed as a carcinoid tumor of the ovary. Following the primary treatment, the patient was admitted to a cardiologist due to carcinoid-induced heart failure. At 67 years old, the patient was referred to Kyoto University Hospital with a solitary mass 8 cm in diameter and located in the paraaortic area, which was detected by routine ultrasonography and subsequent computed tomography (CT) scans. Urinary 5 hydroxyindole acetate (5-HIAA), a serotonin degradation metabolite, was present at elevated levels. With a diagnosis of a recurrent carcinoid tumor, the patient underwent a tumor resection. The pathological diagnosis was that of lymph node metastasis of the trabecular carcinoid. Post-operatively, the 5-HIAA levels returned to normal. Carcinoid tumors occasionally recur following surgery due to borderline malignant potential. Due to the slow growing nature of these tumors, in specific cases, recurrence occurs following a long interval. Therefore, a relatively long follow-up period is required. PMID- 24179503 TI - Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion-negative prostate cancer, but is unrelated to patient prognosis. AB - The cyclin-dependent kinase inhibitor p27Kip1 has been suggested as a prognostic marker in prostate cancer. The aim of this study was to determine the clinical and prognostic role of p27 expression in hormone-naive prostate cancers. A tissue microarray containing samples from 4,699 prostate cancers with attached pathological, clinical follow-up and molecular data was analyzed for nuclear p27 expression by immunohistochemistry. p27 staining was negative in 18.6%, weak in 33.5%, moderate in 28.4% and strong in 19.5% of 3,701 interpretable cancer spots. Loss of p27 immunostaining was linked to tumors of low Gleason grade (P<0.0001) and ERG fusion-negative cancers (P<0.0001). p27 levels were not associated with other parameters, including tumor stage, nodal stage, preoperative prostate specific antigen (PSA) levels, surgical margin status and cell proliferation (as measured by the Ki67 labeling index). p27 expression was also unrelated to clinical outcome in all cancers, as well as in the subsets of ERG fusion-positive and -negative cancers. Overall, the present data demonstrated that elevated p27 expression was often unrelated to prostate cancer phenotype. Furthermore, the lack of an effect of the p27 protein levels on PSA recurrence following radical prostatectomy indicated that factors other than p27 expression are likely to be the major determinants of prostate cancer recurrence. However, a subset of ERG negative, low-grade tumors was frequently characterized by loss of p27, suggesting a role of this alteration for the development of these tumors. PMID- 24179504 TI - Clinical significance of the induction of macrophage differentiation by the costimulatory molecule B7-H3 in human non-small cell lung cancer. AB - B7-H3, a member of the B7 family of molecules, is expressed in certain types of human cancer and is important in tumor development and progression. Although several studies have reported that the expression of B7-H3 is correlated with poor outcomes in patients with cancer, its exact role in cancer remains unknown. In the present study, the expression levels of B7-H3 in the pathological specimens of 105 patients treated for non-small cell lung cancer (NSCLC) were examined by immunohistochemistry. A high expression level of B7-H3 was observed in 46.9% of the 105 NSCLC tissue specimens. These patients demonstrated a more advanced tumor grade and a shorter survival time. In addition, we also examined the levels of tumor-associated macrophages (TAMs) in NSCLC tissues and observed that the levels were positively correlated with the expression of B7-H3, and that higher levels of macrophages were associated with lower levels of infiltrating T cells and a shorter survival time. These results demonstrated that TAMs are important in the evasion of tumor immune surveillance in NSCLC. Furthermore, through knockdown of B7-H3 by RNA interference, we observed that soluble B7-H3 was capable of inducing macrophages to express higher levels of macrophage mannose receptor (MMR) and lower levels of human leukocyte antigen (HLA)-DR, as well as higher levels of interleukin-10 (IL-10) and lower levels of IL-1beta in vitro. These observations are characteristic of an anti-inflammatory/reparatory (alternative/M2) phenotype. Therefore, our data suggests that B7-H3 proteins are involved in the progression of NSCLC by inducing the development of monocytes into anti-inflammatory cells. PMID- 24179505 TI - Occult pulmonary mucosa-associated lymphoid tissue lymphoma presenting as catastrophic antiphospholipid antibody syndrome. AB - Catastrophic antiphospholipid antibody syndrome (CAPS) is characterized by fulminant thrombosis of the arterial and venous beds of multiple organ systems over a relatively short period of time and with a high mortality rate. Mucosa associated lymphoid tissue (MALT) lymphoma of the lung has never been reported as a causative or precipitating factor for CAPS in the CAPS registry database. The present study describes a rare case of pulmonary MALT lymphoma of the lung that presented as CAPS. A 19-year-old Hispanic female presented with shortness of breath and abdominal pain. Computed tomography (CT) scans of the chest and abdomen revealed multiple portal vein thromboses and bilateral pulmonary nodules. Within one week of presentation, the patient developed a straight sinus thrombosis and upper extremity deep vein thrombosis, which led to shortness of breath. A biopsy of the lung nodule revealed MALT lymphoma. The present case illustrates a rarely reported pulmonary MALT lymphoma presenting as CAPS in a young female. The patient was successfully treated with 90 mg/m2 bendamustine on days one and two and rituximab 375 mg/m2 on day one of each 28-day cycle. Complete remission of the lung nodules was observed following three cycles of treatment, as visualized by positron emission tomography (PET)/CT scan. Fondaparinux was identified as a feasible anticoagulation drug of choice for this case. At seven months post-treatment, the patient continues to be stable with no further evidence of thrombosis and is currently undergoing rituximab maintenance therapy every six months for two years. A repeat lupus anticoagulant antibody assay turned and remained negative during the clinical follow-up period. A prompt diagnosis and early aggressive treatment is potentially curative and may dramatically decrease the mortality risk. Future studies should explore the role of rituximab in the management of CAPS-associated B-cell lymphoid malignancies. PMID- 24179506 TI - Predicting brain metastases of breast cancer based on serum S100B and serum HER2. AB - Brain metastases are a major cause of morbidity and mortality in breast cancer. The aim of the current study was to evaluate the prediction of brain metastases based on serum S100B and human epidermal growth factor receptor 2 (HER2). A total of 107 breast cancer patients were included in the current study from two prospective cohort studies with either elevated serum HER2 levels >15 ng/ml or brain metastases verified by magnetic resonance imaging (MRI) or computer tomography (CT). Following the exclusion of six patients, the remaining 101 patients were divided into two groups: Group 0 (n=55), patients with normal MRI results; and group 1 (n=46), patients with brain metastases. The levels of serum S100B and HER2 in the two groups were analyzed prior to MRI or CT of the brain, and no significant differences were identified in the serum HER2 (P=0.060) or S100B levels (P=0.623) between the groups. The univariate analysis of prognostic factors for brain metastases showed a significant correlation with systemic disease (P<0.001), axillary lymph node metastases (P=0.001) and serum HER2 >30 ng/ml (P=0.002). Only systemic disease (P<0.001) remained statistically significant in the multivariate analysis. In conclusion, serum levels of S100B and HER2 did not predict the risk of brain metastases. In the multivariate analysis, brain metastases were only found to correlate with systemic disease. However, in the univariate analysis, serum HER2 levels >30 ng/ml were identified to correlate with increased risk of brain metastases, which calls for further investigation. PMID- 24179507 TI - Correlation of CCL20 expression in rectal mucosa with the development of ulcerative colitis-associated neoplasia. AB - Chronic inflammation increases the risk of developing several gastrointestinal malignancies. Chemokines that are produced by colonic epithelial cells play significant roles in the maintenance and repair of the epithelial barrier. The present study aimed to clarify whether the expression of CCL20 and its receptor, CCR6, was correlated with the development of ulcerative colitis (UC)-associated neoplasia. A total of 93 patients with UC who underwent proctocolectomies were enrolled in the present study. Immunohistochemical analysis for CCL20 and CCR6 expression in the rectal mucosa was performed and the correlation between expression and the pathogenesis of UC-associated neoplasia was investigated. A total of 16 (17.2%) patients presented with UC-associated neoplasia. The immunohistochemistry (IHC) score for CCL20 was significantly increased in the patients with a mild form of the disease (P=0.0363). The IHC score for CCL20 expression in the patients with UC-associated neoplasia was higher compared with the patients without neoplasia (P=0.0294). In contrast, there was no significant correlation between CCR6 expression and the clinicopathological variables. The logistic regression analysis revealed that a high IHC score for CCL20 expression in the rectal mucosa and a disease duration of more than eight years were significantly correlated with the development of UC-associated neoplasia (P<0.05). The results suggest that an evaluation of CCL20 expression in the rectal mucosa may be useful to identify patients who are at a high risk for developing UC-associated neoplasia. However, a selection bias existed in the present study due to the fact that the patient population that was enrolled was not representative of a typical surveillance patient population. PMID- 24179509 TI - Desmoplastic (collagenous) fibroma of the femur: A case report and review of the literature. AB - Desmoplastic fibroma is a rare, benign soft-tissue tumor composed of spindled and stellate-shaped cells that are embedded in a dense collagenous stroma. Clinically, desmoplastic fibroma presents as a firm, mobile, slow-growing mass that is located in the subcutaneous tissue or near the deep aspect of the skeletal muscles. The present study describes the case of a 66-year-old female who presented with an inactive, firm, slightly tender mass in the lower medial segment of the right femur. An open biopsy was performed and the result of the pathological examination indicated a desmoplastic fibroma. The patient underwent a radical resection of the tumor and the accompanying bone, which was then reimplanted using devitalized tumor bone, self-ilium graft and homologous allograft bone transplantation, with an internal fixation by locking the compression plate. This was followed by a reconstruction of the anterior and posterior cruciate ligaments and the lateral and medial collateral ligaments. There was no evidence of local recurrence at five years post-surgery. PMID- 24179508 TI - Clinicopathological and prognostic significance of Ki-67, caspase-3 and p53 expression in gastric carcinomas. AB - The understanding of proliferative and apoptotic changes has aided the improvement of the diagnosis, treatment and prevention of gastric cancer. The present study aimed to investigate the clinicopathological and prognostic significance of Ki-67, caspase-3 and p53 in gastric cancer. The expression levels of Ki-67, caspase-3 and p53 were evaluated on tissue microarrays of gastric carcinomas specimens by immunohistochemistry and compared with the clinicopathological parameters and survival time of the patients. It was observed that the elder or male patients with gastric cancer showed p53 overexpression compared with the younger or female patients, respectively (P<0.05). The expression of Ki-67 and p53 was positively associated with tumor-node-metastasis (TNM) staging (P<0.05). There was higher caspase-3 and p53 expression in the intestinal-type compared with the diffuse-type of carcinomas (P<0.05). There was a positive correlation among Ki-67, caspase-3 and p53 expression in gastric cancer (P<0.05). A Kaplan-Meier analysis indicated that there was positive correlation between caspase-3 expression and the adverse prognosis of the patients (P>0.05). Cox's proportional hazards model indicated that the patient age, gender, depth of invasion, lymphatic invasion, lymph node metastasis, TNM staging, Lauren's classification and caspase-3 expression were independent prognostic factors for gastric carcinomas (P<0.05). The data indicated that the expression of Ki-67, caspase-3 and p53 may be involved in the progression or differentiation of gastric carcinoma. This expression may be employed as an indicator of the pathobiological behavior and prognosis of gastric carcinomas. PMID- 24179510 TI - CD133 and Ki-67 expression is associated with gastrointestinal stromal tumor prognosis. AB - CD133+ tumor cells have a greater potential ability for tumorigenesis, proliferation, invasion and metastasis compared with CD133- tumor cells. Ki-67 is associated with cell proliferation in various tumors and has a markedly positive correlation with the prognosis of patients. However, there are a limited number of studies that have investigated the association between the prognosis of gastrointestinal stromal tumors (GISTs) and the two markers. The present study aimed to investigate CD133 and Ki-67 expression in GISTs and to explore their clinicopathological significance in the prognosis of patients with GISTs. A total of 111 GIST patients from the Chinese People's Liberation Army (PLA) General Hospital were retrospectively followed up and immunohistochemistry was used to detect CD133, Ki-67 and CD117 expression in the tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. The log-rank test, chi2 test and Cox's proportional hazards model were used to determine the association between CD133, Ki-67, CD117 expression and the prognosis of GIST. The 1-, 3- and 5-year survival rates were 93.0, 89.0 and 82.0%, respectively, in all the patients. However, in the patients with CD133+ or Ki-67+, the 1-, 3- and 5 year survival rates were 81.0, 61.5 and 50.0% and 83.0, 66.6 and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were statistically lower (CD133 log-rank, P=0.028; Ki-67 log rank, P=0.002). The multivariate Cox analysis revealed that CD133 and Ki-67 expression were considerable factors in the prognosis of GIST patients (CD117, P=0.495; CD133, P=0.036; Ki-67, P=0.003). In conclusion, the positive expression of CD133 and Ki-67 was associated with a poor prognosis of GIST. PMID- 24179511 TI - A2780 human ovarian cancer cells with acquired paclitaxel resistance display cancer stem cell properties. AB - The use of chemotherapy to treat cancer is effective, but chemoresistance reduces this efficacy. Chemotherapy resistance involves several mechanisms, including the cancer stem cell (CSC) concept. The aim of the present study was to assess whether paclitaxel-resistant epithelial ovarian carcinoma is capable of generating cells with CSC-like properties. Using the paclitaxel-resistant A2780/PTX cell line, it was demonstrated that high aldehyde dehydrogenase 1 (ALDH1) activity identifies CSCs from diverse sources. Furthermore, the A2780/PTX cells had a strong ability to form colonies in soft agar assays. Notably, it was demonstrated that the inhibition of the PI3K signaling pathway abolished colony formation. These data suggest that there is a link between paclitaxel resistance and CSC enrichment. It is possible that therapeutic benefits, such as the restoration of chemosensitivity or the suppression of tumorigenicity, may be enabled by gaining further insights into the mechanisms underlying chemoresistance and the generation of CSCs. PMID- 24179512 TI - Synchronous osteoclastoma and anaplastic astrocytoma: A case report. AB - Multiple primary neoplasms are defined as multiple occurrences of malignant neoplasms of differing histological origin in the same individual. The present study describes the case of a 46-year-old male who suffered from two synchronous primary malignant neoplasms, an osteoclastoma of the left femoral trochanter and an anaplastic astrocytoma of the the Sylvian fissure area in the brain. At the 6 month follow-up, the patient presented no problems following the aggressive treatment, including surgical resection, radiation therapy and chemotherapy. To the best of our knowledge, this is the first study in the medical literature of such a presentation. PMID- 24179513 TI - A novel subtype of primary prostatic adenocarcinoma: A case report. AB - The present study reports the novel case of an 81-year-old male with prostatic adenocarcinoma (PAC), whose histopathological study revealed a pure urothelial carcinoma (UC) that originated, however, from the prostatic glandular epithelium. The levels of serum prostate-specific antigen (PSA) were extraordinarily high in this patient. An MRI scan indicated a prostatic neoplasm and no malignant changes were observed in the bladder or other areas of the urinary tract. Hematoxylin and eosin-stained sections revealed a diagnosis of pure UC with no other form of differentiation (typical adenocarcinoma or squamous differentiation). The immunohistochemical findings were positive for PSA and P504S, and negative for CK7, CK20, 34betaE12 and p63. A diagnosis of primary PAC (solid carcinoma) originating from the prostate was made based on the clinical, histopathological and immunohistochemical observations. This case was susceptible to diagnostic errors, however, a novel subtype of primary PAC was identified and termed the UC like subtype. PMID- 24179514 TI - Intestinal NF-E2-related factor-2 expression and antioxidant activity changes in rats undergoing orthotopic liver autotransplantation. AB - Liver transplantation is known to trigger intestinal injuries. Oxidative damage that is induced by reactive oxygen species (ROS) plays a crucial role in ischemia reperfusion injuries. NF-E2-related factor-2 (Nrf2) and its modulated antioxidant enzymes form the critical endogenous antioxidant system to scavenge ROS. The present study investigated the dynamic changes of intestinal ROS levels, Nrf2 expression and antioxidant enzyme activity following orthotopic liver autotransplantation (OLAT). Sprague-Dawley rats were randomly divided into five groups consisting of one sham group and four groups with rats that underwent OLAT and were evaluated following 4, 8, 16 and 24 h, respectively. The intestinal specimens were collected for histopathological examination and the detection of hydrogen peroxide (H2O2), hydroxyl radical (*OH), malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels and the expression of Nrf2. The present study demonstrated that OLAT resulted in severe intestinal injury, which manifested as a significant change in the intestine pathological scores as early as 4 h and peaking at 8 h post-treatment. Oxidative stress was also revealed by the increase of the H2O2, *OH and MDA levels. Significant decreases were observed in the activity of SOD and CAT and a dramatic decrease occurred in the levels of GSH at 4 and 8 h post-treatment. All the parameters were restored gradually at 16 and 24 h post-treatment. The expression of Nrf2 in the intestinal tissues increased significantly at 4, 16 and 24 h following OLAT. The present study shows that an imbalance between oxidants and antioxidants contributes to intestinal oxidative injury, and that the upregulation of Nrf2 is not sufficient to withstand intestinal oxidative injury following OLAT. PMID- 24179515 TI - Nucleostemin and ASPP2 expression is correlated with pituitary adenoma proliferation. AB - Nucleostemin is a GTP-conjugated protein located in the nucleoli of stem cells and certain cancer cells, and maintains cellular self-renewal. The present study aimed to evaluate nucleostemin as a potential target for pituitary adenoma gene therapy by investigating nucleostemin and apoptosis-stimulating of p53 protein 2 (ASPP2) expression and their effect on pituitary adenoma cell proliferation. A total of 71 samples of pituitary adenomas were collected. Semi-quantitative PCR was used to detect the expression of nucleostemin and ASPP2 mRNA in the samples. Immunochemistry techniques were used to examine Ki-67 expression in the paraffin section of the samples. Coherent clinical data were also collected. Nucleostemin and ASPP2 were detectable in all the pituitary adenoma samples. Significant differences were observed in nucleostemin and ASPP2 expression between invasive pituitary adenoma and non-invasive pituitary adenomas (P<0.01) and the Ki-67 labeling index (LI; P>0.05). The difference in the Ki-67 LI between the recurrence and non-recurrence groups was significant (P<0.05). There was positive correlation between nucleostemin gene expression and the Ki-67 LI levels (P<0.05). The correlation between ASPP2 expression and the Ki-67 LI was negative (P<0.05). Negative correlation was demonstrated between nucleostemin and ASPP2 expression (P<0.01). The nucleostemin and ASPP2 genes were expressed in the human pituitary adenoma tissues. The differences in the expression of nucleostemin, ASPP2 and Ki-67 in the various pathological types of pituitary adenomas represented differences in molecular biological character and were associated with invasion. In the pituitary adenomas, the expression of nucleostemin and ASPP2 was correlated with tumor proliferation. Nucleostemin, ASPP2 and Ki-67 may serve as valid clinical detection markers for the invasion of pituitary adenomas. PMID- 24179516 TI - Leukemia cutis in a patient with acute monocytic leukemia diagnosed simultaneously with hepatocellular carcinoma: A case study. AB - Acute myeloid leukemia presenting as leukemia cutis (LC) with hepatocellular carcinoma is extremely rare. The current study presents a case of a 53-year-old male with generalized cutaneous nodules on the face and anterior chest wall. Laboratory tests, including bone marrow biopsy revealed acute myelomonocytic leukemia (AML-M4) with skin and tonsilar involvement. Liver magnetic resonance imaging (MRI) revealed a 6-cm mass in hepatic segments 4 and 8, and a liver biopsy demonstrated that hepatocellular carcinoma cells and immature blast cells coexisted. Although LC has been reported in Korea, a case of LC associated with acute myelomonocytic leukemia was diagnosed simultaneously with hepatocellular carcinoma and tonsillar involvement. The present study describes this case with a review of the literature. PMID- 24179517 TI - Prosapogenin A induces apoptosis in human cancer cells in vitro via inhibition of the STAT3 signaling pathway and glycolysis. AB - Signal transducer and activator of transcription 3 (STAT3) is considered to be an oncogene. Blocking STAT3 signaling may induce growth arrest and apoptosis in different types of tumors. Cancer cells utilize the glycolytic pathway to maintain cell growth even when adequate oxygen is present. Glycolysis inhibition is a potential therapeutic modality. In the present study, the effects of Prosapogenin A (PSA) from the traditional Chinese medicine, Veratrum, on apoptosis, the STAT3 signaling pathway and glycometabolism in cancer cells were investigated. The results indicated that PSA induced growth inhibition and apoptosis in HeLa, HepG2 and MCF-7 cells. PSA inhibited the STAT3 signaling pathway and modulated the expression of glycometabolism-related genes. The results indicate that the inhibition of the STAT3 signaling and glycometabolism pathways contributes to the PSA-mediated apoptosis of HeLa, HepG2 and MCF-7 cells. PMID- 24179518 TI - Intracranial choriocarcinoma occurrence in males: Two cases and a review of the literature. AB - Choriocarcinomas generally develop in females. Non-gestational choriocarcinoma in males is extremely rare. The present study describes two cases of young males who were diagnosed with intracranial choriocarcinoma. One case was of an aggressive choriocarcinoma with multiple metastases to the brain, but with an unidentified origin. The patient was admitted in the terminal stage of the cancer. Although a tumor resection was performed, the condition of the patient rapidly deteriorated and chemotherapy was not recommended. The patient succumbed nine days after the surgery. The second case was of a primary ventricular choriocarcinoma. The patient was hospitalized for acute hydrocephalus caused by a mass that was located in the ventricle. Following a tumor resection, the patient underwent a course of whole-brain and spinal radiotherapy. The patient was followed up for more than half a year and remained in a good condition. The present study describes the two cases and a comprehensive review of the literature that was performed to identify similar studies that document choriocarcinomas in males. PMID- 24179519 TI - Overexpression of MEKK2 is associated with colorectal carcinogenesis. AB - Mitogen-activated protein kinase kinase kinase 2 (MEKK2) is an important upstream mediator of the extracellular signal-regulated kinase 5 signaling cascade that is essential for a number of cellular functions, including mitogenesis, differentiation and oncogenic transformation. Using western blotting to examine MEKK2 expression in 16 cases of primary colorectal cancer (CRC) lesions with paired normal mucosa, it was identified that MEKK2 is highly expressed in CRC lesions compared with that of the normal mucosa. Immunohistochemistry of 24 normal mucosa, 24 adenoma and 96 adenocarcinoma colorectal specimens indicated that the expression of MEKK2 was significantly increased in the adenoma and carcinoma specimens compared with that of the normal mucosa cases (P<0.0001 for both). However, no significant differences were detected in MEKK2 expression between the carcinoma and adenoma specimens (P=0.85). Similarly, no correlations were identified between MEKK2 expression and clinicopathological features, including gender, age, body mass index, histological differentiation, depth of invasion, lymph node metastasis, UICC stage and K-ras mutations (P>0.05). The present study demonstrated that MEKK2 functions as a promotive factor in CRC. PMID- 24179520 TI - Suppression of metastasis of human pancreatic cancer cells to the liver by small interfering RNA-mediated targeting of the midkine gene. AB - The present study aimed to ascertain whether suppression of midkine (MK) expression in pancreatic cancer cells inhibits metastasis to the liver. Human pancreatic cancer AsPC-1 cells were transfected with small interfering RNA (siRNA) targeting MK. siRNA against MK was observed to reduce the expression of MK mRNA and protein in a concentration- and time-dependent manner, and to decrease the number of migrating and tissue-penetrating cells in a concentration dependent manner (P<0.005). Extracellular vascular endothelial growth factor (VEGF) concentrations were markedly reduced for the siRNA-transfected cells compared with those that were non-siRNA-transfected. The liver transmission rate and tumor nodule number in the animals harboring the siRNA-transfected cells were lower compared with those in the animals harboring the non-siRNA-transfected cells (P<0.005). These data indicate that metastasis of pancreatic cancer cells to the liver requires the expression of MK. The downregulation of VEGF expression is essential to the mechanism whereby suppression of MK expression constrains the metastasis of pancreatic cancer cells to the liver. PMID- 24179521 TI - KRAS mutational status analysis of peripheral blood isolated circulating tumor cells in metastatic colorectal patients. AB - The present study describes an optimized method for isolating peripheral blood circulating tumor cells (CTCs) and performing KRAS mutation analysis. The approach combines isolation of peripheral blood mononuclear cells and immunomagnetic labeling with CD45 and CD326 human microbeads with KRAS analysis performed with a Therascreen KRAS kit by quantitative PCR. KRAS mutations were detected in the CTCs of patients with metastatic colorectal cancer (mCRC). CTCs may represent an alternative to invasive procedures and their analysis may be representative of the current disease status of the patient. This proposed analysis may be performed in a daily clinical practice. PMID- 24179522 TI - Pro-apoptotic and migration-suppressing potential of EGCG, and the involvement of AMPK in the p53-mediated modulation of VEGF and MMP-9 expression. AB - The present study investigated the regulatory mechanisms by which epigallocatechin-3-gallate (EGCG) exerts vascular endothelial growth factor (VEGF)-, p53- and AMP-activated protein kinase (AMPK)-associated pro-apoptotic and migration-suppressing effects on colon cancer cells. EGCG decreased the expression levels of VEGF and matrix metalloproteinase (MMP)-9. EGCG treatment induced apoptosis in the presence of wild-type and mutant p53, indicating that a p53-independent pathway may contribute to EGCG-induced apoptosis in these cells. EGCG showed migration-suppressing effects, suggesting that this activity may also have p53-dependent and -independent components. The interaction between p53 and VEGF in the EGCG-treated cells was investigated using pifithrin-alpha. Notably, the suppression of p53 activity blocked the ability of EGCG to inhibit VEGF and MMP-9 in the cells expressing wild-type p53, but not mutant p53, indicating that the effects of EGCG on VEGF may be p53-dependent or -independent. Finally, although AMPK and VEGF did not appear to co-localize, the results indicated that AMPK controls VEGF in EGCG-treated cells regardless of the p53 status. PMID- 24179523 TI - Inhibition of delta-opioid receptors induces brain glioma cell apoptosis through the mitochondrial and protein kinase C pathways. AB - Brain glioma is a malignant tumor with a high incidence rate and poor prognosis that has become a focus of studies of central nervous system diseases. Previous studies have suggested that delta-opioid receptors may affect the proliferation and apoptosis of numerous types of tumor cells. However, to date, their precise mechanism(s) of action have not been elucidated. The present study aimed to investigate the effects of inhibiting delta-opioid receptors in brain glioma cell proliferation and apoptosis and their relevant molecular mechanisms. Various doses of naltrindole were supplied to treat brain glioma cells using the MTT method to assess the proliferation index. Flow cytometry was used to investigate the changes in cell apoptosis and mitochondrial membrane potential. The expression levels of Bax, Bcl-2, Bcl-xL, cytochrome c, caspase-9, caspase-3 and protein kinase C (PKC) were measured using western blotting. Naltrindole was observed to inhibit brain glioma cell proliferation and promote apoptosis in a dose- and time-dependent manner. Furthermore, the addition of naltrindole lead to changes in the brain glioma cell membrane potential and regulated Bax translocation to the mitochondrial membrane, consequently promoting the release of cytochrome c into the cytoplasm, followed by the activation of caspase-9 and 3, which caused cell apoptosis. In addition, naltrindole was able to regulate the expression levels of the cellular internal phosphorylated PKC proteins, which are closely associated with the inhibition of cell proliferation. In conclusion, the inhibition of delta-opioid receptors may inhibit brain glioma cell proliferation and lead to apoptosis, which is closely associated with the mitochondrial and PKC pathways. PMID- 24179524 TI - Efficacy of krypton laser photodynamic therapy for oral mucosa dysplasia in 9,10 dimethyl-1,2-benzanthracene-treated hamsters. AB - The present study aimed to evaluate the efficacy of krypton laser photodynamic therapy (PDT) with PsD-007 for the treatment of oral mucosa dysplasia in 9,10 dimethyl-1,2-benzanthracene (DMBA)-treated hamsters. A DMBA-induced hamster cheek pouch model of precancerous lesions was created and the resultant 25 hamsters were divided into five groups. The right side was treated with PDT and the left side was used as the positive control. Following systemic anesthesia, an incision was made in the groin area to expose the femoral vein. PsD-007 was administered intravenously through the femoral vein. Various doses of photosensitizer were used to treat groups A-E. Subsequent to closing the incision, the right side of the buccal mucosa was irradiated with light using the krypton laser at a wavelength of 413 nm, a power density of 150 mW/cm2 and an irradiation time of 20 min. At six weeks post-surgery, the response was analyzed using histological examinations of the buccal pouch mucosa. A total of 24 hamsters completed the six week observation period, as one hamster from group C died in the second week following the PDT. Of all 24 irradiated sides, 15 formed normal mucosal tissues and nine demonstrated mild dysplasia. Of the total control sides, six developed moderate dysplasia, five developed severe dysplasia and 13 progressed to carcinoma in situ or squamous cell carcinoma (SCC). The results revealed a significant difference between the two sides (P<0.01) and the various doses of the PsD-007 groups. When the PsD-007 dose was >10 mg/kg, there was no statistical difference (P>0.05). PsD-007-mediated krypton laser PDT is effective for the treatment of oral mucosa dysplasia in hamsters. PMID- 24179525 TI - UNC5H4-induced apoptosis in non-small cell lung cancer is not dependent on p53 status only. AB - The aim of the present study was to investigate the expression profile and prognostic significance of uncoordinated 5 homolog 4 (UNC5H4) in patients with lung cancer and to evaluate whether UNC5H4 expression may serve as an index for radiosensitivity. UNC5H4 and p53 expression levels were detected by immunohistochemistry, apoptosis was determined by a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and caspase 3 activation was determined by western blotting. The results showed that UNC5H4 expression was largely located in the membrane of the normal bronchial epithelium, but absent in the membranous regions or ectopic cytoplasm of 80/130 (61.5%) non-small cell lung cancer (NSCLC) tissue samples. Abnormal UNC5H4 expression was demonstrated to correlate with the degree of differentiation (P=0.015), TNM staging (P=0.037). Cytoplasmic UNC5H4 expression was shown to correlate negatively with p53 mutant type (mt) expression (r=-0.270; P=0.002) and positively with the apoptotic index (r=0.254; P=0.004). The statistical analyses indicated that the prognosis of patients with normal UNC5H4 expression was improved compared with that of patients with abnormal UNC5H4 expression, however, no significant difference was identified (P=0.125). Exposure of NSCLC tissue samples to X-radiation increased UNC5H4 expression and caspase 3 activity significantly, irrespective of p53 mutation status. In conclusion, these results indicate that X-rays induce apoptosis via the p53 pathway, and when this pathway is compromised, an additional pathway is utilized. PMID- 24179527 TI - Gastric cancer with large bowel obstruction as the first presentation: A case report. AB - Gastric adenocarcinoma with a large bowel obstruction as the first presentation of the condition is rare. The present study describes the case of a 59-year-old female who was diagnosed with a large bowel obstruction that was caused by gastric adenocarcinoma. The patient suffered from abdominal pain and had not defecated for 15 days. The patient had no significant medical history. The right epigastric region was slightly tender and active bowel sounds were identified. A computed tomography (CT) scan revealed a dilated fluid-filled colon with a thickened wall and adjacent fat infiltration. An upper gastrointestinal endoscopy revealed that the margin and gastric mucosa in the antrum were raised and thickened without evidence of ulcerative lesions. The patient underwent surgery and was administered adjuvant chemotherapy. The patient was followed-up for 18 months without recurrence of the tumor. This study demonstrates that the presentation of gastric cancer may vary. PMID- 24179526 TI - Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients. AB - CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 (MLH1) and DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized kappa-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (kappa=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation. PMID- 24179528 TI - Lipomatous hemangiopericytoma (adipocytic variant of solitary fibrous tumor) of the parotid gland: A case report and review of the literature. AB - The current study presents the first case of a lipomatous hemangiopericytoma (LHPC) developing in the parotid gland in a 33-year-old male. The patient presented with a 4-year history of a progressively growing painless and fixed mass in the left paratid gland region. The patient underwent radical parotidectomy and was followed-up for 12 months without any evidence of metastasis or recurrence. LHPC, a controversial rare HPC variant, is histologically characterized by a varying admixture of hemangiopericytomatous vasculature and the presence of mature adipocytes. To date, 51 cases of LHPC have been documented in the literature. Although the boundary between HPC and solitary fibrous tumors (SFTs) has become increasingly blurred, neither of these variant growth patterns has previously been recognized in the parotid gland. PMID- 24179529 TI - Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines. AB - The actin cytoskeleton is important in the maintenance of cellular homeostasis and in signal transduction pathways leading to cell growth and apoptotic cell death in eukaryotic cells. Disruption of actin dynamics is associated with morphological changes in cancer cells. Deletion of phosphatase and tensin homolog (PTEN), a tumor suppressor gene involved in the regulation of the cell cycle and apoptosis, leads to cytoskeleton disruption and double-strand breaks (DSBs). To study the mechanism(s) of actin disruption-mediated apoptosis and its potential application for anticancer therapy, PTEN-null PC3M prostate cancer cells were treated with latrunculin B (LB). LB induced destabilization of the actin microfilament and apoptosis in a dose-dependent manner, as demonstrated by morphological changes and nuclear condensation in the PC3M cells. In addition, it resulted in an increase in the levels of gammaH2AX recruitment, implicating the induction of DNA damage, including DSBs. Induction of Bax, with little effect on Bcl-2 expression, indicated that actin disruption causes apoptosis through activation of Bax signaling in PC3M cells. Treatment with U20126, a mitogen activated protein kinase kinase (MEK) inhibitor, resulted in attenuated induction of DSBs and apoptosis through activation of protein kinase B (Akt), suggesting that LB-mediated actin dysfunction induces DSBs via the MEK/extracellular signal regulated kinase (Erk) pathway in cells. Therefore, counteracting activation of phosphorylated Akt stemming from the inhibition of MEK/Erk resulted in attenuation of actin disruption-induced apoptotic events in the PC3M cells. The results of this study provide information not only for use in delineation of the molecular association between actin disruption and tumorigenesis, but also for the development of a strategy for actin-based anticancer chemotherapy against highly metastatic prostate cancer. PMID- 24179530 TI - Role of podocalyxin in astrocytoma: Clinicopathological and in vitro evidence. AB - The present study examined the expression of podocalyxin (PODX) in surgically resected astrocytomas, associated the levels of PODX expression with the clinicopathological characteristics and survival outcomes of astrocytoma and assessed how PODX affected the viability of astrocytoma cells following the administration of chemotherapeutic agents. The immunohistochemical analysis of 102 patient samples revealed that a high expression of PODX was significantly associated with high-grade astrocytomas (P<0.001) and a high Ki-67 labeling index (LI; P<0.001). A Kaplan-Meier survival analysis demonstrated that the high PODX expression group had significantly shorter disease-free survival (DFS) and overall survival (OS) rates compared with the low expression group (P<0.001). The multivariate analysis using the Cox's proportional hazards model revealed that a high expression of PODX, a high World Health Organization grade and a high Ki-67 LI were independent factors for shorter DFS and OS times. A subsequent in vitro study using SW1783 and U-87 human astrocytoma cell lines revealed that knocking down PODX decreased astrocytoma cell viability against temozolomide-induced apoptotic stress through the inhibition of the Akt survival signaling pathway. In conclusion, the in vivo findings indicated that a high expression of PODX is predictive of a poor survival outcome and, thus, may be used as a prognostic factor to predict the survival outcomes of astrocytoma patients. The in vitro findings indicated that PODX may promote astrocytoma cell viability against chemotherapeutic agent-induced apoptotic stress through the Akt pathway, indicating that PODX may be a novel target for overcoming chemoresistance in astrocytomas. PMID- 24179531 TI - Extraventricular neurocytoma in pediatric populations: A case report and review of the literature. AB - Extraventricular neurocytomas (EVNs) are rare neuronal tumors included in the definition of neoplasms in the 2007 World Health Organization classification of tumors of the central nervous system. Although a small case series of EVNs in adults has been previously reported, EVNs in pediatric populations are extremely rare. The current case report presents the clinicopathological features of an EVN in a 2-year-old female who presented with nausea and vomiting that had lasted for five days. In addition, an analysis of the imaging features, histology, treatment and prognosis of these reported rare lesions is presented. Immunohistochemically, EVNs are characterized by the robust expression of synaptophysin, but with a lack of oligodendrocyte transcription factor 2, isocitrate dehydrogenase enzyme isoform 1 (IDH1) R132/IDH2 R172 mutations and p53 immunoexpression. The treatment for EVNs in pediatric and adult populations is gross total resection, with post operative radiation reserved for subtotal resection or recurrent disease. In addition, drop metastasis must be carefully avoided. PMID- 24179532 TI - Solitary infantile myofibromatosis in the bones of the upper extremities: Two rare cases and a review of the literature. AB - Infantile myofibromatosis (IM) is the most common fibrous tumor of infancy. IM may arise in a solitary or multicentric form, with similar histopathological findings, however, the clinical features and prognoses may vary. The solitary form tends to occur predominantly in males and is typically observed in the dermis, subcutis or deep soft tissues. The reported incidence of solitary osseous myofibromatosis is rare. Furthermore, the majority of solitary IM cases of the bone occur in the craniofacial bones, while the occurrence of solitary osseous myofibromatosis on the extremities has been sporadically reported. The present study describes two cases of solitary IM involving the bones of the upper extremities in females who were over two years old. The cases show unusual symptom presentation and the tumor origin is in a rarely observed location. The study discusses the clinical, radiological and pathological features, in addition to the previously described etiology, prognosis and treatment options for this condition. PMID- 24179533 TI - Childhood bronchial mucoepidermoid tumors: A case report and literature review. AB - Primary pulmonary neoplasms rarely occur in children, but the majority of those that do are malignant. Mucoepidermoid carcinoma (MEC) represents ~10% of all primary pulmonary malignant tumors. However, MEC is not usually considered in the clinical differential diagnosis in pediatric practice. The present study presents the case of a seven-year-old female with a one-year history of recurrent hemoptysis. Computerized tomography (CT) scans revealed a tumor originating in the right lower lobe bronchus. The patient did not receive any radiation and chemotherapy following a lobectomy on the right lower lung. The tumor was histopathologically determined to be an MEC of the tracheobronchial tree. Subsequent to a six-year follow-up, the MEC was undetectable in this patient, according to the clinical and radiological evidence. The literature with regard to pediatric MEC is also reviewed in this study. PMID- 24179534 TI - Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study. AB - Microsatellite instability (MSI) is a mutator phenotype that results from a defective mismatch repair (MMR) pathway. The present study examined the incidence of MSI and loss of heterozygosity (LOH) according to five markers from the panel of the National Cancer Institute (NCI) in 38 colorectal cancer (CRC) patients from the United Arab Emirates (UAE). MSI and LOH were analyzed using fragment analyses in a multiplex PCR setting on a capillary array electrophoresis platform. The expression of the MMR proteins, hMLH1 and hMSH2, was analyzed using immunohistochemistry. The cohort consisted of 17 females (44.7%) and 21 males (55.3%) with mean ages of 59.9 and 63.3 years, respectively. The overall MSI incidence was 31.3% (95% CI, 16.1-50.0), and included three patients with high MSI (MSI-H; 9.4%; 95% CI, 2.0-25.0) and seven patients with low MSI (MSI-L; 21.9%; 95% CI, 10.7-39). LOH was detected in three patients, while the remaining 25 patients (65.8%) showed no instability and were therefore classified as microsatellite stable (MSS). MSI was detected in the following screened markers: Bat25 in seven patients, Bat26 in three patients, adenomatous polyposis coli (APC; D5S346) in five patients, AFM093xh3 (D2S123) in two patients and Mfd15 (D17S250) in three patients. Of the five MSI-positive patients, four (80%) were evidently younger, aged 38, 48, 49 and 59 years, respectively. The MSI-H incidence (9.4%) was lower compared with that of other ethnic groups. In terms of the MMR proteins, hMLH1 expression was deficient in seven patients, of whom three were MSI-H patients, and hMSH2 was deficient in three patients. Fisher's exact test showed significant associations between hMLH1 and MSI when classified as MSS, MSI-L or MSI-H (P=0.0003). No such association was observed with abnormal MMR protein expression, age, cancer stage or gender. PMID- 24179535 TI - Expression of peptidyl-prolyl isomerase PIN1 and its role in the pathogenesis of extrahepatic cholangiocarcinoma. AB - The phosphorylation of proteins on serine/threonine residues that immediately precede proline (pSer/Thr-Pro) is a key signaling mechanism by which cell cycle regulation and cell differentiation and proliferation occur. The peptidyl-prolyl isomerase PIN1-catalyzed conformational changes of the pSer/Thr-Pro motifs may have profound effects on the function of numerous oncogenic and cell signaling pathways. To date, no studies have examined the expression of PIN1 and its potential role in the pathogenesis of extrahepatic cholangiocarcinoma (ECC). Therefore, the present study performed an immunohistochemistry analysis of the expression of PIN1 in 67 cases of ECC and evaluated its association with clinicopathological factors. In addition, the role of PIN1 was examined using synthetic small interfering RNA (siRNA) to silence PIN1 gene expression in human CC RBE cells. Positive PIN1 expression was observed in 35 of the 67 (52.2%) ECC cases and was predominantly localized to the nucleus of the tumor cells. The immunoreactive score for PIN1 was significantly higher in the tumor cells (4.07+/ 0.4) compared with the adjacent benign bile duct cells (1.19+/-0.4) (P<0.001). PIN1 expression was significantly correlated with tumor cell proliferation (Ki-67 labeling index; P=0.024). Silencing PIN1 expression using siRNA significantly decreased the proliferation, migration and invasion of the tumor cells. In conclusion, the results indicated that the expression of PIN1 may play a key role in the development and progression of ECC. PMID- 24179536 TI - MicroRNA-373 is upregulated and targets TNFAIP1 in human gastric cancer, contributing to tumorigenesis. AB - The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Previous studies have shown that miRNA-372 plays crucial roles in gastric tumorigenesis by targeting the mRNA of tumor necrosis factor, alpha-induced protein 1 (TNFAIP1). The present study showed that miR-373 is upregulated in gastric adenocarcinoma tissue and gastric carcinoma cell lines when compared to normal gastric tissues. The overexpression of miR-373 in the gastric cancer cells increased cell proliferation. A bioinformatics search revealed a conserved target site within the 3' untranslated region (UTR) of TNFAIP1, an immediate-early response gene of the endothelium induced by TNF alpha. The overexpression of miR-373 caused the suppression of a luciferase reporter containing the TNFAIP1 3'UTR in the HEK293 cells and reduced the levels of TNFAIP1 protein in the AGS cells. The mRNA levels of TNFAIP1 in the gastric cancer and normal gastric tissues were negatively correlated with the expression levels of miR-373 in these tissues. Moreover, the knockdown of TNFAIP1 had a similar effect to the overexpression of miR-373. The overexpression of TNFAIP1 may partly rescue the inhibition of proliferation caused by the inhibitor, miR 373-ASO. Taken together, these findings demonstrate an oncogenic role for miR 373, similar to that of miR-372, in controlling cell growth through the downregulation of TNFAIP1. PMID- 24179537 TI - Honokiol-induced apoptosis and autophagy in glioblastoma multiforme cells. AB - Honokiol, a hydroxylated biphenyl compound isolated from the Chinese herb Magnolia officinalis, has been reported to have anticancer activities in a variety of cancer cell lines. The present study aimed to evaluate the anticancer effect and possible molecular mechanisms of honokiol in a glioblastoma multiforme (GBM) cell line. The anticancer activities of honokiol were investigated in the DBTRG-05MG GBM cell line. The effect of honokiol on cell growth was determined using a sulforhodamine B assay. Flow cytometry and immunoblotting were used to measure honokiol-induced apoptosis (programmed cell death type I) and autophagy (programmed cell death type II). Honokiol was observed to reduce DBTRG-05MG cell viability in a dose-dependent manner. At a dose of 50 MUM, honokiol markedly decreased the expression of Rb protein and led to the cleavage of poly(ADP ribose) polymerase and Bcl-xL to promote apoptosis in the cancer cells. In addition, markers of autophagy, including Beclin-1 and LC3-II, were also significantly increased. In addition to apoptosis, honokiol was also able to induce autophagy in the DBTRG-05MG cells. The mechanisms that are responsible for the correlation between honokiol-induced apoptosis and autophagy require further investigation. Such efforts may provide a potential strategy for improving the clinical outcome of GBM treatment. PMID- 24179538 TI - CD24 induces the invasion of cholangiocarcinoma cells by upregulating CXCR4 and increasing the phosphorylation of ERK1/2. AB - Cholangiocarcinoma is a malignant biliary tract tumor with an extremely poor prognosis. CD24 expression has been linked to the aggressiveness of cholangiocarcinoma cells and the adverse prognosis of cholangiocarcinoma patients. In the present study, the underlying mechanism of aggressive CD24+ cholangiocarcinoma cell behavior was elucidated. The magnetic-activated cell sorting system was used to isolate CD24+ and CD24- cell populations from RMCCA1 cholangiocarcinoma cells. Using a human tumor metastasis PCR array, it was observed that numerous tumor-associated genes were upregulated in the CD24+ cells, including CXC chemokine receptor type 4 (CXCR4). In addition, an intracellular signaling array demonstrated the activation of extracellular signal regulated kinase (ERK)1/2, which is downstream of the CXCR4 signaling cascade, in the CD24+ cells. Inhibition of CXCR4 or ERK1/2 significantly inhibited the motility and invasiveness of the CD24+ cells. The present study indicates that CXCR4 and ERK1/2 are induced by CD24 and that these proteins are associated with cholangiocarcinoma cell invasion. PMID- 24179539 TI - Differential effects of miR-34c-3p and miR-34c-5p on the proliferation, apoptosis and invasion of glioma cells. AB - Glioblastoma is the most malignant and common intrinsic brain tumor, but the molecular mechanism of glioma pathophysiology is poorly understood. Recent data have shown that microRNAs regulate the expression of several genes associated with human cancer. In the present study, the function of miR-34c in glioma cells was analyzed. It was demonstrated that miR-34c-3p and miR-34c-5p were downregulated in gliomas, by performing qPCR on tumor tissues from glioma patients and glioma cell lines, compared with normal brain tissues and a normal glial cell line. Furthermore, the miR-34c expression was found to be inversely correlated with glioma WHO grades. Overexpression of miR-34c-3p inhibited U251 and U87 cell proliferation; however, miR-34c-5p only had an effect on U251 cells. Transfection with miR-34c-3p or miR-34c-5p in U251 cells and with miR-34c-3p in U87 cells produced S-phase arrest with G0/G1 reduction and induced cell apoptosis, but no significant changes were observed with miR-34c-5p transfection in U87 cells, normal or negative control groups. However, significant inhibition of glioma cell invasion was observed following transfection with miR-34c-3p and miR-34c-5p. Moreover, it was identified that miR-34c-3p overexpression reduced the expression of Notch pathway members, but miR-34c-5p overexpression did not. Therefore, these results suggest differential tumor suppressor roles for miR-34c 3p and miR-34c-5p and provide new insights into the role of miR-34c in glioma, which includes tumor-suppressing effects on proliferation, apoptosis and invasiveness. PMID- 24179540 TI - Serum peptidomic profiling identifies a minimal residual disease detection and prognostic biomarker for patients with acute leukemia. AB - The evaluation of minimal residual disease (MRD) in acute leukemia (AL) is currently recognized as a potential critical tool to assess the response and relapse rate of treatments. The present study investigated serum peptides from patients with AL to identify biomarkers that would be useful in providing clinical evaluations and independent prognostic information. The patterns of serum peptides from 123 patients with AL and 49 healthy controls were analyzed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Furthermore, diagnostic models of differential peptides were established using the support vector machine (SVM) algorithm to discriminate between the AL patients and healthy controls or between the AL patients with various degrees of remission. Finally, the peptides were applied to evaluate the prognosis of the affected patients. The area under the receiver operating characteristic (ROC) curve (AUC), analyzed using the SVM algorithm to distinguish between the AL patients and healthy controls, was 0.921. The AUC of the models for distinguishing between the newly-diagnosed AL patients and those in AL hematological complete remission (HCR) and between the AL-HCR patients from those in AL-molecular remission (MR), was 0.824 and 0.919, respectively. A short serum peptide of m/z 4625 was identified to decrease in density in parallel with an increase in the degree of remission, which was used to monitor the MRD level. The intensity of the m/z 4625 peptide was significantly correlated with a poor overall survival (OS). The m/z 4625 peptide was identified to be a partial fragment of SERPINA3. The serum peptide pattern is high in sensitivity and specificity and may be used to discriminate between AL patients with various degrees of remission. The m/z 4625 peptide may be used to monitor the MRD levels and provide independent prognostic information in patients with AL. PMID- 24179541 TI - Metallic expandable stents in the management of malignant tracheal stenosis due to esophageal cancer with lymph node metastasis. AB - Esophageal cancer with post-operative lymph node metastasis (LNM) compressing and infiltrating the trachea causing dyspnea is considered a serious complication. However, chemotherapy or radiotherapy are often ineffective methods for such patients. Approaches employing metallic expandable stents to relieve airway obstruction are extremely effective in advanced-stage cancer patients. The present study reports the use of metallic expandable stents as a treatment for tracheal stenosis. A total of 11 patients with tracheal stenosis due to LNM compressing and infiltrating the trachea were selected between November 2009 and January 2013. All the patients were diagnosed by computed tomography and presented with varying degrees of dyspnea. A total of 13 stents were placed in 11 patients, without significant intraoperative complications. Post-operatively, all patients presented with significant improvement in respiratory function. The Borg score was determined 1 day after stent application. The mean score of dyspnea declined significantly from 7.0 to 0.9 (P<0.01), the mean heart rate decreased from 128 to 86 bpm (P<0.01), the mean respiratory rate decreased from 34 to 23 breaths/min (P<0.01) and the mean oxygen saturation increased from 85 to 97% (P<0.01). Complications included coughing, hemorrhage, chest pain, retention of secretions, halitosis and tumor regrowth. It may be concluded that metallic expandable stent placement is an effective strategy to palliate malignant tracheal stenosis. PMID- 24179542 TI - Inhibition of the mammalian target of rapamycin leads to autophagy activation and cell death of MG63 osteosarcoma cells. AB - It has been well documented that the inhibition of the mammalian target of rapamycin (mTOR) induces autophagy in proliferative cells. Therefore, mTOR inhibitors have been proposed for the treatment of cancer. As autophagy plays significant roles in tumor cell survival, the present study aimed to investigate the contribution of autophagy activation to the antitumor effects of cis diamminedichloroplatinum (CDDP). An MTT assay was used to determine the cytotoxic effects of rapamycin on MG63 osteosarcoma cells. The cell cycle was assessed using a flow cytometry analysis subsequent to staining the DNA with propidium iodide. The mitochondrial membrane potential (Deltapsi) was measured using the fluorescent probe, JC-1. Western blot analysis was used to determine the expression of the proteins that are involved in apoptosis and autophagy, including p53, p62, light chain 3 (LC3) and Beclin-1. The viability of the MG63 cells was inhibited following rapamycin or CDDP treatment. The mitochondrial Deltapsi collapsed following treatment with rapamycin or CDDP. Rapamycin induced cell death and enhanced the effects of the induction of MG63 cell death by CDDP. Western blot analysis detected the induced expression of the p53 and Beclin-1 proteins and the autophagic proteins, LC3 and p62. Rapamycin was observed to induce the death of cancer cells through apoptotic and autophagic mechanisms. Rapamycin may enhance the effects of the activation of autophagy and the induction of apoptosis by CDDP. PMID- 24179543 TI - A novel setup approach for helical tomotherapy in head and neck cancer: A case report. AB - Head and neck cancers that are associated with high-risk factors have a poor prognosis. In such patients, post-operative radiochemotherapy is mandatory. The present study describes the case of a 71-year-old high-risk head and neck cancer patient who was not able to tolerate the supine position for the radiotherapy setup. A lateral immobilization with a head mask and a vacuum cushion was performed. The patient underwent daily computed tomography (CT)-guided radiation therapy [image-guided radiation therapy (IGRT)]. At nine months post radiotherapy, the patient had no xerostomia and no swallowing dysfunction. However, the patient suffered a local recurrence and succumbed due to bleeding of the tumor a number of weeks after the recurrence. A recalculation of the actual delivered dose, taking the daily delivered dose into account, was performed. The recurrence occurred within the high-dose region. In selected cases of patients with head and neck cancers who are unable to tolerate the supine position, lateral positioning and high precision treatment is possible using daily IGRT. PMID- 24179544 TI - Reversal of multidrug resistance by the anti-malaria drug artesunate in the esophageal cancer Eca109/ABCG2 cell line. AB - The overexpression of ATP-binding cassette (ABC) transporters confers multidrug resistance (MDR) to tumor cells. ABCG2 is a member of the ABC superfamily. The present study aimed to investigate the correlation between ABCG2 expression and the MDR of esophageal cancer and to estimate the therapeutic benefit of downregulating ABCG2 expression and reversing chemoresistance in esophageal cells using artesunate (Art). The Eca109/ABCG2 cell line was established by transfecting the ABCG2 gene into Eca109 cells. The Eca109/ABCG2 esophageal cancer cells with ABCG2 gene overexpression were resistant to adriamycin (ADM), daunorubicin (DNR) and mitoxantrone (MIT), which indicated that ABCG2 may be associated with drug resistance in esophageal cancer. Art is a noteworthy antimalarial agent, particularly in severe and drug-resistant cancer cases, as Art is able to reverse drug resistance. In the present study, Art also exerted profound anticancer activity. The mechanism for the reversal of multidrug resistance by Art in esophageal carcinoma was analyzed using cellular experiments, but still remains largely unknown. PMID- 24179545 TI - beta4-integrin-mediated cytotoxic activity of AexU in human prostate cancer PC3 cells. AB - The present study aimed to characterize the cytotoxic activity of AexU, an effector-mediating type three secretion system (TTSS) of gram-negative bacteria, in human prostate cancer cells, focusing on the association with beta4-integrin expression. The cytotoxic effects of AexU either alone or in combination with chemotherapeutic agents were evaluated using several human prostate cancer cell lines. Human prostate cancer PC3 cells, in which an expression vector containing siRNA targeting beta4-integrin had been introduced, were established (PC3/sh-In), and the cytotoxic effects of AexU on the PC3/sh-In cells were compared with the PC3 cells that were transfected with a control vector (PC3/C). The expression levels of beta4-integrin in the PC3 cells were markedly higher compared with those in the LNCaP or DU145 cells, and the cytotoxic effects of AexU in the PC3 cells were more pronounced compared with those in the LNCaP or DU145 cells. The sensitivity of the PC3 cells to docetaxel and cisplatin was significantly enhanced following treatment with AexU, resulting in a decrease in the IC50 of the two agents by ~90%. The cytotoxic effect of AexU in the PC3/C cells was more marked compared with that in the PC3/sh-In cells, and the phosphorylation of Akt in the PC3/C cells appeared to be significantly more inhibited by the treatment with AexU compared with the PC3/sh-In cells. In conclusion, treatment with AexU may be a useful therapeutic option for prostate cancer when beta4-integrin is overexpressed. The treatment appears to exert its effects through growth inhibition and by enhancing the sensitivity of the cancer cells to chemotherapeutic agents. PMID- 24179546 TI - A single nucleotide polymorphism in EZH2 predicts overall survival rate in patients with cholangiocarcinoma. AB - Cholangiocarcinoma (CCA) is a deadly disease arising from the malignant transformation of cholangiocytes. Enhancer of zeste homolog 2 (EZH2) is overexpressed in poorly differentiated CCA. Functional single nucleotide polymorphisms (SNPs) in this gene may affect the role of EZH2 in cholangiocarcinogenesis and chemoresistance. The aim of the current study was to evaluate the correlation between EZH2 SNPs and clinical outcome. Using PROMO3.0, GeneCard and MicroSNiper, 4 EZH2 SNPs with functional relevance in CCA were selected in silico. These SNPs were studied in genomic DNA extracted from the blood samples of 75 patients with advanced CCA, who were treated with epirubicin cisplatin-xeloda (ECX regimen). SNP genotyping was performed with specific PCR assays. The rs887569 TT genotype was correlated with a significantly longer overall survival (OS; TT vs. CT-CC, P=0.026). Moreover, the TT genotype revealed a trend toward a significant association with a reduced risk of mortality (HR, 0.59; 95% CI, 0.33-1.05; P=0.075), by multivariate analysis. These results support future studies on the role of rs887569 EZH2 SNP as a possible predictive marker of OS in advanced CCA patients. PMID- 24179547 TI - Inhibitory effect of valproic acid on bladder cancer in combination with chemotherapeutic agents in vitro and in vivo. AB - Histone deacetylase inhibitors (HDACIs) are a promising class of drugs that act as antiproliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is an HDACI that has been widely used as an anti-convulsant and shows promise as a chemotherapeutic drug for a number of tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of bladder cancer cells and its synergistic effect with chemotherapeutic agents in vitro and in vivo. The cell viability of human bladder cancer cell lines following treatment with VPA and/or VPA in combination with mitomycin C, cisplatin (DDP) and adriamycin were determined using a 3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide assay. Hoechst staining was used to observe the morphology of the apoptotic cells. Survivin protein and acetylated histone H3 levels were quantified using western blot analysis. The in vivo tumor growth inhibition of VPA was determined in rats with N-methyl-N-nitrosourea-induced bladder cancer. VPA significantly inhibited the growth of the bladder cancer cells in a concentration- and time-dependent manner. Furthermore, improved results were achieved for tumor inhibition when VPA was combined with chemotherapeutic agents in vitro and in vivo. Survivin expression decreased and acetylated histone H3 expression increased in the bladder cancer cells following the treatment with VPA. Intravesical injections of VPA were able to inhibit tumor progression when combined with DDP. In conclusion, VPA acts as an HDACI that has a direct anticancer effect and markedly enhances the action of several chemotherapy agents. VPA may sensitize bladder cancer to anticancer drugs by downregulating survivin expression. PMID- 24179548 TI - Glioblastoma mimicking a cerebral contusion: A case report. AB - A 61-year-old male presented with a rare case of glioblastoma mimicking a cerebral contusion subsequent to collapsing. The patient had been medicated for hypertension for seven years and diabetes for eight years prior to hospitalization. Brain computed tomography (CT) revealed a cerebral contusion and intracerebral hemorrhage (ICH) in the left temporal region. The patient was initially administered intravenous drugs to reduce the intracranial pressure following the diagnosis of a cerebral contusion. Serial CT revealed ICH resorption. However, the patient was again admitted due to a headache and vomiting two months later. Magnetic resonance imaging (MRI) demonstrated an enhanced ring-shaped mass around the cyst cavity within the left temporal region, with surrounding edema. The patient underwent cyst puncture drainage in the temporal region. No tumor cells were identified in the cyst fluid and the culture was also negative. The patient was admitted for a headache and vomiting for the third time one month after being discharged. A cyst, tumor and meningoencephalitis were suspected following an MRI scan. The patient was treated with a left temporal craniotomy for a mass resection and biopsy. The histological diagnosis of the biopsy specimen was that of a glioblastoma. Two months later, MRI revealed a recurrence of the glioblastoma. In the present case, a brain tumor should have initially been suspected as the cause of the ICH, despite the history of craniocerebral trauma and hypertension. Early awareness of this potential cause of ICH may facilitate a more prompt diagnosis and treatment. PMID- 24179549 TI - Oridonin induces the apoptosis of metastatic hepatocellular carcinoma cells via a mitochondrial pathway. AB - The selective induction of apoptosis is a promising strategy for cancer therapy. The antitumor effects of oridonin have been reported in several types of malignant tumors. However, the effects of oridonin on MHCC97-H cells, a highly metastatic human hepatocellular carcinoma cell line, have not been reported. The present study aimed to determine the effect of oridonin on the apoptosis of MHCC97-H cells and to identify the underlying molecular mechanisms that are involved. Compared with the untreated control cells, oridonin significantly decreased (P<0.05) cell proliferation in a concentration- and time-dependent manner. Oridonin at concentrations of 12.5, 25, 50 and 100 MUM resulted in increased apoptotic Annexin V-positive and propidium iodide-negative cells by 9.5, 15.6, 22.2 and 31.7%, respectively, compared with the control groups (P<0.05). The mitochondrial membrane potential was significantly decreased by 6.0, 12.9, 18.9 and 27.1% in the MHCC97-H cells that were treated with oridonin at concentrations of 12.5, 25, 50 and 100 MUM, respectively, for 24 h compared with the control groups (P<0.05). Oridonin increased the activity of caspase-3 and the expression of cleaved caspase-9 and cytochrome c in the cytoplasm and decreased the Bcl-2:Bax ratio in a concentration-dependent manner. The data indicate that oridonin inhibited the proliferation of the MHCC97-H cells by inducing apoptosis via a mitochondrial pathway. This mitochondrial pathway of apoptosis involved a reduction in the mitochondrial membrane potential and the subsequent release of cytochrome c and activation of caspase-3 and -9. PMID- 24179550 TI - Age is a prognostic factor affecting survival in lung cancer patients. AB - Despite all efforts at management, prognosis of advanced lung cancer is extremely poor, with a median survival time of ~1 year. The number of cancer patients aged >70 years is significantly increased among the cancer patient population. The aim of this study was to investigate the clinical importance of age in lung cancer. Data from 110 patients with histologically confirmed lung cancer, who were treated and followed up in the Institute of Oncology, University of Istanbul, were recorded from medical charts. There were 100 (91%) males with a median age of 59 years (range, 35-88 years). The majority of patients had non-small cell lung cancer (NSCLC; 84%) and metastatic stage (56%). The rate of positive response to chemotherapy was lower in elderly patients (P=0.01) and the incidence of anemia was higher compared with that in younger patients (P=0.02). The majority of mortalities occurred in elderly patients (P=0.01). The median survival time of elderly patients was significantly lower compared with that of younger patients (37.8 vs. 57 weeks; P=0.009). The 1-year survival rates in younger and elderly patients were 67.3 and 42.5%, respectively. In multivariate analysis, elderly patients also had significantly poorer survival (P=0.023). In the group of elderly patients, analyses revealed that significant prognostic factors, including stage of disease and serum lactate dehydrogenase (LDH) levels, were associated with survival. Elderly patients diagnosed with small cell lung cancer had a poorer outcome compared with those with NSCLC (P=0.009), and older patients with elevated serum LDH levels had a shorter survival time compared with those with normal levels (P=0.042). In conclusion, age is one of the major prognostic factors affecting survival in lung cancer patients; therefore, patients should be managed according to age in clinical practice. PMID- 24179551 TI - High-dose hypofractionated X-ray radiotherapy for hepatocellular carcinoma: Tumor responses and toxicities. AB - Hypofractionated radiotherapy (RT) has been employed to treat hepatocellular carcinoma (HCC). The present study aimed to report the treatment effects, the dose-response associations and the factors that are associated with radiation induced liver disease (RILD) in a high-dose hypofractionated RT procedure. A total of 40 patients with non-metastatic HCC who underwent RT for local control of irradiated tumors were studied. The treatment technique was that of three dimensional conformal or intensity-modulated radiation therapy, with a fraction size of 3 Gy and a total dose of 40-66 Gy in 14-23 fractions. The biologically effective dose (BED) was 52.0-85.8 Gy10 (median, 74.1 Gy10). Tumor regression was observed in 28 patients (70.0%) with a complete response, partial response, stable disease and progressive disease status in 11 (27.5%), 17 (42.5%), five (12.5%) and seven patients (17.5%), respectively. The one-, two- and five-year overall survival (OS) and in-field control (IFC) rates were 60, 40 and 21% and 73, 62 and 56%, respectively. A positive correlation also emerged between the radiation dose and the IFC (P=0.035). Eight of the 40 patients (20%) developed non-classic RILD. A higher Cancer of the Liver Italian Program score was associated with a higher probability of non-classic RILD (P=0.02). The tumor response and IFC rate of HCC following irradiation were significantly dose dependent. High-dose hypofractionated X-ray RT is a feasible and effective treatment for HCC in patients with good liver function and for those who meet the criteria for a curative attempt. PMID- 24179552 TI - Computed tomography-guided radiofrequency ablation for palliation of a painful supraclavicular soft-tissue metastasis invading the brachial plexus. AB - The present study describes a case of a painful supraclavicular soft-tissue metastasis of a skin melanoma invading the brachial plexus in a 38-year-old male. The patient was treated twice with radiofrequency ablation (RFA) under computed tomography (CT) guidance, which caused tumoral necrosis. The patient was originally referred with a 7-cm metastasis in the right supraclavicular fossa, which caused intractable pain and a degree of numbness. These symptoms were unresponsive to chemotherapy and radiotherapy and the pain was not controlled using narcotic analgesics. The lesion was treated with CT-guided RFA causing necrosis, relieving the pain and sparing the patient from using analgesics. The pain recurred 19 months thereafter and a CT scan revealed an 8-cm mass in the right supraclavicular space. The patient underwent repeat CT-guided RFA, which reduced the pain to a level that was controlled with minor oral analgesics. In conclusion, in this case of a painful supraclavicular soft-tissue metastasis invading the brachial plexus, which was intractable to chemotherapy and radiotherapy, RFA was feasible and offered substantial palliation of the symptoms, freedom from the use of narcotic analgesics and improvements to the quality of life. PMID- 24179553 TI - Glioma stem cells enhance endothelial cell migration and proliferation via the Hedgehog pathway. AB - The aim of the present study was to determine the possible mechanism underlying the enhanced migration and proliferation of endothelial cells caused by glioma stem cells (GSCs). Tumor spheres enriched in GSCs derived from the mouse GL261 glioma cell line, and the brain microvessel endothelial cell line, b.END3, were used in this study. A Transwell co-culture system, RNAi experiments, quantitative polymerase chain reaction, western blotting and enzyme-linked immunosorbent, cell counting kit-8 (CCK-8) proliferation, Transwell migration and wound-healing assays were used in this study to determine the migration and proliferation ability, as well as the Hedgehog (HH) pathway-related gene expression in the b.END3 cells. Based on the results, it was demonstrated that the migration and proliferation of the endothelial cells were enhanced following co-culture with GSCs. The gene expression of the HH pathway-related genes, Sonic Hedgehog (Shh) and Hedgehog-interacting protein (Hhip) was altered in the endothelial cells when co-cultured with GSCs. Overexpression of glioma-associated oncogene homolog 1 indicated activation of the HH pathway. Following knockdown of smoothened (Smo) in the endothelial cells, the migration and proliferation abilities of the cells were inhibited. GSCs have little effect on enhancing these behaviors in endothelial cells following Smo-knockdown. Further investigation revealed that Shh levels in the supernatant of the co-culture system were elevated, indicating the importance of secreted Shh from the endothelial cells. In conclusion, GSCs enhanced the migration and proliferation of the endothelial cells in vitro, which was likely associated with the activation of the HH pathway in the endothelial cells, caused by the increased secretion of Shh. PMID- 24179554 TI - Ventricular-arterial coupling: Invasive and non-invasive assessment. AB - Interactions between the left ventricle (LV) and the arterial system, (ventricular-arterial coupling) are key determinants of cardiovascular function. Ventricularearterial coupling is most frequently assessed in the pressure-volume plane using the ratio of effective arterial elastance (EA) to LV end-systolic elastance (EES). EA (usually interpreted as a lumped index of arterial load) can be computed as end-systolic pressure/stroke volume, whereas EES (a load independent measure of LV chamber systolic stiffness and contractility) is ideally assessed invasively using data from a family of pressure-volume loops obtained during an acute preload alteration. Single-beat methods have also been proposed, allowing for non-invasive estimations of EES using simple echocardiographic measurements. The EA/EES ratio is useful because it provides information regarding the operating mechanical efficiency and performance of the ventricular-arterial system. However, it should be recognized that analyses in the pressure-volume plane have several limitations and that "ventricular-arterial coupling" encompasses multiple physiologic aspects, many of which are not captured in the pressure-volume plane. Therefore, additional assessments provide important incremental physiologic information about the cardiovascular system and should be more widely used. In particular, it should be recognized that: (1) comprehensive analyses of arterial load are important because EA poorly characterizes pulsatile LV load and does not depend exclusively on arterial properties; (2) The systolic loading sequence, an important aspect of ventricular arterial coupling, is neglected by pressure-volume analyses, and can profoundly impact LV function, remodeling and progression to heart failure. This brief review summarizes methods for the assessment of ventricular-arterial interactions, as discussed at the Artery 12 meeting (October 2012). PMID- 24179555 TI - Comparison of cardiac rehabilitation programs combined with relaxation and meditation techniques on reduction of depression and anxiety of cardiovascular patients. AB - Cardiovascular disease (CVD) is a major cause of death in developed countries. Most cardiac rehabilitation programs include psychological interventions. The aim of this study was to determine the effectiveness of rehabilitation techniques in cardiac patients including psychological-physical interventions such as Meditation and Relaxation. We enrolled 45 patients with CVD and depression. The patients were allocated to 3 groups (Relaxation, Meditation and Control). There was a significant reduction on depression, systolic blood pressure and heart rate in the Meditation group compared with the control group. Our findings suggest that meditation techniques have better outcomes in cardiac patients for improving depression, reduction of systolic and diastolic blood pressure, and heart rate than relaxation techniques. PMID- 24179556 TI - Efficacy and Safety of Rituximab in Biologic-Naive Patients with Rheumatoid Arthritis vs Anti-Tnf Therapy Failure. AB - OBJECTIVES: Our aim was to compare an AntiCD20 therapy (rituximab) for rheumatoid arthritis in two patient populations (Group 1), anti-TNFalpha naive patients and inadequate responders to Anti-TNFalpha therapy (Group 2). METHODS: We analyzed the efficacy of the drug Rituximab (RTX) in RA patients who failed methotrexate (MTX) or had a relative or absolute contraindication to receive anti-TNFalpha therapy. RESULTS: 25 patients were identified according to the above criteria and followed up for a mean period of 6 months. Thirteen patients were biologic naive and twelve patients had already failed anti-TNFalpha therapy. Group 1 used 2> DMARDs (32% vs 20%, p<0.005), group 2 had more years of disease progression (5+/ 1.89 v s4.10+/-3.92, p<0.001). The remission as measured by the DAS28 reached faster in group 1 (1.25+/-0.12 vs 2.15+/-1.64, p<0,001). Severe infections especially by herpes viruses were more frequent in group 2. CONCLUSIONS: Comparing clinical improvement in both groups the decrease of acute phase reactants and the clinical remission measured by DAS28 was reached in both groups, however it was reached more belatedly in group 2 (at 6 months), this is due to the fact that they have more years of the disease evolution and a higher HAQ. PMID- 24179557 TI - Case Report: Meningioma with Intra-tumoural Haemorrhage Secondary to Ruptured Distal Anterior Cerebral Artery Aneurysm. AB - BACKGROUND: Brain tumours that are associated with cerebral aneurysms are rare occurrences, whereas the coexistence of brain tumours and intra-tumoural aneurysms is even rarer. There have been 12 brain tumour cases that have been reported in the literature that describe an aneurysm within a brain tumour, with 4 of these tumours being meningiomas. CASE DESCRIPTION: A 34-year-old male patient presented with sudden-onset headache, and an inter-hemispheric meningioma with intra-tumoural bleeding was found due to a ruptured embedded anterior cerebral artery aneurysm. The aneurysm was diagnosed incidentally on the third cerebral angiogram, while the initial 2 angiograms were negative. The patient was treated with endovascular aneurysm embolisation that was followed by tumour resection. CONCLUSION: This paper is the first case report to describe the coexistence of a meningioma and an aneurysm, which presented with intra-tumoural haemorrhage that was negative on the initial cerebral angiogram. Unlike previous case reports, the aneurysm in this case was located with an anterior cerebral artery distribution. PMID- 24179558 TI - Mechanisms of Adipocytokine-Mediated Trastuzumab Resistance in HER2-Positive Breast Cancer Cell Lines. AB - Acquired resistance to trastuzumab is a clinical problem in the treatment of HER2 over-expressing metastatic breast cancer. Importantly, an earlier report suggested that high body mass index was associated with reduced overall survival and reduced time to progression in patients with early stage or metastatic HER2 positive breast cancer treated with trastuzumab. Adipocyte-secreted factors may stimulate growth of HER2-positive cancers, blocking the growth inhibitory action of trastuzumab. Leptin and growth differentiation factor 15 (GDF15) are two adipocytokines that have been reported to stimulate HER2-PI3K signaling. We previously showed that cells with acquired trastuzumab resistance express increased levels of GDF15, and that GDF15 knockdown restores sensitivity to trastuzumab. The objective of the current study was to identify potential molecular mechanisms by which adipocytes stimulate resistance to trastuzumab in HER2-over-expressing breast cancer cell lines. Cells were cultured in complete media or conditioned media from differentiated adipocytes (CM). Cell viability of trastuzumab-treated cells was examined under anchorage-dependent and -independent conditions. Phosphorylation of Akt was assessed by Western blotting, and response to trastuzumab was reassessed upon treatment with the PI3K inhibitor LY294002 or after transfection with kinase-dead Akt. We report that CM significantly reduced trastuzumab-mediated growth inhibition of HER2-positive cells, and stimulated rapid phosphorylation of Akt. Pharmacologic or genetic inhibition of PI3K overcame CM-mediated trastuzumab resistance. Leptin and GDF15 were both measured in CM, but only GDF15 conferred resistance to trastuzumab. Leptin, on the other hand, abrogated sensitivity to lapatinib but not trastuzumab. Our observations suggest that adipocyte-secreted factors such as GDF15 stimulate PI3K signaling, resulting in reduced response to trastuzumab. The utility of adipocytokines as predictors of drug resistance and approaches to mitigate the cancer-promoting effects of adipocyte-secreted factors should be further examined. Our work supports additional investigation into GDF15 as a potential biomarker of trastuzumab resistance, and development of approaches to therapeutically target GDF15 in HER2-positive breast cancers that have progressed on trastuzumab. PMID- 24179559 TI - The SHARE operationalized frailty phenotype: a comparison of two approaches. AB - PURPOSE: the phenotype defined by Fried et al. is one of the main operationalizations of frailty. Santos-Eggimann et al. pioneered the adaptation of the phenotype criteria to the Survey of Health, Ageing and Retirement in Europe (SHARE, http://www.share-project.org/). Using the adapted criteria, Romero Ortuno et al. created and validated the SHARE Frailty Instrument for Primary Care (SHARE-FI). In SHARE-FI, the cut-offs for the phenotypic categories (i.e. non frail, pre-frail and frail) are automatically derived from latent variable modelling, while Fried et al. (and also Santos-Eggimann et al.) use a rule based on the number of criteria present (Ncriteria): >= 3: frail; 1 or 2: pre-frail; 0: non-frail. The aim of the present study was to compare the mortality prediction of these two different approaches (latent variable modelling in SHARE-FI vs. Ncriteria in Santos-Eggimann et al.). SUBJECTS AND METHODS: the subjects were 15,420 women and 12,742 men from the first wave of SHARE. A correspondence analysis was used to assess the degree of agreement between phenotypic classifications. The ability of the continuous measures (Ncriteria and SHARE-FI score) to predict mortality (mean follow-up of 2.4 years) was compared using receiver operating characteristic plots and areas under the curve (AUC). RESULTS: in both women and men, there was a high degree of correspondence between phenotypic categories. The two continuous measures performed similarly as mortality predictors (women: SHARE-FI-AUC = 0.77; Ncriteria-AUC = 0.75. Men: SHARE-FI-AUC = 0.76; Ncriteria-AUC = 0.72). CONCLUSION: the two approaches to the SHARE operationalized frailty phenotype performed equally well to predict mortality. PMID- 24179560 TI - The mean, the median, and the St. Petersburg paradox. AB - The St. Petersburg Paradox is a famous economic and philosophical puzzle that has generated numerous conflicting explanations. To shed empirical light on this phenomenon, we examined subjects' bids for one St. Petersburg gamble with a real monetary payment. We found that bids were typically lower than twice the smallest payoff, and thus much lower than is generally supposed. We also examined bids offered for several hypothetical variants of the St. Petersburg Paradox. We found that bids were weakly affected by truncating the gamble, were strongly affected by repeats of the gamble, and depended linearly on the initial "seed" value of the gamble. One explanation, which we call the median heuristic, strongly predicts these data. Subjects following this strategy evaluate a gamble as if they were taking the median rather than the mean of the payoff distribution. Finally, we argue that the distribution of outcomes embodied in the St. Petersburg paradox is so divergent from the Gaussian form that the statistical mean is a poor estimator of expected value, so that the expected value of the St. Petersburg gamble is undefined. These results suggest that this classic paradox has a straightforward explanation rooted in the use of a statistical heuristic. PMID- 24179561 TI - Unveiling N-protonation and anion-binding effects on Fe/N/C-catalysts for O2 reduction in PEM fuel cells. AB - The high cost of proton-exchange-membrane fuel cells would be considerably reduced if platinumbased catalysts were replaced by iron-based substitutes, which have recently demonstrated comparable activity for oxygen reduction, but whose cause of activity decay in acidic medium has been elusive. Here, we reveal that the activity of Fe/N/C-catalysts prepared through a pyrolysis in NH3 is mostly imparted by acid-resistant FeN4-sites whose turnover frequency for the O2 reduction can be regulated by fine chemical changes of the catalyst surface. We show that surface N-groups protonate at pH 1 and subsequently bind anions. This results in decreased activity for the O2 reduction. The anions can be removed chemically or thermally, which restores the activity of acid-resistant FeN4 sites. These results are interpreted as an increased turnover frequency of FeN4 sites when specific surface N-groups protonate. These unprecedented findings provide new perspective for stabilizing the most active Fe/N/C-catalysts known to date. PMID- 24179562 TI - Molecular assays for determining Mycobacterium leprae viability in tissues of experimentally infected mice. AB - BACKGROUND: The inability of Mycobacterium leprae to grow on axenic media has necessitated specialized techniques in order to determine viability of this organism. The purpose of this study was to develop a simple and sensitive molecular assay for determining M. leprae viability directly from infected tissues. METHODOLOGY/PRINCIPLE FINDINGS: Two M. leprae-specific quantitative reverse transcription PCR (qRT-PCR) assays based on the expression levels of esxA, encoding the ESAT-6 protein, and hsp18, encoding the heat shock 18 kDa protein, were developed and tested using infected footpad (FP) tissues of both immunocompetent and immunocompromised (athymic nu/nu) mice. In addition, the ability of these assays to detect the effects of anti-leprosy drug treatment on M. leprae viability was determined using rifampin and rifapentine, each at 10 mg/kg for 1, 5, or 20 daily doses, in the athymic nu/nu FP model. Molecular enumeration (RLEP PCR) and viability determinations (qRT-PCR) were performed via Taqman methodology on DNA and RNA, respectively, purified from ethanol-fixed FP tissue and compared with conventional enumeration (microscopic counting of acid fast bacilli) and viability assays (radiorespirometry, viability staining) which utilized bacilli freshly harvested from the contralateral FP. Both molecular and conventional assays demonstrated growth and high viability of M. leprae in nu/nu FPs over a 4 month infection period. In contrast, viability was markedly decreased by 8 weeks in immunocompetent mice. Rifapentine significantly reduced bacterial viability after 5 treatments, whereas rifampin required up to 20 treatments for the same efficacy. Neither drug was effective after a single treatment. In addition, host gene expression was monitored with the same RNA preparations. CONCLUSIONS: hsp18 and esxA qRT-PCR are sensitive molecular indicators, reliably detecting viability of M. leprae in tissues without the need for bacterial isolation or immediate processing, making these assays applicable for in vivo drug screening and promising for clinical and field applications. PMID- 24179563 TI - Strategies for therapeutic hypometabothermia. AB - Although therapeutic hypothermia and metabolic suppression have shown robust neuroprotection in experimental brain ischemia, systemic complications have limited their use in treating acute stroke patients. The core temperature and basic metabolic rate are tightly regulated and maintained in a very stable level in mammals. Simply lowering body temperature or metabolic rate is actually a brutal therapy that may cause more systemic as well as regional problems other than providing protection. These problems are commonly seen in hypothermia and barbiturate coma. The main innovative concept of this review is to propose thermogenically optimal and synergistic reduction of core temperature and metabolic rate in therapeutic hypometabothermia using novel and clinically practical approaches. When metabolism and body temperature are reduced in a systematically synergistic manner, the outcome will be maximal protection and safe recovery, which happen in natural process, such as in hibernation, daily torpor and estivation. PMID- 24179564 TI - Recent progress in perceptual learning research. AB - Perceptual learning is defined as long-term improvement in perceptual or sensory systems resulting from repeated practice or experience. As the number of perceptual learning studies has increased, controversies and questions have arisen regarding divergent aspects of perceptual learning, including: (1) stages in which perceptual learning occurs, (2) effects of training type, (3) changes in neural processing during the time course of learning, (4) effects of feedback as to correctness of a subject's responses, and (5) double training. Here we review each of these aspects and suggest fruitful directions for future perceptual learning research. WIREs Cogn Sci 2012, 3:293-299. doi: 10.1002/wcs.1175 For further resources related to this article, please visit the WIREs website. PMID- 24179565 TI - Mandible condylar hyperplasia: a review of diagnosis and treatment protocol. AB - Condylar hyperplasia (CH) is a bone disease characterized by the increased development of one mandibular condyle. It regularly presents as an active growth with facial asymmetry generally without pain. Statistically it affects more women in adolescence, although it does not discriminate by age or gender. Its best known consequence is asymmetric facial deformity (AFD), which combined with alteration of the dental occlusion with unilateral crossbite or open bite. It is not known when CH begins and how long it lasts; diagnostic examinations are described and are efficient in some research about diagnosis. Protocol treatment is not well studie and depends on the criteria described in this paper. The aim of this research is to provide up-to-date information about the diagnosis of this disease and to analyze the treatment protocol, visualizing the CH and AFD presented. PMID- 24179566 TI - Non-surgical treatment of an Angle Class III malocclusion in adults. AB - OBJECTIVE: To examine the application of a modified fixed reverse twin-block appliance (TBA) in adults with an Angle Class III malocclusion and anterior crossbite. PARTICIPANTS: Thirty-two adults with an Angle III malocclusion were recruited. An associated temporomandibular disorder (TMD) was found in 18 patients, laterognathism in 21, and both conditions in the remaining 12 patients. METHODS: A modified fixed reverse TBA was used to posture the mandible back, divert bite force and centre the dentition. The malocclusion, laterognathism and temporomandibular disorders were concurrently treated. The outcome was evaluated radiographically and the findings were analyzed via Electronic Measurement Scale software. RESULTS: Treatment was shown to be effective and could significantly shorten the course of treatment and avoid orthognathic surgery. The average course of treatment was 14 months, during which time, the mandible was postured back and the dentition was successfully aligned and levelled. Most patients achieved an edge-to-edge occlusion of the anterior teeth after 7-10 days of appliance wear. Most symptoms of TMD were relieved after 1 month and the laterognathism resolved in 4-5 months. CONCLUSION: A modified fixed reverse TBA was an effective non-surgical strategy for the treatment of selected Angle Class III malocclusions with an anterior crossbite in adults. PMID- 24179567 TI - Symptom improvement after helicobacter pylori eradication in patients with functional dyspepsia-A multicenter, randomized, prospective cohort study. AB - OBJECTIVE: To observe the improvement of functional dyspepsia (FD) after helicobacter pylori (HP) eradication in FD patients. METHODS: 644 FD patients were recruited of whom 585 completed follow up. They were divided into postprandial distress syndrome (PDS) group and epigastric pain syndrome (EPS) group. Patients with HP infection were randomly allocated into eradication group and non-eradication group. Patients in the eradication group were randomly assigned into two groups and treated with triple therapy and sequential therapy, respectively. Patients in non-eradication group and HP non-infection group were treated with Domperidone (PDS patients) or Talcid (EPS patients). Clinical symptoms were evaluated. RESULTS: When compared with patients with unsuccessful HP eradication and without eradication, significant improvement in symptoms was found at 8 w, 12 w, and 26 w in patients with successful HP eradication in EPS group (P < 0.05). However, in PDS group, improvement in symptoms was comparable among patients expect at 26 w after successful HP eradication (P < 0.05). Therapeutic efficacy in patients without HP eradication was poorer than that in HP negative patients in EPS group (P < 0.05), while in PDS group, symptoms were relived at 26 w and 52 w (P < 0.05). CONCLUSIONS: HP is one of pathogenic factors of FD and HP eradication may benefit FD patients, regardless therapeutic regimes, especially in EPS patients. PMID- 24179568 TI - Personal hair dyes use and risk of glioma: a meta-analysis. AB - BACKGROUND AND OBJECTIVE: Use of hair dyes for glioma risk has been investigated in numerous epidemiological studies, but the evidence is inconsistent. Therefore, a meta-analysis was performed to estimate the association between hair dyes use and glioma risk. METHODS: We searched PubMed and EMBASE databases without any limitations, covering all papers published by the end of March 8, 2013. Cohort and case-control studies reporting relative risk estimates (RRs) with corresponding 95% confidence intervals (CIs) (or data to calculate them) on this issue were included. Random effects models were used to calculate the pooled RRs and corresponding 95% CIs. RESULTS: Four case-control and two cohort studies were included in this meta-analysis. The summary RRs and 95 % CIs for ever users of any hair dyes were 1.132 (0.887-1.446) for all studies, 1.291 (0.938-1.777) for case-control studies, and 0.903 (0.774-1.054) for cohort studies. In the subgroup analysis by geographic regions and sex, the similar results were detected. No significant associations were also observed among the studies which reported data involving permanent hair dye use and duration of any hair dye use. CONCLUSION: In summary, the results of our study demonstrated that hair dyes use is not associated with risk of glioma. PMID- 24179569 TI - Relationship between oral health and its impact on the quality life of Alzheimer's disease patients: a supportive care trial. AB - Dental infections have recently been related with a possible risk factor for Neurodegenerative pathologies like Alzheimer's disease (AD). Even if there are no specific studies investigating orofacial pain in this patient group, dental health is known to be a potential cause of pain and to influence quality of life and disease progression. The aim of this study was to investigate how the AD patients' oral health status may influence their quality of life. 158 patients affected by AD were evaluated using Decayed Missed Filled Teeth (DMFT), Oral Health Impact Profile-14 (OHIP-14) and Clinical Investigation consisting in the detection of cavities and measurement of the probing depth in each patient; other parameters like gingival bleeding, biofilm index and tooth mobility degree test have been recorded. The ratio between diagnosis of periodontal disease and impact on quality of life was significant in individuals with periodontitis (p < 0.001) and missed filled teeth. Gingival bleeding, and probing depth > 4 mm were associated with intensely negative impact on quality of life (p = 0.013, p < 0.001, and p = 0.012 respectively). Moreover, the absence of more than 2 molar teeth increases the chewing inability decreasing the patient quality of life. CONCLUSION: It was observed a correlation between the age and the high index of pathologies analyzed, due to the progressive nature of the disease. Concepts of health and disease determined by clinical diagnostic criteria may influence the assessment of the impact of periodontal disease on Alzheimer's quality of life. PMID- 24179570 TI - Cloning and expression of soluble vascular endothelial growth factors receptor-1 (sFlt-1) fragments in CHO-K1. AB - Soluble form of vascular endothelial growth factor (VEGF) receptor (sFlt-1) has been considered a key target in anti angiogenesis strategies. In this study, sFlt 1 was amplified and cloned. For recombinant production of sFlt-1 protein, Chinese hamster ovary cell line (CHO) was used. The liposome-mediated transfection with sFlt-1 gene, were detected in sFlt-1 positive cells as early as 24 hours post transfection. The production of sFlt-1 protein was confirmed using SDS-PAGE and immune blotting results. In present investigation, the recombinant protein of sFlt-1 had expressed with correct folding. The system is economically applicable for large production of sFlt protein and can be used as further therapeutic approaches in targeting the growth of solid tumor tissue. PMID- 24179571 TI - Relationship of serum homocysteine level with nutritional status and HbA1c level in elderly inpatients. AB - BACKGROUND: Hyperhomocysteinemia is a risk factor for vascular diseases. This study aimed to investigate the serum total homocysteine (tHcy) level and nutritional status in elderly inpatients and determine the relationship between tHcy level and nutritional status. METHODS: This cross sectional study was carried out in the Tongji hospital, and 142 subjects were consecutively recruited. Fasting blood was collected, and the liver and kidney function, blood glucose, glycosylated hemoglobin (HbA1c), plasma protein, lipid profile, folic acid, vitamin B12 and serum total tHcy were measured. Anthropometric measurements, grip strength and the shortened MNA form (MNA-SF) were used to assess the nutritional status. RESULTS: Undernutrition was common in this population. Based on MNA-SF scores, 34.2% of subjects were at risk of malnutrition, and malnourished subjects accounted for 4.9%. The mean tHcy was 14.10+/-5.46 MUmol/l, and the prevalence of hyperhomocysteinemia was 32.4% (46/142). Hyperhomocysteinemia was a risk factor of cerebral infarction (RR=1.636, 95% CI: 1.169-2.288); Serum tHcy was negatively correlated with serum folic acid, vitamin B12 and MNA-SF score (r=-0.348,P=0.000; r=-0.236, P=0.005; r= 0.208, P=0.014), and positively with BMI within normal range (18.5-23.9; r=0.232, P=0.044). Serum tHcy was negatively correlated with HbA1c, (r=-0.196, P=0.021) and positively with serum creatinine (r=0.327, P=0.000), but unrelated to fasting blood glucose (r=-0.098, P=0.250). Multivariate stepwise regression analysis showed serum folic acid, serum creatinine, MNA-SF score and HbA1c were independent determinants of serum tHcy. CONCLUSION: Elderly subjects have higher serum tHcy level. Compromised renal function, poor nutritional status and lower blood glucose are likely to influence the serum tHcy level. PMID- 24179572 TI - Analysis for hypertension and related risk factors of physical examination population. AB - BACKGROUND AND OBJECTIVES: Essential hypertension is the most common chronic disease. To provide a basis for developing the prevention and control strategies of hypertension by epidemiological investigation on factors related to hypertension in health examination population. METHODS: Data of health examination population from Jilin municipal enterprise and public institutions during January 2011 and July 2012 were randomly selected, and statistical analysis was performed for the age, gender, body mass index, blood lipids, blood uric acid, serum creatinine, blood glucose and hypertension classification indexes. RESULTS: 1859 patients were diagnosed as hypertension. The detection rate of hypertension, awareness rate, new discovery rate, treatment rate, control rate and rate of the patients with family history of hypertension were 21.0%, 27.5%, 72.5%, 19.1%, 6.0% and 26.7%, respectively. A statistically significant difference was found in serum creatinine, blood glucose, serum cholesterol, L DLC, coronary disease, stroke and diabetes mellitus by the comparison among the different blood pressure grades. There was a difference in blood pressure, blood uric acid, blood creatinine, glucose, total cholesterol, triglycerides, H-DLC, L DLC and other indexes between female and male. No difference was found in the family history of hypertension, renal damage, blood uric acid, triglycerides and H-DLC among the different blood pressure levels. CONCLUSIONS: The hypertension in health examination population has the features of high new discovery rate, low awareness rate and low treatment rate. The factors of age, gender, body mass index, serum creatinine, blood glucose, blood cholesterol, L-DLC, coronary heart disease, stroke and diabetes are associated closely with hypertension. PMID- 24179573 TI - Effect of melatonin on kidney cold ischemic preservation injury. AB - Melatonin is a potent free radical scavenger of reactive oxygen species, nitric oxide synthase inhibitor and a well-known antioxidant secreted from pineal gland. This hormone has been reported to protect tissue from oxidative damage. In this study, we aim to investigate the effect of melatonin on kidney cold ischemia time when added to preservation solution. Thirty male Wistar albino rats were divided equally into three groups; Ringer Lactate (RL) solution, University of Wisconsin (UW) solution with and without melatonin. The serum Lactate Dehydrogenase (LDH) activities of the preservation solutions at 2(nd), 24(th), 36(th), and 48(th) hours were determined. Tissue malondialdehyde (MDA) levels were also measured and a histological examination was performed at 48(th) hour. Melatonin that added to preservation solution prevented enzyme elevation and decreased lipid peroxidation in preservation solution when compared to the control group (p<0.05). The histological examination revealed that UW solution containing melatonin significantly prevented the kidney from pathological injury (p<0.05). Melatonin added to preservation solutions such as UW solution seemed to protect the tissue preserved effectively from cold ischemic injury for up to 48 hour. PMID- 24179574 TI - Prevalence of stress hyperglycemia among hepatopancreatobiliary postoperative patients. AB - OBJECTIVE: The aim of this study was to determine the prevalence of stress hyperglycemia and its association with mortality among hepatopancreatobiliary postoperative patients admitted. METHODS: Retrospectively analysis was made on 706 cases of the hepatopancreatobiliary postoperative patients from three Grade A hospitals in Hunan province from November 2011 to June 2012, including the incidence and risk factors of patients with stress hyperglycemia. RESULTS: The incidence of stress hyperglycemia of pancreatic postoperative patients was 34.28%. The incidence of pancreatic surgery, simple cholecystectomy and biliary tract and liver surgery in patients with stress hyperglycemia was 63.08%, 20.83% and 32.21%, respectively. Stress hyperglycemia was associated with the first postoperative glucose values, duration of surgery, whether the anemia and the presence or absence of hypoproteinemia (P<0.05), but was no related with sex, weight and previous history (P>0.05). CONCLUSION: Stress hyperglycemia is common among emergency admissions and these patients have significantly higher mortality rate compared to other patients (P=0.001). Postoperative first blood glucose levels, duration of surgery, whether the anemia and the presence or absence of hypoproteinemia were stress hyperglycemia risk factors for patients. PMID- 24179575 TI - The prevalence of fibromyalgia among patients with hepatitis B virus infection. AB - Fibromyalgia (FM) is a syndrome characterized by widespread and chronic musculoskeletal pain, fatigue, morning stiffness, and sleep disturbance. However, the etiopathogenesis of FM remains unclear. Various etiological factors have been suggested to trigger FM. These include systemic rheumatismal disease, physical trauma, psychological disorders, and chronic infections. We determined the prevalence of FM in patients with chronic active hepatitis B virus (HBV) and inactive hepatitis B carriers, compared with matched healthy controls. Seventy seven HBV patients (39 HBV carriers and 38 with chronic active hepatitis), were evaluated for FM syndrome. Seventy-seven HBsAg-negative healthy subjects were enrolled as a control group. We found that FM was very prevalent in patients with HBV infections (22% of the total). We found no difference in FM prevalence when patients with chronic active hepatitis B infections (21% FM prevalence) and those who were inactive hepatitis B carriers (23% FM prevalence) were compared. FM was not associated with the levels of HBV-DNA, ALT, or AST. Recognition and management of FM in HBsAg-positive patients will aid in improvement of quality-of life. We fully accept that our preliminary results require confirmation in studies including larger numbers of patients. More work is needed to allow us to understand the role played by, and the relevance of, infections (including HBV) in FM syndrome pathogenesis. PMID- 24179576 TI - Effect of laryngoscopy on middle ear pressure during anaesthesia induction. AB - AIMS: The procedure of laryngoscopic orotracheal intubation (LOTI) has many impacts on several parts of the body. But its effect on middle ear pressure (MEP) is not known well. The purpose of this study is to evaluate the MEP changes subsequent to insertion of endotracheal tube with laryngoscope. SUBJECTS AND METHODS: 44 patients were included in this study with a normal physical examination of ear, nose and throat. A standard general anaesthesia induction without any inhaler agent was performed to the all patients. The MEP measurements for both ears were applied under 1 minute; before induction (BI) and after intubation (AI) with a middle ear analyzer. Also hemodynamic parameters were recorded before induction and after intubation. RESULTS: Of the 44 patients were 25 women and 19 men with a 43.5+/-15.1 mean age. A statistically significant rise in MEP was seen in all patients subsequent to insertion of endotracheal tube (P<0.05). Mean right MEPs were BI: -9.5 and AI: 18.5 daPa. Also mean left MEPs were BI: -21.7 and AI: 29.1 daPa. The amount of increases in left and right MEPs were 50 daPa and 27 daPa, respectively. 20% increase in systolic blood pressure and 19% increase in diastolic blood pressure were determined after intubation. The mean heart rate was 76/min before intubation, whereas it was 102/min after intubation with a 34% increase. CONCLUSION: In this study bilateral significant increases in MEP were determined subsequent to LOTI. Possible factors affecting MEP may be auditory tube, size and type of the blades, drugs and face masking time. But on the other hand in our opinion cardiovascular and haemodynamic response to LOTI has the most impact over the middle ear mucosa with mucosal venous congestion. PMID- 24179577 TI - Multidisciplinary management of multiple spinal dural arteriovenous fistulae. AB - Multiple SDAVFs are quite rare. We present two cases with double synchronous shunts and both were treated during one-stage interventional or surgical procedure. Unique images of the multiple SDAVFs as a PMAVF-like fistula were obtained. These interesting findings suggest the presence of multiple fistulas must be considered in patients being evaluated for SDAVF. A multidisciplinary approach to the management of multiple SDAVFs should depend on the anatomic location and angioarchitecture. PMID- 24179578 TI - Combined treatment for cutaneous Rosai-Dorfman disease: a report of 2 cases. AB - We report 2 cases of cutaneous Rosai-Dorfman disease (CRDD). One was a 46-year old Chinese woman who presented with a 10-year history of multiple papules and nodules on the left cheek. Another one was a 57-year-old Chinese woman who presented with a 7-month history of erythematous pruritic plaque on the Dorsum nasi. Their lesions consisted of proliferative large histiocytes occasionally showing emperipolesis. Immunohistochemistry showed these histiocytes were positive for CD68 and S-100, but negative for CD1a. A diagnosis of CRDD was made. Their lesions were improved after intralesional treatment with Compound Betamethasone, interferon and acitretin. To our knowledge, we for the first time reported the application of intralesional Compound Betamethasone and Lidocaine, intramuscular injection of interferon, and oral acitretin in the treatment of CRDD, and favorable outcome was achieved without recurrence over a 1-year follow up period. PMID- 24179579 TI - Metachronous pancreatic head ductal carcinoma three years after resection of gallbladder cancer. AB - We report a rare case of female patient with metachronous gallbladder cancer and pancreatic head ductal carcinoma. At the age of 53 years, the patient underwent a cholecystectomy and resection of the liver bed for gallbladder cancer. The post operation diagnosis was a well-differentiated adenocarcinoma with serosa involvement(T3N0M0, stage IIA). Three years later, an irregular and enhanced 2.4 cm mass in the pancreatic head with obviously pancreatic duct dilated was found by abdominal imaging. We considered it as pancreatic head cancer and performed pancreaticoduodenectomy. The histological diagnosis was a pancreatic ductal carcinoma (T2N0M0, stage I). No recurrence was found after thirty-three months follow up. PMID- 24179580 TI - Diagnosis and treatment of extra-adrenal pheochromocytoma of urinary bladder: case report and literature review. AB - Pheochromocytoma of the urinary bladder is often misdiagnosed as it is a rare tumor. In this report, we described a case with primary pheochromocytoma of the urinary bladder. We specifically conversed the diagnostic role of X-ray computed tomography and sonography to identify the location of tumor within urinary bladder compared to other malignant or benign tumors in the bladder, and exclude other ectopic pheochromocytoma. Histopathological report from bladder tissue biopsy was confirmative of extra adrenal pheochromocytoma of the urinary bladder finally. Importance in careful management of hypertensive crisis during cystoscope and partial cystectomy was addressed. PMID- 24179581 TI - Facial and cervical emphysema after oral surgery: a rare case. AB - The purpose is to report extensive emphysema resulting from a common procedure in oral surgery. Surgical emphysema developed in a 23-year-old female after removal of a mandible third molar using a high-speed dental hand-piece. The patient was maintained in hospital room and submitted to a medical protocol with antibiotic treatment. Surgical emphysema is an uncommon but potentially serious complication of oral and maxillofacial surgery procedures. The diagnosis and differential diagnosis of surgical emphysema are discussed and the management and prevention of this complication is presented. Adequately treatment with adequately instrument should be providing in oral surgery. Emphysema has complication in oral surgery is a rare condition with future clinical and legal problem to surgeon. PMID- 24179582 TI - Diagnosis and treatment of hepatic tuberculosis: report of five cases and review of literature. AB - Hepatic tuberculosis is uncommon, lack of specific clinical manifestations and imaging features, so it can easily be misdiagnosed in clinical. Herein, we discuss variety of its forms and summarize the diagnosis and treatment of hepatic tuberculosis in this paper. Five cases of hepatic tuberculosis are described. The diagnosis, treatment and outcome of the patients are discussed. Image examination associated with image-guided fine needle aspiration biopsy is the best diagnostic method. In our center, three patients underwent needle biopsy and confirmed hepatic tuberculosis. In addition, two patients preoperative misdiagnosed as cholangiocarcinoma were confirmed hepatic tuberculosis by postoperative pathology. Three patients underwent surgical procedures along with anti tubercular drug therapy, two patients received only anti-tubercular drug therapy. The renal post-transplantation patient with hepatic tuberculosis eventually died of multiple organ failure (MODS). The other four patients were followed for 48~120 months, yielding no recurrence of hepatic tuberculosis. In conclusion, hepatic tuberculosis usually associated with atypical clinical manifestations. Image examination associated with image-guided fine needle aspiration biopsy is the best diagnostic method. Anti-TB treatment is effective in most of cases. However, if there are indications for surgery or difficult to diagnose, surgical procedures along with anti-tubercular drug therapy could be adopted. PMID- 24179583 TI - Treatment of ampullary neuroendocrine tumor by endoscopic snare papillectomy. AB - PATIENT: Female, 45 FINAL DIAGNOSIS: Neuroendocrine tumor Symptoms: Abdominal pain Medication: - Clinical Procedure: - Specialty: Gastroenterology and Hepatology. OBJECTIVE: Unusual setting of medical care. BACKGROUND: Neuroendocrine tumor of the ampulla of Vater is extremely rare and is generally a low-grade endocrine cell tumor. The merits of radical vs. local resection remain uncertain. CASE REPORT: A 45-year-old female patient presented with abdominal pain lasting for 2 months. Papilla that was tumor-like macroscopically was seen in the second part of the duodenum in endoscopic retrograde cholangiopancreatography. Biopsy was histologically confirmed as a low-grade neuroendocrine tumor. No lymphadenopathy or visceral metastasis was found on an abdominal CT scan, In-111 octreotide scan, and EUS. The ampulla was removed by endoscopic snare papillectomy. All margins of resection were negative for tumor. CONCLUSIONS: Endoscopic snare papillectomy may be the first step in the management of neuroendocrine tumors of the ampulla of Vater in high-risk surgical candidates and selected patients such as those with a well differentiated, low grade, small tumor without regional/ distant metastasis. However, it can also be used in younger patients who wish to avoid surgical resection. PMID- 24179584 TI - Return to play in athletes following ankle injuries. AB - BACKGROUND: The decision to return to play following an ankle injury is a multifactorial process involving both physical and psychological parameters. The current body of literature lacks evidence-based guidelines to assist in the decision. OBJECTIVE: THIS ARTICLE REVIEWS THE EVIDENCE TO SUPPORT SUCH TESTING: the dorsiflexion lunge test, star excursion balance test, agility T-test, and sargent/vertical jump test. The importance of psychological factors is also highlighted. EVIDENCE ACQUISITION: The primary literature search was conducted using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) with the search terms "ankle AND injury" and the following limits activated: English language. A secondary search was then conducted with the search terms "return to play" and "sport injuries and return to play." RESULTS: Various functional tests have been used to determine whether a patient is able to return to play following an ankle injury. This study documented four tests that have been used to assess range of motion, balance and proprioception, agility and strength and the reasoning as to why these tests are used. CONCLUSIONS: Functional testing provides objective measures for gauging an athlete's progression through the rehabilitation process. Testing balance and proprioception, strength, range of motion, and agility coupled with psychological assessment evaluates readiness for return to play. PMID- 24179585 TI - Ethical issues in sports medicine: a review and justification for ethical decision making and reasoning. AB - Ethical issues present a challenge for health care professionals working with athletes of sports teams. Health care professionals-including the team physician, the physical therapist, and the athletic trainer-are faced with the challenge of returning an athlete to competition as quickly as possible but as safely as possible. Conflicts of interest arise due to conflicting obligations of the team physician to the athlete and other members of the sports organization, including coaches and the team owner. The multiple stakeholders involved in sports teams challenge the traditional notion of confidentiality and autonomy. The aims of this article are to explicate the ethics of sports medicine, highlight the ethical issues, and provide some strategies and suggestions for ethical decision making. PMID- 24179586 TI - Is there evidence to support a forefoot strike pattern in barefoot runners? A review. AB - CONTEXT: Barefoot running is a trend among running enthusiasts that is the subject of much controversy. At this time, benefits appear to be more speculative and anecdotal than evidence based. Additionally, the risk of injuries is not well established. EVIDENCE ACQUISITION: A PubMed search was undertaken for articles published in English from 1980 to 2011. Additional references were accrued from reference lists of research articles. RESULTS: While minimal data exist that definitively support barefoot running, there are data lending support to the argument that runners should use a forefoot strike pattern in lieu of a heel strike pattern to reduce ground reaction forces, ground contact time, and step length. CONCLUSIONS: Whether there is a positive or negative effect on injury has yet to be determined. Unquestionably, more research is needed before definitive conclusions can be drawn. PMID- 24179589 TI - Scapular stress fracture in water polo: a case report. AB - Water polo is an intense sport with extreme physical contact and repetitive shoulder motion that predisposes to injury. The continuous scapular motion and recruitment of the scapular stabilizers to maintain buoyancy expose water polo athletes to the risk of scapular stress fracture. Suspicion should arise when evaluating water polo athletes presenting with shoulder pain. PMID- 24179588 TI - Sports health benefits of vitamin d. AB - CONTEXT: Vitamin D is a potent secosteroid hormone that provides many skeletal and extraskeletal health benefits. Musculoskeletal injury prevention and recovery are potentially affected by sufficient circulating levels of the storage form of vitamin D: 25-hydroxyvitamin D3, or 25(OH)D. Vitamin D deficiency can exist among young, active, and healthy people, which may put them at increased risk for injury and prolonged recovery. EVIDENCE AQUISITION: PubMed was searched using vitamin D and skeletal muscle, vitamin D and athletic performance, and vitamin D review articles. Studies from the 1930s to 2012 were used for the review. RESULTS: There is strong correlation between vitamin D sufficiency and optimal muscle function. Increasing levels of vitamin D reduce inflammation, pain, and myopathy while increasing muscle protein synthesis, ATP concentration, strength, jump height, jump velocity, jump power, exercise capacity, and physical performance. 25(OH)D levels above 40 ng/mL are required for fracture prevention, including stress fractures. Optimal musculoskeletal benefits occur at 25(OH)D levels above the current definition of sufficiency (> 30 ng/mL) with no reported sports health benefits above 50 ng/mL. CONCLUSIONS: Vitamin D deficiency is common in athletes. For athletes presenting with stress fractures, musculoskeletal pain, and frequent illness, one should have a heightened awareness of the additional likely diagnosis of vitamin D deficiency. Correction of this deficiency is completed by standardized and supervised oral supplementation protocols producing significant musculoskeletal sports health benefits. PMID- 24179587 TI - Common leg injuries of long-distance runners: anatomical and biomechanical approach. AB - CONTEXT: Long-distance running (greater than 3000 m) is often recommended to maintain a healthy lifestyle. Running injury rates increase significantly when weekly mileage extends beyond 40 miles cumulatively. With the development of running analysis and other diagnostic tests, injuries to the leg secondary to bone, musculotendinous, and vascular causes can be diagnosed and successfully managed. EVIDENCE ACQUISITION: Searches used the terms running, injuries, lower extremity, leg, medial tibial stress syndrome, compartment syndrome, stress fractures, popliteal artery entrapment, gastrocnemius soleus tears, and Achilles tendinopathy. Sources included Medline, Google Scholar, and Ovid from 1970 through January 2012. RESULTS: Tibial stress fractures and medial tibial stress syndrome can sometimes be prevented and/or treated by correcting biomechanical abnormalities. Exertional compartment syndrome and popliteal artery entrapment syndrome are caused by anatomic abnormalities and are difficult to treat without surgical correction. CONCLUSION: Leg pain due to bone, musculotendinous, and vascular causes is common among long-distance runners. Knowledge of the underlying biomechanical and/or anatomic abnormality is necessary to successfully treat these conditions. PMID- 24179590 TI - Time to return to play after high ankle sprains in collegiate football players: a prediction model. AB - BACKGROUND: Determining the severity of high ankle sprains in athletes and predicting the time that an athlete can return to unrestricted sport activities following this injury remain significant challenges. PURPOSE: The objectives of this study were (1) to determine if objective measurements of injury severity after high ankle sprains could predict the time to return to play in Division I football players and (2) to determine whether physical examination or diagnostic musculoskeletal ultrasound was more predictive of return to play. The hypothesis was that objective measures of injury severity of a high ankle sprain can be predictive of time to return to athletic participation in collegiate football players. STUDY DESIGN: Prospective case series. METHODS: Twenty consecutive Division I collegiate football players with a diagnosis of a grade I high ankle sprain (syndesmosis sprain without diastasis) were studied. Two clinical measurements of injury severity were determined: the height of the zone of injury on physical examination and the height of the zone of injury as defined by diagnostic musculoskeletal ultrasound examination. All athletes followed a standardized treatment program and return-to-play criteria. A regression model and Cox proportional hazards model were developed to determine time to return to unrestricted play as a function of injury severity and player position. RESULTS: Physical examination but not ultrasound was significantly correlated with time to return to play. Regression and Cox analyses revealed that injury severity on physical examination and player position were significant predictors of time to return to unrestricted play following high ankle sprain. CONCLUSIONS: Injury severity on physical examination and player position are associated with the time to return to unrestricted athletic activity after injury. A model based on the data can be applied to help predict the time to return to unrestricted play in Division I collegiate football players following high ankle sprain. PMID- 24179591 TI - Serum CTXii Correlates With Articular Cartilage Degeneration After Anterior Cruciate Ligament Transection or Arthrotomy Followed by Standardized Exercise. AB - BACKGROUND: Anterior cruciate ligament injury increases risk for accelerated development of osteoarthritis. The effect of exercise on articular cartilage following joint injury is not well understood. Biochemical biomarkers of collagen degradation and proteoglycan turnover are potential indicators for early articular cartilage degeneration. HYPOTHESIS: This study tests the hypothesis that serum concentrations of CS846 and CTXii correlate with structural changes to articular cartilage following joint injury in exercised animals. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-four Sprague-Dawley rats underwent either arthrotomy alone (sham surgery) or anterior cruciate ligament transection (ACLT). Animals were recovered for 3 weeks and then exercised on a treadmill at 18 m per minute, 1 hour per day, 5 days per week, until sacrifice either 6 or 12 weeks later. Articular cartilage was assessed grossly, and histology was graded using modified Mankin, toluidine blue, and modified David-Vaudey scales. Serum collected preoperatively and at sacrifice was assayed by ELISA for CTXii and CS846. RESULTS: At 6 weeks, gross grades (P < 0.01), modified Mankin scores (P < 0.03), and toluidine blue scores (P < 0.04) were higher, reflecting increased degeneration in ACLT animals compared with sham surgery animals. Serum CS846 increased after 6 weeks in ACLT animals (P < 0.05). Serum CTXii levels strongly correlated with Mankin degenerative scores (coefficient = 0.81, P < 0.01) and David-Vaudey histology grades (coefficient = 0.73, P < 0.01) at 6 weeks. While gross grades remained higher at 12 weeks in ACLT animals (P < 0.04), no differences were seen in serum CS846 and CTXii. Histology scores also showed no differences between ACLT and sham due to increasing degeneration in the sham surgery group. CONCLUSION: The strong correlation between serum CTXii and microstructural changes to articular cartilage following joint injury demonstrates potential use of serum biomarkers for early detection of cartilage degeneration. Increasing cartilage degeneration in exercised sham-surgery animals suggests that early loading may have negative effects on articular cartilage due to either mechanical injury or hemarthrosis after arthrotomy. CLINICAL RELEVANCE: Patients with anterior cruciate ligament injury are at increased risk for development of posttraumatic osteoarthritis. CTXii may be useful for early detection of joint degeneration. Further study on the effects of exercise after injury is important to postinjury and postoperative rehabilitation. PMID- 24179592 TI - Imaging of sports-related midfoot and forefoot injuries. AB - Sports-related injuries of the foot are common and may result in significant morbidity, particularly if inaccurate or delayed diagnosis leads to improper management. While less common than injuries of the ankle, sports-related foot injuries account for 2% to 18% of athletic injuries. Injury may occur as a result of acute trauma or chronic overuse, and high-impact sports that involve running, jumping, or contact place the athlete at higher risk for injury. Accurate and timely diagnosis of injury is the key to proper management, and diagnostic imaging studies often play a critical role in this regard. While radiographs, computerized tomography scans, and ultrasound are useful in the evaluation of the foot, magnetic resonance imaging provides superior tissue contrast as well as the ability to detect stress reaction in bone that precedes discernible fracture line on radiographs, allowing accurate detection of both osseous and soft tissue pathology. This review focuses on imaging of common sports-related injuries of the midfoot and forefoot, including osseous, ligamentous, and tendinous pathology, with emphasis on magnetic resonance imaging diagnosis. PMID- 24179593 TI - Magnetic resonance imaging as a predictor of return to play following syndesmosis (high) ankle sprains in professional football players. AB - BACKGROUND: Syndesmosis ankle sprains cause greater disability and longer duration of recovery than lateral ankle sprains. OBJECTIVE: To describe the severity of syndesmosis sprains using several accepted magnetic resonance imaging (MRI) criteria and to assess the interrater reliability of diagnosing syndesmosis injury using these same criteria in professional American football players. HYPOTHESIS: There is a high degree of interrater reliability of MRI findings in American football players with syndesmosis ankle sprains. These radiographic findings will correlate with time lost to injury, indicating severity of the sprain. STUDY DESIGN: Uncontrolled retrospective review. METHODS: Player demographics and time lost to play were recorded among professional football players who had sustained a syndesmosis ankle sprain and underwent standardized ankle MRI. Each image was independently read by 3 blinded musculoskeletal radiologists. RESULTS: Seventeen players met study criteria. There was almost perfect agreement among the radiologists for diagnosing injury to the syndesmotic membrane; substantial agreement for diagnosing injury to the posterior inferior tibiofibular ligament (PITFL) and in determining the proximal extent of syndesmotic edema/injury; but only fair agreement for diagnosing injury to the anterior inferior tibiofibular ligament and in determining the width of syndesmotic separation. There was a significant correlation between the width of syndesmotic separation and time lost, but no significant correlation between individual syndesmotic ligament injury or proximal extent of syndesmotic edema/injury and time lost. CONCLUSION: While ankle MRI can identify syndesmotic disruption with a high degree of interobserver agreement, no association was demonstrated between the extent of injury on MRI and the time to return to play following a high ankle sprain. CLINICAL RELEVANCE: In athletes with suspected high ankle sprains, MRI may help confirm diagnosis or suggest alternative diagnoses when the syndesmotic supporting structures are intact. However, the severity of ligamentous and syndesmotic disruption on MRI cannot help predict recovery times. PMID- 24179595 TI - E-PRESCRIBING AND PATIENT SAFETY: RESULTS FROM A MIXED METHOD STUDY. AB - OBJECTIVES: To describe ambulatory care clinicians' perspectives on the effect of e-prescribing systems on patient safety outcomes. STUDY DESIGN: We used a mixed method study of clinicians and staff in 64 practices using one of six e prescribing technologies in six U.S. states. METHODS: We used clinician surveys (web-based and paper) and focus groups to obtain clinicians' perspectives on e prescribing and patient safety. RESULTS: Providers highly valued having medications prescribed by other providers on the medication list and the ability to access patients' medication lists remotely. Providers felt that there will always be prescription or medication errors and that the implementation of e prescribing software changes rather than eliminates prescription or medication errors. New errors related to the dosing or scheduling of a medication, accidentally prescribing the wrong drug, or duplicate prescriptions. CONCLUSIONS: Lessons from the ambulatory care trenches must be considered as technology moves forward so that the hypothesized patient safety gains will be realized. PMID- 24179596 TI - Malaria Eradication in the Americas: A Retrospective Analysis of Childhood Exposure. AB - This study uses the malaria-eradication campaigns in the United States (circa 1920), and in Brazil, Colombia and Mexico (circa 1955) to measure how much childhood exposure to malaria depresses labor productivity. The campaigns began because of advances in health technology, which mitigates concerns about reverse causality. Malarious areas saw large drops in the disease thereafter. Relative to non-malarious areas, cohorts born after eradication had higher income as adults than the preceding generation. These cross-cohort changes coincided with childhood exposure to the campaigns rather than to pre-existing trends. Estimates suggest a substantial, though not predominant, role for malaria in explaining cross-region differences in income. PMID- 24179597 TI - Systematic Redaction for Neuroimage Data. AB - In neuroscience, collaboration and data sharing are undermined by concerns over the management of protected health information (PHI) and personal identifying information (PII) in neuroimage datasets. The HIPAA Privacy Rule mandates measures for the preservation of subject privacy in neuroimaging studies. Unfortunately for the researcher, the management of information privacy is a burdensome task. Wide scale data sharing of neuroimages is challenging for three primary reasons: (i) A dearth of tools to systematically expunge PHI/PII from neuroimage data sets, (ii) a facility for tracking patient identities in redacted datasets has not been produced, and (iii) a sanitization workflow remains conspicuously absent. This article describes the XNAT Redaction Toolkit-an integrated redaction workflow which extends a popular neuroimage data management toolkit to remove PHI/PII from neuroimages. Quickshear defacing is also presented as a complementary technique for deidentifying the image data itself. Together, these tools improve subject privacy through systematic removal of PII/PHI. PMID- 24179598 TI - Advances in homology directed genetic engineering of human pluripotent and adult stem cells. AB - The ability to introduce precise genomic modifications in human cells has profound implications for both basic and applied research in stem cells, ranging from identification of genes regulating stem cell self-renewal and multilineage differentiation to therapeutic gene correction and creation of in vitro models of human diseases. However, the overall efficiency of this process is challenged by several factors including inefficient gene delivery into stem cells and low rates of homology directed site-specific targeting. Recent studies report the development of novel techniques to improve gene targeting efficiencies in human stem cells; these methods include molecular engineering of viral vectors to efficiently deliver episomal genetic sequences that can participate in homology directed targeting, as well as the design of synthetic proteins that can introduce double-stranded breaks in DNA to initiate such recombination events. This review focuses on the potential of these new technologies to precisely alter the human stem cell genome and also highlights the possibilities offered by the combination of these complementary strategies. PMID- 24179599 TI - New insights for pelvic radiation disease treatment: Multipotent stromal cell is a promise mainstay treatment for the restoration of abdominopelvic severe chronic damages induced by radiotherapy. AB - Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumor. It has been reported that the majority of patients receiving pelvic radiation therapy show early or late tissue reactions of graded severity as radiotherapy affects not only the targeted tumor cells but also the surrounding healthy tissues. The late adverse effects of pelvic radiotherapy concern 5% to 10% of them, which could be life threatening. However, a clear medical consensus concerning the clinical management of such healthy tissue sequelae does not exist. Although no pharmacologic interventions have yet been proven to efficiently mitigate radiotherapy severe side effects, few preclinical researches show the potential of combined and sequential pharmacological treatments to prevent the onset of tissue damage. Our group has demonstrated in preclinical animal models that systemic mesenchymal stromal cell (MSC) injection is a promising approach for the medical management of gastrointestinal disorder after irradiation. We have shown that MSCs migrate to damaged tissues and restore gut functions after irradiation. We carefully studied side effects of stem cell injection for further application in patients. We have shown that clinical status of four patients suffering from severe pelvic side effects resulting from an over dosage was improved following MSC injection in a compationnal situation. PMID- 24179600 TI - Regenerative medicine based applications to combat stress urinary incontinence. AB - Stress urinary incontinence (SUI), as an isolated symptom, is not a life threatening condition. However, the fear of unexpected urine leakage contributes to a significant decline in quality of life parameters for afflicted patients. Compared to other forms of incontinence, SUI cannot be easily treated with pharmacotherapy since it is inherently an anatomic problem. Treatment options include the use of bio-injectable materials to enhance closing pressures, and the placement of slings to bolster fascial support to the urethra. However, histologic findings of degeneration in the incontinent urethral sphincter invite the use of tissues engineering strategies to regenerate structures that aid in promoting continence. In this review, we will assess the role of stem cells in restoring multiple anatomic and physiological aspects of the sphincter. In particular, mesenchymal stem cells and CD34(+) cells have shown great promise to differentiate into muscular and vascular components, respectively. Evidence supporting the use of cytokines and growth factors such as hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and insulin-like growth factor further enhance the viability and direction of differentiation. Bridging the benefits of stem cells and growth factors involves the use of synthetic scaffolds like poly (1,8 octanediol-co-citrate) (POC) thin films. POC scaffolds are synthetic, elastomeric polymers that serve as substrates for cell growth, and upon degradation, release growth factors to the microenvironment in a controlled, predictable fashion. The combination of cellular, cytokine and scaffold elements aims to address the pathologic deficits to urinary incontinence, with a goal to improve patient symptoms and overall quality of life. PMID- 24179601 TI - Engineering stem cell niches in bioreactors. AB - Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as "niches", to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/autocrine signaling and physical forces (i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering. PMID- 24179602 TI - Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts. AB - Bone is a dynamic tissue that is constantly renewed by the coordinated action of two cell types, i.e., the bone-resorbing osteoclasts and the bone-forming osteoblasts. However, in some circumstances, bone regeneration exceeds bone self repair capacities. This is notably often the case after bone fractures, osteolytic bone tumor surgery, or osteonecrosis. In this regard, bone tissue engineering with autologous or allogenic mesenchymal stem cells (MSCs) is been widely developed. MSCs can be isolated from bone marrow or other tissues such as adipose tissue or umbilical cord, and can be implanted in bone defects with or without prior amplification and stimulation. However, the outcome of most pre clinical studies remains relatively disappointing. A better understanding of the successive steps and molecular mechanisms involved in MSC-osteoblastic differentiation appears to be crucial to optimize MSC-bone therapy. In this review, we first present the important growth factors that stimulate osteoblastogenesis. Then we review the main transcription factors that modulate osteoblast differentiation, and the microRNAs (miRs) that inhibit their expression. Finally, we also discuss articles dealing with the use of these factors and miRs in the development of new bone MSC therapy strategies. We particularly focus on the studies using human MSCs, since significant differences exist between osteoblast differentiation mechanisms in humans and mice for instance. PMID- 24179603 TI - Aiming to immune elimination of ovarian cancer stem cells. AB - Ovarian cancer accounts for only 3% of all cancers in women, but it causes more deaths than any other gynecologic cancer. Treatment with chemotherapy and cytoreductive surgery shows a good response to the therapy. However, in a large proportion of the patients the tumor grows back within a few years. Cancer stem cells, that are less responsive to these treatments, are blamed for this recurrence of disease. Immune therapy either cellular or humoral is a novel concept to treat cancer. It is based on the notice that immune cells invade the tumor. However, the tumor invest heavily to escape from immune elimination by recruiting several immune suppressive mechanisms. These processes are normally in place to limit excessive immune activation and prevent autoimmune phenomena. Here, we discuss current knowledge about the immune (suppressive) status in ovarian cancer. Moreover, we discuss the immunological targets of ovarian cancer stem cells. PMID- 24179604 TI - Regenerative therapy for neuronal diseases with transplantation of somatic stem cells. AB - Pluripotent stem cells, which are capable of differentiating in various species of cells, are hoped to be donor cells in transplantation in regenerative medicine. Embryonic stem (ES) cells and induced pluripotent stem cells have the potential to differentiate in approximately all species of cells. However, the proliferating ability of these cells is high and the cancer formation ability is also recognized. In addition, ethical problems exist in using ES cells. Somatic stem cells with the ability to differentiate in various species of cells have been used as donor cells for neuronal diseases, such as amyotrophic lateral sclerosis, spinal cord injury, Alzheimer disease, cerebral infarction and congenital neuronal diseases. Human mesenchymal stem cells derived from bone marrow, adipose tissue, dermal tissue, umbilical cord blood and placenta are usually used for intractable neuronal diseases as somatic stem cells, while neural progenitor/stem cells and retinal progenitor/stem cells are used for a few congenital neuronal diseases and retinal degenerative disease, respectively. However, non-treated somatic stem cells seldom differentiate to neural cells in recipient neural tissue. Therefore, the contribution to neuronal regeneration using non-treated somatic stem cells has been poor and various differential trials, such as the addition of neurotrophic factors, gene transfer, peptide transfer for neuronal differentiation of somatic stem cells, have been performed. Here, the recent progress of regenerative therapies using various somatic stem cells is described. PMID- 24179606 TI - Epithelial-mesenchymal transition - activating transcription factors - multifunctional regulators in cancer. AB - The process of epithelial to mesenchymal transition (EMT), first noted during embryogenesis, has also been reported in tumor formation and leads to the development of metastatic growth. It is a naturally occurring process that drives the transformation of adhesive, non-mobile epithelial like cells into mobile cells with a mesenchymal phenotype that have ability to migrate to distant anatomical sites. Activating complex network of embryonic signaling pathways, including Wnt, Notch, hedgehog and transforming growth factor-beta pathways, lead to the upregulation of EMT activating transcription factors, crucial for normal tissue development and maintenance. However, deregulation of tightly regulated pathways affecting the process of EMT has been recently investigated in various human cancers. Given the critical role of EMT in metastatic tumor formation, better understanding of the mechanistic regulation provides new opportunities for the development of potential therapeutic targets of clinical importance. PMID- 24179607 TI - Mobilization of CD34(+)CD38(-) hematopoietic stem cells after priming in acute myeloid leukemia. AB - AIM: To evaluate quantitatively and qualitatively the different CD34(+) cell subsets after priming by chemotherapy granulocyte colony-stimulating factor (+/- G-CSF) in patients with acute myeloid leukemia. METHODS: Peripheral blood and bone marrow samples were harvested in 8 acute myeloid leukemia patients during and after induction chemotherapy. The CD34/CD38 cell profile was analyzed by multi-parameter flow cytometry. Adhesion profile was made using CXC chemokine receptor 4 (CXCR4) (CD184), VLA-4 (CD49d/CD29) and CD47. RESULTS: Chemotherapy +/ G-CSF mobilized immature cells (CD34(+)CD38(-) population), while the more mature cells (CD34(+)CD38(low) and CD34(+)CD38(+) populations) decreased progressively after treatment. Circulating CD34(+) cells tended to be more sensitive to chemotherapy after priming with G-CSF. CD34(+) cell mobilization was correlated with a gradual increase in CXCR4 and CD47 expression, suggesting a role in cell protection and the capacity of homing back to the marrow. CONCLUSION: Chemotherapy +/- G-CSF mobilizes into the circulation CD34(+) bone marrow cells, of which, the immature CD34(+)CD38(-) cell population. Further manipulations of these interactions may be a means with which to control the trafficking of leukemia stem cells to improve patients' outcomes. PMID- 24179605 TI - MicroRNAs as novel regulators of stem cell fate. AB - Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineage-specific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineage-specific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells. Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted. PMID- 24179608 TI - Human adipose tissue contains erythroid progenitors expressing fetal hemoglobin. AB - AIM: To investigate the origin of hematopoietic progenitors contained in the stromal vascular fraction (SVF) of human adipose tissue. METHODS: Tissue samples obtained from lipectomies were subjected to enzymatic digestion with collagenase to obtain a single-cell suspension. The centrifuged cell pellet, termed SVF, was separated immunomagnetically into CD45(+) and CD45(-) cells and cultured in serum free medium containing hematopoietic cytokines. The freshly isolated and cultured cells were evaluated to determine their ability to form hematopoietic colony forming units in clonogenic assays and for the expression of certain hematopoietic transcription factors by reverse transcription-polymerase chain reaction; the gene expression level was compared to that in CD34(+) hematopoietic progenitor cells from cord blood (CB) and adult peripheral blood (PB). To characterize erythroid progenitors, burst-forming units-erythroid (BFU-E) were developed in a semisolid medium under different culture conditions, and the hemoglobin composition and globin gene expression in the erythroid colonies were determined. RESULTS: The transcription factors SCL/TAL1, RUNX1, RUNX2 and GATA2 were expressed in both the CD45(+) and CD45(-) SVF populations; however, in contrast to our observations in the CD34(+) cells from CB and adult PB, GATA1 was not detected. Nevertheless, GATA1 could be detected in the SVF cells after seven days in culture, whereas its expression was upregulated in the CB CD34(+) cells. The analysis of BFU-E-derived colonies revealed that virtually all erythroid cells produced by SVF cells expressed fetal hemoglobin, and the gamma-globin mRNA levels ranged between those obtained in the adult- and neonatal-derived erythroid cells. Moreover, the SVF-derived erythroid cells synthesized similar levels of alpha- and beta-globin mRNA, whereas the alpha-globin transcript levels were consistently higher those of beta-globin in the cells derived from CB or PB CD34(+) cells. Furthermore, although the cellular distribution of hemoglobin in the erythroid cells derived from the CD34(+) cells obtained from hematopoietic tissues was dependent on the presence or absence of serum in the culture medium, this did not affect the SVF-derived erythroid cells. CONCLUSION: Our results demonstrate that hematopoietic progenitors in SVF have molecular and functional features that differ from those exhibited by circulating progenitors, suggesting the possibility of a different origin. PMID- 24179609 TI - Insulin producing cells established using non-integrated lentiviral vector harboring PDX1 gene. AB - AIM: To investigate reprogramming of human adipose tissue derived stem cells into insulin producing cells using non-integrated lentivirus harboring PDX1 gene. METHODS: In this study, human adipose tissue derived stem cells (hADSCs) were obtained from abdominal adipose tissues by liposuction, selected by plastic adhesion, and characterized by flow cytometric analysis. Human ADSCs were differentiated into adipocytes and osteocytes using differentiating medium to confirm their multipotency. Non-integrated lentiviruses harboring PDX1 (Non integrated LV-PDX1) were constructed using specific plasmids (pLV-HELP, pMD2G, LV 105-PDX1-1). Then, hADSCs were transduced with non-integrated LV-PDX1. After transduction, ADSCs(PDX1+) were cultured in high glucose DMEM medium supplement by B27, nicotinamide and betaFGF for 21 d. Expressions of PDX1 and insulin were detected at protein level by immunofluorescence analysis. Expressions of PDX1, neurogenin3 (Ngn3), glucagon, glucose transporter2 (Glut2) and somatostatin as specific marker genes were investigated at mRNA level by quantitative RT-PCR. Insulin secretion of hADSCs(PDX1+) in the high-glucose medium was detected by electrochemiluminescence test. Human ADSCs(PDX1+) were implanted into hyperglycemic rats. RESULTS: Human ADSCs exhibited their fibroblast-like morphology and made colonies after 7-10 d of culture. Determination of hADSCs identified by FACS analysis showed that hADSCs were positive for mesenchymal cell markers and negative for hematopoietic cell markers that guaranteed the lack of hematopoietic contamination. In vitro differentiation of hADSCs into osteocytes and adipocytes were detected by Alizarin red and Oil red O staining and confirmed their multilineage differentiation ability. Transduced hADSCs(+PDX1) became round and clusters in the differentiation medium. The appropriate expression of PDX1 and insulin proteins was confirmed using immunocytochemistry analysis. Significant expressions of PDX1, Ngn3, glucagon, Glut2 and somatostatin were detected by quantitative RT-PCR. hADSCs(PDX1+) revealed the glucose sensing ability by expressing Glut2 when they were cultured in the medium containing high glucose concentration. The insulin secretion of hADSCs(PDX1+) in the high glucose medium was 2.32 MUU/mL. hADSCs(PDX1+) implantation into hyperglycemic rats cured it two days after injection by reducing blood glucose levels from 485 mg/dL to the normal level. CONCLUSION: Human ADSCs can differentiate into IPCs by non integrated LV-PDX1 transduction and have the potential to be used as a resource in type 1 diabetes cell therapy. PMID- 24179610 TI - Neural stem cells isolated from amyloid precursor protein-mutated mice for drug discovery. AB - AIM: To develop an in vitro model based on neural stem cells derived from transgenic animals, to be used in the study of pathological mechanisms of Alzheimer's disease and for testing new molecules. METHODS: Neural stem cells (NSCs) were isolated from the subventricular zone of Wild type (Wt) and Tg2576 mice. Primary and secondary neurosphere generation was studied, analysing population doubling and the cell yield per animal. Secondary neurospheres were dissociated and plated on MCM Gel Cultrex 2D and after 6 d in vitro (DIVs) in mitogen withdrawal conditions, spontaneous differentiation was studied using specific neural markers (MAP2 and TuJ-1 for neurons, GFAP for astroglial cells and CNPase for oligodendrocytes). Gene expression pathways were analysed in secondary neurospheres, using the QIAGEN PCR array for neurogenesis, comparing the Tg2576 derived cell expression with the Wt cells. Proteins encoded by the altered genes were clustered using STRING web software. RESULTS: As revealed by 6E10 positive staining, all Tg2576 derived cells retain the expression of the human transgenic Amyloid Precursor Protein. Tg2576 derived primary neurospheres show a decrease in population doubling. Morphological analysis of differentiated NSCs reveals a decrease in MAP2- and an increase in GFAP-positive cells in Tg2576 derived cells. Analysing the branching of TuJ-1 positive cells, a clear decrease in neurite number and length is observed in Tg2576 cells. The gene expression neurogenesis pathway revealed 11 altered genes in Tg2576 NSCs compared to Wt. CONCLUSION: Tg2576 NSCs represent an appropriate AD in vitro model resembling some cellular alterations observed in vivo, both as stem and differentiated cells. PMID- 24179611 TI - Chemoprevention of hepatocellular carcinoma in patients with hepatitis C virus related cirrhosis. AB - Interferon (IFN) therapy has been reported to decrease the risk of hepatocellular carcinoma (HCC) and improve survival by preventing liver-related deaths in patients with chronic hepatitis C virus (HCV) infection, while the role of IFN therapy on the natural history of hepatitis C related cirrhosis is still under debate. The ideal goal of therapy is to prevent the progression into end-stage disease. The use of IFN in patients with HCV compensated cirrhosis reduces the negative clinical evolution independently of the type of laboratoristic and virological response. In our experience, IFN therapy in HCV compensated cirrhosis is barely useful in prevention of HCC, as cirrhosis itself represents a risk of cancer. Some authors noted that IFN treatment reduces the risk of HCC independently of the virological response. It would probably be interesting to evaluate the efficacy of weekly low-dose pegylated (PEG)-IFN therapy in patients with HCV cirrhosis and to assess potential benefits of long-term PEG-IFN plus Ribavirin treatment. PMID- 24179613 TI - Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury. AB - The activation of heme oxygenase-1 (HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection. In addition, the products of the HO catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload (with signs of a chronic hepatitis) and iron deficiency anemia (with paradoxical increased levels of ferritin). Hypoxia induces HO-1 expression in multiple rodent, bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types (endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury. PMID- 24179612 TI - Chronic HCV infection and inflammation: Clinical impact on hepatic and extra hepatic manifestations. AB - The liver has a central role in regulating inflammation by its capacity to secrete a number of proteins that control both local and systemic inflammatory responses. Chronic inflammation or an exaggerated inflammatory response can produce detrimental effects on target organs. Chronic hepatitis C virus (HCV) infection causes liver inflammation by complex and not yet well-understood molecular pathways, including direct viral effects and indirect mechanisms involving cytokine pathways, oxidative stress and steatosis induction. An increasing body of evidence recognizes the inflammatory response in chronic hepatitis C as pathogenically linked to the development of both liver-limited injury (fibrosis, cirrhosis and hepatocellular carcinoma) and extrahepatic HCV related diseases (lymphoproliferative disease, atherosclerosis, cardiovascular and brain disease). Defining the complex mechanisms of HCV-induced inflammation could be crucial to determine the global impact of infection, to estimate progression of the disease, and to explore novel therapeutic approaches to avert HCV-related diseases. This review focuses on HCV-related clinical conditions as a result of chronic liver and systemic inflammatory states. PMID- 24179614 TI - Lipotoxicity in the liver. AB - Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21(st) century. With the increasing prevalence of obesity, non-alcoholic fatty liver disease is also emerging as a pandemic. While previously this pathophysiological condition was mainly attributed to triglyceride accumulation in hepatocytes, recent data show that the development of oxidative stress, lipid peroxidation, cell death, inflammation and fibrosis are mostly due to accumulation of fatty acids, and the altered composition of membrane phospholipids. In fact, triglyceride accumulation might play a protective role, and the higher toxicity of saturated or trans fatty acids seems to be the consequence of a blockade in triglyceride synthesis. Increased membrane saturation can profoundly disturb cellular homeostasis by impairing the function of membrane receptors, channels and transporters. However, it also induces endoplasmic reticulum stress via novel sensing mechanisms of the organelle's stress receptors. The triggered signaling pathways in turn largely contribute to the development of insulin resistance and apoptosis. These findings have substantiated the lipotoxic liver injury hypothesis for the pathomechanism of hepatosteatosis. This minireview focuses on the metabolic and redox aspects of lipotoxicity and lipoapoptosis, with special regards on the involvement of endoplasmic reticulum stress responses. PMID- 24179615 TI - Rapid chromatographic method to decipher distinct alterations in lipid classes in NAFLD/NASH. AB - AIM: To establish a simple method to quantify lipid classes in liver diseases and to decipher the lipid profile in p62/IMP2-2/IGF2BP2-2 transgenic mice. METHODS: Liver-specific overexpression of the insulin-like growth factor 2 mRNA binding protein p62/IMP2-2/IGF2BP2-2 was used as a model for steatosis. Steatohepatitis was induced by feeding a methionine-choline deficient diet. Steatosis was assessed histologically. For thin layer chromatographic analysis, lipids were extracted from freeze-dried tissues by hexane/2-propanol, dried, redissolved, and chromatographically separated by a two-solvent system. Dilution series of lipid standards were chromatographed, detected, and quantified. The detection was performed by either 2',7'-dichlorofluoresceine or a sulfuric acid/ethanol mixture. RESULTS: Histological analyses confirmed steatosis and steatohepatitis development. The extraction, chromatographic, and detection method showed high inter-assay reproducibility and allowed quantification of the different lipid classes. The analyses confirmed an increase of triglycerides and phosphatidylethanolamine and a decrease in phosphatidylcholine in the methionine choline deficient diet. The method was used for the first time to asses the lipid classes induced in the p62-overexpressing mouse model and showed a significant increase in all detected lipid species with a prominent increase of triglycerides by 2-fold. Interestingly, the ratio of phosphatidylcholine to phosphatidylethanolamine was decreased, as previously suggested as a marker in the progression from steatosis to steatohepatitis. CONCLUSION: The thin layer chromatography analysis allows a reliable quantification of lipid classes and provides detailed insight into the lipogenic effect of p62. PMID- 24179616 TI - Presence of disease specific autoantibodies against liver sinusoidal cells in primary biliary cirrhosis. AB - AIM: To investigate the presence of autoantibodies directed against liver sinusoidal cells in primary biliary cirrhosis (PBC). METHODS: Liver biopsies from 21 PBC patients were studied and compared with 12 liver biopsies from disease controls [3 patients with hepatitis B (HBV) virus, 3 patients with hepatitis C virus (HCV), 3 patients with non-alcoholic steatohepatitis and 3 patients with acute alcoholic hepatitis (AAH)]. As healthy controls, we used tissue specimens adjacent to metastatic liver adenocarcinoma. Normal serum was taken from staff members of the unit. The determination of the cell type targeted by autoantibodies present in the patients sera was performed by indirect immunofluorescence (IIF) analysis using paraffin-embedded liver sections as a substrate. Sera from homologous or heterologous PBC patients or sera from the disease control group were used as primary antibodies. The presence of autoantibodies was identified using confocal microscopy. RESULTS: In total, 18/21 (85.7%) PBC patients exhibited positive staining in the sinusoidal cells, 10/21 (47.6%) in lymphocytes, 8/21 (38%) in cholangiocytes and 7/21 (33.3%) in hepatocytes, when homologous serum and fluorescein isothiocyanate-conjugated immunoglobulin type G (IgG) secondary antibody were used. PBC sections incubated with heterologous PBC serum showed reduced staining (20% for sinusoidal cells, 20% for lymphocytes, 20% for cholangiocytes and 13.3% for hepatocytes). When IgM immunoglobulin, instead of IgG, was used as secondary antibody, positive staining was observed in 75% of lymphocytes, 62.5% of cholangiocytes, 37.5% of hepatocytes and 50% of the sinusoidal cells with a much stronger staining intensity. No staining was observed when either normal or PBC sera were used as a primary antibody on liver sections from the disease control group. When PBC sera were incubated with healthy control sections, weak positive staining of cholangiocytes was observed in 3/21 (14.3%) PBC serum samples. Steatohepatitis serum on PBC sections gave a positive staining of some hepatocytes and lymphocytes but no staining on viral hepatitis sections. Incubation with HBV sera stained some hepatocytes, cholangiocytes and intra-sinusoidal or portal lymphocytes of PBC, HBV and AAH patients but not HCV patients. CONCLUSION: In this study, for the first time in diseased liver tissue, we have demonstrated that a large proportion of PBC patients have disease specific autoantibodies against liver sinusoidal cells. PMID- 24179617 TI - Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome. AB - AIM: To present the characteristics, management and outcome of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections concurrent with primary biliary cirrhosis (PBC). METHODS: Since January 2001 to September 2009, we retrospectively evaluated the medical records of all HBV (n = 1493) and HCV patients (n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC (8 HCV and PBC; follow-up: 61 +/- 37 mo and 9 HBV and PBC; follow-up: 57 +/- 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC. RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients, while one third (5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV (56.1 +/- 11.2 vs 68.5 +/- 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics (10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency (87.5% vs 33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up. CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC. PMID- 24179618 TI - Risk factors for liver fibrosis among human immunodeficiency virus monoinfected patients using the FIB4 index in Morocco. AB - AIM: To study the prevalence and risk factors of significant hepatic fibrosis in Moroccan human immunodeficiency virus (HIV) monoinfected patients. METHODS: We conducted a cross-sectional study among HIV monoinfected patients (negative for hepatitis B surface antigen and hepatitis C antibody). Clinical and laboratory data were collected from the data base of the Infectious Diseases Unit in Ibn Rochd Hospital Center [age, gender, duration of HIV infection, CD4 T lymphocyte count, HIV viral load, glycemia and current or prior use of antiretroviral and antiretroviral therapy (ART) duration]. The primary outcome was a FIB4 score > 1.45. Multivariable logistic regression identified independent risk factors for FIB4 > 1.45. RESULTS: A FIB4 score > 1.45 was identified in 96 among 619 (15.5%). HIV monoinfected patients followed up between September 1990 and September 2012. Multivariate analysis showed that only a viral load > 75 (OR = 2.23, 95%CI: 1.36 3.67), CD4 > 200 cells/mm(3) (OR = 0.39, 95%CI: 0.21-0.72) and age at FIB4 index calculation (OR = 1.10, 95%CI: 1.07-1.13) were independently associated with the occurrence of FIB4 index (> 1.45). Gender, duration of HIV infection, glycemia, use of antiretroviral therapy and ART duration were not associated with significant fibrosis by FIB4. CONCLUSION: FIB4 score > 1.45 was found in 15.5% of Moroccan HIV monoinfected patients. Age, HIV viremia > 75 copies/mL and CD4 count > 200 cells/mm(3) are associated with liver fibrosis. Further studies are needed to explore mechanisms for fibrosis in HIV monoinfected patients. PMID- 24179619 TI - A fascinating presentation of hepatic hydrothorax. AB - We report this case of a 43-year-old woman with hepatitis-C cirrhosis who presented with a large right sided pleural effusion complicated by hypoxic respiratory failure and altered mentation necessitating dependence on mechanical ventilation. The pleural effusion spontaneously resolved upon initiation of mechanical positive pressure ventilation and recurred almost immediately after weaning the patient off the ventilator. The pre-ventilation, ventilation and post ventilation chest X-ray films in chronological order present a striking visual demonstration of fluid dynamics and pathophysiology of hepatic hydrothorax, thereby obviating the need for a dedicated diagnostic test. We also report this case to highlight the treatment strategies for this often intractable complication. PMID- 24179620 TI - Severe cholestasis due to adalimumab in a Crohn's disease patient. AB - Elevation of liver biochemistry has been reported with anti-tumor necrosis factor agents, but overt liver failure rarely reported. Autoimmune hepatitis has been more commonly reported with infliximab than adalimumab (ADA). Our case, however, describes the first reported case of ADA-associated severe cholestatic injury. A 39-year-old female with Crohn's disease developed severe jaundice after initiation of ADA. All serologic tests and imaging studies were normal. Liver biopsy showed prominent pericentral canalicular cholestasis, without features of steatosis or sclerosing cholangitis, consistent with drug-induced cholestasis. The serum total bilirubin peaked at 280 MUmol/L, and improvement was seen after 5 wk with eventual normalization of liver enzymes at 10 wk. Our case describes the first reported case of ADA-associated severe cholestatic liver disease and the first histopathologic examination of this adverse drug effect. Clinicians need to be aware of this potential drug-induced liver injury when prescribing this commonly used biologic medication. PMID- 24179621 TI - Advanced hepatocellular carcinoma responds to MK615, a compound extract from the Japanese apricot "Prunus mume". AB - MK615, a compound extracted from the Japanese apricot "Prunus mume" has been reported to have in vitro anti-tumor activities against several cancer cell lines, including hepatocellular carcinoma (HCC). However, the clinical effects and feasibility of administering MK615 for patients with HCC were unknown. We experienced a case with advanced HCC for which MK615 was effective against both lymph node and pulmonary metastases. A 60-year-old female underwent surgical resection of a 9 cm HCC in the right lobe. The pathological diagnosis was moderately differentiated HCC with vascular invasion. The HCC recurred in the liver 8 mo after the surgery. Radiofrequency ablation and transarterial infusion chemotherapy were performed, but the recurrence was not controlled. One year after the intrahepatic recurrence, pulmonary and lymph metastasis appeared. Sorafenib was administered, but was not effective. Then, MK615 was administered as a final alternative therapy after informed consent was obtained from the patient. Three months later, her alpha-fetoprotein level decrease and both the lymph node and pulmonary metastases decreased in size. The patient has survived for more than 17 mo after the MK615 administration, and was in good condition. Although further investigations are necessary to clarify its safety and efficacy in humans, MK615 may be useful for the treatment of HCC, without serious adverse effects. PMID- 24179622 TI - A correction of misinformation regarding Herbalife. AB - The authors of the subject article by Senadhi et al have misrepresented the safety and regulatory status of Herbalife's products. While we are very concerned with the unwarranted and unfavorable publicity that the inaccuracies listed could generate for Herbalife, we would welcome any inquiries that these authors may have to better clarify our commitment to the safety and quality of our products as has been demonstrated in part by our ability to establish positive relationships with regulatory authorities worldwide through continued cooperation and compliance. This letter clarifies the misinformation presented about Herbalife in the subject article. PMID- 24179623 TI - Post-colonoscopy appendicitis: A case report and systematic review. AB - Colonoscopy is a widely used diagnostic and therapeutic modality with a relatively low morbidity. However, given the large volume of procedures performed, awareness of the infrequent complications is essential. Perforation is an established complication of colonoscopy, and can range from 0.2%-3% depending on the series, population and modality of colonoscopy. Acute appendicitis after colonoscopy is an extremely rare event, and a cause-effect relationship between the colonoscopy and the appendicitis is not well documented. In addition, awareness of this condition can aid in prompt diagnosis. Relatively mild symptoms and exclusion of bowel perforation by contrast studies do not exclude appendicitis from the differential diagnosis for post-colonoscopy pain. In addition to the difficult diagnosis inherent to postcolonoscopy appendicitis, treatment strategies have varied greatly. This paper reviews these approaches. We also expand upon prior articles by giving guidance for the role of nonoperative management in these patients. This case and review of the literature will help to create awareness about this complication, and guide optimal treatment of pericolonoscopy appendicitis. PMID- 24179624 TI - Giant cystic lymphangioma originating from the lesser curvature of the stomach. AB - Cystic lymphangiomas are rare benign tumors. Most frequently occurring in children and involving the neck or axilla, these tumors are much less common in adults and very rarely involve the abdomen. The known congenital and acquired (traumatic) etiologies result in failure of the lymphatic channels and consequent proliferation of lymphatic spaces. This case report describes a very rare case of a giant mesenteric cystic lymphangioma in an adult male with no clear etiology and successful resolution by standard radical resection. A previously healthy 44 year-old male presented with a 6-wk history of progressive upper abdominal pain, vomiting, anorexia and unintentional weight loss accompanied by rapid abdominal distension. A palpable mass was detected upon physical examination of the distended abdomen and abdominal computed tomography scan showed a giant multilobulated cystic process, measuring 40 cm in diameter. Exploratory laparotomy revealed an enormous cystic mass containing 6 L of serous fluid. The process appeared to originate from the lesser omentum and the lesser curvature of the stomach. Radical resection of the tumor was performed along with a partial gastrectomy to address potential invasion into the adjacent tissues. Histological analysis confirmed the diagnosis of a multicystic lymphangioma. The postoperative recovery was uneventful and the patient was discharged after 6 d. At 3-mo follow up, the patient was in good health with no signs of recurrence. PMID- 24179625 TI - Laparoscopic-assisted catheter insertion for continuous ambulatory peritoneal dialysis: A case report of simple technique for optimal placement. AB - A 40-year-old male underwent tube placement surgery for continuous ambulatory peritoneal dialysis (CAPD). A 2-cm skin incision was made, and the peritoneum was reflected enough to perform secure fixation. A swan-necked, double-felted silicone CAPD catheter was inserted, and the felt cuff was sutured to the peritoneum to avoid postoperative leakage. An adequate gradient for tube fixation to the abdominal wall was confirmed. The CAPD tube was passed through a subcutaneous tunnel. Aeroperitoneum was induced to confirm that there was no air leakage from the sites of CAPD insertion. Two trocars were placed, and we confirmed that the CAPD tube led to the rectovesical pouch. Tip position was reliably observed laparoscopically. Optimal patency of the CAPD tube was confirmed during surgery. Placement of CAPD catheters by laparoscopic-assisted surgery has clear advantages in simplicity, safety, flexibility, and certainty. Laparoscopic technique should be considered the first choice for CAPD tube insertion. PMID- 24179626 TI - Hematogenous umbilical metastasis from colon cancer treated by palliative single incision laparoscopic surgery. AB - Sister Mary Joseph's nodule (SMJN) is a rare umbilical nodule that develops secondary to metastatic cancer. Primary malignancies are located in the abdomen or pelvis. Patients with SMJN have a poor prognosis. An 83-year-old woman presented to our hospital with a 1-month history of a rapidly enlarging umbilical mass. Endoscopic findings revealed advanced transverse colon cancer. computer tomography and fluorodeoxyglucose-positron emission tomography revealed tumors of the transverse colon, umbilicus, right inguinal lymph nodes, and left lung. The feeding arteries and drainage veins for the SMJN were the inferior epigastric vessels. Imaging findings of the left lung tumor allowed for identification of the primary lung cancer, and a diagnosis of advanced transverse colon cancer with SMJN and primary lung cancer was made. The patient underwent local resection of the SMNJ and subsequent single-site laparoscopic surgery involving right hemicolectomy and paracolic lymph node dissection. Intra-abdominal dissemination to the mesocolon was confirmed during surgery. Histopathologically, the transverse colon cancer was confirmed to be moderately differentiated tubular adenocarcinoma. We suspect that SMJN may occur via a hematogenous pathway. Although chemotherapy for colon cancer and thoracoscopic surgery for the primary lung cancer were scheduled, the patient and her family desired home hospice. Seven months after surgery, she died of rapidly growing lung cancer. PMID- 24179627 TI - Surgically resected gastric metastasis of pulmonary squamous cell carcinoma. AB - Gastric metastasis of pulmonary carcinoma has been reported to range from 0.19% 5.1%. An autopsy review of cancer disclosed 1.7%-29.6% of gastric metastases, primarily from breast cancer, lung cancer and melanoma. A 71-year-old man was referred to our department because of persistent cough, sputum and sweating for 20 d. Chest posteroanterior view and chest computed tomography scan demonstrated an irregular tumor mass measuring 5.8 cm with central necrosis at the right lower lung. Bronchoscopic biopsy revealed pulmonary squamous carcinoma. Esophagogastroduodenoscopy revealed a huge bleeding ulcer at the body of the stomach and a biopsy diagnosed a metastatic lesion. We performed a palliative total gastrectomy, splenectomy and distal pancreatectomy. The patient did not receive any adjuvant chemotherapy due to his refusal. He was controlled conservatively and survived for 11 mo after surgery. Surgical resection may provide an option for safe palliative treatment. Although gastric metastasis from lung cancer is associated with dismal outcomes, a longer survival or more favorable outcome has been demonstrated in patients undergoing palliative surgical resection of the metastatic site. Considerable improvements in the understanding of metastatic diseases and therapeutic strategies are needed to improve the clinical outcome. PMID- 24179628 TI - Rapunzel syndrome: A rare presentation with multiple small intestinal intussusceptions. AB - Bezoars are usually confined to the stomach which is seen in individuals with psychiatric illness like trichotillomania, trichophagia and gastric dysmotility. Long standing bezoars may extend into the small intestine leading to a condition known as Rapunzel syndrome. Diagnosis can be established by endoscopy, ultrasonography and computed tomography scan. Treatment includes improvement of general condition and removal of bezoar by laparoscopic approach or laparotomy. Psychiatric consultation is necessary to treat and prevent relapse. We report a case of Rapunzel syndrome in a 16-year-old girl with trichotillomania. She presented with history of epigastric mass for three months and recent onset of pain abdomen, vomiting and early satiety. Skiagram of abdomen was showing distended stomach and endoscopy revealed trichobezoar. At laparotomy, stomach was distended with trichobezoar and there were multiple small intestinal intussusceptions. Gastrotomy and manual reduction of intussusceptions with the removal of trichobezoar with its tail was done. Patient recovered completely after the procedure. PMID- 24179629 TI - Left sided Amyand's hernia. AB - The presence of the appendix in an inguinal hernia sac has been referred to as Amyand's hernia. Vermiform appendix located in an external hernia sac is not an uncommon condition, and the incidence of these cases is approximately 1%. In Amyand's hernias, appendices are frequently found in the hernia sac; but an incarceration particularly on the left side is a very unusual sight. In this report we present 32-year-old male with Amyand's hernia on the left side. PMID- 24179630 TI - Real-time dosimetry in external beam radiation therapy. AB - With growing complexity in radiotherapy treatment delivery, it has become mandatory to check each and every treatment plan before implementing clinically. This process is currently administered by an independent secondary check of all treatment parameters and as a pre-treatment quality assurance (QA) check for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy treatment plans. Although pre-treatment IMRT QA is aimed to ensure the correct dose is delivered to the patient, it does not necessarily predict the clinically relevant patient dose errors. During radiotherapy, treatment uncertainties can affect tumor control and may increase complications to surrounding normal tissues. To combat this, image guided radiotherapy is employed to help ensure the plan conditions are mimicked on the treatment machine. However, it does not provide information on actual delivered dose to the tumor volume. Knowledge of actual dose delivered during treatment aid in confirming the prescribed dose and also to replan/reassess the treatment in situations where the planned dose is not delivered as expected by the treating physician. Major accidents in radiotherapy would have been averted if real time dosimetry is incorporated as part of the routine radiotherapy procedure. Of late real-time dosimetry is becoming popular with complex treatments in radiotherapy. Real-time dosimetry can be either in the form of point doses or planar doses or projected on to a 3D image dataset to obtain volumetric dose. They either provide entrance dose or exit dose or dose inside the natural cavities of a patient. In external beam radiotherapy, there are four different established platforms whereby the delivered dose information can be obtained: (1) Collimator; (2) Patient; (3) Couch; and (4) Electronic Portal Imaging Device. Current real-time dosimetric techniques available in radiotherapy have their own advantages and disadvantages and a combination of one or more of these methods provide vital information about the actual dose delivered to radiotherapy patients. PMID- 24179632 TI - Contrast-enhanced ultrasonography in peripheral lung consolidations: What's its actual role? AB - AIM: To evaluate the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis between neoplastic and non-neoplastic peripheral pleuro-pulmonary lesions. METHODS: One hundred patients with pleural or peripheral pulmonary lesions underwent thoracic CEUS. An 8 microliters/mL solution of sulfur hexafluoride microbubbles stabilized by a phospholipid shell (SonoVue((r))) was used as US contrast agent. The clips were stored and independently reviewed by two readers, who recorded the following parameters: presence/absence of arterial enhancement, time to enhancement (TE), extent of enhancement (EE), pattern of enhancement (PE), presence/absence of wash-out, time to wash-out, and extent of wash-out. After the final diagnosis (based on histopathologic findings or follow-up of at least 15 mo) was reached, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) of each CEUS parameter in the differential diagnosis between neoplastic and non neoplastic lesions were calculated. Furthermore, an arbitrary score based on the ratio between the PPVs of each CEUS parameter was calculated, to evaluate if some relationship could exist between overall CEUS behaviour and neoplastic or non neoplastic nature of the lesions. RESULTS: Five patients were lost at follow-up before a conclusive diagnosis was reached, 53 lesions resulted neoplastic and 42 non-neoplastic. Enhancement in the arterial phase was observed in 53/53 neoplastic lesions and 30/42 non-neoplastic lesions. On the whole, 40/42 non neoplastic lesions showed absence of enhancement or early enhancement (95.2%) vs 3/53 neoplastic lesions (5.7%). EE was marked in 29/53 (54.7%) neoplastic lesions and 25/30 (83.3%) non-neoplastic lesions, moderate in 24/53 (45.5%) and 5/30 (16.7%), respectively. PE was homogeneous in 6/53 (11.3%) neoplastic lesions and 18/30 (60%) non-neoplastic lesions, inhomogeneous in 47/53 (88.7%) and 12/30 (40%), respectively. 19/30 (63.3%) non-neoplastic lesions enhancing in the arterial phase had no wash-out in the venous phase, 11/30 (36.7%) had late and mild wash-out. Wash-out was early in 26/53 (49%) neoplastic lesions, late in 26/53 (49%), absent in 1 (2%); marked in 16/53 (30.2%), and moderate in 36/53 (67.9%). The delayed enhancement in the arterial phase showed a sensitivity of 94.32%, specificity of 95.2%, PPV of 96.2%, NPV of 93%, PLR of 19.81, and NLR of 0.06 in identifying the neoplastic lesions. All other parameters individually considered showed unsatisfactory values of sensitivity, or specificity, or both, in differentiating neoplastic from non-neoplastic lesions. The median of the overall arbitrary score was 3 (range 0-14) in non-neoplastic lesions, and 16.5 (range 7.0-17.5) in neoplastic lesions (P < 0.001). The correlation between the diagnosis of neoplastic vs non-neoplastic lesion and the score value was statistically significant (r = 0.858, P < 0.001). Based on the score distribution, a cut-off of 7.5 enabled to reach a sensitivity of 98.1%, specificity of 95.1%, PPV 96.3%, NPV 97.5%, PVR 20.1 and NVR 0.02 in differentiating neoplastic from non-neoplastic lesions. CONCLUSION: CEUS could be useful in the diagnostic workup of pleuropulmonary lesions. A delayed TE or a score >= 7.5 suggest the neoplastic nature of a lesion. PMID- 24179633 TI - Endovascular interventions for traumatic portal venous hemorrhage complicated by portal hypertension. AB - Life-threatening hemorrhage rarely occurs from the portal vein following blunt hepatic trauma. Traditionally, severe portal bleeding in this setting has been controlled by surgical techniques such as packing, ligation, and venorrhaphy. The presence of portal hypertension could potentially increase the amount of hemorrhage in the setting of blunt portal vein trauma making it more difficult to control. This case series describes the use of indirect carbon dioxide portography to identify portal hemorrhage. Furthermore, these cases illustrate attempted endovascular treatment utilizing a transjugular intrahepatic portosystemic shunt in one scenario and transmesocaval shunt coiling of a jejunal varix in the other. PMID- 24179631 TI - Sonographic markers for early diagnosis of fetal malformations. AB - Fetal malformations are very frequent in industrialized countries. Although advanced maternal age may affect pregnancy outcome adversely, 80%-90% of fetal malformations occur in the absence of a specific risk factor for parents. The only effective approach for prenatal screening is currently represented by an ultrasound scan. However, ultrasound methods present two important limitations: the substantial absence of quantitative parameters and the dependence on the sonographer experience. In recent years, together with the improvement in transducer technology, quantitative and objective sonographic markers highly predictive of fetal malformations have been developed. These markers can be detected at early gestation (11-14 wk) and generally are not pathological in themselves but have an increased incidence in abnormal fetuses. Thus, prenatal ultrasonography during the second trimester of gestation provides a "genetic sonogram", including, for instance, nuchal translucency, short humeral length, echogenic bowel, echogenic intracardiac focus and choroid plexus cyst, that is used to identify morphological features of fetal Down's syndrome with a potential sensitivity of more than 90%. Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies. In the future, sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis (amniocentesis, etc.). PMID- 24179634 TI - Radiographic and functional results in the treatment of early stages of Charcot neuroarthropathy with a walker boot and immediate weight bearing. AB - BACKGROUND: One of the most common gold standards for the treatment of Charcot neuroarthropathy (CN) in the early Eichenholtz stages I and II is immobilization with the total contact casting and lower limb offloading. However, the total amount of offloading is still debatable. OBJECTIVES: This study evaluates the clinical and radiographic findings in the treatment of early stages of CN (Eichenholtz stages I and II) with a walker boot and immediate total weight bearing status. METHODS: Twenty-two patients with type 2 diabetes mellitus (DM) and CN of Eichenholtz stages I and II were selected for non-operative treatment. All patients were educated about their condition, and full weight bearing was allowed as tolerated. Patients were monitored on a fortnightly basis in the earlier stages, with clinical examination, temperature measurement, and standardized weight-bearing radiographs. Their American Orthopedic Foot and Ankle Society (AOFAS) scores were determined before and after the treatment protocol. RESULTS: No cutaneous ulcerations or infections were observed in the evaluated cases. The mean measured angles at the beginning and end of the study, although showing relative increase, did not present a statistically significant difference (p > 0.05). Mean AOFAS scores showed a statistically significant improvement by the end of the study (p < 0.005). CONCLUSION: The treatment of early stages of CN (Eichenholtz stages I and II) with emphasis on walker boot and immediate weight bearing has shown a good functional outcome, non-progressive deformity on radiographic assessment, and promising results as a safe treatment option. PMID- 24179635 TI - Potential role of coronary computed tomography-angiography for guiding perioperative cardiac management for non-cardiac surgery. AB - Perioperative cardiac events can be a major consequence of surgery. The American College of Cardiology Foundation/American Heart Association has set out guidelines to aid physicians in identifying patients at the highest risk for these events. The guidelines do recommend for some patients to undergo non invasive cardiac stress testing for further risk stratification, but their sensitivity and specificity for predicting cardiac events is not optimal. With more data emerging of the superior performance of computed coronary tomography angiography (CCTA) compared to non-invasive stress testing, CCTA could be more useful in risk stratification for these patients. PMID- 24179636 TI - Computer-aided analysis of 64-slice coronary computed tomography angiography: a comparison with manual interpretation. AB - Coronary computed tomography angiography (CCTA) is increasingly used for the assessment of coronary heart disease (CHD) in symptomatic patients. Software applications have recently been developed to facilitate efficient and accurate analysis of CCTA. This study aims to evaluate the clinical application of computer-aided diagnosis (CAD) software for the detection of significant coronary stenosis on CCTA in populations with low (8%), moderate (13%), and high (27%) CHD prevalence. A total of 341 consecutive patients underwent 64-slice CCTA at 3 clinical sites in the United States. CAD software performed automatic detection of significant coronary lesions (>50% stenosis). CAD results were then compared to the consensus manual interpretation of 2 imaging experts. Data analysis was conducted for each patient and segment. The CAD had 100% sensitivity per patient across all 3 clinical sites. Specificity in the low, moderate, and high CHD prevalence populations was 64%, 41%, and 38%, respectively. The negative predictive value at the 3 clinical sites was 100%. The positive predictive value was 22%, 21%, and 38% for the low, moderate, and high CHD prevalence populations, respectively. This study demonstrates the utility of CAD software in 3 distinct clinical settings. In a low-prevalence population, such as seen in the emergency department, CAD can be used as a Computer-Aided Simple Triage tool to assist in diagnostic delineation of acute chest pain. In a higher prevalence population, CAD software is useful as an adjunct for both the experienced and inexperienced reader. PMID- 24179637 TI - Phenotypic patterns of right ventricular dysfunction: analysis by cardiac magnetic imaging. AB - The aim of this study was to use magnetic resonance imaging (MRI) to classify the morphological changes and remodeling of the right ventricle (RV) that occur in different clinical situations and that have an impact on RV function. Most literature has traditionally focused on the left ventricle (LV) and as a result, few studies analyze RV behavior and remodeling. The study evaluated all cardiac MRI performed at our center from 2008 to 2010. We retrospectively identified 159 patients who had some sign of right ventricular dysfunction (RVD) based on MRI findings. We classified patients according to a combination of criteria for RVD and the presence of left ventricle dysfunction (LVD). We considered RVD as any of the following abnormalities: i) depressed RV function; ii) RV dilatation; iii) RV hypertrophy. LVD was considered when there was atrial dilatation, LV hypertrophy, LV dilatation and/or depressed LV function. We obtained 6 pathophysiological patterns: RV pressure overload (1.9%), RV volume overload (15.7%), RV volume overload + LVD (32.7%), depressed RV function + LVD (42.1%), mixed RV overload + LVD (6.9%) and other (0.6%). The most frequent etiology was congenital heart disease (33.3%), followed by idiopathic dilated cardiomyopathy (18.2%), left valvular disease (17.6%), ischemic heart disease (15%), pulmonary disease (9.8%), and other (6.1%). This study helps to classify the different patterns that RV can adopt in different clinical situations and can, therefore, help us to understand the RV pathophysiology. PMID- 24179638 TI - Conservative management of chronic aortic dissection with underlying aortic aneurysm. AB - Aortic dissection is one of the most common aortic emergencies affecting around 2000 Americans each year. It usually presents in the acute state but in a small percentage of patients aortic dissections go unnoticed and these patients survive without any adequate therapy. With recent advances in medical care and diagnostic technologies, aortic dissection can be successfully managed through surgical or medical options, consequently increasing the related survival rate. However, little is known about the optimal long-term management of patients suffering from chronic aortic dissection. The purpose of the present report is to review aortic dissection, namely its pathology and the current diagnostic tools available, and to discuss the management options for chronic aortic dissection. We report a patient in which chronic aortic dissection presented with recurring episodes of vomiting and also discuss the management plan of our patient who had a chronic aortic dissection as well as an underlying aortic aneurysm. PMID- 24179639 TI - Giant cell angioblastoma in an adult: a unique presentation. AB - Giant cell angioblastoma is a very rare, locally destructive vascular tumor of intermediate malignancy without metastatic potential. There are only a few cases reported in the literature exclusively in the soft tissue of children. For the first time, we report on an adult patient with a giant cell angioblastoma in the popliteal fossa. The therapy included tumor resection with favorable clinical, oncological and functional outcome. Due to its locally destructive nature, surgery remains the mainstay of treatment. Histologically, giant cell angioblastoma is comprised of nodular aggregates of histiocytoid cells arranged around bland angiomatous spaces. Because of insufficient available data in regard to the definition of the entity, diagnostic criteria and its biological potential, it is not included in the new World Health Organization classification of tumors of soft tissue and bone. The differential diagnosis includes plexiform fibrohistiocytic tumor, myofibroma and giant cell fibroblastoma. PMID- 24179640 TI - Radiotherapy for metastatic fibrolamellar hepatocellular carcinoma. AB - Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of hepatocellular carcinoma (HCC) that commonly affects young individuals without a prior history of liver disease. FLHCC commonly results in a better prognosis than HCC; however, the risk of recurrence and metastatic disease is high. FLHCC is typically treated by primary resection of the tumor with 50-75% cure rates. The use of radiation therapy in FLHCC has not been assessed on its own, and may show some success in a very few reported combination therapy cases. We report on the successful use of radiation therapy in a case of metastatic FLHCC to the lung following primary and secondary resections. Our treatment of the large, metastatic, pulmonary FLHCC tumor with 40 Gy in 10 fractions resulted in an 85.9% tumor volume decrease over six months. This suggests FLHCC may be a radiosensitive tumor and radiotherapy may be valuable in unresectable or metastatic tumors. PMID- 24179641 TI - Cardiac Metastasis in Renal Cell Carcinoma without Vena Cava or Atrial Involvement: an Unusual Presentation of Metastatic Disease. AB - Cardiac metastasis in renal cell carcinoma is a very rare entity, with only a few previously reported cases. In this series, we report two cases of ventricular metastases from renal cell carcinoma without vena cava or right atrial involvement. The first case involves an initially isolated inoperable metastasis to the left ventricle, which was treated with systemic targeted therapy with favorable local response. Our second case illustrates a patient with an isolated cardiac metastasis in the interventricular septum with extension into the right ventricle, which has also remained stable in size on systemic targeted therapy. Although anti-angiogenic agents such as tyrosine kinase inhibitors have transformed the treatment of metastatic renal cell carcinoma in recent years, their efficacy and safety in treating patients with metastatic disease in highly vascular organs such as the heart are currently unknown, with no prior reports on this topic. We describe our novel management of these unique cases and discuss the current medical and surgical approaches to treating cardiac metastases from renal cell carcinoma. PMID- 24179642 TI - An Oncocytic Variant of Intraductal Papillary Neoplasm of the Bile Duct that Formed a Giant Hepatic Cyst. AB - Intraductal papillary neoplasms of the bile duct (IPNB) is the collective term used to refer to papillary bile duct tumors, mucin producing bile duct tumors, and cystic bile duct tumors. Pathologically, these tumors may be considered a highly differentiated adenocarcinoma or a tumor of borderline malignant potential. IPNB is classified into one of four variants based on cell differentiation. The rarest, oncocytic, is characterized by oxyphilic granular cytoplasm and no mucous cell differentiation. The patient, a 59-year old man, was admitted with a complaint of abdominal fullness and a 30*25 cm cystic mass in the right hepatic lobe demonstrated on computed tomography (CT). The mass had no malignant features on CT or magnetic resonance imaging; however, a portion was FDG avid on (18)F-fluorodeoxyglucose positron emission tomography scan (FDG-PET). A fenestration operation was performed for the presumed diagnosis of a hepatic cyst. Pathological examination of the cyst contents demonstrated some atypical cells suspicious for malignancy. After eight months of observation, abnormal FDG uptake was again observed at the residual cyst. A partial hepatectomy was performed to excise the cyst. Pathological examination demonstrated adenocarcinoma in situ derived from an oncocytic IPNB variant. Following the resection, the patient remained disease free for 40 months. This is an extremely rare case of an oncocytic variant of IPNB that was difficult to distinguish clinically from a solitary hepatic cyst. PMID- 24179643 TI - A Case-Control Study of Oral Epithelial Proliferative Markers among Sudanese Toombak Dippers Using Micronuclei Assay, Argyrophilic Nucleolar Organizer Region, Papanicolaou and Crystal Violet Methods. AB - The use of Toombak has been reported to play a major role in the etiology of oral cancer in Sudan. The cellular proliferative activity on the oral epithelium of 210 Toombak dippers was assessed by applying the micronuclei frequency, mean argyrophilic nucleolar organizer region (AgNOR) counts, Papanicolaou method, and 1% crystal violet stain. Participants were divided into 3 groups: 200 were apparently healthy individuals, 100 were Toombak users (cases), 100 were non tobacco users (control) and 10 were patients with oral squamous cell carcinomas. Cytological atypia was identified among 4 (4%). Toombak users and was not found among the control group (P<0.04). The micronuclei frequencies were higher in Toombak users (1.026) than in the control group (0.356) (P<0.0001). The mean AgNOR counts in Toombak users (2.423) were higher than control group (1.303) (P<0.0001). Neither Toombak users nor control group showed mitotic figures in 1% crystal violet method. The results of this research showed that Toombak dipping is a high risk factor for increase in the cellular proliferation in the oral mucosa. The cytological proliferative marker methods used are useful for screening Toombak users. PMID- 24179644 TI - Combined modalities treatment of pulmonary metastasis from an urachal adenocarcinoma. AB - Urachal adenocarcinoma is a rare neoplasm of the bladder. Most of these tumors arise from urachal remnants in the dome of the bladder and extend into the umbilicus. These tumors can recur and most commonly metastasize to lymph nodes, retroperitoneum, lungs, liver and bone. Here we report a case of an urachal adenocarcinoma followed for seven years with lung metastasis for three years. PMID- 24179645 TI - A rare location for a common bone tumor, meta-diaphyseal giant cell tumor of bone in an adult patient. AB - Primary bone tumors can be either benign or malignant considering their natural history and cellular morphology. Benign bone tumors are much more frequent than malignant ones although some of them like giant cell tumor of bone can behave just like a malignant one that means has the capacity for massive local destruction and remote metastasis. Giant cell tumor of bone in adult people has a very strong and diagnostic predilection for epiphysial location in long bones. Very few cases have been so far reported for a giant cell tumor of bone with non epiphysial location in a long bone. PMID- 24179646 TI - Testicular fibroma of gonadal stromal origin with minor sex cord elements, presenting with hydrocele. AB - Testicular fibroma of gonadal stromal origin is a rare benign tumor of testis which usually presents as a slow growing testicular mass. Only 25 cases of testicular fibroma have been reported in the literature. Presence of minor sex cord elements in this tumor is even rarer. We report a case of testicular fibroma with minor sex cord elements that involved almost the entire testis and tunica vaginalis. The patient presented with hydrocele, a rare presentation for this entity. The rarity of the diagnosis and the clinical presentation prompted this case report. PMID- 24179647 TI - Combination of Capecitabine and Oxaliplatin is an Effective Treatment Option for Advanced Neuroendocrine Tumors. AB - The role of chemotherapy in well differentiated neuroendocrine tumors (NET) has been questioned. It was recently demonstrated that everolimus and sunitinib have activity in low and intermediate grade pancreatic NET. The aim of this study was to evaluate the activity of capecitabine and oxaliplatin (CapOx) combination in treating NET in an unselected population. In this regard, we retrospectively evaluated 24 patients diagnosed with metastatic NET treated with CapOx at two Brazilian institutes that are reference centers in cancer care. Tumor response was measured by RECIST criteria. Median age at diagnosis was 56 years, 71% had ECOG 0 or 1, the majority of tumors were primary from pancreas (67%) followed by lung (17%), and 29% were functional. According to WHO classification criteria, 25% were grade 1, 37.5% grade 2 and 37.5% grade 3. Most patients received CapOx as second-line therapy, with a median of 6 cycles. Twenty-nine percent of patients had partial response by RECIST criteria. No association was observed between response rate and tumor grade, primary site or line of CapOx. The median time to progression was 9.8 months and median time to treatment failure was 12.1 months. Seventy-five percent of patients are alive at the time of this analysis; therefore, median overall survival was not reached. The CapOx combination was shown to be active in an unselected population with metastatic NET and may be a good platform for the incorporation of the newer molecular targeted agents being investigated for the treatment of this entity. PMID- 24179648 TI - Cutaneous malignant rhabdoid tumor in the palm of an adult. AB - Malignant rhabdoid tumor is a rare tumor occurring mostly in the neonatal kidneys and central nervous system. Cutaneous malignant rhabdoid tumors are extremely rare in adults. The aim of the study was to report on the clinical, histologic, and immunophenotypic characteristics of this cutaneous malignant rhabdoid tumor which developed in an adult. A 27-year-old male complained of a right palm neoplasm that had been present for 6 months, which was initially diagnosed as an epithelioid sarcoma by biopsy. However, detailed investigation with immunohistochemistry enabled us to make a diagnosis of a rhabdoid tumor. The patient underwent radical abrasion, chemotherapy, and irradiation, and has survived for 1 year without relapse. Only 20 adult cases have been reported thus far in the English literature. We are reporting the 21(st) case, who remains disease-free at 12 months. Complete resection and local irradiation may increase survival, because there is no standard and reliable curative chemotherapeutic regimen. PMID- 24179649 TI - A role for radiotherapy in the management of advanced medullary thyroid carcinoma: the mayo clinic experience. AB - Outcomes of external beam radiotherapy (EBRT) in advanced medullary thyroid carcinoma (MTC) are largely unknown. Retrospective review of data from patients with MTC, diagnosed from June 1, 1970, through December 31, 2007. Overall survival and locoregional tumor control rates were calculated. Seventeen patients had adjuvant or palliative EBRT delivered to 41 sites. Six patients initially had adjuvant EBRT (median, 60.80 Gy); none had relapse in the treated area. Five patients with locoregional recurrence after surgery were treated (median, 59.40 Gy), and durable disease control was achieved in 3. Twelve patients received palliative EBRT to 29 sites of metastatic disease (median, 30.00 Gy), which provided sustained symptom relief at 45% of sites. Five- and ten-year overall survival rates were 44% and 19%, respectively. Adjuvant EBRT may be most effective for prevention of locoregional recurrence. EBRT may provide sustained control of advanced, metastatic disease in select patients. PMID- 24179650 TI - A rare case of langerhans cell histiocytosis of the skull in an adult: a systematic review. AB - We report a 41-year old male who presented to the Emergency Department after falling while water-skiing. He had a previous medical history included chronic headaches, which had persisted for the last 2-3 months prior to presentation. Computed tomography of the head showed a small hypersensitivity with a small extra axial collection with a maximum thickness of 1mm. Differential diagnoses included an arachnoid cyst, haemangioma, meningioma or a secondary lesion. A diagnosis of Langerhans Cell Histiocytosis was made based on the histopathology examination and the immunoperoxidase staining. PMID- 24179651 TI - Combination of irinotecan and a platinum agent for poorly differentiated neuroendocrine carcinomas. AB - Extrapulmonary poorly differentiated neuroendocrine carcinoma (PDNEC) is a rare and highly aggressive neoplasm for which the optimal chemotherapy remains unclear. The objective of this study was to evaluate the outcomes of patients with PDNEC treated with cisplatin and irinotecan (IP) and perform a review of the literature. From 2008 to 2012, patients with advanced PDNEC (Ki67>=20%) who received the IP combination were selected for analysis. Radiologic responses were determined through Response Evaluation Criteria In Solid Tumors criteria. Twenty eight patients were included. The median age at diagnosis was 57 years and the most common presentation was pancreatic PDNEC. Twenty-five patients (89%) received chemotherapy with cisplatin and irinotecan and three received carboplatin and irinotecan. Forty-six percent of the patients achieved objective response and the median time to tumor progression was 3.7 months. The median overall survival was 11.7 months. Thirteen patients (46%) had treatment interruptions or dose reductions due to grade 3/4 toxicity. This retrospective cohort of advanced extrapulmonary PDNEC patients suggests that the IP combination is feasible and resulted in similar response rate and median survival to other treatments previously reported. PMID- 24179652 TI - Apocrine adenocarcinoma of the vulva. AB - Cutaneous vulvar carcinomas are predominantly of squamous cell carcinoma type. Primary vulvar adenocarcinomas are rare with a poorly understood histogenesis. They are classified into extramammary Paget's disease, sweat gland carcinomas, and breast-like adenocarcinomas of the vulva. Adenocarcinomas, originating from Bartholin glands, can also present as vulvar adenocarcinoma. Rare adenocarcinomas with apocrine features have been described in the literature. The origin of these neoplasms from the native apocrine sweat glands or from anogenital mammary-like glands is still debatable. We report herein a case of a 67 year old female with a rare primary apocrine carcinoma of the vulva. PMID- 24179653 TI - Unusual region for pericardial malignant mesothelioma: cutaneous manifestation in a Turkish woman. AB - Malignant mesothelioma is a disease that originates from mesenchymal cells. It is related to the occupational or environmental exposure to asbestos. The treatment remains controversial because it is commonly diagnosed at a very late stage, and the prognosis is very poor. In this report, we present a 37-year-old female patient who was admitted with shortness of breath, palpitation and inability to sleep on her back for the previous 10 days. A large pericardial effusion was detected on echocardiography. Pericardiocentesis was performed and the patient's symptoms were alleviated. However, approximately 7 months later, she was readmitted to the clinic with complaints of a mass at the incision site. Pathological examination of the mass yielded a diagnosis of pericardial malignant mesothelioma. Malignant mesothelioma is a rare occurrence, and to our knowledge, there are no reports in the English literature of pericardial malignant mesothelioma local invasion to an incision site. PMID- 24179654 TI - Renal leiomyosarcoma. AB - Leiomyosarcoma (LMS) is a rare malignant tumor of smooth muscle origin that generally stems from soft tissues and uterine tissue. Although, a small percentage of these may originate from the smooth muscle or vessel walls, most of which are of venous origin. Renal leiomyosarcomas may arise from the smooth muscle fibers of renal pelvis, renal capsule or renal vessels, last one is the most frequent. We report a case of renal LMS that could be originated in the renal capsule. PMID- 24179655 TI - Secondary aneurysmal bone cyst following chondroblastoma of the patella. AB - Aneurysmal bone cyst (ABC) is a rare benign cystic lesion of the bone that composes 1-2% of the entire bone tumors. Some are idiopathic, and some occur secondary to other tumors such as giant cell tumor and chondroblastoma. In this article, we report the clinical, radiographic, and histological findings of a secondary ABC following chondroblastoma of the patella with a review of the literature. PMID- 24179656 TI - Renal medullary carcinoma response to chemotherapy: a referral center experience in Brazil. AB - Renal medullary carcinoma (RMC) is rare, accounting for less than 1% of all renal neoplasms. Case reports suggest RMC is highly aggressive, poorly responsive to chemotherapy, often metastatic at diagnosis, affects young men with sickle cell trait, and median overall survival (mOS) is less than 12 months. We report the epidemiological characteristics, treatments performed, response rate to each treatment and mOS of five patients with RMC. All patients had sickle cell trait, four were male, three had metastatic disease at diagnosis and mean age at diagnosis was 25 years. Non-metastatic patients were submitted to nephrectomy. Two patients had partial response to first line chemotherapy including cisplatin and gemcitabine. There was no response to sunitinib or second line chemo - therapy; mOS was 6 months. Due to its rarity, case series are the only evidence available to discuss the treatment for RMC. In our experience, only cisplatin and gemcitabine based regimen offered response. PMID- 24179657 TI - Pulmonary atypical carcinoid tumor in a 15-year-old girl: a case report and review of the literature. AB - Primary pulmonary neoplasms in children are very rare, and because of their rarity, delays in diagnosis and treatment are common. Bronchial typical carcinoid accounts for 80% of primary malignant tumors, but, there are less than 40 proven cases in children reported in literature. Atypical carcinoids (AC) are the least common type of pulmonary carcinoids among children and to the best of our knowledge less than 10 cases have been reported in the English literature so far. Herein we present an extremely rare case of AC in a 15-year-old child and review the previously reported and published cases of pulmonary AC in pediatric age group. PMID- 24179658 TI - Fatal malignant metastastic epithelioid angiomyolipoma presenting in a young woman: case report and review of the literature. AB - Epithelioid angiomyolipomas (EAMLs) are rare mesenchymal tumors whose malignant variant is extremely uncommon and highly aggressive. Treatment strategies include chemo radiation, transcatheter arterial embolization and surgical resection, which has remained the mainstay treatment. Targeted therapies including mammalian target of rapamycin (mTOR) inhibitors such as Temsirolimus may offer some hope for progressive malignant EAMLs that are not amenable to other treatment modalities. We report a fatal case in a young female who presented with rapidly progressive metastatic EAML that did not respond to mTOR therapy. The literature has shown reduction in tumor burden with the use of mTOR inhibitors, but unfortunately due to the rarity of malignant EAML, a meaningful approach to treatment remains challenging. PMID- 24179659 TI - Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. AB - Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare and poorly differentiated variant of squamous cell carcinoma. The lesion is histologically identical to undifferentiated nasopharyngeal carcinoma (lymphoepithelioma), but with Epstein-Barr virus involvement documented rarely. The first case of LELCS was described in 1988 by Swanson et al. and since there has been less than a total of 60 cases documented. This case review discusses a 87 year old man who presented to his primary care physician with a 2.5 cm solitary ulcerated nodular lesion on his right chest for two weeks. The patient ultimately had the lesion excised and sent for histological examination. The microscopic examination, ancillary studies used and differential diagnosis considered are discussed in detail in the following report. This case review aims to provide insight and approach to a rare cutaneous neoplasm, with the conclusions supporting a theory that LELCS is a separate entity from lymphoepithelioma. PMID- 24179660 TI - Angiofibrolipoma of the calf. AB - Angiofibrolipoma is a neoplasm composed of fibrocytes, capillaries and matured adipose tissues. It is a rare histopathologic variant of lipoma, characterized by matured adipocytes, blood vessels and dense collagenous tissues. It is an extremely rare tumor with very few cases reported in the literature. We are reporting a 9-year-old boy who presented with a right calf swelling noticed since birth, slowly increasing in size which became painful about a year prior to presentation (at about the age of 8 years). The mass extended from the popliteal fossa to the junction of the gastro-soleus. Mid calf circumference on the right was 44 cm and 24 cm on the left. Clinically there was no foot drop. He had neither preceding trauma nor fall. He had no systemic symptom. Pre-operative plain radiographs, incisional biopsy and other ancillary investigations were done. Histopathology result after excisional biopsy revealed angiofibrolipoma and postoperative clinical improvement was significant. To our knowledge, such a case has not been previously reported in the literature. PMID- 24179661 TI - Peristomal pagetoid spread of urothelial carcinoma of the ureter. AB - Patients with ostomy including urinary stoma often develop peristomal complications, especially skin damage. The patient in this case was a 69-year old female with a history of urothelial carcinoma of the bladder and left ureter who underwent transurethral resection of a bladder tumor, nephroureterectomy and cystectomy combined with ureterocutaneostomy. Later, she had recurrence of urothelial carcinoma in the remaining ureter that spread to the peristomal epidermis, with a skin appearance resembling Paget's disease. We report this case based on its clinical significance since we believe it is the first description of this condition in the literature. PMID- 24179662 TI - A very unusual thyroid tumor: a nodule with mature fat papillary hyperplasia and focal atypia. AB - Fat-containing lesions of the thyroid are rare, encompassing several clinical pathological conditions such adenolipomas, thyrolipomatosis and lipomotous tissue in case of amyloidosis. Furthermore, cases of papillary thyroid carcinoma have been identified in association with thyrolipomatosis. We report a case of 51 years old man referred to surgery for a multinodular goiter, showing multiple cystic and hemorrhagic nodules of up to 3 cm. One of these lesions showed features of papillary hyperplasia with focal cytological atypia and mature fat. Here, we describe and discuss the histological and immunophenotypical features of this rare lesion. PMID- 24179663 TI - Multiple liver abscess formation and primary gastrointestinal stromal tumor. AB - Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. The introduction of a number of small molecule tyrosine kinase inhibitors has revolutionized the management of metastatic disease. Surgery is the mainstay of management for localized disease. Patients with high risk tumors are treated with adjuvant imatinib. We report the rare presentation of a localized primary small bowel gastrointestinal stromal tumor in association with multiple liver abscesses. Cystic liver lesions should be fully evaluated in gastro intestinal tumor patients to exclude an infective cause. Treatment with intravenous antibiotics resulted in clinical and radiological improvement of the liver abscesses. The small bowel tumor was treated with surgical resection. PMID- 24179664 TI - A Case of Small Cell Cancer of the Breast in a Male with Synchronous Stage IV Non Small Cell Lung Carcinoma. AB - Extrapulmonary small cell carcinomas (EPSCC) are extremely rare. Most reports indicate success with therapy directed at the tumor as if it was pulmonary small cell carcinoma Primary small cell carcinoma of the breast is an uncommon form of EPSCC. Differentiating between a primary small cell carcinoma of the breast from metastatic disease to the breast is very important. According to the literature, there have been approximately 70 cases reported worldwide. Of these cases, only two cases are documented in men. Prognosis is varied and depends on stage of disease at presentation. A combination of surgery, chemotherapy and/or radiation is required to adequately treat patients with small cell carcinoma of the breast. We present a case of a male patient diagnosed with stage IV non-small cell lung carcinoma first and then subsequently diagnosed with a concurrent small cell carcinoma of the breast responding to treatment with concurrent chemotherapy and radiation. PMID- 24179665 TI - Primary multicentric angiosarcoma of bone: true entity or metastases from an unknown primary? Value of comparative genomic hybridization on paraffin embedded tissues. AB - Multicentric primary angiosarcoma of bone has been described as a distinct entity from bone metastases from angiosarcoma. Bone angiosarcoma accounts for less than 1% of sarcomas. It has dismal prognosis overall, but the multicentric expression does not confer worse prognosis. We describe the case of an old male with bone angiosarcoma of the extremities with multicentric presentation. He soon after had soft tissue angiosarcoma of the head and neck. Histology and immunohistochemistry were consistent with the diagnosis of high-grade angiosarcoma. Comparative genomic hybridization on paraffin-embedded samples of the bone and head and neck samples suggested additional abnormalities in the bone fragment, thus suggesting than bone lesions were indeed metastatic from his head and neck angiosarcoma; although these preliminary analyses warrant confirmation in other similar rare cases. The patient died after 3 years of relapsed acute leukemia with progressive angiosarcoma. PMID- 24179666 TI - A case of myxoid adrenocortical neoplasm: computed tomography and magnetic resonance imaging characteristics. AB - Myxoid adrenocortical neoplasms are rare; to our knowledge, only 56 cases have been reported in the literature. Therefore, distinguishing benign from malignant cases is challenging. Although the histopathological features of myxoid adrenocortical neoplasia have been amply demonstrated, their imaging characteristics are yet to be reported. We describe here these characteristics for such a neoplasm. Our patient, a 70-year-old male, was found to have a 3-cm left adrenal incidentaloma through a non-enhanced computed tomography. Attenuation measurements were 22 Hounsfield units on precontrast imagery, and percentage enhancement washout was 92%. Magnetic resonance imaging showed no loss of signal intensity in T1-weighted out-of-phase images, but high signal intensity on T2-weighted and diffusion-weighted images. Left adrenalectomy was performed and the pathological diagnosis was confirmed as myxoid adrenocortical neoplasm. The imaging characteristics reported here will be beneficial to the differential diagnosis of myxoid adrenocortical neoplasms based upon image analysis and will help distinguish benign from malignant neoplasms. PMID- 24179667 TI - Ventricular fibrillation after bortezomib therapy in a patient with systemic amyloidosis. AB - A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF) and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis. PMID- 24179668 TI - Pericardial tamponade: a rare complication of sternal bone marrow biopsy. AB - Injury of the heart with concomitant pericardial tamponade as a result of sternal bone marrow biopsy is rare. An 80-year-old man was admitted with dehydration and non-specified abdominal pain to the regional hospital. Sternal aspiration biopsy was performed because of anemia and thrombocytopenia. Later on, because of the back pain, general weakness and blood pressure drop, an echocardiography examination was indicated. Pericardial fluid collection was found. Anticipated ascending aortic dissection was excluded on computed tomography scan, but pericardial fluid collection was confirmed. Transfer to our cardiac surgical facility ensued. Limited heart tamponade was affirmed on echocardiography and surgery was immediately indicated. Blood effusion was found in upper mediastinal fat tissue and 300 mL of blood were evacuated from opened pericardial space. Stab wound by sternal biopsy needle at the upper part of ascending aorta was repaired by pledgeted suture. Postoperative course was uneventful. PMID- 24179669 TI - Linaclotide: new mechanisms and new promise for treatment in constipation and irritable bowel syndrome. AB - Chronic idiopathic constipation (CIC) and irritable bowel syndrome (IBS) are functional disorders of the lower gastrointestinal tract. Their prevalence in the general population is between 5% and 20%. Both disorders are chronic, with a relapsing and remitting natural history. The medical treatment of both conditions is unsatisfactory at present, and they represent a huge burden to the health service. Linaclotide is a first-in-class minimally adsorbed, 14-amino-acid peptide agonist of guanylate cyclase C. The drug acts on the intestinal enterocyte. As a consequence of this, intestinal fluid secretion is increased and intestinal transit is accelerated. The efficacy of linaclotide has been studied in both CIC and constipation-predominant IBS (IBS-C). Randomized controlled trials consistently demonstrate that the drug is effective in the treatment of CIC and IBS-C, across a wide range of continuous and dichotomous endpoints. The number needed to treat with linaclotide to prevent one patient with CIC or IBS-C failing to respond to therapy is between 5 and 8 in studies that have reported these data. Overall, in the majority of trials, total numbers of adverse events have been no more frequent with linaclotide, but rates of diarrhoea have been consistently higher. While the drug is clearly effective in the treatment of CIC, there are other evidence-based therapies available, and head-to-head efficacy and cost-effectiveness studies are therefore required to further delineate the role of linaclotide in the treatment of the condition. In IBS-C there are no other licensed therapies available, and linaclotide therefore represents a novel treatment with great promise. PMID- 24179670 TI - Preventing recurrent acute diverticulitis with pharmacological therapies. AB - Acute diverticulitis of the colon represents a significant burden for national health systems, in terms of direct and indirect costs. Past guidelines claimed that recurrent episodes (two or more) of diverticulitis need surgery, but revised guidelines recommend an individualized approach to patients after an attack of acute diverticulitis. For these reasons, conservative treatment has become the preferred choice after an episode of diverticulitis. Thus, significant efforts are now being focused to identify the correct therapeutic approach to prevent diverticulitis relapses. Nonabsorbable antibiotics, 5-aminosalicylic acid and probiotics are currently being investigated in this way. The effectiveness and the future perspectives of these treatments are discussed herein. PMID- 24179672 TI - Argatroban in heparin-induced thrombocytopenia: rationale for use and place in therapy. AB - Heparin-induced thrombocytopenia (HIT) is a recognized complication of heparin and requires urgent detection and treatment. HIT can be divided into two types, type I and type II, with type I being a transient decrease in platelet count without clinical consequence. For the purpose of this review, the term HIT refers to the immune-mediated type II that causes paradoxical thrombo-emboli. The aim of this review is to familiarize clinicians with a specific direct thrombin inhibitor, argatroban, in the treatment of HIT. Argatroban has been successfully employed in treating HIT in many different subsets of patients, including those with endstage renal disease on hemodialysis and in patients undergoing percutaneous coronary intervention and those with multiorgan dysfunction syndrome. PMID- 24179673 TI - Quasi-Biomimetic Ring Contraction Catalyzed by a Cysteine-Based Nucleophile: Total Synthesis of Sch-642305, Some Analogs and their Putative anti-HIV Activities. AB - Cysteine plays a number of important functional and structural roles in Nature, often in the realm of catalysis. Herein, we present an example of a cysteine catalyzed Rauhut-Currier reaction for a potentially biomimetic synthesis of Sch 642305 and related analogs. In this key step of the synthesis we discuss interesting new discoveries and the importance of substrate-catalyst recognition, as well as cysteine's structural features. Also, we investigate the activity of Sch-642305 and four analogs in HIV-infected T-cells. PMID- 24179671 TI - Optimal treatment of laryngopharyngeal reflux disease. AB - Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A large number of data suggest the growing prevalence of laryngopharyngeal symptoms in patients with gastroesophageal reflux disease. However, laryngopharyngeal reflux is a multifactorial syndrome and gastroesophageal reflux disease is not the only cause involved in its pathogenesis. Current critical issues in diagnosing laryngopharyngeal reflux are many nonspecific laryngeal symptoms and signs, and poor sensitivity and specificity of all currently available diagnostic tests. Although it is a pragmatic clinical strategy to start with empiric trials of proton pump inhibitors, many patients with suspected laryngopharyngeal reflux have persistent symptoms despite maximal acid suppression therapy. Overall, there are scant conflicting results to assess the effect of reflux treatments (including dietary and lifestyle modification, medical treatment, antireflux surgery) on laryngopharyngeal reflux. The present review is aimed at critically discussing the current treatment options in patients with laryngopharyngeal reflux, and provides a perspective on the development of new therapies. PMID- 24179674 TI - In Vivo Nanotoxicity Testing using the Zebrafish Embryo Assay. AB - Nanoparticles are increasingly used for biomedical purposes. Many different diagnostic and therapeutic applications are envisioned for nanoparticles, but there are often also serious concerns regarding their safety. Given the fact that numerous new nanomaterials are being developed every day, and that not much is known about the long-term toxicological impact of exposure to nanoparticles, there is an urgent need to establish efficient methods for nanotoxicity testing. The zebrafish (Danio rerio) embryo assay has recently emerged as an interesting 'intermediate' method for in vivo nanotoxicity screening, enabling (semi-) high throughput analyses in a system significantly more complex than cultured cells, but at the same time also less 'invasive' and less expensive than large-scale biocompatibility studies in mice or rats. The zebrafish embryo assay is relatively well-established in the environmental sciences, but it has not yet gained wide notice in the nanomedicine field. Using prototypic polymeric drug carriers, gold-based nanodiagnostics and nanotherapeutics, and iron oxide-based nanodiagnostics, we here show that toxicity testing using zebrafish embryos is easy, efficient and informative, and faithfully reflects, yet significantly extends, cell-based toxicity testing. We therefore expect that the zebrafish embryo assay will become a popular future tool for in vivo nanotoxicity screening. PMID- 24179675 TI - Chitin Nanofiber Micropatterned Flexible Substrates for Tissue Engineering? AB - Engineered tissues require enhanced organization of cells and extracellular matrix (ECM) for proper function. To promote cell organization, substrates with controlled micro- and nanopatterns have been developed as supports for cell growth, and to induce cellular elongation and orientation via contact guidance. Micropatterned ultra-thin biodegradable substrates are desirable for implantation in the host tissue. These substrates, however, need to be mechanically robust to provide substantial support for the generation of new tissues, to be easily retrievable, and to maintain proper handling characteristics. Here, we introduce ultra-thin (<10 MUm), self-assembled chitin nanofiber substrates micropatterned with replica molding for engineering cell sheets. These substrates are biodegradable, mechanically strong, yet flexible, and easily manipulated into the desired shape. As a proof-of-concept, fibroblast cell proliferation, elongation, and alignment were studied on the developed substrates with different pattern dimensions. On the optimized substrates, the majority of the cells aligned (<10 degrees ) along the major axis of micropatterned features. With the ease of fabrication and mechanical robustness, the substrates presented herein can be utilized as versatile system for the engineering and delivery of ordered tissue in applications such as myocardial repair. PMID- 24179676 TI - CANDIDATE GENES FOR LIMITING CHOLESTATIC INTESTINAL INJURY IDENTIFIED BY GENE EXPRESSION PROFILING. AB - The lack of bile flow from the liver into the intestine can have devastating complications including hepatic failure, sepsis and even death. This pathologic condition known as cholestasis can result from etiologies as diverse as total parenteral nutrition (TPN), hepatitis and pancreatic cancer. The intestinal injury associated with cholestasis has been shown to result in decreased intestinal resistance, increased bacterial translocation and increased endotoxemia. Anecdotal clinical evidence suggests a genetic predisposition to exaggerated injury. Recent animal research on two different strains of inbred mice demonstrating different rates of bacterial translocation with different mortality rates supports this premise. In this study, a microarray analysis of intestinal tissue following common bile duct ligation (CBDL) performed under general anesthesia on these same two strains of inbred mice was done with the goal of identifying the potential molecular mechanistic pathways responsible. Over 500 genes were increased more than 2.0 fold following CBDL. The most promising candidate genes included MUPs, Serpina1a and LCN-2. RT-PCR validated the microarray results for these candidate genes. In an in vitro experiment using differentiated intestinal epithelial cells, inhibition of MUP-1 by siRNA resulted in increased intestinal epithelial cell permeability. Diverse novel mechanisms involving the growth hormone pathway, the acute phase response and the innate immune response are thus potential avenues for limiting cholestatic intestinal injury. Changes in gene expression were at times found to be not only due to the CBDL but also due to the murine strain. Should further studies in cholestatic patients demonstrate inter-individual variability similar to what we have shown in mice, then a "personalized medicine" approach to cholestatic patients may become possible. PMID- 24179677 TI - The Ability of Narrative Communication to Address Health-related Social Norms. AB - Social norms are an important predictor of health behavior and have been targeted by a variety of health communication campaigns. However, these campaigns often encounter challenges related to the socially specific context in which norms exist: specifically, the extent to which the target population identifies with the reference group presented in the ad and the extent to which the target population believes the campaign's message. We argue that because of its capacity to effect identification among viewers, narrative communication is particularly appropriate for impacting social norms and, consequently, behavioral intention. This manuscript presents the results of a randomized trial testing the effectiveness of two films - one narrative, one non-narrative - in changing perceived social norms and behavioral intention regarding Pap testing to detect cervical cancer. Results of the study indicate that the narrative film was in fact more effective at producing positive changes in perceived norm and intention. PMID- 24179678 TI - Intermittent to mild asthma: the need for continued treatment. PMID- 24179679 TI - Mechanisms of asthma and implications for its prevention and treatment: a personal journey. AB - My research career has focused on the causes of asthma and its treatment. After establishing the key role that mast cells play in the inflammatory response in asthma, attention was turned towards understanding disease chronicity and variability across the lifecourse. Through a combination of studies on airway biopsies and primary cell cultures we have established that asthma is primarily an epithelial disease driven by increased environmental susceptibility to injury and an altered repair response as depicted by sustained activation of the epithelial mesenchymal trophic unit (EMTU) that is invoked in foetal branching morphogenesis. Varied activation of the EMTU connects the origins of asthma to its progression over time with involvement of epithelial susceptibility through impaired barrier and innate immune functions and altered mesenchymal susceptibility as exemplified by polymorphisms of the metalloprotease gene, ADAM33. Taken together these observations have led to a fundamental re-evaluation of asthma pathogenesis. Rather than placing allergic inflammation as the prime abnormality, it is proposed that the airway epithelium lies at the center of asthma pathogenesis, and that in conjunction with the underlying mesenchyme, it is the principle orchestrator of both the induction of asthma and its evolution over the lifecourse. This concept has provided 'the basis for a new preventative and therapeutic approach focused more on increasing the airways resistance to environmental insults rather than suppressing downstream inflammation once it is established. PMID- 24179680 TI - Diagnosis and management of grain-induced asthma. AB - Grain-induced asthma is a frequent occupational allergic disease mainly caused by inhalation of cereal flour or powder. The main professions affected are bakers, confectioners, pastry factory workers, millers, farmers, and cereal handlers. This disorder is usually due to an IgE-mediated allergic response to inhalation of cereal flour proteins. The major causative allergens of grain-related asthma are proteins derived from wheat, rye and barley flour, although baking additives, such as fungal alpha-amylase are also important. This review deals with the current diagnosis and treatment of grain-induced asthma, emphasizing the role of cereal allergens as molecular tools to enhance diagnosis and management of this disorder. Asthma-like symptoms caused by endotoxin exposure among grain workers are beyond the scope of this review. Progress is being made in the characterization of grain and bakery allergens, particularly cereal-derived allergens, as well as in the standardization of allergy tests. Salt-soluble proteins (albumins plus globulins), particularly members of the alpha amylase/trypsin inhibitor family, thioredoxins, peroxidase, lipid transfer protein and other soluble enzymes show the strongest IgE reactivities in wheat flour. In addition, prolamins (not extractable by salt solutions) have also been claimed as potential allergens. However, the large variability of IgE-binding patterns of cereal proteins among patients with grain-induced asthma, together with the great differences in the concentrations of potential allergens observed in commercial cereal extracts used for diagnosis, highlight the necessity to standardize and improve the diagnostic tools. Removal from exposure to the offending agents is the cornerstone of the management of grain-induced asthma. The availability of purified allergens should be very helpful for a more refined diagnosis, and new immunomodulatory treatments, including allergen immunotherapy and biological drugs, should aid in the management of patients with this disorder. PMID- 24179681 TI - Lost to follow-up in asthmatics does not mean treatment failure: causes and clinical outcomes of non-adherence to outpatient treatment in adult asthma. AB - PURPOSE: Long-term asthma management is recommended to asthmatics; however, many patients do not adhere to follow-up treatment. It is unclear why many asthmatics do not adhere to follow-up treatment and long-term clinical course after discontinuation of asthma management. This study investigates the factors associated with loss to follow-up and observes the clinical course in asthmatics who discontinued asthma treatment. METHODS: A retrospective investigation was conducted after reviewing medical records of adult patients who were newly diagnosed with asthma at a university hospital in Seoul, South Korea from January 2005 to March 2007. We compared baseline demographics and the clinical and laboratory profiles of patients to see if they successfully adhered to the treatment at an outpatient clinic for at least 3 years. The clinical course and asthma control status were surveyed by telephone for patients who were lost to follow-up within 3 years. RESULTS: A total of 351 (73.9%) out of 475 patients were lost to follow-up within 3 years of asthma diagnosis. Patients lost to follow-up were younger and had clinical features of less severe asthma at time of diagnosis (higher FEV1 and PC20, and lower grade treatments) compared to patients who adhered to the follow-up for longer than 3 years (all P<0.05). Among the 198 responders to the telephone survey, 124 responders (62.6%) answered that they eventually discontinued asthma medication. A significantly higher proportion of the 124 responders who discontinued asthma treatment maintained symptom improvement compared to the 74 responders who continued asthma medication (77.4% vs. 55.4%, P=0.003). CONCLUSIONS: Almost three quarters of newly diagnosed asthmatics discontinued asthma medication within 3 years despite a medical recommendation. There are considerable numbers of asthmatics who can maintain long-term asthma control status without medication. PMID- 24179682 TI - Respiratory effects of the hebei spirit oil spill on children in taean, Korea. AB - PURPOSE: The oil spill from the Heibei Spirit in December 2007 contaminated the Yellow Coast of South Korea. We evaluated the respiratory effects of that spill on children who lived along the Yellow Coast. METHODS: Of 662 children living in the area exposed to the oil spill, 436 (65.9%) were enrolled as subjects. All subjects completed a modified International Study of Asthma and Allergies in Childhood questionnaire. A health examination, including a skin prick test, pulmonary function test, and methacholine bronchial provocation test (MBPT), was administered. The children were assigned to two groups: those who lived close to the oil spill area and those who lived far from the oil spill area. RESULTS: The children who lived close to the oil spill area showed a significantly lower forced expiratory volume in one second (FEV1), an increased prevalence of 'asthma ever' (based on a questionnaire), and 'airway hyperresponsiveness' (based on the MBPT) than those who lived far from the oil spill area (FEV1; P=0.011, prevalence of 'asthma ever' based on a questionnaire; P=0.005, prevalence of 'airway hyperresponsiveness' based on the MBPT; P=0.001). The onset of wheezing after the oil spill was significantly higher in children who lived close to the oil spill area than in those who lived far from the oil spill area among the 'wheeze ever' group (P=0.002). In a multiple logistic regression analysis, male sex, family history of asthma, and residence near the oil spill area were significant risk factors for asthma (sex [male/female]: odds ratio [OR], 2.54; 95% confidence interval [CI], 1.31-4.91; family history of asthma [No/Yes]: OR, 3.77; 95% CI, 1.83-7.75; exposure group [low/high]; OR, 2.43; 95% CI, 1.27-4.65). CONCLUSIONS: This study suggests that exposure to an oil spill is a risk factor for asthma in children. PMID- 24179683 TI - IL-4 Receptor alpha Polymorphisms May Be a Susceptible Factor for Work-Related Respiratory Symptoms in Bakery Workers. AB - PURPOSE: The IL-4 and IL-4 receptor alpha (IL-4Ralpha) genes are the key candidate genes for atopy and asthma susceptibility. Exposure to wheat flour can cause IgE sensitization and respiratory symptoms in bakery workers. Therefore, we hypothesized that IL-4 and IL-4Ralpha single nucleotide polymorphisms (SNPs) may be involved in the pathogenic mechanism of baker's asthma. METHODS: Clinical and genetic data from 373 bakery workers were analyzed. A survey questionnaire, spirometry, and skin prick tests with wheat flour were performed. Serum-specific IgE, IgG1, and IgG4 to wheat flour were determined using ELISA. Five candidate IL 4 (-729 T>G, 589 T>C, and 33 T>C) and IL-4Ralpha (Ile75Val A>G and Gln576Arg A>G) SNPs were genotyped and analyzed. RESULTS: Workers with the G allele of IL 4Ralpha Ile75Val A>G had a significantly higher prevalence of work-related lower respiratory symptoms than those with the AA genotype (P=0.004, 16.0% vs. 2.9%). In the skin prick test, workers with the AA genotype of IL-4Ralpha Gln576Arg A>G had a significantly higher positive rate to wheat flour (P=0.015, 8.2% vs. 1.1%) than those with AG/GG genotype. No significant associations were found in the three genetic polymorphisms of IL-4. For the predicted probabilities, workers with the AA genotype of Gln576Arg A>G had a higher prevalence of IgG1 and IgG4 in response to wheat flour, according to increased exposure intensity (P=0.001 for IgG1 and P=0.003 for IgG4). CONCLUSIONS: These findings suggest that the IL 4Ralpha Ile75Val and Gln576Arg polymorphisms may be associated with work-related respiratory symptom development. PMID- 24179684 TI - IL-13 R110Q, a Naturally Occurring IL-13 Polymorphism, Confers Enhanced Functional Activity in Cultured Human Bronchial Smooth Muscle Cells. AB - PURPOSE: Interleukin (IL)-13, a Th2-type cytokine, plays a pivotal role in the pathogenesis of asthma through its direct effects on airway smooth muscles. A naturally occurring IL-13 polymorphism, R110Q, is strongly associated with increased total serum IgE levels and asthma. In the present study, we aimed to determine whether the IL-13 R110Q variant would display different biochemical properties or altered functions in comparison with wild-type (WT) IL-13 in cultured human bronchial smooth muscle cells (hBSMCs). METHODS: Culture supernatants and cell proteins were collected from cultured hBSMCs that were treated with 50 ng/mL IL-13 or IL-13 R110Q for 24 hours. Eotaxin released into hBSMC culture medium was determined by ELISA. The expression levels of the high affinity IgE receptor (FcepsilonRI) alpha-chain, smooth muscle-specific actin alpha chain (alpha-SMA), smooth muscle myosin heavy chain (SmMHC), and calreticulin in the cells were measured on Western blots. RESULTS: Compared with WT IL-13, treatment with the IL-13 R110Q variant resulted in a significant increase in eotaxin release as well as significant, although modest, increases in the expression levels of alpha-SMA, SmMHC, calreticulin, and FcepsilonRI alpha chain. CONCLUSIONS: The results of the present study suggenst that the IL-13 R110Q variant may enhance enhanced functional activities in hBSMCs. PMID- 24179685 TI - Threshold for positivity and optimal dipyrone concentration in flow cytometry assisted basophil activation test. AB - PURPOSE: Basophil activation occurs both in patients with immediate hypersensitivity reactions to anti-inflammatory drugs and in healthy controls in a dose-dependent manner. Our aims were to define the optimal basophil activation test (BAT) concentration and the threshold for BAT positivity for dipyrone. METHODS: From 45 patients with a positive history of an immediate hypersensitivity reaction to dipyrone, we found 20 patients with dipyrone-induced anaphylaxis demonstrating positive skin tests. All selected patients, as well as 10 healthy controls, were tested in vivo and in vitro. BAT was performed using Flow 2CAST technique with three low dipyrone concentrations: 25 ug/mL (c1), 2.5 ug/mL (c2) and 0.25 ug/mL (c3). The threshold for BAT positivity was established using receiver operating characteristics (ROC) curve analysis. RESULTS: Using ROC curve analysis the highest area under curve, 0.79 (0.63-0.95) (P<0.01), was found for c3. When the highest stimulation indexes from the three concentrations for each patient were used, ROC curve analysis revealed an area under curve of 0.81 (0.65-0.96) (P<0.01), sensitivity and specificity were 0.70 and 1 and the optimal threshold value for BAT positivity was 1.71. Thirteen patients had a positive BAT for at least one of the tested dipyrone concentrations. All healthy controls presented negative BAT. CONCLUSIONS: BAT might be a useful technique to diagnose dipyrone allergy, provided all three low dipyrone concentrations are used together. With an assay-specific threshold of 1.71, ROC curve analysis yields 70% sensitivity and 100% specificity. PMID- 24179686 TI - MRI reveals edema in larynx (but not in brain) during anaphylactic hypotension in anesthetized rats. AB - PURPOSE: Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension. METHODS: Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined. RESULTS: Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus. CONCLUSION: Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain. PMID- 24179687 TI - The effects of storage conditions on the stability of house dust mite extracts. AB - PURPOSE: Allergen extracts from the house dust mite (HDM, Dermatophagoides pteronyssinus) are widely utilized for diagnosis and treatment of allergic diseases. It is known that allergen extracts degrade and lose potency when stored over time. METHODS: This study aimed to determine the optimal conditions for stability of allergen extracts. This study was undertaken to investigate the optimal storage conditions for HDM extracts, the effects of adding 0.03% human serum albumin (HSA) and 50% glycerol were evaluated at -20C, 4C, and room temperature (RT). Changes in protein and group 1 major allergen (Der p 1) concentration, as well as allergenicity were measured over a 1 year period using the Bradford assay, two-site ELISA, and ELISA inhibition. RESULTS: Protein concentrations decreased by 86%, 51%, and 6% at RT, 4C, and -20C, respectively, when stored in distilled water. Overall allergenicity remained high (89.9%) when the extracts was reconstituted in 50% glycerol solution, and was 93.1% when reconstituted in 50% glycerol and 0.03% HSA at RT. Allergenicity was decreased to 36.6% and 33.3%, however, reconstitution in DW or 0.03% HSA solution at RT, respectively. Allergenicity was remained high as 92.0%-97.0% when stored at 4C regardless of the buffer conditions. CONCLUSIONS: Storage temperature is the most important factor in preserving allergenicity of HDM extracts, which is ideal at 4C. The addition of 50% glycerol to the storage buffer was also found to play an important role in increasing the shelf-life of HDM extracts at RT. PMID- 24179688 TI - Effect of cholesterol depletion on interleukin-8 production in human respiratory epithelial cells. AB - PURPOSE: The lipid entities of cell membranes are components of the immune system and important mediators of inflammation. Despite increasing interest in the function of epithelial cells in inflammation, the role of cholesterol in this process has not been described. Here, we investigated the effect of cholesterol depletion on the inflammatory process in airway epithelial cells via the expression of interleukin (IL)-8 as a marker of inflammation. METHODS: A 549 cells were treated with 0.5% methyl-beta-cyclodextrin as a selective cholesterol extractor. The IL-8 level was assessed by enzyme-linked immunosorbent assay and reassessed after cholesterol repletion. Mitogen-activated protein kinase (MAPK) inhibitors were used to determine the upstream signaling pathway for IL-8 production in cholesterol-depleted cells. RESULTS: We found a relationship between the amount of cholesterol in A 549 cells and inflammation of the airway. IL-8 production was increased in cholesterol-depleted A 549 cells and restored by cholesterol repletion. IL-8 production was decreased by pretreatment with the extracellular signal-regulated kinase (ERK) inhibitor U0126 but not with JNK inhibitor II or the p38 MAPK inhibitor SB202190. CONCLUSIONS: Our findings suggest that inflammatory responses are increased in cholesterol-depleted epithelial cells via the MAPK signaling system, predominantly by the ERK pathway. We conclude that the lipid components of airwayepithelial cells may play a role in the inflammatory process. PMID- 24179689 TI - The Influence of IgE on Cultured Human Mast Cells. AB - PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium. PMID- 24179690 TI - A case of sulfasalazine-induced hypersensitivity syndrome confirmed by enzyme linked immunospot assay. AB - A 24-year-old male with a history of spondyloarthropathy presented with high fever, cervical lymphadenopathy and generalized maculopapular rash. He was treated with prednisolone for chronic uveitis before being switched to sulfasalazine 3 weeks prior to admission. Laboratory findings revealed marked leukocytosis with frequent atypical lymphocytes. Sulfasalazine was discontinued and the etiology of mononucleosis syndrome explored. During admission, he developed acalculous cholecystitis and hypotension. All symptoms quickly improved following administration of systemic corticosteroids. The investigation for infectious mononucleosis yielded negative results and a diagnosis of sulfasalazine-induced hypersensitivity syndrome was confirmed using enzyme-linked immunospot assays. PMID- 24179691 TI - Histological assessment of the palatal mucosa and greater palatine artery with reference to subepithelial connective tissue grafting. AB - This study aimed to measure the thickness of the epithelium and lamina propria of the palatal mucosa and to elucidate the location of the greater palatine artery to provide the anatomical basis for subepithelial connective tissue grafting. Thirty-two maxillary specimens, taken from the canine distal area to the first molar distal area, were embedded in paraffin and stained with hematoxylin-eosin. The thickness of the epithelium and lamina propria of the palatal mucosa was measured at three positions on these specimens, starting from 3 mm below the alveolar crest and in 3-mm intervals. The location of the greater palatine artery was evaluated by using image-processing software. The mean epithelial thickness decreased significantly in the posterior teeth; it was 0.41, 0.36, 0.32, and 0.30 mm in the canine, first premolar, second premolar, and first molar distal areas, respectively. The lamina propria was significantly thicker in the canine distal; it was 1.36, 1.08, 1.09, and 1.05 mm, respectively. The mean length from the alveolar crest to the greater palatine artery increased toward the posterior molar; it was 7.76, 9.21, 10.93, and 11.28 mm, respectively. The mean depth from the surface of the palatal mucosa to the greater palatine artery decreased from the canine distal to the first premolar distal but increased again toward the posterior molar; it was 3.97, 3.09, 3.58, and 5.50 mm, respectively. Detailed histological assessments of the lamina propria of the palatal mucosa and the greater palatine artery are expected to provide useful anatomical guidelines for subepithelial connective tissue grafting. PMID- 24179692 TI - The expression of IL-6Ralpha and Gp130 in fallopian tubes bearing an ectopic pregnancy. AB - Women with tubal ectopic pregnancies have high levels of circulating interleukin 6 (IL-6). IL-6 treatment in vitro significantly reduces the ciliary activity of tubal epithelium. The effects of IL-6 on target cells occur via the formation of a high-affinity complex with its receptors IL-6Ralpha and glycoprotein 130 (Gp130). IL-6Ralpha is specifically expressed in the cilia of the epithelial cells. In this study, we performed a quantitative reverse transcriptase polymerase chain reaction to determine the mRNA expression of IL-6Ralpha and Gp130 in the fallopian tubes obtained from 12 women with ectopic pregnancies, 12 women with normal pregnancies, and 12 healthy nonpregnant women in the luteal phase of their menstrual cycle. Fallopian tubes were evaluated from specimens taken during tubal ligation in normal pregnancies and nonpregnant fertile women or during tubal surgery in ectopic pregnancies. We observed that IL-6Ralpha mRNA expression in fallopian tubes was increased in ectopic pregnancy compared with that in the midluteal phase. We also found that the Gp130 mRNA expression was significantly lower in fallopian tubes from ectopic pregnancies than in those from nonpregnant women during the midluteal phase of their menstrual cycle, although its expression was noticeably high in fallopian tubes in the midluteal phase, which suggests that high Gp130 levels may possibly contribute to embryo transport into the uterus. PMID- 24179693 TI - Neuroprotective effects of tanshinone I from Danshen extract in a mouse model of hypoxia-ischemia. AB - Hypoxia-ischemia leads to serious neuronal damage in some brain regions and is a strong risk factor for stroke. The aim of this study was to investigate the neuroprotective effect of tanshinone I (TsI) derived from Danshen (Radix Salvia miltiorrhiza root extract) against neuronal damage using a mouse model of cerebral hypoxia-ischemia. Brain infarction and neuronal damage were examined using 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin histochemistry, and Fluoro-Jade B histofluorescence. Pre-treatment with TsI (10 mg/kg) was associated with a significant reduction in infarct volume 1 day after hypoxia-ischemia was induced. In addition, TsI protected against hypoxia-ischemia induced neuronal death in the ipsilateral region. Our present findings suggest that TsI has strong potential for neuroprotection against hypoxic-ischemic damage. These results may be used in research into new anti-stroke medications. PMID- 24179694 TI - Stereological study of the effects of morphine consumption and abstinence on the number of the neurons and oligodendrocytes in medial prefrontal cortex of rats. AB - Quantitative studies to date on the effects of opioid consumption and abstinence on the nervous system using modern stereological methods have not received enough attention. In addition, they have yielded controversial results. The present study was conducted to investigate the effects of morphine, with or without abstinence, on the neurons and oligodendrocytes of the medial prefrontal cortex (MPFC) in rats using quantitative stereological methods. The male rats were divided into four groups: the first (saline [SAL]) and second (morphine [MOR]) groups were treated with saline and an escalating dose of morphine (5-20 mg/kg) for 30 days, respectively; the third (SAL+abstinence [ABS]) and fourth (MOR+ABS) groups were treated in the same manner as the previous groups plus they had a 30 day abstinence period. The results showed that the volume of the MPFC and its subdivisions decreased by approximately 15% in the MOR group compared with that in the SAL group (P<0.05). In addition, the volume decreased by approximately 24% in the MOR+ABS group compared with that in the SAL+ABS group (P<0.05). The number of neurons in the MOR and MOR+ABS groups decreased by approximately 44% and 35%, respectively, compared with that in their corresponding control groups. Moreover, the number of the oligodendrocytes in the MOR and MOR+ABS groups decreased by approximately 41% and 37%, respectively. No significant difference was noted in the number of cells in the MOR and MOR+ABS groups. In conclusion, morphine consumption leads to a permanent reduction in the number of neurons and oligodendrocytes, and no additional neuron and oligodendrocyte loss occurs after abstinence. PMID- 24179695 TI - Analysis of the morphometry and variations in the extensor digitorum brevis muscle: an anatomic guide for muscle flap and tendon transfer surgical dissection. AB - The extensor digitorum brevis muscle (EDB) is a practical option for use as an island flap or free flap when reconstructing soft tissue defects in the ankle as well as in the entire lower limb. It is frequently used to correct crossover toe deformity and other painful toe disorders. We evaluated the morphometry of the EDB in 44 formalin-fixed limbs. Length and width of the muscles were measured. Surface area was calculated as the product of length and width of the muscle. The length of each tendon was also measured from its origin to the point of distal attachment. Presence of any additional tendons was noted. Mean length, width, and surface area of the muscle were 7.39+/-0.71 cm, 4.1+/-0.37 cm, and 30.5+/-4.78 cm(2) on the right side and 7.2+/-0.84 cm, 3.9+/-0.37 cm, and 28.4+/-5.35 cm(2) on the left side, respectively. Morphometry of the tendons revealed that the tendon of the great toe had the highest mean length (9.5 cm) and the tendon of the fourth toe had the lowest mean length (6.3 cm). Four of the limbs studied (9.09%) had only three tendons. Three of the limbs studied (6.81%) had five tendons, and in one exceptional case (2.27%), six tendons were detected. These observations have significant value and are applicable to plastic and orthopedic surgery. PMID- 24179696 TI - Long bone fractures identified in the Joseon Dynasty human skeletons of Korea. AB - Fracture is one of the pathological signs most frequently encountered in archaeologically obtained bones. To expand the paleopathological knowledge on traumatic injuries, it is desirable to secure data on long bone fractures from as wide a geographic and temporal range as possible. We present, for the first time, evidence of long bone fractures in a 16th-18th century Joseon skeletal series (n=96). In this study, we found 3 Colles' fractures of the radius in 2 individual cases. The pattern of fractures was unique. Although previous reports show that the ulna is broken more often than the radius, ulnar fracture associated with fending off a blunt attack was rare in our series (1/7 cases). Transverse fractures, typically caused by intentional violence, were also very rare (1/7 cases) in this study. These results may reflect the relatively tranquil lives of the Joseon people in 16th-18th century Korea. We also found post-fracture complications such as deformations, bone length shortening, and osteomyelitis. The present study would be of interest to medical scientists in related fields because it is one of the few studies conducted on long bone fractures among pre modern societies in East Asian countries, thus far. PMID- 24179697 TI - Evaluation of anatomy comic strips for further production and applications. AB - The corresponding author of the study has been sketching comic strips to explain anatomy in a humorous manner. All the anatomy comic strips, including those in Korean (650 episodes) and English (451 episodes), can be viewed on the homepage (http://anatomy.co.kr). Such comic strips were created with the aim of assisting medical students. However, their impact was unknown, and therefore, we surveyed the students' responses. We noted that anatomy grades were better in the students who read the comic strips. The comics helped the trainees chat with individuals with and without a medical background. The authors also considered comments on the problems with the comic strips and attempted to find solutions. The episodes are being currently used and further produced for educational purposes. To support this effort, the readers' valuable opinions will be continuously collected and assessed. PMID- 24179698 TI - Vascular variations of liver and gallbladder: a case report. AB - Vascular variations in and around the porta hepatis are common. A sound knowledge of possible variations at these sites is vital for surgeons during laparoscopic cholecystectomy and surgical resection of the liver lobes. We report the case of several variations of the hepatic and cystic arteries in which, the common hepatic artery trifurcated into the gastroduodenal, right hepatic, and left hepatic arteries. The right gastric artery arose from the left hepatic artery and divided into a left and a right branch. The left branch entered the liver through the porta hepatis, while the right branch passed behind the common hepatic duct into the Calot's triangle, provided 2 branches to the gallbladder, and continued to supply the right hepatic lobe. Ligation of the right branch of the right hepatic artery in Calot's triangle during cholecystectomy could cause avascular necrosis of the liver segments it supplies. PMID- 24179699 TI - Anterior cerebral artery aneurysm associated with multiple intracranial aneurysms and abdominal aorta aneurysm. AB - We found multiple aneurysms in the intracranial arteries and abdominal aorta of an 87-year-old Korean female cadaver, whose cause of death was reported as "cholangiocarcinoma." An abdominal aortic aneurysm was observed in the infrarenal aorta, where the inferior mesenteric artery arose. The intracranial aneurysms were found in the A3 segment of the anterior cerebral artery and at the bifurcation of the middle cerebral artery. This case provides an example of the very rare association of peripheral intracranial aneurysms with an abdominal aortic aneurysm. Clinicians as well as anatomists should recognize the potential association between these two aneurysm types. PMID- 24179700 TI - Bilateral single cord of the brachial plexus in an adult female cadaver of South Indian origin. AB - The occurrence of a brachial plexus united into a single cord is very rare. During routine dissection of an elderly female cadaver, the brachial plexus united into a single cord was observed bilaterally. On the left side, C4, C5, and C6 roots combined to form the upper trunk, the C7 root continued as the middle trunk, and C8 and T1 united to form the lower trunk. All three trunks almost immediately fused to form a single cord. On the right side, C5 and C6 roots joined to form the upper trunk, which divided into anterior and posterior divisions. C7, C8, and T1 roots combined to form the lower trunk. The anterior and posterior divisions united with the lower trunk to form a single cord. On both sides, the subclavian artery was superior to the single cord. Supraclavicular brachial plexus injuries in such individuals may have serious clinical manifestations. PMID- 24179701 TI - A Benchmark Study on Error Assessment and Quality Control of CCS Reads Derived from the PacBio RS. AB - PacBio RS, a newly emerging third-generation DNA sequencing platform, is based on a real-time, single-molecule, nano-nitch sequencing technology that can generate very long reads (up to 20-kb) in contrast to the shorter reads produced by the first and second generation sequencing technologies. As a new platform, it is important to assess the sequencing error rate, as well as the quality control (QC) parameters associated with the PacBio sequence data. In this study, a mixture of 10 prior known, closely related DNA amplicons were sequenced using the PacBio RS sequencing platform. After aligning Circular Consensus Sequence (CCS) reads derived from the above sequencing experiment to the known reference sequences, we found that the median error rate was 2.5% without read QC, and improved to 1.3% with an SVM based multi-parameter QC method. In addition, a De Novo assembly was used as a downstream application to evaluate the effects of different QC approaches. This benchmark study indicates that even though CCS reads are post error-corrected it is still necessary to perform appropriate QC on CCS reads in order to produce successful downstream bioinformatics analytical results. PMID- 24179702 TI - FDG-PET, a Complementary Modality to Computed-Tomography in Radiotherapy Target Volume Delineation for Head and Neck Cancer. AB - OBJECTIVES: The objective of the current review was to use published data to assess the role of [18F] fluorodeoxyglucose-positron emission tomography (FDG PET) as a complementary modality to computed-tomography (CT) in radiotherapy target volume delineation for head and neck cancer (HNC). METHODS: Studies were identified by searching PubMed electronic databases. Both prospective and retrospective studies were included. Information regarding the role of FDG-PET for radiotherapy target volume delineation for HNC was analyzed. RESULTS: FDG-PET is a promising tool for improving radiotherapy target volume delineation by defining a metabolically active biological target volume (BTV). The use of novel PET tracers representing properties such as hypoxia, protein synthesis and proliferation remain to be better characterized. CONCLUSIONS: The role of FDG-PET for radiotherapy target volume delineation for patients with HNC is expanding and should be further evaluated in clinical trials. PMID- 24179703 TI - Poly(2 deoxy 2 methacrylamido glucopyranose) b Poly(methacrylate amine)s: Optimization of Diblock Glycopol ycations for Nucleic Acid Delivery. AB - A series of nine poly(2-deoxy-2-methacrylamido glucopyranose)-b-poly(methacrylate amine) diblock copolycations The cationic block was varied in length and in the degree of methyl group substitution (secondary, tertiary, quaternary) on the pendant amine in an effort to optimize the structure and activity for plasmid DNA delivery. Upon a thorough kinetic study of polymerization for each polymer, the glycopolymers were prepared with well-controlled Mn and D. The binding and colloidal stability of the polymer-pDNA nanocomplexes at different N/P ratios and in biological media has been investigated using gel electrophoresis and light scattering techniques. The toxicity and transfection efficiency of the polyplexes has been evaluated with Hep G2 (human liver hepatocellular carcinoma) cells; several polymers displayed excellent delivery and toxicity profiles justifying their further development for in vivo gene therapy. PMID- 24179704 TI - Peripheral T-cell tolerance in hosts with acute myeloid leukemia. AB - Our laboratory investigates the immune tolerance mechanisms promoted by acute myeloid leukemia (AML). In a murine AML model, we have observed that leukemia antigen-specific T cells are specifically deleted from the host, presumably following interactions with immature host antigen-presenting cells (APCs). Ongoing work focuses on identifying APC subsets that induce T-cell tolerance in AML as well as the precise mechanisms that underlie this phenomenon. PMID- 24179705 TI - Recruitment of gammadelta T lymphocytes to tumors: A new role for the pleiotropic chemokine CCL2. AB - Despite the promise of targeting gammadelta T cells for cancer immunotherapy, the mechanisms underpinning the recruitment of this T-cell subsets to neoplastic lesions remain poorly understood. We have recently identified the pro inflammatory chemokine CCL2 and its receptor CCR2 as key molecular determinants of gammadelta T-cell migration and tumor infiltration. PMID- 24179706 TI - Humanizing mice for the identification of novel anticancer lipids targeting iNKT cells. AB - The CD1d-dependent presentation of lipid antigens to natural killer T (NKT) cells is an integral part of the innate immune system. However, the development of anticancer therapies based on NKT-cell agonists has had limited success so far. Humanizing mice with respect to the CD1d/NKT antigen presentation system will provide a tool to identify novel lipids that exert antineoplastic functions by targeting NKT cells before the initiation of costly and lengthy clinical trials. PMID- 24179707 TI - Biological insights into BRAFV600 mutations in melanoma patient: Not mere therapeutic targets. AB - Some experimental evidence indicates that uncommon BRAF mutations consisting in the substitution of 2 adjacent nucleotides within codon 600 are in a cis configuration and associate with BRAF gene amplification. These findings suggest that BRAFV600 mutations are unlikely to occur as homozygous alterations in clinical melanoma samples, with gene amplification perhaps contributing to mask the heterozygous state. PMID- 24179708 TI - GC protein-derived macrophage-activating factor decreases alpha-N acetylgalactosaminidase levels in advanced cancer patients. AB - alpha-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID- 24179710 TI - Writing for the journal of wrist surgery. PMID- 24179709 TI - Immunological effects of the TGFbeta-blocking antibody GC1008 in malignant pleural mesothelioma patients. AB - We evaluated a neutralizing anti-TGFbeta antibody (GC1008) in cancer patients with malignant pleura mesothelioma (MPM). The goal of this study was to assess immunoregulatory effects in relation to clinical safety and clinical response. Patients with progressive MPM and 1-2 prior systemic therapies received GC1008 at 3mg/kg IV over 90 min every 21 d as part of an open-label, two-center Phase II trial. Following TGFbeta blockade therapy, clinical safety and patient survival were monitored along with the effects of anti-TGFbeta antibodies on serum biomarkers and peripheral blood mononuclear cells (PBMC). Although designed as a larger trial, only 13 patients were enrolled when the manufacturer discontinued further development of the antibody for oncology indications. All participants tolerated therapy. Although partial or complete radiographic responses were not observed, three patients showed stable disease at 3 mo. GC1008 had no effect in the expression of NK, CD4+, or CD8+ T cell activating and inhibitory markers, other than a decrease in the expression of 2B4 and DNAM-1 on NK cells. However, serum from 5 patients showed new or enhanced levels of antibodies against MPM tumor lysates as measured by immunoblotting. Patients who produced anti-tumor antibodies had increased median overall survival (OS) (15 vs 7.5 mo, p < 0.03) compared with those who did not. To our knowledge, these data represent the first immune analysis of TGFbeta- blockade in human cancer patients. PMID- 24179711 TI - Motion preserving procedures of the wrist. PMID- 24179712 TI - The modern history of the wrist. PMID- 24179713 TI - Decision making for partial carpal fusions. AB - Limited wrist fusions are effective surgical procedures for providing pain relief while preserving motion of the wrist in patients with localized arthritis of the carpus. In deciding which motion-preserving procedure to perform, the etiology of the arthritis, which joints are involved, and which are spared should be determined. The main principle is to fuse the involved joints and to allow motion through the uninvolved joints. In this article, we discuss the various traumatic and nontraumatic conditions causing arthritis of the wrist and the treatment options for those conditions. Common indications for limited wrist fusions include scapholunate advanced collapse and scaphoid nonunion advanced collapse. Options for treating these conditions include three- and four-corner fusions as well as a proximal row carpectomy. This paper discusses which procedures are the most appropriate as well as the outcomes of these procedures. If the basic principles of limited wrist fusions are adhered to, a good outcome can be obtained. The authors' surgical technique and decision-making processes are discussed. PMID- 24179714 TI - Scaphocapitolunate arthrodesis and radial styloidectomy: a treatment option for posttraumatic degenerative wrist disease. AB - Longstanding scaphoid nonunion, scaphoid malunion, and chronic scapholunate dissociation result in malalignment of the carpal bones, progressive carpal collapse, instability, and osteoarthritis of the wrist. The most commonly used procedures to treat scaphoid nonunion advanced collapse (SNAC) and scapholunate advanced collapse (SLAC) wrists are the four-corner fusion (4CF) and the proximal row carpectomy (PRC). Here we describe a different treatment option: radial styloidectomy and scaphocapitolunate (SCL) arthrodesis. This treatment option is chosen in an effort to maintain the joint contact surface and load transmission across the radiocarpal joint. Twenty patients were treated by the senior author (DLF) with this method with a mean follow-up of 4.6 years. Pain decreased in all patients, and 13 patients were pain-free postoperatively. The average Disabilities of the Arm, Shoulder, and Hand (DASH) scores decreased from 44 preoperatively to 23 postoperatively. One patient's course was complicated by nonunion, which was successfully treated with revision of the SCL arthrodesis. On follow-up radiographs, no patient had progressive osteoarthritis. This method preserves the normal ulnar-sided joints of the carpus, which are sacrificed during 4CF, and maintains a more physiologic joint surface for radiocarpal load sharing. PMID- 24179715 TI - Long-term results after midcarpal arthrodesis. AB - Background and Purpose Midcarpal arthrodesis is a well-accepted treatment option for advanced carpal collapse. In this study, we retrospectively assessed survival, analyzed complications and reviewed the long-term follow-up after midcarpal fusion. Materials and Methods The computerized medical records of 572 patients who had undergone 594 four-corner fusions between 1992 and 2001 were explored. Furthermore 56 patients with 60 midcarpal fusions were randomized for clinical and radiological follow-up at a mean of 14.7 years. Results Forty midcarpal fusions (6.7%) had to be converted into complete wrist arthrodesis. The reasons were ongoing pain in spite of a well-healed midcarpal fusion (31) or nonunion (9). Sixty-three patients (11%) required revision surgery because of nonunion (22), hematoma (8), wound infection (3) or persisting pain (31). In clinical follow-up the mean Disabilities of the Arm, Shoulder, and Hand (DASH) score was 20.4. Pain at rest was infrequent, a mild increase with daily activity was complained of (mean visual analog scale [VAS] 3.3). The mean active range of wrist motion for extension and flexion, ulnar and radial deviation and supination and pronation reached 62.5%, 68.4%, 94.7%, and mean grip strength 84.9% of the unaffected side. All patients had radiographic abnormalities, with frequent evidence of osteoarthritis of the lunate fossa. Patients with preserved carpal height appeared to have less pain, better DASH scores and a better range of motion. Conclusions The midcarpal arthrodesis is a long-lasting treatment option for advanced carpal collapse and has good long-term results. Level of Evidence Level IV, Therapeutic study. PMID- 24179716 TI - Scaphoidectomy and Capsulodesis for SNAC or SLAC Stage II. AB - Two common types of wrist arthritis are scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC). In stage II SLAC or SNAC, there is arthritis between the scaphoid and the radius, sparing the cartilage between the capitate and the lunate and between the lunate and the radius. When nonsurgical treatment failed, scaphoidectomy plus capsulorrhaphy was used in 8 patients to provide pain relief without requiring an arthrodesis or compromising the radiolunate articulation. After surgery the pain scores improved from 8.5 preoperatively to 2.4 postoperatively. The Disabilities of the Arm, Shoulder, and Hand (DASH) score averaged 21, and the grip strength improved from 18 to 28 kg (81% of the contralateral side). PMID- 24179717 TI - Radioscapholunate fusions. AB - Radiocarpal fusions are performed for a variety of indications, most commonly for debilitating painful arthritis. The goal of a wrist fusion is to fuse the painful, diseased joints and to preserve motion through the healthy joints. Depending on the extent of the disease process, radiocarpal fusions may take the form of radiolunate, radioscapholunate, or total wrist fusions. Surgical techniques and instrumentation have advanced over the last few decades, and consequently the functional outcomes have improved and complications decreased. Techniques for partial carpal fusions have improved and now include distal scaphoid and triquetrum excision, which improves range of motion and fusion rates. In this article we discuss the various surgical techniques and fixation methods available and review the corresponding evidence in the literature. The authors' preferred surgical technique of radioscapholunate fusion with distal scaphoid and triquetrum excision is outlined. New implants and new concepts are also discussed. PMID- 24179718 TI - Long-term outcomes of proximal row carpectomy: a systematic review of the literature. AB - Purpose Proximal row carpectomy is a well-established technique for the management of wrist arthritis; however, patient selection and long-term durability of proximal row carpectomy is still a matter of controversy. Hence, we conducted a systematic review of the English literature to determine the best evidence on long-term outcomes following proximal row carpectomy. Methods A MEDLINE search using the term "proximal row carpectomy" was performed. A total of 192 studies were identified. All studies with 10 or more years of follow-up were included in the review. Data extracted included patient demographics, indications for surgery, previous surgery, outcome assessment, and information on complications and failures. Results A total of 147 patients from six studies met the inclusion criteria and were included in the study. The majority of patients were male and involved in manual labor. There was no significant difference between the preoperative and long-term postoperative motion. The weighted mean for postoperative grip strength was 68.4% compared with the contralateral side. Disabilities of the arm, shoulder, and hand; patient-rated wrist examination; and Mayo wrist scores were comparable to those reported for four-corner arthrodesis. There were 21 failures (14.3%) requiring re-operation. Failures were not associated with a specific preoperative diagnosis but distributed among patients with Kienbock disease, scaphoid nonunion advanced collapse, and scapholunate advanced collapse arthritis. Conclusions This systematic review confirms the long term durability of proximal row carpectomy when used for the treatment of wrist arthritis. Although radiocapitate arthritis develops over time in most patients, the clinical significance of this finding is undetermined and does not necessarily correlate with failure of proximal row carpectomy. Poorer long-term outcomes are likely to result in patients engaged in heavy manual labor, whereas better outcomes may be obtained in patients undergoing proximal row carpectomy for trauma or earlier-stage Kienbock disease. PMID- 24179719 TI - Wrist Arthroscopy under Portal Site Local Anesthesia (PSLA) without Tourniquet. AB - Purpose wrist arthroscopy is typically performed under general or regional anesthesia with the aid of a tourniquet to maintain a bloodless field. We have been using portal site local anesthesia (PSLA) for wrist arthroscopy without a tourniquet since 1998. The aim of the study was to assess the efficacy, safety, and complications of PSLA and whether this can be recommended for routine wrist arthroscopy. Method We conducted a retrospective study, identifying 111 consecutive cases of wrist arthroscopies performed from January 2007 to December 2009. All cases were performed under PSLA. The effectiveness of PSLA was assessed by analyzing whether the procedure required adjuvant forms of anesthesia. The subjective effectiveness was assessed via phone questionnaires. Results Sixty eight male and 43 female patients were identified. The average age was 43.2 (range 16-77). The indications included chronic wrist pain of unknown origin (30), posttraumatic arthritis (27), rheumatoid arthritis (5), ganglion (30), triangular fibrocartilage complex (TFCC) injury (14), infectious (1), and carpal instability (4). The average duration of the procedures was 73 minutes (range 20 255 minutes). Therapeutic procedures were performed in all 111 cases in addition to a routine diagnostic assessment. These included arthroscopic debridement (82) synovectomy (6), ganglionectomy (30), TFCC repair (3), TFCC debridement (11), radial styloidectomy (2), wafer procedure (4), thermal shrinkage (2), distal scaphoidectomy (1), and synovial biopsy (4). All procedures could be completed uneventfully. Most patients tolerated the procedure well throughout the operation, and the satisfaction level was high. No complication was encountered. Discussions We concluded that PSLA technique is a feasible mode of anesthesia in selected patients. LEVEL OF EVIDENCE: Level IV. PMID- 24179720 TI - A novel technique for detecting instability of the distal radioulnar joint in complete triangular fibrocartilage complex lesions. AB - We performed this study to investigate whether discrepancy of bilateral dorsovolar shift of the distal radioulnar joint (DRUJ) is decisive for the diagnosis of DRUJ instability. Although several cadaver studies have quantified the amount of physiological dorsovolar shift, so far, there is no reliable method of quantification of DRUJ mobility in daily practice. The aim was to describe a novel sonographic method of quantifying DRUJ instability and evaluate its reliability and validity. In this study, 40 healthy volunteers and 17 patients with complete rupture of the triangular fibrocartilage complex (TFCC) underwent sonographic quantification of the grade of instability of their DRUJ bilaterally. Dorsovolar ulnar head translation relative to the distal radius was quantified by means of ultrasonography performed in a transversal plane through the ulnar head and Lister tubercle. Measurements were done while actively pressing the volar surface of the hand onto a brick 30 degrees pronated, and after lifting the hand. A quotient Q of the radioulnar distance (distance between the dorsal radius surface and the ulnar head) between the unloaded and loaded wrist was calculated for differentiation of a normal and unstable DRUJ. The Q ratio of the 17 patients with unilateral TFCC lesion was significantly different between the pathologic side and the contralateral wrist (1.19 vs. 0.54, p < 0.001). There was no significant difference in the Q ratio in the 40 healthy volunteers between the right and left side or dominant and nondominant wrist. A Q ratio > 0.8 was found to be a reasonable cut-off for pathologic laxity of the DRUJ with a sensitivity of 88% and a specificity of 81%. A quotient Q > 0.8 determines instability of the DRUJ reliably. This was a level II diagnostic study. PMID- 24179721 TI - Treatment of Avascular Necrosis of the Proximal Pole of the Scaphoid by Arthroscopic Resection and Prosthetic Semireplacement Arthroplasty Using the Pyrocarbon Adaptive Proximal Scaphoid Implant (APSI): Long-Term Functional Outcomes. AB - Fractures of the proximal pole of the scaphoid with associated avascular necrosis and nonunion are well known to be problematic. Many techniques for fixation and reconstruction of the proximal pole of the scaphoid have been reported, often with poor results. One of the newer modalities of treatment for these difficult cases is excision of the proximal pole and replacement with a pyrocarbon implant. The ovoid shape of the implant acts as a spacer and repositions itself throughout the range of motion of the wrist. The procedure can be performed arthroscopically, thus reducing the morbidity and allowing the procedure to be a day case. Satisfactory results have been reported in elderly patients, but there is a paucity of literature regarding the outcomes in younger patients. This multicenter retrospective study evaluates the clinical, radiologic, and functional outcomes in patients under the age of 65 years with a minimum follow up of 5 years. There were 14 patients with scaphoid nonunion advanced collapse (SNAC) grade I, II, or III wrists, with a mean age of 53 years and mean follow up of 8.7 years. There were improvements in all of the patient related variables including VAS pain scores (7.5 to 0.7), extension (45 degrees to 60 degrees ), flexion (32 degrees to 53 degrees ), and grip strength (15.8 to 34.6 kg). Complications included volar subluxation of the implant, which was acutely surgically corrected (1), volar subluxation of the implant, with persistent pain that required a four-corner fusion (2), and secondary radial styloidectomy (3). This technique is an attractive, minimally invasive alternative for nonunion and avascular necrosis resulting from fractures of the proximal pole of the scaphoid. The authors provide details of the technique, including technical suggestions for performing the procedure. PMID- 24179722 TI - Total wrist replacement: a retrospective comparative study. AB - Purpose Total wrist arthroplasty (TWA) is an evolving procedure for the treatment of arthritis of the wrist joint. The purpose of this study is to compare outcomes of three different total wrist implants. Methods A retrospective review of the Biaxial, Universal 2, and Re-Motion total wrist arthroplasties was performed. Patients were evaluated for clinical outcome, radiographic analysis, review of complications (incidence and type), and conversion to wrist fusion. Patient function measures included: the Mayo wrist score, the Patient Related Wrist Evaluation, and Disabilities of Arm, Shoulder, and Hand (DASH) score. Results Forty-six wrist implants were performed in 39 patients. There were 36 rheumatoid and 10 posttraumatic cases. The average follow-up was 6 years (3.5 to 15). The total wrist inserted included 16 resectional arthroplasties (Biaxial) and 30 resurfacing designs (Universal 2 and Re-Motion). Nine implant failures were noted. Causes for arthroplasty failure included distal component implant loosening and wrist instability. Salvage procedures included revision TWA or wrist fusion. In successful cases, flexion and extension motion averaged 30 and 38 degrees, respectively, and grip strength improved by 3 kg. Mayo wrist scores, in successful cases, increased from 40 (preoperative) to 76 (postoperative). The Mayo wrist scores for posttraumatic conditions averaged 87 points versus 71 points for rheumatoid arthritis. The average DASH score for the two resurfacing designs were 20 and 37, and 48 for the resectional arthroplasty design. Discussion Total wrist replacement maintains itself and provides good pain relief and functional motion in over 80% of all cases and in 97% of resurfacing implants. Better results were correlated with improved distal component fixation and minimal resection of the distal radius. Level of Evidence Level 3 Case Control. PMID- 24179723 TI - Combined perilunate and axial ulnar dislocation of the wrist. AB - Carpal axial injuries are rare and devastating and can be difficult to classify because of various possible injury combinations. A 54-year-old man was involved in a road accident, resulting in serious injury to his dominant right wrist. An axial injury between the capitate and the hamate was combined with open perilunate dislocation and fracture, metacarpal II and III dislocation, and radial styloid fracture. This specific carpal injury has not been previously described. Our clinical case description will contribute to the understanding of the mechanism and pathology of axial carpal injuries. Proximal row carpectomy and pinning-fixation yielded good result at 3 years follow-up. We posit that these rare axial carpal injuries combined with some stage of perilunar injury can be considered a specific injury type in the classification of axial carpal injuries. PMID- 24179724 TI - Case report of long-term results of biaxial and volz total wrist arthroplasty. AB - The purpose of this case report was to look at the long-term (average 17.8 years) results of total wrist arthroplasty. Of the 12 wrists (9 patients) available for evaluation, 7 wrists still had the arthroplasty in place whereas 5 wrists had been revised to an arthrodesis. The average age at time of arthroplasty for those requiring an arthrodesis was 17 years less than those not requiring an arthrodesis. This suggests that there is a higher incidence of loosening when total wrist arthroplasty is performed in younger patients, perhaps due to these younger patients having higher demands or having more severe rheumatoid arthritis. In this younger population, the implant metacarpal stem cut out in three wrists and ulnar drift occurred in two wrists. All patients said that if given the chance, they would have a total wrist arthroplasty again, despite their long-term results being poor and many of them being revised to a wrist arthrodesis. PMID- 24179725 TI - Locked intramedullary total wrist arthrodesis. AB - Total wrist arthrodesis is commonly performed using fixation plates, which can produce soft tissue irritation, often require removal, and limit the ability to position the hand in space. The Skeletal Dynamics IMPLATE is an intramedullary total wrist fusion device designed to provide stable fixation while avoiding the problems associated with plates. Radial and metacarpal locked intramedullary nails are inserted and joined by a connector. Desired hand placement is achieved by selecting the proper connector length and angle, then orienting it appropriately. Fusion mass compression is obtained by virtue of longitudinal threads on the radial nail that allow for length adjustment. Seven wrists in three men and four women were treated with this device and followed for a minimum of 24 weeks. In all cases, local cancellous bone graft was used and the third carpometacarpal (CMC) joint incorporated into the fusion. The median age was 49 (range, 28-71) years. Indications for fusion were two posttraumatic arthritides, three rheumatoid arthritides, one spastic deformity, and one infection. Patients were evaluated before surgery and at final follow-up using the Fernandez pain score and grip strength measurements using a hand-held dynamometer. All patients improved their grip strength and decreased their pain scores. All fusions united, and none of the patients presented dorsal soft tissue problems or required implant removal. One rheumatoid patient required secondary surgery for removal of a retained palmar osteophyte. This device delivers stable fixation, facilitates hand placement, and does not require removal. PMID- 24179726 TI - The distal ulnar tunnel. PMID- 24179727 TI - The carpal tunnel-exposed. PMID- 24179729 TI - Mimotopic peptide immunotherapy for the treatment of multiple sclerosis, an inflammatory autoimmune disease. AB - Several lines of evidence suggest that mast cells play a key role in the pathogenesis of Multiple Sclerosis (MS). The contribution of mast cells likely depends upon specific adherence to myelin surface-bound IgE, which triggers degranulation and the release of enzymes that damage central nervous system (CNS) neurons. To block mast cell degranulation, a peptide-based system was developed to neutralize endogenous, myelin-targeting autoantibodies, thus halting the pathological autoimmune process. Development of the MS therapeutic involved: (1) identification of relevant myelin epitopes; (2) estimation of endogenous autoantibody quantities to be neutralized; (3) synthesis of epitope mimicking/autoantibody-neutralizing peptides; (4) subcutaneous administration of the peptides; and (5) assessment, over time, of clinical presentation together with matching, residual autoantibody levels. An open label, interventional study was performed involving a single MS patient and five control subjects as a first step towards a potentially larger, more elaborate investigation. The study encompassed serological testing to confirm the IgE-positive status of the MS patient and negative status of the controls, an eight month course of peptide based immunotherapy, and assessment of therapeutic efficacy and potentially adverse effects. Treatment of the MS patient with the peptide-based therapy resulted in a reduction in myelin-specific IgE titers and marked clinical improvement. No subjects experienced adverse effects. Thus, peptide-based immunotherapy could provide improved clinical status or life-long remission to MS patients. Substantiation of this premise requires a follow-up examination by other investigators and institutions with larger and more extensive clinical trials. PMID- 24179728 TI - Collaboration of Toll-like and RIG-I-like receptors in human dendritic cells: tRIGgering antiviral innate immune responses. AB - Dendritic cells (DCs) represent a functionally diverse and flexible population of rare cells with the unique capability of binding, internalizing and detecting various microorganisms and their components. However, the response of DCs to innocuous or pathogenic microbes is highly dependent on the type of microbe associated molecular patterns (MAMPs) recognized by pattern recognition receptors (PRRs) that interact with phylogenetically conserved and functionally indispensable microbial targets that involve both self and foreign structures such as lipids, carbohydrates, proteins, and nucleic acids. Recently, special attention has been drawn to nucleic acid receptors that are able to evoke robust innate immune responses mediated by type I interferons and inflammatory cytokine production against intracellular pathogens. Both conventional and plasmacytoid dendritic cells (cDCs and pDCs) express specific nucleic acid recognizing receptors, such as members of the membrane Toll-like receptor (TLR) and the cytosolic RIG-I-like receptor (RLR) families. TLR3, TLR7/TLR8 and TLR9 are localized in the endosomal membrane and are specialized for the recognition of viral double-stranded RNA, single-stranded RNA, and nonmethylated DNA, respectively whereas RLRs (RIG-I, MDA5, and LGP2) are cytosolic proteins that sense various viral RNA species. In this review we discuss the significance of detecting the genomic content of viruses by DC subsets capable of linking innate and adaptive immunity, and several viral evasion mechanisms that may allow us to better understand these responses. A particular attention is paid to the possible collaboration of TLR and RLR sensors in anti-viral protection. PMID- 24179730 TI - Origin of Foxp3(+) cells during pregnancy. AB - Pregnancy establishment and maintenance represents a challenge for the maternal immune system because it has to be alert against pathogens while tolerating paternal alloantigens expressed in fetal structures. Regulatory T cells (Tregs) are important for successful implantation and involved in allotolerance towards paternal antigens. The origin and mechanisms leading to Treg generation during pregnancy at different stages remain under discussion. We report an accumulation of Helios(+) Tregs in thymus and in the lymph nodes draining the uterus at early pregnancy. At later pregnancy stages an expanded population of Foxp3(+) Tregs was generated in the periphery as we showed in a Rag-1(-/-) model of cell transfer. Our data suggest that Tregs, predominantly of thymic origin, are needed for pregnancy establishment. At later pregnancy stages an extra thymic Treg population contributes to the Treg pool in the periphery. Our data provides new insights in the origin of Tregs during pregnancy that are essential to understand natural mechanisms of tolerance acquisition. PMID- 24179731 TI - Increased levels of interleukins 2 and 17 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension. AB - IIH is a condition of raised intracranial pressure of unknown pathogenesis, which is most commonly seen in young overweight women. This study was designed to confirm and extend previous reports by our and other groups showing increased inflammatory cytokine expression in patients with IIH. We analyzed the concentrations of 14 cytokines (IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL 12p70, IL-17, IL-22, IL-23, IFNgamma, TNFalpha, TGFbeta, and osteopontin) in the serum and cerebrospinal fluid (CSF) of 17 patients with IIH and 53 patients with other neurological conditions. Patients with IIH had highly elevated IL-2, IL-4, IL-10, IL-17 and IFNgamma in the CSF compared to patients with multiple sclerosis or non-organic/non-inflammatory neurological conditions. No significant differences were seen between serum cytokine levels in four patient groups (IIH - multiple sclerosis - inflammatory neurological conditions - non-organic/non inflammatory neurological conditions) and there were no correlations between serum and CSF cytokine levels. In IIH, levels of IL-2, IL-8 and IL-17 were significantly higher in CSF than serum; levels of IL-1beta, IL-4, IL-22, IFNgamma and TNFalpha were significantly higher in serum than CSF. For most cytokines, the CSF/serum cytokine ratio was significantly higher than the CSF/serum albumin ratio, indicating intrathecal synthesis of these cytokines in IIH. We conclude that IIH is associated with elevated levels of IL-17 and IL-2 in the CSF, suggesting the involvement of these cytokines in disease pathogenesis. PMID- 24179733 TI - Computational analysis reveals increased blood deposition following repeated mild traumatic brain injury. AB - Mild traumatic brain injury (mTBI) has become an increasing public health concern as subsequent injuries can exacerbate existing neuropathology and result in neurological deficits. This study investigated the temporal development of cortical lesions using magnetic resonance imaging (MRI) to assess two mTBIs delivered to opposite cortical hemispheres. The controlled cortical impact model was used to produce an initial mTBI on the right cortex followed by a second injury induced on the left cortex at 3 (rmTBI 3d) or 7 (rmTBI 7d) days later. Histogram analysis was combined with a novel semi-automated computational approach to perform a voxel-wise examination of extravascular blood and edema volumes within the lesion. Examination of lesion volume 1d post last injury revealed increased tissue abnormalities within rmTBI 7d animals compared to other groups, particularly at the site of the second impact. Histogram analysis of lesion T2 values suggested increased edematous tissue within the rmTBI 3d group and elevated blood deposition in the rm TBI 7d animals. Further quantification of lesion composition for blood and edema containing voxels supported our histogram findings, with increased edema at the site of second impact in rmTBI 3d animals and elevated blood deposition in the rmTBI 7d group at the site of the first injury. Histological measurements revealed spatial overlap of regions containing blood deposition and microglial activation within the cortices of all animals. In conclusion, our findings suggest that there is a window of tissue vulnerability where a second distant mTBI, induced 7d after an initial injury, exacerbates tissue abnormalities consistent with hemorrhagic progression. PMID- 24179734 TI - Improving the clinical correlation of multiple sclerosis black hole volume change by paired-scan analysis. AB - The change in T 1-hypointense lesion ("black hole") volume is an important marker of pathological progression in multiple sclerosis (MS). Black hole boundaries often have low contrast and are difficult to determine accurately and most (semi )automated segmentation methods first compute the T 2-hyperintense lesions, which are a superset of the black holes and are typically more distinct, to form a search space for the T 1w lesions. Two main potential sources of measurement noise in longitudinal black hole volume computation are partial volume and variability in the T 2w lesion segmentation. A paired analysis approach is proposed herein that uses registration to equalize partial volume and lesion mask processing to combine T 2w lesion segmentations across time. The scans of 247 MS patients are used to compare a selected black hole computation method with an enhanced version incorporating paired analysis, using rank correlation to a clinical variable (MS functional composite) as the primary outcome measure. The comparison is done at nine different levels of intensity as a previous study suggests that darker black holes may yield stronger correlations. The results demonstrate that paired analysis can strongly improve longitudinal correlation (from -0.148 to -0.303 in this sample) and may produce segmentations that are more sensitive to clinically relevant changes. PMID- 24179732 TI - Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction. AB - Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome. PMID- 24179735 TI - A comparison of VLSM and VBM in a cohort of patients with post-stroke aphasia. AB - Studies attempting to map post-stroke cognitive or motor symptoms to lesion location have been available in the literature for over 150 years. In the last two decades, two computational techniques have been developed to identify the lesion sites associated with behavioural impairments. Voxel Based Morphometry (VBM) has now been used extensively for this purpose in many different patient populations. More recently, Voxel-based Lesion Symptom Mapping (VLSM) was developed specifically for the purpose of identifying lesion-symptom relationships in stroke patients, and has been used extensively to study, among others functions, language, motor abilities and attention. However, no studies have compared the results of these two techniques so far. In this study we compared VLSM and VBM in a cohort of 20 patients with chronic post-stroke aphasia. Comparison of the two techniques showed overlap in regions previously found to be relevant for the tasks used, suggesting that using both techniques and looking for overlaps between them can increase the reliability of the results obtained. However, overall VBM and VLSM provided only partially concordant results and the differences between the two techniques are discussed. PMID- 24179736 TI - Differences in white matter reflect atypical developmental trajectory in autism: A Tract-based Spatial Statistics study. AB - Autism is a neurodevelopmental disorder in which white matter (WM) maturation is affected. We assessed WM integrity in 16 adolescents and 14 adults with high functioning autism spectrum disorder (ASD) and in matched neurotypical controls (NT) using diffusion weighted imaging and Tract-based Spatial Statistics. Decreased fractional anisotropy (FA) was observed in adolescents with ASD in tracts involved in emotional face processing, language, and executive functioning, including the inferior fronto-occipital fasciculus and the inferior and superior longitudinal fasciculi. Remarkably, no differences in FA were observed between ASD and NT adults. We evaluated the effect of age on WM development across the entire age range. Positive correlations between FA values and age were observed in the right inferior fronto-occipital fasciculus, the left superior longitudinal fasciculus, the corpus callosum, and the cortical spinal tract of ASD participants, but not in NT participants. Our data underscore the dynamic nature of brain development in ASD, showing the presence of an atypical process of WM maturation, that appears to normalize over time and could be at the basis of behavioral improvements often observed in high-functioning autism. PMID- 24179737 TI - Abnormalities in the brain of streptozotocin-induced type 1 diabetic rats revealed by diffusion tensor imaging. AB - Diabetes mellitus affects the brain. Both type 1 and type 2 diabetic patients are associated with white matter (WM) damage observable to diffusion tensor imaging (DTI). The underlying histopathological mechanisms, however, are poorly understood. The objectives of this study are 1) to determine whether streptozotocin (STZ)-induced type 1 diabetes is associated with WM damage observable to DTI; and 2) to understand the pathophysiological aspects underlying STZ-induced brain injuries. Male Sprague-Dawley rats received a single intraperitoneal injection of STZ (62 mg/kg). DTI was used to assess brain abnormalities at 4 weeks after induction, combined with histological assessments and ultrastructural analysis. Compared to controls, the STZ-induced rats showed significantly reduced fractional anisotropy (FA) in the motor/somatosensory cortex and striatum. Histologically, the cortex and striatum of the diabetic animals are characterized by demyelination and axonal degradation. In conclusion, STZ-induced diabetes is associated with striatal/cortical injuries observable to DTI. The DTI abnormalities are likely manifestations of demyelination and axonal degradation in the affected brain regions, and can potentially be used as surrogates for evaluating diabetic brain injuries. PMID- 24179738 TI - Age dependent forebrain structural changes in mice deficient in the autism associated gene Met tyrosine kinase. AB - The MET tyrosine kinase has been identified as a susceptibility gene in patients with autism spectrum disorders. MET is expressed in the forebrain during prenatal and postnatal development. After birth, MET participates in dendritic outgrowth and circuit formation. Alterations in neuronal development, particularly in the cerebral cortex, may contribute to the pathology of developmental disorders, including autism. Patients with autism can exhibit abnormal cortical volumes and head circumferences. We tested the hypothesis that impaired Met signaling during development alters forebrain structure. We have utilized a conditional mutant mouse line which expresses a kinase-dead Met restricted to the cerebral cortex and hippocampal structures. In these mice, we have used magnetic resonance imaging (MRI) to analyze the structure of the cerebral cortex and related structures across postnatal development. We found that the rostral cortex, caudal hippocampus, dorsal striatum, thalamus, and corpus callosum were all larger in adult, but not juvenile, mutant mice relative to control mice. The specificity of the changes suggests that aberrant expansion of the forebrain is consistent with continued axonal and dendritic growth, potentially leading to improper circuit formation and maintenance. PMID- 24179739 TI - Poor supplementary motor area activation differentiates auditory verbal hallucination from imagining the hallucination. AB - Neuronal underpinnings of auditory verbal hallucination remain poorly understood. One suggested mechanism is brain activation that is similar to verbal imagery but occurs without the proper activation of the neuronal systems that are required to tag the origins of verbal imagery in one's mind. Such neuronal systems involve the supplementary motor area. The supplementary motor area has been associated with awareness of intention to make a hand movement, but whether this region is related to the sense of ownership of one's verbal thought remains poorly known. We hypothesized that the supplementary motor area is related to the distinction between one's own mental processing (auditory verbal imagery) and similar processing that is attributed to non-self author (auditory verbal hallucination). To test this hypothesis, we asked patients to signal the onset and offset of their auditory verbal hallucinations during functional magnetic resonance imaging. During non-hallucination periods, we asked the same patients to imagine the hallucination they had previously experienced. In addition, healthy control subjects signaled the onset and offset of self-paced imagery of similar voices. Both hallucinations and the imagery of hallucinations were associated with similar activation strengths of the fronto-temporal language-related circuitries, but the supplementary motor area was activated more strongly during the imagery than during hallucination. These findings suggest that auditory verbal hallucination resembles verbal imagery in language processing, but without the involvement of the supplementary motor area, which may subserve the sense of ownership of one's own verbal imagery. PMID- 24179740 TI - Magnetic resonance elastography reveals altered brain viscoelasticity in experimental autoimmune encephalomyelitis. AB - Cerebral magnetic resonance elastography (MRE) measures the viscoelastic properties of brain tissues in vivo. It was recently shown that brain viscoelasticity is reduced in patients with multiple sclerosis (MS), highlighting the potential of cerebral MRE to detect tissue pathology during neuroinflammation. To further investigate the relationship between inflammation and brain viscoelasticity, we applied MRE to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EAE was induced and monitored by MRE in a 7 tesla animal MRI scanner over 4 weeks. At the peak of the disease (day 14 after immunization), we detected a significant decrease in both the storage modulus (G') and the loss modulus (G"), indicating that both the elasticity and the viscosity of the brain are reduced during acute inflammation. Interestingly, these parameters normalized at a later time point (day 28) corresponding to the clinical recovery phase. Consistent with this, we observed a clear correlation between viscoelastic tissue alteration and the magnitude of perivascular T cell infiltration at both day 14 and day 28. Hence, acute neuroinflammation is associated with reduced mechanical cohesion of brain tissues. Moreover, the reduction of brain viscoelasticity appears to be a reversible process, which is restored when inflammation resolves. For the first time, our study has demonstrated the applicability of cerebral MRE in EAE, and showed that this novel imaging technology is highly sensitive to early tissue alterations resulting from the inflammatory processes. Thus, MRE may serve to monitor early stages of perivascular immune infiltration during neuroinflammation. PMID- 24179741 TI - Functional brain networks before the onset of psychosis: A prospective fMRI study with graph theoretical analysis. AB - Individuals with an at-risk mental state (ARMS) have a risk of developing a psychotic disorder significantly greater than the general population. However, it is not currently possible to predict which ARMS individuals will develop psychosis from clinical assessment alone. Comparison of ARMS subjects who do, and do not, develop psychosis can reveal which factors are critical for the onset of illness. In the present study, 37 patients with an ARMS were followed clinically at least 24 months subsequent to initial referral. Functional MRI data were collected at the beginning of the follow-up period during performance of an executive task known to recruit frontal lobe networks and to be impaired in psychosis. Graph theoretical analysis was used to compare the organization of a functional brain network in ARMS patients who developed a psychotic disorder following the scan (ARMS-T) to those who did not become ill during the same follow-up period (ARMS-NT) and aged-matched controls. The global properties of each group's representative network were studied (density, efficiency, global average path length) as well as regionally-specific contributions of network nodes to the organization of the system (degree, farness-centrality, betweenness centrality). We focused our analysis on the dorsal anterior cingulate cortex (ACC), a region known to support executive function that is structurally and functionally impaired in ARMS patients. In the absence of between-group differences in global network organization, we report a significant reduction in the topological centrality of the ACC in the ARMS-T group relative to both ARMS NT and controls. These results provide evidence that abnormalities in the functional organization of the brain predate the onset of psychosis, and suggest that loss of ACC topological centrality is a potential biomarker for transition to psychosis. PMID- 24179742 TI - Mesial temporal sclerosis is linked with more widespread white matter changes in temporal lobe epilepsy. AB - Temporal lobe epilepsy patients with unilateral mesial temporal sclerosis (TLE + uMTS) have been demonstrated to have extensive white matter abnormalities both ipsilateral and contralateral to the seizure onset zone. However, comparatively less is known about the white matter integrity of TLE patients without MTS (non lesional TLE, nl-TLE). The purpose of the study was to investigate the diffusion properties of thirteen major white matter tracts in patients with TLE + uMTS and nl-TLE. Diffusion tensor imaging (DTI) was performed on 23 TLE + uMTS (15 left MTS and 8 right MTS), 15 nl-TLE and 21 controls. Thirteen tracts were delineated by tractography and their diffusion parameters compared for the two TLE groups relative to controls, with left and right hemispheres combined per tract. A subgroup analysis investigated left and right MTS separately. Compared to controls, reduced anisotropy was detected in ten tracts for TLE + uMTS, but only the parahippocampal cingulum and tapetum for nl-TLE. Right MTS subgroup showed reduced anisotropy in 7 tracts bilaterally (3 limbic, 3 association, 1 projection) and 2 tracts ipsilaterally (1 association, 1 projection) and the body of the corpus callosum whereas the left MTS subgroup showed reduced anisotropy in 4 tracts bilaterally (2 limbic, 1 association, 1 projection) and 2 tracts ipsilaterally (1 limbic, 1 association). Diffusion abnormalities in tracts were observed within and beyond the temporal lobe in TLE + uMTS and were more widespread than in nl-TLE. Patients with right MTS had more extensive, bilateral abnormalities in comparison to left MTS. These findings suggest different dysfunctional networks in TLE patients with and without MTS. PMID- 24179743 TI - Brain connectivity and postural control in young traumatic brain injury patients: A diffusion MRI based network analysis. AB - Our previous research on traumatic brain injury (TBI) patients has shown a strong relationship between specific white matter (WM) diffusion properties and motor deficits. The potential impact of TBI-related changes in network organization of the associated WM structural network on motor performance, however, remains largely unknown. Here, we used diffusion tensor imaging (DTI) based fiber tractography to reconstruct the human brain WM networks of 12 TBI and 17 control participants, followed by a graph theoretical analysis. A force platform was used to measure changes in body posture under conditions of compromised proprioceptive and/or visual feedback. Findings revealed that compared with controls, TBI patients showed higher betweenness centrality and normalized path length, and lower values of local efficiency, implying altered network organization. These results were not merely a consequence of differences in number of connections. In particular, TBI patients displayed reduced structural connectivity in frontal, parieto-premotor, visual, subcortical, and temporal areas. In addition, the decreased connectivity degree was significantly associated with poorer balance performance. We conclude that analyzing the structural brain networks with a graph theoretical approach provides new insights into motor control deficits following brain injury. PMID- 24179744 TI - Susceptibility-weighted imaging at 7 T: Improved diagnosis of cerebral cavernous malformations and associated developmental venous anomalies. AB - BACKGROUND AND AIM: In the diagnosis of cerebral cavernous malformations (CCMs) magnetic resonance imaging is established as the gold standard. Conventional MRI techniques have their drawbacks in the diagnosis of CCMs and associated venous malformations (DVAs). The aim of our study was to evaluate susceptibility weighted imaging SWI for the detection of CCM and associated DVAs at 7 T in comparison with 3 T. PATIENTS AND METHODS: 24 patients (14 female, 10 male; median age: 38.3 y (21.1 y-69.1 y) were included in the study. Patients enrolled in the study received a 3 T and a 7 T MRI on the same day. The following sequences were applied on both field strengths: a T1 weighted 3D GRE sequence (MP RAGE) and a SWI sequence. After obtaining the study MRIs, eleven patients underwent surgery and 13 patients were followed conservatively or were treated radio-surgically. RESULTS: Patients initially presented with haemorrhage (n = 4, 16.7%), seizures (n = 2, 8.3%) or other neurology (n = 18, 75.0%). For surgical resected lesions histopathological findings verified the diagnosis of CCMs. A significantly higher number of CCMs was diagnosed at 7 T SWI sequences compared with 3 T SWI (p < 0.05). Additionally diagnosed lesions on 7 T MRI were significantly smaller compared to the initial lesions on 3 T MRIs (p < 0.001). Further, more associated DVAs were diagnosed at 7 T MRI compared to 3 T MRI. CONCLUSION: SWI sequences at ultra-high-field MRI improve the diagnosis of CCMs and associated DVAs and therefore add important pre-operative information. PMID- 24179745 TI - Multicentre absolute myelin water content mapping: Development of a whole brain atlas and application to low-grade multiple sclerosis. AB - The current study investigates the whole brain myelin water content distribution applying a new approach that allows for the simultaneous mapping of total and relative myelin water content, T 1 and T 2* with full brain coverage and high resolution (1 * 1 * 2 mm(3)). The data was collected at two different sites in healthy controls to validate the independence of a specific setup. In addition, a group of patients with known white matter affections was investigated to compare two measures of myelin, i.e. relative and absolute myelin water content. Based on the first dataset, a quantitative myelin water content atlas was created which served as a control set for the other two datasets. Both control groups measured at different institutions yielded consistent results. However, distinct regions of reduced myelin water content were observed for the patient dataset, both on an individual basis and in a group-wise comparison. The comparison between the absolute and relative measurement of myelin water content in MS patients showed that the relative measurement, which is employed by many researchers, overestimates both disease volume and the corresponding reduction of myelin water content in white matter lesions. However, for normal appearing white matter, no difference between both approaches was detected. The results obtained in the current study demonstrate that absolute myelin water content can reliably be determined in a multicentre environment using standard MR sequences. The optimised protocol allows for a measurement of four quantitative parameters with full brain coverage in only 10 min. This might expedite a more widespread future use of quantitative MRI methods for clinical research and diagnosis. PMID- 24179746 TI - Right prefrontal activation as a neuro-functional biomarker for monitoring acute effects of methylphenidate in ADHD children: An fNIRS study. AB - An objective biomarker is a compelling need for the early diagnosis of attention deficit hyperactivity disorder (ADHD), as well as for the monitoring of pharmacological treatment effectiveness. The advent of fNIRS, which is relatively robust to the body movements of ADHD children, raised the possibility of introducing functional neuroimaging diagnosis in younger ADHD children. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 16 ADHD children (6 to 13 years old) performing a go/no-go task before and 1.5 h after MPH or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. 16 age- and gender-matched normal controls without MPH administration were also monitored. Relative to control subjects, unmedicated ADHD children exhibited reduced activation in the right inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during go/no-go tasks. The reduced right IFG/MFG activation was acutely normalized after MPH administration, but not after placebo administration. The MPH-induced right IFG/MFG activation was significantly larger than the placebo-induced activation. Post-scan exclusion rate was 0% among 16 right-handed ADHD children with IQ > 70. We revealed that the right IFG/MFG activation could serve as a neuro-functional biomarker for monitoring the acute effects of methylphenidate in ADHD children. fNIRS-based examinations were applicable to ADHD children as young as 6 years old, and thus would contribute to early clinical diagnosis and treatment of ADHD children. PMID- 24179747 TI - Scoring by nonlocal image patch estimator for early detection of Alzheimer's disease. AB - Detection of Alzheimer's disease (AD) at the first stages of the pathology is an important task to accelerate the development of new therapies and improve treatment. Compared to AD detection, the prediction of AD using structural MRI at the mild cognitive impairment (MCI) or pre-MCI stage is more complex because the associated anatomical changes are more subtle. In this study, we analyzed the capability of a recently proposed method, SNIPE (Scoring by Nonlocal Image Patch Estimator), to predict AD by analyzing entorhinal cortex (EC) and hippocampus (HC) scoring over the entire ADNI database (834 scans). Detection (AD vs. CN) and prediction (progressive - pMCI vs. stable - sMCI) efficiency of SNIPE were studied using volumetric and grading biomarkers. First, our results indicate that grading-based biomarkers are more relevant for prediction than volume-based biomarkers. Second, we show that HC-based biomarkers are more important than EC based biomarkers for prediction. Third, we demonstrate that the results obtained by SNIPE are similar to or better than results obtained in an independent study using HC volume, cortical thickness, and tensor-based morphometry, individually and in combination. Fourth, a comparison of new patch-based methods shows that the nonlocal redundancy strategy involved in SNIPE obtained similar results to a new local sparse-based approach. Finally, we present the first results of patch based morphometry to illustrate the progression of the pathology. PMID- 24179748 TI - Egocentric spatial learning in schizophrenia investigated with functional magnetic resonance imaging. AB - Psychotic symptoms in schizophrenia are related to disturbed self-recognition and to disturbed experience of agency. Possibly, these impairments contribute to first-person large-scale egocentric learning deficits. Sixteen inpatients with schizophrenia and 16 matched healthy comparison subjects underwent functional magnetic resonance imaging (fMRI) while finding their way in a virtual maze. The virtual maze presented a first-person view, lacked any topographical landmarks and afforded egocentric navigation strategies. The participants with schizophrenia showed impaired performance in the virtual maze when compared with controls, and showed a similar but weaker pattern of activity changes during egocentric learning when compared with controls. Especially the activity of task relevant brain regions (precuneus and posterior cingulate and retrosplenial cortex) differed from that of controls across all trials of the task. Activity increase within the right-sided precuneus was related to worse virtual maze performance and to stronger positive symptoms in participants with schizophrenia. We suggest that psychotic symptoms in schizophrenia are related to aberrant neural activity within the precuneus. Possibly, first-person large-scale egocentric navigation and learning designs may be a feasible tool for the assessment and treatment of cognitive deficits related to self-recognition in patients with schizophrenia. PMID- 24179749 TI - Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion: Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal. AB - Over the last 15 years, basic thresholding techniques in combination with standard statistical correlation-based data analysis tools have been widely used to investigate different aspects of evolution of acute or subacute to late stage ischemic stroke in both human and animal data. Yet, a wave of biology-dependent and imaging-dependent issues is still untackled pointing towards the key question: "how does an ischemic stroke evolve?" Paving the way for potential answers to this question, both magnetic resonance (MRI) and CT (computed tomography) images have been used to visualize the lesion extent, either with or without spatial distinction between dead and salvageable tissue. Combining diffusion and perfusion imaging modalities may provide the possibility of predicting further tissue recovery or eventual necrosis. Going beyond these basic thresholding techniques, in this critical appraisal, we explore different semi automatic or fully automatic 2D/3D medical image analysis methods and mathematical models applied to human, animal (rats/rodents) and/or synthetic ischemic stroke to tackle one of the following three problems: (1) segmentation of infarcted and/or salvageable (also called penumbral) tissue, (2) prediction of final ischemic tissue fate (death or recovery) and (3) dynamic simulation of the lesion core and/or penumbra evolution. To highlight the key features in the reviewed segmentation and prediction methods, we propose a common categorization pattern. We also emphasize some key aspects of the methods such as the imaging modalities required to build and test the presented approach, the number of patients/animals or synthetic samples, the use of external user interaction and the methods of assessment (clinical or imaging-based). Furthermore, we investigate how any key difficulties, posed by the evolution of stroke such as swelling or reperfusion, were detected (or not) by each method. In the absence of any imaging-based macroscopic dynamic model applied to ischemic stroke, we have insights into relevant microscopic dynamic models simulating the evolution of brain ischemia in the hope to further promising and challenging 4D imaging-based dynamic models. By depicting the major pitfalls and the advanced aspects of the different reviewed methods, we present an overall critique of their performances and concluded our discussion by suggesting some recommendations for future research work focusing on one or more of the three addressed problems. PMID- 24179751 TI - The birth of NeuroImage: Clinical. PMID- 24179750 TI - Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment. AB - A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75 +/- 7.1 years) scanned with brain MRI and genotyped as part of Alzheimer's Disease Neuroimaging Initiative. We carried out a replication study in an independent, non-overlapping sample of 51 elderly Caucasian subjects with MCI (mean age: 76 +/- 5.5 years), scanned with brain MRI and genotyped for MTHFR, as part of the Cardiovascular Health Study. At each voxel in the brain, we tested to see where regional volume differences were associated with carrying one or more MTHFR 'T' alleles. In ADNI subjects, carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2-8% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5-1.5% per T allele at 1 year follow-up, after adjusting for age and sex. We replicated these brain volume deficits of up to 5-12% per MTHFR T allele in the independent cohort of CHS subjects. As expected, the associations weakened after controlling for homocysteine levels, which the risk gene affects. The MTHFR risk variant may thus promote brain atrophy by elevating homocysteine levels. This study aims to investigate the spatially detailed effects of this MTHFR polymorphism on brain structure in 3D, pointing to a causal pathway that may promote homocysteine-mediated brain atrophy in elderly people with MCI. PMID- 24179752 TI - Connectivity in MEG resting-state networks increases after resective surgery for low-grade glioma and correlates with improved cognitive performance. AB - PURPOSE: Low-grade glioma (LGG) patients often have cognitive deficits. Several disease- and treatment related factors affect cognitive processing. Cognitive outcome of resective surgery is unpredictable, both for improvement and deterioration, especially for complex domains such as attention and executive functioning. MEG analysis of resting-state networks (RSNs) is a good candidate for presurgical prediction of cognitive outcome. In this study, we explore the relation between alterations in connectivity of RSNs and changes in cognitive processing after resective surgery, as a stepping stone to ultimately predict postsurgical cognitive outcome. METHODS: Ten patients with LGG were included, who had no adjuvant therapy. MEG recording and neuropsychological assessment were obtained before and after resective surgery. MEG data were recorded during a no task eyes-closed condition, and projected to the anatomical space of the AAL atlas. Alterations in functional connectivity, as characterized by the phase lag index (PLI), within the default mode network (DMN), executive control network (ECN), and left- and right-sided frontoparietal networks (FPN) were compared to cognitive changes. RESULTS: Lower alpha band DMN connectivity was increased after surgery, and this increase was related to improved verbal memory functioning. Similarly, right FPN connectivity was increased after resection in the upper alpha band, which correlated with improved attention, working memory and executive functioning. DISCUSSION: Increased alpha band RSN functional connectivity in MEG recordings correlates with improved cognitive outcome after resective surgery. The mechanisms resulting in functional connectivity alterations after resection remain to be elucidated. Importantly, our findings indicate that connectivity of MEG RSNs may be used for presurgical prediction of cognitive outcome in future studies. PMID- 24179753 TI - Impaired magnocellular/dorsal stream activation predicts impaired reading ability in schizophrenia. AB - In healthy humans, passage reading depends upon a critical organizing role played by the magnocellular/dorsal visual pathway. In a recent study, we found a significant correlation between orthographic reading deficits in schizophrenia and deficits in contrast sensitivity to low spatial frequency stimuli, suggesting an underlying magnocellular processing abnormality. The interrelationship between magnocellular dysfunction and passage reading impairments in schizophrenia was investigated in 21 patients with schizophrenia and 17 healthy control volunteers using behavioral and functional MRI (fMRI) based measures. fMRI activation patterns during passage- and single-word reading were evaluated in relation to cortical areas with differential sensitivity to low versus high spatial frequency cortical regions indentified using a phase-encoded fMRI paradigm. On average, patients with schizophrenia read at the 6th grade level, despite completion of more than 12 years of education and estimated normal pre-morbid IQ. Schizophrenia patients also showed significantly impaired contrast sensitivity to low spatial frequencies and abnormal neural activity in response to stimulation with low spatial frequencies, consistent with dysfunction of magnocellular processing. Further, these magnocellular deficits were predictive of poor performance on a standardized psychoeducational test of passage reading. These findings suggest that reading is an important index of cognitive dysfunction in schizophrenia and highlight the contribution of magnocellular dysfunction to overall cognitive impairments in schizophrenia. PMID- 24179754 TI - The impact of serotonin transporter genotype on default network connectivity in children and adolescents with autism spectrum disorders. AB - Compared to healthy controls, individuals with autism spectrum disorders (ASD) have weaker posterior-anterior connectivity that strengthens less with age within the default network, a set of brain structures connected in the absence of a task and likely involved in social function. The serotonin transporter-linked polymorphic region (5-HTTLPR) genotypes that result in lowered serotonin transporter expression are associated with social impairment in ASD. Additionally, in healthy controls, low expressing 5-HTTLPR genotypes are associated with weaker default network connectivity. However, in ASD, the effect of 5-HTTLPR on the default network is unknown. We hypothesized that 5-HTTLPR's influence on posterior-anterior default network connectivity strength as well as on age-related changes in connectivity differs in the ASD group versus controls. Youth with ASD and healthy controls, ages 8-19, underwent a resting fMRI acquisition. Connectivity was calculated by correlating the posterior hub of the default network with all voxels. Triallelic genotype was assessed via PCR and Sanger sequencing. A genotype-by-diagnosis interaction significantly predicted posterior-anterior connectivity, such that low expressing genotypes (S/S, S/LG, LG/LG) were associated with stronger connectivity than high expressing genotypes (LA/LA, S/LA, LA/LG) in the ASD group, but the converse was true for controls. Also, youth with ASD and low expressing genotypes had greater age-related increases in connectivity values compared to those with high expressing genotypes and controls in either genotype group. Our findings suggest that the cascade of events from genetic variation to brain function differs in ASD. Also, low expressing genotypes may represent a subtype within ASD. PMID- 24179755 TI - Thalamic medial dorsal nucleus atrophy in medial temporal lobe epilepsy: A VBM meta-analysis. AB - PURPOSE: Medial temporal lobe epilepsy (MTLE) is associated with MTLE network pathology within and beyond the hippocampus. The purpose of this meta-analysis was to identify consistent MTLE structural change to guide subsequent targeted analyses of these areas. METHODS: We performed an anatomic likelihood estimation (ALE) meta-analysis of 22 whole-brain voxel-based morphometry experiments from 11 published studies. We grouped these experiments in three ways. We then constructed a meta-analytic connectivity model (MACM) for regions of consistent MTLE structural change as reported by the ALE analysis. KEY FINDINGS: ALE reported spatially consistent structural change across VBM studies only in the epileptogenic hippocampus and the bilateral thalamus; within the thalamus, the medial dorsal nucleus of the thalamus (MDN thalamus) represented the greatest convergence (P < 0.05 corrected for multiple comparisons). The subsequent MACM for the hippocampus and ipsilateral MDN thalamus demonstrated that the hippocampus and ipsilateral MDN thalamus functionally co-activate and are nodes within the same network, suggesting that MDN thalamic damage could result from MTLE network excitotoxicity. SIGNIFICANCE: Notwithstanding our large sample of studies, these findings are more restrictive than previous reports and demonstrate the utility of our inclusion filters and of recently modified meta analytic methods in approximating clinical relevance. Thalamic pathology is commonly observed in animal and human studies, suggesting it could be a clinically useful indicator. Thalamus-specific research as a clinical marker awaits further investigation. PMID- 24179756 TI - The influence of cerebral small vessel disease on default mode network deactivation in mild cognitive impairment. AB - INTRODUCTION: Cerebral small vessel disease (CSVD) is thought to contribute to cognitive dysfunction in patients with mild cognitive impairment (MCI). The underlying mechanisms, and more specifically, the effects of CSVD on brain functioning in MCI are incompletely understood. The objective of the present study was to examine the effects of CSVD on brain functioning, activation and deactivation, in patients with MCI using task-related functional MRI (fMRI). METHODS: We included 16 MCI patients with CSVD, 26 MCI patients without CSVD and 25 controls. All participants underwent a physical and neurological examination, neuropsychological testing, structural MRI, and fMRI during a graded working memory paradigm. RESULTS: MCI patients with and without CSVD had a similar neuropsychological profile and task performance during fMRI, but differed with respect to underlying (de)activation patterns. MCI patients with CSVD showed impaired deactivation in the precuneus/posterior cingulate cortex, a region known to be involved in the default mode network. In MCI patients without CSVD, brain activation depended on working memory load, as they showed relative 'hyperactivation' during vigilance, and 'hypoactivation' at a high working memory load condition in working memory related brain regions. CONCLUSIONS: We present evidence that the potential underlying mechanism of CSVD affecting cognition in MCI is through network interference. The observed differences in brain activation and deactivation between MCI patients with and without CSVD, who had a similar 'clinical phenotype', support the view that, in patients with MCI, different types of pathology can contribute to cognitive impairment through different pathways. PMID- 24179757 TI - Altered emotional interference processing in the amygdala and insula in women with Post-Traumatic Stress Disorder. AB - BACKGROUND: Post-Traumatic Stress Disorder (PTSD) is characterized by distinct behavioral and physiological changes. Given the significant impairments related to PTSD, examination of the biological underpinnings is crucial to the development of theoretical models and improved treatments of PTSD. METHODS: We used an attentional interference task using emotional distracters to test for top down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry. A total of 32 women with PTSD (based on an interpersonal trauma) and 21 matched controls were tested. Event-related functional magnetic resonance imaging was carried out as participants directly attended to, or attempted to ignore, fear-related stimuli. RESULTS: Compared to controls, patients with PTSD showed hyperactivity in several brain regions, including the amygdala, insula, as well as dorsal lateral and ventral PFC regions. CONCLUSIONS: These results are consistent with previous studies that have higher amygdala and insular activation in PTSD subjects. However, inhibition of suppression of PFC regions is inconsistent with the fear circuitry model hypothesized by prior research. We suggest that the specific emotional conflict task used appears to target implicit or automatic emotional regulation instead of explicit or effortful emotional regulation. This is particularly relevant as it posited that emotional regulatory difficulties in anxiety disorders such as PTSD appear to occur in implicit forms of emotion regulation. PMID- 24179758 TI - Changes in the location of cortico-muscular coherence following stroke. AB - Stroke results in reorganization of residual brain networks. The functional role of brain regions within these networks remains unclear, particularly those in the contralesional hemisphere. We studied 25 stroke patients with a range of motor impairment and 23 healthy age-matched controls using magnetoencephalography (MEG) and electromyography (EMG) to measure oscillatory signals from the brain and affected muscles simultaneously during a simple isometric hand grip, from which cortico-muscular coherence (CMC) was calculated. Peaks of cortico-muscular coherence in both the beta and gamma bands were found in the contralateral sensorimotor cortex in all healthy controls, but were more widespread in stroke patients, including some peaks found in the contralesional hemisphere (7 patients for beta coherence and 5 for gamma coherence). Neither the coherence value nor the distance of the coherence peak from the mean of controls correlated with impairment. Peak CMC in the contralesional hemisphere was found not only in some highly impaired patients, but also in some patients with good functional recovery. Our results provide evidence that a wide range of cortical brain regions, including some in the contralesional hemisphere, may have influence over EMG activity in the affected muscles after stroke thereby supporting functional recovery. PMID- 24179759 TI - Impaired acquisition rates of probabilistic associative learning in frontotemporal dementia is associated with fronto-striatal atrophy. AB - Frontotemporal dementia (FTD) is classically considered to be a neurodegenerative disease with cortical changes. Recent structural imaging findings, however, highlight that subcortical and in particular striatal regions are also affected in the FTD syndrome. The influence of striatal pathology on cognitive and behavioural changes in FTD is virtually unexplored. In the current study we employ the Weather Prediction Task (WPT), a probabilistic learning task which taps into striatal dysfunction, in a group of FTD patients. We also regressed the patients' behavioural performance with their grey matter atrophy via voxel-based morphometry (VBM) to identify the grey matter contributions to WPT performance in FTD. Based on previous studies we expected to see striatal and frontal atrophy to be involved in impaired probabilistic learning. Our behavioural results show that patients performed on a similar level to controls overall, however, there was a large variability of patient performance in the first 30 trials of the task, which are critical in the acquisition of the probabilistic learning rules. A VBM analysis covarying the performance for the first 30 trials across participants showed that atrophy in striatal but also frontal brain regions correlated with WPT performance in these trials. Closer inspection of performance across the first 30 trials revealed a subgroup of FTD patients that performed significantly poorly than the remaining patients and controls on the WPT, despite achieving the same level of probabilistic learning as the other groups in later trials. Additional VBM analyses revealed that the subgroup of FTD patients with poor early probabilistic learning in the first 30 trials showed greater striatal atrophy compared to the remaining FTD patients and controls. These findings suggest that the integrity of fronto-striatal regions is important for probabilistic learning in FTD, with striatal integrity in particular, determining the acquisition learning rate. These findings will therefore have implications for developing an easily administered version of the probabilistic learning task which can be used by clinicians to assess striatal functioning in neurodegenerative syndromes. PMID- 24179760 TI - Preparatory neural networks are impaired in adults with attention deficit/hyperactivity disorder during the antisaccade task. AB - Adults with attention-deficit/hyperactivity disorder (ADHD) often display executive function impairments, particularly in inhibitory control. The antisaccade task, which measures inhibitory control, requires one to suppress an automatic prosaccade toward a salient visual stimulus and voluntarily make an antisaccade in the opposite direction. ADHD patients not only have longer saccadic reaction times, but also make more direction errors (i.e., a prosaccade was executed toward the stimulus) during antisaccade trials. These deficits may stem from pathology in several brain areas that are important for executive control. Using functional MRI with a rapid event-related design, adults with combined subtype of ADHD (coexistence of attention and hyperactivity problems), who abstained from taking stimulant medication 20 h prior to experiment onset, and age-match controls performed pro- and antisaccade trials that were interleaved with pro- and anti-catch trials (i.e., instruction was presented but no target appeared, requiring no response). This method allowed us to examine brain activation patterns when participants either prepared (during instruction) or executed (after target appearance) correct pro or antisaccades. Behaviorally, ADHD adults displayed several antisaccade deficits, including longer and more variable reaction times and more direction errors, but saccade metrics (i.e., duration, velocity, and amplitude) were normal. When preparing to execute an antisaccade, ADHD adults showed less activation in frontal, supplementary, and parietal eye fields, compared to controls. However, activation in these areas was normal in the ADHD group during the execution of a correct antisaccade. Interestingly, unlike controls, adults with ADHD produced greater activation than controls in dorsolateral prefrontal cortex during antisaccade execution, perhaps as part of compensatory mechanisms to optimize antisaccade production. Overall, these data suggest that the saccade deficits observed in adults with ADHD do not result from an inability to execute a correct antisaccade but rather the failure to properly prepare (i.e., form the appropriate task set) for the antisaccade trial. The data support the view that the executive impairments, including inhibitory control, in ADHD adults are related to poor response preparation. PMID- 24179761 TI - Altered functional and structural brain network organization in autism. AB - Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small world properties, network level organization has not been carefully examined in ASD. Here we used resting-state functional MRI (n = 42 ASD, n = 37 typically developing; TD) to show that children and adolescents with ASD display reduced short and long-range connectivity within functional systems (i.e., reduced functional integration) and stronger connectivity between functional systems (i.e., reduced functional segregation), particularly in default and higher-order visual regions. Using graph theoretical methods, we show that pairwise group differences in functional connectivity are reflected in network level reductions in modularity and clustering (local efficiency), but shorter characteristic path lengths (higher global efficiency). Structural networks, generated from diffusion tensor MRI derived fiber tracts (n = 51 ASD, n = 43 TD), displayed lower levels of white matter integrity yet higher numbers of fibers. TD and ASD individuals exhibited similar levels of correlation between raw measures of structural and functional connectivity (n = 35 ASD, n = 35 TD). However, a principal component analysis combining structural and functional network properties revealed that the balance of local and global efficiency between structural and functional networks was reduced in ASD, positively correlated with age, and inversely correlated with ASD symptom severity. Overall, our findings suggest that modeling the brain as a complex network will be highly informative in unraveling the biological basis of ASD and other neuropsychiatric disorders. PMID- 24179762 TI - A three dimensional anatomical view of oscillatory resting-state activity and functional connectivity in Parkinson's disease related dementia: An MEG study using atlas-based beamforming. AB - Parkinson's disease (PD) related dementia (PDD) develops in up to 80% of PD patients. The present study was performed to further unravel the underlying pathophysiological mechanisms by applying a new analysis approach that uses an atlas-based MEG beamformer to provide a detailed anatomical mapping of cortical rhythms and functional interactions. Importantly, we used the phase lag index (PLI) as a measure of functional connectivity to avoid any biases due to effects of volume conduction. MEG recordings were obtained in 13 PDD and 13 non-demented PD patients. Beamforming was used to estimate spectral power and PLI in delta, theta, alpha, beta and gamma frequency bands. Compared to PD patients, PDD patients had more delta and theta power in parieto-occipital and fronto-parietal areas, respectively. The PDD patients had less alpha and beta power in parieto temporo-occipital and frontal areas, respectively. Compared to PD patients, PDD patients had lower mean PLI values in the delta and alpha bands in fronto temporal and parieto-temporo-occipital areas, respectively. In addition, in PDD patients connectivity between pairs of regions of interest (Brodmann areas) was stronger in the theta band and weaker in the delta, alpha and beta bands. The added value of the present results over previous studies analysing frequency specific changes in neuronal activity in PD patients, is the anatomical framework in which we demonstrated a slowing in neuronal activity and a reduction in functional connectivity in PD related dementia. Moreover, this study shows a widespread reduction in functional connectivity between different regions in PDD. PMID- 24179763 TI - Imaging gene and environmental effects on cerebellum in Attention Deficit/Hyperactivity Disorder and typical development. AB - This study investigates the effects of XKR4, a recently identified candidate gene for Attention-Deficit/Hyperactivity Disorder (ADHD), birth weight, and their interaction on brain volume in ADHD. XKR4 is expressed in cerebellum and low birth weight has been associated both with changes in cerebellum and with ADHD, probably due to its relation with prenatal adversity. Anatomical MRI scans were acquired in 58 children with ADHD and 64 typically developing controls and processed to obtain volumes of cerebrum, cerebellum and gray and white matter in each structure. DNA was collected from saliva. Analyses including data on birth weight were conducted in a subset of 37 children with ADHD and 51 controls where these data were retrospectively collected using questionnaires. There was an interaction between genotype and birth weight for cerebellum gray matter volume (p = .020). The combination of homozygosity for the G-allele (the allele previously found to be overtransmitted in ADHD) and higher birth weight was associated with smaller volume. Furthermore, birth weight was positively associated with cerebellar white matter volume in controls, but not ADHD (interaction: p = .021). The interaction of genotype with birth weight affecting cerebellum gray matter is consistent with models that emphasize increased influence of genetic risk-factors in an otherwise favorable prenatal environment. The absence of an association between birth weight and cerebellum white matter volume in ADHD suggests that other genetic or environmental effects may be at play, unrelated to XKR4. These results underscore the importance of considering environmental effects in imaging genetics studies. PMID- 24179764 TI - Mapping cortical anatomy in preschool aged children with autism using surface based morphometry. AB - The challenges of gathering in-vivo measures of brain anatomy from young children have limited the number of independent studies examining neuroanatomical differences between children with autism and typically developing controls (TDCs) during early life, and almost all studies in this critical developmental window focus on global or lobar measures of brain volume. Using a novel cohort of young males with Autistic Disorder and TDCs aged 2 to 5 years, we (i) tested for group differences in traditional measures of global anatomy (total brain, total white, total gray and total cortical volume), and (ii) employed surface-based methods for cortical morphometry to directly measure the two biologically distinct sub components of cortical volume (CV) at high spatial resolution-cortical thickness (CT) and surface area (SA). While measures of global brain anatomy did not show statistically significant group differences, children with autism showed focal, and CT-specific anatomical disruptions compared to TDCs, consisting of relative cortical thickening in regions with central roles in behavioral regulation, and the processing of language, biological movement and social information. Our findings demonstrate the focal nature of brain involvement in early autism, and provide more spatially and morphometrically specific anatomical phenotypes for subsequent translational study. PMID- 24179765 TI - Regional cortical thickness in relapsing remitting multiple sclerosis: A multi center study. AB - A comprehensive analysis of the global and regional values of cortical thickness based on 3D magnetic resonance images was performed on 250 relapsing remitting multiple sclerosis (MS) patients who participated in a multi-center, randomized, phase III clinical trial (the CombiRx Trial) and 125 normal controls. The MS cohort was characterized by relatively low clinical disability and short disease duration. An automatic pipeline was developed for identifying images with poor quality and artifacts. The global and regional cortical thicknesses were determined using FreeSurfer software. Our results indicate significant cortical thinning in multiple regions in the MS patient cohort relative to the controls. Both global cortical thinning and regional cortical thinning were more prominent in the left hemisphere relative to the right hemisphere. Modest correlation was observed between cortical thickness and clinical measures that included the extended disability status scale and disease duration. Modest correlation was also observed between cortical thickness and T1-hypointense and T2-hyperintense lesions. These correlations were very similar at 1.5 T and 3 T field strengths. A much weaker inverse correlation between cortical thickness and age was observed among the MS subjects compared to normal controls. This age-dependent correlation was also stronger in males than in females. The values of cortical thickness were very similar at 1.5 T and 3 T field strengths. However, the age-dependent changes in both global and regional cortical thicknesses were observed to be stronger at 3 T relative to 1.5 T. PMID- 24179766 TI - "Awake" intraoperative functional MRI (ai-fMRI) for mapping the eloquent cortex: Is it possible in awake craniotomy? AB - As a promising noninvasive imaging technique, functional MRI (fMRI) has been extensively adopted as a functional localization procedure for surgical planning. However, the information provided by preoperative fMRI (pre-fMRI) is hampered by the brain deformation that is secondary to surgical procedures. Therefore, intraoperative fMRI (i-fMRI) becomes a potential alternative that can compensate for brain shifts by updating the functional localization information during craniotomy. However, previous i-fMRI studies required that patients be under general anesthesia, preventing the wider application of such a technique as the patients cannot perform tasks unless they are awake. In this study, we propose a new technique that combines awake surgery and i-fMRI, named "awake" i-fMRI (ai fMRI). We introduced ai-fMRI to the real-time localization of sensorimotor areas during awake craniotomy in seven patients. The results showed that ai-fMRI could successfully detect activations in the bilateral primary sensorimotor areas and supplementary motor areas for all patients, indicating the feasibility of this technique in eloquent area localization. The reliability of ai-fMRI was further validated using intraoperative stimulation mapping (ISM) in two of the seven patients. Comparisons between the pre-fMRI-derived localization result and the ai fMRI derived result showed that the former was subject to a heavy brain shift and led to incorrect localization, while the latter solved that problem. Additionally, the approaches for the acquisition and processing of the ai-fMRI data were fully illustrated and described. Some practical issues on employing ai fMRI in awake craniotomy were systemically discussed, and guidelines were provided. PMID- 24179767 TI - Neuro-anatomical correlates of a number bisection bias: A neuropsychological voxel-based morphometry study. AB - The number bisection tasks, whereby participants estimate the midpoint of a given number interval, is frequently used to explore the idea that numbers are spatially represented within the brain across a 'mental number line'. Some neuropsychological research supports the argument that number bisection is a spatial task, recruiting parietal brain regions, whereas other data suggest that number bisection is dissociable from spatial processing and is instead dependent on working memory in the prefrontal cortices. This study explored the anatomical correlates of deficits in the number bisection task, using voxel-based morphometry in a sample of 25 neuropsychological patients with both left and right hemisphere damage. Interestingly, impairments in number bisection were strongly associated with grey matter lesions in the left hemisphere including both frontal and prefrontal cortices, extending to inferior parietal cortex. Similar prefrontal and frontal grey matter areas were found to be associated with increased leftward deviations (underestimations of the midpoint), whereas no suprathreshold clusters were observed for rightward deviations from the midpoint. Analysis of white matter integrity revealed that lesions in the tracts connecting the parietal and frontal cortices (i.e. the superior longitudinal fasciculus) were highly associated with leftward deviation impairments in number bisection. The data suggest that there is a common parieto-frontal number processing network underlying performances on number bisection, with larger numbers represented on the left side. PMID- 24179768 TI - Structural imaging differences and longitudinal changes in primary lateral sclerosis and amyotrophic lateral sclerosis. AB - Magnetic resonance imaging measures have been proposed as objective markers to study upper motor neuron loss in motor neuron disorders. Cross-sectional studies have identified imaging differences between groups of healthy controls and patients with amyotrophic lateral sclerosis (ALS) or primary lateral sclerosis (PLS) that correlate with disease severity, but it is not known whether imaging measures change as disease progresses. Additionally, whether imaging measures change in a similar fashion with disease progression in PLS and ALS is unclear. To address these questions, clinical and imaging evaluations were first carried out in a prospective cross-sectional study of 23 ALS and 22 PLS patients with similar motor impairment and 19 age-matched healthy controls. Clinical evaluations consisted of a neurological examination, the ALS Functional rating scale-revised, and measures of finger tapping, gait, and timed speech. Age and ALSFRS score were not different, but PLS patients had longer duration of symptoms. Imaging measures examined were cortical thickness, regional brain volumes, and diffusion tensor imaging of the corticospinal tract and callosum. Imaging measures that differed from controls in a cross-sectional vertex-wise analysis were used as regions of interest for longitudinal analysis, which was carried out in 9 of the ALS patients (interval 1.26 +/- 0.72 years) and 12 PLS patients (interval 2.08 +/- 0.93 years). In the cross-sectional study both groups had areas of cortical thinning, which was more extensive in motor regions in PLS patients. At follow-up, clinical measures declined more in ALS than PLS patients. Cortical thinning and grey matter volume loss of the precentral gyri progressed over the follow-up interval. Fractional anisotropy of the corticospinal tracts remained stable, but the cross-sectional area declined in ALS patients. Changes in clinical measures correlated with changes in precentral cortical thickness and grey matter volume. The rate of cortical thinning was greater in ALS patients with shorter disease durations, suggesting that thickness decreases in a non linear fashion. Thus, cortical thickness changes are a potential imaging marker for disease progression in individual patients, but the magnitude of change likely depends on disease duration and progression rate. Differences between PLS and ALS patients in the magnitude of thinning in cross-sectional studies are likely to reflect longer disease duration. We conclude that there is an evolution of structural imaging changes with disease progression in motor neuron disorders. Some changes, such as diffusion properties of the corticospinal tract, occur early while cortical thinning and volume loss occur later. PMID- 24179769 TI - Assessing residual reasoning ability in overtly non-communicative patients using fMRI. AB - It is now well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are also capable of logical thought. Here, we validate an fMRI paradigm that can detect the neural fingerprint of reasoning processes and moreover, can confirm whether a participant derives logical answers. We demonstrate the efficacy of this approach in a physically non-communicative patient who had been shown to engage in mental imagery in response to simple auditory instructions. Our results demonstrate that this individual retains a remarkable capacity for higher cognition, engaging in the reasoning task and deducing logical answers. We suggest that this approach is suitable for detecting residual reasoning ability using neural responses and could readily be adapted to assess other aspects of cognition. PMID- 24179770 TI - Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study. AB - BACKGROUND: Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two. METHODS: 40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study. Macrostructural volumetrics were obtained for the whole brain, caudate, putamen, corpus callosum (CC) and ventricles. Microstructural diffusion metrics of fractional anisotropy (FA), mean , radial- and axial-diffusivity (MD, RD, AD) were computed for white matter (WM), CC, caudate and putamen. Group differences were examined adjusting for age, gender and site. A formal comparison of effect sizes determined which modality and metrics provided a statistically significant advantage over others. RESULTS: Macrostructural measures showed decreased regional and global volume in HD (p < 0.001); except the ventricles which were enlarged (p < 0.01). In HD, FA was increased in the deep grey-matter structures (p < 0.001), and decreased in the WM (CC, p = 0.035; WM, p = 0.053); diffusivity metrics (MD, RD, AD) were increased for all brain regions (p < 0.001). The largest effect sizes were for putamen volume, caudate volume and putamen diffusivity (AD, RD and MD); each was significantly larger than those for all other metrics (p < 0.05). CONCLUSION: The highest performing macro- and micro-structural metrics had similar sensitivity to HD pathology quantified via effect sizes. Region-of-interest may be more important than imaging modality, with deep grey-matter regions outperforming the CC and global measures, for both volume and diffusivity. FA appears to be relatively insensitive to disease effects. PMID- 24179771 TI - Evaluating multicenter DTI data in Huntington's disease on site specific effects: An ex post facto approach. AB - PURPOSE: Assessment of the feasibility to average diffusion tensor imaging (DTI) metrics of MRI data acquired in the course of a multicenter study. MATERIALS AND METHODS: Sixty-one early stage Huntington's disease patients and forty healthy controls were studied using four different MR scanners at four European sites with acquisition protocols as close as possible to a given standard protocol. The potential and feasibility of averaging data acquired at different sites was evaluated quantitatively by region-of-interest (ROI) based statistical comparisons of coefficients of variation (CV) across centers, as well as by testing for significant group-by-center differences on averaged fractional anisotropy (FA) values between patients and controls. In addition, a whole-brain based statistical between-group comparison was performed using FA maps. RESULTS: The ex post facto statistical evaluation of CV and FA-values in a priori defined ROIs showed no differences between sites above chance indicating that data were not systematically biased by center specific factors. CONCLUSION: Averaging FA maps from DTI data acquired at different study sites and different MR scanner types does not appear to be systematically biased. A suitable recipe for testing on the possibility to pool multicenter DTI data is provided to permit averaging of DTI-derived metrics to differentiate patients from healthy controls at a larger scale. PMID- 24179772 TI - Cerebral vascular control is associated with skeletal muscle pH in chronic fatigue syndrome patients both at rest and during dynamic stimulation. AB - Cerebral blood flow (CBF) is maintained despite changing systemic blood pressure through cerebral vascular control, with such tight regulation believed to be under local tissue control. Chronic fatigue syndrome (CFS) associates with a wide range of symptoms, including orthostatic intolerance, skeletal muscle pH abnormalities and cognitive impairment. CFS patients are known to have reduced CBF and orthostatic intolerance associates with abnormal vascular regulation, while skeletal muscle pH abnormalities associate with autonomic dysfunction. These findings point to autonomic dysfunction as the central feature of CFS, and cerebral vascular control being influenced by factors outside of the brain, a macroscopic force affecting the stability of regional regulation. We therefore explored whether there was a physiological link between cerebral vascular control and skeletal muscle pH management in CFS. Seventeen consecutive CFS patients fulfilling the Fukuda criteria were recruited from our local CFS clinical service. To probe the static scenario, CBF and skeletal muscle pH were measured at rest using MRI and (31)P magnetic resonance spectroscopy ((31)P-MRS). To examine dynamic control, brain functional MRI was performed concurrently with Valsalva manoeuvre (VM), a standard autonomic function challenge, while (31)P-MRS was performed during plantar flexion exercise. Significant inverse correlation was seen between CBF and skeletal muscle pH at rest (r = - 0.67, p < 0.01). Prolonged cerebral vascular constriction during the sympathetic phase of VM was associated with higher pH in skeletal muscle after plantar flexion exercise (r = 0.69, p < 0.008). In conclusion, cerebral vascular control is closely related to skeletal muscle pH both at rest and after dynamic stimulation in CFS. PMID- 24179773 TI - A comprehensive approach to the segmentation of multichannel three-dimensional MR brain images in multiple sclerosis. AB - Accurate classification and quantification of brain tissues is important for monitoring disease progression, measurement of atrophy, and correlating magnetic resonance (MR) measures with clinical disability. Classification of MR brain images in the presence of lesions, such as multiple sclerosis (MS), is particularly challenging. Images obtained with lower resolution often suffer from partial volume averaging leading to false classifications. While partial volume averaging can be reduced by acquiring volumetric images at high resolution, image segmentation and quantification can be technically challenging. In this study, we integrated the brain anatomical knowledge with non-parametric and parametric statistical classifiers for automatically classifying tissues and lesions on high resolution multichannel three-dimensional images acquired on 60 MS brains. The results of automatic lesion segmentation were reviewed by the expert. The agreement between results obtained by the automated analysis and the expert was excellent as assessed by the quantitative metrics, low absolute volume difference percent (36.18 +/- 34.90), low average symmetric surface distance (1.64 mm +/- 1.30 mm), high true positive rate (84.75 +/- 12.69), and low false positive rate (34.10 +/- 16.00). The segmented results were also in close agreement with the corrected results as assessed by Bland-Altman and regression analyses. Finally, our lesion segmentation was validated using the MS lesion segmentation grand challenge dataset (MICCAI 2008). PMID- 24179774 TI - Medial prefrontal brain activation to anticipated reward and loss in obsessive compulsive disorder. AB - Obsessive-compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation. PMID- 24179775 TI - Primary motor cortex activation and lateralization in patients with tumors of the central region. AB - Hemispheric lateralization is a frequently encountered phenomenon of cortical function. It describes the functional specialization of a region on one side of the brain for a given task. It is well characterized in motor and sensory, as well as language systems and becomes more and more known for various cognitive domains. While in the adult healthy brain hemispheric lateralization is mostly set, pathological processes may lead to cortical reorganization. In these cases neuroplasticity of the corresponding region in the non-dominant hemisphere seems to play an important role. In a previous study we investigated language associated regions in right-handed patients with frontal and temporal tumors of the left hemisphere. We observed a marked change of language lateralization in these patients towards the non-dominant hemisphere as measured by functional MRI (Partovi et al., 2012). In the present study we evaluated activation and lateralization of cortical motor areas in patients with tumors of the central region. BOLD fMRI was performed during unilateral voluntary movements of the contralesional hand in 87 patients. Individual correlations of measured BOLD signals with the model hemodynamic reference function were determined on a ROI basis in single subjects and compared to those of 16 healthy volunteers. In volunteers the strongest activation is usually found in the M1 hand representation contralateral to the movement, while a weaker homotopic co activation is observed in ipsilateral M1 (Stippich et al., 2007a). In the patient group our results show significant changes of motor activations, ranging from a reduction of M1 lateralization to equalization of M1 activations or even inversion of M1 lateralization during contralesional movements. This study corroborates in a large patient group the idea that lesions affecting M1 may lead to functional reorganization of cortical motor systems and in particular equalize hemispheric lateralization. However, it is not yet clear whether these changes are only an epiphenomenon or indeed reflect an attempt of recovery of brain function. PMID- 24179776 TI - Electrophysiological responses to emotional prosody perception in cochlear implant users. AB - The present electroencephalographic (EEG) study investigated the ability of cochlear implant (CI) users to recognize emotional prosody. Two CI speech processing strategies were compared: the ACE (Advance Combination Encoder) and the newly developed MP3000. Semantically neutral sentences spoken in three different emotional prosodies (neutral, angry, happy) were presented to 20 post lingually deafened CI users and age-matched normal-hearing controls. Event related potentials (ERPs) were recorded to study the N100 and the P200 responses. In addition, event-related spectral power modulations were calculated to study the brain activity corresponding to the recognition of prosody in earlier (0-400) as well as later (600-1200) part of the stimuli where the prosodic features differed maximally. CI users with MP3000 strategy showed a higher proportion of correctly recognized prosodic information compared to the ACE strategy users. Our ERP results demonstrated that emotional prosody elicited significant N100 and P200 peaks. Furthermore, the P200 amplitude in response to happy prosodic information was significantly more positive for the MP3000 strategy compared to the ACE strategy. On spectral power analysis, two typical gamma activities were observed in the MP3000 users only: (1) an early gamma activity in the 100-250 ms time window reflecting bottom-up attention regulation; and (2) a late gamma activity between 900 and 1100 ms post-stimulus onset, probably reflecting top down cognitive control. Our study suggests that the MP3000 strategy is better than ACE in regard to happy prosody perception. Furthermore, we show that EEG is a useful tool that, in combination with behavioral analysis, can reveal differences between two CI processing strategies for coding of prosody-specific features of language. PMID- 24179777 TI - Reduced functional integration of the sensorimotor and language network in rolandic epilepsy. AB - INTRODUCTION: Over the last years, evidence has accumulated that rolandic epilepsy (RE) is associated with serious cognitive comorbidities, including language impairment. However, the cerebral mechanism through which epileptiform activity in the rolandic (sensorimotor) areas may affect the language system is unknown. To investigate this, the connectivity between rolandic areas and regions involved in language processing is studied using functional MRI (fMRI). MATERIALS AND METHODS: fMRI data was acquired from 22 children with rolandic epilepsy and 22 age-matched controls (age range: 8-14 years), both at rest and using word generation and reading tasks. Activation map analysis revealed no group differences (FWE-corrected, p < 0.05) and was therefore used to define regions of interest for pooled (patients and controls combined) language activation. Independent component analysis with dual regression was used to identify the sensorimotor resting-state network in all subjects. The associated functional connectivity maps were compared between groups at the regions of interest for language activation identified from the task data. In addition, neuropsychological language testing (Clinical Evaluation of Language Fundamentals, 4th edition) was performed. RESULTS: Functional connectivity with the sensorimotor network was reduced in patients compared to controls (p = 0.011) in the left inferior frontal gyrus, i.e. Broca's area as identified by the word generation task. No aberrant functional connectivity values were found in the other regions of interest, nor were any associations found between functional connectivity and language performance. Neuropsychological testing confirmed language impairment in patients relative to controls (reductions in core language score, p = 0.03; language content index, p = 0.01; receptive language index, p = 0.005). CONCLUSION: Reduced functional connectivity was demonstrated between the sensorimotor network and the left inferior frontal gyrus (Broca's area) in children with RE, which might link epileptiform activity/seizures originating from the sensorimotor cortex to language impairment, and is in line with the identified neuropsychological profile of anterior language dysfunction. PMID- 24179778 TI - Repeat after me: Replication in clinical neuroimaging is critical. PMID- 24179780 TI - DTI detects water diffusion abnormalities in the thalamus that correlate with an extremity pain episode in a patient with multiple sclerosis. AB - BACKGROUND: Various types of multiple sclerosis (MS) related pain have been discussed. One concept is that deafferentation secondary to lesions in the spino thalamo-cortical network can cause central pain. However, this hypothesis is somehow limited by a lack of a robust association between pain episodes and sites of lesion location. OBJECTIVE: We tested the hypothesis that temporary tissue alterations in the thalamus that are not detectable by conventional magnetic resonance imaging (T1w, FLAIR) can potentially explain a focal, paroxysmal central pain episode of a patient with MS. For microstructural tissue assessment we employed ten longitudinal diffusion tensor imaging (DTI) examinations. RESULTS: We could demonstrate an abnormal, unilateral temporary increase of the fractional anisotropy (FA) in the thalamus contralateral to the affected body side. Before the pain episode and after pain relief the FA reached completely normal values as seen in identically investigated age and gender matched 100 healthy control subjects. CONCLUSION: THESE FINDINGS SUGGEST THAT: i.) frequently applied and quantitatively evaluated DTI could be used as a sensitive imaging technique for detection of pathological processes associated with MS not detectable with conventional imaging strategies, ii.) temporary pathological processes in the "normal-appearing" thalamus may explain waxing and waning symptoms like episodes of central pain, and iii.) cross-sectional case examinations on (MS) patients with central pain should be performed to investigate how often thalamic alterations occur together with central pain. PMID- 24179779 TI - Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects? AB - The objective of our study was to evaluate whether cognitively normal (CN) elderly participants showing elevated cortical beta-amyloid (Abeta) deposition have a consistent neuroanatomical signature of brain atrophy that may characterize preclinical Alzheimer's disease (AD). 115 CN participants who were Abeta-positive (CN +) by amyloid PET imaging; 115 CN participants who were Abeta negative (CN -); and 88 Abeta-positive mild cognitive impairment or AD participants (MCI/AD +) were identified. Cortical thickness (FreeSurfer) and gray matter volume (SPM5) were measured for 28 regions-of-interest (ROIs) across the brain and compared across groups. ROIs that best discriminated CN - from CN + differed for FreeSurfer cortical thickness and SPM5 gray matter volume. Group wise discrimination was poor with a high degree of uncertainty in terms of the rank ordering of ROIs. In contrast, both techniques showed strong and consistent findings comparing MCI/AD + to both CN - and CN + groups, with entorhinal cortex, middle and inferior temporal lobe, inferior parietal lobe, and hippocampus providing the best discrimination for both techniques. Concordance across techniques was higher for the CN - and CN + versus MCI/AD + comparisons, compared to the CN - versus CN + comparison. The weak and inconsistent nature of the findings across technique in this study cast doubt on the existence of a reliable neuroanatomical signature of preclinical AD in elderly PiB-positive CN participants. PMID- 24179781 TI - Money for nothing - Atrophy correlates of gambling decision making in behavioural variant frontotemporal dementia and Alzheimer's disease. AB - Neurodegenerative patients show often severe everyday decision making problems. Currently it is however not clear which brain atrophy regions are implicated in such decision making problems. We investigated the atrophy correlates of gambling decision making in a sample of 63 participants, including two neurodegenerative conditions (behavioural variant frontotemporal dementia - bvFTD; Alzheimer's disease - AD) as well as healthy age-matched controls. All participants were tested on the Iowa Gambling Task (IGT) and the behavioural IGT results were covaried against the T1 MRI scans of all participants to identify brain atrophy regions implicated in gambling decision making deficits. Our results showed a large variability in IGT performance for all groups with both patient groups performing especially poor on the task. Importantly, bvFTD and AD groups did not differ significantly on the behavioural performance of the IGT. However, by contrast, the atrophy gambling decision making correlates differed between bvFTD and AD, with bvFTD showing more frontal atrophy and AD showing more parietal and temporal atrophy being implicated in decision making deficits, indicating that both patient groups fail the task on different levels. Frontal (frontopolar, anterior cingulate) and parietal (retrosplenial) cortex atrophy covaried with poor performance on the IGT. Taken together, the atrophy correlates of gambling decision making show that such deficits can occur due to a failure of different neural structures, which will inform future diagnostics and treatment options to alleviate these severe everyday problems in neurodegenerative patients. PMID- 24179782 TI - Disrupted segregation of working memory networks in temporal lobe epilepsy. AB - Working memory is a critical building block for almost all cognitive tasks, and impairment can cause significant disruption to daily life routines. We investigated the functional connectivity (FC) of the visuo-spatial working memory network in temporal lobe epilepsy and its relationship to the underlying white matter tracts emanating from the hippocampus. Fifty-two patients with unilateral hippocampal sclerosis (HS) (30 left) and 30 healthy controls underwent working memory functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). Six seed regions were identified for FC analysis; 4 within a task-positive network (left and right middle frontal gyri and superior parietal lobes), and 2 within a task-negative network (left and right hippocampi). FC maps were created by extracting the time series of the fMRI signal in each region in each subject and were used as regressors of interest for additional GLM fMRI analyses. Structural connectivity (SC) corresponding to areas to which the left and right hippocampi were connected was determined using tractography, and a mean FA for each hippocampal SC map was calculated. Both left and right HS groups showed atypical FC between task positive and task-negative networks compared to controls. This was characterised by co-activation of the task-positive superior parietal lobe ipsilateral to the typically task-negative sclerosed hippocampus. Correlational analysis revealed stronger FC between superior parietal lobe and ipsilateral hippocampus, was associated with worse performance in each patient group. The SC of the hippocampus was associated with the intra-hemispheric FC of the superior parietal lobe, in that greater SC was associated with weaker parieto-frontal FC. The findings suggest that the segregation of the task-positive and task-negative FC networks supporting working memory in TLE is disrupted, and is associated with abnormal structural connectivity of the sclerosed hippocampus. Co-activation of parieto-temporal regions was associated with poorer working memory and this may be associated with working memory dysfunction in TLE. PMID- 24179783 TI - Computer-aided detection of radiation-induced cerebral microbleeds on susceptibility-weighted MR images. AB - Recent interest in exploring the clinical relevance of cerebral microbleeds (CMBs) has motivated the search for a fast and accurate method to detect them. Visual inspection of CMBs on MR images is a lengthy, arduous task that is highly prone to human error because of their small size and wide distribution throughout the brain. Several computer-aided CMB detection algorithms have recently been proposed in the literature, but their diagnostic accuracy, computation time, and robustness are still in need of improvement. In this study, we developed and tested a semi-automated method for identifying CMBs on minimum intensity projected susceptibility-weighted MR images that are routinely used in clinical practice to visually identify CMBs. The algorithm utilized the 2D fast radial symmetry transform to initially detect putative CMBs. Falsely identified CMBs were then eliminated by examining geometric features measured after performing 3D region growing on the potential CMB candidates. This algorithm was evaluated in 15 patients with brain tumors who exhibited CMBs on susceptibility-weighted images due to prior external beam radiation therapy. Our method achieved heightened sensitivity and acceptable amount of false positives compared to prior methods without compromising computation speed. Its superior performance and simple, accelerated processing make it easily adaptable for detecting CMBs in the clinic and expandable to a wide array of neurological disorders. PMID- 24179784 TI - Common and distinct neural mechanisms of visual and tactile extinction: A large scale VBM study in sub-acute stroke. AB - Extinction is diagnosed when patients respond to a single contralesional item but fail to detect this item when an ipsilesional item is present concurrently. Extinction has been studied mainly in the visual modality but it occurs also in other sensory modalities (touch, audition) and hence can be considered a multisensory phenomenon. The functional and neuroanatomical relations between extinction in different modalities are poorly understood. Here, we used voxel based mophometry (VBM) to examine the neuronal substrates of visual versus tactile extinction in a large group of sub-acute patients (n = 454) with strokes affecting different vascular territories. We found that extinction deficits in tactile and visual modalities were significantly correlated (r = 0.341; p < 0.01). Several lesions within the right hemisphere were linked to extinction including the inferior parietal lobule, the superior parietal lobule, the middle frontal and occipital gyri, while lesions involving the superior temporal gyrus, inferior temporal gyrus and putamen were associated with tactile extinction. Damage within the middle temporal gyrus and superior temporal sulcus was linked to both deficits. We conclude that extinction in different modalities emerges after damage to both common (supra-modal) and distinct (modality specific) brain regions, and that contrasting sites emerge after damage to different vascular territories. We discuss the implications for understanding extinction as a multisensory disorder. PMID- 24179785 TI - fMRI investigation of visual change detection in adults with autism. AB - People with autism spectrum disorders (ASD) may show unusual reactions to unexpected changes that appear in their environment. Although several studies have highlighted atypical auditory change processing in ASD, little is known in this disorder about the brain processes involved in visual automatic change detection. The present fMRI study was designed to localize brain activity elicited by unexpected visual changing stimuli in adults with ASD compared to controls. Twelve patients with ASD and 17 healthy adults participated in the experiment in which subjects were presented with a visual oddball sequence while performing a concurrent target detection task. Combined results across participants highlight the involvement of both occipital (BA 18/19) and frontal (BA 6/8) regions during visual change detection. However, adults with ASD display greater activity in the bilateral occipital cortex and in the anterior cingulate cortex (ACC) associated with smaller activation in the superior and middle frontal gyri than controls. A psychophysiological interaction (PPI) analysis was performed with ACC as the seed region and revealed greater functionally connectivity to sensory regions in ASD than in controls, but less connectivity to prefrontal and orbito-frontal cortices. Thus, compared to controls, larger sensory activation associated with reduced frontal activation was seen in ASD during automatic visual change detection. Atypical psychophysiological interactions between frontal and occipital regions were also found, congruent with the idea of atypical connectivity between these regions in ASD. The atypical involvement of the ACC in visual change detection can be related to abnormalities previously observed in the auditory modality, thus supporting the hypothesis of an altered general mechanism of change detection in patients with ASD that would underlie their unusual reaction to change. PMID- 24179786 TI - A quantitative link between face discrimination deficits and neuronal selectivity for faces in autism. AB - Individuals with Autism Spectrum Disorder (ASD) appear to show a general face discrimination deficit across a range of tasks including social-emotional judgments as well as identification and discrimination. However, functional magnetic resonance imaging (fMRI) studies probing the neural bases of these behavioral differences have produced conflicting results: while some studies have reported reduced or no activity to faces in ASD in the Fusiform Face Area (FFA), a key region in human face processing, others have suggested more typical activation levels, possibly reflecting limitations of conventional fMRI techniques to characterize neuron-level processing. Here, we test the hypotheses that face discrimination abilities are highly heterogeneous in ASD and are mediated by FFA neurons, with differences in face discrimination abilities being quantitatively linked to variations in the estimated selectivity of face neurons in the FFA. Behavioral results revealed a wide distribution of face discrimination performance in ASD, ranging from typical performance to chance level performance. Despite this heterogeneity in perceptual abilities, individual face discrimination performance was well predicted by neural selectivity to faces in the FFA, estimated via both a novel analysis of local voxel-wise correlations, and the more commonly used fMRI rapid adaptation technique. Thus, face processing in ASD appears to rely on the FFA as in typical individuals, differing quantitatively but not qualitatively. These results for the first time mechanistically link variations in the ASD phenotype to specific differences in the typical face processing circuit, identifying promising targets for interventions. PMID- 24179787 TI - Mobility impairment is associated with reduced microstructural integrity of the inferior and superior cerebellar peduncles in elderly with no clinical signs of cerebellar dysfunction. AB - While the cerebellum plays a critical role in motor coordination and control no studies have investigated its involvement in idiopathic mobility impairment in community-dwelling elderly. In this study we tested the hypothesis that structural changes in the cerebellar peduncles not detected by conventional magnetic resonance imaging are associated with reduced mobility performance. The analysis involved eighty-five subjects (age range: 75-90 years) who had no clinical signs of cerebellar dysfunction. Based on the short physical performance battery (SPPB) score, we defined mobility status of the subjects in the study as normal (score 11-12, n = 26), intermediate (score 9-10, n = 27) or impaired (score < 9, n = 32). We acquired diffusion tensor imaging data to obtain indices of white matter integrity: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Using a parcellation atlas, regional indices within the superior, middle, and inferior cerebellar peduncles (ICP, MCP, SCP) were calculated and their associations with mobility performance were analyzed. Subjects with impaired mobility showed reduced FA and AD values in the ICP and SCP but not in the MCP. The ICP-FA, ICP-AD and SCP-FA indices showed a significant association with the SPPB score. We also observed significant correlation between ICP-FA and walk time (r = - 0.311, p = 0.004), as well as between SCP-AD and self-paced maximum walking velocity (r = 0.385, p = 0.003) and usual walking velocity (r = 0.400, p = 0.002). In logistic regression analysis ICP-FA and ICP-AD together explained 51% of the variability in the mobility status of a sample comprising the normal and impaired subgroups, and correctly classified more than three-quarters of those subjects. Our findings suggest that presence of microstructural damage, likely axonal, in afferent and efferent connections of the cerebellum contributes to the deterioration of motor performance in older people. PMID- 24179788 TI - Catecholamine depletion in first-degree relatives of individuals with mood disorders: An [(18)F]fluorodeoxyglucose positron emission tomography study. AB - Catecholamine depletion with alpha-methylparatyrosine (AMPT) has previously been shown to induce depressive symptoms in currently remitted patients with major depressive disorder (MDD) but not healthy controls. Thus sensitivity to catecholamine depletion has been hypothesized to be an endophenotype of MDD. Here we tested this hypothesis in the context of a randomized, double-blinded, placebo controlled design by measuring changes in mood in a group of psychiatrically healthy individuals at risk of mood disorders by virtue of family history (high risk subjects, HRs). In addition, we tested whether HRs differed from healthy controls with no family-history of mood disorders (low-risk controls, LRs) in their cerebral metabolic response when undergoing catecholamine depletion. Eight healthy LRs (6 males, mean age = 34.1 +/- 7.1) and 6 healthy HRs (3 males, mean age = 29.3 +/- 4.6) participated in two, 3-day-long identical sessions during which they completed standardized measures of depression, anxiety and fatigue and an [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan. On one occasion participants received 4 weight-adjusted doses of AMPT and on the other occasion participants received 4 doses of placebo. The LR and HR groups did not differ from each other in their mood during sham depletion. However, during the period of peak catecholamine depletion, the HR group reported significantly more depression, anxiety and fatigue than the LR group. A region-of-interest analysis showed that during catecholamine depletion versus placebo the combined LR and HR groups displayed a significant increase in cerebral metabolic rate in the left and right ventral striata, left and right amygdalae, and left and right hippocampi (FWE-corrected p < 0.05). Whole brain voxel-wise analyses indicated significantly increased glucose metabolism in the left and right putamina (FWE corrected p < 0.05) in the combined LR and HR groups in the AMPT versus the placebo session. In the LR group, alone, no significant elevation in glucose metabolism was observed in the regions-of-interest in the catecholamine depletion versus placebo condition. In the HR group, alone, the region-of-interest analysis showed a significant increase in cerebral metabolic rate in the left and right ventral striata (FWE-corrected p < 0.05). No regions-of-interest showed significantly different metabolism in the HR group versus the LR group in the placebo condition, however compared with the LR group, the HR group displayed nominally increased glucose metabolism in the left amygdala during catecholamine depletion (SVC-corrected p = 0.05). A region-of-interest analysis for the interaction contrast confirmed that catecholamine depletion had differential effects on HR and LR participants. Compared with the LR group, the HR group displayed significantly increased glucose metabolism in the left ventral striatum, left amygdala, and left lateral orbitofrontal cortex (OFC) (FWE corrected p < 0.05). Our results suggest that sensitivity to catecholamine depletion may be a phenotypic marker of vulnerability to mood disorders that is characterized at the neurophysiological level by disinhibition of the striatum and its efferent projections comprising the limbic-cortical-striatal-pallidal thalamic circuitry. PMID- 24179789 TI - Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease. AB - Recent developments of PET amyloid ligands have made it possible to visualize the presence of Abeta deposition in the brain of living participants and to assess the consequences especially in individuals with no objective sign of cognitive deficits. The present review will focus on amyloid imaging in cognitively normal elderly, asymptomatic at-risk populations, and individuals with subjective cognitive decline. It will cover the prevalence of amyloid-positive cases amongst cognitively normal elderly, the influence of risk factors for AD, the relationships to cognition, atrophy and prognosis, longitudinal amyloid imaging and ethical aspects related to amyloid imaging in cognitively normal individuals. Almost ten years of research have led to a few consensual and relatively consistent findings: some cognitively normal elderly have Abeta deposition in their brain, the prevalence of amyloid-positive cases increases in at-risk populations, the prognosis for these individuals is worse than for those with no Abeta deposition, and significant increase in Abeta deposition over time is detectable in cognitively normal elderly. More inconsistent findings are still under debate; these include the relationship between Abeta deposition and cognition and brain volume, the sequence and cause-to-effect relations between the different AD biomarkers, and the individual outcome associated with an amyloid positive versus negative scan. Preclinical amyloid imaging also raises important ethical issues. While amyloid imaging is definitely useful to understand the role of Abeta in early stages, to define at-risk populations for research or for clinical trial, and to assess the effects of anti-amyloid treatments, we are not ready yet to translate research results into clinical practice and policy. More researches are needed to determine which information to disclose from an individual amyloid imaging scan, the way of disclosing such information and the impact on individuals and on society. PMID- 24179790 TI - Osmotic release oral system-methylphenidate improves neural activity during low reward processing in children and adolescents with attention deficit/hyperactivity disorder. AB - Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) studies revealed that acute treatment with MPH alters activation of the nucleus accumbens during delay aversion in children and adolescents with ADHD, the effects a relatively long period of OROS-MPH treatment on delay aversion as well as reward sensitivity remain unclear. Thus, we evaluated brain activation with fMRI during a reward sensitivity paradigm that consists of high monetary reward and low monetary reward conditions before and after a 3-month treatment with OROS-MPH in 17 children and adolescents with ADHD (mean age, 13.3 +/- 2.2) and 17 age- and sex-matched healthy controls (mean age, 13.0 +/- 1.9). We found that before treatment there was decreased activation of the nucleus accumbens and thalamus in patients with ADHD during only the low monetary reward condition, which was improved to same level as those of the healthy controls after the treatment. The observed change in brain activity was associated with improved ADHD symptom scores, which were derived from Japanese versions of the ADHD rating scale-IV. These results suggest that treatment with OROS-MPH for a relatively long period is effective in controlling reward sensitivity in children and adolescents with ADHD. PMID- 24179791 TI - Reduced functional brain connectivity prior to and after disease onset in Huntington's disease. AB - BACKGROUND: Huntington's disease (HD) is characterised by both regional and generalised neuronal cell loss in the brain. Investigating functional brain connectivity patterns in rest in HD has the potential to broaden the understanding of brain functionality in relation to disease progression. This study aims to establish whether brain connectivity during rest is different in premanifest and manifest HD as compared to controls. METHODS: At the Leiden University Medical Centre study site of the TRACK-HD study, 20 early HD patients (disease stages 1 and 2), 28 premanifest gene carriers and 28 healthy controls underwent 3 T MRI scanning. Standard and high-resolution T1-weighted images and a resting state fMRI scan were acquired. Using FSL, group differences in resting state connectivity were examined for eight networks of interest using a dual regression method. With a voxelwise correction for localised atrophy, group differences in functional connectivity were examined. RESULTS: Brain connectivity of the left middle frontal and pre-central gyrus, and right post central gyrus with the medial visual network was reduced in premanifest and manifest HD as compared to controls (0.05 > p > 0.0001). In manifest HD connectivity of numerous widespread brain regions with the default mode network and the executive control network were reduced (0.05 > p > 0.0001). DISCUSSION: Brain regions that show reduced intrinsic functional connectivity are present in premanifest gene carriers and to a much larger extent in manifest HD patients. These differences are present even when the potential influence of atrophy is taken into account. Resting state fMRI could potentially be used for early disease detection in the premanifest phase of HD and for monitoring of disease modifying compounds. PMID- 24179792 TI - Fronto-striatal dysregulation in drug addiction and pathological gambling: Consistent inconsistencies? AB - Alterations in appetitive processing are central to the major psychological theories of addiction, with differential predictions made by the reward deficiency, incentive salience, and impulsivity hypotheses. Functional MRI has become the chief means of testing these predictions, with experiments reliably highlighting disturbances at the level of the striatum, medial prefrontal cortex, and affiliated regions. However, demonstrations of hypo-reactivity and hyper reactivity of this circuitry in drug addicted groups are reported in approximately equal measure. Similar findings are echoed in the emergent neuroimaging literature on pathological gambling, which has recently witnessed a coming of age. The first aim of this article is to consider some of the methodological aspects of these experiments that could influence the observed direction of group-level effects, including the baseline condition, trial structure and timing, and the nature of the appetitive cues (drug-related, monetary, or primary rewards). The second aim is to highlight the conceptual traction that is offered by pathological gambling, as a model of a 'toxicity free' addiction and an illness where tasks of monetary reinforcement afford a more direct mapping to the abused commodity. Our conclusion is that relatively subtle decisions in task design appear capable of driving group differences in fronto-striatal circuitry in entirely opposing directions, even with tasks and task variants that look ostensibly similar. Differentiation between the psychological theories of addiction will require a greater breadth of experimental designs, with more research needed on processing of primary appetitive cues, aversive processing, and in vulnerable/at-risk groups. PMID- 24179793 TI - Altered brain connectivity in 3-to 7-year-old children with autism spectrum disorder. AB - Autism spectrum disorder (ASD) is often described as a disorder of aberrant neural connectivity and/or aberrant hemispheric lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, the physiological connectivity of the brain in young children with ASD under conscious conditions has not yet been described. Magnetoencephalography (MEG) is a noninvasive brain imaging technique that is practical for use in young children. MEG produces a reference-free signal and is, therefore, an ideal tool for computing the coherence between two distant cortical rhythms. Using a custom child-sized MEG, we recently reported that 5- to 7-year-old children with ASD (n = 26) have inherently different neural pathways than typically developing (TD) children that contribute to their relatively preserved performance of visual tasks. In this study, we performed non-invasive measurements of the brain activity of 70 young children (3-7 years old, of which 18 were aged 3-4 years), a sample consisting of 35 ASD children and 35 TD children. Physiological connectivity and the laterality of physiological connectivity were assessed using intrahemispheric coherence for 9 frequency bands. As a result, significant rightward connectivity between the parietotemporal areas, via gamma band oscillations, was found in the ASD group. As we obtained the non-invasive measurements using a custom child-sized MEG, this is the first study to demonstrate a rightward-lateralized neurophysiological network in conscious young children (including children aged 3-4 years) with ASD. PMID- 24179794 TI - OASIS is Automated Statistical Inference for Segmentation, with applications to multiple sclerosis lesion segmentation in MRI. AB - Magnetic resonance imaging (MRI) can be used to detect lesions in the brains of multiple sclerosis (MS) patients and is essential for diagnosing the disease and monitoring its progression. In practice, lesion load is often quantified by either manual or semi-automated segmentation of MRI, which is time-consuming, costly, and associated with large inter- and intra-observer variability. We propose OASIS is Automated Statistical Inference for Segmentation (OASIS), an automated statistical method for segmenting MS lesions in MRI studies. We use logistic regression models incorporating multiple MRI modalities to estimate voxel-level probabilities of lesion presence. Intensity-normalized T1-weighted, T2-weighted, fluid-attenuated inversion recovery and proton density volumes from 131 MRI studies (98 MS subjects, 33 healthy subjects) with manual lesion segmentations were used to train and validate our model. Within this set, OASIS detected lesions with a partial area under the receiver operating characteristic curve for clinically relevant false positive rates of 1% and below of 0.59% (95% CI; [0.50%, 0.67%]) at the voxel level. An experienced MS neuroradiologist compared these segmentations to those produced by LesionTOADS, an image segmentation software that provides segmentation of both lesions and normal brain structures. For lesions, OASIS out-performed LesionTOADS in 74% (95% CI: [65%, 82%]) of cases for the 98 MS subjects. To further validate the method, we applied OASIS to 169 MRI studies acquired at a separate center. The neuroradiologist again compared the OASIS segmentations to those from LesionTOADS. For lesions, OASIS ranked higher than LesionTOADS in 77% (95% CI: [71%, 83%]) of cases. For a randomly selected subset of 50 of these studies, one additional radiologist and one neurologist also scored the images. Within this set, the neuroradiologist ranked OASIS higher than LesionTOADS in 76% (95% CI: [64%, 88%]) of cases, the neurologist 66% (95% CI: [52%, 78%]) and the radiologist 52% (95% CI: [38%, 66%]). OASIS obtains the estimated probability for each voxel to be part of a lesion by weighting each imaging modality with coefficient weights. These coefficients are explicit, obtained using standard model fitting techniques, and can be reused in other imaging studies. This fully automated method allows sensitive and specific detection of lesion presence and may be rapidly applied to large collections of images. PMID- 24179796 TI - Predicting outcome and recovery after stroke with lesions extracted from MRI images. AB - Here, we present and validate a method that lets us predict the severity of cognitive impairments after stroke, and the likely course of recovery over time. Our approach employs (a) a database that records the behavioural scores from a large population of patients who have, collectively, incurred a comprehensive range of focal brain lesions, (b) an automated procedure to convert structural brain scans from those patients into three-dimensional images of their lesions, and (c) a system to learn the relationship between patients' lesions, demographics and behavioural capacities at different times post-stroke. Validation against data collected from 270 stroke patients suggests that our first set of variables yielded predictions that match or exceed the predictive power reported in any comparable work in the available literature. Predictions are likely to improve when other determinants of recovery are included in the system. Many behavioural outcomes after stroke could be predicted using the proposed approach. PMID- 24179795 TI - Disturbed resting state EEG synchronization in bipolar disorder: A graph theoretic analysis. AB - Disruption of functional connectivity may be a key feature of bipolar disorder (BD) which reflects disturbances of synchronization and oscillations within brain networks. We investigated whether the resting electroencephalogram (EEG) in patients with BD showed altered synchronization or network properties. Resting state EEG was recorded in 57 BD type-I patients and 87 healthy control subjects. Functional connectivity between pairs of EEG channels was measured using synchronization likelihood (SL) for 5 frequency bands (delta, theta, alpha, beta, and gamma). Graph-theoretic analysis was applied to SL over the electrode array to assess network properties. BD patients showed a decrease of mean synchronization in the alpha band, and the decreases were greatest in fronto central and centro-parietal connections. In addition, the clustering coefficient and global efficiency were decreased in BD patients, whereas the characteristic path length increased. We also found that the normalized characteristic path length and small-worldness were significantly correlated with depression scores in BD patients. These results suggest that BD patients show impaired neural synchronization at rest and a disruption of resting-state functional connectivity. PMID- 24179797 TI - Early onset of cortical thinning in children with rolandic epilepsy. AB - INTRODUCTION: Rolandic epilepsy, a childhood epilepsy associated with language impairments, was investigated for language-related cortical abnormalities. METHODS: Twenty-four children with rolandic epilepsy and 24 controls (age 8-14 years) were recruited and underwent the Clinical Evaluation of Language Fundamentals test. Structural MRI was performed at 3 T (voxel size 1 * 1 * 1 mm(3)) for fully automated quantitative assessment of cortical thickness. Regression analysis was used to test for differences between patients and controls and to assess the effect of age and language indices on cortical thickness. RESULTS: For patients the core language score (mean +/- SD: 92 +/- 18) was lower than for controls (106 +/- 11, p = 0.0026) and below the norm of 100 +/ 15 (p = 0.047). Patients showed specific impairments in receptive language index (87 +/- 19, p = 0.002) and language content index (87 +/- 18, p = 0.0016). Cortical thickness was reduced in patients (p < 0.05, multiple-comparisons corrected) in left perisylvian regions. Furthermore, extensive cortical thinning with age was found in predominantly left-lateralized frontal, centro-parietal and temporal regions. No associations were found between cortical thickness and language indices in the regions of aberrant cortex. CONCLUSION: The cortical abnormalities described represent subtle but significant pathomorphology in this critical phase of brain development (8-14 years) and suggest that rolandic epilepsy should not be considered merely a benign condition. Future studies employing longitudinal designs are prompted for further investigations into cerebral abnormalities in RE and associations with cognitive impairment and development. PMID- 24179798 TI - Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts. AB - Cerebral palsy (CP) is a heterogeneous group of non-progressive motor disorders caused by injury to the developing fetal or infant brain. Although the defining feature of CP is motor impairment, numerous other neurodevelopmental disabilities are associated with CP and contribute greatly to its morbidity. The relationship between brain structure and neurodevelopmental outcomes in CP is complex, and current evidence suggests that motor and developmental outcomes are related to the spatial pattern and extent of brain injury. Given that multiple disabilities are frequently associated with CP, and that there is increasing burden of neurodevelopmental disability with increasing motor severity, global white matter (WM) connectivity was examined in a cohort of 17 children with bilateral CP to test the hypothesis that increased global WM damage will be seen in the group of severely affected (Gross Motor Function Classification Scale (GMFCS) level of IV) as compared to moderately affected (GMFCS of II or III) individuals. Diffusion tensor tractography was performed and the resulting fibers between anatomically defined brain regions were quantified and analyzed in relation to GMFCS levels. Overall, a reduction in total WM connectivity throughout the brain in severe versus moderate CP was observed, including but not limited to regions associated with the sensorimotor system. Our results also show a diffuse and significant reduction in global inter-regional connectivity between severity groups, represented by inter-regional fiber count, throughout the brain. Furthermore, it was also observed that there is a significant difference (p = 0.02) in long-range connectivity in patients with severe CP as compared to those with moderate CP, whereas short-range connectivity was similar between groups. This new finding, which has not been previously reported in the CP literature, demonstrates that CP may involve distributed, network-level structural disruptions. PMID- 24179799 TI - Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training. AB - Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patients with a current DSM-IV GAD diagnosis were randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala-prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements. PMID- 24179800 TI - Deficits in cortical, diencephalic and midbrain gray matter in alcoholism measured by VBM: Effects of co-morbid substance abuse. AB - OBJECTIVE: Alcoholism has been associated with a widespread pattern of gray matter atrophy. This study sought to investigate the spectrum of volume alterations in a population of alcoholics with only alcohol dependence, polysubstance abusing alcoholics, and a comparison population of healthy controls. METHOD: Thirty-seven 'pure' alcoholics, 93 polysubstance abusing alcoholics, and 69 healthy controls underwent structural T1 MRI scans. Voxel based morphometry was performed to investigate gray matter alterations. RESULTS: Alcoholic dependent inpatients (both with and without a history of DSM-IV substance abuse/dependence diagnosis) displayed significant gray matter differences in the mesial region of the frontal lobe and right temporal lobe. 'Pure' alcoholics exhibited a pattern of subcortical changes similar to that seen in Wernicke-Korsakoff Syndrome when compared to polysubstance abusing alcoholics. 'Pure' alcoholics and polysubstance abusing alcoholics did not differ significantly in measures of cortical gray matter, liver function, or nutrition. CONCLUSIONS: These findings reinforce the accepted literature in regards to frontal lobe gray matter atrophy in alcohol dependence. This study calls for additional research in order to investigate the spectrum from uncomplicated alcoholism to Wernicke-Korsakoff Syndrome. Further research is needed to elucidate the exact cause of this pattern of differences and to determine what factors are responsible for the patterns of gray matter reduction or difference in 'pure' and polysubstance abusing alcoholics. PMID- 24179801 TI - In vivo evaluation of gray and white matter volume loss in the parkinsonian variant of multiple system atrophy using SPM8 plus DARTEL for VBM. AB - In multiple system atrophy with predominant parkinsonism (MSA-P), several voxel based morphometry (VBM) studies have revealed gray matter loss; however, the white matter volume changes have been rarely reported. We investigated the volume changes of white matter as well as gray matter by VBM. A retrospective MRI study was performed in 20 patients with MSA-P and 30 age-matched healthy controls. We applied VBM with statistical parametric mapping (SPM8) plus diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) to explore the regional atrophy of gray and white matter in all of the MSA-P patients, 14 patients with left-side dominant and 6 patients with right-side dominant onset as compared to controls. In all of the MSA-P patients, VBM revealed a significant volume reduction of gray matter in the bilateral putamina, cerebellums and dorsal midbrain. White matter loss was located in bilateral globus pallidi, external capsules extending to the midbrain, right subcortical to precentral area through internal capsule, the pons, bilateral middle cerebellar peduncles and left cerebellum. In left-side dominant MSA-P patients, the gray and white matter volume loss was detected predominantly on the right side and vice versa in right side dominant MSA-P patients. A correlation with disease duration and severity was not detected. VBM using SPM8 plus DARTEL detected significant volume loss not only in the gray but also in the white matter of the area affected by MSA-P. PMID- 24179803 TI - Polymorphism of brain derived neurotrophic factor influences beta amyloid load in cognitively intact apolipoprotein E epsilon4 carriers. AB - Aside from apolipoprotein E (APOE), genetic risk factors for beta amyloid deposition in cognitively intact individuals remain to be identified. Brain derived neurotrophic factor (BDNF) modulates neural plasticity, which has been implicated in Alzheimer's disease. We examined in cognitively normal older adults whether the BDNF codon 66 polymorphism affects beta amyloid burden and the relationship between beta amyloid burden and cognitive scores, and how this relates to the effect of APOE. Amyloid load was measured by means of (18)F flutemetamol PET in 64 community-recruited cognitively intact individuals (mean age 66, S.D. 5.1). Recruitment was stratified according to a factorial design with APOE (epsilon4 allele present vs absent) and BDNF (met allele at codon 66 present vs absent) as factors. Individuals in the four resulting cells were matched by the number of cases, age, and gender. Among the APOE epsilon4 carriers, BDNF met positive subjects had a significantly higher amyloid load than BDNF met negative subjects, while BDNF met carrier status did not have an effect in APOE epsilon4 noncarriers. This interaction effect was localized to precuneus, orbitofrontal cortex, gyrus rectus, and lateral prefrontal cortex. In the APOE epsilon4/BDNF met carriers, a significant inverse relationship existed between episodic memory scores and amyloid burden but not in any of the other groups. This hypothesis-generating experiment highlights a potential role of BDNF polymorphisms in the preclinical phase of beta amyloid deposition and also suggests that BDNF codon 66 polymorphisms may influence resilience against beta amyloid-related effects on cognition. PMID- 24179802 TI - Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease. AB - Amyloid imaging is currently introduced to the market for clinical use. We will review the evidence demonstrating that the different amyloid PET ligands that are currently available are valid biomarkers for Alzheimer-related beta amyloidosis. Based on recent findings from cross-sectional and longitudinal imaging studies using different modalities, we will incorporate amyloid imaging into a multidimensional model of Alzheimer's disease. Aside from the critical role in improving clinical trial design for amyloid-lowering drugs, we will also propose a tentative algorithm for when it may be useful in a memory clinic environment. Gaps in our evidence-based knowledge of the added value of amyloid imaging in a clinical context will be identified and will need to be addressed by dedicated studies of clinical utility. PMID- 24179804 TI - Assessing a standardised approach to measuring corticospinal integrity after stroke with DTI. AB - The structural integrity of the corticospinal tract (CST) after stroke is closely linked to the degree of motor impairment. Simple and reliable methods of assessing white matter integrity within the CST would facilitate the use of this measure in routine clinical practice. Commonly, diffusion tensor imaging is used to measure voxel-wise fractional anisotropy (FA) in a variety of regions of interest (ROIs) representing the CST. Several methods are currently in use with no consensus about which approach is best. ROIs are usually either the whole CST or the posterior limb of the internal capsule (PLIC). These are created manually on brain images or with reference to an individual's CST determined by tractography. Once the ROI has been defined, the FA can be reported as an absolute measure from the ipsilesional side or as a ratio in comparison to the contralesional side. Both corticospinal tracking and manual ROI definition in individual stroke patients are time consuming and subject to bias. Here, we investigated whether using a CST template derived from healthy volunteers was a feasible method for defining the appropriate ROI within which to measure changes in FA. We reconstructed the CST connecting the primary motor cortex to the ipsilateral pons in 23 age-matched control subjects and 21 stroke patients. An average healthy CST template was created from the 23 control subjects. For each patient, FA values were then calculated for both the template CST and for their own CST. We compared patients' FA metrics between the two tracts by considering four measures (FA in the ipsilesional side, FA in the contralesional side, FA ratio of the ipsilesional side to the contralesional side and FA asymmetry between the two sides) and in two tract-based ROIs (whole tract and tract section traversing the PLIC). There were no significant differences in FA metrics for either method, except for contralesional FA. Furthermore, we found that FA metrics relating to CST damage all correlated with motor ability post-stroke equally well. These results suggest that the healthy CST template could be a surrogate structure for defining tract-based ROIs with which to measure stroke patients' FA metrics, avoiding the necessity for CST tracking in individual patients. CST template-based automated quantification of structural integrity would greatly facilitate implementation of practical clinical applications of diffusion tensor imaging. PMID- 24179805 TI - MRI findings in AOA2: Cerebellar atrophy and abnormal iron detection in dentate nucleus. AB - Ataxia with Oculomotor Apraxia type 2 (AOA2) is one of the most frequent types of autosomal degenerative cerebellar ataxia. The first objective of this work was to identify specific cerebellar atrophy using MRI in patients with AOA2. Since increased iron deposits have been reported in degenerative diseases, our second objective was to report iron deposits signals in the dentate nuclei in AOA2. Five patients with AOA2 and 5 age-matched controls were subjects in a 3T MRI experiment that included a 3D turbo field echo T1-weighted sequence. The normalized volumes of twenty-eight cerebellar lobules and the percentage of atrophy (relative to controls) of the 4 main cerebellar regions (flocculo nodular, vermis, anterior and posterior) were measured. The dentate nucleus signals using 3D fast field echo sequence for susceptibility-weighted images (SWI) were reported, as a measure of iron content. We found that all patients had a significant atrophy of all cerebellar lobules as compared to controls. The percentage of atrophy was the highest for the vermis, consistent with patients' oculomotor presentation, and for the anterior lobe, consistent with kinetic limb ataxia. We also describe an absence of hypointensity of the iron signal on SWI in the dentate nucleus of all patients compared to control subjects. This study suggests that patients with Ataxia with Oculomotor Apraxia type 2 present MRI patterns consistent with their clinical presentation. The absence of SWI hypointensity in dentate nucleus is a new radiological sign which was identified in all patients. The specificity of this absence of signal must be further determined in AOA2. PMID- 24179806 TI - Imaging of non-tumorous and tumorous human brain tissues with full-field optical coherence tomography. AB - A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of full-field optical coherence tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1 MUm resolution in 3D to a penetration depth of around 200 MUm. A 1 cm(2) specimen is scanned at a single depth and processed in about 5 min. This rapid imaging process is non-invasive and requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and brain tumors such as meningiomas, low-grade and high-grade gliomas, and choroid plexus papilloma were imaged. A subpopulation of neurons, myelin fibers and CNS vasculature were clearly identified. Cortex could be discriminated from white matter, but individual glial cells such as astrocytes (normal or reactive) or oligodendrocytes were not observable. This study reports for the first time on the feasibility of using FF-OCT in a real-time manner as a label-free non invasive imaging technique in an intraoperative neurosurgical clinical setting to assess tumorous glial and epileptic margins. PMID- 24179807 TI - White matter microstructural abnormalities in bipolar disorder: A whole brain diffusion tensor imaging study. AB - BACKGROUND: Bipolar disorder (BD) is a chronic mental illness characterized by severe disruptions in mood and cognition. Diffusion tensor imaging (DTI) studies suggest that white matter (WM) tract abnormalities may contribute to the clinical hallmarks of the disorder. Using DTI and whole brain voxel-based analysis, we mapped the profile of WM anomalies in BD. All patients in our sample were euthymic and lithium free when scanned. METHODS: Diffusion-weighted and T1 weighted structural brain images were acquired from 23 lithium-free euthymic subjects with bipolar I disorder and 19 age- and sex-matched healthy control subjects on a 1.5 T MRI scanner. Scans were processed to provide measures of fractional anisotropy (FA) and mean and radial diffusivity (MD and RD) at each WM voxel, and processed scans were nonlinearly aligned to a customized brain imaging template for statistical group comparisons. RESULTS: Relative to controls, the bipolar group showed widespread regions of lower FA, including the corpus callosum, cortical and thalamic association fibers. MD and RD were abnormally elevated in patients in many of these same regions. CONCLUSIONS: Our findings agree with prior reports of WM abnormalities in the corpus callosum and further link a bipolar diagnosis with structural abnormalities of the tapetum, fornix and stria terminalis. Future studies assessing the diagnostic specificity and prognostic implications of these abnormalities would be of interest. PMID- 24179808 TI - Evaluation of white matter myelin water fraction in chronic stroke. AB - Multi-component T2 relaxation imaging (MCRI) provides specific in vivo measurement of myelin water content and tissue water environments through myelin water fraction (MWF), intra/extra-cellular water fraction (I/EWF) and intra/extracellular and global geometric mean T2 (GMT2) times. Quantitative MCRI assessment of tissue water environments has provided new insights into the progression and underlying white matter pathology in neural disorders such as multiple sclerosis. It has not previously been applied to investigate changes in white matter in the stroke-affected brain. Thus, the purposes of this study were to 1) use MCRI to index myelin water content and tissue water environments in the brain after stroke 2) evaluate relationships between MWF and diffusion behavior indexed by diffusion tensor imaging-based metrics and 3) examine the relationship between white matter status (MWF and fractional anisotropy) and motor behavior in the chronic phase of stroke recovery. Twenty individuals with ischemic stroke and 12 matched healthy controls participated. Excellent to good test/re-test and inter-rater reliability was observed for region of interest-based voxelwise MWF data. Reduced MWF was observed in whole-cerebrum white matter (p < 0.001) and in the ipsilesional (p = 0.017) and contralesional (p = 0.037) posterior limb of internal capsule (PLIC) after stroke compared to whole-cerebrum and bilateral PLIC MWF in healthy controls. The stroke group also demonstrated increased I/EWF, I/E GMT2 and global GMT2 times for whole-cerebrum white matter. Measures of diffusion behavior were also significantly different in the stroke group across each region investigated (p < 0.001). MWF was not significantly correlated with specific tensor-based measures of diffusion in the PLIC for either group. Fractional anisotropy in the ipsilesional PLIC correlated with motor behavior in chronic stroke. These results provide novel insights into tissue-specific changes within white matter after stroke that may have important applications for the understanding of the neuropathology of stroke. PMID- 24179809 TI - Proactive and reactive cognitive control and dorsolateral prefrontal cortex dysfunction in first episode schizophrenia. AB - Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between two theoretically separable modes of cognitive control reactive and proactive. However, it remains unclear the extent to which these processes are uniquely associated with dysfunctional neural recruitment in individuals with schizophrenia. This functional magnetic resonance imaging (fMRI) study utilized the color word Stroop task and AX Continuous Performance Task (AX CPT) to tap reactive and proactive control processes, respectively, in a sample of 54 healthy controls and 43 patients with first episode schizophrenia. Healthy controls demonstrated robust dorsolateral prefrontal, anterior cingulate, and parietal cortex activity on both tasks. In contrast, patients with schizophrenia did not show any significant activation during proactive control, while showing activation similar to control subjects during reactive control. Critically, an interaction analysis showed that the degree to which prefrontal activity was reduced in patients versus controls depended on the type of control process engaged. Controls showed increased dorsolateral prefrontal cortex (DLPFC) and parietal activity in the proactive compared to the reactive control task, whereas patients with schizophrenia did not demonstrate this increase. Additionally, patients' DLPFC activity and performance during proactive control was associated with disorganization symptoms, while no reactive control measures showed this association. Proactive control processes and concomitant dysfunctional recruitment of DLPFC represent robust features of schizophrenia that are also directly associated with symptoms of disorganization. PMID- 24179810 TI - Corrigendum to "Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion: Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal" [NeuroImage: Clinical 1 (2012) 164-178]. AB - [This corrects the article DOI: 10.1016/j.nicl.2012.10.003.]. PMID- 24179811 TI - Reduced cortical thickness with increased lifetime burden of PTSD in OEF/OIF Veterans and the impact of comorbid TBI. AB - Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) in military personnel is increasing dramatically following the OEF/OIF conflicts and is associated with alterations to brain structure. The present study examined the relationship between PTSD and cortical thickness, and its possible modification by mTBI, in a 104-subject OEF/OIF veteran cohort ranging in age from 20 to 62 years. For each participant, two T1-weighted scans were averaged to create high resolution images for calculation of regional cortical thickness. PTSD symptoms were assessed using the Clinician Administered PTSD Scale (CAPS) and scores were derived based on the previous month's symptoms ("current") and a Cumulative Lifetime Burden of PTSD (CLB-P) reflecting the integral of CAPS scores across the lifetime. Mild TBI was diagnosed using the Boston Assessment of TBI-Lifetime (BAT L). Results demonstrated a clear negative relationship between current PTSD severity and thickness in both postcentral gyri and middle temporal gyri. This relationship was stronger and more extensive when considering lifetime burden (CLB-P), demonstrating the importance of looking at trauma in the context of an individual's lifetime, rather than only at their current symptoms. Finally, interactions with current PTSD only and comorbid current PTSD and mTBI were found in several regions, implying an additive effect of lifetime PTSD and mTBI on cortical thickness. PMID- 24179812 TI - Resting-state functional connectivity as a marker of disease progression in Parkinson's disease: A longitudinal MEG study. AB - The assessment of resting-state functional connectivity has become an important tool in studying brain disease mechanisms. Here we use magnetoencephalography to longitudinally evaluate functional connectivity changes in relation to clinical measures of disease progression in Parkinson's disease (PD). Using a source-space based approach with detailed anatomical mapping, functional connectivity was assessed for temporal, prefrontal and high order sensory association areas known to show neuropathological changes in early clinical disease stages. At baseline, early stage, untreated PD patients (n = 12) had lower parahippocampal and temporal delta band connectivity and higher temporal alpha1 band connectivity compared to controls. Longitudinal analyses over a 4-year period in a larger patient group (n = 43) revealed decreases in alpha1 and alpha2 band connectivity for multiple seed regions that were associated with motor or cognitive deterioration. In the earliest clinical stages of PD, delta and alpha1 band resting-state functional connectivity is altered in temporal cortical regions. With disease progression, a reversal of the initial changes in alpha1 and additional decreases in alpha2 band connectivity evolving in a more widespread cortical pattern. These changes in functional connectivity appear to reflect clinically relevant phenomena and therefore hold promise as a marker of disease progression, with potential predictive value for clinical outcome. PMID- 24179813 TI - Identification of promethazine as an amyloid-binding molecule using a fluorescence high-throughput assay and MALDI imaging mass spectrometry. AB - The identification of amyloid-binding compounds is a crucial step in the development of imaging probes and therapeutics for the detection and cure of Alzheimer's disease. Unfortunately, the process typically lags during the translation from in vitro to in vivo studies due to the impenetrable nature of the blood brain barrier (BBB). Here, we integrate fluorescence assay with MALDI imaging mass spectrometry to screen known compounds and repurpose their properties to enable the second function of binding to amyloid plaques. Through this approach, we identified an antihistamine compound, promethazine, that can bind to amyloid plaques. Finally, we demonstrate that promethazine is retained in the amyloid-burdened brain compared to a normal brain and that its distribution within the brain corroborates with that of amyloid plaques. PMID- 24179814 TI - Arterial spin labeled MRI in prodromal Alzheimer's disease: A multi-site study. AB - We examined differences in cerebral blood flow (CBF) measured by Arterial Spin Labeled perfusion MRI (ASL MRI) across the continuum from cognitively normal (CN) older adults to mild Alzheimer's Disease (AD) using data from the multi-site Alzheimer's Disease Neuroimaging Initiative (ADNI). Measures of CBF, in a predetermined set of regions (meta-ROI), and hippocampal volume were compared between CN (n = 47), patients with early and late Mild Cognitive Impairment [EMCI (n = 32), LMCI (n = 35)], and AD (n = 15). Associations between these measures and disease severity, assessed by Clinical Dementia Rating scale sum of boxes (CDR SB), were also assessed. Mean meta-ROI CBF was associated with group status and significant hypoperfusion was observed in LMCI and AD relative to CN. Hippocampal volume was associated with group status, but only AD patients had significantly smaller volumes than the CN. When examining the relationship between these measures and disease severity, both were significantly associated with CDR SB and appeared to provide independent prediction of status. In light of the tight link between CBF and metabolism, ASL MRI represents a promising functional biomarker for early diagnosis and disease tracking in AD and this study is the first to demonstrate the feasibility in a multi-site context in this population. Combining functional and structural measures, which can be acquired in the same scanning session, appears to provide additional information about disease severity relative to either measure alone. PMID- 24179816 TI - Measurement of blood-brain barrier permeability in acute ischemic stroke using standard first-pass perfusion CT data. AB - BACKGROUND AND PURPOSE: Increased blood-brain barrier permeability is believed to be associated with complications following acute ischemic stroke and with infarct expansion. Measurement of blood-brain barrier permeability requires a delayed image acquisition methodology, which prolongs examination time, increasing the likelihood of movement artefacts and radiation dose. Existing quantitative methods overestimate blood-brain barrier permeability when early phase CT perfusion data are used. The purpose of this study is to develop a method that yields the correct blood-brain barrier permeability value using first-pass perfusion CT data. METHODS: We acquired 43 CT perfusion datasets, comprising experimental (n = 30) and validation subject groups (n = 13). The Gjedde-Patlak method was used to estimate blood-brain barrier permeability using first-pass (30 60 s after contrast administration) and delayed phase (30-200 s) data. In the experimental group, linear regression was used to obtain a function predicting first-pass blood-brain barrier permeability estimates from delayed phase estimates in each stroke compartment. The reliability of prediction with this function was then tested using data from the validation group. RESULTS: The predicted delayed phase blood-brain barrier permeability was strongly correlated with the measured delayed phase value (r = 0.67 and 0.6 for experimental and validation group respectively; p < 0.01). Predicted and measured delayed phase blood-brain barrier permeability in each stroke compartment were not significantly different in both experimental and validation groups. CONCLUSION: We have developed a method of estimating blood-brain barrier permeability using first-pass perfusion CT data. This predictive method allows reliable blood-brain barrier permeability estimation within standard acquisition time, minimizing the likelihood of motion artefacts thereby improving image quality and reducing radiation dose. PMID- 24179815 TI - Cardio-metabolic risk factors and cortical thickness in a neurologically healthy male population: Results from the psychological, social and biological determinants of ill health (pSoBid) study. AB - INTRODUCTION: Cardio-metabolic risk factors have been associated with poor physical and mental health. Epidemiological studies have shown peripheral risk markers to be associated with poor cognitive functioning in normal healthy population and in disease. The aim of the study was to explore the relationship between cardio-metabolic risk factors and cortical thickness in a neurologically healthy middle aged population-based sample. METHODS: T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness in 40 adult males (average age = 50.96 years), selected from the pSoBid study. The relationship between cardio-vascular risk markers and cortical thickness across the whole brain, was examined using the general linear model. The relationship with various covariates of interest was explored. RESULTS: Lipid fractions with greater triglyceride content (TAG, VLDL and LDL) were associated with greater cortical thickness pertaining to a number of regions in the brain. Greater C reactive protein (CRP) and intercellular adhesion molecule (ICAM-1) levels were associated with cortical thinning pertaining to perisylvian regions in the left hemisphere. Smoking status and education status were significant covariates in the model. CONCLUSIONS: This exploratory study adds to a small body of existing literature increasingly showing a relationship between cardio-metabolic risk markers and regional cortical thickness involving a number of regions in the brain in a neurologically normal middle aged sample. A focused investigation of factors determining the inter-individual variations in regional cortical thickness in the adult brain could provide further clarity in our understanding of the relationship between cardio-metabolic factors and cortical structures. PMID- 24179817 TI - Minimum norm estimates in MEG can delineate the onset of interictal epileptic discharges: A comparison with ECoG findings. AB - The analysis of epileptic discharges in magnetoencephalography with minimum norm estimates (MNE) is expected to provide more precise localization of epileptic discharges compared with electroencephalographic estimations. However, the clinical feasibility of MNE remains unclear. In this study, we aimed to elucidate the onset and propagation patterns of interictal spikes using MNE. Seven patients with intractable epilepsy whose epileptogenicity was assumed to exist in the convexity of the cerebral cortex were studied. For MNE and electrocorticography (ECoG), we characterized the propagation patterns of interictal epileptic discharges according to the area in which they originated and where they extended; we then examined whether the propagation patterns observed in MNE were identified by ECoG. We also examined the relationship between the positions of spikes estimated by the equivalent current dipole (ECD) method and MNE. Among the seven patients, nine propagation patterns of epileptic discharges were observed by MNE, all of which were also identified by ECoG. In seven patterns, the epileptic activity propagated around the initial portion. However, in two patterns, the center of activities moved according to propagation with maintained activity of the initial portion. The locations of spikes identified by the ECD method were within the areas estimated by MNE when the epileptic activity propagated. However, the ECD method failed to detect onset activities identified by MNE in three of nine patterns. Thus, MNE is more useful as a means of presurgical evaluation for epilepsy than the ECD method because it can delineate the onset of epileptic activities as shown in ECoG. PMID- 24179818 TI - Early adversity and combat exposure interact to influence anterior cingulate cortex volume in combat veterans. AB - OBJECTIVE: Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach. METHOD: Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis. RESULTS: As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes. CONCLUSIONS: In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma. PMID- 24179819 TI - Pattern classification of valence in depression. AB - Neuroimaging biomarkers of depression have potential to aid diagnosis, identify individuals at risk and predict treatment response or course of illness. Nevertheless none have been identified so far, potentially because no single brain parameter captures the complexity of the pathophysiology of depression. Multi-voxel pattern analysis (MVPA) may overcome this issue as it can identify patterns of voxels that are spatially distributed across the brain. Here we present the results of an MVPA to investigate the neuronal patterns underlying passive viewing of positive, negative and neutral pictures in depressed patients. A linear support vector machine (SVM) was trained to discriminate different valence conditions based on the functional magnetic resonance imaging (fMRI) data of nine unipolar depressed patients. A similar dataset obtained in nine healthy individuals was included to conduct a group classification analysis via linear discriminant analysis (LDA). Accuracy scores of 86% or higher were obtained for each valence contrast via patterns that included limbic areas such as the amygdala and frontal areas such as the ventrolateral prefrontal cortex. The LDA identified two areas (the dorsomedial prefrontal cortex and caudate nucleus) that allowed group classification with 72.2% accuracy. Our preliminary findings suggest that MVPA can identify stable valence patterns, with more sensitivity than univariate analysis, in depressed participants and that it may be possible to discriminate between healthy and depressed individuals based on differences in the brain's response to emotional cues. PMID- 24179820 TI - Multiparametric brainstem segmentation using a modified multivariate mixture of Gaussians. AB - The human brainstem is a densely packed, complex but highly organised structure. It not only serves as a conduit for long projecting axons conveying motor and sensory information, but also is the location of multiple primary nuclei that control or modulate a vast array of functions, including homeostasis, consciousness, locomotion, and reflexive and emotive behaviours. Despite its importance, both in understanding normal brain function as well as neurodegenerative processes, it remains a sparsely studied structure in the neuroimaging literature. In part, this is due to the difficulties in imaging the internal architecture of the brainstem in vivo in a reliable and repeatable fashion. A modified multivariate mixture of Gaussians (mmMoG) was applied to the problem of multichannel tissue segmentation. By using quantitative magnetisation transfer and proton density maps acquired at 3 T with 0.8 mm isotropic resolution, tissue probability maps for four distinct tissue classes within the human brainstem were created. These were compared against an ex vivo fixated human brain, imaged at 0.5 mm, with excellent anatomical correspondence. These probability maps were used within SPM8 to create accurate individual subject segmentations, which were then used for further quantitative analysis. As an example, brainstem asymmetries were assessed across 34 right-handed individuals using voxel based morphometry (VBM) and tensor based morphometry (TBM), demonstrating highly significant differences within localised regions that corresponded to motor and vocalisation networks. This method may have important implications for future research into MRI biomarkers of pre-clinical neurodegenerative diseases such as Parkinson's disease. PMID- 24179821 TI - Frontal and superior temporal auditory processing abnormalities in schizophrenia. AB - BACKGROUND: Although magnetoencephalography (MEG) studies show superior temporal gyrus (STG) auditory processing abnormalities in schizophrenia at 50 and 100 ms, EEG and corticography studies suggest involvement of additional brain areas (e.g., frontal areas) during this interval. Study goals were to identify 30 to 130 ms auditory encoding processes in schizophrenia (SZ) and healthy controls (HC) and group differences throughout the cortex. METHODS: The standard paired click task was administered to 19 SZ and 21 HC subjects during MEG recording. Vector-based Spatial-temporal Analysis using L1-minimum-norm (VESTAL) provided 4D maps of activity from 30 to 130 ms. Within-group t-tests compared post-stimulus 50 ms and 100 ms activity to baseline. Between-group t-tests examined 50 and 100 ms group differences. RESULTS: Bilateral 50 and 100 ms STG activity was observed in both groups. HC had stronger bilateral 50 and 100 ms STG activity than SZ. In addition to the STG group difference, non-STG activity was also observed in both groups. For example, whereas HC had stronger left and right inferior frontal gyrus activity than SZ, SZ had stronger right superior frontal gyrus and left supramarginal gyrus activity than HC. CONCLUSIONS: Less STG activity was observed in SZ than HC, indicating encoding problems in SZ. Yet auditory encoding abnormalities are not specific to STG, as group differences were observed in frontal and SMG areas. Thus, present findings indicate that individuals with SZ show abnormalities in multiple nodes of a concurrently activated auditory network. PMID- 24179822 TI - Abnormal brain synchrony in Down Syndrome. AB - Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks. PMID- 24179823 TI - Abnormalities in fronto-striatal connectivity within language networks relate to differences in grey-matter heterogeneity in Asperger syndrome. AB - Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD. PMID- 24179824 TI - Cognition in MS correlates with resting-state oscillatory brain activity: An explorative MEG source-space study. AB - Clinical and cognitive dysfunction in Multiple Sclerosis (MS) is insufficiently explained by structural damage as identified by traditional magnetic resonance imaging (MRI) of the brain, indicating the need for reliable functional measures in MS. We investigated whether altered resting-state oscillatory power could be related to clinical and cognitive dysfunction in MS. MEG recordings were acquired using a 151-channel whole-head MEG system from 21 relapsing remitting MS patients and 17 healthy age-, gender-, and education-matched controls, using an eyes closed no-task condition. Relative spectral power was estimated for 78 regions of interest, using an atlas-based beamforming approach, for classical frequency bands; delta, theta, alpha1, alpha2, beta and gamma. These cortical power estimates were compared between groups by means of permutation analysis and correlated with clinical disability (Expanded Disability Status Scale: EDSS), cognitive performance and MRI measures of atrophy and lesion load. Patients showed increased power in the alpha1 band and decreased power in the alpha2 band, compared to controls, mainly in occipital, parietal and temporal areas, confirmed by a lower alpha peak-frequency. Increased power in the alpha1 band was associated with worse overall cognition and especially with information processing speed. Our quantitative relative power analysis of MEG recordings showed abnormalities in oscillatory brain dynamics in MS patients in the alpha band. By applying source-space analyses, this study provides a detailed topographical view of abnormal brain activity in MS patients, especially localized to occipital areas. Interestingly, poor cognitive performance was related to high resting-state alpha1 power indicating that changes in oscillatory activity might be of value as an objective measure of disease burden in MS patients. PMID- 24179825 TI - Accurate multimodal probabilistic prediction of conversion to Alzheimer's disease in patients with mild cognitive impairment. AB - Accurately identifying the patients that have mild cognitive impairment (MCI) who will go on to develop Alzheimer's disease (AD) will become essential as new treatments will require identification of AD patients at earlier stages in the disease process. Most previous work in this area has centred around the same automated techniques used to diagnose AD patients from healthy controls, by coupling high dimensional brain image data or other relevant biomarker data to modern machine learning techniques. Such studies can now distinguish between AD patients and controls as accurately as an experienced clinician. Models trained on patients with AD and control subjects can also distinguish between MCI patients that will convert to AD within a given timeframe (MCI-c) and those that remain stable (MCI-s), although differences between these groups are smaller and thus, the corresponding accuracy is lower. The most common type of classifier used in these studies is the support vector machine, which gives categorical class decisions. In this paper, we introduce Gaussian process (GP) classification to the problem. This fully Bayesian method produces naturally probabilistic predictions, which we show correlate well with the actual chances of converting to AD within 3 years in a population of 96 MCI-s and 47 MCI-c subjects. Furthermore, we show that GPs can integrate multimodal data (in this study volumetric MRI, FDG-PET, cerebrospinal fluid, and APOE genotype with the classification process through the use of a mixed kernel). The GP approach aids combination of different data sources by learning parameters automatically from training data via type-II maximum likelihood, which we compare to a more conventional method based on cross validation and an SVM classifier. When the resulting probabilities from the GP are dichotomised to produce a binary classification, the results for predicting MCI conversion based on the combination of all three types of data show a balanced accuracy of 74%. This is a substantially higher accuracy than could be obtained using any individual modality or using a multikernel SVM, and is competitive with the highest accuracy yet achieved for predicting conversion within three years on the widely used ADNI dataset. PMID- 24179826 TI - Neural correlates of the DemTect in Alzheimer's disease and frontotemporal lobar degeneration - A combined MRI & FDG-PET study. AB - Valid screening devices are critical for an early diagnosis of dementia. The DemTect is such an internationally accepted tool. We aimed to characterize the neural networks associated with performance on the DemTect's subtests in two frequent dementia syndromes: early Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Voxel-based group comparisons of cerebral glucose utilization (as measured by F-18-fluorodeoxyglucose positron emission tomography) and gray matter atrophy (as measured by structural magnetic resonance imaging) were performed on data from 48 subjects with AD (n = 21), FTLD (n = 14) or subjective cognitive impairment (n = 13) as a control group. We performed group comparisons and correlation analyses between multimodal imaging data and performance on the DemTect's subtests. Group comparisons showed regional patterns consistent with previous findings for AD and FTLD. Interestingly, atrophy dominated in FTLD, whereas hypometabolism in AD. Across diagnostic groups performance on the "wordlist" subtest was positively correlated with glucose metabolism in the left temporal lobe. The "number transcoding" subtest was significantly associated with glucose metabolism in both a predominantly left lateralized frontotemporal network and a parietooccipital network including parts of the basal ganglia. Moreover, this subtest was associated with gray matter density in an extensive network including frontal, temporal, parietal and occipital areas. No significant correlates were observed for the "supermarket task" subtest. Scores on the "digit span reverse" subtest correlated with glucose metabolism in the left frontal cortex, the bilateral putamen, the head of caudate nucleus and the anterior insula. Disease-specific correlation analyses could partly verify or extend the correlates shown in the analyses across diagnostic groups. Correlates of gray matter density were found in FTLD for the "number transcoding" subtest and the "digit span reverse" subtest. Correlates of glucose metabolism were found in AD for the "wordlist" subtest and in FTLD for the "digit span reverse" subtest. Our study contributes to the understanding of the neural correlates of cognitive deficits in AD and FTLD and supports an external validation of the DemTect providing preliminary conclusions about disease specific correlates. PMID- 24179827 TI - White matter structural connectivity is associated with sensorimotor function in stroke survivors. AB - PURPOSE: Diffusion tensor imaging (DTI) provides functionally relevant information about white matter structure. Local anatomical connectivity information combined with fractional anisotropy (FA) and mean diffusivity (MD) may predict functional outcomes in stroke survivors. Imaging methods for predicting functional outcomes in stroke survivors are not well established. This work uses DTI to objectively assess the effects of a stroke lesion on white matter structure and sensorimotor function. METHODS: A voxel-based approach is introduced to assess a stroke lesion's global impact on motor function. Anatomical T1-weighted and diffusion tensor images of the brain were acquired for nineteen subjects (10 post-stroke and 9 age-matched controls). A manually selected volume of interest was used to alleviate the effects of stroke lesions on image registration. Images from all subjects were registered to the images of the control subject that was anatomically closest to Talairach space. Each subject's transformed image was uniformly seeded for DTI tractography. Each seed was inversely transformed into the individual subject space, where DTI tractography was conducted and then the results were transformed back to the reference space. A voxel-wise connectivity matrix was constructed from the fibers, which was then used to calculate the number of directly and indirectly connected neighbors of each voxel. A novel voxel-wise indirect structural connectivity (VISC) index was computed as the average number of direct connections to a voxel's indirect neighbors. Voxel-based analyses (VBA) were performed to compare VISC, FA, and MD for the detection of lesion-induced changes in sensorimotor function. For each voxel, a t-value was computed from the differences between each stroke brain and the 9 controls. A series of linear regressions was performed between Fugl-Meyer (FM) assessment scores of sensorimotor impairment and each DTI metric's log number of voxels that differed from the control group. RESULTS: Correlation between the logarithm of the number of significant voxels in the ipsilesional hemisphere and total Fugl-Meyer score was moderate for MD (R2 = 0.512), and greater for VISC (R2 = 0.796) and FA (R2 = 0.674). The slopes of FA (p = 0.0036), VISC (p = 0.0005), and MD (p = 0.0199) versus the total FM score were significant. However, these correlations were driven by the upper extremity motor component of the FM score (VISC: R2 = 0.879) with little influence of the lower extremity motor component (FA: R2 = 0.177). CONCLUSION: The results suggest that a voxel-wise metric based on DTI tractography can predict upper extremity sensorimotor function of stroke survivors, and that supraspinal intraconnectivity may have a less dominant role in lower extremity function. PMID- 24179828 TI - Distinctive neural responses to pain stimuli during induced sadness in patients with somatoform pain disorder: An fMRI study. AB - Pain is a multidimensional phenomenon. Patients with somatoform pain disorder suffer from long-lasting pain, with the pathology being closely associated with cognitive-emotional components. Differences between these patients and controls in cerebral responses to pain stimuli have been reported. However, to our knowledge, no studies of somatoform pain disorder have evaluated altered pain related brain activation as modulated by emotional dysregulation. We examined the distinct neural mechanism that is engaged in response to two different pain intensities in a sad emotional condition, performing functional magnetic resonance imaging (fMRI) on a group of 11 somatoform pain patients and an age matched control group. Our results showed that the ratio for low-pain intensity ratings between the sad and neutral conditions in patients was higher than in controls. They also showed significant increased activation in the anterior/posterior insula in the low pain sadness condition. Furthermore, there was specific functional connectivity between the anterior insula and the parahippocampus in patients during presentation of low-pain stimuli in the sad context. These findings suggest that a negative emotional context such as sadness contributes to dysfunctional pain processing in somatoform pain disorder. Greater sensitivity to low levels of pain in an emotional context of sadness might be an important aspect of the psychopathology of somatoform pain disorder. PMID- 24179829 TI - Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder: Abnormal salience circuitry and relations to positive emotionality. AB - Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether patients with MDD show distributed changes in functional connectivity with a set of independently derived brain networks that have shown high correspondence with different task demands, including stimulus salience and emotional processing. We further explored if connectivity during emotional word processing related to the tendency to engage in positive or negative emotional states. In this study, 25 medication free MDD patients without current or past comorbidity and matched controls (n = 25) performed an emotional word-evaluation task during functional MRI. Using a dual regression approach, individual spatial connectivity maps representing each subject's connectivity with each standard network were used to evaluate between group differences and effects of positive and negative emotionality (extraversion and neuroticism, respectively, as measured with the NEO-FFI). Results showed decreased functional connectivity of the medial prefrontal cortex, ventrolateral prefrontal cortex, and ventral striatum with the fronto-opercular salience network in MDD patients compared to controls. In patients, abnormal connectivity was related to extraversion, but not neuroticism. These results confirm the hypothesis of a relative (para)limbic-cortical decoupling that may explain dysregulated affect in MDD. As connectivity of these regions with the salience network was related to extraversion, but not to general depression severity or negative emotionality, dysfunction of this network may be responsible for the failure to sustain engagement in rewarding behavior. PMID- 24179830 TI - Cortical thickness changes in the non-lesioned hemisphere associated with non paretic arm immobilization in modified CI therapy. AB - Recent evidence suggests that immobilization of the upper limb for 2-3 weeks induces changes in cortical thickness as well as motor performance. In constraint induced (CI) therapy, one of the most effective interventions for hemiplegia, the non-paretic arm is constrained to enforce the use of the paretic arm in the home setting. With the present study we aimed to explore whether non-paretic arm immobilization in CI therapy induces structural changes in the non-lesioned hemisphere, and how these changes are related to treatment benefit. 31 patients with chronic hemiparesis participated in CI therapy with (N = 14) and without (N = 17) constraint. Motor ability scores were acquired before and after treatment. Diffusion tensor imaging (DTI) data was obtained prior to treatment. Cortical thickness was measured with the Freesurfer software. In both groups cortical thickness in the contralesional primary somatosensory cortex increased and motor function improved with the intervention. However the cortical thickness change was not associated with the magnitude of motor function improvement. Moreover, the treatment effect and the cortical thickness change were not significantly different between the constraint and the non-constraint groups. There was no correlation between fractional anisotropy changes in the non-lesioned hemisphere and treatment outcome. CI therapy induced cortical thickness changes in contralesional sensorimotor regions, but this effect does not appear to be driven by the immobilization of the non-paretic arm, as indicated by the absence of differences between the constraint and the non-constraint groups. Our data does not suggest that the arm immobilization used in CI therapy is associated with noticeable cortical thinning. PMID- 24179831 TI - Not lesser but Greater fractional anisotropy in adolescents with alcohol use disorders. AB - OBJECTIVE: The objective of this study is to examine white matter microstructure using diffusion tensor imaging (DTI) in a sample of adolescents with alcohol use disorders (AUD) and no psychiatric or substance co-morbidity. METHODS: Fifty adolescents with AUD and fifty non-alcohol abusing controls matched on gender and age were studied with DTI, neurocognitive testing, and a clinical assessment that included measures of alcohol use and childhood trauma. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were computed, registered to a common template, and voxel-wise statistical analysis used to assess group differences. Associations between regions of altered WM microstructure and clinical or neurocognitive measures were also assessed. RESULTS: Compared with controls, adolescent drinkers without co-morbid substance abuse or externalizing disorder, showed 1) no regions of significantly lower FA, 2) increased FA in WM tracts of the limbic system; 3) no MD differences; and 4) within the region of higher FA in AUD, there were no associations between FA and alcohol use, cognition, or trauma. DISCUSSION: The most important observation of this study is our failure to observe significantly smaller FA in this relatively large alcohol abuse/dependent adolescent sample. Greater FA in the limbic regions observed in this study may index a risk for adolescent AUD instead of a consequence of drinking. Drinking behavior may be reinforced in those with higher FA and perhaps greater myelination in these brain regions involved in reward and reinforcement. PMID- 24179832 TI - In-vivo multi-exponential T2, magnetization transfer and quantitative histology in a rat model of intramyelinic edema. AB - Two MRI methods, multi-exponential analysis of transverse relaxation (MET2) and quantitative magnetization transfer (qMT), were used along with quantitative evaluation of histology in a study of intra-myelinic edema in rat spinal white matter. The results showed a strong linear correlation between a distinct long-T2 signal from MET2 analysis and the edema water volume fraction as measured by histology, although this analysis overestimated the edema water content by ~ 100% relative to quantitative histological measurements. This overestimation was reasoned to result from the effects of inter-compartmental water exchange on observed transverse relaxation. Commonly studied MRI markers for myelin, the myelin water fraction (from MET2 analysis) and the macromolecular pool size ratio (from qMT analysis) produced results that could not be explained purely by changes in myelin content. The results demonstrate the potential for MET2 analysis as well as the limits of putative myelin markers for characterizing white matter abnormalities involving intra-myelinic edema. PMID- 24179833 TI - Brain-wide functional inter-hemispheric disconnection is a potential biomarker for schizophrenia and distinguishes it from depression. AB - Schizophrenia is associated with disconnectivity in the brain although it is still unclear whether changes within or between hemispheres are of greatest importance. In this paper, an analysis of 152 schizophrenia patients compared with 122 healthy controls was carried out. Comparisons were also made with 39 depression patients and 37 controls to examine whether brain-wide changes in inter- or intra-hemispheric functional connectivity are most associated with the disorder and can distinguish it from depression. The authors developed new techniques (first and second order symmetry) to investigate brain-wide changes in patients (45 regions per hemisphere) and their association with illness duration and symptom severity. Functional connectivity between the same regions in left- and right-hemispheres (first order symmetry) was significantly reduced as was that between the same pairs of regions in the left- and right-hemispheres (second order symmetry) or using all possible inter-hemispheric connections in schizophrenia patients. By contrast, no significant changes were found for brain wide intra-hemispheric links. First order symmetry changes correlated significantly with positive and negative symptom severity for functional connections linked via the anterior commissure and negative symptoms for those linked via the corpus callosum. Support vector machine analysis revealed that inter-hemispheric symmetry changes had 73-81% accuracy in discriminating schizophrenia patients and either healthy controls or depressed patients. In conclusion, reduced brain-wide inter-hemispheric functional connectivity occurs in schizophrenia, is associated with symptom severity, and can discriminate schizophrenia patients from depressed ones or healthy controls. Brain-wide changes in inter-hemispheric connections may therefore provide a useful potential biomarker for schizophrenia. PMID- 24179834 TI - Multilocus genetic profiling to empower drug trials and predict brain atrophy. AB - Designers of clinical trials for Alzheimer's disease (AD) and mild cognitive impairment (MCI) are actively considering structural and functional neuroimaging, cerebrospinal fluid and genetic biomarkers to reduce the sample sizes needed to detect therapeutic effects. Genetic pre-selection, however, has been limited to Apolipoprotein E (ApoE). Recently discovered polymorphisms in the CLU, CR1 and PICALM genes are also moderate risk factors for AD; each affects lifetime AD risk by ~ 10-20%. Here, we tested the hypothesis that pre-selecting subjects based on these variants along with ApoE genotype would further boost clinical trial power, relative to considering ApoE alone, using an MRI-derived 2-year atrophy rate as our outcome measure. We ranked subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) based on their cumulative risk from these four genes. We obtained sample size estimates in cohorts enriched in subjects with greater aggregate genetic risk. Enriching for additional genetic biomarkers reduced the required sample sizes by up to 50%, for MCI trials. Thus, AD drug trial enrichment with multiple genotypes may have potential implications for the timeliness, cost, and power of trials. PMID- 24179835 TI - Neural substrates of episodic memory dysfunction in behavioural variant frontotemporal dementia with and without C9ORF72 expansions. AB - The recently discovered hexanucleotide repeat expansion, C9ORF72, has been shown to be among the most common cause of familial behavioural variant frontotemporal dementia (bvFTD) and to be present in a significant minority of apparently sporadic cases. While mounting evidence points to prominent episodic memory dysfunction in bvFTD cases, recent reports have also suggested an amnestic profile in C9ORF72 mutation carriers. No study to date, however, has formally characterised the extent to which episodic memory is impaired in C9ORF72 mutation versus sporadic cases, or the underlying neural substrates of such deficits. We conducted a comparison of C9ORF72 (n = 8) and sporadic (n = 15) bvFTD cases using a battery of verbal and visual episodic memory tasks, and contrasted their performance with that of Alzheimer's disease (AD, n = 15) and healthy older control (n = 15) participants. Behaviourally, the two bvFTD groups displayed comparable episodic memory profiles, irrespective of task administered, with prominent impairments evident relative to Controls. Whole-brain voxel-based morphometry analyses revealed distinct neural correlates of episodic memory dysfunction in each patient group. Widespread atrophy in medial prefrontal, medial and lateral temporal cortices correlated robustly with episodic memory dysfunction in sporadic bvFTD cases. In contrast, atrophy in a distributed set of regions in the frontal, temporal, and parietal lobes including the posterior cingulate cortex, was implicated in episodic memory dysfunction in C9ORF72 cases. Our results demonstrate that while episodic memory is disrupted to the same extent irrespective of genetic predisposition in bvFTD, distinct neural changes specific to each patient group are evident. The involvement of medial and lateral parietal regions in episodic memory dysfunction in C9ORF72 cases is of particular significance and represents an avenue of considerable interest for future studies. PMID- 24179836 TI - Abnormal white matter microstructure in children with sensory processing disorders. AB - Sensory processing disorders (SPD) affect 5-16% of school-aged children and can cause long-term deficits in intellectual and social development. Current theories of SPD implicate primary sensory cortical areas and higher-order multisensory integration (MSI) cortical regions. We investigate the role of white matter microstructural abnormalities in SPD using diffusion tensor imaging (DTI). DTI was acquired in 16 boys, 8-11 years old, with SPD and 24 age-, gender-, handedness- and IQ-matched neurotypical controls. Behavior was characterized using a parent report sensory behavior measure, the Sensory Profile. Fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were calculated. Tract-based spatial statistics were used to detect significant group differences in white matter integrity and to determine if microstructural parameters were significantly correlated with behavioral measures. Significant decreases in FA and increases in MD and RD were found in the SPD cohort compared to controls, primarily involving posterior white matter including the posterior corpus callosum, posterior corona radiata and posterior thalamic radiations. Strong positive correlations were observed between FA of these posterior tracts and auditory, multisensory, and inattention scores (r = 0.51-0.78; p < 0.001) with strong negative correlations between RD and multisensory and inattention scores (r = - 0.61-0.71; p < 0.001). To our knowledge, this is the first study to demonstrate reduced white matter microstructural integrity in children with SPD. We find that the disrupted white matter microstructure predominantly involves posterior cerebral tracts and correlates strongly with atypical unimodal and multisensory integration behavior. These findings suggest abnormal white matter as a biological basis for SPD and may also distinguish SPD from overlapping clinical conditions such as autism and attention deficit hyperactivity disorder. PMID- 24179837 TI - Impact of regional cortical and subcortical changes on processing speed in cerebral small vessel disease. AB - Slowed processing speed is common in elderly subjects and frequently related to cerebral small vessel disease. Previous studies have demonstrated associations between processing speed and subcortical ischemic lesions as well as cortical alterations but the precise functional-anatomical relationships remain poorly understood. Here we assessed the impact of both cortical and subcortical changes on processing speed by measuring regional cortical thickness and regional lesion volumes within distinct white-matter tracts. To limit confounding effects from age-related pathologies we studied patients with CADASIL, a genetic small vessel disease. General linear model analysis revealed significant associations between cortical thickness in the medial frontal and occipito-temporal cortex and processing speed. Bayesian network analysis showed a robust conditional dependency between the volume of lacunar lesions in the left anterior thalamic radiation and cortical thickness of the left medial frontal cortex, and between thickness of the left medial frontal cortex and processing speed, whereas there was no direct dependency between lesion volumes in the left anterior thalamic radiation and processing speed. Our results suggest that the medial frontal cortex has an intermediate position between lacunar lesions in the anterior thalamic radiation and deficits in processing speed. In contrast, we did not observe such a relationship for the occipito-temporal region. These findings reinforce the key role of frontal-subcortical circuits in cognitive impairment resulting from cerebral small vessel disease. PMID- 24179838 TI - Impaired evoked and resting-state brain oscillations in patients with liver cirrhosis as revealed by magnetoencephalography. AB - A number of studies suggest that the clinical manifestation of neurological deficits in hepatic encephalopathy results from pathologically synchronized neuronal oscillations and altered oscillatory coupling. In the present study spontaneous and evoked oscillatory brain activities were analyzed jointly with established behavioral measures of altered visual oscillatory processing. Critical flicker and fusion frequencies (CFF, FUF) were measured in 25 patients diagnosed with liver cirrhosis and 30 healthy controls. Magnetoencephalography (MEG) data were collected at rest and during a visual task employing repetitive stimulation. Resting MEG and evoked fields were analyzed. CFF and FUF were found to be reduced in patients, providing behavioral evidence for deficits in visual oscillatory processing. These alterations were found to be related to resting brain activity in patients, namely that the lower the dominant MEG frequency at rest, the lower the CFF and FUF. An analysis of evoked fields at sensor level indicated that in comparison to normal controls, patients were not able to dynamically adapt to flickering visual stimulation. Evoked activity was also analyzed based on independent components (ICs) derived by independent component analysis. The similarity between the shape of each IC and an artificial sine function representing the stimulation frequency was tested via magnitude squared coherence. In controls, we observed a small number of components that correlated strongly with the sine function and a high number of ICs that did not correlate with the sine function. Interestingly, patient data were characterized by a high number of moderately correlating components. Taken together, these results indicate a fundamental divergence of the cerebral resonance activity in cirrhotic patients. PMID- 24179839 TI - Multiclass classification of FDG PET scans for the distinction between Parkinson's disease and atypical parkinsonian syndromes. AB - Most available pattern recognition methods in neuroimaging address binary classification problems. Here, we used relevance vector machine (RVM) in combination with booststrap resampling ('bagging') for non-hierarchical multiclass classification. The method was tested on 120 cerebral (18)fluorodeoxyglucose (FDG) positron emission tomography (PET) scans performed in patients who exhibited parkinsonian clinical features for 3.5 years on average but that were outside the prevailing perception for Parkinson's disease (PD). A radiological diagnosis of PD was suggested for 30 patients at the time of PET imaging. However, at follow-up several years after PET imaging, 42 of them finally received a clinical diagnosis of PD. The remaining 78 APS patients were diagnosed with multiple system atrophy (MSA, N = 31), progressive supranuclear palsy (PSP, N = 26) and corticobasal syndrome (CBS, N = 21), respectively. With respect to this standard of truth, classification sensitivity, specificity, positive and negative predictive values for PD were 93% 83% 75% and 96%, respectively using binary RVM (PD vs. APS) and 90%, 87%, 79% and 94%, respectively, using multiclass RVM (PD vs. MSA vs. PSP vs. CBS). Multiclass RVM achieved 45%, 55% and 62% classification accuracy for, MSA, PSP and CBS, respectively. Finally, a majority confidence ratio was computed for each scan on the basis of class pairs that were the most frequently assigned by RVM. Altogether, the results suggest that automatic multiclass RVM classification of FDG PET scans achieves adequate performance for the early differentiation between PD and APS on the basis of cerebral FDG uptake patterns when the clinical diagnosis is felt uncertain. This approach cannot be recommended yet as an aid for distinction between the three APS classes under consideration. PMID- 24179840 TI - Intra-individual variability in information processing speed reflects white matter microstructure in multiple sclerosis. AB - Slowed information processing speed is commonly reported in persons with multiple sclerosis (MS), and is typically investigated using clinical neuropsychological tests, which provide sensitive indices of mean-level information processing speed. However, recent studies have demonstrated that within-person variability or intra-individual variability (IIV) in information processing speed may be a more sensitive indicator of neurologic status than mean-level performance on clinical tests. We evaluated the neural basis of increased IIV in mildly affected relapsing-remitting MS patients by characterizing the relation between IIV (controlling for mean-level performance) and white matter integrity using diffusion tensor imaging (DTI). Twenty women with relapsing-remitting MS and 20 matched control participants completed the Computerized Test of Information Processing (CTIP), from which both mean response time and IIV were calculated. Other clinical measures of information processing speed were also collected. Relations between IIV on the CTIP and DTI metrics of white matter microstructure were evaluated using tract-based spatial statistics. We observed slower and more variable responses on the CTIP in MS patients relative to controls. Significant relations between white matter microstructure and IIV were observed for MS patients. Increased IIV was associated with reduced integrity in more white matter tracts than was slowed information processing speed as measured by either mean CTIP response time or other neuropsychological test scores. Thus, despite the common use of mean-level performance as an index of cognitive dysfunction in MS, IIV may be more sensitive to the overall burden of white matter disease at the microstructural level. Furthermore, our study highlights the potential value of considering within-person fluctuations, in addition to mean-level performance, for uncovering brain-behavior relationships in neurologic disorders with widespread white matter pathology. PMID- 24179841 TI - Prediction of post-surgical seizure outcome in left mesial temporal lobe epilepsy. AB - Mesial temporal lobe epilepsy is the most common type of focal epilepsy and in its course often becomes refractory to anticonvulsant pharmacotherapy. A resection of the mesial temporal lobe structures is a promising option in these cases. However, approximately 30% of all patients remain with persistent seizures after surgery. In other words, reliable criteria for patients' outcome prediction are absent. To address this limitation, we investigated pre-surgical brain morphology of patients with unilateral left mesial temporal lobe epilepsy who underwent a selective amygdalohippocampectomy. Using support vector classification, we aimed to predict the post-surgical seizure outcome of each patient based on the pre-surgical T1-weighted structural brain images. Due to morphological gender differences and the evidence that men and women differ in onset, prevalence and symptomology in most neurological diseases, we investigated male and female patients separately. Thus, we benefitted from the capability to validate the reliability of our method in two independent samples. Notably, we were able to accurately predict the individual patients' outcome in the male (94% balanced accuracy) as well as in the female (96% balanced accuracy) group. In the male cohort relatively larger white matter volumes in the favorable as compared to the non-favorable outcome group were identified bilaterally in the cingulum bundle, fronto-occipital fasciculus and both caudate nuclei, whereas the left inferior longitudinal fasciculus showed relatively larger white matter volume in the non-favorable group. While relatively larger white matter volumes in the female cohort in the left inferior and right middle longitudinal fasciculus were associated with the favorable outcome, relatively larger white matter volumes in the non-favorable outcome group were identified bilaterally in the superior longitudinal fasciculi I and II. Here, we observed a clear lateralization and distinction of structures involved in the classification in men as compared to women with men exhibiting more alterations in the hemisphere contralateral to the seizure focus. In conclusion, individual post-surgical outcome predictions based on a single T1-weighted magnetic resonance image seem plausible and may thus support the routine pre-surgical workup of epilepsy patients. PMID- 24179842 TI - Diffusion MRI connectometry automatically reveals affected fiber pathways in individuals with chronic stroke. AB - Building a human connectome database has recently attracted the attention of many researchers, although its application to individual subjects has yet to be explored. In this study, we acquired diffusion spectrum imaging of 90 subjects and showed that this dataset can be used as a norm to examine pathways with deviant connectivity in individuals. This analytical approach, termed diffusion MRI connectometry, was realized by reconstructing patient data to a common stereotaxic space and calculating the percentile rank of the diffusion quantities with respect to those of the norm. The affected tracks were constructed with deterministic tractography using the local tract orientations with substantially low percentile ranks as seeds. To demonstrate the performance of the connectometry, we applied it to 7 patients with chronic stroke and compared the results with lesions shown on T2-weighted images, apparent diffusion coefficient (ADC) maps, and fractional anisotropy (FA) maps, as well as clinical manifestations. The results showed that the affected tracks revealed by the connectometry corresponded well with the stroke lesions shown on T2-weighted images. Moreover, while the T2-weighted images, as well as the ADC and FA maps, showed only the stroke lesions, connectometry revealed entire affected tracks, a feature that is potentially useful for diagnostic or prognostic evaluation. This unique capability may provide personalized information regarding the structural connectivity underlying brain development, plasticity, or disease in each individual subject. PMID- 24179844 TI - Left ear advantage in speech-related dichotic listening is not specific to auditory processing disorder in children: A machine-learning fMRI and DTI study. AB - Dichotic listening (DL) tests are among the most frequently included in batteries for the diagnosis of auditory processing disorders (APD) in children. A finding of atypical left ear advantage (LEA) for speech-related stimuli is often taken by clinical audiologists as an indicator for APD. However, the precise etiology of ear advantage in DL tests has been a source of debate for decades. It is uncertain whether a finding of LEA is truly indicative of a sensory processing deficit such as APD, or whether attentional or other supramodal factors may also influence ear advantage. Multivariate machine learning was used on diffusion tensor imaging (DTI) and functional MRI (fMRI) data from a cohort of children ages 7-14 referred for APD testing with LEA, and typical controls with right-ear advantage (REA). LEA was predicted by: increased axial diffusivity in the left internal capsule (sublenticular region), and decreased functional activation in the left frontal eye fields (BA 8) during words presented diotically as compared to words presented dichotically, compared to children with right-ear advantage (REA). These results indicate that both sensory and attentional deficits may be predictive of LEA, and thus a finding of LEA, while possibly due to sensory factors, is not a specific indicator of APD as it may stem from a supramodal etiology. PMID- 24179845 TI - Permeability-diffusivity modeling vs. fractional anisotropy on white matter integrity assessment and application in schizophrenia. AB - INTRODUCTION: Diffusion tensor imaging (DTI) assumes a single pool of anisotropically diffusing water to calculate fractional anisotropy (FA) and is commonly used to ascertain white matter (WM) deficits in schizophrenia. At higher b-values, diffusion-signal decay becomes bi-exponential, suggesting the presence of two, unrestricted and restricted, water pools. Theoretical work suggests that semi-permeable cellular membrane rather than the presence of two physical compartments is the cause. The permeability-diffusivity (PD) parameters measured from bi-exponential modeling may offer advantages, over traditional DTI-FA, in identifying WM deficits in schizophrenia. METHODS: Imaging was performed in N = 26/26 patients/controls (age = 20-61 years, average age = 40.5 +/- 12.6). Imaging consisted of fifteen b-shells: b = 250-3800 s/mm(2) with 30 directions/shell, covering seven slices of mid-sagittal corpus callosum (CC) at 1.7 * 1.7 * 4.6 mm. 64-direction DTI was also collected. Permeability-diffusivity-index (PDI), the ratio of restricted to unrestricted apparent diffusion coefficients, and the fraction of unrestricted compartment (Mu) were calculated for CC and cingulate gray matter (GM). FA values for CC were calculated using tract-based-spatial statistics. RESULTS: Patients had significantly reduced PDI in CC (p ? 10(- 4)) and cingulate GM (p = 0.002), while differences in CC FA were modest (p ? .03). There was no group-related difference in Mu. Additional theoretical-modeling analysis suggested that reduced PDI in patients may be caused by reduced cross membrane water molecule exchanges. CONCLUSION: PDI measurements for cerebral WM and GM yielded more robust patient-control differences than DTI-FA. Theoretical work offers an explanation that patient-control PDI differences should implicate abnormal active membrane permeability. This would implicate abnormal activities in ion-channels that use water as substrate for ion exchange, in cerebral tissues of schizophrenia patients. PMID- 24179846 TI - Abnormal corticostriatal-limbic functional connectivity in obsessive-compulsive disorder during reward processing and resting-state. AB - Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward processing mediated by corticostriatal circuitry, a brain network implicated in the pathophysiology of OCD. Performing compulsive actions can be perceived as a reward to OCD patients because it temporarily reduces the anxiety provoked by obsessions. Although most OCD literature provides evidence of altered regional activity in these corticostriatal circuits, very little is known about the connectivity between individual regions of the corticostriatal-limbic circuits, including the cognitive and affective neural circuitry associated with OCD. Thus, this study investigated the differences in functional connectivity (FC) patterns in this network during resting-state and incentive processing. Nineteen patients with OCD and 18 well-matched healthy controls were scanned during resting-state and a monetary incentive delay task (task state). FC was assessed using both voxel-wise and region-of-interest (ROI)-wise analyses. Voxel wise FC analysis with the nucleus accumbens seed revealed that patients with OCD exhibited increased FC between the nucleus accumbens and the lateral orbitofrontal cortex during resting-state. Additionally, these patients showed decreased FC between the nucleus accumbens and limbic areas such as the amygdala during incentive processing. Exploratory ROI-wise FC analysis revealed that OCD patients demonstrated enhanced FC between the nucleus accumbens and the lateral orbitofrontal cortex and increased total connectivity of the lateral orbitofrontal cortex during resting-state. Additionally, patients showed alterations in FC between resting and task state. This study provides evidence that patients with OCD have altered FC in the corticostriatal-limbic network, particularly in striatal-amygdala and striatal-orbitofrontal circuitry, during incentive processing and resting-state. These findings also emphasize that functional connections in the network are modulated by affective/motivational states and further suggest that OCD patients may have abnormalities of such modulation in this network. PMID- 24179847 TI - Beta oscillatory responses in healthy subjects and subjects with mild cognitive impairment. AB - The aim of the present study was to investigate the role of beta oscillatory responses upon cognitive load in healthy subjects and in subjects with mild cognitive impairment (MCI). The role of beta oscillations upon cognitive stimulation is least studied in comparison to other frequency bands. The study included 17 consecutive patients with MCI (mean age = 70.8 +/- 5.6 years) according to Petersen's criteria, and 17 age- and education-matched normal elderly controls (mean age = 68.5 +/- 5.5 years). The experiments used a visual oddball paradigm. EEG was recorded at 30 cortical locations. EEG-evoked power, inter-trial phase synchronization, and event-related beta responses filtered in 15-20 Hz were obtained in response to target and non-target stimuli for both groups of subjects. In healthy subjects, EEG-evoked beta power, inter-trial phase synchronization of beta responses and event-related filtered beta responses were significantly higher in responses to target than non-target stimuli (p < 0.05). In MCI patients, there were no differences in evoked beta power between target and non-target stimuli. Furthermore, upon presentation of visual oddball paradigm, occipital electrodes depict higher beta response in comparison to other electrode sites. The increased beta response upon presentation of target stimuli in healthy subjects implies that beta oscillations could shift the system to an attention state, and had important function in cognitive activity. This may, in future, open the way to consider beta activity as an important operator in brain cognitive processes. PMID- 24179848 TI - Subcortical volumes are reduced in short-term and long-term abstinent alcoholics but not those with a comorbid stimulant disorder. AB - Chronic alcohol abuse affects brain structure and function. We examined subcortical structure volumes in 77 short (6-15 week) and 90 long (multi-year) term abstinent alcoholics, along with 74 controls. We used a 3T Siemens MPRAGE sequence for image acquisition and FSL FIRST software for measuring subcortical volumes. When examining alcoholics without a comorbid stimulant disorder we found reduced hippocampal, pallidum and thalamus volumes in short term abstinence compared to a non-substance abusing control sample with numerically smaller yet still significant reductions compared to controls in long term abstinence. When examining alcoholics with a comorbid stimulant disorder, no difference from controls was found for any subcortical volume. Alcoholics with a stimulant disorder had significantly larger subcortical volumes than alcoholics without a stimulant disorder. This study replicates past research showing that chronic alcohol abuse is associated with lower subcortical volumes in short-term abstinent chronic alcoholics and extends this finding, although with smaller effects to long-term abstinent samples. The absence of this effect in the presence of a comorbid stimulant disorder suggests either a protective effect of stimulant abuse/dependence or that the measurements reflect the aggregate of alcohol dependence associated atrophy and stimulant abuse associated inflammation. Associations with function suggest the second of these two alternatives. PMID- 24179849 TI - Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder. AB - OBJECTIVE: The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as "Emotional Parts" (EP), but mentally avoid these as "Apparently Normal Parts" of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently. METHODS: Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black-and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures. RESULTS: Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP biopsychosocially. CONCLUSIONS: DID patients have dissociative part-dependent biopsychosocial reactions to masked neutral and angry faces. As EP, they are overactivated, and as ANP underactivated. The findings support TSDP. Major clinical implications are discussed. PMID- 24179850 TI - Atypical excitation-inhibition balance in autism captured by the gamma response to contextual modulation. AB - Atypical visual perception in people with autism spectrum disorders (ASD) is hypothesized to stem from an imbalance in excitatory and inhibitory processes in the brain. We used neuronal oscillations in the gamma frequency range (30-90 Hz), which emerge from a balanced interaction of excitation and inhibition in the brain, to assess contextual modulation processes in early visual perception. Electroencephalography was recorded in 12 high-functioning adults with ASD and 12 age- and IQ-matched control participants. Oscillations in the gamma frequency range were analyzed in response to stimuli consisting of small line-like elements. Orientation-specific contextual modulation was manipulated by parametrically increasing the amount of homogeneously oriented elements in the stimuli. The stimuli elicited a strong steady-state gamma response around the refresh-rate of 60 Hz, which was larger for controls than for participants with ASD. The amount of orientation homogeneity (contextual modulation) influenced the gamma response in control subjects, while for subjects with ASD this was not the case. The atypical steady-state gamma response to contextual modulation in subjects with ASD may capture the link between an imbalance in excitatory and inhibitory neuronal processing and atypical visual processing in ASD. PMID- 24179851 TI - Preoperative language lateralization in temporal lobe epilepsy (TLE) predicts peri-ictal, pre- and post-operative language performance: An fMRI study. AB - In patients with temporal lobe epilepsy (TLE), assessment of language lateralization is important as anterior temporal lobectomy may lead to language impairments. Despite the widespread use of fMRI, evidence of its usefulness in predicting postsurgical language performance is scant. We investigated whether preoperative functional lateralization is related to the preoperative language performance, peri-ictal aphasia, and can predict language outcome one year post surgery. We studied a total of 72 TLE patients (42 left, 30 right), by using three fMRI tasks: Naming, Verb Generation and Fluency. Functional lateralization indices were analyzed with neuropsychological scores and presence of peri-ictal aphasia. The key findings are:1)Both left and right TLE patients show decreased left lateralization compared to controls.2)Lateralization correlates with language performance before surgery. In left TLE, decreased left lateralization correlates with better fluency performance. In right TLE, increased left lateralization during the Naming task correlates with better naming.3)Left lateralization correlates with peri-ictal aphasia in left TLE patients.4)Lateralization correlates with language performance after surgery. In a subgroup of left TLE who underwent surgery (17 left), decreased left lateralization is predictive of better naming performance at 6 and 12 months after surgery. The present study highlights the clinical relevance of fMRI language lateralization in TLE, especially to predict language outcome one year post-surgery. We also underline the importance of using fMRI tasks eliciting frontal and anterior temporal activations, when studying left and right TLE patients. PMID- 24179852 TI - Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease. AB - The early diagnostic value of glucose hypometabolism and atrophy as potential neuroimaging biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been extensively explored using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI). The vast majority of previous imaging studies neglected the effects of single factors, such as age, symptom severity or time to conversion in MCI thus limiting generalisability of results across studies. Here, we investigated the impact of these factors on metabolic and structural differences. FDG-PET and MRI data from AD patients (n = 80), MCI converters (n = 65) and MCI non-converters (n = 64) were compared to data of healthy subjects (n = 79). All patient groups were split into subgroups by age, time to conversion (for MCI), or symptom severity and compared to the control group. AD patients showed a strongly age-dependent pattern, with younger patients showing significantly more extensive reductions in gray matter volume and glucose utilisation. In the MCI converter group, the amount of glucose utilisation reduction was linked to the time to conversion but not to atrophy. Our findings indicate that FDG-PET might be more closely linked to future cognitive decline whilst MRI being more closely related to the current cognitive state reflects potentially irreversible damage. PMID- 24179853 TI - Structural basis of the fronto-thalamic dysconnectivity in schizophrenia: A combined DCM-VBM study. AB - Several lines of evidence suggest that cognitive control deficits may be regarded as a connecting link between reported impairments in different cognitive domains of schizophrenia. However, the precise interplay within the fronto-cingulo thalamic network known to be involved in cognitive control processes and its structural correlates has only been sparsely investigated in schizophrenia. The present multimodal study was therefore designed to model cognitive control processes within the fronto-cingulo-thalamic network. A disruption in effective connectivity in patients in association with abnormal white matter (WM) structure in this network was hypothesized. 36 patients with schizophrenia and 36 healthy subjects participated in the present study. Using functional magnetic resonance imaging (fMRI) a Stroop task was applied in an event-related design. For modeling effective connectivity dynamic causal modeling (DCM) was used. Voxel-based morphometry (VBM) was employed to study WM abnormalities. In the fMRI analysis, the patients demonstrated a significantly decreased BOLD signal in the fronto cingulo-thalamic network. In the DCM analysis, a significantly decreased bilateral endogenous connectivity between the mediodorsal thalamus (MD) and the anterior cingulate cortex (ACC) was detected in patients in comparison to healthy controls, which was negatively correlated with the Stroop interference score. Furthermore, an increased endogenous connectivity between the right DLPFC and the right MD was observed in the patients. WM volume decreases were observed in the patients in the MD and the frontal cortex. The present results provide strong evidence for the notion that an abnormal fronto-cingulo-thalamic effective connectivity may represent the basis of cognitive control deficits in schizophrenia. Moreover, the data indicate that disrupted white matter connectivity in the mediodorsal thalamus and in the fronto-cingulo-thalamic network may constitute the determining cause of fronto-cingulo-thalamic dysconnectivity. PMID- 24179854 TI - White matter microstructure correlates with autism trait severity in a combined clinical-control sample of high-functioning adults. AB - Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical-neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p = 0.004), whilst MD and RD were positively related to AQ (p = 0.002; p = 0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits. PMID- 24179855 TI - The effect of injury timing on white matter changes in the corpus callosum following unilateral brain injury. AB - Motor impairments following unilateral brain injuries may be related to changes in the corpus callosum. The purpose of this study was to determine if the corpus callosum is impacted differently in pediatric versus adult hemiplegia. Diffusion tensor imaging was completed on 41 participants (11 pediatric hemiplegia, 10 adult hemiplegia, 10 pediatric control and 10 adult control). Fractional anisotropy values and cross-sectional areas for five regions of the corpus callosum were compared between subject groups. Additionally, the amount of involuntary activity in the paretic elbow was quantified during non-paretic elbow flexion tasks for a subset of pediatric hemiplegia participants. Fractional anisotropy values were reduced in pediatric hemiplegia compared to pediatric control subjects in callosal regions corresponding to premotor and supplementary motor areas, primary sensory cortex, and parietal, temporal, and occipital cortices. Differences in fractional anisotropy between adult stroke and adult controls were only found in the region corresponding to parietal, temporal, and occipital cortices. Cross-sectional area was affected in all regions of the corpus callosum in pediatric hemiplegia, but only in the primary sensory region in adult hemiplegia. Additionally, changes in the cross-sectional areas were correlated with involuntary mirror movements in the pediatric hemiplegia group. In conclusion, the corpus callosum is affected to a greater extent in pediatric compared to adult hemiplegia, which may explain why unsuppressed mirror movements and difficulty with bimanual coordination are greater problems in this population. PMID- 24179856 TI - Complex biomarker discovery in neuroimaging data: Finding a needle in a haystack. AB - Neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease are major public health problems. However, despite decades of research, we currently have no validated prognostic or diagnostic tests that can be applied at an individual patient level. Many neuropsychiatric diseases are due to a combination of alterations that occur in a human brain rather than the result of localized lesions. While there is hope that newer imaging technologies such as functional and anatomic connectivity MRI or molecular imaging may offer breakthroughs, the single biomarkers that are discovered using these datasets are limited by their inability to capture the heterogeneity and complexity of most multifactorial brain disorders. Recently, complex biomarkers have been explored to address this limitation using neuroimaging data. In this manuscript we consider the nature of complex biomarkers being investigated in the recent literature and present techniques to find such biomarkers that have been developed in related areas of data mining, statistics, machine learning and bioinformatics. PMID- 24179857 TI - Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment. AB - Cognitive impairment and brain injury are common in people with HIV/AIDS, even when viral replication is effectively suppressed with combined antiretroviral therapies (cART). Metabolic and structural abnormalities may promote cognitive decline, but we know little about how these measures relate in people on stable cART. Here we used tensor-based morphometry (TBM) to reveal the 3D profile of regional brain volume variations in 210 HIV + patients scanned with whole-brain MRI at 1.5 T (mean age: 48.6 +/- 8.4 years; all receiving cART). We identified brain regions where the degree of atrophy was related to HIV clinical measures and cerebral metabolite levels assessed with magnetic resonance spectroscopy (MRS). Regional brain volume reduction was linked to lower nadir CD4 + count, with a 1-2% white matter volume reduction for each 25-point reduction in nadir CD4 +. Even so, brain volume measured by TBM showed no detectable association with current CD4 + count, AIDS Dementia Complex (ADC) stage, HIV RNA load in plasma or cerebrospinal fluid (CSF), duration of HIV infection, antiretroviral CNS penetration-effectiveness (CPE) scores, or years on cART, after controlling for demographic factors, and for multiple comparisons. Elevated glutamate and glutamine (Glx) and lower N-acetylaspartate (NAA) in the frontal white matter, basal ganglia, and mid frontal cortex - were associated with lower white matter, putamen and thalamus volumes, and ventricular and CSF space expansion. Reductions in brain volumes in the setting of chronic and stable disease are strongly linked to a history of immunosuppression, suggesting that delays in initiating cART may result in imminent and irreversible brain damage. PMID- 24179858 TI - Comparison of randomized multifocal mapping and temporal phase mapping of visual cortex for clinical use. AB - fMRI is becoming an important clinical tool for planning and guidance of surgery to treat brain tumors, arteriovenous malformations, and epileptic foci. For visual cortex mapping, the most popular paradigm by far is temporal phase mapping, although random multifocal stimulation paradigms have drawn increased attention due to their ability to identify complex response fields and their random properties. In this study we directly compared temporal phase and multifocal vision mapping paradigms with respect to clinically relevant factors including: time efficiency, mapping completeness, and the effects of noise. Randomized, multifocal mapping accurately decomposed the response of single voxels to multiple stimulus locations and made correct retinotopic assignments as noise levels increased despite decreasing sensitivity. Also, multifocal mapping became less efficient as the number of stimulus segments (locations) increased from 13 to 25 to 49 and when duty cycle was increased from 25% to 50%. Phase mapping, on the other hand, activated more extrastriate visual areas, was more time efficient in achieving statistically significant responses, and had better sensitivity as noise increased, though with an increase in systematic retinotopic mis-assignments. Overall, temporal phase mapping is likely to be a better choice for routine clinical applications though random multifocal mapping may offer some unique advantages for selected applications. PMID- 24179859 TI - Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia. AB - BACKGROUND: Hippocampal atrophy is a well-known feature of Alzheimer's disease (AD), but sensitivity and specificity of hippocampal volumetry are limited. Neuropathological studies have shown that hippocampal subfields are differentially vulnerable to AD; hippocampal subfield volumetry may thus prove to be more accurate than global hippocampal volumetry to detect AD. METHODS: CA1, subiculum and other subfields were manually delineated from 40 healthy controls, 18 AD, 17 amnestic Mild Cognitive Impairment (aMCI), and 8 semantic dementia (SD) patients using a previously developed high resolution MRI procedure. Non parametric group comparisons and receiver operating characteristic (ROC) analyses were conducted. Complementary analyses were conducted to evaluate differences of hemispheric asymmetry and anterior-predominance between AD and SD patients and to distinguish aMCI patients with or without beta-amyloid deposition as assessed by Florbetapir-TEP. RESULTS: Global hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p < 0.001). In aMCI, CA1 volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve = 0.88 and 0.76, respectively; p = 0.05) and preliminary analyses suggest that it was independent from the presence of beta-amyloid deposition. In patients with SD, whereas the degree of CA1 and subiculum atrophy was similar to that found in AD patients, hemispheric and anterior-posterior asymmetry were significantly more marked than in AD with greater involvement of the left and anterior hippocampal subfields. CONCLUSIONS: The findings suggest that CA1 measurement is more sensitive than global hippocampal volumetry to detect structural changes at the pre-dementia stage, although the predominance of CA1 atrophy does not appear to be specific to AD pathophysiological processes. PMID- 24179860 TI - Structural alterations in brainstem of fibromyalgia syndrome patients correlate with sensitivity to mechanical pressure. AB - Fibromyalgia syndrome is a chronic pain disorder characterised by widespread pain and tenderness in muscles and deep tissues. Current theories regarding the pathophysiological origins of fibromyalgia syndrome point towards central sensitisation and a decreased capacity of descending nociceptive controls. Morphological alterations to subcortical brain regions may contribute to such pathophysiological mechanisms, and to pain and other symptoms seen in fibromyalgia. Therefore, we evaluated geometric differences in subcortical structures in fibromyalgia patients relative to healthy people using a novel method of shape analysis. Sixteen female fibromyalgia patients and 15 age and sex matched, healthy control subjects underwent high-resolution T1-weighted magnetic resonance image scanning. Data was analysed using shape analysis of 15 subcortical regions and standard voxel-based morphometry analysis. Fibromyalgia syndrome patients, relative to healthy control participants, exhibited alterations to the shape of the left lateral aspect of the lower brainstem (medulla). The mean total volume of the brainstem was also found to be significantly reduced in the patient group compared to healthy control subjects, and this brainstem volume reduction in patient group significantly correlated with clinical manual tender point scale scores. Voxel-based morphometry analysis revealed that patients also demonstrated decreased local grey matter volumes in the brainstem (pons) and left precuneus, and increased grey matter volumes in bilateral primary somatosensory cortices. Results suggest that the volume reduction and associated geometric shape alterations seen in the brainstem of the patient group may contribute to sensitivity to pressure pain in fibromyalgia syndrome. This finding may be due to structure-related deficiencies in regions subserving descending nociceptive control. PMID- 24179861 TI - Quantification of multiple-sclerosis-related brain atrophy in two heterogeneous MRI datasets using mixed-effects modeling. AB - Brain atrophy, measured by MRI, has been proposed as a useful surrogate marker for disease progression in multiple sclerosis (MS). However, it is conventionally assumed that the accurate quantification of brain atrophy is made difficult, if not impossible, by changes in the parameters of the MRI acquisition, which are almost inevitable over the course of a longitudinal study since MRI technology changes rapidly. This state of affairs can negatively affect clinical trial design and limit the use of historical data. Here, we investigate whether we can coherently estimate brain atrophy rates in a heterogeneous MS sample via linear mixed-effects multivariable regression, incorporating three critical assumptions: (1) using age at time of scanning, rather than time since baseline, as the regressor of interest; (2) scanning individuals with a variety of techniques; and (3) introducing a simple additive correction for major differences in MRI protocol. We fit the model to several measures of brain volume as the outcome in two MS populations: 1123 scans from 195 cases acquired for over approximately 7 years in two natural history protocols (Cohort 1), and 1331 scans from 69 cases seen for over 11 years who were primarily treated with two specific MS disease modifying therapies (Cohort 2). We compared the mixed-effects model with additive correction for MRI acquisition parameters to a model fit without this correction and performed sample-size calculations to provide an estimate of the number of participants in an MS clinical trial that might be required to see a therapeutic effect of treatment using the approach described here. The results show that without the additive correction for T1-weighted protocol parameters, atrophy was underestimated and subject-specific estimates were more narrowly distributed about the population mean. Ventricular CSF is the most consistently estimated brain volume, with a mean of 2.8%/year increase in Cohort 1 and 4.4%/year increase in Cohort 2. An interesting observation was that gray matter volume decreased and white matter volume remained essentially unchanged in both cohorts, suggesting that changes in ventricular CSF volume are a surrogate for changes in gray matter volume. In conclusion, the mixed-effects modeling framework presented here allows effective use of heterogeneously acquired and historical data in the study of brain atrophy in MS, potentially simplifying the design of future single and multi-site clinical trials and natural history studies. PMID- 24179863 TI - Hippocampal T2 hyperintensities on 7 Tesla MRI. AB - Hippocampal focal T2 hyperintensities (HT2Hs), also referred to as hippocampal sulcal cavities, are a common finding on Magnetic Resonance (MR) images. There is uncertainty about their etiology and clinical significance. In this study we aimed to describe these HT2Hs in more detail using high resolution 7 Tesla MR imaging, addressing 1) the MR signal characteristics of HT2Hs, 2) their occurrence frequency, 3) their location within the hippocampus, and 4) their relation with age. We also performed an explorative post-mortem study to examine the histology of HT2Hs. Fifty-eight persons without a history of invalidating neurological or psychiatric disease (mean age 64 +/- 8 years; range 43-78 years), recruited through their general practitioners, were included in this study. They all underwent 7 Tesla MRI, including a T1, T2, and FLAIR image. MR signal characteristics of the HT2Hs were assessed on these images by two raters. Also, the location and number of the HT2Hs were assessed. In addition, four formalin fixed brain slices from two subjects were scanned overnight. HT2Hs identified in these slices were subjected to histopathological analysis. HT2Hs were present in 97% of the subjects (median number per person 10; range 0-20). All HT2Hs detected on the T2 sequence were hypointense on T1 weighted images. Of all HT2Hs, 94% was hypointense and 6% hyperintense on FLAIR. FLAIR hypointense HT2Hs were all located in the vestigial sulcus of the hippocampus, FLAIR hyperintense HT2Hs in the hippocampal sulcus or the gray matter. Post-mortem MRI and histopathological analysis suggested that the hypointense HT2Hs on FLAIR were cavities filled with cerebrospinal fluid. A hyperintense HT2H on FLAIR proved to be a microinfarct upon microscopy. In conclusion, hippocampal T2Hs are extremely common and unrelated to age. They can be divided into two types (hypo- and hyperintense on FLAIR), probably with different etiology. PMID- 24179862 TI - Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging. AB - The Alzheimer's Disease Neuroimaging Initiative (ADNI) recently added diffusion tensor imaging (DTI), among several other new imaging modalities, in an effort to identify sensitive biomarkers of Alzheimer's disease (AD). While anatomical MRI is the main structural neuroimaging method used in most AD studies and clinical trials, DTI is sensitive to microscopic white matter (WM) changes not detectable with standard MRI, offering additional markers of neurodegeneration. Prior DTI studies of AD report lower fractional anisotropy (FA), and increased mean, axial, and radial diffusivity (MD, AxD, RD) throughout WM. Here we assessed which DTI measures may best identify differences among AD, mild cognitive impairment (MCI), and cognitively healthy elderly control (NC) groups, in region of interest (ROI) and voxel-based analyses of 155 ADNI participants (mean age: 73.5 +/- 7.4; 90 M/65 F; 44 NC, 88 MCI, 23 AD). Both VBA and ROI analyses revealed widespread group differences in FA and all diffusivity measures. DTI maps were strongly correlated with widely-used clinical ratings (MMSE, CDR-sob, and ADAS-cog). When effect sizes were ranked, FA analyses were least sensitive for picking up group differences. Diffusivity measures could detect more subtle MCI differences, where FA could not. ROIs showing strongest group differentiation (lowest p-values) included tracts that pass through the temporal lobe, and posterior brain regions. The left hippocampal component of the cingulum showed consistently high effect sizes for distinguishing groups, across all diffusivity and anisotropy measures, and in correlations with cognitive scores. PMID- 24179865 TI - [(123)I]-IBVM SPECT imaging of cholinergic systems in multiple system atrophy: A specific alteration of the ponto-thalamic cholinergic pathways (Ch5-Ch6). AB - We evaluated in vivo the integrity of brain cholinergic pathways in Multiple System Atrophy (MSA) and the relationship between cholinergic dysfunction and motor disturbances, by measuring the vesicular acetylcholine transporter (VAChT) expression using Single Photon Emission Computed Tomography (SPECT) and [(123)I] iodobenzovesamicol ([(123)I]-IBVM). METHODS: Nine patients with probable MSA and 12 healthy volunteers underwent a dynamic [(123)I]-IBVM SPECT-CT scan and a magnetic resonance imaging (MRI) scan. All patients were examined with the Unified MSA Rating Scale (UMSARS; subscale I = activities of daily living (ADL), II = motor and IV = disability). CT and MRI images were used to register the dynamic SPECT image to the Montreal Neurological Institute brain template, which includes the regions of interest (ROI) of striatum and Ch1 (medial septum nucleus hippocampus), Ch4 (nucleus basalis of Meynert-cortex) and Ch5-Ch6 (pedunculopontine and laterodorsal tegmental nuclei-thalamus) cholinergic pathways. For each ROI, pharmacokinetic modeling of regional time activity curves led to the calculation of [(123)I]-IBVM to VAChT binding potential (BPND) value, proportional to VAChT expression. RESULTS: When compared to controls, BPND values for MSA in Ch5-Ch6 were significantly decreased in both the pedunculopontine laterodorsal nuclei and the thalamus (p = 0.004 and p = 0.006, respectively). Additionally, thalamus BPND values were correlated with UMSARS ADL (p = 0.006), motor (p = 0.002) and disability (p = 0.02) sub-scores. UMSARS motor subscale items 13 (postural instability) and 14 (gait) were also correlated with thalamus BPND values (p = 0.04). CONCLUSION: Ch5-Ch6 are the most affected cholinergic pathways in MSA at both cell bodies and thalamic cholinergic terminals. These results underscore the relevant role of [(123)I]-IBVM SPECT for improving our understanding of the pathophysiology in MSA. PMID- 24179864 TI - Gross feature recognition of Anatomical Images based on Atlas grid (GAIA): Incorporating the local discrepancy between an atlas and a target image to capture the features of anatomic brain MRI. AB - We aimed to develop a new method to convert T1-weighted brain MRIs to feature vectors, which could be used for content-based image retrieval (CBIR). To overcome the wide range of anatomical variability in clinical cases and the inconsistency of imaging protocols, we introduced the Gross feature recognition of Anatomical Images based on Atlas grid (GAIA), in which the local intensity alteration, caused by pathological (e.g., ischemia) or physiological (development and aging) intensity changes, as well as by atlas-image misregistration, is used to capture the anatomical features of target images. As a proof-of-concept, the GAIA was applied for pattern recognition of the neuroanatomical features of multiple stages of Alzheimer's disease, Huntington's disease, spinocerebellar ataxia type 6, and four subtypes of primary progressive aphasia. For each of these diseases, feature vectors based on a training dataset were applied to a test dataset to evaluate the accuracy of pattern recognition. The feature vectors extracted from the training dataset agreed well with the known pathological hallmarks of the selected neurodegenerative diseases. Overall, discriminant scores of the test images accurately categorized these test images to the correct disease categories. Images without typical disease-related anatomical features were misclassified. The proposed method is a promising method for image feature extraction based on disease-related anatomical features, which should enable users to submit a patient image and search past clinical cases with similar anatomical phenotypes. PMID- 24179866 TI - Binge drinking influences the cerebral processing of vocal affective bursts in young adults. AB - Binge drinking is now considered a central public health issue and is associated with emotional and interpersonal problems, but the neural implications of these deficits remain unexplored. The present study aimed at offering the first insights into the effects of binge drinking on the neural processing of vocal affect. On the basis of an alcohol-consumption screening phase (204 students), 24 young adults (12 binge drinkers and 12 matched controls, mean age: 23.8 years) were selected and performed an emotional categorisation task on morphed vocal stimuli (drawn from a morphed fear-anger continuum) during fMRI scanning. In comparison to controls, binge drinkers presented (1) worse behavioural performance in emotional affect categorisation; (2) reduced activation of bilateral superior temporal gyrus; and (3) increased activation of right middle frontal gyrus. These results constitute the first evidence of altered cerebral processing of emotional stimuli in binge drinking and confirm that binge drinking leads to marked cerebral changes, which has important implications for research and clinical practice. PMID- 24179867 TI - Rhox in mammalian reproduction and development. AB - Homeobox genes play essential roles in embryonic development and reproduction. Recently, a large cluster of homeobox genes, reproductive homeobox genes on the X chromosome (Rhox) genes, was discovered as three gene clusters, alpha, beta, and gamma in mice. It was found that Rhox genes were selectively expressed in reproduction-associated tissues, such as those of the testes, epididymis, ovaries, and placenta. Hence, it was proposed that Rhox genes are important for regulating various reproductive features, especially gametogenesis in male as well as in female mammals. It was first determined that 12 Rhox genes are clustered into alpha (Rhox1-4), beta (Rhox5-9), and gamma (Rhox10-12) subclusters, and recently Rhox13 has also been found. At present, 33 Rhox genes have been identified in the mouse genome, 11 in the rat, and three in the human. Rhox genes are also responsible for embryonic development, with considerable amounts of Rhox expression in trophoblasts, placenta tissue, embryonic stem cells, and primordial germ cells. In this article we summarized the current understanding of Rhox family genes involved in reproduction and embryonic development and elucidated a previously unreported cell-specific expression in ovarian cells. PMID- 24179868 TI - Stereological study of the effects of letrozole and estradiol valerate treatment on the ovary of rats. AB - OBJECTIVE: Letrozole and estradiol valerate are used to treat some hormonally responsive symptoms and also in modeling of the polycystic ovary syndrome. However, the stereological analysis of the ovary has received less attention. Estimation of the whole ovary volume using the Cavalieri method can be applied in any orientation desired, but estimation of the mean volume of the oocytes requires isotropic uniform random sectioning. Here, a combined method was developed for estimating the parameters. To our knowledge, no comparison has been made of the effects of letrozole and estradiol on the ovary. METHODS: Sixty rats were divided into 4 groups receiving estradiol (4 mg/kg), olive oil, letrozole (1 mg/kg), or normal saline. After 21 days, their ovaries were studied. RESULTS: Relative to the control group, the total volume of the ovary and the cortex increased in the letrozole-treated and estradiol-treated rats. In addition, the number of the preantral, antral, and granulosa cells decreased by 43% to 56% in the letrozole- and estradiol-treated rats. On average, a 19% increase was observed in the atretic oocytes of the letrozole-treated and estradiol-treated rats, but the mean oocyte volume decreased by 29% to 44% in letrozole- and estradiol-treated rats. Furthermore, the letrozole-treated rats showed a 5-fold and 7-fold increase in the volume of the cysts and corpus luteum, respectively. A 3-fold increase was found in the volume of both the cysts and corpus luteum in the estradiol group. CONCLUSION: The structural changes of the ovary were most pronounced in the letrozole-treated animals. PMID- 24179869 TI - Comparison of the clinical outcomes of day 4 and 5 embryo transfer cycles. AB - OBJECTIVE: The majority of embryo transfers (ETs) to date have been performed on day 3 to reduce the potential risk of developmental arrest of in vitro cultured embryos before ET. Development of sequential media has significantly improved culture conditions and allowed blastocyst transfer on day 5. While day 5 ET provides higher clinical pregnancy outcomes with reduced risks of multiple pregnancies, it still has potential risks of developmental arrest of IVF embryos. The aim of this study was to evaluate the clinical outcomes of day 4 ETs and compare the efficacy of day 4 ET with day 5 ET. METHODS: From 2006 to 2009, a total of 747 fresh IVF-ET cycles were retrospectively analyzed (day 4, n=440 or and day 5, n=307). The cycles with any genetic factors were excluded. The rates of matured oocytes, fertilization, good embryos, and clinical pregnancy of the two groups were compared. The chi-square test and t-test were used for statistical analysis. RESULTS: There were no significant differences between the two groups with respect to the mean age of the females and rates of matured oocytes. The pregnancy outcomes of day 4 ET (40.7%) were similar to those of day 5 ET (44.6%). The implantation rate of day 5 ET (24.2%) was significantly higher than that of day 4 ET (18.4%) (p=0.003). CONCLUSION: Day 4 ET can be chosen to avoid ET cancellation in day 5 ET resulting from suboptimal circumstances in the IVF laboratory, but the decremented quality of embryos for transfer and the decreased pregnancy rate must be taken into consideration. PMID- 24179870 TI - Effectiveness of emergency contraception in women after sexual assault. AB - OBJECTIVE: To assess the effectiveness of emergency single-dose levonorgestrel contraception in preventing unintended pregnancies among woman who visited the emergency department (ED) due to sexual assault (SA). METHODS: We conducted a retrospective chart review in a university hospital in South Korea. Cases from November 10, 2006 to November 9, 2009 were enrolled. Information from the initial visit to the ED and subsequent follow-up visits to the gynecology outpatient clinic was collected. RESULTS: In total, 1,179 women visited the ED due to SA. Among them, 416 patients had a gynecological examination and 302 patients who received emergency contraception (EC) (1.5 mg single-dose levonorgestrel) at the ED due to SA were enrolled. Ten patients did not return for follow-up examinations. In follow-up visits at the outpatient clinic, two pregnancies were confirmed, which showed the failure rate of the EC to be 0.68%. CONCLUSION: Single-dose levonorgestrel EC is extremely effective at preventing pregnancy among victims of SA. PMID- 24179871 TI - Luteal estradiol supplementation in gonadotropin-releasing hormone antagonist cycles for infertile patients in vitro fertilization. AB - OBJECTIVE: To evaluate the effect of the addition of estradiol to luteal progesterone supplementation in GnRH antagonist cycles for infertile patients undergoing IVF/ICSI. METHODS: One hundred and ten infertile patients, aged 28 to 39 years, were recruited for this prospective randomized study. They were randomly assigned to receive vaginal progesterone gel (Crinone) along with 4 mg estradiol valerate (group 1, n=55) or only Crinone (group 2, n=55) for luteal support. A GnRH antagonist multiple dose protocol using recombinant human FSH was used for controlled ovarian stimulation (COS) in all of the subjects. The COS results and pregnancy outcomes of the two groups were compared. RESULTS: Group 1 and 2 were comparable with respect to the patient characteristics. The COS and IVF results were also comparable between the two groups. There were no differences in the clinical pregnancy rate (PR) and multiple PR between the two groups. However, the embryo implantation rate were significantly higher in group 1 than that in group 2 (22.2% vs. 13.3%, p=0.035). The incidence of luteal vaginal bleeding (LVB) was significantly lower in group 1 (7.4% vs. 27.8%, p=0.010). CONCLUSION: The addition of estradiol to luteal progesterone supplementation in GnRH antagonist cycles reduces the incidence of LVB and increases the embryo implantation rate in infertile patients undergoing IVF/ICSI. PMID- 24179872 TI - Can high serum anti-Mullerian hormone levels predict the phenotypes of polycystic ovary syndrome (PCOS) and metabolic disturbances in PCOS patients? AB - OBJECTIVE: To evaluate correlations between serum anti-Mullerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS. METHODS: A total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) >=25 kg/m(2) (n=34). RESULTS: The mean age was 25.9+/-5.7 year and mean AMH level was 10.1+/-5.4 ng/mL. The BMI (kg/m(2)) was higher in group 1 (24.2+/-6.3) than in group 2 (21.9+/-4.3, p=0.046) or group 3 (21.6+/-3.3, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH (7.7+/-3.9 ng/mL vs. 10.7+/-5.6 ng/mL), p=0.004) and low density lipoprotein levels (93.1+/-21.2 mg/dL vs. 107.5+/-39.3 mg/dL, p=0.031), and showed higher total T (0.74+/-0.59 ng/mL vs. 0.47+/-0.36 ng/mL, p=0.001), free T (2.01+/-1.9 vs. 1.04+/-0.8 pg/mL, p=0.0001), and free androgen index (6.2+/-7.9 vs. 3.5+/-3.0, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters. CONCLUSION: For PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly. PMID- 24179874 TI - A study on sacral index in Tamil Nadu and andhra pradesh population of southern India. AB - INTRODUCTION: Human sacral bones are of great interest to the anatomists, forensic experts and anthropologists as it is one of the important bones used for identification of sex in skeletal remains. Various parameters and indices are available based on which the sex can be determined using sacrum. One such important parameter is the SI. Studies shows that SI significantly varies among male and female gender and among different populations. The calculation of Demarcation Point (DP) of SI increases the accuracy of identification of sex. A review of literature showed that many studies are available in the North Indian population whereas there is a dearth of information about the normal SI and DP in South Indian population particularly in the Tamil Nadu and Andhra Pradesh, Inida region. Therefore, the present study aims to create a database for the SI in the above mentioned population. MATERIAL AND METHODS: One hundred twenty three bones of known sex (63 males and 60 females) belonging to Tamil Nadu and Andhra Pradesh, India region were studied. Bones with obvious pathology were excluded. The breadth and length of the sacra were measured using vernier calipers based on standard guidelines. The SI and DP were calculated. The statistical analysis was done using SPSS 15.0 package. RESULTS: The mean SI for male and female sacra were found to be 96.32 + 5.40 and 102.92 +4.00 respectively. The Demarcating Point was found to be <90.29 in males and >112.43 in females. The mean length of male and female sacra was 97.8 mm and 90.6mm respectively. The mean width was 93.7mm and 92.91mm respectively for males and females. CONCLUSION: The average SI and DP identified in the present study would be of use to the anatomists, forensic experts and anthropologists of Tamil Nadu and Andhra Pradesh population. PMID- 24179875 TI - An osteological study of occipitocervical synostosis: its embryological and clinical significance. AB - BACKGROUND: Synostosis or fusion of atlas with occipital bone is known as occipitocervical synostosis, occipitalization of the atlas, or atlanto-occipital fusion. This is a rare congenital malformation at craniovertebral junction. Its incidence ranges from 0.08%-3% in general population. Occipitocervical synostosis result in narrowing of foramen magnum which may compress the brain stem, vertebral artery and cranial nerves. Knowledge of occipitocervical synostosis is important for the surgeons during the surgeries in the craniovertebral region. Hence, the present study was undertaken to determine the incidence and to describe the morphology of the occipitocervical synostosis. MATERIAL AND METHODS: Two-hundred dry adult human skulls of Indian origin were studied in the Department of anatomy. The base of these skulls was observed for presence of atlanto-occipital fusion. The anteroposterior and transverse diameter of the foramen magnum and diameter of the inferior articular facets were measured in these skulls using digital vernier caliper. RESULTS: Two skulls showed occipitalization of Atlas (1%). One of the skulls showed partial fusion (0.5%) while the other showed complete occipitalization (0.5%). CONCLUSION: The knowledge of bony fusion between the cranial base and the first cervical vertebra is important as such skeletal anomaly may result in sudden unexpected death due to compression of the vital structures such as brain stem and vertebral arteries. PMID- 24179876 TI - Anatomical variations in formation of sural nerve in adult Indian cadavers. AB - BACKGROUND: Sural nerve is formed by communication of medial sural cutaneous nerve, that arise from tibial nerve in popliteal fossa and peroneal communicating nerve, a branch directly from common peroneal nerve or from lateral sural cutaneous nerve. The sural nerve is universally recognized by surgeons as a site for harvesting an autologous nerve graft and for nerve biopsies in case of neuropathies. SETTING AND DESIGN: Anatomy department and an observational study. STATISTICAL ANALYSIS: The Mean, Standard Deviation, relevant percentages and p value was calculated by Chi-square test. MATERIAL AND METHODS: The study consists of 50 lower limb specimens in 25 cadavers. All the male and female complete cadavers were included in the study. The data was collected by dissection method by using dissection instruments and parameters (measurements) were obtained by using measuring tape. RESULTS: The sural nerve complex was dissected and observed in 50 formalin fixed lower limb specimens. Study was done in 16 male and 9 female cadavers. Three types of formation of sural nerve were observed were - Type A was seen in 36 specimens (72%) of cases. Type B was seen in 14 specimens (28%) of cases. Type C sural nerve was not found in present study. Site of union of components of SN was seen in the upper 3(rd) of leg in 5.6%, in middle 3(rd) it was in 33.3% and in lower 3(rd) it was in 58.3% of cases. The length of the sural nerve shows a wide range from 2 cm to 32 cm. The symmetrical distribution was seen in 62.5% in males and 55.6% in female. CONCLUSION: The normal anatomy and variations may help to guide during surgeries in the region. PMID- 24179877 TI - Aortic valve annular dimension in Indian population. AB - AIM: The Aortic Valve (AV) annular dimension with respect to the Body Surface Area (BSA) of the Indian population is compared against the standard values. Presence of discrepancies can lead to patient prosthesis mismatch during aortic valve replacement surgeries. METHODS: This study was conducted on 406 subjects. AV diameter was examined by using parasternal long axis view, where the imaging plane transects the AV in an anteroposterior direction and its x axis is aligned parallel to the long axis of aorta. Data were statistically analysed with western population. RESULTS: The AV dimension ranged from 12.2 mm to 21.2 mm in the BSA range of 0.6 to 1.9 m(2), showing a linear increase in diameter with increasing BSA. There was an increase of about 2 mm, from 0.61 - 0.7 m(2) BSA to 0.71 - 0.8 m(2) BSA. A linear increase which ranged from 0.3 to 1 mm was observed for BSA which ranged from 0.81 m(2) to 1.2 m(2). In the BSA range of 1.21 - 1.3 m(2), there was an increase of 1.5 mm. A steady increase which ranged from 0.4-1 mm was observed in the BSA which ranged from 1.31- 1.9 m(2). CONCLUSIONS: There is a significant difference between Indian and western population in the aortic dimension, in the body surface ranges of 0.61-0.7, 1.11-1.2, 1.21-1.3, 1.51-1.6, 1.61-1.7, 1.71-1.8 and 1.8-1.9 m(2). In the range of 1.21-1.3 m(2), the diameter was larger than standard, whereas in all the other ranges, AV diameter was smaller than standard values. BSA, as a good predictor of AV dimension, has also been proved. PMID- 24179878 TI - Detection of proteinuria in pregnancy: comparison of qualitative tests for proteins and dipsticks with urinary protein creatinine index. AB - BACKGROUND AND OBJECTIVES: Excretion of urinary protein increases to 300 mg/d (from up to 150 mg/d) in normal pregnancy. Values above this may be due to disorders that can endanger the patient or her pregnancy. Quantitative analysis of 24-hour urine is considered the gold standard for ascertaining daily protein excretion. Routine laboratory tests performed on spot urine samples indicate protein concentration in the particular sample, and can lead to diagnostic error if urine output is less or more than 1L/d. The Protein Creatinine Index (PCI) shows good correlation with 24-hour protein estimation. However, PCI varies with sex and race. We have correlated the results of qualitative estimation procedures and the dipstick values with protein creatinine index. MATERIAL AND METHODS: We measured protein and creatinine in spot urine samples obtained from 57 pregnant and 80 non-pregnant healthy women of 18-36 years, and calculated PCI. We also tested the samples qualitatively for proteins by routine tests and dipsticks. RESULTS: Normal range of PCI in non-pregnant women, determined by a non parametric method was 30-150. PCI was increased significantly in pregnancy (maximum increase in the third trimester). Amongst the qualitative tests, heat coagulation test gave the lowest percentage of false positives and a slightly higher percentage of false negatives compared to Heller's nitric acid and sulphosalicylic acid tests, and dipsticks. INTERPRETATIONS AND CONCLUSIONS: We conclude that heat coagulation test be used for initial screening, with PCI being performed on all samples testing positive to rule out false positives. PMID- 24179879 TI - Prevalence of metabolic syndrome in turkmen ethnic groups in gorgan. AB - INTRODUCTION: It has been estimated that the metabolic syndrome may predict cardiovascular disease and the occurrence of sudden death, independent of the presence of other cardiovascular risk factors. The aim of the present study was to assess the metabolic syndrome among Turkmen women in this area. MATERIAL AND METHODS: The present study consisted of 160 Turkmen women. Baseline data and prevalence of metabolic syndrome and the components of metabolic syndrome in Turkmen women were determined. OBSERVATIONS AND RESULTS: The prevalence of high levels of fasting glucose, low levels of high density lipoprotein-cholesterol, high triglyceride levels, high waist circumference and high blood pressure were shown to be 29.37%, 70.62%, 35.62%, 75% and 26.25%, respectively. It was shown that high waist circumference (75%) and Low HDL-cholesterol levels (70.62%) were the most frequent characteristics in comparison to other metabolic components. The prevalence of high waist circumference, high triglyceride levels, high levels of fasting glucose, high blood pressure and BMIs which were >=25 were higher in subjects with metabolic syndrome (92.85%, 73.21%, 73.21%, 57.14% and 83.92%, respectively). CONCLUSION: Metabolic syndrome is more prevalent among Turkmen women. Our data has shown that the prevalence of abnormal waist circumference in this ethnic group was highest. The waist circumference can be used as a predictor for cardiovascular disease and coronary heart disease. PMID- 24179880 TI - The association of hypomagnesaemia, high normal uricaemia and dyslipidaemia in the patients with diabetic retinopathy. AB - CONTEXT: Diabetic retinopathy is fast becoming an important cause of a visual disability. The visual disability which results from diabetes is a significant public health problem; however, this morbidity is largely preventable and treatable. If it is managed with a timely intervention, the quality of life can be preserved. AIMS: The objective of this study was to investigate the association of serum uric acid, magnesium and the lipid profile in diabetic retinopathy with Normal subjects and Diabetes mellitus without retinopathy, among the south Indian population. SETTINGS AND DESIGN: The diabetic retinopathy patients were identified from the diabetic health camps which were held in rural areas, and they were compared with those with diabetes without complications and the normal subjects. MATERIAL AND METHODS: The diabetic retinopathy patients were compared with the healthy subjects and with diabetes without retinopathy. Furthermore, the Diabetic retinopathy patients were grouped as proliferative and non-proliferative, based on the fundoscopic findings. Magnesium, uric acid, FPG, fructosamine and the lipid profile were measured in the above groups and they were analyzed. STATISTICAL ANALYSIS: The statistical analysis was done by using the SPSS software, by applying the Student 't' test. RESULTS: The mean serum magnesium concentration was observed to be low in the diabetic retinopathy group (1.43mg/dl) as compared to those in the controls and the diabetic subjects. The serum Uric acid concentration was high normal (4.84mg/dl), which was associated with the dyslipidaemia in diabetic retinopathy. CONCLUSION: The poor glycaemic control in diabetes is associated with hypomagnesaemia, and increased uric acid concentration with dyslipidaemia, which can be an initial picture of the ongoing biochemical changes in the complication of diabetes, which can help in predicting the onset of diabetic retinopathy in diabetes. PMID- 24179881 TI - Oxidative stress, vitamin e, and antioxidant capacity in knee osteoarthritis. AB - BACKGROUND: Osteoarthritis (OA) is a chronic progressive degenerative joint disorder which is characterised by strongly age-related regressive changes in articular cartilage. The objective of this study was to evaluate oxidative stress and antioxidant parameters in plasma and synovial fluid of patients with primary knee osteoarthritis. MATERIAL AND METHODS: Thirty-five OA patients and 35 healthy controls were recruited for this study. Nitrite, malondialdehyde (MDA), vitamin E, Trolox Equivalent Antioxidant Capacity (TEAC), and Ferric Reducing Antioxidant Power (FRAP) levels in plasma and synovial fluid were determined. RESULTS: Plasma nitrite levels in OA patients were significantly higher than those in healthy controls (p = 0.037). Furthermore, plasma MDA levels were significantly higher in OA patients than those in healthy controls (p < 0.001). Moreover, plasma vitamin E levels in OA patients were significantly lower than those in healthy controls (p < 0.001). Synovial fluid vitamin E levels of OA patients were significantly lower than paired plasma samples (p < 0.001). The total antioxidant capacities, as were measured by TEAC and FRAP assays in plasma of OA patients, were significantly lower than those in healthy controls (p < 0.01). MDA concentrations were positively correlated with nitrite concentrations but they were negatively associated with vitamin E and TEAC levels in synovial fluid of OA patients. CONCLUSION: The increased plasma levels of nitrite and MDA and the decreased plasma levels of vitamin E, TEAC, and FRAP indicated that oxidative stress was present in OA patients. These findings suggest that oxidative stress plays a potential role in pathophysiology of knee osteoarthritis. PMID- 24179882 TI - Attenuation of oxidative stress, inflammation and insulin resistance by allium sativum in fructose-fed male rats. AB - BACKGROUND: Fructose is widely used as a food ingredient and has potential to increase oxidative stress. Moreover, the beneficial health effects of medicinal plants are frequently attributed to their potent antioxidant effects. OBJECTIVES: The present study was aimed to explore the effects of garlic (Allium sativum) extract on insulin resistance, inflammation and oxidative stress in male wistar rats fed with high fructose diet. MATERIAL AND METHODS: Diabetes was induced in male albino Wistar rats by feeding 60% fructose rich diet. The fasting plasma glucose, insulin, insulin resistance, tumour necrosis factor alpha, total antioxidant status and the whole blood reduced glutathione, erythrocyte antioxidant enzyme activities were measured. Differences between the groups were assessed by using One Way Analysis of Variance with (ANOVA) Tukey post-hoc test. RESULTS: The diabetic rats showed a significant increase in plasma fasting glucose, insulin, insulin resistance, tumour necrosis factor alpha and malondialdehyde level and decreased levels of total antioxidant status, reduced glutathione, catalase and glutathione peroxidase. Treatment with garlic extract restored all these biochemical changes. CONCLUSION: The garlic extract is effective in improving the high fructose induced oxidative stress, inflammation and insulin resistance in male wistar rats. PMID- 24179883 TI - Trace elements in diabetes mellitus. AB - INTRODUCTION: Diabetes Mellitus is the commonest major metabolic disease and most prevalent diseases worldwide.Its related morbidity is due to its micro and macro angiopathic complications. AIM: The aim of this study was to measure and compare the serum levels of zinc and magnesium in normal individuals and in diabetic patients. METHOD: Analysis of minerals was done in plasma by using a Varian Spectra AA 220 model atomic absorption spectrophotometer. RESULT: Our observations showed a definite lowering of serum magnesium (p<0.001) and serum zinc levels (p<0.001) were significant in diabetic group. CONCLUSION: The cause of diabetic hypomagnesaemia is multifactorial. An altered metabolism, a poor glycaemic control and osmotic diuresis may be contributory factors. Decreased serum zinc levels in diabetes may be caused by an increase in urinary loss. These decreased levels of trace elements cause disturbances in glucose transport across cell membrane lead to insufficient formation and secretion of insulin by pancreas which compromise in the antioxidant defense mechanisms. PMID- 24179884 TI - Anti mullerian hormone: a potential marker for recruited non growing follicle of ovarian pool in women with polycystic ovarian syndrome. AB - BACKGROUND: Polycystic ovarian disease is one of the most common causes of infertility in women of reproductive age. Anti- mullerian hormone (AMH), a member of transforming growth factor (TGF) family which is secreted by granulosa cells of growing follicle, is found to be increased to three to four fold in Poly Cystic Ovarian Syndrome (PCOS) patients as evidenced by previous studies. But the level of AMH in relation to the infertile status of PCOS was not studied yet. The present study was focused to determine the discriminative power of AMH in infertility subjects with regular cycles and infertility subjects associated with PCOS. METHODS: The subjects under study were one hundred and twenty infertile women of age group ranging from 27-35 years. Subjects, were further divided into sixty infertile with regular cycles as controls (Group1) and sixty infertile subjects with PCOS as cases (Group 2). Hormones like FSH, E2 and AMH were assayed for all the subjects. Mean and student t- test for all hormones were compared between controls and cases. The diagnostic power of AMH pertaining to sensitivity and specificity was evaluated by Receiver operating characteristic (ROC) curve. RESULTS: Serum AMH level were two fold higher in PCOS patients than in controls. The mean value of AMH also shows a test of significance between the two groups. The area under the receiver operating characteristic curve for the AMH assay was 0.95 in infertile group when 3.34ng/ml was used as cut off point indicating its better discriminative power and good diagnostic potency. Setting the AMH value at 3.34ng/ml sensitivity, specificity,Positive Predictive Value(PPV) and Negative Predictive Value(NPV) were observed 98% ,93%, 93% and 98% respectively. CONCLUSION: The diagnostic potency of Area Under Curve (AUC) for AMH in infertile subjects reflects that AMH is a potential marker for recruited non growing follicles rather than a simple marker for ovarian reserve as it is predominantly produced by small follicles rather than a simple marker for ovarian reserve. PMID- 24179885 TI - Effect of Various Eye Exercise Techniques along with Pranayama on Visual Reaction Time: A Case Control Study. AB - INTRODUCTION: We depend on eyesight more than any other of our senses to maneuver through the space around us. In a fraction of a second, our eyes work with our brain to tell us the size, shape, colour, and texture of an object. Our eyes are body's most highly developed sensory organs. The use of computers and television in the era of information technology has given new heights to the professional success rate and it saves time but on the other hand, it has led to an increase in the number of patients with ocular complaints. AIMS: The objective of the study was to study the effect of eye exercise techniques along with kapalbhati pranayama on Visual Reaction Time (VRT). MATERIAL & METHODS: Total 60 subjects in an age group of 18-30 were recruited in the study. All the subjects were divided into two equal groups (study group and control group) containing 30 subjects (18 male & 12 female) each. Both the male and female subjects were selected on the basis of their voluntary involvement. Visual reaction time for red and green light was recorded from all 60 subjects before the start of the study. Study group subjects were trained to practice various eye exercise techniques and kapalbhati pranayama for 8 weeks regularly whereas control group were busy with their routine activities. After 8 weeks, visual reaction time was measured for red and green light from all 60 subjects. STATISTICAL ANALYSIS: Data expressed as Mean +/- S.D, Student t -test was applied for analysis of data, p value <0.05 is taken as statistically significant. RESULTS: Statistical analysis of data shows that there is a significant decrease in the visual reaction time for red and green light after intervention in study group (p value <0.05). Whereas there is no significant decrease in VRT in control group (p value >0.05). CONCLUSION: The results of our study suggest that simple eye exercises along with pranayama helps in improvement of visual reaction time. PMID- 24179886 TI - Alveolar Gas Exchange and Pulmonary Functions in Patients with Type II Diabetes Mellitus. AB - BACKGROUND: The incidence of diabetes is increasing tremendously throughout the world especially in the developing countries. This disease affects various organs like eyes, nerves, kidneys and the heart. In this study, we investigated whether lungs are also one of the target organs of diabetes mellitus or not. AIM: To assess the pulmonary function parameters including alveolar gas exchange in patients with Type 2 Diabetes mellitus and to find the influence of hyperglycaemia and duration of diabetes. METHODOLOGY: This cross sectional study involved 30 type II diabetic patients of age 30-60 years attending the diabetic outpatient department of SRM Medical College & Research Centre and 30 age and sex matched non-diabetic subjects as controls. The glycated haemoglobin (HbA1c) levels, fasting and post prandial blood glucose levels, pulmonary function parameters such as Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), Forced Expiratory Volume Percentage (FEV1 /FVC), Peak Expiratory Flow Rate (PEFR), Forced Expiratory Flow (25 - 75%), Peak Inspiratory flow ( PIF), Forced Inspiratory Vital Capacity ( FIVC), Total Lung Capacity ( TLC),Diffusing capacity of lung for carbon monoxide( DLCO) were measured for all the participants using Easyone Pro computerised spirometer. DLCO was measured by single breath Carbon Monoxide (CO) diffusion test. The alveolar membrane permeability was assessed by evaluating the ratio of DLCO to Alveolar Ventilation (VA). RESULTS: The pulmonary function parameters FVC, FEV1, PEFR, PIF, FIVC, TLC , DLCO and DLCO/VA were significantly low (p<0.05) in patients with type II diabetes mellitus when compared to control group. The DLCO and DLCO/VA were significantly lower (p<0.05) in patients with poor glycemic control(HbA1c > 7). CONCLUSION: We conclude that the pulmonary function parameters like FVC, FEV1, PEFR, PIF, FIVC, TLC and alveolar gas exchange were significantly reduced in patients with type II diabetes. The patients with Type II diabetes mellitus had a restrictive pattern of respiratory abnormality. The patients with poor glycaemic control( HbA1c > 7) had reduced alveolar diffusion which was not dependent on the duration of diabetes. The impaired respiratory function may give way for the development of pulmonary complications. Spirometry can be used as a screening tool among diabetics as an early preventive measure. PMID- 24179887 TI - Comparison of effect of regular unstructured physical training and athletic level training on body composition and cardio respiratory fitness in adolescents. AB - BACKGROUND: Childhood obesity and hypertension are global problems that are on the rise in India. Improving physical activity is an accepted main line of strategy for overcoming poor body composition, hypertension and reduced cardio respiratory fitness (CRF) all of which are considered as independent risk factors for the development of future cardiovascular complications. AIM: Present study was conducted to evaluate the effect of regular unstructured physical training and athletic level training on anthropometric measures, body composition, blood pressure and cardio respiratory fitness in adolescents. SETTINGS AND DESIGN: This is a collaborative study between the Department of physiology, Jawaharlal Institute of Postgraduate Medical Education and Research and Residential school, Jawahar Navodhya Vidyalaya, Puducherry, India. METHOD AND MATERIAL: Student volunteers in the age group of 12-17 years were classified into athletes (group 1) and physically active non-athletes (group 2). Parameters measured and calculated were weight, height, body mass index, waist and hip circumference, body fat percentage (BF%), fat free mass (FFM), Systolic (SBP) & Diastolic blood pressure (DBP), Mean arterial pressure (MAP), Rate pressure product (RPP) and Predicted VO2 max. STATISTICAL ANALYSIS USED: Mean difference between the groups was analysed using unpaired Student's t-test. All statistical analysis was carried out for two-tailed significance at the 5 % level using SPSS version 19 (SPSSInc, USA). RESULTS: Anthropometric measures, body composition measures and blood pressure values of both the group students were within the normal limits. There was no significant difference in anthropometric and body composition parameters between the group 1 and group 2 students. DBP, MAP and RPP were significantly lower in group 1 students when compared to group 2 students. VO2 max values were more in group 1 girls as compared to group 2 girls while the values of boys were comparable between the two groups. CONCLUSION: Regular unstructured physical activity for 60 minutes daily for the duration of one year can help the students to maintain their anthropometric parameters, body composition measures and CRF at par with the athletes of the same age and gender. However, athletic level training further reduces the cardiovascular load of the adolescent students. PMID- 24179888 TI - The Acute Effects of a Single Bout of Moderate-intensity Aerobic Exercise on Cognitive Functions in Healthy Adult Males. AB - INTRODUCTION: Single acute bouts of moderately-intense aerobic exercise like walking have been found to improve cognitive control of attention in children, but some studies have reported no improvement in cognitive flexibility following acute aerobic exercise. Submaximal aerobic exercise performed for 60 minutes facilitated specific aspects of information processing in adults but extended exercises leading to dehydration compromised both information processing and memory functions. Improvement in executive functions has also been reported during cycling at 70% of Heart Rate Reserve (HRR) across young and older age groups. However, there are studies which have reported no correlation between physical activity and academic performance in children and a recent systematic review of 30 relevant studies reported no significant improvement in cognition with physical activity or exercise in adults. There seems to be lack of consensus on the effect of exercise on cognition, which may be because the exercise protocols used and cognitive functions tested by different researchers were not uniform. AIM: The primary aim of this study was to investigate the acute effects of aerobic exercise across different cognitive domains in healthy young individuals. METHODS: A homogeneous group of 10 right handed healthy adult males participated in the study and was subjected to 8 cognitive function tests including 2 tests each across the four categories: Memory, Reasoning, Concentration and Planning using a pre-validated web based tool. Following baseline testing, subjects performed 30 minutes' of cycling on a stationary bicycle ergometer at moderate intensity (60-70% of HRR). Post-test scores were recorded when heart rate returned to within 10% of baseline. Pre and post-test scores were compared using the paired t-test. RESULTS: After exercise, there was significant improvement (Mean +/- SD) in the Paired Associates (4.8+/-1.0 Vs 5.5 +/- 1.0), Odd One Out (10.5 +/- 3.0 Vs 13 +/- 3.1) and Spatial Slider test (30.4 +/- 17.8 Vs 40.5 +/- 13.9), the tests of Memory, Reasoning and Planning respectively. No significant improvement was found for concentration. Total post test time was significantly lower than the pre-test time (23.5 +/- 2.55 Vs 21.2 +/- 1.48 minutes). CONCLUSION: A single bout of moderate intensity aerobic exercise for as less as 30 minutes can improve some aspects of cognition, most prominently for memory, reasoning and planning and can shorten the time taken to complete the tests. PMID- 24179889 TI - Effect of cigarette and cigar smoking on peak expiratory flow rate. AB - BACKGROUND: Tobacco smoking in India has been increasing alarmingly. Smoking is a known risk factor for chronic obstructive pulmonary disease (COPD), cardiovascular diseases and certain cancers, especially, the lung cancer. The percentage prevalence of cigarette smoking (18.5%) and cigar smoking (4%) in males is high in Andhra Pradesh compared to other southern states. There is not enough scientific literature to correlate about intensity of cigarette and cigar smoking and their impact on lung function though high prevalence is reported in Andhra Pradesh, India. OBJECTIVES: The purpose of this study was to examine whether PEFR differs between cigarette and cigar smokers compared to non-smokers and also to estimate the intensity of cigarette and cigar smoking on PEFR. METHODS: PEFR was recorded in cigarette smokers (n=49) and cigar smokers (n=10) as well as in non-smokers (n=64) using Wright's mini Peak Flow Meter. RESULTS: PEFR is decreased in both cigarette as well in cigar smokers compared to non smokers and the magnitude of decline was higher in cigar smoking elderly individuals. CONCLUSION: The intensity of cigarette and cigar smoking (pack years) emerged as the main variable to influence airway obstruction in smokers that caused greater reduction in PEFR. PMID- 24179890 TI - Effect of traditional aerobic exercises versus sprint interval training on pulmonary function tests in young sedentary males: a randomised controlled trial. AB - BACKGROUND: Physical inactivity is now a global non-communicable disease. Current recommendations from American College of Sports Medicine, American Heart Association and UK medical officers for physical activity are difficult to implement, due to time constraints and hence, they have less compliance. PURPOSE: To compare Sprint Interval Training (SIT) and traditional aerobic exercise (AE) with respect to changes in Vital capacity (VC), Maximum Voluntary Ventilation (MVV) and Physical Fitness Index (PFI) in young sedentary males. STUDY DESIGN: This was a randomised, controlled trial. METHODS: Fourteen young, sedentary, healthy males who were aged 18-25 years were randomly allocated to SIT group and AE group for 3 weeks. SIT group exercised at high intensity for 10 minutes a day, three days a week. AE group exercised at moderate intensity for 30 minutes a day, five days a week. RESULTS: Improvement in FVC (litres) in AE group was 0.31 +/- 0.11 and that in SIT group was 0.48 +/- 0.17. The improvement in MVV (litres) in AE Group was 21.5 +/- 11.6 and that in SIT group was 27.77 +/- 7.03. Thus, SIT showed a better improvement in primary outcome i.e. FVC and MVV, although difference in improvement was statistically not significant (p= 0.09 and 0.29 respectively). Secondary outcome i.e. PFI improved by 5.57 +/- 1.71% in AE group and by 10.28 +/- 3.03% in SIT group. The difference in improvement was statistically significant (p= 0.003). CONCLUSIONS: SIT can be suggested as a time efficient option for improving cardiorespiratory fitness and hence, it can be used as a health promotion strategy. PMID- 24179891 TI - Effect of 'water induced thermogenesis' on body weight, body mass index and body composition of overweight subjects. AB - CONTEXT: Drinking lots of water is commonly suggested as a part of weight loss regimens. However, only few systematic studies have addressed this notion. In this study, the effect of drinking 1500 ml of water, over and above the daily water intake on body weight, body mass index (BMI) and body composition of overweight subjects was assessed. AIM: To evaluate the role of drinking excessive water in weight reduction and body fat reduction of overweight subjects. SETTINGS AND DESIGN: This study was conducted on 50 overweight girls for eight weeks, during which they were instructed to drink 500 ml of water, three times a day, half an hour before breakfast, lunch and dinner, which was over and above their daily water intake. MATERIAL AND METHODS: Body weight was measured in kilograms (kgs). BMI was calculated as weight in kilograms, which was divided by the square of height in metres. Body composition score was calculated as a sum of skin fold thickness in millimetres at three different sites, which was measured by using skin fold calipers. Pre and post-study body weight, body mass index and body composition scores were measured. STATISTICAL ANALYSIS: SPSS, version 14.0.1 and paired t-test were used to find out the statistical significance of the results. RESULTS: The mean values of the pre-study and post-study body weight, body mass index and body composition scores were 65.86 kg and 64.42 kg, 26.7002 and 26.1224 and 79.626 mm and 76.578 mm respectively. All the three results were highly significant statistically. CONCLUSIONS: The decrease in body weight, body mass index and body composition scores of overweight subjects at the end of study period establishes the role of water induced thermogenesis in weight reduction of overweight subjects. PMID- 24179892 TI - To compare the effect of camylofin dihydrochloride (anafortin) with combination of valethamate bromide (epidosin) and hyoscine butyl-N-bormide (buscopan) on cervical dilation. AB - BACKGROUND: Various drugs have been tried to hasten cervical dilatation so that problems and hazards of prolonged labour both for the mother and fetus are minimised without increasing maternal or perinatal mortality and morbidity. AIMS AND OBJECTIVES: To compare the effect of camylofin dihydrochloride with combination of valethemate bromide (epidosin) & hyoscine N butyl bromide (buscopan) on cervical dilatation, evaluate the incidence of side effects and to look for neonatal outcome. MATERIAL AND METHODS: Two hundred cases were included of primigravidae or multigravidae with gestational age of 37 to 40 weeks with full term with single foetus,vertex presentation and no major antenatal complication of women in labour, admitted to labour room of gynaecology Department, Government Medical College, Patiala, India, was studied and divided into 2 groups Group A-100 Cases - labour accelerated by camylofin dihydro chloride and Group B-100 Cases-labour accelerated by valethemate bromide (epidosin) and hyoscine N butyl bromide. OBSERVATIONS: The mean age, parity and period of gestation in Anafortan group was 24.13 +/- 3.60 years, 49% primigravidae and 51% multigravidae and 38.81 +/- 1.09 weeks, while that in Epidosin + Buscopan group was 24.43 +/- 3.42 years, 45% primigravidae and 51% multigravidae and 38.94 +/- 1.09 weeks respectively. The difference was insignificant and both the groups were comparable. RESULTS: Mean duration of Active phase of 1st stage of labor was 141.40 +/- 55.41 minutes in Anafortan group and 181.46 +/- 75.58 minutes in Epidosin + Buscopan group. Mean rate of cervical dilatation according to active phase of first stage was 3.33 +/- 1.03 cm/hours in Anafortan group and 2.69 +/- 1.03 cm/hr in Epidosin + Buscopan group. The difference between the two groups is highly significant (p < 0.01) thus it is concluded that Anafortan hastened the rate of cervical dilatation. PMID- 24179893 TI - The effect of carvedilol on blood glucose levels in normal albino rats. AB - BACKGROUND: Carvedilol is a commonly used drug in hypertension, congestive heart failure in diabetics. It has moderate calcium channel blocking property in addition to alpha1 and non selective beta antagonistic activity. Though some studies bring forth the beneficial effects of Carvedilol in cardiovascular comorbidities in diabetes, there is no consensus on its effects on glycaemic levels. AIMS: To evaluate the effect of oral Carvedilol administration for 5 days on blood glucose levels in normal albino rats through Oral Glucose Tolerance Test. MATERIAL AND METHODS: Twelve adult albino rats of either sex weighing between 150 - 200 g were selected from central animal facility and randomly divided into 2 groups - Control [Distilled water (1ml/rat orally)] and Test (0.8mg/kg body weight orally) and the respective drugs were administered over 5 days. Following overnight fasting, on the fifth day 1 hour after the last dose of the respective drug, OGTT was performed. The CBG (Capillary Blood Glucose) levels were measured at 0 min, glucose (2g/kg body weight) dissolved in water was administered to all the rats orally. The blood sample from tail vein (obtained by tail snipping) at 60 and 150 minutes were analysed for CBG levels using a standardized glucometer. STATISTICAL ANALYSIS: Data was presented as Mean +/- SEM. One way ANOVA, independent samples t-test, non-parametric tests, percentages and cross tabs were used in the analysis of data within the same group and between different groups when required. RESULTS: Carvedilol group showed higher CBG levels at all time intervals of OGTT as compared to the Control group i.e., 0, 60 and 150 minutes, the highest being (103.8+/-5.029 )mg/dl at 60 minutes and was statistically significant. Carvedilol group however showed lesser inter interval variation compared to the Control group at the same time intervals respectively but was statistically insignificant. CONCLUSIONS: Carvedilol has hyperglycaemic potential when given orally for 5 days in normal albino rats. Though it may be beneficial in diabetics for various comorbid conditions, the glycaemic control may worsen during its use in subjects with prediabetes, diabetes, high risk diabetes. PMID- 24179894 TI - Bromocriptine, a Dopamine (d2) Receptor Agonist, Used Alone and in Combination with Glipizide in Sub-Therapeutic Doses to Ameliorate Hyperglycaemia. AB - INTRODUCTION: Bromocriptine, an ergot derivative, is an agonist at the dopamine 2 receptor and a sympatholytic. It is a well established drug in Parkinsonism, hyperprolactinaemia and acromegaly and it has various other clinical indications like induction of ovulation in female infertility. Bromocriptine has been evaluated in alloxan induced diabetic rats for its anti-hyperglycaemic effect with and without simultaneous use of glipizide. METHODS: Diabetes was induced in albino rats by giving a single subcutaneous injection of alloxan in a dose of 150 mg/kg body weight. After 72 hours of giving alloxan injection, depending upon their blood glucose levels (350mg/dl and above), the rats were included into the study and they were divided into four groups, each comprising of 6 rats (n=24): Group 1 which was taken as control was given distilled water. Group 2 was treated with glipizide, a standard drug. Group 3 was treated with the test drug, bromocriptine and Group 4 was treated with sub therapeutic doses of test and standard drugs. The drugs were given to the diabetic rats once daily by oral route for 30 consecutive days, in order to assess their effects in terms of reduction in blood glucose levels. Blood glucose was estimated on 0(th), 10(th), 20(th), and 30(th) days of the study at fixed time intervals. RESULTS AND CONCLUSION: Bromocriptine, which was used alone, lowered the blood glucose levels appreciably; whereas the concomitant administration of bromocriptine and glipizide in sub therapeutic doses produced a much more appreciable reduction. The results which were obtained in the group which received simultaneous administration of test and standard drugs in sub therapeutic doses were comparable to those of the group which received reference drug, glipizide. Hence, it can be concluded that bromocriptine may serve as a valuable adjunct to available anti-diabetic medication. PMID- 24179895 TI - Influence of delivery devices on efficacy of inhaled fluticasone propionate: a comparative study in stable asthma patients. AB - BACKGROUND: Inhaled corticosteroids are the preferred treatment for long-term control of all grades of persistent asthma. These are administered by various delivery devices with very little information whether these devices can affect the efficacy of inhaled corticosteroids. Fluticasone propionate is a relatively new inhalational corticosteroid compared to older ones like beclomethasone and budesonide. Aims & Objective: To assess the relative efficacy of fluticasone propionate administered from different delivery devices to adult patients of chronic stable bronchial asthma as measured by pulmonary function test parameters. MATERIAL AND METHODS: This prospective study was undertaken to assess the relative efficacy of fluticasone propionate administered from different delivery devices to adult patients of chronic stable bronchial asthma as measured by pulmonary function test parameters. Fourty eight subjects were administered, fluticasone propionate (250 MUg) by dry powder inhaler, metered dose inhaler, metered dose inhaler with spacer and fluticasone (1mg) via nebulizer consecutively each week for four weeks under direct supervision. Pulmonary function test was done before and one hour after administration of the drug on each visit. RESULTS: After excluding nine patients who were lost to follow up, data was analysed for the remaining thirty nine patients and no significant difference in peak expiratory flow rate (p=0.77), forced expiratory volume in one second (p=0.95), forced vital capacity (p=0.24) and forced expiratory volume in one second and forced vital capacity ratio (p=0.22) was seen after giving fluticasone by different devices. CONCLUSION: Fluticasone propionate delivered by different devices like dry powder inhaler, metered dose inhaler, metered dose inhaler with spacer and nebulizer have similar effect on lung function in patients of chronic stable bronchial asthma and may be used interchangeably. PMID- 24179896 TI - A population based case control study on breast cancer and the associated risk factors in a rural setting in kerala, southern India. AB - INTRODUCTION: The incidence of breast cancer is increasing in developing countries over three decades. Despite good health indicators breast cancer is a public health problem in Kerala with an annual incidence of 14.9/100000 population. Identifying the risk factors helps to reduce the incidence in future. METHOD: A Population based case control study was conducted among all the breast cancer cases in the Arpookara Panchayat of Kottayam district in Kerala. 20 cases of breast cancer were paired with age matched controls from the same geographic area (ratio 1:4) with a total of 100 study participants. Data were collected by interviewing the participants using a pre tested structured questionnaire. Analysis was done by the authors using SPSS version 16.0 RESULTS: Age group of participants ranged from 32-70 years with mean age of 49.7 + 10.39. Early menarche < 13 years [Odds Ratio =3.2, p= 0.03], being unmarried and single, family history of breast cancer [Odds Ratio = 3.5, p = 0.02], previous history of benign breast tumours [Odds Ratio =8.14, p= 0.04], breast feeding less than 2 years [Odds Ratio = 2.28, p = 0.01 ] were found to be the risk factors for the breast cancer and the birth of first child before 30 years [Odds Ratio =0.302, p = 0.03 ] was found to be a protective factor for breast cancer. 60% of cases belonged to lower socioeconomic status [Odds Ratio = 14.47, p = 0.03]. Despite high literacy status, significantly lower awareness about symptoms of breast cancer and self examination of the breast were noted [Odds Ratio =11.6, p= 0.03]. CONCLUSION: Awareness about symptoms of breast cancer and self examination of the breast were lacking in the study population. Health care personnel should be trained to spread the awareness of breast cancer in the community and to identify the vulnerable groups at the primary care settings itself. The policy makers can consider encouraging community participation by involving the non-governmental organizations, women self help groups and Public Private Partnerships in spreading the awareness of breast cancer. PMID- 24179897 TI - A hospital based serosurveillance study of dengue infection in jaipur (rajasthan) , India. AB - BACKGROUND: Dengue has been known to be endemic in India for over two centuries. There is a need to assess the magnitude of dengue virus establishment in the state of Rajasthan. A surveillance study was conducted to analyze dengue seropositivity among patients with clinical suspicion of dengue fever like illness, who presented to or were admitted at a tertiary care private hospital at Jaipur. METHODS: Serum samples from 2169 suspected dengue cases (1356 males and 813 females) were received in the Serology lab over the four year study period (2008-2011). The samples were subjected to a rapid immuno-chromatography assay with differential detection of IgM and IgG antibodies. A primary dengue infection was defined by a positive IgM band and a negative IgG band, whereas a secondary infection was defined by a positive Ig G band with or without an IgM band. RESULT: Among the 2169 patients who were screened; 18.99% (412) were dengue specific IgM positive cases. 64. 49% (1399) cases were negative for dengue specific antibodies, 5.67% (123) were primary dengue cases, and 23.51% (510) were total secondary dengue cases. During the study period, the Dengue IgM seropositivity was highest in the year 2009 and was lowest in the year 2011. Most of the cases occurred in the post-monsoon season, with a peak in the month of October, each year. CONCLUSION: A detailed and continuous epidemiological surveillance is required, for monitoring the incrusion and spread of dengue viruses. This will help in undertaking and implementing effective control and management strategies. PMID- 24179898 TI - Prevalence of unrecognised depression among outpatient department attendees of a rural hospital in delhi, India. AB - BACKGROUND: Depression is one of the most common mental disorders affecting 121 million people in the world and it frequently goes unrecognised among patients. This study was carried out to find out the prevalence of unrecognised depression among out patient attendees of a rural hospital in Delhi, India and its socio demographic correlates. MATERIAL AND METHODS: This is a rural hospital based cross sectional study among 395 patients attending different non-psychiatric outpatient departments. Data was collected by using predesigned & pretested questionnaire and prevalence of depression was determined by PRIME MD (PHQ-9) and analysed by using SPSS version 16. Data was analysed using chi-square test with "p" value < 0.05 considered as significant. Independent association of socio demographic variables were determined by multi-variate logistic regression analysis using WHO EPI INFO software. RESULTS: The study included 67% females and 33% males with mean age 31.73 + 12 years. Most were Hindu (80%), married (75%), illiterate (47%) and were unemployed (65%). Out of 395 patients, 119 (30.1%) were diagnosed to be having depression. Out of 119 patients who were found depressed, 25 (21%) were already diagnosed case of depression and 94 (79%) were detected by using PRIME-MD, giving prevalence of unrecognised depression 23.8%. Among socio demographic factors, gender, religion, education status and being widow/separated were found to be statistically significantly associated with hidden depression among the patients. CONCLUSION: Unrecognized depression is a common in non psychiatric OPDs. There is a need to screen patients presenting in such OPDs for depression. PMID- 24179899 TI - Menstrual Pattern among Unmarried Women from Northern India. AB - BACKGROUND: Menstruation disorders are also responsible for emotional, physical, behavioural and dietary practice changes. These changes affect their normal functioning and social life. The present study was carried out to find the prevalence of menstrual problems among unmarried girls of Chandigarh, India and to compare their knowledge and beliefs regarding menstruation in different sub groups. METHODOLOGY: A community based cross-sectional study was conducted among 744 unmarried females in Rural, Urban and Slum strata of UT Chandigarh, India. Data were collected using a self-administered structured questionnaire on menstruation. Chi-square value was used for testing statistical significance. RESULTS: The mean age of the respondents was 16.84+/-3.05 years. Maximum respondents (40.9%) were educated up to 10th standard/High school. 448 (60.2%) were aware of menstruation before starting of menarche. Awareness was found to be significantly associated (p=0.02) with age. Socio-economic status and prior knowledge of respondents was also found to be significantly associated (p< 0.001). 61% (454) of the respondents had a regular flow during menses. Normal flow was reported by 70.2 %(522) of the respondents. Dysmenorrhea was found to be the most common problem suffered by 429 (57.7%) respondents. CONCLUSION: Menstrual hygiene is an issue that needs to be addressed at all levels. A variety of factors are known to affect menstrual behaviors, the most influential ones being economic status. It is essential to design a mechanism to address and for the access of healthy menstrual practices. PMID- 24179900 TI - Possible Correlation of Transfusion Transmitted Diseases with Rh type and ABO Blood Group System. AB - BACKGROUND: Screening of blood is mandatory for transfusion transmitted diseases and is routinely done in the blood banks. As blood is the major source transmission of hepatitis B, hepatitis C, human immunodeficiency virus & many other diseases the hazards can be minimised by effective donor selection and screening. AIM: To find out the correlation between the transfusion transmitted diseases and blood groups and the seroprevalence of HIV, HBV, HCV & syphilis among the apparently healthy human blood donors. Study, Setting & Design: This retrospective study was conducted at the blood bank of a tertiary health care teaching centre for a period of four years. MATERIAL AND METHODS: All voluntary and replacement donors reporting to the blood bank were screened for HIV-1 & 2, HBsAg, HCV and Syphilis. Anti-HIV -1 & 2, HBsAg & anti - HCV was tested using the appropriate Enzyme-linked immunosorbent assay (ELISA) technique using micro-elisa kit supplied by J.Mitra & Co.Ltd. The seropositive samples were again tested on ELISA kits of RFCL &/or BIORAD for further confirmation & ruling out any false positive or false negative results. The rapid plasma reagain (RPR) test was used for estimation of syphilis infection. STATISTICAL ANALYSIS: The data entry was carried out using Microsoft office excel worksheet and was analysed by percentage and comparison. RESULTS: Total of 6000 donors were screened which included voluntary and replacement donors. Seroprevalence of HIV (0.1833 %), HCV (1.28%), HBsAg (1.5833 %) and syphilis (0.4333 %) was detected. In the study done it was also noted - that the NEGATIVE blood groups were more prone to TTIs. Blood group A negative was more prone to TTIs with HIV, HBsAg and VDRL while blood group B negative was more affected by HCV. CONCLUSION: Seroprevalence of these infections shows that routine screening is a must for blood and blood product safe transfusion. Do negative blood groups predispose to TTIs? A finding which makes us think.... PMID- 24179901 TI - Sclerosing stromal tumour in young women: clinicopathologic and immunohistochemical spectrum. AB - AIM: Sclerosing stromal tumor is a benign tumor of ovary. We aimed to review the clinical findings and immunohistochemical results of SSTs through the 7 diagnosed cases in our hospital. MATERIAL AND METHODS: As immunohistochemical, blocks were applied with estrogen receptor , progesterone receptor, inhibin, calretinin, melan-A, CD10, smooth muscle actin, desmine, vimentin, CD34, S-100, C-kit, cytokeratin , cytokeratin7. RESULTS: Macroscopically, while 5 tumors had solid appearance, 2 tumors were composed of solid and cystic areas. All the tumors were in shape of ovarian masses with good limits. Microscopically, two types of cells were observed as fusiform fibroblast-like cells and theca-like cells with vacuolised cytoplasm. Immunohistochemical results: vimentin, smooth muscle actin, desmine, progesterone receptor, calretinin, inhibin were positive in all the cases; S-100, cytokeratin, cytokeratin7, estrogen receptor were negative in all the cases; CD-10 was positive in 2 cases; C-kit was positive in 5 cases; melan-A was positive in 4 cases. CONCLUSIONS: The significance of these tumors is that it is necessary to distinguish the histopathology in the frozen section in order to protect the other adnexa because of the characteristics to be observed at early ages (2(nd) and 3(rd) decades). Our findings support the conclusion that sclerosing stromal tumors are benign-character tumors that stem from over stroma and are hormonally active tumors because of the detected clinical and immunohistochemical results, although no hormonal effect that could be supported with laboratory tests was observed. PMID- 24179902 TI - Pterygium - a study which was done on a rural based population. AB - INTRODUCTION: Pterygium is a fibrous growth seen in bulber conjunctiva.It is a non malignant growth which may cause visual impairment. MATERIAL AND METHODS: Pterygium study was done on rural population in out patient department of NIMS Hospital and medical college, Jaipur, Rajasthan, India.Two hundred patients with 300 eyes which had Pterygium who attended the Eye OPD during 01/06/2011 to 01/03/2012 were taken for study. A detailed history, Visual Acuity, Refractive Status, Size of Pterygium and duration of the work which was done outdoors were recorded. All other physical illness were ruled out. The aim of the study is to find the incidence of Pterygium, male/female ratio, Comparison of size of Pterygium with duration of working hours in the outfield. CONCLUSION: The maximum number of patients of pterygium were seen in the age group 20-60 years and there is no difference in male/female ratio.The size of pterygium depends on their duration of working hours in outfield. PMID- 24179903 TI - Metabolic Syndrome among Urban and Rural Women Population - A Cross Sectional Study. AB - INTRODUCTION: There is increased incidence of Metabolic Syndrome across the globe. Metabolic Syndrome a strong predictor of coronary vascular disorder and Diabetes Mellitus is not highlighted enough especially in women. This study was undertaken to learn the prevalence of Metabolic Syndrome among urban and rural women. MATERIAL AND METHODS: A detailed history, clinical examination along with mini glucose tolerance test, FBS and PPBS in a known diabetic and fasting lipid profile were done in 590 urban and 433 rural women. Metabolic Syndrome was defined using Modified NCEP ATP III Criteria. RESULTS: Metabolic Syndrome was detected in 342 (57.96%) urban and 239 (55.19%) rural women. Individual components of Metabolic Syndrome like Waist circumference of > 80 cm was found in 283 (82.74%) urban and 171 (71.54 %) rural women, Systolic blood pressure > 130 mm Hg was found in 261 (76.31%) urban and 187 (78.24 %) rural women, Diastolic blood pressure of > 85 mm Hg was found in 201 (58.77%) urban and 143 (59.83 %) rural women, Triglycerides of > 150 mg/dl was found in 187 (43.85%) urban and 159 (66.52 %) rural women, High density lipoprotein of < 50 mg/dl was found in 309 (90.35%) urban and 224 (93.72 %) rural women and Fasting blood sugars of > 110 mg/dl was found in 93 (27.19%) urban and 44 (18.41 %) rural women. CONCLUSION: Our study showed increased prevalence of Metabolic Syndrome in urban women however there is also increasing prevalence in rural women due to changing life style pattern. PMID- 24179904 TI - The Value of Magnetic Resonance Cholangio-Pancreatography (MRCP) in the Detection of Choledocholithiasis. AB - INTRODUCTION: Magnetic Resonance Cholangio-Pancreatography (MRCP) is a non invasive radiological investigation which can be performed rapidly and which does not expose the patients to ionised radiations or iodinated contrast material. The present study was conducted to evaluate the role of MRCP in detection of Common Bile Duct (CBD) stones in patients with suspected choledocholithiasis. MATERIAL AND METHODS: This prospective study included 30 patients with a suspicion of choledocholithiasis which was based on clinical evaluation, biochemical or radiological investigations. Ultrasonography and MRCP were performed in all patients. All patients underwent open surgery. CBD exploration was performed in all patients, either due to presence of palpable stones or due to the presence of dilated CBD (> 7 mm). Demonstration of CBD stones intra-operatively was considered the 'gold standard' for their presence, defined as stones visualised and extracted or attempted for extraction during surgical CBD exploration. RESULTS: Intra-operatively, 21 (70%) out of 30 patients had cholelithiasis. 26 (86.67%) out of 30 patients had dilated CBD stones intra-operatively. In 20 (66.67%) out of 30 patients, choledocholithiasis was detected intra-operatively. The sensitivity, specificity, positive and negative predictive value of ultrasonography in detecting CBD stones in the present study was 65%, 60%, 76.47% and 46.15% respectively. The sensitivity, specificity, positive and negative predictive value of MRCP in diagnosis of CBD stones in the present study was 95%, 90%, 95% and 90% respectively. CONCLUSIONS: MRCP is a non-invasive investigation without complications and it has high sensitivity, specificity and positive and negative predictive values in detection of CBD stones. MRCP should be done in all cases with a suspicion of CBD stones, where facilities and expertise are available. PMID- 24179905 TI - Mortality in typhoid intestinal perforation-a declining trend. AB - BACKGROUND: Typhoid fever is an important public health problem in developing countries. Intestinal perforation is one of the leading fatal complications of typhoid fever. Typhoid perforation occurs more commonly in terminal ileum. Morbidity and Mortality associated with typhoid perforation are high (9-22%). However this study aims to know whether there are any changes of the same. AIM: To analyse the clinical presentation, management, complications, morbidity and mortality associated with typhoid intestinal perforation and assess changing trends in mortality in typhoid intestinal perforation. MATERIAL & METHODS: This is a retrospective observational study. Cases regarding the study have been analyzed by reviewing the patient records. It includes 40 patients who were diagnosed with typhoid intestinal perforation, admitted and treated in the Department of General Surgery from February 2011 to January 2012. RESULTS: A total of 40 patients were considered for the study and their mean age was 35.75 years. 80% of patients were male. Pain abdomen was their main symptom which lasted for an average of 2.95 days. Leukocytosis (11,000 cells/cumm) was present in 57.5% patients. Single perforation was present in 31(77.5%) patients and primary closure was done in 30 of them. Culture sensitivity showed E coli as the main organism. Complications were seen in 42.5% of patients in post-operative period. CONCLUSION: Early recognition, timely surgical intervention with appropriate surgery and antibiotics, and effective peri-operative care reduces the mortality in typhoid intestinal perforation. PMID- 24179906 TI - Stapled hemorrhoidectomy; results of a prospective clinical trial in saudi arabia. AB - OBJECTIVES: This study was designed to evaluate the effectiveness of stapled hemorrhoidectomy (SH) in terms of cure of the symptoms and post-operative pain control. MATERIAL AND METHODS: In this prospective clinical study, SH (Ethicon Endo-surgery, Cincinnati, OH) was performed for all patients with grade III and grade IV hemorrhoids, presenting to the surgical clinics of Ohud and Meeqat Hospitals Almadinah Almunawwarah Saudi Arabia. The results of SH were evaluated by a questionnaire focusing on the relief of symptoms, severity of post operative pain, and complications of SH. RESULTS: Thirty patients (21 males and 9 females); with a mean age of 39.6 years were recruited in this study. Twenty six (86%) patients had grade III and 4 (14%) presented with grade IV hemorrhoids. Perianal prolapse was the most frequent presentation reported in 23 (76%). Mean operating time was 21.7 minutes (range; 17-36 minutes) whereas mean hospital stay was 1.9 days. Post-operative pain was tolerable (non-persistent) in 28 (93%) cases whereas 2 (7%) experienced mild pain requiring additional analgesia. Urinary retention was the most common complication found in 5 (16%) patients. All patients were cured of the hemorrhoids Conclusion: SH is a safe, rapid, and convenient surgical remedy for grade III and grade IV hemorrhoids with low rate of complications, minimal postoepative pain, and early discharge from the hospital. PMID- 24179907 TI - Prognostic scoring indicator in evaluation of clinical outcome in intestinal perforations. AB - INTRODUCTION: Acute generalised peritonitis coming forth due to underlying intestinal perforation is a critical & life-threatening medical condition. It is a common surgical emergency most of the times across the world. Misleading data on crude morbidity and mortality due to the condition usually contaminates substantially the very purpose of medical audit. Thus, early prognostic evaluation is not only desirable but mandate to much extent. High-risk patients require timely & aggressive treatment especially in severe peritonitis & to select them reasonably well, evaluation through prognostic scoring is an approach of choice. Well sought after & reasonably reliable APACHE II scoring system is used for the purpose & scores are correlated well to accentuate & measure the various factors needed for better management of condition. MATERIAL AND METHODS: The study was conducted over the period of 18 months (Jan 2010 to June 2011) on 50 patients with confirmed diagnosis of intestinal perforation. APACHE II score was calculated and correlated with their symptoms & clinical outcomes regarding morbidity and mortality. RESULTS: APACHE II score correlated well with the outcome of the study, showing score affects of two major aspects in the treatment outcome & management.1.) APACHE II score of less than 10 included 30 low risk group patients discharged in a satisfactory gratifying manner. Three out of four in high risk group with APACHE II score >20, shown adverse outcomes. 2.)Mean ICU stay of 9.75 days was found in patients with APACHE II score 20 or more compared to those with mean ICU stay of 0.13 days in patients with APACHE II score 10 or less. CONCLUSION: Acute generalized peritonitis being life-threatening medical emergency requires careful consideration in its management that needs to be economically viable, acceptably feasible and outcome oriented with better allocation & utilization of ICU resources that needs meticulous case analysis & prioritization. This present study helps the clinicians in three major ways: a) To take better decisions on case to case basis; b) To design strategies in order to prevent adverse outcomes; c) Last but not least, to make better use of ICU resources. PMID- 24179908 TI - One- vs two stage surgery technique for implant placement in finger prosthesis. AB - BACKGROUND: The loss of the finger can lead to psychological problems. Although several reconstructive techniques may exist, the use of osseous-integrated implants to anchor digital prosthesis presents a suitable alternative for the amputation of finger. The surgery for implant placement has initially been described as a two-stage technique. However, no study in the literature has attempted to compare this technique with one-stage technique and stated a clear superiority technique in the implant retained finger prosthesis. METHODS: This article describes two cases of digital amputation as a result of accident; a 45 year-old female whose second finger of right hand was lost and a 25-year-old male patient with amputation of the first finger of right hand. RESULT AND CONCLUSION: One-stage implant placement technique for implant retained finger prosthesis is a reliable, safe and efficient option that allows a good result in a significantly lower operating time and hospital visits compared to the two-stage technique. It could therefore, be considered as good option for implant retained finger prosthesis. PMID- 24179909 TI - Experience with biodegradable polymer coated sirolimus-eluting coronary stent system in "real-life" percutaneous coronary intervention: 24-month data from the manipal-s registry. AB - INTRODUCTION: Despite the undeniable clinical efficacy of drug-eluting stents with durable polymers, concerns regarding their long-term safety have been raised, especially in more complex subsets. The Manipal-S Registry was designed to evaluate the safety and effectiveness of the biodegradable polymer coated Supralimus((r)) Sirolimus-Eluting Coronary Stent for the treatment of coronary artery disease, across a wide range of patients who are treated in real-life clinical practice. METHODS: All the consecutive 116 patients who underwent single vessel or multiple vessel percutaneous coronary interventions with the use of Supralimus((r)) sirolimus-eluting stents between September 2009 and December 2010, were included in this study. Patients were clinically followed-up at 1, 9, 12 and 24 months post-procedure. All clinical, procedural, and follow-up information were collected and analysed. RESULTS: In total 116 patients, 126 lesions were implanted with 144 stents which had an average stent length of 25.8+/-8.0 mm. The incidences of any major adverse cardiac and cerebral events at 1, 9, 12 and 24 months were 0, 5 (4.3%), 8 (6.9%), and 10 (8.6%) respectively. CONCLUSION: These 24-month results clearly provide evidence for safety and effectiveness of the Supralimus((r)) Sirolimus-eluting coronary stent system with the biodegradable polymer in real-life patients, even in those with acute myocardial infarctions. PMID- 24179910 TI - The unusual presentation of a usual organism - the changing spectrum of the clinical manifestations of Plasmodium vivax malaria in children: a retrospective study. AB - BACKGROUND: Malaria is a major public health problem in the south-east Asian region. Among all countries in the SE Asian region the highest number of cases and deaths are reported from India. Children below 14 years of age contribute to approximately 42% of all the deaths. A majority of the deaths are attributed to severe malaria which is caused by Plasmodium falciparum. It is considered that causes a benign causing febrile illness without significant complications. However, in recent years, the spectrum of is shifting from being the cause of benign fever, to more severe complications. There have been case reports of complications like thrombocytopaenia, cerebral malaria, a disseminated intravascular coagulation, the acute respiratory distress syndrome, hepatic dysfunction and renal involvement. Most of the case reports are from the adult population, with an occasional occurrence of paediatric cases. OBJECTIVE: To highlight the increasing number of severe manifestations in P.vivax malaria in the children who were admitted in the malaria transmission season of 2011, at a tertiary care hospital. DESIGN: A descriptive, cross-sectional study. MATERIAL AND METHODS: STUDY SUBJECTS: Children with an acute febrile illness of a duration of < 7 days, which was confirmed as Plasmodium vivax positive malaria by testing the peripheral smears and/or by Rapid Diagnostic Testing, who were admitted in the paediatric ward of a tertiary care hospital in New Delhi (India), during May 2011 to October 2011, Case records of context cases were analysed retrospectively. STATISTICS: The data was summarised by calculating the rates, ratios, proportions, means, standard deviations and the 95% confidence intervals. The Chi square test was applied to assess the significant difference between two qualitative variables. RESULTS: Among the case records of 54 patients, 40.7% were below 5 years. 61% were males and 38.9% were females. Besides hepatomegaly and splenomegaly which were the most common symptoms, which were seen in 81.5% and 72.2% children respectively, the various unusual manifestations seen were severe thrombocytopaenia (37%), jaundice with deranged LFT values (25.9%), abnormal bleeding (18.5%), impaired consciousness with a GCS of < 9 (18.5%), severe anaemia (14.8%), hypotension (11.1%), repeated convulsions (7.6%), pulmonary oedema/ARDS (5.6%) and ascites (5.6%). One case each showed haemoglobinuria, and pleural effusion. CONCLUSION: Plasmodium vivax is emerging as a cause of severe malaria. There is a further need to study the pathophysiology, virulence factors and the molecular mechanisms which are involved in malaria. PMID- 24179911 TI - Pattern of bacterial colonization of atopic dermatitis in saudi children. AB - BACKGROUND: Atopic dermatitis is an inflammatory skin disorder. Although it is not a life threatening condition, it may become infected with microorganisms, especially in children. OBJECTIVES: The aim of this study was to determine bacterial colonisation in children with atopic dermatitis. METHODS: A total of 80 children were randomly included in this study. Two swabs were taken from each child, one from the eczematous skin lesion and the other from apparently healthy skin, as a control. Bacteria were isolated and identified on the basis of the colonial morphology, gram staining and the Vitek System. RESULTS: The mean age of children in this study was 1.4 years, with no gender difference (p=0.98) (n=80). A total of 240 bacterial colonies were grown from atopic dermatitis lesions in contrast to 193 colonies from non-lesional skin. Gram-positive cocci were found in 78 (97.5%) lesions and in 77 (96.2%) non-lesional skin. Staphylococci species were significantly detected in the lesions than in the non-lesional skin. Ent. Faecalis, Ent. Faecium, Ent. gallinarium and C. minutissium were significantly isolated from lesions as compared to non-lesional skin, whereas C. xerosis was insignificantly found to be more in the lesions (p=0.21). Gram-negative bacteria were isolated from 7(8.8%) lesions, but none were isolated from non-lesional skin. Recovered species were Pantoea agglomerans, Enterobacter cloacae, Chryseobacterium indologenes and Acinetobacter Iwoffii. CONCLUSION: Atopic dermatitis in children is complicated with streptococcal and gram-negative bacterial colonisations and the latter was correlated with the severity of the lesions. Enterococci and Corynebacterium species were significant residents. S. aureus remained the chief inhabitant. No causal relationship could be established between the skin microbiota and atopic dermatitis. PMID- 24179912 TI - Managing adnexal masses: a medical quandary. AB - INTRODUCTION: Management of Adnexal masses poses a double edged problem. There is a dilemma of performing extensive surgery in the form of staging laparotomy for a benign disease on one hand and the lurking fear of missing the diagnosis of malignancy on the other. Thus, it seems that it is important to establish risk profiles of all patients with adnexal masses so that they can reap the benefit of minimally invasive surgery wherever possible and be rightly subjected to staging laparotomy where indicated. MATERIAL AND METHODS: This prospective study was carried out at a Tertiary care Hospital. 136 women with an adnexal mass on ultrasound which met the said criteria were enrolled into the study from January 2008 to July 2011. They were then taken up for laparoscopic management. RESULTS: All but 2 cases were found to be benign (134/136) after the final histopathology report using the said criteria. CONCLUSION: Hence, by using simple readily available investigations like ultrasound (pattern recognition approach, Tumour morphology and ascites) and CA-125, the nature of adnexal mass can be reliably predicted and these patients can be safely offered the benefits of laparoscopic surgery. PMID- 24179913 TI - Phenotypic and Genotypic Methods for Detection of Extended Spectrum beta Lactamase Producing Escherichia coli and Klebsiella pneumoniae Isolated from Ventilator Associated Pneumonia. AB - BACKGROUND: Ventilator Associated Pneumonia (VAP) is one of the common nosocomial infections associated with high morbidity due to multidrug resistant pathogens. Rapid spread of resistance to broad spectrum beta-lactams in pathogenic strains causes antibiotics ineffectiveness and increased severity of illness. The CTX-M is the most dominant Extended Spectrum beta Lactamase (ESBL) among Enterobacteriaceae in many regions of the world. The aim of the study was to identify the occurrence of ESBL and detect the genes responsible for ESBL production by conventional Polymerase Chain Reaction (PCR) method. METHODS: This prospective study included patients, clinically diagnosed as VAP. Endotracheal aspirates (EA) were collected and cultured by quantitative method. The bacterial isolates were identified as per standard methods. Isolates resistant to 3(rd) generation cephalosporins were screened for ESBL production by disk approximation method and combination disc diffusion method. Isolates confirmed as ESBL producers were subjected to genotyping by conventional PCR. STATISTICAL ANALYSIS: Statistical analysis was done by using MS Excel sheet. Descriptive statistics like percentage was done in the study. RESULTS: Among the isolates from 428 patients who developed VAP, 144 isolates belonged to the Enterobacteriaceae family (Klebsiella pneumoniae 87 and Escherichia coli 57). A total of 66 isolates (28 Klebsiella pneumoniae and 38 Escherichia coli) were confirmed as ESBL producer by disc approximation method and 63 isolates by double disc combination method. In the present study by conventional PCR bla CTX-M was the common gene in 48.5% strains followed by 22.22% bla SHV and 14.81% bla TEM. CONCLUSION: The genotypic methods using specific PCR amplification of resistance genes seems to have 100% specificity and sensitivity in detection of ESBL when compared to phenotypic methods which lacks the constant sensitivity. PMID- 24179914 TI - Changing Trends in Resistance Pattern of Methicillin Resistant Staphylococcus aureus. AB - BACKGROUND: Methicillin resistance in Staphylococcus aureus is associated with multidrug resistance, an aggressive course, increased mortality and morbidity in both community and health care facilities. Monitoring of newly emerging and prevalent Methicillin Resistant Staphylococcus aureus (MRSA) strains for their resistance patterns to conventional as well as novel drugs, are essential for infection control. AIMS: To study the changing trends in resistance patterns of MRSA at our hospital. SETTINGS AND DESIGN: This cross sectional study was carried out in a 750 bed tertiary care hospital in south India. MATERIAL AND METHODS: One hundred and two clinical isolates of MRSA which were obtained in 2004-2011 were identified by using oxacillin, cefoxitin disc diffusion test and oxacillin screening agar test. Antibiotic susceptibility test was done for commonly used non beta lactam anti-Staphylococcal drugs, as well as for anti-MRSA drugs like vancomycin, linezolid, mupirocin and rifampicin. Minimum inhibitory concentration (MIC) of vancomycin was determined by using Vancomycin HiComb strip (Himedia, Mumbai, India). Statistical Analysis which was done: Chi-square test and proportions were used to compare the two groups. RESULTS: MRSA isolates showed high resistance to co-trimoxazole (82.3%), ciprofloxacin (76.4%), gentamicin (64.7%) and tetracycline (49%) as compared to other drugs. High prevalence of ciprofloxacin resistance was detected, particularly among outpatients. Multi resistant MRSA with a >= 3 non-beta lactam agent resistance was 79%. All MRSA isolates were sensitive to vancomycin, linezolid, mupirocin and rifampicin. MRSA had displayed increase in resistance to most antibiotics except tetracycline in recent years. CONCLUSIONS: Taking into consideration the prevalence of multidrug resistance in MRSA, resistance patterns should be evaluated periodically and antibiotic therapy should be guided by susceptibility testing. PMID- 24179915 TI - A study on clinico-mycological profile, aetiological agents and diagnosis of onychomycosis at a government medical college hospital in kashmir. AB - BACKGROUND: Onychomycosis is a major public health problem with a high incidence, associated morbidity and a long lasting treatment with anti-fungal agents. This study was carried out to know the clinico-mycological pattern of onychomycosis, which could help in the control of this infection. AIMS: The aim of this study was to determine the prevalence of various causative agents of onychomycosis and to study the clinical and mycological patterns of onychomycosis. MATERIAL AND METHODS: This was a prospective study which was carried over a period of one year, from 1(st) February 2011 to 31(st) January 2012 on samples from 150 patients with clinically suspected nail infections, who attended the Dermatology Department of SKIMS Medical college, Kashmir, India. The nails were evaluated clinically and the nail samples were subjected to direct microscopy and culture. RESULTS: 60% samples were found to be positive by direct microscopy and culture. Males were infected more than females. The commonest age group which was infected was the 21-30 years age group. Finger nails were affected more frequently than toe nails and distolateral subungal onychomycosis was the most common clinical type of infection which was seen in 64.44% patients. The aetiological agents were dermatophytes (61.66%), Non-Dermatophyte Moulds (NDM) (31.66%) and yeasts (6.66%). Among dermatophytes, T. rubrum was the commonest aetiological agent. CONCLUSION: Although dermatophytes were the main causative agents, NDM and yeasts were also not uncommon aetiological agents of onychomycosis. This study also emphasized the need of performing both a direct examination and culture to improve sensitivity. Since onychomycosis can cause physical, psycological and occupational problems, the clinico-epidemiological data can be helpful in development of preventive and diagnostic strategies. PMID- 24179916 TI - OXA-181 Beta Lactamase is not a Major Mediator of Carbapenem Resistance in Enterobacteriaceae. AB - BACKGROUND: Detection of carbapenem hydrolyzing class D beta lactamase OXA-181, (a variant of OXA-48) in Enterobacteriaceae, is important, to institute appropriate therapy and to initiate preventive measures. This study was done to determine the presence of OXA 48 and its derivative OXA-181 in Enterobacteriaceae of pathogenic significance. MATERIAL AND METHODS: One hundred and eleven non repetitive Enterobacteriaceae isolates which were resistant to any of the cephalosporin subclasses III and which exhibited reduced susceptibility to carbapenems were included in the study. Minimum inhibitory concentrations (MICs) to imipenem and meropenem was determined by broth microdilution. Production of carbapenamase was screened by Modified Hodge test (MHT). Polymerase Chain Reaction (PCR) was done to detect the presence of bla OXA-181 and bla OXA-48 .Coexistence of other carbapenemase encoding genes, namely, NDM-1, VIM, IMP and KPC were also looked for, by PCR. RESULTS: Of all the isolates which were tested, only 2 (1.8%) revealed the presence of OXA-181 and OXA-48. These were Klebsiella pneumoniae and Citrobacter freundii. MICs of imipenem and meropenem for Klebsiella pneumoniae were 128mg/l and 64 mg/l and for Citrobacter freundii, they were 32mg/l and 16mg/l respectively. MHT was positive in both isolates. CONCLUSION: Production of OXA-48 / OXA-181 is not a major mechanism of carbapenem resistance. PCR is the gold standard for its routine identification in clinical microbiology laboratory. PMID- 24179917 TI - Introducing physiology practical demonstration in course curriculum for the first year nursing students. AB - INTRODUCTION: Combination of didactic lecture, practical demonstration and performing experiments by students is followed in medicine, dentistry and bachelor of pharmaceutical sciences. The purpose of this study was to assess the attitudes of nursing students towards practical demonstration in physiology. MATERIAL AND METHODS: Seventy three nursing students of the first year underwent practical demonstration of Physiology experiments. Students indicated their agreement or disagreement with the 8 items by ticking one of the five alternative responses. Mean attitude scores were calculated for each item and for the total scale. RESULTS: The overall mean attitude score of 3.76 was towards the favourable side. Eighty seven percent of students agreed that practical demonstration reinforces concepts. Eighty nine percent of students found practical demonstration is a good form of learning experience. CONCLUSION: The introduction of practical demonstration in addition to didactic lectures may help the students in understanding concepts in Physiology. PMID- 24179918 TI - Sub-hepatic caecum. AB - Malrotation of gut is an intestinal gestational disorder which not only affects the positioning of the midgut, but also its vascular supply. It usually presents with the syndrome of bouts of colic and vomiting with little distention of abdomen and diarrhea. Though midgut malrotation is a common cause of intestinal obstruction in newborn, scant attention is given to this developmental anomaly as a cause of symptoms in adults. The development of midgut portion of alimentary canal suffers a large variety of variations. The surgical importance of abdominal situation of the portions of intestine derived from the midgut loop requires little attention. Sub-hepatic anatomical location of the appendix makes it more difficult to diagnose acute appendicitis at any age, including in older adults. Failure to recognize the nature and characteristic features of these misplacements may lead to grave errors in procedure, or to injurious prolongation of the operation. Here in we found a rare abnormality of caecum, which was present in the sub hepatic region with the absence of ascending colon during routine dissection classes for undergraduate students. PMID- 24179919 TI - An accessory muscle of pectoral region: a case report. AB - Among the variations of pectoral muscles, this case appears to be unique in the literature. This was a case of an accessory pectoral muscle which was located between pectoralis major and pectoralis minor muscles, which was discovered during a routine anatomy dissection. The accessory muscle originated from 6(th) and 7(th) ribs at costo-chondral junction, which travelled supero-laterally and inserted by fusing with fibres of pectoralis minor. This unusual muscle holds importance for surgeons while they perform dissectomies, in avoiding complications. PMID- 24179920 TI - Primary splenic tubercular abscess in an immunocompromised patient-rapid diagnosis by line probe assay. AB - Diagnosing extra-pulmonary tuberculosis is a challenge that can confound even the most practiced clinicians as clinical manifestations are vague, non-specific and typical chest radiograph findings may not be evident till late in the disease. Conventional methods for mycobacteriological culture and drug susceptibility testing are slow and cumbersome. Novel technologies for rapid detection of Mycobacterium tuberculosis and its anti-TB drug resistance have therefore become a priority hence with the development of molecular line probe assays are most advanced. Herewith we are reporting a case of splenic tuberculosis in an immunocompromised patient for its rarity and to emphasis the fact that such patients can be diagnosed early for better treatment outcome to enhance the longevity if a health setup possesses all the modern diagnostic services. PMID- 24179921 TI - Neoplastic (solid) Calcifying Ghost Cell Tumor, Intraosseous Variant: Report of A Rare Case and Review of Literature. AB - A neoplastic (solid), calcifying ghost cell tumour is a rare subtype of Calcifying Odontogenic Cyst. The most important features of this pathologic entity are histopathological features, which include a proliferating cystic lining which demonstrates characteristic "Ghost" epithelial cells which have a propensity to calcify. We are reporting a case of a 61-year-old male with a painful swelling in the lower right jaw. Radiology showed a bilocular, well circumscribed, radiolucent lesion in the mandible, which measured 2x1 cm, with radiopaque structures within it. Tooth extraction was done, with enucleation of the lesion, which histopathologically revealed features of a solid, calcifying ghost cell tumour, with an intraosseous variant. The case has been presented, with a brief review of literature. PMID- 24179922 TI - Chronic Constipation Caused by Neurofibromatous Proliferation in A Case of Von Recklinghausen's Disease - A Case Report. AB - Neurofibromatosis (NF) is an autosomal dominant genetic disorder with a myriad of clinical manifestations . A gastrointestinal involvement which is present in 10 25% of patients, is usually a systemic manifestation of generalised NF. We are describing a case of NF 1 with chronic constipation, in whom colonoscopy revealed a thickening of the colon wall with narrowing. A mucosal biopsy showed neural hyperplasia .This case emphasizes the value of minimally invasive endoscopic biopsies of GI lesions in NF1, where despite a limited sampling, correlation with clinical and endoscopic features may help in reaching a diagnosis of a neurofibromatous proliferation. We have also discussed the differential diagnosis of gastrointestinal lesions in NF with neural hyperplasia. PMID- 24179923 TI - Osseous metaplasia in a juvenile polyp: a rare case report in India. AB - Osseous metaplasia is a phenomenon which is described in a variety of tissue types with respect to both neoplastic and non-neoplastic conditions. In the gastrointestinal tract, osseous metaplasia (heterotopic bone formation) is rarely detected. Most of the reported cases were associated with malignant lesions. Here, we are reporting a rare case of a juvenile rectal polyp in a 14 years male, which showed osseous metaplasia on histological examination. This feature is a striking phenomenon on histological examination. PMID- 24179924 TI - A rare case of renal tumour. AB - Primary Renal Lymphoma (PRL) is an unusual and a rare tumour of the kidney. By definition, PRL is a lymphoma without evidence of any systemic involvement. This report describes a case of PRL, which included clinical presentation, imaging findings, histopathology and immunohistochemistry. PMID- 24179925 TI - Ganglioneuroma, base of tongue: a rare entity. AB - We have discussed the case of a solitary polypoid ganglioneuroma in a 45-year-old male patient, at the base of tongue, which mimicked a malignancy. The interest of this case lay in the rarity of its incidence at the base of tongue and its gross resemblance to the more common malignant polypoidal growths at this site. The presence of neural elements and ganglion cells at this site makes it important for an inexperienced histopathologist to differentiate it from other neural lesions of the tongue, in order to avoid a misdiagnosis and this can prevent the clinician from administering an inappropriate treatment. Exhaustive search revealed only a very few case reports on the tongue. PMID- 24179926 TI - Bardet biedel syndrome: a very rare entity in India. AB - Bardet Biedel Syndrome (BBS) is a rare autosomal recessive disease which is characterized by obesity, retinitis pigmentosa, polydactyly, neuro-developmental retardation and renal defects amongst others. It is a genetically heterogeneous ciliopathic disorder with inter and intra familial variations. Very few cases have been reported from India. We are reporting here a case of an adolescent girl who was diagnosed at the age of 16, with additional features of insulin resistance and non-alcoholic fatty liver disease. A review of recent literature and a short discussion on the care and management of this uncommon condition follow. PMID- 24179927 TI - Spontaneous Intrahepatic Type II Gallbladder Perforation: A Rare Cause of Liver Abscess - Case Report. AB - A liver abscess formation is a rare complication of a gallbladder perforation, with a cholecystohepatic communication. Niemeier, in 1934, classified free gallbladder perforations and generalised biliary peritonitis as an acute or a Type I gallbladder perforation, a pericholecystic abscess and localised peritonitis as a subacute or a Type II gallbladder perforation, and cholecystoenteric fistulas as chronic or Type III gallbladder perforations. We are describing a 50-year-old male patient who presented with right upper quadrant pain and was found to have an intrahepatic perforation of the gallbladder. Our patient had a Type II perforation. We have discussed the diagnostic work-up and the management of this rare entity. Due to the high mortality that can be caused by a delay in making the correct diagnosis, a gallbladder perforation represents a special diagnostic and surgical challenge. PMID- 24179928 TI - Recurrent phaeohyphomycosis: a case report. AB - Phaeohyphomycoses are rare, opportunistic, fungal infections which are usually seen in immunocompromised individuals. We are reporting a case of a 40-year-old man with recurrent cutaneous phaeohyphomycosis, who did not have any clinical evidence of immunodeficiency, who presented with signs which resembled a malignancy of the skin. PMID- 24179929 TI - Peculiar case of mucocele of appendiceal tip. AB - Mucocele of Appendix is a gross or clinical descriptive term for dilatation of the appendiceal lumen by mucus.It is a rare pathology with an overall incidence of 0.2 to 0.3% of all appendectomies. Majority of these cases present with mucocele involved whole length of the appendix. On extensive literature search,exact incidence of mucocele confined only to the tip of appendix is not known, though there are very few case reports. Here we report a peculiar case of large mucocele of appendix confined only to the tip, sparing significant length of proximal appendix and causing diagnostic dilemma pre-operatively in a 43 years -old lady. PMID- 24179930 TI - Mixed tumour of ala-nasi: a rare case report and review. AB - A chondroid syringoma or a mixed tumour of skin, is a rare, benign skin adnexal tumour of sweat gland origin, which is most commonly seen in the head and neck region of patients who are in the sixth and seventh decades. These tumours usually present as asymptomatic, slowly growing masses. We are reporting a rare case of a chondroid syringoma of Rt. ala nasi in a 50 years old female. The swelling had started 4 years back as a small nodule and it had gradually increased in size to 2x2 cms. It was located subcutaneously and it was projecting into the anterior nares. A clinical diagnosis of a benign adnexal tumour (adenoma) or a solitary neurofibroma was made and an excision was planned. Histopathology revealed features of a chondroid adenoma. We are reporting this case because of its rare and unusual site of occurrence and so far, in the available literature, no such case has been reported on tumours of alanasi. PMID- 24179931 TI - Ovarian Gonadoblastoma with Dysgerminoma in a Young Girl with 46, XX Karyotype: A Case Report. AB - Gonadoblastoma is a rare gonadal tumour consisting of a mixture of germ cells and sex cord stromal derivatives resembling immature granulosa and Sertoli cells. It usually arises in various types of gonadal dysgenesis containing Y chromosome like pure or mixed gonadal dysgenesis. Occurrence in phenotypically and chromosomally normal women is very rare. We report here a case of gonadoblastoma with dysgerminoma in a 14-years-old girl who presented with a huge tumour, virilisation and normal 46XX karyotype. Association of dysgerminoma is seen in 50% cases of gonadoblastomas. Elevated tumour markers like hCG and alpha Fetoprotein may make the diagnosis challenging. PMID- 24179932 TI - Case Report : Hermansky Pudlak Syndrome (Presenting as late onset heavy Menstrual Bleeding). AB - Inherited bleeding disorders contribute significantly to the incidence and prevalence of Heavy Menstrual Bleeding (HMB), and contrary to popular belief can present any time during the reproductive years of a woman's life. The following case exemplifies this and is being presented as part of a rare syndrome. The incidence of this syndrome in the general population ranges from 1:500,000 to 1:1000, 000. Besides being rare the presentation was quite uncommon as majority of these cases present with pulmonary fibrosis. PMID- 24179933 TI - Craniofacial duplication: a case report. AB - A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature. PMID- 24179934 TI - Brain abscess as a complication of chronic thromboembolic pulmonary hypertension a rare case report. AB - A brain abscess is a life threatening condition which can occur as a complication of various clinical conditions. An intra-cerebral abscess which occurs as a complication of pulmonary arterial hypertension is extremely rare. The present report has described such an uncommon case of an intra-cerebral abscess in a chronic pulmonary thrombo embolism patient with pulmonary hypertension. A-34-year old male who was a known case of chronic pulmonary thrombo embolism with pulmonary artery hypertension, who was diagnosed 6 months back, presented to the Out Patients Department (OPD) with headache and vomiting. He had right homonymous hemianopia. Contrast MRI (Magnetic Resonance Imaging) of brain showed a peripherally enhancing lesion in the left temporo-occipital lobe, with oedema and a mass effect. Left parieto-occipital craniotomy and excision of the abscess was done. Staphylococcus aureus was isolated from the aspirated pus. PMID- 24179935 TI - Unfused crossed renal ectopia with ipsilateral anorchia-a rare entity. AB - The reported incidence of unfused crossed renal ectopia is 1 in 75,000 autopsies. A majority of such cases go unnoticed, as they remain asymptomatic and are found incidentally at autopsy. We have presented such a case for its rarity, unusual presentation and association, and have discussed it in light of the available literature. In this report, a 7-year-old boy was pre-operatively diagnosed as having left crossed renal ectopia with a cryptorchid left testis. At surgery, we noticed an ectopic, hydronephrotic left kidney with an absent left testis. Left Nephrectomy was performed, based on findings of a DTPA scan which was done. Post operative course was uneventful. Histopathology revealed chronic pyelonephritis without any evidence of dysplastic changes. PMID- 24179936 TI - Urolithiasis in a child with Spondylocarpotarsal Synostosis Syndrome: A Co Incidence. AB - Spondylocarpotarsal synostosis syndrome (SSS) is an autosomal recessive condition which is characterized by short stature, a carpotarsal coalition and a vertebral fusion, but without any rib anomaly. We are presenting a 7- year- old boy, who had uroliathiasis with the spondylocarpotarsal synostosis syndrome. This association, to the best of our knowledge, has not been reported so far. PMID- 24179937 TI - Electronic biomedical literature search for budding researcher. AB - Search for specific and well defined literature related to subject of interest is the foremost step in research. When we are familiar with topic or subject then we can frame appropriate research question. Appropriate research question is the basis for study objectives and hypothesis. The Internet provides a quick access to an overabundance of the medical literature, in the form of primary, secondary and tertiary literature. It is accessible through journals, databases, dictionaries, textbooks, indexes, and e-journals, thereby allowing access to more varied, individualised, and systematic educational opportunities. Web search engine is a tool designed to search for information on the World Wide Web, which may be in the form of web pages, images, information, and other types of files. Search engines for internet-based search of medical literature include Google, Google scholar, Scirus, Yahoo search engine, etc., and databases include MEDLINE, PubMed, MEDLARS, etc. Several web-libraries (National library Medicine, Cochrane, Web of Science, Medical matrix, Emory libraries) have been developed as meta sites, providing useful links to health resources globally. A researcher must keep in mind the strengths and limitations of a particular search engine/database while searching for a particular type of data. Knowledge about types of literature, levels of evidence, and detail about features of search engine as available, user interface, ease of access, reputable content, and period of time covered allow their optimal use and maximal utility in the field of medicine. Literature search is a dynamic and interactive process; there is no one way to conduct a search and there are many variables involved. It is suggested that a systematic search of literature that uses available electronic resource effectively, is more likely to produce quality research. PMID- 24179938 TI - History of medical understanding and misunderstanding of Acid base balance. AB - To establish how controversies in understanding acid base balance arose, the literature on acid base balance was reviewed from 1909, when Henderson described how the neutral reaction of blood is determined by carbonic and organic acids being in equilibrium with an excess of mineral bases over mineral acids. From 1914 to 1930, Van Slyke and others established our acid base principles. They recognised that carbonic acid converts into bicarbonate all non-volatile mineral bases not bound by mineral acids and determined therefore that bicarbonate represents the alkaline reserve of the body and should be a physiological constant. They showed that standard bicarbonate is a good measure of acidosis caused by increased production or decreased elimination of organic acids. However, they recognised that bicarbonate improved low plasma bicarbonate but not high urine acid excretion in diabetic ketoacidosis, and that increasing pCO2 caused chloride to shift into cells raising plasma titratable alkali. Both indicate that minerals influence pH. In 1945 Darrow showed that hyperchloraemic metabolic acidosis in preterm infants fed milk with 5.7 mmol of chloride and 2.0 mmol of sodium per 100 kcal was caused by retention of chloride in excess of sodium. Similar findings were made but not recognised in later studies of metabolic acidosis in preterm infants. Shohl in 1921 and Kildeberg in 1978 presented the theory that carbonic and organic acids are neutralised by mineral base, where mineral base is the excess of mineral cations over anions and organic acid is the difference between mineral base, bicarbonate and protein anion. The degree of metabolic acidosis measured as base excess is determined by deviation in both mineral base and organic acid from normal. PMID- 24179939 TI - Effect of Two Desensitizing Agents in Reducing Dentin Hypersensitivity: An in vivo Comparative Clinical Trial. AB - OBJECTIVE: A randomized, double blind, split mouth, controlled clinical trial was conducted to evaluate the effect of two desensitizing agents on reduction of Dentin Hypersensitivity (DH). MATERIAL AND METHODOLOGY: A sample of 73 teeth from 13 patients, among which at least 3 teeth had dentin hypersensitivity, was randomly allocated into 3 treatment groups: Group A: treated with 30% ethenolic extract of Indian Propolis, Group B: treated with GC tooth mousse, and Group C: treated with sterile water. A Verbal Rating Scale (VRS) was used to record the degree of hypersensitivity, based on patient's response to tactile and air blast stimuli. The baseline scores were obtained. Each intervention group received applications of their respective agents consecutively on 1(st), 7(th), 14(th) and 21(st) days. After each application, the scores were recorded. RESULTS: Both the 30% Indian Propolis and GC tooth mousse showed significant reductions in dentin hypersensitivity. CONCLUSION: GC tooth mousse was found to be significantly better in reducing the dentinal hypersensitivity as compared to Propolis and sterile water (p< 0.01). PMID- 24179940 TI - Oral health status in haemodialysis patients. AB - OBJECTIVE: To assess the oral and dental manifestations in non- diabetic and diabetic uraemic patients who were undergoing haemodialysis and to estimate and compare the salivary pH in these two groups. MATERIAL AND METHODS: Ninety Seven uraemic patients who were undergoing maintenance haemodialysis were included in the study. Subjective and objective findings were evaluated and recorded in a specially designed proforma. Predialytic unstimulated whole salivary pH was recorded by using pH-measuring strips. Dental health assessment consisted of DMFT and CPITN indices. RESULTS: A subjective oral manifestation of dysguesia was found to be more significant in non-diabetic patients (p<0.008). Statistically, a high significance was observed with mucosal petechiae in 31.9% patients of diabetic group .The overall DMFT score was significantly higher in diabetic group. A moderate significance was found with a CPI score of 5 (p<0.015). The pH of saliva was significantly higher among diabetic patients. CONCLUSION: The diabetic subjects who were on haemodialysis were at a high risk for developing periodontal disease and they exhibited a potential threat for dental decay and xerostomia. A lower salivary pH and a poor glycaemic control may affect their oral health. Further research is required to clarify the combined influence of diabetic nephropathy on oral health. PMID- 24179941 TI - Evaluation of panoramic Radiographs as a Screening Tool of Osteoporosis in Post Menopausal Women: A Cross Sectional Study. AB - BACKGROUND: Indian women, especially those from low-income groups consume diets that are deficient of calcium, proteins and micronutrients. Hence, they are prone to suffer from osteoporotic hip fractures at a much earlier age than western women. To detect early signs of osteoporosis, it is ideal to perform Bone Mineral Density testing of all post-menopausal women who are at risk. AIM: (i) To assess and compare the relative efficacy, ease of application and measurement of the various mandibular cortical indices which were obtained on the panoramic radiographs with bone densitometry data of post-menopausal women. and (ii) To evaluate the effectiveness of these measurements in the identification of cases of osteoporosis/osteopaenia. METHOD: A cross sectional sample which consisted of 40 randomly selected post menopausal women who were aged 40-69 years was subjected to dental panoramic radiography. Mental index, panoramic mandibular index, gonion index, mandibular cortical index and antegonial index were measured on each radiograph. The data were expressed as mean and standard deviation. Analysis of variance with post-hoc Tukey's test was performed to determine group differences in mandibular measurements. RESULTS: Based on the bone densitometry results, the sample was classified into normal (n=9), osteopaenic (n=15) and osteoporotic (n=16) groups. Statistically significant differences were found for mean Mental index (p=0.000), mean Panoramic Mandibular Index (p=0.007) and mean Gonial Index (p=0.000). The sensitivity (100%) and specificity (88.88%) of MCI showed good results. CONCLUSION: Dentists who use orthopantomographs may play a vital role in screening patients with osteoporosis, mainly among post menopausal women. PMID- 24179943 TI - Oral Health of Pre-School Aged Children in Dhanbad District, Jharkhand, India- A Peek into their Mother's Attitude. AB - INTRODUCTION: Mothers are directly responsible for the dental health of their children and play a major role in shaping the dental health behaviors of their children. They also play an important role in preventing oral diseases in them. OBJECTIVE: To assess the level of attitude of mothers in relation to their pre school aged children, which in turn can influence the level of oral health. METHOD: A cross-sectional study was carried out among 312 mothers, selected randomly from eight blocks of Dhanbad district, Jharkhand, India. They were administered with a structured questionnaire on attitude, by an interviewer. RESULTS: The overall data indicated that the attitude of mothers about oral health in their pre-school children increased as their age increased which was not statistically significant (p>.066). Mothers who had less than higher secondary school education and belonged to socio-economically lower groups had poor knowledge of oral health which was statistically significant (p<.001). CONCLUSION: Mothers should be motivated so that their attitude about their child's oral health is enhanced which in turn would improve their oral health related quality of life. PMID- 24179942 TI - Effect of cigarette smoke on acrylic resin teeth. AB - BACKGROUND: The discolouration of artificial teeth, which hampers aesthetics, is one of the negative effects of cigarette smoking. Therefore, the effect of cigarette smoke on the colour stability of commercially available acrylic resin teeth needs to be evaluated for clinical success and to ascertain as to which brand has superior properties. MATERIAL AND METHODS: Three commercially available acrylic teeth were evaluated, after division into Group A (Premadent), Group B (Astra), and Group C (Sanyo- Dent). Selected brands were subdivided as study group and control group. Each set of acrylic resin teeth were stored in artificial saliva at 37+/-1 degrees C for 24 hours. After 24 hours of immersion, the colour measurement of each tooth (T0) was performed. Second colour measurements were done after 21 days (T21) of exposure to cigarette smoke for study group and after immersion in artificial saliva for control group. All data was statistically analyzed by using Repeated Measures ANOVA and Two-way ANOVA (p<0.05). RESULTS: Group A showed least total colour change on exposure to cigarette smoke, followed by Group B and Group C had the highest total colour change. In control group, after immersion in artificial saliva, a slight increase in total colour change was observed for all groups, which was clinically acceptable. CONCLUSION: Group A (crosslinked acrylic resin teeth) was more colour stable and more resistant to the discolouration which was caused by cigarette smoke, followed by Group B (crosslinked acrylic resin teeth). Group C (Non crosslinked acrylic resin teeth) was least colour stable and most susceptible to discolouration which was caused by cigarette smoke. PMID- 24179944 TI - Assessment of Oral Health Related Quality of Life Among Completely Edentulous Patients in Western India by Using GOHAI. AB - BACKGROUND: Quality of life in elderly is a very sensitive issue. It is important to know if the dental problems, general health and dental treatment have an impact on the quality of life in elderly. The elderly population has a typical set of mind regarding their oral health. This study examines the trends in patients' behavioral patterns due to tooth loss, suggestive of some change in quality of life. AIMS: The purpose of this study was to identify and acknowledge the problems of completely edentulous patients and their relationship to the Quality of Life (QOL). Also, the study was aimed at exploring the changes in global self-rated general health between the pre and post-treatment scores. SETTINGS AND DESIGN: This is a randomized controlled clinical trial study which is done to evaluate the problems in the elderly and quality of life as long as their oral health is concerned. It is conducted on a group of people representing the elderly population with complete edentulism. MATERIAL AND METHODS: Sixty three patients with mean age 69.41 who needed dentures were investigated before and after 6 months of their treatment by administration of GOHAI (Geriatric Oral Health Assessment Index) scale. Comparison between Pre & Post-treatment values of various scores were done with McNemar-Bowker Test. Quantitative data was represented using Mean +/- SD and Median, IQR (Interquartile range). Analysis of Pre & Post-treatment quantitative data was done using Wilcoxon Signed Rank Test. RESULTS: The results of the present study showed GOHAI scores increased from 28.90 + 7.28 to 42.19 + 7.60 (p=highly significant). There was a significant change in the quality of life in elderly after their prosthodontic rehabilitation, though the self rated general health did not show any significant improvement. CONCLUSION: It is the responsibility of the entire dental fraternity to understand the needs of elderly associated to their oral health. It is important to evaluate and assess the psychological effects of tooth loss on their quality of life. A thorough investigation is necessary before and after the dental/prosthodontic care. PMID- 24179945 TI - Oral Lichen Planus as an Extra-hepatic Manifestation of Viral Hepatitis Evaluation in Indian Subpopulation. AB - BACKGROUND: Oral Lichen Planus (OLP) is considered to be associated with numerous systemic conditions one of which includes Chronic Liver Disease (CLD). Hepatitis virus B and C (HBV and HCV) have known to be important causative agents of CLD and can be prevalent in asymptomatic carriers that can make them difficult to identify. Off late, the association of viral hepatitis with OLP has been a subject of controversy due to conflicting reports. Indian studies on this regard are sparse to evaluate the same. Association between the hepatitis virus and OLP, if present and established, can be of great help to format a protocol for identifying carrier states of viral hepatitis due to HBV and HCV. METHODOLOGY: Forty five cases of clinically and histologically confirmed OLP were subjected to a serological screening of hepatitis B and C viruses by detection of hepatitis B surface antigen and anti-hepatitis C virus antibodies. RESULTS: None of OLP cases were seropositive for the hepatitis viruses. CONCLUSION: We could not demonstrate any association between OLP and viral hepatitis. This could be attributed to lower prevalence of hepatitis viruses compared to the countries hyper endemic for these viruses or genotypic variation of the viruses or other etiological factors contributing for the present group of patients. PMID- 24179946 TI - Minimally invasive transmucosal insertion and immediate provisonalization of one piece implant in partially edentulous posterior mandible. AB - Although dental implantology had evolved over number of years, many dental surgeons are unaware of the concept of immediate loading with use of titanium one piece implants that began in the early 1960s. Although long term success have been revealed with the use of two piece implants over the period of years, many obstacles like pain, inflammation and the bacterial migration into the micro-gap of two-piece implants when they are loaded; loosening and even fractures of the internal screws when they are loaded which limits patient acceptance towards dental implants. Immediate loading of one piece implants by using provisional acrylic resin crown with minimally invasive or atraumatic, flapless surgical procedures provides a better soft tissue adhesion and seal to form a healthy collar, avoids a second stage surgical procedure and with higher patient acceptance . One-piece implant also allows a minimally invasive trans-mucosal flapless placement and limits the requirement of hard tissue grafting procedures. With all these conception, the present case report evaluated the clinical performance of a one-piece implant in a partially edentulous posterior mandible. PMID- 24179947 TI - Hereditary hypohidrotic ectodermal dysplasia: report of a rare case. AB - Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition. PMID- 24179948 TI - Peripheral ossifying fibroma secondary to pulpo-periodontal irritation. AB - This report has discussed the endodontic and surgical management of a peripheral ossifying fibroma that had occurred in the anterior maxillary anterior region, between a central and a lateral incisor in a 12-year-old child. The lesion was diagnosed to have occurred secondary to a pulpo-periodontal irritation. PMID- 24179949 TI - Accessory mental nerve: a case report. AB - The presence of an Accessory Mental Nerve (AMN) is rare. The mental foramen is an important landmark in the mandible for administration of local anaesthesia and mental nerve identification and its preservation is of paramount importance in various surgical procedures. This article presents a case of an incidental finding of accessory mental nerves during open reduction and fixation of a compound fracture of left body of mandible. Knowledge on anatomic variations is helpful in diagnosis, treatment planning and management during surgical procedures. PMID- 24179950 TI - Oral blistering - report of two cases of erythema multiforme & literature review. AB - Erythema multiforme and related disorders comprise a group of mucocutaneous disorders that often compromise the quality of life. The clinical classification of these disorders is variable, thus making definitive diagnosis difficult. Early recognition and prompt management will benefit the patients. This article highlights two such cases of erythema multiforme with detailed literature review on etiopathogenesis, clinical features, and treatment. PMID- 24179951 TI - An Unusual Type II Dens Invaginatus with Calcified Canals in a Maxillary Lateral Incisor - A Case Report. AB - Dens invaginatus is a developmental malformation resulting from the invagination of enamel organ into the dental papilla. Management of dens invaginatus is an endodontic challenge. Presence of calcified canals in dens invaginatus makes it even more complicated. Modification of the treatment plan is required to treat such cases. This case report deals with the management of a Type II Dens Invaginatus in a lateral incisor with calcified canals. PMID- 24179952 TI - Surgical and prosthetic management of suction cup induced palatal perforation: case report. AB - Construction of complete dentures with adequate retention is a complex procedure. Various techniques have been tried to improve the retention of dentures. Use of suction cup in maxillary denture is one of the techniques to improve retention. Suction cup provides retention and stability by inducing negative pressure on the mucosal surface. Palatal Suction cups which provide high retention are not being recommended because of their pathological effects on the palatal tissues. Here a case report of complete denture with suction cup induced palatal perforation which was surgically treated is presented. PMID- 24179953 TI - Embryonal rhabdomyosarcoma occurring on mandibular gingiva in an adult. AB - An embryonal rhabdomyosarcoma (ERMS) is a primitive, malignant, soft tissue sarcoma that recapitulates the phenotypic and biological features of embryonic skeletal muscles. Occurrence of intraoral ERMS in adults is extremely rare. This unique case report highlights the clinical, radiographic, histopathological and immunohistochemical findings of an intraoral ERMS. PMID- 24179954 TI - Solitary plexiform neurofibroma of the gingiva: unique presentation in the oral cavity. AB - Neurofibromas are benign tumours originating from the nerve sheath. Amongst the histological variants, plexiform types are considered exclusive. These are poorly circumscribed, locally invasive and may exhibit sarcomatous potential. Plexiform neurofibromas are key features of Neurofibromatosis - 1 and their solitary intra oral presentation is uncommon. The following case report describes a unique case of an isolated solitary plexiform neurofibroma of the maxillary anterior gingival region in a middle aged female patient. PMID- 24179955 TI - Stereolithographic surgical template: a review. AB - Implant placement has become a routine modality of dental care.Improvements in surgical reconstructive methods as well as increased prosthetic demands,require a highly accurate diagnosis, planning and placement. Recently,computer-aided design and manufacturing have made it possible to use data from computerised tomography to not only plan implant rehabilitation,but also transfer this information to the surgery.A review on one of this technique called Stereolithography is presented in this article.It permits graphic and complex 3D implant placement and fabrication of stereolithographic surgical templates. Also offers many significant benefits over traditional procedures. PMID- 24179956 TI - Microenvironment-a role in tumour progression and prognosis. AB - In addition to malignant cells, solid tumours comprise supporting stromal tissue that consists of Extra Cellular Matrix (ECM), connective tissue cells, inflammatory cells and blood vessels. The stromal compartment and the malignant cells together shape the tumour microenvironment that in turn determines tumour progression and efficacy of anti-tumour treatments. It is now recognized that the host microenvironment undergoes extensive change during the evolution and progression of cancer. This involves the generation of Tumour-Associated Fibroblasts (TAFs), which, through release of growth factors and cytokines, lead to enhanced angiogenesis, increased tumour growth and invasion. It has also been demonstrated that TAFs may modulate the Cancer Stem Cell (CSC) phenotype, which has therapeutic implications. Understanding the various components in the tumour microenvironment may afford us the opportunity to develop new drugs that target these reversible nonmutational events in the prevention and treatment of cancer. PMID- 24179957 TI - Salmonella typhi isolation in a pregnant woman: determining the importance. PMID- 24179958 TI - Meckel gruber syndrome. PMID- 24179959 TI - Evaluation of Early Infant Diagnosis of HIV 1 in Government hospital, Dhule. PMID- 24179960 TI - Short communication: drug information unit as an effective tool for promoting rational drug use. AB - BACKGROUND: The rapid developments in medical and biological sciences have led to emergence of huge information on drugs and various diseases. But accessing this vast information has limits and rational selection of drugs and utilization of drugs have become more complex. Information regarding the various aspects of drugs may be conveyed by drug information units which run only in specified tertiary care institutional units, to the physicians who treat the patients in the hospital and to the general practitioners outside, in emergencies and in normal situations. METHODS: The queries of clients were obtained by means of phone calls from 9.00 a.m to 5. 00 pm, during 1 month's stay in a DIU. A resident of Clinical Pharmacology collected necessary data on therapeutic problems of patients (age and sex of the patient, other drugs which were taken, present diseases, whether department was in PGIMER, the place etc.). After solving the problems by using electronic databases or hardcopy sources like established facts in standard text book of medicine , pharmacology or in standard articles and with a final approval from the senior clinical pharmacologist, resident delivered the information to the clients as early as possible, without any delay (by phone). RESULTS AND CONCLUSION: From the results, it was found that around 59% of the phone calls were regarding drug interactions and adverse reactions, 11% were regarding efficacy and that 30% were regarding the preferred routes and dosing. We concluded that the information that most of the healthcare professionals aimed to get, were the various drug interactions which had taken place during their therapeutic interventions. PMID- 24179961 TI - On International College of Prosthodontists meetings. PMID- 24179962 TI - The All-on-Four implant therapy protocol in the management of edentulous Chinese patients. AB - PURPOSE: To evaluate the outcome and special characteristics of immediate implant rehabilitation using the All-on-Four treatment concept in completely or potentially completely edentulous Chinese patients. MATERIALS AND METHODS: A convenience sample consisted of 69 consecutive patients (37 men, 32 women; mean age: 56.7 years) treated with immediate implant placement and full-arch prosthodontic provisional prostheses between April 2008 and December 2011. Of 344 implants (192 mandibular, 152 maxillary), 240 implants were placed in fresh extraction sites. The remaining 104 implants were placed in healed sites. Implants were immediately loaded with a fixed full-arch provisional prosthesis. Implant survival rate, marginal bone loss, abutment selection, complications, and subjective patient responses were recorded during follow-up. RESULTS: Implant survival rate was 96.2% at 33.7 months of mean follow-up (range: 12 to 56 months). A statistically significantly higher implant survival rate was found in the mandible (99.0% vs 92.8%) (P < .05). No significant difference existed between survival rates for implants placed in postextraction sites and healed sites (P > .05). Peri-implant marginal bone loss around upright implants and tilted implants was 0.7 +/- 0.2 mm and 0.8 +/- 0.4 mm, respectively. All patients reported satisfactory treatment outcomes. CONCLUSIONS: The modified All-on-Four treatment concept provides predictably favorable outcomes in completely or potentially completely edentulous patients and is well suited to the sociodemographic needs of Chinese patients. Exploratory use of a surgical guide was limited because of mouth opening, and more angulated abutments were needed in anterior upright implants of the maxilla. PMID- 24179963 TI - Treatment with implant-supported fixed dental prostheses in patients with congenital and acquired neurologic disabilities: a prospective study. AB - PURPOSE: To study the medium- to long-term outcome of implant treatment in patients with neurologic disabilities. MATERIALS AND METHODS: Twenty-seven patients with different disabilities and in need of prosthodontic treatment were treated with various implant-supported prostheses. Altogether, 88 threaded titanium implants were placed. General anesthesia was used in 21 patients and local anesthesia in 6 patients. Patients were recalled every 3 months by a dental hygienist and annually by a prosthodontist. RESULTS: Five of the original 27 patients died during the 5- to 10-year follow-up period (mean, 7.2 years), but the remaining 22 patients with 70 implants could be clinically examined at the final follow-up. Twelve implants (14%) were lost, 3 before loading and 9 after insertion of the implant-supported fixed prostheses. The cumulative survival rate for placed implants was 85.8% after 10 years. Perimucositis was diagnosed in 10 patients and for 14 of the 70 implants. Three of the 15 patients with measurable radiographs and 4 implants were diagnosed with peri-implantitis. Several prosthodontic complications occurred, from minor and easily correctable to severe and requiring retreatment. CONCLUSIONS: Patients with different neurologic disabilities present more problems during implant treatment and maintenance compared with healthy patients. Nevertheless, it was possible to carry out treatment, and outcomes were relatively favorable. The results indicate that implant treatment can be a valid option in oral rehabilitation of patients with neurologic disabilities. PMID- 24179964 TI - The prevalence of xerostomia in patients with removable prostheses. AB - PURPOSE: The objective of this study was to determine the prevalence of xerostomia among patients attending a dental clinic for provision of dentures and to investigate the oral cleanliness in those patients. MATERIALS AND METHODS: Denture-wearing patients who reported dry mouth completed a questionnaire related to xerostomia. Dryness of the mouth was determined by clinical observation. Dental and denture cleanliness was determined using the Modified Debris Index. RESULTS: One hundred twenty patients had xerostomia. Oral cleanliness was generally poor. CONCLUSION: There was a high prevalence of xerostomia in the patient population. A high proportion of subjects had poor oral cleanliness. PMID- 24179965 TI - Identification of sleep bruxism with an ambulatory wireless recording system. AB - PURPOSE: To examine whether an ambulatory bruxism recording system, including a biologic monitor, that measures sleep variables and sympatho-vagal balance can specifically identify sleep bruxism (SB) at home. MATERIALS AND METHODS: Twenty six volunteers, including 16 SB subjects, were recruited. Each participant recorded his or her electromyogram (EMG), sympatho-vagal balance, and sound level for 3 consecutive nights using an audio-video recorder to identify SB. Data of sleep variables were compared among the 3 experimental nights. The episodes were classified into SB episodes with and without grinding and non-SB episodes. EMG patterns, amplitude, sympatho-vagal balance, and sound level of all episodes were analyzed so as to determine the appropriate thresholds to detect SB episodes and grinding sound. Then, all episodes without video-recording data were classified into SB and non-SB episodes by using the appropriate thresholds, and the sensitivity and specificity to detect SB episodes were calculated. RESULTS: With regard to sleep variables, there were no significant differences except for sleep latency between the first and second nights. The appropriate EMG pattern and thresholds of amplitude, sympatho-vagal balance, and sound level were phasic or mixed EMG pattern, 20% of maximum voluntary contraction, mean + 1 SD, and mean + 2 SDs, respectively. The sensitivity and specificity to detect SB episodes were 88.4% and 74.2%, respectively. CONCLUSION: The results suggest that this system enables the detection of SB episodes at home with considerably high accuracy and little interference with sleep. PMID- 24179966 TI - Combined tooth-implant-supported telescopic prostheses in a midterm follow-up of > 2 years. AB - PURPOSE: The aim of this trial was to evaluate telescopic-retained prostheses on teeth and implants. MATERIALS AND METHODS: Ten patients with a mean of 2.8 teeth received strategic implants to achieve triangular/quadrangular support. Survival and complication rates were estimated for telescopic abutments and prostheses. RESULTS: After a mean observation period of > 2 years, no abutment was lost and all prostheses were in function. Complication rates were low, and maintenance services were limited to minor interventions. CONCLUSIONS: Combined tooth-implant retained telescopic prostheses improve prosthetic support and offer successful function over a midterm period in patients with a severely reduced dentition. PMID- 24179967 TI - Clinical evaluation of chlorine dioxide for disinfection of dental instruments. AB - This study aimed to clinically evaluate the disinfection efficacy of chlorine dioxide (ClO2) for used dental instruments. An imprint culture technique demonstrated that ultrasonic cleaning of intraorally applied dental mirrors in 0.02% ClO2 for 10 minutes resulted in compete removal of microorganisms for 10 subjects. Hepatitis C virus (HCV) RNA was detected by real-time polymerase chain reaction on periodontal curettes after subgingival scaling in four HCV-infected patients and was completely removed by the same treatment procedure. Therefore, the combination of ultrasonic cleaning with ClO2 may provide an alternative to toxic disinfectants, such as glutaraldehyde and sodium hypochlorite, for disinfecting dental instruments. PMID- 24179968 TI - Volumetric measurements of removed tooth structure associated with various preparation designs. AB - The amount of tooth structure that is removed as a consequence of tooth preparation has rarely been quantified. The aim of this study was to quantify the volume of reduction of tooth structure associated with different commonly used preparation designs. Eighty extracted teeth were divided into eight groups according to the type of preparation design and tooth type. Each specimen underwent pre- and post preparation scanning using microcomputed tomography. The volume of the resultant tooth structure removed was analyzed. Significant differences in the amount of tooth structure removal were noted between types of coverage and types of teeth. PMID- 24179969 TI - Shock absorption capacity of restorative materials for dental implant prostheses: an in vitro study. AB - PURPOSE: To measure the vertical occlusal forces transmitted through crowns made of different restorative materials onto simulated peri-implant bone. MATERIALS AND METHODS: The study was conducted using a masticatory robot that is able to reproduce the mandibular movements and forces exerted during mastication. During robot mastication, the forces transmitted onto the simulated peri-implant bone were recorded using nine different restorative materials for the simulated single crown: zirconia, two glass-ceramics, a gold alloy, three composite resins, and two acrylic resins. Three identical sample crowns for each material were used. Each crown was placed under 100 masticatory cycles, occluding with the flat upper surface of the robot to evaluate the vertical forces transmitted. Two-way analysis of variance was used. Alpha was set at .05. RESULTS: The statistical evaluation of the force peaks recorded on the vertical z-axis showed mean values of 641.8 N for zirconia; 484.5 N and 344.5 N, respectively, for the two glass ceramics; 344.8 N for gold alloy; 293.6 N, 236 N, and 187.4 N, respectively, for the three composite resins; and 39.3 N and 28.3 N, respectively, for the two acrylic resins. Significant differences were found between materials (P < .0001), except for the comparison between gold alloy and one of the glass-ceramics. CONCLUSION: Composite and above all acrylic resin crowns were more able to absorb shock from occlusal forces than crowns made of zirconia, ceramic material, or gold alloy. PMID- 24179970 TI - Prosthetic rehabilitation of head and neck cancer patients focusing on mandibular dentures in irradiated patients. AB - PURPOSE: This retrospective study assessed treatment outcomes and patient satisfaction of irradiated head and neck cancer patients treated with mandibular implant overdentures (IODs) or conventional dentures (CDs). MATERIALS AND METHODS: Fifty-one irradiated head and neck cancer patients, out of a total of 158 patients included, completed the standardized questionnaire and underwent a clinical assessment. Nineteen patients were treated with removable CDs and 32 patients received IODs between January 2006 and January 2011. The mean follow-up of patients was 5.75 years (range: 1 to 23 years). RESULTS: A total of 45 (88.3%) mandibular dentures were in function at the time of assessment. The overall denture satisfaction was 7.3 (range: 1 to 10, SD: 2.14). Patients being treated with adjuvant concepts, including surgical tumor ablation, scored worse than patients after radiation therapy alone. Edentulous patients seem to benefit from implants, especially with respect to prosthesis retention. Men take more benefit from IODs compared with women. CONCLUSIONS: The results are comparable to other studies of head and neck cancer patients and also of healthy individuals. Surgical interventions in adjuvant therapy concepts lead to reduced denture satisfaction. The concept of prosthetic rehabilitation as part of oncologic treatment can be judged as successful. PMID- 24179971 TI - Magnetic attachment for implant overdentures: influence of contact relationship with the denture base on stability and bending strain. AB - This study evaluated how the contact height between the magnetic attachment and denture base influences stability and bending strain. An implant modified with strain gauges and a magnetic attachment mounted in an acrylic resin block were used to characterize systems with varying degrees or heights of contact with the abutment. Bending strain under lateral loading increased significantly as the contact height decreased. In the no contact and resilient contact groups, magnetic assemblies separated at reduced bending strain in all loading conditions. The contact height of the magnetic attachment influenced the stability and the amount of bending strain on the implant. PMID- 24179972 TI - A 3-year prospective clinical study of telescopic crown, bar, and locator attachments for removable four implant-supported maxillary overdentures. AB - PURPOSE: To evaluate telescopic crown (TC), bar, and locator attachments used in removable four implant-supported overdentures for patients with edentulous maxillae. MATERIALS AND METHODS: A total of 30 maxillary edentulous patients were enrolled in a 3-year prospective study. Ten patients (group A) were treated with overdentures supported by TCs, 10 patients (group B) with overdentures supported by bar attachments, and 10 patients (group C) with overdentures supported by locator attachments. A total of 120 implants were used to restore oral function. During the 3-year follow-up period, implant survival and success rates, biologic and mechanical complications, prosthodontic maintenance efforts, and patient satisfaction were evaluated. RESULTS: All 30 patients were available for the 3 year follow-up and exhibited 100% implant survival and success rates. Peri implant marginal bone resorption was not statistically significant for the three groups. There were lower plaque, bleeding, gingiva, and calculus indices in group C compared with groups A and B. The number of prosthodontic maintenance visits revealed eight complications in the TC group, seven complications in the bar group, and four complications in the locator group. However, there were no differences in the clinical effects of the overdentures in the three groups. CONCLUSION: Within the limits of this prospective study, it was concluded that the locator system produced superior clinical results compared with the TC and bar attachments in terms of peri-implant hygiene parameters, the frequency of prosthodontic maintenance measures, cost, and ease of denture preparation. However, longer-term prospective studies are required to confirm these results. PMID- 24179973 TI - Occlusion and weight change in a patient after esophagectomy: success derived from restoration of occlusal support. AB - Occlusal support may be an important factor affecting nutritional support after major surgery. This report presents a patient who gained body weight after receiving a new prosthesis. The patient was an 82-year-old man with thoracic esophageal carcinoma. He did not have occlusal support because of multiple caries lesions. His body weight slowly increased after surgery, but almost stopped in the period of 54 to 68 days after surgery. After treatment with dentures (day 72 postsurgery), body weight gain was observed again, although his medical treatment had not changed. An appropriate prosthesis could contribute to perioperative nutrition support and may lead to earlier recovery after surgery. PMID- 24179974 TI - A method to improve passive fit of frameworks on implant-supported prostheses: an in vivo study. AB - PURPOSE: A die stone jig was evaluated as to its ability to clinically verify the position of the abutment replicas on the master cast. MATERIALS AND METHODS: A clinical evaluation was made on 58 edentulous arches necessitating rehabilitation with fixed partial dentures. Any broken jigs detected were replaced with a new set of jigs and clinically retested. Data were statistically confirmed. RESULTS: Fifty-five percent of the 58 jigs broke, with a 95% confidence interval (CI) of 42.5 to 67.3; after replacement, there were no breakages (95% CI: 0 to 6.2). CONCLUSIONS: The jig detected misfits in clinical trials, according to the parameters defined in the literature. PMID- 24179975 TI - On cleaning and sterilisation of customised abutments and disappearing implant failures. PMID- 24179976 TI - A 3-year report from a multicentre randomised controlled trial: immediately versus early loaded implants in partially edentulous patients. AB - PURPOSE: To compare implant failure, prosthesis failure and radiographic bone level changes of immediate non-occlusal loading versus early loading in partially edentulous patients 3 years after implant placement. MATERIALS AND METHODS: A total of 80 patients with partial edentulism were selected for a two implant supported immediate restoration and randomised to immediate loading (test group) or early loading (control group) after 2 months, 40 patients for each group. To be included in the study, implants had to be inserted with a torque >= 30 Ncm. In the test group, implants were provided with non-occluding temporary restorations. In the control group, healing abutments were attached and implants were left to heal nonsubmerged. Definitive prostheses were delivered 2 months after surgery with full occlusal contacts. The outcome variables were implant failure, prosthesis failure, complications and radiographic bone level changes at implants 3 years after loading. The assessor was blinded to group assignment. RESULTS: Eighty-one implants were immediately loaded and 80 were early loaded. Two immediately loaded patients and 1 early loaded patient dropped out at 3 years. No implant failed. Two complications occurred in the immediate loading group and 1 in the early loading group. There were no significant differences in bone levels changes at 36 months between the two groups (P = 0.67; difference 0.2 mm; 95% CI 0.23, 0.63). Immediately loaded implants lost 0.90 mm (95% CI 0.63, 1.17) and early loaded implants 1.10 mm (95% CI 0.81, 1.39). CONCLUSION: If adequate primary stability was achieved, no statistically significant difference in failure rates, complications or bone level changes between implants loaded immediately or early were observed 3 years after placement in partially edentulous patients. PMID- 24179977 TI - Safety and efficacy of a biomimetic monolayer of permanently bound multi phosphonic acid molecules on dental implants: 1 year post-loading results from a pilot quadruple-blinded randomised controlled trial. AB - PURPOSE: To evaluate the safety and clinical efficacy of a novel surface treatment (SurfLink(r), Nano Bridging Molecules, Gland, Switzerland) on titanium dental implants. SurfLink consists of a monolayer of permanently bound multi phosphonic acid molecules, which mimics the surface of naturally occurring hydroxyapatite. MATERIALS AND METHODS: Twenty-three patients requiring at least two single dental implants had their sites randomised according to a split-mouth design to receive one titanium grade 4 implant treated with SurfLink and one untreated control implant. Additional SurfLink-treated implants were placed if needed. Implants were submerged for 3 months in mandibles and 6 months in maxillae, were loaded with definitive metal-ceramic crowns, and followed up for 1 year after loading. Outcome measures were crown/implant failures, any complication, radiographic peri-implant marginal bone level changes and marginal bleeding. RESULTS: One patient dropped out after abutment connection. All remaining patients were followed up to 1 year post-loading. No implant failed and only 1 postoperative complication (pain) occurred, but it may not have been related to the implant treatment. No bleeding was observed when a periodontal probe was used to examine the peri-implant soft tissues around the implants. There were no statistically significant differences in marginal bone level changes between the two groups (P = 0.057, mean difference = -0.27, SE = 0.13; 95% CI -0.55 to 0.01). CONCLUSIONS: Preliminary short-term data (1 year post loading) of implants with a biomimetic monolayer of permanently bound multi phosphonic acid molecules (SurfLink surface treatment) presented no safety issues. Clinical healing in both the control and SurfLink-treated implant group was uneventful and did not differ significantly between groups. More challenging clinical situations need to be investigated to evaluate the real effectiveness of this surface treatment. PMID- 24179978 TI - Socket grafting with or without buccal augmentation with anorganic bovine bone at immediate post-extractive implants: 6-month after loading results from a multicenter randomised controlled clinical trial. AB - PURPOSE: To evaluate whether grafting with additional anorganic bovine bone to augment horizontally the buccal plate (internal and external grafting [IEG]) at single post-extractive implants preserves the alveolar ridge, improving aesthetics, better than internal socket grafting alone (ISGA). MATERIAL AND METHODS: A total of 78 patients, treated in four Italian private practices, requiring a single immediate post-extractive implant, having at least 1 mm of implant-to-buccal bone gap after implant insertion and a preserved buccal bone, had the residual bone-to-implant gap filled with anorganic bovine bone. Thirty nine randomly allocated patients received additional buccal horizontal augmentation of about 2 mm thickness with the same bone substitute (IEG group) covered with collagen resorbable membranes. Implants were submerged for 4 months before being loaded with provisional acrylic crowns. Definitive crowns were delivered after 6 months. Outcome measures were crown/implant failures, complications and aesthetics recorded by blinded assessors 6 months after initial loading, at delivery of definitive crowns. RESULTS: Six months after initial loading, 8 patients dropped out, did not complete the treatment or were treated twice and therefore had to be excluded (4 from each group). There were no statistically significant differences for implant failures and complications between the two groups. Two implants failed in the IEG group versus 1 in the ISGA group. Four complications occurred, 2 in each group. The mean implant aesthetic score (IAS) was 7.8 at ISGA sites and 8.0 at IEG sites. There were no statistically significant differences between the two groups (P = 0.492; difference 0.2 mm; 95% CI -0.769, 0.369) for IAS score. There were no statistically significant differences in the outcomes between the centres. CONCLUSIONS: The use of adjunctive anorganic bovine bone placed buccally at preserved buccal sites of immediate post-extractive implants may not improve the aesthetic outcome, however additional research is needed to confirm or reject these preliminary findings. PMID- 24179980 TI - Prostheses supported by four immediately loaded zygomatic implants: a 3-year prospective study. AB - PURPOSE: To assess the clinical 3-year outcome of prostheses supported by four immediately loaded zygomatic implants. MATERIALS AND METHODS: A total of 17 consecutively treated patients (7 men, 10 women, mean age 57.7 years) with severe maxillary atrophy were immediately rehabilitated with prostheses supported by four immediately loaded zygomatic implants. The patients were followed up for 3 years and the outcome measures included success rates of the prostheses, success rates of the zygomatic implants, complications and oral-health related quality of life (OHRQoL). RESULTS: No patients dropped out. No prosthesis or zygomatic implants failed, though one implant was not used to support the final prosthesis because it emerged in an unfavourable position. Seven complications occurred: penetration of the orbital cavity during the drilling procedure with no relevant consequences; an infection followed by a fistula at one zygomatic implant, which was resolved with antibiotic treatment and surgical drainage; two patients developed sinusitis, and were successfully treated with antibiotics and meatotomy; fracture of the abutment screw occurred in one patient; and fracture of the prosthesis occurred in two patients and the definitive prostheses were repaired. The average score for the OHIP-14 questionnaire was 2.7, which was similar to that of the general population. CONCLUSIONS: The present 3-year study suggests that prostheses supported by four immediately loaded zygomatic implants can be used for successful rehabilitation of patients with severely atrophic maxillae. PMID- 24179979 TI - Hard tissue response to argon plasma cleaning/sterilisation of customised titanium abutments versus 5-second steam cleaning: results of a 2-year post loading follow-up from an explanatory randomised controlled trial in periodontally healthy patients. AB - PURPOSE: The aim of this triple-blinded randomised controlled trial was to test if argon plasma cleaning/ sterilisation of customised abutments can affect peri implant marginal bone levels when compared to 5 seconds of steam cleaning. MATERIALS AND METHODS: A total of 20 consecutive periodontally healthy patients requiring single implant-supported restorations in the maxillary premolar or anterior area were selected. All patients received a single implant. At abutment connection, customised abutments were randomly allocated to control (subjected only to usually adopted steam cleaning, CG) and test groups (subjected to plasma cleaning/sterilisation, TG). Abutments were screwed in at 32 Ncm, provisional restorations adapted and periapical radiographs were taken using customised film holders. Two weeks later, definitive restorations were placed. Patients were followed-up for 2 years post-loading. Outcome measures were implant/crown success, complications, periapical marginal bone level changes on periapical standardised radiographs, and microbiological analyses of the abutments after customisation and cleaning procedures but before connection. Comparisons between groups were performed by independent sample t tests (significance threshold of P <= 0.05). RESULTS: No patient dropped out 2 years after loading. The presence of bacterial growth (staphylococci, including Staphylococcus aureus) was observed only on the CG abutments. No implant failed and no complications occurred. After 2 years of prosthetic loading, radiographic analysis revealed a statistically significantly higher mean bone loss for the CG group (mean difference 0.4 mm; 95% CI 0.08-0.73; P = 0.018). CONCLUSIONS: This study suggests that removal of contaminants from titanium abutments using plasma of argon can allow for better bone level maintenance when compared to 5-second steam cleaning of titanium abutments. It is therefore important to use cleaned and sterilised customised abutments in patients. PMID- 24179981 TI - Immediate loading of 'All-on-4' maxillary prostheses using trans-sinus tilted implants without sinus bone grafting: a retrospective study reporting the 3-year outcome. AB - PURPOSE: To report the outcome of trans-sinus tilted implants for the rehabilitation of the complete edentulous atrophic maxilla using the All-on-4 concept with immediate loading. MATERIALS AND METHODS: This retrospective clinical study included 70 patients treated with 280 implants (Nobel Biocare), 83 of which were trans-sinus implants supporting 70 prostheses. The inclusion criteria were need of maxillary complete edentulous rehabilitation without enough bone height posterior to the canines to anchor the implants. The trans-sinus implant head was anchored on the bone available just posterior to the anterior sinus wall and inferior to the sinus floor. The trans-sinus implant body was inside the sinus, and its apex anchored in the bone between the anterior sinus wall and the nasal cortical. The nasal cortical was used, if necessary, to achieve a double bicortical anchorage. Implants were immediately loaded with cross-arch fixed prostheses. Follow-up examinations were performed after 10 days, 2, 4 and 6 months, and 1, 2 and 3 years. Radiographic evaluations were performed after 1 and 3 years of function. Outcome measures were success of the prostheses, success of the implants, complications, peri-implant marginal bone levels, and aesthetic and functional complaints. Survival was calculated at implant level and using the patient as the unit of analysis (first implant failure in any given patient) using life-table analysis. RESULTS: Seven patients dropped out of the study. Three trans-sinus tilted implants were lost in 3 patients, giving a cumulative survival rate of 95.7% and 96.4% at patient and implant level, respectively. One conventional tilted implant was lost in 1 patient (one of the patients that lost a trans-sinus tilted implant), giving a cumulative survival rate of 98.1%. One straight implant was lost in one patient (a second patient that lost a trans-sinus implant), giving a cumulative survival rate of 98.6% and 99.3% at patient and implant level, respectively. The survival rate of prostheses was 100%. Sinusitis occurred in 2 patients (2.9%). The marginal bone resorption was on average (standard deviation) 0.96 mm (0.62 mm) and 1.14 mm (0.74 mm) for the trans-sinus tilted implants, 0.89 mm (0.54 mm) and 1.06 mm (0.71 mm) for the conventional tilted implants, and 0.62 mm (0.35 mm) and 1.15 mm (0.51 mm) for the straight implants after 1 and 3 years of follow-up, respectively. CONCLUSIONS: The high survival rate registered at patient and implant level indicates that the outcome of immediately loaded trans-sinus implants for the rehabilitation of edentulous atrophic maxillae to avoid sinus lift procedures is a viable treatment in the short and medium term. Future studies should focus on the long-term outcome of this rehabilitation modality. PMID- 24179982 TI - Immediate provisionalisation of single post-extractive implants versus implants placed in healed sites in the anterior maxilla: 1-year results from a multicentre controlled cohort study. AB - PURPOSE: The purpose of the study was to compare the clinical and aesthetic outcome of single post-extractive implants versus implants placed in a preserved socket after 4 months of healing in the anterior maxilla. All of the implants were immediately non-occlusally loaded. MATERIALS AND METHODS: A total of 50 patients were treated in the two groups of study. The Delayed Group had a maxillary tooth (premolar, canine, lateral or central incisor) removed, with immediate socket grafting, followed by implant placement and provisionalisation 4 months later. The Immediate Group had immediate implant placement and provisionalisation. Outcome measures were implant failures, biological and biomechanical complications, peri-implant radiographic bone level changes, and gingival aesthetics. RESULTS: At the 12-month follow-up, two implants failed in the Immediate Group (8%) versus one in the Delayed Group (4%), with a comparable rate of implant failure (P = 0.55). No complications occurred for either group. The 12-month peri-implant bone resorption was similar in both groups (P = 0.23): 0.71 mm (95% CI 0.45, 0.97) in the Immediate Group versus 0.60 mm (95% CI 0.38, 0.82) in the Delayed Group. The mean difference in bone resorption was 0.13 mm (95% CI -0.21, 0.47). An ideal gingival marginal level was reached most frequently in the Delayed Group (83.3% versus 52.1%, P = 0.04). Rates of full closure of the papilla were similar between the two groups (82.6% for the Immediate Group versus 62.5% for the Delayed Group, P = 0.12). CONCLUSIONS: Given the limitation that this was not a randomised controlled trial, there were no differences in complications or crestal bone response at immediate post extractive implants when compared to delayed implants. A delayed protocol might be considered in the aesthetic zone due to the gingival recession that occurs after post-extractive implant placement. PMID- 24179983 TI - Prefabricated veneers - bond strengths and ultramorphological analyses. AB - PURPOSE: To measure the microshear bond strengths (MUSBS) of composite resin to the intaglio surface of prefabricated indirect veneers and analyze the FE-SEM ultramorphology of the pretreated intaglio surfaces as well as the fracture modes. MATERIALS AND METHODS: Three veneer systems (veneer and respective luting material) were used in this study: two prefabricated veneer types, Cerinate One hour (CER, DenMat) and Componeer (CMP, Coltene), and a laboratory- made veneer, IPS e.max Press (IPS, Ivoclar Vivadent) used as the control. For each group, 10 veneers were used. After delimitation of the bonding area with a double-faced adhesive tape, 0.8-mm-diameter cylinders of composite luting material were bonded to the pretreated intaglio surface. After polymerization, the specimens were fractured in shear mode using the wire-loop method in a universal testing machine. The pretreated intaglio surface of two extra veneers and four fractured specimens per group were morphologically characterized using FE-SEM. RESULTS: CER resulted in statistically lower mean MUSBS (7.1 +/- 1.2 MPa) than the other two veneer systems, CMP (15.2 +/- 2.5 MPa) and IPS (14.7 +/- 1.7 MPa) at p < 0.0001. As seen with the FE-SEM, the intaglio surface of CMP did not display microretentive features, while multiple microretentions were observed in both CER and IPS after HF etching. CONCLUSION: Within the limitations of this in vitro study, the CMP and IPS veneer systems resulted in greater bond strengths than those of the CER veneer system. PMID- 24179984 TI - Push-out bond strength of fiber posts to root canal dentin using a one-step self etching adhesive: the effect of solvent removal and light-curing methods. AB - PURPOSE: To evaluate the effect of solvent removal and light-curing methods on the push-out bond strength of fiber posts to root canal dentin using a one-step self-etching adhesive. MATERIALS AND METHODS: Eighty single-rooted, single-canal human mandibular premolars were used in this study. After removal of the crown, the pulp was extirpated and the post space was prepared. The teeth were divided into two main groups according to the solvent removal method, either using the paper point or the air-drying method. Each of the above main groups was further subdivided into 4 subgroups according to the light-curing method: group 1: both adhesive and resin cement were cured from the top of the post in the same step (cocuring) for 40 s; group 2: the adhesive was light cured for 20 s and the resin cement for 40 s; group 3: the adhesive was light cured for 40 s as was the resin cement; group 4: an intracanal tip was used to cure the adhesive inside the post space for 20 s. In groups 1 to 4, the solvent was evaporated using oil-free compressed air for 5 s from the root surface and excess adhesive was removed from inside the canal using a paper point. In groups 5 to 8, the adhesive and cement were applied and light cured as in groups 1 to 4, except the solvent was evaporated (air dried) from inside the post space using an intra-canal disposable plastic tip attached to the tip of a 3-way syringe. After 24 hours, three 2-mm thick root slices were obtained from each root. Each slice was subjected to the push-out bond strength test at a crosshead speed of 0.5 mm/min. Factorial analysis (two-way ANOVA) was run to test the effect of solvent evaporation method, light-curing method, and their interactions on bond strength. One-way ANOVA followed by Duncan's Multiple Range Test were used to test the effect of lightcuring method on bond strength within each solvent evaporation method. Student's t-test was performed to compare the effect of solvent evaporation method on bond strength within each light-curing method. RESULTS: Two-way ANOVA revealed that the solvent removal method had a significant effect on the bond strength of fiber post to root canal dentin. Neither the light-curing method nor the interaction between the two independent variables had a significant effect on the push-out bond strength. CONCLUSIONS: Only air drying the one-step self etching adhesive could influence the bond strength of the fiber post to root canal dentin. PMID- 24179986 TI - Effect of surface treatments of zirconia ceramics on the bond strength to resin cement. AB - PURPOSE: The purpose of this in vitro study was to evaluate the bond strength of a resin luting cement to zirconia surfaces that had received two novel surface pretreatment methods: etching of a pre-fired overglaze or paste liner on the zirconia substrate. MATERIALS AND METHODS: Fully sintered zirconia disks were assigned to 6 groups according to the surface pretreatment: firing of 2 layers of paste liner which was then etched with hydrofluoric acid and treated with silane (Liner group); firing of 2 layers of overglaze which were then etched with hydrofluoric acid and treated with silane (glaze group); Rocatec treatment and silane application (Rocatec group); Rocatec treatment followed by ultrasonic cleaning and silanization (ultrasonic-Rocatec group); sandblasted with alumina (alumina group); as-sintered with no pretreatment (control group). Twenty composite resin cylinders were bonded to each group with Panavia F 2.0. Each group was further divided into 2 subgroups (n = 10) for 2 different storage conditions: 24 h water storage or 3 weeks water storage plus 6000 thermocycles between 5 degrees C and 55 degrees C. The shear bond strength was then determined. Statistical analyses with two-way ANOVA were conducted; the level of significance was set at p < 0.05. RESULTS: At 24 h, the shear bond strength values of all groups except the control showed no statistically significant difference. After artificial aging, the mean bond strength of all groups dropped, but the decrease in the glaze group was not statistically significant. The glaze group showed the highest shear bond strength. However, that was not statistically different from the liner or the Rocatec group without ultrasonic cleaning (p < 0.05). All the control specimens debonded spontaneously after aging. Ultrasonic cleaning after Rocatec treatment caused a reduction in shear bond strength, but the difference was not statistically significant. CONCLUSION: Both the fired paste liner and overglazed ceramic treated zirconia surfaces provided a strong and durable bond to resin cement under the conditions tested. PMID- 24179985 TI - Exposed collagen in resin bonds to caries-affected dentin after dentin treatment with aqueous and alcoholic chlorhexidine solutions. AB - PURPOSE: To evaluate the effect of saturation of demineralized dentin with aqueous and alcoholic excipients of chlorhexidine (CHX) on the exposure of collagen fibrils in resin-dentin bonds in sound and caries-affected dentin. MATERIALS AND METHODS: Flat midcoronal dentin surfaces were prepared from 24 noncarious molars, and artificial caries was induced in half of the sample. For each substrate, the surfaces were assigned to 4 groups (n = 3) according to the saturation solution of the dentin: water, ethanol, 1% CHX aqueous or alcoholic solution. Infected dentin was removed by abrasive papers. After acid etching, the dentin surface was saturated with each solution for 60 s followed by application of Single Bond. The specimens were processed for Goldner's trichrome staining and the thickness of the exposed collagen zone (ECZ) at the resin/dentin interfaces was measured under optical microscopy. Data were analyzed statistically by Kruskal-Wallis and Mann-Whitney tests (alpha = 0.05). RESULTS: Regardless of the saturation solution, caries-affected dentin presented a thicker ECZ at the bottom of the hybrid layer than did sound dentin. For both substrates, 100% ethanol had a negative influence on collagen exposure in comparison with water, but the same was not observed for the CHX alcoholic solution. CHX solutions did not differ significantly from each other or from their respective solvents. CONCLUSION: The saturation of phosphoric acid-demineralized dentin with either CHX aqueous or alcoholic solutions did not affect the exposure of collagen fibrils in the resin dentin bonds produced in sound and caries-affected dentin. A thicker zone of exposed collagen was found in hybridized caries-affected dentin compared to noncarious dentin. PMID- 24179987 TI - Dental preparation with sonic vs high-speed finishing: analysis of microleakage in bonded veneer restorations. AB - PURPOSE: To compare marginal microleakage in porcelain veneer restorations following dental finishing using two types of instruments to test the hypothesis that microleakage will be less when teeth are prepared with sonic oscillating burs than when prepared with high-speed rotating burs. MATERIALS AND METHODS: Fifty-six extracted human maxillary central incisors were selected and divided randomly into two groups. Group 1 samples underwent dental finishing using high speed rotating diamond burs, while group 2 used sonic oscillating diamond burs. Buccal chamfer preparation was carried out for both groups. Forty eight of the samples (24 per group) were restored using IPS Empress ceramic veneers. 2% methylene blue was used to evaluate microleakage at the tooth/composite veneer interface. Teeth were sectioned lengthwise into three parts and microleakage was measured at two points - cervical and incisal - on each section. Before bonding, four teeth per group underwent SEM examination. RESULTS: Evaluation of microleakage at the cervical dentin margin showed a value of 10.5% in group 1 and 6.6% in group 2, which was statistically significantly different (p < 0.05). Incisal microleakage was 1.3% for group 1 and 1.2% for group 2, which was not significantly different. SEM revealed different patterns of surface texture in both areas according to the instrument used. Group 1 exhibited parallel horizontal abrasion grooves with a milled effect and thick smear layers; group 2 showed abrasive erosion, discontinuous perpendicular depressions, and thin smear layers. CONCLUSION: Tooth preparations finished with sonic burs produced significantly less microleakage in the cervical dentin area of bonded veneer restorations. No differences were found in the incisal enamel area. PMID- 24179988 TI - Fiber-reinforced composite fixed dental prostheses with various pontics. AB - PURPOSE: To evaluate the load-bearing capacities of fiber-reinforced composite (FRC) fixed dental prostheses (FDP) with pontics of various materials and thicknesses. MATERIALS AND METHODS: Inlay preparations for retaining FDPs were made in a polymer phantom model. Seventy-two FDPs with frameworks made of continuous unidirectional glass fibers (everStick C&B) were fabricated. Three different pontic materials were used: glass ceramics, polymer denture teeth, and composite resin. The FDPs were divided into 3 categories based on the occlusal thicknesses of the pontics (2.5 mm, 3.2 mm, and 4.0 mm). The framework's vertical positioning varied respectively. Each pontic material category contained 3 groups (n = 8/group). In group 1, pontics were fabricated conventionally with composite resin (G-aenial, GC) with one additional transversal fiber reinforcement. In group 2, the pontics were polymer denture teeth (Heraeus- Kulzer). Group 3 had an IPS-Empress CAD pontic (Ivoclar Vivadent) milled using a Cerec CAD/CAM unit. Groups 1 and 2 served as controls. Each FDP was statically loaded from the pontic until initial fracture (IF) and final fracture (FF). Initial-fracture data were collected from the load-deflection graph. RESULTS: ANOVA indicated statistically significant differences between the materials and occlusal thicknesses (p < 0.001). Quadratic analysis demonstrated the highest correlation between the thickness of the pontic and IF and FF values with ceramic pontics (IF: p < 0.001; R2 = 0.880; FF: p < 0.001; R2 = 0.953). CONCLUSION: By increasing the occlusal thickness of the pontic, the load-bearing capacity of the FRC FDPs may be increased. The highest load-bearing capacity was obtained with 4.0 mm thickness in the ceramic pontic. However, with thinner pontics, polymer denture teeth and composite pontics resulted in higher load-bearing values. PMID- 24179989 TI - Effect of exposure time on the polymerization of resin cement through ceramic. AB - PURPOSE: This study measured the effects of using three different exposure times to cure one resin cement through two types of ceramic. MATERIALS AND METHODS: One light-curing resin cement (Variolink II, Ivoclar Vivadent) was exposed for 20 s, 40 s, or 60 s with a BluePhase G2 light (Ivoclar Vivadent) on the high power setting through 1.0 mm of either ZirPress (ZR) or Empress Esthetic (EST) ceramic (Ivoclar Vivadent). The degree of conversion (DC) of the resin was measured 100 s after light exposure. The Knoop microhardness (KHN) was measured 5 min after light exposure and again after 24 h. The DC and KHN results were analyzed with ANOVA followed by Scheffe's post-hoc multiple comparison tests at alpha = 0.05. RESULTS: Increasing exposure time had a significant effect on the KHN and DC values for the resins exposed through both ceramics. As exposure times increased, the influence of the ceramic was reduced; however, the microhardness values were greater for the cement exposed through EST ceramic. When the exposure time was increased from 20 s to 40 s, microhardness values for the resin increased by 39.6% through the EST ceramic. When exposed for 60 s, there were no differences between the 100-s DC values or 5-min KHN values using either ceramic (p > 0.05). There was an excellent correlation between the DC at 100 s and the microhardness values measured at 5 min. CONCLUSION: Resin polymerization was greater through EST than ZR ceramic. At least 40 s to 60 s from the Blue- Phase G2 on high power mode is required to cure this resin cement through 1.0 mm of ceramic. PMID- 24179990 TI - Secondary structure of proteins analyzed ex vivo in vascular wall in diabetic animals using FT-IR spectroscopy. AB - In recent years many methods for ex vivo tissue analysis or diagnosis of diseases have been applied, including infrared absorption spectroscopy. Fourier-transform infrared (FT-IR) absorption microspectroscopy allows the simultaneous monitoring of the content of various chemical compounds in tissues with both high selectivity and resolution. Imaging of tissue samples in very short time can be performed using a spectrometer equipped with a Focal Plane Array (FPA) detector. Additionally, a detection of minor components or subtle changes associated with the functional status of a tissue sample is possible when advanced methods of data analysis, such as chemometric techniques, are applied. Monitoring of secondary structures of proteins has already proved to be useful in the analysis of animal tissues in disease states. The aim of this work was to build a mathematical model based on FT-IR measurements for the prediction of alterations in the content of secondary structures of proteins analyzed by FT-IR in the vascular wall of diabetic animals. For that purpose a spectral database of proteins of known crystallography and secondary structures was assembled. Thirty seven proteins were measured by means of two FT-IR techniques: transflection and Attenuated Total Reflectance (ATR). The obtained model was tested on cross sections of rat tail, for which the content of proteins and their secondary structures was well characterized. Then, the model was applied for the detection of possible alterations in the secondary structures of proteins in the vascular wall of diabetic rats and mice. The obtained results suggest a prominent increase in E- and S-structures and a decrease in the content of H-structures in the vascular wall from diabetic mice and rats. FT-IR-based studies of secondary structures of proteins may be a novel approach to study complex processes ongoing in the vascular wall. The obtained results are satisfactory; however, the existing limitations of the method are also discussed. PMID- 24179991 TI - A highly sensitive LED-induced chemiluminescence platform for aptasensing of platelet-derived growth factor. AB - In this work, we demonstrated a simple and highly sensitive LED-induced chemiluminescence (LED-CL) platform for aptasensing of proteins. It was based on the fact that fluorescein isothiocyanate (FITC) strongly catalyzed the reaction between luminol and dissolved oxygen under LED irradiation. Using FITC as a new catalytic tag, a highly sensitive sandwich type LED-CL aptasensor was fabricated for quantification of the model protein (platelet-derived growth factor-BB, PDGF BB). Under optimized conditions, the assay for PDGF-BB was linear from 0.1 nM to 100 nM, and the detection limit was as low as 50 pM, which is better than most of other aptamer-based assays without an amplification procedure. Thrombin, bovine serum albumin, hemoglobin, cytochrome C and adenosine triphosphate showed no obvious interferences for the determination of PDGF-BB. The advantages of high sensitivity and selectivity provided by this LED-CL aptasensor will facilitate its wide application in protein assays. PMID- 24179992 TI - Goat anti-rabbit IgG conjugated fluorescent dye-doped silica nanoparticles for human breast carcinoma cell recognition. AB - We report an indirect method for cancer cell recognition using photostable fluorescent silica nanoprobes as biological labels. The dye-doped fluorescent silica nanoparticles were synthesized using the water-in-oil (W/O) reverse microemulsion method. The silica matrix was produced by the controlled hydrolysis of tetraethylorthosilicate (TEOS) in water nanodroplets with the initiation of ammonia (NH3.H2O). Fluorescein isothiocyanate (FITC) or rhodamine B isothiocyanate conjugated with dextran (RBITC-Dextran) was doped in silica nanoparticles (NPs) with a size of 60 +/- 5 nm as a fluorescent signal element by covalent bonding and steric hindrance, respectively. The secondary antibody, goat anti-rabbit IgG, was conjugated on the surface of the PEG-terminated modified FITC-doped or RBITC-Dextran-doped silica nanoparticles (PFSiNPs or PBSiNPs) by covalent binding to the PEG linkers using the cyanogen bromide method. The concentrations of goat anti-rabbit IgG covering the nanoprobes were quantified via the Bradford method. In the proof-of-concept experiment, an epithelial cell adhesion molecule (EpCAM) on the human breast cancer SK-Br-3 cell surface was used as the tumor marker, and the nanoparticle functionalized with rabbit anti EpCAM antibody was employed as the nanoprobe for cancer cell recognition. Compared with fluorescent dye labeled IgG (FITC-IgG and RBITC-IgG), the designed nanoprobes display dramatically increased stability of fluorescence as well as photostability under continuous irradiation. PMID- 24179993 TI - Advancements in nanosensors using plastic antibodies. AB - Biosensors possess recognition elements that bind to target molecules which lead to detectable signals. Incorporation of noble metal nanomaterials into biosensors allows for rapid and simple biomolecule detection. Herein, recent developments in affinity nanosensors will be discussed. These sensors often include naturally occurring recognition elements such as antibodies and DNA. As samples become more complex, new recognition elements are sought. For instance, plastic antibodies provide alternative and more environmentally stable recognition elements than traditional antibodies. Molecular imprinted polymers, a class of plastic antibodies, promote biomolecule recognition and detection. The incorporation of noble metal nanomaterials into molecular imprinted polymer biosensors for real world applications will be explored. Further improvements in the design of artificial recognition agents are envisioned to facilitate new methods for complex biological and chemical analyses. PMID- 24179994 TI - Translational pharmacology: from animal to man and back. PMID- 24179995 TI - Evaluation of symptomatic drug effects in Alzheimer's disease: strategies for prediction of efficacy in humans. AB - In chronic diseases such as Alzheimer's disease (AD), the arsenal of biomarkers available to determine the effectiveness of symptomatic treatment is very limited. Interpretation of the results provided in literature is cumbersome and it becomes difficult to predict their standardization to a larger patient population. Indeed, cognitive assessment alone does not appear to have sufficient predictive value of drug efficacy in early clinical development of AD treatment. In recent years, research has contributed to the emergence of new tools to assess brain activity relying on innovative technologies of imaging and electrophysiology. However, the relevance of the use of these newer markers in treatment response assessment is waiting for validation. This review shows how the early clinical assessment of symptomatic drugs could benefit from the inclusion of suitable pharmacodynamic markers. This review also emphasizes the importance of re-evaluating a step-by-step strategy in drug development. PMID- 24179996 TI - Informatics, docking and data investigation. PMID- 24179997 TI - Automation of decision making in drug design. PMID- 24179998 TI - Rating evidence in treatment guidelines: a case example of when to initiate combination antiretroviral therapy (cART) in HIV-positive asymptomatic persons. AB - Guidelines for the initiation of combination antiretroviral therapy (cART) in those living with HIV are provided by several national and international treatment guidelines committees. Following recent changes to some of these guidelines, there is now considerable variation between the guidelines in terms of the recommendations for initiation of cART among asymptomatic individuals with high (>350 cells/ul) CD4 cell counts. In this review we compare the schemes used for rating evidence by the various committees and assess the strengths and weaknesses of the available evidence for initiating cART at higher CD4 cell counts. PMID- 24179999 TI - NKp44L expression on CD4+ T cells is associated with impaired immunological recovery in HIV-infected patients under highly active antiretroviral therapy. AB - OBJECTIVE: HIV-infected immunological nonresponders (InRs) patients fail to show satisfactory CD4+ T-cell recovery despite virologically effective HAART. We propose that NKp44L, the cellular ligand of an activating natural killer (NK) receptor, expressed only on uninfected bystander CD4+ T cells from HIV-1 infected patients, could play a major role in this phenomenon by sensitizing these cells to NK killing. DESIGN: Phenotype and multifunctional status of CD4+ T cells, especially the subsets expressing and not expressing NKp44L, were characterized for HIV-infected patients receiving HAART for at least 2 years, during which their viral load remained less than 40 copies/ml; 53 were InRs (CD4 cell count always <350 cells/ul), and 82 immunological responders (CD4 cell count always >=350 cells/ul). Flow cytometry determined NKp44L expression in association with specific markers of proliferation, maturation, activation, homeostasis, and intracellular cytokine production. Degranulation of NKp44+ determined the functional capacity of NK cells. RESULTS: InRs exhibited high levels of NKp44L+CD4+ T cells. Compared with NKp44L negative cells, the frequency of naive CD45RA+CCR7+ T cells expressing NKp44L fell (P < 0.001) and their proliferative capacity grew. Moreover, apoptosis and a unique ability to produce multiple cytokines (IL-2, IFN-gamma, and TNF-alpha) without or after phytohemagglutinin or anti-CD3/CD28 stimulation distinguished NKp44L+ T cells. CONCLUSION: InR status is associated to a significant expansion of highly differentiated, multifunctional and apoptotic CD4+ T cells expressing NKp44L. This could explain a rapid CD4+ T-cell turnover in InR preventing immune recovery. These data suggest a new target for developing therapeutic strategies to prevent NKp44L expression and then stimulating immune recovery in InRs. PMID- 24180000 TI - HIV transmission and 24-month survival in a randomized trial of HAART to prevent MTCT during pregnancy and breastfeeding in Botswana. AB - OBJECTIVES: HAART for prevention of mother-to-child HIV transmission (MTCT) may impact long-term survival of women and children. DESIGN: Randomized clinical trial. METHODS: HIV-infected pregnant women with CD4+ cell count at least 200 cells/ul were randomly assigned to abacavir, zidovudine, lamivudine (arm A) or lopinavir-ritonavir, zidovudine-lamivudine (arm B) from week 26 to 34 gestation through planned weaning by 6 months postpartum. Women with baseline CD4+ cell count less than 200 cells/ul received nevirapine-zidovudine-lamivudine indefinitely (Obs arm), as did randomized women later qualifying for treatment. RESULTS: Among 560 randomized and 170 observational women enrolled, there were 14 deaths (1.9%) - one antenatally (Obs), three from delivery to 6 months postpartum (1 arm A, 2 Obs), and 10 from 6 to 24 months postpartum (5 arm A, 3 arm B, 2 Obs). Time to death or CD4+ cell count below 200 cells/ul was shorter in arm A vs. B (P = 0.03). Of the 709 live-born children, 97% breastfed for a median of 5.8 months. Of 37 (5.2%) deaths by 24 months, nine were before breastfeeding initiated (3 arm A, 2 arm B, 4 Obs); six while breastfeeding (1 arm A, 2 arm B, 3 Obs); and 22 after weaning (9 arm A, 11 arm B, 2 Obs). Only eight children (1.1%) were HIV-infected at 24 months (6 arm A, 1 arm B, 1 Obs), all before 6 months. CONCLUSION: Low MTCT was maintained through extended follow-up in all arms. Disease progression appeared slower after discontinuing protease inhibitor-based HAART, but a concerning number of maternal deaths occurred after stopping either regimen. Strategies to improve maternal and child survival in the postintervention period are required. PMID- 24180002 TI - Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype. AB - OBJECTIVES: An efavirenz-based antiretroviral therapy (ART) regimen is preferred for children more than 3 years of age with tuberculosis. However, rifampin, a key component of antituberculosis therapy, induces CYP2B6. An increased dose of efavirenz is recommended in adults weighing more than 50 kg who require rifampin, but there is scant information in children being treated for tuberculosis. DESIGN: Plasma efavirenz concentrations were compared in 40 children during concomitant treatment for tuberculosis and HIV-1, after stopping rifampicin, and in a control group of children without tuberculosis. Associations with antituberculosis treatment, metabolizer genotype (based on CYP2B6 516G->T, 983T >C, and 15582C->T), weight, and time after dose were evaluated. RESULTS: Compared to children with extensive metabolizer genotypes, efavirenz concentrations were increased 1.42-fold (95% confidence interval, CI 0.94-2.15) and 2.85-fold (95% CI 1.80-4.52) in children with intermediate and slow metabolizer genotypes, respectively. Concomitant antituberculosis treatment increased efavirenz concentrations 1.49-fold (95% CI 1.10-2.01) in children with slow metabolizer genotypes, but did not affect efavirenz concentrations in extensive or intermediate metabolizer genotypes. After adjustment for dose/kg, each kilogram of weight was associated with a 2.8% (95% CI 0.9-4.7) decrease in efavirenz concentrations. Despite higher milligram per kilogram doses, a higher proportion of children in the lowest weight band (10-13.9 kg) had efavirenz concentrations less than 1.0 mg/l than larger children. CONCLUSION: Antituberculosis treatment was not associated with reduced efavirenz concentrations in children, which does not support increased efavirenz doses. Children with slow metabolizer genotype have increased efavirenz concentrations during antituberculosis treatment, likely due to isoniazid inhibiting enzymes involved in accessory metabolic pathways for efavirenz. PMID- 24180001 TI - Gut Lactobacillales are associated with higher CD4 and less microbial translocation during HIV infection. AB - OBJECTIVE: Early HIV infection is characterized by a dramatic depletion of CD4 T cells in the gastrointestinal tract and translocation of bacterial products from the gut into the blood. In this study, we evaluated if gut bacterial profiles were associated with immune status before and after starting antiretroviral therapy (ART). DESIGN: We evaluated the gut microbiota of men recently infected with HIV (n = 13) who were participating in a randomized, double-blind controlled trial of combination ART and maraviroc versus placebo and who were followed for 48 weeks. METHODS: To evaluate the gut microbiota of participants, we pyrosequenced the bacterial populations from anal swabs collected before and longitudinally after the initiation of ART. Associations of the gut flora with clinical variables (lymphocyte profiles and viral loads), activation and proliferation markers in peripheral blood mononuclear cells and gut biopsies (measured by flow cytometry) and markers of microbial translocation (lipopolysaccharide and soluble CD14) were performed by regression analyses using R statistical software. RESULTS: Using pyrosequencing, we identified that higher proportions of Lactobacillales in the distal gut of recently HIV-infected individuals were associated with lower markers of microbial translocation, higher CD4% and lower viral loads before ART was started. Similarly, during ART, higher proportions of gut Lactobacillales were associated with higher CD4%, less microbial translocation, less systemic immune activation, less gut T lymphocyte proliferation, and higher CD4% in the gut. CONCLUSION: Shaping the gut microbiome, especially proportions of Lactobacillales, could help to preserve immune function during HIV infection. PMID- 24180004 TI - Resource allocation for HIV prevention: ethics and human rights. PMID- 24180003 TI - Efficacy of a culturally congruent HIV risk-reduction intervention for behaviorally bisexual black men: results of a randomized trial. AB - OBJECTIVES: Black men who have sex with men and women (MSMW) experience high HIV rates and may not respond to interventions targeting gay-identified men. We tested the efficacy of the Men of African American Legacy Empowering Self (MAALES), a multisession, small-group holistically framed intervention designed to build skills, address sociocultural issues, and reduce risk behaviors in black MSMW. DESIGN: From 2007 to 2011, we enrolled 437 black MSMW into a parallel randomized controlled trial that compared MAALES to the control condition, a single, individualized HIV risk-reduction session. METHODS: Participants completed surveys at baseline, 3 months, and 6 months postintervention. We used multiple regressions to compare risk behaviors at follow-up between the intervention and control groups while adjusting for baseline risk behaviors, time between assessments, other covariates, and clustering. We used inverse probability weighting (IPW) to adjust for loss-to-follow-up while carrying out these regressions with the 291 (76.4%) randomized participants who completed at least one follow-up. RESULTS: Participants were largely low-income (55% reported monthly incomes <$1000); nearly half had previously tested HIV positive. At 6 months of follow-up, unadjusted within-group analyses demonstrated reduced risk behaviors for the MAALES but not the control group. Adjusted results indicated significant intervention-associated reductions in the numbers of total anal or vaginal sex acts [risk ratio = 0.61; 95% confidence interval (CI) 0.49-0.76], unprotected sex acts with women (risk ratio = 0.50; 95% CI 0.37-0.66), and female partners (risk ratio = 0.56; 95% CI 0.44-0.72). Near significant reductions were observed for number of male intercourse partners. CONCLUSION: The MAALES intervention was efficacious at reducing HIV risk behaviors in black MSMW. PMID- 24180005 TI - Why vulnerable young women at risk of HIV should be prioritized for access to preexposure prophylaxis. PMID- 24180006 TI - [Pathologic anatomy and cytology: a specialty at the heart of innovations]. PMID- 24180007 TI - [Not Available]. PMID- 24180008 TI - Europe: Swedish success story. PMID- 24180009 TI - Behavioral health data in the electronic health record: privacy concerns slow sharing. PMID- 24180010 TI - Think fungus-prevention and control of fungal infections. PMID- 24180011 TI - Training for healthy older drivers. PMID- 24180012 TI - All together now. PMID- 24180013 TI - Time to talk. PMID- 24180014 TI - Playful paradoxes. PMID- 24180015 TI - Environment: Waste production must peak this century. PMID- 24180016 TI - Climate change: Melting glaciers bring energy uncertainty. PMID- 24180017 TI - Reply to Kawada. PMID- 24180018 TI - Implementing a pressure ulcer prevention bundle into practice. AB - The implementation of a care bundle approach to delivering fundamental care in practice is now a recognised and effective way of translating research into practice, offering consistent care with resulting positive outcomes for the patient. A care bundle consists ofa relatively small number of interventions for every patient to whom the bundle is applied. However, there must be evidence behind each individual intervention to indicate, if delivered, how it will reduce the risk to the patient. This paper reports on a strategy for developing and implementing a pressure ulcer (PU) combined prevention care bundle/ care plan into practice. The effectiveness of the care bundle can be measured when it is in use in the practice setting with an audit tool. PMID- 24180019 TI - Managing highly exuding wounds. PMID- 24180020 TI - Steven Jeffery. PMID- 24180021 TI - Hidradenitis suppurativa: a case study. AB - This article identifies the care and treatment of a male patient during an acute flare up of hidradenitis suppurativa (HS). This article looks at HS, which can be a progressive chronic condition that impacts heavily on all aspects of a patient's quality of life. The choice of a silver alginate dressing proved effective in managing multiple surgical wounds in a comfortable and effective manner, improving the patient's quality of life. PMID- 24180022 TI - A special case: treatment of a patient with necrotising fasciitis. AB - The case study in this article describes the rapid and accurate diagnosis of a critically ill patient with necrotising fasciitis (NF). Full-thickness patchy skin necrosis of the right thigh, buttock and flank was detected on admission. Prompt radical debridement together with aggressive fluid resuscitation and broad spectrum antibiotic administration was initiated. Case ascertainment was used to evaluate the effectiveness of a debridement and wound treatment regime,using a monofilament debridement product, negative wound pressure treatment and, after the critical period had ended, a bio-cellulose+ polyhexamethylene biguanide (PHMB) dressing, followed by a collagen dressing. NF after open haemorrhoidectomy represents a life-threatening complication to otherwise healthy patients. Accurate diagnosis, prompt critical care and surgical treatment, together with debridement using the monofilament product and effective wound bed preparation, lead to a successful outcome. PMID- 24180023 TI - Cavity wounds management: a multicentre pilot study. AB - The objective of this study was to assess acceptability (based on pain at removal), efficacy and tolerance of an absorbent and cohesive rope(UrgoClean Rope, Laboratoires Urgo) in the local management of deep cavity wounds. This study was a prospective, multicentre (13), non comparative clinical study. Patients presenting with an acute or chronic non-infected cavity wound were followed up for four weeks and assessed weekly with a physical examination, in addition to volumetric,planimetric and photographic evaluations. Pain at removal was the primary criterion, assessed on a Visual Analogic Scale. The percentage of the wound surface area reduction and volumetric reduction were considered as secondary efficacy criteria. Forty three patients were included in this study. After one week of treatment dressing removal was painless and continued to be so throughout the period of the trial(four weeks). Median surface area at baseline was 7.74 cm2 and was reduced by 54.5% at week 4 (relative area reduction). Median wound volumetric value was noted 12 ml at baseline and was reduced by 72.7% by the end of treatment. The cohesiveness of the new rope was considered very good by health professionals. No residue was observed on the wound bed during the dressing change with the new rope. There were no adverse events related to the tested rope, during this trial.Pain-free removal associated with good efficacy and tolerance were observed with this new cohesive rope in the healing process of deep cavity wounds and could represent a therapeutic alternative to the usual ropes used in such indications. PMID- 24180024 TI - [Clinical application of a new titanium clip applier in transsphenoidal surgery]. AB - OBJECTIVE: To explore the efficacy and safety of a new titanium clip applier in transsphenoidal surgery for the A specially devised surgery instrument was developed and effectively applied in the management of intercavernous sinus hemorrhage and cerebrospinal fluid (CSF) leakage in transsphenoidal surgery. METHODS: A total of 34 consecutive patients with pituiary adenoma underwent transsphenoidal surgery via a new deep pistol-shaped clip applier versus titanium clip. It was 21 cm long with a rectangular forepart. All patients were evaluated clinically and radiologically at 24 months and magnetic resonance imaging (MRI) was performed at Months 3-18 postoperation. RESULTS: The application of such a new clip applier was effective. No operation was terminated due to ineffective hemorrhage, postoperative CSF leakage or related complications. Postoperative imaging studies revealed no significant evidence of clip artifact. CONCLUSION: The technique of hemostasis and leakage clogging with such a new clip applier is safer, faster and more reliable than its conventional counterpart in achieving dural closure and intercavernous sinus hemostasis. PMID- 24180025 TI - Why biomedical engineers should study biology. PMID- 24180026 TI - The ebb and flow of patent law. PMID- 24180027 TI - Leonardo: the bioengineer. PMID- 24180028 TI - Hugh Cameron Burry. PMID- 24180029 TI - Barrie David Evans. PMID- 24180030 TI - The relationship between personality and sexual motivation: an investigation based on Cloninger's model in nonclinical Italian subjects. AB - BACKGROUND: The aim of this study was to investigate the relationship between personality and sexual motivation according to Cloninger's psychobiological model of the personality. METHODS: Three hundred and ten volunteers recruited among the students of the University of Messina, Italy, participated in the study. All subjects underwent a psychometric examination with the following instruments: Temperament and Character Inventory (TCI) and Sex and the Average Woman (or Man; SAWM). RESULTS: The best negative predictor of Sexual Excitement and Satisfaction was the temperamental dimension Harm Avoidance; as it regards character dimensions, Cooperativeness was the best negative predictor of Sexual Excitement, while Self-Directedness was the best positive predictor of Sexual Satisfaction. CONCLUSIONS: Overall, inhibitory aspects of the personality have deeper effects on sexual motivation than excitatory ones. The results of this research suggest the importance of studying the relationship between personality and sexual behavior. An integrative psychobiological approach to the study of sexual excitement and satisfaction may give a fundamental contribution to the assessment and psychological treatment of predisposing personality factors (like avoidant tendencies) involved in the development and persistence of sexual dysfunction. PMID- 24180031 TI - [My technique: bilateral pulmonary artery banding]. PMID- 24180032 TI - [Variation of the Norwood procedure using a RV-PA conduit method for left heart hypoplastic syndrome]. PMID- 24180033 TI - [Diagnostic imaging Q & A. Inflammatory myofibroblastic tumor]. PMID- 24180034 TI - Effect of patient positioning on left lateral thallium-201 myocardial images. AB - The effect of patient positioning on thallium-201 images in the left lateral projection was evaluated in 28 patients. The left lateral image was performed with the patient on his right side (LLrs) and also supine (LLsup). False-positive inferoposterior defects were reported in five patients (18%) in the LLsup view, but not in the LLrs view. Image quality was better in the LLrs view. The false positive results in the LLsup view may result from two factors: a) overlap of the left hemidiaphragm and myocardium; or b) changes in orientation of the heart in the two lateral positions. Therefore, thallium-201 images in the LL position should be performed with the patient lying on his right side. PMID- 24180035 TI - Left-ventricular peak ejection rate, filling rate, and ejection fraction--frame rate requirements at rest and exercise: concise communication. AB - The effect of framing rate on the measurement of left-ventricular (LV) ejection fraction (EF), peak ejection rate (PER), and peak filling rate (PFR) was evaluated at rest and during exercise in 11 normal subjects and 21 patients who underwent gated equilibrium blood-pool imaging. Left-ventricular time-activity curves were obtained in each subject, at rest and during stress, at temporal resolutions of 10, 20, 30, 40, and 50 msec per frame. Ejection fraction, PER, and PFR were determined for each frame duration. By observing changes in the measured values of these quantities with framing rate we conclude that: a) for the measurement of EF, 50 msec per frame at rest and 40 msec per frame at exercise is sufficient; b) PER requires 40 msec per frame at rest and 20 msec per frame during exercise; and c) for the measurement of PFR, at least 40 msec per frame at rest and 20 msec per frame during exercise are needed. These results should hold for both first-pass and gated equilibrium studies. PMID- 24180036 TI - A comparison between monodisperse Tc-99m-labeled aerosol particles and Kr-81m for the assessment of lung function. AB - A quantitative method for study of the penetration and clearance of inhaled particles (5-micron Tc-99m-labeled polystyrene) in the human lung is described and compared with a Kr-81m technique for ventilation imaging. Volunteer healthy subjects and patients with chronic obstructive airway disease (COAD) were studied. Following inhalation of radioaerosol, data were recorded by a gamma camera/computer system over a period of 6 hr. An aerosol penetration index (API) measures the proportion of aerosol reaching the peripheral region of the lung relative to that deposited in the larger central airways. A significant difference in the mean values of API for both groups was observed. Aerosol clearance rates from the whole lung and from central, intermediate and peripheral compartments of each lung field were studied. The healthy group showed a total clearance rate consistent with data from earlier work; the patients with COAD showed no clearance over the same period. Some healthy subjects were smokers, and differences in their penetration and clearance rates were evident, in spite of normal results from their conventional pulmonary function tests and Kr-81m ventilation studies. The aerosol technique, if carefully controlled, can be a more sensitive index for early lung abnormality than Kr-81m ventilation imaging. PMID- 24180037 TI - Bone scintigraphy in uremic pulmonary calcification. AB - The value of Tc-99m HEDP bone scintigraphy as a means of detecting uremic pulmonary calcification was studied in 30 chronic dialysis patients. A high incidence of currently recognized predisposing factors for metastatic calcification was found and calcification was recorded at other sites. Scintigraphy was performed after reducing background activity by hemodialysis to levels found in normals. From chest images and chest-to-spine activity ratios, evidence of pulmonary calcification could be obtained in only one patient, and subsequent histologic examination revealed extensive calcification. High chest-to spine activity ratios suggested increased pulmonary radionuclide uptake in several other patients, but these findings were not conclusive. These results indicate that uremic pulmonary calcification--which, according to autopsy studies, develops in about 60-75% of dialysis patients--cannot be detected with bone-seeking radiopharmaceuticals, unless the calcification is severe. This is probably due to the unusual crystalline and chemical composition of uremic pulmonary calcification. PMID- 24180038 TI - Localization of gallium-67 in the normally functioning Allografted kidney: concise communication. AB - Radiogallium localization in the normally functioning renal allograft is a normal finding in the immediate postoperative period. The intensity of tracer accumulation decreases with time and is no longer demonstrable by the end of the second postoperative month. PMID- 24180039 TI - Serial Ga-67 citrate imaging in children with neoplastic disease: concise communication. AB - To investigate the role of Ga-67 imaging in children with neoplastic disease, 83 Ga-67 scans, obtained in 46 children with neoplastic disease, were retrospectively analyzed. The series included 19 children who had two to five serial Ga-67 scans while undergoing therapy over periods as long as 4 yr. Three patterns were identified in the children who had serial Ga-67 imaging: a) twelve children with tumors that were initially gallium-avid had normal scans after chemotherapy and/or radiotherapy; b) four children had persistently positive Ga 67 scans while being treated; and c) three children with gallium-avid tumors developed a normal scan after therapy, but later had a gallium-avid recurrence. All 12 children in the first group were alive and clinically disease-free after a mean followup time of 38 mo. Six of the seven children with persistently gallium avid tumors or gallium-avid recurrent tumors died during a mean followup time of 15.5 mo. The results of this small series suggest that further investigation is warranted to determine whether the results of serial Ga-67 imaging have any prognostic significance in children with neoplastic disease. PMID- 24180040 TI - Value of gallium-67 citrate scanning in Crohn's disease: concise communication. AB - A frequent problem in Crohn's disease is the distinction between exacerbated inflammation of the bowel, which can be treated medically, and intra-abdominal abscess, a common complication that requires surgical management. We present evidence that the gallium scan is of value in making this distinction. From a series of 11 studies, negative gallium scans correctly excluded abscess in over half. All patients were symptomatic at the time of the scan. Most patients with active Crohn's disease do not have abnormal gallium uptake and in these patients the gallium scan is useful to exclude the possibility of abscess. PMID- 24180041 TI - Kinetics of the human thyroid trap: experience in normal subjects and in thyroid disease. AB - Kinetics of the thyroid pertechnetate trap were assessed in 85 studies of 39 normal subjects, in five untreated patients with Graves' disease (two of them both before and after treatment), in two hypothyroid patients, and in one patient each with Hashimoto's thyroiditis of recent onset, subacute thyroiditis, and massive anaplastic carcinoma. In normal subjects, the effects of sex, time of day, and the order of experimental sessions were studied. For the analysis, a three-compartment model was assumed for all studies. Data on thyroidal and neck background pertechnetate were collected with a multi-crystal camera during 40 min after i.v. injection. Input to the two thyroidal compartments in the model--the follicular cell, V2, and the colloidal plasma-equivalent space, V3--is a multi exponential function of plasma radioactivity, V1, which was measured frequently. None of the model parameters was systematically affected by the sex of the subject, and order of session did not consistently alter any parameter, except for V3, which was greater in session 2 than in session 1. That increase was not consistent among data subsets, however, and is believed to be spurious. Time of day affected only the exit rate constant from the colloid, lambda23, which is increased later in the day (P < 0.02). Distribution of the normal parameters was more nearly log-normal than normal. After 5% were excluded at the high end and 5% at the low end, the range for a parameter, p, was found empirically to be: antiln (mean ln p - 1.7 s.d. ln p), and antiln (mean ln p + 1.5 s.d. ln p). In Graves' disease, V2 is increased (P < 0.02), but the increases in V3 and in lambda21 (the clearance into the thyroid from serum) are much more dramatic (P < 10(-8)). After treatment, V3 and lambda21 fell toward normal. The hypothyroid patients showed no trap activity, and the trap was normal in the patient with early Hashimoto's thyroiditis. The patients with subacute thyroiditis and with anaplastic carcinoma had increases in V2, V3, and lambda21, but the pattern differed from that seen in Graves' disease. PMID- 24180042 TI - A comparison of radiotracer and biochemical methods for the quantitation of experimental myocardial infarct weight: in vitro relationships. AB - Anterior myocardial infarction (MI) was produced in conscious dogs to evaluate the relationships among: a) cardiac technetium-99m stannous pyrophosphate (TcPPi) accretion, b) creatine phosphokinase (CPK) depletion, and c) postmortem MI weight, infarct structure, and histology. In vitro, there was a close relationship between measured MI weight and MI weight calculated by the TcPPi accretion (r = 0.96) or CPK depletion (r = 0.93) in representative "cross sectional" MI samples. Cardiac TcPPi accretion and CPK depletion showed a curvilinear relationship over the spectrum of tissue samples. Adjacent to infarcts, there was marked TcPPi uptake and modest CPK depletion where histology suggested ischemia without infarction. Within infarcts, microscopically visible calcium was rare in this series, suggesting little intracellular calcium accumulation, insensitivity of the von Kossa staining technique, and/or other cellular mechanisms to account for Tc-PPi uptake in this conscious dog model without reperfusion. PMID- 24180043 TI - Radioimmunoassay for carcinoembryonic antigen as an adjunct to liver scan in the detection of liver metastases from digestive-tract cancer. AB - In a series of 327 patients with primary GI malignancies, the occurrence of hepatic metastases was correctly detected in 70% of 113 cases by focal defects in the radiocolloid scintiscan. Only 1% of false positives were observed among the 214 patients without hepatic metastases. For these patients, the predictive value of the liver scan was 97%, and the overall accuracy, 89%. A composite test formed by disjoining focal radionuclide defects with the combination of elevated CEA and hepatomegaly, or elevated CEA and high alkaline phosphatase activity, exhibited a predictive value of 92% and an overall accuracy of 92%. Formation of such a composite test may be useful for preserving high accuracy when very strict scintigraphic criteria for metastases are employed. PMID- 24180044 TI - Radionuclide demonstration of urinary extravasation with ureteral obstruction. AB - Two cases of urinary extravasation with ureteral obstruction demonstrated by the radionuclide studies are reported. The value of radionuclide studies in patients with renal transplantation has been reported previously, but studies in patients without transplantation have rarely been described in the literature. Ureteral obstruction may cause urinary extravasation, which may be demonstrated by radiouclide studies even when radiologic studies are inconclusive. In one case, urinary extravasation was detected in the sitting position but not in the supine position. Renal imaging should probably be performed not only with multiple projections but also in different positions. PMID- 24180045 TI - Positive Ga-67 citrate scan in retroperitoneal fibrosis. AB - A patient with retroperitoneal fibrosis was evaluated by Ga-67 citrate imaging. The radionuclide study accurately demonstrated the location and extent of the disease. PMID- 24180046 TI - Brain and lung involvement of mycosis fungoides demonstrated by radionuclide imaging. AB - A patient with advanced mycosis fungoides developed neurologic and respiratory symptoms and signs following multiple courses of chemotherapy and radiotherapy. Various repeated diagnostic procedures--including cranial computerized tomography and fiberoptic bronchoscopy with transbronchial lung biopsy--failed to demonstrate an unusual involvement of the brain and lungs by mycosis fungoides. Radionuclide brain imaging and gallium imaging of the lungs demonstrated diffuse lesions confirmed at autopsy. PMID- 24180047 TI - Effect of iron deficiency on the biodistribution and tumor uptake of Ga-67 citrate in animals: concise communication. AB - To investigate the effect of iron deficiency on the biodistribution and tumor uptake of Ga-67 citrate, 20 weanling Sprague-Dawley rats were maintained for 6-8 wk on a low-iron diet. Eighteen littermates were maintained on a normal iron diet and served as controls. Animals received 10 microCi Ga-67 citrate, and urine and feces were collected for 48 hr. The animals were then killed, tissue samples were obtained, and serum iron and unsaturated iron-binding capacity (UIBC) were measured. The accumulation of Ga-67 in the liver and spleen (% ID/g) was markedly increased in iron-deficient animals and urinary excretion was reduced. Tumor uptake was not significantly different in iron-deficient and control animals, but tumor-to-blood ratios were elevated (p < .001) in the iron-deficient animals because of low blood levels of Ga-67. The liver and spleen accumulation of Ga-67 correlated significantly (p < .001) with the UIBC. The results show that iron deficiency alters the distribution of Ga-67 citrate, and suggest that the variable liver-spleen uptake seen in clinical Ga-67 images may be explained, in part, by changes in serum iron and UIBC. PMID- 24180048 TI - Effect of desferoxamine on tissue and tumor retention of gallium-67: concise communication. AB - Desferoxamine (DEF) was administered intramuscularly (0.25 mg/g body weight) to mice harboring a Cloudman's melanoma S-91 3 hr before, simultaneously with, and 3 hr after i.v. injection of Ga-67 citrate (approximately 1 microCi/g body weight). Relative Ga-67 retention was compared with that in non-DEF controls at 24 hr. The chemical nature of Ga-67 excreted in urine following DEF was also studied in healthy mice. Desferoxamine administered 3 hr before Ga-67 had little effect on radiogallium localization; administration coincident with or 3 hr after radiogallium resulted in decreased retention at 24 hr. The effect was most profound when Ga-67 and DEF were administered simultaneously. In DEF-injected animals Ga-67 was excreted in the urine as a Ga-67-DEF complex. When DEF was administered 3 hr after Ga-67, there was a trend to greater tumor-to-blood activity ratios (.2 > p > .1). PMID- 24180049 TI - Effect of spatial distortion on anger camera field-uniformity correction: concise communication. AB - The field uniformity of a computer-assisted Anger-camera system, and the effect of field correction on quantitative data, have been studied. Our results show that the total counts of a source imaged across the crystal face varies with a s.d. of only 2.0%, but routine flood-field correction degrades the data to a s.d. of 9.4%. On the other hand, the area of a source 1.75 in. in diameter, imaged across the crystal face, varies with a s.d. of 9.7%. We conclude that the major source of field nonuniformity for an Anger camera is spatial distortion and not varying sensitivity across the crystal face. PMID- 24180050 TI - Cellular radiation doses of labeled neutrophils and platelets. AB - Radiation doses were calculated for human neutrophils and platelets labeled by phosphorus-32, chromium-51, gallium-67, technetium-99m, indium-111, and mercury 197. The cells were assumed to be spheres with radii of 4.87 microm and 1.07 microm, respectively, with all the radioactivity at either the center or uniformly distributed on the surface. Surprisingly high dose rates were found, due primarily to the small mass and therefore high radioactive concentration and to low-energy electrons, such as Auger electrons. Average total doses to these cells during their effective lifetime in the blood are presented. PMID- 24180051 TI - Distortion of bar-phantom image by collimator. AB - Distortion of the bar-phantom scintiphoto using the medium-energy collimator may lead to the misconception that the resolution of the medium-energy collimator is better than that of the low-energy collimator. The distortion is illustrated by superposition of the transparent films of the bar-phantoms and collimator. PMID- 24180052 TI - Automatic reservoir for serial pipetting. AB - An automatic reservoir for serial pipetting was constructed and used in radioimmunoassay determinations. This device features negligible priming volume, minimal solution loss, and lowered overall cost. In our experience, it has proven valuable when used with an automatic pipetting station. This apparatus has not affected the precision or accuracy of the procedure. It has made it possible to economize on costly antibody reagents supplied with radioimmunoassay kits, especially in use with low-volume assays. PMID- 24180053 TI - Optimizing the detection of hepatic metastases. PMID- 24180054 TI - Hypothyroidism after radioiodine treatment. PMID- 24180055 TI - Ventilation studies and the perfusion lung scan. PMID- 24180056 TI - Technical errors in scintigraphic measurements of gastric emptying. PMID- 24180057 TI - Ventilation studies performed after the perfusion lung scan. PMID- 24180058 TI - Echography compared with radiotracer scanning for parathyroid adenoma. PMID- 24180059 TI - The bone scan in thyroid cancer. PMID- 24180060 TI - Regional delivery of radioaerosol. PMID- 24180061 TI - The role of gap analyses in energy assurance planning. AB - Energy-related emergencies, such as power outages or interruptions to other energy supplies, can arise from a number of factors. Common causes include severe weather events--such as snowstorms, hurricanes, or summer storms with strong winds--as well as energy infrastructure that is overburdened, aging, or in need of repair. As past experience indicates, jurisdictions will continue to experience severe weather events, as well as confront infrastructure issues that make future power outages likely. As a result, state and local governments have turned to energy assurance planning, an energy-specific form of planning that helps jurisdictions prepare for and recover from energy emergencies. Energy assurance recognizes that power loss/disruption cannot be eradicated completely, but jurisdictions can mitigate the impact of power loss through effective planning. This article discusses the role of energy assurance planning and provides a description of what energy assurance means and why developing such plans at the state and local levels is important. In addition, this article discusses the role of statutory gap analyses in energy assurance planning and discusses how a gap analysis can be used by planners to identify trends and gaps in energy assurance. To provide context, a recently conducted statutory gap analysis analyzing national emergency backup power trends is provided as a case study. A summary of this project and key findings is included. Finally, this article briefly touches on legislation as an alternative to energy assurance planning, and provides summaries of recent legislative proposals introduced in the aftermath of Hurricane Sandy. PMID- 24180062 TI - Emergency warning for people with disabilities. AB - The intent of this article is to assess the current state of Emergency Warning capabilities in the United States and make recommendations on what needs to be done to cost effectively establish a National Emergency Warning System to best serve the people of the United States, including those with disabilities. As part of this assessment, terminology will be defined, existing systems will be examined, critical needs and functions will be explained, and recommendations made for a system to deliver emergency messages to those people immediately at risk from natural and human-caused disasters in a timely and effective manner, regardless of location or situational circumstance. The assessment will include the needs and available technologies for delivering emergency warnings to people with disabilities, which are generally little understood, poorly addressed, and often ignored. PMID- 24180063 TI - Accounting for vulnerable populations in rural hazard mitigation plans: results of a survey of emergency managers. AB - Rural areas of the United States are uniquely vulnerable to the impacts of natural disasters. One possible way to mitigate vulnerability to disasters in rural communities is to have a high-quality hazard mitigation plan in place. To understand the resources available for hazard mitigation planning and determine how well hazard mitigation plans in rural counties meet the needs of vulnerable populations, we surveyed the lead planning or emergency management official responsible for hazard mitigation plans in 96 rural counties in eight states in the Southeastern United States. In most counties, emergency management was responsible for implementing the county's hazard mitigation plan and the majority of counties had experienced a presidentially declared disaster in the last 5 years. Our research findings demonstrated that there were differences in subjective measures of vulnerability (as reported by survey respondents) and objective measures of vulnerability (as determined by US Census data). In addition, although few counties surveyed included outreach to vulnerable groups as a part of their hazard mitigation planning process, a majority felt that their hazard mitigation plan addressed the needs of vulnerable populations "well" or "very well." These differences could result in increased vulnerabilities in rural areas, particularly for certain vulnerable groups. PMID- 24180064 TI - Communication, information seeking, and evacuation plans for a disaster using Community Assessment for Public Health Emergency Response in the GulF Coast counties of Alabama and Mississippi, 2011. AB - OBJECTIVE: To determine communication, information seeking, and evacuation behaviors of coastal residents in a disaster-prone area. DESIGN: A two-stage, probability sampling design to select 210 households in each assessment area was used. Data were analyzed using a weighted cluster analysis to report projected households for each assessment area. SETTING: Public health services areas of coastal Alabama and Mississippi. PARTICIPANTS: Eligible respondents were 18 years of age or older, had lived in the community for at least 30 days, and were residents of the selected household. MAIN OUTCOME MEASURES: Evacuation propensity, primary communication forms, primary information forms, and special needs. RESULTS: Most coastal residents would evacuate if recommended by public health authorities. Fewer residents had landlines (45.9-58.8 percent) compared to residents using cellular or mobile phone service only (84.3-95.8 percent), and these residents were significantly older compared to non-landline owning residents. Most residents own pets (61.9-70.1 percent). CONCLUSIONS: Our assessment suggests that the majority of Alabama and Mississippi coastal residents plan to evacuate during a disaster if recommended by public health authorities. However, public health authorities should strive to evaluate multiple forms of communication to disseminate disaster preparedness and response messages to reach all vulnerable residents, especially in situations where electric services might be compromised. Emergency preparedness personnel should also be prepared for a large pet population in the event of an evacuation. PMID- 24180065 TI - The road less taken: modularization and waterways as a domestic disaster response mechanism. AB - Preparedness scenarios project the need for significant healthcare surge capacity. Current planning draws heavily from the military model, leveraging deployable infrastructure to augment or replace extant capabilities. This approach would likely prove inadequate in a catastrophic disaster, as the military model relies on forewarning and an extended deployment cycle. Local equipping for surge capacity is prohibitively costly while movement of equipment can be subject to a single point of failure. Translational application of maritime logistical techniques and an ancient mode of transportation can provide a robust and customizable approach to disaster relief for greater than 90 percent of the American population. PMID- 24180066 TI - Location selection criteria for a second data center or off-site storage of materials. AB - As organizations develop secondary data centers, it is critical that they be placed in locations that serve the organization yet do not have a shared risk with the primary data center. The organization needs to consider factors or guidelines which mitigate potential issues that could affect both the primary and secondary data center. It is impossible to eliminate all risk to a single data center but an organization needs to ensure that at least one data center remains operable. The article will propose that data centers be located 50 km or approximately 30 miles apart. The proposal is supported by evaluating earthquake intensity maps that will show that earthquakes damage drops to relatively safe levels after the 30 miles from the epicenter. The article will show that other environmental factors such as power, floods, fire, transportation, fire, and soil are also mitigated by a 30-mile separation guideline. PMID- 24180067 TI - SNP genotyping with the next generation of CGH microarray. AB - Enabling the simultaneous detection of CNV and copy-neutral aberrations within one test, the combined aCGH and SNP array has the potential to vastly improve both workflow efficiency and productivity within the cytogenetics research laboratory. The applications of the combined array are summarized in Figure 4. Standard aCGH is a rapid, sensitive, and high-throughput approach for CNV detection, and although central to many cytogenetic studies, approximately 80% of developmental disorder samples yield a normal result, highlighting the need for additional information. Incorporating SNP analysis into the aCGH array provides insight into the underlying genetic causes, while retaining the benefits of the well-established aCGH platform. In many cases this removes the need for time consuming follow-up studies, and is particularly beneficial considering the costs and labor involved in a high-resolution SNP array. Due to the prevalence of ancestral ROH, it is clear that there is little additional benefit to analyzing ROH at high resolution, which adds to the complexity of the data, increasing the laboratory workload. The most effective combined aCGH and SNP arrays instead provide sufficient resolution to detect abnormally long ROH stretches present in UPD or consanguineous samples, while excluding standard length ancestral ROH that are not biologically relevant, without compromising CNV detection. his new generation of combined aCGH and SNP array presents a high-throughput and efficient alternative to high-resolution SNP platforms, incorporating SNP analysis into existing aCGH workflows, and yielding unique biological insights with minimal additional cost. PMID- 24180069 TI - Addressing challenges of molecular diagnostics through LIS. PMID- 24180068 TI - Molecular testing moves to Main street. PMID- 24180070 TI - A case for point-of-care testing for HbA1c. PMID- 24180072 TI - Recent studies in virology: a roundup. PMID- 24180071 TI - New guidelines to evaluate and manage chronic kidney disease. PMID- 24180073 TI - Automation in the clinical lab: a reliable tool gets even better. PMID- 24180074 TI - Real-time PCR II: probe methods. PMID- 24180076 TI - Where are they now? API medical laboratory science scholars. PMID- 24180075 TI - Proposed, enacted, and future laboratory legislation. PMID- 24180077 TI - Dementia diagnostics: preparing for a pending healthcare epidemic. PMID- 24180078 TI - Blood biomarkers as diagnostic tools for Alzheimer's disease. PMID- 24180079 TI - Five good reasons: the argument for pipetting technique training. PMID- 24180080 TI - The stage 3 meaningful use preliminary recommendations: concerns are being raised. PMID- 24180082 TI - [Submicron particles in smoke resulting from welding alloys and cast alloy in metalworking industry]. AB - BACKGROUND: The toxicity of welding fumes depends on both chemical composition and ability to penetrate and deposit deeply in the lungs. Their penetration and deposition in the regions of the respiratory system is mainly determined by their size. OBJECTIVES: The knowledge of the size distribution of welding fumes is a crucial information towards the estimate of the doses of toxic compounds delivered into the respiratory tract. METHODS: Particle number size distribution was continuously measured during different welding operations by means of a Fast Mobility Particle Sizer, which counts and classifies particles, according to their electrical mobility, in 32 size-channels, in the range from 5.6 to 523 nm, with is time resolution. RESULTS: The temporal evolution of submicrometric particles (6-523 nm), nucleation mode particles (6-16 nm) and the fraction 19-523 nm before, during and after the welding operations performed with/without local exhaust ventilation are reported and extensively discussed. Before welding, nucleation mode particles represent about 7% of submicrometric particles; after about 40 s from the welding start, the percent contribution of nucleation mode particles increases to 60%. Total and nucleation mode particle concentrations increase from 2.1 x 10(4) to 2.0 x 10(6) and from 1.6 x 10(3) to 1.0 x 10(6), respectively. CONCLUSIONS: The temporal variation of the particle number size distribution across the peaks, evidences the strong and fast-evolving contribution of nucleation mode particles: peak values are maintained for less than 10 s. The implication of such contribution on human health is linked to high deposition efficiency of the submicrometric particles in the alveolar interstitial region of the human respiratory system, where gas exchange occurs. PMID- 24180083 TI - Post-occupational health surveillance of asbestos workers. AB - BACKGROUND: Italian law requires an extensive health surveillance of workers after cessation of their employment status in the case of occupational exposure to carcinogens, including asbestos. Nonetheless, Italian law does not specify the timeframe of these clinical checks, nor who has financial and organizational responsibility for this surveillance. A literature search confirmed a lack of consensus around the objectives and methods to follow up workers with past occupational exposure to asbestos. OBJECTIVES: To develop an updated evidence based methodology for an appropriate health surveillance programme. METHODS: We present an overview of the field experience developed by the Veneto Region from 2000 to 2011, and new studies that could contribute to establishing a national policy for the medical surveillance of workers with past asbestos exposure. RESULTS: There were three specific topics: (1) definition of a reliable method to identify asbestos workers (through multiple sources and procedures that meet current confidentiality regulations); (2) detection of asbestos fibres in biological media (to support the etiological diagnosis of asbestos-related diseases); (3) creation of a national protocol of health surveillance (through the assessment of policies developed by other Regions in this field, and recruiting from these regions a cohort of past-exposed workers: the epidemiological study should offer relevant suggestions for specific surveillance approaches, based on either estimated cumulative asbestos exposure or detection of x-ray patterns of pleural plaques and/or asbestosis). CONCLUSIONS: These studies will support the Regions in setting up health care policies directed at workers with past asbestos exposure. PMID- 24180084 TI - "Phthisiophobia": the difficult recognition of transmission of tuberculosis to health care workers. AB - BACKGROUND: Even if the contagious nature of tuberculosis was universally accepted during the nineteenth century, its transmission to health care workers (HCWs) was initially denied by the scientific community. Working among TB patients was not considered dangerous for healthy adults, so the potential risks for HCWs were branded as unwarranted "phthisiophobia" (fear of contracting tuberculosis). OBJECTIVES: This study aims at analyzing the problem of tuberculosis transmission among health care workers from an historical perspective, particularly highlighting the contribution made by the Italian Occupational Medicine community. METHODS: Scientific literature and historical sources on different theories regarding tuberculosis transmission were investigated, specially focusing on the period at the turn of the 19th and 20th centuries. RESULTS: At the beginning of the twentieth century, Luigi Devoto (1864 1936), an Italian pioneer in the field of Occupational Medicine, was one of the first scientists to conduct research on the transmission of tuberculosis among nurses. Since the 1920s several studies, conducted mainly on medical and nursing students, confirmed the risk for HCWs. However an international consensus on this issue was only achieved during the 1950s, when the institution of mandatory chest radiographs on admission for all patients significantly decreased the cases of tuberculosis among HCWs. CONCLUSIONS: Devoto was one of the first scholars who postulated the transmission of tuberculosis to HCWs. He also theorized that hospital personnel with active disease could also be a source of contagion to patients. Nowadays, "third party risk" and latent tuberculosis infection pose a new challenge for occupational physicians in hospitals. PMID- 24180085 TI - The influence of operational and organizational stressors on the well-being of municipal police officers. AB - BACKGROUND: Helping professions are at a high risk of developing occupational stress that can cause negative effects at individual and organizational levels. OBJECTIVES: This article attempts to examine the presence of operational and organizational stressors as potential predictors of burnout and psychosomatic symptoms among municipal police officers. METHODS: A cross-sectional study of municipal police officers working in a town in Northern Italy was conducted. A self-report questionnaire was administered to all the officers serving the population of this town (N = 88). RESULTS: Regression analyses revealed that organizational stressors affected emotional exhaustion and cynicism, whereas operational stressors were associated with psychosomatic symptoms. CONCLUSIONS: These findings suggest that operational and organizational stressors can affect the level of psychosomatic well-being of municipal police officers, but at the same time reveal the existence of their specific effects on the outcome variables. In this perspective, individual psychological support and group interventions should be carried out not only to deal with traumatic events but also to manage chronic stressors. This is one of the first studies in Italy investigating municipal police officers' well-being as potentially related to specific job stressors. Nevertheless, our results are based on police officers employed by the municipality of a single town; it would be therefore useful to extend the research to larger samples. PMID- 24180086 TI - The effect of a multimodal group programme in hospital workers with persistent low back pain: a prospective observational study. AB - BACKGROUND: Low Back Pain (LBP) is a very common disorder in hospital workers. Several studies examined the efficacy of multimodal interventions for health care providers suffering from LBP; nevertheless their results did not appear to be consistent. OBJECTIVE: The aim of the study was to determine the effect of a multimodal group programme (MGP) on pain and disability in a sample of hospital workers with persistent LBP. METHODS: A prospective cohort study was conducted to compare baseline measurements with changes over an eight-month period. The study focused on 109 workers suffering from persistent LBP with or without radiating pain. 62 nurses and 47 blue collars not involved in health care. The MGP consisted of six group sessions including supervised exercises, an at-home programme and ergonomic advice. The primary outcome measurement was the level of disability recorded with the Roland & Morris Disability Questionnaire, while the secondary outcome measurement was the evaluation of lumbar physical discomfort with the Visual Analogue Scale. Data were analyzed using the Multiple Imputation method for dropouts. RESULTS: At the short-term follow-up participants showed a statistically significant reduction (from baseline) of all outcome measurements, particularly for the nurses group. Moreover, about a third of the subjects showed clinically significant improvement. No significant reduction in pain and disability (from baseline) was observed at the mid-term follow-up in either group. CONCLUSIONS: An MGP dedicated to hospital workers seems to be partially useful only for short-term follow-up, particularly for health care providers. PMID- 24180087 TI - Analysis of appeals against the ruling of occupational physicians lodged with the Prevention and Occupational Epidemiology Operative Unit, ASP Palermo (Palermo Health Authority), from 2008-2010. AB - INTRODUCTION: The responsibility of the Department for Prevention and Safety at the workplace of the Palermo Health Authority (ASP) is to monitor and coordinate the activity of occupational physicians operating in Palermo and its province. One of its obligations is to examine appeals "against the judgment of occupational physicians", "..and, after carrying out further investigation, confirm, modify or reverse the ruling itself" (art. 41, par. 6, legislative Decree 81/08). OBJECTIVES: The purpose of this study was to analyze the appeals lodged against a judgment of fitness for work" submitted to the "Health Prevention and Occupational Epidemiology Operative Unit" of the Department of Prevention and Safety at the Workplace of the ASP Palermo, from 2008 to 2010. METHODS: The total number of appeals lodged during the three-year period was 211, 174 of which were finalized. RESULTS: The most frequent job category among the appellants was that of blue-collar workers, in various sectors, covering 44.5% of the subjects under study (93 cases). In 64.2% of the processed appeals (131 cases), the judgment of the physician was modified, while in the remaining 36.8% (73 cases) it was confirmed. The work fitness judgment with restrictions was the category against which most appeals were lodged, and the diseases in question mostly concerned the osteoarticular and cardiovascular systems. CONCLUSION: In a context of continuous change in the labour field and the related risks to the health and safety of workers, the occupational physician must approach the worker in a comprehensive manner, through an assessment of the possible health problems and the working environment in which he/she operates. PMID- 24180088 TI - [Centrality of the role of the company physician in preventive care: the point of view of the Societa Nazionale degli Operatori della Prevenzione. The role of the company physician]. PMID- 24180089 TI - [Not Available]. PMID- 24180090 TI - [Author's reply]. PMID- 24180091 TI - Applying a community resilience framework to examine household emergency planning and exposure-reducing behavior among residents of Louisiana's industrial corridor. AB - Residents facing environmental hazards can take steps to reduce their exposure risks, and these actions may be considered adaptations that can enhance the overall resilience of communities. Applying concepts from social-ecological resilience theory, the authors examine emergency planning and exposure-reducing behaviors among residents of the upper Industrial Corridor of Louisiana and explore the extent to which the behaviors are associated with key theoretical influences on community resilience: exposure, vulnerability, and the "adaptive capacity" of residents. The behaviors of interest are adoption of a household emergency plan in the case of acute exposure events (like chemical spills), and limiting outdoor activities in response to Air Quality Index reports, thus potentially reducing chronic exposure risks. Statistical analyses indicate that adaptive behaviors are associated both with greater exposure to hazards and confidence in one's knowledge and ability to reduce exposure risks. Thus, the study yields evidence that "adaptive capacity" is particularly relevant to understanding and encouraging household emergency planning. Residents who believe that they are well-informed about risk-reducing strategies, regardless of education or income, were found to be more likely to have adopted these measures. Evidence that knowledge and confidence levels are linked to adaptive behaviors is good news for those working in public education and outreach programs, as these are attitudes and skills that can be nurtured. While factors associated with exposure and vulnerability to hazards are difficult to change, knowledge of risk reducing strategies and confidence in one's abilities to reduce exposure risks can be improved through well-designed public education efforts. PMID- 24180092 TI - Local hazard mitigation plans: a preliminary estimation of state-level completion from 2004 to 2009. AB - According to the Disaster Mitigation Act of 2000 and subsequent federal policy, local governments are required to have a Hazard Mitigation Plan (HMP) written and approved by the Federal Emergency Management Agency (FEMA) to be eligible for federal mitigation assistance. This policy took effect on November 1, 2004. Using FEMA's database of approved HMPs and US Census Bureau's 2002 Survey of Local Governments, it is estimated that 3 years after the original deadline, 67 percent of the country's active local governments were without an approved HMP. A follow up examination in 2009 of the eight states with the lowest completion percentages did not indicate significant improvement following the initial study and revealed inconsistencies in plan completion data over time. The completion percentage varied greatly by state and did not appear to follow any expected pattern such as wealth or hazard vulnerability that might encourage prompt completion of a plan. Further, the results indicate that -92 percent of the approved plans were completed by a multijurisdictional entity, which suggests single governments seldom complete and gain approval for plans. Based on these results, it is believed that state-level resolution is not adequate for explaining the variation of plan completion, and further study at the local level is warranted. PMID- 24180093 TI - Comparison of ArcToolbox and Terrain Tiles processing procedures for inundation mapping in mountainous terrain. AB - Floodplain management consists of efforts to reduce flood damage to critical infrastructure and to protect the life and health of individuals from flooding. A major component of this effort is the monitoring of flood control structures such as dams because the potential failure of these structures may have catastrophic consequences. To prepare for these threats, engineers use inundation maps that illustrate the flood resulting from high river stages. To create the maps, the structure and river systems are modeled using engineering software programs, and hydrologic events are used to simulate the conditions leading to the failure of the structure. The output data are then exported to other software programs for the creation of inundation maps. Although the computer programs for this process have been established, the processing procedures vary and yield inconsistent results. Thus, these processing methods need to be examined to determine the functionality of each in floodplain management practices. The main goal of this article is to present the development of a more integrated, accurate, and precise graphical interface tool for interpretation by emergency managers and floodplain engineers. To accomplish this purpose, a potential dam failure was simulated and analyzed for a candidate river system using two processing methods: ArcToolbox and Terrain Tiles. The research involved performing a comparison of the outputs, which revealed that both procedures yielded similar inundations for single river reaches. However, the results indicated key differences when examining outputs for large river systems. On the basis of criteria involving the hydrologic accuracy and effects on infrastructure, the Terrain Tiles inundation surpassed the ArcToolbox inundation in terms of following topography and depicting flow rates and flood extents at confluences, bends, and tributary streams. Thus, the Terrain Tiles procedure is a more accurate representation of flood extents for use by floodplain engineers, hydrologists, geographers, and emergency managers. PMID- 24180094 TI - Self-reported training needs of emergency responders in disasters requiring military interface. AB - OBJECTIVE: The purpose of this study is to identify perceived training needs of emergency responders to understand their needs to interface effectively with military operations for emergency response in the event of a disaster. DESIGN: A Web-based survey with civilian medical practitioners and public health professionals was conducted to identify their perceptions of training needs related to civilian-military interface in disaster response. SETTING: Lists of potential survey participants were obtained from local health departments and LISTSERVS in the two regions of interest: the South and the Midwest. PARTICIPANTS: Participants (n = 673) included health practitioners (medical, emergency care, and public health personnel) from hospitals, public service, and other nonprofit and governmental workers. MAIN OUTCOME MEASURE(S): Outcomes include perceived training needs, barriers to training, and preferred training formats and modalities. RESULTS: Data indicate a perceived knowledge gap of civilian healthcare providers to interface effectively with military healthcare providers. Nearly three-fourths of respondents did not feel well-trained to work with the military during a disaster response or were unsure if they were well trained. Key areas for training include communication, chain of command during a disaster, and logistics of working with military personnel. Barriers to training include expense; ineffective, boring formats; and excessive time requirements. Most respondents favor interactive exercises rather than didactic training. CONCLUSIONS: Poor communication and lack of familiarity with military operations create barriers to effective coordinated response between military units and civilian responders in federal disaster response. Identifying gaps and training needs for these responders have far-reaching implications in public health's ability to coordinate medical response as part of Emergency Support Function-8. PMID- 24180095 TI - Building community resilience to disasters through a community-based intervention: CART applications. AB - The Communities Advancing Resilience Toolkit (CART)* is a community-driven, publicly available, theory-based, and evidence-informed community intervention designed to build community resilience to disasters and other adversities. Based on principles of participatory action research, CART applications contribute to community resilience by encouraging and supporting community participation and cooperation, communication, self-awareness, and critical reflection. The primary value of CART lies in its ability to stimulate analysis, collaboration, skill building, resource sharing, and purposeful action. In addition to generating community assessment data, CART can be used as a vehicle for delivering other interventions and creating sustainable capacity within communities. Two models for CART implementation are described. PMID- 24180096 TI - Analyzing after-action reports from Hurricanes Andrew and Katrina: repeated, modified, and newly created recommendations. AB - Thirteen years after Hurricane Andrew struck Homestead, FL, Hurricane Katrina devastated the Gulf Coast of Mississippi, Alabama, and southeastern Louisiana. Along with all its destruction, the term "catastrophic" was redefined. This article extends the literature on these hurricanes by providing a macrolevel analysis of The Governor's Disaster Planning and Response Review Committee Final Report from Hurricane Andrew and three federal after-action reports from Hurricane Katrina, as well as a cursory review of relevant literature. Results provide evidence that previous lessons have not been learned or institutionalized with many recommendations being repeated or modified. This article concludes with a discussion of these lessons, as well as new issues arising during Hurricane Katrina. PMID- 24180097 TI - Forensic entomology investigations from Doctor Marcel Leclercq (1924-2008): a review of cases from 1969 to 2005. AB - Dr. Marcel Leclercq was a pioneer in the field of forensic entomology. He has provided his knowledge of insect biology to many forensic cases, and most of them have found the way to publication. Most of the articles he has written were focused on individual cases, and despite the abundance of entomoforensic investigations he conducted, no synthesis has been published. This article summarizes 36 yr of forensic entomological investigations in temperate Europe, mainly in Belgium. Dr. Leclercq's work includes 132 entomological cases involving 141 human corpses found in various death scenes. Under certain conditions, insect specimens found at death scene can provide information on when (postmortem interval estimation), where and how a person died. More or less 100 insect species associated with a dead body have been identified by Dr. Leclercq. PMID- 24180098 TI - The effect of temperature on Leishmania (Kinetoplastida: Trypanosomatidae) development in sand flies. AB - The spread of leishmaniasis to areas where it was previously considered nonendemic has been recently found in the New and Old Worlds, and climate changes are suspected as a crucial factor responsible for this spread. Ambient temperature is known to significantly affect the metabolism of sand flies and their developmental times, but little is known about the effect of temperature on the Leishmania life cycle in vectors. This study assesses the effect of temperature on the development of two closely related New World Viannia species, Leishmania braziliensis and Leishmania peruviana, in the permissive vector Lutzomyia longipalpis, and on the development of New and Old World Leishmania infantum in its natural vectors Lu. longipalpis and Phlebotomus perniciosus, respectively. The mountain species L. peruviana developed well in sand fly females kept at 20 degrees C, whereas at 26 degrees C, most infections were lost during the defecation ofbloodmeal remains; this suggests an adaptation to the slower metabolism of sand flies living at lower ambient temperature. On the contrary, L. infantum and L. braziliensis developed well at both temperatures tested; heavy late-stage infections were observed in a majority of sand fly females maintained at 20 degrees C as well 26 degrees C. Frequent fully developed infections of L. infantum and L. braziliensis at 20 degrees C suggest a certain risk of the spread of these two Leishmania species to higher latitudes and altitudes. PMID- 24180099 TI - First description of the nymph and larva of Dermacentor raskemensis (Acari: Ixodidae), parasites of pikas and other small mammals in Central Asia. AB - Dermacentor raskemensis Pomerantzev, 1946 is one of the rare Asian species in this genus. The immature stages of this species have never been described. Reexamination of D. raskemensis holdings stored in the United States National Tick Collection revealed a collection lot containing reared nymphs and larvae of this species. This collection made it possible for us to find numerous nymphs and larvae of D. raskemensis among previously unidentified material collected in the field. Both immature stages of D. raskemensis are described here for the first time. Nymphs of D. raskemensis can be distinguished from those of other Dermacentor species in the region by small spiracular plate, relatively short and obtuse lateral projections of basis capituli dorsally, relatively short spurs on coxa I and the internal spur is characteristically very broadly rounded at its apex, and very small spur on coxa IV, whereas larvae of D. raskemensis can be distinguished from other Dermacentor by relatively short and obtuse lateral projections of basis capituli, approximately 6 denticles in the median files on hypostome, and relatively short, broad, and rounded spur on coxa I. The nymphs and larvae of D. raskemensis studied originate from Afghanistan, India, Iran, and Pakistan, where they were collected from pikas and other small mammals. PMID- 24180100 TI - Population studies of the filarial vector Aedes polynesiensis (Diptera: Culicidae) in two island settings of French Polynesia. AB - A mark-release-recapture study was conducted to estimate the adult population size, migration, and dispersal patterns of male and female Aedes (Stegomyia) polynesiensis (Marks) in a valley of Moorea, a volcanic island, and a motu (islet) on the atoll of Tetiaroa, two settings typical of the Society Islands. Aedes polynesiensis recapture rate was high for females and low for males. The distribution of Aedes species in the valley was heterogeneous. Marked individuals dispersed to most parts of the motu and over great distances in the valley for some females. The study provides insights into the field dynamics of Ae. polynesiensis populations and confirms that more efficient sampling methods are warranted. There was no evidence of active migration between motus on the atoll, suggesting that Tetiaroa is a suitable site for small-scale initial open releases of Wolbachia incompatible insect technique and other sterile insect technique like suppression or replacement strategies. PMID- 24180101 TI - Movement of male Dermacentor andersoni (Acari: Ixodidae) among cattle. AB - Movement of male Dermacentor andersoni (Stiles) was examined among 54 pairs of artificially infested donor and recipient cattle during a 3-yr period. The number of males declined at a rate independent of the initial level of infestation, while the rate of decline of females on the donor animals tended to increase with initial infestation level. Male tick movement to recipient cattle was observed in 26 of 54 (48%) of the animal pairs, but varied among years and trials. Movement tended to be greater during April compared with May and June. The daily probability of movement averaged (SD) 0.067 (0.082), and the number of males moving per day averaged (SD) 0.083 (0.228). Logistic and Poisson regression models were developed and indicated that movement was determined by interactions between the number of males on the donor animals, differences in the number of females on the donor and recipient cattle, temperature, and female age. These models can be used to incorporate movement into tick population models. PMID- 24180102 TI - Dispersal and memory of sand flies in an endemic area of cutaneous leishmaniasis, southern Brazil. AB - The dispersal of and the existence of memory in sand flies were measured in a transmission area of cutaneous leishmaniasis, in the municipality of Bandeirantes, Parana, Brazil. Sand flies were caught in a rural area, with Shannon trap installed in the forest and three Falcao traps installed in a human inhabited environment (HIE) and three others in an impacted environment presently uninhabited by humans (EUH), from 1800 to 0600 hours. The captured sand flies were marked with yellow, blue, or red fluorescent powder, according to the environments where they were captured. All marked sand flies were released at 0700 hours at a point between the three environments. The recaptures were made with 28 Falcao traps, distributed in the environments from for 10 consecutive days. The sand flies recaptured were examined under a stereomicroscope and later identified. It was concluded that sand flies are able to disperse over an average distance of 73 m, reaching 130 m in 24 h, showing that: 1) the sand flies were attracted with different intensities to each environment, and the ability to move among different environments allows the existence of enzootic cycle of Leishmania; 2) the sand flies possess a spatial memory, olfactory memory, or both, that enable them to return to the environment where they were captured initially, although the distances were different. PMID- 24180103 TI - Off-host collection methods of the Otobius megnini (Acari: Argasidae). AB - Otobius megnini (Duges), often referred to as the spinose ear tick, is a one-host tick infesting the ear canal of a variety of ungulate species. The objective of this study was to develop sampling methods for collecting free-living stages of O. megnini and to collect preliminary data on habitat distribution. Sampling occurred during 2010 and 2011 at Fossil Rim Wildlife Center (FRWC) near Glen Rose, TX, where tick presence has been observed in the ears of a variety of ungulates. To sample for nonfeeding adult stage presence, a debris-filtering method was developed using screens of varying gauges. To sample host-seeking larval-stage tick presence, a carbon dioxide (CO2) trap was developed using compressed CO2 released through tubing along with cotton fabric used for tick attachment. Both methods proved successful with adults and larvae collected from animal shelters, with larvae also collected from oak leaf litter away from any structure. Locating both life stages off the host is the first crucial step toward the management of this tick species at facilities such as FRWC. PMID- 24180104 TI - Effects of compaction and wetting of laterite cover soil on development and survival of Musca domestica (Diptera: Muscidae) immatures. AB - Effects of laterite cover soil with different characteristics on survival of buried eggs, third instar larvae, and pupae of Musca domestica (L.) were studied experimentally. Soil treatments were loose dry soil, loose wet soil, compacted dry soil, and compacted wet soil (CWS). Eggs, third instar larvae, and pupae were buried under 30 cm of the different soil treatments and placed under field conditions until adults emerged. Rearing medium was provided for eggs and larvae, and control treatments of all stages were unburied immatures placed on soil surface. Egg and pupal survival to adult were significantly affected by the cover soil treatments, but third instars were more resilient. Wet soil treatments (loose wet soil and CWS) resulted in significantly reduced pupal survival, but increased survival of eggs. However, CWS significantly reduced adult emergence from buried eggs. Though emergence of house flies buried as eggs was significantly reduced, some were able to hatch and emerging first instar larvae developed to pupation. Although cover soil does not completely prevent fly emergence, it did limit development and emergence of buried house flies. PMID- 24180105 TI - Influence of temperature on survival and water relations of Paederus fuscipes (Coleoptera: Staphylinidae). AB - The effects of four temperatures (15, 23.5, 28, and 35 degrees C) on the biological characteristics of the rove beetle Paederus fuscipes Curtis were studied, and its cuticular permeability also was measured. Specimens successfully developed to adulthood at each temperature tested, but development time of each preadult stage significantly decreased with increasing temperature. Both egg and L1 stages required at least 80 degree days above a threshold of approximately 10 degrees C to develop to the subsequent stage. The lengthy development time and high survival rate of preadults at 15 degrees C suggests that P. fuscipes can survive in a harsh environment during cold weather by hibernating, and this ability could allow preadults to succeed ecologically in temperate countries. However, adult longevity was short, and no fecundity was recorded at 15 degrees C. At 28 degrees C, P. fuscipes exhibited a high survival rate of adults, which had a longer life span and high fecundity; thus, the population had the highest intrinsic rate of increase (0.0788 +/- 0.0051 d(-1)) and the shortest mean generation time (48.57 +/- 1.43 d) at 28 degrees C. At this temperature, the population might reach a size that could facilitate invasion into residential areas. However, in the absence of a hygric environment, P. fuscipes was unable to survive despite favorable temperature. Unlike in adults and pupae, high cuticular permeability values were found in the larval stages. This indicates that larvae are highly susceptible to desiccation, and it explains why the distribution of P. fuscipes is restricted to moist habitats. PMID- 24180106 TI - Lethal and sublethal impacts of predaceous backswimmer Anisops wakefieldi (Hemiptera: Notonectidae) on the life-history traits of the New Zealand mosquito Culex pervigilans (Diptera: Culicidae). AB - The presence of predators can have dramatic consequences on prey communities, not only by the direct effects of consumption but also through sublethal effects. We investigated the survival rate and subsequent life history of the mosquito Culex pervigilans Bergroth under the influence of its major predator, the backswimmer Anisops wakefieldi White. We established a field experiment with various treatments: 1) control without predators, 2) free-roaming A. wakefieldi (with one, three, or nine A. wakefieldi per container), 3) caged A. wakefieldi (empty cage without predators, with one, three, or nine A. wakefieldi in each cage, and 4) A. wakefieldi cues (with cues concentrations of one, three, or nine A. wakefieldi). Cx. pervigilans eggs were then taken from these four experimental treatments and reared in two different laboratory conditions: 1) in clean water without any traces of predators, or 2) in water with the same treatments as in field. The survival rate of Cx. pervigilans was significantly reduced by the presence of predators or their cues. Even after a brief exposure to waters containing predators or residual cues, the subsequent progeny and the ontogeny of the remaining survivors were still affected. The percentage of eggs that hatched, and the resulting mosquito population, was influenced by the presence of predators or their cues. Our results suggest that sublethal effects may be carried by surviving individuals primarily through the effects of stress, perhaps by epigenetic mechanisms. We may expect to observe similar plasticity in species or populations with high temporal or spatial variability in predation. PMID- 24180107 TI - Amplified fragment length polymorphism used to investigate genetic variability of the stable fly (Diptera: Muscidae) across North America. AB - The stable fly, Stomoxys calcitrans (L.), is a cosmopolitan pest of livestock and humans. The pestiferous nature and painful bite cause stress to cattle and other animals. The stress and resulting avoidance behaviors manifest as reductions in weight gain or milk production in cattle; estimated annual economic loss in the United States exceeds US$2 billion. Understanding the population genetics of stable flies could provide information on their population dynamics, origins of outbreaks, and geographical patterns of insecticide resistance, resulting in a tactical advantage for developing management strategies. Previous studies, mostly on a local scale, reported a high level of gene flow between locations. Here, we report results wherein amplified fragment length polymorphism was used to determine genetic diversity of stable fly samples consisting of 11-40 individuals from 12 locations representing the United States, Canada, and Panama. The Analysis of Molecular Variance showed that the majority of genetic diversity was within groups; very little was among groups. The F(ST) and G(ST) values were low (< 0.4), Nm values high (> 1.0). The tests of neutrality suggested population expansion, and no genetic differentiation was found between locations. These results show that stable flies have a high level of gene flow on a continental scale, with limited isolation owing to distance or geographical barriers. PMID- 24180108 TI - Resistance to malathion and deltamethrin in Aedes aegypti (Diptera: Culicidae) from western Venezuela. AB - Resistance to the insecticides deltamethrin and malathion and the enzymes associated with metabolic resistance mechanisms were determined in four field populations of Aedes aegypti (L.) from western Venezuela during 2008 and 2010 using the bottle assay and the microplate biochemical techniques. For deltamethrin, mortality rates after 1 h exposure and after a 24-h recovery period were determined to calculate the 50% knock-downconcentration (KC50) and the lethal concentration (LC50), respectively. For malathion, mortality was recorded at 24 h to determine the LC50. For deltamethrin, resistance ratios of knock-down resistance and postrecovery were determined by calculating the RRKC50 and RRLC50, comparing the KC50 and LC50 values of the field populations and those of the susceptible New Orleans strain. Knock-down resistance to deltamethrin was moderate in the majority of the populations in 2008 (RRKC50 values were between 5 and 10-fold), and only one population showed high resistance in 2010 (RRKC50 > 10-fold). Moderate and high postrecovery resistance to deltamethrin was observed in the majority of the populations for 2008 and 2010, respectively. There was significantly increased expression of glutathione-S-tranferases and mixed function oxidases. All populations showed low resistance to malathion in 2008 and 2010 with significantly higher levels of alpha-esterases for 2008 and 2010 and beta-esterases for 2008. PMID- 24180109 TI - Behavioral and toxicological responses of Rhodnius prolixus and Triatoma infestans (Hemiptera: Reduviidae) to 10 monoterpene alcohols. AB - The effect on locomotor activity, the repellency, and the knock-down produced by 10 monoterpene alcohols were evaluated on first-instar nymphs of Rhodnius prolixus and Triatoma infestans, vectors of Chagas disease. A video tracking technique was used to evaluate locomotor activity and repellency by exposure to papers impregnated with monoterpenes. Eugenol on R. prolixus and (S)-cis-verbenol on T. infestans did not modify the locomotor activity. The remaining monoterpenes produced hyperactivity on both species, although the concentration required was at least a 1,000 times higher than that of deltamethrin (positive control). Carvacrol, eugenol, and geraniol resulted as repellent as N,N-diethyl-m-toluamide (positive control) for both species. A similar result was observed for almost every monoterpene on T. infestans. Knock-down effect was evaluated by exposing the nymphs in closed recipients. The order of increasing toxicity on R. prolixus was (KT50 values in min): geraniol (213.7) < alpha-terpineol (164.5) < linalool (124.2) < carvacrol (111.6) < eugenol (89.8) < thymol (78.9), and on T. infestans: alpha-terpineol (289.8) < eugenol (221.3) < carvacrol (164.2) < linalool (154.9) < thymol (96.7). All monoterpenes were less toxic than the positive control, dichlorvos (3.6 min for R. prolixus and 3.9 min for T. infestans). After 7 h of exposure, (-)-carveol, citronellol, and menthol (on both species) and geraniol (on T. infestans) produced < 50% of knock-down. After these results, it is worthwhile to explore more deeply the potential of these compounds as tools for controlling Chagas disease vectors. PMID- 24180110 TI - Flight capacity of adult Culex pipiens pallens (Diptera: Culicidae) in relation to gender and day-age. AB - Culex pipiens pallens (L.) is the most common mosquito in houses of central and northern China. It is the primary vector of lymphatic filariasis and Japanese encephalitis. The flight range of mosquitoes is an important factor predicting the risk area of transmission of mosquito-borne pathogens to vertebrate hosts. The flight performance of Cx. pipiens pallens was measured with a 26-channel computer-monitored flight-mill system. We found that females had longer flight capability than males for total flight distance (TFD) and total flight duration (TFDr), and females flew faster than males based on mean flight velocity. No significant difference in flight capability was found between different age groups in males. However, certain age-groups of females showed significant differences in TFDr and TFD. Specifically, TFD and TFDr tended to be shortest for 5- and 6-d-old females. These significant differences in flight capability between ages and genders provide insights to determine the size of operational area to achieve effective control of Cx. pipiens pallens and minimize the risk of the related mosquito-borne epidemic diseases of lymphatic filariasis and Japanese encephalitis. PMID- 24180111 TI - Behavioral responses of two dengue virus vectors, Aedes aegypti and Aedes albopictus (Diptera: Culicidae), to DUET and its components. AB - Ultralow volume droplets of DUET, prallethrin, and sumithrin at a sublethal dose were applied to unfed (nonbloodfed) and bloodfed female Aedes aegypti L. and Aedes albopictus (Skuse) in a wind tunnel. Control spray droplets only contained inert ingredients. Individual mosquitoes were videotaped before, during, and after spraying and various behaviors analyzed. During the spray periods of all three pesticide treatments, mosquitoes spent a greater percentage of time moving, and the distance moved was greater than for mosquitoes in the control treatments. In the postspray period, the percent of time moving increased for mosquitoes exposed to all pesticide treatments compared with the controls. After treatment, all females spent more time walking compared with controls, with unfed Ae. aegypti females walking more after exposure to DUET and sumithrin than after exposure to prallethrin and the control. Pesticide exposure increased flying in both species. Sumithrin exposure increased activity and velocity of unfed mosquitoes more than bloodfed mosquitoes. DUET and sumithrin treatments enhanced activity of Ae. aegypti females more than Ae. albopictus females. PMID- 24180112 TI - Host selection patterns of Culex tarsalis (Diptera: Culicidae) at wetlands near the Salton Sea, Coachella Valley, California, 1998-2002. AB - The bloodmeal hosts used by Culex tarsalis Coquillett collected along the Salton Sea in Coachella Valley, CA, during 1998-2002 were identified using sequences of the cytochrome c oxidase I gene identified from Barcode of Life database. Overall, 265 (83.3%) of 318 bloodmeals were identified, of which 76.6% fed on birds, 18.1% on mammals, and 5.3% on reptiles. Forty-seven different hosts were identified, none of which comprised > 12.5% of the total. Although Cx. tarsalis exhibits specific host-seeking flight patterns, bloodmeals seemed to be acquired opportunistically, thereby limiting potential arbovirus transmission efficiency in species-rich environments. PMID- 24180113 TI - Quantitative proteomic analysis of the Anopheles gambiae (Diptera: Culicidae) midgut infected with o'nyong-nyong virus. AB - Alphaviruses are arthropod-borne pathogens that infect a range of hosts. In humans and other mammals, alphavirus infection can cause severe disease. In mosquito hosts, however, there are generally few symptoms. Little is known about the cellular responses of mosquitoes that allow them to cope with infection. In this investigation, a six-plex tandem mass tagging proteomic approach was used to study protein accumulation changes in the midgut of Anopheles gambiae (Giles) (Diptera: Culicidae) mosquitoes infected with o'nyong-nyong virus (Togaviridae, Alphavirus). Five hundred thirty-six nonredundant proteins were identified. Twenty-two were found in significantly different quantities in infected midguts compared with controls. Of interest, analysis revealed molecular pathways possibly targeted by virus proteins, such as those involving TAF4 and DNA polymerase phi proteins. Also identified was an FK506-binding protein. FK506 binding protein orthologs have been described as conserved host resistance factors, which suppress dengue and West Nile virus infection in human HeLa cells. This investigation constitutes the first study of the midgut-specific proteome of An. gambiae in relation to alphavirus infection. Our findings offer insight into mosquito immunity, including factors that possibly contribute to the different pathological outcomes observed in vertebrate and insect hosts. PMID- 24180114 TI - Gene expression of tissue-specific molecules in ex vivo Dermacentor variabilis (Acari: Ixodidae) during rickettsial exposure. AB - Ticks serve as both vectors and the reservoir hosts capable of transmitting spotted fever group Rickettsia by horizontal and vertical transmission. Persistent maintenance of Rickettsia species in tick populations is dependent on the specificity of the tick and Rickettsia relationship that limits vertical transmission of particular Rickettsia species, suggesting host-derived mechanisms of control. Tick-derived molecules are differentially expressed in a tissue specific manner in response to rickettsial infection; however, little is known about tick response to specific rickettsial species. To test the hypothesis that tissue-specific tick-derived molecules are uniquely responsive to rickettsial infection, a bioassay to characterize the tick tissue-specific response to different rickettsial species was used. Whole organs of Dermacentor variabilis (Say) were exposed to either Rickettsia montanensis or Rickettsia amblyommii, two Rickettsia species common, or absent, in field-collected D. variabilis, respectively, for 1 and 12 h and harvested for quantitative real time-polymerase chain reaction assays of putative immune-like tick-derived factors. The results indicated that tick genes are differently expressed in a temporal and tissue specific manner. Genes encoding glutathione S-transferase 1 (dvgst1) and Kunitz protease inhibitor (dvkpi) were highly expressed in midgut, and rickettsial exposure downregulated the expression of both genes. Two other genes encoding glutathione S-transferase 2 (dvgst2) and beta-thymosin (dvpbeta-thy) were highly expressed in ovary, with dvbeta-thy expression significantly downregulated in ovaries exposed to R. montanensis, but not R. amblyommii, at 12-h postexposure, suggesting a selective response. Deciphering the tissue-specific molecular interactions between tick and Rickettsia will enhance our understanding of the key mechanisms that mediate rickettsial infection in ticks. PMID- 24180115 TI - Feeding behavior and spatial distribution of Culex mosquitoes (Diptera: Culicidae) in wetland areas of the Czech Republic. AB - Mosquito feeding behavior determines the degree of vector-host contact and may have a serious impact on the risk of pathogen transmission, including that of the West Nile virus (WNV). To measure the role of Culex mosquitoes as WNV vectors, host-seeking females were collected using animal-baited traps containing live birds (quail) or mammals (rabbits) and CO2-baited Center for Disease Control and Prevention traps placed in several wetland areas in the Czech Republic. Culex pipiens (L.) and Culex modestus (F.) were the most frequently collected species. Although Cx. modestus did not distinguish between baits, Cx. pipiens was collected significantly more frequently in bird-baited traps. Based on mitochondrial DNA analysis of bloodmeals from engorged females collected by CO2 baited traps situated within reed beds, a diverse group of birds were the predominant hosts (93.7%), followed by mammals (4.2%) including humans, and amphibians (2.1%). Among birds, Anseriformes were fed upon most frequently by Cx. modestus, whereas Cx. pipiens fed most frequently on Passeriformes. To measure the infection risk and confirm the distribution of mosquito species in various biotopes, transects of CO2-baited CDC traps were operated from wetland reed beds into upland vegetated areas. Even though both Culex species occurred in all biotopes sampled and frequently dispersed hundreds of meters away from fishpond shore vegetation, the spatial distribution of Cx. modestus was significantly associated with reed beds at wetlands. The first detection of WNV (subtype RabV) in Cx. modestus in Bohemia and confirmation of WNV presence in Cx. pipiens in Moravia together with observed feeding behavior supports the presumed role of both Culex species in the avian-to-avian enzootic WNV cycle and in avian-to mammal transmission in the Czech Republic. PMID- 24180116 TI - Molecular identification of field-collected Culicoides larvae in the southern part of Japan. AB - Although Culicoides biting midges act as a vector of important human and domestic animal diseases, their ecology is poorly understood. The lack of proper identification systems of Culicoides larvae is one of the main obstacles to progress in research. Based on mitochondrial sequences of 19 Japanese Culicoides species, we designed a universal primer set to amplify the partial sequence of the mitochondrial cytochrome c oxidase I (cox 1). The polymerase chain reaction product amplified from extracted DNA of Culicoides larvae using the primer set was directly sequenced, and species identification based on the variation at cox1 was conducted. Using the molecular identification system, we sorted 243 specimens of field-collected larvae from the southern part of Japan into 10 species including Culicoides arakawae (Arakawa), Culicoides oxystoma Kieffer, and Culicoides brevitarsis Kieffer, which are regarded as vectors of important livestock animal diseases. Eight species of Culicoides larvae, including C. arakawae and C. oxystoma, were recovered from active paddy fields and an abandoned paddy field. The result suggests that paddy fields contribute to breeding a variety of Culicoides species and maintenance and spread of Culicoides borne pathogens. In contrast, larvae of C. brevitarsis were collected from cattle dung in pastures. The molecular identification system described herein using nucleotide sequences successfully achieved larval identification and will be useful for a better understanding of larval habitats of Culicoides biting midges. PMID- 24180117 TI - Potential for mosquitoes (Diptera: Culicidae) from Florida to transmit Rift Valley fever virus. AB - We evaluated Aedes atlanticus Dyar and Knab, Aedes infirmatus Dyar and Knab, Aedes vexans (Meigen), Anopheles crucians Wiedemann, Coquillettidia perturbans (Walker), Culex nigripalpus Theobald, Mansonia dyari Belkin, Heinemann, and Page, and Psorophora ferox (Von Humboldt) from Florida to determine which of these species should be targeted for control should Rift Valley fever virus (RVFV) be detected in North America. Female mosquitoes that had fed on adult hamsters inoculated with RVFV were incubated for 7-21 d at 26 degrees C, then allowed to refeed on susceptible hamsters, and tested to determine infection, dissemination, and transmission rates. We also inoculated mosquitoes intrathoracically, held them for 7 d, and then allowed them to feed on a susceptible hamster to check for a salivary gland barrier. When exposed to hamsters with viremias > or = 10(7.6) plaque-forming units per milliliter of blood, at least some individuals in each of the species tested became infected; however, Cx. nigripalpus, An. crucians, and Ae. infirmatus were essentially incompetent vectors in the laboratory because of either a midgut escape or salivary gland barrier. Each of the other species should be considered as potential vectors and would need to be controlled if RVFV were introduced into an area where they were found. Additional studies need to be conducted with other geographic populations of these species and to determine how environmental factors affect transmission. PMID- 24180118 TI - Isolation of "Candidatus Rickettsia andeanae" (Rickettsiales: Rickettsiaceae) in embryonic cells of naturally infected Amblyomma maculatum (Ixodida: Ixodidae). AB - The Gulf Coast tick, Amblyomma maculatum Koch, has become increasingly important in public health for its role as a vector of the recently recognized human pathogen, Rickettsia parkeri. More recently, these ticks were also found to harbor a novel spotted fever group rickettsia, "Candidatus Rickettsia andeanae." First identified in Peru, and subsequently reported in ticks collected in the United States, Chile, and Argentina, "Ca. R. andeanae" remains largely uncharacterized, in part because of the lack of a stable isolate. Although the isolation of "Ca. R. andeanae" was recently described in DH82, Vero, and Drosophila S2 cells, its stability in these cell lines was not shown. To evaluate "Ca. R. andeanae" transmission and pathogenicity in vertebrates, as well as further describe biological characteristics of this candidate species to fulfill criteria for its establishment as a new species, availability of a stable isolate is essential. Here we describe the propagation of "Ca. R. andeanae" by using a primary culture derived from naturally infected A. maculatum embryos. Subsequent passage of the "Ca. R. andeanae" isolate to ISE6 (Ixodes scapularis embryonic) and Vero (African green monkey kidney epithelial) cell lines demonstrated limited propagation of the rickettsiae. Treatment of the infected primary cells with tetracycline resulted in cultures negative for "Ca. R. andeanae" by polymerase chain reaction and microscopy. Establishment of an isolate of "Ca. R. andeanae" will promote further investigation into the significance of this tick-associated rickettsia, including its role in spotted fever and interactions with the sympatric species, R. parkeri in A. PMID- 24180121 TI - Wolbachia re-replacement without incompatibility: potential for intended and unintended consequences. AB - Recent releases of mosquitoes infected with different Wolbachia types into Australia have led to conditions that have not been observed naturally and that have not been considered theoretically. In an ongoing public health campaign, two Wolbachia infection types have been introduced, and the infections differ in their fitness cost imposed on the host mosquito. The dynamics of each infection type as it interacts with the indigenous uninfected host population have been previously examined via models and empirical tests. Here we conduct a modeling analysis to predict the dynamics when the two infection types do not remain geographically isolated. The results demonstrate the potential replacement and loss of the more costly infection type, which may not be the desired public health outcome. PMID- 24180119 TI - Identification of bloodmeal sources and Trypanosoma cruzi infection in triatomine bugs (Hemiptera: Reduviidae) from residential settings in Texas, the United States. AB - The host-vector-parasite interactions in Chagas disease peridomestic transmission cycles in the United States are not yet well understood. Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) infection prevalence and bloodmeal sources were determined for adult and immature triatomine (Hemiptera: Reduviidae) specimens collected from residential settings in central Texas. Sequenced cytochrome b DNA segments obtained from triatomine digestive tract identified nine vertebrate hosts and one invertebrate host in four triatomine species (Triatoma gerstaeckeri, Triatoma indictiva, Triatoma protracta, and Triatoma sanguisuga). The broad range of wild and domestic host species detected in triatomine specimens collected from residential sites indicates high host diversity and potential movement between the sylvatic and peridomestic settings. Domestic dogs appear to be key in the maintenance of the peridomestic transmission cycle as both a blood host for the triatomine vectors and a potential reservoir for the parasite. The high rate of T. cruzi infection among triatomine specimens that were collected from inside houses, outside houses, and dog kennels (69, 81, and 82%, respectively) suggests a current risk for Chagas disease vector-borne transmission for humans and domestic animals in residential settings in Texas because of overlap with the sylvatic cycle. PMID- 24180120 TI - Monitoring malaria vector control interventions: effectiveness of five different adult mosquito sampling methods. AB - Long-term success of ongoing malaria control efforts based on mosquito bed nets (long-lasting insecticidal net) and indoor residual spraying is dependent on continuous monitoring of mosquito vectors, and thus on effective mosquito sampling tools. The objective of our study was to identify the most efficient mosquito sampling tool(s) for routine vector surveillance for malaria and lymphatic filariasis transmission in coastal Kenya. We evaluated relative efficacy of five collection methods--light traps associated with a person sleeping under a net, pyrethrum spray catches, Prokopack aspirator, clay pots, and urine-baited traps--in four villages representing three ecological settings along the south coast of Kenya. Of the five methods, light traps were the most efficient for collecting female Anopheles gambiae s.l. (Giles) (Diptera: Culicidae) and Anopheles funestus (Giles) (Diptera: Culicidae) mosquitoes, whereas the Prokopack aspirator was most efficient in collecting Culex quinquefasciatus (Say) (Diptera: Culicidae) and other culicines. With the low vector densities here, and across much of sub-Saharan Africa, wherever malaria interventions, long-lasting insecticidal nets, and/or indoor residual spraying are in place, the use of a single mosquito collection method will not be sufficient to achieve a representative sample of mosquito population structure. Light traps will remain a relevant tool for host-seeking mosquitoes, especially in the absence of human landing catches. For a fair representation of the indoor mosquito population, light traps will have to be supplemented with aspirator use, which has potential for routine monitoring of indoor resting mosquitoes, and can substitute the more labor-intensive and intrusive pyrethrum spray catches. There are still no sufficiently efficient mosquito collection methods for sampling outdoor mosquitoes, particularly those that are bloodfed. PMID- 24180122 TI - Oviposition site selection in Aedes albopictus (Diptera: Culicidae): are the effects of predation risk and food level independent? AB - For organisms lacking parental care and where larval dispersal is limited, oviposition site selection decisions are critical fitness-enhancing choices. However, studies usually do not consider the interdependence of the two. In this study, we evaluated the effect of food level on the oviposition behavior of Aedes albopictus (Skuse) in the presence or the absence of a nonlethal predator (caged dragonfly nymph). We also attempted to quantify the perceived cost of predation to ovipositioning mosquitoes. Mosquitoes were presented with oviposition cups containing four levels of larval food (fermented leaf infusion) with or without a caged libellulid nymph. By titrating larval food, we estimated the amount of food needed to attract the female mosquito to oviposit in the riskier habitat. As expected, oviposition rate increased with food level and decreased in the presence of a predator. However, the effect of food level did not differ between predator treatments. By calculating the difference in the amount of food for points of equal oviposition rate in the predator-present and predator-absent regression lines, we estimated the cost of predation risk to be 1950 colony forming-units per milliliter. Our study demonstrated the importance of considering the possible interdependence of predation risk and food abundance for oviposition-site-seeking insects. This study also quantified the perceived cost of predation and found it to be relatively low, a fact with positive implications for biological control. PMID- 24180123 TI - Genetic recombination events between sympatric Clade A and Clade C lice in Africa. AB - Human head and body lice have been classified into three phylogenetic clades (Clades A, B, and C) based on mitochondrial DNA. Based on nuclear markers (the 18S rRNA gene and the PM2 spacer), two genotypes of Clade A head and body lice, including one that is specifically African (Clade A2), have been described. In this study, we sequenced the PM2 spacer of Clade C head lice from Ethiopia and compared these sequences with sequences from previous works. Trees were drawn, and an analysis of genetic diversity based on the cytochrome b gene and the PM2 spacer was performed for African and non-African lice. In the tree drawn based on the PM2 spacer, the African and non-African lice formed separate clusters. However, Clade C lice from Ethiopia were placed within the African Clade A subcluster (Clade A2). This result suggests that recombination events have occurred between Clade A2 lice and Clade C lice, reflecting the sympatric nature of African lice. Finally, the PM2 spacer and cytochrome b gene sequences of human lice revealed a higher level of genetic diversity in Africa than in other regions. PMID- 24180124 TI - Residual treatment of Aedes aegypti (Diptera: Culicidae) in containers using pyriproxyfen slow-release granules (Sumilarv 0.5G). AB - The residual efficacy of pyriproxyfen against Aedes aegypti (L.) was examined by treating 2-liter buckets with a range of rates of Sumilarv 0.5G (100, 10, 1, and 0.1 mg product/liter or nominal dose of 500, 50, 5, and 0.5 ppb active ingredient) under semifield conditions. Approximately every 2 wk, pupal emergence inhibition (EI) was measured by using Cairns colony Ae. aegypti. Pooled water samples from the five replicate buckets were analyzed for active pyriproxyfen by using ultra-high-pressure liquid chromatography with tandem mass spectrometry detection. A strong dose-response in EI was exhibited, with the 0.1 mg/liter giving approximately 50% EI for only the initial week, whereas the 10 and 100 mg/liter doses produced EI > 90% for 8 and 40 wk, respectively. Measurable levels of active ingredient were detected in the 100, 10, and 1 mg/liter treatments, with measured starting concentrations of just 1-2-1.4% of the delivered (active ingredient) dose. Pyriproxyfen was detected in the 100 mg/liter treatment through the entire course of the trial (60 wk). PMID- 24180125 TI - New record of Lipoptena fortisetosa (Diptera: Hippoboscidae) collected from Siberian roe deer on Jeju Island, Korea. AB - Lipoptena deer keds (Diptera: Hippoboscidae) are blood-sucking ectoparasites of mammals, and only one species, Lipoptena cervi (L.), has previously been reported from the Republic of Korea. A study of Siberian roe deer Capreolus pygargus Pallas on Jeju Island, south of the Korean mainland, led to the discovery of a second species of deer ked, Lipoptena fortisetosa Maa, for Korea. In total, 518 deer keds were collected from 19 adult and juvenile deer examined from May to October 2012. The infestation of all of the deer examined and the occurrence on newly born deer suggest a high prevalence and abundance of L. fortisetosa parasitizing Siberian roe deer throughout Jeju Island. This deer represents a new host species for L. fortisetosa. PMID- 24180126 TI - [The studies of elimination of nontypeable Haemophilus influenzae strains using the animal model of infection]. AB - INTRODUCTION: The intranasal immunization is considered the effective method to induce immunological response in the mucosa and the model useful to develop the vaccine against otitis media due to nontypaeble Haemophilus influenzae infections. In the study, elimination of NTHi strains isolated from healthy and carrier individuals, varying with several genetic determinants, from mice nasopharynx, lungs and ears tissues and the interactions among strains during mixed infections were evaluated. METHODS: Mice were infected with single and mixture of NTHi strains previously identified as non or potentially invasive. The curves of infections were drown from the averages of log cfu/mg values obtained for nasopharynx or ears leavages or lungs homogenates coupled with standard deviation at each time point using 5 mice. The significance of the differences was confirmed using ANOVA method. RESULTS: The course of infections induced with a single noninvasive or potentially invasive strains in the mice nasopharynx, ear or lung tissues were not found to differ in respect to the level and duration. Regardless the strain used, higher elimination rates in the ear and lung tissues in comparison with nasopharynx were fund. Different rate of elimination was found in the case of mixture infections where the strain, determined in the previous study as potentially invasive, was dominating. CONCLUSION: The concurrence model among not-invasive and potentially invasive NTHi strains in the host niche was thus confirmed using in vivo model of infection. PMID- 24180127 TI - [Influence of Lactobacillus casei on biofilm formation by enteroaggregative Escherichia coli strains isolated from irritable bowel syndrome (IBS)]. AB - INTRODUCTION: Many pathogenic bacterial species have the ability to biofilm formation. In our study we determined the influence of Lactobacillus casei on biofilm formation by enteroaggregative Escherichia coli (EAEC) strains obtained from irritable bowel syndrome patients. METHODS: The ability of EAEC isolates to biofilm formation was assessed in the presence of various concentrations of the probiotic L. casei strain in an a semi- quantitative microtitre plate assays under culture conditions, similar to those prevailing in the human intestine. RESULTS: Depending on the concentrations L. casei inhibited biofilm formation of the majority (> 80%) of the EAEC strains. Concentration of 4.5 x 10(7) cfu/ml of L. casei was the most effective inhibitory dose, although a few strains (approximately 18%) formed the biofilm regardless of the presence and concentration of the probiotic L. casei strain. CONCLUSION: The inhibitory effect of L. casei on biofilm formation at most of studied EAEC strains suggest that L. casei may reduce the risk of developing persistent intestinal infections in humans. PMID- 24180128 TI - [Evaluation of the effect of glucose on Staphylococcus aureus and Escherichia coli biofilm formation on the surface of polypropylene mesh]. AB - INTRODUCTION: One of the most serious complications associated with the use of implants in hernia surgery is deep surgical site infection involving an implanted biomaterial. Among the major etiological factors of this complication are Staphylococcus aureus and Escherichia coli strains, which have the ability to form a biofilm on the surface of the mesh implant. This process is influenced by many factors, of which, according to current medical knowledge, the concentration of glucose may have a clinical significance. The aim of the presented study was to evaluate the effect of glucose on the formation of biofilm on the surface of monofilament polypropylene mesh. METHODS: The study included 140 bacterial strains (70 S. aureus and 70 E. coli) from the collection of Department of Microbiology Collegium Medicum im. L. Rydygier in Bydgoszcz, Nicolaus Copernicus University in Torun. Evaluation of the effect of two glucose concentrations (0.1% and 0.2%) on biofilm formation was performed using a qualitative (2,3,5 triphenyltetrazolium chloride reduction) and a quantitative ( serial 10-fold dilutions) methods. RESULTS: A qualitative analysis, performed after a period of incubation on substrates containing various concentrations of glucose, has revealed a statistically significant increase in the percentage of S. aureus strains with a very high potential for biofilm formation, while for E. coli an increase was observed in the percentage of strains with a low potential for biofilm formation. In a quantitative analysis of the biofilm of S. aureus forming after incubation on a substrate containing 0.1% and 0.2% glucose, significantly more colony forming units (CFUs) were isolated per one milliliter of the suspension (CFU/ml) than in the control group biofilm samples. On the other hand, the biofilm created by E. coli after a period of incubation on a substrate containing 0.2% glucose yielded significantly fewer CFUs per one milliliter than from the biofilm resulting from incubation on substrate with 0.1% glucose or the control group. No statistically significant difference was found between the numbers of CFUs per one milliliter isolated from E. coli strains after incubation on a substrate with 0.1% glucose and the control group. CONCLUSIONS: At concentrations of 0.1% and 0.2%, glucose increases biofilm formation by S. aureus strains on the surface of monofilament polypropylene mesh; at 0.2% glucose limits biofilm formation in E. coli. PMID- 24180129 TI - Carbapenem-resistant strains from the family Enterobacteriaceae isolated in the period 2006-2011 from clinical specimens of patients treated at the university hospital in northeastern Poland. AB - INTRODUCTION: In recent years an alarming increase of carbapenem-resistant Enterobacteriaceae has been noticed, which creates frequent therapeutic problems, especially for patients residing in intensive care units (ICU). The aim of this study was to evaluate the prevalence of carbapenem-resistant strains of Enterobacteriaceae isolated in the years 2006-2011 at the University Hospital in Bialystok (UHB). METHODS: Based on microbiological analysis reports we conducted a retrospective study of strains resistant to carbapenems. We assigned strains to three carbapenem-resistance phenotypes, and analyzed susceptibility to antibiotics and prevalence of these strains in hospital wards and in clinical specimens collected from hospitalized patients. During a six-year period, 216 strains resistant to carbapenems were tested, which represents 0.96% of all Enterobacteriaceae (n = 22.391) isolated during this period. RESULTS: The greatest number of carbapenem-resistant strains was identified in 2011 (96 strains, 44.44%). Antibiotics that showed the highest activity against strains occurring most frequently (Klebsiella pneumoniae [n = 103] and Enterobacter cloacae [n = 85]) were tigecycline (102 [99.03%] of K. pneumoniae tested strains and 61 [100%] of E. cloacae strains were susceptible), colistin (33 [86.84%] of K. pneumoniae tested strains and 84 [100%] of E. cloacae were susceptible), and amikacin (86 [83.49%] of K. pneumoniae tested strains and 26 [30.58%] of E. cloacae strains were susceptible). CONCLUSIONS: Carbapenem resistance among Enterobacteriaceae isolates showed a trend to increase during the six-year period of study. Because infections caused by carbapenem-resistant strains are frequently life-threatening, the effective strategies to control the spreading of antibiotic resistance are necessary. PMID- 24180130 TI - [Occurrence and characterisation of aac(6')-Ib-cr gene encoding fluoroquinolone modifying enzyme in clinical ciprofloxacin-resistant Enterobacteriaceae strains isolated in Poland]. AB - INTRODUCTION: The aac(6')-Ib-cr gene encodes a variant of aminoglycoside acetyltransferase that confers reduced susceptibility to hydrophilic fluoroquinolones such as ciprofloxacin and norfloxacin. AAC(6')-Ib-cr has two amino acid changes, Trp 102Arg and Asp179Tyr, which together are necessery and sufficient for the enzyme's ability to reduce the activity of fluoroquinolones, including ciprofloxacin and norfloxacin. The aim of this study was to evaluate the prevelance of aac(6')-Ib-cr determinant among 15 Enterobacteriaceae isolates randomly chosen from 215 fluorochinolone resistant strains recovered during the 6 months of 2010. METHODS: The aac(6')-Ib was detected by PCR. The presence of aac(6')-Ib-cr gene variant was futher identified by digestion with BseGI (BtsCI) and sequencing. RESULTS: 11/15 of the resistant (MIC CIP 2-1024 microg/ml) Enterobacteriaceae strains carried aac(6')-Ib-cr variant. CONCLUSION: This is the first study identifying the variant of aminoglycoside acetyltransferase determinant in Poland. Our results demonstrate that this enzym may be even more widespread than Qnr determinants among fluoroquinolone resistant Enterobacteriaceae in Poland. PMID- 24180131 TI - [Phenotypic and genotypic characterization of probiotic bacterial strains used in medicinal products]. AB - INTRODUCTION: The optimization of quality testing strategy of products containing probiotics might allow to general improvement of its safer use in humans. The goal of the study was the evaluation of quality expressed by identity, colony forming unit (CFU) and antibiotic sensitivity ofprobiotics used in medicinal products available in Poland using the appropriate and validated procedures. METHODS: The medicinal products containing L. rhamnosus, L. acidophilus, L. delbrueckii subsp. bulgaricus and B. animalis subsp. lactis, L. helveticus, and L. gasseri were tested for species identity performed with validated rep-PCR (BOXA 1R) method. The antimicrobial susceptibility of working seeds and strains isolated to 26 antibiotics were tested by disk diffusion and E-test methods using relevant references as recommended by EUCAST. The numbers of probiotic strains, expressed as cfu count per package, was done using plating plunge method. RESULTS: All strains tested, except B. lactis, were found to be resistant to trimethoprim-sulphamethoxazole, nalidixic acid, metronidazole, and colistin. B. lactis was resistant to aminoglycosides. L. rhamnosus strains were found to be resistant to vancomycin, (MIC > 256 microg/ml) similarly to ATCC strains (L. rhamnosus GG 53103 and 244). The sensitivity to other antibiotics was strain specific. The rep-PCR method was found species and strain specific. All products tested fulfilled declared countent as measured by cfu count/package. CONCLUSIONS: Quality of medicinal products containing probiotics was found undoubted and confirmed. The optimized strategy of quality monitoring of probiotics used in medicinal products can be used in dietary supplements and foodstuffs intended for particular nutritional uses. PMID- 24180132 TI - [Analysis of norovirus and rotavirus infections of patients hospitalized in the General Specialist Hospital in Lublin. Retrospective studies]. AB - INDRODUCTION: Recent years have brought reports about increasing role of the viruses among the pathogens causing gastro-intestinal acute infections. Among them norovirus and rotavirus dominate. Rotavirus infections are the major reason of nosocomial infections in pediatric wards, and norovirus are the most common factors ofepidemiological gastrointestinal infections among adults. The knowledge about epidemiology of nosocomial diarrheas and microbiological characteristics of mentioned viruses is very useful in the process of prevention of spreading infections. The aim of the study was the laboratory diagnostics of etiology factors inducing intestinal infections of hospitalized patients as well as the evaluation of hospital epidemiological situation in terms of gastro-intestinal infections caused by viruses in the year 2011. METHODS: Pathogen causing infections was determined on the basis of results of stool samples analysis. Samples were collected from patients with infection's symptoms. The process of rotaviruses diagnosis was using single-stage membrane test based on immunochromathographic technology, by STAMAR. Norovirus infections were detected by immunoenzymatic third-generation qualitative test "Norovirus RIDASCREEN" by R Biopharm. Analysis of gastrointestinal infections caused by norovirus and rotavirus was carried out on the basis of diagnostic tests results of infected patients and data from the infection registry of hospital epidemiological surveillance in the year 2011. Reported infections of rotavirus or norovirus were analyzed with regard to gender of patients, hospital ward, time (month) of occurrence and type of infection (nosocomial or non-nosocomial). The data were statistically analyzed using non-parametrical chi2 test of the statistical package SPSS 12.0PL. RESULTS: The results showed considerably greater number of rotavirus infections (176 cases - 0.87% of hospitalized patients) than norovirus infections (118 cases - 0.58% of hospitalized). Majority of rotavirus infections (96.6%) applied to pediatric ward patients, their occurrence indicated seasonality of this infections. All of norovirus infections were classified as nosocomial. CONCLUSIONS: Following hospital dyscypline increases safety of hospitalized patients and reduction of epidemiological focuses, what was confirmed by relatively low rate of patients diagnosed with defined nosocomial infections. PMID- 24180133 TI - [The effects of topical fluoridation of Ketac Molar Aplicap glass-ionomer material on the growth of cariogenic bacteria contained in the dental plaque]. AB - INTRODUCTION: Dental caries is a bacterial disease. The most important element used in caries prevention is fluoride, which is derived from the air, diet or fluoride-containing preparations and materials, e.g. glass-ionomer restorations. Modern fluoride-containing restorative materials are capable of releasing fluoride to the environment. Fluoride can be also accumulated in glass-ionomer cements, thus an attempt was made to saturate these materials with fluoride. The aim of the study was to evaluate the effect of topical fluoridation of Ketac Molar Aplicap glass-ionomer cement on the growth of Lactobacillus spp. in the dental plaque. METHODS: The study was carried out in 15 patients with good oral hygiene, in whom 35 fillings with conventional glass-ionomer material, Ketac Molar Aplicap, were performed. After 6 months, three-day dental plaque from these fillings was examined. Next, fluoride was rubbed on the glass-ionomer surface and the examination of three-day dental plaque was repeated. RESULTS: No statistically significant differences (p = 0.143) in the amounts of Lactobacillus spp. in the plaque collected prior to and after topical fluoridation were revealed. CONCLUSIONS: Fluoride rubbed in the conventional glass-ionomer cement, Ketac Molar Aplicap, did not affect the amount of Lactobacillus spp. in the dental plaque growing on this material. PMID- 24180134 TI - [In vitro efficacy analysis of absorbent dressing modified with essential oils, against Staphylococcus aureus and Candida albicans]. AB - INTRODUCTION: The widespread use of antiseptics for wound dressings, unfortunately, not always effective, prompted us to search for alternative solutions, tailored to individual patient's needs. The aim of the study was checking the validity of the idea to apply some selected essential oils in order to modify active dressings which are routinely used in the care of chronically infected wounds. Our choice is commercially available an absorptive wound dressing which does not contain antiseptics (Sorbact). METHODS: The proposed is modification of dressing by its immersion in essential oil solution and then estimation of the biocide availability and stability during storage. Evaluation of inhibition of microbial surface growth (zone inhibition) and survival of absorbed microorganisms (retentivity by CFU counting) was performed directly after modification and repeated after 7 days of their storage at 4 degrees C. RESULTS: This study indicated that the dressings containing essential oils can keep absorbed bacteria/fungi inside and efficiently limit their growth. Depending on the properties (composition of volatile fraction) of the tested essential oil, saturated dressings were more active when stored at 4 degrees C for 7 days after their modification. The differences of antimicrobial strength, duration of the effect and retentivity between essential oils used for dressing modification have been shown. CONCLUSIONS: Modification of absorbent dressings with essential oils is a good option to achieve better therapeutic effect. Using a mixture of these four essential in several different quantitative ratios can be considered and is worthy of further research. PMID- 24180135 TI - [The evaluation of lipolytic activity of strains of Enterococcus faecium]. AB - INTRODUCTION: Little is known about the involvement of hydrolytic enzymes such as lipases as virulence factors in infections involving Enterococcus spp. METHODS: A total of 45 isolates of E. faecium were investigated. Lipolytic activity of enterococcal strains was determined by Tryptic Soy Agar containing Tween 20, Tween 40, Tween 60, Tween 80 and egg yolk. RESULTS: We detected that E. fecium strains produced lipases more frequently on Tween 20 agar (71.1% strains) than on Tween 40 agar, Tween 60 agar, Tween 80 agar, egg yolk agar (respectively 33.3%, 24.4%, 20.0%, 31.1%). Our results indicate that lipase may be a virulence factor in E. faecium. CONCLUSIONS: Studies suggest that source of isolation from clinical materials (blood, wound and fluid from the abdominal cavity) does not have an influence on the ability hydrolysis esters. PMID- 24180136 TI - [Evaluation of selected properties of morphological variants of Acinetobacter baumannii complex]. AB - INTRODUCTION: The ability of growth of Acinetobacter baumannii as morphology colony variants have been observed. However, the importance of this phenomenon for its biology is not known. The aim of this study was to evaluate some properties of light and dark morphology colony variants. METHODS: Fifty two isolates were identified by MALDI TOF MS method (MALDI Biotyper, BRUKER). It was evaluated the adhesion to polystyrene and extracellular mucus production of morphology colony variants and its susceptibility to imipenem and meropenem by agar dilution method. RESULTS: Forty eight (92.3%) out of the 52 morphotypes Acinetobacter sp. were identified as A. baumannii, two (5.8%) as A. genomospecies 3, one as the A. calcoaceticus. Sixteen (61.0%) pairs of isolates showed differences in the similarity of the spectra to the spectra of reference strains in the MALDI-TOF MS method. Adhesion to polystyrene was observed in all dark and 92.3% light morphotypes. Extracellular slime was produced by 15 (57.7%) dark morphotypes, and 7 (26.9%) of clear. The differences in susceptibility to imipenem occurred in two (7.7%), and meropenem in three (11.5%) pairs of morphotypes. CONCLUSIONS: The results show diversity of biological properties of morphology colony variants of A. baumannii complex. Differences in the level of adhesion to polystyrene and slime production may indicate the importance of morphological differentiation in virulence of A. baumannii complex. PMID- 24180137 TI - [Sequence-based typing--molecular typing of Legionella pneumophila strains within the framework of an international external quality assessment]. AB - INTRODUCTION: The aim of the study was evaluation results of molecular typing L. pneumophila strains that was carried by using SBT (Sequence-Based Typing) method, obtained by laboratory of Department of Bacteriology NIZP-PZH within the framework of the ninth international external quality assessment (ELDSNet Legionella pneumophila DNA SBT) and their comparision with the results obtained by other reference laboratories in EU. MATERIAL AND METHODS: The panel of five coded isolates of L. pneumophila was investigated. Genomic DNA of Legionella were extracted and defined regions of seven genes were amplified by PCR and sequenced. Then, consensus sequence of the correct length were generated. In order to determine the complete allelic profile and Seqence Type (ST) forward and reverse sequence for each allele were submitted online by using the L. pneumophila database. RESULTS: All of L. pneumoniae isolates sent to genotyping by SBT method were correctly identified in our laboratory. CONCLUSIONS: Results of the ninth international external quality assessment have confirmed competences of laboratory of Department of Bacteriology NIZP-PZH in typing of L. pneumophila isolates accordance with the requirements of the international classification. PMID- 24180138 TI - [The use of molecular methods in the diagnosis of Clostridium difficile infections]. AB - INTRODUCTION: The aim of this study was to use molecular methods to identify selected strains of C. difficile isolated from patients hospitalized at Independent Public Central Teaching Hospital [SP CSK] between 2008 and 2011 in order to demonstrate their toxicgenic character and to determine their epidemic potential, including the incidence of a suspected C. difficile strain 027/NAP1/B1. MATERIAL AND METHODS: Originally evaluated material consisted of freshly collected stool samples from patients who had developed diarrhea. Stool samples were assessed for toxins A and B via an immunoenzymatic method and for the presence of C. difficile via the first culture method. The isolated strains were stored on MICROBANK mediums, at -70 degrees C. From this sample collection, 48 strains isolated in 2008 and 28 strains isolated in 2011 were selected for molecular analysis. RESULTS: Among the C. difficile isolates that underwent molecular analysis there were 6 strains 027/NAP1/BI out of the 48 evaluated strains isolated in 2008, which constituted 12.5% and 24 strains 027/NAP1/BI out of the 28 strains isolated in 2011, which constituted 85.7%. CONCLUSIONS: Identification of a possible hyperepidemic strain of C. difficile is crucial for undertaking any anti-epidemic activities in health care facilities, where such activities are more and more common and are responsible for nosocomial foci of infection. PMID- 24180139 TI - Cell wall carbohydrates content of pathogenic Candida albicans strain morphological forms. AB - INTRODUCTION: The study evaluated the cell wall carbohydrates fraction in blastoconidia grown in YEPD medium at 30 degrees C and in the conglomerate of true hyphae grown in human serum at 37 degrees C. MATERIAL AND METHODS: The clinical isolate obtained from a child with widespread C. albicans infection was used in the study. The cells were broken with glass beads, centrifuged to harvest the cell wall followed by subjection to TFA hydrolysis and in the result of that released monosaccharides were detected by HPAEC-PAD. Both, serum and temperature conditions (37 degrees C) affected germination process influencing the cell wall carbohydrates content when incubation in serum was prolonged from 1 to 18 h. RESULTS: The mannan content of blastoconidia was almost twofold higher compared to filamentous forms (149.25 +/- 299.24 vs 77.26 +/- 122.07). The glucan content was threefold lower in blastoconidia compared to hyphae (251.86 +/- 243.44 vs 755.81 +/- 1299.30). The chitin level was fourfold lower in blastoconidia compared to filaments (23.86 +/- 54.09 vs 106.29 +/- 170.12). The reason for the differences in the carbohydrates content may be related to type of morphology induced in different environmental conditions. Among tested carbohydrates, glucan appeared to be present in appreciably larger amounts in both tested morphological fractions. The ultrastructure of the blastoconidial cell wall revealed striking differences compared to the hyphae indicating the carbohydrates content alterations for wall assembly during hyphal growth at alkaline pH and temp. 37 degrees C. CONCLUSIONS: The study provided evidence for the relationship between morphogenesis, cell-cell adhesion induced by serum and changes in the level of carbohydrates content. PMID- 24180140 TI - Is herbal medicine the panacea? PMID- 24180141 TI - The role of ultrasonography in in-vitro fertilization and embryo transfer (IVF ET). AB - BACKGROUND: Although ultrasonography was introduced into Obstetrics and Gynaecology by a British Gynaecologist over five decades ago, the requirements for formal training in its use by gynecologists in Nigeria is just beginning to catch on, despite its indispensible role in various aspects of our clinical practice. OBJECTIVE: To describe the role of ultrasonography in in-vitro fertilization and the indispensability of the instrument to reproductive medicine. METHOD: A review of literature written in English language on the use and application ofultrasonography. in in-vitro fertilization was done. The review covered articles published between 1980-2012. RESULTS: Ultrasound is the most versatile method for pre-treatment assessment in IVF being the dominant instrument for assessing ovarian reserve, pelvic pathologies and for assessing the uterine cavity. The ability of ultrasonography to measure endometrial thickness in addition to detecting uterine masses gives it an edge over laparoscopy/hysteroscopy as a diagnostic procedure in uterine cavity assessment, although hysteroscopy has the advantage of therapeutic potential. Similarly, ultrasonography is superior to biochemical methods for follicular monitoring because of its ability to demonstrate the number and sizes of follicles, and guide preparations for oocyte retrieval. The relative ease of ultrasound guided oocyte retrieval; its less technical demands and the possibility of conducting the procedure under local anaesthesia have made ultrasound guided oocyte retrieval more popular across the world. Randomized controlled trials show that ultrasound-guided transfer techniques have better outcomes than the clinical touch technique in terms of on-going pregnancies and Clinical pregnancies. Ultrasonography is now the key instrument for diagnosing and monitoring pregnancy following embryo transfer, biochemical methods being complimentary. CONCLUSION: Ultrasonography is now the single most important instrument in in-vitro fertilization .programmes and gynaecologists with interest in reproductive medicine need necessarily to obtain a formal training in its use. PMID- 24180142 TI - Prevalence of overweight and obesity in Maiduguri, North-Eastern Nigeria. AB - BACKGROUND: The prevalence of obesity is on the increase worldwide including in many developing countries. There is no report on the magnitude of obesity among adults in Maiduguri, a major city in northeastern Nigeria. MATERIALS AND METHODS: We selected a sample of 1650 men and women aged 15 years and above resident in Gwange ward in Maiduguri metropolitan council using a multistage sampling technique. Height, weight, waist (WC) and hip circumferences w measured. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Data were analyzed using SPSS version13. The ethics committee of the University of Maiduguri Teaching Hospital approved the study and consent was sought individually from the participants before being enlisted. RESULTS: The mean (SD) age of the respondents was 36.2 (14.4) years, with a range of 15 to 70 years. The mean (SD) ages of the males and females were 34.9 4.3) and 38.9 (14.0) years, respectively, (p < 0.001). The overall crude prevalence rates of overweight and obesity were 27.1% and 17.1%, respectively. In men, 40.6% were either overweight or obese, while in women 51.9% were either overweight or obese. We observed the highest prevalence rates of overweight and obesity in the middle age group. There were more obese females than males (14.05 vs. 4.3%) among both young and elderly (12.1% vs. 10.5%) subjects. CONCLUSION: The prevalence of overweight and obesity is high in Maiduguri metropolis particularly among women. Concerted efforts should be made to curb the menace of increasing rate of obesity in the metropolis through public enlightenment on the risks associated with obesity and the benefits of adopting a healthy lifestyle. PMID- 24180143 TI - The prevalence of orthostatic hypotension in type 2 diabetes mellitus patients in a diabetic clinic in Enugu South-East Nigeria. AB - BACKGROUND: Orthostatic Hypotension is a serious and common complication of diabetes mellitus. AIMS: To determine the prevalence and risk factors of Orthostatic Hypotension in type 2 diabetic patients in a diabetes mellitus clinic in Enugu South-East Nigeria. METHOD AND MATERIALS: A structured questionnaire was administered to the eligible and consenting seventy type 2 diabetes mellitus patients. The supine and erect blood pressures of each patient were recorded. The patients with Orthostatic Hypotension were compared with those without Orthostatic Hypotension for different clinical and biochemical parameters. STATISTICAL ANALYSIS USED: The data was analyzed using Statistical Package for Social Sciences (SPSS) version 19 software. Odds ratio was calculated for the presence of Orthostatic Hypotension amongst the variables and p-value < 0.05 was considered statistically significant. RESULTS: The prevalence of Orthostatic Hypotension in type 2 diabetic patients was 23.3%. Orthostatic Hypotension had statistically significant association with the presence of peripheral neuropathy, retinopathy and proteinuria. CONCLUSIONS: Orthostatic Hypotension is a common complication in type 2 diabetes mellitus patients seen at Enugu. It is recommended that measurement of erect and supine blood pressures should be part of the standard care of type 2 diabetic patients. PMID- 24180144 TI - Sleep disturbances in patients with rheumatoid arthritis. AB - BACKGROUND: Sleep problems are frequent in chronic diseases like rheumatoid arthritis (RA). The present study was conducted to determine frequency of sleep disturbances and their relations with disease severity. METHODS: The present case control study was performed on 100 rheumatoid patients who were referred to the rheumatology clinic at the Avicenna hospital. A hundred age- and sex-matched healthy individuals were recruited in the study as a control group. Pittsburgh Sleep, 1Quality questionnaire, Insomnia Severity Index questionnaire and Epworth Sleepiness Scale were used. The disease activity was caIculated with the disease activity score 28. The collected data were analyzed using SPSS version 19. RESULTS: Mean scores of the sleep quality were 6.2 +/- 4.3 in patients and 4.6 +/ 2.5 in control group. 28% of the patients had good sleep quality whereas 72% had poor sleep quality. Daytime sleepiness was present in 24.8% of the patients and 15% of the control group. Multiple logistic regressions showed that insomnia, pain and disease intensity were the most important factors that determine patients' sleep quality. CONCLUSION: The present study showed that sleep disturbances are frequent in patients with RA and may contribute to disease severity. It is recommended that rheumatoid patients be evaluated for sleep disturbances during routine examinations. PMID- 24180145 TI - Prevalence of hyperuricaemia in a rural population of Nigerian Niger Delta region. AB - INTRODUCTION: Hyperuricemia is a cardiovascular disease risk factor that has been poorly researched into in Africa and its prevalence is largely unknown in the rural areas in Nigeria and in the Niger Delta region of Nigeria in particular. METHODS: A cross-sectional rural survey involving 500 subjects aged 15 years and above. Demographic and social data were obtained using a questionnaire. Anthropometric (height, weight, waist circumference) and blood pressure measurements were taken. Blood samples were taken for blood uric acid, glucose and lipid check. RESULTS: The mean age of the study subjects was 41.32 +/- 17.0 (males, 42.84 +/- 17.8; females, 40.62 +/- 16.6) with a range of 15 years to 95 years. The male to female ratio was 1:2.3. The mean serum uric acid was 337.58 +/ 94.59 mmol/l with a significant higher mean for females (males 333.20 +/- 88.70, females 339.56 +/- 97.21, p < 0.001). Hyperuricemia was found in 86 subject giving a prevalence of 17.2% with higher prevalence in males (males 25%, females 13.7%; x2 = 7.75, p = 0.006). Correlational analysis of serum uric acid with other parameters revealed that waist circumference, total cholesterol, low density lipoprotein and gender had significant association with uric acid. Male gender was found to be a significant predictor for hyperuricaemia following a logistic regression. CONCLUSION: The prevalence of hyperuricemia is high in this rural community of study. There is need for more research considering the cardiovascular and other implications of hyperuricaemia. PMID- 24180146 TI - Trend in the use of intra-uterine contraceptive device (IUCD ,TCU 380A), in Enugu, Nigeria. AB - OBJECTIVE: To estimate the acceptance rate and trend of Intrauterine Contraceptive Device (IUCD) use in Enugu, Nigeria PATIENTS AND METHODS: A review of all new acceptors of intrauterine contraceptive device (IUCD) over a nine year period (1999-2007). RESULTS: A total of 133,375 clients were seen at the UNTH family planning clinic between 1999 and 2007. Out of 6,947 users of IUCD, during the period, 1,659 were new acceptors. The IUCD acceptance rate was 5.21%. Majority of the clients (29.7%) were aged 40 years and above. Eight hundred and forty seven (51.4%) had attained post secondary education. Majority of the clients (99.4%) were married . Twenty-six percent (26.0%) had completed their desired family size. Majority 1,359 (82.4%) did not use any method contraception prior to IUCD insertion. The commonest complication was menorrhagia (5.8%) and this was responsible for removal in 3.0% of cases. Eight (0.5%) and nine (0.6%) requested for removal for fear of causing cancer and migration to the brain or heart respectively. Two (0.1%) became pregnant while having the IUCD in-situ. Majority of the clients (50.5%) had the knowledge of lUCD through friends. CONCLUSION: This study has shown that IUCD (TCU 380A) is both safe and effective in Enugu, Nigeria. Its use is for both child spacing and limiting family size. PMID- 24180147 TI - An overview on the use of the laryngeal mask airway amongst anaesthesia practitioners in a developing country. AB - BACKGROUND: The aim of this study is to provide an overview on the use of the Laryngeal Mask Airway (LMA) amongst anaesthesia practitioners in Nigeria MATERIALS AND METHODS: This is a multicentre questionnaire based study involving eight tertiary health care institutions in Nigeria. The questionnaires were administered to anaesthetists. They were standardised open- and close-ended questions which were completed in person. The questionnaire was subdivided into a set of questions which include: status of the anaesthetist; the routine use of LMA in general anaesthesia and as a device for airway management in difficult airway. Statistical analyses were done by simple percentages. RESULTS: The numbers of respondents were seventy; 38 were junior residents, 20 were senior residents and 12 were consultants. Sixty (85.7%) respondent had personally used LMA, while 10 had never used it and they were all junior residents. Classic LMA was most commonly used (88%), followed by intubating LMA (7.5%), and proseal LMA (4.5%). Most of the respondents (67.1%) have used LMA in difficult airway management while 10% of respondents had used it in airway management during cardiopulmonary resuscitation (CPR). The reason for not using LMA routinely for general anaesthesia was due to unavailability in 15.7% of respondents, inexperience in 8.6% and habitual in 30%. CONCLUSION: Airway management is a vital discipline in the specialty of anaesthesia. The use of LMA as an airway device in the practice of anaesthesia in our setting is inadequate. Training, re training and continuous medical education of anaesthetists' very necessary to improve our practice. PMID- 24180148 TI - Predictors of indoor insecticides spray utilization in the prevention of malaria related mosquito bites in Ogun State, Nigeria: a community based study. AB - BACKGROUND: Modern medicine tends to interpret health in terms of medical interventions and to overemphasize the importance of medical technology. It is important to promote the concept of health as the result of the interaction of human beings and their total environment. METHODS: This was a descriptive cross sectional study. A cluster sampling technique was used to select the participants into the study. The study was carried out between January 2012 and February 2012. One participant per household was selected into the study. A semi-structured questionnaire was used to collect relevant information which was collated and analyzed using SPSS 15 statistical software. RESULTS: A total of 400 households were recruited into the study. The prevalence of insecticide spray utilization in the last 6months was 18.5%. Source of information on the use of insecticides included the radio/TV 174 (43.5%), Relatives 78 (19.5%), Health workers 54 (13.5%), friends 68 (17.0%) and others 26 (6.5%). Reasons for not using insecticides included being expensive (cost) 94 (23.5%), fear of side effect 16 (4.0%), Inconvenience 38 (9.5%) and un-availability 74 (18.5%). Predictors of utilization of insecticide spray were young age (< 30 yrs) of heads of household (OR = 5.10, CI = 1.06-21.7), tertiary education (OR = 9.14 CI = 1.13-53.08), Nuclear family structure (OR = 2.45 CI = 1.13-3.74) and availability of insecticide spray CONCLUSION: The study shows that households with heads that are young and educated are more likely use insecticide spray. The study indicates that programs that will be geared towards increasing the knowledge and awareness of indoor insecticide spray in the prevention of Malaria should be introduced at the community level. PMID- 24180149 TI - Single dose of dexamethasone for prevention of nausea and vomiting after major gynaecological surgery. AB - BACKGROUND: Post-operative nausea and vomiting (PONV) is a common complications following general anaesthesia and is a leading cause of morbidity following surgery. The mainstay of management them is by the use of antiemetic. METHOD: It was a randomized double blind placebo controlled study. The sample size was calculated as 90 from previous study with 10% attrition to make the 100. They were randomly divided into two groups; group B received dexamethasone prophylactically at induction while group A received placebo also at induction. All patients had balanced general anaesthesia and were taken to the recovery room postoperatively where incidences of postoperative nausea and vomiting were recorded. Patients with incidences of nausea and vomiting were treated with 10 mg metoclopramide intravenously while postoperative complications that may be associated with dexametnasone prophylaxis were also noted. RESULTS: The groups were comparable with respect to demographic characteristics. More patients in group A (placebo group)) had incidence of nausea than group B (dexamethasone group) with p value of 0.01 and also more patients in group A had vomiting than group B with p value of 0.02; which was significant. The duration of stay in the recovery room for both groups A and B were however comparable with no statistical difference. CONCLUSION: Dexamethasone when given prophylactically at induction reduces incidence of postoperative nausea and vomiting after gynaecological surgeries. PMID- 24180150 TI - Oral health practices of adult inhabitants of a traditional community in Ibadan, Nigeria. AB - BACKGROUND: Although, the association between oral health care practices and sociodemographic characteristics of populations have been documented, information is sparse on sociodemographic indices influencing oral health practices of residents of traditional communities. The study aimed to describe the oral health practices of adult inhabitants of a traditional community in Nigeria. METHODS: A descriptive, cross-sectional study involving adult residents in randomly selected houses in Idikan, Ibadan, Nigeria. Data on their oral health care practices was obtained with the use of structured interviewer administered questionnaires. Data was analysed with SPSS and test of association carried out using Chi square. RESULTS: A total of 390 adult residents participated in the study, of which 56.2% were males. A total of 196 (50.3%) participants used toothbrush solely to clean their teeth, 72 (18.5%) used chewing sticks alone while 119 (30.5%) used both tooth brush and chewing stick. Older residents of the community, those with no formal education and in lower occupational classes were more likely to use chewing stick (p < 0.05). The majority (68.7%) cleaned their teeth once daily, 30% cleaned twice while 1.3% cleaned infrequently. Educational level attained and occupational class were significantly related to frequency of oral hygiene. Nearly all (95.4%) of the participants knew that oral health services are available in most hospitals, yet only 35.9% had ever visited a dental centre with a significantly higher proportion being males (p < 0.05). CONCLUSION: The study showed that the oral health practices of a typical traditional community in Nigeria are highly influenced by socioeconomic considerations. PMID- 24180151 TI - Patients' satisfaction with the healthcare services at a north central Nigerian tertiary hospital. AB - BACKGROUND: This study sought to determine the level of satisfaction of patients with the healthcare services at Federal Medical Centre, Bida (FMCB) Nigeria and the factors associated with patients' satisfaction. METHODS: The study utilized exit interview of 480 patients, sampled at the 9 service points of the Centre. The questions covered socio-demographic factors and the 3 core elements of healthcare service delivery namely quality, access and interpersonal issues. The evaluation of satisfaction on the 5 point Likert scale were categorized into dissatisfied {very dissatisfied, dissatisfied and Neutral} and satisfied {satisfied and very satisfied}, setting the threshold for satisfaction at a relatively higher level. RESULTS: On the overall, 78.5% of them were satisfied with the hospital services and 78.3% had their expectations met. Satisfaction was lowest (72.7%) at the revenue section and highest (96.1%) at the maternity section. Nine of every 10 respondents (91.7%) would recommend the facility to a friend. The patients' satisfaction had significant positive correlation with promptness of staff, communication level of staff, staff relationship with patients, environmental cleanliness and comfort facilities. Cost of services and delay in obtaining services had negative but relatively weak correlation with satisfaction. CONCLUSION: The observed level of patients' satisfaction at FMC Bida is high. This can be maintained and enhanced by improvement in waiting time, sustenance of the satisfactory hospital ambiance and staff attitude/aptitude. However, enlightenment of the hospital patients on the status of the hospital and the nature of services offered is necessary. PMID- 24180152 TI - The clinical and laboratory features of plasma cell neoplasialn the University of Port Harcourt Teaching Hospital. AB - OBJECTIVE: To analyze the clinical and laboratory features of Multiple Myeloma at presentation in a tertiary centre in Port Harcourt Southern Nigeria. METHODS: The medical records of all patients diagnosed for plasma cell neoplasia within a 10 year period at the University of Port Harcourt Teaching Hospital were reviewed retrospectively. Clinical presentation, investigation results, support and specific therapy used were documented. RESULTS: A total 20 patients were diagnosed with multiple myeloma, 70% were male, the mean age was 61.30 +/- 8.8 years, 50% of them had pathological fractures. The mean duration before presentation was 11.89 +/- 11.7 months (Median = 7 months) and associated with poor outcome. The most common method treatment was chemotherapy with Melphalan and Predisolone. CONCLUSION: MM is a disease of the elderly that can negatively impact on the quality of life due to the complications associated with it. A long duration of symptoms before presentation is a common problem and it has been associated with substantial morbidity and mortality in this study. PMID- 24180153 TI - Irreducible inguinal hernias in the paediatric age group. AB - BACKGROUND: An inguinal hernia is said to be irreducible when the content fails to return into the peritoneal cavity without surgical intervention. Irreducibility is an ever present risk in untreated inguinal hernias and its management remains an important part of pediatric surgery practice. When a hernia is irreducible, morbidity and mortality increase This risk of irreducibility is more in some patient groups. METHODS: A retrospective analysis of all irreducible inguinal hernias in children of both sexes from neonatal age to 15 years who presented at the University of Nigeria Teaching Hospital from January 2000 to June 2010 and needed emergency groin exploration when reduction failed on conservative management. RESULTS: There were 25 irreducible inguinal hernias requiring emergency groin exploration. This represents 10.2% of all inguinal hernias managed within the period, with a male:female ratio of 11.5:1. Nineteen (76%) were on the right while six (24%) were on the left. Forty percent (40%) of the irreducible hernias were in older infants. Sixty-seven (67%) of the neonatal hernias presented as irreducible. There were 3 bowel resections (12% bowel resection rate), 2 testicular losses (8% testicular loss rate) and one death (4% mortality). CONCLUSION: There is a high rate of irreducibility of inguinal hernias in neonates, and in right-sided hernias Identification of risk factors in and risk stratification of patients with uncomplicated inguinal hernias will help reduce the rate of irreducible inguinal hernias and their attendant morbidities. PMID- 24180154 TI - Management outcomes of abruptio placentae at Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria. AB - BACKGROUND: The objective of this study is to determine incidence, risk factors and management outcomes of abruptio placentae (AP) and comparing them with cases without AP who delivered within the same period. METHODS: A 10 year retrospective study of AP managed at Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria, between January 2001 and December 2010 was undertaken. Proforma was initially used for data collection before transfer to Epi-info 2008 software. Test of associations were evaluated and P < 0.05 was considered significant. RESULTS: Sixty nine cases out of a total delivery of 8,811 were seen, giving an incidence of 0.8%. The mean age and parity of women with AP were 30.8 +/- 0.9 years and 4.1 +/- 0.6 respectively and majority (78.3%) of cases were unbooked (p = 0.0019). Grand multiparity and age = 35 years were significant risk factors ( p < 0.05). Fifty two (75.4%) cases were delivered by caesarean section (c/s) ( P = 0.0000). The sex ratio was 160 ( p = 0.0134). The overall maternal mortality ratio during the study period was 987 per 100,000 live births with AP contributing 3.8% of the maternal deaths while perinatal mortality rate was 52.2%. CONCLUSION: A significant number of cases have high perinatal mortality. Unbooked, high parity, advanced maternal age and previous c/s scar were significant aetiological risk factors. PMID- 24180155 TI - An unusual foreign body in the ear of an elderly Nigerian patient. AB - This was a case of an incidental finding of an unusual foreign body in the right ear of an elderly Nigerian patient. The mode of presentation, the manner of discovery and how it was managed successfully were highlighted. We reported this case to create awareness, and encourage physicians to always observe effluents obtained from irrigation of body cavities for confirmation of diagnosis and documentation. PMID- 24180156 TI - Sideswipes injuries of upper limbs: a case series report and review of literature. AB - BACKGROUND: Sideswipe injuries are consequent to object striking an elbow on the window edge of a moving vehicle. It often results in severe soft tissue and bony injuries or partial amputation of the upper limb. Functional outcome in most patients is poor. The aim is to highlight the occurrence and functional outcome of these injuries. METHOD: In our series we report three cases which presented to us in succession within four weeks. RESULTS: Two of the patients were passengers of commercial buses while one patient is the driver of a private car. Two were males. All were protruding their arm from the open vehicle window at the time of impact. All presented within five hours of injury. All sustained open fracture dislocations. All were managed with external fixation and soft tissue cover. They all had poor outcome as evidenced by joint stiffness. CONCLUSION: The functional outcome of such injuries is usually poor especially if the dominant limb is involved. Therefore the need for prevention cannot be overemphasized. Simple measures like ensuring that no part of the limb is Sticking outside a moving vehicle, winding up glass up to mid window level etc will greatly reduce the occurrence of these injuries. PMID- 24180157 TI - Vision 2020 the right to sight: where exactly are we in Nigeria? PMID- 24180158 TI - Choriocarcinoma in Enugu, South east Nigeria: a need for a shift from mortality to survival. AB - BACKGROUND: The diagnosis of cancer in Nigeria is often translated to mean an imminent death for the patients. This contrasts the situation in some developed settings where cancer survivorship and its management have evolved. Choriocarcinoma is a rare but curable tumour so; it became necessary to review cases of this curable cancer managed at a tertiary health center in a typical resourced-constrained setting. METHODS: A retrospective analysis of consecutive choriocarcinoma cases managed at a tertiary hospital in Enugu, South-eastern Nigeria over a five year period. Data analysis was descriptive. RESULTS: Five non metastatic and 10 metastatic cases of choriocarcinoma were managed. The mean age of patients was 33.6 +/- 9.1 years. All patients had vaginal bleeding with a mean duration of 4 +/- 5.19 months. The commonest predisposing factor and metastatic site were abortion (46.7%) and lungs (40.0%) respectively. The mean unit of blood transfusion during treatment was 5.3 +/- 3.8 units. Eight patients (53.3%) died on admission while 7 (46.7%) were lost to follow-up during chemotherapy 20.0% or after chemotherapy (26.7%). CONCLUSION: The case fatality for choriocarcinoma and loss of patients to follow-up in Enugu, Nigeria were high. To shift from this situation of high mortality to that of survival, an improved follow-up of post abortal patients and aggressive tracing of defaulters are recommended. PMID- 24180159 TI - "Neostigmine-resistant curarization". PMID- 24180160 TI - Airtraq optical laryngoscope: advantages and disadvantages. AB - Difficult or unsuccesful tracheal intubation is one of the important causes for morbidity and mortality in susceptible patients. Almost 30% of the anesthesia related deaths are induced by the complications of difficult airway management and more than 85% of all respiratory related complications cause brain injury or death. Nowadays, due to the advances in technology, new videolaryngoscopic devices became available. Airtraq is a novel single-use laryngoscope which provides glottis display without any deviation in the normal position of the oral, pharyngeal or the tracheal axes. With the help of the display lens glottis and the surrounding structures are visualised and under direct view of its tip the tracheal tube is introduced between the vocal cords. In patients having restricted neck motion or limited mouth opening (provided that it is greater than 3 cm) Airtraq offers the advantage of a better display. Moreover the video image can be transfered to an external monitor thus an experienced specialist can provide assistance and an educational course can be conducted simultaneously. On the other hand the Airtraq videolaryngoscopic devices possess certain disadvantages including the need of experience and the time demand for the operator to learn how to use them properly, the rapid deterioration of their display in the presence of a swelling or a secretion and the fact that they are rather complicated and expensive devices. The Airtraq device has already documented benefits in the management of difficult airways, however serial utilization obviously necessitates experience. PMID- 24180161 TI - Post-operative cognitive functions after general anesthesia with sevoflurane and desflurane in South Asian elderly. AB - BACKGROUND: The duration of the recovery of cognition after anesthesia and surgery is multifactorial and is dependent on the type of anesthesia used, the type of surgery, and the patient. The present study compared the speed of recovery in elderly patients undergoing general anesthesia with sevoflurane or desflurane and the incidence and duration of cognitive impairment in them. METHODS: The prospective study was conducted at a tertiary care centre in Bangalore from November 2008 to March 2010. Patients aged above 65 years with American Society of Anaesthesiology (ASA) physical status I, II, III undergoing surgeries under general anesthesia lasting from 45 min up to 3 hours were included in the study. The times from discontinuing nitrous oxide to eye opening, tracheal extubation, obeying commands, and the time to orientation to name and place were assessed at 30-60 s intervals. At 1, 3, 6 h after the end of anesthesia, the patient's cognitive functions were assessed by asking them to repeat the Mini Mental Score Examination. STATISTICAL ANALYSIS USED: Student t test, Chi-square test. RESULTS: The time to eye opening, time until extubation, time to follow commands and orientation to time, place were significantly better with desflurane compared to sevoflurane (p < .001). Hundred percent of patients in the desflurane group and 97% in the sevoflurane group demonstrated completely normal cognitive function at 6 h postoperatively (p = 0.31). CONCLUSION: Desflurane was associated with a faster early recovery than sevoflurane in elderly patients. However, postoperative recovery of cognitive function was similar with both volatile anaesthetics. PMID- 24180162 TI - Ultrasound guided peritubal infiltration of 0.25% ropivacaine for postoperative pain relief in percutaneous nephrolithotomy. AB - BACKGROUND: Percutaneous nephrolithotomy (PCNL) is a common endourologic procedure with less morbidity than open surgery. However, pain around the nephrostomy tube requires good post operative analgesia. So we hypothesize that infiltration of local anesthetic from the renal capsule to the skin around the nephrostomy tract would relieve the pain in the initial postoperative period. METHODS: 60 adult patients of either sex with ASA physical status I to III and undergoing percutaneous nephrolithotomy were randomized for a prospective double blind controlled study. Patients were divided into control group (n = 30) and ropivacaine group (n = 30). Balanced general anesthesia was given. After completion of surgical procedure, 23 gauge spinal needle was inserted at 6 and 12 o'clock position under ultrasonic guidance up to therenal capsule along the nephrostomy tube. 10 ml of 0.25% ropivacaine or normal saline solution was infiltrated in each tract while withdrawing the needle from renal capsule to the skin. Post-operative pain was assessed using visual analogue scale (VAS) and dynamic visual analogue scale (D-VAS) during deep breathing and coughing on a scale of 0-10 during the initial postoperative 24 hours. Rescue analgesia was given in the form of injection tramadol 1.0 mg/kg intravenously when VAS > 4 and maximum up to 400mg in 24 hours. Time to first rescue analgesic, number of doses of tramadol and total amount of tramadol required in the initial postoperative 24 hours were noted. Patients were observed for any side effect and treated accordingly. RESULTS: VAS at rest (VAS) as well as during deep breathing and coughing (DVAS) were significantly lower in ropivacaine group during first 24 hours. Mean time to 1st rescue analgesic in ropivacaine group was longer (10.7 +/ 2.64 hours) as compared to control group (2.05 +/- 1.44 hours) (P = 0.0001). Mean number of doses of tramadol in 24 hours in group-R were less (2.25 +/- 0.51) than group-C (4.4 +/- 0.68) (P = 0.0001). The mean total amount of tramadol in 24 hours in group-R was significantly lower than group-C. Side effects like nausea and vomiting and sedation were minimum and non-significant in both groups. CONCLUSION: Local anesthetic infiltration of 0.25% ropivacaine along the nephrostomy tract is efficient in alleviating post-operative pain after percutaneous nephrolithotomy surgery. The number of doses and total consumption of rescue analgesic were also decreased in the initial postoperative 24 hours. PMID- 24180163 TI - Ketamine improves postoperative pain and emergence agitation following adenotonsillectomy in children. A randomized clinical trial. AB - BACKGROUND: Management of postoperative pain and emergence agitation following adenotonsillectomy in pediatrics has been a major challenge for anesthesiologists. Although analgesic sparing effect of ketamine has been studied during tonsillectomy in pediatrics, there is a lot of controversy about its efficacy. Present study was designed to evaluate the effect of intravenous low dose ketamine (0.25 mg/kg) during induction of anesthesia on postoperative pain and emergence agitation following adenotonsillectomy in children. METHODS: In this randomized clinical trial 66 children aged 5 to 15 years who underwent elective adenotonsillectomy were randomly allocated into two groups. Patients in the control group received 5 ml of normal saline while patients in the ketamine group received 0.25 mg/kg of ketamine in 5 ml volume during induction of anesthesia. After termination of surgeries and transferring the patients to recovery, emergence agitation, pain score, paracetamol requirements and incidence of postoperative nausea & vomiting were assessed every hour for 6 hours. RESULTS: Emergence agitation score was significantly lower in the ketamine group (P = 0.002). Pain score at all hours was lower in the ketamine group than the control group (P < 0.05). The requirements for intravenous paracetamol were significantly lower in the ketamine group (P = 0.0036). There was no difference in the incidence of postoperative nausea and vomiting between the two groups (P = 0.99). CONCLUSION: Low-dose ketamine during induction of anesthesia improves emergence agitation and postoperative pain following adenotonsillectomy in children. PMID- 24180164 TI - Use of the bilateral BIS monitor as an indicator of cerebral vasospasm in ICU patients. AB - Earlier diagnosis of cerebral vasospasm and delayed cerebral ischemia (DCI) and treatment has the potential to decrease post-bleed morbidity after subarachnoid hemorrhage (SAH). Previous studies have shown that electroencephalogram (EEG) can detect blood flow changes associated with DCI sooner than other modalities potentially leading to earlier diagnosis. However, continual monitoring with raw EEG requires significant expertise and effort, and may be difficult due to the intermittent need for MRI studies in these patients. Here we describe a series of patients with subarachnoid hemorrhage in the Neurosurgical ICU who underwent monitoring with the Bilateral Bispectral Index (BIS) monitor. PMID- 24180165 TI - Effects of liberal vs. conventional volume regimen on pulmonary function in posterior scoliosis surgery. AB - BACKGROUND: We observed an increased rate of pulmonary complications (hypoxemia, pulmonary edema, re-intubation) in some patients after posterior spinal fusion, though standardized intraoperative volume regimens for major surgery were used. Therefore, we focused on the effects of two different standardized fluid regimens (liberal vs. conventional) as well as on two different types of postoperative pain management (thoracic epidural catheter vs. intravenous analgesia) concerning pulmonary function in patients undergoing posterior spinal fusion. METHODS: 23 patients received a conventional intraoperative fluid management (crystalloids 5.5 ml/kg/h), whereas 22 patients obtained a liberal regimen (crystalloids approximately 11 ml/kg/h) during surgery. After surgery a thoracic epidural catheter was used in 29 patients, whereas 16 patients got a conventional intravenous analgesia. Regarding pulmonary outcome, the re-intubation rate, the postoperative oxygen saturations as well as delivery volumes and retention times of pleural drainages were evaluated. RESULTS: Patients with conventional intraoperative fluid management had a less frequent reintubation rate (p = 0.015), better postoperative oxygen saturations (p = 0.043) and lower delivery volumes of pleural drainages (p = 0.027) compared to those patients with liberal volume regimen. Patients with thoracic epidural catheter had improved oxygen saturations on pulse oximetry at the first day after surgery (p < 0.001) and lower delivery volumes of pleural drainages than patients with intravenous analgesia (p = 0.008). CONCLUSIONS: The combination of a more restrictive fluid management (better pulmonary oxygen uptake and ventilation, less pulmonary edema) and a thoracic epidural catheter (sympatholysis, pain management) in posterior spinal fusion may be advantageous as both factors can improve pulmonary outcome. PMID- 24180166 TI - Effect of preoperative licorice lozenges on incidence of postextubation cough and sore throat in smokers undergoing general anesthesia and endotracheal intubation. AB - INTRODUCTION: Post-Operative Sore Throat (POST) is an undesirable side effect ofendotracheal intubation. Pharmacological and non-pharmacological measures have been utilized for minimizing the morbidity caused by POST. We have tested whether medicated lozenges of Licorice provides efficacy in decreasing POST in smokers presenting for surgery under general anesthesia with endotracheal intubation. METHODS: 100 patients, 20 - 65 years, American Society ofAnaesthesiologists (ASA) physical status Grade I & II, of either sex, with history of smoking, and posted for elective surgical procedure lasting more than one hour and requiring general anesthesia with endotracheal intubation were included and randomly divided into two groups (n = 50) to receive Licorice lozenges (Group A) and Sugar Candy (Group B). The patients were assessed for cough, sore throat and hoarseness of voice immediately after extubation and then at 30 min, 12 hrs and 24 hrs after extubation utilizing scoring system of Harding and McVey. RESULTS: Overall incidence of postextubation cough was less in Group A (12 patients, 24%) compared to Group B (26 patients, 52%) (p = 0.002). Magnitude of sore throat (Grades 0/1/2/3) was seen in 48/2/0/0 patients (Group A) and 46/4/0/0 (Group B) at extubation (p = 0.40) and 34/16/0/0 (Group A) and 28/20/2/0 (Group B) at 30 min (p = 0.17). At 12 and 24 hours, the magnitudes of sore throats were 24/25/1/0 (Group A) & 12/38/0/0 (Group B) (p = 0.02) and 26/23/1/0 (Group A) & 15/35/0/0 (Group B) (p = 0.03) respectively. CONCLUSION: Use of licorice lozenges is efficacious for reducing the distressing complaint of POST in postoperative period among smokers. PMID- 24180167 TI - Success of ultrasound guided popliteal sciatic nerve catheters is not influenced by nerve stimulation. AB - BACKGROUND: There is debate as to whether nerve stimulation (NS) is required to place peripheral nerve catheters when using ultrasound (US) guidance. There is conflicting evidence for whether stimulating catheters improve postoperative analgesia compared to non-stimulating catheters. The use of US in combination with NS has been shown to be superior to NS alone in terms of popliteal nerve blockade. Given the previously published reports, we hypothesized that there is improvement in sensory and motor blockade for stimulating popliteal perineural catheters placed under US guidance when NS is used. METHODS: Following IRB approval, 21 patients undergoing elective foot and ankle surgery were randomly assigned to either a US or US+NS-guided continuous popliteal sciatic nerve block using a lateral approach. The primary end-point of the study was successful nerve blockade at 20 minutes. Secondary end-points included: block performance time, minimum stimulating current, pain scores on postoperative day 1 and day 2, and patient satisfaction. RESULTS: There was no significant difference in successful nerve blockade at 20 minutes in the US versus US+NS groups (73% vs. 80%, p = 1). Procedure time was significantly shorter in the US only group (median 62 seconds vs. 130.5 seconds, p < 0.01). Postoperative pain scores and overall patient satisfaction were not significantly different between the two groups. CONCLUSION: We have found that the addition of NS provides no benefit over US alone. US alone was associated with a significantly shorter block performance time. US+NS showed no significant difference in pain control, patient satisfaction, or block success. PMID- 24180168 TI - Monitored anesthesia care for a patient with advanced Huntington's chorea. PMID- 24180169 TI - Use of airway exchange catheter for bronchoscopy of a patient with Down's syndrome. AB - Tracheobronchial injuries (TBI) are highly fatal, and early diagnosis and repair are crucial for survival. The anesthesiologist and the surgeon must secure the integrity and patency of the airway for these cases. These injuries remain infrequent, and are becoming less fatal due to the availability of the resources necessary to achieve a secure airway, and thus some of them can be managed conservatively. We report an unusual case of upper airway compromise and extensive subcutaneous emphysema due to traumatic bronchial rupture and its conservative repair in a patient with Down's syndrome. PMID- 24180170 TI - Incidental finding of foreign bodies during nasal intubation in a mentally challenged patient. AB - Nasal foreign bodies are frequently encountered among children and mentally challenged patients. They are often asymptomatic and may remain undetected for years. We are presenting a case of an incidental finding of foreign bodies during nasal intubation in a mentally challenged patient. PMID- 24180171 TI - Cardiorespiratory crisis at the end of pregnancy: a case of pheochromocytoma. AB - Pheochromocytoma during pregnancy is extremely rare. Its clinical manifestation includes hypertension with various clinical presentations, possibly resembling those of pregnancy-induced hypertension. The real challenge for clinicians is differentiating pheochromocytoma from other causes of hypertension (preeclampsia, gestational hypertension, and pre-existing or essential hypertension), from other cause of pulmonary edema (preeclampsia, peripartum cardiomyopathy, stress or Takotsubo cardiomyopathy, pre-existing cardiac disease [mitral stenosis], and high doses betamimetics), and from other causes of cardiovascular collapse (pulmonary embolism, and amniotic fluid embolism). Although, several cases of pheochromocytoma during pregnancy have been published, fetal and maternal mortalities due to undiagnosed cases are still reported. We report a case of a patient whose delivery by cesarean section was complicated by severe hemodynamic instability resulting in a cardiac arrest. Later on, pheochromocytoma was suspected based on computed tomography (CT) scan findings. Diagnosis was confirmed with special biochemical investigations that showed markedly elevated catecholamines in urine and metanephrines in serum, and later by histopathology of the excised left adrenal mass. This case illustrates the difficulty of diagnosing pheochromocytoma in pregnancy and raises the awareness to when this rare disease should be suspected. PMID- 24180172 TI - Echocardiography guided therapy for massive intra-operative pulmonary emboli during arterio-venous fistula/graft thrombectomy. AB - Various techniques' are currently employed for thrombectomies of the arterio venous (AV) fistula/graft to restore flow. Sub massive or massive pulmonary emboli's have been reported following such procedures both intra-operatively and post-operatively. The hemodynamic responses depend not only on the size of the emboli's but also on the pre existing cardiac or pulmonary reserve of the patient. Rapid intra-operative echocardiography by anesthesiologist not only will help the clinicians with diagnosis but also can guide treatment plan as well as prognosis. PMID- 24180173 TI - High dose streptokinase for thrombolysis in the immediate postoperative period: a case report. AB - Venous thrombo-embolism is a life threatening condition with often non specific presentation. The detection of massive pulmonary embolism in the intra and immediate post-operative period is not only difficult due to the variety of conditions with similar presentation, but the therapy for the same is complicated with concerns of surgical and intracranial bleeding precluding various options. We present a case of massive pulmonary embolism presenting as intraoperative hypotension with an increased alveolar to arterial CO2 gradient which was subsequently managed with an accelerated regimen of streptokinase without increased postoperative bleeding. Accelerated regimen of streptokinase may be used as a safe low cost alternative modality in selected cases of massive pulmonary embolism in the immediate postoperative period. PMID- 24180174 TI - Pathology quiz: oncocytic cyst of the ventricular fold. PMID- 24180175 TI - Anesthesia considerations in stiff person syndrome. AB - A 34 year old morbidly obese stiffperson syndrome (SPS) patient was scheduled for a permanent catheter placement. SPS is a rare neurologic condition with a suspected autoimmune etiology. SPS most common manifestations are progressive, including severe muscle rigidity or stiffness affecting the spine and lower extremities more than other muscle groups. SPS have superimposed episodic muscle spasms that may resemble myotonic-like contractions and are precipitated by unexpected noises, tactile stimuli, or emotional stress. This case report describes a patient with SPS and morbid obesity, and his subsequent management perioperatively for a permanent catheter placement under monitored anesthesia care. Careful and methodical management of patients with SPS is strongly suggested given their sensitivity to inhalational anesthetics and neuromuscular blockers. PMID- 24180176 TI - Role of laryngeal mask airway in interventional bronchoscopy procedures for upper tracheal stenosis: case series. AB - BACKGROUND: Bronchoscopic interventional procedures are novel means of treating airway lesions which are less invasive and well tolerated for patients with endo luminal lesions, but managing the airway and oxygenating the patient in a field that is shared by both anesthesiologist and bronchoscopist is a major concern. Also in cases with subglottic and upper tracheal stenotic lesions an airway device placed inside the lumen interferes with the procedure and occasionally bears the hazard of ignition. Therefore, an airway device placing above the glottis with effective oxygenation is required. Laryngeal mask airway is a supra glottic device which facilitates assisted or spontaneous positive pressure ventilation. METHODS: In this study, eight patients with subglottic stenoses due to different etiologies are presented who underwent fiberoptic bronchoscopy and therapeutic interventions through laryngeal mask. RESULTS: In all these patients, we experienced simple access to the vocal cord, glottis and trachea and also the lesion, besides effective oxygenation of the patient. Furthermore, bronchoscopist and patients were both comfortable with the procedures. CONCLUSION: Laryngeal mask airway could be regarded as a reliable alternative for airway management during interventional bronchoscopic procedures, especially when they are located near the glottis or in the upper third of the trachea. PMID- 24180177 TI - Transglottic basaloid squamous cell carcinoma of the larynx. AB - OBJECTIVE: To report a rare case of Transglottic Basaloid Squamous cell carcinoma of the larynx and review the pathologic features of these lesions. CASE REPORT: A 64 year old male, heavy smoker and alcohol abuser, presented with a 6 month history of hoarseness. Laryngoscopy revealed a right transglottic lesion involving the epiglottis, aryepiglottic fold, ventricle and true vocal fold. Microscopically, the tumor was characterized by infiltrating solid sheets of basaloid cells showing palisading pattern along the edges. In areas of solid growth, tumor cells displayed scant cytoplasm, and hyperchromatic nuclei. A portion of the tumor abutting the thyroid cartilage showed squamous differentiation. An island of tumor cells with comedonecrosis was also noted. Immunohistochemical staining for a number of markers was performed. CONCLUSION: Basaloid squamous cell carcinoma displays a biphasic histology. The stage of the disease at presentation is invariably advanced with metastatic lymphadenopathy in two thirds of the patients. PMID- 24180178 TI - Prevention of blood return into intravenous infusion tubing. PMID- 24180179 TI - Radial nerve lesion after malposition and sedation by continuous target controlled infusion of propofol for extracorporeal shock wave lithotripsy. PMID- 24180180 TI - High inspired carbon dioxide levels due to misplaced central tubing of the absorbent canister. AB - The authors present a case of unusual rise in inspired carbon dioxide due to misplaced absorbent canister. PMID- 24180181 TI - Community--more than just a word. PMID- 24180183 TI - The ballet of negotiations. PMID- 24180182 TI - Tapping the power of narrative to facilitate change, secure commitment and improve care delivery. PMID- 24180184 TI - Effective strategy to reduce Medicare length of stay with a voluntary medical staff model. PMID- 24180185 TI - Enhancing physician adoption of CPOE: the search for a perfect order set. PMID- 24180186 TI - Continuous quality monitoring through analytics and cloud computing. PMID- 24180187 TI - Soften up: the importance of soft skills for job success. PMID- 24180188 TI - Disruptive innovation: contributing to a value-based health care system. PMID- 24180189 TI - Aligning physicians and managing service in a regional transfer center. PMID- 24180190 TI - Leading innovations in prevention and cure. PMID- 24180191 TI - A long road home. PMID- 24180192 TI - Creating interpersonal power. PMID- 24180193 TI - Understanding the Affordable Care Act bit by bit: will transparency and sunshine shrink costs? PMID- 24180194 TI - 8 keys to effectively hire physician executives. Interview by Stephen Moulton. PMID- 24180195 TI - Evolving trends in social media compliance in medicine. PMID- 24180196 TI - [Image of the month. Pulmonary sequestration]. PMID- 24180197 TI - [How I treat dandruff]. AB - Dandruff and seborrheic dermatitis form a continuum of desquamative conditions associated with the excessive colonization of the stratum corneum by yeasts of the genus Malassezia spp. Such colonization is heterogeneous in density, ranging from discrete to abundant according to the fungal ability to adhere to individual corneocytes. The rate of action of antidandruff shampoos shed some doubts about a direct antifungal effect, but rather suggests the involvement of innate immune defenses and the chemical alteration of molecular adhesion modalities between Malassezia and corneocytes. PMID- 24180198 TI - [Mirror syndrome: a case report in fetal medicine]. AB - Mirror syndrome is a rare entity describing the association of foetal hydrops and maternal symptoms as general oedema and excessive weight gain mimicking preeclampsia. We report the case of a patient who developed symptoms of oedema, weight gain, headache and biological hemodilution associated with foetal hydrops due to a complex congenital heart defect. This symptomatology spontaneously resolved after foetal expulsion. Mirror or Ballantyne's syndrome needs to be identified on time and well differentiated from preeclampsia. Its consequences may involve the maternal and foetal prognosis. PMID- 24180199 TI - [Metformin, an antidiabetic molecule with anti-cancer properties]. AB - Numerous epidemiological cohort and case-control studies showed that type 2 diabetes is a risk factor for cancer and that metformin therapy is associated with a significant reduction in the incidence of cancer and cancer-related death when compared to other glucose-lowering agents. Such beneficial effect is observed whatever the type of cancer, but seems to be more prominent in case of gastrointestinal and breast cancers. In general, the protective effect was more evident in observational cohort studies (however, more exposed to bias due to confounding factors) than in case-control studies. However, the results of the rather rare controlled clinical trials available are not conclusive, but none of them was performed with the objective to specifically assess cancer risk. Several meta-analyses recently confirmed that metformin therapy reduces the incidence of cancers (including colorectal cancer, hepatocarcinoma, breast cancer) and cancer related mortality. Metformin may exert its anti-cancer activity by a direct effect (insulin) and an indirect effect (AMPK and mTOR). Considering all promising clinical information in patients with type 2 diabetes, further clinical trials are currently ongoing with the aim of assessing the role of metformin in oncology, especially as adjuvant in breast cancer therapy. PMID- 24180200 TI - [European Society of Cardiology guidelines for the management of grown-up congenital heart disease]. AB - Improved survival of patients with congenital heart disease has increased the number of these patients at adulthood. In 2010, the European Society of Cardiology has published new guidelines for the management of grown-up congenital heart disease. They provide more detailed information on specific defects in adults. This article summarizes the guidelines for the management of the most common adult congenital heart diseases. PMID- 24180201 TI - [Vitamin D and the skin]. AB - Vitamin D is well known for its beneficial effects on phosphocalcic homeostasis. The discovery of the role of vitamin D in cancers, infections, cardiovascular or autoimmune pathologies have promoted interest for this molecule. Skin and vitamin D are closely related. The skin is not only the site of vitamin D synthesis, but also a target organ as calcitriol plays an important hormonal and regulatory role, acting on cell proliferation, differentiation and immunomodulation. Furthermore, vitamin D influences the incidence and therapeutic response of certain dermatoses. In addition, many medical situations, mainly dermatological, require strict photoprotection and may therefore indirectly be responsible for a vitamin D deficiency in patients. The current role of vitamin D in skin cancers, inflammatory and autoimmune skin diseases is summarized. PMID- 24180202 TI - [Iodinated contrast media and iodine allergy: myth or reality?]. AB - The term "iodine allergy" is an old phrase that refers to a reaction to iodinated contrast media. After a brief review of definitions, pathophysiological mechanisms and risk factors of this clinical entity, management is urged immediate and delayed according to the most recent recommendations from the literature. We underline that iodine allergy, as such, does not really exist. PMID- 24180203 TI - [How I explore the various statistical facets of 2 x 2 tables in medicine]. AB - In the medical scientific literature, 2 x 2 contingency tables are widely used to display the distribution of binary data. They are associated with the definition of basic concepts in medicine and epidemiology that are universally utilized. They are usually taught in any basic course in biostatistics early in the medical curriculum; their interpretation however is not always straightforward. We have discerned at least eight different facets of such fourfold tables: homogeneity test, independence test, McNemar test, Cohen kappa coefficient, incidence relative risk, prevalence relative risk, odds ratio, diagnostic value of a clinical test. Each facet is illustrated by a clinical problem used as an example. This article should help the reader to understand which table he/she is actually dealing with. PMID- 24180204 TI - [Jentadueto, fixed combination of linagliptin plus metformin for the treatment of type 2 diabetes]. AB - In case of failure of metformin monotherapy, several pharmacological strategies may be considered for the treatment of type 2 diabetes. Among these, the addition of an inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme, a medication commonly named as gliptin, is increasingly used because of two main advantages over sulfonylureas, i.e. the absence of both hypoglycaemia and weight gain. The combination of a gliptin and metformin further improves glycaemic control compared to either monotherapy, due to complementary mechanisms of action. Most patients with type 2 diabetes are treated every day with numerous drugs because of the presence of comorbidities so that poor drug compliance is a major concern in such a population. The use of fixed-dose combinations (FDCs) may improve compliance and, therefore, several gliptin-metformin FDCs are now available. The most recent one is Jentadueto, which combines linagliptin, a selective DPP-4 inhibitor without renal excretion, and metformin, the first-line antidiabetic compound. This FDC is commercialized with two dosages of metformin, i.e. 2.5 mg linagliptin/850 mg metformin and 2.5 mg linagliptin/1.000 mg metformin, and should be administered twice daily with meal.While linagliptin may be prescribed whatever the renal function, the use of FDC should take into account classical restrictions imposed by the presence of metformin. PMID- 24180205 TI - [TOBI Podhaler for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis patients]. AB - TOBI Podhaler is the first dry powder formulation of tobramycin for inhaled therapy of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients from the age of 6 years. Clinical studies show a safety and efficacy profile comparable to tobramycin inhaled solution (TOBI). The short administration time and the convenient use of the system may significantly decrease the treatment burden. This paper gives a short review of the clinical studies and some practical information. PMID- 24180206 TI - [Management of gestational diabetes]. AB - Pregnancy is associated with relative carbohydrate intolerance and insulin resistance. Gestational diabetes mellitus (GDM) is recognized as a risk factor for a number of adverse outcomes during pregnancy, including excessive fetal growth, increased incidence of birth trauma and neonatal metabolic abnormalities. This recognition has led to recommendations to screen all pregnant women for GDM and to treat those whose glucose tolerance tests exceed threshold criteria. Numerous epidemiological studies show that GDM affects between 1 and 25% of pregnancies, depending on the ethnicity of the population studied and the diagnostic criteria. Intervention to change lifestyle and, if maternal hyperglycemia persists, treatment with additional oral medication or insulin injections have shown to improve perinatal outcomes. Patients with GDM have a high risk of developing type 2 diabetes in the years after delivery and these women are encouraged to practice specific health behaviours (dietary habits, physical activity) during the postpartum period. The present article discusses the management of GDM in the light of data from the latest studies and international recommendations. PMID- 24180207 TI - Oral intensity: reducing non-ventilator-associated hospital-acquired pneumonia in care-dependent, neurologically impaired patients. AB - INTRODUCTION: The purpose of this point-of-care study was to test the efficacy of a prevention-based oral care protocol in reducing non-ventilator-associated hospital-acquired pneumonia in a neurosurgical population outside the critical care environment. The researchers hypothesized that an enhanced oral care protocol would decrease the incidence of pneumonia. METHODS: This quasi experimental, comparative study took place on an acute neurosurgical unit at a tertiary care trauma hospital in Western Canada. Subjects were non-intubated, care-dependent adults with a primary diagnosis of neurologic injury/insult, and at high risk for pneumonia. The prospective study group comprised 34 subjects; two subjects were excluded from the study analysis. The retrospective study group comprised 51 subjects. Data were collected for both groups for a six-month period. Retrospective data were collected through chart review. The prospective group were eligible neurosurgical patients who received the enhanced oral care protocol. Data collection tools were developed and diagnostic criteria for hospital-acquired pneumonia were determined. The pneumonia rates between subjects who received standard oral care (retrospective group) and those who received an enhanced, prevention-based, oral care protocol (prospective group) were compared. RESULTS: A statistically significant decrease in the pneumonia rate occurred in the prospective group (p < 0.05). DISCUSSION: An enhanced oral care protocol was beneficial in reducing the incidence of non-ventilator-associated hospital acquired pneumonia. IMPLICATIONS: Nurses play a vital role in preventing hospital acquired pneumonia. Foundational nursing practices, such as regular oral hygiene, are important aspects of care in preventing nosocomial infections and related costs, optimizing health, and promoting quality care. PMID- 24180208 TI - Pilot evaluation of the family informal caregiver stroke self-management program. AB - BACKGROUND: Due to the abrupt onset of a stroke, caregivers are often unprepared for the role, have extensive needs and are at risk for negative outcomes. Interventions facilitating development of coping and problem solving skills are shown to decrease the negative effects of caregiving. The Family Informal Caregiver Stroke Self-Management (FICSS) program was developed to address the unmet needs of family caregivers of stroke survivors. OBJECTIVE: To evaluate the content, format and resource materials of the FICSS program with 10-12 family caregivers of stroke survivors within Central South Ontario. METHODS: The FICSS program is a four-module education and support series of facilitated small group discussions. Topics included: balancing changing roles, managing behaviour changes, sexuality/intimacy, and community linkages. Each module was evaluated weekly and by focus group one month after the program. RESULTS: Eleven family caregivers of stroke survivors with three years of mean caregiving experience participated. Caregivers valued the opportunity to share experiences and learn from others who understood what they were going through. Recommendations were made to improve the program topic areas, content and flow. CONCLUSIONS: The pilot evaluation of the program validated the content of the FICSS program and indicated recommendations for improvement. PMID- 24180209 TI - How do you know when your patient is "waking up": coma recovery assessment in a complex continuing care setting. AB - Coma, vegetative state (VS) and minimally conscious state (MCS) are disastrous outcomes following severe traumatic brain injury. Due to the extent of the resultant neurological deficits including hemisphere damage, loss of cellular integrity, altered and abnormal movements such as flexor and extensor patterns, and alterations in cranial nerve function, it can become difficult for the interprofessional team to identify when a patient is emerging from their coma. The Glasgow Coma Scale (GCS), commonly used to assess patients with traumatic brain injury (TBI) is not comprehensive or sensitive enough to provide concrete evidence that a patient is emerging from VS to an MCS. The purpose of this paper is to present a case study of a patient who has emerged from a persistent VS to promote a deeper understanding of what is involved when working with this clientele. Challenges in assessment of cognitive functioning, the development of successful communication through the use of technology and the goals of therapy amongst the various health team members will be provided. Collaborative support with the family will also be discussed. Members of the interprofessional team explored the literature to determine coma recovery assessment tools and best evidence guidelines to direct their interventions with this patient. PMID- 24180210 TI - Extending the record of bis-gamma-pyrone polypropionates from marine pulmonate mollusks. AB - The isolation and structure elucidation of 10 unreported polypropionate metabolites (compounds 6-15), structurally related to either ilikonapyrone (1) or onchidione (3), from two onchidiid pulmonate mollusk species are discussed. Structure elucidation was achieved by NMR spectroscopy and chemical correlation with model compounds. Evaluation of in vitro growth-inhibitory properties in human cancer cells was also carried out on some of the isolated polypropionates including previously reported onchidione metabolites. PMID- 24180211 TI - Nonvalence correlation-bound anion state of C6F6: doorway to low-energy electron capture. AB - The ground-state anion of perfluorobenzene is investigated by means of equation of-motion (EOM) methods. It is found that at the geometry of the neutral, the excess electron is bound by 0.135 eV. This anion state is nonvalence in nature with the excess electron bound in a very diffuse orbital with dispersion-type interactions between the excess electron and the valence electrons being pivotal to the binding. The diffuse correlation-bound state is shown to evolve into a more stable compact valence-bound anion state with a buckled structure having an adiabatic EA of 0.5 eV. Results are also presented for the bound anion states of the C6F6 dimer. PMID- 24180213 TI - Two new glycosides from Carduus acanthoides. AB - Two new glycosides, syringic acid-4-O-beta-L-arabinopyranoside and kaempferol-3-O alpha-L-rhamnopyranosyl-7-O-beta-D-glucuronopyranoside, were isolated from whole plants of Carduus acanthoides (Asteraceae), and their structures were elucidated on the basis of spectroscopic analysis. PMID- 24180212 TI - Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy. AB - BACKGROUND: Endoplasmic reticulum (ER) stress is considered one of the mechanisms contributing to reactive oxygen species (ROS)-mediated cell apoptosis. In diabetic cardiomyopathy (DCM), cell apoptosis is generally accepted as the etiological factor and closely related to cardiac ROS generation. ER stress is proposed the link between ROS and cell apoptosis; however, the signaling pathways and their roles in participating ER stress-induced apoptosis in DCM are still unclear. METHODS: In this study, we investigated the signaling transductions in ROS-dependent ER stress-induced cardiomocyte apoptosis in animal model of DCM. Moreover, in order to clarify the roles of IRE1 (inositol-requiring enzyme-1), PERK (protein kinase RNA (PKR)-like ER kinase) and ATF6 (activating transcription factor-6) in conducting apoptotic signal in ROS- dependent ER stress-induced cardiomocyte apoptosis, we further investigated apoptosis in high-glucose incubated cardiomyocytes with IRE1, ATF6 and PERK-knocked down respectively. RESULTS: we demonstrated that the ER stress sensors, referred as PERK, IRE1 and ATF6, were activated in ROS-mediated ER stress-induced cell apoptosis in rat model of DCM which was characterized by cardiac pump and electrical dysfunctions. The deletion of PERK in myocytes exhibited stronger protective effect against apoptosis induced by high-glucose incubation than deletion of ATF6 or IRE in the same myocytes. By subcellular fractionation, rather than ATF6 and IRE1, in primary cardiomyocytes, PERK was found a component of MAMs (mitochondria associated endoplasmic reticulum membranes) which was the functional and physical contact site between ER and mitochondria. CONCLUSIONS: ROS-stimulated activation of PERK signaling pathway takes the major responsibility rather than IRE1 or ATF6 signaling pathways in ROS-medicated ER stress-induced myocyte apoptosis in DCM. PMID- 24180214 TI - Fluorescence correlation spectroscopy study on the effects of the shape and size of a protein on its diffusion inside a crowded environment. AB - Fluorescence correlation spectroscopy (FCS) has been commonly used to study the diffusional and conformational fluctuations of labeled molecules at single molecule resolution. Here, we explored the applications of FCS inside a polyacrylamide gel to study the effects of molecular weight and molecular shape in a crowded environment. To understand the effect of molecular weight, we carried out FCS experiments with four model systems of different molecular weights in the presence of varying concentrations of acrylamide. The correlation curves were fit adequately using a model containing two diffusing components: one representing unhindered diffusion and one representing slow hindered diffusion in the gel phase. A large number of measurements carried out at different randomly chosen spots on a gel were used to determine the most probable diffusion time values using Gaussian distribution analysis. The variation of the diffusivity with the molecular weight of the model systems could be represented well using the effective medium model. This model assumes a combination of hydrodynamic and steric effects on solute diffusivity. To study the effects of solute shape, FCS experiments were carried inside a urea gradient gel to probe the urea-induced unfolding transition of Alexa488Maleimide-labeled bovine serum albumin. We showed that the scaling behavior, relating the hydrodynamic radius and the number of amino acids, changes inside an acrylamide gel for both folded and unfolded proteins. We showed further that crowding induced by a polyacrylamide gel increases the resolution of measuring the difference in hydrodynamic radii between the unfolded and folded states. PMID- 24180215 TI - Dental manpower planning in India: current scenario and future projections for the year 2020. AB - Dental manpower issues in India are discussed in this article which consists of both qualitative and quantitative research. The output of qualified dentists has increased substantially over last decade and at present there are over 117,825 dentists working in India. Although India has a dentist to population ratio of 1:10,271, the newly graduating dentists find it difficult to survive in the private sector. At present less than approximately 5% graduated dentists are working in the Government sector. If the present situation continues there will be more than one lakh dentists over supply by the year 2020. Continuation of the current situation will lead to wastage of highly trained dental manpower and create a threat to the professional integrity of the dentists. This research highlights the fact that there is an urgent need for an organised national human resource planning system to control the supply and demand of dental manpower, to ensure a uniform distribution of manpower and to give future directions to policy makers. PMID- 24180216 TI - Ionizing radiation-induced DNA damage, response, and repair. AB - SIGNIFICANCE: Ionizing radiation (IR) is an effective and commonly employed treatment in the management of more than half of human malignancies. Because IR's ability to control tumors mainly relies on DNA damage, the cell's DNA damage response and repair (DRR) processes may hold the key to determining tumor responses. IR-induced DNA damage activates a number of DRR signaling cascades that control cell cycle arrest, DNA repair, and the cell's fate. DNA double strand breaks (DSBs) generated by IR are the most lethal form of damage, and are mainly repaired via either homologous recombination (HR) or nonhomologous end joining (NHEJ) pathways. RECENT ADVANCES: In recent years, immense effort to understand and exploit the differences in the use of these repair pathways between tumors and normal cells will allow for an increase in tumor cell killing and a decrease in normal tissue injury. CRITICAL ISSUES: Regulation of the two major DSB repair mechanisms (HR and NHEJ) and new strategies, which may improve the therapeutic ratio of radiation by differentially targeting HR and NHEJ function in tumor and normal tissues, is of intense interest currently, and is the focus of this article. FUTURE DIRECTIONS: By utilizing the strategies outlined above, it may be possible to exploit differences between tumor and somatic cell DRR pathways, specifically their DSB repair mechanisms, to improve the therapeutic ratio of IR. PMID- 24180217 TI - Experimental analysis of the catalytic cycle of the borane-promoted imine reduction with hydrosilanes: spectroscopic detection of unexpected intermediates and a refined mechanism. AB - The discovery of intermediates that had not been seen before in imine reduction involving borane-mediated Si-H bond activation provided new insight into the mechanism, eventually leading to a refined catalytic cycle that also bears relevance to asymmetric variants. The catalysis proceeds through an ion pair composed of a silyliminium ion and a borohydride that subsequently reacts to yield an N-silylated amine and the borane catalyst. The latter step is enantioselectivity-determining when using a chiral borane. It was now found that there are additional intermediates that profoundly influence the outcome of such enantioselective transformations. Significant amounts of the corresponding free amine and N-silylated enamine are present in equimolar ratio during the catalysis. The free amine emerges from a borohydride reduction of an iminium ion (protonated imine) that is, in turn, generated in the enamine formation step. The unexpected alternative pathway adds another enantioselectivity-determining hydride transfer to reactions employing chiral boranes. The experiments were done with an axially chiral borane that was introduced by us a few years ago, and the refined mechanistic picture helps to understand previously observed inconsistencies in the level of enantioinduction in reductions catalyzed by this borane. Our findings are general because the archetypical electron-deficient borane B(C6F5)3 shows the same reaction pattern. This must have been overlooked in the past because B(C6F5)3 is substantially more reactive than our chiral borane with just one C6F5 group. Reactions with B(C6F5)3 must be performed at low catalyst loading to allow for detection of these fundamental intermediates by NMR spectroscopy. PMID- 24180219 TI - Selective sorption of actinides by titania nanoparticles covalently functionalized with simple organic ligands. AB - Although current and proposed reprocessing of used nuclear fuel is performed predominantly by solvent extraction processes, solid phase sorbent materials have many advantages including the ability to avoid production of large volumes of organic waste. Therefore, three titania nanoparticle based sorbent materials have been developed, functionalized with organic ligands designed to impart selectivity for elements relevant to important separations at the back end of the nuclear fuel cycle. A novel, simplified method of covalent functionalization to the titania surface has been utilized, and the resulting materials have been shown to be hydrolytically stable at pH 2. The sorption behavior of these organofunctionalized titania materials was investigated over a wide pH range with a selection of elements including fission products and actinides. Titania nanoparticles functionalized with an amine or phosphate moiety were able to demonstrate exclusive extraction of uranium under optimized conditions. Titania nanoparticles functionalized with a picolinamide moiety exhibited superior minor actinide sorption properties, in terms of both efficiency and selectivity, to solvent extraction processes using similar organic moieties. As such, organo functionalized titania materials as solid phase sorbents show promise as a future alternative to solvent extraction processes for nuclear separations. PMID- 24180218 TI - Sulfidation of silver nanoparticles: natural antidote to their toxicity. AB - Nanomaterials are highly dynamic in biological and environmental media. A critical need for advancing environmental health and safety research for nanomaterials is to identify physical and chemical transformations that affect the nanomaterial properties and their toxicity. Silver nanoparticles, one of the most toxic and well-studied nanomaterials, readily react with sulfide to form Ag(0)/Ag2S core-shell particles. Here, we show that sulfidation decreased silver nanoparticle toxicity to four diverse types of aquatic and terrestrial eukaryotic organisms (Danio rerio (zebrafish), Fundulus heteroclitus (killifish), Caenorhabditis elegans (nematode worm), and the aquatic plant Lemna minuta (least duckweed)). Toxicity reduction, which was dramatic in killifish and duckweed even for low extents of sulfidation (about 2 mol % S), is primarily associated with a decrease in Ag(+) concentration after sulfidation due to the lower solubility of Ag2S relative to elemental Ag (Ag(0)). These results suggest that even partial sulfidation of AgNP will decrease the toxicity of AgNPs relative to their pristine counterparts. We also show that, for a given organism, the presence of chloride in the exposure media strongly affects the toxicity results by affecting Ag speciation. These results highlight the need to consider environmental transformations of NPs in assessing their toxicity to accurately portray their potential environmental risks. PMID- 24180220 TI - Pericardioscopic imaging findings in cadaveric dogs: comparison of an apical pericardial window and sub-phrenic pericardectomy. AB - OBJECTIVE: To compare the pericardioscopic cardiovascular anatomy visible between apical pericardial window (PW) and sub-phrenic pericardectomy (SPP). STUDY DESIGN: Experimental study. ANIMALS: Canine cadavers (n = 5). METHODS: Thoracoscopy was performed using a transdiaphragmatic subxyphoid and right and left intercostal portals. A 4 cm * 4 cm apical PW was created with endoscopic scissors. The intra-pericardiac structures were then pericardioscopically assessed using a subjective ordinal scale (0: not visible, 1: <50% seen, 2: >50% seen) before SPP. Assessment was repeated after SPP. RESULTS: An apical PW provided limited access to the cardiac structures, with only the right ventricle >50% visible in all cadavers. The right atrium, right auricle, left ventricle, right coronary artery, and interventricular paraconal branch of the left coronary artery were observed but were typically <50% visible after apical PW. The left atrium and auricle, and heart base could not be consistently seen through an apical PW. Sub-phrenic pericardectomy significantly improved observation of all intrapericardiac structures assessed, except for the right atrium and right ventricle. CONCLUSIONS: PW centered over the cardiac apex limits evaluation of the pericardial space during pericardioscopy compared to SPP in cadaveric dogs. PMID- 24180221 TI - A case with transient refractive change after removal of pituitary tumor. AB - BACKGROUND: Refractive change can be caused by systemic illnesses such as Lupus erythematosus, thyroid deficiency, and diabetes mellitus. However, refractive change after pituitary tumor removal has so far not been reported. CASE PRESENTATION: A 62-year-old woman presented with blurred near vision 10 days after trans-sphenoidal surgery (TSS) for a pituitary tumor. Around the same time, she experienced intercurrent hyponatremia. The corrected visual acuity of both eyes was 20/20, the spherical equivalent of the right eye was -2.125 diopters, and of the left eye was -2.0 diopters before TSS. However, 11 days after TSS, the spherical equivalent of the right eye changed to -0.75 diopters, and that of left eye changed to -1.125 diopters without hyperglycemia. There were no changes in the corrected visual acuity during the follow-up. CONCLUSION: We demonstrated a case with transient refractive change after TSS. The following mechanism is proposed: Hyponatremia induced by the pituitary tumor removal causes an osmotic change in the aqueous humor with lens swelling. This case report is a reminder to both ophthalmologists and neurosurgeons that ophthalmological factors such as lens thickness and axial length should be taken into account when conducting preoperative examinations especially for patients undergoing TSS. PMID- 24180222 TI - Work status in patients with early rheumatoid arthritis: emphasis on shoulder function and mechanical exposure. AB - OBJECTIVES: The aim of this study was to investigate work status and associated factors in patients with early rheumatoid arthritis (RA), with the emphasis on shoulder function, work-related mechanical exposure, and activity limitations related to the shoulder-arm-hand. METHOD: Patients with early RA were provided with self-report questionnaires quantifying work-related mechanical exposure and activity limitations. Shoulder function (i.e. isometric muscle strength, shoulder arm movement, and shoulder pain), hand-grip force, and number of tender and swollen joints were assessed. RESULTS: The study comprised 135 patients (103 women and 32 men), with a mean age of 48 (SD 9.6) years, a mean disease duration of 21 (SD 9.6) months, and a mean Disease Activity Score using 28 joint counts (DAS28) of 3.7 (SD 1.4). The majority (75.6%) were working full- or part-time. Work hours correlated with work-related mechanical exposure (rs = -0.34, p < 0.001) and with physical work load (rs = 0.26, p = 0.0036). Work hours also correlated with shoulder function, that is shoulder-arm movement (rs = 0.34, p < 0.0001), shoulder strength (rs = 0.25, p = 0.0032), and activity-induced shoulder pain (rs = -0.45, p < 0.0001). Significant correlations were found between work hours and hand-grip force (rs = 0.45, p < 0.0001), activity limitations related to the shoulder-arm-hand (using the Disabilities of the Arm, Shoulder and Hand Questionnaire, DASH) (rs = -0.61, p < 0.0001), and DAS28 (rs = -0.43, p < 0.0001). DASH was found to be the only significant (p < 0.001) variable to independently explain the ability of working full-time [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.29-0.55 per 10 increments, area under the receiver operating characteristic (ROC) curve (AUC) 0.81, 95% CI 0.74-0.89]. CONCLUSIONS: Work status in early RA is associated with shoulder function and activity limitations related to the shoulder-arm-hand accentuated by work-related mechanical exposure. PMID- 24180223 TI - Face to face versus Facebook: does exposure to social networking web sites augment or attenuate physiological arousal among the socially anxious? AB - The present study tested two competing hypotheses about the effect of Facebook exposure on the physiological arousal level of participants who then encountered the stimulus person in a face-to-face situation. Facebook exposure may attenuate later arousal by providing increased comfort and confidence, but it is also possible that Facebook exposure will augment arousal, particularly among the socially anxious. Participants completed a measure of social anxiety and were exposed to a stimulus person via Facebook, face to face, or both. Galvanic skin response was recorded during the exposures to the stimulus person. Results were consistent with the augmentation hypothesis: a prior exposure on Facebook will lead to increased arousal during a face-to-face encounter, particularly for those high in social anxiety. PMID- 24180224 TI - Proteomic and metabolomic profiles of larval hemolymph associated with diapause in the cotton bollworm, Helicoverpa armigera. AB - BACKGROUND: Diapause is programmed developmental arrest coupled with the depression of metabolic activity and the enhancement of stress resistance. Pupal diapause is induced by environmental signals and is prepared during the prediapause phase. In the cotton bollworm, Helicoverpa armigera, the prediapause phase, which contains two sub-phases, diapause induction and preparation, occurs in the larval stage. Here, we performed parallel proteomic and metabolomic analyses on H. armigera larval hemolymph during the prediapause phase. RESULTS: By two-dimensional electrophoresis, 37 proteins were shown to be differentially expressed in diapause-destined larvae. Of these proteins, 28 were successfully identified by MALDI-TOF/TOF mass spectrometry. Moreover, a total of 22 altered metabolites were found in diapause-destined larval hemolymph by GC-MS analysis, and the levels of 17 metabolites were elevated and 5 were decreased. CONCLUSIONS: The proteins and metabolites with significantly altered levels play different roles in diapause-destined larvae, including diapause induction, metabolic storage, immune response, stress tolerance, and others. Because hemolymph circulates through the whole body of an insect, these differences found in diapause-destined larvae most likely correspond to upstream endocrine signals and would further influence other organ/tissue activities to determine the insect's fact: diapause or development. PMID- 24180225 TI - Horizontal acquisition and a broad biodistribution typify simian foamy virus infection in a cohort of Macaca fascicularis. AB - BACKGROUND: Foamy viruses are non-pathogenic in vivo and naturally infect all species of non-human primates (NHP). Simian foamy viruses (SFV) are highly prevalent in both free ranging and captive NHP but few longitudinal studies have been performed to assess the prevalence and biodistribution of SFV within captive NHP. METHOD: LTR and pol gene along with Gag antibody detection were undertaken to identify infection in a cohort of over 80 captive macaques. RESULTS: The prevalence of SFV was between 64% and 94% in different groups. Access to 23 dam infant pairs allowed us to reveal horizontal transfer as the dominant route of SFV transmission in our cohort. Further, analysis of SFV from a range of tissues and blood revealed that macaques as young as six months old can be infected and that proviral biodistribution increases with age. CONCLUSIONS: These are the first data of this type for a captive cohort of cynomolgus macaques. PMID- 24180226 TI - Hand, foot, and mouth syndrome in an immunocompetent adult: a case report. AB - BACKGROUND: Hand, foot, and mouth syndrome (HFMS) is a common acute illness. It is characterized by mild clinical symptoms including fever, blisters, and sores in the mouth and on the palms and soles following a 3- to 7-day incubation period. This syndrome is rarely seen in adults. CASE PRESENTATION: A 35-year-old male Caucasian patient had a history of multiple episodes of acute pharyngitis, hypertension, hypercholesterolemia, and occasional abdominal pain. He presented with polyarthralgia in the knees and hands and odynophagia, followed by fever, oral mucosal aphthous lesions, and vesicles on the palms and soles. Three weeks after presentation, he was admitted to the emergency room with acute myocarditis. The in-hospital evaluation revealed positive serology for coxsackie A9 (1:160), positive anti-transglutaminase and anti-gliadin antibodies, normal immunoglobulins, and human immunodeficiency virus negativity. CONCLUSION: We herein describe a case of HFMS that was associated with coxsackie A9 infection complicated by acute myocarditis. Although an association between celiac disease and HFMS has not been described, this patient's immunologic disruption could have favored the development of infection and ultimately HFMS. PMID- 24180229 TI - Phonology in Swedish-speaking 3-year-olds born with cleft lip and palate and the relationship with consonant production at 18 months. AB - BACKGROUND: Approximately 50% of children born with cleft palate present speech difficulties around 3 years of age, and several studies report on persisting phonological problems after palatal closure. However, studies on early phonology related to cleft palate are few and have so far mainly been carried out on English-speaking children. Studies on phonology related to cleft palate in languages other than English are also warranted. AIMS: To assess phonology in Swedish-speaking children born with and without unilateral cleft lip and palate (UCLP) at 3 years of age, and to identify variables at 18 months that are associated with restricted phonology at age 3 years. METHODS & PROCEDURES: Eighteen consecutive children born with UCLP and 20 children without cleft lip and palate were included. Transcriptions of audio recordings at 18 months and 3 years were used. Per cent correct consonants adjusted for age (PCC-A), the number of established phonemes, and phonological simplification processes at 3 years were assessed and compared with different aspects of consonant inventory at 18 months. OUTCOMES & RESULTS: PCC-A, the number of established phonemes, and the total number of phonological processes differed significantly at 3 years between the two groups. Total number of oral consonants, oral stops, dental/alveolar oral stops and number of different oral stops at 18 months correlated significantly with PCC-A at 3 years in the UCLP group. CONCLUSIONS & IMPLICATIONS: As a group, children born with UCLP displayed deviant phonology at 3 years compared with peers without cleft lip and palate. Measures of oral consonant and stop production at 18 months might be possible predictors for phonology at 3 years in children born with cleft palate. PMID- 24180230 TI - The effects of sarcopenia on muscles with different recruitment patterns and myofiber profiles. AB - Sarcopenia, or the age-related loss of muscle size/mass, is a major health concern in western societies where aging is prevalent. Currently, more is known about sarcopenia's impact on health and quality of life, than its physiological etiology. It remains to be clearly determined whether the onset and progression of sarcopenia is similar throughout the body (systemic), or is more localized to certain muscles and myofiber types comprising those muscles (local). The objective of this project was to quantify the systemic vs. local nature of sarcopenia. Three muscles of different myofiber type composition and/or function (Soleus, Plantaris, EDL) were collected from 10 young adult rats, and 10 aged rats. Immunohistochemical procedures were then performed on frozen muscle sections to determine average myofiber size, fiber type composition, and relative areas of muscles occupied by each myofiber type. Significant (P <= 0.05) overall age-related myofiber atrophy occurred in the predominantly fast-twitch, non postural Plantaris and EDL muscles, but not in the primarily slow-twitch, postural Soleus. Moreover, age-related atrophy was significantly (~100%) greater in the EDL than the Plantaris. Age-related myofiber type conversion also demonstrated muscle specificity in that all fiber types were affected in the Soleus, compared to three of the four myofiber types of the Plantaris, and only one of the four myofiber types identified in the EDL. In sum, these data suggest that although sarcopenia may be ubiquitous among skeletal muscles, the degree of its impact displays specificity based not only on myofiber type composition, but also on muscle function. PMID- 24180231 TI - Synthesis of 2-hydroxypropyl-beta-cyclodextrin/pluronic-based polyrotaxanes via heterogeneous reaction as potential Niemann-Pick type C therapeutics. AB - Five polyrotaxanes were synthesized by threading 2-hydroxypropyl-beta cyclodextrin (HP-beta-CD) onto a variety of alpha,omega-ditriethylenediamino-N carbamoyl-poly-(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (Pluronic) triblock copolymers using a two-pot strategy under heterogeneous, nonaqueous conditions. The threaded HP-beta-CD units were retained on the pseudopolyrotaxane precursors by end-capping the branched diamine termini with sodium 2,4,6-trinitrobenzene sulfonate. Inclusion of the Pluronic copolymers within the HP-beta-CD cavities was more favorable in nonpolar solvents, such as diethyl ether and n-hexane, both of which gave better coverage ratios than polar solvents. (1)H NMR and MALDI-TOF were used to estimate the average molecular weights of the purified polyrotaxane products. A globular morphology of aggregated polyrotaxanes was observed by tapping-mode AFM imaging of dried samples. Treatment of Niemann-Pick C (NPC) type 2-deficient fibroblasts with the polyrotaxane derivatives produced substantial reductions in sterol accumulation, as seen by diminished filipin staining in these cells, suggesting that Pluronic based polyrotaxanes may be promising vehicles for delivery of HP-beta-CD to cells with abnormal cholesterol accumulation. PMID- 24180233 TI - Branch retinal artery occlusion following radiation therapy to the head and neck: a case report. AB - BACKGROUND: Previous studies have established that radiation to the head and neck leads to atherosclerosis and stenosis of the carotid artery and subsequent increased stroke risk, but the ophthalmic sequella following cervical irradiation is less well-defined. CASE PRESENTATION: We present a single case of branch retinal artery occlusion (BRAO) in a 55 year-old Caucasian male seen at the University of Michigan in 2008 following unilateral head and neck radiation. CONCLUSION: This case demonstrates that patients receiving radiation to the head and neck may be at increased risk for developing a BRAO secondary to atherosclerotic changes of vessels adjacent to the radiation target. Given this risk, it may be reasonable to obtain carotid artery imaging in patients with a history of cervical radiation who present with sudden or transient visual field defects, even in the absence of other conventional risk factors for atherosclerosis. PMID- 24180232 TI - Comparative effect of angiotensin II type I receptor blockers on serum uric acid in hypertensive patients with type 2 diabetes mellitus: a retrospective observational study. AB - BACKGROUND: Angiotensin II type 1 receptor blockers (ARB) are a frequently used class of antihypertensive drug. The ARB losartan is known to decrease the serum uric acid (SUA) level. However, there are very few clinical data comparing the effects of other ARBs on SUA level under the conditions of clinical practice. This study evaluated and compared the long-term effects of monotherapy with five ARBs on SUA level in Japanese hypertensive patients with type 2 diabetes mellitus (DM). METHODS: We identified hypertensive patients with type 2 DM who had been treated with monotherapy with losartan (n = 214), valsartan (n = 266), telmisartan (n = 185), candesartan (n = 458), or olmesartan (n = 192), in whom laboratory data of SUA between November 1, 2004 and July 31, 2011 were available, from the Nihon University School of Medicine's Clinical Data Warehouse (NUSM's CDW). We used a propensity-score weighting method and a multivariate regression model to adjust for differences in the background among ARB users, and compared the SUA level. The mean exposure of losartan was 264.7 days, valsartan 245.3 days, telmisartan 235.9 days, candesartan 248.9 days, and olmesartan 234.5 days. RESULTS: In losartan users, mean SUA level was significantly decreased from baseline, while it was conversely increased in users of other ARBs; valsartan, telmisartan, candesartan, and olmesartan. The mean reduction of SUA level from baseline was significantly greater in losartan users compared with that in other ARB users. Comparison of ARBs other than losartan showed no significant difference in mean change in SUA level from baseline. CONCLUSIONS: Our study showed that losartan had the most beneficial effect on SUA level among five ARBs, and that there was no significant difference in the unfavorable effects on SUA level among four ARBs other than losartan, at least during one year. These findings provide evidence of an effect of ARBs on SUA level, and support the benefit of the use of losartan in hypertensive patients with type 2 DM. PMID- 24180234 TI - Global transcriptome analysis of AtPAP2--overexpressing Arabidopsis thaliana with elevated ATP. AB - BACKGROUND: AtPAP2 is a purple acid phosphatase that is targeted to both chloroplasts and mitochondria. Over-expression (OE) lines of AtPAP2 grew faster, produced more seeds, and contained higher leaf sucrose and glucose contents. The present study aimed to determine how high energy status affects leaf and root transcriptomes. RESULTS: ATP and ADP levels in the OE lines are 30-50% and 20-50% higher than in the wild-type (WT) plants. Global transcriptome analyses indicated that transcriptional regulation does play a role in sucrose and starch metabolism, nitrogen, potassium and iron uptake, amino acids and secondary metabolites metabolism when there is an ample supply of energy. While the transcript abundance of genes encoding protein components of photosystem I (PS I), photosystem II (PS II) and light harvesting complex I (LHCI) were unaltered, changes in transcript abundance for genes encoding proteins of LHCII are significant. The gene expressions of most enzymes of the Calvin cycle, glycolysis and the tricarboxylic acid (TCA) cycle were unaltered, as these enzymes are known to be regulated by light/redox status or allosteric modulation by the products (e.g. citrate, ATP/ADP ratio), but not at the level of transcription. CONCLUSIONS: AtPAP2 overexpression resulted in a widespread reprogramming of the transcriptome in the transgenic plants, which is characterized by changes in the carbon, nitrogen, potassium, and iron metabolism. The fast-growing AtPAP2 OE lines provide an interesting tool for studying the regulation of energy system in plant. PMID- 24180235 TI - Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial. AB - BACKGROUND: Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. METHODS/DESIGN: This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ?1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. DISCUSSION: This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. TRIAL REGISTRATION: NCT01695850. PMID- 24180236 TI - Policy on Hazard Analysis and Critical Control Point (HACCP) and adherence to food preparation guidelines: a cross sectional survey of stakeholders in food service in Kumasi, Ghana. AB - BACKGROUND: Food borne diseases claim more lives and are growing public health concerns. Simple preventive techniques such as adoption and adherence to hazard analysis and critical control point (HACCP) policy can significantly reduce this disease burden. Though food screening and inspection are done, the ultimate regulation, Hazard Analysis and Critical Control Point, which is known and accepted worldwide, appears not to be popular among food operators in Ghana. This paper examines the level of awareness of the existence of policy on hazard analysis and critical control point (HACCP) and its adherence to food preparation guidelines among food service providers in Ghana. RESULTS: The results revealed the mean age of food providers as 33.1 years with a standard deviation of 7.5, range of 18-55 years, more females, in full time employment and with basic education. Of the fifty institutional managers, 42 (84%) were senior officers and had worked for more than five years. Education and type of food operator had strong statistically significant relationship with the implementation of HCCP policy and adherence with food preparation guidelines. The enforcement of HACCP policy and adherence with food safety guidelines was led by the Ghana Tourist Board, Public Health officers, and KMA, respectively. While a majority of food operators 373/450 (83.3%) did not know HACCP policy is part of food safety guidelines, staff of food safety law enforcement 44/50 (88%) confirmed knowing that food operators were not aware of the HACCP policy. CONCLUSION: The study documents evidence on the practice of food safety principles or HACCP policy or adherence to food preparation guidelines. Existing food safety guidelines incorporate varying principles of HACCP, however, awareness is low among food operators. The implication is that food production is likely to fall short of acceptable standards and not be wholesome putting consumers at health risk. Repeating this study in rural and urban areas in Ghana is necessary to provide much more evidence to inform food safety guidelines. Further studies on chemical analysis of food and implementing training modules on HACCP policy for food producers and law enforcement agencies may be helpful to improve existing situation. PMID- 24180237 TI - An alternative protocol for Plasmodium falciparum culture synchronization and a new method for synchrony confirmation. AB - BACKGROUND: Although the Percoll/sorbitol synchronization method is widely accepted, its use for achieving tight synchronizations is cumbersome. In addition, subsequent conclusions on the synchrony status are often based on visual inspection of parasites and few reports provide an unbiased estimate confirming the degree of synchrony. This report presents a simpler synchronization procedure and offers an objective method to validate parasite synchrony. METHODS: Parasite synchronization was performed by culturing late stage schizont parasites for a defined period of time, subjecting them to Percoll density centrifugations, and collecting the newly formed rings. Repeating the process several times on the un-egressed schizonts maximizes the recovery of several synchronized ring-stage parasite populations. The culture synchrony for each population was verified by allowing the synchronized rings to mature to late stage schizonts and collecting ring-stage sample aliquots at three-hour intervals for nine hours. The aliquots were then measured, using the SyBr Green I assay, to determine when the ring-stage parasitaemia stops increasing. RESULTS: Quantitative measurements of ring-stage parasites showed that under the conditions described, a four to six-hour synchrony period is obtained. CONCLUSION: By taking advantage of Plasmodium's periodic lifecycle in erythrocytes, it is shown that Percoll density centrifugation alone is sufficient to tightly synchronize cultures with minimal parasite loss. In addition, the degree of culture synchrony is validated using the SyBr Green I assay. PMID- 24180239 TI - Early feeding of fortified breast milk and in-hospital-growth in very premature infants: a retrospective cohort analysis. AB - BACKGROUND: Fortified human milk may not meet all nutritional needs of very preterm infants. Early transition from complementary parenteral nutrition to full enteral feeds might further impair in-hospital growth. We aimed to investigate the impact of the cumulative intake of fortified human milk on early postnatal growth in a cohort of very low birth weight infants after early transition to full enteral feeds. METHODS: Retrospective single-centre observational study. Data are presented as median (interquartile range). RESULTS: N = 206 very preterm infants were analysed (gestational age at birth 27.6 (25.6-29.6) weeks, birth weight 915 (668-1170) g). Full enteral feeds were established at postnatal day 8 (6-10) and adequate postnatal growth was achieved (difference in standard deviation score for weight from birth to discharge -0.105(-0.603 - -0.323)). Standard deviation score for weight from birth to day 28 decreased more in infants with a cumulative human milk intake > 75% of all enteral feeds (-0.64( 1.08 - -0.34)) compared to those with < 25% human milk intake (-0.41(-0.7 - 0.17); p = 0.017). At discharge, a trend towards poorer weight gain with higher proportions of human milk intake persisted. In contrast, we observed no significant difference for head circumference growth. CONCLUSIONS: Our current standardized fortification of human milk may not adequately support early postnatal growth. PMID- 24180238 TI - Signaling function of heme oxygenase proteins. AB - SIGNIFICANCE: Many reports have underscored the importance of the heme degradation pathway that is regulated by heme oxygenase (HO). This reaction releases bile pigments and carbon monoxide (CO), which are important antioxidant and signaling molecules. Thus, the reaction of HO-1 would have significant cytoprotective effects. Nevertheless, the importance of this protein goes beyond its enzymatic action. New evidence outlines significant effects of inactive forms of the HO-1 protein. RECENT ADVANCES: In fact, the role of the HO protein in cellular signaling, including transcription factor activation, binding to proteins, phosphorylation, and modulation of protein function, among others, has started being elucidated. The mechanism by which the inducible form of HO-1, in particular, can migrate to various cellular compartments to mediate important signaling or how and why it binds to key transcription factors and other proteins that are important in DNA repair is also described in several physiologic systems. CRITICAL ISSUES: The signaling functions of HO-1 may have particular relevance in clinical circumstances, including cancer, as redistribution of HO-1 into the nuclear compartment is observed with cancer progression and metastasis. In addition, along with oxidative stress, the pleiotropic functions of HO-1 modulate antioxidant defense. In organ transplantation, HO and its byproducts suppress rejection at multiple levels and in sepsis-induced pulmonary dysfunction, inhaled CO or modulation of HO activity can change the course of the disease in animals. FUTURE DIRECTIONS: It is hoped that a more detailed understanding of the various signaling functions of HO will guide therapeutic approaches for complex diseases. PMID- 24180241 TI - Life based on phosphite: a genome-guided analysis of Desulfotignum phosphitoxidans. AB - BACKGROUND: The Delta-Proteobacterium Desulfotignum phosphitoxidans is a type strain of the genus Desulfotignum, which comprises to date only three species together with D. balticum and D. toluenicum. D. phosphitoxidans oxidizes phosphite to phosphate as its only source of electrons, with either sulfate or CO2 as electron acceptor to gain its metabolic energy, which is of exclusive interest. Sequencing of the genome of this bacterium was undertaken to elucidate the genomic basis of this so far unique type of energy metabolism. RESULTS: The genome contains 4,998,761 base pairs and 4646 genes of which 3609 were assigned to a function, and 1037 are without function prediction. Metabolic reconstruction revealed that most biosynthetic pathways of Gram negative, autotrophic sulfate reducers were present. Autotrophic CO2 assimilation proceeds through the Wood Ljungdahl pathway. Additionally, we have found and confirmed the ability of the strain to couple phosphite oxidation to dissimilatory nitrate reduction to ammonia, which in itself is a new type of energy metabolism. Surprisingly, only two pathways for uptake, assimilation and utilization of inorganic and organic phosphonates were found in the genome. The unique for D. phosphitoxidans Ptx-Ptd cluster is involved in inorganic phosphite oxidation and an atypical C-P lyase coding cluster (Phn) is involved in utilization of organophosphonates. CONCLUSIONS: We present the whole genome sequence of the first bacterium able to gain metabolic energy via phosphite oxidation. The data obtained provide initial information on the composition and architecture of the phosphite-utilizing and energy-transducing systems needed to live with phosphite as an unusual electron donor. PMID- 24180242 TI - Phenylboronic-acid-modified nanoparticles: potential antiviral therapeutics. AB - Phenylboronic-acid-modified nanoparticles (NPs) are attracting considerable attention for biological and biomedical applications. We describe here a convenient and general protocol for attaching multiple copies of para-substituted phenylboronic acid moieties onto either iron-oxide-, silica- or diamond-derived NPs. The boronic acid functionalized NPs are all fabricated by first modifying the surface of each particle type with 4-azidobenzoic ester functions. These azide-terminated nanostructures were then reacted with 4-[1-oxo-4-pentyn-1-yl) amino]phenylboronic acid units via a Cu(I) catalyzed Huisgen cycloaddition to furnish, conveniently, the corresponding boronic-acid modified NPs (or "borono lectins") targeted in this work. The potential of these novel "borono-lectins" as antiviral inhibitors was investigated against the Hepatitis C virus (HCV) exploiting a bioassay that measures the potential of drugs to interfere with the ability of cell-culture-derived JFH1 virus particles to infect healthy hepatocytes. As far as we are aware, this is the first report that describes NP derived viral entry inhibitors and thus serves as a "proof-of-concept" study. The novel viral entry activity demonstrated, and the fact that the described boronic acid-functionalized NPs all display much reduced cellular toxicities compared with alternate NPs, sets the stage for their further investigation. The data supports that NP-derived borono-lectins should be pursued as a potential therapeutic strategy for blocking viral entry of HCV. PMID- 24180243 TI - Acute drug toxicity related to drinking herbal tea in a kidney transplant recipient. AB - Calcineurin and mTOR inhibitors are commonly used immunosuppressive agents with narrow therapeutic range. As the drugs are mainly metabolized by the P450 cytochrome system, the interaction between food and herbs are also commonly seen and affect the drug levels. We present a case of a kidney transplant recipient with toxic therapeutic levels of cyclosporine A and sirolimus due to interaction between the immunosuppressive agents and Chinese herbal tea. Ingredients within the herbal tea were reported to have inhibitory effect on cytochrome CYP3A4 in vitro studies. Transplant recipients should be alert that there may be potent interaction between the immunosuppressive drugs and herbs resulting in adverse effect on allograft function. PMID- 24180244 TI - Oral intralipid emulsion use: a novel therapeutic approach to pancreatic beta cell injury caused by malathion toxicity in rats. AB - We aimed to investigate whether oral intralipid emulsion (OIE) reduces pancreatic beta-cell injury (PbetaCI) by chelating with malathion (M), or increases PbetaCI by increasing M absorption in the stomach. Fifty rats were randomly divided into six groups: control group (C); OIE administered group (L); M-treated group (M); OIE-administered group immediately after given M (M0L); OIE-administered group 6 hours after being given M (M6L) and OIE administered group 12 hours after being given M (M12L). M induced PbetaCI, hyperglycemia, temporary hyperinsulinemia and oxidative stress (OS). However, there was no significant difference in serum levels of glucose, insulin, total oxidants (TOS) and liver TOS between the M0L group and groups C and L. Also, insulin levels of M12L significantly increased, compared to the M6L group. Biochemical results, which were confirmed by histopathology, indicate that administering OIE after 6 hours and immediately after taking M may markedly prevent PbetaCI, hyperglycemia and OS. In addition, OIE's effectiveness decreased after 6 hours and was totally ineffective after 12 hours. We concluded that OIE may help to achieve a better prognosis and reduce mortality rate in cases presented to the emergency department, particularly within the first 6 hours, resulting from organophosphate pesticide poisoning by oral ingestion. PMID- 24180245 TI - Plasma-assisted nanoscale protein patterning on Si substrates via colloidal lithography. AB - Selective immobilization of proteins in well-defined patterns on substrates has recently attracted considerable attention as an enabling technology for applications ranging from biosensors and BioMEMS to tissue engineering. In this work, a method is reported for low-cost, large scale and high throughput, selective immobilization of proteins on nanopatterned Si, based on colloidal lithography and plasma processing to define the areas (<300 nm) where proteins are selectively immobilized. A close-packed monolayer of PS microparticles is deposited on oxidized Si and, either after microparticle size reduction or alternatively after metal deposition through the PS close-packed monolayer, is used as etching mask to define SiO2 nanoislands (on Si). C4F8 plasma was used to selectively etch and modify the SiO2 nanoislands while depositing a fluorocarbon layer on the Si surface. The plasma-treated surfaces were chemically characterized in terms of functional group identification through XPS analysis and reaction with specific molecules. Highly selective protein immobilization mainly through physical adsorption on SiO2 nanoislands and not on surrounding Si was observed after C4F8 plasma-induced chemical modification of the substrate. The thickness of the immobilized protein monolayer was estimated by means of AFM image analysis. The method reported herein constitutes a cost-efficient route toward rapid, large surface, and high-density patterning of biomolecules on solid supports that can be easily applied in BioMEMS or microanalytical systems. PMID- 24180247 TI - Tuning the K+ concentration in the tunnel of OMS-2 nanorods leads to a significant enhancement of the catalytic activity for benzene oxidation. AB - OMS-2 nanorods with tunable K(+) concentration were prepared by a facile hydrothermal redox reaction of MnSO4, (NH4)2S2O8, and (NH4)2SO4 at 120 degrees C by adding KNO3 at different KNO3/MnSO4 molar ratios. The OMS-2 nanorod catalysts are characterized by X-ray diffraction, transmission electron microscopy, N2 adsorption and desorption, inductively coupled plasma, and X-ray photoelectron spectrometry. The effect of K(+) concentration on the lattice oxygen activity of OMS-2 is theoretically and experimentally studied by density functional theory calculations and CO temperature-programmed reduction. The results show that increasing the K(+) concentration leads to a considerable enhancement of the lattice oxygen activity in OMS-2 nanorods. An enormous decrease (DeltaT50 = 89 degrees C; DeltaT90 > 160 degrees C) in reaction temperatures T50 and T90 (corresponding to 50 and 90% benzene conversion, respectively) for benzene oxidation has been achieved by increasing the K(+) concentration in the K(+) doped OMS-2 nanorods due to the considerable enhancement of the lattice oxygen activity. PMID- 24180248 TI - Lipid directed intrinsic membrane protein segregation. AB - We demonstrate a new approach for direct reconstitution of membrane proteins during giant vesicle formation. We show that it is straightforward to create a tissue-like giant vesicle film swelled with membrane protein using aquaporin SoPIP2;1 as an illustration. These vesicles can also be easily harvested for individual study. By controlling the lipid composition we are able to direct the aquaporin into specific immiscible liquid domains in giant vesicles. The oligomeric alpha-helical protein cosegregates with the cholesterol-poor domains in phase separating ternary mixtures. PMID- 24180249 TI - Negative cognitive style and looming cognitive style synergistically predict stress generation. AB - There is a growing body of evidence that suggests that cognitive vulnerabilities to depression or anxiety may lead individuals to generate negative interpersonal life events. However, there has been no study to date that examines the effects of co-occurring vulnerabilities to depression and anxiety. In a sample of 304 participants, we examined the potential interaction of co-occurring negative cognitive style, a vulnerability to depression and looming cognitive style, vulnerability to anxiety. Results indicate that co-occurring cognitive vulnerabilities synergistically predict higher levels of negative interpersonal life events six weeks later, even when controlling for initial levels of stressful life events and symptoms of depression and anxiety. Thus, co-occurring vulnerabilities may have stronger stress generating effects than would be expected from the additive effects of each vulnerability considered separately. This finding highlights the importance of examining cognitive vulnerabilities as interactive effects rather than as individual vulnerabilities. PMID- 24180250 TI - Exposure of health workers in primary health care to glutaraldehyde. AB - BACKGROUND: In order to avoid proliferation of microorganisms, cleaning, disinfection and sterilisation in health centres is of utmost importance hence reducing exposure of workers to biological agents and of clients that attend these health centres to potential infections. One of the most commonly-used chemical is glutaraldehyde. The effects of its exposure are well known in the hospital setting; however there is very little information available with regards to the primary health care domain. OBJECTIVE: To determine and measure the exposure of health workers in Primary Health Care Centres. Environmental to glutaraldehyde and staff concentration will be measured and compared with regulated Occupational Exposure Limits. METHODS/DESIGN: Observational, cross sectional and multi-centre study. The study population will be composed of any health professionals in contact with the chemical substance that work in the Primary Health Care Centres in the areas of Barcelones Nord, Maresme, and Barcelona city belonging to the Catalan Institute of Health.Data will be collected from 1) Glutaraldhyde consumption from the previous 4 years in the health centres under study. 2) Semi-structured interviews and key informants to gather information related to glutaraldehyde exposure. 3) Sampling of the substance in the processes considered to be high exposure. DISCUSSION: Although glutaraldehyde is extensively used in health centres, scientific literature only deals with certain occupational hazards in the hospital setting.This study attempts to take an in-depth look into the risk factors and environmental conditions that exist in the primary care workplace with exposure to glutaraldehyde. PMID- 24180252 TI - Effects of gas or vapor adsorption on adhesion, friction, and wear of solid interfaces. AB - The adsorption of vapor molecules plays an important role in countless fields and is increasingly realized to be critical in tribology, which encompasses adhesion, friction, and wear of surfaces. This feature article reviews experimental methods for quantifying gas and vapor adsorption on flat solid surfaces under equilibrium conditions (ambient pressure and temperature) as well as the effects of these adsorbates on the adhesion, friction, and wear of various materials. Particular attention is given to species that are present in the ambient environment such as water (humidity) and organic vapors. These adsorbed species can have drastic yet varied influences on tribology depending on the surface chemistry of materials. Despite prolonged and ubiquitous observations in a broad range of materials and vapors, a fundamental understanding of the effect of adsorbed gases and vapors on the adhesion, friction, and wear of surfaces has begun only recently through surface-sensitive characterization. PMID- 24180251 TI - Association of LXRalpha polymorphisms with obesity and obesity-related phenotypes in an Iranian population. AB - BACKGROUND: Obesity is a multifactorial disorder due to the complex interaction between genetic and environmental factors. Liver X receptor alpha (LXRalpha), encoded by the gene NR1H3, is involved in lipoprotein metabolism and its genetic variations may also play a role in the aetiology of obesity. AIM: To assess the association of two NR1H3 polymorphisms (rs11039155 and rs2279238) and their haplotypes with obesity in an Iranian population. SUBJECTS AND METHODS: A total of 447 unrelated subjects (including 206 overweight, 162 obese and 79 controls) were enrolled in the study and were genotyped by TaqMan assay using DNA from peripheral blood. The association of these two LXRalpha polymorphisms with the presence of obesity and overweight was assessed. RESULTS: There was no significant association between the two SNPs and obesity, even after adjustment for age and sex. By logistic regression using a dominant model, the odds ratios for obesity were: 1.32 (0.85-2.74) for rs11039155 and 0.77 (0.30--1.99) for rs2279238. Haplotype analyses identified three common haplotypes GC, GT and AC with frequency greater than 1%, but none of the haplotypes was associated with the risk of obesity. CONCLUSIONS: This study revealed that there was no significant association between LXRalpha polymorphisms and the presence of obesity in an Iranian population and suggests that these two SNPs are not major contributors to obesity risk in this population. PMID- 24180253 TI - Cytokine response to pregnancy-associated recrudescence of Plasmodium berghei infection in mice with pre-existing immunity to malaria. AB - BACKGROUND: During childhood, residents of areas with stable transmission of Plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults therefore rarely experience clinical disease episodes. However, susceptibility to infection reappears in pregnant women, particularly primigravidae. This is due to appearance of antigenic parasite variants that are restricted to pregnancy. Variant-specific immunity also governs pregnancy associated recrudescence of Plasmodium berghei infection in pregnant mice. Pregnancy-related changes in the plasma cytokine levels of mice with immunity acquired prior to first pregnancy have not been studied in detail previously, and were the topic of the present study. METHODS: A multiplexed bead assay was used to measure plasma levels of IL-5, IL-10, IL-12, IL-13, IFN-gamma and TNF in BALB/c mice immunized against P. berghei K173 by repeated infection and drug cure before the first pregnancy. The association between cytokine levels on the one hand and parasitaemia and haemoglobin levels on the other, in mice that had never been pregnant or were pregnant for the first, second or third time were evaluated by Mann-Whitney test and Spearman rank-order correlation analysis. RESULTS: Pregnancy per se did not further increase the already high cytokine levels in mice previously immunized by repeated infection and drug cure. Levels of all the cytokines except IL-10 were correlated with each other, and with parasitaemia and haemoglobin levels. Furthermore, levels of all cytokines were positively correlated with parity, except IL-10, which was negatively correlated with parity. High levels of IL-10 and low levels of the other cytokines were associated with poor pregnancy outcome. CONCLUSIONS: High levels of IL-10 and low levels of the other cytokines were associated with poor pregnancy outcome in this mouse model of placental malaria. Since the model replicates key parasitological and immunological features of placental P. falciparum malaria, it underpins its usefulness in immunology and pathogenesis studies of this important cause of mother/child morbidity in endemic areas. PMID- 24180255 TI - Heterochrony in a complex world: disentangling environmental processes of facultative paedomorphosis in an amphibian. AB - Heterochrony, the change in the rate or timing of development between ancestors and their descendants, plays a major role in evolution. When heterochrony produces polymorphisms, it offers the possibility to test hypotheses that could explain its success across environments. Amphibians are particularly suitable to exploring these questions because they express complex life cycles (i.e. metamorphosis) that have been disrupted by heterochronic processes (paedomorphosis: retention of larval traits in adults). The large phenotypic variation across populations suggests that more complex processes than expected are operating, but they remain to be investigated through multivariate analyses over a large range of natural populations across time. In this study, we compared the likelihood of multiple potential environmental determinants of heterochrony. We gathered data on the proportion of paedomorphic and metamorphic palmate newts (Lissotriton helveticus) across more than 150 populations during 10 years and used an information-theoretic approach to compare the support of multiple potential processes. Six environmental processes jointly explained the proportion of paedomorphs in populations: predation, water availability, dispersal limitation, aquatic breathing, terrestrial habitat suitability and antipredator refuges. Analyses of variation across space and time supported models based on the advantage of paedomorphosis in favourable aquatic habitats. Paedomorphs were favoured in deep ponds, in conditions favourable to aquatic breathing (high oxygen content), with lack of fish and surrounded by suitable terrestrial habitat. Metamorphs were favoured by banks allowing easy dispersal. These results indicate that heterochrony relies on complex processes involving multiple ecological variables and exemplifies why heterochronic patterns occur in contrasted environments. On the other hand, the fast selection of alternative morphs shows that metamorphosis and paedomorphosis developmental modes could be easily disrupted in natural populations. PMID- 24180254 TI - Interactions between risky decisions, impulsiveness and smoking in young tattooed women. AB - BACKGROUND: According to previous studies, one of the common problems of everyday life of persons with tattoos is risky behavior. However, direct examination of the decision making process, as well as factors which determine women's risk taking decisions to get tattoos, have not been conducted. This study investigates whether risk taking decision-making is associated with the self-assessment impulsiveness in tattooed women. METHODS: Young women (aged 18-35 years) with (N = 60) and without (N = 60) tattoos, performed the Iowa Gambling Task (IGT), as a measure of decision-making processes, as well as completing the Barratt Impulsivity Scale (BIS-11). RESULTS: Tattooed women showed significantly higher scores in the BIS-11 and preference for disadvantageous decks on the IGT compared to non-tattooed women. There was no significant correlation between risky decision-making in the IGT and BIS-11 impulsivity measures. A significantly higher rate of smoking was observed in the tattooed women. However, the analysis did not reveal a group effect after adjustment for smoking in the IGT and the BIS 11 measures. CONCLUSIONS: The present study was specifically designed to resolve questions regarding associations between impulsiveness and risky decision-making in tattooed women. It shows that in tattooed women, risky decisions are not a direct result of their self-reported impulsiveness. Smoking does not explain the psychometric differences between tattooed women and controls. PMID- 24180256 TI - Cervical dentin hypersensitivity: a cross-sectional investigation in Athens, Greece. AB - The purpose of this study was to identify the prevalence of cervical dentin hypersensitivity in a cross-sectional investigation of Greek adults. Seven hundred and sixty-seven subjects were examined. Participants were patients processed for first examination in the Clinic of Oral Diagnosis and Radiology at the Faculty of Dentistry, University of Athens. The evaluation of hypersensitivity was performed using two methods: for each tooth, the response to a) tactile stimulus and b) air-blast stimulus was measured. Additional factors such as smoking habits, oral health behaviour, consumption of acidic foods, type of toothbrush, daily use of fluoride solution and of desensitising toothpaste, gingival recession and non-carious cervical lesions were recorded and evaluated as causative factors. Descriptive statistics on the demographics of the study sample, of oral health behaviour characteristics and of oral examination findings were performed. Comparisons of these characteristics in the presence or absence of hypersensitivity were conducted with the chi-square test. Data were further analysed using multiple logistic regression modelling. Among study participants, 21.3% had at least one cervical dentin hypersensitivity reaction to the tactile stimulus, and 38.6%, to the air-blast stimulus. Multivariate analysis detected association of the hypersensitivity in tactile or air-blast stimulus with the non carious lesions and with the gingival recessions. Additionally, a relation between hypersensitivity and air-blast stimulus with gender (female) was found. There was no association between the hypersensitivity in both of the stimuli and the level of education, smoking, consumption of acidic foods, type of toothbrush and daily use of fluoride solution or desensitising toothpaste. The overall prevalence of cervical dentin hypersensitivity in the adult population in Athens ranged from 21.3% to 38.6% depending on the type of stimuli. Cervical non-carious lesions and gingival recessions were determined as significant predictors of dentin hypersensitivity. PMID- 24180258 TI - Synthesis of palladium/helical carbon nanofiber hybrid nanostructures and their application for hydrogen peroxide and glucose detection. AB - We report on a novel sensing platform for H2O2 and glucose based on immobilization of palladium-helical carbon nanofiber (Pd-HCNF) hybrid nanostructures and glucose oxidase (GOx) with Nafion on a glassy carbon electrode (GCE). HCNFs were synthesized by a chemical vapor deposition process on a C60 supported Pd catalyst. Pd-HCNF nanocomposites were prepared by a one-step reduction free method in dimethylformamide (DMF). The prepared materials were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Raman spectroscopy. The Nafion/Pd HCNF/GCE sensor exhibits excellent electrocatalytic sensitivity toward H2O2 (315 mA M(-1) cm(-2)) as probed by cyclic voltammetry (CV) and chronoamperometry. We show that Pd-HCNF-modified electrodes significantly reduce the overpotential and enhance the electron transfer rate. A linear range from 5.0 MUM to 2.1 mM with a detection limit of 3.0 MUM (based on the S/N = 3) and good reproducibility were obtained. Furthermore, a sensing platform for glucose was prepared by immobilizing the Pd-HCNFs and glucose oxidase (GOx) with Nafion on a glassy carbon electrode. The resulting biosensor exhibits a good response to glucose with a wide linear range (0.06-6.0 mM) with a detection limit of 0.03 mM and a sensitivity of 13 mA M(-1) cm(-2). We show that small size and homogeneous distribution of the Pd nanoparticles in combination with good conductivity and large surface area of the HCNFs lead to a H2O2 and glucose sensing platform that performs in the top range of the herein reported sensor platforms. PMID- 24180259 TI - Media milling process optimization for manufacture of drug nanoparticles using design of experiments (DOE). AB - Design of experiments (DOE), a component of Quality by Design (QbD), is systematic and simultaneous evaluation of process variables to develop a product with predetermined quality attributes. This article presents a case study to understand the effects of process variables in a bead milling process used for manufacture of drug nanoparticles. Experiments were designed and results were computed according to a 3-factor, 3-level face-centered central composite design (CCD). The factors investigated were motor speed, pump speed and bead volume. Responses analyzed for evaluating these effects and interactions were milling time, particle size and process yield. Process validation batches were executed using the optimum process conditions obtained from software Design-Expert(r) to evaluate both the repeatability and reproducibility of bead milling technique. Milling time was optimized to <5 h to obtain the desired particle size (d90 < 400 nm). The desirability function used to optimize the response variables and observed responses were in agreement with experimental values. These results demonstrated the reliability of selected model for manufacture of drug nanoparticles with predictable quality attributes. The optimization of bead milling process variables by applying DOE resulted in considerable decrease in milling time to achieve the desired particle size. The study indicates the applicability of DOE approach to optimize critical process parameters in the manufacture of drug nanoparticles. PMID- 24180257 TI - Heme oxygenase-1: a metabolic nike. AB - SIGNIFICANCE: Heme degradation, which was described more than 30 years ago, is still very actively explored with many novel discoveries on its role in various disease models every year. RECENT ADVANCES: The heme oxygenases (HO) are metabolic enzymes that utilize NADPH and oxygen to break apart the heme moiety liberating biliverdin (BV), carbon monoxide (CO), and iron. Heme that is derived from hemoproteins can be toxic to the cells and if not removed immediately, it causes cell apoptosis and local inflammation. Elimination of heme from the milieu enables generation of three products that influences numerous metabolic changes in the cell. CRITICAL ISSUES: CO has profound effects on mitochondria and cellular respiration and other hemoproteins to which it can bind and affect their function, while BV and bilirubin (BR), the substrate and product of BV, reductase, respectively, are potent antioxidants. Sequestration of iron into ferritin and its recycling in the tissues is a part of the homeodynamic processes that control oxidation-reduction in cellular metabolism. Further, heme is an important component of a number of metabolic enzymes, and, therefore, HO-1 plays an important role in the modulation of cellular bioenergetics. FUTURE DIRECTIONS: In this review, we describe the cross-talk between heme oxygenase-1 (HO-1) and its products with other metabolic pathways. HO-1, which we have labeled Nike, the goddess who personified victory, dictates triumph over pathophysiologic conditions, including diabetes, ischemia, and cancer. PMID- 24180260 TI - Design, optimization and evaluation of poly-epsilon-caprolactone (PCL) based polymeric nanoparticles for oral delivery of lopinavir. AB - Lopinavir (LPV)-loaded poly-epsilon-caprolactone (PCL) nanoparticles (NPs) were prepared by emulsion solvent evaporation technique. Effects of various critical factors in preparation of loaded NPs were investigated. Box-Behnken design (BBD) was employed to optimize particle size and entrapment efficiency (EE) of loaded NPs. Optimized LPV NPs exhibited nanometeric size (195.3 nm) with high EE (93.9%). In vitro drug release study showed bi-phasic sustained release behavior of LPV from NPs. Pharmacokinetic study results in male Wistar rats indicated an increase in oral bioavailability of LPV by 4-folds after incorporation into PCL NPs. From tissue distribution studies, significant accumulation of loaded NPs in tissues like liver and spleen indicated possible involvement of lymphatic route in absorption of NPs. Mechanistic studies using rat everted gut sac model revealed endocytosis as a principal mechanism of NPs uptake. In vitro rat microsomal metabolism studies demonstrated noticeable advantage of LPV NPs by affording metabolic protection to LPV. These studies indicate usefulness of PCL NPs in enhancing oral bioavailability and improving pharmacokinetic profile of LPV. PMID- 24180261 TI - Oxidative stress, a common molecular pathway for kidney disease: role of the redox enzyme p66Shc. AB - Accumulation of oxidative stress is considered to be a causative mediator of kidney disease, and oxidative stress can affect some key regulators of kidney homeostasis and control a number of signaling pathways that are relevant to kidney disease. The p66Shc adaptor protein was discovered more than two decades ago as a pivotal regulator of oxidative stress. Given the importance of oxidative stress in kidney homeostasis, several molecular and cellular studies using a p66Shc antagonist have depicted a role for p66Shc in renal pathophysiology. The specificity of p66Shc functions may depend upon their intracellular localization and expression in the kidney. This review focuses on the biochemical functions of the p66Shc adaptor protein, as well as its potential implications in the pathophysiology of kidney disease. In addition, the concept that pharmacologic modulation of p66Shc expression and activity may serve as a novel and effective target for the treatment of kidney disease is discussed. PMID- 24180262 TI - Biased cyclical electrical field flow fractionation for separation of sub 50 nm particles. AB - Cyclical electrical field flow fractionation (CyElFFF) is a technique for characterizing and separating nanoparticles based on their size and charge using cyclical electric fields. The high diffusion rate of nanoparticles has prevented CyElFFF from being applicable to particles smaller than 100 nm. In this work, the diffusion challenges associated with nanoparticles was resolved using biased cyclical electric fields. This new method, biased cyclical electrical field flow fractionation (BCyElFFF), achieves baseline separation of 15 and 40 nm gold nanoparticles. Theoretical considerations show that the optimal resolution is achieved when the applied bias yields electrical transport that counteracts the diffusive transport of nanoparticles. BCyElFFF greatly extends separation capabilities of the cyclical electrical field flow fractionation to sub 50 nm nanoparticles and provides a powerful alternative to other separation and characterization techniques capable of separating nanoparticles smaller than 50 nm. PMID- 24180264 TI - Randomised controlled pilot trial of mindfulness training for stress reduction during pregnancy. AB - This randomised controlled pilot trial tested a six-week mindfulness-based intervention in a sample of pregnant women experiencing high levels of perceived stress and pregnancy anxiety. Forty-seven women enrolled between 10 and 25 weeks gestation were randomly assigned to either a series of weekly Mindful Awareness Practices classes (n = 24) with home practice or to a reading control condition (n = 23). Hierarchical linear models of between-group differences in change over time demonstrated that participants in the mindfulness intervention experienced larger decreases from pre-to post-intervention in pregnancy-specific anxiety and pregnancy-related anxiety (PRA) than participants in the reading control condition. However, these effects were not sustained through follow-up at six weeks post-intervention. Participants in both groups experienced increased mindfulness, as well as decreased perceived stress and state anxiety over the course of the intervention and follow-up periods. This study is one of the first randomised controlled pilot trials of a mindfulness meditation intervention during pregnancy and provides some evidence that mindfulness training during pregnancy may effectively reduce PRA and worry. We discuss some of the dilemmas in pursuing this translational strategy and offer suggestions for researchers interested in conducting mind-body interventions during pregnancy. PMID- 24180265 TI - Microbial inactivation by cupric ion in combination with H2O2: role of reactive oxidants. AB - The cupric ion mediated inactivation of Escherichia coli was enhanced by the presence of hydrogen peroxide (H2O2), with increasing inactivation efficacy observed in response to increasing concentrations of H2O2. The biocidal activity of the Cu(II)/H2O2 system is believed to result from the oxidative stress caused by reactive oxidants such as the hydroxyl radical ((*)OH), cupryl species (Cu(III)), and the superoxide radical (O2(*-)), which are produced via the catalytic decomposition of H2O2. In E. coli cells treated with Cu(II) and H2O2, the intracellular level of (*)OH and Cu(III) increased significantly, leading to complete disruption of cell membranes. On the basis of experimental observations made using an (*)OH scavenger, copper-chelating agents, and superoxide dismutase, it is concluded that Cu(III) is the predominant species responsible for the death of E. coli cells. It was also found that the production of Cu(III) was promoted by the reactions of copper with intracellular O2(*-). MS2 coliphage was found to be even more susceptible than E. coli to the oxidative stress induced by the Cu(II)/H2O2 system. PMID- 24180266 TI - Metagenomics of rumen bacteriophage from thirteen lactating dairy cattle. AB - BACKGROUND: The bovine rumen hosts a diverse and complex community of Eukarya, Bacteria, Archea and viruses (including bacteriophage). The rumen viral population (the rumen virome) has received little attention compared to the rumen microbial population (the rumen microbiome). We used massively parallel sequencing of virus like particles to investigate the diversity of the rumen virome in thirteen lactating Australian Holstein dairy cattle all housed in the same location, 12 of which were sampled on the same day. RESULTS: Fourteen putative viral sequence fragments over 30 Kbp in length were assembled and annotated. Many of the putative genes in the assembled contigs showed no homology to previously annotated genes, highlighting the large amount of work still required to fully annotate the functions encoded in viral genomes. The abundance of the contig sequences varied widely between animals, even though the cattle were of the same age, stage of lactation and fed the same diets. Additionally the twelve animals which were co-habited shared a number of their dominant viral contigs. We compared the functional characteristics of our bovine viromes with that of other viromes, as well as rumen microbiomes. At the functional level, we found strong similarities between all of the viral samples, which were highly distinct from the rumen microbiome samples. CONCLUSIONS: Our findings suggest a large amount of between animal variation in the bovine rumen virome and that co habiting animals may have more similar viromes than non co-habited animals. We report the deepest sequencing to date of the rumen virome. This work highlights the enormous amount of novelty and variation present in the rumen virome. PMID- 24180267 TI - Strategy for enhancing second-order nonlinear optical properties of the Pt(II) dithienylethene complexes: substituent effect, pi-conjugated influence, and photoisomerization switch. AB - The second-order nonlinear optical (NLO) properties of a series of Pt(II) dithienylethene (DTE) complexes possessing the reversible photochromic behavior have been investigated by density functional theory (DFT) combined with the analytic derivatives method. The results show that the calculated static first hyperpolarizabilities (betatot) of the open-ring and closed-ring systems significantly increase in the range of 2.1-4.5 times through strengthening of the electron-withdrawing ability of the substituent R (R = H, CF3, NO2) and an increase of the number of thiophene rings. Moreover, there is a large enhancement of the betatot values from the open-ring systems to the corresponding closed-ring systems. This efficient enhancement is attributed to the better delocalization of the pi-electron system, the more obvious degree of charge transfer, and the larger f(os)/E(gm)(3) (f(os) is the oscillator strength, and E(gm) is the transition energy between the ground and the excited states) values in the closed forms according to the bond length alternation (BLA) and time-dependent density functional theory (TDDFT) calculations. In addition, the dispersion has less influence on the frequency-dependent first hyperpolarizabilities (betatot(omega)) of the studied systems at the low-frequency area omega (0.000-0.040 au). Our present work would be beneficial for further theoretical and experimental studies on large second-order NLO responses of metal complexes. PMID- 24180268 TI - Occupational, life stress and family functioning: does it affect semen quality? AB - BACKGROUND AND AIMS: Although psychological stress has been implicated as a cause of idiopathic infertility in both men and women, it has received little scientific attention among males as compared to females. The aim of the study was to examine the association between occupational, life stress, family functioning and semen quality. METHODS AND RESULTS: The study population consisted of 327 men who were attending an infertility clinic for diagnostic purposes. Psychological stress was assessed based on two questionnaires: The Subjective Work Characteristics Questionnaire and the Perceived Stress Scale. The level of satisfaction with family functioning and support was evaluated by means of the APGAR Family Scale. The findings suggest that, on the one hand, exposure to occupational stressors can be negatively associated with semen quality (there was a positive association between stress and the percentage of sperm with DNA damage (p = 0.03) and atypical sperm (p = 0.05)); on the other hand, there was no correlation between the level of life stress and semen quality indicators. Negative associations were found between satisfaction with family functioning and the percentage of motile sperm cells (p = 0.02), VAP (p = 0.05), VSL (p = 0.05) and VCL (p = 0.04). CONCLUSION: The study indicates that occupational stress can affect male semen quality; however, due to limited data on this issue, the obtained results should be confirmed in longitudinal studies. PMID- 24180269 TI - Robust measurement of membrane bending moduli using light sheet fluorescence imaging of vesicle fluctuations. AB - The mechanical rigidity of lipid membranes is a key determinant of the energetics of cellular membrane deformation. Measurements of membrane bending moduli remain rare, however, and show a large variance, a situation that can be addressed by the development of improved techniques and by comparisons between disparate techniques applied to the same systems. We introduce here the use of selective plane illumination microscopy (SPIM, also known as light sheet fluorescence microscopy) to image thermal fluctuations of giant vesicles. The optical sectioning of SPIM enables high-speed fluorescence imaging of freely suspended vesicles and quantification of edge localization precision, yielding robust fluctuation spectra and rigidity estimates. For both lipid-only membranes and membranes bound by the intracellular trafficking protein Sar1p, which lowers membrane rigidity in a concentration-dependent manner, we show that the resulting bending modulus values are in close agreement with those derived from an independent assay based on membrane tether pulling. We also show that the fluctuation spectra of vesicles bound by the mammalian Sar1A protein, which stiffens membranes at high concentrations, are not well fit by a model of homogeneous quasi-spherical vesicles, suggesting that SPIM-based analysis can offer insights into spatially inhomogeneous properties induced by protein assemblies. PMID- 24180270 TI - Commemorating the 1913 Michaelis-Menten paper Die Kinetik der Invertinwirkung: three perspectives. AB - Methods and equations for analysing the kinetics of enzyme-catalysed reactions were developed at the beginning of the 20th century in two centres in particular; in Paris, by Victor Henri, and, in Berlin, by Leonor Michaelis and Maud Menten. Henri made a detailed analysis of the work in this area that had preceded him, and arrived at a correct equation for the initial rate of reaction. However, his approach was open to the important objection that he took no account of the hydrogen-ion concentration (a subject largely undeveloped in his time). In addition, although he wrote down an expression for the initial rate of reaction and described the hyperbolic form of its dependence on the substrate concentration, he did not appreciate the great advantages that would come from analysis in terms of initial rates rather than time courses. Michaelis and Menten not only placed Henri's analysis on a firm experimental foundation, but also defined the experimental protocol that remains standard today. Here, we review this development, and discuss other scientific contributions of these individuals. The three parts have different authors, as indicated, and do not necessarily agree on all details, in particular about the relative importance of the contributions of Michaelis and Menten on the one hand and of Henri on the other. Rather than force the review into an unrealistic consensus, we consider it appropriate to leave the disagreements visible. PMID- 24180271 TI - Stilbene vinyl sulfonamides as fluorogenic sensors of and traceless covalent kinetic stabilizers of transthyretin that prevent amyloidogenesis. AB - Small molecules that react selectively with a specific non-enzyme drug-target protein in a complex biological environment without displacement of a leaving group (tracelessly) are rare and highly desirable. Herein we describe the development of a family of fluorogenic stilbene-based vinyl amides and vinyl sulfonamides that covalently modify transthyretin (TTR) tracelessly. These small molecules bind selectively to TTR in complex biological environments and then undergo a rapid and chemoselective 1,4-Michael addition with the pKa-perturbed Lys-15 epsilon-amino group of TTR. Replacing the vinyl amide in 2 with the more reactive vinyl sulfonamide in 4 hastens the conjugation kinetics. X-ray cocrystallography verified the formation of the secondary amine bond mediating the conjugation in the case of 2 and 4 and confirmed the expected orientation of the stilbene within the TTR binding sites. Vinyl amide 2 and vinyl sulfonamide 4 potently inhibit TTR dissociation and amyloid fibril formation in vitro. The TTR binding selectivity, modification yield, and reaction chemoselectivity of vinyl sulfonamide 4 are good enough in human plasma to serve as a starting point for medicinal chemistry efforts. Moreover, vinyl sulfonamide 4 is fluorogenic: it exhibits minimal background fluorescence in complex biological environments, remains dark upon binding to TTR, and becomes fluorescent only upon reaction with TTR. The fluorogenicity of 4 was utilized to accurately quantify the native TTR concentration in Escherichia coli lysate using a fluorescence plate reader. PMID- 24180272 TI - Cysteamine-based cell-permeable Zn(2+)-specific molecular bioimaging materials: from animal to plant cells. AB - Structure-interaction/fluorescence relationship studies led to the development of a small chemical library of Zn(2+)-specific cysteamine-based molecular probes. The probe L5 with higher excitation/emission wavelengths, which absorbs in the visible region and emits in the green, was chosen as a model imaging material for biological studies. After successful imaging of intracellular zinc in four different kinds of cells including living organisms, plant, and animal cells, in vivo imaging potential of L5 was evaluated using plant systems. In vivo imaging of translocation of zinc through the stem of a small herb with a transparent stem, Peperomia pellucida, confirmed the stability of L5 inside biological systems and the suitability of L5 for real-time analysis. Similarly, fluorescence imaging of zinc in gram sprouts revealed the efficacy of the probe in the detection and localization of zinc in cereal crops. This imaging technique will help in knowing the efficiency of various techniques used for zinc enrichment of cereal crops. Computational analyses were carried out to better understand the structure, the formation of probe-Zn(2+) complexes, and the emission properties of these complexes. PMID- 24180273 TI - What is the potential for social networks and support to enhance future telehealth interventions for people with a diagnosis of schizophrenia: a critical interpretive synthesis. AB - BACKGROUND: Digital technologies are increasingly directed at improved monitoring, management and treatment of mental health. However, their potential contribution to social networks and self-management support for people diagnosed with a serious mental illness has rarely been considered. This review and meta synthesis aimed to examine the processes of engagement and perceived relevance and appropriateness of telehealth interventions for people with a diagnosis of schizophrenia. The review addresses three key questions. How is the use of digital communications technologies framed in the professional psychiatric literature? How might the recognised benefits of telehealth translate to people with a diagnosis of schizophrenia? What is the user perspective concerning Internet information and communication technologies? METHODS: A critical interpretive synthesis (CIS) of published findings from quantitative and qualitative studies of telehealth interventions for people with a diagnosis of schizophrenia. RESULTS: Most studies were of an exploratory nature. The professional discourse about the use of different technologies was overlain by concerns with surveillance and control, focusing on the Internet as a potential site of risk and danger. The critical synthesis of findings showed that the key focus of the available studies was on the delivery of existing traditional approaches (e.g. improving medications adherence, provision of medical information about the condition, symptom monitoring and cognitive behavioural therapy). Even though it was clear that the Internet has considerable potential in terms of accessing and utilising lay support, the potential of communication technologies in mobilising of resources for personal self-management or peer support was a relatively absent or hidden a focus of the available studies. CONCLUSIONS: Based on an interpretive synthesis of available studies, people with a diagnosis of schizophrenia or psychosis use the Internet primarily for the purposes of disclosure and information gathering. Empowerment, regulation and surveillance emerged as the key dimensions of engagement (or not) with telehealth interventions. The findings suggest that telehealth interventions are disproportionately used by particular patient groups (e.g.women, people who are employed). Further research needs to ascertain the mechanisms by which telehealth interventions may be potentially beneficial or harmful for engagement and management to people with a diagnosis of schizophrenia. PMID- 24180274 TI - Design, synthesis and in vitro evaluation of 18beta-glycyrrhetinic acid derivatives for anticancer activity against human breast cancer cell line MCF-7. AB - In the present work, QSAR model was derived by multiple linear regression method for the prediction of anticancer activity of 18beta-glycyrrhetinic acid derivatives against the human breast cancer cell line MCF-7. The QSAR model for anti-proliferative activity against MCF-7 showed high correlation (r(2)=0.90 and rCV(2)=0.83) and indicated that chemical descriptors namely, dipole moment (debye), steric energy (kcal/mole), heat of formation (kcal/mole), ionization potential (eV), LogP, LUMO energy (eV) and shape index (basic kappa, order 3) correlate well with activity. The QSAR virtually predicted that active derivatives were first semi-synthesized and characterized on the basis of their (1)H and (13)C NMR spectroscopic data and then were in-vitro tested against MCF-7 cancer cell line. In particular, octylamide derivative of glycyrrhetinic acid GA 12 has marked cytotoxic activity against MCF-7 similar to that of standard anticancer drug paclitaxel. The biological assays of active derivative selected by virtual screening showed significant experimental activity. PMID- 24180275 TI - Targeting MDM2-p53 interaction for cancer therapy: are we there yet? AB - Inactivation of the tumor suppressor p53 and/or overexpression of the oncogene MDM2 frequently occur in human cancers, and are associated with poor prognosis, advanced forms of the disease, and chemoresistance. MDM2, the major negative regulator of p53, induces p53 degradation and inactivates its tumor suppressing activity. In turn, p53 regulates MDM2 expression. This MDM2-p53 negative feedback loop has been widely studied and presents an attractive target for cancer therapy, with a few of the inhibitors of this interaction already having advanced into clinical trials. Additionally, there is an increasing interest in understanding MDM2's p53-independent activities in carcinogenesis and cancer progression, which may also have implications for cancer therapy. This review aims to highlight the various roles that the MDM2-p53 interaction plays in cancer, the p53 independent oncogenic activities of MDM2 and the various strategies that may be used to target MDM2 and the MDM2-p53 interaction. We will summarize the major preclinical and clinical evidences of MDM2 inhibitors for human cancer treatment and make suggestions to further improve efficacy and safety of this interesting class of cancer therapeutics. PMID- 24180276 TI - The inhibition of extended spectrum beta-lactamases: hits and leads. AB - The ongoing emergence of bacterial strains resistant to even third- and fourth generation beta-lactam antibiotics is one of the most pressing and challenging issues in clinical therapy. Furthermore, under the pressure of antibiotics used ubiquitously over the last 80 years, functional mutations and new resistances are continuously increasing. Therefore, new drugs and new approaches to the infections produced by multidrug-resistant Gram-negative bacteria are categorically necessary and expected by the scientific community. This review describes the most deleterious known extended-spectrum beta- lactamases and the molecules now available for targeting bacterial infections. The active-site chemical and geometric properties that are potentially exploitable for the design of both broad-spectrum and selective compounds are described. PMID- 24180277 TI - Cobra cardiotoxins: membrane interactions and pharmacological potential. AB - Natural polycationic membrane-active peptides typically lack disulfide bonds and exhibit fusion, cell-penetrating, antimicrobial activities. They are mostly unordered in solution, but adopt a helical structure, when bound to phospholipid membranes. Structurally different are cardiotoxins (or cytotoxins, CTs) from cobra venom. They are fully beta- structured molecules, characterized by the three-finger fold (TFF). Affinity of CTs to lipid bilayer was shown to depend on amino acid sequence in the tips of the three loops. In the present review, CT membrane interactions are analyzed through the prism of data on binding of the toxins to phospholipid liposomes and detergent micelles, as well as their structural and computational studies in membrane mimicking environments. We assess different hydrophobicity scales to compare membrane partitioning of various CTs and their membrane effects. A comparison of hydrophobic/hydrophilic properties of CTs and linear polycationic peptides provides a key to their biological activity and creates a fundamental basis for rational design of new membrane-interacting compounds, including new promising drugs. For instance, from the viewpoint of the data obtained on model lipid membranes, cytotoxic activity of CTs against cancer cells is discussed. PMID- 24180278 TI - New poteintial serum biomarkers in multiple sclerosis identified by proteomic strategies. AB - Proteome analysis of body fluids is a powerful tool to identify biomarkers of neurological disorders. Multiple sclerosis (MScl) is a chronic disabling disorder of central nervous system (CNS) and is regarded as an autoimmune disease to myelin components. Clinical subtypes of MScl differ in course, prognosis and response to available therapy. There is evidence of a different pattern of CNS lesions in subtypes, suggesting different immunological mechanisms are relevant in inflammatory demyelination. In order to elucidate proteome signatures, we used two-dimensional differential gel electrophoresis (2D-DIGE) to compare the protein expression profile in serum of different clinical subtypes of MScl patients and of healthy volunteers, resp. controls. Significant expression differences were detected by 2D-DIGE for 241 serum proteins, and transthyretin, zinc-alpha-2 glycoprotein, alpha-1-antitrypsin, immunoglobulin and complement factors (C4, C6 and C8) were identified as potential disease signatures for MScl patients. Three highly-expressed proteins were selected for further evaluation in individual patients by independent immunoassays, and the up-regulation of transthyretin, zinc alpha-2-glycoprotein and immunoglobulin kappa light chain was validated in sera of relapsing-remitting (CIS and RRMScl) patients, when compared to healthy donors. To present significant expression differences in PPMScl, analysis with a larger patient population is required. PMID- 24180279 TI - Synthesis and antiproliferative activity of substituted 3[2-(1H-indol-3-yl)- 1,3 thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsentin analogues. AB - A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G2/M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr(34) and to increase the cytotoxic activity of paclitaxel in STO cells. PMID- 24180280 TI - Stimulation of DDX3 expression by ginsenoside Rg3 through the Akt/p53 pathway activates the innate immune response via TBK1/IKKepsilon/IRF3 signalling. AB - DEAD-box RNA helicase DDX3 is a well-known host factor that inhibits hepatitis B viral proliferation and boosts innate immune responses via TANK-binding kinase 1 (TBK1)/IKKepsilon-mediated and/or interferon (IFN)-beta promoter stimulator-1 (IPS-1)-mediated IFN-beta induction. Previously, we demonstrated the anti hepatitis B activity of Rg3 via stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signaling. To determine the effects of Rg3 on innate immunity, an IFN-beta promoter assay was performed. Rg3 ameliorated IFN-beta expression via upregulation of both the TBK1/IKKepsilon pathway and DDX3 expression. In addition, Rg3 induced the phosphorylation of IRF3 and its translocation into nucleus, which is a key molecule to induction of IFN-beta expression. To evaluate the molecular mechanism of Rg3 on DDX3 expression, the DDX3 promoter (-1406/+105) was subjected to luciferase assay and ChIP analysis. p53 phosphorylation resulted in upregulation of DDX3 expression, which enhanced DDX3 promoter transactivation activity. Transient transfection with wild-type p53 increased DDX3 promoter activity in Hep3B cells which have null mutant of p53, whereas knockdown p53 by si-p53 reduced DDX3 promoter activity in HepG2.2.15 and HepG2 cells, respectively. Rg3- mediated phosphorylation of p53 resulted in inhibition of Akt phosphorylation, which in turn reduced MDM2-mediated p53 degradation. An Akt inhibitor augmented DDX3 promoter activity and reduced the secretion of hepatitis B surface antigen. Our data indicate that Rg3 enhances innate immunity by inducing IFN-beta expression through upregulation of DDX3 promoter activity via p53-mediated transactivation and activation of the TBK1/IKKepsilon/IRF3 pathway. PMID- 24180281 TI - Neurophysiological measures of nociceptive brain activity in the newborn infant- the next steps. AB - Infants within neonatal intensive care units can receive multiple medically essential painful procedures per day. How they respond to these events, how best to alleviate the negative effects, and the long-term consequences for the infant are all significant questions that have yet to be fully answered. In recent years, several studies have examined cortical responses to noxious stimuli in the neonate through the use of near-infrared spectroscopy (NIRS) and electroencephalography (EEG). These investigations dispel any notion that the newborn infant does not process noxious stimuli at a cortical level and open the way for future research. In this Viewpoint Article, we review these studies and discuss key clinical challenges which may be elucidated with the use of these techniques. CONCLUSION: Simultaneously measuring the changes that are evoked in behaviour, physiology and the cortex following noxious events will provide the best approach to understanding the neonate's experience of pain. PMID- 24180282 TI - Assessment of organ dose reduction and secondary cancer risk associated with the use of proton beam therapy and intensity modulated radiation therapy in treatment of neuroblastomas. AB - BACKGROUND: To compare proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT) with conformal radiation therapy (CRT) in terms of their organ doses and ability to cause secondary cancer in normal organs. METHODS: Five patients (median age, 4 years; range, 2-11 years) who underwent PBT for retroperitoneal neuroblastoma were selected for treatment planning simulation. Four patients had stage 4 tumors and one had stage 2A tumor, according to the International Neuroblastoma Staging System. Two patients received 36 Gy, two received 21.6 Gy, and one received 41.4 Gy of radiation. The volume structures of these patients were used for simulations of CRT and IMRT treatment. Dose-volume analyses of liver, stomach, colon, small intestine, pancreas, and bone were performed for the simulations. Secondary cancer risks in these organs were calculated using the organ equivalent dose (OED) model, which took into account the rates of cell killing, repopulation, and the neutron dose from the treatment machine. RESULTS: In all evaluated organs, the mean dose in PBT was 20-80% of that in CRT. IMRT also showed lower mean doses than CRT for two organs (20% and 65%), but higher mean doses for the other four organs (110-120%). The risk of secondary cancer in PBT was 24-83% of that in CRT for five organs, but 121% of that in CRT for pancreas. The risk of secondary cancer in IMRT was equal to or higher than CRT for four organs (range 100-124%). CONCLUSION: Low radiation doses in normal organs are more frequently observed in PBT than in IMRT. Assessments of secondary cancer risk showed that PBT reduces the risk of secondary cancer in most organs, whereas IMRT is associated with a higher risk than CRT. PMID- 24180283 TI - Pulsed resources and the coupling between life-history strategies and exploration patterns in eastern chipmunks (Tamias striatus). AB - Understanding the causes of animal personality (i.e. consistent behavioural differences) is a major aim of evolutionary studies. Recent theoretical work suggests that major personality traits may contribute to evolutionary trade-offs. However, such associations have only been investigated in a few study systems, and even less so in free ranging animal populations. Eastern chipmunks exhibit consistent individual differences in exploration, ranging from slow to fast. Birth cohorts also experience dramatic differences in age at first breeding opportunity due to annual differences in beech mast. Individuals may breed for the first time at 24, 33 or 50% of their average life span, depending on year of birth. Here, we used data from a long-term survey on a wild population to investigate the relationship between reproductive life history and consistent individual differences in exploration. We determined whether predictable differences in age at first breeding opportunity among birth cohorts were associated with exploration differences and favoured individuals with different exploration. Birth cohorts with a predictably earlier age at first breeding opportunity were faster explorers on average. Slower explorers displayed their highest fecundity (females) or highest fertilization success (males) later in their life compared with faster explorers. Overall, slow explorers attained a higher lifetime reproductive success than fast explorers when given an opportunity to reproduce later in their life. Our results suggest that the timing of mating seasons, associated with fluctuating food abundance, may favour individual variation in exploration and maintain population variation through its effects on reproductive life history. Together, our result shed light on how fluctuation in ecological conditions may maintain personality differences and on the nature of the relationships between animal personality and life history. PMID- 24180284 TI - Optical chemical pH sensors. PMID- 24180285 TI - Catalytic C-C and C-heteroatom bond formation reactions: in situ generated or preformed catalysts? Complicated mechanistic picture behind well-known experimental procedures. AB - In situ generated catalysts and preformed catalysts are two practical strategies widely used in cross-coupling methodology that have long been considered to involve the same active species in the catalytic cycle. Recent mechanistic studies have revealed two fundamentally different pictures of catalytic reactions in solution. Preformed catalysts with strongly bound ligands initiate transformations mainly involving single type of metal species. In contrast, in situ generated catalysts give rise to cocktail-type systems with different metal species presented in solution. The role of catalyst precursor, interconversions of catalytic species during reaction, stability and recycling of catalyst, catalysis by autocatalyst exhaust and plausible sources of metal-containing contaminants are the key points discussed in this review. PMID- 24180286 TI - Catalytic production of hydrogen peroxide and water by oxygen-tolerant [NiFe] hydrogenase during H2 cycling in the presence of O2. AB - Hydrogenases control the H2-related metabolism in many microbes. Most of these enzymes are prone to immediate inactivation by O2. However, a few members of the subclass of [NiFe]-hydrogenases are able to convert H2 into protons and electrons even in the presence of O2, making them attractive for biotechnological application. Recent studies on O2-tolerant membrane-bound hydrogenases indicate that the mechanism of O2 tolerance relies on their capability to completely reduce O2 with four electrons to harmless water. In order to verify this hypothesis, we probed the O2 reduction capacity of the soluble, NAD(+)-reducing [NiFe]-hydrogenase (SH) from Ralstonia eutropha H16. A newly established, homologous overexpression allowed the purification of up to 90 mg of homogeneous and highly active enzyme from 10 g of cell material. We showed that the SH produces trace amounts of superoxide in the course of H2-driven NAD(+) reduction in the presence of O2. However, the major products of the SH-mediated oxidase activity was in fact hydrogen peroxide and water as shown by the mass spectrometric detection of H2(18)O formed from H2 and isotopically labeled (18)O2. Water release was also observed when the enzyme was incubated with NADH and (18)O2, demonstrating the importance of reverse electron flow to the [NiFe] active site for O2 reduction. A comparison of the turnover rates for H2 and O2 revealed that in the presence of twice the ambient level of O2, up to 3% of the electrons generated through H2 oxidation serve as "health insurance" and are reused for O2 reduction. PMID- 24180288 TI - Further evidence for an anti-inflammatory role of artesunate in experimental cerebral malaria. AB - BACKGROUND: Cerebral malaria (CM) is a clinical syndrome resulting from Plasmodium falciparum infection. A wide range of clinical manifestations follow the disease including cognitive dysfunction, seizures and coma. CM pathogenesis remains incompletely understood and without treatment this condition is invariably fatal. Artesunate has been accepted as the most effective drug for treating severe malaria. Besides its antiparasitic activity, an anti-inflammatory property has also been reported. In the current study, the immunomodulatory role of artesunate was investigated using a Plasmodium berghei ANKA model of CM, trough evaluation of behavioural changes and cytokines expression in hippocampus and in frontal cortex. METHODS: C57Bl/6 mice were infected with P. berghei by intraperitoneal route, using a standardized inoculation of 106 parasitized erythrocytes. Memory function was evaluated using the step-down inhibitory avoidance test. The mRNA expression of IFN-gamma, IL-1beta, IL-6 and TNF in the frontal cortex and hippocampus of control and infected mice on day 5 post infection were estimated by quantitative real time PCR. Plasmodium berghei infected mice also received intraperitoneally a single dose of artesunate (32 mg/kg) on day 4 post-infection, and 24 hours after treatment behavioural and immunological analysis were performed. The protein levels of cytokines IL-2, IL 6, IL-10, IL-17, IFN-gamma, TNF in the serum, frontal cortex and hippocampus of controls and P. berghei -infected mice treated or not treated with artesunate were determined using a cytometric bead array (CBA) kit. The survival and neurological symptoms of CM were also registered. RESULTS: CM mice presented a significant impairment of aversive memory compared to controls on day 5 post infection. A higher mRNA expression of pro-inflammatory cytokines was found in the hippocampus and frontal cortex of infected mice. A single dose of artesunate was also able to decrease the expression of inflammatory cytokines in the hippocampus and frontal cortex of P. berghei-infected mice. In parallel, a significant improvement in neurological symptoms and survival were observed in artesunate treated mice. CONCLUSIONS: In summary, the current study provided further evidence that CM affects key brain areas related to cognition process. In addition, different patterns of cytokine expression during the course of CM could be modulated by a single administration of the anti-malarial artesunate. PMID- 24180289 TI - Application of catalyst-free click reactions in attaching affinity molecules to tips of atomic force microscopy for detection of protein biomarkers. AB - Atomic force microscopy (AFM) has been extensively used in studies of biological interactions. Particularly, AFM based force spectroscopy and recognition imaging can sense biomolecules on a single molecule level, having great potential to become a tool for molecular diagnostics in clinics. These techniques, however, require affinity molecules to be attached to AFM tips in order to specifically detect their targets. The attachment chemistry currently used on silicon tips involves multiple steps of reactions and moisture sensitive chemicals, such as (3 aminopropyl)triethoxysilane (APTES) and N-hydroxysuccinimide (NHS) ester, making the process difficult to operate in aqueous solutions. In the present study, we have developed a user-friendly protocol to functionalize the AFM tips with affinity molecules. A key feature of it is that all reactions are carried out in aqueous solutions. In summary, we first synthesized a molecular anchor composed of cyclooctyne and silatrane for introduction of a chemically reactive function to AFM tips and a bifunctional polyethylene glycol linker that harnesses two orthogonal click reactions, copper free alkyne-azide cycloaddition and thiol vinylsulfone Michael addition, for attaching affinity molecules to AFM tips. The attachment chemistry was then validated by attaching antithrombin DNA aptamers and cyclo-RGD peptides to silicon nitride (SiN) tips, respectively, and measuring forces of unbinding these affinity molecules from their protein cognates human alpha-thrombin and human alpha5beta1-integrin immobilized on mica surfaces. In turn, we used the same attachment chemistry to functionalize silicon tips with the same affinity molecules for AFM based recognition imaging, showing that the disease-relevant biomarkers such as alpha-thrombin and alpha5beta1-integrin can be detected with high sensitivity and specificity by the single molecule technique. These studies demonstrate the feasibility of our attachment chemistry for the use in functionalization of AFM tips with affinity molecules. PMID- 24180287 TI - New insights into intracellular locations and functions of heme oxygenase-1. AB - SIGNIFICANCE: Heme oxygenase-1 (HMOX1) plays a critical role in the protection of cells, and the inducible enzyme is implicated in a spectrum of human diseases. The increasing prevalence of cardiovascular and metabolic morbidities, for which current treatment approaches are not optimal, emphasizes the necessity to better understand key players such as HMOX1 that may be therapeutic targets. RECENT ADVANCES: HMOX1 is a dynamic protein that can undergo post-translational and structural modifications which modulate HMOX1 function. Moreover, trafficking from the endoplasmic reticulum to other cellular compartments, including the nucleus, highlights that HMOX1 may play roles other than the catabolism of heme. CRITICAL ISSUES: The ability of HMOX1 to be induced by a variety of stressors, in an equally wide variety of tissues and cell types, represents an obstacle for the therapeutic exploitation of the enzyme. Any capacity to modulate HMOX1 in cardiovascular and metabolic diseases should be tempered with an appreciation that HMOX1 may have an impact on cancer. Moreover, the potential for heme catabolism end products, such as carbon monoxide, to amplify the HMOX1 stress response should be considered. FUTURE DIRECTIONS: A more complete understanding of HMOX1 modifications and the properties that they impart is necessary. Delineating these parameters will provide a clearer picture of the opportunities to modulate HMOX1 in human disease. PMID- 24180291 TI - Galactose-functionalized polyHIPE scaffolds for use in routine three dimensional culture of mammalian hepatocytes. AB - Three-dimensional (3D) cell culture is regarded as a more physiologically relevant method of growing cells in the laboratory compared to traditional monolayer cultures. Recently, the application of polystyrene-based scaffolds produced using polyHIPE technology (porous polymers derived from high internal phase emulsions) for routine 3D cell culture applications has generated very promising results in terms of improved replication of native cellular function in the laboratory. These materials, which are now available as commercial scaffolds, are superior to many other 3D cell substrates due to their high porosity, controllable morphology, and suitable mechanical strength. However, until now there have been no reports describing the surface-modification of these materials for enhanced cell adhesion and function. This study, therefore, describes the surface functionalization of these materials with galactose, a carbohydrate known to specifically bind to hepatocytes via the asialoglycoprotein receptor (ASGPR), to further improve hepatocyte adhesion and function when growing on the scaffold. We first modify a typical polystyrene-based polyHIPE to produce a cell culture scaffold carrying pendent activated-ester functionality. This was achieved via the incorporation of pentafluorophenyl acrylate (PFPA) into the initial styrene (STY) emulsion, which upon polymerization formed a polyHIPE with a porosity of 92% and an average void diameter of 33 MUm. Histological analysis showed that this polyHIPE was a suitable 3D scaffold for hepatocyte cell culture. Galactose functionalized scaffolds were then prepared by attaching 2'-aminoethyl-beta-D galactopyranoside to this PFPA functionalized polyHIPE via displacement of the labile pentafluorophenyl group, to yield scaffolds with approximately ca. 7-9% surface carbohydrate. Experiments with primary rat hepatocytes showed that cellular albumin synthesis was greatly enhanced during the initial adhesion/settlement period of cells on the galactose-functionalized material, suggesting that the surface carbohydrates are accessible and selective to cells entering the scaffold. This porous polymer scaffold could, therefore, have important application as a 3D scaffold that offers enhanced hepatocyte adhesion and functionality. PMID- 24180292 TI - Cardiorespiratory fitness and incident metabolic syndrome in middle-aged Korean men. AB - This study investigated the relationship of cardiorespiratory fitness (CRF) with incident metabolic syndrome in 810 middle aged Korean men. All subjects were free of metabolic syndrome at baseline examination. The metabolic syndrome was defined by NCEP criteria and CRF was directly measured by peak oxygen uptake during a treadmill test. During an average of 3.3 years of follow-up, 155 (19.1%) men developed the metabolic syndrome. The incidence of metabolic syndrome was inversely associated with CRF quartiles (p < 0.05). The relative risk (RR) of incident metabolic syndrome in the lowest CRF quartile vs the highest CRF quartile was 1.67 (95% CI = 1.07-2.60) after adjustment for covariates. Each metabolic equivalent (MET) increment in peak oxygen consumption was associated with a 17% (RR = 0.83, 95% CI = 0.73-0.94) lower incidence of metabolic syndrome. These results demonstrate that cardiorespiratory fitness was associated with the incidence of metabolic syndrome independent of covariates in middle aged Korean men. PMID- 24180293 TI - Reply to "comments on Petrak et al.'s 'psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin': considerations for language and communication". PMID- 24180294 TI - Nonmetabolic complications of continuous subcutaneous insulin infusion: a patient survey. AB - BACKGROUND: Little is known about the frequencies and types of nonmetabolic complications occurring in type 1 diabetes patients being treated by modern insulin pump therapy (continuous subcutaneous insulin infusion [CSII]), when recorded by standardized questionnaire rather than clinical experience. SUBJECTS AND METHODS: A self-report questionnaire was completed by successive subjects with type 1 diabetes attending an insulin pump clinic, and those with a duration of CSII of >=6 months were selected for analysis (n=92). Questions included pump manufacturer, insulin, infusion set type and duration of use, frequency of infusion set and site problems, pump malfunctions, and patient-related problems such as weight change since starting CSII. RESULTS: Median (range) duration of CSII was 3.3 (0.5-32.0) years, and mean +/- SD duration of infusion set use was 3.2 +/- 0.7 (range 2-6) days. The commonest infusion set problems were kinking (64.1% of subjects) and blockage (54.3%). Blockage was associated with >3 days of use of infusion sets plus lispro insulin in the pump (relative risk [95% confidence interval], 1.71 [1.03-2.85]; P=0.07). The commonest infusion site problem was lipohypertrophy (26.1%), which occurred more often in those with long duration of CSII (4.8 [2.38-9.45] vs. 3.0 [1.50-4.25] years; P=0.01). Pump malfunction had occurred in 48% of subjects (43% in the first year of CSII), with "no delivery," keypad, and battery problems commonly occurring. Although some patients reported weight gain (34%) and some weight loss (15%) on CSII, most patients (51%) reported no change in weight. CONCLUSIONS: Pump, infusion set, and infusion site problems remain common with CSII, even with contemporary technology. PMID- 24180296 TI - Investigation of poly (ADP-ribose) polymerase-1 genetic variants as a possible risk for allergic rhinitis. AB - Recent studies point toward the involvement of poly (ADP-ribose) polymerase-1 (PARP-1) in the pathogenesis of allergic airway inflammation, such as asthma and allergic rhinitis (AR). It has been suggested that inhibition of PARP-1 provides significant protection against systemic or tissue inflammation in animal models. The objective of this study was to investigate whether single-nucleotide polymorphisms of PARP-1 gene are associated with genetic susceptibility to AR. We studied the effect of promoter variations and Val762Ala polymorphism of the PARP 1 gene on the risk for developing AR in a case-control association study with 110 RA patients and 130 control subjects in a Turkish population. The polymorphisms of 410 C/T, -1672G/A, and Val762Ala in the PARP-1 gene were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Haplotype analysis of these groups was also performed. The results were statistically analyzed by calculating the odds ratio (OR) and their 95% confidence intervals using chi(2) tests. The heterozygote genotype of the promoter polymorphism (-1672) was significantly found to be associated with susceptibility to AR (OR: 0.56) among the tested single-nucleotide polymorphisms. Haplotypes of PARP-1 -410, -1672, and 762 were not associated with an increased risk for AR. These results raise the possibility that the promoter (-1672) polymorphism of the PARP-1 gene may be a risk factor for AR. PMID- 24180295 TI - Improving psychotropic drug prescription in nursing home patients with dementia: design of a cluster randomized controlled trial. AB - BACKGROUND: Neuropsychiatric symptoms are highly prevalent in nursing home patients with dementia. Despite modest effectiveness and considerable side effects, psychotropic drugs are frequently prescribed for these neuropsychiatric symptoms. This raises questions whether psychotropic drugs are appropriately prescribed. The aim of the PROPER (PRescription Optimization of Psychotropic drugs in Elderly nuRsing home patients with dementia) II study is to investigate the efficacy of an intervention for improving the appropriateness of psychotropic drug prescription in nursing home patients with dementia. METHODS/DESIGN: The PROPER II study is a multi-center cluster randomized controlled, pragmatic trial using parallel groups. It has a duration of eighteen months and four six-monthly assessments. Six nursing homes will participate in the intervention and six will continue care as usual. The nursing homes will be located throughout the Netherlands, each participating with two dementia special care units with an average of fifteen patients per unit, resulting in 360 patients. The intervention consists of a structured and repeated multidisciplinary medication review supported by education and continuous evaluation. It is conducted by pharmacists, physicians, and nurses and consists of three components: 1) preparation and education, 2) conduct, and 3) evaluation/guidance. The primary outcome is the proportion of patients with appropriate psychotropic drug use. Secondary outcomes are the overall frequency of psychotropic drug use, neuropsychiatric symptoms, quality of life, activities of daily living, psychotropic drug side effects and adverse events (including cognition, comorbidity, and mortality). Besides, a process analysis on the intervention will be carried out. DISCUSSION: This study is expected to improve the appropriateness of psychotropic drug prescription for neuropsychiatric symptoms in nursing home patients with dementia by introducing a structured and repeated multidisciplinary medication review supported by education and continuous evaluation. TRIAL REGISTRATION: Netherlands Trial Registry (NTR): NTR3569. PMID- 24180297 TI - Relationship between response to colchicine treatment and MDR1 polymorphism in familial Mediterranean fever patients. AB - AIM: Investigate the relationship between MDR1 C3435T polymorphism and colchicine response in Familial Mediterranean fever (FMF) patients. MATERIALS AND METHODS: Patients (n=50) who received colchicine regularly, were willing to participate in the study, and attended control visits were included in the study. MDR1 C3435T genotype was defined by the real-time polymerase chain reaction method. Patients were divided into three groups. Patients, who recovered from episodes with standard colchicine treatment, and had no attack in the last 1 year were accepted as complete; patients whose episode number and intensity were decreased with the ongoing standard treatment as partial; and patients whose episodes were not decreased despite the standard treatment as nonresponders. RESULTS: MDR1 C and T allele frequencies of FMF patients with colchicine responses of complete, partial, and nonresponders were C=0.75 and T=0.25; C=0.56 and T=0.44; and C=0.50 and T=0.50, respectively. When complete responding patients were compared with the partial responding patients, subjects with CT genotype had 6.18 times more increased risk than with CC genotype (OR=6.18; p=0.015). Poor response risk of subjects with the T allele was increased 2.45 times more when compared with the C allele (p=0.03). CONCLUSION: MDR1 gene C3435T polymorphism enacts an important role on colchicine response in FMF; good response to colchicine treatment was related to the C allele, whereas poor response was related to the T allele in FMF. PMID- 24180290 TI - Gene expression studies for the analysis of domoic acid production in the marine diatom Pseudo-nitzschia multiseries. AB - BACKGROUND: Pseudo-nitzschia multiseries Hasle (Hasle) (Ps-n) is distinctive among the ecologically important marine diatoms because it produces the neurotoxin domoic acid. Although the biology of Ps-n has been investigated intensely, the characterization of the genes and biochemical pathways leading to domoic acid biosynthesis has been limited. To identify transcripts whose levels correlate with domoic acid production, we analyzed Ps-n under conditions of high and low domoic acid production by cDNA microarray technology and reverse transcription quantitative PCR (RT-qPCR) methods. Our goals included identifying and validating robust reference genes for Ps-n RNA expression analysis under these conditions. RESULTS: Through microarray analysis of exponential- and stationary-phase cultures with low and high domoic acid production, respectively, we identified candidate reference genes whose transcripts did not vary across conditions. We tested eleven potential reference genes for stability using RT qPCR and GeNorm analyses. Our results indicated that transcripts encoding JmjC, dynein, and histone H3 proteins were the most suitable for normalization of expression data under conditions of silicon-limitation, in late-exponential through stationary phase. The microarray studies identified a number of genes that were up- and down-regulated under toxin-producing conditions. RT-qPCR analysis, using the validated controls, confirmed the up-regulation of transcripts predicted to encode a cycloisomerase, an SLC6 transporter, phosphoenolpyruvate carboxykinase, glutamate dehydrogenase, a small heat shock protein, and an aldo-keto reductase, as well as the down-regulation of a transcript encoding a fucoxanthin-chlorophyll a-c binding protein, under these conditions. CONCLUSION: Our results provide a strong basis for further studies of RNA expression levels in Ps-n, which will contribute to our understanding of genes involved in the production and release of domoic acid, an important neurotoxin that affects human health as well as ecosystem function. PMID- 24180299 TI - Cardiovascular disease knowledge and weight perception among Hispanic and non Hispanic white women. AB - BACKGROUND: While knowledge of cardiovascular disease (CVD) has improved, it remains low among minority women, thereby contributing to disparities and posing health challenges. Moreover, substantial numbers of women do not recognize that excess weight imposes CVD risk and increases morbidity and decreases survival. In order to test the hypothesis that CVD knowledge is reduced among overweight and obese women, CVD knowledge and weight perception was compared among Hispanic and non-Hispanic white (NHW) women. METHODS: Data from 382 Hispanic and 301 NHW women, participants in the Heart Health in Action database (n=829), were analyzed from a structured behavioral risk factor surveillance system (BRFSS) questionnaire to assess demographics, risk factors, and CVD knowledge. Multivariable logistic regression analysis was utilized to test for differences between Hispanic and NHW women regarding knowledge with covariates of age, education, and body mass index (BMI). RESULTS: Hispanics (27%) were less likely than NHW (88%) to correctly identify the leading cause of death among women, (p<0.0001). Years living in the United States did not relate to the percentage of respondents who correctly identified the leading cause of death among women or knew the symptoms of a heart attack. Differences between Hispanic and NHW remained significant after adjustment for age, education, and BMI (p<0.0001). Hispanics (69.4%) were less likely than NHW (82.9 %) to correctly estimate weight (p<0.0001). Underestimation of weight was greater among Hispanics (24.8%) than NHW (5.0%); 48.5% of overweight Hispanic participants versus 12.7% of overweight NHW participants underestimated weight (p<0.0001) and 17.2% of obese Hispanic versus 0% of NHW obese participants (p=0.001) underestimated weight. The percentage underestimating the silhouette corresponding to their weight was related to years in the United States: 29.3% for<10 years, 38.3% with 10-19 years, and 49.3% with >=20 years (p=0.01 for trend). CONCLUSIONS: Effective prevention strategies for at-risk populations need to target CVD knowledge and awareness among overweight and obese Hispanic women. PMID- 24180300 TI - Optimizing the magnetic response of suspensions by tailoring the spatial distribution of the particle magnetic material. AB - We report an experimental enhancement of the magnetic susceptibility of suspensions of particles that is related to the spatial distribution of the magnetic phase in the particles. At low field, the susceptibility of suspensions of nickel-coated diamagnetic spheres was approximately 75% higher than that of suspensions of solid nickel spheres with the same nickel content. This result was corroborated by magnetostatics theory and simulation. The distribution of the magnetic phase in a shell also led to an improvement of the field-induced rheological response of the suspensions. PMID- 24180301 TI - Crystal and magnetic structure in co-substituted BiFeO3. AB - Ultra-high-resolution neutron diffraction studies of BiFe(0.8)Co(0.2)O3 show a transition from a cycloidal space modulated spin structure at T = 10 K to a collinear G-type antiferromagnetic structure at T = 120 K. The model of antiparallel directions of Fe(3+) and Co(3+) magnetic moments at the shared Wyckoff position describes well the observed neutron diffraction intensities. On heating above RT, the crystal structure of BiFe(0.8)Co(0.2)O3 changes from a rhombohedral R3c to a monoclinic Cm. At 573 K only the Cm phase is present. The collinear C-type antiferromagnetic structure is present in the Cm phase of BiFe(0.8)Co(0.2)O3 at RT after annealing. PMID- 24180298 TI - Gender analysis of moxifloxacin clinical trials. AB - PURPOSE: To determine the inclusion of women and the sex-stratification of results in moxifloxacin Clinical Trials (CTs), and to establish whether these CTs considered issues that specifically affect women, such as pregnancy and use of hormonal therapies. Previous publications about women's inclusion in CTs have not specifically studied therapeutic drugs. Although this type of drug is taken by men and women at a similar rate, adverse effects occur more frequently in the latter. METHODS: We reviewed 158 published moxifloxacin trials on humans, retrieved from MedLine and the Cochrane Library (1998-2010), to determine whether they complied with the gender recommendations published by U.S. Food and Drug Administration Guideline. RESULTS: Of a total of 80,417 subjects included in the moxifloxacin CTs, only 33.7% were women in phase I, in contrast to phase II, where women accounted for 45%, phase III, where they represented 38.3% and phase IV, where 51.3% were women. About 40.9% (n=52) of trials were stratified by sex and 15.3% (n=13) and 9% (n=7) provided data by sex on efficacy and adverse effects, respectively. We found little information about the influence of issues that specifically affect women. Only 3 of the 59 journals that published the moxifloxacin CTs stated that authors should stratify their results by sex. CONCLUSIONS: Women are under-represented in the published moxifloxacin trials, and this trend is more marked in phase I, as they comprise a higher proportion in the other phases. Data by sex on efficacy and adverse effects are scarce in moxifloxacin trials. These facts, together with the lack of data on women specific issues, suggest that the therapeutic drug moxifloxacin is only a partially evidence-based medicine. PMID- 24180302 TI - First evaluation of the paediatric version of the Swedish rapid emergency triage and treatment system shows good reliability. AB - AIM: To investigate the reliability of Retts-p, Rapid emergency triage and treatment system-paediatric, with regard to inter-rater and intra-rater agreement. METHOD: Twenty nurses responsible for triaging both children and adults at the Emergency Department, Ostersund County Hospital, Sweden, were randomly selected to take part in the study. The nurses were asked to use the Retts-p triage system to retrospectively assess the written case reports on 40 paediatric cases, aged from 6 month to 17.5 years, who attended the Emergency Department in 2010 with surgical, orthopaedic and medical symptoms. Using the information provided regarding appearance, symptoms, previous medical history and vital signs, the nurses selected the most appropriate Emergency Symptoms and Signs algorithm and placed the child in one of the five triage categories. Two test rounds were performed, 3 months apart, using the same cases, to study both the inter-rater and intra-rater agreement for the priority level and the triage algorithm chosen by the triage nurses. RESULTS: Good to very good agreement were shown for both inter-rater (quadratic kappaw 0.86, 95% CI 0.85-0.87) and intra rater testing (quadratic kappaw 0.92, 95% CI 0.88-0.96). CONCLUSION: Retts-p provided good to very good reliability in this first evaluation study of the triage system. PMID- 24180303 TI - Fingermark evidence evaluation based on automated fingerprint identification system matching scores: the effect of different types of conditioning on likelihood ratios. AB - In recent studies, the evidential value of the similarity of minutiae configurations of fingermarks and fingerprints, for example expressed by automated fingerprint identification systems (AFIS), is determined by likelihood ratios (LRs). The paper explores whether there is an effect on LRs if conditioning takes place on specified fingers, fingerprints, or fingermarks under competing hypotheses: In addition, an approach is explored where conditioning is asymmetric. Comparisons between fingerprints and simulated fingermarks with eight minutiae are performed to produce similarity score distributions for each type of conditioning, given a fixed AFIS matching algorithm. Both similarity scores and LRs are significantly different if the conditioning changes. Given a common source scenario, "LRs" resulting from asymmetric conditioning are on average higher. The difference may reach a factor of 2000. As conditioning on a suspect's finger(print) is labor-intensive and requires a cooperating suspect, it is recommended to just condition on the number of minutiae in the fingermark. PMID- 24180304 TI - State-selective excitation of the CO stretch in carboxyhemoglobin by mid-IR laser pulse shaping: a theoretical investigation. AB - We present simulations of the excitation of specific vibrational levels of the CO stretch in carboxyhemoglobin by shaped mid-IR laser pulses. The pulses are calculated using local control theory, adapted to account for the protein fluctuations, which are included using a microscopic model developed previously. We show that efficient selective vibrational state preparation can be obtained, despite the presence of the fluctuations and orientational averaging, and can be monitored using transient absorption spectra. The mid-IR pulses are found to be in a realistic intensity regime and might soon be available by IR pulse shaping. This opens the way to a direct monitoring of vibrational relaxation from individually prepared, high-lying vibrational states of complex systems. PMID- 24180305 TI - Method for accurate determination of dissociation constants of optical ratiometric systems: chemical probes, genetically encoded sensors, and interacting molecules. AB - Ratiometric chemical probes and genetically encoded sensors are of high interest for both analytical chemists and molecular biologists. Their high sensitivity toward the target ligand and ability to obtain quantitative results without a known sensor concentration have made them a very useful tool in both in vitro and in vivo assays. Although ratiometric sensors are widely used in many applications, their successful and accurate usage depends on how they are characterized in terms of sensing target molecules. The most important feature of probes and sensors besides their optical parameters is an affinity constant toward analyzed molecules. The literature shows that different analytical approaches are used to determine the stability constants, with the ratio approach being most popular. However, oversimplification and lack of attention to detail results in inaccurate determination of stability constants, which in turn affects the results obtained using these sensors. Here, we present a new method where ratio signal is calibrated for borderline values of intensities of both wavelengths, instead of borderline ratio values that generate errors in many studies. At the same time, the equation takes into account the cooperativity factor or fluorescence artifacts and therefore can be used to characterize systems with various stoichiometries and experimental conditions. Accurate determination of stability constants is demonstrated utilizing four known optical ratiometric probes and sensors, together with a discussion regarding other, currently used methods. PMID- 24180306 TI - Understanding of and possible strategies to avian influenza outbreak. AB - Swine flu and avian flu outbreaks have occurred in recent years in addition to seasonal flu. As mortality rate records are not available at the early stage of an outbreak, two parameters may be useful to assess the viral virulence : 1. the time required for the first domestic case in a newly involved region, and 2. the doubling time of new infected cases. Viral virulence is one of the most important factors in guiding short term and immediate responses. Although routine surveillance and repeated vaccination are useful efforts, some novel strategies that may be relevant to prevent and control the spread of influenza among human beings and domestic animals are discussed. PMID- 24180307 TI - Challenges and opportunities for bacterial vaccine development in the 21(st) century. AB - With the convergence of modern technology in genomics, proteomics, carbohydrate, protein and lipid biochemistry as well as decades of experience in vaccine development and delivery of immunization programs, the Global Vaccine Action Plan has declared 2011 to 2020 as 'The Decade of Vaccines'. This review focuses on bacterial vaccines and summarises the current state of vaccinology in bacteriology and looks forward to the potential of how the newer technologies can impact our knowledge of bacterial diseases and their control through vaccine development. The major breakthroughs in the last couple of decades include low cost high throughput genomics, proteomics, cellular immunology and the delicate network of immune-cytokines, bioinformatics, immune-informatics, and disease modelling. Together, these newer developments can provide a real impact on our understanding of infectious diseases and their control by vaccination. PMID- 24180308 TI - Time recall; future concept of chronomodulating chemotherapy for cancer. AB - The human metabolism is regulated by our internal clock; the circadian rhythm (24h-25h). There are several factors included in the regulatory pathway such as; genes (PER1-3), (CRY1-2), TIM hormones (cortisol, catecholamines, melatonin and insulin) drugs, enzymes, sleep disorders and diseases. Each one contributes in a different degree and in order to enhance the therapeutic result; we should include these factors into clusters instead of targeting each factor one by one. Malignances deregulate gene-protein expression/production, enzyme production, and in addition they induce fatigue, insomnia, stress and sleep disorders. All these factors finally contribute in minimizing the efficiency of chemotherapy treatment and quality of life. In addition, the circadian rhythm disruption induces tumor genesis, stress, and downregulates the defense and repair mechanisms of the human body. In the current mini review the underlying mechanism of the circadian rhythm is provided, along with the influence of sleep disturbances in cancer patient therapy. A proposal is presented to divide circadian rhythm and sleep disturbances into two major clusters with different management, however; with a common target to improve treatment efficiency and quality of life. Finally, a chrono-chemotherapy administration model is proposed in order to have less chemotherapy side effects. PMID- 24180310 TI - Relationship between biomechanical changes at adjacent segments and number of fused bone grafts in multilevel cervical fusions: a finite element investigation. AB - OBJECT: Biomechanical studies have shown that anterior cervical fusion construct stiffness and arthrodesis rates vary with different reconstruction techniques; however, the behavior of the adjacent segments in the setting of different procedures is poorly understood. This study was designed to investigate the adjacent-segment biomechanics after 3 different anterior cervical decompression and fusion techniques, including 3-level discectomy and fusion, 2-level corpectomy and fusion, and a corpectomy-discectomy hybrid technique. The authors hypothesized that biomechanical changes at the segments immediately superior and inferior to the multilevel fusion would be inversely proportional to the number of fused bone grafts and that these changes would be related to the type of fusion technique. METHODS: A previously validated 3D finite element model of an intact C3-T1 segment was used. Three C4-7 fusion models were built from this intact model by varying the number of bone grafts used to span the decompression: a 1-graft model (2-level corpectomy), a 2-graft model (C-5 corpectomy and C6-7 discectomy), and a 3-graft model (3-level discectomy). The corpectomy and discectomy models were also previously validated and compared well with the literature findings. Range of motion, disc stresses, and posterior facet loads at the segments superior (C3-4) and inferior (C7-T1) to the fusion construct were assessed. RESULTS: Motion, disc stresses, and posterior facet loads generally increased at both of the adjacent segments in relation to the intact model. Greater biomechanical changes were noted in the superior C3-4 segment than in the inferior C7-T1 segment. Increasing the number of bone grafts from 1 to 2 and from 2 to 3 was associated with a lower magnitude of biomechanical changes at the adjacent segments. CONCLUSIONS: At segments adjacent to the fusion level, biomechanical changes are not limited solely to the discs, but also propagate to the posterior facets. These changes in discs and posterior facets were found to be lower for discectomy than for corpectomy, thereby supporting the current study hypothesis of inverse relationship between the adjacent-segment variations and the number of fused bone grafts. Such changes may go on to influence the likelihood of adjacent-segment degeneration accordingly. Further studies are warranted to identify the causes and true impact of these observed changes. PMID- 24180311 TI - Calcified meningiomas. PMID- 24180312 TI - Risk factors for intraoperative lateral mass fracture of lateral mass screw fixation in the subaxial cervical spine. AB - OBJECT: Although lateral mass screw fixation for the cervical spine is a safe technique, lateral mass fracture during screw fixation is occasionally encountered intraoperatively. This event is regarded as a minor complication; however, it poses difficulties in management that may affect fixation stability and clinical outcome. The purpose of this study is to determine the incidence and etiology of lateral mass fractures during cervical lateral mass screw fixation. METHODS: A retrospective clinical review of patient records was performed in 117 consecutive patients (mean age 57 years, range 15-86 years) who underwent lateral mass screw fixation using a modified Magerl method from 1997 to 2010 at a single institution. A total of 555 lateral masses were included in this study. The outer diameters of the screws were 3.5 or 4.0 mm. In the retrospective clinical analysis, the incidence of intraoperative lateral mass fractures was reviewed. Potential risk factors for this complication were assessed using multivariate analysis. RESULTS: The incidence of lateral mass fractures during cervical lateral mass screw fixation was 4.7% (26 lateral masses) among all cases. Among the disorders, the incidence was highest in patients with destructive spondyloarthropathy (DSA) (18.8%, 12 lateral masses). There was no significant difference with respect to lateral mass fracture between the use of 4.0-mm screws (5.6%) and 3.5-mm screws (3.6%). Independent risk factors identified by logistic regression were DSA (OR 7.89, p < 0.001) and screw insertion in the C-6 lateral masses (OR 2.80, p = 0.018). CONCLUSIONS: The overall incidence of lateral mass fracture during cervical lateral mass screw fixation was 4.7%. Destructive spondyloarthropathy as an underlying cause of morbidity and screw placement in the C-6 lateral mass were identified as independent risk factors. Use of a 4.0-mm screw in patients with DSA may be a principal risk factor for this complication. PMID- 24180309 TI - Mitochondrial ion channels/transporters as sensors and regulators of cellular redox signaling. AB - SIGNIFICANCE: Mitochondrial ion channels/transporters and the electron transport chain (ETC) serve as key sensors and regulators for cellular redox signaling, the production of reactive oxygen species (ROS) and nitrogen species (RNS) in mitochondria, and balancing cell survival and death. Although the functional and pharmacological characteristics of mitochondrial ion transport mechanisms have been extensively studied for several decades, the majority of the molecular identities that are responsible for these channels/transporters have remained a mystery until very recently. RECENT ADVANCES: Recent breakthrough studies uncovered the molecular identities of the diverse array of major mitochondrial ion channels/transporters, including the mitochondrial Ca2+ uniporter pore, mitochondrial permeability transition pore, and mitochondrial ATP-sensitive K+ channel. This new information enables us to form detailed molecular and functional characterizations of mitochondrial ion channels/transporters and their roles in mitochondrial redox signaling. CRITICAL ISSUES: Redox-mediated post translational modifications of mitochondrial ion channels/transporters and ETC serve as key mechanisms for the spatiotemporal control of mitochondrial ROS/RNS generation. FUTURE DIRECTIONS: Identification of detailed molecular mechanisms for redox-mediated regulation of mitochondrial ion channels will enable us to find novel therapeutic targets for many diseases that are associated with cellular redox signaling and mitochondrial ion channels/transporters. PMID- 24180313 TI - Operative nuances to safeguard anomalous vertebral artery without compromising the surgery for congenital atlantoaxial dislocation: untying a tough knot between vessel and bone. AB - OBJECT: Stabilization of the craniovertebral junction (CVJ) by using lateral masses requires extensive dissection. The vertebral artery (VA) is commonly anomalous in patients with congenital CVJ anomaly. Such a vessel is likely to be injured during dissection or screw placement. In this study the authors discuss the importance of preoperative evaluation and certain intraoperative steps that reduce the chances of injury to such vessels. METHODS: A 3D CT angiogram was obtained in 15 consecutive patients undergoing surgery for congenital atlantoaxial dislocation. The course of the VA and its relationship to the C1-2 facets was studied in these patients. The anomalous VA was exposed intraoperatively, facet surfaces were drilled in all, and the screws were placed according to the disposition of the vessel. RESULTS: A skeletal anomaly was found in all 10 patients who had an anomalous VA. Four types of variations were noted: 1) the first intersegmental artery in 5 patients (bilateral in 1); 2) fenestration of VA in 1 patient; 3) anomalous posterior inferior cerebellar artery crossing the C1-2 joint in 1 patient; and 4) medial loop of VA in 5 patients. The anomalous vessel was dissected and the facet surfaces were drilled in all. The C-1 lateral mass screw was placed under vision, taking care not to compromise the anomalous vessel, although occipital screws or sublaminar wires were used in the initial cases. A medial loop of the VA necessitated placement of transpedicular or C-2 lateral mass screws instead of pars interarticularis screws. The anomalous vessel was injured in none. CONCLUSIONS: Preoperative 3D CT angiography is a highly useful method of imaging the artery in patients with CVJ anomaly. It helps in identifying the anomalous VA or its branch and its relationship to the C1-2 facets. The normal side should be surgically treated and distracted first because this helps in opening the abnormal side, aiding in dissection. In the posterior approach the C-2 nerve root is always encountered before the anomalous vessel. The defined vascular anatomy helps in choosing the type of screw. The vessel should be mobilized so as to aid the drilling of facets and the placement of screws and spacers under vision, avoiding its injury (direct or indirect) or compression. With these steps, C1-2 (short segment) rigid fusion can be achieved despite the presence of anomalous VA. PMID- 24180314 TI - Transpsoas approach. PMID- 24180315 TI - Vascular injury following microendoscopic lumbar discectomy treated with stent graft placement. AB - The risk of great vessel injury is low in microendoscopic lumbar discectomy applied in a favorable visual field. However, it is important to be aware of the depth of the pituitary rongeur. In this article, the authors report the case of a 55-year-old woman with lumbar disc herniation who underwent microendoscopic discectomy and subsequently presented with an aneurysm and arteriovenous fistula located at the bifurcation of the right common iliac artery. The patient was treated with endoscopic placement of a stent graft and recovered uneventfully. PMID- 24180316 TI - Cluster randomised controlled trial of a peer-led lifestyle intervention program: study protocol for the Kerala diabetes prevention program. AB - BACKGROUND: India currently has more than 60 million people with Type 2 Diabetes Mellitus (T2DM) and this is predicted to increase by nearly two-thirds by 2030. While management of those with T2DM is important, preventing or delaying the onset of the disease, especially in those individuals at 'high risk' of developing T2DM, is urgently needed, particularly in resource-constrained settings. This paper describes the protocol for a cluster randomised controlled trial of a peer-led lifestyle intervention program to prevent diabetes in Kerala, India. METHODS/DESIGN: A total of 60 polling booths are randomised to the intervention arm or control arm in rural Kerala, India. Data collection is conducted in two steps. Step 1 (Home screening): Participants aged 30-60 years are administered a screening questionnaire. Those having no history of T2DM and other chronic illnesses with an Indian Diabetes Risk Score value of >=60 are invited to attend a mobile clinic (Step 2). At the mobile clinic, participants complete questionnaires, undergo physical measurements, and provide blood samples for biochemical analysis. Participants identified with T2DM at Step 2 are excluded from further study participation. Participants in the control arm are provided with a health education booklet containing information on symptoms, complications, and risk factors of T2DM with the recommended levels for primary prevention. Participants in the intervention arm receive: (1) eleven peer-led small group sessions to motivate, guide and support in planning, initiation and maintenance of lifestyle changes; (2) two diabetes prevention education sessions led by experts to raise awareness on T2DM risk factors, prevention and management; (3) a participant handbook containing information primarily on peer support and its role in assisting with lifestyle modification; (4) a participant workbook to guide self-monitoring of lifestyle behaviours, goal setting and goal review; (5) the health education booklet that is given to the control arm. Follow up assessments are conducted at 12 and 24 months. The primary outcome is incidence of T2DM. Secondary outcomes include behavioural, psychosocial, clinical, and biochemical measures. An economic evaluation is planned. DISCUSSION: Results from this trial will contribute to improved policy and practice regarding lifestyle intervention programs to prevent diabetes in India and other resource-constrained settings. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry: ACTRN12611000262909. PMID- 24180317 TI - Potency preservation following stereotactic body radiation therapy for prostate cancer. AB - BACKGROUND: Erectile dysfunction after prostate radiation therapy remains an ongoing challenge and critical quality of life issue. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT impotency would be higher than conventional radiation therapy approaches. This study sought to evaluate potency preservation and sexual function following SBRT for prostate cancer. METHODS: Between February 2008 and March 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. Potency was defined as the ability to have an erection firm enough for intercourse with or without sexual aids while sexual activity was defined as the ability to have an erection firm enough for masturbation and foreplay. Patients who received androgen deprivation therapy (ADT) were excluded from this study. Ninety-seven hormone-naive men were identified as being potent at the initiation of therapy and were included in this review. All patients were treated to 35-36.25 Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Prostate specific antigen (PSA) and total testosterone levels were obtained pre-treatment, every 3 months for the first year and every 6 months for the subsequent year. Sexual function was assessed with the Sexual Health Inventory for Men (SHIM), the Expanded Prostate Index Composite (EPIC)-26 and Utilization of Sexual Medication/Device questionnaires at baseline and all follow-up visits. RESULTS: Ninety-seven men (43 low-, 50 intermediate- and 4 high-risk) at a median age of 68 years (range, 48-82 years) received SBRT. The median pre-treatment PSA was 5.9 ng/ml and the minimum follow-up was 24 months. The median pre-treatment total serum testosterone level was 11.4 nmol/L (range, 4.4-27.9 nmol/L). The median baseline SHIM was 22 and 36% of patients utilized sexual aids prior to treatment. Although potency rates declined following treatment: 100% (baseline); 68% (6 months); 62% (12 months); 57% (18 months) and 54.4% (24 months), 78% of previously potent patients had erections sufficient for sexual activity at 24 months post-treatment. Overall sexual aid utilization increased from 36% at baseline to 49% at 24 months. Average EPIC sexual scores showed a slow decline over the first two years following treatment: 77.6 (baseline); 68.7 (6 months); 63.2 (12 months); 61.9 (18 months); 59.3 (24 months). All sexual functions including orgasm declined with time. Prior to treatment, 13.4% of men felt their sexual function was a moderate to big problem which increased to 26.7% two years post treatment. Post-treatment testosterone levels gradually decreased with a median value at two year follow-up of 10.7 nmol/L. However, the average EPIC hormonal scores did not illustrate a statistically significant difference two years post-treatment. Review of the radiation doses to the penile bulb in this study, a potential marker of post-treatment sexual function, revealed that the dose was relatively low and at these low doses the percentage of the penile bulb receiving 29.5 Gy did not correlate with the development of ED. CONCLUSIONS: Men undergoing SBRT monotherapy for prostate cancer report sexual outcomes comparable to those reported for conventional radiation modalities within the first 24 months after treatment. Longer follow-up is required to confirm the durability of these findings. PMID- 24180318 TI - Carrier rates of four single-gene disorders in Croatian Bayash Roma. AB - To assess how specific population history, different migration routes, isolation, and endogamy practices contributed to the distribution of several rare diseases found in specific Roma groups, we conducted a population-based research study of rare disease mutations in Croatian Vlax Roma. We tested a total of 427 subjects from Baranja and Medimurje for the presence of four mutations causing hereditary motor and sensory neuropathy type Lom (HMSNL), GM1 gangliosidosis (GM1), congenital cataracts, facial dysmorphism and neuropathy (CCFDN), and limb girdle muscle dystrophy type 2C (LGMD2C), using the RFLP-PCR method to estimate carrier frequencies. We identified a total of four individuals heterozygous for the mutation causing HMSNL in the Baranja population, with a carrier rate amounting to 1.5%. Carriers for other three mutations causing GM1, CCFDN, and LGMD2C were not found in our sample. The carrier rate for the HMSNL mutation in Baranja is lower than in other Vlax Roma groups. In addition, distinct differences in carrier rates between the Croatian Vlax groups point to different genetic history, despite their belonging to the same Roma migration category and subgroup. The difference in carrier rates is either the result of admixture or the reflection of a greater extent of genetic drift since recent founding, maintained by a high degree of endogamy. PMID- 24180319 TI - Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome. AB - BACKGROUND: Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. METHODS: Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient's condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. RESULTS: Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. DISCUSSION: In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. CONCLUSION: Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission. PMID- 24180321 TI - Real-time monitoring of in situ polyethyleneimine-silica particle formation. AB - Silica particles are traditionally made via the hydrolysis and condensation of tetraalkoxysilanes with the use of methanol and ammonia as a basic catalyst. More recently, bioinspired polyamines have been used in place of ammonia. Particle formation via the use of tetraalkoxysilanes typically occurs extremely quickly with cloudy precipitates forming immediately, making it practically impossible to characterize the reaction in real time. Our study uses trimethoxymethylsilane (TMOMS) and the polyamine polyethyleneimine (PEI) to form PEI-silica particles via a reaction that takes place over several minutes, allowing us to study the reaction in real time. The acidic hydrolysis of TMOMS and basic polymerization condensation of TMOMS via PEI to form solid PEI-silica particles were observed in situ over time using attenuated total reflectance-Fourier transform infrared (ATR FTIR) spectroscopy and dynamic light scattering (DLS) for the first time. The ATR FTIR data suggest that dimer formation occurs during acidic hydrolysis followed by PEI-catalyzed condensation to form silsesquioxane structures. The results for the particles formed in situ were then compared with those for particle samples that had been washed to remove excess reactants. The ATR-FTIR results were corroborated via scanning electron microscopy and DLS, which suggest that the growth of PEI-silica particles occurs by aggregation of smaller particles to larger ones, because the data show the presence of small particles and much larger particles at the same time throughout the whole particle growth process. PMID- 24180320 TI - Visible light-promoted metal-free C-H activation: diarylketone-catalyzed selective benzylic mono- and difluorination. AB - We report herein an operationally simple method for the direct conversion of benzylic C-H groups to C-F. We show that visible light can activate diarylketones to abstract a benzylic hydrogen atom selectively. Adding a fluorine radical donor yields the benzylic fluoride and regenerates the catalyst. The selective formation of mono- and difluorination products can be achieved by catalyst control. 9-Fluorenone catalyzes benzylic C-H monofluorination, while xanthone catalyzes benzylic C-H difluorination. The scope and efficiency of this new C-H fluorination method are significantly better than those of the existing methods. This is also the first report of selective C-H gem-difluorination. PMID- 24180322 TI - Ethnic composition and genetic differentiation of the Libyan population: insights on Alu polymorphisms. AB - BACKGROUND: It is thought that the ancient population of Libya was mainly composed of Saharan Berbers. Socio-geographic conditions and historical events have exerted some changes on the composition of the present-day Libyan population. AIM: To screen a set of autosomal Alu markers in a representative sample of the general Libyan population in order to study its ethnic and genetic structure and to re-examine its genetic relationships with Mediterranean and Middle Eastern groups. SUBJECTS AND METHODS: A sample of 190 Libyans was analysed for 17 Alu insertions. The sample was divided according to the Arabic or Berber origin of individuals' surnames. RESULTS: The current general Libyan population is homogeneous and shows considerable genetic diversity compared with other North Mediterranean and North African populations. It shows intermediate genetic distances between Moroccans, Algerians and Tunisians on one side and Egyptian Siwa Berbers on the other. No particular affinities with Middle Eastern groups were detected. CONCLUSION: Alu insertions are useful markers to contribute to the reconstruction of human population history at a microgeographic scale, in particular when the analyses include anthropologically well sampled populations. The present results provide new information to improve understanding some aspects of the complex peopling of North Africa. PMID- 24180324 TI - Inter and intra-rater repeatability of the scoring of foot pain drawings. AB - BACKGROUND: Foot pain drawings (manikins) are commonly used to describe foot pain location in self-report health surveys. Respondents shade the manikin where they experience pain. The manikin is then scored via a transparent overlay that divides the drawings into areas. In large population based studies they are often scored by multiple raters. A difference in how different raters score manikins (inter-rater repeatability), or in how an individual rater scores manikins over time (intra-rater repeatability) can therefore affect data quality. This study aimed to assess inter- and intra-rater repeatability of scoring of the foot manikin. METHODS: A random sample was generated of 50 respondents to a large population based survey of adults aged 50 years and older who experienced foot pain and completed a foot manikin. Manikins were initially scored by any one of six administrative staff (Rating 1). These manikins were re-scored by a second rater (Rating 2). The second rater then re-scored the manikins one week later (Rating 3). The following scores were compared: Rating 1 versus Rating 2 (inter rater repeatability), and Rating 2 versus Rating 3 (intra-rater repeatability). A novel set of clinically relevant foot pain regions made up of one or more individual areas on the foot manikin were developed, and assessed for inter- and intra-rater repeatability. RESULTS: Scoring agreement of 100% (all 50 manikins) was seen in 69% (40 out of 58) of individual areas for inter-rater scoring (range 94 to 100%), and 81% (47 out of 58) of areas for intra-rater scoring (range 96 to 100%). All areas had a kappa value of >=0.70 for inter- and intra-rater scoring. Scoring agreement of 100% was seen in 50% (10 out of 20) of pain regions for inter-rater scoring (range 96 to 100%), and 95% (19 out of 20) of regions for intra-rater scoring (range 98 to 100%). All regions had a kappa value of >0.70 for inter- and intra-rater scoring. CONCLUSIONS: Individual and multiple raters can reliably score the foot pain manikin. In addition, our proposed regions may be used to reliably classify different patterns of foot pain using the foot manikin. PMID- 24180323 TI - Estrogen replacement modulates voltage-gated potassium channels in rat presympathetic paraventricular nucleus neurons. AB - BACKGROUND: The hypothalamic paraventricular nucleus (PVN) is an important site in the regulation of the autonomic nervous system. Specifically, PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) play a regulatory role in the determination of the sympathetic outflow in the cardiovascular system. In the PVN-RVLM neurons, the estrogen receptor beta is expressed. However, to date, the effects of estrogen on PVN-RVLM neurons have not been reported. The present study investigated estrogen-mediated modulation of two voltage-gated potassium channel (Kv) subunits, Kv4.2 and Kv4.3, that are expressed predominantly in PVN neurons and the functional current of Kv4.2 and Kv4.3, the transient outward potassium current (IA). RESULTS: Single-cell real-time RT-PCR analysis showed that 17beta-estradiol (E2) replacement (once daily for 4 days) selectively down regulated Kv4.2 mRNA levels in the PVN-RVLM neurons of ovariectomized female rats. There was no change in Kv4.3 levels. Whole-cell patch-clamp recordings demonstrated that E2 also diminished IA densities. Interestingly, these effects were most apparent in the dorsal cap parvocellular subdivision of the PVN. E2 also shortened a delay in the excitation of the PVN-RVLM neurons. CONCLUSIONS: These findings demonstrate that E2 exerts an inhibitory effect on the functions of IA, potentially by selectively down-regulating Kv4.2 but not Kv4.3 in PVN-RVLM neurons distributed in a specific parvocellular subdivision. PMID- 24180325 TI - Design and synthesis of high performance multifunctional ultrathin hematite nanoribbons. AB - 1D porous ultrathin nanoribbons of hematite (alpha-Fe2O3) were prepared by controlled annealing of different oxides and hydroxides of iron obtained from a solvothermal synthesis method. It is found that calcination at a temperature of 500 degrees C for 150 min decomposes these iron hydroxides into their most stable oxide form, i.e., alpha-Fe2O3. Driven by different attractive forces, these porous alpha-Fe2O3 nanoparticles get aggregated in an ordered fashion to form an ultrathin 1D nanoribbon structure, as observed by detailed time dependent TEM and HRTEM analysis. It has been found that the high aspect ratio and porous surface morphology of these nanoribbons have significantly improved their electronic and spintronic properties as manifested by their photocatalysis, gas sensing, electrochemical, and magnetic behaviors. These hematite nanoribbons exhibit a weak ferromagnetic behavior due to surface spin disorder and shape anisotropy. Lateral confinement of electrons increases the band gap of the nanoribbons, as evident from the UV absorption analysis, which in turn improves their photocatalytic degradation efficiency (rate constant ~0.95 h(-1)) by delaying the electron-hole recombination process. However, their liquid petroleum gas sensing properties have been found to be mainly governed by the improved (porous) surface of the hematite nanoribbons that provides huge interaction sites for the analyte gas. Most of all, these hematite nanoribbons show a significantly enhanced pseudocapacitive performance exhibited by their high specific capacitance of about 145 F g(-1) at a current density of 1 A g(-1), high rate capability, and also long cycle stability (nearly 96% of capacity retention after 1600 charging/discharging cycles). PMID- 24180326 TI - Lean people with dysglycemia have a worse metabolic profile than centrally obese people without dysglycemia. AB - AIM: This study compared metabolic profiles of Asian Indians with normal waist circumference (WC) and dysglycemia versus those with high WC without dysglycemia. SUBJECTS AND METHODS: In 2,350 subjects >=20 years of age from the Chennai Urban Rural Epidemiology Study with full anthropometric and biochemical characterization, high WC was defined as >=90 cm in males and >=80 cm in females. Dysglycemia was defined as prediabetes (fasting plasma glucose >=100 mg/dL and/or 2-h plasma glucose >=140 mg/dL) or diabetes (fasting plasma glucose >=126 mg/dL, 2-h plasma glucose >=200 mg/dL, or treatment for diagnosed diabetes). Coronary artery disease (CAD) was defined as known myocardial infarction or Q waves on electrocardiography. Multivariable logistic regression models were used to explore factors associated with CAD. RESULTS: Of the subjects, 260 (11.1%) had dysglycemia with normal WC, and 679 (28.9%), had high WC without dysglycemia. Compared with subjects with high WC without dysglycemia, those with dysglycemia/normal WC, adjusted for age, were more likely to be males (P<0.001) and have higher systolic blood pressure (P<0.05), higher serum triglycerides (P<0.001), higher tumor necrosis factor-alpha (P<0.001), lower high-density lipoprotein cholesterol (P<0.05), and higher prevalence of CAD (6.3% vs. 2.0%; odds ratio 3.25 [95% confidence interval 1.52-6.94]; P=0.002). CONCLUSIONS: Dysglycemia is associated with a worse cardiometabolic profile than central obesity alone. PMID- 24180327 TI - Accuracy of subcutaneous continuous glucose monitoring in critically ill adults: improved sensor performance with enhanced calibrations. AB - OBJECTIVE: Accurate real-time continuous glucose measurements may improve glucose control in the critical care unit. We evaluated the accuracy of the FreeStyle((r)) Navigator((r)) (Abbott Diabetes Care, Alameda, CA) subcutaneous continuous glucose monitoring (CGM) device in critically ill adults using two methods of calibration. SUBJECTS AND METHODS: In a randomized trial, paired CGM and reference glucose (hourly arterial blood glucose [ABG]) were collected over a 48-h period from 24 adults with critical illness (mean+/-SD age, 60+/-14 years; mean+/-SD body mass index, 29.6+/-9.3 kg/m(2); mean+/-SD Acute Physiology and Chronic Health Evaluation score, 12+/-4 [range, 6-19]) and hyperglycemia. In 12 subjects, the CGM device was calibrated at variable intervals of 1-6 h using ABG. In the other 12 subjects, the sensor was calibrated according to the manufacturer's instructions (1, 2, 10, and 24 h) using arterial blood and the built-in point-of-care glucometer. RESULTS: In total, 1,060 CGM-ABG pairs were analyzed over the glucose range from 4.3 to 18.8 mmol/L. Using enhanced calibration median (interquartile range) every 169 (122-213) min, the absolute relative deviation was lower (7.0% [3.5, 13.0] vs. 12.8% [6.3, 21.8], P<0.001), and the percentage of points in the Clarke error grid Zone A was higher (87.8% vs. 70.2%). CONCLUSIONS: Accuracy of the Navigator CGM device during critical illness was comparable to that observed in non-critical care settings. Further significant improvements in accuracy may be obtained by frequent calibrations with ABG measurements. PMID- 24180328 TI - Epstein-Barr virus present in T cells or B cells shows differential effects on hemophagocytic symptoms associated with outcome in T-cell lymphomas. AB - Non-specific peripheral (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) frequently show Epstein-Barr virus (EBV) expression in lymphoma or bystander B cells. However, whether EBV localization affects clinicopathologic features is unclear. We correlated EBV localization with clinicopathologic findings in PTCL NOS (n = 63) and AITL (n = 26). PTCL-NOS showed EBV+ in 41%, with 22% in lymphoma T cells (T-EBV) and 19% in bystander B cells (B-EBV), and more EBV+ cells in T EBV cases (39.3% vs. 11.8%, p = 0.003). Compared to B-EBV cases, T-EBV PTCL-NOS had higher rates of type II EBV latency (p = 0.003), leukopenia (p = 0.020) and hemophagocytosis (p = 0.061), which predicted a poor outcome (p < 0.001). In contrast, 88% of AITLs were EBV+, exclusively in B cells. EBV+ cases showed lower rates of hemophagocytosis (p = 0.006), but this was insignificant for prognosis. Therefore, hemophagocytic symptoms in PTCL-NOS are much more tightly associated with T-EBV and carry poor prognoses. In contrast, hemophagocytosis in AITL is correlated with EBV-, but is not significant for outcome. PMID- 24180329 TI - Soluble interleukin-2 receptor level predicts survival in patients with follicular lymphoma treated with cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy in the rituximab era. AB - This study analyzed the prognostic significance of soluble interleukin-2 receptor alpha (sIL-2Ralpha) levels in 100 prospectively enrolled patients with previously untreated follicular lymphoma. It showed that sIL-2Ralpha level >= 115 pmol/L at the time of treatment initiation correlated with a high Follicular Lymphoma International Prognostic Index-2 (FLIPI-2), bulky disease, advanced clinical stage, number of involved lymph nodes, bone marrow involvement and elevated beta2 microglobulin (B2M) level. When testing all patients, sIL-2Ralpha >= 115 pmol/L was associated with significantly shorter progression-free (PFS; p < 0.03, hazard ratio [HR] 2.04) but not overall (OS; p = 0.06, HR 2.36) survival rates. Subanalysis of patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) +/- rituximab showed higher predictive power for both PFS (HR 2.75, 95% confidence interval [CI] 1.24-6.11, p = 0.01) and OS (HR 3.33, 95% CI 1.15-9.63, p = 0.02). In the whole population (n = 100), only B2M proved a significant univariate predictor (p = 0.007, HR = 2.8) of PFS. When testing patients treated with CHOP +/- rituximab, sIL-2Ralpha was found to be the best univariate predictor for PFS among all FLIPI-2 factors (HR = 2.68, p = 0.015). Serum IL-2Ralpha levels may help to refine risk assessment in the modern immunotherapy era complementary to FLIPI-2 factors. PMID- 24180330 TI - Advances in umbilical cord blood transplant: a summary of the 11th International Cord Blood Symposium, San Francisco, 6-8 June 2013. AB - The 11th International Cord Blood Symposium was devoted to advances in umbilical cord blood (UCB) research and transplant. Results of cord blood transplant (UCB SCT) for congenital storage disease and hemoglobinopathies are encouraging, but UCB SCT may also be useful for older adults with hematologic malignancies, and UCB cells have potential in regenerative medicine, particularly for neurological disorders, and may serve as excellent targets for gene therapy. UCB donor selection should consider high resolution human leukocyte antigen (HLA) typing, maternal HLA typing and detection of donor specific HLA antibodies. The issue of delayed hematopoietic reconstitution has hamstrung UCB SCT, but is addressed to a large extent by co-infusion of third-party progenitor cells. A number of cell expansion technologies also have great potential. Novel data show more limited benefits of double versus single umbilical cord blood transplant. Advances in quality control (QC) of UCB products and other improvements in cord blood banking technology will further improve the quality of stored UCB products. PMID- 24180331 TI - A multicenter phase II study of single-agent enzastaurin in previously treated multiple myeloma. AB - Enzastaurin is an oral serine/threonine kinase inhibitor of the protein kinase C (PKC) and phosphatidylinositol 3 (PI3) kinase/Akt pathways that induces apoptosis in multiple myeloma (MM) cell lines in a caspase-independent manner. A phase II study was conducted to assess response rate, time to progression (TTP), safety and biomarker association with clinical outcomes after monotherapy with the PKC inhibitor enzastaurin in previously treated patients with MM. Eligible patients (n = 14) were treated with enzastaurin 250 mg twice daily after receiving loading doses on day 1. One minimal response was observed. The median TTP was 5.11 months. There were two grade 3 adverse events, anemia and prolonged QTc interval, and no grade 4 adverse events. Single-agent enzastaurin was well tolerated but not effective in this heavily pretreated population with MM. PMID- 24180332 TI - Functional mesenchymal stem cells remain present in bone marrow microenvironment of patients with leukemia post-allogeneic hematopoietic stem cell transplant. AB - Mesenchymal stem cells (MSCs) and their progenies are important supporting cells in the bone marrow (BM) microenvironment. However, the function and kinetics of MSCs post-hematopoietic stem cell transplant (HSCT) remain unknown. In the present study, MSCs were cultured from a total of 76 BM samples from 15 patients receiving HSCT. Colony-forming unit fibroblasts in BM before pre-conditioning and 1, 3, 6 and 9 months post-HSCT were cultured and counted to quantify MSCs. Hematopoiesis-supporting activity of MSCs was observed with long-term culture of hematopoietic progenitors. An inhibitory effect of MSCs on in vitro lymphocyte proliferation was also observed. Results showed that post-HSCT MSCs supported in vitro hematopoiesis and inhibited lymphocyte growth. Moreover, the quantity of MSCs was reduced at an early stage and restored to baseline level 9 months post transplant. The results indicate that functional MSCs remain present in the BM microenvironment, and these findings shed light on the understanding of BM microenvironment reconstitution post-HSCT. PMID- 24180333 TI - Familial CD3+ T large granular lymphocyte leukemia: evidence that genetic predisposition and antigen selection promote clonal cytotoxic T-cell responses. AB - CD3+ T-large granular lymphocyte (T-LGL) proliferations often present with cytopenias and splenomegaly and are linked to autoimmunity, especially rheumatoid arthritis and Felty's syndrome. We report here the intra-family occurrence of T LGL leukemia in a father and son, both presenting with cytopenias and splenomegaly. Both patients carried the HLA-DRB1*04 allele, strongly associated with rheumatoid arthritis and Felty's syndrome, exhibited distinctive histopathological features suggestive of immune-mediated suppression of hematopoiesis and expressed a remarkably skewed T-cell receptor beta chain gene repertoire with overtime evolution (clonal drift). Immunoinformatics analysis and comparisons with clonotype sequences from various entities revealed (quasi)identities between (i) father and son, and (ii) father or son and patients with autoimmune disorders, T-LGL leukemia or chronic idiopathic neutropenia. Altogether, our results further corroborate antigen selection in the ontogeny of T-LGL leukemia and point to the interplay between genetics and the (micro)environment in shaping the outcome of cytotoxic T cell responses. PMID- 24180334 TI - Bendamustine: role and evidence in lymphoma therapy, an overview. AB - Bendamustine is a bifunctional molecule with both alkylating and antimetabolite properties, synthesized in 1963 by Ozegowski and Krebs in East Germany (German Democratic Republic). Widely used in Eastern Europe for lymphoma and myeloma therapy during the 1970s and 1980s, bendamustine was not studied in well-designed clinical trials until the 2000s. Unique among other recently developed antineoplastic drugs, bendamustine shows high activity and is now approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), being part of the therapeutic armamentarium in indolent and aggressive B-cell non Hodgkin lymphomas (NHLs), chronic lymphocytic leukemia (CLL), Hodgkin lymphoma (HL) and multiple myeloma (MM). "Bendamustine: role and clinical evidence in lymphoma therapy" is the title of a workshop which took place in Bologna, Italy, on 28 January 2013. This meeting focused on the development, mechanisms of action and evidence supporting the use of bendamustine in lymphoma therapy. This report summarizes the drug development steps, mechanisms of action, clinical results and rationale of use of bendamustine in different lymphoma subtypes, as discussed during the meeting, with the aim of helping the clinician regarding optimal use of this compound in a wide spectrum of lymphoproliferative disorders. PMID- 24180335 TI - Analysis and interpretation of imaging mass spectrometry data by clustering mass to-charge images according to their spatial similarity. AB - Imaging mass spectrometry (imaging MS) has emerged in the past decade as a label free, spatially resolved, and multipurpose bioanalytical technique for direct analysis of biological samples from animal tissue, plant tissue, biofilms, and polymer films. Imaging MS has been successfully incorporated into many biomedical pipelines where it is usually applied in the so-called untargeted mode-capturing spatial localization of a multitude of ions from a wide mass range.3 An imaging MS data set usually comprises thousands of spectra and tens to hundreds of thousands of mass-to-charge (m/z) images and can be as large as several gigabytes. Unsupervised analysis of an imaging MS data set aims at finding hidden structures in the data with no a priori information used and is often exploited as the first step of imaging MS data analysis. We propose a novel, easy-to-use and easy-to-implement approach to answer one of the key questions of unsupervised analysis of imaging MS data: what do all m/z images look like? The key idea of the approach is to cluster all m/z images according to their spatial similarity so that each cluster contains spatially similar m/z images. We propose a visualization of both spatial and spectral information obtained using clustering that provides an easy way to understand what all m/z images look like. We evaluated the proposed approach on matrix-assisted laser desorption ionization imaging MS data sets of a rat brain coronal section and human larynx carcinoma and discussed several scenarios of data analysis. PMID- 24180337 TI - Synthesis and structural characterization of molybdenum(VI) and iron(II) coordination compounds with S-alkyl-N-methyl-S-(2-pyridyl)sulfoximines and catalytic epoxidation activity of the molybdenum complexes. AB - Coordination compounds oxido(diperoxido)(S-butyl-N-methyl-S-(2 pyridyl)sulfoximine)molybdenum(VI), [MoO(O2)2{SO(NMe)(n)Bu(NC5H4)}] (5c), and bis{(dichlorido)(N,S-dimethyl-2-pyridylsulfoximine)iron(II)}, tetrahydrofuran solvate (1:1) (6), [FeCl2{SO(NMe)Me(NC5H4)}]2.THF are prepared from the free ligand 4 and molybdenum(VI) oxidediperoxide(dihydrate) and iron dichloride, respectively. The crystal structures reveal a trigonal bipyramid with the pyridine ring and the single oxygen on molybdenum in a trans arrangement for 5c and a planar MU(2)-Cl2Fe2 ring with trans-oriented exocyclic Cl atoms for 6 whereas the structures of the N,N-dicoordinated ligands are only little effected by the metals. Coordination compounds (5) efficiently catalyze the epoxidation of cyclooctene or of monosubstituted alkenes by tert-butyl hydroperoxide. PMID- 24180336 TI - Effects of yeast immobilization on bioethanol production. AB - The current study evaluated a newer method, which includes a dehydration step, of immobilizing Saccharomyces cerevisiae L-77 and S. cerevisiae L-73 onto hydroxylapatite and chamotte ceramic supports. The efficiency of cell immobilization on chamotte was significantly higher than hydroxylapatite. Immobilized yeast preparations were investigated for their ethanol-producing capabilities. The glucose concentration in a fermentation medium was 100 mg/mL. Immobilized preparations produced the same amount of ethanol (48 +/- 0.5 mg/mL) as free cells after 36 H of fermentation. During the early stages of fermentation, immobilized yeast cells produced ethanol at a higher rate than free cells. Yeast preparations immobilized on both supports (hydroxylapatite and chamotte) were successfully used in six sequential batch fermentations without any loss of activity. The chamotte support was more stable in the fermentation medium during these six cycles of ethanol production. In addition to the high level of ethanol produced by cells immobilized on chamotte, the stability of this support and its low cost make it a promising material for biotechnologies associated with ethanol production. PMID- 24180338 TI - Lymphocyte activation gene-3 expression defines a discrete subset of HIV-specific CD8+ T cells that is associated with lower viral load. AB - Mechanisms leading to the observed immune dysregulation in chronic HIV infection are not well understood. The MHC-II class ligand, lymphocyte activation gene-3 (LAG-3, CD223), has been implicated in the complex regulation mechanism of immune functions. In this study, we describe a new population of HIV-specific CD8(+) T cells expressing LAG-3. These LAG-3(+)CD8(+) T cells do not display immunophenotypic patterns traditionally attributed to regulatory T cells. The LAG3(+)CD8(+) T cells are CCR7(+),CD127(-), and display heterogeneous surface expressions of CD45RA and CD25. Interestingly, HIV-specific LAG-3(+)CD8(+) T cells do not substantially express CTLA-4 and LAG-3 expression does not correlate with interleukin (IL)-10 or tumor growth factor (TGF)-beta production. In addition, HIV-specific LAG3(+)CD8(+) T cells do not produce interferon (IFN gamma) or express CD107a. The frequency of HIV-specific LAG3(+)CD8(+) T cells negative correlated with plasma viral load. Our study introduces a new population of HIV-specific CD8(+) T cells and proposes additional mechanisms of immune regulation in chronic HIV infection. PMID- 24180339 TI - Beyond Bushfires: Community, Resilience and Recovery - a longitudinal mixed method study of the medium to long term impacts of bushfires on mental health and social connectedness. AB - BACKGROUND: Natural disasters represent an increasing threat both in terms of incidence and severity as a result of climate change. Although much is known about individual responses to disasters, much less is known about the social and contextual response and how this interacts with individual trajectories in terms of mental health, wellbeing and social connectedness. The 2009 bushfires in Victoria, Australia caused much loss of life, property destruction, and community disturbance. In order to progress future preparedness, response and recovery, it is crucial to measure and understand the impact of disasters at both individual and community levels. METHODS/DESIGN: This study aims to profile the range of mental health, wellbeing and social impacts of the Victorian 2009 bushfires over time using multiple methodologies and involving multiple community partners. A diversity of communities including bushfire affected and unaffected will be involved in the study and will include current and former residents (at the time of the Feb 2009 fires). Participants will be surveyed in 2012, 2014 and, funding permitting, in 2016 to map the predictors and outcomes of mental health, wellbeing and social functioning. Ongoing community visits, as well as interviews and focus group discussions in 2013 and 2014, will provide both contextual information and evidence of changing individual and community experiences in the medium to long term post disaster. The study will include adults, adolescents and children over the age of 5. DISCUSSION: Conducting the study over five years and focussing on the role of social networks will provide new insights into the interplay between individual and community factors and their influence on recovery from natural disaster over time. The study findings will thereby expand understanding of long term disaster recovery needs for individuals and communities. PMID- 24180341 TI - 6-Hydroxydaidzein enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. AB - Fermented soybean foods have been shown to reduce incidence of diabetes and improve insulin sensitivity. 6-Hydroxydaidzein (6-HD) is a bioactive ingredient isolated from fermented soybean. In this study, we examined the effects of 6-HD on adipocyte differentiation and insulin-stimulated glucose uptake, as well as the mechanisms involved. In our experiments, 6-HD enhanced 3T3-L1 adipocyte differentiation and insulin-stimulated glucose uptake in a dosage-dependent manner. In addition, 6-HD increased peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression and PPARgamma transcriptional activity. 6-HD increased CCAAT/enhanced binding protein alpha (C/EBPalpha) expression as well. Although having no effects on glucose transporter type 4 (GLUT4) gene expression, 6-HD facilitated GLUT4 protein translocation to the cell membranes. Our results indicate that 6-HD exhibited the actions of promoting adipocyte differentiation and improving insulin sensitivity by increasing the expression of C/EBPalpha and facilitating the translocation of GLUT4 via the activation of PPARgamma, suggesting that 6-HD can be promising in diabetes management. PMID- 24180342 TI - Surgical site infections in genital reconstruction surgery for gender reassignment, Detroit: 1984-2008. AB - BACKGROUND: Gender reassignment surgery (i.e., male-to-female or female-to-male) entails a series of complex surgical procedures. We conducted a study to explore epidemiologic characteristics of patients who underwent genital reconstruction operations as components of gender reassignment and to analyze risk factors for surgical-site infections (SSIs) following these operations. METHODS: The study was a retrospective cohort study conducted from 1984-2008 at Harper University Hospital, a tertiary hospital with 625 beds in Detroit, Michigan. Surgical site infection was defined according to established criteria. RESULTS: Records were available for 82 patients who underwent a total of 1,383 operations as part of genital-reconstruction processes. Thirty-nine (47.6%) of the patients underwent female-to-male reassignment (FTM) and 43 (52.4%) underwent male-to-female reassignment (MTF). The average age of the study cohort was 39.5+/-9.8 y. Of the patients in the cohort, 56 (68.3%) were Caucasian and 67 (81.7%) were single. The average number of operative encounters per patient was 11.8+/-4.6 for FTM and 4.9+/-2.4 for MTF. Forty-three (52.4%) patients developed an SSI at least once during their genital reconstruction process, of whom 34 (87%) were in the FTM group and nine (21%) in the MTF group (p<0.001). Staphylococci were the most common pathogens (61%) isolated in these infections, followed by Enterobacteriaceae (50%), Enterococcus (39%), and Pseudomonas aeruginosa (33.3%). Surgical site infection was associated independently with an increased frequency of operative procedures and operating room encounters. CONCLUSIONS: More than 50% of patients who underwent genital reconstruction operations developed an SSI at some point during the genital reconstruction process. Surgical site infections are more common in FTM than in MTF reconstruction operations, and for both FTM and MTF, SSIs are associated independently with an increased frequency of total operative procedures and encounters. PMID- 24180343 TI - Effect of peritoneal cavity lavage with 0.9% and 3.0% saline solution in the lung and spleen of gerbils with induced peritonitis. AB - BACKGROUND: Peritoneal cavity lavage is used widely in the treatment of peritonitis. Nonetheless, some studies question its rationale and prove it to be deleterious to the mesothelium. The present study aims to determine whether 0.9% and 3.0% saline lavage of the peritoneal cavity have an effect on the early systemic inflammatory response, namely, in the lung injury and splenic cellularity of gerbils with induced peritonitis. METHODS: Thirty-four male gerbils were divided into four groups: Control (n=9), submitted to laparotomy at time zero, re-laparotomy after 2 h, and sacrificed after a total of 6 h from start; untreated (n=8), submitted to peritonitis induction through cecal ligation and puncture (CLP) at time zero, re-laparotomy intended for drying of abdominal cavity and resection of the ischemic cecum after 2 h, and sacrifice after a total of 6 h from start; saline (n=8), submitted to peritonitis induction through CLP at time zero, re-laparotomy intended for warm 0.9% saline lavage of the abdominal cavity and resection of the ischemic cecum after 2 h, and sacrificed after a total of 6 h from start; and hypertonic (n=9), submitted to peritonitis induction through CLP at time zero, re-laparotomy intended for warm hypertonic saline (3.0%) lavage of the abdominal cavity and resection of the ischemic cecum after 2 h, and sacrificed after a total of 6 h from start. After sacrifice, we collected the left lung and the spleen for morphometric analysis. RESULTS: In the both the saline and hypertonic groups, there was significant decrease in the mean nuclei count in the lungs, compared with the untreated group (p<0.01). There was no difference in terms of nuclei count in the spleen among groups (p>0.05). CONCLUSIONS: The present study demonstrated that the peritoneal lavage with large volumes of warm 0.9% and 3.0% saline has a beneficial effect on the early systemic inflammatory response in infected animals, modulating and reducing the lung injury but having no effect on splenic cell count. PMID- 24180344 TI - Intravenous administration of high-dose Paclitaxel reduces gut-associated lymphoid tissue cell number and respiratory immunoglobulin A concentrations in mice. AB - BACKGROUND: Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice. METHODS: Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), alphabetaTCR(+), gammadeltaTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings. RESULTS: Total, CD4(+) and gammadeltaTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group. CONCLUSION: The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy. PMID- 24180345 TI - Perforated appendicitis with gastrointestinal basidiobolomycosis: a rare finding. AB - Background: Basidiobolomycosis is a rare fungal infection caused by the fungus Basidiobolus ranarum. Gastrointestinal basidiobolomycosis (GIB) is an unusual presentation of the fungal infection that is reported sparsely in the literature, but is an emerging infection in the southwestern United States. Lack of awareness of GIB has resulted in its delayed diagnosis and in extensive morbidity and mortality in patients with GIB. METHODS: Case report and literature review. CASE REPORT: We report the rare case of a young female with GIB that presented as perforated appendicitis with abscess formation. CONCLUSION: Although GIB is rare, immediate and aggressive therapy should be initiated when it is diagnosed. Both long-term medical and surgical treatment is required for its definitive management. PMID- 24180340 TI - Cell cycle regulators guide mitochondrial activity in radiation-induced adaptive response. AB - SIGNIFICANCE: There are accruing concerns on potential genotoxic agents present in the environment including low-dose ionizing radiation (LDIR) that naturally exists on earth's surface and atmosphere and is frequently used in medical diagnosis and nuclear industry. Although its long-term health risk is being evaluated and remains controversial, LDIR is shown to induce temporary but significant adaptive responses in mammalian cells and animals. The mechanisms guiding the mitochondrial function in LDIR-induced adaptive response represent a unique communication between DNA damage and cellular metabolism. Elucidation of the LDIR-regulated mitochondrial activity may reveal new mechanisms adjusting cellular function to cope with hazardous environmental stress. RECENT ADVANCES: Key cell cycle regulators, including Cyclin D1/CDK4 and Cyclin B1/cyclin dependent kinase 1 (CDK1) complexes, are actively involved in the regulation of mitochondrial functions via phosphorylation of their mitochondrial targets. Accumulating new evidence supports a concept that the Cyclin B1/CDK1 complex acts as a mediator in the cross talk between radiation-induced DNA damage and mitochondrial functions to coordinate cellular responses to low-level genotoxic stresses. CRITICAL ISSUES: The LDIR-mediated mitochondrial activity via Cyclin B1/CDK1 regulation is an irreplaceable network that is able to harmonize vital cellular functions with adjusted mitochondrial metabolism to enhance cellular homeostasis. FUTURE DIRECTIONS: Further investigation of the coordinative mechanism that regulates mitochondrial activities in sublethal stress conditions, including LDIR, will reveal new insights of how cells cope with genotoxic injury and will be vital for future targeted therapeutic interventions that reduce environmental injury and cancer risk. PMID- 24180346 TI - Peak event analysis: a novel empirical method for the evaluation of elevated particulate events. AB - BACKGROUND: We report on a novel approach to the analysis of suspended particulate data in a rural setting in southern Ontario. Analyses of suspended particulate matter and associated air quality standards have conventionally focussed on 24-hour mean levels of total suspended particulates (TSP) and particulate matter <10 microns, <2.5 microns and <1 micron in diameter (PM10, PM2.5, PM1, respectively). Less emphasis has been placed on brief peaks in suspended particulate levels, which may pose a substantial nuisance, irritant, or health hazard. These events may also represent a common cause of public complaint and concern regarding air quality. METHODS: Measurements of TSP, PM10, PM2.5, and PM1 levels were taken using an automated device following local complaints of dusty conditions in rural south-central Ontario, Canada. The data consisted of 126,051 by-minute TSP, PM10, PM2.5, and PM1 measurements between May and August 2012. Two analyses were performed and compared. First, conventional descriptive statistics were computed by month for TSP, PM10, PM2.5, and PM1, including mean values and percentiles (70th, 90th, and 95th). Second, a novel graphical analysis method, using density curves and line plots, was conducted to examine peak events occurring at or above the 99th percentile of per-minute TSP readings. We refer to this method as "peak event analysis". Findings of the novel method were compared with findings from the conventional approach. RESULTS: Conventional analyses revealed that mean levels of all categories of suspended particulates and suspended particulate diameter ratios conformed to existing air quality standards. Our novel methodology revealed extreme outlier events above the 99th percentile of readings, with peak PM10 and TSP levels over 20 and 100 times higher than the respective mean values. Peak event analysis revealed and described rare and extreme peak dust events that would not have been detected using conventional descriptive statistics. CONCLUSIONS: Peak event analysis underscored extreme particulate events that may contribute to local complaints regarding intermittently dusty conditions. These outlier events may not appear through conventional analytical approaches. In comparison with conventional descriptive approaches, peak event analysis provided a more analytical and data driven means to identify suspended particulate events with meaningful and perceptible effects on local residents. PMID- 24180347 TI - Use of advanced treatment technologies among men at low risk of dying from prostate cancer. PMID- 24180348 TI - Comparing long term impact on ovarian reserve between laparoscopic ovarian cystectomy and open laprotomy for ovarian endometrioma. AB - OBJECTIVE: To compare the long term impact on ovarian reserve between laparoscopic ovarian cystectomy with bipolar electrocoagulation and laparotomic cystectomy with suturing for ovarian endometrotic cyst. PATIENT AND METHOD(S): 121 patients with benign ovarian endometroitic cysts were randomised to either laparoscopic ovarian cystectomy using bipolar electrocoagulation (61 patients) or laparotomic ovarian cystectomy using sutures (60 patients). Serum follicle stimulating hormone, Antimullerian hormon, Basal antral follicle Count, mean ovarian diameter, and ovarian stromal blood flow velocity were measured at 6, 12 and 18 months after surgery and compared in both groups. RESULT(S): A statistically significant increase of serum FSH was found in the laproscopic bipolar group at 6-, 12 and 18-month postoperativly compared to open laparotomy suture group. Also, a statistically significant decrease of the mean AMH value occurred in laproscopic bipolar group at 6-, 12 and 18-month follow- up compared to open laparotomy suture group. Basal antral follicle number, mean ovarian diameter and peak systolic velocity were significantly decreased during the 6-, 12,18 -month follow-up in laproscopic bipolar group compared to open laparotomy suture group. CONCLUSION(S): After laproscopic ovarian cystecomy for endometrioma all pareameter of ovarian reseve are significantly decreased on long term follow up as compared to open laprotomy. PMID- 24180349 TI - Alleged biological father incest: a forensic approach. AB - Paternal incest is one of the most serious forms of intrafamilial sexual abuse with clinical, social, and legal relevance. A retrospective study was performed, based on forensic reports and judicial decisions of alleged cases of biological paternal incest of victims under 18 years old (n = 215) from 2003 to 2008. Results highlight that in a relevant number of cases: victims were female; the abuse begun at an early age with reiteration; the alleged perpetrator presented a history of sexual crimes against children; sexual practices were physically poorly intrusive, which associated with a forensic medical evaluation performed more than 72 h after the abuse, explain partially the absence of physical injuries or other evidence-these last aspects are different from extrafamilial cases. In conclusion, observations about paternal incest are likely to exacerbate the psychosocial consequences of the abuse and may explain the difficulty and delay in detect and disclose these cases. Few cases were legally prosecuted and convicted. PMID- 24180350 TI - Rheumatic mitral stenosis in children: more accelerated course in sub-Saharan patients. AB - BACKGROUND: Mitral stenosis, one of the grave consequences of rheumatic heart disease, was generally considered to take decades to evolve. However, several studies from the developing countries have shown that mitral stenosis follows a different course from that seen in the developed countries. This study reports the prevalence, severity and common complications of mitral stenosis in the first and early second decades of life among children referred to a tertiary center for intervention. METHODS: Medical records of 365 patients aged less than 16 and diagnosed with rheumatic heart disease were reviewed. Mitral stenosis was graded as severe (mitral valve area < 1.0 cm2), moderate (mitral valve area 1.0-1.5 cm2) and mild (mitral valve area > 1.5 cm2). RESULTS: Mean age at diagnosis was 10.1 +/- 2.5 (range 3-15) years. Of the 365 patients, 126 (34.5%) were found to have mitral stenosis by echocardiographic criteria. Among children between 6-10 years, the prevalence of mitral stenosis was 26.5%. Mean mitral valve area (n = 126) was 1.1 +/- 0.5 cm2 (range 0.4-2.0 cm2). Pure mitral stenosis was present in 35 children. Overall, multi-valvular involvement was present in 330 (90.4%). NYHA functional class was II in 76% and class III or IV in 22%. Only 25% of patients remember having symptoms of acute rheumatic fever. Complications at the time of referral include 16 cases of atrial fibrillation, 8 cases of spontaneous echo contrast in the left atrium, 2 cases of left atrial thrombus, 4 cases of thrombo embolic events, 2 cases of septic emboli and 3 cases of airway compression by a giant left atrium. CONCLUSION: Rheumatic mitral stenosis is common in the first and early second decades of life in Ethiopia. The course appeared to be accelerated resulting in complications and disability early in life. Echocardiography-based screening programs are needed to estimate the prevalence and to provide support for strengthening primary and secondary prevention programs. PMID- 24180352 TI - Exploiting enzyme catalysis in ultra-low ion strength media for impedance biosensing of avian influenza virus using a bare interdigitated electrode. AB - Enzyme catalysis is broadly used in various fields but generally applied in media with high ion strength. Here, we propose the exploitation of enzymatic catalysis in ultra-low ion strength media to induce ion strength increase for developing a novel impedance biosensing method. Avian influenza virus H5N1, a serious worldwide threat to poultry and human health, was adopted as the analyte. Magnetic beads were modified with H5N1-specific aptamer to capture the H5N1 virus. This was followed by binding concanavalin A (ConA), glucose oxidase (GOx), and Au nanoparticles (AuNPs) to create bionanocomposites through a ConA-glycan interaction. The yielded sandwich complex was transferred to a glucose solution to trigger an enzymatic reaction to produce gluconic acid, which ionized to increase the ion strength of the solution, thus decreasing the impedance on a screen-printed interdigitated array electrode. This method took advantages of the high efficiency of enzymatic catalysis and the high susceptibility of electrochemical impedance on the ion strength and endowed the biosensor with high sensitivity and a detection limit of 8 * 10(-4) HAU in 200 MUL sample, which was magnitudes lower than that of some analogues based on biosensing methods. Furthermore, the proposed method required only a bare electrode for measurements of ion strength change and had negligible change on the surficial properties of the electrode, though some modification of magnetic beads/Au nanoparticles and the construction of a sandwich complex were still needed. This helped to avoid the drawbacks of commonly used electrode immobilization methods. The merit for this method makes it highly useful and promising for applications. The proposed method may create new possibilities in the broad and well-developed enzymatic catalysis fields and find applications in developing sensitive, rapid, low-cost, and easy-to-operate biosensing and biocatalysis devices. PMID- 24180351 TI - Generation and primary phenotypes of imidazoline receptor antisera-selected (IRAS) knockout mice. PMID- 24180353 TI - Absorption spectrum and absolute absorption cross sections of CH3O2 radicals and CH3I molecules in the wavelength range 7473-7497 cm(-1). AB - The absorption spectrum of CH3O2 radicals and CH3I molecules has been measured in the range 7473-7497 cm(-1). CH3O2 radicals have been generated by 248 nm laser photolysis of CH3I in the presence of O2, and the relative absorption has been measured by time-resolved continuous-wave cavity ring-down spectroscopy (cw CRDS). Calibration of the relative absorption spectrum has been carried out on three distinct wavelengths by carefully measuring CH3O2 decays under different experimental conditions and extracting the initial radical concentration (and with this the absolute absorption cross sections) by using the well-known rate constant for the CH3O2 self-reaction. The following, pressure-independent absorption cross sections were determined: 3.41 * 10(-20), 3.40 * 10(-20), and 2.11 * 10(-20) cm(2) at 7748.18, 7489.16, and 7493.33 cm(-1). These values are 2 3 times higher than previous determinations ( Pushkarsky, M. B.; Zalyubovsky, S. J.; Miller, T. A. J. Chem. Phys. 2000, 112 (24), 10695 - 10698 and Atkinson, D. B.; Spillman, J. L. J. Phys. Chem. A 2002, 106 (38), 8891 - 8902). The absorption spectrum of the stable precursor CH3I has also been determined and three characteristic sharp absorption lines with absorption cross sections up to 2 * 10(-21) cm(2) have been observed in this wavelength range. PMID- 24180354 TI - Efficacy of electrocoagulation in sealing the cystic artery and cystic duct occluded with only one absorbable clip during laparoscopic cholecystectomy. AB - BACKGROUND: Even though laparoscopic cholecystectomy (LC) emerged over 20 years ago, controversies persist with regard to the best method to ligate the cystic duct and artery. We proposed to assess the effectiveness and safety of electrocoagulation to seal the cystic artery and cystic duct after their occlusion with only one absorbable clip. MATERIALS AND METHODS: We retrospectively compared the clinical data for 635 patients undergoing LC using electrocoagulation to seal the cystic artery and cystic duct that were occluded with only one absorbable clip (Group 1) and 728 patients undergoing LC using titanium clips (Group 2). In parallel, 30 rabbits randomized into six groups underwent cholecystectomy. After cystic duct ligation with absorbable or titanium clips, the animals were sacrificed 1, 3, or 6 months later, and intraabdominal adhesions were assessed after celiotomy. RESULTS: The mean operative time was significantly shorter (41.6 versus 58.9 minutes, P<.01) in Group 1 than in Group 2. No cystic duct leaks occurred in any patients from Group 1, compared with seven leaks among the 728 (0.96%) patients from Group 2 (P<.05). The morbidity was significantly higher in Group 2 than in Group 1 (3.43% versus 1.58%). Mean intraoperative blood loss and hospitalization length were not significantly different between the two groups, and no deaths occurred in either group. In animal experiments, adhesion was tighter for absorbable than for titanium clips, but fibrous tissue encapsulation was thinner at the site of titanium clips. CONCLUSIONS: Electrocoagulation of the cystic artery and cystic duct that were occluded with only one absorbable clip is safe and effective during LC. This approach is associated with shortened operative times and reduced leakage, compared with the standard method using metal clips. PMID- 24180355 TI - Contralateral metachronous hernia following negative laparoscopic evaluation for contralateral patent processus vaginalis: a meta-analysis. AB - OBJECTIVE: To conduct a meta-analysis of contralateral metachronous inguinal hernia (CMIH) that originated from negative laparoscopic evaluation for contralateral patent processus vaginalis (CPPV) in children who presented with a unilateral inguinal hernia and to determine the incidence of and factors associated with such a CMIH. MATERIALS AND METHODS: A PubMed search was performed for all studies concerning laparoscopic repair or evaluation of inguinal hernia in children. The search strategy was as follows: (laparoscop* OR coelioscop* OR peritoneoscop* OR laparoendoscop* OR minilaparoscop*) AND ("inguinal hernia" OR "metachronous hernia") AND child*. Inclusion criteria included unilateral inguinal hernia in children, negative laparoscopic evaluation of CPPV, without history of contralateral inguinal surgery previously, and clearly reporting CMIH development or not. Editorials, letters, review articles, case reports, animal studies, and duplicate patient series were excluded. RESULTS: Twenty-three studies comprising 6091 children with negative CPPV fulfilled the inclusion criteria and were included in the final analysis, of whom 80 (1.31%) subsequently presented with a CMIH. Subgroup analysis showed that CMIH incidence was lower through an umbilical approach than via an inguinal one (0.85% versus 1.78%, P=.009). As for the transinguinal approach, there was a CMIH incidence of 0.78% and 2.05%, respectively, for laparoscopy with a small angle (30 degrees and 70 degrees ), whereas there was no CMIH development for that with a large angle (110 degrees , 120 degrees , and flexible). A high pneumoperitoneum pressure (>10 mm Hg, >12 mm Hg, and >14 mm Hg) was usually associated with a slightly higher CMIH incidence than a low one (<=10 mm Hg, <=12 mm Hg, and <=14 mm Hg), all without significant difference. CMIH incidence was slightly lower for using a broad CPPV definition than for using a narrow one (0.64% versus 1.35%, P=.183). CONCLUSIONS: CMIH following negative laparoscopic evaluation for CPPV was a rare but possible phenomenon. Choosing the transumbilical approach, transinguinal laparoscopy with a large angle, low-pressure pneumoperitoneum, and broad CPPV definition would probably reduce the occurrence of such CMIHs. PMID- 24180356 TI - Safety and efficacy of laparoscopic percutaneous extraperitoneal closure for inguinal hernias and hydroceles in children: a comparison with traditional open repair. AB - INTRODUCTION: Laparoscopic procedures for inguinal hernias and hydroceles in children have become widespread in the past few decades. The purpose of this study was to perform a retrospective analysis of our experience in order to assess the safety and efficacy of laparoscopic percutaneous extraperitoneal closure (LPEC) and to compare the findings with those of conventional open repair (OR). SUBJECTS AND METHODS: We analyzed the medical records of 488 patients who underwent LPEC or OR for inguinal hernia or hydrocele at our institute between April 2008 and December 2012. The indications for the operation, length of the operation, complications, day surgery, contralateral patent processus vaginalis, and incidence of metachronous contralateral hernia were investigated. The chi squared test, unpaired t test, and Steel-Dwass test were used to analyze the significance of the data. RESULTS: Among a total of 488 patients, 326 patients underwent LPEC (125 males and 201 females), and 162 underwent OR (140 males and 22 females). There was no significant difference in the incidence of recurrence (three in the LPEC and none in the OR group, P=.55) or in the success rates of day surgery (97.8% in LPEC versus 97.6% in OR). The incidence of metachronous contralateral hernias in the LPEC group was lower than that in the OR group (LPEC 0%; OR 2.2%, P=.03). Seventeen subjects with hydroceles were treated by LPEC without any complications. CONCLUSIONS: LPEC is safe and effective for inguinal hernias and hydroceles in children, regardless of age, sex, and incarceration and could reduce the incidence of metachronous contralateral hernias. PMID- 24180357 TI - Diabetes mellitus increases the risk of bladder cancer: an updated meta-analysis of observational studies. AB - BACKGROUND: Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. We performed an updated meta analysis to examine the association between DM and risk of bladder cancer. MATERIALS AND METHODS: We systematically searched the EMBASE and Medline (PubMed) databases (from inception through February 1, 2013) and reviewed the reference lists of relevant publications to search for additional studies. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random effects models. RESULTS: In total, 10 case-control and 14 cohort studies met the inclusion criteria. Analysis of all studies showed that DM was associated with an increased risk of bladder cancer (RR 1.30, 95% CI 1.18-1.43). There was heterogeneity among studies (Pheterogeneity <0.001, I(2)=81.5%). Cohort studies showed a lower risk (RR 1.23, 95% CI 1.09-1.37) than case-control studies (odds ratio 1.46, 95% CI 1.20-1.78). The positive association was significant only in women (RR 1.23, 95% CI 1.02-1.49), but not in men (RR 1.07, 95% CI 0.97-1.18). The combined RRs remained unchanged before and after the studies on type 1 diabetes were excluded from analysis. The association between DM and bladder cancer risk did not differ significantly by methods of DM ascertainment. The combined RRs were 1.17 (95% CI 1.03-1.34), 1.34 (95% CI 1.19-1.51), and 1.57 (95% CI 0.96-2.55), respectively, when restricting the analysis to the studies accounting for body mass index, cigarette smoking, or glucose-lowering drug use. CONCLUSIONS: This meta-analysis indicates a positive association between DM and risk of bladder cancer. Further studies are warranted to determine whether DM prevention and control can reduce risk of bladder cancer. PMID- 24180358 TI - MyoD and Myf6 gene expression patterns in skeletal muscle during embryonic and posthatch development in the domestic duck (Anas platyrhynchos domestica). AB - The MyoD and Myf6 genes, which are muscle regulatory factors (MRFs), play major roles in muscle growth and development and initiate muscle fibre formation via the regulation of muscle-specific gene translation. Therefore, MyoD and Myf6 are potential candidate genes for meat production traits in animals and poultry. The objective of this study was to evaluate MyoD and Myf6 gene expression patterns in the skeletal muscle during early developmental stage of ducks. Gene expression levels were detected using the quantitative RT-PCR method in the breast muscle (BM) and leg muscle (LM) at embryonic days 13, 17, 21, 25, 27, as well as at 1 week posthatching in Gaoyou and Jinding ducks (Anas platyrhynchos domestica). The MyoD and Myf6 gene profiles in the two duck breeds were consistent during early development, and MyoD gene expression showed a 'wave' trend in BM and an approximate 'anti-?' trend in LM. Myf6 gene expression in BM showed the highest level at embryonic day 21, which subsequently decreased, although remained relatively high, while levels at embryonic days 13, 17 and 21 were higher in LM. The results of correlation analysis showed that MyoD and Myf6 gene expression levels were more strongly correlated in LM than in BM in both duck breeds. These results indicated that different expression patterns of the MyoD and Myf6 genes in BM and LM may be related to muscle development and differentiation, suggesting that MyoD and Myf6 are integral to skeletal muscle development. PMID- 24180359 TI - In vitro irradiation system for radiobiological experiments. AB - BACKGROUND: Although two-dimensional (2-D) monolayer cell cultures provide important information on basic tumor biology and radiobiology, they are not representative of the complexity of three-dimensional (3-D) solid tumors. In particular, new models reproducing clinical conditions as closely as possible are needed for radiobiological studies to provide information that can be translated from bench to bedside. METHODS: We developed a novel system for the irradiation, under sterile conditions, of 3-D tumor spheroids, the in vitro model considered as a bridge between the complex architectural organization of in vivo tumors and the very simple one of in vitro monolayer cell cultures. The system exploits the same equipment as that used for patient treatments, without the need for dedicated and highly expensive instruments. To mimic the passage of radiation beams through human tissues before they reach the target tumor mass, 96-multiwell plates containing the multicellular tumor spheroids (MCTS) are inserted into a custom-built phantom made of plexiglass, the material most similar to water, the main component of human tissue. RESULTS: The system was used to irradiate CAEP- and A549-derived MCTS, pre-treated or not with 20 MUM cisplatin, with a dose of 20 Gy delivered in one session. We also tested the same treatment schemes on monolayer CAEP and A549 cells. Our preliminary results indicated a significant increment in radiotoxicity 20 days after the end of irradiation in the CAEP spheroids pre-treated with cisplatin compared to those treated with cisplatin or irradiation alone. Conversely, the effect of the radio- chemotherapy combination in A549-derived MCTS was similar to that induced by cisplatin or irradiation alone. Finally, the 20 Gy dose did not affect cell survival in monolayer CAEP and A549 cells, whereas cisplatin or cisplatin plus radiation caused 100% cell death, regardless of the type of cell line used. CONCLUSIONS: We set up a system for the irradiation, under sterile conditions, of tumor cells grown in 3-D which allows for the use of the same dose intensities and schedules utilized in clinical practice. This irradiation system, coupled with 3-D cell cultures, has the potential to generate information that could be used to individually tailor radiotherapy. PMID- 24180361 TI - Thermochromism, the Alexandrite effect, and dynamic Jahn-Teller distortions in Ho2Cu(TeO3)2(SO4)2. AB - A 3d-4f heterobimetallic material with mixed anions, Ho2Cu(TeO3)2(SO4)2, has been prepared under hydrothermal conditions. Ho2Cu(TeO3)2(SO4)2 exhibits both thermochromism and the Alexandrite effect. Variable temperature single crystal X ray diffraction and UV-vis-NIR spectroscopy reveal that changes in the Cu(II) coordination geometry result in negative thermal expansion of axial Cu-O bonds that plays a role in the thermochromic transition of Ho2Cu(TeO3)2(SO4)2. Magnetic studies reveal an effective magnetic moment of 14.97 MUB. which has a good agreement with the calculated value of 15.09 MUB. PMID- 24180360 TI - Designing preclinical perceptibility measures to evaluate topical vaginal gel formulations: relating user sensory perceptions and experiences to formulation properties. AB - Abstract The effectiveness of any biomedical prevention technology relies on both biological efficacy and behavioral adherence. Microbicide trials have been hampered by low adherence, limiting the ability to draw meaningful conclusions about product effectiveness. Central to this problem may be an inadequate conceptualization of how product properties themselves impact user experience and adherence. Our goal is to expand the current microbicide development framework to include product "perceptibility," the objective measurement of user sensory perceptions (i.e., sensations) and experiences of formulation performance during use. For vaginal gels, a set of biophysical properties, including rheological properties and measures of spreading and retention, may critically impact user experiences. Project LINK sought to characterize the user experience in this regard, and to validate measures of user sensory perceptions and experiences (USPEs) using four prototype topical vaginal gel formulations designed for pericoital use. Perceptibility scales captured a range of USPEs during the product application process (five scales), ambulation after product insertion (six scales), and during sexual activity (eight scales). Comparative statistical analyses provided empirical support for hypothesized relationships between gel properties, spreading performance, and the user experience. Project LINK provides preliminary evidence for the utility of evaluating USPEs, introducing a paradigm shift in the field of microbicide formulation design. We propose that these user sensory perceptions and experiences initiate cognitive processes in users resulting in product choice and willingness-to-use. By understanding the impact of USPEs on that process, formulation development can optimize both drug delivery and adherence. PMID- 24180363 TI - Lipid parameters in a hyperendemic area for malaria. AB - BACKGROUND: This is a cross-sectional study with the objective to analyze lipid parameters of individuals living in Brazilian Amazon, where malaria is endemic. METHODS: The city chosen was Anajas in the state of Para, Brazil, in Amazon region. The study analyzed lipid parameters of 46 subjects, 31 male and 15 female, aged between 20-60 years without malaria, and residents for more than five years in this city considered an area hyperendemic for disease. It was established three groups according to the number of previous episodes of malaria: group I (n = 22) one to five episodes, group II (n = 20) six to ten episodes and group III (n = 4) eleven to fifteen episodes. Total cholesterol, high density lipoprotein (HDL cholesterol), and low density lipoprotein (LDL cholesterol) were measured and was confected the thick smear for malaria of all individuals. RESULTS: The hypocholesterolemia, the main characteristic of hyperendemic areas for malaria, was confirmed, but the mean of HDL cholesterol levels were 9.78% higher than the reference of World Health Organization. CONCLUSION: Although other factors might have contributed to lipid profile, the constant exposure to infection by Plasmodium, according to the physiology of the parasite, may have played an important role in defining the lipid parameters observed for this region. Further studies, such as the case-control is needed to confirm this hypothesis. PMID- 24180364 TI - Emission characteristics of particulate matter and volatile organic compounds in cow dung combustion. AB - Biomass fuel is used for cooking and heating, especially in developing countries. Combustion of biomass fuel can generate high levels of indoor air pollutants, including particulate matter (PM) and volatile organic compounds (VOCs). This study characterized PM and VOC emissions from cow dung combustion in a controlled experiment. Dung from grass-fed cows was dried and combusted using a dual-cone calorimeter. Heat fluxes of 10, 25, and 50 kW/m(2) were applied. The concentrations of PM and VOCs were determined using a dust spectrometer and gas chromatography/mass spectrometry, respectively. PM and VOC emission factors were much higher for the lower heat flux, implying a fire ignition stage. When the heat flux was 50 kW/m(2), the CO2 emission factor was highest and the PM and VOC emission factors were lowest. Particle concentrations were highest in the 0.23 0.3 MUm size range at heat fluxes of 25 and 50 kW/m(2). Various toxic VOCs, including acetone, methyl ethyl ketone, benzene, and toluene, were detected at high concentrations. Although PM and VOC emission factors at 50 kW/m(2) were lower, they were high enough to cause extremely high indoor air pollution. The characteristics of PM and VOC emissions from cow dung combustion indicated potential health effects of indoor air pollution in developing countries. PMID- 24180365 TI - Role of multiparametric magnetic resonance imaging (MRI) in focal therapy for prostate cancer: a Delphi consensus project. AB - OBJECTIVE: To define the role of multiparametric MRI (mpMRI) for treatment planning, guidance and follow-up in focal therapy for prostate cancer based on a multidisciplinary Delphi consensus project. MATERIALS AND METHODS: An online consensus process based on a questionnaire was circulated according to the Delphi method. Discussion points were identified by literature research and were sent to the panel via an online questionnaire in three rounds. A face-to-face consensus meeting followed the three rounds of questions that were sent to a 48-participant expert panel consisting of urologists, radiologists and engineers. Participants were presented with the results of the previous rounds. Conclusions formulated from the results of the questionnaire were discussed in the final face-to-face meeting. RESULTS: Consensus was reached in 41% of all key items. Patients selected for focal therapy should have biopsy-proven prostate cancer. Biopsies should ideally be performed after mpMRI of the prostate. Standardization of imaging protocols is essential and mpMRIs should be read by an experienced radiologist. In the follow-up after focal therapy, mpMRI should be performed after 6 months, followed by a yearly mpMRI. mpMRI findings should be confirmed by targeted biopsies before re-treatment. No consensus was reached on whether mpMRI could replace transperineal template saturation biopsies to exclude significant lesions outside the target lesion. CONCLUSIONS: Consensus was reached on a number of areas related to the conduct, interpretation and reporting of mpMRI for use in treatment planning, guidance and follow-up of focal therapy for prostate cancer. Future studies, comparing mpMRI with transperineal saturation mapping biopsies, will confirm the importance of mpMRI for a variety of purposes in focal therapy for prostate cancer. PMID- 24180366 TI - Socio-economic inequality and HIV in South Africa. AB - BACKGROUND: The linkage between the socio-economic inequality and HIV outcomes was analysed using data from a population-based household survey that employed multistage-stratified sampling. The goal is to help refocus attention on how HIV is linked to inequalities. METHODS: A socio-economic index (SEI) score, derived using Multiple Correspondence Analysis of measures of ownership of durable assets, was used to generate three SEI groups: Low (poorest), Middle, and Upper (no so poor). Distribution of HIV outcomes (i.e. HIV prevalence, access to HIV/AIDS information, level of stigma towards HIV/AIDS, perceived HIV risk and sexual behaviour) across the SEI groups, and other background characteristics was assessed using weighted data. Univariate and multivariate logistic regression was used to assess the covariates of the HIV outcomes across the socio-economic groups. The study sample include 14,384 adults 15 years and older. RESULTS: More women (57.5%) than men (42.3%) were found in the poor SEI [P<0.001]. HIV prevalence was highest among the poor (20.8%) followed by those in the middle (15.9%) and those in the upper SEI (4.6%) [P<0.001]. It was also highest among women compared to men (19.7% versus 11.4% respectively) and among black Africans (20.2%) compared to other races [P<0.001]. Individuals in the upper SEI reported higher frequency of HIV testing (59.3%) compared to the low SEI (47.7%) [P< 0.001]. Only 20.5% of those in poor SEI had "good access to HIV/AIDS information" compared to 79.5% in the upper SEI (P<0.001). A higher percentage of the poor had a stigmatizing attitude towards HIV/AIDS (45.6%) compared to those in the upper SEI (34.8%) [P< 0.001]. There was a high personal HIV risk perception among the poor (40.0%) and it declined significantly to 10.9% in the upper SEI. CONCLUSIONS: Our findings underline the disproportionate burden of HIV disease and HIV fear among the poor and vulnerable in South Africa. The poor are further disadvantaged by lack of access to HIV information and HIV/AIDS services such as testing for HIV infection. There is a compelling urgency for the national HIV/AIDS response to maximizing program focus for the poor particularly women. PMID- 24180367 TI - Effects of multidisciplinary teamwork on lead times and patient flow in the emergency department: a longitudinal interventional cohort study. AB - BACKGROUND: Long waiting times for emergency care are claimed to be caused by overcrowded emergency departments and non-effective working routines. Teamwork has been suggested as a promising solution to these issues. The aim of the present study was to investigate the effects of teamwork in a Swedish emergency department on lead times and patient flow. METHODS: The study was set in an emergency department of a university hospital where teamwork, a multi professional team responsible for the whole care process for a group of patients, was introduced. The study has a longitudinal non-randomized intervention study design. Data were collected for five two-week periods during a period of 1.5 years. The first part of the data collection used an ABAB design whereby standard procedure (A) was altered weekly with teamwork (B). Then, three follow-ups were conducted. At last follow-up, teamwork was permanently implemented. The outcome measures were: number of patients handled within teamwork time, time to physician, total visit time and number of patients handled within the 4-hour target. RESULTS: A total of 1,838 patient visits were studied. The effect on lead times was only evident at the last follow-up. Findings showed that the number of patients handled within teamwork time was almost equal between the different study periods. At the last follow-up, the median time to physician was significantly decreased by 11 minutes (p = 0.0005) compared to the control phase and the total visit time was significantly shorter at last follow-up compared to control phase (p = <0.0001; 39 minutes shorter on average). Finally, the 4-hour target was met in 71% in the last follow-up compared to 59% in the control phase (p = 0.0005). CONCLUSIONS: Teamwork seems to contribute to the quality improvement of emergency care in terms of small but significant decreases in lead times. However, although efficient work processes such as teamwork are necessary to ensure safe patient care, it is likely not sufficient for bringing about larger decreases in lead times or for meeting the 4-hour target in the emergency department. PMID- 24180368 TI - QCM-4 a novel 5-HT3 antagonist attenuates the behavioral and biochemical alterations on chronic unpredictable mild stress model of depression in Swiss albino mice. AB - OBJECTIVES: The inconsistent therapeutic outcome necessitates identifying novel compounds for the treatment of depression. Therefore, the present study is aimed at evaluating the antidepressant-like effects of a novel 5-HT3 receptor antagonist 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alterations in mice. METHODS: Animals were subjected to different stressors for a period of 28 days. Thereafter, battery tests like locomotor score, sucrose preference test, forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM) and open field test (OFT) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione (GSH), catalase and superoxide dismutase (SOD) were assessed in brain homogenate. KEY FINDINGS: QCM-4 dose dependently reversed the CUMS induced behavioral and biochemical alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the percent time in open arm in EPM and increasing the ambulation along with the rearings and decreased number of fecal pellets in OFT. Further, biochemical alterations were attenuated by QCM-4 as indicated by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD. CONCLUSIONS: QCM-4 attenuated the behavioral and biochemical derangements induced by CUMS in mice, indicating antidepressant behavior of the novel compound. PMID- 24180369 TI - Using phosphatases to generate self-assembled nanostructures and their applications. AB - SIGNIFICANCE: Self-assembled nanostructures have received significant research interest in the last decade, because they show great promise for drug delivery, diagnostics, tissue engineering, and regenerative medicine. Recently, the development of enzyme-assisted self-assembled nanostructures has become an active area of research because of the attractive characteristics of enzymes, such as ready availability, good biocompatibility, and high selectivity and specificity. Phosphatases, taking part in approximately 30% of intra- and extracellular activities, have been widely employed as triggers for the generation of self assembled biomaterials, including static, reversible, and dynamic systems. RECENT ADVANCES: In this review, we highlight the generation of self-assembled systems of synthetic molecules using phosphatases and their potential applications. We first summarize the generation of different kinds of static and dynamic self assembled structures, including nanofibers and nanoparticles, by the dephosphorylation reaction catalyzed by phosphatases. The antagonistic interactions of phosphatases and kinases make this system one of the most attractive candidates for biotransformation. Diverse biomedical applications of phosphatases/kinases-involved self-assembled systems have been extensively explored in fields such as bacterial growth inhibition, drug delivery, imaging of self-assembly inside live cells, and biomineralization. We then summarize the reversible self-assembled systems controlled by the pair enzymes of phosphatases/kinases, in which different morphologies of self-assembled nanostructures can be achieved and switched by the pair enzymes. These phosphatase-involved self-assembled systems can be used for many applications such as controlled drug delivery, enzyme activity imaging, and cancer cell inhibition. CRITICAL ISSUES: Phosphatases are over-expressed in several cancer cell lines. Their detection is, therefore, important for cancer diagnostics. Nanomaterials that can respond to abnormal phosphatase activities also have big potential for the delivery of therapeutic agents on demand. The study of reversible self-assembling systems control by the phosphatase/kinase switch may provide useful insights to understand the working principle of this important biological switch. FUTURE DIRECTIONS: The design principle mentioned in this review may stimulate the generation of smart self-assembled systems by other enzymes or other pairs of enzymes. The combination of environment-sensitive fluorescence property of fluorescent dyes and self-assembling molecules that can respond to enzymes may lead to the development of smart probes to monitor important biological processes. PMID- 24180370 TI - Traceless labeling of glycoproteins and its application to the study of glycoprotein-protein interactions. AB - A new chemical method for the traceless labeling of glycoproteins with synthetic boronic acid (BA)-tosyl probes was successfully developed. The BA moiety acts as an affinity head to direct the formation of a cyclic boronate diester with the diol groups of glycans. Following this step, the electrophilic tosyl group is displaced by an SN2 reaction with a nucleophilic residue of the boronated glycoprotein, and finally, a reporter group is tagged onto the glycoprotein via an ether linkage. In the presence of polyols, a competition reaction recovers the native glycan of the tagged glycoprotein, conserving its biological significance. The BA-tosyl probes were used successfully for the specific labeling of glycosylated fetuins in a mixed protein pool and from crude Escherichia coli (E. coli) lysate. Further, a BA-tosyl-functionalized glass slide was used to fabricate glycoprotein microarrays with highly conserved glycans. By interacting with various lectins (carbohydrate-binding proteins), such as Concanavalin A (Con A) and wheat germ agglutinin (WGA), the types of carbohydrates and specific linkages of glycoproteins (alpha or beta) could be systematically monitored. It is believed that the newly developed method will greatly accelerate the understanding of glycoproteins. PMID- 24180371 TI - When it is time to hang up the keys: the driving and dementia toolkit - for persons with dementia (PWD) and caregivers - a practical resource. AB - BACKGROUND: The aim of this project was to develop a toolkit to assist persons with dementia (PWD) and their caregivers, in planning for retirement from driving. The information gathered was used to develop a tool that can assist reflection about, and make sound decisions in this challenging area of the dementia journey. The purpose is to keep safe drivers on the road and to prepare those who are moving towards being at risk of being involved in crashes, to eventually stop driving when they are unsafe.The toolkit was prepared to address the concerns of both the PWD as well as the caregivers. Strategies and solutions are presented for both the PWD and the caregivers. A grief insert was also developed that can assist caregivers in supporting the PWD in the grief process that can accompany losing one's driving privileges. PMID- 24180372 TI - Sleep in children with disruptive behavioral disorders. AB - This study compared sleep in patients with Conduct Disorder/Oppositional Defiant Disorder (CD/ODD) and normative children and evaluated the associations between sleep and behavioral symptoms in patients. Participants were 30 patients, aged 7 to 12 years, with diagnoses of CD/ODD and their age and gender matched controls. Patients with CD/ODD and their parents reported significantly more sleep problems than did the control children and their parents (p values < 0.01). By actigraphy, CD/ODD children with comorbid ADHD slept significantly less than did the patients with CD/ODD alone and the controls. In patients, low sleep amount and efficiency associated with increased amount of parent-reported externalizing symptoms (r = 0.72, 0.66, p values < 0.001). Results highlight the need of evaluating sleep in children with CD/ODD. Improving their sleep may ease their symptoms. PMID- 24180373 TI - Effect of vaccination of cattle with the low virulence Nc-Spain 1H isolate of Neospora caninum against a heterologous challenge in early and mid-gestation. AB - Live vaccines have emerged as one of the most potentially cost-effective measures for the control of bovine neosporosis. Previous studies have shown that Nc-Spain 1H is a naturally attenuated isolate of Neospora caninum and that immunisation with live Nc-Spain 1H tachyzoites generated a protective immune response in mice. The aim of this study was to evaluate the safety and efficacy of immunisation in cattle. N. caninum-seronegative heifers were immunised subcutaneously twice with 107 live Nc-Spain 1H tachyzoites prior to artificial insemination. No adverse reactions or negative effects on reproductive parameters were recorded following immunisation. In immunised and non-challenged heifers, no foetal deaths were observed, and none of the calves was congenitally infected. The efficacy against N. caninum-associated foetal death and vertical transmission was determined after challenge with high doses of the Nc-1 isolate at 70 and 135 days of gestation, respectively. After the challenge in early gestation, the immunisation induced a protection of 50% against foetal death. In addition, the microsatellite analysis performed in PCR-positive tissue samples from foetuses that died after challenge infection showed that the profiles corresponded to the challenge isolate Nc-1. A degree of protection against vertical transmission was observed after challenge at mid-gestation; calves from immunised heifers showed significantly lower pre colostral Neospora-specific antibody titres than calves from the non immunised/challenge group (P < 0.05). Strong antibody and interferon gamma responses were induced in the immunised heifers. This study indicates that the immunisation before pregnancy with the Nc-Spain 1H vaccine isolate appeared to be safe and reduced the occurrence of N. caninum-associated abortion and vertical transmission in experimentally infected cattle. In light of these encouraging results, the next step for testing this live attenuated candidate should be the assessment of its efficacy and safety in naturally infected cattle. PMID- 24180374 TI - The effects of di(2-ethylhexyl)phthalate on rat liver in relation to selenium status. AB - This study was performed to determine the hepatotoxicity of di(2 ethylhexyl)phthalate (DEHP) in relation to selenium status. In 3-week-old Sprague Dawley rats, selenium deficiency was induced by a <=0.05 selenium mg/kg. A selenium supplementation group was given 1 mg selenium/kg diet for 5 weeks. Di(2 ethylhexyl)phthalate-treated groups received 1000 mg/kg dose by gavage during the last 10 days of the experiment. Histopathology, peroxisome proliferation, catalase (CAT) immunoreactivity and activity and apoptosis were assessed. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR1)], superoxide dismutase (SOD), and glutathione S-transferase (GST); aminotransferase, total glutathione (tGSH), and lipid peroxidation (LP) levels were measured. Di(2 ethylhexyl)phthalate caused cellular disorganization while necrosis and inflammatory cell infiltration were observed in Se-deficient DEHP group (DEHP/SeD). Catalase activity and immunoreactivity were increased in all DEHP treated groups. Glutathione peroxidase 1 and GPx4 activities decreased significantly in DEHP and DEHP/SeD groups, while GST activities decreased in all DEHP-exposed groups. Thioredoxin reductase activity increased in DEHP and DEHP/SeS, while total SOD activities increased in all DEHP-treated groups. Lipid peroxidation levels increased significantly in SeD (26%), DEHP (38%) and DEHP/SeD (71%) groups. Selenium supplementation partially ameliorated DEHP-induced hepatotoxicity; while in DEHP/SeD group, drastic changes in hepatic histopathology and oxidative stress parameters were observed. PMID- 24180376 TI - Characterization of phosphatidylcholine oxidation products by MALDI MS(n). AB - Phospholipid oxidation has been implicated in the pathogenesis and progression of numerous age-related and neurodegenerative diseases. Despite these implications, this broad class of biomolecules remains poorly characterized. In this work, the fragmentation patterns of [M + H](+) and [M + Na](+) ions of intact phosphatidylcholine oxidation products (OxPCs) were characterized by matrix assisted laser desorption/ionization tandem mass spectrometry (MALDI MS(n), n = 2, 3, and 4). MS(2) of both the [M + H](+) and [M + Na](+) ions of short-chain OxPCs yielded product ions related to the PC headgroup and the fatty acid substituents. MS(3) of the [M + Na - N(CH3)3](+) ions yielded fragmentation indicative of the OxPC modification; specifically, a product ion corresponding to the neutral loss of CO2 (NL of 44) was observed for OxPCs containing a terminal carboxylic acid rather than an aldehyde. Furthermore, MS(4) of the [M + Na - HPO4(CH2)2N(CH3)3](+) ions resulted in fragmentation pathways dependent on the sn 2 fatty acid chain length and type of functional group(s). Specifically, CHO containing OxPCs with palmitic acid esterified to the sn-1 position of the glycerol backbone yielded a NL of 254, 2 u less than the nominal mass of palmitic acid, whereas the analogous terminal COOH-containing OxPCs demonstrated a NL of 256. Finally, the presence of a gamma-ketone relative to the terminal carboxyl group resulted in C-C bond cleavages along the sn-2 substituent, providing diagnostic product ions for keto-containing OxPCs. This work illustrates the enhanced selectivity afforded by MS(n) on the linear ion trap and develops a method for the identification of individual products of PC oxidation. PMID- 24180375 TI - The high cost of fidelity. AB - The notoriously low fidelity of HIV-1 replication is largely responsible for the virus's rapid mutation rate, facilitating escape from immune or drug control. The error-prone activity of the viral reverse transcriptase (RT) is predicted to be the most influential mechanism for generating mutations. The low fidelity of RT has been successfully exploited by nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs) that halt viral replication upon incorporation. Consequently, drug-resistant strains have arisen in which the viral RT has an increased fidelity of replication, thus reducing analogue incorporation. Higher fidelity, however, impacts on viral fitness. The appearance of compensatory mutations in combination with higher fidelity NRTI resistance mutations and the subsequent reversion of NRTI-resistant mutations upon cessation of antiretroviral treatment lend support to the notion that higher fidelity exacts a fitness cost. Potential mechanisms for reduced viral fitness are a smaller pool of mutant strains available to respond to immune or drug pressure, slower rates of replication, and a limitation to the dNTP tropism of the virus. Unraveling the relationship between replication fidelity and fitness should lead to a greater understanding of the evolution and control of HIV. PMID- 24180377 TI - Inferring species trees from incongruent multi-copy gene trees using the Robinson Foulds distance. AB - BACKGROUND: Constructing species trees from multi-copy gene trees remains a challenging problem in phylogenetics. One difficulty is that the underlying genes can be incongruent due to evolutionary processes such as gene duplication and loss, deep coalescence, or lateral gene transfer. Gene tree estimation errors may further exacerbate the difficulties of species tree estimation. RESULTS: We present a new approach for inferring species trees from incongruent multi-copy gene trees that is based on a generalization of the Robinson-Foulds (RF) distance measure to multi-labeled trees (mul-trees). We prove that it is NP-hard to compute the RF distance between two mul-trees; however, it is easy to calculate this distance between a mul-tree and a singly-labeled species tree. Motivated by this, we formulate the RF problem for mul-trees (MulRF) as follows: Given a collection of multi-copy gene trees, find a singly-labeled species tree that minimizes the total RF distance from the input mul-trees. We develop and implement a fast SPR-based heuristic algorithm for the NP-hard MulRF problem.We compare the performance of the MulRF method (available at http://genome.cs.iastate.edu/CBL/MulRF/) with several gene tree parsimony approaches using gene tree simulations that incorporate gene tree error, gene duplications and losses, and/or lateral transfer. The MulRF method produces more accurate species trees than gene tree parsimony approaches. We also demonstrate that the MulRF method infers in minutes a credible plant species tree from a collection of nearly 2,000 gene trees. CONCLUSIONS: Our new phylogenetic inference method, based on a generalized RF distance, makes it possible to quickly estimate species trees from large genomic data sets. Since the MulRF method, unlike gene tree parsimony, is based on a generic tree distance measure, it is appealing for analyses of genomic data sets, in which many processes such as deep coalescence, recombination, gene duplication and losses as well as phylogenetic error may contribute to gene tree discord. In experiments, the MulRF method estimated species trees accurately and quickly, demonstrating MulRF as an efficient alternative approach for phylogenetic inference from large-scale genomic data sets. PMID- 24180378 TI - Pomegranate vinegar attenuates adiposity in obese rats through coordinated control of AMPK signaling in the liver and adipose tissue. AB - BACKGROUND: The effect of pomegranate vinegar (PV) on adiposity was investigated in high-fat diet (HF)-induced obese rats. METHODS: The rats were divided into 5 groups and treated with HF with PV or acetic acid (0, 6.5 or 13% w/w) for 16 weeks. Statistical analyses were performed by the Statistical Analysis Systems package, version 9.2. RESULTS: Compared to control, PV supplementation increased phosphorylation of AMP-activated protein kinase (AMPK), leading to changes in mRNA expressions: increases for hormone sensitive lipase and mitochondrial uncoupling protein 2 and decreases for sterol regulatory element binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptorgamma (PPARgamma) in adipose tissue; increases for PPARalpha and carnitinepalmitoyltransferase-1a (CPT 1a) and decrease for SREBP-1c in the liver. Concomitantly, PV reduced increases of body weight (p = 0.048), fat mass (p = 0.033), hepatic triglycerides (p = 0.005), and plasma triglycerides (p = 0.001). CONCLUSIONS: These results suggest that PV attenuates adiposity through the coordinated control of AMPK, which leads to promotion of lipolysis in adipose tissue and stimulation of fatty acid oxidation in the liver. PMID- 24180379 TI - The basidiomycetous yeast Trichosporon may cause severe lung exacerbation in cystic fibrosis patients - clinical analysis of Trichosporon positive patients in a Munich cohort. AB - BACKGROUND: The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated. METHODS: The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 - 52.4 years; mean FEV1 2010 81.4% pred) were investigated. RESULTS: In 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition. CONCLUSIONS: This study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients. PMID- 24180380 TI - Testicular-sparing surgery for bilateral or monorchide testicular tumours: a multicenter study of long-term oncological and functional results. AB - OBJECTIVE: To review long-term oncological and functional outcomes of testicular sparing surgery (TSS) in men presenting with bilateral or monorchide testicular tumours at one of five reference centres for testicular neoplasm and infertility. PATIENTS AND METHODS: We review 25 cases of bilateral synchrone and metachrone testicular tumours treated in five academic centres between 1984 and 2013. Clinical, biological, ultrasonography and pathological tumour findings, overall survival (OS) times, local or metastatic recurrence, pre- and postoperative hormonal profile, paternity and the need for androgen substitution were assessed. RESULTS: Eleven patients with a bilateral synchrone tumour and 14 patients with a testicular tumour on a solitary testicle underwent a tumorectomy. The mean (sem) patient age was 31.9 (1.04) years, total testosterone level was 4.5 (0.57) ng.mL and tumour size was 11.66 (1.49) mm. Tumour types were as follows: 11 seminoma, nine non-seminomatous or mixed germ cell tumours, four Leydig tumours, and one hamartoma. Frozen-section examination was performed in 14 patients, and matched the final pathological analysis in 11 patients. There was an OS rate of 100% and three patients (12%) presented with a local recurrence after a mean follow-up of 42.7 months. Radical orchiectomy was performed for six patients. No patient with a preserved testicle required androgen therapy; the mean postoperative total testosterone level was 4.0 ng/mL. No patient remained fertile after radiation therapy. CONCLUSIONS: TSS for bilateral testicular tumour is safe and effective in selected patients, and should be considered to avoid definitive androgen therapy. Adjuvant radiotherapy remains poorly described in the literature, leading to adjuvant treatment heterogeneity for testicular tumours. PMID- 24180381 TI - eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation. AB - Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the "kindling radical" hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. According to recent reports, vascular dysfunction in general and cardiovascular complications such as hypertension, atherosclerosis and coronary artery diseases may be connected to inflammatory processes. The present review is focusing on the uncoupling of endothelial nitric oxide synthase (eNOS) by different mechanisms involving so-called "redox switches". The oxidative depletion of tetrahydrobiopterin (BH4), oxidative disruption of the dimeric eNOS complex, S-glutathionylation and adverse phosphorylation as well as RONS triggered increases in levels of asymmetric dimethylarginine (ADMA) will be discussed. But also new concepts of eNOS uncoupling and state of the art detection of this process will be described. Another part of this review article will address pharmaceutical interventions preventing or reversing eNOS uncoupling and thereby normalize vascular function in a given disease setting. We finally turn our attention to the inflammatory mechanisms that are also involved in the development of endothelial dysfunction and cardiovascular disease. Inflammatory cell and cytokine profiles as well as their interactions, which are among the kindling mechanisms for the development of vascular dysfunction will be discussed on the basis of the current literature. PMID- 24180382 TI - Editorial: therapeutic strategies to target endothelial nitric-oxide synthase (eNOS). PMID- 24180383 TI - Regulation of endothelial nitric oxide synthase activity by protein-protein interaction. AB - Endothelial nitric oxide synthase (eNOS) is expressed in vascular endothelial cells and plays an important role in the regulation of vascular tone, platelet aggregation and angiogenesis. Protein-protein interactions represent an important posttranslational mechanism for eNOS regulation. eNOS has been shown to interact with a variety of regulatory and structural proteins which provide fine tuneup of eNOS activity and eNOS protein trafficking between plasma membrane and intracellular membranes in a number of physiological and pathophysiological processes. eNOS interacts with calmodulin, heat shock protein 90 (Hsp90), dynamin 2, beta-actin, tubulin, porin, high-density lipoprotein (HDL) and apolipoprotein AI (ApoAI), resulting in increases in eNOS activity. The negative eNOS interacting proteins include caveolin, G protein-coupled receptors (GPCR), nitric oxide synthase-interacting protein (NOSIP), and nitric oxide synthase trafficking inducer (NOSTRIN). Dynamin-2, NOSIP, NOSTRIN, and cytoskeleton are also involved in eNOS trafficking in endothelial cells. In addition, eNOS associations with cationic amino acid transporter-1 (CAT-1), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), and soluble guanylate cyclase (sGC) facilitate directed delivery of substrate (L-arginine) to eNOS and optimizing NO production and NO action on its target. Regulation of eNOS by protein-protein interactions would provide potential targets for pharmacological interventions in NO compromised cardiovascular diseases. PMID- 24180384 TI - Activation of eNOS by polyphenol-rich products and polyphenolic compounds. AB - Numerous epidemiological studies indicate that consumption of polyphenol-rich food and beverages is associated with a protective effect on the cardiovascular system. The beneficial effect has been attributable to several mechanisms including the improvement of the vascular function. Indeed, polyphenols have been shown to be potent stimulators of endothelial vasoprotective mechanisms including the formation of nitric oxide (NO) and the induction of endothelium-derived hyperpolarization (EDH). The aim of this review is to provide a non-exhaustive analysis of the literature regarding polyphenols-rich sources capable of activating endothelial NO synthase and the characterization of the underlying mechanism as well as the beneficial effects of polyphenols on the endothelial function in both experimental models of cardiovascular diseases and in Humans. PMID- 24180385 TI - Pharmacology and clinical pharmacology of methylarginines used as inhibitors of nitric oxide synthases. AB - The methylarginines asymmetric dimethylarginine (ADMA) and monomethylarginine (L NMMA) are endogenously formed inhibitors of nitric oxide synthases (NOS), which have extensively been investigated as risk markers and used as pharmacological tools to study the L-arginine-nitric oxide (NO) pathway in vitro and in vivo. It is the aim of the present review to summarize the clinical and experimental data on the pharmacological properties that are of relevance when planning and conducting experiments and clinical studies involving methylarginines. Key pharmacodynamic and pharmacokinetic data including IC50 values of ADMA and L-NMMA for NOS isoforms and transport proteins, as well as metabolism by dimethylarginine dimethylaminohydrolases (DDAH1 and DDAH2) and alanine-glyoxylate aminotransferase 2 (AGXT2) are discussed. PMID- 24180386 TI - Pharmacological prevention of eNOS uncoupling. AB - Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial NO synthase (eNOS). This endothelium-derived NO is a protective molecule with antihypertensive, antithrombotic and anti atherosclerotic properties. Cardiovascular risk factors such as hypertension, hypercholesterolemia, cigarette smoking and diabetes mellitus induce oxidative stress mostly by stimulation of the NADPH oxidase. Overproduction of reactive oxygen species leads to oxidation of tetrahydrobiopterin (BH4), the essential cofactor of eNOS. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting eNOS to a superoxide- producing enzyme. Consequently, NO production is reduced and the pre-existing oxidative stress is enhanced, which contribute significantly to cardiovascular pathology. Therefore, pharmacological approaches that prevent eNOS uncoupling are of therapeutic interest. Among the drugs currently in clinical use, the renin inhibitor aliskiren, angiotensin-converting enzyme inhibitors, AT1 receptor blockers, the selective aldosterone antagonist eplerenone, statins, nebivolol and pentaerithrityl tetranitrate have been shown to have the potential to prevent or reverse eNOS uncoupling under experimental conditions. Resveratrol, BH4, sepiapterin, folic acid and AVE3085 have also been shown to recouple eNOS and improve endothelial function. The long-term benefit of these compounds, however, is still controversial. PMID- 24180387 TI - Tetrahydrobiopterin regulation of eNOS redox function. AB - Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS). In the cardiovascular system, endothelial NOS (eNOS) has a major role in maintaining vascular tone and endothelial function, as well as in mediating many other vascular protective properties. Evidence from humans and animals have demonstrated that decreased BH4 bioavailability, with subsequent uncoupling of eNOS, has significant effects on the pathogenesis of endothelial dysfunction, which is a hallmark of vascular injury in cardiovascular disorders, including hypertension, hyperlipidemia, and diabetes. In this review, we discuss the synthesis of BH4, its molecular mechanisms regulating eNOS coupling, the pathophysiologic roles of decreased BH4 bioavailability in cardiovascular diseases, and the potential therapeutic application of BH4 in clinics. PMID- 24180388 TI - Molecular mechanisms of endothelial NO synthase uncoupling. AB - Nitric oxide (NO) is a gaseous signaling molecule and effector in various biological processes. In mammalian cells, NO is produced by a family of NO synthases (NOS). Three NOS isoforms have been identified as: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). In addition to NO, NOS also produces superoxide anion. This phenomenon is named NOS uncoupling as superoxide generation mainly occurs when NOS is not coupled with its cofactor or substrate. nNOS was first found to produce superoxide under L-arginine depletion condition. Further studies demonstrated that superoxide production is a general feature of all three NOS isoforms. In particular, superoxide generated from uncoupled eNOS has been found to play critical roles in the process of various cardiovascular diseases. Although NOS was first found to produce superoxide only when uncoupled with its cofactor or substrate, recent studies reveal that oxygen reduction to superoxide is an intrinsic process amid NO synthesis. Tetrahydrobiopterin plays a controlling role in preventing superoxide release from the eNOS oxygenase domain. Besides tetrahydrobiopterin, the regulation of eNOS uncoupling by the interactions with other proteins, protein phosphorylation, S-glutathionylation, and endogenous L-arginine derivatives, will be discussed in this review. PMID- 24180390 TI - Roles of cardiovascular risk factors in endothelial nitric oxide synthase regulation: an update. AB - Cardiovascular disease remains the number one killer in the United States and many other countries. Each year, there are enormous research efforts on its pathogenesis, prevention and treatment led by scientists worldwide. One of the most significant research areas is the impact and mechanisms of existing or new cardiovascular risk factors on the vascular system. The current review provides the most updated research advances in the area of the regulation of the endothelial nitric oxide synthase-nitric oxide (eNOS-NO) system by several cardiovascular risk factors. There are many exciting discoveries made from the studies of several major cardiovascular risk factors such as hypertension, cigarette smoking, dyslipidemia and diabetes mellitus as well as emerging risk factors such as HIV infection, antiretroviral therapy, genomic variability, and cytokines. In general, cardiovascular risk factors could impair the eNOS-NO system with a variety of molecular mechanisms including decrease in NO bioavailability by excess reactive oxygen species, inhibition of eNOS expression and activity, and deficiency of eNOS cofactors. Special attention is paid to the impact of several new or emerging risk factors on cardiovascular disease and the eNOS-NO system. These mechanistic studies are clinically significant because they may lead towards new and effective strategies for the prevention and treatment of cardiovascular disease. PMID- 24180391 TI - Editorial: Future trends in the development of new antidepressant drugs. PMID- 24180389 TI - Regulation of eNOS enzyme activity by posttranslational modification. AB - The regulation of endothelial NO synthase (eNOS) employs multiple different cellular control mechanisms impinging on level and activity of the enzyme. This review aims at summarizing the current knowledge on the posttranslational modifications of eNOS, including acylation, nitrosylation, phosphorylation, acetylation, glycosylation and glutathionylation. Sites, mediators and impact on enzyme localization and activity of the single modifications will be discussed. Moreover, interdependence, cooperativity and competition between the different posttranslational modifications will be elaborated with special emphasis on the susceptibility of eNOS to metabolic cues. PMID- 24180392 TI - Genetically modified mice as tools to understand the neurobiological substrates of depression. AB - The pathophysiological mechanisms underlying depression are still poorly understood. An initial hypothesis postulated to explain the substrates of depression was based on the involvement of monoaminergic systems. This early theory was proposed from different findings obtained using pharmacological tools and can explain the mechanism of action of the drugs currently used to treat depression. However, more recent studies have revealed that other neurobiological processes different from monoamines also participate in the substrates of depression. These mechanisms include the participation of several neuromodulatory systems, stress-related circuits and neuroplastic changes that could represent a direct substrate for these pathophysiological processes. The lack of selective pharmacological tools for several of these potential targets of depression represents an important limitation to study their potential involvement. In the last two decades, different lines of genetically modified mice have been generated with selective deletions in specific genes related to the control of emotional responses. This review summarizes the main findings that have been obtained with these novel genetic tools to clarify the neurobiological substrates of depression. A particular focus has been devoted to the advances obtained with mice deficient in specific components of the monoaminergic, opioid and cannabinoid system and those with mutations in elements of the hypothalamic pituitary-adrenal axis. PMID- 24180394 TI - Neurogenesis as a new target for the development of antidepressant drugs. AB - Thirteen years have passed since the neurogenic hypothesis of depression was postulated. One of its aspects, that decreased neurogenesis could be causative of the onset of depression has been difficult to prove. Another aspect, the prediction that increasing neurogenesis would not only be supportive but also required to produce clinical results by antidepressants has gathered experimental validation. Thus a question arises: should new antidepressant strategies based solely on increasing neurogenesis be pursued? At the risk of disappointing the audience, we will not provide a straight answer to this question in this review, but we do hope to enlighten the reader regarding what is known about adult hippocampal neurogenesis, the indications and evidence of its involvement in the onset and treatment of depression, and the advances that have been made in the field in recent years. As we will recount here, the main body of support in favor of the neurogenic hypothesis of depression is based more on intimation than actual proof. However the rare examples that provide support are sufficiently robust to justify investment of resources and effort to clarify the issue, even if the involvement of neurogenesis, both in the etiology and the treatment of depression, is only partial and comprises only subtle components of this complex mental disorder. PMID- 24180395 TI - Oxidative/nitrosative stress and immuno-inflammatory pathways in depression: treatment implications. AB - This paper reviews recent work on the biological underpinnings of clinical depression emphasizing the crucial role of immunoinflammatory and oxidative and nitrosative stress (O&NS) pathways in driving changes in neuronal regulating tryptophan catabolites (TRYCATs). The essence of the association of O&NS pathways with autoimmune responses in depression is via damage to lipid membranes, anchorage molecules and functional proteins that lead to changes in their chemical structures creating new modified epitopes (neoepitopes), which are highly immunogenic. The abovementioned pathways together with decreased antioxidant levels, including zinc, coenzyme Q10, glutathione and vitamin E, and melatonin are intimately involved in different aspects of depression, including mitochondrial functions and the regulation of cAMP / circadian genes, allowing for impacts across different aspects of symptom patterning. Immuno- inflammatory and O&NS processes may additionally cause alterations in blood-brain barrier permeability and neuroprogression, that is tissue damage, including neurodegeneration and apoptosis, and decreased neurogenesis and neuroplasticity. Activation of those interconnected pathways is relevant to the pathophysiology of acute and chronic depression and the progressive course (staging) of clinical depression. This implies that compounds that target these pathways may be useful to treat acute episodes and prevent further progression of the disease. We herein review some promising compounds, such as melatonin, melatonin receptor agonists, allopregnanolone, PDE4 inhibitors, statins, aspirin, sodium benzoate, tryptophan enriched diets, and antioxidants, including epigallocatechin gallate, curcumin, quercitin, alpha-lipoic acid and resveratrol. PMID- 24180396 TI - Novel therapeutic strategies in major depression: focus on RNAi and ketamine. AB - Major depression is a severe psychiatric syndrome with very high prevalence and - socioeconomic impact. Despite extensive research, its pathophysiology is poorly understood, yet several neurotransmitter systems and brain areas have been implicated. The pharmacological treatment of major depression is mainly based on drugs inhibiting serotonin (5-hydroxytryptamine, 5-HT) and/or noradrenaline (NA) reuptake. These drugs evoke a series of neuronal adaptive mechanisms that limit their full clinical action, making necessary for many patients the use of augmentation strategies. In spite of such strategies, many depressed patients show limited or no improvement, which worsens their quality of life and increases the risk of suicide. Several novel observations in recent years have shaken the antidepressant field, by showing that depressed patients with severe treatment resistance can rapidly experience clinical remission. Hence, deep brain stimulation (DBS) of ventral anterior cingulate cortex (Cg25) evokes rapid mood improvements in treatment-resistant patients. Likewise, single doses of the non competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine evoke rapid and long-lasting (up to 10 days) antidepressant responses in treatment-resistant patients. On the other hand, new molecular strategies aimed at modulating the expression of certain genes show great potential in the antidepressant field. In particular, RNAi strategies have been used to evoke antidepressant-like effects in laboratory animals by knocking-down the expression of genes involved in antidepressant effects, such as the serotonin transporter (SERT) or the 5-HT1A autoreceptor. Here we review these novel strategies due to their potential impact in the identification of new targets and the further development of new antidepressant drugs. PMID- 24180393 TI - Transcriptional dys-regulation in anxiety and major depression: 5-HT1A gene promoter architecture as a therapeutic opportunity. AB - The etiology of major depression remains unclear, but reduced activity of the serotonin (5-HT) system remains implicated and treatments that increase 5-HT neurotransmission can ameliorate depressive symptoms. 5-HT1A receptors are critical regulators of the 5- HT system. They are expressed as both presynaptic autoreceptors that negatively regulate 5-HT neurons, and as post-synaptic heteroreceptors on non-serotonergic neurons in the hippocampus, cortex, and limbic system that are critical to mediate the antidepressant actions of 5-HT. Thus, 5-HT1A auto- and heteroreceptors have opposite actions on serotonergic neurotransmission. Because most 5-HT1A ligands target both auto- and heteroreceptors their efficacy has been limited, resulting in weak or unclear responses. We propose that by understanding the transcriptional regulation of the 5-HT1A receptor it may be possible to regulate its expression differentially in raphe and projection regions. Here we review the transcriptional architecture of the 5-HT1A gene (HTR1A) with a focus on specific DNA elements and transcription factors that have been shown to regulate 5-HT1A receptor expression in the brain. Association studies with the functional HTR1A promoter polymorphism rs6295 suggest a new model for the role of the 5-HT1A receptor in susceptibility to depression involving early deficits in cognitive, fear and stress reactivity as stressors that may ultimately lead to depression. We present evidence that by targeting specific transcription factors it may be possible to oppositely regulate 5-HT1A auto- and heteroreceptor expression, synergistically increasing serotonergic neurotransmission for the treatment of depression. PMID- 24180397 TI - Signaling pathways involved in antidepressant-induced cell proliferation and synaptic plasticity. AB - In the last years it has been proposed that the antidepressant action is mediated not only by changes in monoamine levels but also in association with modifications involving cell proliferation and plasticity in some brain limbic areas as hippocampus, and also frontal cortex and amygdala. This leads to the merging of the classic "monoaminergic hypothesis of depression", with the newer "neurotrophic hypothesis of depression". Here we review two important signaling pathways: the Wnt/beta-catenin pathway -implicated in cellular proliferation and synaptic plasticity- that is downregulated in major depression and upregulated after antidepressant treatment; and the mTOR pathway -controling synaptic plasticity- recently related to present disrupted functioning in major depression, and as the target of some drugs with fast-acting potential antidepressant action. These pieces of evidences are confirmed in a variety of animal models of depression and are predictive of antidepressant actions. We also review the role of another two important neurotrophic factors: brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) that mediate the antidepressant effects. All of the above intracellular pathways interact by a crosstalk mediated by Akt, a key regulator molecule that may underlie the fine tuning between proliferative and neuroplasticity changes induced by antidepressant drugs. PMID- 24180399 TI - Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants? AB - The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants. PMID- 24180401 TI - Editorial: Gut Microbiota and Gastrointestinal Diseases: to Treat or Not To Treat. PMID- 24180400 TI - Leptin and the OB-receptor as anti-obesity target: recent in silico advances in the comprehension of the protein-protein interaction and rational drug design of anti- obesity lead compounds. AB - The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neuro-circuitry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased leptin concentrations lead to opposite effects. Therefore, rational design of leptin agonists/antagonists could be an appealing challenge in the battle against obesity. The Leptin/LR interactions have been studied in several works by means of different molecular modelling approaches, spreading from homology modelling to manual docking. No small molecules have ever been proposed as agonists of the Ob receptor but researchers' efforts focused only on leptin-related synthetic peptides as receptor antagonists and on peptidomimetics. In this review we try to track a timeline of obtained in silico information to clarify the mechanism of interaction between leptin and its receptor, together to summarize the more recent efforts to propose new drugs usable in anti-obesity therapy. Final considerations could be useful starting points for the rational drug design of new lead compounds. PMID- 24180402 TI - Strategy for the treatment of Helicobacter pylori infection. AB - The eradication of Helicobacter pylori not only heals peptic ulcers but also prevents their recurrence and reduces the risk of development of gastric cancer and other H. pylori-associated disorders. H. pylori eradication heals gastritis and may prevent the spread of infection, reducing the future costs required for the treatment of subsequent H. pylori-associated diseases. There are various guidelines for the management of H. pylori infection worldwide, such as the guidelines of the American College of Gastroenterology, Maastricht IV, the Second Asia-Pacific Consensus Conference, and Japan. The Japanese health insurance system approved H. pylori eradication therapy for H. pylori-related chronic gastritis in 2013. Triple therapy regimens comprising 1 proton pump inhibitor and 2 antimicrobial agents such as amoxicillin, clarithromycin, metronidazole, levofloxacin, or tetracycline have been widely used to eradicate this bacterium. The rate of successful eradication has declined owing to the increased rate of drug resistance stemming from the wide usage of antibiotics. This issue is of particular relevance with regard to clarithromycin. In worldwide, clarithromycin based triple therapy should be abandoned, as it is no longer effective. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. First-line treatment should be recommended on the basis of an understanding of the local prevalence of H. pylori antimicrobial resistance. PMID- 24180403 TI - Population based Helicobacter pylori screening and eradication: advances versus side effects. AB - Gastric cancer is the fourth most common cancer in the world and second most common reason for cancer related death. Projections for the future predict that gastric cancer incidence will continue to rise. Risk factors for gastric cancer are Helicobacter pylori (H pylori) infection, host genetic factors and environmental factors. H pylori is a class I carcinogen and responsible for 60 % 80 % of all gastric cancers of intestinal and diffuse type, as well as gastric MALT lymphoma. From animal and intervention studies we know that premalignant gastric lesions development and gastric cancer can be prevented with early H pylori eradication. In countries with gastric cancer incidence higher than 20 / 100 000 per year national screening for H pylori infection and eradication of all H pylori infections should be performed. Type of eradication therapy depends on local antimicrobial resistance rates. Quadruple bismuth or non- bismuth therapies can achive more than 90 % eradication rate. The success of eradication therapy must be controlled with noninvasive test. Patients with extensive preneoplastic changes (atrophy, intestinal metaplasia) should have endoscopic and histologic controls. Endoscopic screening should be performed in intervals according to the risk stratification by OLGA / OLGIM staging system or A-D staging system. In countries with high gastric cancer incidence national screening with serological tests for pepsinogen I (PGI), PGI/PGII ratio and H pylori antibodies can select patients at higher risk for gastric cancer. PMID- 24180404 TI - Impact of antibiotics on the intestinal microbiota and on the treatment of Shiga toxin-producing Escherichia coli and Salmonella infections. AB - This review evaluates the current literature based on the impact of antibiotics on the intestinal microbiota and the critical role of intestinal bacteria in controlling infection and subsequent clinical disease caused by STEC and Salmonella, and the transmissibility of these important pathogens.A number of studies have indicated that antibiotic therapy could result in unexpected changes in the clinical picture of disease. This is observed, for example, in the case of infections associated with Shiga-toxin-producing Escherichia coli (STEC), when antibiotics used in treatment of the disease may increase the risk of hemolytic uremic syndrome (HUS) and thus fatal outcomes. In the case of such infections, treatment with antibiotics is usually discouraged. The use of antibiotics could cause also undesirable changes in the intestinal microbial flora and prolonged pathogen shedding, which is observed in the case of Salmonella infections. Inappropriate antibiotic therapy can result in Salmonella remaining in the host's cells (intracellular) and thus resulting in further asymptomatic carriage and a further complication is the development of resistance. PMID- 24180398 TI - Endocannabinoid signaling in the etiology and treatment of major depressive illness. AB - The purpose of this review is to examine human and preclinical data that are relevant to the following hypotheses. The first hypothesis is that deficient CB1R mediated signaling results in symptoms that mimic those seen in depression. The second hypothesis is that activation of CB1R-mediated signaling results in behavioral, endocrine and other effects that are similar to those produced by currently used antidepressants. The third hypothesis is that conventional antidepressant therapies act through enhanced CB1R mediated signaling. Together the available data indicate that activators of CB1R signaling, particularly inhibitors of fatty acid amide hydrolase, should be considered for clinical trials for the treatment of depression. PMID- 24180405 TI - Clostridium difficile infection in children with inflammatory bowel disease: current evidence. AB - Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease of the gastrointestinal tract that develops in genetically susceptible individuals. Questions about the role of infections in the development and exacerbations of inflammatory bowel disease remain unanswered. Among numerous bacteria that have been linked to IBD, the most frequently associated is Clostridium difficile. Clinical symptoms of C. difficile infection and an exacerbation of inflammatory bowel disease are often indistinguishable. In cases of diarrhea in patients with IBD and C. difficile infection, antibiotic treatment is recommended. This review attempts to summarize C. difficile infection's epidemiology and clinical features and describes current evidence on treatment of C. difficile infection in children with IBD. PMID- 24180407 TI - Probiotics in the management of Crohn's disease and ulcerative colitis. AB - Probiotics are nowadays frequently used by patients with inflammatory bowel disease, however literature data are conflicting related to their importance. In mild to moderate ulcerative colitis probiotics can be used effectively in induction and maintaining remission, and prevention of pouchitis. As the other side of the shield, there is not sufficient evidence to support the use of probiotics in daily clinical practice in Crohn's disease. The aim of the present review is to provide help for clinicians about the probiotic use in patients with inflammatory bowel disease. The comparison of literature data is limited by the large number of probiotic strains, various combined preparations, and different doses applied in the clinical studies. Small number of comparable protocols and lack of standardization encumber the analysis of study results. PMID- 24180406 TI - Choosing optimal first-line Helicobacter pylori therapy: a view from a region with high rates of antibiotic resistance. AB - Helicobacter pylori is a gram-negative, microaerophilic spiral bacillus that is associated with life-threatening diseases such as gastric cancer, gastric MALT lymphoma, and peptic ulcer disease. The definition of an effective therapy is one that achieves at least a 90% eradication rate on a per-protocol basis with the first attempt. Eradication rates of H. pylori have declined to unacceptable levels worldwide, mostly due to antibiotic resistance and standard triple therapy gradually has lost its efficacy in most counties. However, bismuth quadruple therapy, when prescribed properly, has maintained its effectiveness. Alternative first-line regimens such as sequential and concomitant therapy were developed to substitute for standard triple therapy and were highly effective in the countries where they were developed, but proved susceptible to failure in regions with high rates of antibiotic resistance. Antibiotic resistance rates in Russia are high, however there is lack of data regarding comparative efficacy of first-line eradication options. The authors of this review extrapolate the knowledge of H. pylori first-line eradication options in Russia based on data from other countries, as well as from domestic studies. The available data support use of 14 day regimens with concomitant therapy, bismuth quadruple therapy, or furazolidone quadruple therapy for empiric use in adults. In addition, 14-day levofloxacin containing therapies could be used if resistance is relatively low or lacking as triple therapy or possibly as a 5-day concomitant levofloxacin therapy. PMID- 24180408 TI - Current and future insights in H. pylori eradication regimens: the need of tailoring therapy. AB - Treatment of Helicobacter pylori (H. pylori) infection is crucial for the management of prevalent digestive and more recently also extra-digestive disorders. Rising prevalence of clarithromycin resistance worldwide has accounted for a dramatic decline in the efficacy of standard triple therapies, which should not be prescribed, unless local clarithromycin-resistance is low (<20%) or culture confirms susceptibility to this antibiotic (i,e,; as tailored treatments). Bismuth-quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens have been shown to overcome clarithromycin resistance and are now preferred empirical treatments achieving improved eradication rates (>90% in per protocol analysis). In the future, empiric use of both clarithromycin and levofloxacin is likely to become steadily more challenging as even these novel eradication therapies may be prone to the effect of increasing antibiotic resistance. Tailored treatment based on the individual characterization of H. pylori therapeutic susceptibility appears to be a reasonable future alternative, currently limited by the shortcomings of systematically performing H. pylori culture (invasive, expensive, time consuming). However, recent advances in the genotypic detection of H. pylori susceptibility to antibiotics, and in pharmacogenomics, may represent a breakthrough in our future approach to tailored therapy. Until then, efforts to optimize empirical treatments should continue. PMID- 24180409 TI - Is Helicobacter pylori always a "bad guy"? AB - Various clinical presentations have been ascribed to Helicobacter (H.) pylori. Most importantly, H. pylori is considered the leading cause of gastric cancer worldwide and because of that, in adult population, it is listed as a number one carcinogen. However, children are less prone to develop H. pylori related serious diseases such as peptic ulcer disease (PUD) and cases of malignancy are only sporadically reported. On the other hand, there is an increasing level of evidence suggesting that H. pylori in children could also have a beneficial effect. Recently, several data confirmed previously described inverse relationship of H. pylori infection and gastroesophageal reflux disease. Furthermore, it has been hypothesized that an increased prevalence of allergic diseases could be, at least partially, explained by the decreased incidence of H. pylori infection. H. pylori can, to some degree, influence immunological response. It has an ability to promote high proinflammatory cytokine expression in the gastric mucosa shifting immunity towards Th1 response, which could be a plausible explanation for the down-regulated clinical expression of allergies (including asthma) in patients with H. pylori gastritis. Based on these findings the aim of this review is to present "pros and cons" for H. pylori eradication in children. PMID- 24180410 TI - Role of probiotics in the management of pouchitis. AB - The concept that the gut microbiota plays a major role in the development of pouchitis in ulcerative colitis patients after restorative proctocolectomy with ileal pouch-anal anastomosis, is widely accepted and supported by a widespread use of some antibiotics (metronidazole and/or ciprofloxacin, rifaximin) to treat this condition. A possible, safer therapeutic alternative is represented by probiotics. To date the controlled studies addressing the possible efficacy of probiotic agents in the treatment of active pouchitis are few and inconclusive. By contrast the prophylactic use of a probiotic mixture (VSL #3) appears to be able to prevent development of pouchitis. The most convincing results have been observed in the maintenance of remission, where the probiotic mixture has been found, in most of the performed controlled trials, significantly effective in preventing pouchitis recurrence. PMID- 24180411 TI - Role of yeasts in healthy and impaired gut microbiota: the gut mycome. AB - Although several studies have been published on the gut microbiota composition, they are mainly focused on bacteria. Therefore, the world of gut yeasts, the "gut mycome", is still unclear. Over the last years, brand new gut microbiota analysis techniques have been applied to the study of yeasts, with exciting results both in health and in disease. A therapeutic potential for many gastrointestinal and extra-intestinal diseases has been recognized for selected yeast strains, such as Saccharomyces boulardii. This narrative review represents an overview of the new evidences regarding the "gut mycome". PMID- 24180412 TI - An in-vivo and in-vitro taste masking evaluation of bitter melt-extruded drugs. AB - OBJECTIVES: The purpose of this study was to investigate the potential of hot melt extrusion (HME) for masking the taste of bitter active pharmaceutical ingredients (APIs) when incorporated into different polymer formulations. METHODS: Extrudates were produced by HME using two water soluble cationic model drugs (cetirizine HCl and verapamil HCl) processed with various grades of anionic polymers (Eudragit L100 and Eudragit L100-55 (Acryl EZE)). The process was optimised by using a single screw extruder to produce extruadates with the desirable characteristics. KEY FINDINGS: In-vivo results obtained from a panel of six healthy human volunteers demonstrated that the HME extruded formulations improved the taste significantly compared with that of the pure APIs. In addition, an in-vitro evaluation carried out by an Astree e-tongue equipped with seven specific sensors demonstrated significant taste improvement of the extrudates compared with placebo polymers and the pure APIs. Furthermore, the extrudates characterised by SEM, X-ray and differential scanning calorimetry studies showed the existence of molecularly dispersed APIs while in-vitro dissolution showed fast release for all drug substances. CONCLUSIONS: HME can effectively be used to mask the taste of bitter APIs by enhancing drug-polymer interactions. PMID- 24180413 TI - PGBD5: a neural-specific intron-containing piggyBac transposase domesticated over 500 million years ago and conserved from cephalochordates to humans. AB - BACKGROUND: piggyBac domain (PGBD) transposons are found in organisms ranging from fungi to humans. Three domesticated piggyBac elements have been described. In the ciliates Paramecium tetraurelia and Tetrahymena thermophila, homologs known as piggyMacs excise internal eliminated sequences from germline micronuclear DNA during regeneration of the new somatic macronucleus. In primates, a PGBD3 element inserted into the Cockayne syndrome group B (CSB) gene over 43 Mya serves as an alternative 3' terminal exon, enabling the CSB gene to generate both full length CSB and a conserved CSB-PGBD3 fusion protein that joins an N-terminal CSB domain to the C-terminal transposase domain. RESULTS: We describe a fourth domesticated piggyBac element called PGBD5. We show that i) PGBD5 was first domesticated in the common ancestor of the cephalochordate Branchiostoma floridae (aka lancelet or amphioxus) and vertebrates, and is conserved in all vertebrates including lamprey but cannot be found in more basal urochordates, hemichordates, or echinoderms; ii) the lancelet, lamprey, and human PGBD5 genes are syntenic and orthologous; iii) no potentially mobile ancestral PGBD5 elements can be identified in other more deeply rooted organisms; iv) although derived from an IS4-related transposase of the RNase H clan, PGBD5 protein is unlikely to retain enzymatic activity because the catalytic DDD(D) motif is not conserved; v) PGBD5 is preferentially expressed in certain granule cell lineages of the brain and in the central nervous system based on available mouse and human in situ hybridization data, and the tissue-specificity of documented mammalian EST and mRNA clones; vi) the human PGBD5 promoter and gene region is rich in bound regulatory factors including the neuron-restrictive silencer factors NRSF/REST and CoREST, as well as SIN3, KAP1, STAT3, and CTCF; and vii) despite preferential localization within the nucleus, PGBD5 protein is unlikely to bind DNA or chromatin as neither DNase I digestion nor high salt extraction release PGBD5 from fractionated mouse brain nuclei. CONCLUSIONS: We speculate that the neural-specific PGBD5 transposase was domesticated >500 My after cephalochordates and vertebrates split from urochordates, and that PGBD5 may have played a role in the evolution of a primitive deuterostome neural network into a centralized nervous system. PMID- 24180414 TI - General method for regulating protein stability with light. AB - Post-translational regulation of protein abundance in cells is a powerful tool for studying protein function. Here, we describe a novel genetically encoded protein domain that is degraded upon exposure to nontoxic blue light. We demonstrate that fusion proteins containing this domain are rapidly degraded in cultured cells and in zebrafish upon illumination. PMID- 24180415 TI - Aggregate-prone R120GCRYAB triggers multifaceted modifications of the thioredoxin system. AB - AIMS: The human mutation R120G in the alphaB-crystallin (CRYAB) causes a multisystemic disease that is characterized by hypertrophic cardiomyopathy and cytoplasmic protein aggregates. In transgenic mice, human R120GCRYAB (hR120GTg) expression in heart sequentially modifies the REDOX status, in part by the activation of the nuclear factor, erythroid derived 2, like 2 (Nrf2). Thioredoxin system (TS) components are NRF2 target genes, so it could be hypothesized that TS was affected in hR120GTg mice. RESULTS: Transgenic hearts overexpressed thioredoxin 1 (Trx1), which was identified by isotope coded affinity tag-mass spectrometry, among hundreds of peptides displaying an increased reduced/oxidized ratio. Coupled to this higher level of reduced cysteines, the activity of thioredoxin reductase 1 (TrxR1) was augmented by 2.5-fold. Combining mutiple experimental approaches, the enzymatic regulation of TrxR1 by a histone deacetylase 3 (HDAC3)-dependent level of acetylation was confirmed. In vitro and in vivo functional tests established that TrxR1 activity is required to mitigate aggregate development, and this could be mediated by Bcl-2-associated athanogene 3 (BAG3) as a potential TS substrate. INNOVATION AND CONCLUSIONS: This study uncovers the compartmentalized changes and the involvement of TS in the cardiac stress response elicited by misfolded proteins such as R120GCRYAB. Our work suggests that R120GCRYAB triggers a defensive pathway acting through the newly identified interacting partners HDAC3, TrxR1, and BAG3 to counter aggregate growth. Therefore, those interactors may function as modifier genes contributing to the variable onset and expressivity of such human diseases. Furthermore, our work underscores the potential organismal effects of pharmacological interventions targeting TS and HDAC. PMID- 24180416 TI - The value of radiographic findings for the progression of pandemic 2009 influenza A/H1N1 virus infection. AB - BACKGROUND: Most illnesses caused by pandemic influenza A (H1N1) pdm09 virus (A/H1N1) infection are acute and self-limiting among children. However, in some children, disease progression is rapid and may require hospitalization and transfer to a pediatric intensive care unit (PICU). We investigated factors associated with rapid disease progression among children admitted to hospital for A/H1N1 infection, particularly findings on initial chest radiographs. METHODS: In this retrospective study, we investigated the records of children who had received a laboratory or clinical diagnosis of A/H1N1 infection and were admitted to the largest children's hospital in Japan between May 2009 and March 2010. The medical records were reviewed for age, underlying diseases, vital signs on admission, initial chest radiographic findings, and clinical outcomes. According to chest radiographic findings, patients were classified into 4 groups, as follows: [1] normal (n = 46), [2] hilar and/or peribronchial markings alone (n = 64), [3] consolidation (n = 64), and [4] other findings (n = 29). Factors associated with clinical outcomes were analyzed using logistic regression. RESULTS: Two hundreds and three patients (median 6.8 years) were enrolled in this study. Fifteen percent (31/203) of patients were admitted to PICU. Among 31 patients, 39% (12/31) of patients required mechanical ventilation (MV). When the initial chest radiographic findings were compared between patients with consolidation (n = 64) and those without consolidation (n = 139), a higher percentage of patients with consolidation were admitted to PICU (29.7% vs.8.6%, P < 0.001) and required MV (17.2% vs. 0.7%, P < 0.001). These findings remain significant when the data were analyzed with the logistic regression (P < 0.001, P < 0.001, respectively). CONCLUSIONS: Consolidation on initial chest radiographs was the most significant factor to predict clinical course of hospitalized children with the 2009 A/H1N1 infection. PMID- 24180417 TI - Challenges in identifying asthma subgroups using unsupervised statistical learning techniques. AB - RATIONALE: Unsupervised statistical learning techniques, such as exploratory factor analysis (EFA) and hierarchical clustering (HC), have been used to identify asthma phenotypes, with partly consistent results. Some of the inconsistency is caused by the variable selection and demographic and clinical differences among study populations. OBJECTIVES: To investigate the effects of the choice of statistical method and different preparations of data on the clustering results; and to relate these to disease severity. METHODS: Several variants of EFA and HC were applied and compared using various sets of variables and different encodings and transformations within a dataset of 383 children with asthma. Variables included lung function, inflammatory and allergy markers, family history, environmental exposures, and medications. Clusters and original variables were related to asthma severity (logistic regression and Bayesian network analysis). MEASUREMENTS AND MAIN RESULTS: EFA identified five components (eigenvalues >= 1) explaining 35% of the overall variance. Variations of the HC (as linkage-distance functions) did not affect the cluster inference; however, using different variable encodings and transformations did. The derived clusters predicted asthma severity less than the original variables. Prognostic factors of severity were medication usage, current symptoms, lung function, paternal asthma, body mass index, and age of asthma onset. Bayesian networks indicated conditional dependence among variables. CONCLUSIONS: The use of different unsupervised statistical learning methods and different variable sets and encodings can lead to multiple and inconsistent subgroupings of asthma, not necessarily correlated with severity. The search for asthma phenotypes needs more careful selection of markers, consistent across different study populations, and more cautious interpretation of results from unsupervised learning. PMID- 24180418 TI - Poor sleep quality in Australian adults with comorbid psychological distress and physical illness. AB - A population-based questionnaire study of 1,818 Australian adults investigated associations of sleep quality with psychological distress and comorbid physical health disorders. The Kessler Psychological Distress Scale and the Behavioral Risk Factor Surveillance System assessed psychological distress and physical health. The Pittsburgh Sleep Quality Index assessed sleep quality. Participants with physical illness or psychological distress had increased odds for reporting poor sleep quality, compared to those with no illness (odds ratios [ORs] = 2.22, for both; 95% confidence intervals [CIs] = 1.53-3.23 and 3.54-10.36, respectively), but those with comorbid illness had markedly higher odds for poor sleep quality (OR = 11.99, 95% CI = 7.90-18.20). Adults with comorbid psychological distress and physical health disorders are at substantially increased risk of poor sleep quality. PMID- 24180419 TI - Telemedicine in Alentejo. AB - Alentejo covers a third of Portugal, yet it is home to only 5% of the population. Residents of the region are poorer, older, and less educated than the rest of the country. There is a shortage of physicians in several specialties. The low population density, a concentration of specialized services, and a poor public transportation network all create barriers to access. Telemedicine was introduced in 1998 to help address these challenges. In this article, we provide an overview of the program and its current status, focusing on infrastructure, services, and activity volume. We also discuss the impact the program has had from the perspectives of patients and healthcare professionals. From 1998 to 2011, there were 132,546 episodes of service using telemedicine, including real-time teleconsultations, teleradiology, teleultrasound, and telepathology. At present, the network includes 20 primary care units and five hospitals, covering almost 30,000 km(2) and 500,000 people. Units have high-resolution videoconferencing equipment, access to patients' clinical records, an image archive, and peripherals, such as electronic dermatoscopes and phonendoscopes. Teleconsultations are available in 15 medical specialties and areas, ranging from neurology to pediatric surgery. In 2008, regional health authorities started a tele-education program, and by the end of 2011, 876 healthcare professionals, across 52 locations, had participated in remote learning sessions. More than a decade since telemedicine was introduced in Alentejo, it is now an integral part of everyday service provision. A comprehensive assessment of the costs and consequences of the program is currently underway. PMID- 24180421 TI - Organ-level tissue engineering using bioreactor systems and stem cells: implications for transplant surgery. AB - Vascularized composite allotransplantation (VCA) enables surgeons to address complex problems that exceed the possibilities of traditional autologous reconstruction. However, logistical and immunologic challenges currently limit the widespread application of VCA. Recent breakthroughs in the field of stem cells and tissue engineering have direct implications for the advancement of VCA. Specifically, the use of bioreactors may prolong ex vivo allograft survival and enable allograft modulations that mitigate immunogenicity and enhance graft function. Additionally, novel approaches utilizing bioreactor systems for stem cell seeding of vascularized bioscaffolds provide a blueprint for the de novo generation of complex tissues. These promising bioreactor-based strategies have the potential to expand the reconstructive applications of VCA, and could one day allow the fabrication of customized complex tissue grafts. PMID- 24180420 TI - Pharmacological inhibition of GSK-3 in a guinea pig model of LPS-induced pulmonary inflammation: II. Effects on skeletal muscle atrophy. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is accompanied by pulmonary inflammation and associated with extra-pulmonary manifestations, including skeletal muscle atrophy. Glycogen synthase kinase-3 (GSK-3) has been implicated in the regulation of muscle protein- and myonuclear turnover; two crucial processes that determine muscle mass. In the present study we investigated the effect of the selective GSK-3 inhibitor SB216763 on muscle mass in a guinea pig model of lipopolysaccharide (LPS)-induced pulmonary inflammation associated muscle atrophy. METHODS: Guinea pigs were pretreated with either intranasally instilled SB216763 or corresponding vehicle prior to each LPS/saline challenge twice weekly. Pulmonary inflammation was confirmed and indices of muscle mass were determined after 12 weeks. Additionally, cultured skeletal muscle cells were incubated with tumor necrosis factor alpha (TNF-alpha) or glucocorticoids (GCs) to model the systemic effects of pulmonary inflammation on myogenesis, in the presence or absence of GSK-3 inhibitors. RESULTS: Repeated LPS instillation induced muscle atrophy based on muscle weight and muscle fiber cross sectional area. Intriguingly, GSK-3 inhibition using SB216763 prevented the LPS induced muscle mass decreases and myofiber atrophy. Indices of protein turnover signaling were unaltered in guinea pig muscle. Interestingly, inhibition of myogenesis of cultured muscle cells by TNF-alpha or synthetic GCs was prevented by GSK-3 inhibitors. CONCLUSIONS: In a guinea pig model of LPS-induced pulmonary inflammation, GSK-3 inhibition prevents skeletal muscle atrophy without affecting pulmonary inflammation. Resistance to inflammation- or GC-induced impairment of myogenic differentiation, imposed by GSK-3 inhibition, suggests that sustained myogenesis may contribute to muscle mass maintenance despite persistent pulmonary inflammation. Collectively, these results warrant further exploration of GSK-3 as a potential novel drug target to prevent or reverse muscle wasting in COPD. PMID- 24180422 TI - Electrokinetic assembly of one-dimensional nanoparticle chains with cucurbit[7]uril controlled subnanometer junctions. AB - One-dimensional (1D) nanoparticle chains with defined nanojunctions are of strong interest due to their plasmonic and electronic properties. A strategy is presented for the assembly of 1D gold-nanoparticle chains with fixed and rigid cucurbit[n]uril-nanojunctions of 9 A. The process is electrokinetically accomplished using a nanoporous polycarbonate membrane and controlled by the applied voltage, the nanoparticle/CB[n] concentration ratio, time and temperature. The spatial structure and time-resolved analysis of chain plasmonics confirm a growth mechanism at the membrane nanopores. PMID- 24180423 TI - Comparison of child self-reports and parent proxy-reports on quality of life of children with attention deficit hyperactivity disorder. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a neurobiological condition that affects 3%-7% of the pediatric population and significantly compromises the quality of life (QoL) of these individuals. The aim of the current study was to compare child self-reports and parent proxy reports on the QoL of children with ADHD. METHODS: Forty-five children with ADHD, combined type, aged 8-12 years without comorbidities, were compared with 43 typically developing children. PedsQLTM 4.0 (Pediatric QoL InventoryTM) Generic Core Scales (physical, emotional, social, and school functioning) were completed by families and children self-reporting their health-related QoL. RESULTS: Children with ADHD reported themselves significantly lowered their PedsQLTM scores on all dimensions in comparison to typically developing children. Statistically significant differences were observed in social functioning (p = 0.010), school functioning (p <0.001), psychosocial health (p <0.001), and total score (p = 0.002). The physical functioning and emotional functioning dimensions did not differ significantly between groups, with p = 0.841 and p = 0.070, respectively. Parents of children with ADHD also reported lower PedsQLTM scores, with statistically significant differences in all dimensions. The relationship between child self reports and parent proxy reports indicated that there is greater agreement among children with ADHD, except for the school functioning. CONCLUSIONS: This suggests that children with the disorder and their parents have a perception of the functional limitations the disorder brings. It is therefore important to undertake studies to verify the QoL in children with ADHD that aim to provide and measure the scope of the well-being of these children. PMID- 24180424 TI - Isoxazoles: synthesis, evaluation and bioinformatic design as acetylcholinesterase inhibitors. AB - OBJECTIVES: Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of Alzheimer's disease. In this study, nine isoxazoles derivatives were tested for their in-vitro AChE activity. The molecular docking showed the interaction of the compounds with the active site. METHODS: The isoxazoles were synthesized using 1,3-dipolar cycloaddition in the presence of sodium hypochlorite. They were also isolated and characterized by spectroscopic methods. The in-vitro activity was measured by an adapted version of Ellman's assay. KEY FINDINGS: The isoxazoles are described as inhibitors of AChE. The most potent compound in the series exhibited a moderate inhibitory activity (50% inhibitory concentration = 134.87 MUm). The design of new compounds was created by using the RACHEL module of the SYBYL software. CONCLUSIONS: Our research provided enough evidence of the efficacy of isoxazoles as AChE inhibitors. The isoxazoles were synthesized and evaluated as inhibitors of AChE. The docking study based on a novel series of complexes isoxazole with AChE from Electroporus electricus has demonstrated that the ligand bind is similar to the compounds used as reference. To find new candidates with the isoxazole core that act as inhibitors of AChE, part of the structure of the compound 9 was used for de-novo design. Molecular docking models of the ligand-AChE complexes suggest that the compound 10 is located on the periphery of the AChE active site. PMID- 24180426 TI - A case-control study: are urological procedures risk factors for the development of infective endocarditis? AB - OBJECTIVE: To evaluate the association between urological procedures and the development of infective endocarditis (IE), as there are case-reports linking urological procedures to IE but evidence of a causal relationship is lacking and no major guidelines advise prophylaxis to prevent development of IE during transurethral urological procedures. No case-control study has been undertaken to examine the relationship between urological procedures and the development of IE. PATIENTS AND METHODS: Retrospective evaluation of the IE database at our institution. The population consisted of patients diagnosed with enterococcal, staphylococcal, Streptococcus bovis-group and oral streptococcal IE over a 10 year period. Possible risk factors for the development of IE, including urological procedures were collected. A case-control design was used and univariable and multivariable analyses were carried out. Missing data was accounted for using the multiple imputations method. RESULTS: We included 384 patients with IE. There was a statistical association between the development of enterococcal IE and preceding urological procedures (odds ratio 8.21, 95% confidence interval 3.54-19.05, P < 0.05). Increasing age and being an intravenous drug user were also associated with enterococcal IE. Haemodialysis and the presence of an intracardiac device were associated with the development of coagulase-negative staphyloccal IE. CONCLUSION: This is the first study to show a statistical association between urological procedures and the development of IE. The bacteraemia leading to IE may be a result of the urological procedures or a consequence of the underlying urological pathology causing recurrent subclinical bacteraemias. PMID- 24180427 TI - Hypertension and prehypertension among adolescents in secondary schools in Enugu, South East Nigeria. AB - BACKGROUND: Hypertension is a prevalent cardiovascular disease risk factor among blacks and adolescent hypertension can progress into adulthood. OBJECTIVE: To determine the prevalence of hypertension and prehypertension among secondary school adolescents in Enugu South East Nigeria. METHODOLOGY: A study of 2694 adolescents aged 10-18 years in Enugu metropolis was carried out. Socio demographic profile anthropometric and blood pressure readings were obtained. Derived measurements such as Prehypertension, hypertension and BMI were obtained. RESULTS: The results showed that the mean systolic blood pressure and diastolic blood pressure for males were 106.66+ 11.80 mmHg and 70.25 + 7.34 mmHg respectively. The mean SBP and DBP for females were 109.83+ 11.66 mmHg and 72.23 + 8.26 mmHg respectively (p < 0.01). Blood pressure was found to increase with age. Prevalence of hypertension and prehypertension was 5.4% and 17.3% respectively with a higher rate in females (6.9%) than males (3.8%). Prevalence of prehypertension among males and females were 14.3% and 20.1% respectively. The prevalence of obesity was 1.9%. CONCLUSION: Modifiable risk factors exist among adolescents. Early lifestyle modification and a strengthened school health are recommended. PMID- 24180428 TI - Mass defect-based pseudo-isobaric dimethyl labeling for proteome quantification. AB - Discovering differentially expressed proteins in various biological samples requires proteome quantification methods with accuracy, precision, and wide dynamic range. This study describes a mass defect-based pseudo-isobaric dimethyl labeling (pIDL) method based on the subtle mass defect differences between (12)C/(13)C and (1)H/(2)H. Lys-C protein digests were labeled with CD2O/(13)CD2O and reduced with NaCNBD3/NaCNBH3 as heavy and light isotopologues, respectively. The fragment ion pairs with mass differences of 5.84 mDa were resolved by high resolution tandem mass spectrometry (MS/MS) and used for quantification. The pIDL method described here resulted in highly accurate and precise quantification results with approximately 100-fold dynamic range. Furthermore, the pIDL method was extended to 4-plex proteome quantification and applied to the quantitative analysis of proteomes from Hca-P and Hca-F, two mouse hepatocarcinoma ascites syngeneic cell lines with low and high lymph node metastasis rates. PMID- 24180429 TI - Annexin 1 regulates the H2O2-induced calcium signature in Arabidopsis thaliana roots. AB - Hydrogen peroxide is the most stable of the reactive oxygen species (ROS) and is a regulator of development, immunity and adaptation to stress. It frequently acts by elevating cytosolic free Ca(2+) ([Ca(2+) ]cyt ) as a second messenger, with activation of plasma membrane Ca(2+) -permeable influx channels as a fundamental part of this process. At the genetic level, to date only the Ca(2) (+) -permeable Stelar K(+) Outward Rectifier (SKOR) channel has been identified as being responsive to hydrogen peroxide. We show here that the ROS-regulated Ca(2+) transport protein Annexin 1 in Arabidopsis thaliana (AtANN1) is involved in regulating the root epidermal [Ca(2+) ]cyt response to stress levels of extracellular hydrogen peroxide. Peroxide-stimulated [Ca(2+) ]cyt elevation (determined using aequorin luminometry) was aberrant in roots and root epidermal protoplasts of the Atann1 knockout mutant. Similarly, peroxide-stimulated net Ca(2+) influx and K(+) efflux were aberrant in Atann1 root mature epidermis, determined using extracellular vibrating ion-selective microelectrodes. Peroxide induction of GSTU1 (Glutathione-S-Transferase1 Tau 1), which is known to be [Ca(2+) ]cyt -dependent was impaired in mutant roots, consistent with a lesion in signalling. Expression of AtANN1 in roots was suppressed by peroxide, consistent with the need to restrict further Ca(2+) influx. Differential regulation of annexin expression was evident, with AtANN2 down-regulation but up-regulation of AtANN3 and AtANN4. Overall the results point to involvement of AtANN1 in shaping the root peroxide-induced [Ca(2+) ]cyt signature and downstream signalling. PMID- 24180431 TI - Knee loading reduces MMP13 activity in the mouse cartilage. AB - BACKGROUND: Moderate loads with knee loading enhance bone formation, but its effects on the maintenance of the knee are not well understood. In this study, we examined the effects of knee loading on the activity of matrix metalloproteinase13 (MMP13) and evaluated the role of p38 MAPK and Rac1 GTPase in the regulation of MMP13. METHODS: Knee loading (0.5-3 N for 5 min) was applied to the right knee of surgically-induced osteoarthritis (OA) mice as well as normal (non-OA) mice, and MMP13 activity in the femoral cartilage was examined. The sham loaded knee was used as a non-loading control. We also employed primary non-OA and OA human chondrocytes as well as C28/I2 chondrocyte cells, and examined MMP13 activity and molecular signaling in response to shear at 2-20 dyn/cm2. RESULTS: Daily knee loading at 1 N for 2 weeks suppressed cartilage destruction in the knee of OA mice. Induction of OA elevated MMP13 activity and knee loading at 1 N suppressed this elevation. MMP13 activity was also increased in primary OA chondrocytes, and this increase was attenuated by applying shear at 10 dyn/cm2. Load-driven reduction in MMP13 was associated with a decrease in the phosphorylation level of p38 MAPK (p-p38) and NFkappaB (p-NFkappaB). Molecular imaging using a fluorescence resonance energy transfer (FRET) technique showed that Rac1 activity was reduced by shear at 10 dyn/cm2 and elevated by it at 20 dyn/cm2. Silencing Rac1 GTPase significantly reduced MMP13 expression and p-p38 but not p-NFkappaB. Transfection of a constitutively active Rac1 GTPase mutant increased MMP13 activity, while a dominant negative mutant decreased it. CONCLUSIONS: Knee loading reduces MMP13 activity at least in part through Rac1 mediated p38 MAPK signaling. This study suggests the possibility of knee loading as a therapy not only for strengthening bone but also preventing tissue degradation of the femoral cartilage. PMID- 24180432 TI - Mode of action framework analysis for receptor-mediated toxicity: The peroxisome proliferator-activated receptor alpha (PPARalpha) as a case study. AB - Several therapeutic agents and industrial chemicals induce liver tumors in rodents through the activation of the peroxisome proliferator-activated receptor alpha (PPARalpha). The cellular and molecular events by which PPARalpha activators induce rodent hepatocarcinogenesis has been extensively studied and elucidated. This review summarizes the weight of evidence relevant to the hypothesized mode of action (MOA) for PPARalpha activator-induced rodent hepatocarcinogenesis and identifies gaps in our knowledge of this MOA. Chemical specific and mechanistic data support concordance of temporal and dose-response relationships for the key events associated with many PPARalpha activators including a phthalate ester plasticizer di(2-ethylhexyl) phthalate (DEHP) and the drug gemfibrozil. While biologically plausible in humans, the hypothesized key events in the rodent MOA, for PPARalpha activators, are unlikely to induce liver tumors in humans because of toxicodynamic and biological differences in responses. This conclusion is based on minimal or no effects observed on growth pathways, hepatocellular proliferation and liver tumors in humans and/or species (including hamsters, guinea pigs and cynomolgous monkeys) that are more appropriate human surrogates than mice and rats at overlapping dose levels. Overall, the panel concluded that significant quantitative differences in PPARalpha activator-induced effects related to liver cancer formation exist between rodents and humans. On the basis of these quantitative differences, most of the workgroup felt that the rodent MOA is "not relevant to humans" with the remaining members concluding that the MOA is "unlikely to be relevant to humans". The two groups differed in their level of confidence based on perceived limitations of the quantitative and mechanistic knowledge of the species differences, which for some panel members strongly supports but cannot preclude the absence of effects under unlikely exposure scenarios. PMID- 24180434 TI - Accelerating calculations of RNA secondary structure partition functions using GPUs. AB - BACKGROUND: RNA performs many diverse functions in the cell in addition to its role as a messenger of genetic information. These functions depend on its ability to fold to a unique three-dimensional structure determined by the sequence. The conformation of RNA is in part determined by its secondary structure, or the particular set of contacts between pairs of complementary bases. Prediction of the secondary structure of RNA from its sequence is therefore of great interest, but can be computationally expensive. In this work we accelerate computations of base-pair probababilities using parallel graphics processing units (GPUs). RESULTS: Calculation of the probabilities of base pairs in RNA secondary structures using nearest-neighbor standard free energy change parameters has been implemented using CUDA to run on hardware with multiprocessor GPUs. A modified set of recursions was introduced, which reduces memory usage by about 25%. GPUs are fastest in single precision, and for some hardware, restricted to single precision. This may introduce significant roundoff error. However, deviations in base-pair probabilities calculated using single precision were found to be negligible compared to those resulting from shifting the nearest-neighbor parameters by a random amount of magnitude similar to their experimental uncertainties. For large sequences running on our particular hardware, the GPU implementation reduces execution time by a factor of close to 60 compared with an optimized serial implementation, and by a factor of 116 compared with the original code. CONCLUSIONS: Using GPUs can greatly accelerate computation of RNA secondary structure partition functions, allowing calculation of base-pair probabilities for large sequences in a reasonable amount of time, with a negligible compromise in accuracy due to working in single precision. The source code is integrated into the RNAstructure software package and available for download at http://rna.urmc.rochester.edu. PMID- 24180433 TI - Mode of action and human relevance analysis for nuclear receptor-mediated liver toxicity: A case study with phenobarbital as a model constitutive androstane receptor (CAR) activator. AB - The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are important nuclear receptors involved in the regulation of cellular responses from exposure to many xenobiotics and various physiological processes. Phenobarbital (PB) is a non-genotoxic indirect CAR activator, which induces cytochrome P450 (CYP) and other xenobiotic metabolizing enzymes and is known to produce liver foci/tumors in mice and rats. From literature data, a mode of action (MOA) for PB induced rodent liver tumor formation was developed. A MOA for PXR activators was not established owing to a lack of suitable data. The key events in the PB induced liver tumor MOA comprise activation of CAR followed by altered gene expression specific to CAR activation, increased cell proliferation, formation of altered hepatic foci and ultimately the development of liver tumors. Associative events in the MOA include altered epigenetic changes, induction of hepatic CYP2B enzymes, liver hypertrophy and decreased apoptosis; with inhibition of gap junctional intercellular communication being an associative event or modulating factor. The MOA was evaluated using the modified Bradford Hill criteria for causality and other possible MOAs were excluded. While PB produces liver tumors in rodents, important species differences were identified including a lack of cell proliferation in cultured human hepatocytes. The MOA for PB-induced rodent liver tumor formation was considered to be qualitatively not plausible for humans. This conclusion is supported by data from a number of epidemiological studies conducted in human populations chronically exposed to PB in which there is no clear evidence for increased liver tumor risk. PMID- 24180436 TI - Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua. AB - Ambiguines belong to a family of hapalindole-type indole alkaloid natural products, with many of the members possessing up to eight consecutive carbon stereocenters in a fused pentacyclic 6-6-6-5-7 ring scaffold. Here, we report the identification of a 42 kbp ambiguine (amb) biosynthetic gene cluster that harbors 32 protein-coding genes in its native producer Fischerella ambigua UTEX1903. Association of the amb cluster with ambiguine biosynthesis was confirmed by both bioinformatic analysis and in vitro characterizations of enzymes responsible for 3-((Z)-2'-isocyanoethenyl) indole and geranyl pyrophosphate biosynthesis and a C 2 indole dimethylallyltransferase that regiospecifically tailors hapalindole G to ambiguine A. The presence of five nonheme iron-dependent oxygenase coding genes (including four Rieske-type oxygenases) within the amb cluster suggests late stage C-H activations are likely responsible for the structural diversities of ambiguines by regio- and stereospecific chlorination, hydroxylation, epoxidation, and sp(2)-sp(3) C-C bond formation. PMID- 24180435 TI - Urinary expression of novel tissue markers of kidney injury after ureteroscopy, shockwave lithotripsy, and in normal healthy controls. AB - BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) and ureteroscopy (URS) are minimally invasive treatment alternatives for kidney stones. Although less invasive, SWL subjects the renal parenchyma to a high level of energy and the potential to cause renal injury. The ability to detect renal injury post-SWL in a reliable and noninvasive way would be clinically beneficial. Kidney injury molecule 1 (KIM-1) and N-acetyl-beta-D-glucosaminidase (NAG) are two proteins secreted by the kidney into the urine and have been found to be sensitive markers of acute kidney injury in transplant patients. The aim of this work was to measure urinary levels of KIM-1 and NAG in patients with kidney stone who were treated by SWL or URS and in nonstone volunteers. PATIENTS AND METHODS: Patients with kidney stones who were treated by SWL (n = 50) or URS (n = 10) were recruited. Voided urine samples were collected before and 2 to 3 hours after URS and SWL. In addition, further urinary specimens were collected 2 days and 2 weeks post-SWL treatment. Voided urine samples from healthy volunteers were also collected. RESULTS: Mean KIM-1 values were increased in patients with kidney stones when compared with volunteers. KIM-1 and NAG levels significantly increased post-SWL and returned to baseline within 2 weeks post-SWL. Poor kidney function was significantly associated with increased biomarker activity both in baseline and post-SWL measurements. There was no significant change in urinary KIM-1 and NAG concentrations before and after URS. CONCLUSIONS: Kim-1 and NAG levels significantly increased post-SWL treatment suggesting a potential role for these urinary markers in identifying patients at higher risk of tissue injury. PMID- 24180437 TI - The search for distinct and clinically useful phenotypes in chronic obstructive pulmonary disease. PMID- 24180438 TI - AECOPD: Acute exacerbations of chronic obstructive cardiopulmonary disease? PMID- 24180439 TI - beta-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Necessity is the mother of invention. PMID- 24180440 TI - DNA methylation and ancestry. The smoke starts to clear. PMID- 24180441 TI - An official American Thoracic Society systematic review: Influence of psychosocial characteristics on workplace disability among workers with respiratory impairment. AB - RATIONALE: Psychosocial characteristics likely play an important role in the severity of workplace disability for workers with a respiratory impairment. OBJECTIVES: We performed a systematic review of the available literature to examine the impact of psychosocial characteristics on workplace disability among workers with a respiratory impairment. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, we searched Medline and other published and unpublished sources using the PubMed and Cochrane Central Register of Controlled Clinical Trials (CENTRAL) search engines from January 1, 1990 through March 8, 2013 for quantitative studies that examined the association of psychosocial characteristics with workplace disability among workers with a respiratory impairment. We also searched related citations and the bibliographies of selected studies and relevant review articles. One investigator abstracted data about study design and quality, psychosocial characteristics, and outcome measures. MEASUREMENTS AND MAIN RESULTS: Of 5,746 potentially relevant studies, 20 met eligibility criteria and were included. Studies reported heterogeneous outcomes among heterogeneous samples of workers that precluded a quantitative synthesis. In general, mental illness was associated with increased workplace disability among workers with respiratory impairments. Few studies adjusted for disease severity, so the independent association of psychosocial characteristics and workplace disability is unclear. Most studies were cross sectional, so the direction of the association could not be determined. We found only one trial of targeted therapy for the psychosocial condition, which was not effective at reducing disability. CONCLUSIONS: Psychosocial characteristics likely influence workplace disability in workers with respiratory impairments. The impact of targeted therapies is unclear and warrants further study. PMID- 24180442 TI - Pulmonary artery sarcoma masquerading as pulmonary embolism. PMID- 24180443 TI - Objective measurement of the therapeutic effectiveness of continuous positive airway pressure versus oral appliance therapy for the treatment of obstructive sleep apnea. PMID- 24180444 TI - Reply: Objective measurement of the therapeutic effectiveness of continuous positive airway pressure versus oral appliance therapy for the treatment of obstructive sleep apnea. PMID- 24180445 TI - Reply: Objective measurement of the therapeutic effectiveness of continuous positive airway pressure versus oral appliance therapy for the treatment of obstructive sleep apnea. PMID- 24180446 TI - Reply: Optimum performance of endobronchial ultrasound-guided transbronchial needle aspiration. PMID- 24180447 TI - Importance of onsite cytopathology at endobronchial ultrasound. PMID- 24180448 TI - Rhinovirus and asthma: reinfection, not persistence. PMID- 24180449 TI - Pulmonary vascular shunts in exercise-intolerant patients with lymphangioleiomyomatosis. PMID- 24180450 TI - Heavy smog and hospital visits in Beijing, China. PMID- 24180451 TI - Reversal of vascular leak with imatinib. PMID- 24180453 TI - Intracardiac breast tumor presenting as acute cor pulmonale. PMID- 24180454 TI - Apurinic/apyrimidinic endonuclease 1 upregulation reduces oxidative DNA damage and protects hippocampal neurons from ischemic injury. AB - AIMS: Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that participates in base-excision repair of oxidative DNA damage and in the redox activation of transcription factors. We tested the hypothesis that APE1 upregulation protects neuronal structure and function against transient global cerebral ischemia (tGCI). RESULTS: Upregulation of APE1 by low-dose proton irradiation (PI) or by transgene overexpression protected hippocampal CA1 neurons against tGCI-induced cell loss and reduced apurinic/apyrimidinic sites and DNA fragmentation. Conversely, APE1 knockdown attenuated the protection afforded by PI and ischemic preconditioning. APE1 overexpression inhibited the DNA damage response, as evidenced by lower phospho-histone H2A and p53-upregulated modulator of apoptosis levels. APE1 overexpression also partially rescued dendritic spines and attenuated the decrease in field excitatory postsynaptic potentials in hippocampal CA1. Presynaptic and postsynaptic markers were reduced after tGCI, and this effect was blunted in APE1 transgenics. The Morris water maze test revealed that APE1 protected against learning and memory deficits for at least 27 days post-injury. Animals expressing DNA repair-disabled mutant APE1 (D210A) exhibited more DNA damage than wild-type controls and were not protected against tGCI-induced cell loss. INNOVATION: This is the first study that thoroughly characterizes structural and functional protection against ischemia after APE1 upregulation by measuring synaptic markers, electrophysiological function, and long-term neurological deficits in vivo. Furthermore, disabling the DNA repair activity of APE1 was found to abrogate its protective impact. CONCLUSION: APE1 upregulation, either endogenously or through transgene overexpression, protects DNA, neuronal structures, synaptic function, and behavioral output from ischemic injury. PMID- 24180456 TI - Regio- and enantiospecific rhodium-catalyzed allylic substitution with an acyl anion equivalent. AB - The construction of enantiomerically enriched acyclic quaternary substituted ketones via the regio- and enantiospecific rhodium-catalyzed allylic alkylation reaction of chiral nonracemic tertiary alcohols with cyanohydrin pronucleophiles is described. This approach provides an alternative method to the alpha-arylation and vinylation of acyclic disubstituted ketone enolates, which remains a challenging endeavor. The combination of the allylic alkylation with ring-closing metathesis facilitates the preparation of enantiomerically enriched 2,2 disubstituted naphthalene-1-ones, which have proven very difficult to prepare using a more conventional dearomatization strategy. PMID- 24180458 TI - Impact of oral 1,25-dihydroxy vitamin D (calcitriol) replacement therapy on coronary artery risk factors in type 2 diabetic patients. AB - BACKGROUND: Observational data suggest that low 25-hyroxyvitamin D is associated with cardiovascular disease (CVD) and its risk factors include diabetes, metabolic syndrome, insulin resistance, hypertension, microalbuminuria and inflammation. We examined the differences between risk factors of CVD before and after treatment with calcitriol in type 2 diabetic patients with vitamin D deficiency. METHODS: This study was a clinical trial consisting of 119 type 2 diabetic patients. Forty three patients had vitamin D insufficiency (25 OH D less than 30 ng/dl) who underwent calcitriol treatment with 0.5 microgram per day for 8 weeks. Blood pressure, fasting blood sugar (FBS), glycosylated hemoglobin (HbA1C), lipid profile, high sensitive C-reactive protein (HsCRP), Homocysteine and albumin to creatinine ratio were measured, before and after the treatment period. Then the two sets of results were compared with each other. RESULTS: Following treatment with calcitriol HbA1C, total cholesterol, low density lipoprotein(LDL), high density lipoprotein(HDL) and diastolic blood pressure decreased significantly (p = 0.01, 0.01, 0.04, 0.001 and 0.04 respectively) but the changes in other parameters were not significant. CONCLUSION: Replacement of vitamin D may have a beneficial effect on some of the risk factors of CVD in diabetic patients. PMID- 24180455 TI - HIV-1 drug resistance-associated mutations among HIV-1 infected drug-naive antenatal clinic attendees in rural Kenya. AB - BACKGROUND: Access to antiretroviral therapy (ART) has increased dramatically in Sub-Saharan Africa. In Kenya, 560,000 people had access to ART by the end of 2011. This scaling up of ART has raised challenges to the Kenyan health system due to emergence of drug resistant viruses among those on treatment and possible onward transmission. To counter this, and come up with an effective treatment strategy, it has become vital to determine baseline mutations associated with drug resistance among the circulating strains of HIV-1 in Kenya. METHODS: The prevalence of mutations associated with drug resistance in HIV-1 protease (PR) and reverse transcriptase (RT) regions from 188 HIV-1 infected treatment-naive pregnant women was investigated in Kapsabet, Nandi Hills and Kitale district hospitals of Kenya. Blood samples were collected between April 2005 and June 2006. The HIV-1 pol gene was amplified using primers for HIV-1 PR and RT and sequenced using the BigDye chemistry. The mutations were analyzed based on the IAS algorithm as well as the Stanford University HIV Drug Resistance Database. RESULTS: Based on the PR and RT sequences, HIV-1 subtypes A1 (n=117, 62.2%), A2 (n=2, 1.1%), D (n=27, 14.4%), C (n=13, 6.9%), G (n=3, 1.6%), and possible recombinants (n=26, 13.8%) were detected. Mutations associated with nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside RTI (NNRTI)-resistance were detected in 1.6% (3 of 188) and 1.1% (2 of 188), respectively. Mutations associated with PI resistance were detected in 0.5% (1 of 188) of the study population. CONCLUSION: The prevalence of drug resistance among drug-naive pregnant women in rural North Rift, Kenya in 2006 was 3.2%. Major drug resistance mutations associated with PIs, NRTIs and NNRTIs do exist among treatment-naive pregnant women in North Rift, Kenya. There is a need for consistent follow-up of drug-naive individuals in this region to determine the impact of mutations on treatment outcomes. PMID- 24180459 TI - Limited genetic variability and phenotypic plasticity detected for cavitation resistance in a Mediterranean pine. AB - Resistance to cavitation is a major determinant of plant survival under severe drought and can be used to quantify species adaptive potential. Interspecific variation in this key trait is well defined in woody species, but intraspecific variation (level and structure) resulting from standing genetic variation and phenotypic plasticity has never been determined. Combining for the first time in situ characterization of natural populations and two reciprocal common gardens in dry and wet sites, we estimated variance components (phenotypic, genetic, environmental, and genetic * environmental) of cavitation resistance based on 513 genotypes of a Mediterranean pine, Pinus pinaster. Despite the selected populations being climatically contrasted, phenotypic plasticity in resistance to cavitation remained low and was essentially attributed to family level. Between population variation in cavitation resistance for both phenotypic and genetic variation was limited. These results strongly suggest that cavitation resistance is buffered against genetic and to a lesser extent environmental variation (canalization) in maritime pine. Consequently, in a drier world, the increasing drought tolerance of Pinus species might be severely constrained by the low level of cavitation resistance variation, resulting in a large-scale loss of productivity. PMID- 24180460 TI - Development of a regioselective N-methylation of (benz)imidazoles providing the more sterically hindered isomer. AB - An efficient and highly regioselective N-methylation of (NH)-(benz)imidazoles furnishing the sterically more hindered, less stable, and usually minor regioisomer has been developed. The methodology involves very mild reaction conditions and tolerates a wide range of functional groups. PMID- 24180461 TI - Prognostic value of microRNA expression pattern in upper tract urothelial carcinoma. AB - OBJECTIVE: To examine the microRNA (miRNA) expression pattern in tumour samples from patients with progressing and non-progressing upper tract urothelial carcinoma (UTUC) in order to identify putative miRNAs that may be used as prognostic markers. PATIENTS AND METHODS: We conducted a multicentre, retrospective study of formalin-fixed paraffin-embedded tissue samples from 150 patients with UTUC who had undergone radical nephroureterectomy. Global miRNA expression patterns were analysed in 18 selected samples from patients with UTUC using TaqMan arrays. The differential expression of five key miRNAs was validated by quantitative polymerase chain reaction in an independent cohort of 132 samples from patients with UTUC. Models to predict tumour progression and cancer-specific survival that included miRNA expression patterns were developed by Cox regression analysis. RESULTS: Twenty-six miRNAs were found to be aberrantly expressed between samples from patients with progressing and non-progressing UTUC and five of these were selected for subsequent studies. The regression analysis identified tumour stage and miR-31 and miR-149 expression as independently associated with tumour progression and tumour stage and miR-149 expression as independently associated with cancer-specific survival. The risk scores derived from these miRNA models were able to discriminate two groups with a highly significantly different probability of tumour progression (hazard ratio [HR] 4.78; P < 0.001) and death (HR 276; P = 0.004). CONCLUSIONS: There is a differential miRNA expression pattern between patients with progressing and non-progressing UTUC. The identification of new miRNAs associated with a high probability of tumour recurrence and cancer-specific survival in patients with UTUC and their combination in a robust, easy-to-use and reliable algorithm may help tailor treatment and surveillance strategies in these patients. PMID- 24180462 TI - Total gastrectomy increases the incidence of grade III and IV toxicities in patients with gastric cancer receiving adjuvant TS-1 treatment. AB - BACKGROUND: We aimed to evaluate the safety and efficacy of TS-1 adjuvant chemotherapy in Taiwanese patients with gastric cancer. METHODS: We included in this study patients with locally advanced gastric cancer who received adjuvant TS 1 or 5-fluorouracil chemotherapy after curative surgery and extended lymph node dissection between 1 June 2008 and 31 December 2012 at Chang Gung Memorial Hospital. Patient characteristics, tumor features, safety profiles and compliance with TS-1 treatment were retrospectively analyzed from medical charts. RESULTS: Forty patients received adjuvant chemotherapy with TS-1 and 193 with 5 fluorouracil within the study period. The 1- and 2-year overall survival rates were 90.6% and 87% in the TS-1 group and 95.4% and 86.8% in the 5-fluorouracil group (P = 0.34). The 1- and 2-year disease-free survival rates were 90.6% and 74.7% in the TS-1 group and 88% and 75.7% in the 5-fluorouracil group (P = 0.66). In the TS-1 group, tumor recurrence was more frequent in those with >15 metastatic lymph nodes than <=15. Overall, 78.9%, 74.3%, 62.1% and 56% of patients underwent TS-1 treatment for at least 3, 6, 9 and 12 months, respectively. The most common adverse events of TS-1 were skin hyperpigmentation (55%), diarrhea (27.5%), dizziness (27.5%) and leucopenia (20%). Severe adverse events (SAEs; grade III or IV toxicity) were diarrhea (7.5%), stomatitis (7.5%), leukopenia (5%), vomiting (2.5%), anorexia (2.5%) and dizziness (2.5%). Patients who underwent total gastrectomy had a significantly greater risk of TS-1-related SAEs than patients who underwent subtotal gastrectomy (40% versus 8%, P = 0.014). CONCLUSIONS: The incidence of SAEs during TS-1 therapy was more common in Taiwanese patients with gastric cancer who underwent total gastrectomy compared with those who underwent subtotal gastrectomy. Clinicians must be aware of and able to manage these SAEs to maximize patient compliance with adjuvant TS-1. PMID- 24180463 TI - Late-onset sacsinopathy diagnosed by exome sequencing and comparative genomic hybridization. AB - The molecular diagnosis of adult-onset autosomal recessive cerebellar ataxias remains challenging because of genetic heterogeneity. However, recently developed molecular genetic techniques will potentially revolutionize the diagnostic approach. Here we set out to define the genetic basis of the ataxia in two brothers with no molecular diagnosis. Clinical evaluation was followed by whole exome second-generation sequencing and comparative genomic hybridization to determine the diagnosis. Whole-exome sequencing identified a hemizygous novel spastic ataxia of Charlevoix-Saguenay (SACS) stop-codon mutation in both brothers (c.13048G->T, p.E4350*) that was present in the mother, but not the father. Comparative genomic hybridization revealed a 0.7-Mb deletion on chromosome 13q12.12 in both brothers, which included SACS and was heterozygous in the asymptomatic father. The milder phenotype, caused by a whole-gene deletion and a stop-codon mutation in SACS, indicates a loss-of-function mechanism in late-onset autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), and illustrates the importance of chromosomal rearrangements in the investigation of adult-onset ataxia. PMID- 24180464 TI - Multiplexed target detection using DNA-binding dye chemistry in droplet digital PCR. AB - Two years ago, we described the first droplet digital PCR (ddPCR) system aimed at empowering all researchers with a tool that removes the substantial uncertainties associated with using the analogue standard, quantitative real-time PCR (qPCR). This system enabled TaqMan hydrolysis probe-based assays for the absolute quantification of nucleic acids. Due to significant advancements in droplet chemistry and buoyed by the multiple benefits associated with dye-based target detection, we have created a "second generation" ddPCR system compatible with both TaqMan-probe and DNA-binding dye detection chemistries. Herein, we describe the operating characteristics of DNA-binding dye based ddPCR and offer a side-by side comparison to TaqMan probe detection. By partitioning each sample prior to thermal cycling, we demonstrate that it is now possible to use a DNA-binding dye for the quantification of multiple target species from a single reaction. The increased resolution associated with partitioning also made it possible to visualize and account for signals arising from nonspecific amplification products. We expect that the ability to combine the precision of ddPCR with both DNA-binding dye and TaqMan probe detection chemistries will further enable the research community to answer complex and diverse genetic questions. PMID- 24180466 TI - Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes. AB - BACKGROUND: Insulin-like growth factor-binding protein 7 (IGFBP-7) is able to interact with insulin-like growth factor 1 (IGF-1) as well as insulin. Previous studies have suggested that serum IGFBP-7 levels may be associated with insulin resistance in type 2 diabetes (T2D). This study aimed to evaluate IGFBP-7 serum protein and IGFBP7 DNA methylation levels in the subjects with and without T2D. RESULTS: A total of 340 Swedish subjects including 100 newly diagnosed T2D patients (50 women/50 men), 100 age-matched nondiabetic control subjects (50/50) and 140 treated T2D patients (54/86) were studied. Serum IGFBP-7 levels were measured with a novel ELISA. IGF1, IGFBP-1, and insulin were determined by in house radioimmunoassays. DNA methylation levels in the IGFBP7 gene were analyzed with a bisulfite-pyrosequencing technique. Serum IGFBP-7 protein levels were similar among nondiabetic subjects, newly diagnosed, and treated T2D patients and were not correlated with IGFBP7 DNA methylation. However, IGFBP7 DNA methylation was increased in men with newly diagnosed T2D compared with nondiabetic controls (17.6% vs. 12.5%, P < 0.01). Serum IGFBP-7 levels correlated (r = 0.331, P = 0.019) with serum IGFBP-1 levels, a marker of insulin production, in men but not women with newly diagnosed T2D. CONCLUSIONS: This study demonstrates for the first time that IGFBP7 DNA methylation levels are increased in Swedish men with newly diagnosed T2D. The correlation between IGFBP-7 and IGFBP-1 suggests that low IGFBP-7 may be associated with insulin resistance in T2D. PMID- 24180465 TI - Inter-regulation of the unfolded protein response and auxin signaling. AB - The unfolded protein response (UPR) is a signaling network triggered by overload of protein-folding demand in the endoplasmic reticulum (ER), a condition termed ER stress. The UPR is critical for growth and development; nonetheless, connections between the UPR and other cellular regulatory processes remain largely unknown. Here, we identify a link between the UPR and the phytohormone auxin, a master regulator of plant physiology. We show that ER stress triggers down-regulation of auxin receptors and transporters in Arabidopsis thaliana. We also demonstrate that an Arabidopsis mutant of a conserved ER stress sensor IRE1 exhibits defects in the auxin response and levels. These data not only support that the plant IRE1 is required for auxin homeostasis, they also reveal a species specific feature of IRE1 in multicellular eukaryotes. Furthermore, by establishing that UPR activation is reduced in mutants of ER-localized auxin transporters, including PIN5, we define a long-neglected biological significance of ER-based auxin regulation. We further examine the functional relationship of IRE1 and PIN5 by showing that an ire1 pin5 triple mutant enhances defects of UPR activation and auxin homeostasis in ire1 or pin5. Our results imply that the plant UPR has evolved a hormone-dependent strategy for coordinating ER function with physiological processes. PMID- 24180468 TI - Schwannoma of the brachial plexus; report of two cases involving the C7 root. AB - Brachial plexus schwannomas are rare tumors. They are benign nerve sheath tumors and only about 5% of Schwannoma arise from the brachial plexus. They pose a great challenge to surgeons due to their rare occurrence and complex anatomical location. We present two cases who presented with a supraclavicular swelling, that were proven to be schwannoma on histopathology. PMID- 24180467 TI - Psychological stressors in the context of commercial sex among female sex workers in China. AB - Because of the illegality and stigma associated with female sex workers (FSWs) in China, data were limited regarding their psychological stressors examined through the lens of occupational health. Analyzing qualitative data from 16 gatekeepers and 38 FSWs, we explored these stressors in the context of commercial sex in China. We found that FSWs faced a continuum of stressors that resulted from poverty, limited employment, lack of social protection, violence perpetrated by clients, and limited social support from peers and stable partners. We call for empowerment and a structural approach to address the needs of FSWs to improve their psychological well-being. PMID- 24180469 TI - Dietary strategies to recover from exercise-induced muscle damage. AB - Exhaustive or unaccustomed intense exercise can cause exercise-induced muscle damage (EIMD) and its undesirable consequences may decrease the ability to exercise and to adhere to a training programme. This review briefly summarises the muscle damage process, focusing predominantly on oxidative stress and inflammation as contributing factors, and describes how nutrition may be positively used to recover from EIMD. The combined intake of carbohydrates and proteins and the use of antioxidants and/or anti-inflammatory nutrients within physiological ranges are interventions that may assist the recovery process. Although the works studying food instead of nutritional supplements are very scarce, their results seem to indicate that food might be a favourable option as a recovery strategy. To date, the only tested foods were milk, cherries, blueberries and pomegranate with promising results. Other potential solutions are foods rich in protein, carbohydrates, antioxidants and/or anti-inflammatory nutrients. PMID- 24180470 TI - Iodine nutritional status and risk factors for goitre among schoolchildren in South Tajikistan. AB - BACKGROUND: Iodine deficiency affects nearly 1.9 billion people worldwide, but it can be prevented by salt iodization. This cross-sectional survey assessed current iodine status, iodized salt coverage and risk factors for goitre among schoolchildren in South Tajikistan. METHODS: Ten primary schools in four districts in South Tajikistan were randomly selected. In schoolchildren aged 7 to 11 years, a spot urine sample was collected for measurement of urinary iodine, dried blood spots were collected for measurement of thyroglobulin, and goitre was assessed by palpation. Iodine content of salt samples and local selling points was determined by coloration using rapid test kits and titration method. RESULTS: Of 623 schoolchildren enrolled, complete data was obtained from 589. The overall median urinary iodine concentration (UIC) was 51.2 MUg/L indicating mild-to moderate iodine deficiency. Among all children, 46.6% (95% Confidence Interval (CI) = 42.4%-50.6%) of children were found to be goitrous (grade 1 goitre: 30.6%, 95% CI = 26.9%-34.5%; grade 2 goitre: 16.0%, 95% CI = 13.1%-19.2%). The risk factor for goitre remaining significant in the multivariable logistic regression model was 'buying salt once a month' (OR = 2.89, 95% CI = 1.01-8.22) and 'buying salt once every six months' (OR = 2.26, 95% CI = 1.01-5.04) compared to 'buying salt every one or two weeks'. The overall median thyroglobulin concentration was elevated at 13.9 MUg/L. Of the salt samples from households and selling points, one third were adequately iodised, one third insufficiently and one third were not iodised. CONCLUSION: Iodine deficiency remains a serious health issue among children in southern Tajikistan. There is a persisting high prevalence of goitre, elevated thyroglobulin and low UIC despite interventions implemented by Tajikistan and international partners. Quality control of salt iodine content needs to be improved. Continued efforts to raise awareness of the health effects of iodine deficiency are needed to increase consumer demand for iodised salt. PMID- 24180471 TI - Human milk glycosaminoglycans in feces of breastfed newborns: preliminary structural elucidation and possible biological role. PMID- 24180472 TI - The affecting factors of breast anthropometry in Korean women. AB - BACKGROUND: Breast anthropometric morphology affects various factors with diverse physiognomy, making accurate measurements very difficult. The aim of this study was to measure the female breast using anthropometry and to use this method on normal subjects to examine breast asymmetry and consider the influence of age, height, weight, body mass index (BMI), parity, delivery mode, and breastfeeding in premenopausal Korean women. SUBJECTS AND METHODS: In total, 17 parameters of breast were measured with participants in a standing position. Breast volume was also assessed. RESULTS: The mean values of the right and left breast volumes were calculated as 386.0+/-342.5 mL and 393.3+/-347.2 mL, respectively. With aging, the height of women decreased, but the weight, BMI, upper chest, middle chest, lower chest, waist, and hip widths, nipple-nipple length, and ptosis increased with statistical significance. No asymmetric differences were observed between each breast, except for nipple-inframammary fold length in 20-30-year-old women and upper arm length in 41-50-year-old women. In our study, the breast volume increased with age as a result of weight gain, but the delivery mode and breastfeeding did not affect anthropometric breast measurements. CONCLUSIONS: In conclusion, age, weight, and BMI are important factors in determining breast anthropometry in our study. The results of the present study will help in the comparison of the anthropometric breast values of Korean women with those of women in other countries and may also be useful in the understanding of breast physiologic change-related obstetrical factors and epidemiologic factors. PMID- 24180475 TI - Laparoscopic appendectomy: quality care and cost-effectiveness for today's economy. AB - BACKGROUND: Open appendectomy (OA) has traditionally been the treatment for acute appendicitis (AA). Beneficial effects of laparoscopic appendectomy (LA) for the treatment of AA are still controversial. AIM: To present our technique for LA and to determine whether LA should be the technique of choice of any case of AA instead of OA. MATERIAL AND METHODS: All cases operated for AA (February 2011 through February 2012) by means of LA or OA were prospectively evaluated. Data regarding length of stay, complications, emergency department consultation after discharge or readmission were collected. Patients were classified into four groups depending on the severity of the appendicitis. Economic data were obtained based on the cost of the disposable material. Cost of hospital stay was calculated based on the Ley de Tasas of the Generalitat Valenciana according to the DRG and the length of stay. RESULTS: One hundred and forty-two cases were included. Ninety-nine patients underwent OA and 43 LA. Average length of stay for LA group was 2,6 days and 3,8 for OA. Average cost of the stay for OA was 1.799 euros and 1.081 euros for LA. Global morbidity rate was 16%, 5% for LA and 20% for OA. CONCLUSIONS: LA is nowadays the technique of choice for the treatment of AA. PMID- 24180477 TI - Links between emotion perception and social participation restriction following stroke. AB - OBJECTIVES: Stroke can cause impairment in emotion perception, but the social consequences of these problems have not been explored to date. In a group of patients with stroke, this study investigated whether difficulties in emotion perception related to social participation and quality-of-life. It also assessed whether these relationships remained significant when controlling for activity limitations. METHOD: Individuals 1 year post-stroke (n = 28) and control participants (n = 40) were assessed on emotion perception across different modalities. Activity limitations, social participation, and multiple domains of quality-of-life were assessed in patients. RESULTS: Participants with stroke were impaired on emotion perception compared to controls. Emotion perception problems in stroke were significantly correlated with social participation and psychological aspects of QoL, but not with activity limitations. CONCLUSIONS: The strong relationships of emotion perception with social participation and psychological aspects of QoL following stroke may have implications for post stroke outcomes. PMID- 24180478 TI - Health-related quality-of-life in the first year following a childhood concussion. AB - OBJECTIVES: (1) To compare pre-injury health-related quality-of-life (HRQoL) of children who have sustained mild traumatic brain injury (mTBI) to their HRQoL at 1, 3, 6 and 12 months post-injury and (2) to compare the HRQoL of children with mTBI, children with mild non-brain injuries and children who were uninjured at the same time points. Child and parent responses were obtained for both objectives. PATIENTS AND METHODS: This prospective cohort study involved a self selected convenience sample to evaluate child and parent perspectives of the HRQoL of 5-17 year old children with mTBI using the PedsQL Generic Core Scales and Cognitive Functioning Scale. Total sample size was 120 child/parent dyads, with 40 dyads each in the study and two control groups. Children who required hospitalization greater than 24 hours were excluded from the study. RESULTS: HRQoL of children with mTBI was not significantly different between pre- and post injury at all-time points. However, children and parents in the mild non-brain injury group reported significantly lower physical HRQoL 1 month post-injury. CONCLUSIONS: Children with mTBI had similar pre- and post-injury HRQoL. Thus, children who sustain mTBI and have significantly lower HRQoL within the first year post-injury merit further evaluation. PMID- 24180479 TI - Clinical benefits of non-taxane chemotherapies in unselected patients with symptomatic metastatic castration-resistant prostate cancer after docetaxel: the GETUG-P02 study. AB - OBJECTIVE: To evaluate the overall benefits of non-taxane chemotherapies in a non selected population including unfit patients presenting with symptoms and pain. PATIENTS AND METHODS: This randomized phase II study reports data from 92 patients (52% >70 years old; 40% with a performance score of 2) previously treated with taxane-based chemotherapy, collected from 15 centres in France. Patients received i.v. mitoxantrone (MTX), oral vinorelbine, or oral etoposide, together with oral prednisone. Palliative benefit (pain response without progression of the disease), biological and tumoural responses, and toxicity profile as well as geriatric assessment (in elderly population) were analysed on an intention-to-treat basis. RESULTS: The palliative response rate was 17% for the whole population, and reached 29% when considering the MTX arm. Pain control was achieved in 40% of the patients. The median overall survival was 10.4 months, and was longer in palliative responders. Few grade 3-4 toxicities were observed. The subgroup analysis of elderly patients showed similar results regarding the number and dose intensity of treatments, efficacy and safety. CONCLUSION: In a population including frail and/or elderly patients, who are poorly represented in most clinical studies, non-taxane chemotherapy may remain a relevant option for metastatic prostate cancer having relapsed after a docetaxel-based regimen. Although new treatment options are now approved, the decision-making process should take into account their expected benefit/risk ratio based on the patient status. PMID- 24180474 TI - NADPH oxidases in vascular pathology. AB - SIGNIFICANCE: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of "kindling radicals," which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. RECENT ADVANCES: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. CRITICAL ISSUES: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. FUTURE DIRECTIONS: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice. PMID- 24180480 TI - (18)F-labeled-bioorthogonal liposomes for in vivo targeting. AB - Liposomes are attractive vehicles for the controlled release of drugs and cytotoxins and have a long-standing history in medical research and clinical practice. In addition to established therapeutic indications, liposomes have several favorable properties for molecular imaging, including high stability and the ability to be labeled with radioisotopes, as well as paramagnetic and fluorescent contrast agents. However, long circulation times and difficulties in creating targeted liposomes have proven challenges for imaging. In this study, we have addressed these limitations using a recently developed strategy for bioorthogonal conjugation, the reaction between tetrazines and trans cyclooctenes. By coating radiolabeled liposomes with trans-cyclooctene and pretargeting with a tetrazine coupled to a targeted peptide, we were able to selectively enhance the retention of liposomes and bind them to tumor tissue in live animals. The rapid reaction between tetrazines and trans-cyclooctenes allowed imaging to be performed with the short-lived PET tracer (18)F, yielding signal-to-background activity ratios of 7:1. The covalent, bioorthogonally driven tumor-targeting of liposomes by in vivo click chemistry is promising and should be explored for more selective and rapid delivery of radiodiagnostics and radiotherapeutics, two classes of drugs which particularly benefit from fast clearance, low nonspecific binding, and the associated reduced toxicity to kidneys and bone marrow. PMID- 24180481 TI - FGF-23 associated with the progression of coronary artery calcification in hemodialysis patients. AB - BACKGROUND: Disordered mineral metabolism is implicated in the pathogenesis of vascular calcification in hemodialysis (HD) patients. Fibroblast growth factor 23 (FGF-23) is the main regulator of phosphate metabolism. In this prospective study, we aimed to investigate the association of serum FGF-23 with progression of coronary artery calcification in HD patients. METHODS: Seventy-four HD patients (36 male/38 female, mean age: 52 +/- 14 years) were included. Serum FGF 23 levels were measured by ELISA. Coronary artery calcification score (CACS) was measured twice with one year interval. Patients were grouped as progressive (PG) (36 patients-48%) and non-progressive (NPG). RESULTS: Age, serum phosphorus, baseline and first year CACS were found to be significantly higher in the PG compared to NPG group. Serum FGF-23 levels were significantly higher in PG [155 (80-468) vs 147 (82-234), p = 0.04]. Patients were divided into two groups according to baseline CACS (low group, CACS <= 30; high group, CACS > 30). Serum FGF-23 levels were significantly correlated with the progression of CACS (DeltaCACS) in the low baseline CACS group (r = 0.51, p = 0.006), but this association was not found in high baseline CACS group (r = 0.11, p = 0.44). In logistic regression analysis for predicting the PG patients; serum FGF-23, phosphorus levels and baseline CACS were retained as significant factors in the model. CONCLUSIONS: Serum FGF-23 was found to be related to progression of CACS independent of serum phosphorus levels. FGF-23 may play a major role in the progression of vascular calcification especially at the early stages of calcification process in HD patients. PMID- 24180482 TI - MicroRNA-124-3p inhibits cell migration and invasion in bladder cancer cells by targeting ROCK1. AB - BACKGROUND: Increasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to human disease including carcinogenesis and tumor metastasis in human. miR-124-3p is down-regulated in various cancers, and modulates proliferation and aggressiveness of cancer cells. However, the roles of miR-124-3p in human bladder cancer are elusive. Thus, this study was conducted to investigate the biological functions and its molecular mechanisms of miR-124-3p in human bladder cancer cell lines, discussing whether it has a potential to be a therapeutic biomarker of bladder cancer. METHODS: Three human bladder cancer cell lines and samples from ten patients with bladder cancer were analyzed for the expression of miR-124-3p by quantitative RT--PCR. Exogenetic overexpression of miR-124-3p was established by transfecting mimics into T24, UM-UC-3 and J82 cells, after that cell proliferation and cell cycle were assessed by MTT assay, flow cytometry and Colony-forming assay. Cell motility and invasion ability were evaluated by wound healing assay and transwell assay. Tissue microarray, and immunohistochemistry with antibodies against ROCK1, MMP2 and MMP9 was performed using the peroxidase and DAB methods. The target gene of miR-124-3p was determined by luciferase assays, quantitative RT--PCR and western blot. The regulation of epithelial-to-mesenchymal transition by miR-124-3p was analyzed by western blot. RESULTS: miR-124-3p is frequently down-regulated in bladder cancer both in three bladder cancer cell lines, T24, UM-UC-3, J82 and clinical samples. Overexpression of miR-124-3p induced G1-phase arrest in T24, UM-UC-3 and J82 cell lines and suppressed cell growth in colony-forming assay. miR-124-3p significantly repressed the capability of migration and invasion of bladder cancer cells. In addition, ROCK1 was identified as a new target of miR-124-3p. ROCK1, MMP2, MMP9 were up-regulated in bladder cancer tissues. Furthermore, we demonstrated miR-124-3p could inhibit bladder cancer cell epithelial mesenchymal transfer, and regulated the expression of c-Met, MMP2, MMP9. CONCLUSIONS: miR-124 3p can repress the migration and invasion of bladder cancer cells via regulating ROCK1. Our data indicate that miR-124-3p could be a tumor suppressor and may have a potential to be a diagnostics or predictive biomarker in bladder cancer. PMID- 24180483 TI - An examination of domestic partner violence and its justification in the Republic of Georgia. AB - BACKGROUND: Little research on Intimate Partner Violence (IPV) and social perceptions toward this behavior has been disseminated from Eastern Europe. This study explores the prevalence and risk factors of IPV and the justification of this behavior among women in the Republic of Georgia. It seeks to better understand how IPV and IPV justification relate and how social justification of IPV differs across socio-economic measures among this population of women. METHODS: This study utilizes a national sample of ever-married women from the Republic of Georgia (N = 4,302). We describe the factors that predict IPV justification among these women and the relationship between of the acceptability of IPV and victimization overall and across socio-demographic factors. RESULTS: While the overall lifetime prevalence of IPV in this sample was relatively low (4%), these women were two to four times more likely to justify IPV, Just under one-quarter of the sample agreed that IPV was justified in at least one scenario, namely when the wife was unfaithful, compared with women who had no experience being abused by a partner. Georgian women who were poor, from a rural community, had lower education, were not working and who experienced child abuse or IPV among their parents were more likely to justify this behavior. CONCLUSIONS: These findings begin to fill a gap in our understanding of IPV experienced by women in Eastern Europe. In addition, these findings emphasize the need for researchers, practitioners and policy makers to contextualize IPV in terms of the justification of this behavior among the population being considered as this can play an important role in perpetration, victimization and response. PMID- 24180484 TI - Systematic evaluation of non-inferiority and equivalence randomized trials of anti-infective drugs. AB - The non-inferiority (NI) and equivalence (EQ) design is used widely in the clinical trials of anti-infective drugs, but still many arguments for, and against, conducting active control NI/EQ trials rather than simple placebo controlled trials. We searched Pubmed database and conducted a systematic literature review (1992-2011) to assess the methodological aspects of NI and EQ randomized trials of anti-infective drugs. A total of 335 publications with 337 trials were included. Of them, 235 trials reported a pre-specified margin of 10 15%. A proportion (e.g., cure, successful, failure) was used as the primary outcome in 316 trials (93.8%). Test treatments were non-inferior or equivalent to the control treatment in 325 trials (93.4%). The historical evidence for the effect of the control drug was specified in 38 trials (11.3%). For the literature of NI/EQ trials in anti-infective treatment, aspects that need improvement include the description of study participation, trial implementation, historical evidence and endpoint for the efficacy of control, inclusion of flow diagrams and figures that present margins and confidence intervals according to CONSORT criteria. PMID- 24180485 TI - Difficult to wean patients: cultural factors and their impact on weaning decision making. AB - AIMS AND OBJECTIVES: To examine the elements of the intensive care environment and consider the impact on nurses' involvement in decision-making when weaning from mechanical ventilation. BACKGROUND: Optimal management of difficult to wean patients requires the dynamic collaboration of all clinicians and the contribution of their knowledge and skills. The introduction of weaning protocols has increased nurses' input in decision-making, but there are various elements of the decision environment that impact on their involvement, which have been given little consideration. DESIGN: Ethnography was used as the research design for this study. METHODS: Fieldwork took place in two tertiary hospitals in Greece and Scotland for five months each to unveil clinicians' behaviour and interactions during the weaning practice. Observation was based on the weaning process of 10 Scottish and 9 Greek long-term ventilated patients. Semi-structured interviews followed with nurses (n = 33) and doctors (n = 9) in both settings to understand nurses' perceived involvement in weaning decision-making. Thematic analysis of interviews and field notes followed using the Qualitative Data Analysis software NVivo. Clinicians' participation was voluntary. RESULTS: The main themes identified were the (1) organisation of the units (time and structure of the ward rounds, staff levels and staff allocation system), (2) the inter- professional relationships, (3) the ownership and accountability in weaning decision-making and (4) the role of the weaning protocols. These elements described the culture of the ICUs and defined nurses' role in weaning decision-making. CONCLUSIONS: Clinical decision-making is a multi-dynamic process specifically in complex clinical situations such as weaning from mechanical ventilation. This paper suggests that weaning practice should be considered in relation to the elements of the clinical environment to provide an individualised and patient-centred weaning approach. RELEVANCE TO CLINICAL PRACTICE: Methods to enhance nurses' role in teamwork and collaborative decision-making are suggested. PMID- 24180486 TI - A synthesis of (1E,3E)-TMS dienes from keto-xanthates via Chugaev-type elimination. AB - An efficient route leading to exclusively (1E,3E)-TMS dienes is described. Radical xanthate addition of keto-xanthates to vinyltrimethylsilane followed by one-pot Chugaev elimination/cyclization and in situ oxidation with m-CPBA afforded the corresponding TMS 2-sulfolenes. Isomerization to 3-sulfolenes by the action of DBU with the extrusion of sulfur dioxide in refluxing toluene gave the titled (1E,3E)-TMS dienes. PMID- 24180487 TI - ZNF16 (HZF1) promotes erythropoiesis and megakaryocytopoiesis via regulation of the c-KIT gene. AB - We previously characterized the zinc finger protein gene HZF1 [also known as ZNF16 (zinc finger protein 16)] and demonstrated its important roles in erythroid and megakaryocytic differentiation of K562 cells. In the present study, we investigated its effect on erythroid and megakaryocytic differentiation of HSPCs (haemopoietic stem/progenitor cells). We observed up-regulation of ZNF16 during erythroid and megakaryocytic differentiation of the CD34+ HSPCs, and demonstrated that ZNF16 promotes erythroid and megakaryocytic differentiation by gain-of function and loss-of-function experiments. Using a luciferase reporter and ChIP assays ZNF16 was demonstrated to bind to the c-KIT gene promoter and inhibit its expression in K562 cells. Enforced expression and knockdown of ZNF16 down regulated and up-regulated the expression of the c-KIT gene in K562 cells and HSPCs respectively. Significantly decreased levels of the c-Kit protein were observed following erythroid and megakaryocytic differentiation of K562 and CD34+ cells. The knockdown of c-KIT partially rescued the differentiation inhibition caused by ZNF16 knockdown. The knockdown of c-KIT also blocked the activity of the c-Raf/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal regulated kinase) kinase]/ERK/c-Jun signal pathway and reduced further the level of HEY1 (hes-related family bHLH transcription factor with YRPW motif 1), a repressor of GATA1 (GATA-binding protein 1) transcription, which finally up regulated the expression of GATA1, a central regulator of erythroid and megakaryocytic differentiation. In conclusion the results of the present study demonstrate that ZNF16 plays an important role in erythropoiesis and megakaryocytopoiesis via its regulation of the c-Kit/c-Raf/MEK/ERK/c Jun/HEY1/GATA1 cascade. PMID- 24180488 TI - The novel allele of the LhMYB12 gene is involved in splatter-type spot formation on the flower tepals of Asiatic hybrid lilies (Lilium spp.). AB - Many angiosperm families develop spatially regulated anthocyanin spots on their flowers. The Asiatic hybrid lily (Lilium spp.) cv 'Latvia' develops splatter-type spots on its tepals. The splatters arise simply from the deposition of anthocyanin pigments in the tepal epidermis. To determine how splatter development was regulated, we analysed the transcription of anthocyanin biosynthesis genes, and isolated and characterized an R2R3-MYB gene specific to splatter pigmentation. All anthocyanin biosynthesis genes were expressed in splatter-containing regions of tepals, but not in other regions, indicating that splatter pigmentation is caused by the transcriptional regulation of biosynthesis genes. Previously characterized LhMYB12 regulators were not involved in splatter pigmentation, but, instead, a new allele of the LhMYB12 gene, LhMYB12-Lat, isolated in this study, contributed to splatter development. In 'Latvia' and other lily plants expressing splatters, LhMYB12-Lat was preferentially transcribed in the splatter-containing region of tepals. Progeny segregation analysis showed that LhMYB12-Lat genotype and splatter phenotype were co segregated among the F1 population, indicating that LhMYB12-Lat determines the presence or absence of splatters. LhMYB12-Lat contributes to splatter development, but not to full-tepal pigmentation and raised spot pigmentation. As a result of its unique sequences and different transcription profiles, this new allele of LhMYB12 should be a novel R2R3-MYB specifically associating with splatter spot development. PMID- 24180489 TI - The sounds of silence-a hermeneutic interpretation of childbirth post excision. AB - Four women who had been excised were interviewed about their experiences of giving birth. Using hermeneutic phenomenology we analyzed their narratives to more fully understand their experiences of childbirth in the context of excision. Childbirth is characterized by silence related to excision. To ensure safe care, increased communication is needed. The onus for opening channels of communication rests with health professionals whose aim is to provide safe, appropriate care to women and their families. In this article we give voice to women's call for sensitive communication that acknowledges their excision and supports them through the challenges it presents for birth. PMID- 24180490 TI - Deuterium isotope effect on bulk heterojunction solar cells. Enhancement of organic photovoltaic performances using monobenzyl substituted deuteriofullerene acceptors. AB - A series of novel monobenzyl-substituted deuteriofullerenes (BnDCs) were synthesized efficiently through Co-catalyzed selective monofunctionalization of C60. Bulk heterojunction solar cells, based on poly(3-hexylthiophene) as the donor and BnDCs as the acceptors, exhibited higher photovoltaic performances as compared to the corresponding protonated BnHCs devices. PMID- 24180491 TI - Detrimental effect of the 6 His C-terminal tag on YedY enzymatic activity and influence of the TAT signal sequence on YedY synthesis. AB - BACKGROUND: YedY, a molybdoenzyme belonging to the sulfite oxidase family, is found in most Gram-negative bacteria. It contains a twin-arginine signal sequence that is cleaved after its translocation into the periplasm. Despite a weak reductase activity with substrates such as dimethyl sulfoxide or trimethylamine N oxide, its natural substrate and its role in the cell remain unknown. Although sequence conservation of the YedY family displays a strictly conserved hydrophobic C-terminal residue, all known studies on Escherichia coli YedY have been performed with an enzyme containing a 6 histidine-tag at the C-terminus which could hamper enzyme activity. RESULTS: In this study, we demonstrate that the tag fused to the C-terminus of Rhodobacter sphaeroides YedY is detrimental to the enzyme's reductase activity and results in an eight-fold decrease in catalytic efficiency. Nonetheless this C-terminal tag does not influence the properties of the molybdenum active site, as assayed by EPR spectroscopy. When a cleavable His-tag was fused to the N-terminus of the mature enzyme in the absence of the signal sequence, YedY was expressed and folded with its cofactor. However, when the signal sequence was added upstream of the N-ter tag, the amount of enzyme produced was approximately ten-fold higher. CONCLUSION: Our study thus underscores the risk of using a C-terminus tagged enzyme while studying YedY, and presents an alternative strategy to express signal sequence-containing enzymes with an N-terminal tag. It brings new insights into molybdoenzyme maturation in R. sphaeroides showing that for some enzymes, maturation can occur in the absence of the signal sequence but that its presence is required for high expression of active enzyme. PMID- 24180492 TI - Parallel syntheses of eight-membered ring sultams via two cascade reactions in water. AB - From vinyl sulfonamides as precursors to vinyl sulfonamide epoxides, two cascade reaction protocols were developed to synthesize eight-membered ring sultams in water. These protocols employ intermolecular Michael addition by NaOH or NaHS in water, followed by rapid proton transfer and intramolecular 8-endo-tet epoxide ring-opening to give medium-size sultams selectively in one-pot. Novel core structures and high synthetic efficiency make these cascade reactions highly suitable for sultam library production. Both reactions proceeded well and afforded the respective sultams in good yields under environmentally friendly conditions. PMID- 24180493 TI - Relationship between adult height and body weight and risk of carotid atherosclerosis assessed in terms of carotid intima-media thickness: the Nagasaki Islands study. AB - BACKGROUND: Previous studies have reported an inverse association between height and risk of cardiovascular disease. However, evidence is limited for the association between risk of atherosclerosis and height. Further, although the association between atherosclerosis and body mass index (BMI) is reportedly positive, there have been no reports of studies on associations between height and atherosclerosis in relation to BMI. METHODS: We conducted a cross-sectional study of Japanese men aged 30 to 89 years undergoing general health check-ups. RESULTS: Of the 1,337 men, 312 were diagnosed with carotid atherosclerosis (carotid intima-media thickness (CIMT) >= 1.1 mm), but no significant association was found between height and carotid atherosclerosis for the entire study group. Stratification by BMI status of those analytical findings disclosed a significant inverse association between height and carotid atherosclerosis among overweight (BMI >= 25 kg/m(2)) but not among non-overweight (BMI < 25 kg/m(2)) men. The classical cardiovascular risk factors-adjusted odds ratio (OR) and 95% confidence interval (CI) of carotid atherosclerosis for an increment of one SD (standard deviation) in height (6.70 cm) were 0.71 (0.54 to 0.94) for overweight (BMI >= 25 kg/m(2)) and 1.05 (0.87 to 1.27) for non-overweight (BMI < 25 kg/m(2)) men. CONCLUSION: Independent from classical cardiovascular risk factors, height was found to be inversely associated with carotid atherosclerosis for overweight but not for non-overweight men. PMID- 24180495 TI - Overcoming resistance to targeted anticancer drugs. PMID- 24180496 TI - Cancer-drug discovery and cardiovascular surveillance. PMID- 24180497 TI - Reactive oxygen species regulation of autophagy in skeletal muscles. AB - OBJECTIVE: To evaluate the effects of physiological levels of mitochondrial derived reactive oxygen species (ROS) on skeletal muscle autophagy, a proteolytic pathway designed to regulate contractile and myofilament homeostasis and to recycle long-lived proteins and damaged organelles. RESULTS: Basal levels of autophagy and autophagy triggered by 1.5 to 4 h of acute nutrient deprivation, rapamycin treatment, or leucine deprivation were measured in differentiated C2C12 myotubes using long-lived protein degradation assays, LC3B lipidation, autophagy related gene expression, and electron microscopy. Preincubation with the general antioxidants tempol (superoxide dismutase mimic) and N-acetyl cysteine (NAC) or the mitochondria-specific antioxidants mito-tempol and SS31 significantly decreased the rates of long-lived protein degradation and LC3B flux and blocked the induction of autophagy-related gene expression. Mitochondrial ROS levels significantly increased in response to acute nutrient deprivation and rapamycin treatment. Mito-tempol and tempol blocked this response. Antioxidants decreased AMP-activated protein kinase (AMPK) phosphorylation by 40% and significantly increased protein kinase B (AKT) phosphorylation, but exerted no effects on mTORC1-dependent ULK1 phosphorylation on Ser(555). NAC significantly decreased basal LC3B autophagic flux in skeletal muscles of mice. INNOVATION: We report for the first time that endogenous ROS promote skeletal muscle autophagy at the basal level and in response to acute nutrient starvation and mTORC1 inhibition. We also report for the first time that mitochondrial-derived ROS promote skeletal muscle autophagy and that this effect is mediated, in part, through regulation of autophagosome initiation and AKT inhibition. CONCLUSION: Mitochondrial-derived ROS promote skeletal muscle autophagy and this effect is mediated, in part, through activation of AMPK and inhibition of AKT. PMID- 24180494 TI - A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. AB - BACKGROUND: Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 (T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). METHODS: We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months. RESULTS: Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event. CONCLUSIONS: Ponatinib had significant antileukemic activity across categories of disease stage and mutation status. (Funded by Ariad Pharmaceuticals and others; PACE ClinicalTrials.gov number, NCT01207440 .). PMID- 24180498 TI - Surgical approach for the treatment of aortoesophageal fistula combined with dual aortic aneurysms: a case report. AB - Aortoesophageal fistula is a rare disease with a high mortality rate. The disease is with high mortality due to aneurysm rupture, and thus successfully managed cases are rarely reported. Here, we report a case of aortoesophageal fistula caused by a huge descending aneurysm and another smaller aneurysm found in the aortic arch. Such case was relatively rare in the cardiovascular field. Due to the limited experience, it was difficult to determine the proper therapeutic strategy. For this case, for the dual aneurysm, we surgically inserted an aortic endovascular stent-graft to exclusive the aneurysm and simultaneously repair the other aortic arch aneurysm. The patient had an uneventful recovery and was discharged after 1 month antibiotics therapy for the palliative treatment of the esophageal fistula. She survived for 8 months at home before dying of massive hematemesis. Here, we present the operative method and our therapeutic experience for this extremely rare case. PMID- 24180499 TI - Single-drop microextraction for bioanalysis: present and future. PMID- 24180501 TI - New setting for the Land O'Lakes Bioanalytical Conference. AB - The University of Wisconsin bioanalytical conference is presented each year by the Extension Services in Pharmacy, the professional development department within the School of Pharmacy. The purpose of this 3-day conference was to provide an educational forum to discuss issues and applications associated with the analysis of xenobiotics, metabolites, biologics and biomarkers in biological matrices. The conference was designed to include and encourage an open exchange of scientific and methodological applications for bioanalysis. To increase the interactive nature of the conference the program was composed of a mixture of lectures, interactive discussions, poster sessions and roundtables. This paper summarizes the presentations at the Fourteenth Annual Conference, offered in a new venue. PMID- 24180502 TI - The effect of ketamine-contaminated control plasma on small-molecule plasma protein binding. AB - Due to macroeconomic factors, the pharmaceutical industry has progressively outsourced larger amounts of its internal research efforts. One such example is the purchase of large volumes of control nonhuman primate (nhp) plasma from external vendors. During the bioanalysis of plasma samples collected during a Cynomolgus monkey PK study with racemic (+/-) ketamine, it was discovered that the vendor control nhp plasma used for standard curve samples contained ketamine (32 uM). This ketamine concentration correlated to an anesthetic dose of ketamine (10-15 mg/kg, IM), which was not cited in the vendor's plasma harvesting protocol. This study evaluated the effect of ketamine in control nhp plasma on the in vitro-derived unbound plasma fraction of small molecules, which would cause erroneous nhp efficacy and safety values. PMID- 24180503 TI - Assessment of the within- and between-lot variability of WhatmanTM FTA((r)) DMPK and 903((r)) DBS papers and their suitability for the quantitative bioanalysis of small molecules. AB - BACKGROUND: To ensure that PK data generated from DBS samples are of the highest quality, it is important that the paper substrate is uniform and does not unduly contribute to variability. This study investigated any within and between lot variations for four cellulose paper types: WhatmanTM FTA((r)) DMPK-A, -B and -C, and 903((r)) (GE Healthcare, Buckinghamshire, UK). The substrates were tested to demonstrate manufacturing reproducibility (thickness, weight, chemical coating concentration) and its effect on the size of the DBS produced, and the quantitative data derived from the bioanalysis of human DBS samples containing six compounds of varying physicochemical properties. RESULTS & DISCUSSION: Within and between lot variations in paper thickness, mass and chemical coating concentration were within acceptable manufacturing limits. No variation in the spot size or bioanalytical data was observed. CONCLUSION: Bioanalytical results obtained for DBS samples containing a number of analytes spanning a range of chemical space are not affected by the lot used or by the location within a lot. PMID- 24180504 TI - Simultaneous determination of dipyrone metabolites in rat hypothalamus, cerebrospinal fluid and plasma samples by LC-MS/MS. AB - BACKGROUND: After oral administration dipyrone is rapidly hydrolyzed to 4 methylaminoantipyrine, which is absorbed and further metabolized to 4 formylaminoantipyrine and to 4-aminoantipyrine, which is acetylated by a polymorphic N-acetyltransferase system to 4-acetylaminoantipyrine. To evaluate the presence of dipyrone metabolites in different rat matrices after intraperitoneal administration, an analytical method was developed and validated. METHODOLOGY: The four main dipyrone metabolites were extracted from plasma, cerebrospinal fluid and hypothalamus samples by LLE prior to LC-MS/MS. RESULTS: Standard calibration graphs for all metabolites were linear (r > 0.99). The intra and inter-day precision and accuracy values were both inferior to 15%. CONCLUSION: This method is simple and specific for studying dipyrone metabolites after intraperitoneal administration. PMID- 24180505 TI - Accessing microenvironment compartments in formalin-fixed paraffin-embedded tissues by protein expression analysis. AB - BACKGROUND: Formalin-fixed paraffin-embedded (FFPE) samples are an outstanding source of new information regarding disease evolvements. Current research on new biomarkers and diseases features has recently invested resources in FFPE-related projects. RESULTS: In order to initiate clinical protein-expression studies using minute amount of biological material, a workflow based on the combination of filter-assisted sample preparation with MS analysis and label-free quantification was developed. Xenograft lung tumor tissue was investigated as a model system. The workflow was optimized and characterized in terms of its reproducibility from a quantitative and qualitative point of view. We proposed a modification of the original filter-assisted sample preparation protocol to improve reproducibility and highlight its potential for the investigation of hydrophobic proteins. CONCLUSIONS: Altogether the presented workflow allows analysis of FFPE samples with improvements in the analytical time and performance, and we show its application for lung cancer xenograft tissue samples. PMID- 24180506 TI - Current status and bioanalytical challenges in the detection of unknown anabolic androgenic steroids in doping control analysis. AB - Androgenic anabolic steroids (AAS) are prohibited in sports due to their anabolic effects. Doping control laboratories usually face the screening of AAS misuse by target methods based on MS detection. Although these methods allow for the sensitive and specific detection of targeted compounds and metabolites, the rest remain undetectable. This fact opens a door for cheaters, since different AAS can be synthesized in order to evade doping control tests. This situation was evidenced in 2003 with the discovery of the designer steroid tetrahydrogestrinone. One decade after this discovery, the detection of unknown AAS still remains one of the main analytical challenges in the doping control field. In this manuscript, the current situation in the detection of unknown AAS is reviewed. Although important steps have been made in order to minimize this analytical problem and different analytical strategies have been proposed, there are still some drawbacks related to each approach. PMID- 24180507 TI - Life cycle management of critical ligand-binding reagents. AB - Bioanalytical laboratories develop and validate ligand-binding assays (LBA) used to quantify the concentration of analytes of interest in various buffers and relevant biological matrices. The building blocks of LBA are reagents that recognize molecular and structural motifs on ligands, which are combined in various LBA formats to minimize biological matrix interferences and specifically detect and quantify the analyte of interest. The use of these LBA-requiring critical reagents, can span decades as programs mature to commercialization. Since critical reagents are generated mostly from biological systems, attention to their life cycle management, quality, characterization and sustainability are vital to the success of bioanalytical laboratories. Integrating de novo reagent generation, reagent biophysical characterization, LBA development, validation, and use, with reagent resupply processes leverages interdisciplinary activities and ensures smooth operations of a bioanalytical laboratory. PMID- 24180508 TI - Exploiting biospectroscopy as a novel screening tool for cervical cancer: towards a framework to validate its accuracy in a routine clinical setting. AB - Biospectroscopy is an emerging field that harnesses the platform of physical sciences with computational analysis in order to shed novel insights on biological questions. An area where this approach seems to have potential is in screening or diagnostic clinical settings, where there is an urgent need for new approaches to objectively interrogate large numbers of samples in an objective fashion with acceptable levels of sensitivity and specificity. This review outlines the benefits of biospectroscopy in screening for precancer lesions of the cervix due to its ability to separate different grades of dysplasia. It evaluates the feasibility of introducing this technique into cervical screening programs on the basis of its ability to identify biomarkers of progression within derived spectra ('biochemical-cell fingerprints'). PMID- 24180509 TI - Recent advances in LC-MS/MS analysis of Delta(9)-tetrahydrocannabinol and its metabolites in biological matrices. AB - Cannabis is the most widely used illicit drug in the world. The pharmacological properties of Delta(9)-tetrahydrocannabinol also make it a promising molecule in the treatment of different pathologies. Understanding the PKs and PDs of this drug requires the determination of the concentration of Delta(9) tetrahydrocannabinol and metabolites in biological matrices. For this purpose many analytical methodologies using mass spectrometric detection have been developed. In recent years, LC-MS/MS has become the gold standard in analysis of tetrahydrocannabinol and its metabolites due to the high selectivity and sensitivity, but above all, due to the ability to determine free and conjugate analytes in one run. PMID- 24180511 TI - Silica nanoparticles and polyethyleneimine (PEI)-mediated functionalization: a new method of PEI covalent attachment for siRNA delivery applications. AB - Small-interfering RNA (siRNA) is a synthetic double-stranded RNA that consists of approximately 21 nucleotides (nts). It induces degradation of target mRNAs in a sequence-specific manner by the RNA interference (RNAi) mechanism. Thus, siRNAs offer a potential strategy for silencing mutated or defective genes that cause a variety of human diseases. The main obstacles of harnessing siRNAs as drugs are their inefficient delivery to cells and off-target effect making clinical applications very challenging. To address these issues, researchers have studied a variety of nanocarrier systems for siRNA delivery. This study presents the design, fabrication, and full characterization of innovative polyethyleneimine (PEI)-decorated polycationic 34.2 +/- 4.2 nm silica (SiO2) NPs for siRNA-mediated gene silencing. More specifically, a new means of introduction (covalent mode of attachment) of the polycationic 25 kDa PEI polymer onto the SiO2 NP surface has been developed that makes use of an effective electrophilic double Michael acceptor, divinyl sulfone (DVS). The resulting novel SiO2-PEI nanoparticles (SPEI NPs) have been fully characterized using a wide range of analytical, spectroscopic, and microscopic methods (TEM, DLS, zeta potential, elemental analysis (EA), XPS, TGA, and FTIR). Disclosing quite low cytotoxicity due to this unique mode of PEI covalent grafting, SPEI NPs/siRNA polyplexes have been successfully tested for the induction of gene silencing using dual-reporter luciferase transfected human osteosarcoma U2OS cells. The corresponding gene silencing data showed a clear correlation between PEI/siRNA ratios, siRNA concentration(s), and the level of gene silencing. Moreover, these SPEI NPs have been demonstrated to be thermodynamically stable with an ability to efficiently bind siRNAs and induce silencing for at least a one-year-long storage. PMID- 24180512 TI - Development of a new measurement scale for interprofessional collaborative competency: a pilot study in Japan. AB - The objective of this study was to develop and test a competency scale, which measures the competency of interprofessional collaborative practice of health professionals. A total of 32 health professionals were interviewed, and then an item pool of 255 items was created to measure the competency of interprofessional collaboration. A questionnaire study was conducted with 1552 health professionals from four different hospitals located in the Kanto region of Japan. The questionnaires were distributed and collected by gatekeepers in each section. The valid response rate was 62.6%. There were a total of 65 questionnaire items measuring the competency of interprofessional collaboration. Each item was assessed by the number of valid responses, distribution of scores, item-total correlation analysis and good-poor analysis. Construct validity was assessed using factor analysis and the relationships among the total scores of each factor with interprofessional education experience during education before and after graduating. Moreover, Cronbach's alpha coefficient was calculated to assess reliability. Finally, 30 items were excluded, and a scale for interprofessional collaborative competency comprising 35 items and 6 factors was developed. From the perspective of construct validity and internal consistency, the scale in its pilot form shows some promising aspects. PMID- 24180513 TI - Legalizing a market for cannabis for pleasure: Colorado, Washington, Uruguay and beyond. AB - Colorado, Washington state and Uruguay are currently designing legal non-medical markets for cannabis. These clearly contravene the 1961 and 1988 drug conventions; options for what may happen next are discussed. The current provisions in the three regulatory schemes are summarized. From a public health perspective, the emphasis should be on holding down consumption with regulatory measures, but the public health agenda does not seem to be a strong consideration in the implementation of the US schemes, and they are paying little attention to what can be learned from the history of alcohol and tobacco regulation. While alternative paths to a cannabis market under the conventions are noted, the legalization initiatives underline the need to revise the drug conventions, making prohibition of domestic markets an optional matter. Such changes would also ease the path for including alcohol under the conventions, which would be an important step forward in global health. PMID- 24180514 TI - Diagnosis of human nematode infections. AB - Many hundreds of millions of people throughout the world are infected by nematodes found in the intestine or tissues with a high prevalence in developing countries. Despite their frequency and morbidity, these infections, which may affect migrants and travelers, remain difficult to diagnosis even in developed countries. This is primarily due to the variety of clinical signs often associated with a lack of highly sensitive and specific diagnostic tools. Parasitological diagnosis is often difficult to achieve and can neither be applied during the pre-patent period nor for parasitic impasses. Serological diagnosis is frequently hampered by a lack of specificity due to cross-reaction with others helminthes. Molecular biology methods still require optimization. The diagnostic approach applied by a clinician of a suspected nematode infection is based on a vast set of data including patient history and way of life, clinical examination, non-specific biological tests and, when available, specific diagnostic tests. PMID- 24180515 TI - Patient outcomes and experiences of an acupuncture and self-care service for persistent low back pain in the NHS: a mixed methods approach. AB - BACKGROUND: Supported self-management, acupuncture and information can help reduce the symptoms of low back pain. These approaches are currently recommended by NICE guidance as treatment options for patients with persistent low back pain. However, there has been no previous evaluation of a service providing them together for this common problem. The purpose of this service evaluation was to report patient outcomes and experiences of the Beating Back Pain Service (BBPS), a pilot service based in a primary and community care setting, delivering acupuncture, self-management and information to patients with chronic low back pain. METHODS: Patients completed a questionnaire at three time points: pre-BBPS, immediately post-BBPS and three months post-BBPS. Outcome measures included the Bournemouth Questionnaire (measuring musculoskeletal, MSK, problems), EuroQoL-5D (measuring quality of life), Pain and Self-efficacy Questionnaire, and additional questions on medication use, physical activity, understanding of pain and positive well-being. Additionally, the STarT Back (measuring risk of developing chronic pain) was collected at BBPS information sessions. Non-parametric tests were used to evaluate pre- and post- variables. Questionnaires also collected qualitative data (open-text responses) regarding patient views and experiences of the BBPS, which were analysed using thematic analysis. RESULTS: 80 (out of 108) patients who attended the initial BBPS information session agreed to participate in the service evaluation (mean age 47 years, 65% female). 65 patients attended subsequent BBPS acupuncture and/or self-management sessions and were asked to complete post-treatment questionnaires; complete datasets were available for 61 patients.There were statistically significant improvements over time for pain (p <0.0001), quality of life (p = 0.006), understanding of pain (p <0.001), physical activity (p = 0.047) and relaxation (p = 0.012). Post-hoc analysis revealed that scores improved between baseline and post-treatment, these improvements were maintained at 3-month follow-up (except relaxation). Patients receiving a combination of acupuncture and self-management sessions produced the most positive results. Patient satisfaction with the BBPS was high. CONCLUSIONS: The BBPS provided a MSK pain management service that many patients found effective and valuable. Combining self-management with acupuncture was found to be particularly effective, although further consideration is required regarding how best to engage patients in self-management. PMID- 24180516 TI - Abnormal expression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer. AB - BACKGROUND: Paxillin (PXN) has been found to be aberrantly regulated in various malignancies and involved in tumor growth and invasion. The clinicopathological and prognostic significance of PXN in gastric cancer is still unclear. METHODS: The expression of PXN was determined in paired gastric cancer tissues and adjacent normal tissues by Western blotting and real-time PCR. Immunohistochemistry was performed to detect the expression of PXN in 239 gastric cancer patients. Statistical analysis was applied to investigate the correlation between PXN expression and clinicopathological characteristics and prognosis in patients. Additionally, the effects of PXN on gastric cancer cell proliferation and migration were also evaluated. RESULTS: PXN was up-regulated in gastric cancer tissues and cell lines as compared with adjacent normal tissues and normal gastric epithelial cell line GES-1. Overexpression of PXN was correlated with distant metastasis (P=0.001) and advanced tumor stage (P=0.021) in gastric cancer patients. Patients with high PXN expression tended to have poor prognosis compared with patients with low PXN expression (P<0.001). Multivariate analysis demonstrated that PXN expression was an independent prognostic factor (P=0.020). Moreover, ectopic expression of PXN promotes cell proliferation and migration in AGS cells whereas knockdown of PXN inhibits cell proliferation and migration in SGC7901 cells. CONCLUSIONS: PXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer. PMID- 24180517 TI - Copper-catalyzed etherification of arene C-H bonds. AB - A method for direct, auxiliary-assisted alkoxylation and phenoxylation of beta sp(2) C-H bonds of benzoic acid derivatives and gamma-sp(2) C-H bonds of amine derivatives is reported. The reaction employs (CuOH)2CO3 catalyst, air as an oxidant, phenol or alcohol coupling partner, DMF, pyridine, or DMPU solvent, and K2CO3, tetramethylguanidine, or K3PO4 base at 70-130 degrees C. PMID- 24180518 TI - Metabolic atrophy and 3-T 1H-magnetic resonance spectroscopy correlation after radiation therapy for prostate cancer. AB - OBJECTIVE: To correlate 3-T magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels in patients with prostate cancer treated with external beam radiation therapy to assess the potential advantages of MRSI. MATERIALS AND METHODS: A total of 50 patients (age range 65-83 years) underwent PSA and MRSI surveillance before and at 3, 6, 12, 18 and 24 months after radiotherapy. RESULTS: Of the 50 patients examined, 13 patients completely responded to therapy showing metabolic atrophy (MA), defined as a choline-plus creatine/citrate (CC/C) ratio <0.2, at 3 months; in this group none had biochemical relapse (PSA nadir + 2 ng/mL) by the end of the follow-up. Of the 50 patients, 35 showed a partial response to therapy (CC/C ratio between 0.2 and 0.8) at 3 and 6 months and, of these 35 patients, 30 reached MA at 12 months, while five developed a recurrence (CC/C ratio >0.8). Three of those patients with recurrence had a biochemical relapse at 18 months and the other two at 24 months. Two of the 50 patients did not respond to the treatment, showing persistent disease from the 3rd month (CC/C ratio >0.8); one patient had biochemical relapse at 6 and the other at 12 months. CONCLUSIONS: MRSI was shown to have a greater potential than PSA level in monitoring patients after radiotherapy, because it anticipates PSA nadir, and biochemical relapse in particular. PMID- 24180519 TI - Safety and efficacy of a new parenteral lipid emulsion (SMOF) for surgical patients: a systematic review and meta-analysis of randomized controlled trials. AB - To assess the comparative safety and efficacy of a new parenteral lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOFlipid20%) for postoperative patients, a meta-analysis of randomized controlled trials (RCTs) was conducted. Six RCTs with a total of 306 patients were included in the analysis. The overall quality of evidence for each outcome was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) software. Compared with a soybean-based (Lipoven20%) and a soybean- and olive oil-based (ClinOleic20%) lipid emulsion, SMOFlipid20% was associated with lower levels of hepatic enzymes, suggesting less toxicity. Changes in low-density lipoprotein triglyceride and C-reactive protein levels were also lower with SMOFlipid20% compared with Lipoven20%. Differences between SMOFlipid20% and a lipid emulsion containing medium- and long-chain triglycerides (MCT/LCT20%) were not statistically significant. For all trials, there were no significant differences in adverse events and length of hospital stay. The quality of evidence from the RCTs evaluating SMOF20% versus Lipoven20% was moderate, while most of the evidence from RCTs of SMOF20% versus ClinOleic20% and MCT/LCT20% lipid emulsions was low. PMID- 24180520 TI - Computational studies on a carbenoid mechanism for the Doering-Moore-Skattebol reaction. AB - The reaction of geminal dihalocyclopropanes with metals or alkyllithiums affords carbenoids which undergo low-temperature ring opening to allenes; this is known as the Doering-Moore-Skattebol reaction. DFT and CCSD(T)//DFT computations have been used to model the structure, coordination state, and ring opening of 1-bromo 1-lithiocyclopropane as a model for cyclopropylcarbenoid chemistry. Both implicit (PCM) and explicit solvation models have been applied. Carbenoid ring opening is similar to the process predicted in earlier studies on cyclopropylidene. The initial disrotatory stereochemistry becomes conrotatory en route to the allene LiBr complex. Predissociation of the carbenoid to cyclopropylidene + LiBr is not supported by computations. DFT computations predict modestly exergonic dimerization of the carbenoid, with or without solvation, and the dimer appears to be the most likely reactive species in solution. Predicted barriers to ring opening are only modestly affected by solvation or by dimer formation, remaining in the range of 9-12 kcal/mol throughout. PMID- 24180521 TI - Insights, attitudes, and perceptions about asthma and its treatment: findings from a multinational survey of patients from Latin America. AB - BACKGROUND: In 2011 the Latin America Asthma Insight and Management (LA AIM) survey explored the realities of living with asthma. We investigated perception, knowledge, and attitudes related to asthma among Latin American asthma patients. METHODS: Asthma patients aged >=12 years from four Latin American countries (Argentina, Brazil, Mexico, Venezuela) and the Commonwealth of Puerto Rico responded to questions during face-to-face interviews. A sample size of 2,169 patients (approximately 400 patients/location) provided an accurate representation of asthma patients' opinions. Questions probed respondents' views on topics such as levels of asthma control, frequency and duration of exacerbations, and current and recent use of asthma medications. RESULTS: A total of 2,169 adults or parents of children with asthma participated in the LA AIM survey. At least 20% of respondents experienced symptoms every day or night or most days or nights. Although 60% reported their disease as well or completely controlled, only 8% met guideline criteria for well-controlled asthma. 47% of respondents reported episodes when their asthma symptoms were more frequent or severe than normal, and 44% reported seeking acute care for asthma in the past year. Asthma patients in Latin America overestimated their degree of asthma control. CONCLUSIONS: The LA AIM survey demonstrated the discrepancy between patient perception of asthma control and guideline-mandated criteria. Additional education is required to teach patients that, by more closely following asthma management strategies outlined by current guidelines more patients can achieve adequate asthma control. PMID- 24180522 TI - Synthesis and biological evaluation of nitromethylene neonicotinoids based on the enhanced conjugation. AB - The neonicotinoids with a nitroconjugated system had excellent bioactivity, which could rival imidacloprid, and has been previously reported. However, the photodegradation and hydrolysis of this series of neonicotinoids was very quick according to our further investigation, which cannot be developed as a pesticide further. The approach to further enhance the conjugation was tried not only to increase the bioactivities but also to improve the stability in water and in the sun. A substituted phenyl group was introduced into the furan ring of compound 3. A total of 13 novel neonicotinoid analogues with a higher conjugation system were designed and synthesized. The target molecular structures have been confirmed on the basis of satisfactory analytical and spectral data. All compounds presented significant insecticidal activities on cowpea aphid ( Aphis craccivora ), cotton aphid ( Aphis gossypii ), and brown planthopper ( Nilaparvata lugens ). The stability test exhibited that the stability of novel analogues in water and under the mercury lamp has been improved significantly in comparison to compound 3. PMID- 24180523 TI - Binary and ternary phase behaviors of short double-chain quaternary ammonium amphiphiles: surface tension, polarized optical microscopy, and SAXS investigations. AB - A series of short chain dialkyldimethylammonium amphiphiles ([DiC(n)][X] and [DiC(n)]2[X] with n = 6, 8, or 10) has been investigated as a function of the nature of the counteranion [X] (Cl(-) and Br(-) as classical references and MoO4(2-) and WO4(2-) as catalytic anions). Critical aggregation concentrations (CACs) in water were determined by surface tension measurements, and the binary phase diagrams of the surfactant/water systems were established using polarized optical microscopy (POM) and small angle X-ray scattering (SAXS). The evolution of microstructures and lyotropic phases were discussed in terms of surfactant chain length and counterion effect. A cubic phase region was observed for the divalent counteranions associated with the intermediate chain length, i.e., [DiC8]2[MoO4] and [DiC8]2[WO4]. Finally, the fish diagrams reflecting the polyphasic microemulsion phase behavior of the water/amphiphile/oil ternary systems were established using the carbon number of mono- and dichlorinated n alkanes as a scan variable. The amphiphile efficiency was also discussed according to the chain length and the nature of the counterions. The hydrophilic lipophilic behavior of the amphiphiles was evaluated on the basis of the fish diagrams allowing their classification according to the Hofmeister anion sequence. The unusual behavior of [DiC8][Cl] and [DiC8]2[MO4] (M = W or Mo) is highlighted by all experiments: these compounds are clearly intermediates between hydrotropes, [DiC6] cation, and surfactants, [DiC10] cation. PMID- 24180524 TI - Mammalian sterile 20-like kinase 1/2 inhibits the Wnt/beta-catenin signalling pathway by directly binding casein kinase 1epsilon. AB - The Hippo signalling pathway can suppress the Wnt/beta-catenin signalling pathway through the last downstream effectors YAP (Yes-associated protein)/TAZ (tafazzin). MST (mammalian sterile 20-like kinase) 1 functions as the upstream kinase of the Hippo pathway, and CK1epsilon (casein kinase 1epsilon) plays roles in the up-stream signal transduction of the Wnt/beta-catenin pathway. In the present study, using tandem affinity purification and MS analysis, CK1epsilon was identified as a novel partner of MST1. Further analysis showed that the interaction between MST1 and CK1epsilon was mediated by their kinase domains and enhanced by the activation of MST1. To exclude the interference of the phosphorylated YAP/TAZ, the transduction from MST1 to YAP/TAZ was blocked using anti-WW45 shRNA. In the sh-WW45 cells, MST1 still inhibited the Wnt3A-induced phosphorylation of DVL2 (dishevelled 2) and Wnt/beta-catenin signalling by disturbing the interaction of DVL2 and CK1epsilon. The growth-suppressive effect of MST1 in the presence of Wnt3A was effectively relieved by the downstream activation of the Wnt/beta-catenin pathway. Moreover, MST2, the close homologue of MST1, also displayed the similar function in suppressing the Wnt/beta-catenin pathway. Therefore the results of the present study revealed that, in addition to the phosphorylated YAP/TAZ, the Hippo pathway can suppress the Wnt/beta-catenin pathway directly through MST1/2. PMID- 24180525 TI - Transdisciplinary women's health: a call to action. AB - Various women's health concerns (e.g., hormonal changes, cardiovascular disease, diabetes mellitus, osteoporosis, immune deficiencies, respiratory diseases, eating disorders, substance use/abuse, sexually transmitted infections, stress, poverty, poor nutrition, and early childhood caries) are associated with oral systemic etiologies that can either cause or form as a result of poor oral health. Nonetheless, the intersections of biological, social-behavioral, and structural factors that impact women's oral-systemic health are rarely examined. We argue for the need for transdisciplinary research, grounded in team science, for incorporating and transcending multiple discipline-specific frameworks and models to examine the complexity of women's health issues holistically across the lifespan. PMID- 24180526 TI - A novel strategy for classifying the output from an in silico vaccine discovery pipeline for eukaryotic pathogens using machine learning algorithms. AB - BACKGROUND: An in silico vaccine discovery pipeline for eukaryotic pathogens typically consists of several computational tools to predict protein characteristics. The aim of the in silico approach to discovering subunit vaccines is to use predicted characteristics to identify proteins which are worthy of laboratory investigation. A major challenge is that these predictions are inherent with hidden inaccuracies and contradictions. This study focuses on how to reduce the number of false candidates using machine learning algorithms rather than relying on expensive laboratory validation. Proteins from Toxoplasma gondii, Plasmodium sp., and Caenorhabditis elegans were used as training and test datasets. RESULTS: The results show that machine learning algorithms can effectively distinguish expected true from expected false vaccine candidates (with an average sensitivity and specificity of 0.97 and 0.98 respectively), for proteins observed to induce immune responses experimentally. CONCLUSIONS: Vaccine candidates from an in silico approach can only be truly validated in a laboratory. Given any in silico output and appropriate training data, the number of false candidates allocated for validation can be dramatically reduced using a pool of machine learning algorithms. This will ultimately save time and money in the laboratory. PMID- 24180528 TI - Toxicity inspired cross-linking for probing DNA-peptide interactions. AB - A cross-linking methodology for the study of DNA-protein interactions is described. The method is inspired by the metabolic activation of furans causing toxic DNA damage, including DNA-protein cross-links (DPC). The furan moiety, representing a latent functionality, is easily incorporated into oligonucleotides, and can be activated on demand to release a reactive aldehyde. Reaction with nucleophilic lysine side chains is shown to be distance-sensitive and allows for site-selective DPC formation. PMID- 24180527 TI - Speech-induced atrial tachycardia: an unusual presentation of supraventricular tachycardia. AB - A 63-year-old male radio announcer was admitted with a narrow complex, long RP tachycardia. While in the awake state, the patient spoke in his radio voice, initiating and maintaining the tachycardia. Three-dimensional electroanatomic mapping during electrophysiology study localized the tachycardia to the ostium of the right superior pulmonary vein. After single radiofrequency energy application, no further arrhythmias were inducible with speech. At more than 1 year of follow-up, the patient had no recurrences and continues to work as a radio announcer. PMID- 24180529 TI - Maturation of stem cell-derived human heart tissue by mimicking fetal heart rate. PMID- 24180531 TI - Antiplatelet therapy strategies after percutaneous coronary intervention in patients needing oral anticoagulation. AB - Long-term oral anticoagulant (OAC) and dual-antiplatelet therapy are commonly needed in patients with atrial fibrillation and in patients undergoing percutaneous coronary intervention (PCI), respectively. The combination of atrial fibrillation and PCI is frequent, and leads to a dilemma for antithrombotic therapy, where risk of stroke or stent thrombosis must be balanced with bleeding risk. In the WOEST study, 573 patients on OAC undergoing PCI were randomly assigned to receive clopidogrel alone or clopidogrel plus aspirin. The primary end point was the occurrence of any bleeding episode during 1-year follow-up. Clopidogrel alone administered to patients taking OAC after PCI was associated with a significantly lower rate of bleeding complications than clopidogrel plus aspirin. Moreover, a composite secondary end point of death, myocardial infarction and stent thrombosis was significantly lower in the dual-therapy group compared with the triple-therapy group. In spite of its limitations, the WOEST study constitutes a major breakthrough, showing that long-term aspirin after PCI may be obsolete in certain circumstances. This needs to be confirmed in further studies. PMID- 24180532 TI - Cardiac rhythm device surgery with uninterrupted oral anticoagulation. AB - Current guidelines recommend interrupting anticoagulation and bridging therapy with heparin or low-molecular-weight heparin for cardiac rhythm device surgeries in patients with high thrombotic risk. However, there are some studies that suggest continuing warfarin may be safe. The study by Birnie et al. investigates this important clinical question in a randomized controlled trial setting. They randomly assigned 681 patients with high thrombotic risk (5% or more per year), in 18 centers, to receive either stopping warfarin combined with heparin bridging (standard of care) or continued uninterrupted warfarin therapy for cardiac rhythm device surgery. The trial was terminated after a second prespecified interim analysis by the data and safety monitoring board. Clinically significant device pocket hematoma was noted in 12 out of 343 patients (3.5%) in the uninterrupted warfarin group, compared with 54 out of 338 (16.0%) in the heparin-bridging group (relative risk: 0.19; 95% CI: 0.10-0.36; p < 0.001). Uninterrupted warfarin was associated with better patient satisfaction, and there was no significant difference in thromboembolic or surgical complications between the two groups. These results demonstrate that device surgeries can be safely performed with continued warfarin, and bridging with heparin is associated with high risk of device-pocket hematoma. PMID- 24180533 TI - Muscle wasting is associated with reduced exercise capacity and advanced disease in patients with chronic heart failure. AB - Muscle atrophy of the lower limbs is a comorbidity that can develop in advanced stages of chronic heart failure (HF). The article by Fulster et al. prospectively examined the association of muscle mass volume and muscle strength, gait speed, walking distance and treadmill performance in 200 stable HF patients. Muscle wasting was legitimately defined as the appendicular muscle mass two standard deviations below the mean of a healthy reference group. Muscle wasting was detected in 39 (19.5%) patients. Patients with muscle atrophy had significantly lower values for muscle strength, as well as lower total peak oxygen consumption (1173 +/- 433 vs 1622 +/- 456 ml/min), lower exercise time (7.7 +/- 3.8 vs 10.2 +/- 2.0 min; both p < 0.001) and lower left ventricular ejection fraction (p = 0.05). In addition, the distance walked and gait speed were also lower in patients with muscle wasting than those without (p < 0.05). Logistic regression analyses revealed that muscle wasting was independently associated with reduced peak oxygen consumption after adjustment for cofounders. These findings suggest that skeletal muscle wasting is common in chronic HF patients and is associated with worse exercise capacity and reduced left ventricular ejection fraction. PMID- 24180534 TI - New multipoint pacing technology for heart failure patients. Interview by Caroline Telfer. AB - Tim Betts speaks to Caroline Telfer, Assistant Commissioning Editor. Tim Betts is currently a consultant cardiologist and electrophysiologist at the Oxford Heart Centre, John Radcliffe Hospital (Oxford, UK). Dr Betts gained his MB ChB from Birmingham Medical School (Birmingham, UK) in 1991, and his MD on the relationship between atrial anatomy and electrophysiology was awarded by Southampton University (UK) in June 2003. Dr Betts' special interests include diagnosis, investigation and treatment of heart rhythm disorders, including blackouts, palpitations and risk assessment for sudden cardiac death. He performs diagnostic electrophysiology and catheter ablation. He also specializes in cardiac devices including pacemakers, defibrillators and cardiac resynchronization therapy (biventricular pacing). PMID- 24180535 TI - Advances in cardiac lead extraction. Interview by Caroline Telfer. AB - Amir Zaidi speaks to Caroline Telfer, Assistant Commissioning Editor. Amir Zaidi qualified in 1989 from Manchester University (UK) and undertook postgraduate training in London and in the northwest of England. Dr Zaidi worked as a consultant cardiologist at Royal Bolton Hospital (Lancashire, UK) from 2002 until 2009 before moving to his current position of consultant at the Manchester Royal Infirmary (Manchester, UK). Dr Zaidi is currently the training program director for cardiology in North-Western Deanery and a member of the Cardiology Specialist Advisory Committee. PMID- 24180536 TI - Fractional flow reserve assessment of the unprotected left main artery: a case of the cart before the horse? PMID- 24180537 TI - PA tablets: investigational compounds combining aspirin and omeprazole for cardioprotection. AB - For most patients with prior cardiovascular events, preventing future secondary cardiovascular events requires life-long persistence with antiplatelet therapy. PA tablets (P: proton pump inhibitors; A: aspirin) are investigational compounds that were developed to provide the cardioprotective benefits of aspirin with the upper gastrointestinal protection of a proton pump inhibitor (e.g., omeprazole). The tablets are film-coated, coordinated-release tablets for oral administration that contain 40 mg immediate-release omeprazole and either 81 or 325 mg delayed release aspirin. The goals of the clinical development program were to demonstrate the following: improved gastrointestinal safety of PA relative to enteric-coated aspirin alone; bioequivalence and comparative bioavailability between the PA compounds and currently marketed enteric-coated aspirin; and long term safety. Two clinical pharmacology studies were also conducted to study the potential for interaction between PA32540 and clopidogrel. PMID- 24180538 TI - Recent developments in the ablation of ventricular arrhythmias. AB - Catheter ablation for the management of recurrent ventricular arrhythmias (VAs) is an emerging technology, with good efficacy in selected patients. It is an effective treatment for recurrent VA and can terminate VA during electrical storm. Recent innovations enhance the accuracy of ventricular mapping, allowing for substrate modification while the patient remains in sinus rhythm, thus facilitating the treatment of different types of VA. Epicardial ablation is now a feasible option for treating VA and increases the likelihood of success in certain types of VA. Percutaneous hemodynamic support facilitates successful ablation during poorly tolerated VA. This article reviews recent advances in catheter ablation techniques for VA and approaches to the management of specific types of VA, with a view toward future developments. PMID- 24180539 TI - Earlier detection can help avoid many serious complications of peripartum cardiomyopathy. AB - Peripartum cardiomyopathy (PPCM) has a remarkable potential for recovery. It may be within our capability to help almost all women with PPCM not only to survive, but also to completely recover heart function. Time-of-diagnosis left ventricular ejection fraction (LVEF) >=0.35 is associated with better survival rates and higher full recovery rates. Increased mortality, chronic cardiomyopathy, thromboembolic complications and serious ventricular tachyarrhythmias are associated with diagnostic LVEF <0.30. Delays in diagnosis may result in lower LVEF at diagnosis and subsequent lower recovery rates. Greater awareness of the possibility of heart failure developing in previously healthy young women, with no history of heart disease, will contribute to earlier diagnosis, with potentially better preserved heart function. Women of African descent may be at higher risk for poorer outcomes. Recent investigations suggest newer biomarkers may help with earlier detection of PPCM. PMID- 24180541 TI - Novel oral anticoagulants for the prevention and treatment of thromboembolism. AB - Over the last 5 years, new oral anticoagulant options, including dabigatran, rivaroxaban and apixaban, have become available. Prior to this, vitamin K antagonists were the sole oral anticoagulants, which have been in use for more than 60 years. These novel agents have been studied in a variety of patient populations, including atrial fibrillation, acute coronary syndrome, treatment of venous thromboembolism and thromboprophylaxis. Compared with standard care, these agents have largely been found to be noninferior or superior for efficacy end points, with similar or improved rates of bleeding. As a result, these agents have become attractive alternatives to vitamin K antagonists for the prevention and treatment of thromboembolic disease. This article provides a summary of clinical trial data to help clinicians determine which agent is most appropriate for a given patient. PMID- 24180542 TI - Role of manual and mechanical chest compressions during resuscitation efforts throughout cardiac arrest. AB - The previously published randomized trials of mechanical versus manual resuscitation of patients with cardiac arrest are inconclusive, but a recent systematic review concluded: "There is no evidence that mechanical cardiopulmonary resuscitation devices improve survival; to the contrary they may worsen neurological outcome." However, in our view, none of the randomized trials to date are definitive as the manual groups with primary cardiac arrest have not been treated optimally; that is, with minimally interrupted manual chest compressions, as advocated with cardiocerebral resuscitation. Since the mechanical chest compression devices work on different principles, it is possible that, while they may not be as effective and may even be worse in some subsets of patients, they may be preferable in others. Nevertheless, there are situations where manual chest compressions are not practical and, in these, mechanical devices may well be preferable. The Thumper(r) (Michigan Instruments, MI, USA) and the LUCASTM (Jolife AB, Lund, Sweden) devices produce sternal compressions at 100 per min. By contrast, the AutoPulse(r) (ZOLL Circulation, CA, USA) produces chest compressions at a rate of only 80 per min. Since chest compression rate, as reviewed in this article, is important, one would guess that the devices that can produce a faster rate would be more effective. On the other hand, it could be that sternal compressions with manual or mechanical devices may be more or less effective depending on the arrested patient's chest configuration. We speculate that in the subset of patients with barrel chests, where sternal compressions are less likely to be operative, the AutoPulse might be more effective, but less effective in thin-chested individuals, where direct cardiac compression is the major mechanism of forward blood flow in the manual, Thumper and LUCAS methods. The original LUCAS device had the potential of active decompression as well as compression. To market in the USA, holes had to be placed in the 'suction cup'. It would be informative to know whether the original LUCAS device is more effective than the device in which the active decompression has been deactivated. PMID- 24180543 TI - Stem cells for cardiac repair: problems and possibilities. AB - Ischemic heart disease is a major cause of death throughout the world. In order to limit myocardial damage and possibly generate new myocardium, stem cells are currently being injected into patients with ischemic heart disease. Three major patient investigations, The LateTIME, the TIME and the Swiss Myocardial Infarction trials, have recently addressed the questions of whether progenitor cells from unfractionated bone marrow mononuclear cells limit myocardial damage and what the optimal time to inject these cells after acute myocardial infarctions (AMIs) is. In each of these trials, there were no significant differences between treated and control patients when bone marrow cells were administered 5-7 days or 2-3 weeks after AMIs. Nevertheless, these investigations provide important information regarding clinical trial designs. Patients with AMIs in these trials were treated with percutaneous coronary intervention within a median of 4-5 h after the onset of chest pain. Thereafter, all patients received guideline-guided optimal medical therapy. Consequently, the sizes of AMIs were significantly limited. In patients with small AMIs and near-normal left ventricular ejection fractions, progenitor cells are least effective. However, these trials do question whether autologous bone marrow mononuclear cells are the optimal cells for myocardial repair owing to low numbers of progenitor cells in bone marrow aspirates and the significant variability in potency and efficacy of these cells in patients with chronic multisystem diseases. In contrast, the SCIPIO and the CAUDUCEUS trials examined cardiac progenitor cells in patients with ischemic cardiomyopathies. These trials reported over 1-2 years that cardiac progenitor cells produced significant improvements in left ventricular contractility due to 12-24 g decreases in myocardial scars and 18-23 g increases in viable myocardial muscle. However, caution must be exercised in the interpretation of these studies due to the small numbers of highly selected patients and intra- and inter-observer variability in infarct size measurements. Anatomical and histological examinations of large numbers of patients treated with these cells are necessary to confirm significant generation of myocytes and decreases in infarct size and fibrosis. PMID- 24180544 TI - Deactivation of implantable cardioverter-defibrillators at end of life. AB - It is inevitable that all patients with implantable cardioverter-defibrillators (ICDs) will die during extended follow-up. End-of-life care planning may become appropriate as a patient's condition deteriorates. There is concern about multiple futile shocks in the final hours of life, although the incidence of this problem has been estimated at only 8-16%. Despite broad consensus that ICD deactivation should be discussed as part of end-of-life care planning, the effect of ICD deactivation, in particular whether life expectancy is altered, is uncertain. Many clinicians are reluctant to discuss ICD deactivation. Many patients have misconceptions regarding ICD function and value longevity above quality of life. As such, ICD deactivation is often discussed late or not at all. The management of ICDs in patients approaching death is likely to become a major problem in the coming years. This article will discuss directions in which clinical practice might develop and areas for future research. PMID- 24180540 TI - Pediatric cardiomyopathies: causes, epidemiology, clinical course, preventive strategies and therapies. AB - Pediatric cardiomyopathies, which are rare but serious disorders of the muscles of the heart, affect at least one in every 100,000 children in the USA. Approximately 40% of children with symptomatic cardiomyopathy undergo heart transplantation or die from cardiac complications within 2 years. However, a significant number of children suffering from cardiomyopathy are surviving into adulthood, making it an important chronic illness for both pediatric and adult clinicians to understand. The natural history, risk factors, prevalence and incidence of this pediatric condition were not fully understood before the 1990s. Questions regarding optimal diagnostic, prognostic and treatment methods remain. Children require long-term follow-up into adulthood in order to identify the factors associated with best clinical practice including diagnostic approaches, as well as optimal treatment approaches. In this article, we comprehensively review current research on various presentations of this disease, along with current knowledge about their causes, treatments and clinical outcomes. PMID- 24180545 TI - Role of ion channels in coronary microcirculation: a review of the literature. AB - In normal coronary arteries, several different mechanisms of blood flow regulation exist, acting at different levels of the coronary tree: endothelial, nervous, myogenic and metabolic regulation. In addition, physiologic blood flow regulation is also dependent on the activity of several coronary ion channels, including ATP-dependent K(+) channels, voltage-gated K(+) channels and others. In this context, ion channels contribute by matching demands for homeostatic maintenance. They play a primary role in rapid response of both endothelium and vascular smooth muscle cells of larger and smaller arterial vessels of the coronary bed, leading to coronary vasodilation. Consequently, an alteration in ion channel function or expression could be directly involved in coronary vasomotion dysfunction. PMID- 24180548 TI - Use of alternative medicine for hypertension in Buikwe and Mukono districts of Uganda: a cross sectional study. AB - BACKGROUND: Use of alternative medicine for chronic diseases such as hypertension is common in low as well as high income countries. This study estimated the proportion of people who were aware of their hypertension that use alternative medicine and identified factors predicting the use of alternative medicine. METHODS: In a community based cross sectional survey among people >= 15 years in Buikwe and Mukono districts of Uganda 258 people aware of their hypertension were questioned about use of alternative medicine for hypertension, advice about uptake of life style intervention for hypertension control such as reduction of salt intake and about their attitude towards use of alternative medicine. Proportions of people who used alternative medicine and adopt life style interventions and their 95% confidence intervals (CI) were calculated. Predictors of using alternative medicine were identified using logistic binary regression analysis. RESULTS: More than a half 144 (56.2%) had ever used alternative medicine whereas more than one in four 74 (28.6%) were currently using alternative medicine alone or in combination with modern medicine (50%). People who were using alternative medicine alone (29.7% CI 17.5-45.9) were less likely to have received advice on reduction of salt intake compared to those using modern medicine alone or in combination with traditional medicine (56.6%, CI 47.7 65.0). The only independent predictor for using alternative medicine was agreeing that alternative medicine is effective for treatment of hypertension (adjusted odds ratio [AOR] 2.6; 95% CI 1.40-4.82). CONCLUSION: The use of alternative medicine was common among patients with hypertension and usage was underpinned by the belief that alternative medicine is effective. As patients with hypertension use alternative medicine and modern medicine concurrently, there is need for open communication between health workers and patients regarding use of alternative medicine. PMID- 24180549 TI - Current evidence for the hepatoprotective activities of the medicinal mushroom Antrodia cinnamomea. AB - Antrodia cinnamomea (AC) is an endemic mushroom species of Taiwan, and has been demonstrated to possess diverse biological and pharmacological activities, such as anti-hypertension, anti-hyperlipidemia, anti-inflammation, anti-oxidation, anti-tumor, and immunomodulation. This review focuses on the inhibitory effects of AC on hepatitis, hepatocarcinoma, and alcohol-induced liver diseases (e.g., fatty liver, fibrosis). The relevant biochemical and molecular mechanisms are addressed. Overall, this review summarizes the hepatoprotective activities in vitro and in vivo. However, there is no doubt that human and clinical trials are still limited, and further studies are required for the development of AC-related products. PMID- 24180550 TI - Inhibitory effects of salidroside on nitric oxide and prostaglandin E2 production in lipopolysaccharide-stimulated RAW 264.7 macrophages. AB - The aim of this study was to evaluate the effect of salidroside on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophages and related anti-inflammatory mechanism. PGE2 production was measured by enzyme-linked immunosorbent assay (ELISA); NO production was tested by Griess reagent. Inducible nitric oxidesynthase (iNOS) and COX-2 were determined by RT-PCR and Western blot analysis; IkappaB and P IkappaB protein express were detected by Western blot analysis; cytosolic free Ca2+ ([Ca2+](i)) was measured by a fluorescent microscope. The data showed salidroside inhibited LPS-induced NO and PGE2 production and reduced iNOS and COX 2 protein expression in RAW 264.7 macrophages. Consistent with these observations, salidroside inhibited LPS-induced cytosolic free Ca2+ concentration ([Ca2+](i)) elevation. In addition, we further investigated signal transduction mechanisms and found that the activation of NF-kappaB was suppressed by salidroside in a dose-dependent manner. These results suggest that salidroside suppresses NO and PGE2 production by inhibiting iNOS and COX-2 protein expression, level of [Ca2+](i), and activation of NF-kappaB signal transduction pathway. PMID- 24180551 TI - Bioactive lipids, radical scavenging potential, and antimicrobial properties of cold pressed clove (Syzygium aromaticum) oil. AB - Health promoting cold pressed oils may improve human health and prevent certain diseases. It is hard to find any research concerning the composition and functional properties of cold pressed clove (Syzygium aromaticum) oil (CO). Cold pressed CO was evaluated for its lipid classes, fatty acid profiles, and tocol contents. In addition, antiradical and antimicrobial properties of CO were evaluated. The amounts of neutral lipids in CO was the highest (~94.7% of total lipids), followed by glycolipids and phospholipids. The main fatty acids in CO were linoleic and oleic, which comprise together ~80% of total fatty acids. Stearic and palmitic acids were the main saturated fatty acids. alpha- and gamma tocopherols and delta-tocotrienol were the main detected tocols. CO had higher antiradical action against DPPH* and galvinoxyl radicals than virgin olive oil. The results of antimicrobial properties revealed that CO inhibited the growth of all tested microorganisms. CO had a drastic effect on the biosynthesis of proteins and lipids in cells of Bacillus subtilis. In consideration of potential utilization, detailed knowledge on the composition and functional properties of CO is of major importance. PMID- 24180552 TI - Dietary and serum lycopene levels in prostate cancer patients undergoing intensity-modulated radiation therapy. AB - Tomato products, good sources of lycopene, may lower the incidence of prostate cancer, but data on the effectiveness of lycopene supplementation during radiation therapy are lacking. This study aimed to evaluate the tolerance and acceptance of three different amounts (4, 8, or 12 oz) of tomato juice (TJ) and their effect on serum lycopene during radiotherapy in 20 men with localized prostate cancer. Participants were randomized into a control group or one of three intervention groups who consumed TJ daily during treatment. Dietary lycopene intake was estimated using the National Cancer Institute (NCI) Diet History Questionnaire, and gastrointestinal tolerance of TJ was evaluated using the NCI Cancer Therapy Evaluation Program: Common Toxicity Criteria v 2.0. Serum and TJ lycopene levels were measured by liquid chromatography-mass spectrometry. TJ was well tolerated without any gastrointestinal side effects, and increased serum lycopene levels were observed in the 8 and 12 oz groups from baseline to endpoint. No correlation between serum and dietary lycopene was detected. Despite no reported change in dietary intake, non-significant weight loss was observed in the control group but not the intervention group participants. A significant positive correlation between serum lycopene, weight, and body mass index, and a negative correlation between serum lycopene and piror nutritional supplement use was detected. Weight change should be monitored and evaluated during treatment. Larger clinical trials are needed to validate the use of TJ to increase serum/dietary lycopene intake and correlate with side effects during radiotherapy in men with prostate cancer. PMID- 24180553 TI - Comparative study of volatile oil content and antimicrobial activity of pecan cultivars growing in Egypt. AB - The volatile oils obtained from the leaves of four pecan cultivars growing in Egypt were evaluated for their chemical composition and antimicrobial activity. The selected cultivars (cv.) were Carya illinoinensis (Wangneh.) K. Koch. cv. Wichita, C. illinoinensis cv. Western Schley, C. illinoinensis cv. Cherokee, and C. illinoinensis cv. Sioux. The gas chromatography-mass spectrometry analyses revealed that the volatile oils from samples of the different cultivars differ in composition and percentage of their components. beta-Curcumene was found as the major constituent of the cv. Wichita oil, whereas germacrene D was the major component of cv. Sioux, cv. Cherokee, and cv. Western Schley. The antimicrobial activity was assayed using the Kirby-Bauer Method by measuring the zone of inhibition of growth. All volatile oils displayed an antimicrobial activity against the tested bacterial strains. On the other hand, only the volatile oil of cv. Wichita showed an antifungal effect on Aspergillus flavus. This work has identified candidates of volatile oils for future in vivo studies to develop antibiotic substitutes for the diminution of human and animal pathogenic bacteria. Nevertheless, the variations of the volatile oil components and antimicrobial potencies of the different studied cultivars, necessitate identifying the cultivars used in future studies. PMID- 24180554 TI - Detection of colon polyps by a novel, polymer pattern-based full blood test. AB - Numerous studies have shown that early screening for the presence of pre cancerous colon polyps and their subsequent removal decreases the risk of developing colon cancer. Colonoscopy is currently the most effective screening method, but due to the invasive nature of the procedure many patients avoid forgo testing. Futhermore, the procedure itself requires perfect execution by the gastroenterologist. Against this backdrop, a non-invasive blood screening method for the detection of colon polyps that has higher sensitivity than current screening techniques would be beneficial in the early identification of patients at risk for colon cancer. A prospective, double-blinded, controlled clinical study was designed to demonstrate the diagnostic performance of Polyp Specific Polymer analysis, a novel laboratory methodology. The primary objective of this clinical trial was to estimate the diagnostic accuracy of the Polyp Specific Polymer analysis for colon polyps using colonoscopy and histological tests as the diagnostic accuracy standards. Secondary objectives of this trial included estimating positive and negative predictive values for colon polyps, investigating reliability, determining covariates influencing diagnostic accuracy and obtaining absolute and relative frequencies of valid test results.In patients undergoing screening colonoscopy and histology examination, a sensitivity of 72.4% and a specificity of 62.3% could be proven.These results indicate that using this improved screening method it is possible to effectively identify the highest-risk candidates for endoscopy, thereby advancing the goal of decreasing the incidence or mortality of colorectal cancer in the selected population. Moreover, this diagnostic tool has potential socio-economic implications, conserving healthcare resources by enabling higher patient selectivity for endoscopy and eventual transfer to curative prevention via polypectomy.By combining the best-established low-risk screening elements together with a validated, highly sensitive blood test as described in this study, a steadfast increase in the estimation of colorectal cancer-risk before colonoscopy can be expected. PMID- 24180555 TI - Electrophilic difluoro(phenylthio)methylation: generation, stability, and reactivity of alpha-fluorocarbocations. AB - Electrophilic difluoro(phenylthio)methylation of allylsilanes has been achieved using bromodifluoro(phenylthio)methane (PhSCF2Br) and silver hexafluoroantimonate (AgSbF6). The structural assignment and observation of alpha-fluorocarbocation were substantiated by NMR and theoretical calculations. Detailed mechanistic and electronic studies have provided a fundamental understanding of the reactivity and stability of the difluoro(phenylthio)methylium cation (PhSCF2(+)). PMID- 24180556 TI - Phenolics from Ageratina adenophora roots and their phytotoxic effects on Arabidopsis thaliana seed germination and seedling growth. AB - A bioassay-directed phytochemical study was conducted to investigate potential allelochemicals in the roots of the invasive plant Ageratina adenophora. Eleven phenolic compounds, including seven new ones, 7-hydroxy-8,9-dehydrothymol 9-O trans-ferulate (1), 7-hydroxythymol 9-O-trans-ferulate (2), 7,8-dihydroxythymol 9 O-trans-ferulate (3), 7,8-dihydroxythymol 9-O-cis-ferulate (4), methyl (7R)-3 deoxy-4,5-epoxy-D-manno-2-octulosonate 8-O-trans-p-coumarate (5), methyl (7R)-3 deoxy-4,5-epoxy-D-manno-2-octulosonate 8-O-cis-p-coumarate (6), and 3-(2 hydroxyphenyl)propyl methyl malonate (7), were isolated from a bioactive subfraction of the ethanol extract of the roots of A. adenophora. The new structures were established on the basis of detailed spectroscopic analysis. The potential phytotoxic effects of these compounds on the germination of Arabidopsis thaliana seeds were tested by a filter paper assay. Compound 7 and known compounds 3-(2-hydroxyphenyl)-1-propanol (8) and o-coumaric acid (9) remarkably showed inhibition activity against Arabidopsis seed germination at a concentration of 1.0 mM. Compounds 1, 2, 5, 6, and 10 showed slight inhibitory activity at the test concentration after treatment for 3 days, while the other compounds showed no obvious inhibitory effects. Moreover, 7-9 were further found to show obvious inhibitory activity on retarding the seedling growth of Ar. thaliana cultured in soil medium. PMID- 24180557 TI - Hydroxyindole carboxylic acid-based inhibitors for receptor-type protein tyrosine protein phosphatase beta. AB - AIMS: Protein tyrosine phosphatases (PTPs) play an important role in regulating a wide range of cellular processes. Understanding the role of PTPs within these processes has been hampered by a lack of potent and selective PTP inhibitors. Generating potent and selective probes for PTPs remains a significant challenge because of the highly conserved and positively charged PTP active site that also harbors a redox-sensitive Cys residue. RESULTS: We describe a facile method that uses an appropriate hydroxyindole carboxylic acid to anchor the inhibitor to the PTP active site and relies on the secondary binding elements introduced through an amide-focused library to enhance binding affinity for the target PTP and to impart selectivity against off-target phosphatases. Here, we disclose a novel series of hydroxyindole carboxylic acid-based inhibitors for receptor-type tyrosine protein phosphatase beta (RPTPbeta), a potential target that is implicated in blood vessel development. The representative RPTPbeta inhibitor 8b 1 (L87B44) has an IC50 of 0.38 MUM and at least 14-fold selectivity for RPTPbeta over a large panel of PTPs. Moreover, 8b-1 also exhibits excellent cellular activity and augments growth factor signaling in HEK293, MDA-MB-468, and human umbilical vein endothelial cells. INNOVATION: The bicyclic salicylic acid pharmacophore-based focused library approach may provide a potential solution to overcome the bioavailability issue that has plagued the PTP drug discovery field for many years. CONCLUSION: A novel method is described for the development of bioavailable PTP inhibitors that utilizes bicyclic salicylic acid to anchor the inhibitors to the active site and peripheral site interactions to enhance binding affinity and selectivity. PMID- 24180558 TI - DCE@urLAB: a dynamic contrast-enhanced MRI pharmacokinetic analysis tool for preclinical data. AB - BACKGROUND: DCE@urLAB is a software application for analysis of dynamic contrast enhanced magnetic resonance imaging data (DCE-MRI). The tool incorporates a friendly graphical user interface (GUI) to interactively select and analyze a region of interest (ROI) within the image set, taking into account the tissue concentration of the contrast agent (CA) and its effect on pixel intensity. RESULTS: Pixel-wise model-based quantitative parameters are estimated by fitting DCE-MRI data to several pharmacokinetic models using the Levenberg-Marquardt algorithm (LMA). DCE@urLAB also includes the semi-quantitative parametric and heuristic analysis approaches commonly used in practice. This software application has been programmed in the Interactive Data Language (IDL) and tested both with publicly available simulated data and preclinical studies from tumor bearing mouse brains. CONCLUSIONS: A user-friendly solution for applying pharmacokinetic and non-quantitative analysis DCE-MRI in preclinical studies has been implemented and tested. The proposed tool has been specially designed for easy selection of multi-pixel ROIs. A public release of DCE@urLAB, together with the open source code and sample datasets, is available at http://www.die.upm.es/im/archives/DCEurLAB/. PMID- 24180559 TI - Bronsted acid catalyzed and NIS-promoted cyclization of diynones: selective synthesis of 4-pyrone, 4-pyridone, and 3-pyrrolone derivatives. AB - Bronsted acid catalyzed tandem cyclization was found to be highly effective for the preparation of a series of polysubstituted 4-pyrones from diynones (yield up to 99%). 4-Pyridone and 3-pyrrolone derivatives were also selectively synthesized by employing NIS and/or Bronsted acid. NIS as an electrophilic reagent could promote these reactions efficiently and rapidly under very mild reaction conditions. PMID- 24180560 TI - Cost-effectiveness of hysterectomy for benign gynecological conditions: a systematic review. AB - The objective of this study was to assess the cost-effectiveness of hysterectomy performed for benign indications. Hysterectomy remains the most common major gynecological operation in the Western world. Rates of hysterectomy have not declined as expected with the introduction of new treatment options. Furthermore, use of laparoscopic techniques varies widely within the Nordic countries. We designed a systematic review in a University Central Hospital. The sample included all published studies regarding the cost-effectiveness of hysterectomy performed for benign indications (n = 1666). Medline, Cochrane Library, PsycINFO, CINAHL, and Nursing databases were searched. Inclusion criteria were the availability of pre- and post-intervention health-related quality of life measures (HRQoL) and data on costs. HRQoL, costs, and cost-effectiveness of treatment were the main outcome measures. Studies (n = 24) focused on treatment of symptomatic fibroids (n = 8), treatment of heavy menstrual bleeding (n = 10), various surgical techniques (n = 5) and the effect of various indications for hysterectomy (n = 2). Follow-up periods varied from 4 months to over 10 years. SF/RAND-36 or EQ-5D measures and societal cost perspective were most commonly used. Only 11 studies used individual patient data. HRQoL following hysterectomy was generally good but costs were high. The cost-effectiveness depended on indication, age, and duration of follow-up. The cost-effectiveness of hysterectomy has been surprisingly poorly studied. Conclusions are difficult to draw due to different study designs, indications, follow-up times, and HRQoL instruments used. Rates of hysterectomy have declined less than expected with the introduction of new treatment modalities. Costs of surgery are high. Laparoscopic hysterectomy seems to be the least cost-effective, although further data from original patient cohorts with long-term follow-up are needed. PMID- 24180561 TI - Role of alkyl group in the aromatic extraction using pyridinium-based ionic liquids. AB - The performance of N-alkylpyridinium-based ionic liquids with a SCN anion (PyILs) was evaluated for the selective extraction of aromatics from aliphatic hydrocarbons. The aromatic extraction ability of PyILs was greatly enhanced by the presence of a methyl group on the pyridinium ring at the 3- or 4-position, whereas the solubility of the aromatics in the PyILs decreased with increasing the number of methyl groups on the benzene ring. The FT-IR studies revealed that the solubility of an aromatic compound in a PyIL is closely correlated with the degree of aromatic C-H bending frequency shift observed during the dissolution of the aromatic compound in the PyIL: the larger the shift, the higher the solubility. The computational calculations on the dispersion interactions between aromatics and PyILs demonstrated that the anion-aromatic interaction is much more important than the cation-aromatic interaction in determining the aromatic solubility in PyILs, and such anion-aromatic interaction can be enhanced by introducing a methyl group at the carbon atom of the pyridinium ring. PMID- 24180562 TI - Implementation of a Standard Verbal Sign-Out Template Improves Sign-Out Process in a Pediatric Intensive Care Unit. AB - Sign-out of patient data at change of shifts is vulnerable to errors that impact patient safety. Although sign-outs are complex in intensive care units (ICU), a paucity of studies exists evaluating optimal ICU sign-out. Our prospective interventional study investigated the use of a standard verbal template in a Pediatric ICU to improve the sign-out process. We designed and validated a survey tool to measure 10 items of optimal sign-out. The survey and analysis of sign-out information exchanged was performed pre- and postintervention. Forty-eight clinicians participated, with a survey response rate of 88% and 81% in the pre- and postintervention phases, respectively. Seventy-nine percent clinicians identified the need for sign-out improvement. Clinician satisfaction with sign out increased postintervention (preintervention survey scores: 3.26 (CI: 3.09 3.43), postintervention 3.9 (CI: 3.76-4.04) [p < .01]). Three scorers analyzed the verbal and written sign-out content with good inter-rater reliability. After the intervention, sign-out content revealed increased patient identification, background description, account of system-based clinical details [p = .001] and notation of clinical details, code status, and goals [p < .002]. Interruptions decreased [p = .04] without any change in sign-out duration [p = .86]. The standard verbal template improved clinician satisfaction with sign-out, augmented the amount of information transferred and decreased interruptions without increasing the duration of sign-out. PMID- 24180563 TI - Measuring gender satisfaction among women aging with paralytic polio. AB - In this study we tested the Gendered Outcome Scale as a measure of gender satisfaction among 295 women aging with the disabling effects of paralytic polio. Principal components analysis, reliability analyses, and content validity were analyzed on the scale. The scale had a Cronbach's alpha of.90. Younger women had more gender satisfaction (r =.181, p <.01), and women who had greater disability had greater gender satisfaction. (r = -.127, p <.05). The results support that the scale is a valid and reliable measure for determing gender satisfaction. Further work is needed to test the scale in diversified samples. PMID- 24180564 TI - Fiber intake and glycemic control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials. AB - This systematic review with meta-analysis of randomized controlled trials (RCT) aimed to analyze the effect of fiber intake on glycemic control in patients with type 2 diabetes. Databases were searched up to November 2012 using the following medical subject headings: diabetes, fiber, and randomized controlled trial. Absolute changes in glycated hemoglobin and fasting plasma glucose were reported as differences between baseline and end-of-study measures. Pooled estimates were obtained using random-effects models. Of the 22,046 articles initially identified, 11 (13 comparisons; range of duration, 8-24 weeks) fulfilled the inclusion criteria, providing data from 605 patients. High-fiber diets, including diets with foods rich in fiber (up to 42.5 g/day; four studies) or supplements containing soluble fiber (up to 15.0 g/day; nine studies), reduced absolute values of glycated hemoglobin by 0.55% (95% CI -0.96 to -0.13) and fasting plasma glucose by 9.97 mg/dL (95% CI -18.16 to -1.78). In conclusion, increased fiber intake improved glycemic control, indicating it should be considered as an adjunctive tool in the treatment of patients with type 2 diabetes. PMID- 24180565 TI - Propofol for severe traumatic brain injury. PMID- 24180566 TI - Surgical management of traumatic brain injury: a comparative-effectiveness study of 2 centers. AB - OBJECT: Mass lesions from traumatic brain injury (TBI) often require surgical evacuation as a life-saving measure and to improve outcomes, but optimal timing and surgical technique, including decompressive craniectomy, have not been fully defined. The authors compared neurosurgical approaches in the treatment of TBI at 2 academic medical centers to document variations in real-world practice and evaluate the efficacies of different approaches on postsurgical course and long term outcome. METHODS: Patients 18 years of age or older who required neurosurgical lesion evacuation or decompression for TBI were enrolled in the Co Operative Studies on Brain Injury Depolarizations (COSBID) at King's College Hospital (KCH, n = 27) and Virginia Commonwealth University (VCU, n = 24) from July 2004 to March 2010. Subdural electrode strips were placed at the time of surgery for subsequent electrocorticographic monitoring of spreading depolarizations; injury characteristics, physiological monitoring data, and 6 month outcomes were collected prospectively. CT scans and medical records were reviewed retrospectively to determine lesion characteristics, surgical indications, and procedures performed. RESULTS: Patients enrolled at KCH were significantly older than those enrolled at VCU (48 vs 34 years, p < 0.01) and falls were more commonly the cause of TBI in the KCH group than in the VCU group. Otherwise, KCH and VCU patients had similar prognoses, lesion types (subdural hematomas: 30%-35%; parenchymal contusions: 48%-52%), signs of mass effect (midline shift >= 5 mm: 43%-52%), and preoperative intracranial pressure (ICP). At VCU, however, surgeries were performed earlier (median 0.51 vs 0.83 days posttrauma, p < 0.05), bone flaps were larger (mean 82 vs 53 cm(2), p < 0.001), and craniectomies were more common (performed in 75% vs 44% of cases, p < 0.05). Postoperatively, maximum ICP values were lower at VCU (mean 22.5 vs 31.4 mm Hg, p < 0.01). Differences in incidence of spreading depolarizations (KCH: 63%, VCU: 42%, p = 0.13) and poor outcomes (KCH: 54%, VCU: 33%, p = 0.14) were not significant. In a subgroup analysis of only those patients who underwent early (< 24 hours) lesion evacuation (KCH: n = 14; VCU: n = 16), however, VCU patients fared significantly better. In the VCU patients, bone flaps were larger (mean 85 vs 48 cm(2) at KCH, p < 0.001), spreading depolarizations were less common (31% vs 86% at KCH, p < 0.01), postoperative ICP values were lower (mean: 20.8 vs 30.2 mm Hg at KCH, p < 0.05), and good outcomes were more common (69% vs 29% at KCH, p < 0.05). Spreading depolarizations were the only significant predictor of outcome in multivariate analysis. CONCLUSIONS: This comparative-effectiveness study provides evidence for major practice variation in surgical management of severe TBI. Although ages differed between the 2 cohorts, the results suggest that a more aggressive approach, including earlier surgery, larger craniotomy, and removal of bone flap, may reduce ICP, prevent cortical spreading depolarizations, and improve outcomes. In particular, patients requiring evacuation of subdural hematomas and contusions may benefit from decompressive craniectomy in conjunction with lesion evacuation, even when elevated ICP is not a factor in the decision to perform surgery. PMID- 24180567 TI - Comprehensive analysis of neurobehavior associated with histomorphological alterations in a chronic constrictive nerve injury model through use of the CatWalk XT system. AB - OBJECT: Neuropathic pain is debilitating, and when chronic, it significantly affects the patient physically, psychologically, and socially. The neurobehavior of animals used as a model for chronic constriction injury seems analogous to the neurobehavior of humans with neuropathic pain. However, no data depicting the severity of histomorphological alterations of the nervous system associated with graded changes in neurobehavior are available. To determine the severity of histomorphological alteration related to neurobehavior, the authors created a model of chronic constrictive injury of varying intensity in rats and used the CatWalk XT system to evaluate neurobehavior. METHODS: A total of 60 Sprague Dawley rats, weighing 250-300 g each, were randomly assigned to 1 of 5 groups that would receive sham surgery or 1, 2, 3, or 4 ligatures of 3-0 chromic gut loosely ligated around the left sciatic nerve. Neurobehavior was assessed by CatWalk XT, thermal hyperalgesia, and mechanic allodynia before injury and periodically after injury. The nerve tissue from skin to dorsal spinal cord was obtained for histomorphological analysis 1 week after injury, and brain evoked potentials were analyzed 4 weeks after injury. RESULTS: Significant differences in expression of nerve growth factor existed in skin, and the differences were associated with the intensity of nerve injury. After injury, expression of cluster of differentiation 68 and tumor necrosis factor-alpha was increased, and expression of S100 protein in the middle of the injured nerve was decreased. Increased expression of synaptophysin in the dorsal root ganglion and dorsal spinal cord correlated with the intensity of injury. The amplitude of sensory evoked potential increased with greater severity of nerve damage. Mechanical allodynia and thermal hyperalgesia did not differ significantly among treatment groups at various time points. CatWalk XT gait analysis indicated significant differences for print areas, maximum contact maximum intensity, stand phase, swing phase, single stance, and regular index, with sham and/or intragroup comparisons. CONCLUSIONS: Histomorphological and electrophysiological alterations were associated with severity of nerve damage. Subtle neurobehavioral differences were detected by the CatWalk XT system but not by mechanical allodynia or thermal hyperalgesia. Thus, the CatWalk XT system should be a useful tool for monitoring changes in neuropathic pain, especially subtle alterations. PMID- 24180568 TI - Perforators. PMID- 24180569 TI - Durable thrombosis in a rat model of arteriovenous malformation treated with radiosurgery and vascular targeting. AB - OBJECT: Radiosurgical treatment of brain arteriovenous malformations (AVMs) has the significant shortcomings of being limited to lesions smaller than 3 cm in diameter and of a latency-to-cure time of up to 3 years. A possible method of overcoming these limitations is stimulation of thrombosis by using vascular targeting. Using an animal model of AVM, the authors examined the durability of the thrombosis induced by the vascular-targeting agents lipopolysaccharide and soluble tissue factor conjugate (LPS/sTF). METHODS: Stereotactic radiosurgery or sham radiation was administered to 32 male Sprague-Dawley rats serving as an animal model of AVM; 24 hours after this intervention, the rats received an intravenous injection of LPS/sTF or normal saline. The animals were killed at 1, 7, 30, or 90 days after treatment. Immediately beforehand, angiography was performed, and model AVM tissue was harvested for histological analysis to assess rates of vessel thrombosis. RESULTS: Among rats that received radiosurgery and LPS/sTF, induced thrombosis occurred in 58% of small AVM vessels; among those that received radiosurgery and saline, thrombosis occurred in 12% of small AVM vessels (diameter < 200 MUm); and among those that received LPS/sTF but no radiosurgery, thrombosis occurred at an intermediate rate of 43%. No systemic toxicity or intravascular thrombosis remote from the target region was detected in any of the animals. CONCLUSIONS: Vascular targeting can increase intravascular thrombosis after radiosurgery, and the vessel occlusion is durable. Further work is needed to refine this approach to AVM treatment, which shows promise as a way to overcome the limitations of radiosurgery. PMID- 24180570 TI - Arteriovenous malformations. PMID- 24180571 TI - Blood-brain barrier. PMID- 24180572 TI - Effects of erythropoietin. PMID- 24180573 TI - Thyroid and meningioma. PMID- 24180574 TI - High incidence of ICA anterior wall aneurysms in patients with an anomalous origin of the ophthalmic artery: possible relevance to the pathogenesis of aneurysm formation. AB - OBJECT: Surgery for aneurysms at the anterior wall of the internal carotid artery (ICA), which are also referred to as ICA anterior wall aneurysms, is often challenging. A treatment strategy needs to be determined according to the pathology of the aneurysm-namely, whether the aneurysm is a saccular aneurysm with firm neck walls that would tolerate clipping or coiling, a dissecting aneurysm, or a blood blister-like aneurysm. However, it is not always possible to properly evaluate the condition of the aneurysm before surgery solely based on angiographic findings. METHODS: The authors focused on the location of the ophthalmic artery (OA) in determining the pathology of ICA anterior wall aneurysms. Between January 2006 and December 2012, diagnostic cerebral angiography, for any reason, was performed on 1643 ICAs in 855 patients at Saitama Medical Center. The authors also investigated the relationship between the origin of the OA and the incidence of ICA anterior wall aneurysms. The pathogenesis was also evaluated for each aneurysm based on findings from both angiography and open surgery to identify any correlation between the location where the OA originated and the conditions of the aneurysm walls. RESULTS: Among 1643 ICAs, 31 arteries (1.89%) were accompanied by an anomalous origin of the OA, including 26 OAs originating from the C3 portion, 3 originating from the C4 portion, and 2 originating from the anterior cerebral artery. The incidence of an anomalous origin of the OA had no relationship to age, sex, or side. Internal carotid artery anterior wall aneurysms were observed in 16 (0.97%) of 1643 ICAs. Female patients had a significantly higher risk of having ICA anterior wall aneurysms (p = 0.026). The risk of ICA anterior wall aneurysm formation was approximately 50 times higher in patients with an anomalous origin of the OA (25.8% [8 of 31]) than in those with a normal OA (0.5% [8 of 1612], p < 0.0001). Based on angiographic classifications, saccular aneurysms were significantly more common in patients with an anomalous origin of the OA than in those with a normal OA (p = 0.041). Ten of 16 patients with ICA anterior wall aneurysms underwent craniotomies. Based on the intraoperative findings, all 6 aneurysms with normal OAs were dissecting or blood blister-like aneurysms, not saccular aneurysms. CONCLUSIONS: There was a close relationship between the location of the OA origin and the predisposition to ICA anterior wall aneurysms. Developmental failure of the OA and subsequent weakness of the vessel wall might account for this phenomenon, as previously reported regarding other aneurysms related to the anomalous development of parent arteries. The data also appear to indicate that ICA anterior wall aneurysms in patients with an anomalous origin of the OA tend to be saccular aneurysms with normal neck walls. These findings provide critical information in determining therapeutic strategies for ICA anterior wall aneurysms. PMID- 24180575 TI - Trigeminal neuralgia. PMID- 24180576 TI - Cell transplantation. PMID- 24180577 TI - Hyperbranched quasi-1D nanostructures for solid-state dye-sensitized solar cells. AB - In this work we demonstrate hyperbranched nanostructures, grown by pulsed laser deposition, composed of one-dimensional anatase single crystals assembled in arrays of high aspect ratio hierarchical mesostructures. The proposed growth mechanism relies on a two-step process: self-assembly from the gas phase of amorphous TiO2 clusters in a forest of tree-shaped hierarchical mesostructures with high aspect ratio; oriented crystallization of the branches upon thermal treatment. Structural and morphological characteristics can be optimized to achieve both high specific surface area for optimal dye uptake and broadband light scattering thanks to the microscopic feature size. Solid-state dye sensitized solar cells fabricated with arrays of hyperbranched TiO2 nanostructures on FTO-glass sensitized with D102 dye showed a significant 66% increase in efficiency with respect to a reference mesoporous photoanode and reached a maximum efficiency of 3.96% (among the highest reported for this system). This result was achieved mainly thanks to an increase in photogenerated current directly resulting from improved light harvesting efficiency of the hierarchical photoanode. The proposed photoanode overcomes typical limitations of 1D TiO2 nanostructures applied to ss-DSC and emerges as a promising foundation for next-generation high-efficiency solid-state devices comprosed of dyes, polymers, or quantum dots as sensitizers. PMID- 24180578 TI - Stable hemoglobin in hemodialysis patients: forest for the trees--a 12-week pilot observational study. AB - BACKGROUND: Hemoglobin (Hb) variability is a common occurrence in hemodialysis patients treated with erythropoiesis-stimulating agents. High amplitude fluctuations have been associated with greater risk of morbidity and mortality. METHODS: This prospective, single centre pilot observational study was conducted over a 3-month period in daily practice patterns, to assess per-dialysis events and inter-dialysis complications that could interfere with erythropoiesis in patients undergoing hemodialysis. RESULTS: Mean Hb levels remained stable in the 78 evaluable patients, as did darbepoetin alfa (DA) doses, including in patients suffering from diabetes or cardiac affections. In total, an average of 7.7 events / patient / month occurred, but no significant relationship with Hb excursions was shown. CONCLUSION: The observation of 7.7 events per patient per month suggests a careful monitoring of Hb and DA dosing every other week, in order to maintain Hb level within the target. PMID- 24180579 TI - Membrane TNF-alpha-activated programmed necrosis is mediated by Ceramide-induced reactive oxygen species. AB - BACKGROUND: Programmed necrosis is a form of caspase-independent cell death whose molecular regulation is poorly understood. While tumor necrosis factor-alpha (TNF alpha) has been identified as an activator of programmed necrosis, the specific context under which this can happen is unclear. Recently we reported that TNF alpha can be expressed by human tumor cells as both a membrane tethered (mTNF alpha) and a soluble (sTNF-alpha) form. Whereas low level, tumor-derived sTNF alpha acts as a tumor promoter, tumor cell expression of mTNF-alpha significantly delays tumor growth in mice, in large part by induction of programmed necrosis of tumor associated myeloid cells. In this study we sought to determine the molecular mechanism involved in mTNF-alpha oxidative stress-induced cell death by evaluating the known pathways involved in TNF receptor-induced programmed necrosis. METHODS: The source of Reactive Oxygen Species (ROS) in mTNF-alpha treated cells was determined by coculturing RAW 264.7 monocytic and L929 fibroblasts cells with fixed B16F10 control or mTNF-alpha expressing-melanoma cells in the presence of inhibitors of NADPH and mitochondria ROS. To identify the down-stream effector of TNF-a receptors (TNFR), level of phospho-RIP-1 and ceramide activity were evaluated.To determine whether mTNF-mediated cell death was dependent on a specific TNFR, cell death was measured in primary CD11b myeloid cells isolated from wild-type or TNFR-1, TNFR-2, TNFR-1 and TNFR-2 double knockout mice, cocultured with various TNF-alpha isoform. RESULTS: Tumor derived mTNF-alpha increased ROS-mediated cytotoxicity, independent of caspase-3 activity. Although TNFR on target cells were required for this effect, we observed that mTNF-induced cell death could be mediated through both TNFR-1 and the death domain-lacking TNFR-2. ROS generation and cytotoxicity were inhibited by a mitochondrial respiratory chain inhibitor but not by an inhibitor of NADPH oxidase. mTNF-alpha mediated cytotoxicity was independent of RIP-1, a serine/threonine kinase that serves as a main adaptor protein of sTNF-alpha induced programmed necrosis. Instead, mTNF-alpha-induced ROS and cell death was prohibited by the ceramide-activated protein kinase (CAPK) inhibitor. CONCLUSION: These findings demonstrate that the mTNF-alpha isoform is an effective inducer of programmed necrosis through a caspase independent, ceramide-related pathway. Interestingly, unlike sTNFalpha, mTNF-induced programmed necrosis is not dependent on the presence of TNFR1. PMID- 24180580 TI - Time to reinvent the science of dementia: the need for care and social integration. AB - OBJECTIVES: The increasing number of older adults with dementia is a large and growing public health problem. Alzheimer's disease, the prevailing form of dementia, is projected to quadruple worldwide. To date, the care and social integration of individuals with dementia is complicated by limited collaborations between biomedicine and other disciplines. The objective of this paper is therefore to reflect on the orientation of biomedicine with regard to the science of dementia, and to articulate a path for moving forward. METHODS: The authors drew upon, and expanded, the insights of an interdisciplinary, international workshop entitled 'Bioethics and the Science of Aging: The Case of Dementia' held in October 2012 at the University of California in Berkeley. RESULTS: The care of individuals with dementia compels solid interdisciplinary collaborations. There are several issues affecting the care of individuals with dementia: (1) an evolving definition of dementia; (2) the ambiguous benefits of the diagnosis of dementia; (3) ethical conflicts concerning consent processes and clinical trials; and (4) a limited understanding of the perspective of the person with dementia. CONCLUSION: We argue that it is time for a renewed dialogue between biomedicine and other disciplines -- particularly public health, the social sciences, the medical humanities and bioethics. This interdisciplinary dialogue would facilitate a process of self-reflection within biomedicine. This dialogue will also provide the foundation for equitable public health interventions and will further prioritize the values and preferences of individuals with dementia, as well as their care and social integration. PMID- 24180581 TI - Daphnid life cycle responses to new generation flame retardants. AB - Relatively hazardous brominated flame retardants (BFRs) are currently substituted with halogen-free flame retardants (HFFRs). Consequently, information on their persistence, bioaccumulation and toxicity (PBT) is urgently needed. Therefore, we investigated the chronic toxicity to the water flea Daphnia magna of two HFFRs, aluminum diethylphosphinate (ALPI) and 9,10-dihyro-9-oxa-10-phosphaphenanthrene oxide (DOPO). The toxicity of ALPI increased from a 48 h LC50 of 18 mg L(-1) to a 21 day LC50 value of 3.2 mg L(-1), resulting in an acute-to-chronic ratio of 5.6. This may imply a change in classification from low to moderate toxicity. ALPI also affected sublethal life cycle parameters, with an EC50 of 2.8 mg L(-1) for cumulative reproductive output and of 3.4 mg L(-1) for population growth rate, revealing a nonspecific mode of action. DOPO showed only sublethal effects with an EC50 value of 48 mg L(-1) for cumulative reproductive output and an EC50 value of 73 mg L(-1) for population growth rate. The toxicity of DOPO to D. magna was classified as low and likely occurred above environmentally relevant concentrations, but we identified specific effects on reproduction. Given the low chronic toxicity of DOPO and the moderate toxicity of ALPI, based on this study only, DOPO seems to be more suitable than ALPI for BFR replacement in polymers. PMID- 24180583 TI - Editorial: Opinion Pieces. PMID- 24180582 TI - Efficacy of clindamycin in reducing pain following tonsillectomy in adults: a double-blind, randomised trial. AB - OBJECTIVE: Tonsillectomy is a common operation performed in children and young adults. Pain and post-operation haemorrhage are its most common complications. This study was designed to evaluate the efficacy of topical antibiotics in reducing throat pain after tonsillectomy in adult patients. METHODS: A double blind, placebo-controlled, randomised clinical trial was conducted, enrolling 30 patients older than 18 years who were scheduled to undergo tonsillectomy. Patients were randomly assigned to receive either clindamycin or normal saline (as placebo). Throat pain severity was evaluated using a visual analogue scale. RESULTS: All patients in both groups had experienced a reduction in pain by the seventh day after surgery. There was no statistically significant difference in the extent of visual analogue scale pain score reduction, comparing the placebo and clindamycin groups throughout the study course (p = 0.424). CONCLUSION: Topical clindamycin was not demonstrated to be more effective than normal saline in the reduction of throat pain following tonsillectomy in adults. PMID- 24180584 TI - An oriented handcuff rotaxane. AB - The first example of an oriented handcuff rotaxane has been obtained by through the-annulus threading of a double-calix[6]arene system with a bis-ammonium axle. The relative orientation of the two calix-wheels can be predefined by exploiting the "endo-alkyl rule" which controls the directionality of the threading of alkylbenzylammonium axles with calixarene macrocycles. PMID- 24180585 TI - Total nasal resistance among Sasang constitutional types: a population-based study in Korea. AB - BACKGROUND: There have been many attempts to find an objective phenotype by Sasang constitutional types (SCTs) on an anatomical, physiological, and psychological basis, but there has been no research on total nasal resistance (TNR) among SCTs. METHODS: We assessed the value of the TNR in the SCTs classified by an integrated diagnostic model. Included in the study were 1,346 individuals (701 males, 645 females) who participated in the Korean Genome and Epidemiology Study (KoGES). The TNR was measured by active anterior rhinomanometry (AAR) at transnasal pressures of 100 and 150 Pascal (Pa). RESULTS: The average TNR was 0.186 +/- 0.004 Pa/cm3/second at 100 Pa in the Tae-eum (TE), 0.193 +/- 0.007 in the So-eum (SE), and 0.208 +/- 0.005 in the So-yang (SY) types. Under condition of 150 Pa the TE type had a TNR value of 0.217 +/- 0.004, the SE type was 0.230 +/- 0.008, and the SY type was 0.243 +/- 0.005. Higher values of TNR were more likely to be reported in the SY type at 100 Pa and 150 Pa. In the stratified analysis by sex, the SY type in males and females tended to have higher TNR value than the TE and SE types at transnasal pressure of both 100 Pa and 150 Pa. CONCLUSIONS: These results provide new approaches to understand the functional characteristics among the SCTs in terms of nasal physiology. Further studies are required to clarify contributing factors for such a difference. PMID- 24180586 TI - Phosphorylated fragile X mental retardation protein at serine 499, is reduced in cerebellar vermis and superior frontal cortex of subjects with autism: implications for fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling. AB - Lohith et al. (Mol Autism 4:15, 2013) recently identified increased metabotropic glutamate receptor 5 (mGluR5) expression in the frontal cortex (FC) of subjects with fragile X syndrome. These results are consistent with postmortem findings in cerebellar vermis and FC of subjects with autism (Fatemi and Folsom, Mol Autism 2:6, 2011; Fatemi et al. Anat Rec 294:1635-1645, 2011), suggesting that increased mGluR5 signaling is common to multiple autism spectrum disorders. Increased mGluR5 signaling may be associated with reduced phosphorylation of fragile X mental retardation protein (FMRP), which could result in the inactivation of this protein. In the current study, we report on reduced expression of phosphorylated FMRP in cerebellar vermis of adults and children with autism and in FC of adults with autism. PMID- 24180587 TI - Prevalence and characteristics of Listeria monocytogenes in feces of black beef cattle reared in three geographically distant areas in Japan. AB - This study was conducted to determine the prevalence and characteristics of Listeria monocytogenes in the feces of black beef cattle reared in geographically distant areas in Japan. We surveyed 130 farms in the following three areas: northern (Hokkaido prefecture), central (Gifu and Mie prefectures), and southern (Oita, Miyazaki, and Kagoshima prefectures) areas and collected 1738 fecal samples. Our data showed the following isolation rate for each area: northern, 11.4% of 651; central, 2.8% of 572; and southern, 2.9% of 515, indicating that the isolation rate in the northern area was significantly higher than that in the central or southern areas (p<0.01). Moreover, serotyping of 996 isolates identified 1/2b as the most prevalent serotype (40.5%), followed by 1/2a (36.9%), 4b (21.6%), and 4ab (1.0%). In the northern area, multiple serotypes were isolated from 60% of L. monocytogenes-positive farms. In addition, multiple serotypes were isolated from individual fecal samples from 18 cattle. Pulsed field gel electrophoresis (PFGE) characterization of 239 isolates detected 48 different PFGE types. We found that isolates from northern farms were genetically diverse compared to those from central and southern farms. Five isolates from human clinical cases and three isolates from animal clinical cases were identical to isolates from black beef cattle. Furthermore, the isolates from northern and central farms were characterized to possess epidemic clone II or III markers. We next showed that the isolates were susceptible to penicillin, ampicillin, amoxicillin, gentamicin, kanamycin, streptomycin, erythromycin, vancomycin, tetracycline, chloramphenicol, ciprofloxacin, and trimethoprim/sulfamethoxazole. Taken together, our survey provides crucial data regarding the prevalence and characteristics of L. monocytogenes in black beef cattle farms throughout Japan. PMID- 24180588 TI - Clinical evaluation of two desensitizing treatments in southern Brazil: A 3-month follow-up. AB - OBJECTIVE: This study aimed to evaluate and compare the effectiveness of two treatments for dentin hypersensitivity in vivo during 90 days of follow-up. MATERIALS AND METHODS: The sample consisted of 117 teeth (13 patients) that were divided into three groups: control with carbomer 940 gel (n = 32) (placebo treatment), 2% sodium fluoride gel (n = 31) and low-level infrared diode laser (n = 54). Prior to the desensitizing treatment, the dentin hypersensitivity status of each tooth was assessed by an evaporative stimulus; the patient's response was evaluated using the Visual Analogue Scale (VAS) and by counting the Exposure Time to Air Blast (ETAB) with a dental air syringe. Re-evaluations of the treatments occurred after 5 min, 7, 15, 30 and 90 days. The statistical analysis was performed using the Kruskal-Wallis test, Friedman test, one-way ANOVA, Tukey's test and Spearman's rank correlation (alpha = 5%). RESULTS: No significant differences were observed among the low-level laser, 2% topical fluoride and carbomer 940 gel applications. When the methods of evaluation (VAS and ETAB) were compared, there was no difference among the groups with respect to the values for every period of evaluation (p < 0.001), verifying that the scores obtained with the VAS decreased at the same proportion as the remaining time of ETAB increased. CONCLUSIONS: This study showed that both tested therapies were efficacious in controlling painful symptoms associated with dentin hypersensitivity over the entire 90-day follow-up period. The treatments were able to reduce the painful symptoms caused by dentin hypersensitivity, including placebo. PMID- 24180589 TI - Antifungal activity of several root canal sealers against Candida albicans. AB - OBJECTIVE: The purpose of this in vitro study was to evaluate the antifungal activity of several root canal sealers (iRoot SP, MTA Fillapex and GuttaFlow) against Candida albicans and compare them to that of AH Plus Jet. MATERIALS AND METHODS: A 10 MUL fungi in suspension was allowed to directly contact the sealers, which were freshly mixed or allowed to set for 1 or 7 days. Fresh media was then added and survival of fungi was determined by using 10-fold serial dilution and inoculated onto agar plates. After incubation for 48 h, colony forming units (CFU) were calculated and their log10 values converted. The data were analyzed using ANOVA and Tukey tests (alpha = 0.05). RESULTS: Freshly mixed AH Plus Jet totally inhibited the growth of fungi and showed the highest antifungal activity. GuttaFlow did not show any significant antifungal activity at all times. Freshly mixed iRoot SP and MTA Fillapex were found to be antifungal. Statistical differences were found between freshly mixed and set samples (p < 0.05) in favor of the former, except GuttaFlow. No statistically significant differences were found among the tested sealers at the 1 and 7-day samples (p > 0.05). CONCLUSIONS: Fresh AH Plus Jet had very potent antifungal activity. All sealers, except GuttaFlow, exhibited antifungal activity when freshly mixed. PMID- 24180590 TI - Changes in the supragingival microbiota surrounding brackets of upper central incisors during orthodontic treatment. AB - OBJECTIVE: The aim of this study was to determine how fixed orthodontic appliances affect microbiota of supragingival plaque over 5 months. MATERIALS AND METHODS: Twenty individuals of Scandinavian origin, aged 10-16 years, were included. All subjects were fitted with fixed orthodontic appliances in both the maxillary and mandibular tooth arches. Pooled supragingival plaque samples from the labial surface of the two maxillary central incisors were collected before bonding (T1) and afterwards at 4 weeks (T2), 3 months (T3) and 5 months (T4). The plaque index (PI) was recorded for each sampling. The gingival status was documented at T1 and T4 by using clinical photographs. Plaque microbiota was identified using the Human Oral Microbe Identification Microarray (HOMIM). RESULTS: Increased plaque levels were recorded after bonding, however the increase was not significant. The prevalence of gingivitis at the maxillary central incisors increased from 25% at T1 to 74% at T4. No significant changes of the plaque microbiota from the sample area were detected during the 5-month period. Trends toward a microbiota containing more periodontitis- and caries associated bacteria were detected. CONCLUSIONS: Although trends toward a microbiota containing more periodontitis- and caries-associated bacteria were detected, the changes were not severe enough to be significant. Treatment with fixed orthodontics does not necessarily shift the microbiota to a more pathogenic composition. PMID- 24180591 TI - Nucleophilic catalysis of MeON-neoglycoside formation by aniline derivatives. AB - Neoglycosylations are increasingly being employed in the synthesis of natural products, drug candidates, glycopeptide mimics, oligosaccharide analogues, and other applications, but the efficiency of these reactions is usually limited by slow reaction times. Here, we show that aniline derivatives such as 2-amino-5 methoxybenzoic acid enhance the rate of acid-catalyzed neoglycosylation for a range of sugar substrates up to a factor of 32 relative to the uncatalyzed reaction. PMID- 24180592 TI - The role of c-Src in integrin (alpha6beta4) dependent translational control. AB - BACKGROUND: Integrin alpha6beta4 contributes to cancer progression by stimulating transcription as well as translation of cancer related genes. Our previous study demonstrated that alpha6beta4 stimulates translation initiation of survival factors such as VEGF by activating mTOR pathway. However, the immediate early signaling events that link alpha6beta4 to mTOR activation needs to be defined. RESULTS: In the current studies, we demonstrated that c-Src is an immediate early signaling molecule that acts upstream of alpha6beta4 dependent mTOR activation and subsequent translation of VEGF in MDA-MB-435/beta4 and MDA-MB-231 cancer cells. m7GTP-Sepharose-binding assay revealed that Src activity is required to form eIF4F complex which is necessary for Cap-dependent translation in alpha6beta4 expressing human cancer cells. CONCLUSIONS: Overall, our studies suggest that integrin beta4 and c-Src activation is important early signaling events to lead mTOR activation and cap-dependent translation of VEGF. PMID- 24180593 TI - Urinary excretion of phenolic acids in rats fed cranberry, blueberry, or black raspberry powder. AB - Dietary polyphenolics can be converted into smaller phenolic acids (PA) by microorganisms in the colon and may contribute to health benefits associated with the parent polyphenolics. Urinary excretion of 18 PA and their conjugates was studied, using HPLC-MS/MS, in rats fed AIN93G-based diets containing 5% (dry weight basis) of either cranberry (CB), blueberry (BB), or black raspberry (BRB). Hippuric, 4-hydroxyphenylacetic, 3-methoxy-4-hydroxyphenylacetic, and 4 hydroxybenzoic acids were excreted in greatest quantity in the urine over a 24 h period in all diets. Primary PA excreted in the berry diets were 4 hydroxycinnamic acid for CB; chlorogenic, ferulic, and 3,4-dihydroxycinnamic acids for BB; and 3-hydroxyphenylpropionic, 3-hydroxybenzoic, and 3 hydroxycinnamic acids for BRB. PA were present in conjugated form with cinnamic acid derivatives being 50-70% and phenylacetic acid derivatives conjugated <10%. Conjugated, and not just the free, PA are significant contributors to total urinary excretion. PMID- 24180594 TI - Hypergammaglobulinemia in the pediatric population as a marker for underlying autoimmune disease: a retrospective cohort study. AB - BACKGROUND: The significance of hypergammaglobulinemia as a marker of immune activation is unknown, as a differential diagnosis for hypergammaglobulinemia in children has not been adequately established. The goal of this study was to identify conditions associated with hypergammaglobulinemia in children, with the hypothesis that elevated immunoglobulin levels may precede or predict the development of autoimmune conditions. METHODS: We reviewed the medical records for all children with IgG level >=2000 mg/dL treated at a tertiary care children's hospital from January 1, 2000 through December 31, 2009. We compared clinical and laboratory features of these patients, and developed an algorithm to predict the likelihood of underlying autoimmunity based on these characteristics. RESULTS: After excluding children who had received IVIG, a total of 442 patients with hypergammaglobulinemia were identified. Of these, nearly half had autoimmune conditions, most frequently systemic lupus erythematosus and lupus-related disorders. Autoimmune gastrointestinal disorders such as inflammatory bowel disease were also common. Infectious diseases were the next largest category of diseases, followed with much less frequency by malignant, drug-related, and other conditions. In comparison with non-autoimmune conditions, patients with autoimmune disease had higher IgG levels, lower white blood cell counts, lower hemoglobin values, and lower C-reactive protein (CRP) levels. Multivariable logistic regression confirmed that CRP (P = 0.002), white blood cell count (P < 0.001), hemoglobin (P = 0.015), and female gender (P < 0.001) are independent risk factors for autoimmune disease in patients with high IgG levels. CONCLUSIONS: In a cohort of pediatric patients at a tertiary care children's hospital, hypergammaglobulinemia was most commonly associated with autoimmune diseases. In female patients with hypergammaglobulinemia, the presence of leukopenia, anemia, and normal CRP was 95% predictive of underlying autoimmune disease. PMID- 24180595 TI - Vitamin D as an adjunct to subcutaneous allergen immunotherapy in asthmatic children sensitized to house dust mite. AB - BACKGROUND: We aimed to investigate the efficacy, safety, and T regulatory cell response of vitamin D as an adjunct to allergen-specific immunotherapy (IT). METHODS: Fifty children with asthma and receiving pharmacotherapy were randomized into three groups as: subcutaneous IT (SCIT) along with vitamin D supplementation (650 U/day; n: 17), SCIT alone (n: 15), and pharmacotherapy alone (n: 18). All patients were evaluated at baseline, 6th and 12th months for scorings of symptoms and medication, skin prick testing, total IgE, specific IgE, and Der p 1-specific IgG4. In addition, D. pteronyssinus-induced CD4(+) CD25(+) FOXP3(+) T regulatory cell percentage, intracellular Foxp3 expression, and peripheral blood mononuclear cell IL-10 and TGF-beta responses were assessed. RESULTS: In the SCIT + vitamin D and SCIT alone groups, total asthma symptom score (TASS), total symptom score (TSS), and total medication scores (TMS) were significantly lower than pharmacotherapy group at the end of 1 year. While the comparison of delta values (Delta 6th and Delta 12th month - baseline) of those scores revealed no significant differences between the two IT groups, TASS at the 6th month was lower in the SCIT + vitamin D group compared with others. There was a significant and positive trend in the levels of Der p 1-specific IgG4 in both IT groups throughout the study period. Whereas the levels of Der p 1-induced IL-10 and TGF beta were similar between IT groups, the mean fluorescence intensity of Foxp3 was highest in the SCIT + vitamin D group compared with others at the 12th month. The rate of discontinuation of inhaled corticosteroid (ICS) was 6/17 in SCIT + vitamin D, 3/15 in SCIT, and 0/18 in the pharmacotherapy group (P = 0.02). CONCLUSION: Both SCIT groups fared better than pharmacotherapy alone at the end of 1 year. Although the clinical and immunologic outcomes were mostly similar between the two IT groups, some favorable outcomes of vitamin D warrant further investigation in more selected populations with varying doses as adjunct to IT. PMID- 24180597 TI - Large counterions boost the solubility and renormalized charge of suspended nanoparticles. AB - Colloidal particles are ubiquitous in biology and in everyday products such as milk, cosmetics, lubricants, paints, or drugs. The stability and aggregation of colloidal suspensions are of paramount importance in nature and in diverse nanotechnological applications, including the fabrication of photonic materials and scaffolds for biological assemblies, gene therapy, diagnostics, targeted drug delivery, and molecular labeling. Electrolyte solutions have been extensively used to stabilize and direct the assembly of colloidal particles. In electrolytes, the effective electrostatic interactions among the suspended colloids can be changed over various length scales by tuning the ionic concentration. However, a major limitation is gelation or flocculation at high salt concentrations. This is explained by classical theories, which show that the electrostatic repulsion among charged colloids is significantly reduced at high electrolyte concentrations. As a result, these screened colloidal particles are expected to aggregate due to short-range attractive interactions or dispersion forces as the salt concentration increases. We discuss here a robust, tunable mechanism for colloidal stability by which large counterions prevent highly charged nanoparticles from aggregating in salt solutions with concentrations up to 1 M. Large counterions are shown to generate a thicker ionic cloud in the proximity of each charged colloid, which strengthens short-range repulsions among colloidal particles and also increases the corresponding renormalized colloidal charge perceived at larger separation distances. These effects thus provide a reliable stabilization mechanism in a broad range of biological and synthetic colloidal suspensions. PMID- 24180596 TI - Potential role of gastrointestinal microbiota composition in prostate cancer risk. AB - BACKGROUND: Among men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk. PRESENTATION OF THE HYPOTHESIS: The composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents. TESTING THE HYPOTHESIS: Because very little preliminary data exist on this potential association, a case-control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time. IMPLICATIONS OF THE HYPOTHESIS: Given the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host's risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies. PMID- 24180598 TI - Effect of voice therapy after phonomicrosurgery for vocal polyps: a prospective, historically controlled, clinical study. AB - OBJECTIVE: This study aimed to evaluate the efficacy of post-operative voice therapy after phonomicrosurgery for vocal polyp removal. METHODS: The study retrospectively enrolled 55 consecutive patients who had undergone voice therapy after phonomicrosurgery for vocal polyp removal occurring between June 2010 and June 2011. A historical group of 63 similar patients not receiving voice therapy was used as an external control. We compared voice analysis parameters and Voice Handicap Index scores for the two groups. RESULTS: Most objective and subjective voice outcome parameters were significantly improved after surgical treatment. Although the study and control groups showed no significant difference regarding objective parameters (using acoustic and aerodynamic analysis) or the subjective parameters assessed using the grade-roughness-breathiness-asthenia-strain scale, the study group had significantly better final Voice Handicap Index scores. CONCLUSION: Following surgery for vocal polyps, post-operative voice therapy can improve patients' vocal discomfort, emotional responses and everyday self perception. PMID- 24180599 TI - Food industry: friend or foe? AB - Open discourse and tolerance between the food industry and public sector is limited. As a result, the public and private sectors are reluctant to collaborate on pressing nutritional issues. Those in the public sector have never heard what they could do to encourage a food company's transition towards healthier foods and beverages, whereas many in the private sector dismissed policies and actions initiated within the public sector. During my career, I have sought to engage the broadest possible stakeholder groups required to develop evidence-based policies and with the aim of improving public health. My recent experience in industry confirmed my view about the need for scientific exchange regardless of the disagreements about policy. Open discourse and partnering is essential if we are to tackle complex food and health issues and improve the global food system. Private-public engagement can provide faster and more sustainable results than government alone without impacting profits. Moreover, a high-quality product in smaller portions will have higher profit margins than a bargain-sized product of lower quality. The food industry and private sector must come together to implement innovative strategies to address urgent nutritional needs. PMID- 24180600 TI - Temporal variability of indoor air concentrations under natural conditions in a house overlying a dilute chlorinated solvent groundwater plume. AB - Current vapor intrusion (VI) pathway assessment heavily weights concentrations from infrequent (monthly-seasonal) 24 h indoor air samples. This study collected a long-term and high-frequency data set that can be used to assess indoor air sampling strategies for answering key pathway assessment questions like: "Is VI occurring?", and "Will VI impacts exceed thresholds of concern?". Indoor air sampling was conducted for 2.5 years at 2-4 h intervals in a house overlying a dilute chlorinated solvent plume (10-50 MUg/L TCE). Indoor air concentrations varied by 3 orders of magnitude (<0.01-10 ppbv TCE) with two recurring behaviors. The VI-active behavior, which was prevalent in fall, winter, and spring involved time-varying impacts intermixed with sporadic periods of inactivity; the VI dormant behavior, which was prevalent in the summer, involved long periods of inactivity with sporadic VI impacts. These data were used to study outcomes of three simple sparse data sampling plans; the probabilities of false-negative and false-positive decisions were dependent on the ratio of the (action level/true mean of the data), the number of exceedances needed, and the sampling strategy. The analysis also suggested a significant potential for poor characterization of long-term mean concentrations with sparse sampling plans. The results point to a need for additional dense data sets and further investigation into the robustness of possible VI assessment paradigms. As this is the first data set of its kind, it is unknown if the results are representative of other VI-sites. PMID- 24180601 TI - Getting serious about treatment engagement and partnership with families. PMID- 24180602 TI - Reflections on T. Berry Brazelton, MD's influence on pediatric nursing. AB - PURPOSE: The purpose of this article is to provide examples of Dr. Brazelton's important influence on pediatric nursing, and by extension, the work of child psychiatric mental health nurses, the care of children and families, and ultimately, the healthcare delivery system. SOURCES: Dr. Brazelton's professional colleagues, research, professional journals, and books. CONCLUSION: Over the past 40 years, T. Berry Brazelton has had a major impact on the development of pediatric nursing, infant mental health, and the nurse practitioner movement. He has influenced the growth and development of nursing organizations, nursing education, nursing research, nursing practice, and health policy affecting nurses. PMID- 24180603 TI - Intention to seek mental health treatment for adolescent girls: comparison of predictors in mothers and daughters. AB - PROBLEM: To examine predictors of intention to seek mental health treatment for adolescent girls in mothers and daughters. METHODS: In this cross-sectional study, mothers and adolescent daughters (n = 71) completed measures of behavioral attitudes, subjective norms, perceived behavioral control, and intention to seek mental health treatment for the adolescent daughter. FINDINGS: Behavioral attitude and perceived behavioral control predicted intention to seek mental health treatment among mothers. Behavioral attitude predicted intention among daughters. There were no associations between mothers and daughters on study variables. CONCLUSIONS: To promote shared decision making and engagement in mental health treatment, clinicians may target interventions to the mother's perceived behavioral control and behavioral attitudes of daughters and mothers. Based upon study results, clinicians should promote shared decision making and concordance between mothers and daughters on attitudes toward mental health treatment. PMID- 24180604 TI - Characteristics of natural mentoring relationships from the perspectives of homeless youth. AB - PROBLEM: Homeless youth experience high risks for poor mental health outcomes. The purpose of this qualitative study was to explore the characteristics of natural mentoring relationships among homeless youth and to identify possible mechanisms that can enhance social support for this population. METHODS: Semi structured interviews were conducted with 23 homeless youth aged 14-21 who had natural mentors. The interviews focused on how youth met their natural mentors, the function of these relationships, and how natural mentoring relationships differed from other relationships in the youth's social networks. FINDINGS: Main themes that emerged from the interviews included parental absence, natural mentors as surrogate parents, and social support from mentors. CONCLUSIONS: Findings suggest that social supports provided by mentors enhance youth's adaptive functioning and may promote resilience, thus the use of natural mentors may be an important untapped asset in designing interventions to improve outcomes for homeless youth. PMID- 24180605 TI - Responses to CES-D: European American versus Korean American adolescents. AB - PROBLEM: No study has examined variations in the responses to CES-D (Center for Epidemiologic Studies Depression Scale) scoring among different ethnic group adolescents. METHODS: This study compared response differences to CES-D between 51 European American and 58 Korean American (KA) adolescents. FINDINGS: Thirty nine percent of KA adolescents reported higher depressive symptoms compared to 33% European American adolescents. Controlling for child age, significant mean differences were found on six items between the two groups. When within-group difference was examined among KA adolescents using a bi-dimensional acculturation approach, no differences were found except one item. CONCLUSIONS: KA adolescents did not show response bias toward positive affect items in CES-D when compared to European American adolescents. PMID- 24180606 TI - Children's Mental Health Awareness Day. PMID- 24180608 TI - Heme oxygenase-1 as a target for drug discovery. AB - SIGNIFICANCE: Heme oxygenase enzymes, which exist as constitutive (HO-2) and inducible (HO-1) isoforms, degrade heme to carbon monoxide (CO) and the bile pigment biliverdin. In the last two decades, substantial scientific evidence has been collected on the function of HO-1 in cell homeostasis, emphasizing these two important features: (i) HO-1 is a fundamental "sensor" of cellular stress and directly contributes toward limiting or preventing tissue damage; (ii) the products of HO-1 activity dynamically participate in cellular adaptation to stress and are inherently involved in the mechanisms of defence. RECENT ADVANCES: On the basis of its promising cytoprotective features, scientists have pursued the targeting of HO-1 as an attractive cellular pathway for drug discovery. Three different pharmacological approaches are currently being investigated in relation to HO-1, namely the use of CO gas, the development of CO-releasing molecules (CO RMs), and small molecules possessing the ability to up-regulate HO-1 in cells and tissues. CRITICAL ISSUE: Studies on the regulation and amplification of the HO 1/CO pathway by selective pharmacological approaches may lead to the discovery of novel drugs for the treatment of a variety of diseases. FUTURE DIRECTIONS: In this review, we will discuss in detail the importance of pharmacologically manipulating the HO-1 pathway and its products for conferring protection against a variety of conditions that are characterized by oxidative stress and inflammation. We will also evaluate each of the strategic approaches being developed by considering their intrinsic advantages and disadvantages, which may have implications for their use as therapeutics in specific pathological conditions. PMID- 24180609 TI - The expression of prostaglandin receptors EP3 and EP4 in human cervix in post term pregnancy differs between failed and successful labor induction. AB - OBJECTIVE: To investigate expression and localization of prostaglandin receptors EP1-4 and FP and localization of stromal factors CTGF (connective tissue growth factor), furin, calgranulin B and ALOX15 (arachidonate 15-lipooxygenase) in human cervical tissue from post-term women with failed or successful labor induction after prostaglandin priming. DESIGN: Experimental prospective clinical study. SETTING: Tertiary obstetric care center. POPULATION: Twenty-six women giving birth post-term, with failed or successful labor induction, and a control group consisting of 19 women with spontaneous onset of labor and delivery at term. METHODS: Biopsies were obtained from post-term women with successful (responders; R) and failed (non-responders; NR) labor induction. Women with spontaneous delivery at term were included as controls (C). mRNA expression was determined with real time PCR, protein expression and localization with immunohistochemistry. MAIN OUTCOME MEASURES: Comparisons of mRNA and protein expressions between post-term pregnancies with failed and successful labor induction as well as term controls. RESULTS: EP4 mRNA expression was down regulated concomitant with an up-regulation of EP3 mRNA expression in cervix from the NR group as compared with the R group. In stroma, immunoreactivity of the EP4 protein was increased in the NR group as compared with R and C groups. CONCLUSIONS: Failure of cervical ripening, after local application of prostaglandins for labor induction, may be caused by the increased expression of EP3 and concomitant decrease in EP4 expression. PMID- 24180610 TI - Ruthenium hydride/Bronsted acid-catalyzed tandem isomerization/N-acyliminium cyclization sequence for the synthesis of tetrahydro-beta-carbolines. AB - This paper describes an efficient tandem sequence for the synthesis of 1,2,3,4 tetrahydro-beta-carbolines (THBCs) relying on a ruthenium hydride/Bronsted acid catalyzed isomerization of allylic amides to N-acyliminium ion intermediates which are trapped by a tethered indole nucleophile. The methodology provides not only a convenient "aldehyde-free" alternative to the classical Pictet-Spengler reaction but also attractive possibilities for total synthesis, including rapid generation of molecular complexity and formation of quaternary stereogenic centers. TBHCs can also be accessed by harnessing the Suzuki cross-coupling reaction to the isomerization/N-acyliminium cyclization sequence. Finally, diastereo- and enantioselective versions of the title reaction have been examined using substrate control (with dr >15: 1) and asymmetric catalysis (ee up to 57%), respectively. PMID- 24180612 TI - Reframing menstruation in India: metamorphosis of the menstrual taboo with the changing media coverage. AB - In this study I hypothesize metamorphosis of the menstrual taboo by examining the image and perception shifts of two social taboos-HIV/AIDS and homosexuality-from estranged taboos to embraced social issues. Trends identified in their media framing and respective image shifts were applied to menstruation in India. Based on my understanding of theory, topic, and geographical location, I construct a metamorphosis. I contribute the hypothesized final stage of metamorphosis, and explain how framing is likely instrumental in bringing about these changes. PMID- 24180611 TI - Mossbauer study and modeling of iron import and trafficking in human jurkat cells. AB - The Fe content of Jurkat cells grown on transferrin-bound iron (TBI) and Fe(III) citrate (FC) was characterized using Mossbauer, electron paramagnetic resonance, and UV-vis spectroscopies, as well as electron and inductively coupled plasma mass spectrometry. Isolated mitochondria were similarly characterized. Fe-limited cells contained ~100 MUM essential Fe, mainly as mitochondrial Fe and nonmitochondrial non-heme high-spin Fe(II). Cells replete with Fe also contained ferritin-bound Fe and Fe(III) oxyhydroxide nanoparticles. Only 400 +/- 100 Fe ions were loaded per ferritin complex, regardless of the growth medium Fe concentration. Ferritin regulation thus appears to be more complex than is commonly assumed. The magnetic and structural properties of Jurkat nanoparticles differed from those of yeast mitochondria. They were smaller and may be located in the cytosol. The extent of nanoparticle formation scaled nonlinearly with the concentration of Fe in the medium. Nanoparticle formation was not strongly correlated with reactive oxygen species (ROS) damage. Cells could utilize nanoparticle Fe, converting such aggregates into essential Fe forms. Cells grown on galactose rather than glucose respired faster, grew slower, exhibited more ROS damage, and generally contained more nanoparticles. Cells grown with TBI rather than FC contained less Fe overall, more ferritin, and fewer nanoparticles. Cells in which the level of transferrin receptor expression was increased contained more ferritin Fe. Frataxin-deficient cells contained more nanoparticles than comparable wild-type cells. Data were analyzed by a chemically based mathematical model. Although simple, it captured essential features of Fe import, trafficking, and regulation. TBI import was highly regulated, but FC import was not. Nanoparticle formation was not regulated, but the rate was third-order in cytosolic Fe. PMID- 24180613 TI - Clinicians and journalists responding to disasters. AB - OBJECTIVE: Mass casualty events pose dilemmas for community clinicians, often challenging their existing clinical toolkits. However, few clinicians were trained to be experts in explaining the unfolding events to the community, creating resources, and interacting with journalists. The objective of this article is to explain knowledge, skills, and attitudes that mental health professionals need to consider when working with journalists, especially those covering children affected by disaster. METHODS: In service of these objectives, this article reviews controversies, evidence, and best practices to facilitate effective collaborations and consultations with journalists. Advice includes information on how to be a good source to journalists. RESULTS AND CONCLUSIONS: Clinicians can ethically and effectively help journalists tell accurate and compelling stories about the psychological effects of disasters when they understand and respect the aims, culture, and ethics of journalism. PMID- 24180614 TI - Nuclearization of beta-catenin in ectodermal precursors confers organizer-like ability to induce endomesoderm and pattern a pluteus larva. AB - BACKGROUND: In many bilaterians, asymmetric activation of canonical Wnt (cWnt) signaling at the posterior pole is critical for anterior-posterior (AP) body axis formation. In 16-cell stage sea urchins, nuclearization of beta-catenin in micromeres activates a gene regulatory network that defines body axes and induces endomesoderm. Transplanting micromeres to the animal pole of a host embryo induces ectopic endomesoderm in the mesomeres (ectoderm precursors) whereas inhibiting cWnt signaling blocks their endomesoderm-inducing activity and the micromeres become ectoderm-like. We have tested whether ectopic activation of cWnt signaling in mesomeres is sufficient to impart the cells with organizer-like abilities, allowing them to pattern normal embryonic body axes when recombined with a field of mesomeres. RESULTS: Fertilized eggs were microinjected with constitutively active Xenopus beta-catenin (actbeta-cat) mRNA and allowed to develop until the 16-cell stage. Two mesomeres from injected embryos were then recombined with isolated animal halves (AH) from uninjected 16-cell stage embryos. Control chimeras produced animalized phenotypes (hollow balls of ectoderm) and rarely formed skeletogenic mesoderm (SM)-derived spicules, endoderm or pigment cells, a type of non-skeletogenic mesoderm (NSM). In contrast, over half of the 0.5 pg/pL actbeta-cat mesomere/AH chimeras formed a partial or complete gut (exhibiting AP polarity), contained mesenchyme-like cells similar to SM, and produced pigment cells. At three days, chimeras formed plutei with normal embryonic body axes. When fates of the actbeta-cat mRNA-injected mesomeres were tracked, we found that injected mesomeres formed mesenchyme-like and pigment cells, but endoderm was induced. Higher concentrations of actbeta-cat mRNA were less likely to induce endoderm or pigment cells, but had similar mesenchyme-like cell production to 0.5 pg/pL actbeta-cat mesomere/AH chimeras. CONCLUSIONS: Our results show that nuclear beta-catenin is sufficient to endow naive cells with the ability to act as an organizing center and that beta-catenin has both cell autonomous and non-autonomous effects on cell fate specification in a concentration-dependent manner. These results are consistent with the hypothesis that a shift in the site of early cWnt signaling in cleaving embryos could have modified polarity of the main body axes during metazoan evolution. PMID- 24180615 TI - Multisource feedback analysis of pediatric outpatient teaching. AB - BACKGROUND: This study aims to evaluate the outpatient communication skills of medical students via multisource feedback, which may be useful to map future directions in improving physician-patient communication. METHODS: Family respondents of patients, a nurse, a clinical teacher, and a research assistant evaluated video-recorded medical students' interactions with outpatients by using multisource feedback questionnaires; students also assessed their own skills. The questionnaire was answered based on the video-recorded interactions between outpatients and the medical students. RESULTS: A total of 60 family respondents of the 60 patients completed the questionnaires, 58 (96.7%) of them agreed with the video recording. Two reasons for reluctance were "personal privacy" issues and "simply disagree" with the video recording. The average satisfaction score of the 58 students was 85.1 points, indicating students' performance was in the category between satisfied and very satisfied. The family respondents were most satisfied with the "teacher"s attitude," followed by "teaching quality". In contrast, the family respondents were least satisfied with "being open to questions". Among the 6 assessment domains of communication skills, the students scored highest on "explaining" and lowest on "giving recommendations". In the detailed assessment by family respondents, the students scored lowest on "asking about life/school burden". In the multisource analysis, the nurses' mean score was much higher and the students' mean self-assessment score was lower than the average scores on all domains. CONCLUSION: The willingness and satisfaction of family respondents were high in this study. Students scored the lowest on giving recommendations to patients. Multisource feedback with video recording is useful in providing more accurate evaluation of students' communication competence and in identifying the areas of communication that require enhancement. PMID- 24180616 TI - Comparison of American Joint Committee on Cancer TNM-based staging system (7th edition) and Ann Arbor classification for predicting outcome in ocular adnexal lymphoma. AB - OBJECTIVE: To compare the TNM and Ann Arbor staging systems in predicting outcome in ocular adnexal lymphoma (OAL). METHODS: Retrospective review of the clinical, imaging and histopathologic records of OALs between 1986 and 2009. Outcome measures included local recurrence and progression. RESULTS: One hundred and sixty patients of OAL were included. Mean age was 65 +/- 15 years (range 20-97) and 68 (43%) were male. The median follow-up of all OAL patients was 65 months (range 2.5-238). Histopathology identified low-grade, indolent B-cell lymphomas in 140 patients (87.5%) and rest had aggressive grades. Of 134 indolent OAL patients, those with unilateral disease had a 10-year progression free survival of 72% versus 48% in their bilateral counterparts (p = 0.001). Amongst unilateral OAL patients staged within the T1-2 group, a significantly better outcome was noted for patients without nodal or metastatic involvement compared to those with such involvement (p = 0.0001). The above observations helped to formulate a simple scoring system to prognosticate OALs based on their laterality and node/metastatic status. Amongst the 3 groups identified, group 1 with a score of 0 (unilateral OALs with no nodes or metastasis) had a 10-year progression free survival of 75%; group 2 with score 1 (either bilateral or positive nodes/metastasis) 50% and group 3 with score 2 (both bilateral OAL with positive nodes/metastasis) zero at 10 years (p < 0.00001). CONCLUSIONS: The TNM-based staging system better predicts outcome in OAL than the Ann Arbor system primarily by delineation of bilateral disease and nodal/metastatic involvement at presentation. PMID- 24180617 TI - Lymphoma presenting as neck lumps: causes of waiting time target breaches and potential solutions. AB - OBJECTIVES: This study aimed to assess the speed of referral, diagnosis and treatment of patients with lymphoma presenting with a neck lump, and to identify where delays are occurring that prevent UK national targets from being met. METHOD: The study entailed a retrospective survey of patients presenting with a neck lump secondary to lymphoma between 2006 and 2008 in Gloucestershire, UK. RESULTS: Forty-seven of 54 patients (87 per cent) were seen within 2 weeks of referral. However, the 62-day rule, which covers the time from referral to the initiation of treatment, was met in only 32 of the 54 cases (59 per cent). There were no breaches of the 31-day target, which concerned the time from decision to treat to the initiation of treatment. Subsequent target breaches were due to longer waiting times for radiological and pathological investigations. CONCLUSION: Radiological examinations should be ordered at the first consultation and biopsies performed as soon as possible. Establishing one-stop, rapid access clinics should improve the achievement of a maximum 62-day wait for patients with lymphoma presenting with neck lumps. PMID- 24180618 TI - Synthesis of formylsilanes through oxidative cleavage of alpha-silyl glycols. AB - A convenient method for the synthesis and isolation of highly reactive formylsilanes by oxidative cleavage of alpha-silyl glycols is presented. The mild conditions provide an entry to acid- and heat-sensitive members of this theoretically intriguing class of compounds. The utility of the method is demonstrated through the isolation and subsequent diastereoselective derivatization of t-BuMe2- and t-BuPh2-formylsilanes, previously not reported in isolated form. PMID- 24180619 TI - The role of TLR4 in pathophysiology of antiphospholipid syndrome-associated thrombosis and pregnancy morbidity. AB - The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Antiphospholipid antibodies (aPL), particularly against the phospholipid binding protein beta-2 glycoprotein I (beta2GPI), play an important role in APS pathological mechanisms. aPL can activate intracellular signal transduction in a beta2GPI-dependent manner to induce inflammatory responses, and promote hypercoagulable state and recurrent spontaneous abortion when beta2GPI is associated with the cell surface receptor. In vivo and in vitro studies show that Annexin A2 (ANXA2) is the high affinity receptor that connects beta2GPI to the target cells. However, ANXA2 is not a transmembrane protein and lacks an intracellular signal transduction pathway. Growing evidences suggest that the transmembrane protein toll-like receptor 4 (TLR4) might act as an 'adaptor' for intracellular signal transduction. This review focuses on the role of TLR4 and its signalling pathway in APS pathological mechanisms which will help us better understand the pathological processes of this syndrome. PMID- 24180620 TI - Enantioselective synthesis of isotopically labeled homocitric acid lactone. AB - A concise synthesis of homocitric acid lactone was developed to accommodate systematic placement of carbon isotopes (specifically (13)C) for detailed studies of this cofactor. This new route uses a chiral allylic alcohol, available in multigram quantities from enzymatic resolution, as a starting material, which transposes asymmetry through an Ireland-Claisen rearrangement. PMID- 24180621 TI - Serological markers of Bornavirus infection found in horses in Iceland. AB - BACKGROUND: In a stable of eight horses in Northern Iceland, six horses presented with clinical signs, such as ataxia and reduced appetite, leading to euthanasia of one severely affected horse. Serological investigations revealed no evidence of active equine herpes virus type 1 infection, a common source of central nervous system disease in horses, nor equine arteritis virus and West Nile virus. Another neurotropic virus, Borna disease virus, was therefore included in the differential diagnosis list. FINDINGS: Serological investigations revealed antibodies against Borna disease virus in four of five horses with neurological signs in the affected stable. One horse without clinical signs was seronegative. Four clinically healthy horses in the stable that arrived and were sampled one year after the outbreak were found seronegative, whereas one of four investigated healthy horses in an unaffected stable was seropositive. CONCLUSIONS: This report contains the first evidence of antibodies to Borna disease virus in Iceland. Whether Borna disease virus was the cause of the neurological signs could however not be confirmed by pathology or molecular detection of the virus. As Iceland has very restricted legislation regarding animal imports, the questions of how this virus has entered the country and to what extent markers of Bornavirus infection can be found in humans and animals in Iceland remain to be answered. PMID- 24180622 TI - The thorax musculature of Anisoptera (Insecta: Odonata) nymphs and its evolutionary relevance. AB - BACKGROUND: Among the winged insects (Pterygota) the Odonata (dragon- and damselflies) are special for several reasons. They are strictly aerial predators showing remarkable flight abilities and their thorax morphology differs significantly from that of other Pterygota in terms of the arrangement and number of muscles. Even within one individual the musculature is significantly different between the nymphal and adult stage. RESULTS: Here we present a comparative morphological investigation of the thoracic musculature of dragonfly (Anisoptera) nymphs. We investigated representatives of the Libellulidae, Aeshnidae and Cordulegasteridae and found 71 muscles: 19 muscles in the prothorax, 26 in the mesothorax and 27 in the metathorax. Nine of these muscles were previously unknown in Odonata, and for seven muscles no homologous muscles could be identified in the neopteran thorax. CONCLUSION: Our results support and extend the homology hypotheses for the thoracic musculatures of Odonata and Neoptera, thus supplementing our understanding of the evolution of Pterygota and providing additional characters for phylogenetic analyses comprising all subgroups of Pterygota. PMID- 24180623 TI - Self-propelled micromotors for cleaning polluted water. AB - We describe the use of catalytically self-propelled microjets (dubbed micromotors) for degrading organic pollutants in water via the Fenton oxidation process. The tubular micromotors are composed of rolled-up functional nanomembranes consisting of Fe/Pt bilayers. The micromotors contain double functionality within their architecture, i.e., the inner Pt for the self propulsion and the outer Fe for the in situ generation of ferrous ions boosting the remediation of contaminated water.The degradation of organic pollutants takes place in the presence of hydrogen peroxide, which acts as a reagent for the Fenton reaction and as main fuel to propel the micromotors. Factors influencing the efficiency of the Fenton oxidation process, including thickness of the Fe layer, pH, and concentration of hydrogen peroxide, are investigated. The ability of these catalytically self-propelled micromotors to improve intermixing in liquids results in the removal of organic pollutants ca. 12 times faster than when the Fenton oxidation process is carried out without catalytically active micromotors. The enhanced reaction-diffusion provided by micromotors has been theoretically modeled. The synergy between the internal and external functionalities of the micromotors, without the need of further functionalization, results into an enhanced degradation of nonbiodegradable and dangerous organic pollutants at small-scale environments and holds considerable promise for the remediation of contaminated water. PMID- 24180624 TI - Hemolytic anemia after ingestion of the natural hair dye Lawsonia inermis (henna) in a dog. AB - OBJECTIVES: To describe the clinical presentation and case management of a dog that developed hemolytic anemia and evidence of renal tubular dysfunction after ingestion of a natural hair dye containing Lawsonia inermis (henna). To review cases of henna toxicity reported in the human literature. CASE SUMMARY: An 8-year old female spayed Border Collie was presented 5 days after ingestion of a box of natural hair dye. The dog was showing signs of lethargy, vomiting, diarrhea, and weakness. A serum biochemistry profile, complete blood count, and urinalysis demonstrated evidence of renal tubular dysfunction and a regenerative anemia without spherocytosis. The dog was treated with a transfusion of packed RBCs and IV fluids, resulting in significant clinical improvement. Repeat diagnostics showed resolution of the anemia and no lasting evidence of tubular dysfunction. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first reported case in the veterinary literature of toxicity following ingestion of Lawsonia inermis (henna). Henna ingestion was associated with the development of hemolytic anemia and acute kidney injury. PMID- 24180626 TI - Small-area and compact CMOS emulator circuit for CMOS/nanoscale memristor co design. AB - In this paper, a CMOS emulator circuit that can reproduce nanoscale memristive behavior is proposed. The proposed emulator circuit can mimic the pinched hysteresis loops of nanoscale memristor memory's current-voltage relationship without using any resistor array, complicated circuit blocks, etc. that may occupy very large layout area. Instead of using a resistor array, other complicated circuit blocks, etc., the proposed emulator circuit can describe the nanoscale memristor's current-voltage relationship using a simple voltage controlled resistor, where its resistance can be programmed by the stored voltage at the state variable capacitor. Comparing the layout area between the previous emulator circuit and the proposed one, the layout area of the proposed emulator circuit is estimated to be 32 times smaller than the previous emulator circuit. The proposed CMOS emulator circuit of nanoscale memristor memory will be very useful in developing hybrid circuits of CMOS/nanoscale memristor memory. PMID- 24180625 TI - Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients. AB - BACKGROUND: Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. METHODS: We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. RESULTS: Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. CONCLUSIONS: This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients. PMID- 24180627 TI - Novel hydrophobically modified asymmetric RNAi compounds (sd-rxRNA) demonstrate robust efficacy in the eye. AB - PURPOSE: The major challenges of developing an RNAi therapeutic include efficient delivery to and entry into the cell type of interest. Conventional ("naked" and chemically stabilized) small interfering RNAs (siRNAs) have been used in the eye in the past but they demonstrated limited clinical efficacy. Here we investigated a recently developed class of small, hydrophobic, asymmetric RNAi compounds. These compounds, termed "self-delivering rxRNAs" (sd-rxRNA((r))), are extensively modified, have a small duplex region of <15 base pairs, contain a fully phosphorothioated single-stranded tail, and readily enter cells and tissues without the requirement for a delivery vehicle. METHODS: We compared sd-rxRNA compounds with stabilized siRNAs in vitro (in ARPE-19 cells) and in vivo (intravitreal injection in mouse and rabbit eyes). Specifically, we investigated the retinal uptake, distribution, efficacy, and preliminary safety of sd-rxRNAs. RESULTS: Treatment with sd-rxRNAs resulted in uniform cellular uptake and full retina penetration in both animal models while no detectable cellular uptake was observed with stabilized siRNAs either in vitro or in vivo. Further, both in vitro and in vivo delivery (without any transfection reagent or formulation) resulted in a significant reduction of the targeted mRNA levels, which lasted 14 21 days in vivo. Retinal morphology and function were unaltered following a single administration of sd-rxRNAs. CONCLUSION: These data support the potential of developing sd-rxRNAs as a therapeutic for ocular disease. PMID- 24180628 TI - The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. AB - PURPOSE: The aim of this study was to compare the intraocular pressure (IOP) lowering efficacy and to determine patient preference based on ocular discomfort with fixed combination brinzolamide/timolol and fixed combination dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension who required a change in therapy due to elevated IOP while receiving IOP-lowering medication. METHODS: This was a 3-month, randomized, double-blinded, active controlled, parallel-group trial. Patients had open-angle glaucoma or ocular hypertension, which could not be controlled with monotherapy and were randomized to twice daily therapy with either brinzolamide 1%/timolol 0.5% or dorzolamide 2%/timolol 0.5%. IOP assessments were taken at 8 AM, 10 AM, and 4 PM at week 2 as well as at months 1, 2, and 3. Patients completed ocular discomfort assessments (based on stinging, burning, feeling of heat or warmth, or sharp pain) on their current IOP lowering therapy at baseline. RESULTS: Of the 114 patients enrolled, 57 received Brinz/Tim and 57 received Dorz/Tim twice daily. Both medications produced statistically relevant IOP reductions, which were similar in both groups at each visit. The IOP reductions with Brinz/Tim ranged from 6.42 to 9.74 mmHg (26.09%-37.46%), whereas Dorz/Tim produced mean IOP reductions ranging from 8.16 to 12.41 mmHg (31.19%-41.44%) (P>0.05). Brinz/Tim showed significantly less ocular irritation (0.5% vs. 15.7%, respectively; P=0.0004) than Dorz/Tim. CONCLUSIONS: Both Brinz/Tim and Dorz/Tim showed similar significant and clinically relevant IOP-lowering efficacy, whereas Brinz/Tim provided superior outcomes in terms of ocular comfort. PMID- 24180629 TI - Prospective clinical evaluation of 1.5% levofloxacin ophthalmic solution in ophthalmic perioperative disinfection. AB - PURPOSE: Gram-positive cocci and Propionibacterium acnes are widely reported agents of infectious postoperative endophthalmitis. This multicenter study was conducted to evaluate the eradication effectiveness and safety profile of levofloxacin 1.5% ophthalmic solution (LVFX 1.5%) for use in perioperative disinfection. METHODS: Patients who were scheduled for cataract surgery were enrolled. The perioperative regimen of LVFX 1.5% was administered 3 times daily as follows: preoperative 3 days; the day of surgery (in the morning, 1 h before surgery, and immediately after surgery); and postoperative 2 weeks. Conjunctival sac scrapings were collected 3 times in the observation period; before preoperative administration, before iodine eyewash on the day of surgery, and after completion of postoperative administration. Isolated and identified microbial strains were assessed for antibacterial susceptibility. RESULTS: One hundred patients were enrolled and data obtained from 96 patients (mean age, 72.7 +/- 8.9 years). The preoperative eradication rate was 86.7% in total microbes. In the case of gram-positive cocci, the preoperative eradication rate was 100%, even though there were LVFX-registrant methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus, which had a high minimum inhibitory concentration against LVFX, such as 32 MUg/mL. On the other hand, that of P. acnes was 78.3%. No acquired drug resistance was suspected in all strains. Adverse drug reactions occurred in 4.2% patients, and all were slight. CONCLUSIONS: For ophthalmic perioperative disinfection, the LVFX 1.5% ophthalmic solution showed a good safety profile, and critical eradication of gram-positive cocci, including the fluoroquinolone-resistant strains. PMID- 24180630 TI - Impact of higher alcohols blended in gasoline on light-duty vehicle exhaust emissions. AB - Certification gasoline was splash blended with alcohols to produce four blends: ethanol (16 vol%), n-butanol (17 vol%), i-butanol (21 vol%), and an i-butanol (12 vol%)/ethanol (7 vol%) mixture; these fuels were tested in a 2009 Honda Odyssey (a Tier 2 Bin 5 vehicle) over triplicate LA92 cycles. Emissions of oxides of nitrogen, carbon monoxide, non-methane organic gases (NMOG), unburned alcohols, carbonyls, and C1-C8 hydrocarbons (particularly 1,3-butadiene and benzene) were determined. Large, statistically significant fuel effects on regulated emissions were a 29% reduction in CO from E16 and a 60% increase in formaldehyde emissions from i-butanol, compared to certification gasoline. Ethanol produced the highest unburned alcohol emissions of 1.38 mg/mile ethanol, while butanols produced much lower unburned alcohol emissions (0.17 mg/mile n-butanol, and 0.30 mg/mile i butanol); these reductions were offset by higher emissions of carbonyls. Formaldehyde, acetaldehyde, and butyraldehyde were the most significant carbonyls from the n-butanol blend, while formaldehyde, acetone, and 2-methylpropanal were the most significant from the i-butanol blend. The 12% i-butanol/7% ethanol blend was designed to produce no increase in gasoline vapor pressure. This fuel's exhaust emissions contained the lowest total oxygenates among the alcohol blends and the lowest NMOG of all fuels tested. PMID- 24180632 TI - Percutaneous peripheral neuromodulation lead insertion using a novel stimulating Coude needle. PMID- 24180631 TI - S-propargyl-cysteine, a novel water-soluble modulator of endogenous hydrogen sulfide, promotes angiogenesis through activation of signal transducer and activator of transcription 3. AB - AIMS: Conventional revascularization strategies or drug therapies for ischemic heart disease (IHD) are designed for reperfusion of coronary arteries to salvage cardiomyocytes, but occasionally, myocardial reperfusion injury can occur because of microcirculatory dysfunction. Therefore, a more microcirculation-friendly strategy should be explored to overcome and compensate for the shortcomings of conventional strategies. In this work, we investigated the proangiogenic effect of S-Propargyl-Cysteine (SPRC), a novel water-soluble modulator of endogenous hydrogen sulfide, and elucidated the possible mechanisms involved to provide an experimental basis for angiogenesis-mediated drug therapy for IHD. RESULTS: SPRC promoted cell proliferation, adhesion, migration, and tube formation of primary human umbilical vein endothelial cells (HUVEC) and increased angiogenesis in the rat aortic ring and Matrigel plug models. In a mouse model of hindlimb ischemia and a rat model of myocardial ischemia, SPRC also promoted angiogenesis after ligation of the left femoral artery or coronary artery to ameliorate ischemic conditions. In primary HUVEC, STAT3 phosphorylation was significantly induced after SPRC treatment. The critical roles of STAT3 in mediating the proangiogenic effect of SPRC were confirmed by RNA interference. Co-crystallization excluded the possible direct interaction between SPRC and STAT3, whereas co immunoprecipitation revealed an enhanced interaction between VEGFR2 and STAT3 after SPRC treatment. Meanwhile, immunofluorescence and chromatin immunoprecipitation showed that SPRC induced the nuclear translocation of STAT3, followed by transcriptional activation of downstream promoters, particularly the Vegf promoter. INNOVATION AND CONCLUSION: We present a novel STAT3-mediated mechanism in SPRC-induced angiogenesis and demonstrate the therapeutic potential of SPRC in ischemic disease through angiogenesis promotion. PMID- 24180633 TI - Should paramedics ever accept patients' refusal of treatment or further assessment? AB - BACKGROUND: This case report discusses an ethical communication dilemma in prehospital patient interaction, involving a patient who was about to board a plane at a busy airport. The article argues that the situation raised dilemmas about communication, patient autonomy and paternalism. Paramedics should be able to find good solutions to these dilemmas, but they have not received much attention in the literature on prehospital ambulance work. CASE PRESENTATION: The patient had chest pains that were consistent with serious heart disease, but she wanted to catch her plane and was unwilling to let paramedics assess her heart activity by means of an electrocardiogram (ECG). The paramedics had to decide, there and then, whether the patient's refusal to submit to an ECG should be respected, or whether they should set the patient's expressed wishes aside by exercising verbal power and persuasive communication techniques. The paramedics chose to do the latter. It later turned out that the patient was grateful that the paramedics had been very direct, almost brutal, in their communication. When the patient regained her autonomy, she saw clearly that taking time to obtain and monitor an ECG was the best option for her. CONCLUSION: Looking forward in time might be a good professional strategy for deciding whether ethical paternalism in communication is justified. If there is good reason to believe that patients who later regain their autonomy will agree that paternalistic verbal actions were in their best interests, and if acting in accordance with patients' preferences can have severe negative health consequences for them, then paramedics have good reason to believe that ethical paternalism is justified. PMID- 24180634 TI - Cu-catalyzed couplings of aryl iodonium salts with sodium trifluoromethanesulfinate. AB - A convenient method for the preparation of aryl trifluoromethylsulfones from the reactions of diaryliodonium salts with sodium trifluoromethanesulfinate in the presence of copper catalysts is described. Cuprous oxide in DMF was found to be the optimal catalyst for the reaction. The reaction conditions are tolerant of various functional groups as well as of various counteranions of the iodonium salt. The synthetic utility of the process is demonstrated by performing the reaction on a preparative scale (88 g). PMID- 24180635 TI - Pivotal response treatment for children with autism spectrum disorder: a systematic review of research quality. AB - OBJECTIVE: Research has indicated support for pivotal response treatment (PRT) as an effective, efficacious and naturalistic intervention for communication and social functioning of children with autism spectrum disorder (ASD). Previously not undertaken, this article describes a systematic evaluation of the adherence of PRT research studies to standards of ASD research quality. METHOD: A systematic search was conducted on two databases. Seventeen PRT studies were evaluated on their use of seven specified research standards. RESULTS: Strong adherence to research quality standards was demonstrated in the use of standardized protocols, systematic application of intervention procedures, inter rater reliability and objective evaluators. Variation was found in adherence to treatment fidelity standards and in the use of longitudinal designs. Only two studies implemented comparison designs. CONCLUSION: It is recommended that researchers compare interventions, use longitudinal designs, better describe their methodology and implement greater adherence to treatment fidelity to enhance research quality and strengthen conclusions. PMID- 24180636 TI - Arts-based social skills interventions for adolescents with acquired brain injuries: five case reports. AB - OBJECTIVE: Previous research has demonstrated the value of arts-based programs for adolescents with childhood brain disorder to facilitate social skills and participation. The current study extends this work by examining the feasibility and effectiveness of an arts-based intervention for youth with acquired brain injuries (ABI). METHODS: A case study approach was used with four adolescent participants and one case control. A battery of quantitative measures were administered four and one week pre-intervention, one week post-intervention, as well six to eight month post-intervention. RESULTS: Improvements in pragmatic communication skills and social and participation goals were observed across intervention participants. Similar improvements were not seen with the case control participant. CONCLUSION: Results support the use of an arts-based intervention for youth with ABI to facilitate social skills and participation. Findings also highlight the need for more sensitive measures of these skills for these youth. Suggested guidelines for program implementation are provided. PMID- 24180637 TI - Reported communication ability of persons with trisomy 18 and trisomy 13. AB - OBJECTIVE: The aim of this study was to describe the communication ability of individuals with trisomy 18 and trisomy 13 syndromes. METHODS: Parents reported on children's potential communication acts, words, spontaneous gesture, and augmentative and alternative communication (AAC) using a parent report inventory (n = 32; age range 3-35 years). Potential communicative acts are defined as behaviors produced by an individual that may be interpreted by others to serve communicative functions. RESULTS: Potential communicative acts categorized as body movement displayed the highest median rank for reported occurrence followed by vocalization and facial expression. Although symbolic forms were ranked lower, more than half of the parents (66%) reported that their children produced at least one word, gesture or AAC form. Challenging behaviors or stereotypic movement displayed lowest median ranks. CONCLUSIONS: Results are discussed in terms of communication potential and the need to address AAC in trisomy 18 and 13. PMID- 24180638 TI - Phase and period responses to short light pulses in a wild diurnal rodent, Funambulus pennanti. AB - Photic phase response curves (PRCs) have been extensively studied in many laboratory-bred diurnal and nocturnal rodents. However, comparatively fewer studies have addressed the effects of photic cues on wild diurnal mammals. Hence, we studied the effects of short durations of light pulses on the circadian systems of the diurnal Indian Palm squirrel, Funambulus pennanti. Adult males entrained to a light-dark cycle (12 h-12 h) were transferred to constant darkness (DD). Free-running animals were exposed to brief light pulses (250 lux) of 15 min, 3 circadian hours (CT) apart (CT 0, 3, 6, 9, 12, 15, 18 and 21). Phase shifts evoked at different phases were plotted against CT and a PRC was constructed. F. pennanti exhibited phase-dependent phase shifts at all the CTs studied, and the PRC obtained was of type 1 at the intensity of light used. Phase advances were evoked during the early subjective day and late subjective night, while phase delays occurred during the late subjective day and early subjective night, with maximum phase delay at CT 15 (-2.04 +/- 0.23 h), and maximum phase advance at CT 21 (1.88 +/- 0.31 h). No dead zone was seen at this resolution. The free-running period of the rhythm was concurrently lengthened (deceleration) during the late subjective day and early subjective night, while period shortening (acceleration) occurred during the late subjective night. The maximum deceleration was noticed at CT 15 (-0.40 +/- 0.09 h) and the maximum acceleration at CT 21 (0.39 +/- 0.07 h). A significant positive correlation exists between the phase shifts and the period changes (r = 0.684, p = 0.001). The shapes of both the PRC and period response curve (tauRC) qualitatively resemble each other. This suggests that the palm squirrel's circadian system is entrained both by phase and period responses to light. Thus, F. pennanti exhibits robust clock-resetting in response to light pulses. PMID- 24180639 TI - Swallowing outcomes following surgical and non-surgical treatment for advanced laryngeal cancer. AB - BACKGROUND: Treatment for advanced laryngeal cancer includes surgery, and/or chemoradiotherapy or radiotherapy. Each of these treatments results in major changes to the swallowing mechanism. Dysphagia is strongly correlated with poorer quality of life. A good understanding of outcomes is needed for well-informed treatment decisions. METHOD: This study reports on patients' swallowing outcomes following surgical and non-surgical treatments based on the results of three different swallowing tests. A total of 123 data sets were collected in out patient clinics across two hospitals in North East England. RESULTS: There were no significant differences between treatment groups for patient-reported swallowing outcomes or swallowing performance. However, patients who had undergone chemoradiotherapy or radiotherapy (with or without laryngectomy) had significantly more diet restrictions than other groups. CONCLUSION: Long-term dysphagia is a common outcome of treatment for advanced laryngeal cancer. Patients treated with chemoradiotherapy and laryngectomy reported the worst overall outcomes. More longitudinal prospective research with large treatment groups is needed to investigate swallowing outcomes following different treatment methods. PMID- 24180640 TI - The molecular basis for the selectivity of tadalafil toward phosphodiesterase 5 and 6: a modeling study. AB - Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalafil gives a high selectivity of 1020-fold against PDE6. Till now, their molecular mechanisms of selectivity of PDE5 versus PDE6 have remained unknown in the absence of the crystal structure of PDE6. In order to elucidate its isoform selective inhibitory mechanism, a 3D model of PDE6 was constructed by homology modeling, and its interaction patterns with tadalafil plus sildenafil were exploited by molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations. The present work reveals that tadalafil exhibits a less negative predicted binding free energy of -35.21 kcal/mol with PDE6 compared with the value of -41.12 kcal/mol for PDE5, which suggests that tadalafil prefers PDE5 rather than PDE6 and confers a high selectivity for PDE5 versus PDE6. The binding free energy results for tadalafil were consistent with external bioassay studies (IC50 = 5100 and 5 nM toward PDE6 and PDE5, respectively). Two important residues from the Q2 pockets (Val782 and Leu804 in PDE5 and their corresponding Val738 and Met760 in PDE6) were further identified to account for the high selectivity of tadalafil for PDE5 versus PDE6. These findings have shed light on the continuous puzzle of why sildenafil (IC50 = 74 and 6 nM toward PDE6 and PDE5, respectively) causes visual disorders because of its poor selectivity but tadalafil does not. In addition, the homology model of PDE6 can be used to design more potent and selective second-generation PDE5 inhibitors with less inhibitory potency against PDE6. PMID- 24180641 TI - Validation and reliability of a disease-specific quality of life measure (the TranQol) in adults and children with thalassaemia major. AB - This study aimed to demonstrate the validity, reliability and responsiveness of a new disease-specific quality of life (QoL) questionnaire for children and adults with thalassaemia major, the Transfusion-dependent QoL questionnaire (TranQol). 106 participants (51 adults and 55 children) were recruited from six North American thalassaemia treatment centres with a mean age of 20.7 years (standard deviation [SD] 9, range 7-51 years). The mean total TranQol score was 71 (SD 17, 32-97) on a scale of 0-100. Patients with co-morbidities had significantly lower scores (63 vs. 75, P = 0.001). TranQol scores showed substantial agreement (P < 0.001) with the Health Utilities Index Mark 3 (all patients, r = 0.65), the Pediatric QoL (children, r = 0.77) and the Short Form (36) physical (adults, r = 0.69) and mental summary scores (r = 0.76). In the subgroup who rated their QoL as better, there was a 4.0 point (SD 9.0) improvement in TranQol scores, from baseline of 67.1-71.1 one week later (P = 0.008). Test-retest reliability was excellent (intra-class correlation coefficient, 0.93). The TranQol was valid, with acceptable correlation for all administered measures and was reliable and responsive to change. The TranQol can be incorporated into future studies of thalassaemia major. PMID- 24180642 TI - Harvesting energy from the natural vibration of human walking. AB - The triboelectric nanogenerator (TENG), a unique technology for harvesting ambient mechanical energy based on the triboelectric effect, has been proven to be a cost-effective, simple, and robust approach for self-powered systems. However, a general challenge is that the output current is usually low. Here, we demonstrated a rationally designed TENG with integrated rhombic gridding, which greatly improved the total current output owing to the structurally multiplied unit cells connected in parallel. With the hybridization of both the contact separation mode and sliding electrification mode among nanowire arrays and nanopores fabricated onto the surfaces of two contact plates, the newly designed TENG produces an open-circuit voltage up to 428 V, and a short-circuit current of 1.395 mA with the peak power density of 30.7 W/m(2). Relying on the TENG, a self powered backpack was developed with a vibration-to-electric energy conversion efficiency up to 10.62(+/-1.19) %. And it was also demonstrated as a direct power source for instantaneously lighting 40 commercial light-emitting diodes by harvesting the vibration energy from natural human walking. The newly designed TENG can be a mobile power source for field engineers, explorers, and disaster relief workers. PMID- 24180643 TI - Organocatalyzed direct glycosylation of unprotected and unactivated carbohydrates. AB - Organocatalyzed direct glycosylation of unprotected and unactivated carbohydrates is reported. This process is catalyzed by triphenylphosphine and tetrabromomethane at room temperature under neutral conditions. With this operationally simple protocol thermodynamically favored, glycosides were obtained in a very straightforward reaction. PMID- 24180644 TI - The protein structure determines the sensitizing capacity of Brazil nut 2S albumin (Ber e1) in a rat food allergy model. AB - : It is not exactly known why certain food proteins are more likely to sensitize. One of the characteristics of most food allergens is that they are stable to the acidic and proteolytic conditions in the digestive tract. This property is thought to be a risk factor in allergic sensitization. The purpose of the present study was to investigate the contribution of the protein structure of 2S albumin (Ber e1), a major allergen from Brazil nut, on the sensitizing capacity in vivo using an oral Brown Norway rat food allergy model. Disulphide bridges of 2S albumin were reduced and alkylated resulting in loss of protein structure and an increased pepsin digestibility in vitro. Both native 2S albumin and reduced/alkylated 2S albumin were administered by daily gavage dosing (0.1 and 1 mg) to Brown Norway rats for 42 days. Intraperitoneal administration was used as a positive control. Sera were analysed by ELISA and passive cutaneous anaphylaxis. Oral exposure to native or reduced/alkylated 2S albumin resulted in specific IgG1 and IgG2a responses whereas only native 2S albumin induced specific IgE in this model, which was confirmed by passive cutaneous anaphylaxis. This study has shown that the disruption of the protein structure of Brazil nut 2S albumin decreased the sensitizing potential in a Brown Norway rat food allergy model, whereas the immunogenicity of 2S albumin remained preserved. This observation may open possibilities for developing immunotherapy for Brazil nut allergy. PMID- 24180645 TI - Interspecific differences in egg production affect egg trace element concentrations after a coal fly ash spill. AB - In oviparous vertebrates, trace elements transfer from mother to offspring during egg production. For animals that produce eggs slowly, like turtles, the trace element concentration of each egg reflects an integration of dietary and stored accumulation over the duration of vitellogenesis. Because turtles also produce eggs synchronously, all eggs within a clutch should exhibit uniform trace element concentrations. In contrast, for animals that produce eggs in sequence and primarily from current dietary resources, like many birds, the trace element concentrations of eggs should be less uniform within a clutch, and likely reflect short-term changes in dietary exposure. We tested the hypothesis that stinkpot turtle (Sternotherus odoratus) clutches exhibit lower variability and higher repeatability in barium, selenium, strontium, and thallium concentrations than those of tree swallows (Tachycineta bicolor) from a site impacted by a recent coal ash spill. All four trace elements exhibited significantly lower variability and significantly higher repeatability in stinkpot clutches than in swallow clutches. Mean trace element concentrations of stinkpot eggs were also significantly higher than those of swallow eggs although both species feed primarily on aquatic invertebrates. Variability in swallow egg trace element concentrations was partially due to significant laying order effects. Our results support the hypothesis that interspecific variation in the source of resources and in the synchronicity and rate of egg production can lead to interspecific differences in the variability of egg trace element concentrations. PMID- 24180646 TI - Absence of cross-reactivity to carbapenems in patients with delayed hypersensitivity to penicillins. AB - Studies performed on subjects with IgE-mediated hypersensitivity to penicillins have demonstrated a 1% rate of cross-reactivity between penicillins and both imipenem and meropenem, while a single study found a 5.5% rate of cross reactivity with imipenem/cilastatin in subjects with T-cell-mediated hypersensitivity to beta-lactams, mostly penicillins. We studied 204 consecutive subjects with a well-demonstrated T-cell-mediated hypersensitivity to assess the cross-reactivity with carbapenems and the tolerability of such alternative beta lactams. All 204 subjects underwent skin tests with imipenem/cilastatin and meropenem; 130 of them were skin-tested also with ertapenem. Subjects with negative test results were challenged with these carbapenems. All subjects displayed negative skin tests to carbapenems and tolerated challenges. These data demonstrate the absence of clinically significant T-cell-mediated cross reactivity between penicillins and carbapenems. Negative delayed-reading skin testing with carbapenems in individuals with documented T-cell-mediated hypersensitivity to penicillins correlates well with subsequent clinical tolerance of therapeutic doses of carbapenems. PMID- 24180647 TI - Partnering with residents for evidence-based practice. AB - Medical residents are a distinct group of health sciences library users that need detailed instruction in literature searching. Core residency competencies from the Accreditation Council for Graduate Medical Education require that all residents be competent in finding, critically appraising, and incorporating the latest clinical evidence into their daily practice with patients. With the collaboration of the library and a clinical department of pediatrics, a program was developed that teaches residents the basic elements of EBM searching and then reinforces this learning over the course of three years. PMID- 24180648 TI - Using Google blogs and discussions to recommend biomedical resources: a case study. AB - This case study investigated whether data gathered from discussions within the social media provide a reliable basis for a biomedical resources recommendation system. Using a search query to mine text from Google Blogs and Discussions, a ranking of biomedical resources was determined based on those most frequently mentioned. To establish quality, these results were compared with rankings by subject experts. An overall agreement between the frequency of social media discussions and subject expert recommendations was observed when identifying key bioinformatics and consumer health resources. Testing the method in more than one biomedical area implies this procedure could be employed across different subjects. PMID- 24180649 TI - Real-time peer review: an innovative feature to an evidence-based practice conference. AB - Many health sciences librarians as well as other professionals attend conferences on a regular basis. This study sought to link an innovative peer review process of presented research papers to long-term conference outcomes in the peer reviewed professional journal literature. An evidence-based conference included a proof-of-concept study to gauge the long-term outcomes from research papers presented during the program. Real-time peer review recommendations from the conference were linked to final versions of articles published in the peer reviewed literature. The real-time peer review feedback served as the basis for further mentoring to guide prospective authors toward publishing their research results. These efforts resulted in the publication of two of the four research papers in the peer-viewed literature. A third presented paper appeared in a blog because the authors wanted to disseminate their findings more quickly than through the journal literature. The presenters of the fourth paper never published their study. Real-time peer review from this study can be adapted to other professional conferences that include presented research papers. PMID- 24180650 TI - Factors that influence effective evidence-based medicine instruction. AB - Evidence-based medicine (EBM) as a health care practice is being incorporated into education programs across the spectrum of medical education to develop lifelong learning skills and to enhance the practice of evidence-based health care. Since improving the quality of patient care is the ultimate goal of EBM, EBM learning must be integrated with clinical application, and resulted outcomes must be reflected in learning transfer (or EBM practice) within the context of solving patient problems. Different factors may constitute the context or environment in which EBM is learned, practiced, and sustained. However, these contextual factors are seldom considered and examined in the development, implementation, and evaluation of EBM instruction for learners at different levels. This article will introduce several contextual factors as tips and strategies that affect EBM learning and transfer. Also included in the article are recommended practices for designing effective EBM instruction that would contribute to a sustainable change in learner behavior. PMID- 24180651 TI - Joanna Briggs Institute: an evidence-based practice database. AB - The Joanna Briggs Institute Evidence-Based Practice Database offers systematic reviews, practice recommendations, and consumer information designed to support evidence-based practice. A sample search was conducted within the Ovid platform to demonstrate functionality and available tools. PMID- 24180652 TI - Personas: stepping into the shoes of the library user. AB - Personas are researched-based user archetypes which can help uncover gaps, highlight new opportunities, and inform the functionality of a space, resource, or service. Personas are a useful tool for organizations, such as libraries, which are interested in improving the user experience, since they tap into users' expectations, behaviors, and attitudes. This column will explain what personas are, the advantages and disadvantages of using personas, and where personas are used. A list of resources for exploring and creating personas is also provided. PMID- 24180653 TI - Lifelong learning for nurses-building a strong future. AB - Lifelong learning is a key issue for the nursing profession. The literature reports effective collaboration between nurses and health sciences librarians to develop evidence-based programs for hospital staff nurses. In this collaboration the nurse provides the real-time practice issues and the health sciences librarian provides the expertise to retrieve the information from the literature. This column presents a current overview of the participation of health sciences librarians, particularly hospital librarians, in the development of programs and resources for nurses' lifelong learning. PMID- 24180654 TI - The librarian's role in linking patients to their personal health data and contextual information. AB - The objective of this project was to make an institution's patients aware of a new patient portal with contextual links to MedlinePlus. Through partnerships with information technology personnel and LSU Health Shreveport clinics, the Health Sciences Library created and distributed promotional and educational materials and instructed patients on how to use MyChart and access reliable consumer health information via MedlinePlus Connect. Although most patients were not interested in coming to the library for demonstrations, many of them expressed interest in using MyChart. The contextual information in MedlinePlus Connect worked well for most topics. The institutional team leader for MyChart expressed gratitude for librarian involvement. PMID- 24180662 TI - The vertebrate ancestral repertoire of visual opsins, transducin alpha subunits and oxytocin/vasopressin receptors was established by duplication of their shared genomic region in the two rounds of early vertebrate genome duplications. AB - BACKGROUND: Vertebrate color vision is dependent on four major color opsin subtypes: RH2 (green opsin), SWS1 (ultraviolet opsin), SWS2 (blue opsin), and LWS (red opsin). Together with the dim-light receptor rhodopsin (RH1), these form the family of vertebrate visual opsins. Vertebrate genomes contain many multi membered gene families that can largely be explained by the two rounds of whole genome duplication (WGD) in the vertebrate ancestor (2R) followed by a third round in the teleost ancestor (3R). Related chromosome regions resulting from WGD or block duplications are said to form a paralogon. We describe here a paralogon containing the genes for visual opsins, the G-protein alpha subunit families for transducin (GNAT) and adenylyl cyclase inhibition (GNAI), the oxytocin and vasopressin receptors (OT/VP-R), and the L-type voltage-gated calcium channels (CACNA1-L). RESULTS: Sequence-based phylogenies and analyses of conserved synteny show that the above-mentioned gene families, and many neighboring gene families, expanded in the early vertebrate WGDs. This allows us to deduce the following evolutionary scenario: The vertebrate ancestor had a chromosome containing the genes for two visual opsins, one GNAT, one GNAI, two OT/VP-Rs and one CACNA1-L gene. This chromosome was quadrupled in 2R. Subsequent gene losses resulted in a set of five visual opsin genes, three GNAT and GNAI genes, six OT/VP-R genes and four CACNA1-L genes. These regions were duplicated again in 3R resulting in additional teleost genes for some of the families. Major chromosomal rearrangements have taken place in the teleost genomes. By comparison with the corresponding chromosomal regions in the spotted gar, which diverged prior to 3R, we could time these rearrangements to post-3R. CONCLUSIONS: We present an extensive analysis of the paralogon housing the visual opsin, GNAT and GNAI, OT/VP-R, and CACNA1-L gene families. The combined data imply that the early vertebrate WGD events contributed to the evolution of vision and the other neuronal and neuroendocrine functions exerted by the proteins encoded by these gene families. In pouched lamprey all five visual opsin genes have previously been identified, suggesting that lampreys diverged from the jawed vertebrates after 2R. PMID- 24180663 TI - Structure vs chemistry: friction and wear of Pt-based metallic surfaces. AB - In comparison of a Pt57.5Cu14.7Ni5.3P22.5 metallic glass with a Pt(111) single crystal we find that wearless friction is determined by chemistry through bond formation alloying, while wear is determined by structure through plasticity mechanisms. In the wearless regime, friction is affected by the chemical composition of the counter body and involves the formation of a liquid-like neck and interfacial alloying. The wear behavior of Pt-based metallic surfaces is determined by their structural properties and corresponding mechanisms for plastic deformation. In the case of Pt(111) wear occurs by dislocation-mediated homogeneous plastic deformation. In contrast the wear of Pt57.5Cu14.7Ni5.3P22.5 metallic glass occurs through localized plastic deformation in shear bands that merge together in a single shear zone above a critical load and corresponds to the shear softening of metallic glasses. These results open a new route in the control of friction and wear of metals and are relevant for the development of self-lubricated and wear-resistant mechanical devices. PMID- 24180661 TI - Specificity in ROS signaling and transcript signatures. AB - SIGNIFICANCE: Reactive oxygen species (ROS), important signaling molecules in plants, are involved in developmental control and stress adaptation. ROS production can trigger broad transcriptional changes; however, it is not clear how specificity in transcriptional regulation is achieved. RECENT ADVANCES: A large collection of public transcriptome data from the model plant Arabidopsis thaliana is available for analysis. These data can be used for the analysis of biological processes that are associated with ROS signaling and for the identification of suitable transcriptional indicators. Several online tools, such as Genevestigator and Expression Angler, have simplified the task to analyze, interpret, and visualize this wealth of data. CRITICAL ISSUES: The analysis of the exact transcriptional responses to ROS requires the production of specific ROS in distinct subcellular compartments with precise timing, which is experimentally difficult. Analyses are further complicated by the effect of ROS production in one subcellular location on the ROS accumulation in other compartments. In addition, even subtle differences in the method of ROS production or treatment can lead to significantly different outcomes when various stimuli are compared. FUTURE DIRECTIONS: Due to the difficulty of inducing ROS production specifically with regard to ROS type, subcellular localization, and timing, we propose that the concept of a "ROS marker gene" should be re evaluated. We suggest guidelines for the analysis of transcriptional data in ROS signaling. The use of "ROS signatures," which consist of a set of genes that together can show characteristic and indicative responses, should be preferred over the use of individual marker genes. PMID- 24180669 TI - Radiometabolic treatment of bone-metastasizing cancer: from 186rhenium to 223radium. AB - Skeletal metastases occur in many patients with different kinds of malignant tumors, especially in advance stage of breast cancer (in 47%-85% of patients), prostate cancer (33-85%), and lung cancer (32%-60%). The management of painful skeletal metastases is complicated and should be carried out by a multidisciplinary approach including conventional analgesics, antitumor therapy (chemo- and hormone therapy), osteoclast-inhibitory agents (bisphosphonates), corticosteroids, external-beam radiotherapy, surgery, and nuclear medicine therapy. The nuclear medicine therapy for palliation of pain from bone metastases is a systemic radionuclide therapy based on the use of radiopharmaceuticals. In several studies the efficacy of bone-seeking radiopharmaceuticals have been demonstrated in terms of pain reduction from diffuse skeletal metastases. In this review, we will summarize the current literature on bone-seeking radiopharmaceuticals for the treatment of painful bone metastases (Phosphorus-32, Strontium-89, Rhenium-186, Rhenium-188, Samarium-153, and Radium-223) and the combination therapy with biphosphonates and chemotherapy. PMID- 24180668 TI - Path2Models: large-scale generation of computational models from biochemical pathway maps. AB - BACKGROUND: Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data. RESULTS: To increase the efficiency of model creation, the Path2Models project has automatically generated mathematical models from pathway representations using a suite of freely available software. Data sources include KEGG, BioCarta, MetaCyc and SABIO-RK. Depending on the source data, three types of models are provided: kinetic, logical and constraint-based. Models from over 2 600 organisms are encoded consistently in SBML, and are made freely available through BioModels Database at http://www.ebi.ac.uk/biomodels main/path2models. Each model contains the list of participants, their interactions, the relevant mathematical constructs, and initial parameter values. Most models are also available as easy-to-understand graphical SBGN maps. CONCLUSIONS: To date, the project has resulted in more than 140 000 freely available models. Such a resource can tremendously accelerate the development of mathematical models by providing initial starting models for simulation and analysis, which can be subsequently curated and further parameterized. PMID- 24180671 TI - 15-Deoxy-Delta(12,14)-prostaglandin J2 prevents oxidative injury by upregulating the expression of aldose reductase in vascular smooth muscle cells. AB - The omega-6 fatty acid derivative 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d PGJ2) is believed to play a role in cellular protection against oxidative stress in diverse cell systems. However, the cellular mechanisms by which protection is afforded by 15d-PGJ2 are not fully elucidated in vascular smooth muscle cells (VSMCs). In this study, we report the finding that 15d-PGJ2 elicited a time and concentration- dependent increase in aldose reductase (AR) expression. This induction was independent of the activation of peroxisome proliferator- activated receptor gamma. Inhibition of phosphatidylinositol 3-kinase (PI3K) significantly suppressed the increase in expression and promoter activity of AR induced by 15d PGJ2. Luciferase reporter assays demonstrated that 15d-PGJ2 targets the multiple stress response regions comprising the antioxidant response element in the promoter of the AR gene. 15d-PGJ2-mediated induction of AR promoter activity was potentiated in the presence of nuclear factor-erythroid 2-related factor 2 (Nrf2), but not in cells expressing dominant negative Nrf2. Cells treated with 15d-PGJ2 were resistant to oxidant-induced apoptotic cell death by inhibiting production of reactive oxygen species. These effects were significantly attenuated in the presence of an AR inhibitor or small interfering RNA against AR, indicating that AR plays a protective role against oxidative injury. Taken together, these findings demonstrate that activation of PI3K by 15d-PGJ2 increases the expression of AR through Nrf2, and increased AR activity may function as an important cellular response against oxidative injury. PMID- 24180670 TI - CD26 expression on T-anaplastic large cell lymphoma (ALCL) line Karpas 299 is associated with increased expression of versican and MT1-MMP and enhanced adhesion. AB - BACKGROUND: CD26/dipeptidyl peptidase IV (DPPIV) is a multifunctional membrane protein with a key role in T-cell biology and also serves as a marker of aggressive cancers, including T-cell malignancies. METHODS: Versican expression was measured by real-time RT-PCR and Western blots. Gene silencing of versican in parental Karpas 299 cells was performed using transduction-ready viral particles. The effect of versican depletion on surface expression of MT1-MMP was monitored by flow cytometry and surface biotinylation. CD44 secretion/cleavage and ERK (1/2) activation was followed by Western blotting. Collagenase I activity was measured by a live cell assay and in vesicles using a liquid-phase assay. Adhesion to collagen I was quantified by an MTS assay. RESULTS: Versican expression was down-regulated in CD26-depleted Karpas 299 cells compared to the parental T-ALCL Karpas 299 cells. Knock down of versican in the parental Karpas 299 cells led to decreased MT1-MMP surface expression as well as decreased CD44 expression and secretion of the cleaved form of CD44. Parental Karpas 299 cells also exhibited higher collagenase I activity and greater adhesion to collagenase I than CD26-knockdown or versican-knockdown cells. ERK activation was also highest in parental Karpas 299 cells compared to CD26-knockdown or versican knockdown clones. CONCLUSIONS: Our data indicate that CD26 has a key role in cell adhesion and invasion, and potentially in tumorigenesis of T-cell lines, through its association with molecules and signal transduction pathways integral to these processes. PMID- 24180672 TI - Lifesaving emergency obstetric services are inadequate in south-west Ethiopia: a formidable challenge to reducing maternal mortality in Ethiopia. AB - BACKGROUND: Most maternal deaths take place during labour and within a few weeks after delivery. The availability and utilization of emergency obstetric care facilities is a key factor in reducing maternal mortality; however, there is limited evidence about how these institutions perform and how many people use emergency obstetric care facilities in rural Ethiopia. We aimed to assess the availability, quality, and utilization of emergency obstetric care services in the Gamo Gofa Zone of south-west Ethiopia. METHODS: We conducted a retrospective review of three hospitals and 63 health centres in Gamo Gofa. Using a retrospective review, we recorded obstetric services, documents, cards, and registration books of mothers treated and served in the Gamo Gofa Zone health facilities between July 2009 and June 2010. RESULTS: There were three basic and two comprehensive emergency obstetric care qualifying facilities for the 1,740,885 people living in Gamo Gofa. The proportion of births attended by skilled attendants in the health facilities was 6.6% of expected births, though the variation was large. Districts with a higher proportion of midwives per capita, hospitals and health centres capable of doing emergency caesarean sections had higher institutional delivery rates. There were 521 caesarean sections (0.8% of 64,413 expected deliveries and 12.3% of 4,231 facility deliveries). We recorded 79 (1.9%) maternal deaths out of 4,231 deliveries and pregnancy-related admissions at institutions, most often because of post-partum haemorrhage (42%), obstructed labour (15%) and puerperal sepsis (15%). Remote districts far from the capital of the Zone had a lower proportion of institutional deliveries (<2% of expected births compared to an overall average of 6.6%). Moreover, some remotely located institutions had very high maternal deaths (>4% of deliveries, much higher than the average 1.9%). CONCLUSION: Based on a population of 1.7 million people, there should be 14 basic and four comprehensive emergency obstetric care (EmOC) facilities in the Zone. Our study found that only three basic and two comprehensive EmOC service qualifying facilities serve this large population which is below the UN's minimum recommendation. The utilization of the existing facilities for delivery was also low, which is clearly inadequate to reduce maternal deaths to the MDG target. PMID- 24180673 TI - Modeling effects of scar on patterns of dorsal column stimulation. AB - OBJECTIVE: The purpose of this study was to examine how scar formation may affect electrical current distribution in the spinal cord when using paddle leads placed in the epidural space during treatment with spinal cord stimulation. MATERIALS AND METHODS: A finite element model of the spinal cord was used to examine changes in stimulation using a guarded cathode configuration with and without scar. Additionally, two potential "compensatory" programming patterns were examined in order to understand how the three-dimensional electrical field may be affected by scar. Direct comparisons with prior studies in the literature and use of known anatomy of dorsal column fiber distributions also enabled a computational estimate of the number of fibers likely reaching threshold with each stimulus pattern. RESULTS: Notable potential and current distribution changes were found related to the modeled scar. Compensatory stimulation patterns (both in spatial and in amplitude dimensions) affect the fiber activation patterns in complex ways that may not be easily predetermined by a programming specialist. CONCLUSIONS: This study is one of the first to examine the effects of scar tissue on dorsal column stimulation and the only one using a detailed computational approach toward that end. It appears that different thickness and location of scar between electrode contacts and the dura may likely lead to a significant number and location of complex changes in the activated fibers. It is likely that a more complete assessment of scarring and its effect on the electrical environment of any given paddle lead would allow more accurate and predictable reprogramming of patients with commercially available systems in place. PMID- 24180674 TI - Rapid detection of glycopeptide-resistant enterococci: impact on decision-making and costs. AB - BACKGROUND: According to French national recommendations, the detection of a patient colonized with glycopeptide-resistant enterococci (GRE) leads to interruption of new admissions and transfer of contact patients (CPs) to another unit or healthcare facility, with weekly screening of CPs. FINDINGS: We evaluated the medical and economic impact of a pragmatic adaptation of national guidelines associated with a real-time PCR (RTP) (Cepheid XpertTM vanA/vanB) as part of the strategy for controlling GRE spread in two medical wards. Screening was previously performed using chromogenic selective medium (CSM). Turn around time (TAT), costs of tests and cost of missed patient days were prospectively collected. In February 2012, the identification of GRE in one patient in the diabetology ward led to the screening of 31 CPs using CSM; one secondary case was identified in a CP already transferred to the Nephrology ward. Awaiting the results of SCM (median TAT, 70.5 h), 41 potential patient days were missed, due to interruption of admissions. The overall cost (screening tests + missing patient.days) was estimated at 14, 302.20 ?. The secondary case led to screening of 22 CPs in the Nephrology ward using RTP. Because of a short median TAT of 4.6 h, we did not interrupt admissions and patients' transfers. Among 22 CPs, 19 (86%) were negative for vanA, 2 were positive for vanB and 3 had invalid results needing CSM. The overall cost of the strategy was estimated at 870.40 ? (cost of screening tests only), without missing patient days. CONCLUSION: The rapid PCR test for vanA-positive GRE detection both allowed rapid decision about the best infection control strategy and prevented loss of income due to discontinuation of patient transfers and admissions. PMID- 24180675 TI - Influence of the vertical position of maxillary central incisors on the perception of smile esthetics among orthodontists and laypersons. AB - OBJECTIVE: The purpose of this study was to determine the perception of smile esthetics among orthodontists and laypeople with respect to different upper central incisor vertical positions in a frontal smile analysis. MATERIALS AND METHODS: A frontal close-up smile photo of an adult Caucasian woman was selected. The patient had healthy upper anterior dentition and had no history of orthodontic treatment. Images were altered in order to create six different central incisor vertical positions in 0.5-mm increments. All images were assessed in three different views: full smile, gingival close-up excluding incisal edges, and incisal close-up excluding gingival margins. Images were randomly assembled in an album, which was given to 120 judges: 60 orthodontists and 60 laypersons. Each rater was asked to evaluate the attractiveness of the images using the visual analog scale. The data collected were then statistically analyzed. RESULTS: The highest rated smiles showed two notable characteristics: the central to-lateral incisal step was 1.5 mm; and the central incisor gingival margins matched the laterals, and both were 0.5 mm below the line of the canine gingival margins. The least attractive smile was the one with no step between the centrals and laterals, and with the central incisor gingival margins 1.0 mm above the canine gingival margins. CONCLUSION: The results of this study indicate that slightly extruded upper central incisors are more esthetically preferred than intruded. CLINICAL SIGNIFICANCE: The upper central incisors are the key determinant in evaluating smile esthetics, and thus, the assessment of their ideal vertical positioning is an aspect of paramount importance. PMID- 24180676 TI - Optimistic update bias increases in older age. AB - BACKGROUND: Healthy older adults report greater well-being and life satisfaction than their younger counterparts. One potential explanation for this is enhanced optimism. We tested the influence of age on optimistic and pessimistic beliefs about the future and the associated structural neural correlates. METHOD: Eighteen young and 18 healthy older adults performed a belief updating paradigm, measuring differences in updating beliefs for desirable and undesirable information about future negative events. These measures were related to regional brain volume, focusing on the anterior cingulate cortex (ACC) because this region is strongly linked to a positivity bias in older age. RESULTS: We demonstrate an age-related reduction in updating beliefs when older adults are faced with undesirable, but not desirable, information about negative events. This greater 'update bias' in older age persisted even after controlling for a variety of variables including subjective rating scales and poorer overall memory. A structural brain correlate of this greater 'update bias' was evident in greater grey matter volume in the dorsal ACC in older but not in young adults. CONCLUSIONS: We show a greater update bias in healthy older age. The link between this bias and relative volume of the ACC suggests a shared mechanism with an age related positivity bias. Older adults frequently have to make important decisions relating to personal, health and financial issues. Our findings have wider behavioural implications in these contexts because an enhanced optimistic update bias may skew such real-world decision making. PMID- 24180677 TI - Source attribution of air pollutant concentrations and trends in the southeastern aerosol research and characterization (SEARCH) network. AB - A new approach for determining the contributions of emission sources to trends in concentrations of particulate matter and gases is developed using the chemical mass balance (CMB) method and the U.S. EPA's National Emission Inventory (NEI). The method extends our earlier analysis by using temporally varying emission profiles and includes accounting of primary and secondary particulate organic carbon with an empirical regression calculation. The model offers a potentially important tool for verifying that annual emission reductions by major source category have yielded changes in ambient pollutant concentrations. Using long term measurements from well-instrumented monitoring sites, observed trends in ambient pollutant concentrations at urban and rural locations can be attributed to emission changes. Trends apportionment is conducted on 2000-2011 ambient monitoring data from the SEARCH network with NEI emissions data adjusted to improve interinventory consistency. The application accounts for major source category influences in southeastern U.S. regional trends; local anomalies are noted. In the SEARCH region, open burning is important as a source of CO and carbonaceous particles. Improved agreement between predicted and measured particulate carbon is obtained by increasing mobile diesel exhaust and area source particulate carbon emissions by 1 and 20%, respectively, compared with NEI values. The method is general and is applicable to data from any monitoring site that is instrumented for criteria air pollutants, associated gases, and particle composition. PMID- 24180678 TI - Laminin gamma-1 and collagen alpha-1 (VI) chain are galactose-alpha-1,3-galactose bound allergens in beef. AB - BACKGROUND: Sensitization to the carbohydrate galactose-alpha-1,3-galactose (alpha-Gal) has been reported in patients with beef allergy. However, the proteins responsible for this allergy have not yet been identified. This study aimed to identify beef proteins that predominantly react with serum IgE in Japanese patients with beef allergy. METHODS: Sera were collected from 29 patients with beef allergy who had allergic reaction(s) such as urticaria, abdominal pain, vomiting, and anaphylactic shock after ingestion of beef and pork; the sera tested positive for IgE against beef and pork. IgE-binding proteins were detected by immunoblotting sera from the patients and identified using a combination of two-dimensional gel electrophoresis and peptide mass fingerprinting techniques. The involvement of carbohydrate in the binding of IgE to allergens was examined by periodate treatment and an inhibition assay with cetuximab by immunoblotting. Specific IgE binding to cetuximab was measured using the CAP-fluorescent enzyme immunoassay. RESULTS: Two IgE-binding proteins (240 kDa and 140 kDa) were detected in beef extract and identified as laminin gamma-1 and the collagen alpha-1 (VI) chain from Bos taurus, respectively. Periodate treatment or the inhibition assay resulted in the loss of IgE binding to these proteins. Immunoblotting with anti-alpha-Gal antibody revealed the presence of alpha-Gal on the 240- and 140-kDa beef proteins. The amount of IgE bound to cetuximab was significantly correlated with that to beef in the patients with beef allergy. CONCLUSION: The carbohydrate moiety (alpha-Gal) on laminin gamma-1 and collagen alpha-1 (VI) chain are possibly common IgE-reactive proteins in the Japanese patients with beef allergy. PMID- 24180679 TI - Endovascular thrombolysis for pediatric cerebral sinus venous thrombosis with tissue plasminogen activator and abciximab. AB - Cerebral sinus venous thrombosis (CSVT) is a relatively rare but potentially devastating disease. Medical management of CSVT with systemic anticoagulation has been the mainstay treatment strategy with these patients. However, some patients may not respond to this treatment or may present with very severe symptoms indicating more aggressive management strategies. The authors present the case of a pediatric patient who presented with severe CSVT, who underwent successful recanalization with endovascular tissue plasminogen activator (tPA) and abciximab. To the authors' knowledge there are no cases of endovascular thrombolysis for CSVT described in the literature in which abciximab has been used in conjunction with tPA. The authors also review the literature regarding the agents used and outcome in pediatric patients with CSVT after endovascular thrombolysis. The use of abciximab in conjunction with tPA may be considered in patients whose blood is hypercoagulable and in whom the treatment strategy is to obtain acute recanalization and long-term venous patency. However, the use of adjunctive agents increases the risk of hemorrhagic complications and must be done judiciously. PMID- 24180680 TI - Pediatric tectal plate gliomas: clinical and radiological progression, MR imaging characteristics, and management of hydrocephalus. AB - OBJECT: Tectal plate gliomas are generally low-grade astrocytomas with favorable prognosis, and observation of the lesion and management of hydrocephalus remain the mainstay of treatment. METHODS: A cohort of patients with tectal plate gliomas at 2 academic institutions was retrospectively reviewed. RESULTS: Forty four patients with a mean age of 10.2 years who harbored tectal plate gliomas were included in the study. The mean clinical and radiological follow-up was 7.6 +/- 3.3 years (median 7.9 years, range 1.5-14.7 years) and 6.5 +/- 3.1 years (median 6.5 years, range 1.1-14.7 years), respectively. The most frequent intervention was CSF diversion (81.8% of patients) followed by biopsy (11.4%), radiotherapy (4.5%), chemotherapy (4.5%), and resection (2.3%). On MR imaging tectal plate gliomas most commonly showed T1-weighted isointensity (71.4%), T2 weighted hyperintensity (88.1%), and rarely enhanced (19%). The initial mean volume was 1.6 +/- 2.2 cm(3) and it increased to 2.0 +/- 4.4 cm(3) (p = 0.628) at the last follow-up. Frontal and occipital horn ratio (FOHR) and third ventricular width statistically decreased over time (p < 0.001 and p < 0.05, respectively). CONCLUSIONS: The authors' results support existing evidence that tectal plate gliomas frequently follow a benign clinical and radiographic course and rarely require any intervention beyond management of associated hydrocephalus. PMID- 24180681 TI - A management strategy for intraventricular subependymal giant cell astrocytomas in tuberous sclerosis complex. AB - OBJECT: Subependymal giant cell astrocytomas (SEGAs) are benign tumors, most commonly associated with tuberous sclerosis complex (TSC). The vast majority of these tumors arise from the lateral ependymal surface adjacent to the foramen of Monro, therefore potentially encroaching on one or both foramina, and resulting in obstructive hydrocephalus that necessitates surgical decompression. The indications for surgery, intraoperative considerations, and evolution of the authors' management paradigm are presented. METHODS: Patients with TSC who underwent craniotomy for SEGA resection at New York University Langone Medical Center between January 1997 and March 2011 were identified. Preoperative imaging, clinical characteristics, management decisions, operative procedures, and outcomes were reviewed. RESULTS: Eighteen patients with TSC underwent 22 primary tumor resections for SEGAs. The indication for surgery was meaningful radiographic tumor progression in 16 of 21 cases. The average age at the time of operation was 10.3 years. Average follow-up duration was 52 months (range 12-124 months). The operative approach was intrahemispheric-transcallosal in 16 cases, transcortical-transventricular in 5, and neuroendoscopic in 1. Nine tumors were on the right, 9 on the left, and 3 were bilateral. Gross-total resection was documented in 16 of 22 cases in our series, with radical subtotal resection achieved in 4 cases, and subtotal resection (STR) in 2 cases. Two patients had undergone ventriculoperitoneal shunt placement preoperatively and 7 patients required shunt placement after surgery for moderate to severe ventriculomegaly. Two patients experienced tumor progression requiring reoperation; both of these patients had initially undergone STR. CONCLUSIONS: The authors present their management strategy for TSC patients with SEGAs. Select patients underwent microsurgical resection of SEGAs with acceptable morbidity. Gross-total resection or radical STR was achieved in 90.9% of our series (20 of 22 primary tumor resections), with no recurrences in this group. Approximately half of our patient series required CSF diversionary procedures. There were no instances of permanent neurological morbidity associated with surgery. PMID- 24180682 TI - Novel pressure-sensing skin for detecting impending tissue damage during neuroendoscopy. AB - OBJECT: Endoscopy plays an increasingly important role in minimally invasive neurosurgery. Visual feedback from the endoscope tip helps the surgeon prevent unwanted tissue contact. However, critical feedback regarding tissue deformation and trauma from proximal endoscope components is currently unavailable. A system for force feedback along the endoscope length could provide significant clinical benefit by warning of impending damage. The authors manufactured and tested a novel pressure-sensing polymer skin for use in pressure feedback during intracranial endoscopy. METHODS: A photolithography process on a silicon wafer was used to produce a pattern of 80-MUm-tall extrusions to serve as a positive mold for the sensor array. A thin layer of polydimethylsiloxane polymer was molded onto these features. Demolding the polymer from the wafer and sealing with another polymer layer resulted in microchannels. These microchannels were filled with a conductive liquid metal and connected to recording hardware. Spiral channel patterns were designed to create a 3 * 3 array of pressure-sensor pads, which were wrapped around a standard neuroendoscope operating sheath. Pressure readings from the compressed sensor array were translated into a color-coded graphic user interface. Calibration experiments were conducted, and the sensor was evaluated through cortical compression tests on explanted ovine brain. RESULTS: The sensing endoscope operating sheath was successfully calibrated to detect and display pressures within a range consistent with normal and tissue threatening compressions. CONCLUSIONS: Force-feedback mechanisms for the neuroendoscopist are critically lacking with contemporary endoscopes. The authors designed a pressure-sensing skin technology for improved pressure feedback during endoscopy as a means for minimizing collateral tissue damage during endoscopy. PMID- 24180683 TI - Letter to the Editor: oxygen monitoring. PMID- 24180684 TI - Use of thulium-sensitized rare earth-doped low phonon energy crystalline hosts for IR sources. AB - Crystalline hosts with low phonon energies enable novel energy transfer processes when doped with rare earth ions. Two applications of energy transfer for rare earth ions in thulium-sensitized low phonon energy crystals that result in infrared luminescence are discussed. One application is an endothermic, phonon assisted cross-relaxation process in thulium-doped yttrium chloride that converts lattice phonons to infrared emission, which raises the possibility of a fundamentally new method for achieving solid-state optical cooling. The other application is an optically pumped mid-IR phosphor using thulium-praseodymium doped potassium lead chloride that converts 805-nm diode light to broadband emission from 4,000 to 5,500 nm. These two applications in chloride crystals are discussed in terms of critical radii calculated from Forster-Dexter energy transfer theory. It is found that the critical radii for electric dipole-dipole interactions in low phonon energy chloride crystals are comparable to those in conventional oxide and fluoride crystals. It is the reduction in multi-phonon relaxation rates in chloride crystals that enable these additional energy transfer processes and infrared luminescence. PMID- 24180685 TI - Asymmetric lithiation trapping of N-Boc heterocycles at temperatures above -78 degrees C. AB - The asymmetric lithiation trapping of N-Boc heterocycles using s-BuLi/chiral diamines at temperatures up to -20 degrees C is reported. Depending on the N-Boc heterocycle, lithiation is accomplished using s-BuLi and (-)-sparteine or the (+) sparteine surrogate in the temperature range -50 to -20 degrees C for short reaction times (2-20 min). Subsequent electrophilic trapping or transmetalation Negishi coupling delivered functionalized N-Boc heterocycles in 47-95% yield and 77:23-93:7 er. With N-Boc pyrrolidine, trapped products can be generated in ~90:10 er even at -20 degrees C. PMID- 24180686 TI - Isocyanide insertion: de novo synthesis of trifluoromethylated phenanthridine derivatives. AB - A mechanistically new strategy has been described for the simple, practical, and environmentally friendly preparation of 6-(trifluoromethyl)phenanthridine derivatives using ionic isocyanide insertion from biphenyl isocyanide derivatives and Umemoto's reagent. These reactions were promoted only by inorganic base in good-to-excellent chemical yields without any external stoichiometric oxidants and radical initiators. PMID- 24180687 TI - Highly diastereoselective DABCO-catalyzed [3 + 3]-cycloaddition of 1,4-dithiane 2,5-diol with azomethine imines. AB - An effective diastereoselective [3 + 3] cycloaddition of 1,4-dithiane-2,5-diol with azomethine imines catalyzed by DABCO is described. A variety of highly functionalized six-membered dinitrogen-fused heterocycles can be obtained in good yield with excellent diastereoselectivity, which was controlled by anomeric effect. PMID- 24180688 TI - Exercise echocardiography predicts postoperative left ventricular remodeling in aortic regurgitation. AB - OBJECTIVE: We aimed to investigate if preoperative left ventricular (LV) function assessed by exercise echocardiography could predict late postoperative LV function in aortic regurgitation (AR) patients and to evaluate how LV long-axis function is affected late after aortic valve surgery. DESIGN: A total of 21 male chronic AR patients, aged 49 ( 12 ) years, accepted for surgery were examined preoperatively, 6 months-, and 4 years postoperatively, at rest and during exercise. Besides conventional echocardiographic parameters, the atrioventricular plane displacement (AVPD) by M-mode and peak systolic velocity (s') in the basal LV by color tissue Doppler were measured. RESULTS: Preoperatively EF rest and EF exercise, were 55( 7 )% and 54( 9 )%, respectively, and ?EF 0( 8 )%. LV dimensions and volumes indexed to BSA had decreased at the 6-month follow-up and were stable at late follow-up. s'rest, s'exercise, AVPD rest, and AVPD exercise were unchanged at both the postoperative examinations (all P >= 0.05). Preoperative EF exercise and AVPD exercise showed inverse correlation to late postoperative indexed LV enddiastolic volume (r = -0.68, p < 0.004 and r = -0.86, P < 0.001) and indexed LV endsystolic volume (r = -0.68, P = 0.004 and r = -0.81, P < 0.001), while there was no correlation to preoperative EF rest and AVPD rest (all r < 0.2). CONCLUSIONS: Preoperative exercise echocardiography can detect AR patients with suboptimal LV remodeling late postoperatively. PMID- 24180690 TI - Nitric oxide scavenging by cell-free hemoglobin may be a primary factor determining hypertension in polycythemic patients. AB - We tested the hypothesis that hypertension associated with polycythemia vera (PV) may be related to hemoglobin released from erythrocytes (cell-free hemoglobin, fHb). We assessed hematocrit, mean arterial pressure (MAP), blood viscosity, and the level of fHb and nitrite/nitrate (NOx) in the plasma of 73 PV patients and 38 healthy controls. The effect of isovolemic erythrocytapheresis (ECP) on the considered parameters was also studied. From the whole group of PV patients a subset of subjects with normal (normotensive patients, n = 16) and elevated MAP (hypertensive patients, n = 57) can be subtracted. It was found that in comparison with healthy controls, PV patients have significantly (p <= 0.01) elevated Hct (0.567 vs. 0.422), blood viscosity (5.45 vs. 3.56 cP), MAP (106.8 vs. 93.8 mmHg), plasma fHb (9.7 vs. 2.8 mg/dL), and NOx levels (34.1 vs. 27.5 MUM). Compared with normotensive patients, hypertensive PV patients demonstrated a higher rise in fHb (10.2 vs. 8.0) and plasma NOx levels (35.8 vs. 31.0). In PV patients, fHb positively correlates with MAP (r = 0.489), NOx levels (r = 0.461), hematocrit (r = 0.428), and viscosity (r = 0.393). Blood viscosity positively correlated with hematocrit (r = 0.894), but not with other considered parameters. In PV patients MAP poorly correlated with hematocrit, whereas the correlation between MAP and NOx altered from - 0.325 (healthy control) to + 0.268 (PV patients). ECP procedure was associated with a significant (p < 0.01) reduction of hematocrit, fHb, blood viscosity, and MAP. In the normotensive subgroup of PV patients the ECP procedure did not affect MAP. It can be concluded that accelerated scavenging of nitric oxide by fHb rather than high Hct may be a key factor determining the development of hypertension in PV patients. PMID- 24180691 TI - Bio-inspired anti-oil-fouling chitosan-coated mesh for oil/water separation suitable for broad pH range and hyper-saline environments. AB - Here, we report a bio-inspired chitosan (CS)-based mesh with high separation efficiency, oil-fouling repellency, and stability in a complex liquid environment. The surface of the CS coating maintains underwater superoleophobicity and low oil adhesion (<1 MUN) in pure water and hyper-saline solutions, and it can keep stable special wettability in broad pH range environments after the CS mesh is fully cross-linked with glutaraldehyde and then reduced by sodium borohydride to form a stable carbon-nitrogen single bond. The separation process is solely gravity-driven, and the mesh can separate a range of different oil/water mixtures with >99% separation efficiency in hyper-saline and broad pH range conditions. We envision that such a separation method will be useful in oil spill cleanup and industrial oily wastewater treatment in extreme environments. PMID- 24180692 TI - Correlates of monoicy and dioicy in hornworts, the apparent sister group to vascular plants. AB - BACKGROUND: Whether male and female gametes are produced by single or separate individuals shapes plant mating and hence patterns of genetic diversity among and within populations. Haploid-dominant plants ("bryophytes": liverworts, mosses and hornworts) can have unisexual (dioicous) or bisexual (monoicous) gametophytes, and today, 68% of liverwort species, 57% of moss species, and 40% of hornwort species are dioicous. The transitions between the two sexual systems and possible correlations with other traits have been studied in liverworts and mosses, but not hornworts. Here we use a phylogeny for 98 of the 200 species of hornworts, the sister group to vascular plants, representing roughly equal proportions of all monoicous and all dioicous species, to test whether transitions in sexual systems are predominantly from monoicy to dioicy as might be expected based on studies of mosses. We further investigate possible correlations between sexual system and spore size, antheridium number, ploidy level, and diversification rate, with character selection partly based on findings in mosses and liverworts. RESULTS: Hornworts underwent numerous transitions between monoicy and dioicy. The transition rate from dioicy to monoicy was 2* higher than in the opposite direction, but monoicous groups have higher extinction rates; diversification rates do not correlate with sexual system. A correlation important in mosses, that between monoicy and polyploidy, apparently plays a small role: of 20 species with chromosome counts, only one is polyploid, the monoicous Anthoceros punctatus. A contingency test revealed that transitions to dioicy were more likely in species with small spores, supporting the hypothesis that small but numerous spores may be advantageous for dioicous species that depend on dense carpets of gametophytes for reproductive assurance. However, we found no evidence for increased antheridium-per-chamber numbers in dioicous species. CONCLUSIONS: Sexual systems in hornworts are labile, and the higher number of extant monoicous species (60%) may be largely due to frequent transitions to monoicy. PMID- 24180689 TI - Redox regulation of plant development. AB - SIGNIFICANCE: We provide a conceptual framework for the interactions between the cellular redox signaling hub and the phytohormone signaling network that controls plant growth and development to maximize plant productivity under stress-free situations, while limiting growth and altering development on exposure to stress. RECENT ADVANCES: Enhanced cellular oxidation plays a key role in the regulation of plant growth and stress responses. Oxidative signals or cycles of oxidation and reduction are crucial for the alleviation of dormancy and quiescence, activating the cell cycle and triggering genetic and epigenetic control that underpin growth and differentiation responses to changing environmental conditions. CRITICAL ISSUES: The redox signaling hub interfaces directly with the phytohormone network in the synergistic control of growth and its modulation in response to environmental stress, but a few components have been identified. Accumulating evidence points to a complex interplay of phytohormone and redox controls that operate at multiple levels. For simplicity, we focus here on redox dependent processes that control root growth and development and bud burst. FUTURE DIRECTIONS: The multiple roles of reactive oxygen species in the control of plant growth and development have been identified, but increasing emphasis should now be placed on the functions of redox-regulated proteins, along with the central roles of reductants such as NAD(P)H, thioredoxins, glutathione, glutaredoxins, peroxiredoxins, ascorbate, and reduced ferredoxin in the regulation of the genetic and epigenetic factors that modulate the growth and vigor of crop plants, particularly within an agricultural context. PMID- 24180693 TI - A Swedish national adoption study of criminality. AB - BACKGROUND: To clarify the role of genetic and environmental factors in criminal behavior (CB), we examined all CB and violent and non-violent subtypes (VCB and NVCB, respectively) in a Swedish national sample of adoptees and their relatives. METHOD: CB was defined by a conviction in the Swedish Crime Register with standard definitions for VCB and NVCB subtypes. We examined adoptees born 1950 1991 (n = 18 070) and their biological (n = 79 206) and adoptive (n = 47 311) relatives. RESULTS: The risk for all CB was significantly elevated in the adopted away offspring of biological parents of which at least one had CB [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.4-1.6] and in the biological full and half-siblings of CB adoptees (OR 1.4, 95% CI 1.2-1.6 and OR 1.3, 95% CI 1.2-1.3, respectively). A genetic risk index (including biological parental/sibling history of CB and alcohol abuse) and an environmental risk index (including adoptive parental and sibling CB and a history of adoptive parental divorce, death, and medical illness) both strongly predicted probability of CB. These genetic and environmental risk indices acted additively on adoptee risk for CB. Moderate specificity was seen in the transmission of genetic risk for VCB and NVCB between biological parents and siblings and adoptees. CONCLUSIONS: CB is etiologically complex and influenced by a range of genetic risk factors including a specific liability to CB and a vulnerability to broader externalizing behaviors, and by features of the adoptive environment including parental CB, divorce and death. Genetic risk factors for VCB and NVCB may be at least partially distinct. PMID- 24180694 TI - Field effect biosensing platform based on 2D alpha-MoO(3). AB - Electrical-based biosensing platforms offer ease of fabrication and simple sensing solutions. Recently, two-dimensional (2D) semiconductors have been proven to be excellent for the fabrication of field effect transistors (FETs) due to their large transconductance, which can be efficiently used for developing sensitive bioplatforms. We present a 2D molybdenum trioxide (MoO3) FET based biosensing platform, using bovine serum albumin as a model protein. The conduction channel is a nanostructured film made of 2D alpha-MoO3 nanoflakes, with the majority of nanoflake thicknesses being equal to or less than 2.8 nm. The response time is impressively low (less than 10 s), which is due to the high permittivity of the 2D alpha-MoO3 nanoflakes. The system offers a competitive solution for future biosensing applications. PMID- 24180695 TI - Programmed pore architectures in modular quaternary metal-organic frameworks. AB - To generate metal-organic frameworks (MOFs) that are complex and modular yet well ordered, we present a strategy employing a family of three topologically distinct linkers that codes for the assembly of a highly porous quaternary MOF. By introducing substituted analogues of the ligands, a set of eight isoreticular frameworks is delivered, with the MOF structure systematically varied while the topology is maintained. To combat randomness and disorder, the substitution patterns of the ligands are designed to be compatible with their crystallographic site symmetries. MOFs produced in this way feature "programmed pores"--multiple functional groups compartmentalized in a predetermined array within a periodic lattice--and are capable of complex functional behavior. In these examples unconventional CO2 sorption trends, including capacity enhancements close to 100%, emerge from synergistic effects. Future PP-MOFs may be capable of enzyme like heterogeneous catalysis and ultraselective adsorption. PMID- 24180696 TI - Dielectric relaxation of high-k oxides. AB - Frequency dispersion of high-k dielectrics was observed and classified into two parts: extrinsic cause and intrinsic cause. Frequency dependence of dielectric constant (dielectric relaxation), that is the intrinsic frequency dispersion, could not be characterized before considering the effects of extrinsic frequency dispersion. Several mathematical models were discussed to describe the dielectric relaxation of high-k dielectrics. For the physical mechanism, dielectric relaxation was found to be related to the degree of polarization, which depended on the structure of the high-k material. It was attributed to the enhancement of the correlations among polar nanodomain. The effect of grain size for the high-k materials' structure mainly originated from higher surface stress in smaller grain due to its higher concentration of grain boundary. PMID- 24180697 TI - Merging concepts - coupling an agent-based model of hematopoietic stem cells with an ODE model of granulopoiesis. AB - BACKGROUND: Hematopoiesis is a complex process involving different cell types and feedback mechanisms mediated by cytokines. This complexity stimulated various models with different scopes and applications. A combination of complementary models promises to provide their mutual confirmation and to explain a broader range of scenarios. Here we propose a combination of an ordinary differential equation (ODE) model of human granulopoiesis and an agent-based model (ABM) of hematopoietic stem cell (HSC) organization. The first describes the dynamics of bone marrow cell stages and circulating cells under various perturbations such as G-CSF treatment or chemotherapy. In contrast to the ODE model describing cell numbers, our ABM focuses on the organization of individual cells in the stem population. RESULTS: We combined the two models by replacing the HSC compartment of the ODE model by a difference equation formulation of the ABM. In this hybrid model, regulatory mechanisms and parameters of the original models were kept unchanged except for a few specific improvements: (i) Effect of chemotherapy was restricted to proliferating HSC and (ii) HSC regulation in the ODE model was replaced by the intrinsic regulation of the ABM. Model simulations of bleeding, chronic irradiation and stem cell transplantation revealed that the dynamics of hybrid and ODE model differ markedly in scenarios with stem cell damage. Despite these differences in response to stem cell damage, both models explain clinical data of leukocyte dynamics under four chemotherapy regimens. CONCLUSIONS: ABM and ODE model proved to be compatible and were combined without altering the structure of both models. The new hybrid model introduces model improvements by considering the proliferative state of stem cells and enabling a cell cycle dependent effect of chemotherapy. We demonstrated that it is able to explain and predict granulopoietic dynamics for a large variety of scenarios such as irradiation, bone marrow transplantation, chemotherapy and growth factor applications. Therefore, it promises to serve as a valuable tool for studies in a broader range of clinical applications, in particular where stem cell activation and proliferation are involved. PMID- 24180699 TI - Pharmacokinetics and physiological effects of repeated oral administrations of tramadol in horses. AB - This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10 mg/kg orally every 12 h for 5 days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored and adverse events were recorded. Data were analysed with two-way repeated measures anova or Kruskal Wallis one-way anova on ranks with P < 0.05 considered statistically significant. There were no significant effects of tramadol on the physiological variables. One horse receiving 10 mg/kg tramadol developed mild colic. Following tramadol at 5 and 10 mg/kg, respectively, maximum plasma concentrations (Cmax ) of tramadol ranged from 82-587 and 127-1280 ng/mL, nonconjugated M1 ranged from 2.51-26.7 and 4.88-34.3 ng/mL, and nonconjugated M2 from 12.5-356 and 35.4-486 ng/mL. Corresponding minimum plasma concentrations (Cmin ) of tramadol at 12 h following each dose ranged from 0.8-24 and 3-117 ng/mL. Tramadol accumulated considerably over time, more markedly when given at 10 mg/kg than at 5 mg/kg (accumulation indexes of 3.51 and 1.73 respectively). There was no accumulation of M1 but substantial accumulation of M2. In conclusion, there was accumulation and increase in exposure to tramadol and M2, but not M1, during repeated oral administrations in horses. PMID- 24180698 TI - Identification of the angiogenic gene signature induced by EGF and hypoxia in colorectal cancer. AB - BACKGROUND: Colorectal cancer (CRC) is characterised by hypoxia, which activates gene transcription through hypoxia-inducible factors (HIF), as well as by expression of epidermal growth factor (EGF) and EGF receptors, targeting of which has been demonstrated to provide therapeutic benefit in CRC. Although EGF has been demonstrated to induce expression of angiogenic mediators, potential interactions in CRC between EGF-mediated signalling and the hypoxia/HIF pathway remain uncharacterised. METHODS: PCR-based profiling was applied to identify angiogenic genes in Caco-2 CRC cells regulated by hypoxia, the hypoxia mimetic dimethyloxallylglycine (DMOG) and/or EGF. Western blotting was used to determine the role of HIF-1alpha, HIF-2alpha and MAPK cell signalling in mediating the angiogenic responses. RESULTS: We identified a total of 9 angiogenic genes, including angiopoietin-like (ANGPTL) 4, ephrin (EFNA) 3, transforming growth factor (TGF) beta1 and vascular endothelial growth factor (VEGF), to be upregulated in a HIF dependent manner in Caco-2 CRC cells in response to both hypoxia and the hypoxia mimetic dimethyloxallylglycine (DMOG). Stimulation with EGF resulted in EGFR tyrosine autophosphorylation, activation of p42/p44 MAP kinases and stabilisation of HIF-1alpha and HIF-2alpha proteins. However, expression of 84 angiogenic genes remained unchanged in response to EGF alone. Crucially, addition of DMOG in combination with EGF significantly increased expression of a further 11 genes (in addition to the 9 genes upregulated in response to either DMOG alone or hypoxia alone). These additional genes included chemokines (CCL-11/eotaxin-1 and interleukin-8), collagen type IV alpha3 chain, integrin beta3 chain, TGFalpha and VEGF receptor KDR. CONCLUSION: These findings suggest that although EGFR phosphorylation activates the MAP kinase signalling and promotes HIF stabilisation in CRC, this alone is not sufficient to induce angiogenic gene expression. In contrast, HIF activation downstream of hypoxia/DMOG drives expression of genes such as ANGPTL4, EFNA3, TGFbeta1 and VEGF. Finally, HIF activation synergises with EGF-mediated signalling to additionally induce a unique sub-group of candidate angiogenic genes. Our data highlight the complex interrelationship between tumour hypoxia, EGF and angiogenesis in the pathogenesis of CRC. PMID- 24180702 TI - The breathing tube was never withdrawn. PMID- 24180700 TI - Interprofessional communication skills training for serious illness: evaluation of a small-group, simulated patient intervention. AB - BACKGROUND: Communication with patients and families is an essential component of high-quality care in serious illness. Small-group skills training can result in new communication behaviors, but past studies have used facilitators with extensive experience, raising concerns this is not scalable. OBJECTIVE: The objective was to investigate the effect of an experiential communication skills building workshop (Codetalk), led by newly trained facilitators, on internal medicine trainees' and nurse practitioner students' ability to communicate bad news and express empathy. DESIGN: Trainees participated in Codetalk; skill improvement was evaluated through pre- and post- standardized patient (SP) encounters. SETTING AND SUBJECTS: The subjects were internal medicine residents and nurse practitioner students at two universities. INTERVENTION AND MEASUREMENTS: The study was carried out in anywhere from five to eight half-day sessions over a month. The first and last sessions included audiotaped trainee SP encounters coded for effective communication behaviors. The primary outcome was change in communication scores from pre-intervention to post-intervention. We also measured trainee characteristics to identify predictors of performance and change in performance over time. RESULTS: We enrolled 145 trainees who completed pre- and post-intervention SP interviews-with participation rates of 52% for physicians and 14% for nurse practitioners. Trainees' scores improved in 8 of 11 coded behaviors (p<0.05). The only significant predictors of performance were having participated in the intervention (p<0.001) and study site (p<0.003). The only predictor of improvement in performance over time was participating in the intervention (p<0.001). CONCLUSIONS: A communication skills intervention using newly trained facilitators was associated with improvement in trainees' skills in giving bad news and expressing empathy. Improvement in communication skills did not vary by trainee characteristics. PMID- 24180703 TI - Commentary: influence of the vertical position of maxillary central incisors on the perception of smile esthetics among orthodontists and laypersons. PMID- 24180704 TI - Properties of complexes H2C?(X)P:PXH2, for X = F, Cl, OH, CN, NC, CCH, H, CH3, and BH2: P...P pnicogen bonding at sigma-holes and pi-holes. AB - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out on complexes H2C?(X)P:PXH2, for X = F, Cl, OH, CN, NC, CCH, H, CH3, and BH2. Three sets of complexes have been found on the potential surfaces. Conformation A complexes have A-P...P-A approaching linearity, with A the atom of X directly bonded to P. Conformation B complexes have A-P...P linear, but the P...P?C orientation of H2C?PX may differ significantly from linearity. Conformation C complexes are unique, since the pnicogen bond involves pi-electron donation and acceptance by H2C?PX. The order of binding energies of the three conformations of H2C?(X)P:PXH2 is C > A > B, with two exceptions. Although the binding energies of conformation C complexes tend to be greater than the corresponding conformation A complexes, intermolecular distances in conformation C tend to be longer than those in conformation A. Charge transfer stabilizes H2C?(X)P:PXH2 complexes. The preferred direction of charge transfer is from H2C?PX to PXH2. In conformations A and B, charge transfer occurs from a P lone pair on one molecule to an antibonding sigma* orbital on the other. However, in conformation C, charge transfer occurs from the pi orbital of H2C?PX to the sigma*P-A orbital of PXH2, and from the lone pair on P of PXH2 through the pi-hole to the pi*P?C orbital of H2C?PX. Changes in charges on P upon complexation do not correlate with changes in (31)P chemical shieldings. Computed EOM-CCSD spin-spin coupling constants correlate with P-P distances. At each distance, the ordering of (1p)J(P-P) is A > B > C. Binding energies and spin-spin coupling constants of conformation A complexes of (PH2X)2, H2C?(X)P:PXH2, and (H2C?PX)2 with A-P...P-A approaching linearity have been compared. For complexes with the more electronegative substituents, binding energies are ordered (PH2X)2 > H2C?(X)P:PXH2 > (H2C?PX)2, while the order is reversed for complexes formed from the more electropositive substituents. A plot of DeltaE(PH2X)2/DeltaE(H2C?PX)2 versus DeltaE[H2C?(X)P:PXH2]/DeltaE(H2C?PX)2 indicates that there is a systematic relationship among the stabilities of these complexes. Complexes (PH2X)2 tend to have larger spin-spin coupling constants and shorter P-P distances than H2C?(X)P:PXH2, which in turn have larger coupling constants and shorter P-P distances than (H2C?PX)2, although there is some overlap. Complexes having similar P-P distances have similar values of (1p)J(P P). PMID- 24180706 TI - Impact of wastewater treatment configuration and seasonal conditions on thyroid hormone disruption and stress effects in Rana catesbeiana tailfin. AB - Improved endocrine disrupting compound (EDC) removal is desirable in municipal wastewater treatment plants (MWWTPs) although increased removal does not always translate into reduced biological activity. Suitable methods for determining reduction in biological activity of effluents are needed. In order to determine which MWWTPs are the most effective at removing EDC activities, we operated three configurations of pilot sized biological reactors (conventional activated sludge, CAS; nitrifying activated sludge, NAS; and biological nutrient removal, BNR) receiving the same influent under simulated winter and summer conditions. As frogs are model organisms for the study of thyroid hormone (TH) action, we used the North American species Rana catesbeiana in a cultured tadpole tailfin (C-fin) assay to compare the effluents. TH-responsive (thyroid hormone receptors alpha (thra) and beta (thrb)) and stress-responsive (superoxide dismutase, catalase, and heat shock protein 30) mRNA transcript levels were examined. Effluents infrequently perturbed stress-responsive transcript abundance but thra/thrb levels were significantly altered. In winter conditions, CAS caused frequent TH perturbations while BNR caused none. In summer conditions, however, BNR caused substantial TH perturbations while CAS caused few. Our findings contrast other studies of seasonal variations of EDC removal and accentuate the importance of utilizing appropriate biological readouts for assessing EDC activities. PMID- 24180707 TI - CXCR4 blockade and sphingosine-1-phosphate activation facilitate engraftment of haematopoietic stem and progenitor cells in a non-myeloablative transplant model. AB - Both immunosuppressive and cytoreductive effects of gamma-irradiation contribute to engraftment of allogeneic haematopoietic stem and progenitor cells. We hypothesized that a release of host stem and progenitor cells from the niche prior to conditioning would permit engraftment after less intensive conditioning. Administration of AMD3100 and SEW2871 on days -4 to -2 followed by irradiation on day -1 in a non-myeloablative zebrafish transplant model resulted in a reduced radiation minimum dose of 10 Gy from 15 Gy being sufficient for engraftment. Targeting the SDF-1 (CXCL12)/CXCR4- and S1P/S1P1 -axis increased the efficacy of allografting in an experimental transplant model. PMID- 24180708 TI - Molecular weight effect on the efficiency of polymer solar cells. AB - In this study, we report the investigation of the influence of molecular weight (MW) on power conversion efficiency (PCE) of bulk heterojunction (BHJ) polymer solar cells (PSCs). It was found that PCEs of PSCs fabricated by poly[[4,8-bis[(2 ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2 ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] (PTB7) blended with [6,6]-phenyl C71 butyric acid methyl ester (PC71BM) as the active layer, are significantly enhanced from 5.41 to 6.27 and 8.50% along with the MW of PTB7 increased from 18 to 40 and 128 kg/mol, respectively. This enhancement is attributed to the enhanced light absorption and increased charge carrier mobility of PTB7 with high MW, and a proper phase separation in BHJ composite of PTB7:PC71BM interpenetrating network. All these results demonstrate that the MW of donor polymer plays an important role in the performance of BHJ PSCs. PMID- 24180709 TI - Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders. AB - BACKGROUND AND PURPOSE: High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship to the AB0 blood type system. METHODS: In a prospective study 34 de novo treated patients were given 2.0 g/kg bodyweight of Privigen and 50 patients received either Privigen [n = 28; 1.53 +/- 0.4 g/kg (mean +/- SD)] or Kiovig (n = 22; 1.7 +/- 0.4 g/kg) as maintenance therapy. The de novo patients all had a post polio syndrome, whereas the remaining patients received maintenance therapy for the neuromuscular disorders chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy. Blood sampling was performed before and 2 weeks after infusion of IVIG. RESULTS: Following IVIG treatment blood hemoglobin declined from 8.6 +/- 0.9 to 8.0 +/- 1.2 mM, P < 0.001. Reticulocyte counts and levels of bilirubin and lactate dehydrogenase were increased and haptoglobin levels decreased. The decline of hemoglobin was 0.9 +/- 1.2 mM after de novo therapy versus 0.4 +/- 0.8 mM after maintenance therapy with Privigen (P = 0.05) and 0.2 +/- 0.3 mM after maintenance therapy with Kiovig (P = 0.47). In de novo patients compared with patients on maintenance therapy reticulocyte count and lactate dehydrogenase level increased whereas haptoglobin level decreased. Anemia correlated with the AB0 blood type system with a significant difference between type 0 (n = 17; +0.3 +/- 0.4 mM) and type A, B and AB (n = 48; -1.0 +/- 1.0 mM), anemia being most pronounced in type AB. CONCLUSION: Moderate hemolytic anemia is a concomitant complication of high dose IVIG in subjects with blood types A, B and AB. PMID- 24180710 TI - Cardiopulmonary bypass has a modest association with cancer progression: a retrospective cohort study. AB - BACKGROUND: Given their frequency of occurrence in the United States, cancer and heart disease often coexist. For patients requiring open-heart surgery, this raises concern that the use of cardiopulmonary bypass (CPB) may cause a transient immunosuppression with the potential to promote the spread and growth of coexisting cancer cells. This study examined the association of cardiopulmonary bypass with cancer progression in a large population-based setting using linked data from several state-wide registries. METHODS: A retrospective cohort study of cancer risk, stage, and mortality in 43,347 patients who underwent coronary artery bypass graft (CABG) surgery with and without CPB in New Jersey between 1998-2004 was conducted. A competing risk analogue of the Cox proportional hazards model with propensity score adjustment and regression on the cause specific hazard was used to compute relative risk ratios (95% confidence intervals [CIs]) for patients undergoing CABG surgery with and without CPB. RESULTS: An increased risk for overall cancer incidence (17%) and cancer-specific mortality (16% overall, 12% case fatality) was observed; yet these results did not reach statistical significance. Of 11 tumor-specific analyses, an increased risk of skin melanoma (1.66 [95% CI, 1.08-2.55: p=0.02]) and lung cancer (1.36 [95% CI, 1.02-1.81: p=0.03]) was observed for patients with pump versus off-pump open-heart surgery. No association was found with cancer stage. CONCLUSIONS: These results suggest that there may be a relationship between CPB and cancer progression. However, if real, the effect is likely modest at most. Further research may still be warranted with particular focus on skin melanoma and lung cancer which had the strongest association with CPB. PMID- 24180711 TI - Veterinary and human anaesthesia: an overview of some parallels and contrasts. AB - The history of human and veterinary anaesthesia is both intertwined and parallel. Physicians and anaesthetists often first experimented on animals and developments from human anaesthesia have been incorporated into veterinary medicine. Within veterinary medicine, anaesthesia is a specialty discipline as it is in human medicine. Veterinary anaesthetists undertake additional training and rigorous examinations for a diploma or fellowship. In contrast to human anaesthesia in Australia and New Zealand, veterinary anaesthesia is often performed by non specialists and by veterinary nurses. Veterinary anaesthesia uses many of the same drugs for premedication, induction and maintenance of anaesthesia as human anaesthesia. However, there are species specific effects of some of the drugs used that differ from the effects in humans. Furthermore, some agents, particularly alpha-2 adrenoreceptor agonists and ketamine, are used very widely in veterinary practice. Also in contrast to most human anaesthesia, in large animal and exotic animal practice the patients can present a physical danger to the anaesthetist. The most notable contrast between human and veterinary anaesthesia is in the reported perioperative complication and mortality rates, with a species dependent perianaesthetic mortality of up to 2% in dogs, cats and horses and greater than 2% in guinea pigs and birds, which is up to 100-fold higher than in human anaesthesia. PMID- 24180712 TI - A comparison of dobutamine and levosimendan on hepatic blood flow in patients with a low cardiac output state after cardiac surgery: a randomised controlled study. AB - Liver dysfunction due to a low cardiac output state after cardiac surgery is associated with a poor prognosis, but whether one inotrope is superior to another in improving hepatic perfusion remains uncertain. This study compared the systemic and hepatic haemodynamic effects of levosimendan to dobutamine in patients with a low cardiac output state (cardiac index < 2.2 l/min/m2) after on pump cardiac surgery. A total of 25 patients were randomised to receive either an intravenous bolus of levosimendan (12 ug/kg) over 15 minutes, followed by an infusion of 0.2 ug/kg/min for 24 hours, or an infusion of dobutamine 7.5 ug/kg/min for 24 hours and completed the study. The systemic and hepatic haemodynamics at 24 and 48 hours were all better after levosimendan than dobutamine (dobutamine group: cardiac index (l/min/m2)=2.51 [standard deviation +/-0.29], 2.40+/-0.23; portal vein flow (ml/min): 614.0+/-124.7, 585.9+/-144.8; pulsatility index: 2.02+/-0,28, 2.98+/-0.27 versus the levosimendan group: cardiac index: 3.02+/- 0.27, 2.98+/- 0.30; portal vein flow: 723.0+/- 143.5, 702.9+/-117.8; pulsatility index: 1.71+/-0.26, 1.73+/-0.27). The improvement in portal vein blood flow at 48 hours was significantly better after levosimendan than dobutamine (41% vs. 11% increment from baseline, P<0.05). In addition, there was a significant reduction in hepatic artery resistance after levosimendan but not dobutamine (resistance index reduction 6.5% vs. 0%, P<0.05). In summary, levosimendan can be considered as a selective liver vasodilator and can improve hepatic blood flow through both the hepatic artery and portal venous system, whereas dobutamine can only improve the portal venous blood flow without vasodilating the hepatic artery. PMID- 24180713 TI - Effects of prolonged mechanical ventilation with a closed suction system on endotracheal tube resistance and its reversibility by a closed suction cleaning system. AB - The study objective was to evaluate endotracheal tubes (ETT) from extubated adult patients and compare them to new, unused, size-matched control tubes for changes in inspiratory resistance (Rinsp) and peak inspiratory pressure (PIP) before and immediately after suctioning with the Airway Medix Closed Suction System (AMCSS) (Biovo Technologies, 2013 Tel Aviv, Israel). Sixteen ETTs were recovered from predominantly medical patients who had required intubation and mechanical ventilation for more than 12 hours. ETTs were evaluated within 4.5 hours of extubation. Readings were taken during square wave flow, at rates of 40 and 60 l/minute. Cleaning of extubated ETTs using the AMCSS was able to restore them to almost original conditions in terms of Rinsp and PIP. The examined ETTs included tubes of various sizes ranging from internal diameter (ID) 7 to 8.5 mm and intubation periods ranging from 12 hours to 21 days. The mean Rinsp for the used and uncleaned ETTs was equivalent to 275% of the Rinsp of sized-matched new and unused ETTs. For 8 mm ID ETTs this was comparable to a measured Rinsp of a 5 mm tube. Following a single cleaning episode with the AMCSS, Rinsp decreased, regaining an effective ETT ID of a 7.5 to 8 mm tube. A single suctioning episode with this device resulted in a significant reduction in Rinsp, virtually restoring original flow variable values. The AMCSS represents a novel technology in closed suction systems, designed to achieve more effective inner lumen cleaning in prolonged mechanical ventilation. PMID- 24180714 TI - Assessment of the plethysmographic variability index as a predictor of fluid responsiveness in critically ill patients: a pilot study. AB - Optimising intravascular volume in patients with hypotension requiring vasopressor support is a key challenge of critical care medicine. The optimal haemodynamic parameter to assess fluid responsiveness in critically ill patients, particularly those requiring a noradrenaline infusion and mechanical ventilation, remains uncertain. This pilot study assessed the accuracy of the plethysmographic variability index (PVI), (Radical-7 pulse co-oximeter, Masimo(r), Irvine, CA, USA) in predicting fluid responsiveness in 25 patients who required noradrenaline infusion to maintain mean arterial pressure over 65 mmHg and were mechanically ventilated with a 'lung-protective' strategy, and whether administering a fluid bolus was associated with a change in PVI (Delta PVI). In this study, fluid responsiveness was defined as an increase in stroke volume of greater than 15% after a 500 ml bolus of colloid infusion over 20 minutes. Of the 25 patients included in the study, only 12 (48%) were considered fluid responders. As static haemodynamic parameters, PVI, central venous pressure and inferior vena cava distensibility index were all inaccurate at predicting volume responsiveness with PVI being the least accurate (area under the receiver operating characteristic curve=0.41, 95% confidence interval 0.18 to 0.65). However, fluid responsiveness was associated with a change in PVI, but not a change in heart rate or central venous pressure. This association between Delta PVI and fluid responsiveness may be a surrogate marker of improved cardiac output following a fluid bolus and warrants further investigation. PMID- 24180715 TI - A comparison between total intravenous anaesthesia using propofol plus remifentanil and volatile induction/ maintenance of anaesthesia using sevoflurane in children undergoing flexible fibreoptic bronchoscopy. AB - Flexible fibreoptic bronchoscopy is an important tool in the evaluation and management of paediatric respiratory disease. Total intravenous anaesthesia (TIVA) and volatile agent induction and maintenance of anaesthesia (VIMA) are commonly used for these procedures. The aim of this study was to determine which is superior for children undergoing flexible fibreoptic bronchoscopy.The study included two phases. In Phase 1, ED99 of propofol in TIVA and ED99 of sevoflurane in VIMA were first determined. In Phase 2, 50 children aged from one to three years were recruited and randomly assigned to either a TIVA or a VIMA group. An ED99 dose of propofol with remifentanil was administered to the TIVA group and sevoflurane to the VIMA group. Haemodynamic variables, stress hormone responses, anaesthesia profiles, adverse reactions and physicians' levels of satisfaction were compared between the two groups. The ED99 values of propofol in the TIVA group and sevoflurane in the VIMA group were 8.9 ug/ml and 6.8% respectively. Haemodynamic variables and stress hormone levels were higher in the VIMA group than in the TIVA group. Agitation and coughing also occurred less frequently in the TIVA group. In addition, physicians' levels of satisfaction were greater in the TIVA group. Our results suggest that TIVA with propofol plus remifentanil is superior to VIMA using sevoflurane alone for children undergoing flexible fibreoptic bronchoscopy. PMID- 24180716 TI - Insomnia and associated factors among anaesthetists in Hong Kong. AB - The primary objective of this survey was to investigate the prevalence of insomnia among anaesthetists in Hong Kong. The use of sleeping aids, factors associated with insomnia and the effect of insomnia on work performance were also studied. We surveyed all locally registered anaesthesia specialists and trainees by post. The response rate was 50%. We found that the prevalence of insomnia among the respondents was 22.4% (95% confidence interval 16.7 to 28.1%). Insomnia was positively associated with the number of on-call shifts per month (P=0.002) and poor relationship with supervisors (P=0.009). Alcohol was the most frequently used aid to assist sleep, followed by zolpidem. The majority of respondents using sleeping medication obtained the drug over-the-counter, by self-prescription or prescription by colleagues. Only 4.3% (95% confidence interval 0 to 10.2%) of respondents suffering from insomnia had formal medical consultation for sleep disturbance. Insomnia was associated with increased subjective sleepiness at work (P=0.007) and subjective decline in work performance during both daytime (P <0.001) and night-time (P <0.001). However, it was not associated with the tendency to fall asleep at work. The results of this survey suggest that insomnia is a common problem among the anaesthetists of Hong Kong. By restricting the amount of on-call duty and improving relationships with supervisors, the prevalence of insomnia may be reduced and the quality of patient care improved. PMID- 24180717 TI - Intraoperative hypothermia is associated with an increased intensive care unit length-of-stay in patients undergoing elective open abdominal aortic aneurysm surgery: a retrospective cohort study. AB - Intraoperative hypothermia in open elective abdominal aortic aneurysm repair may be associated with increased hospital morbidity. This retrospective, single centre study investigated whether there was an association between intraoperative hypothermia in open elective abdominal aortic aneurysm repair and postoperative in-hospital morbidity. The data of 119 patients who underwent open infrarenal abdominal aortic aneurysm repair between January 2006 and January 2011 were collected. The electronic databases from the hospital, intensive care unit, transfusion medicine and operating theatres were linked by the patient's unique identifiers including date of birth and unit record number. Intraoperative nasopharyngeal temperature measurements were collected manually from paper-based anaesthetic records. The study group included 102 out of the 119 patients. Sixty six patients (64.6%) had intraoperative hypothermia as defined by temperature <36 degrees C. Intraoperative temperature was not predictive of hospital length-of stay or any of the other perioperative complications such as acute renal failure, acute respiratory complications, acute myocardial infarction, transfusion requirements or postoperative infection. In the normothermic group, the number of hours in the intensive care unit was 35% lower (ratio of means=0.65; 95% confidence interval 0.51 to 0.84; P=0.0008), even after adjusting for possible confounders such as age, duration of anaesthesia, size of aneurysm, comorbidities and transfusion. Intraoperative hypothermia is a persisting problem and more aggressive warming strategies may need to be identified and employed to achieve normothermia. PMID- 24180718 TI - Time to achieve target mean arterial pressure during resuscitation from experimental anaphylactic shock in an animal model. A comparison of adrenaline alone or in combination with different volume expanders. AB - Anaphylactic shock is a rare, but potentially lethal complication, combining life threatening circulatory failure and massive fluid shifts. Treatment guidelines rely on adrenaline and volume expansion by intravenous fluids, but there is no solid evidence for the choice of one specific type of fluid over another. Our purpose was to compare the time to achieve target mean arterial pressure upon resuscitation using adrenaline alone versus adrenaline with different resuscitation fluids in an animal model and to compare the tissue oxygen pressures (PtiO2) with the various strategies. Twenty-five ovalbumin-sensitised Brown Norway rats were allocated to five groups after anaphylactic shock induction: vehicle (CON), adrenaline alone (AD), or adrenaline with isotonic saline (AD+IS), hydroxyethyl starch (AD+HES) or hypertonic saline (AD+HS). Time to reach a target mean arterial pressure value of 75 mmHg, cardiac output, skeletal muscle PtiO2, lactate/pyruvate ratio and cumulative doses of adrenaline were recorded. Non-treated rats died within 15 minutes. The target mean arterial pressure value was reached faster with AD+HES (median: 10 minutes, range: 7.5 to 12.5 minutes) and AD+IS (median: 17.5 minutes, range: 5 to 25 minutes) versus adrenaline alone (median: 25 minutes, range: 20-30 minutes). There were also reduced adrenaline requirements in these groups. The skeletal muscle PtiO2 was restored only in the AD+HES group. Although direct extrapolation to humans should be made with caution, our results support the combined use of adrenaline and volume expansion for resuscitation from anaphylactic shock. When used with adrenaline the most effective fluid was hydroxyethyl starch, whereas hypertonic saline was the least effective. PMID- 24180719 TI - Effect of an anaesthesia information video on preoperative maternal anxiety and postoperative satisfaction in elective caesarean section: a prospective randomised trial. AB - Video-based patient information supplementing clinician interview has been shown to reduce anxiety and improve satisfaction in patients undergoing procedures. In Queensland more than 90% of caesarean sections are performed under regional anaesthesia. We aimed to assess the effect of using an information video about neuraxial blockade in patients having regional anaesthesia for elective caesarean section. Subjects were randomised to undergo usual care (Group C), or to view a video and undergo usual care (Group V). Subjects completed the Spielberger State Trait Anxiety Inventory preoperatively and the Maternal Satisfaction with Caesarean Section Score questionnaire postoperatively. Satisfaction with, and duration of the preoperative anaesthetic interview, were noted. One-way analysis of variance (ANOVA) and Chi-squared tests were used in statistical analysis. One hundred and forty three subjects were randomised and 110 completed the protocol and analysis. Group C and Group V were similar in terms demographic and anaesthesia data. There was no difference in anxiety score (41.2 versus 39.8, P=0.50), maternal satisfaction score (118.5 versus 122.7, P=0.22) or interview duration (16.3 versus 15.8 min, P=0.69) between the two groups. The use of an anaesthesia information video does not reduce preoperative anxiety or increase the duration of the anaesthetic interview. Maternal satisfaction with neuraxial blockade for elective caesarean is high and not improved by an anaesthesia information video. PMID- 24180720 TI - Incidence of inferior vena cava thrombosis detected by transthoracic echocardiography in the immediate postoperative period after adult cardiac and general surgery. AB - Venous thromboembolism is an important complication after general and cardiac surgery. Using transthoracic echocardiography, this study assessed the incidence of inferior vena cava (IVC) thrombosis among a total of 395 and 289 cardiac surgical and major surgical patients in the immediate postoperative period after cardiac and major surgery, respectively. All transthoracic echocardiography was performed by a specialist intensivist within 24 hours after surgery with special emphasis on using the subcostal view in the supine position to visualise the IVC. Of the 395 cardiac surgical patients studied, the IVC was successfully visualised using the subcostal view in 315 patients (79.8%) and eight of these patients (2.5%) had a partially obstructive thrombosis in the IVC. In 250 out of 289 (85%) general surgical patients, the IVC was also clearly visualised, but only one patient (0.4%) had an IVC thrombosis (2.5 vs 0.4%, P <0.05). In summary, visualisation of the IVC was feasible in most patients in the immediate postoperative period after both adult cardiac and major surgery. IVC thrombosis appeared to be more common after adult cardiac surgery than general surgery. A large prospective cohort study is needed to define the risk factors for IVC thrombus and whether early thromboprophylaxis can reduce the incidence of IVC thrombus after adult cardiac surgery. PMID- 24180721 TI - Timing of blood transfusion in relation to ICU admission-a single centre audit. AB - There is growing concern that blood transfusion may be associated with adverse outcomes in critically ill patients. Timing of transfusion in relation to intensive care unit (ICU) stay may be important in designing and understanding transfusion studies. The objective of this study was to determine the timing of red blood cell transfusion in relation to admission to an Australian ICU and to describe associations with transfusion requirements. We undertook a retrospective, observational, single-centre cohort study of all patients admitted to the ICU at The Northern Hospital, Melbourne, Australia, between 1 January and 31 December 2008 in order to measure the timing of transfusion in relation to ICU admission and the demographic and outcome data of the cohort. 674 individual hospital admissions were analysed. Overall, 28% (188/674) of patients admitted to ICU received a red cell transfusion during their hospital stay. A total of 55 (28.5%) patients were transfused either before and/or after ICU discharge but never in the ICU. Thirty-five percent (258/741) of red cell units were transfused outside the ICU. The median number of red cell units transfused was three units per patient (interquartile range 1 to 5). There was no difference between transfused and non-transfused groups in either crude mortality or severity adjusted mortality. In approximately one-third of ICU patients in our study transfusions occurred before admission to, and/or after discharge from, the ICU. This has implications for designing and interpreting transfusion studies in the ICU and requires confirmation in a multi-centre study. PMID- 24180722 TI - Audit of co-management and critical care outreach for high risk postoperative patients (The POST audit). AB - Co-management and critical care outreach for high risk surgical patients have been proposed to decrease postoperative complications and mortality. We proposed that a clinical project with postoperative comanagement and critical care outreach, the Post Operative Surveillance Team: (POST), would be associated with decreased hospital length of stay. We conducted a retrospective before (control group) and after (POST group) audit of this hospital program. POST was staffed for four months in 2010 by two intensive care nurses and two senior registrars who conducted daily ward rounds for the first five postoperative days on high risk patients undergoing inpatient general or urological surgery. The primary endpoint was length of hospital stay and secondary endpoints were Medical Emergency Team (MET) calls, cardiac arrests and in-hospital mortality. There were 194 patients in the POST group and 1,185 in the control group. The length of stay in the POST group, median nine days (Inter-quartile range [IQR]: 5 to 17 days), was longer than the control group, median seven days (IQR: 4 to 13 days): difference two days longer (95.0% confidence interval [95.0% CI]: 1 to 3 days longer, P <0.001). There were no important differences in the proportion of patients having MET calls (16.0% POST versus. 13% control (P=0.25)) or mortality (2.1% POST versus 2.8% Control (P=0.82)). Our audit found that the POST service was not associated with reduced length of stay. Models of co-management, different to POST, or with different performance metrics, could be tested. PMID- 24180723 TI - Utility of thromboelastography in managing acquired Factor VIII inhibitor associated massive haemorrhage. AB - Disorders of clotting and coagulation are common in the intensive care unit. Diagnosis, treatment and monitoring of these disorders are traditionally based on conventional coagulation tests such as activated partial thromboplastin time (APTT) and international normalised ratio (INR). We present here a patient who developed massive postoperative haemorrhage secondary to an acquired factor VIII inhibitor. The case highlights the utility and sensitivity of thromboelastography (TEG) in the diagnosis of the condition and monitoring the response to therapy. PMID- 24180724 TI - Frozen platelets for rural Australia: the CLIP trial. PMID- 24180725 TI - Spinal pethidine and shivering for elective caesarean section. PMID- 24180726 TI - Fatal rhabdomyolysis following volatile induction in a six-year-old boy with Duchenne Muscular Dystrophy. PMID- 24180727 TI - Tracheo-innominate artery fistula: report of two fatal cases and preventive measures. PMID- 24180728 TI - Successful combined use of the Airtraq optical laryngoscope DL and a preconfigured intubating stylet when the glottis is off-centre of the viewfinder. PMID- 24180729 TI - A case of opsoclonus-myoclonus syndrome following a septic shock. PMID- 24180730 TI - Therapeutic plasma exchange as de-coppering technique in intensive care for an adult in a Wilson's crisis. PMID- 24180731 TI - A value of cardiac imaging in Takotsubo cardiomyopathy. PMID- 24180732 TI - Preparing patients for colonoscopy sedation. PMID- 24180733 TI - Consciousness during planned unconscious sedation with propofol-risk vs uncertainty. PMID- 24180734 TI - Postoperative hyperthermic syndrome following antiparkinsonian drugs withdrawal: the pitfall of enteral refeeding. PMID- 24180735 TI - Wernicke encephalopathy following nutritional deficiency in a patient with multiple trauma. PMID- 24180736 TI - Beta-blocker therapy in cardiogenic shock: a therapeutical dilemma. PMID- 24180737 TI - Compliance with manual vaporiser block checking of automated electronic anaesthesia machines. PMID- 24180738 TI - CT images of LMA mistaken for oesophageal foreign body. PMID- 24180739 TI - Patient-centred care: what's important to our patients? PMID- 24180740 TI - Experience with an innovative operating room dashboard system to improve quality and efficiency in an Academic Medical Center in Singapore. PMID- 24180741 TI - Photosystem I reduction in diatoms: as complex as the green lineage systems but less efficient. AB - Diatoms occupy a key branch in the evolutionary tree of oxygen-evolving photosynthetic organisms. Here, the electron transfer reaction mechanism from cytochrome c6 to photosystem I from the diatom Phaeodactylum tricornutum has been analyzed by laser-flash absorption spectroscopy. Kinetic traces of photosystem I reduction fit to biphasic curves, the analysis of the observed rate constants indicating that electron transfer occurs in a cytochrome c6/photosystem I transient complex, which undergoes a reorganization process from the initial encounter complex to the optimized final configuration. The mild ionic strength dependence of the rate constants makes evident the relatively weak electrostatically attractive nature of the interaction. Taken together, these results indicate that the "red" Phaeodactylum system is less efficient than "green" systems, both in the formation of the properly arranged (cytochrome c6/photosystem I) complex and in the electron transfer itself. The results obtained from cross-reactions with cytochrome c6 and photosystem I from cyanobacteria, green algae, and plants shed light on the different evolutionary pathway of the electron transfer to photosystem I in diatoms with regard to the way that it evolved in higher plants. PMID- 24180742 TI - Effect of histone deacetylase inhibitor valproic acid treatment on donor cell growth characteristics, cell cycle arrest, apoptosis, and handmade cloned bovine embryo production efficiency. AB - In this study, we tested the effects of valproic acid (VPA), a known histone deacetylase inhibitor (HDACi), on the growth characteristics, apoptosis, and cell cycle stages distribution of donor cells, as well as cloning efficiency, embryo development, and histone methylation. Our results showed that treatment of donor cells with VPA (2.5 mM, 5.0 mM, 7.5 mM, or 10 mM) for 24 h resulted in altered cell proliferation, extent of apoptosis and necrosis, and cell cycle stage distribution, whereas no changes in cell viability and chromosomal complements were observed. Measurement of relative gene expression using real-time PCR of a few developmentally important genes in treated donor cells showed decreased expression of HDAC1 and increased expression of BAX (p<0.05). No change in relative expression of HDAC2 and Bcl2 was noticed. Treatment of donor cells with VPA for 24 h before electrofusion significantly (p<0.05) increased the blastocyst formation rate of somatic cell nuclear transfer (SCNT) embryos compared to the control embryos. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei in SCNT blastocysts derived from VPA-treated donor cells were significantly decreased compared to the control blastocysts (p<0.05). Immunolocalization studies revealed that the levels of histone H3 at lysine 9 (H3K9me3) were lower in VPA-treated donor cells derived cloned blastocysts than nontreated cloned embryos, and was at the level of in vitro fertilization (IVF) counterparts, although no effects of treatments were found in donor cells. Our study demonstrates that the use of VPA in SCNT has been beneficial for efficient reprogramming of donor cells. Its effect on histone methylation in cloned embryos correlates with their developmental potential and may be a useful epigenetic marker to predict the efficiency of SCNT. PMID- 24180743 TI - Somatic cell nuclear transfer-derived embryonic stem cell lines in humans: pros and cons. AB - The recent paper, published by Mitalipov's group in Cell (Tachibana et al., 2013 ), reporting the production of human somatic cell nuclear transfer (SCNT) embryonic stem cells (ESCs), opens again the debate if, in the era of induced pluripotent stem cells (iPSCs), the production of these cells is indeed necessary and, if so, whether they are different from ESCs produced from spare embryos and iPSCs. It is our opinion that these questions are very difficult to answer because it is still unclear whether and how normal ESCs differ from iPSCs. PMID- 24180744 TI - Inflammatory responses in primary muscle cell cultures in Atlantic salmon (Salmo salar). AB - BACKGROUND: The relationship between fish health and muscle growth is critical for continued expansion of the aquaculture industry. The effect of immune stimulation on the expression of genes related to the energy balance of fish is poorly understood. In mammals immune stimulation results in major transcriptional changes in muscle, potentially to allow a reallocation of amino acids for use in the immune response and energy homeostasis. The aim of this study was to investigate the effects of immune stimulation on fish muscle gene expression. RESULTS: Atlantic salmon (Salmo salar) primary muscle cell cultures were stimulated with recombinant (r)IL-1beta, a major proinflammatory cytokine, for 24 h in order to simulate an acute immune response. The transcriptomic response was determined by RNA hybridization to a 4 * 44 K Agilent Atlantic salmon microarray platform. The rIL-1beta stimulation induced the expression of genes related to both the innate and adaptive immune systems. In addition there were highly significant changes in the expression of genes related to regulation of the cell cycle, growth/structural proteins, proteolysis and lipid metabolism. Of interest were a number of IGF binding proteins that were differentially expressed, which may demonstrate cross talk between the growth and immune systems. CONCLUSION: We show rIL-1beta modulates the expression of not only immune related genes, but also that of genes involved in processes related to growth and metabolism. Co stimulation of muscle cells with both rIGF-I and rIL-1beta demonstrates cross talk between these pathways providing potential avenues for further research. This study highlights the potential negative effects of inflammation on muscle protein deposition and growth in fish and extends our understanding of energy allocation in ectothermic animals. PMID- 24180746 TI - Predictors of Nursing Home Placement from Assisted Living Settings in Canada. AB - We sought to estimate the incidence of long-term care (LTC) placement and to identify resident- and facility-level predictors of placement among older residents of designated assisted living (AL) facilities in Alberta, Canada. Included were 1,086 AL residents from 59 facilities. Research nurses completed interRAI-AL resident assessments and interviewed family caregivers and administrators. Predictors of placement were identified with multivariable Cox proportional hazards models. The cumulative incidence of LTC admission was 18.3 per cent by 12 months. Significantly increased risk for placement was evident for older residents and those with poor social relationships, little involvement in activities, cognitive and/or functional impairment, health instability, recent falls and hospitalizations/emergency department visits, and severe bladder incontinence. Residents from larger facilities, with an LPN and/or RN on-site 24/7 and with an affiliated primary care physician, showed lower risk of placement. Our findings highlight clinical and policy areas where targeted interventions may delay LTC admissions. PMID- 24180745 TI - Modeling, synthesis, and biological evaluation of potential retinoid X receptor (RXR) selective agonists: novel analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8 tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) and (E)-3-(3-(1,2,3,4 tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid (CD3254). AB - Three unreported analogues of 4-[1-(3,5,5,8,8-pentamethyl-5-6-7-8-tetrahydro-2 naphthyl)ethynyl]benzoic acid (1), otherwise known as bexarotene, as well as four novel analogues of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7 yl)-4-hydroxyphenyl)acrylic acid (CD3254), are described and evaluated for their retinoid X receptor (RXR) selective agonism. Compound 1 has FDA approval as a treatment for cutaneous T-cell lymphoma (CTCL), although treatment with 1 can elicit side-effects by disrupting other RXR-heterodimer receptor pathways. Of the seven modeled novel compounds, all analogues stimulate RXR-regulated transcription in mammalian 2 hybrid and RXRE-mediated assays, possess comparable or elevated biological activity based on EC50 profiles, and retain similar or improved apoptotic activity in CTCL assays compared to 1. All novel compounds demonstrate selectivity for RXR and minimal crossover onto the retinoic acid receptor (RAR) compared to all-trans-retinoic acid, with select analogues also reducing inhibition of other RXR-dependent pathways (e.g., VDR-RXR). Our results demonstrate that further improvements in biological potency and selectivity of bexarotene can be achieved through rational drug design. PMID- 24180747 TI - Molecular characterization of inhibiting biochar water-extractable substances using electrospray ionization fourier transform ion cyclotron resonance mass spectrometry. AB - Biochar has gained significant interest worldwide for its potential use as both a carbon sequestration technique and soil amendment. Recently, research has shown that pinewood-derived biochar water extracts inhibited the growth of aquatic photosynthetic microorganisms, both prokaryotic and eukaryotic algae, while chicken litter- and peanut shell-derived biochar water extracts showed no growth inhibition. With the use of electrodialysis, the pinewood-derived biochar water extract is separated into 3 fractions (anode-isolated, center chamber retained, and cathode-isolated substances) all with varying toxic effects. Because of its ultrahigh resolution and mass precision, electrospray ionization (ESI) coupled to Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is utilized in this study to analyze biochar water extracts at a molecular level to enhance our understanding of the toxic nature of pinewood-derived biochar water extracts as compared to benign peanut shell-derived biochar water extracts. The molecular composition of pinewood-derived biochar water extracts shows unique carbohydrate ligneous components and sulfur containing condensed ligneous components that are both absent from the peanut shell water extracts and more prevalent in the anode-isolated substances. Using Kendrick mass defect analysis, we also determine that the most likely inhibitor species contain carboxyl and hydroxyl homologous series, both of which are characteristic functional groups hypothesized in our previous research for the inhibitor species. We have suggested that inhibition of aquatic photosynthetic microorganism growth is most likely due to degraded lignin-like species rich in oxygen containing functionalities. From the study conducted here, we show the potential of ultrahigh resolution FTICR-MS as a valuable analytical technique for determining whether certain biochars are safe and benign for use as carbon sequestration and soil amendment. PMID- 24180748 TI - Discrimination of virtual auditory distance using level and direct-to-reverberant ratio cues. AB - The study investigated how listeners used level and direct-to-reverberant ratio (D/R) cues to discriminate distances to virtual sound sources. Sentence pairs were presented at virtual distances in simulated rooms that were either reverberant or anechoic. Performance on the basis of level was generally better than performance based on D/R. Increasing room reverberation time improved performance based on the D/R cue such that the two cues provided equally effective information at further virtual source distances in highly reverberant environments. Orientation of the listener within the virtual room did not affect performance. PMID- 24180749 TI - Response to "Comment on 'Resonant acoustic scattering by swimbladder-bearing fish'" [J. Acoust. Soc. Am. 64, 571-580 (1978)]. AB - In the 1970s a model of resonant scattering from a swimbladder-bearing fish was developed. The fish was modeled as an air bubble, representing a swimbladder, encased in a viscous spherical shell, representing the fish flesh. This model has been used successfully to correlate acoustic scattering data with fish information in a number of ocean locations. Recently, questions have arisen about viscous damping of the flesh and the thickness of the shell [K. Baik, J. Acoust. Soc. Am. 133, 5-8 (2013)]. This Letter responds to those questions and provides practical insight into the model's use. PMID- 24180750 TI - Experimental verification of enhanced sound transmission from water to air at low frequencies. AB - Laboratory measurements of enhanced sound transmission from water to air at low frequencies are presented. The pressure at a monitoring hydrophone is found to decrease for shallow source depths in agreement with the classical theory of a monopole source in proximity to a pressure release interface. On the other hand, for source depths below 1/10 of an acoustic wavelength in water, the radiation pattern in the air measured by two microphones becomes progressively omnidirectional in contrast to the classical geometrical acoustics picture in which sound is contained within a cone of 13.4 degrees half angle. The measured directivities agree with wavenumber integration results for a point source over a range of frequencies and source depths. The wider radiation pattern owes itself to the conversion of evanescent waves in the water into propagating waves in the air that fill the angular space outside the cone. A ratio of pressure measurements made using an on-axis microphone and a near-axis hydrophone are also reported and compared with theory. Collectively, these pressure measurements are consistent with the theory of anomalous transparency of the water-air interface in which a large fraction of acoustic power emitted by a shallow source is radiated into the air. PMID- 24180751 TI - An axisymmetric boundary element formulation of sound wave propagation in fluids including viscous and thermal losses. AB - The formulation presented in this paper is based on the boundary element method (BEM) and implements Kirchhoff's decomposition into viscous, thermal, and acoustic components, which can be treated independently everywhere in the domain except on the boundaries. The acoustic variables with losses are solved using extended boundary conditions that assume (i) negligible temperature fluctuations at the boundary and (ii) normal and tangential matching of the boundary's particle velocity. The proposed model does not require constructing a special mesh for the viscous and thermal boundary layers as is the case with the existing finite element method (FEM) implementations with losses. The suitability of this approach is demonstrated using an axisymmetrical BEM and two test cases where the numerical results are compared with analytical solutions. PMID- 24180752 TI - An asymptotic model in acoustics: acoustic drift equations. AB - A rigorous asymptotic procedure with the Mach number as a small parameter is used to derive the equations of mean flows which coexist and are affected by the background acoustic waves in the limit of very high Reynolds number. PMID- 24180753 TI - Effects of coupling, bubble size, and spatial arrangement on chaotic dynamics of microbubble cluster in ultrasonic fields. AB - Microbubble clustering may occur when bubbles become bound to targeted surfaces or are grouped by acoustic radiation forces in medical diagnostic applications. The ability to identify the formation of such clusters from the ultrasound echoes may be of practical use. Nonlinear numerical simulations were performed on clusters of microbubbles modeled by the modified Keller-Miksis equations. Encapsulated bubbles were considered to mimic practical applications but the aim of the study was to examine the effects of inter-bubble spacing and bubble size on the dynamical behavior of the cluster and to see if chaotic or bifurcation characteristics could be helpful in diagnostics. It was found that as microbubbles were clustered closer together, their oscillation amplitude for a given applied ultrasound power was reduced, and for inter-bubble spacing smaller than about ten bubble radii nonlinear subharmonics and ultraharmonics were eliminated. For clustered microbubbles, as for isolated microbubbles, an increase in the applied acoustic power caused bifurcations and transition to chaos. The bifurcations preceding chaotic behavior were identified by Floquet analysis and confirmed to be of the period-doubling type. It was found that as the number of microbubbles in a cluster increased, regularization occurred at lower ultrasound power and more windows of order appeared. PMID- 24180754 TI - Nonlinear derating of high-intensity focused ultrasound beams using Gaussian modal sums. AB - A method is introduced for using measurements made in water of the nonlinear acoustic pressure field produced by a high-intensity focused ultrasound transducer to compute the acoustic pressure and temperature rise in a tissue medium. The acoustic pressure harmonics generated by nonlinear propagation are represented as a sum of modes having a Gaussian functional dependence in the radial direction. While the method is derived in the context of Gaussian beams, final results are applicable to general transducer profiles. The focal acoustic pressure is obtained by solving an evolution equation in the axial variable. The nonlinear term in the evolution equation for tissue is modeled using modal amplitudes measured in water and suitably reduced using a combination of "source derating" (experiments in water performed at a lower source acoustic pressure than in tissue) and "endpoint derating" (amplitudes reduced at the target location). Numerical experiments showed that, with proper combinations of source derating and endpoint derating, direct simulations of acoustic pressure and temperature in tissue could be reproduced by derating within 5% error. Advantages of the derating approach presented include applicability over a wide range of gains, ease of computation (a single numerical quadrature is required), and readily obtained temperature estimates from the water measurements. PMID- 24180755 TI - Infrasonic ray tracing applied to mesoscale atmospheric structures: refraction by hurricanes. AB - A ray-tracing program is used to estimate the refraction of infrasound by the temperature structure of the atmosphere and by hurricanes represented by a Rankine-combined vortex wind plus a temperature perturbation. Refraction by the hurricane winds is significant, giving rise to regions of focusing, defocusing, and virtual sources. The refraction of infrasound by the temperature anomaly associated with a hurricane is small, probably no larger than that from uncertainties in the wind field. The results are pertinent to interpreting ocean wave generated infrasound in the vicinities of tropical cyclones. PMID- 24180756 TI - Acoustic scattering from a double periodically bulkheaded and ribbed finite cylindrical shell. AB - The sound scattering from a finite vacuumed cylindrical shell simultaneously loaded with the bulkheads and the ribs are studied. The motions of the shell are described by the Donnell equations. Each rib is modeled as a rod of circular curvature where only the normal force is applied. The motions of the bulkheads are decomposed into the out-plate bending motions and the in-plate extensional motions, which are independent of each other. The backscattered sound field is analyzed via the frequency-angle spectra. Compared against the backscattered sound from a ribbed cylindrical shell, the Bloch-Floquet waves disappear at low frequencies but still exist at mid and high frequencies. The Bragg scattering excited by the ribs is unchanged at mid and high frequencies. Besides the ribs' Bloch-Floquet waves and Bragg scattering, there exists the Bragg scattering excited by the bulkheads. The backscattering from a cylindrical shell loaded with just the bulkheads is calculated. When the spacing and the thickness of the bulkheads are equal to those of the ribs, the crests of the Bragg scattering and the Bloch-Floquet waves on the frequency-angle spectra are almost the same as those of the ribbed cylindrical shell. The resonances of the bulkheads are also excited in this case. PMID- 24180757 TI - Decadal trends in Indian Ocean ambient sound. AB - The increase of ocean noise documented in the North Pacific has sparked concern on whether the observed increases are a global or regional phenomenon. This work provides evidence of low frequency sound increases in the Indian Ocean. A decade (2002-2012) of recordings made off the island of Diego Garcia, UK in the Indian Ocean was parsed into time series according to frequency band and sound level. Quarterly sound level comparisons between the first and last years were also performed. The combination of time series and temporal comparison analyses over multiple measurement parameters produced results beyond those obtainable from a single parameter analysis. The ocean sound floor has increased over the past decade in the Indian Ocean. Increases were most prominent in recordings made south of Diego Garcia in the 85-105 Hz band. The highest sound level trends differed between the two sides of the island; the highest sound levels decreased in the north and increased in the south. Rate, direction, and magnitude of changes among the multiple parameters supported interpretation of source functions driving the trends. The observed sound floor increases are consistent with concurrent increases in shipping, wind speed, wave height, and blue whale abundance in the Indian Ocean. PMID- 24180758 TI - Temporal coherence of the acoustic field forward propagated through a continental shelf with random internal waves. AB - An analytical model derived from normal mode theory for the accumulated effects of range-dependent multiple forward scattering is applied to estimate the temporal coherence of the acoustic field forward propagated through a continental shelf waveguide containing random three-dimensional internal waves. The modeled coherence time scale of narrow band low-frequency acoustic field fluctuations after propagating through a continental-shelf waveguide is shown to decay with a power-law of range to the -1/2 beyond roughly 1 km, decrease with increasing internal wave energy, to be consistent with measured acoustic coherence time scales. The model should provide a useful prediction of the acoustic coherence time scale as a function of internal wave energy in continental-shelf environments. The acoustic coherence time scale is an important parameter in remote sensing applications because it determines (i) the time window within which standard coherent processing such as matched filtering may be conducted, and (ii) the number of statistically independent fluctuations in a given measurement period that determines the variance reduction possible by stationary averaging. PMID- 24180759 TI - Assessing the coastal occurrence of endangered killer whales using autonomous passive acoustic recorders. AB - Using moored autonomous acoustic recorders to detect and record the vocalizations of social odonotocetes to determine their occurrence patterns is a non-invasive tool in the study of these species in remote locations. Acoustic recorders were deployed in seven locations on the continental shelf of the U.S. west coast from Cape Flattery, WA to Pt. Reyes, CA to detect and record endangered southern resident killer whales between January and June of 2006-2011. Detection rates of these whales were greater in 2009 and 2011 than in 2006-2008, were most common in the month of March, and occurred with the greatest frequency off the Columbia River and Westport, which was likely related to the presence of their most commonly consumed prey, Chinook salmon. The observed patterns of annual and monthly killer whale occurrence may be related to run strength and run timing, respectively, for spring Chinook returning to the Columbia River, the largest run in this region at this time of year. Acoustic recorders provided a unique, long term, dataset that will be important to inform future consideration of Critical Habitat designation for this U.S. Endangered Species Act listed species. PMID- 24180760 TI - Classification of mysticete sounds using machine learning techniques. AB - Automatic classification of mysticete sounds has long been a challenging task in the bioacoustics field. The unknown statistical properties of the signals as well as the use of different recording apparatus and low signal-to-noise ratio conditions often lead to non-optimal systems. The goal of this paper is to design methods for the automatic classification of mysticete sounds using a restricted Boltzmann machine and a sparse auto-encoder that are widely used in the field of artificial intelligence. Experiments on five species of mysticetes are presented. The different methods are employed on the subset of species whose frequency range overlaps, as well as in all five species' calls. Moreover, results are offered with and without the use of a noise class. Overall, the systems are able to achieve an average classification accuracy of over 69% (with noise) and 80% (without noise) given the different architectures. PMID- 24180761 TI - Neglect of bandwidth of Odontocetes echo location clicks biases propagation loss and single hydrophone population estimates. AB - Passive acoustic monitoring with a single hydrophone has been suggested as a cost effective method to monitor population density of echolocating marine mammals, by estimating the distance at which the hydrophone is able to intercept the echolocation clicks and distinguish these from the background. To avoid a bias in the estimated population density, this method relies on an unbiased estimate of the detection range and therefore of the propagation loss (PL). When applying this method, it is common practice to estimate PL at the center frequency of a broadband echolocation click and to assume this narrowband PL applies also to the broadband click. For a typical situation this narrowband approximation overestimates PL, underestimates the detection range and consequently overestimates the population density by an amount that for fixed center frequency increases with increasing pulse bandwidth and sonar figure of merit. PMID- 24180762 TI - Offshore killer whale tracking using multiple hydrophone arrays. AB - To study delphinid near surface movements and behavior, two L-shaped hydrophone arrays and one vertical hydrophone line array were deployed at shallow depths (<125 m) from the floating instrument platform R/P FLIP, moored northwest of San Clemente Island in the Southern California Bight. A three-dimensional propagation model based passive acoustic tracking method was developed and used to track a group of five offshore killer whales (Orcinus orca) using their emitted clicks. In addition, killer whale pulsed calls and high-frequency modulated (HFM) signals were localized using other standard techniques. Based on these tracks sound source levels for the killer whales were estimated. The peak to peak source levels for echolocation clicks vary between 170-205 dB re 1 MUPa @ 1 m, for HFM calls between 185-193 dB re 1 MUPa @ 1 m, and for pulsed calls between 146-158 dB re 1 MUPa @ 1 m. PMID- 24180763 TI - Applying distance sampling to fin whale calls recorded by single seismic instruments in the northeast Atlantic. AB - Automated methods were developed to detect fin whale calls recorded by an array of ocean bottom seismometers (OBSs) deployed off the Portuguese coast between 2007 and 2008. Using recordings collected on a single day in January 2008, a standard seismological method for estimating earthquake location from single instruments, the three-component analysis, was used to estimate the relative azimuth, incidence angle, and horizontal range between each OBS and detected calls. A validation study using airgun shots, performed prior to the call analysis, indicated that the accuracy of the three-component analysis was satisfactory for this preliminary study. Point transect sampling using cue counts, a form of distance sampling, was then used to estimate the average probability of detecting a call via the array during the chosen day. This is a key step to estimating density or abundance of animals using passive acoustic data. The average probability of detection was estimated to be 0.313 (standard error: 0.033). However, fin whale density could not be estimated due to a lack of an appropriate estimate of cue (i.e., vocalization) rate. This study demonstrates the potential for using a sparse array of widely spaced, independently operating acoustic sensors, such as OBSs, for estimating cetacean density. PMID- 24180764 TI - Investigation of sonar transponders for offshore wind farms: modeling approach, experimental setup, and results. AB - The installation of offshore wind farms in the German Exclusive Economic Zone requires the deployment of sonar transponders to prevent collisions with submarines. The general requirements for these systems have been previously worked out by the Research Department for Underwater Acoustics and Marine Geophysics of the Bundeswehr. In this article, the major results of the research project "Investigation of Sonar Transponders for Offshore Wind Farms" are presented. For theoretical investigations a hybrid approach was implemented using the boundary element method to calculate the source directivity and a three dimensional ray-tracing algorithm to estimate the transmission loss. The angle dependence of the sound field as well as the weather-dependence of the transmission loss are compared to experimental results gathered at the offshore wind farm alpha ventus, located 45 km north of the island Borkum. While theoretical and experimental results are in general agreement, the implemented model slightly underestimates scattering at the rough sea surface. It is found that the source level of 200 dB re 1 MUPa at 1 m is adequate to satisfy the detectability of the warning sequence at distances up to 2 NM (~3.7 km) within a horizontal sector of +/-60 degrees if realistic assumptions about signal processing and noise are made. An arrangement to enlarge the angular coverage is discussed. PMID- 24180765 TI - Researches and applications of the ultrasonic emulsifications and dispersions. AB - This paper defines power ultrasonics and their two important directions: Ultrasonic emulsification and dispersion from a practical point of view, brief reports on recent research results are ultrasonic emulsification to be used for the preparation of composite electrorheological fluid, and ultrasonic dispersion to be used dispersion as a new type cold cloud catalytic agent metaldehyde [CH3CH]4-6 (this is used for artificial rain), etc., and produce good results or gain progress. Then, the principle and applications of power ultrasonics (including magnetostriction type ultrasonic transducer and piezoelectric type ultrasonic transducer) in the emulsification or dispersion, are pointed out. Also, ultrasonic extensive applications in chemistry, materials, and life sciences are briefly introduced. PMID- 24180766 TI - Coupled wedge waves. AB - The interface between two wedges can be treated as a displacement discontinuity characterized by elastic stiffnesses. By representing the boundary between the two quarter-spaces as a displacement discontinuity, coupled wedge waves were determined theoretically to be dispersive and to depend on the specific stiffness of the non-welded contact between the two wedges. Laboratory experiments on isotropic and anisotropic aluminum confirmed the theoretical prediction that the velocity of coupled wedge waves, for a non-welded interface, ranged continuously from the single wedge wave velocity at low stress to the Rayleigh velocity as the load applied normal to the interface was increased. Elastic waves propagating along the coupled wedges of two quarter-spaces in non-welded contact are found to exist theoretically even when the material properties of the two quarter-spaces are the same. PMID- 24180767 TI - Defining the coupling coefficient for electrodynamic transducers. AB - This paper provides a simple, practical definition of the coupling coefficient for electrodynamic transducers. Comparing to efforts made in previous works that assumed a lossless spring-inductor model, the definition presented here is based on a lossy mass-inductor model. Time-harmonic analysis is used to model the energy flow in the transducer. Both energy storage and energy dissipation are included in the electrodynamic coupling coefficient definition. An in-depth discussion is provided to explain and justify the derivation and overall methodology. This definition is expected to provide a useful and practical measure of the electromechanical energy conversion performance of electrodynamic transducers, both actuators and generators. PMID- 24180768 TI - Analytical and numerical modeling of an axisymmetrical electrostatic transducer with interior geometrical discontinuity. AB - The main purpose of the paper is to contribute at presenting an analytical and a numerical modeling which would be relevant for interpreting the couplings between a circular membrane, a peripheral cavity having the same external radius as the membrane, and a thin air gap (with a geometrical discontinuity between them), and then to characterize small scale electrostatic receivers and to propose procedures that could be suitable for fitting adjustable parameters to achieve optimal behavior in terms of sensitivity and bandwidth expected. Therefore, comparison between these theoretical methods and characterization of several shapes is dealt with, which show that the models would be appropriate to address the design of such transducers. PMID- 24180769 TI - An extended lumped-element model and parameter estimation technique to predict loudspeaker responses with possible surround-dip effects. AB - Lumped-element models have long been used to estimate the basic vibration and radiation characteristics of moving-coil loudspeakers. The classical low frequency model combines and simplifies several important driver elements, predicting only a single mechanical resonance wherein the diaphragm (e.g., cone and dust cap) and the inner portion of the surround move together as an effective piston. Even if the diaphragm maintains piston-like motion with increasing frequency, the flexible surround eventually vibrates out of phase, producing another resonance whereby a noticeable "surround dip" may occur in the radiated pressure spectrum. The classical model is unable to predict this behavior. This paper explores an extended lumped-element model that better characterizes the distinct diaphragm, surround, spider, and other properties of a loudspeaker in a plane rigid baffle. It extends effective modeling to mid frequencies and readily predicts a surround dip in the radiated response. The paper also introduces a method to estimate model parameters using a scanning laser Doppler vibrometer, a surround resonance indicator function, and a constrained optimization routine. The approach is validated by its ability to better predict on-axis pressure responses of several baffled loudspeakers in an anechoic environment. PMID- 24180770 TI - An inverse method for estimating the electromechanical parameters of moving-coil loudspeakers. AB - This article presents an inverse method for estimating the electromechanical parameters of a moving-coil loudspeaker with or without the eddy current and suspension creep effects. With known voice-coil displacement, voice-coil current, and stimulus signal as inputs, four calculation procedures for the direct problem, adjoint problem, sensitivity problem, and conjugate gradient method are involved in inversely solving the unknown electromechanical parameters. The proposed method features high efficiency in solving the direct problem through a hybrid spline difference method. It requires a small number of iterations for the computational algorithm, while offering excellent accuracy in parameter estimations. Analysis results demonstrate small differences between the estimated and measured electromechanical parameters under a variety of stimulus signals, excitation times, and initial guesses. The results are also confirmed by experimental measurements. These results indicate that the proposed method has a strong potential for estimating the electromechanical parameters of moving-coil loudspeakers. PMID- 24180771 TI - The "round trip" theory for reconstruction of Green's functions at passive locations. AB - An expression for the Green's function at an arbitrary set of passive locations (no applied force) is derived and validated by experiment. Three sets of points are involved, the passive reconstruction points, c, which lie on a virtual boundary and two sets of auxiliary points, denoted a and b, located either side. The reconstruction is achieved using Green's functions forming a "round trip" from and to the reconstruction points via a and b. A two stage measurement procedure is described involving excitation at b and a but with no excitation required at the reconstruction points. A known "round trip" relationship is first introduced which is theoretically exact for points on a multi-point interface between two linear, time invariant subsystems. Experimental results for frequency response functions of a beam-plate structure show that this relationship gives good results in practice. It is then shown that the theory provides an Nth order approximation for the Green's function at arbitrary points, where N is the number of points at b. The expression is validated by reconstructing point and transfer frequency response functions at two passive points on an aluminum plate. PMID- 24180772 TI - Acoustic waveguiding by pliable conduits with axial cross sections as linear waveguides in two-dimensional sonic crystals. AB - Pliable conduits composed of periodically arranged concentric aluminum tori in air, with their axial cross sections acting as linear waveguides in two dimensional sonic crystals, are numerically shown to guide acoustic waves in three dimensions in a flexible manner. Waveguide band structures are obtained by exploiting axial symmetry in a super-cell approach through two-dimensional finite element simulations under the periodic boundary conditions. One isolated band having a bandwidth of 19.66% or 10.10% is observed for each guide, whose cross section is either in square or triangular geometry, respectively. Corresponding mode profiles indicate efficient guiding, as the acoustic energy is mainly concentrated in the hollow-core region of the guides. Transmittance spectra calculated through finite-element simulations are in agreement with the computed guiding bands. Transmittance along the waveguides with square and triangular axial cross sections around mid-band frequencies of their guiding bands varies slightly from -6.05 and -6.65 dB to -5.98 and -8.86 dB, respectively, as the guide length is increased from 10 to 200 periods. Efficient guiding across the smooth bends over circular arcs up to 90 deg is also demonstrated through three dimensional finite-element method simulations. PMID- 24180773 TI - Comparisons of two effective medium approaches for predicting sound scattering by periodic arrays of elastic shells. AB - Two effective medium models are presented and used to predict complex reflection and transmission coefficients of finite periodic arrays of resonant elastic shells as well as their effective density and bulk modulus at low frequencies. Comparisons with full multiple scattering theory and measurements show that the self-consistent model fails to correctly predict the shape of the transmission/reflection curves when scatterer resonances are close to the first Bragg bandgap. The low frequency grating model, which neglects the evanescent modes and considers scattered wave propagation only in the same direction as the incident one, gives a much better agreement with both measurements and the full multiple scattering theory. Moreover, because it does not require the wavelength to strongly exceed the size of scatterers, the model gives reliable predictions even at frequencies around the first periodicity related bandgap. In contrast to the self-consistent model, the low frequency grating model is applicable when the resonant scatterers have more than two low frequency resonances. PMID- 24180774 TI - Integrated tuned vibration absorbers: a theoretical study. AB - This article presents a simulation study on two integrated tuned vibration absorbers (TVAs) designed to control the global flexural vibration of lightly damped thin structures subject to broad frequency band disturbances. The first one consists of a single axial switching TVA composed by a seismic mass mounted on variable axial spring and damper elements so that the characteristic damping and natural frequency of the absorber can be switched iteratively to control the resonant response of three flexural modes of the hosting structure. The second one consists of a single three-axes TVA composed by a seismic mass mounted on axial and rotational springs and dampers, which are arranged in such a way that the suspended mass is characterized by uncoupled heave and pitch-rolling vibrations. In this case the three damping and natural frequency parameters of the absorber are tuned separately to control three flexural modes of the hosting structure. The simulation study shows that the proposed single-unit absorbers produce, respectively, 5.3 and 8.7 dB reductions of the global flexural vibration of a rectangular plate between 20 and 120 Hz. PMID- 24180775 TI - Aircraft noise-induced awakenings are more reasonably predicted from relative than from absolute sound exposure levels. AB - Assessment of aircraft noise-induced sleep disturbance is problematic for several reasons. Current assessment methods are based on sparse evidence and limited understandings; predictions of awakening prevalence rates based on indoor absolute sound exposure levels (SELs) fail to account for appreciable amounts of variance in dosage-response relationships and are not freely generalizable from airport to airport; and predicted awakening rates do not differ significantly from zero over a wide range of SELs. Even in conjunction with additional predictors, such as time of night and assumed individual differences in "sensitivity to awakening," nominally SEL-based predictions of awakening rates remain of limited utility and are easily misapplied and misinterpreted. Probabilities of awakening are more closely related to SELs scaled in units of standard deviates of local distributions of aircraft SELs, than to absolute sound levels. Self-selection of residential populations for tolerance of nighttime noise and habituation to airport noise environments offer more parsimonious and useful explanations for differences in awakening rates at disparate airports than assumed individual differences in sensitivity to awakening. PMID- 24180776 TI - Influence of "omnidirectional" loudspeaker directivity on measured room impulse responses. AB - Measured room impulse responses (RIR) strongly depend on the directivity of the sound source used for the measurement. An analysis method is presented that is capable of pinpointing the influence of the loudspeaker's directivity on a set of RIRs. Taking into account the rotational symmetries of a dodecahedron loudspeaker, it detects the effects that the changing directional pattern induces in the RIR. The analysis of RIRs measured in completely different acoustical environments reveals that the influence of the loudspeaker's directivity can still be observed in the very late part of the RIR-even in very reverberant rooms. These results are presented and the consistency with general room acoustical theory is revised and discussed. PMID- 24180777 TI - Enhancing sound absorption and transmission through flexible multi-layer micro perforated structures. AB - Theoretical and experimental results are presented into the sound absorption and transmission properties of multi-layer structures made up of thin micro perforated panels (ML-MPPs). The objective is to improve both the absorption and insulation performances of ML-MPPs through impedance boundary optimization. A fully coupled modal formulation is introduced that predicts the effect of the structural resonances onto the normal incidence absorption coefficient and transmission loss of ML-MPPs. This model is assessed against standing wave tube measurements and simulations based on impedance translation method for two double layer MPP configurations of relevance in building acoustics and aeronautics. Optimal impedance relationships are proposed that ensure simultaneous maximization of both the absorption and the transmission loss under normal incidence. Exhaustive optimization of the double-layer MPPs is performed to assess the absorption and/or transmission performances with respect to the impedance criterion. It is investigated how the panel volumetric resonances modify the excess dissipation that can be achieved from non-modal optimization of ML-MPPs. PMID- 24180778 TI - Measurement of complex acoustic intensity in an acoustic waveguide. AB - Acoustic intensity is normally treated as a real quantity, but in recent years, many articles have appeared in which intensity is treated as a complex quantity where the real (active) part is related to local mean energy flow and the imaginary (reactive) part to local oscillatory transport of energy. This offers the potential to recover additional information about a sound field and then to relate this to the properties of the sound source and the environment that surrounds it. However, this approach is applicable only to multi-modal sound fields, which places significant demands on the accuracy of the intensity measurements. Accordingly, this article investigates the accuracy of complex intensity measurements obtained using a tri-axial Microflown intensity probe by comparing measurement and prediction for sound propagation in an open flanged pipe. Under plane wave conditions, comparison between prediction and experiment reveals good agreement, but when a higher order mode is present, the reactive intensity field becomes complicated and agreement is less successful. It is concluded that the potential application of complex intensity as a diagnostic tool is limited by difficulties in measuring reactive intensity in complex sound fields when using current state of the art acoustic instrumentation. PMID- 24180779 TI - Compression of head-related transfer function using autoregressive-moving-average models and Legendre polynomials. AB - Head-related transfer functions (HRTFs) are generally large datasets, which can be an important constraint for embedded real-time applications. A method is proposed here to reduce redundancy and compress the datasets. In this method, HRTFs are first compressed by conversion into autoregressive-moving-average (ARMA) filters whose coefficients are calculated using Prony's method. Such filters are specified by a few coefficients which can generate the full head related impulse responses (HRIRs). Next, Legendre polynomials (LPs) are used to compress the ARMA filter coefficients. LPs are derived on the sphere and form an orthonormal basis set for spherical functions. Higher-order LPs capture increasingly fine spatial details. The number of LPs needed to represent an HRTF, therefore, is indicative of its spatial complexity. The results indicate that compression ratios can exceed 98% while maintaining a spectral error of less than 4 dB in the recovered HRTFs. PMID- 24180780 TI - Beamforming of sound from two-dimensional arrays using spatial matched filters. AB - Fully-sampled two-dimensional (2D) arrays can have two-way focusing of the ultrasound beam in both lateral directions leading to high quality, real-time three-dimensional (3D) imaging. However, fully-sampled 2D arrays with very large element counts (>16,000) are difficult to manufacture due to interconnect density and large element electrical impedance. As an alternative, row-column or crossed electrode arrays have been proposed to simplify transducer fabrication and system integration. These types of arrays consist of two one-dimensional arrays oriented perpendicular to each other. Using conventional delay-and-sum beamforming, each array performs one-way focusing in perpendicular lateral directions which yield higher sidelobe and acoustic clutter levels compared to fully-sampled 2D arrays with two-way focusing. In this paper, the use of spatial matched filters to improve focusing of row-column arrays is investigated. On receive, data from each element are first spatial match filtered in the elevation direction. After summation, the data are filtered again in the azimuth direction. Beam widths comparable to one-way focusing are seen in azimuth and beam widths comparable to two-way focusing are achieved in elevation. 3D beam patterns from computer simulation results using a 7.5 MHz 128 * 128 row-column array are shown with comparison to a fully sampled 2D array. PMID- 24180781 TI - Comparing passive source localization and tracking approaches with a towed horizontal receiver array in an ocean waveguide. AB - Approaches for instantaneous passive source localization using a towed horizontal receiver array in a random range-dependent ocean waveguide are examined. They include: (1) Moving array triangulation, (2) array invariant, (3) bearings-only target motion analysis in modified polar coordinates via the extended Kalman filter, and (4) bearings-migration minimum mean-square error. These methods are applied to localize and track a vertical source array deployed in the far-field of a towed horizontal receiver array during the Gulf of Maine 2006 Experiment. The source transmitted intermittent broadband pulses in the 300 to 1200 Hz frequency range. A nonlinear matched-filter kernel designed to replicate the acoustic signal measured by the receiver array is applied to enhance the signal to-noise ratio. The source localization accuracy is found to be highly dependent on source-receiver geometry and the localization approach. For a relatively stationary source drifting at speeds much slower than the receiver array tow speed, the mean source position can be estimated by moving array triangulation with less than 3% error near broadside direction. For a moving source, the Kalman filter method gives the best performance with 5.5% error. The array invariant is the best approach for localizing sources within the endfire beam of the receiver array with 7% error. PMID- 24180782 TI - Sound field reproduction as an equivalent acoustical scattering problem. AB - Given a continuous distribution of acoustic sources, the determination of the source strength that ensures the synthesis of a desired sound field is shown to be identical to the solution of an equivalent acoustic scattering problem. The paper begins with the presentation of the general theory that underpins sound field reproduction with secondary sources continuously arranged on the boundary of the reproduction region. The process of reproduction by a continuous source distribution is modeled by means of an integral operator (the single layer potential). It is then shown how the solution of the sound reproduction problem corresponds to that of an equivalent scattering problem. Analytical solutions are computed for two specific instances of this problem, involving, respectively, the use of a secondary source distribution in spherical and planar geometries. The results are shown to be the same as those obtained with analyses based on High Order Ambisonics and Wave Field Synthesis, respectively, thus bringing to light a fundamental analogy between these two methods of sound reproduction. Finally, it is shown how the physical optics (Kirchhoff) approximation enables the derivation of a high-frequency simplification for the problem under consideration, this in turn being related to the secondary source selection criterion reported in the literature on Wave Field Synthesis. PMID- 24180783 TI - A simple electrical lumped-element model simulates intra-cochlear sound pressures and cochlear impedance below 2 kHz. AB - Low-frequency sounds displace large parts of the basilar membrane (BM) and can have a modulating and possibly disturbing effect on hearing at other frequencies. A better understanding of the transfer of such sounds onto the BM is therefore desirable. Lumped-element models have previously been employed to determine the low-frequency acoustic properties of the cochlea. Although helpful in illustrating schematically the role of the helicotrema, BM compliance, and the round window on low-frequency hearing, these models, when applied quantitatively, have not been able to explain experimental data in detail. Building on these models, an extended electrical analog requires just 13 lumped elements to capture, in surprising detail, the physiologically determined frequency dependence of intra-cochlear pressure and cochlear impedance between 10 Hz and 2 kHz. The model's verification is based on data from cat, guinea pig, and humans, who differ principally in their low-frequency cochlear acoustics. The modeling data suggest that damping within the helicotrema plays a less prominent role than previously assumed. A resonance feature, which is often observed experimentally near 150 Hz in these animals and near 50 Hz in humans, is presumably a phenomenon local to the apex and not the result of a standing wave between stapes and helicotrema. PMID- 24180784 TI - Otoacoustic emission sensitivity to exposure to styrene and noise. AB - The ototoxic effect of the exposure to styrene is evaluated, also in the presence of simultaneous exposure to noise, using otoacoustic emissions as biomarkers of mild cochlear damage. Transient-evoked and distortion product otoacoustic emissions were recorded and analyzed in a sample of workers (15 subjects) exposed to styrene and noise in a fiberglass manufacturing facility and in a control group of 13 non-exposed subjects. Individual exposure monitoring of the airborne styrene concentrations was performed, as well as biological monitoring, based on the urinary concentration of two styrene metabolites, the Mandelic and Phenylglyoxylic acids. Noise exposure was evaluated using wearable phonometers, and hearing loss with pure tone audiometry. Due to their different job tasks, one group of workers was exposed to high noise and low styrene levels, another group to higher styrene levels, close to the limit of 20 ppm, and to low noise levels. A significant negative correlation was found between the otoacoustic emission levels and the concentration of the styrene urinary metabolites. Otoacoustic emissions, and particularly distortion products, were able to discriminate the exposed workers from the controls, providing also a rough estimate of the slope of the dose-response relation between otoacoustic levels and styrene exposure. PMID- 24180785 TI - The effect of rocking stapes motions on the cochlear fluid flow and on the basilar membrane motion. AB - The basilar membrane (BM) and perilymph motion in the cochlea due to rocking stapes motion (RSM) and piston-like stapes motion (PSM) is modeled by numerical simulations. The full Navier-Stokes equations are solved in a two-dimensional box geometry. The BM motion is modeled by independent oscillators using an immersed boundary technique. The traveling waves generated by both stimulation modes are studied. A comparison of the peak amplitudes of the BM motion is presented and their dependence on the frequency and on the model geometry (stapes position and cochlear channel height) is investigated. It is found that the peak amplitudes for the RSM are lower and decrease as frequency decreases whereas those for the PSM increase as frequency decreases. This scaling behavior can be explained by the different mechanisms that excite the membrane oscillation. Stimulation with both modes at the same time leads to either a slight increase or a slight decrease of the peak amplitudes compared to the pure PSM, depending on the phase shift between the two modes. While the BM motion is dominated by the PSM mode under normal conditions, the RSM may lead to hearing if no PSM is present or possible, e.g., due to round window atresia. PMID- 24180786 TI - Simultaneous suppression of noise and reverberation in cochlear implants using a ratio masking strategy. AB - Cochlear implant (CI) recipients' ability to identify words is reduced in noisy or reverberant environments. The speech identification task for CI users becomes even more challenging in conditions where both reverberation and noise co-exist as they mask the spectro-temporal cues of speech in a rather complementary fashion. Ideal channel selection (ICS) was found to result in significantly more intelligible speech when applied to the noisy, reverberant, as well as noisy reverberant speech. In this study, a blind single-channel ratio masking strategy is presented to simultaneously suppress the negative effects of reverberation and noise on speech identification performance for CI users. In this strategy, noise power spectrum is estimated from the non-speech segments of the utterance while reverberation spectral variance is computed as a delayed and scaled version of the reverberant speech spectrum. Based on the estimated noise and reverberation power spectra, a weight between 0 and 1 is assigned to each time-frequency unit to form the final mask. Listening experiments conducted with CI users in two reverberant conditions (T60 = 0.6 and 0.8 s) at a signal-to-noise ratio of 15 dB indicate substantial improvements in speech intelligibility in both reverberant alone and noisy reverberant conditions considered. PMID- 24180787 TI - Inter-speaker articulatory variability during vowel-consonant-vowel sequences in twins and unrelated speakers. AB - The purpose of this study is to examine and compare the amount of inter-speaker variability in the articulation of monozygotic twin pairs (MZ), dizygotic twin pairs (DZ), and pairs of unrelated twins with the goal of examining in greater depth the influence of physiology on articulation. Physiological parameters are assumed to be very similar in MZ twin pairs in contrast to DZ twin pairs or unrelated speakers, and it is hypothesized that the speaker specific shape of articulatory looping trajectories of the tongue is at least partly dependent on biomechanical properties and the speaker's individual physiology. By means of electromagnetic articulography (EMA), inter-speaker variability in the looping trajectories of the tongue back during /VCV/ sequences is analyzed. Results reveal similar looping patterns within MZ twin pairs but in DZ pairs differences in the shape of the loop, the direction of the upward and downward movement, and the amount of horizontal sliding movement at the palate are found. PMID- 24180788 TI - Developmental and gender-related trends of intra-talker variability in consonant production. AB - This study investigates the effect of age and gender on the internal structure, cross-category distance, and discriminability of phonemic categories for two contrasts varying in fricative place of articulation (/s/-/?/) and stop voicing (/b/-/p/) in word-initial tokens spoken by adults and normally developing children aged 9-14 yr. Vast between- and within-talker variability was observed with 16% of speakers exhibiting some degree of overlap between phonemic categories-a possible contribution to the range of talker intelligibility found in the literature. Females of all ages produced farther and thus more discriminable categories than males, although gender-marking for fricative between-category distance did not emerge until approximately 11 yr of age. Children produced farther yet also much more dispersed categories than adults with increasing discriminability with age, such that by age 13, children's categories were no less discriminable than those of adults. However, children's ages did not predict category distance or dispersion, indicating that convergence on adult-like category structure must occur later in adolescence. PMID- 24180789 TI - Clarity in communication: "clear" speech authenticity and lexical neighborhood density effects in speech production and perception. AB - Speech produced in the context of real or imagined communicative difficulties is characterized by hyperarticulation. Phonological neighborhood density (ND) conditions similar patterns in production: Words with many neighbors are hyperarticulated relative to words with fewer; Hi ND words also show greater coarticulation than Lo ND words [e.g., Scarborough, R. (2012). "Lexical similarity and speech production: Neighborhoods for nonwords," Lingua 122(2), 164 176]. Coarticulatory properties of "clear speech" are more variable across studies. This study examined hyperarticulation and nasal coarticulation across five real and simulated clear speech contexts and two neighborhood conditions, and investigated consequences of these details for word perception. The data revealed a continuum of (attempted) clarity, though real listener-directed speech (Real) differed from all of the simulated styles. Like the clearest simulated context speech (spoken "as if to someone hard-of-hearing"-HOH), Real had greater hyperarticulation than other conditions. However, Real had the greatest coarticulatory nasality while HOH had the least. Lexical decisions were faster for words from Real than from HOH, indicating that speech produced in real communicative contexts (with hyperarticulation and increased coarticulation) was perceptually better than simulated clear speech. Hi ND words patterned with Real in production, and Real Hi ND words were clear enough to overcome the dense neighborhood disadvantage. PMID- 24180790 TI - Hearing tongue loops: perceptual sensitivity to acoustic signatures of articulatory dynamics. AB - Previous work has shown that velar stops are produced with a forward movement during closure, forming a forward (anterior) loop for a VCV sequence, when the preceding vowels are back or mid. Are listeners aware of this aspect of articulatory dynamics? The current study used articulatory synthesis to examine how such kinematic patterns are reflected in the acoustics, and whether those acoustic patterns elicit different goodness ratings. In Experiment I, the size and direction of loops was modulated in articulatory synthesis. The resulting stimuli were presented to listeners for a naturalness judgment. Results show that listeners rate forward loops as more natural than backward loops, in agreement with typical productions. Acoustic analysis of the synthetic stimuli shows that forward loops exhibit shorter and shallower VC transitions than CV transitions. In Experiment II, three acoustic parameters were employed incorporating F3-F2 distance, transition slope, and transition length to systematically modulate the magnitude of VC and CV transitions. Listeners rated the naturalness in accord with those of Experiment I. This study reveals that there is sufficient information in the acoustic signature of "velar loops" to affect perceptual preference. Similarity to typical productions seemed to determine preferences, not acoustic distinctiveness. PMID- 24180791 TI - Comparison of a short-time speech-based intelligibility metric to the speech transmission index and intelligibility data. AB - Several algorithms have been shown to generate a metric corresponding to the Speech Transmission Index (STI) using speech as a probe stimulus [e.g., Goldsworthy and Greenberg, J. Acoust. Soc. Am. 116, 3679-3689 (2004)]. The time domain approaches work well on long speech segments and have the added potential to be used for short-time analysis. This study investigates the performance of the Envelope Regression (ER) time-domain STI method as a function of window length, in acoustically degraded environments with multiple talkers and speaking styles. The ER method is compared with a short-time Theoretical STI, derived from octave-band signal-to-noise ratios and reverberation times. For windows as short as 0.3 s, the ER method tracks short-time Theoretical STI changes in stationary speech-shaped noise, fluctuating restaurant babble and stationary noise plus reverberation. The metric is also compared to intelligibility scores on conversational speech and speech articulated clearly but at normal speaking rates (Clear/Norm) in stationary noise. Correlation between the metric and intelligibility scores is high and, consistent with the subject scores, the metrics are higher for Clear/Norm speech than for conversational speech and higher for the first word in a sentence than for the last word. PMID- 24180792 TI - Native language affects rhythmic grouping of speech. AB - Perceptual attunement to one's native language results in language-specific processing of speech sounds. This includes stress cues, instantiated by differences in intensity, pitch, and duration. The present study investigates the effects of linguistic experience on the perception of these cues by studying the Iambic-Trochaic Law (ITL), which states that listeners group sounds trochaically (strong-weak) if the sounds vary in loudness or pitch and iambically (weak strong) if they vary in duration. Participants were native listeners either of French or German; this comparison was chosen because French adults have been shown to be less sensitive than speakers of German and other languages to word level stress, which is communicated by variation in cues such as intensity, fundamental frequency (F0), or duration. In experiment 1, participants listened to sequences of co-articulated syllables varying in either intensity or duration. The German participants were more consistent in their grouping than the French for both cues. Experiment 2 was identical to experiment 1 except that intensity variation was replaced by pitch variation. German participants again showed more consistency for both cues, and French participants showed especially inconsistent grouping for the pitch-varied sequences. These experiments show that the perception of linguistic rhythm is strongly influenced by linguistic experience. PMID- 24180793 TI - Perception of spectrally degraded reflexives and pronouns by children. AB - Speech perception skills in cochlear-implant users are often measured with simple speech materials. In children, it is crucial to fully characterize linguistic development, and this requires linguistically more meaningful materials. The authors propose using the comprehension of reflexives and pronouns, as these specific skills are acquired at different ages. According to the literature, normal-hearing children show adult-like comprehension of reflexives at age 5, while their comprehension of pronouns only reaches adult-like levels around age 10. To provide normative data, a group of younger children (5 to 8 yrs old), older children (10 and 11 yrs old), and adults were tested under conditions without or with spectral degradation, which simulated cochlear-implant speech transmission with four and eight channels. The results without degradation confirmed the different ages of acquisition of reflexives and pronouns. Adding spectral degradation reduced overall performance; however, it did not change the general pattern observed with non-degraded speech. This finding confirms that these linguistic milestones can also be measured with cochlear-implanted children, despite the reduced quality of sound transmission. Thus, the results of the study have implications for clinical practice, as they could contribute to setting realistic expectations and therapeutic goals for children who receive a cochlear implant. PMID- 24180794 TI - Absolute pitch among students at the Shanghai Conservatory of Music: a large scale direct-test study. AB - This paper reports a large-scale direct-test study of absolute pitch (AP) in students at the Shanghai Conservatory of Music. Overall note-naming scores were very high, with high scores correlating positively with early onset of musical training. Students who had begun training at age <=5 yr scored 83% correct not allowing for semitone errors and 90% correct allowing for semitone errors. Performance levels were higher for white key pitches than for black key pitches. This effect was greater for orchestral performers than for pianists, indicating that it cannot be attributed to early training on the piano. Rather, accuracy in identifying notes of different names (C, C#, D, etc.) correlated with their frequency of occurrence in a large sample of music taken from the Western tonal repertoire. There was also an effect of pitch range, so that performance on tones in the two-octave range beginning on Middle C was higher than on tones in the octave below Middle C. In addition, semitone errors tended to be on the sharp side. The evidence also ran counter to the hypothesis, previously advanced by others, that the note A plays a special role in pitch identification judgments. PMID- 24180795 TI - Finite difference time domain simulation for the brass instrument bore. AB - In this article, interleaved finite difference time domain methods are developed for the purpose of simulating the dynamics of the acoustic bore, using, as a starting point, an impedance formulation of wave propagation in an acoustic tube; attention is focused here on modeling of viscothermal and radiation losses in the time domain. In particular, in contrast to other methods, the bore, including the mouth-piece and bell, is treated as a unit, and is not subdivided into smaller units such as cylindrical or conical segments. Numerical simulations of input impedances are then compared with measurement for a variety of brass instruments. PMID- 24180796 TI - Trumpet mouthpiece manufacturing and tone quality. AB - This article investigates the relationship between the shape of the mouthpiece and its acoustical properties in brass instruments. The hypothesis is that not only different volumes but also particular cup shapes affect the embouchure and the tone quality in both a physical and perceivable way. Three professional trumpet players were involved, and two different internal cup contours characterized by a "U" and a "V" shape with two types of throat junction (round and sharp) were chosen, based on a Vincent Bach 1 [1/2] C medium mouthpiece. A third intermediate contour was designed as a combination of these. Over 600 sound samples were produced under controlled conditions, the study involving four different stages: (1) Simulation of air-flow, (2) analysis of the sound spectra, (3) study of the players' subjective responses, and (4) perceptual analysis of their timbral differences. Results confirm the U shape is characterized by a stronger air recirculation and produces stronger spectral components above 8 kHz, compared to the V shape. A round throat junction may also be preferable to a sharp one in terms of playability. There is moderate agreement on the aural perception of these differences although the verbal attributes used to qualify these are not shared. PMID- 24180797 TI - Acoustical interaction between vibrating lips, downstream air column, and upstream airways in trombone performance. AB - This paper presents experimental results on the acoustical influence of the vocal tract in trombone performance. The experimental approach makes use of measurements at the interface between the player and instrument, allowing a relative comparison between upstream airways and the downstream air column impedances, as well as an estimation of the phase of the impedance of the upstream and downstream systems. Measurements were conducted over the full traditional range of playing, during sustained tones with varying dynamic, as well as in special effects such as pitch bending. Subjects able to play over the full range demonstrated significant upstream influence in the higher register of the instrument. These players were categorized in two groups according to their ability to control the phase of the upstream impedance and their ability to generate powerful downstream acoustic energy. Sustained tones played with varying dynamics showed a general tendency of a decrease in vocal-tract support with increase in loudness. Although pitch bends did not involve significant upstream influence at f0, results suggest modification of the lip behavior during bending. Vocal-tract tuning at tone transitions was also investigated and found to potentially contribute to slur articulations. PMID- 24180798 TI - High initial and minimum frequencies of Sotalia guianensis whistles in the southeast and south of Brazil. AB - Recent studies have proposed latitudinal variations for the whistles of Sotalia guianensis, since parameters of frequency increase from the southernmost distribution of the species (State of Santa Catarina, Brazil) toward the North. The last study on the whistles of S. guianensis, conducted in Costa Rica, confirmed the geographical variation of whistles, regardless of frequency responses used in the samples. Initial and minimum frequencies of whistles of the Costa Rican populations were higher than were the frequencies of Brazilian populations. In this current study, the whistles of S. guianensis were recorded with a sampling frequency of 48 kHz, the highest frequency band used in Brazilian studies. The initial and minimum frequency of whistles recorded and analyzed were similar to parameters of Costa Rican populations and show little or no difference when compared to the average of each study. Therefore, whistle frequency variables do not increase with latitude. It is likely that variations in acoustic parameters S. guianensis are mainly linked to environmental characteristics of the habitats in which the populations occur. Thus, the repertoire sound S. guianensis appears linked to similar environments with similar physical characteristics and not linked to population characteristics (dialects). PMID- 24180799 TI - Description of sounds associated with Sowerby's beaked whales (Mesoplodon bidens) in the western North Atlantic Ocean. AB - Several groups of Sowerby's beaked whales (Mesoplodon bidens) were encountered on July 4, 2011, during a shipboard cetacean survey conducted off the eastern seaboard of the United States. Acoustic recordings were collected using a three element towed hydrophone array. Many echolocation clicks were recorded during the encounter, but no tonal sounds were detected. A total of 2969 echolocation clicks were included in analyses of frequency and temporal characteristics. A Gaussian mixture model with four mixtures was fitted to the histogram of peak frequencies; four subsets of clicks were designated. The majority of clicks (n = 2048) contained a median peak frequency of 33 kHz, while the others contained a median peak frequency of 25 kHz (n = 324), 51 kHz (n = 304), or 67 kHz (n = 293). Most clicks did not contain a clear frequency-modulated upsweep, though some clicks exhibited a slight sweep from 30-36 kHz. Seven burst pulses were detected in the encounter, two of which were of high enough quality for detailed analysis. The acoustic characteristics of Sowerby's beaked whales have not previously been described; the current study will facilitate incorporation of these data into passive acoustic monitoring programs in the North Atlantic Ocean. PMID- 24180800 TI - Using the auditory steady-state response to assess temporal dynamics of hearing sensitivity during bottlenose dolphin echolocation. AB - The auditory steady-state response (ASSR) to an external tone was measured in an echolocating dolphin to determine if hearing sensitivity changes could be tracked over time scales corresponding to single click-echo pairs. Individual epochs containing click-echo pairs were first extracted from the instantaneous electroencephalogram. Epochs were coherently averaged using the external tone modulation rate as a timing reference, then Fourier transformed using a sliding, 10-ms temporal window to obtain the ASSR amplitude as a function of time. The results revealed a decrease in the ASSR amplitude at the time of click emission, followed by a 25-70 ms recovery. PMID- 24180801 TI - Acoustic characterization and contrast imaging of microbubbles encapsulated by polymeric shells coated or filled with magnetic nanoparticles. AB - The combination of superparamagnetic iron oxide nanoparticles with polymeric air filled microbubbles is used to produce two types of multimodal contrast agents to enhance medical ultrasound and magnetic resonance imaging. The nanoparticles are either covalently linked to the shell or physically entrapped into the shell. In this paper, the characterization of the acoustic properties (backscattered power, fracturing pressure, attenuation and dispersion of the ultrasonic wave) and ultrasound imaging of the two types of magnetic microbubbles are presented. In vitro B-mode images are generated using a medical ultrasound scanner by applying a nonconventional signal processing technique that is suitable to detect polymeric bubbles and based on the combination of multipulse excitation and chirp coding. Even if both types of microbubbles can be considered to be effective ultrasound contrast agents, the different structure of the shell loaded with nanoparticles has a pronounced effect on the echogenicity and the detection sensitivity of the imaging technique. The best results are obtained using microbubbles that are externally coated with nanoparticles. A backscattered power of 20 dB was achieved at lower concentration, and an increment of 8 dB in the contrast-to-tissue ratio was observed with respect to the more rigid microbubbles with particles entrapped into the shell. PMID- 24180802 TI - Simulation of nonlinear Westervelt equation for the investigation of acoustic streaming and nonlinear propagation effects. AB - This study investigates the influence of blood flow on temperature distribution during high-intensity focused ultrasound (HIFU) ablation of liver tumors. A three dimensional acoustic-thermal-hydrodynamic coupling model is developed to compute the temperature field in the hepatic cancerous region. The model is based on the nonlinear Westervelt equation, bioheat equations for the perfused tissue and blood flow domains. The nonlinear Navier-Stokes equations are employed to describe the flow in large blood vessels. The effect of acoustic streaming is also taken into account in the present HIFU simulation study. A simulation of the Westervelt equation requires a prohibitively large amount of computer resources. Therefore a sixth-order accurate acoustic scheme in three-point stencil was developed for effectively solving the nonlinear wave equation. Results show that focused ultrasound beam with the peak intensity 2470 W/cm(2) can induce acoustic streaming velocities up to 75 cm/s in the vessel with a diameter of 3 mm. The predicted temperature difference for the cases considered with and without acoustic streaming effect is 13.5 degrees C or 81% on the blood vessel wall for the vein. Tumor necrosis was studied in a region close to major vessels. The theoretical feasibility to safely necrotize the tumors close to major hepatic arteries and veins was shown. PMID- 24180803 TI - On the lateral resolution of focused ultrasonic fields from spherically curved transducers. AB - Focused ultrasonic fields produced by spherically curved transducers occur in many areas, as, for example, in medical ultrasonics. Recently, transducers with a central hole have increasingly appeared in practice. The present paper theoretically investigates the lateral field distribution in the geometric focal plane, based on an approach with the Rayleigh integral. Results for the lateral width of the focal maximum in that plane are presented. It turns out that the appearance of a central hole leads to a reduction in the lateral width of the focal maximum, contrary to the behavior of the longitudinal width of that maximum shown earlier. PMID- 24181979 TI - Correlations of linear and nonlinear ultrasound parameters with density and microarchitectural parameters in trabecular bone. AB - In the present study, correlations of linear and nonlinear ultrasound parameters (speed of sound, normalized broadband ultrasound attenuation, and nonlinear parameter B/A) with bone mineral density and microarchitectural parameters were investigated in 28 bovine femoral trabecular bone samples in vitro. All three ultrasound parameters exhibited relatively high correlation coefficients with the indexes of bone quantity (bone mineral density and bone volume fraction) and lower correlation coefficients with the remaining microarchitectural parameters. These results suggest that B/A, in addition to speed of sound and attenuation, may have potential as an index for the assessment of bone status and osteoporosis. PMID- 24181980 TI - Reduced efficiency of audiovisual integration for nonnative speech. AB - The role of visual cues in native listeners' perception of speech produced by nonnative speakers has not been extensively studied. Native perception of English sentences produced by native English and Korean speakers in audio-only and audiovisual conditions was examined. Korean speakers were rated as more accented in audiovisual than in the audio-only condition. Visual cues enhanced word intelligibility for native English speech but less so for Korean-accented speech. Reduced intelligibility of Korean-accented audiovisual speech was associated with implicit visual biases, suggesting that listener-related factors partially influence the efficiency of audiovisual integration for nonnative speech perception. PMID- 24181981 TI - Inversion of seabed attenuation using time-warping of close range data. AB - An inversion scheme based on time-warping is presented for estimating seabed sound attenuation from modal dispersion of close-range single-hydrophone data. The dispersion information is extracted directly from the warped signal spectrum. Seabed sound speed and density are inverted from the modal group velocity curves, and the attenuation is inverted from the normalized modal amplitudes. The method is applied to experimental data collected in the Yellow Sea of China during the winter of 2002. The inverted sound speed and density are consistent with the sand silt-clay sediment at the site, and the attenuation is nonlinear over the frequency band from 125-500 Hz. PMID- 24181982 TI - Calibrating passive acoustic monitoring: correcting humpback whale call detections for site-specific and time-dependent environmental characteristics. AB - This paper demonstrates the importance of accounting for environmental effects on passive underwater acoustic monitoring results. The situation considered is the reduction in shipping off the California coast between 2008-2010 due to the recession and environmental legislation. The resulting variations in ocean noise change the probability of detecting marine mammal vocalizations. An acoustic model was used to calculate the time-varying probability of detecting humpback whale vocalizations under best-guess environmental conditions and varying noise. The uncorrected call counts suggest a diel pattern and an increase in calling over a two-year period; the corrected call counts show minimal evidence of these features. PMID- 24181983 TI - Comparison of across-frequency integration strategies in a binaural detection model. AB - Breebaart et al. [J. Acoust. Soc. Am. 110, 1089-1104 (2001)] reported that the masker bandwidth dependence of detection thresholds for an out-of-phase signal and an in-phase noise masker (N0Spi) can be explained by principles of integration of information across critical bands. In this paper, different methods for such across-frequency integration process are evaluated as a function of the bandwidth and notch width of the masker. The results indicate that an "optimal detector" model assuming independent internal noise in each critical band provides a better fit to experimental data than a best filter or a simple across-frequency integrator model. Furthermore, the exponent used to model peripheral compression influences the accuracy of predictions in notched conditions. PMID- 24181984 TI - Unexpected intensity changes in the ear canal during a F(0)-shifted feedback experiment. AB - Effects of frequency-shifted feedback are typically examined using Eventide Harmonizer Series processors to shift the fundamental frequency (F0) of auditory feedback during vocalizations, eliciting compensatory shifts in speaker F0. Recently, unexpected intensity changes were observed in speakers' ear canals, corresponding with F0 shifts. An investigation revealed that feedback time delays introduced by the processor resulted in phase shifts between feedback and unprocessed voice signals radiating into the ear canal via bone conduction, producing combination waves with gains as high as 6 dB. Shifts of this magnitude potentially alter the interpretation of previously published results and should be controlled in future studies. PMID- 24181985 TI - On the suitability of ISO 16717-1 reference spectra for rating airborne sound insulation. AB - A standard proposal for rating airborne sound insulation in buildings [ISO 16717 1 (2012)] defines the reference noise spectra. Since their shapes influence the calculated values of single-number descriptors, reference spectra should approximate well typical noise spectra in buildings. There is, however, very little data in the existing literature on a typical noise spectrum in dwellings. A spectral analysis of common noise sources in dwellings is presented in this paper, as a result of an extensive monitoring of various noisy household activities. Apart from music with strong bass content, the proposed "living" reference spectrum overestimates noise levels at low frequencies. PMID- 24181986 TI - Three-dimensional multiple-source focalization in an uncertain ocean environment. AB - This letter develops a Bayesian focalization approach for three-dimensional localization of an unknown number of sources in shallow water with uncertain environmental properties. The algorithm minimizes the Bayesian information criterion using adaptive hybrid optimization for environmental parameters, Metropolis sampling for source bearing, and Gibbs sampling for source ranges and depths. Maximum-likelihood expressions are used for unknown complex source strengths and noise variance, which allows these parameters to be sampled implicitly. An efficient scheme for adding/deleting sources is used during the optimization. A synthetic example considers localizing a quiet source in the presence of multiple interferers using a horizontal line array. PMID- 24181987 TI - A lightweight push-pull acoustic transducer composed of a pair of dielectric elastomer films. AB - A lightweight push-pull acoustic transducer using dielectric elastomer films was proposed for use in advanced audio systems in homes. The push-pull structure consists of two dielectric elastomer films developed to serve as an electroactive polymer. The transducer utilizes the change in the surface area of the dielectric elastomer film, induced by an electric-field-induced change in the thickness, for sound generation. The resonance frequency of the transducer was derived from modeling the push-pull configuration to estimate the lower limit of the frequency range. Measurement results presented an advantage of push-pull driving in the suppression of harmonic distortion. PMID- 24181988 TI - Speech quality estimation of voice over internet protocol codec using a packet loss impairment model. AB - This letter proposes a degradation and cognition model to estimate speech quality impairment because of packet loss concealment (PLC) algorithm implemented in the speech CODEC SILK. By considering the fact that the quality degradation caused by packet loss is highly related to the PLC algorithm, the impact of quality degradation on various types of previous and lost packet classes is analyzed. Then, the PLC effects to the proposed class types are measured by the class conditional expectation of the degradation scores. Finally, the cognition module is derived to estimate the total quality degradation in a mean opinion score (MOS) scale. When assessed for correlation with subject test results, the correlation coefficient of the encoder-based class model is 0.93, and that of the decoder-based model is 0.87. PMID- 24181989 TI - Compressive sensing beamforming based on covariance for acoustic imaging with noisy measurements. AB - Compressive sensing, a newly emerging method from information technology, is applied to array beamforming and associated acoustic applications. A compressive sensing beamforming method (CSB-II) is developed based on sampling covariance matrix, assuming spatially sparse and incoherent signals, and then examined using both simulations and aeroacoustic measurements. The simulation results clearly show that the proposed CSB-II method is robust to sensing noise. In addition, aeroacoustic tests of a landing gear model demonstrate the good performance in terms of resolution and sidelobe rejection. PMID- 24181990 TI - The optimal ratio time-frequency mask for speech separation in terms of the signal-to-noise ratio. AB - In this paper, a computational goal for a monaural speech separation system is proposed. Since this goal is derived by maximizing the signal-to-noise ratio (SNR), it is called the optimal ratio mask (ORM). Under the approximate W Disjoint Orthogonality assumption which almost always holds due to the sparse nature of speech, theoretical analysis shows that the ORM can improve the SNR about 10log(10)2 dB over the ideal ratio mask. With three kinds of real-world interference, the speech separation results of SNR gain and objective quality evaluation demonstrate the correctness of the theoretical analysis, and imply that the ORM achieves a better separation performance. PMID- 24181991 TI - Improved estimation of frequency importance functions. AB - The Speech Intelligibility Index (SII) estimates speech intelligibility based on the audibility of speech cues across frequency. The frequency importance function gives the relative contribution to the SII of the speech audibility at different frequencies. The frequency importance function is usually estimated from the intelligibility data using a complicated multi-step procedure. This paper presents a new procedure for computing the frequency importance function directly from the intelligibility data based on nonlinear joint optimization of the frequency importance function and the SII curve-fitting parameters. An example of using the new approach is presented for previously published W-22 word list intelligibility data. PMID- 24181992 TI - Voice segregation by difference in fundamental frequency: effect of masker type. AB - Speech reception thresholds were measured for a voice against two different maskers: Either two concurrent voices with the same fundamental frequency (F0) or a harmonic complex with the same long-term excitation pattern and broadband temporal envelope as the masking sentences (speech-modulated buzz). All sources had steady F0s. A difference in F0 of 2 or 8 semitones provided a 5-dB benefit for buzz maskers, whereas it provided a 3- and 8-dB benefit, respectively, for masking sentences. Whether intelligibility of a voice increases abruptly with small DeltaF0s or gradually toward larger DeltaF0s seems to depend on the nature of the masker. PMID- 24181993 TI - Deduction of the acoustic impedance of the ground via a simulated three dimensional microphone array. AB - While commonly used ground impedance deduction methods often utilize pairs of vertically separated microphones, deployed arrays rarely have this configuration, which increases the difficulty in automatically deducing local ground impedance from these arrays. The ability to deduce ground impedance using random sounds incident on a three-dimensional array would increase, for example, the accuracy of estimated elevation angles. The methods described by the American National Standards Institute Method for Determining the Acoustic Impedance of Ground Surfaces are extended to simulate deducing ground impedance by a three dimensional array. Ground parameters indicative of grassland are successfully determined using a simulated three-dimensional array. PMID- 24181994 TI - Automatic assessment of vowel space area. AB - Vowel space area (VSA) is an attractive metric for the study of speech production deficits and reductions in intelligibility, in addition to the traditional study of vowel distinctiveness. Traditional VSA estimates are not currently sufficiently sensitive to map to production deficits. The present report describes an automated algorithm using healthy, connected speech rather than single syllables and estimates the entire vowel working space rather than corner vowels. Analyses reveal a strong correlation between the traditional VSA and automated estimates. When the two methods diverge, the automated method seems to provide a more accurate area since it accounts for all vowels. PMID- 24181995 TI - Communication: Ultrafast vibrational dynamics of hydrogen bond network terminated at the air/water interface: a two-dimensional heterodyne-detected vibrational sum frequency generation study. AB - Ultrafast vibrational dynamics of hydrogen bond network at the air/water interface is revealed by two-dimensional heterodyne-detected vibrational sum frequency generation (2D HD-VSFG) spectroscopy. Three diagonal peaks are clearly observed in the 2D HD-VSFG spectrum, which correspond to the negative and positive hydrogen-bonded OH stretch bands and the positive "free" OH stretch band in the steady-state HD-VSFG spectrum. A diagonally elongated bleaching lobe of the hydrogen-bonded OH at 0 ps indicates that it is partly inhomogeneously broadened. This diagonal elongation vanishes in a few hundred femtoseconds, implying the ultrafast spectral diffusion in the hydrogen-bonded OH band. Off diagonal cross peaks between each OH oscillator are clearly observed instantaneously within the time resolution of 0.2 ps, suggesting that they are vibrationally coupled through anharmonicity and/or energy transfer. PMID- 24181996 TI - Communication: Fine discretization of pair interactions and an approximate analytical strategy for predicting equilibrium behavior of complex fluids. AB - We study whether fine discretization (i.e., terracing) of continuous pair interactions, when used in combination with first-order mean-spherical approximation theory, can lead to a simple and general analytical strategy for predicting the equilibrium structure and thermodynamics of complex fluids. Specifically, we implement a version of this approach to predict how screened electrostatic repulsions, solute-mediated depletion attractions, or ramp-shaped repulsions modify the radial distribution function and the potential energy of reference hard-sphere fluids, and we compare the predictions to exact results from molecular simulations. PMID- 24181997 TI - Communication: Site-dependent reactivity between chlorine atoms and mixed-chain length alkanethiolate monolayers. AB - The chemical reaction of atomic chlorine with mixed monolayers of alkanethiolates having different chain lengths was investigated. In situ scanning tunneling microscopy was used to acquire time-lapsed series of images, allowing the measurement of the effect of monolayer structure and composition on reactivity. The rate of chemical reaction is strongly site-dependent. In particular, the boundary between two different-length alkanethiolates greatly promotes the reactivity of nearby molecules, much more so than any other native defect typical of single-component alkanethiolate monolayers. PMID- 24181998 TI - Ab initio analytical Raman intensities for periodic systems through a coupled perturbed Hartree-Fock/Kohn-Sham method in an atomic orbital basis. I. Theory. AB - We present a fully analytical formulation for calculating Raman intensities of crystalline periodic systems using a local basis set. Numerical differentiation with respect to atomic coordinates and with respect to wavevectors is entirely avoided as is the determination of crystal orbital coefficient derivatives with respect to nuclear displacements. Instead, our method utilizes the orbital energy weighted density matrix and is based on the self-consistent solution of first- and second-order Coupled Perturbed Hartree-Fock/Kohn-Sham equations for the electronic response to external electric fields at the equilibrium geometry. This method has also been implemented in the Crystal program, which uses a Gaussian type basis set. PMID- 24181999 TI - Ab initio analytical Raman intensities for periodic systems through a coupled perturbed Hartree-Fock/Kohn-Sham method in an atomic orbital basis. II. Validation and comparison with experiments. AB - In this work, we validate a new, fully analytical method for calculating Raman intensities of periodic systems, developed and presented in Paper I [L. Maschio, B. Kirtman, M. Rerat, R. Orlando, and R. Dovesi, J. Chem. Phys. 139, 164101 (2013)]. Our validation of this method and its implementation in the CRYSTAL code is done through several internal checks as well as comparison with experiment. The internal checks include consistency of results when increasing the number of periodic directions (from 0D to 1D, 2D, 3D), comparison with numerical differentiation, and a test of the sum rule for derivatives of the polarizability tensor. The choice of basis set as well as the Hamiltonian is also studied. Simulated Raman spectra of alpha-quartz and of the UiO-66 Metal-Organic Framework are compared with the experimental data. PMID- 24182000 TI - Sub-Ohmic spin-boson model with off-diagonal coupling: ground state properties. AB - We have carried out analytical and numerical studies of the spin-boson model in the sub-ohmic regime with the influence of both the diagonal and the off-diagonal coupling accounted for, via the Davydov D1 variational ansatz. While a second order phase transition is known to be exhibited by this model in the presence of diagonal coupling only, we demonstrate the emergence of a discontinuous first order phase transition upon incorporation of the off-diagonal coupling. A plot of the ground state energy versus magnetization highlights the discontinuous nature of the transition between the isotropic (zero magnetization) state and nematic (finite magnetization) phases. We have also calculated the entanglement entropy and a discontinuity found at a critical coupling strength further supports the discontinuous crossover in the spin-boson model in the presence of off-diagonal coupling. It is further revealed via a canonical transformation approach that for the special case of identical exponents for the spectral densities of the diagonal and the off-diagonal coupling, there exists a continuous crossover from a single localized phase to doubly degenerate localized phase with differing magnetizations. PMID- 24182001 TI - Application of recent double-hybrid density functionals to low-lying singlet singlet excitation energies of large organic compounds. AB - The present work assesses some recently developed double-hybrid density functionals (B2pi-PLYP, PBE0-DH, and PBE0-2) using linear-response Tamm-Dancoff Time-Dependent Density Functional Theory. This assessment is achieved against experimentally derived low-lying excitation energies of large organic dyes of recent interest, including some excitations dominated by charge-transfer transitions. Comparisons are made with some of the best-performing methods established from the literature, such as PBE0 or B3LYP hybrid or the recently proposed B2-PLYP and B2GP-PLYP double-hybrid models, to ascertain their quality and robustness on equal footing. The accuracy of parameter-free or empirical forms of double-hybrid functionals is also briefly discussed. Generally speaking, it turns out that double-hybrid expressions always provide more accurate estimates than corresponding hybrid methods. Double-hybrid functionals actually reach averaged accuracies of 0.2 eV, that can be admittedly considered close to any intended accuracy limit within the present theoretical framework. PMID- 24182002 TI - Neural networks for local structure detection in polymorphic systems. AB - The accurate identification and classification of local ordered and disordered structures is an important task in atomistic computer simulations. Here, we demonstrate that properly trained artificial neural networks can be used for this purpose. Based on a neural network approach recently developed for the calculation of energies and forces, the proposed method recognizes local atomic arrangements from a set of symmetry functions that characterize the environment around a given atom. The algorithm is simple and flexible and it does not rely on the definition of a reference frame. Using the Lennard-Jones system as well as liquid water and ice as illustrative examples, we show that the neural networks developed here detect amorphous and crystalline structures with high accuracy even in the case of complex atomic arrangements, for which conventional structure detection approaches are unreliable. PMID- 24182003 TI - Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure. AB - In molecular dynamics simulations, control over temperature and pressure is typically achieved by augmenting the original system with additional dynamical variables to create a thermostat and a barostat, respectively. These variables generally evolve on timescales much longer than those of particle motion, but typical integrator implementations update the additional variables along with the particle positions and momenta at each time step. We present a framework that replaces the traditional integration procedure with separate barostat, thermostat, and Newtonian particle motion updates, allowing thermostat and barostat updates to be applied infrequently. Such infrequent updates provide a particularly substantial performance advantage for simulations parallelized across many computer processors, because thermostat and barostat updates typically require communication among all processors. Infrequent updates can also improve accuracy by alleviating certain sources of error associated with limited precision arithmetic. In addition, separating the barostat, thermostat, and particle motion update steps reduces certain truncation errors, bringing the time average pressure closer to its target value. Finally, this framework, which we have implemented on both general-purpose and special-purpose hardware, reduces software complexity and improves software modularity. PMID- 24182004 TI - Extension of the non-Markovian Energy-Corrected Sudden model to the case of parallel and perpendicular infrared bands. AB - The non-Markovian Energy-Corrected Sudden approach [J. Buldyreva and L. Bonamy, Phys. Rev. A 60, 370 (1999)] previously developed for wide-band rototranslational Raman spectra of linear rotors is extended to the case of infrared absorption by linear molecules with stretching and bending modes. Basic relations such as detailed balance and double-sided sum rules for the rotational relaxation matrix are easily satisfied owing to the specific choice of a symmetric metric in the Liouville space. A single set of model parameters deduced from experimental widths of isolated isotropic Raman lines enables calculations of line-shape characteristics and full spectra up to the far wings. Applications to the important but quite complex example of pure carbon dioxide indicate the crucial role of the frequency dependence in the relaxation operator even for calculations of isolated-line characteristics. PMID- 24182005 TI - Control of Turing patterns and their usage as sensors, memory arrays, and logic gates. AB - We study a model system of three diffusively coupled reaction cells arranged in a linear array that display Turing patterns with special focus on the case of equal coupling strength for all components. As a suitable model reaction we consider a two-variable core model of glycolysis. Using numerical continuation and bifurcation techniques we analyze the dependence of the system's steady states on varying rate coefficient of the recycling step while the coupling coefficients of the inhibitor and activator are fixed and set at the ratios 100:1, 1:1, and 4:5. We show that stable Turing patterns occur at all three ratios but, as expected, spontaneous transition from the spatially uniform steady state to the spatially nonuniform Turing patterns occurs only in the first case. The other two cases possess multiple Turing patterns, which are stabilized by secondary bifurcations and coexist with stable uniform periodic oscillations. For the 1:1 ratio we examine modular spatiotemporal perturbations, which allow for controllable switching between the uniform oscillations and various Turing patterns. Such modular perturbations are then used to construct chemical computing devices utilizing the multiple Turing patterns. By classifying various responses we propose: (a) a single-input resettable sensor capable of reading certain value of concentration, (b) two-input and three-input memory arrays capable of storing logic information, (c) three-input, three-output logic gates performing combinations of logical functions OR, XOR, AND, and NAND. PMID- 24182006 TI - N-density representability and the optimal transport limit of the Hohenberg-Kohn functional. AB - We derive and analyze a hierarchy of approximations to the strongly correlated limit of the Hohenberg-Kohn functional. These "density representability approximations" are obtained by first noting that in the strongly correlated limit, N-representability of the pair density reduces to the requirement that the pair density must come from a symmetric N-point density. One then relaxes this requirement to the existence of a representing symmetric k-point density with k < N. The approximate energy can be computed by simulating a fictitious k-electron system. We investigate the approximations by deriving analytically exact results for a 2-site model problem, and by incorporating them into a self-consistent Kohn Sham calculation for small atoms. We find that the low order representability conditions already capture the main part of the correlations. PMID- 24182007 TI - Variationally localized search direction method for constrained optimization of non-orthogonal, localized orbitals in electronic structure calculations. AB - A new method for the constrained optimization of non-orthogonal, spatially localized orbitals using direct energy minimization techniques, in the context of electronic structure calculations, is presented. The variationally localized search direction (VLSD) method, as it was named, ensures that strict localization constraints are imposed upon the search direction vectors exactly, analytically and in a fully variational fashion. In contrast, the truncated search direction (TSD) method, of standard use in many electronic structure approaches with localization constraints, relies on the approximation that the truncated search direction vectors of the unconstrained problem resemble the exact search direction vectors of the constrained problem. With the TSD method, in order to maintain the localization constraints, a part of the pre-calculated information that is stored in the search direction vectors has to be deleted via an ad hoc, non-variational truncation step. The results on an extensive set of test molecules show that, in general, calculations with the VLSD method require less iterations to converge than with the TSD method for any size of the localization region. It was found that in calculations on certain systems where the TSD method is forced to delete a very large amount of information, the VLSD method is capable of achieving convergence in up to three times less iterations. Validation tests show that structural and electronic properties calculated with either method are accurate and in agreement with other electronic structure approaches. PMID- 24182008 TI - Time-dependent resonant scattering: an analytical approach. AB - A time-dependent description is given of a scattering process involving a single resonance embedded in a set of flat continua. An analytical approach is presented which starts from an incident free particle wave packet and yields the Breit Wigner cross-section formula at infinite times. We show that at intermediate times the so-called Wigner-Weisskopf approximation is equivalent to a scattering process involving a contact potential. Applications in cold-atom scattering and resonance enhanced desorption of molecules are discussed. PMID- 24182009 TI - Chemical oscillator as a generalized Rayleigh oscillator. AB - We derive the conditions under which a set of arbitrary two dimensional autonomous kinetic equations can be reduced to the form of a generalized Rayleigh oscillator which admits of limit cycle solution. This is based on a linear transformation of field variables which can be found by inspection of the kinetic equations. We illustrate the scheme with the help of several chemical and bio chemical oscillator models to show how they can be cast as a generalized Rayleigh oscillator. PMID- 24182011 TI - Ionization potentials of semiconductors from first-principles. AB - The ionization potential is the key to determine the absolute positions of valence and conduction bands of a semiconductor with respect to the vacuum level, which play a crucial role in physical and chemical properties of surfaces and interfaces. In spite of its far-reaching significance, theoretical determination of ionization potentials has not attained as much attention as that of band gaps. In this work, a set of prototypical semiconductors are considered to establish the performance of the state-of-the-art first-principles approaches. We have shown that in general Kohn-Sham density functional theory with local density approximation or generalized gradient approximation (LDA/GGA) significantly underestimates the ionization potentials of semiconductors. When the quasi particle correction from many-body perturbation theory in the GW approximation is taken into account, the agreement between theory and experiment can be greatly improved. We have made a critical comparison between two GW correction schemes, one taking into account the GW correction to the valence band maximum (VBM) of the bulk system, and the other based on the assumption that the LDA/GGA gives correct band gap center (BGC). Our study shows that the VBM scheme is better founded theoretically and leads to closer agreement with experiment practically than the BGC scheme. For semiconductors with shallow semicore states, for which the band gaps from the GW approach also exhibit significant errors, there is still significant discrepancy between GW and experiment, indicating the necessity to go beyond the standard GW approach for these materials. PMID- 24182010 TI - Coherent-control of linear signals: frequency-domain analysis. AB - The dependence of various types of linear signals on the phase profile of broadband optical pulses is examined using fundamental time translation invariance symmetry of multipoint correlation functions. The frequency-domain wave-mixing analysis presented here unifies several arguments made earlier with respect to the conditions whereby coherent control schemes may be used. PMID- 24182012 TI - On-the-fly ab intito calculations of anharmonic vibrational frequencies: local monomer theory and application to HCl clusters. AB - We present an on-the-fly quantum mechanical method to obtain anharmonic vibrational frequencies for molecular clusters. The basis for the method is the local-monomer model, a "divide and conquer" approach to theoretical spectroscopy, previously applied using full-dimensional surfaces [Y. Wang and J. M. Bowman, J. Chem. Phys. 134, 154510 (2011)]. The model consists of performing a local normal mode analysis for each monomer in a cluster in the field of the surrounding monomers. Anharmonic vibrational frequencies are then determined for each monomer by numerically solving the Schrodinger equation in terms of the local coordinates using ab initio energies obtained directly. Residual monomer-monomer coupling is accounted for using the Huckel-coupling extension [Y. Wang and J. M. Bowman, J. Chem. Phys. 136, 144113 (2012)]. In addition to the direct local-monomer approach, we propose and demonstrate a composite ab initio technique to reduce computational costs for calculating the anharmonic frequencies of large clusters. This technique utilizes two ab initio methods, a lower level of theory to compute geometries and perform harmonic analyses and a subsequent higher level of theory to compute the energies used in the anharmonic frequency calculations. We demonstrate the on-the-fly approach on hydrogen chloride clusters ranging in size from the dimer to the hexamer. Comparisons of the theoretical frequencies are made to previous experiments. We find the method to be an effective and computationally efficient approach to compute anharmonic frequencies. PMID- 24182013 TI - Efficient and accurate treatment of weak pairs in local CCSD(T) calculations. AB - Local coupled cluster theory is based on (i) a restriction of the list of pairs (or triples) of occupied molecular orbitals, and (ii) a truncation of the virtual space to orbital pair (or triple) specific subspaces. The latter is motivated by an exponential decay of the contributions to the pair energy with respect to the distance between related local occupied and virtual orbitals; the former only by a polynomial R(-6) decay with respect to the distance R between the two occupied orbitals of the pair. Consequently, the restriction of the pair list is more critical, and contributions of pairs should not be neglected unless the corresponding interorbital distance is really large. In local coupled cluster theory pairs are usually discriminated on the basis of the interorbital distance, or the size of the 2nd order Moller-Plesset perturbation theory (MP2) estimate of the pair energy. Only strong pairs are treated at the full coupled cluster level, while weak pairs are treated just at the level of MP2. Yet MP2 might be problematic in certain cases, for example, pi-stacking is badly described by MP2, etc. We propose to substitute the MP2 treatment of weak pairs by an approach based on ring-CCD by including third-order diagrams with R(-6) decay behavior. Such an approach is clearly superior; it provides higher accuracy, while the computational cost is not significantly higher than that of a MP2 based treatment of weak pairs. PMID- 24182014 TI - Apparent violation of the sum rule for exchange-correlation charges by generalized gradient approximations. AB - The exchange-correlation potential of Kohn-Sham density-functional theory, vXC(r), can be thought of as an electrostatic potential produced by the static charge distribution qXC(r) = -(1/4pi)?(2)vXC(r). The total exchange-correlation charge, QXC = ?qXC(r) dr, determines the rate of the asymptotic decay of vXC(r). If QXC ? 0, the potential falls off as QXC/r; if QXC = 0, the decay is faster than coulombic. According to this rule, exchange-correlation potentials derived from standard generalized gradient approximations (GGAs) should have QXC = 0, but accurate numerical calculations give QXC ? 0. We resolve this paradox by showing that the charge density qXC(r) associated with every GGA consists of two types of contributions: a continuous distribution and point charges arising from the singularities of vXC(r) at each nucleus. Numerical integration of qXC(r) accounts for the continuous charge but misses the point charges. When the point-charge contributions are included, one obtains the correct QXC value. These findings provide an important caveat for attempts to devise asymptotically correct Kohn Sham potentials by modeling the distribution qXC(r). PMID- 24182015 TI - Non-perturbative treatment of molecules in linear magnetic fields: calculation of anapole susceptibilities. AB - In the present study a non-perturbative approach to ab initio calculations of molecules in strong, linearly varying, magnetic fields is developed. The use of London atomic orbitals (LAOs) for non-uniform magnetic fields is discussed and the standard rationale of gauge-origin invariance is generalized to invariance under arbitrary constant shifts of the magnetic vector potential. Our approach is applied to study magnetically induced anapole moments (or toroidal moments) and the related anapole susceptibilities for a test set of chiral and nonchiral molecules. For the first time numerical anapole moments are accessible on an ab initio level of theory. Our results show that the use of London atomic orbitals dramatically improves the basis set convergence also for magnetic properties related to non-uniform magnetic fields, at the cost that the Hellmann-Feynman theorem does not apply for a finite LAO basis set. It is shown that the mixed anapole susceptibility can be related to chirality, since its trace vanishes for an achiral molecule. PMID- 24182016 TI - An algorithm for non-Born-Oppenheimer quantum mechanical variational calculations of N = 1 rotationally excited states of diatomic molecules using all-particle explicitly correlated Gaussian functions. AB - An algorithm for quantum mechanical variational calculations of bound states of diatomic molecules corresponding to the total angular momentum quantum number equal to one (N = 1) is derived and implemented. The approach employs all particle explicitly correlated Gaussian function for the wave-function expansion. The algorithm is tested in the calculations of the N = 1, v = 0, ..., 22 states of the HD(+) ion. PMID- 24182017 TI - Single molecule counting statistics for systems with periodic driving. AB - We extend the generating function approach for calculation of event statistics observed in single molecule spectroscopy to cases where the single molecule evolves under explicitly time-dependent and periodic perturbation. Floquet theory is used to recast the generating function equations for the periodically driven system into effective equations devoid of explicit time-dependence. Two examples are considered, one employing simple stochastic dynamics and the other quantum dynamics, to demonstrate the versatility and numerical accuracy of the methodology. PMID- 24182018 TI - The role of Rydberg and continuum levels in computing high harmonic generation spectra of the hydrogen atom using time-dependent configuration interaction. AB - We study the role of Rydberg bound-states and continuum levels in the field induced electronic dynamics associated with the High-Harmonic Generation (HHG) spectroscopy of the hydrogen atom. Time-dependent configuration-interaction (TD CI) is used with very large atomic orbital (AO) expansions (up to L = 4 with sextuple augmentation and off-center functions) to describe the bound Rydberg levels, and some continuum levels. To address the lack of ionization losses in TD CI with finite AO basis sets, we employed a heuristic lifetime for energy levels above the ionization potential. The heuristic lifetime model is compared against the conventional atomic orbital treatment (infinite lifetimes), and a third approximation which is TD-CI using only the bound levels (continuum lifetimes go to zero). The results suggest that spectra calculated using conventional TD-CI do not converge with increasing AO basis set size, while the zero lifetime and heuristic lifetime models converge to qualitatively similar spectra, with implications for how best to apply bound state electronic structure methods to simulate HHG. The origin of HHG spectral features including the cutoff and extent of interference between peaks is uncovered by separating field-induced coupling between different types of levels (ground state, bound Rydberg levels, and continuum) in the simulated electronic dynamics. Thus the origin of deviations between the predictions of the semi-classical three step model and the full simulation can be associated with particular physical contributions, which helps to explain both the successes and the limitations of the three step model. PMID- 24182019 TI - Kernels of the linear Boltzmann equation for spherical particles and rough hard sphere particles. AB - Kernels for the collision integral of the linear Boltzmann equation are presented for several cases. First, a rigorous and complete derivation of the velocity kernel for spherical particles is given, along with reductions to the smooth, rigid sphere case. This combines and extends various derivations for this kernel which have appeared previously in the literature. In addition, the analogous kernel is derived for the rough hard sphere model, for which a dependence upon both velocity and angular velocity is required. This model can account for exchange between translational and rotational degrees of freedom. Finally, an approximation to the exact rough hard sphere kernel is presented which averages over the rotational degrees of freedom in the system. This results in a kernel depending only upon velocities which retains a memory of the exchange with rotational states. This kernel tends towards the smooth hard sphere kernel in the limit when translational-rotational energy exchange is attenuated. Comparisons are made between the smooth and approximate rough hard sphere kernels, including their dependence upon velocity and their eigenvalues. PMID- 24182020 TI - Mechanisms in environmentally assisted one-photon phase control. AB - The ability of an environment to assist in one-photon phase control relies upon entanglement between the system and bath and on the breaking of the time reversal symmetry. Here, one-photon phase control is examined analytically and numerically in a model system, allowing an analysis of the relative strength of these contributions. Further, the significant role of non-Markovian dynamics and of moderate system-bath coupling in enhancing one-photon phase control is demonstrated, and an explicit role for quantum mechanics is noted in the existence of initial non-zero stationary coherences. Finally, desirable conditions are shown to be required to observe such environmentally assisted control, since the system will naturally equilibrate with its environment at longer times, ultimately resulting in the loss of phase control. PMID- 24182021 TI - Femtosecond two-photon photoassociation of hot magnesium atoms: a quantum dynamical study using thermal random phase wavefunctions. AB - Two-photon photoassociation of hot magnesium atoms by femtosecond laser pulses, creating electronically excited magnesium dimer molecules, is studied from first principles, combining ab initio quantum chemistry and molecular quantum dynamics. This theoretical framework allows for rationalizing the generation of molecular rovibrational coherence from thermally hot atoms [L. Rybak, S. Amaran, L. Levin, M. Tomza, R. Moszynski, R. Kosloff, C. P. Koch, and Z. Amitay, Phys. Rev. Lett. 107, 273001 (2011)]. Random phase thermal wavefunctions are employed to model the thermal ensemble of hot colliding atoms. Comparing two different choices of basis functions, random phase wavefunctions built from eigenstates are found to have the fastest convergence for the photoassociation yield. The interaction of the colliding atoms with a femtosecond laser pulse is modeled non-perturbatively to account for strong-field effects. PMID- 24182022 TI - High-precision and high-accuracy rovibrational spectroscopy of molecular ions. AB - We present a versatile new instrument capable of measuring rovibrational transition frequencies of molecular ions with sub-MHz accuracy and precision. A liquid-nitrogen cooled positive column discharge cell, which can produce large column densities of a wide variety of molecular ions, is probed with sub-Doppler spectroscopy enabled by a high-power optical parametric oscillator locked to a moderate finesse external cavity. Frequency modulation (heterodyne) spectroscopy is employed to reduce intensity fluctuations due to the cavity lock, and velocity modulation spectroscopy permits ion-neutral discrimination. The relatively narrow Lamb dips are precisely and accurately calibrated using an optical frequency comb. This method is completely general as it relies on the direct measurement of absorption or dispersion of rovibrational transitions. We expect that this new approach will open up many new possibilities: from providing new benchmarks for state-of-the-art ab initio calculations to supporting astronomical observations to helping assign congested spectra by combination differences. Herein, we describe the instrument in detail and demonstrate its performance by measuring ten R-branch transitions in the nu2 band of H3(+), two transitions in the nu1 band of HCO(+), and the first sub-Doppler transition of CH5(+). PMID- 24182023 TI - Stability of fluctuating and transient aggregates of amphiphilic solutes in aqueous binary mixtures: studies of dimethylsulfoxide, ethanol, and tert-butyl alcohol. AB - In aqueous binary mixtures, amphiphilic solutes such as dimethylsulfoxide (DMSO), ethanol, tert-butyl alcohol (TBA), etc., are known to form aggregates (or large clusters) at small to intermediate solute concentrations. These aggregates are transient in nature. Although the system remains homogeneous on macroscopic length and time scales, the microheterogeneous aggregation may profoundly affect the properties of the mixture in several distinct ways, particularly if the survival times of the aggregates are longer than density relaxation times of the binary liquid. Here we propose a theoretical scheme to quantify the lifetime and thus the stability of these microheterogeneous clusters, and apply the scheme to calculate the same for water-ethanol, water-DMSO, and water-TBA mixtures. We show that the lifetime of these clusters can range from less than a picosecond (ps) for ethanol clusters to few tens of ps for DMSO and TBA clusters. This helps explaining the absence of a strong composition dependent anomaly in water-ethanol mixtures but the presence of the same in water-DMSO and water-TBA mixtures. PMID- 24182024 TI - An integrated experimental and quantum-chemical investigation on the vibrational spectra of chlorofluoromethane. AB - The vibrational analysis of the gas-phase infrared spectra of chlorofluoromethane (CH2ClF, HCFC-31) was carried out in the range 200-6200 cm(-1). The assignment of the absorption features in terms of fundamental, overtone, combination, and hot bands was performed on the medium-resolution (up to 0.2 cm(-1)) Fourier transform infrared spectra. From the absorption cross section spectra accurate values of the integrated band intensities were derived and the global warming potential of this compound was estimated, thus obtaining values of 323, 83, and 42 on a 20-, 100-, and 500-year horizon, respectively. The set of spectroscopic parameters here presented provides the basic data to model the atmospheric behavior of this greenhouse gas. In addition, the obtained vibrational properties were used to benchmark the predictions of state-of-the-art quantum-chemical computational strategies. Extrapolated complete basis set limit values for the equilibrium geometry and harmonic force field were obtained at the coupled-cluster singles and doubles level of theory augmented by a perturbative treatment of triple excitations, CCSD(T), in conjunction with a hierarchical series of correlation consistent basis sets (cc-pVnZ, with n = T, Q, and 5), taking also into account the core-valence correlation effects and the corrections due to diffuse (aug) functions. To obtain the cubic and quartic semi-diagonal force constants, calculations employing second-order Moller-Plesset perturbation (MP2) theory, the double-hybrid density functional B2PLYP as well as CCSD(T) were performed. For all anharmonic force fields the performances of two different perturbative approaches in computing the vibrational energy levels (i.e., the generalized second order vibrational treatment, GVPT2, and the recently proposed hybrid degeneracy corrected model, HDCPT2) were evaluated and the obtained results allowed us to validate the spectroscopic predictions yielded by the HDCPT2 approach. The predictions of the deperturbed second-order perturbation approach, DVPT2, applied to the computation of infrared intensities beyond the double harmonic approximation were compared to the accurate experimental values here determined. Anharmonic DFT and MP2 corrections to CCSD(T) intensities led to a very good agreement with the absorption cross section measurements over the whole spectral range here analysed. PMID- 24182025 TI - Phonon-induced pure-dephasing of luminescence, multiple exciton generation, and fission in silicon clusters. AB - The size and temperature dependence of the pure-dephasing processes involved in luminescence, multiple exciton generation (MEG), and multiple exciton fission (MEF) are investigated for Sin clusters (n = 5-10, 15) using ab initio molecular dynamics and optical response function theory. The cluster bandgaps correlate with two types of binding energy, indicating that bandgaps can be used to characterize cluster stability. Ranging from 5 to 100 fs, the dephasing times are found to be longest for MEF and shortest for MEG, with luminescence falling in the middle range. Generally, the dephasing is fast, if the orbitals supporting the pair of states involved in the superpositions differ in energy, atomic localization, and number of nodes. The dephasing accelerates with temperature, because more phonon modes are activated, and lower frequency acoustic modes are able to explore the anhamonic part of the potential energy surface. The temperature dependence is stronger for larger clusters, since they possess a wider range of low-frequency anharmonic modes. Our research indicates that rapid dephasing in Si clusters favors generation of independent charge carriers from single and multiple excitons, making the clusters a promising material for photon energy conversion. The simulations of the dephasing processes reported in this work assist in understanding of the exciton evolution pathways in inorganic semiconductor clusters and other nanoscale materials. PMID- 24182026 TI - Photo excitation and laser detachment of C60(-) anions in a storage ring. AB - We have studied the photo physics of C60(-) anions in the electrostatic storage ring ELISA with ions produced in a plasma source and cooled and bunched in a He filled ion trap. A previous study using delayed electron detachment as a signal of resonance-enhanced multiphoton electron detachment (REMPED) has been repeated both at room temperature and with the trap cooled to liquid nitrogen temperature. However, wavelength dependence of the overlap of the strongly focused laser beam with the ion beam introduces distortions of the absorption spectrum. We have therefore applied a new method, combining the IR light with a slightly delayed, powerful UV pulse (266 nm). After absorption of three UV photons, the ions decay by delayed (thermal) electron emission, and time spectra are recorded for varying wavelength. The fraction of ions heated by absorption of a single IR photon is then extracted from a principal component analysis of these spectra. In good agreement with the earlier REMPED experiment, an origin band for transitions between the two lowest electronic levels of the anion, with t1u and t1g symmetry, is observed at 9380 cm(-1), with strong sidebands from excitation of the two A(g) and eight H(g) vibrations. As before, a hot band is observed at about 9150 cm(-1) and assigned to a transition from an excited vibronic Jahn-Teller state. However, an earlier observed band at higher energy, interpreted as a transition from this excited state to an excited vibronic state in the t1g electronic level, is much weaker in the new measurements and could be an H(g) vibrational sideband. Also earlier studies of direct laser detachment from C60(-) in the storage ring ASTRID have been revisited, with ions cooled by liquid nitrogen in the ion trap. We confirm the previous measurement with a determination of the threshold for s-wave detachment at 2.664 +/- 0.005 eV, slightly lower than a recent value of the electron binding, 2.683 +/- 0.008 eV, obtained from the energy spectrum of photo electrons. The detachment yield is observed to increase sharply for photon energies above a threshold at 2.78 eV, maybe caused by either Feshbach resonances or a shape resonance due to the presence of a bound electron state in the continuum. PMID- 24182027 TI - The stereodynamics of the Penning ionization of water by metastable neon atoms. AB - The stereodynamics of the Penning ionization of water molecules by collision with metastable neon atoms, occurring in the thermal energy range, is of great relevance for the understanding of fundamental aspects of the physical chemistry of water. This process has been studied by analyzing the energy spectrum of the emitted electrons previously obtained in our laboratory in a crossed beam experiment [B. G. Brunetti, P. Candori, D. Cappelletti, S. Falcinelli, F. Pirani, D. Stranges, and F. Vecchiocattivi, Chem. Phys. Lett. 539-540, 19 (2012)]. For the spectrum analysis, a novel semiclassical method is proposed, that assumes ionization events as mostly occurring in the vicinities of the collision turning points. The potential energy driving the system in the relevant configurations of the entrance and exit channels, used in the spectrum simulation, has been formulated by the use of a semiempirical method. The analysis puts clearly in evidence how different approaches of the metastable atom to the water molecule lead to ions in different electronic states. In particular, it provides the angular acceptance cones where the selectivity of the process leading to the specific formation of each one of the two energetically possible ionic product states of H2O(+) emerges. It is shown how the ground state ion is formed when neon metastable atoms approach water mainly perpendicularly to the molecular plane, while the first excited electronic state is formed when the approach occurs preferentially along the C2v axis, on the oxygen side. An explanation is proposed for the observed vibrational excitation of the product ions. PMID- 24182028 TI - Systematic theoretical studies of the interaction of 1,4-diazabicyclo [2.2.2]octane (DABCO) with rare gases. AB - We investigate the intermolecular 1,4-diazabicyclo [2.2.2] octane (DABCO) interaction potential with He, Ne, Ar, and Kr rare gases (Rg) by means of post Hartree-Fock and the newly implemented explicitly correlated coupled cluster approaches in connection with several basis sets. After benchmarking computations, we show that the inclusion of diffuse atomic orbitals is mandatory for the accurate description of structures, energetics, and spectroscopic properties of DABCO-Rg van der Waals clusters and that the (R)MP2/aug-cc-pVXZ (X = D, T) level is accurate enough for that purposes. For the neutral and ionic DABCO-Rg complexes, we characterized the low energy stationary points on the ground state potential. Most of the computed structures show a distortion along the low frequency mode of the van der Waals complex. Tunneling through this potential barrier leads to a splitting of the ground vibrational levels of several cm(-1). Our results served to reassign the available experimental spectra for DABCO(0,+1)-Ar and DABCO(0,+1)-Kr. PMID- 24182029 TI - Cross sections for the formation of H(n = 2) atom via superexcited states in photoexcitation of methane and ammonia. AB - The absolute cross sections for the formation of the H(2s) and H(2p) atoms, sigma2s and sigma2p, respectively, in photoexcitation of CH4 and NH3 were measured in the range of the incident photon energy 15-48 eV for studying superexcited states of the molecules. The same superexcited states were found to contribute to the sigma2s and sigma2p cross sections. It was concluded that the non-adiabatic transitions play a significant role during the dissociation of the superexcited states and ionic states. PMID- 24182031 TI - Three body dissociation of CS2(2+) subsequent to various S(2p) Auger transitions. AB - Fragmentation kinematics of CS2 following various S(2p) Auger transitions is studied. Employing a combination of electron energy analysis and recoil ion momentum spectroscopy, changes in the dissociation channel yields, as well as the differences in the kinematical parameters for various bands of Auger hole states are presented. The fragmentation mechanism for dissociative channels leading to complete atomization of CS2(2+) molecular ion is studied in detail. We find that CS2(2+) does not retain linear geometry and is bent before undergoing concerted break-up. It is also observed that different geometric configurations of the CS2(2+) precursor result in different kinetic energy release values. PMID- 24182030 TI - Structural transition of zinc oxide cluster cations: smallest tube like structure at (ZnO)6(+). AB - Zinc oxide cluster cations have been analyzed by ion mobility spectrometry using a home-made drift cell combined with a time-of-flight reflectron mass spectrometer. Structural changes from cyclic to tube like structures were observed around n = 8, corresponding to predictions by theoretical calculations. The structures were assigned by comparing with the arrival time simulation using MOBCAL software. We have also observed ion-injection energy dependence of the structures of (ZnO)n(+). The smallest tube structure of (ZnO)6(+) has predominantly been observed at an injection energy of 200 eV. The extraordinary stability of the compact structure at this size has been observed for the first time. PMID- 24182032 TI - The H + CO ? HCO reaction studied by ab initio benchmark calculations. AB - The title reaction has been calculated using complete active space self consistent field and internally contracted multi-reference configuration interaction, including Davidson correction, calculations. Dunning's correlation consistent atomic basis sets, together with several complete basis set extrapolation schemes, were employed. Core-valence and scalar relativistic effects were also taken into account, as well as anharmonicity of the vibrational modes. Core-valence correlation appears to have a large impact on the calculated frequencies, spectroscopic constants, and on the energetics. In particular, the best estimate for the HCO (DCO) formation barrier height at 0 K, 4.54 +/- 0.14 (4.43 +/- 0.14) kcal mol(-1) is larger than previous theoretical works and well above the usually accepted value of 2.0 +/- 0.4 kcal mol(-1), measured at room temperature. Inclusion of temperature and entropy at 298 K does not seem to be able to solve this discrepancy. The present theoretical barrier height is therefore the recommended value. The exo-ergicity of the HCO (DCO) dissociation reaction, predicted to be -13.36 +/- 0.57 (-14.72 +/- 0.57) kcal mol(-1), is slightly below the experimental value. Finally, all tested density functionals fail to reproduce accurately both the formation and dissociation barriers. PMID- 24182033 TI - Study of argon flowing afterglow with nitrogen injection. AB - In this work, the reaction kinetics in argon flowing afterglow with nitrogen addition was studied by optical emission spectroscopy. The DC flowing post discharge in pure argon was created in quartz tube at the total gas pressure of 1000 Pa and discharge power of 60 W. The nitrogen was added into the afterglow at the distance of 9 cm behind the active discharge. The optical emission spectra were measured along the flow tube. The argon spectral lines and after nitrogen addition also nitrogen second positive system (SPS) were identified in the spectra. The measurement of spatial dependence of SPS intensity showed a very slow decay of the intensity and the decay rate did not depend on the nitrogen concentration. In order to explain this behavior a kinetic model for reaction in afterglow was developed. This model showed that C (3)Piu state of molecular nitrogen, which is the upper state of SPS emission, is produced by excitation transfer from argon metastables to nitrogen molecules. However, the argon metastables are also produced at Ar2(+) ion recombination with electrons and this limits the decay of argon metastable concentration and it results in very slow decay of SPS intensity. PMID- 24182034 TI - A parallel tempering based study of Coulombic explosion and identification of dissociating fragments in charged noble gas clusters. AB - In this communication, we would like to test the feasibility of a parallel tempering based study of dissociation in dicationic noble gas clusters, namely, Ar(n)(2+), Kr(n)(2+), and Xe(n)(2+), where "n" is the size of the cluster units. We would like to find out the correct limit for sizes of each of these systems, above which the clusters stay intact as a single unit and does not dissociate into fragments by the process of Coulomb explosion. Moreover, we would also like to, for a specific case, i.e., Ar(n)(2+), study in detail the fragmentation patterns and point out the switchover from the non-fission way to the fission mechanism of dissociation. In all these calculations, we would like to analyse, how close we are in our predictions with that of experimental results. As a further check on the dissociating patterns found out by parallel tempering, we also conduct basin hopping based study on representative sizes of the clusters and find that parallel tempering, as used for this present work as an optimizer, is able to predict correct features when compared with other celebrated methods like the basin hopping algorithm. PMID- 24182035 TI - A diabatic parameterization of the twofold ground state potential energy surface of the H2O-OH molecular complex. AB - We present a matrix functional form to fit the nearly degenerated potential energy surface of the H2O-OH molecular complex. The functional form is based on second order perturbation theory, which allows us to define two diabatic states coupled together in the field of the surrounding water molecules. The fit reproduces faithfully the fine details of the potential energy surface (PES) like the crossings and the shallow barrier between the main and secondary minima. The explicit dependence of the model on polarization ensures its transferability to systems made of several water molecules. The potential is used to investigate the structural properties of the OH radical in solution by Monte Carlo simulation. The twin surface fit shows that the second PES is shifted above the ground state by typically 1600 cm(-1) for the configurations explored at a temperature of 300 K and a density of 1.0 g/cm(3). The second PES has thus little influence on the structuring of water around the OH radical at such a temperature and density. Our study confirms that under these thermodynamic conditions, OH is a weak hydrogen acceptor. PMID- 24182036 TI - Iminopropadienones RN=C=C=C=O and bisiminopropadienes RN=C=C=C=NR: matrix infrared spectra and anharmonic frequency calculations. AB - Methyliminopropadienone MeN=C=C=C=O 1a was generated by flash vacuum thermolysis from four different precursors and isolated in solid argon. The matrix-isolation infrared spectrum is dominated by unusually strong anharmonic effects resulting in complex fine structure of the absorptions due to the NCCCO moiety in the 2200 cm(-1) region. Doubling and tripling of the corresponding absorption bands are observed for phenyliminopropadienone PhN=C=C=C=O 1b and bis(phenylimino)propadiene PhN=C=C=C=NPh 9, respectively. Anharmonic vibrational frequency calculations allow the identification of a number of overtones and combination bands as the cause of the splittings for each molecule. This method constitutes an important tool for the characterization of reactive intermediates and unusual molecules by matrix-isolation infrared spectroscopy. PMID- 24182037 TI - Analytic Morse/long-range potential energy surfaces and predicted infrared spectra for CO-H2 dimer and frequency shifts of CO in (para-H2)N N = 1-20 clusters. AB - A five-dimensional ab initio potential energy surface (PES) for CO-H2 that explicitly incorporates dependence on the stretch coordinate of the CO monomer has been calculated. Analytic four-dimensional PESs are obtained by least-squares fitting vibrationally averaged interaction energies for vCO = 0 and 1 to the Morse/long-range potential function form. These fits to 30,206 points have root mean-square (RMS) deviations of 0.087 and 0.082 cm(-1), and require only 196 parameters. The resulting vibrationally averaged PESs provide good representations of the experimental infrared data: for infrared transitions of para H2-CO and ortho H2-CO, the RMS discrepancies are only 0.007 and 0.023 cm( 1), which are almost in the same accuracy as those values of 0.010 and 0.018 cm( 1) obtained from full six-dimensional ab initio PESs of V12 [P. Jankowski, A. R. W. McKellar, and K. Szalewicz, Science 336, 1147 (2012)]. The calculated infrared band origin shift associated with the fundamental of CO is -0.179 cm(-1) for para H2-CO, which is the same value as that extrapolated experimental value, and slightly better than the value of -0.176 cm(-1) obtained from V12 PESs. With these potentials, the path integral Monte Carlo algorithm and a first order perturbation theory estimate are used to simulate the CO vibrational band origin frequency shifts of CO in (para H2)N-CO clusters for N = 1-20. The predicted vibrational frequency shifts are in excellent agreement with available experimental observations. Comparisons are also made between these model potentials. PMID- 24182038 TI - Electromagnetically induced transparency and fluorescence in blockaded Rydberg atomic system. AB - We investigate the interaction between dark states and Rydberg excitation blockade by using electromagnetically induced transparency (EIT), fluorescence, and four-wave mixing (FWM) signals both theoretically and experimentally. By scanning the frequency detunings of the probe and dressing fields, respectively, we first observe these signals (three coexisting EIT windows, two fluorescence signals, and two FWM signals) under Rydberg excitation blockade. Next, frequency detuning dependences of these signals are obtained, in which the modulated results are well explained by introducing the dressing effects (leading to the dark states) with the corrected factor of the Rydberg excitation blockade. In addition, the variations by changing the principal quantum number n of Rydberg state shown some interesting phenomena resulting from Rydberg blockade are observed. The unique nature of such blockaded signals can have potential application in the demonstration of quantum computing. PMID- 24182039 TI - The effect of sulfur covalent bonding on the electronic shells of silver clusters. AB - The nature of the bonding in Ag(n)S(m)(0/-) clusters, n = 1-7; m = 1-4, has been analyzed to understand its effect on the electronic shell structure of silver clusters. First-principle investigations reveal that the sulfur atoms prefer 2 or 3-coordinate sites around a silver core, and that the addition of sulfur makes the planar structures compact. Molecular orbital analysis finds that the 3p orbitals of sulfur form a bonding orbital and two weakly bonding lone pairs with silver. We examine the electronic shell structures of Ag6Sm, which are two electrons deficient of a spherical closed electronic shell prior to the addition of sulfur, and Ag7S(m)(-) clusters that contain closed electronic shells prior to the addition of sulfur. The Ag6S4 cluster has a distorted octahedral silver core and an open shell with a multiplicity of 3, while the Ag7S(n_(-) clusters have compact geometries with enhanced stability, confirming that the clusters maintain their electronic shell structure after bonding with sulfur. PMID- 24182040 TI - Resonant photoemission at the iron M-edge of Fe(CO)5. AB - High resolution electron kinetic energy spectra of iron pentacarbonyl (Fe(CO)5) are studied in the photon energy range of 40-90 eV. The relative yield of photolines associated with the Fe 3d level shows a Fano line shape at photon energies of 61 eV. The increase in signal from the 3d level is indicative of resonant photoemission involving 3p-3d transitions at the M edge of iron. The signature of this resonance is also present in photolines typically attributed to be mostly CO in character. We use the modulation depth of the Fano resonances to reinterpret the photoelectron lines in the literature. PMID- 24182041 TI - New insights into designing metallacarborane based room temperature hydrogen storage media. AB - Metallacarboranes are promising towards realizing room temperature hydrogen storage media because of the presence of both transition metal and carbon atoms. In metallacarborane clusters, the transition metal adsorbs hydrogen molecules and carbon can link these clusters to form metal organic framework, which can serve as a complete storage medium. Using first principles density functional calculations, we chalk out the underlying principles of designing an efficient metallacarborane based hydrogen storage media. The storage capacity of hydrogen depends upon the number of available transition metal d-orbitals, number of carbons, and dopant atoms in the cluster. These factors control the amount of charge transfer from metal to the cluster, thereby affecting the number of adsorbed hydrogen molecules. This correlation between the charge transfer and storage capacity is general in nature, and can be applied to designing efficient hydrogen storage systems. Following this strategy, a search for the best metallacarborane was carried out in which Sc based monocarborane was found to be the most promising H2 sorbent material with a 9 wt.% of reversible storage at ambient pressure and temperature. PMID- 24182042 TI - CO dissociation on iron nanoparticles: size and geometry effects. AB - The reactivity of 0.5-1.4 nm iron nanoparticles and corresponding bulk surfaces has been systematically studied using density functional theory. The study includes both ideally symmetric and more realistic rugged nanoparticles. The activation energies for CO dissociation vary between 1.1 and 2.1 eV. An increasing particle size and roughness result in lower activation energies. For a single particle, variations as large as 0.9 eV occur indicating the importance of local particle morphology. Depending on the nanoparticle size, geometry, and CO dissociation pathway the reaction rates span five orders of magnitude at conditions relevant for gas-phase chemical vapor deposition synthesis of carbon nanotubes. Studies on the smallest particles and bulk surfaces show that these systems cannot be used as reliable models for catalysis on larger iron nanoparticles. It has also been demonstrated that predictive d-band and linear energy relationships cannot be used to explain the reactivity of iron for CO dissociation as reaction mechanisms vary from one particle to another. The changes in reaction mechanisms can be rationalized by the varying Fe-Fe bond lengths in different particles leading to changes in back-bonding between the iron surface and CO. CO dissociation on nano-sized iron seems to be more complex than that seen on more conventional non-magnetic noble metal particles. PMID- 24182044 TI - Dimensional dependence of the Stokes-Einstein relation and its violation. AB - We generalize to higher spatial dimensions the Stokes-Einstein relation (SER) as well as the leading correction to diffusivity in finite systems with periodic boundary conditions, and validate these results with numerical simulations. We then investigate the evolution of the high-density SER violation with dimension in simple hard sphere glass formers. The analysis suggests that this SER violation disappears around dimension d(u) = 8, above which it is not observed. The critical exponent associated with the violation appears to evolve linearly in 8 - d, below d = 8, as predicted by Biroli and Bouchaud [J. Phys.: Condens. Matter 19, 205101 (2007)], but the linear coefficient is not consistent with the prediction. The SER violation with d establishes a new benchmark for theory, and its complete description remains an open problem. PMID- 24182043 TI - Self-Consistent Ornstein-Zernike Approximation (SCOZA) and exact second virial coefficients and their relationship with critical temperature for colloidal or protein suspensions with short-ranged attractive interactions. AB - We focus on the second virial coefficient B2 of fluids with molecules interacting through hard-sphere potentials plus very short-ranged attractions, namely, with a range of attraction smaller than half hard-sphere diameter. This kind of interactions is found in colloidal or protein suspensions, while the interest in B2 stems from the relation between this quantity and some other properties of these fluid systems. Since the SCOZA (Self-Consistent Ornstein-Zernike Approximation) integral equation is known to yield accurate thermodynamic and structural predictions even near phase transitions and in the critical region, we investigate B2(SCOZA) and compare it with B2(exact), for some typical potential models. The aim of the paper is however twofold. First, by expanding in powers of density the condition of thermodynamic consistency included in the SCOZA integral equation, a general analytic expression for B2(SCOZA) is derived. For a given potential model, a comparison between B2(SCOZA) and B2(exact) may help to estimate the regimes where the SCOZA closure is reliable. Second, following the Vliegenthart-Lekkerkerker (VL) and Noro-Frenkel suggestions, the relationship between the critical B2 and the critical temperature Tc is discussed in detail for two prototype models: the square-well (SW) potential and the hard-sphere attractive Yukawa (HSY) one. The known simulation data for the SW model are revisited, while for the HSY model new SCOZA results have been generated. Although B2(HSY) at the critical temperature is found to be a slowly varying function of the range of Yukawa attraction DeltaY over a wide interval of DeltaY, it turns out to diverge as DeltaY vanishes. For fluids with very short-ranged attractions, such a behavior contrasts with the VL assumption that B2 at the critical temperature should be nearly independent of the range of attraction. A very simple analytic representation is found for the available Monte Carlo data for Tc(HSY) and B2(HSY) as functions of the range of attraction, for DeltaY smaller than half hard-sphere diameter. PMID- 24182045 TI - Stokes shift dynamics of ionic liquids: solute probe dependence, and effects of self-motion, dielectric relaxation frequency window, and collective intermolecular solvent modes. AB - In this paper we have used a semi-molecular theory for investigating the probe dependence of Stokes shift dynamics in room temperature ionic liquids (ILs) by considering three different but well-known dipolar solvation probes--coumarin 153, trans-4-dimethylamino-4(')-cyanostilbene, and 4-aminophthalimide. In addition, effects on polar solvation energy relaxation in ILs of solute motion, frequency coverage (frequency window) accessed by dielectric relaxation measurements and collective IL intermolecular modes (CIMs) at tera-hertz range have been explored. Eleven different ILs have been considered for the above theoretical study. Calculated results show better agreement with the recent (fluorescence up-conversion (FLUPS) + time-correlated single photon counting (TCSPC)) experimental results, particularly at short times, when the CIM contribution to the frequency dependent dielectric function (E(omega)) is included. This is done via assigning the missing dispersion in an experimental E(omega) to an IL intermolecular mode at 30 cm(-1). No significant probe dependence has been observed for solvation energy relaxation although the magnitude of dynamic Stokes shift varies with the dipole moment of the excited solute. Calculations using experimental E(omega) measured with broader frequency window generate solvation response functions closer to experiments. However, average solvation rates predicted by using different E(omega) for the same IL do not differ appreciably, implying over-all validity of these dielectric relaxation measurements. Results presented here indicate that inclusion of solvent molecularity via wavenumber dependent static correlations and ion dynamic structure factor relaxation improves significantly the comparison between theory and experiments over the continuum model predictions for polar solvation dynamics in these solvents. PMID- 24182046 TI - Dielectric relaxation of long-chain glass-forming monohydroxy alcohols. AB - The dielectric relaxation of two long-chain glass forming monohydroxy alcohols, 2 butyl-1-octanol and 2-hexyl-1-decanol, is studied at low temperature. Remarkable broadening from the pure Debye relaxation is identified for the slowest dynamics, differing from the dielectric spectra of short-chain alcohols. The broadening of the Debye-like relaxation in the two liquids develops as temperature increases, and the approaching of the Debye-like and structural relaxation widths is shown. Similar results are observed in the dielectric spectra of dilute 2-ethyl-1 hexanol in either 2-hexyl-1-decanol or squalane. The results of the liquids and mixtures reveal a correlation between the broadening and the Debye-like relaxation strength. Molecular associations in monohydroxy alcohols are discussed with the modification of the Debye relaxation. PMID- 24182047 TI - Common behavior of the critical properties of the 2D and 3D square-well fluids. AB - We have analyzed the behavior of the critical properties and second virial coefficient of the square well fluids in two (2D) and three dimensions (3D) as a function of the interaction range. In both systems, the critical density shows an oscillating-like behavior as the interaction range increases. The second virial coefficient evaluated at the critical temperature as a function of the interaction range shows a general behavior for both cases, and quite surprisingly, there is a minimum of this parameter, for the 2D and 3D fluids, located approximately at the same interaction range. These findings are discussed in terms of the structure of the fluids, via the analysis of the radial distribution function evaluated at the critical point. PMID- 24182048 TI - A quantum molecular dynamics study of aqueous solvation dynamics. AB - Ring polymer molecular dynamics experiments have been carried out to examine effects derived from nuclear quantum fluctuations at ambient conditions on equilibrium and non-equilibrium dynamical characteristics of charge solvation by a popular simple, rigid, water model, SPC/E , and for a more recent, and flexible, q-TIP4P/F model, to examine the generality of conclusions. In particular, we have recorded the relaxation of the solvent energy gap following instantaneous, +/-e charge jumps in an initially uncharged Lennard-Jones-like solute. In both charge cases, quantum effects are reflected in sharper decays at the initial stages of the relaxation, which produce up to a ~20% reduction in the characteristic timescales describing the solvation processes. For anionic solvation, the magnitude of polarization fluctuations controlling the extent of the water proton localization in the first solvation shell is somewhat more marked than for cations, bringing the quantum solvation process closer to the classical case. Effects on the solvation response from the explicit incorporation of flexibility in the water Hamiltonian are also examined. Predictions from linear response theories for the overall relaxation profile and for the corresponding characteristic timescales are reasonably accurate for the solvation of cations, whereas we find that they are much less satisfactory for the anionic case. PMID- 24182049 TI - Experimental inelastic neutron scattering spectrum of hydrogen hexagonal clathrate-hydrate compared with rigorous quantum simulations. AB - We have performed high-resolution inelastic neutron scattering (INS) measurements on binary hydrogen clathrate hydrates exhibiting the hexagonal structure (sH). Two samples, differing only in the ortho/para fraction of hydrogen, were prepared using heavy water and methyl tert-butyl ether as the promoter in its perdeuterated form. The INS spectrum of the translation-rotation (TR) excitations of the guest H2 molecule was obtained by subtracting the very weak signal due to the D2O lattice modes. By means of a subtraction procedure, it has been possible to obtain separately the spectra of caged p-H2 and o-H2. sH clathrates are comprised of three distinct types of cages, two of which, differing in shape and size, are each occupied by one H2 molecule only. Both contribute to the measured INS spectrum which is, therefore, rather complex and challenging to assign unambiguously. To assist with the interpretation, the INS spectra are calculated accurately utilizing the quantum methodology which incorporates the coupled five dimensional TR energy levels and wave functions of the H2 molecule confined in each type of nanocage. The computed INS spectra are highly realistic and reflect the complexity of the coupled TR dynamics of the guest H2 in the anisotropic confining environment. The simulated INS spectra of p-H2 and o-H2 in the small and medium cages are compared with the experimental data, and are indispensable for their interpretation. PMID- 24182050 TI - Facilitation and correlation of flow in metallic supercooled liquid. AB - Elucidation of the flow mechanism of the supercooled liquid near the glass transition temperature Tg is crucial for understanding the nature of glass transition. Dynamic facilitation between adjacent flow events in the supercooled liquid is believed to be crucial in the process of glass transition. In this work, it is shown that shear dilatation-based dynamic facilitation plays an important role in the supercooled liquid state of Zr58.5Cu15.6Al10.3Ni12.8Nb2.8, as revealed by the observed strain rate softening in the stress-strain curves above Tg = 684 K. Interestingly, along with strain rate softening, damped oscillations in the stress-strain curve emerge below 713 K, suggesting large scale correlation between flow events as temperature approaches Tg. Such oscillations are absent above 713 K although strain rate softening remains even at 733 K. Analysis indicates that facilitation and correlation are both crucial for the flow of metallic supercooled liquid approaching Tg. PMID- 24182051 TI - The liquid structure of tetrachloroethene: molecular dynamics simulations and reverse Monte Carlo modeling with interatomic potentials. AB - The liquid structure of tetrachloroethene has been investigated on the basis of measured neutron and X-ray scattering structure factors, applying molecular dynamics simulations and reverse Monte Carlo (RMC) modeling with flexible molecules and interatomic potentials. As no complete all-atom force field parameter set could be found for this planar molecule, the closest matching all atom Optimized Potentials for Liquid Simulations (OPLS-AA) intra-molecular parameter set was improved by equilibrium bond length and angle parameters coming from electron diffraction experiments [I. L. Karle and J. Karle, J. Chem. Phys. 20, 63 (1952)]. In addition, four different intra-molecular charge distribution sets were tried, so in total, eight different molecular dynamics simulations were performed. The best parameter set was selected by calculating the mean square difference between the calculated total structure factors and the corresponding experimental data. The best parameter set proved to be the one that uses the electron diffraction based intra-molecular parameters and the charges qC = 0.1 and qCl = -0.05. The structure was further successfully refined by applying RMC computer modeling with flexible molecules that were kept together by interatomic potentials. Correlation functions concerning the orientation of molecular axes and planes were also determined. They reveal that the molecules closest to each other exclusively prefer the parallel orientation of both the molecular axes and planes. Molecules forming the first maximum of the center-center distribution have a preference for <30 degrees and >60 degrees axis orientation and >60 degrees molecular plane arrangement. A second coordination sphere at ~11 A and a very small third one at ~16 A can be found as well, without preference for any axis or plane orientation. PMID- 24182052 TI - Excess protons in water-acetone mixtures. II. A conductivity study. AB - In the present work we complement a previous simulation study [R. Semino and D. Laria, J. Chem. Phys. 136, 194503 (2012)] on the disruption of the proton transfer mechanism in water by the addition of an aprotic solvent, such as acetone. We provide experimental measurements of the mobility of protons in aqueous-acetone mixtures in a wide composition range, for water molar fractions, xw, between 0.05 and 1.00. Furthermore, new molecular dynamics simulation results are presented for rich acetone mixtures, which provide further insight into the proton transport mechanism in water-non-protic solvent mixtures. The proton mobility was analyzed between xw 0.05 and 1.00 and compared to molecular dynamics simulation data. Results show two qualitative changes in the proton transport composition dependence at xw ~ 0.25 and 0.8. At xw < 0.25 the ratio of the infinite dilution molar conductivities of HCl and LiCl, Lambda(0)(HCl).Lambda(0)(LiCl)(-1), is approximately constant and equal to one, since the proton diffusion is vehicular and equal to that of Li(+). At xw ~ 0.25, proton mobility starts to differ from that of Li(+) indicating that above this concentration the Grotthuss transport mechanism starts to be possible. Molecular dynamics simulation results showed that at this threshold concentration the probability of interconversion between two Eigen structures starts to be non negligible. At xw ~ 0.8, the infinite molar conductivity of HCl concentration dependence qualitatively changes. This result is in excellent agreement with the analysis presented in the previous simulation work and it has been ascribed to the interchange of water and acetone molecules in the second solvation shell of the hydronium ion. PMID- 24182053 TI - Superstrong nature of covalently bonded glass-forming liquids at select compositions. AB - Variation of fragility (m) of specially homogenized Ge(x)Se(100-x) melts is established from complex specific heat measurements and shows that m(x) has a global minimum at an extremely low value (m = 14.8(0.5)) in the 21.5% < x < 23% range of Ge. Outside of that compositional range, m(x) then increases first rapidly and then slowly to about m = 25-30. By directly mapping melt stoichiometry as a function of reaction time at a fixed temperature T > Tg, we observe a slowdown of melt-homogenization by the super-strong melt compositions, 21.5% < x < 23%. This range furthermore appears to be correlated to the one observed between the flexible and stressed rigid phase in network glasses. These spectacular features underscore the crucial role played by topology and rigidity in the properties of network-forming liquids and glasses which are highlighted when fragility is represented as a function of variables tracking the effect of rigidity. Finally, we investigate the fragility-glass transition temperature relationship, and find that reported scaling laws do not apply in the flexible phase, while being valid for intermediate and stressed rigid compositions. PMID- 24182054 TI - Local vibrational properties of GaAs studied by extended X-ray absorption fine structure. AB - Extended X-ray absorption fine structure (EXAFS) has been measured at both the K edges of gallium and arsenic in GaAs, from 14 to 300 K, to investigate the local vibrational and thermodynamic behaviour in terms of bond expansion, parallel, and perpendicular mean square relative displacements and third cumulant. The separate analysis of the two edges allows a self-consistent check of the results and suggests that a residual influence of Ga EXAFS at the As edge cannot be excluded. The relation between bond expansion, lattice expansion, and expansion due to anharmonicity of the effective potential is quantitatively clarified. The comparison with previous EXAFS results on other crystals with the diamond or zincblende structure shows that the values of a number of parameters determined from EXAFS are clearly correlated with the fractional ionicity and with the strength and temperature interval of the lattice negative expansion. PMID- 24182055 TI - Molecular dynamics study of nanobubbles in the equilibrium Lennard-Jones fluid. AB - We employ a model, in which the density fluctuations in a bulk liquid are represented as presence of the clusters of molecules with the lowered number of nearest neighbors (number of bonds). The nanobubble size distribution is calculated on the basis of a close analogy between the surface part of the work of formation for a cluster and for a nanobubble. The pre-exponential factor for this distribution is related to the fluid compressibility. Estimates made for different liquids show that it can be noticeably different from that adopted in the classical nucleation theory (CNT). Molecular dynamics (MD) simulation is performed for a liquid inside a macroscopic droplet of molecules interacting via the Lennard-Jones potential plus a long-range tail. The nanobubbles are identified by clusters of bond-deficient particles with the optimum number of bonds that provide the maximum nanobubble number density and maximum resolvable nanobubble equimolar size. The results of MD simulation are in qualitatively better agreement with proposed theory than with CNT. PMID- 24182056 TI - Vibrational dynamics of a non-degenerate ultrafast rotor: the (C12,C13)-oxalate ion. AB - Molecular ions undergoing ultrafast conformational changes on the same time scale of water motions are of significant importance in condensed phase dynamics. However, the characterization of systems with fast molecular motions has proven to be both experimentally and theoretically challenging. Here, we report the vibrational dynamics of the non-degenerate (C12,C13)-oxalate anion, an ultrafast rotor, in aqueous solution. The infrared absorption spectrum of the (C12,C13) oxalate ion in solution reveals two vibrational transitions separated by approximately 40 cm(-1) in the 1500-1600 cm(-1) region. These two transitions are assigned to vibrational modes mainly localized in each of the carboxylate asymmetric stretch of the ion. Two-dimensional infrared spectra reveal the presence and growth of cross-peaks between these two transitions which are indicative of coupling and population transfer, respectively. A characteristic time of sub-picosecond cross-peaks growth is observed. Ultrafast pump-probe anisotropy studies reveal essentially the same characteristic time for the dipole reorientation. All the experimental data are well modeled in terms of a system undergoing ultrafast population transfer between localized states. Comparison of the experimental observations with simulations reveal a reasonable agreement, although a mechanism including only the fluctuations of the coupling caused by the changes in the dihedral angle of the rotor, is not sufficient to explain the observed ultrafast population transfer. PMID- 24182057 TI - Two-dimensional core-softened model with water like properties: Monte Carlo and integral equation study. AB - Monte Carlo simulations and integral equation theory were used to study the thermodynamics and structure of particles interacting through the smooth version of Stell-Hemmer interaction. We checked the possibility that a fluid with a core softened potential reproduces anomalies of liquid water such as the density anomaly, the minimum in the isothermal compressibility as a function of temperature, and others. Critical points of the fluid were also determined. We showed that a potential with two characteristic distances is sufficient for the system to exhibit water-like behavior and anomalies, including the famous density maximum. We also showed that some versions of the integral equation theory completely fail to predict structure of such system, while others only predict it qualitatively. PMID- 24182058 TI - Local order variations in confined hard-sphere fluids. AB - Pair distributions of fluids confined between two surfaces at close distance are of fundamental importance for a variety of physical, chemical, and biological phenomena, such as interactions between macromolecules in solution, surface forces, and diffusion in narrow pores. However, in contrast to bulk fluids, properties of inhomogeneous fluids are seldom studied at the pair-distribution level. Motivated by recent experimental advances in determining anisotropic structure factors of confined fluids, we analyze theoretically the underlying anisotropic pair distributions of the archetypical hard-sphere fluid confined between two parallel hard surfaces using first-principles statistical mechanics of inhomogeneous fluids. For this purpose, we introduce an experimentally accessible ensemble-averaged local density correlation function and study its behavior as a function of confining slit width. Upon increasing the distance between the confining surfaces, we observe an alternating sequence of strongly anisotropic versus more isotropic local order. The latter is due to packing frustration of the spherical particles. This observation highlights the importance of studying inhomogeneous fluids at the pair-distribution level. PMID- 24182059 TI - Mechanisms of H2O desorption from amorphous solid water by 157-nm irradiation: an experimental and theoretical study. AB - The photodesorption of water molecules from amorphous solid water (ASW) by 157-nm irradiation has been examined using resonance-enhanced multiphoton ionization. The rotational temperature has been determined, by comparison with simulations, to be 425 +/- 75 K. The time-of-flight spectrum of H2O (v = 0) has been fit with a Maxwell-Boltzmann distribution with a translational temperature of 700 +/- 200 K (0.12 +/- 0.03 eV). H(+) and OH(+) fragment ions have been detected with non resonant multiphoton ionization, indicating vibrationally excited parent water molecules with translational energies of 0.24 +/- 0.08 eV. The cross section for water removal from ASW by 7.9-eV photons near 100 K is (6.9 +/- 1.8) * 10(-20) cm(2) for >10 L H2O exposure. Electronic structure computations have also probed the excited states of water and the mechanisms of desorption. Calculated electron attachment and detachment densities show that exciton delocalization leads to a dipole reversal state in the first singlet excited state of a model system of hexagonal water ice. Ab Initio Molecular Dynamics simulations show possible desorption of a photo-excited water molecule from this cluster, though the non hydrogen bonded OH bond is stretched significantly before desorption. Potential energy curves of this OH stretch in the electronic excited state show a barrier to dissociation, lending credence to the dipole reversal mechanism. PMID- 24182060 TI - Strain effects on ensemble populations in AuPd/Pd(100) surface alloys. AB - The effects of applied strain on the arrangement of atoms in AuPd/Pd(100) surface alloys are studied using Monte Carlo simulations and cluster expansion Hamiltonians. The strain effects are found to be significant, with heteronuclear (Au-Pd) interactions more strongly enhanced by biaxial compression than homonuclear (Pd-Pd) ones. In particular, compressive strain causes an increase in the population of Pd monomers and second nearest-neighbor pairs of Pd monomers, both of which have been identified previously as important ensembles for various catalytic reactions. We also discuss the origin of these effects using density functional theory calculations of the surface electronic structure of strained AuPd/Pd(100). Our findings may suggest an additional means of employing strain to tune the catalytic properties of surface alloys. PMID- 24182061 TI - Shock response of single crystal and nanocrystalline pentaerythritol tetranitrate: Implications to hotspot formation in energetic materials. AB - We investigate shock response of single crystal and nanocrystalline pentaerythritol tetranitrate (PETN) with a coarse-grained model and molecular dynamics simulations, as regards mechanical hotspot formation in the absence or presence of grain boundaries (GBs). Single crystals with different orientations, and columnar nanocrystalline PETN with regular hexagonal, irregular hexagonal, and random GB patterns, are subjected to shock loading at different shock strengths. In single crystals, shock-induced plasticity is consistent with resolved shear stress calculations and the steric hindrance model, and this deformation leads to local heating. For regular-shaped hexagonal columnar nanocrystalline PETN, different misorientation angles lead to activation of different/same slip systems, different deformation in individual grains and as a whole, different GB friction, different temperature distributions, and then, different hotspot characteristics. Compared to their regular-shaped hexagonal counterpart, nanocrystalline PETN with irregular hexagonal GB pattern and that with random GBs, show deformation and hotspot features specific to their GBs. Driven by stress concentration, hotspot formation is directly related to GB friction and GB-initiated crystal plasticity, and the exact deformation is dictated by grain orientations and resolved shear stresses. GB friction alone can induce hotspots, but the hotspot temperature can be enhanced if it is coupled with GB-initiated crystal plasticity, and the slip of GB atoms has components out of the GB plane. The magnitude of shearing can correlate well with temperature, but the slip direction of GB atoms relative to GBs may play a critical role. Wave propagation through varying microstructure may also induce differences in stress states (e.g., stress concentrations) and loading rates, and thus, local temperature rise. GB-related friction and plasticity induce local heating or mechanical hotspots, which could be precursors to chemical hotspot formation related to initiation in energetic materials, in the absence of other, likely more effective, means for hotspot formation such as void collapse. PMID- 24182062 TI - A simple mechanism for emergent chirality in achiral hard particle assembly. AB - For centuries, chirality has been appreciated as a key component in understanding how matter orders. While intuitively chiral particles can self-assemble into chiral superstructures, it is often less obvious how achiral particles can do the same. Here we show that there is a potentially general, packing-based mechanism that explains why many simple, two-dimensional achiral particles assemble into chiral materials. Namely, we use simulations of hard, regular polygons to show that the subtle shape modification of corner rounding surprisingly can induce chiral symmetry breaking by deforming the underlying close-packed lattice. The mechanism quantitatively explains recent experimental results reporting chiral symmetry breaking in the hard triangle system. Moreover, it predicts similar symmetry breaking in the rounded hard rectangle system, which we verify through simulations. Because effective corner rounding is easily realized by modulating repulsive interactions in real systems, this simple mechanism suggests tremendous potential for creating dynamically tunable chiral surfaces with a variety of applications. PMID- 24182063 TI - Adsorption and reaction of acetylene on clean and oxygen-precovered Pd(100) studied with high-resolution X-ray photoelectron spectroscopy. AB - We investigated the adsorption and thermal evolution of acetylene on clean Pd(100) and Pd(100) precovered with 0.25 ML oxygen. The measurements were performed in situ by fast XPS at the synchrotron radiation facility BESSY II. On Pd(100) acetylene molecularly adsorbs at 130 K. Upon heating transformation to a CCH species occurs around 390 K along with the formation of a completely dehydrogenated carbon species. On the oxygen-precovered surface partial CCH formation already occurs upon adsorption at 130 K, and the dehydrogenation temperature and the stability range of CCH are shifted to lower temperatures by ~200 K. PMID- 24182064 TI - Hydrodynamic instability in the open system of the iodate-arsenous acid reaction. AB - Hydrodynamic instability arising in horizontally propagating vertical chemical fronts leading to the formation of a single stable convection roll is investigated experimentally in the iodate-arsenous acid reaction for various stoichiometry. In the presence of a free surface, the tilted reaction front becomes more elongated due to the evaporation of the surface active iodine and the decrease in the surface tension during the reaction. The experimental conditions are then identified where Marangoni instability represents the driving force for the distortion of the reaction front at the surface. PMID- 24182065 TI - Divalent pseudoatoms for modeling Si(100) surfaces. AB - An accurate first-principles treatment of complex systems, such as surfaces, continues to be a major challenge in computational chemistry. A popular approach to treat such systems is the use of cluster models, where a moderately sized model system is constructed by excising a cluster from the extended surface. This requires cutting chemical bonds, creating dangling bonds on the cluster boundary atoms that can introduce unphysical errors. Pseudobond, pseudoatom, and quantum capping potential approaches have been developed to treat such systems using a boundary "design-atom" subject to an appropriately fitted effective potential. However, previous approaches have been developed only for truncation of a single covalent bond. They may not be adequate for many important problems involving surface chemistry or materials chemistry, where multiple covalent bonds are severed between layers. In this paper, we have extended the pseudoatom formulation for divalent silicon, which can be employed to describe accurate Si(100) surface chemistry. The effective core potential parameters of our pseudoatom are obtained by fitting to geometrical parameters and atomic charges of molecules containing Si-Si and Si-O bonds, making our pseudoatom robust for applicability in different bonding environments. We calibrate the performance of our pseudoatom approach in small molecules and surface models, and also discuss its ability to describe heteroatomic bonds using multiple theoretical methods. PMID- 24182066 TI - MCTDH study on vibrational states of the CO/Cu(100) system. AB - Full (6D) and reduced (4D and 2D) dimensional multiconfiguration time-dependent Hartree (MCTDH) calculations for the vibrational fundamentals and overtones of the CO/Cu(100) system are carried out using the recently reported [R. Marquardt, F. Cuvelier, R. A. Olsen, E. J. Baerends, J. C. Tremblay, and P. Saalfrank, J. Chem. Phys. 132, 074108 (2010)] SAP potential energy surface (PES). To efficiently perform MCTDH calculations with the Heidelberg package (http://mctdh.uni-hd.de), the SAP-PES is first refitted in a sum-of-products form. Then extensive MCTDH calculations are carefully performed including thorough convergence checks to ensure the accuracy of our results. Full dimensional improved-relaxations and/or block-improved-relaxations are then performed to obtain vibrational ground and excited states of CO/Cu(100). In addition, we investigate the frustrated rotation (R mode) and vertical CO-Cu stretch (S mode), as well as C-O stretch, using a 4D Hamiltonian, which includes the distance between CO and the surface, z, bond length of CO, r, and orientation angles of CO, theta, and phi. The complement of this 4D Hamiltonian, a 2D Hamiltonian including only x and y coordinates, is used to alternatively calculate the states of frustrated translation (T mode). The comparison of reduced- with full-dimensional results show that the couplings between the R or S mode and the T mode do not influence the fundamentals and overtones of the R and S modes, however, do considerably influence those of the T mode. For the fundamental of the T mode, the 6D calculation yields an energy of 25.09 cm(-1), a value closer to the experimental result of 31.8 cm(-1) [A. P. Graham, F. Hofmann, J. P. Toennies, G. P. Williams, C. J. Hirschmugl, and J. Ellis, J. Chem. Phys. 108, 7825-7834 (1998)] than previously reported 19.6 cm(-1) [R. Marquardt, F. Cuvelier, R. A. Olsen, E. J. Baerends, J. C. Tremblay, and P. Saalfrank, J. Chem. Phys. 132, 074108 (2010)] although both investigations are based on the SAP-PES. On the other hand, the present calculations give similar results for the fundamentals of the S mode and C-O stretch to previous ones [R. Marquardt, F. Cuvelier, R. A. Olsen, E. J. Baerends, J. C. Tremblay, and P. Saalfrank, J. Chem. Phys. 132, 074108 (2010)]. Furthermore, for the lateral T and R modes, the present calculations give the same excitation pattern. Our calculations also show that the couplings between the R mode and surface are weaker than those between the T mode and surface. PMID- 24182067 TI - Polymerization of nitrogen in lithium azide. AB - Additional electrons can drastically change the bonding trend of light elements. For example, N atoms in alkali metal azides form the linear N3(-) anions instead of N2 molecules with the introduction of additional electrons. The effect of the additional electrons on the polymerization of N under pressure is important and thus far unclear. Using first principles density functional methods and the particle swarm optimization structure search algorithm, we systematically study the evolution of LiN3 structures under pressures up to 600 GPa. A stable structure featuring polymerized N under pressures higher than 375 GPa is identified for the first time. It consists of zig-zag N polymer chains that are formed by N5(-) five-member rings sharing N-N pairs. Throughout the stable pressure range, the structure is insulating and consists of N atoms in sp(3) hybridizations. Comparing with the atomic and electronic structures of previous phases, our study completes the structural evolution of LiN3 under pressure and reveals the structural changes which are accompanied and driven by the change of atomic orbital hybridization, first from sp to sp(2) and then from sp(2) to sp(3). PMID- 24182068 TI - Detailed atomistic simulation of the nano-sorption and nano-diffusivity of water, tyrosol, vanillic acid, and p-coumaric acid in single wall carbon nanotubes. AB - We report results from a detailed computer simulation study for the nano-sorption and mobility of four different small molecules (water, tyrosol, vanillic acid, and p-coumaric acid) inside smooth single-wall carbon nanotubes (SWCNTs). Most of the results have been obtained with the molecular dynamics (MD) method, but especially for the most narrow of the CNTs considered, the results for one of the molecules addressed here (water) were further confirmed through an additional Grand Canonical (MUVT) Monte Carlo (GCMC) simulation using a value for the water chemical potential MU pre-computed with the particle deletion method. Issues addressed include molecular packing and ordering inside the nanotube for the four molecules, average number of sorbed molecules per unit length of the tube, and mean residence time and effective axial diffusivities, all as a function of tube diameter and tube length. In all cases, a strong dependence of the results on tube diameter was observed, especially in the way the different molecules are packed and organized inside the CNT. For water for which predictions of properties such as local structure and packing were computed with both methods (MD and GCMC), the two sets of results were found to be fully self-consistent for all types of SWCNTs considered. Water diffusivity inside the CNT (although, strongly dependent on the CNT diameter) was computed with two different methods, both of which gave identical results. For large enough CNT diameters (larger than about 13 A), this was found to be higher than the corresponding experimental value in the bulk by about 55%. Surprisingly enough, for the rest of the molecules simulated (phenolic), the simulations revealed no signs of mobility inside nanotubes with a diameter smaller than the (20, 20) tube. This is attributed to strong phenyl-phenyl attractive interactions, also to favorable interactions of these molecules with the CNT walls, which cause them to form highly ordered, very stable structures inside the nanotube, especially under strong confinement. The interaction, in particular, of the methyl group (present in tyrosol, vanillic acid, and p-coumaric acid) with the CNT walls seems to play a key role in all these compounds causing them to remain practically immobile inside nanotubes characterized by diameters smaller than about 26 A. It is only for larger-diameter CNTs that tyrosol, vanillic acid, and p-coumaric acid were observed to demonstrate appreciable mobility. PMID- 24182069 TI - Modified energetics and growth kinetics on H-terminated GaAs (110). AB - Atomic hydrogen modification of the surface energy of GaAs (110) epilayers, grown at high temperatures from molecular beams of Ga and As4, has been investigated by friction force microscopy (FFM). The reduction of the friction force observed with longer exposures to the H beam has been correlated with the lowering of the surface energy originated by the progressive de-relaxation of the GaAs (110) surface occurring upon H chemisorption. Our results indicate that the H terminated GaAs (110) epilayers are more stable than the As-stabilized ones, with the minimum surface energy value of 31 meV/A(2) measured for the fully hydrogenated surface. A significant reduction of the Ga diffusion length on the H terminated surface irrespective of H coverage has been calculated from the FFM data, consistent with the layer-by-layer growth mode and the greater As incorporation coefficient determined from real-time reflection high-energy electron diffraction studies. Arsenic incorporation through direct dissociative chemisorption of single As4 molecules mediated by H on the GaAs (110) surface has been proposed as the most likely explanation for the changes in surface kinetics observed. PMID- 24182070 TI - Engineering the plasmonic optical properties of cubic silver nanostructures based on Fano resonance. AB - The plasmonic optical properties of nanostructures including a dimer, a linear chain, a T-shaped nanostructure, and a 2D array consisting of Ag nanocubes have been investigated using the discrete dipole approximation method. The simulation results indicate that both the interparticle gap and polarization have an important impact on far-field and near-field characteristics. With decreasing interparticle distance for four nanostructures, the plasmon resonance peak is monotonically red-shifted and the electric intensity enhancement factor increases rapidly due to increased interparticle coupling interaction. Moreover, we also find that a T-shaped nanostructure has the largest electric intensity enhancement factor compared with other three nanostructures due to the coupling interaction at the intersection. This coupling is caused by the radiative interference between subradiant and superradiant resulting in Fano resonance. These results show how nanostructure arrangement design, gap adjustment, and polarization control can be used to achieve high field enhancements. PMID- 24182071 TI - Cause of the fragile-to-strong transition observed in water confined in C-S-H gel. AB - In this study, the rotational dynamics of hydration water confined in calcium silicate-hydrate (C-S-H) gel with a water content of 22 wt.% was studied by broadband dielectric spectroscopy in broad temperature (110-300 K) and frequency (10(-1)-10(8) Hz) ranges. The C-S-H gel was used as a 3D confining system for investigating the possible existence of a fragile-to-strong transition for water around 220 K. Such transition was observed at 220 K in a previous study [Y. Zhang, M. Lagi, F. Ridi, E. Fratini, P. Baglioni, E. Mamontov and S. H. Chen, J. Phys.: Condens. Matter 20, 502101 (2008)] on a similar system, and it was there associated with a hidden critical point of bulk water. However, based on the experimental results presented here, there is no sign of a fragile-to-strong transition for water confined in C-S-H gel. Instead, the fragile-to-strong transition can be explained by a merging of two different relaxation processes at about 220 K. PMID- 24182072 TI - Immobilization of [60]fullerene on silicon surfaces through a calix[8]arene layer. AB - In this work, we report the functionalization of flat Si(100) surfaces with a calix[8]arene derivative through a thermal hydrosilylation process, followed by docking with [60]fullerene. Chemical grafting of calix[8]arene on silicon substrates was evaluated by X-ray photoelectron spectroscopy, whereas host-guest immobilization of fullerene was demonstrated by atomic force microscopy and sessile drop water contact angle measurements. Surface topographical variations, modelled on the basis of calix[8]arene and [60]fullerene geometrical parameters, are consistent with the observed morphological features relative to surface functionalization and to non-covalent immobilization of [60]fullerene. PMID- 24182073 TI - Distinction in binding of peptides (P2E) and its mutations (P2G, P2Q) to a graphene sheet via a hierarchical coarse-grained Monte Carlo simulation. AB - A hierarchical coarse-grained approach is used to study the binding of peptides (P2E: (1)E(2)P(3)L(4)Q(5)L(6)K(7)M) and variants (P2G: (1)G(2)P(3)L(4)Q(5)L(6)K(7)M and P2Q: (1)Q(2)L(3)P(4)M(5)E(6)K(7)L) with a graphene sheet. Simulation-based residue-substrate and hydropathy index-based residue-residue interaction is used as input to a phenomenological interaction potential for peptide chains to execute the stochastic motion with a graphene sheet at the center of a box. Large-scale Monte Carlo simulations are performed at a range (low to high) of temperatures to identify peptides binding with the graphene sheet with a constant peptide concentration (Cp = 0.01). A number of local (energy, mobility, and substrate contact profiles) and global (density profiles, mean square displacement of the center of mass of a peptide and its radius of gyration) physical quantities are examined to monitor the patterns. We find that each peptide can bind to a graphene sheet at low temperatures but the residues that can anchor their binding vary among these three peptides. For example, P2E is anchored by (1)E, (4)Q, and (6)K, P2Q by (1)Q, (5)E, and (6)K, and P2G by nearly all its residues with about the same strength except (1)G and (2)P. The site-specific binding is reflected in the thermal response of the radius of gyration of the peptides. Despite the lack of a large difference in binding patterns, a systematic variation in radius of gyration and surface binding profile with the temperature reveals the distinction in their binding: the probability of P2E binding is the highest and that of P2G is the lowest. PMID- 24182074 TI - Tension moderation and fluctuation spectrum in simulated lipid membranes under an applied electric potential. AB - We investigate the effect of an applied electric potential on the mechanics of a coarse grained POPC bilayer under tension. The size and duration of our simulations allow for a detailed and accurate study of the fluctuations. Effects on the fluctuation spectrum, tension, bending rigidity, and bilayer thickness are investigated in detail. In particular, the least square fitting technique is used to calculate the fluctuation spectra. The simulations confirm a recently proposed theory that the effect of an applied electric potential on the membrane will be moderated by the elastic properties of the membrane. In agreement with the theory, we find that the larger the initial tension the larger the effect of the electric potential. Application of the electric potential increases the amplitude of the long wavelength part of the spectrum and the bending rigidity is deduced from the short wavelength fluctuations. The effect of the applied electric potential on the bending rigidity is non-existent within error bars. However, when the membrane is stretched there is a point where the bending rigidity is lowered due to a decrease of the thickness of the membrane. All these effects should prove important for mechanosensitive channels and biomembrane mechanics in general. PMID- 24182075 TI - Fluctuation driven height reduction of crosslinked polymer brushes: a Monte Carlo study. AB - We study the changes in the conformations of brushes upon the addition of crosslinks between the chains using the bond fluctuation model. The Flory-Rehner model applied to uniaxially swollen networks predicts a collapse for large degrees of crosslinking q proportional to q(-1/3) in disagreement with our simulation data. We show that the height reduction of the brushes is driven by monomer fluctuations in a direction perpendicular to the grafting plane and not due to network elasticity. We observe that the impact of crosslinking is different for reactions between monomers of the same or on different chains. If the length reduction of the effective chain length due to both types of reactions is accounted for in a function beta(q), the height of the brush can be derived from a Flory approach for the equilibrium brush height leading to H(q) ~ Hbbeta(q)(1/3), whereby Hb denotes the height of the non-crosslinked brush. PMID- 24182076 TI - Large scale behavior of a two-dimensional model of anisotropic branched polymers. AB - We study critical properties of anisotropic branched polymers modeled by semi directed lattice animals on a triangular lattice. Using the exact transfer-matrix approach on strips of quite large widths and phenomenological renormalization group analysis, we obtained pretty good estimates of various critical exponents in the whole high-temperature region, including the point of collapse transition. Our numerical results suggest that this collapse transition belongs to the universality class of directed percolation. PMID- 24182077 TI - Anisotropic diffusion of concentrated hard-sphere colloids near a hard wall studied by evanescent wave dynamic light scattering. AB - Evanescent wave dynamic light scattering and Stokesian dynamics simulations were employed to study the dynamics of hard-sphere colloidal particles near a hard wall in concentrated suspensions. The evanescent wave averaged short-time diffusion coefficients were determined from experimental correlation functions over a range of scattering wave vectors and penetration depths. Stokesian dynamics simulations performed for similar conditions allow a direct comparison of both the short-time self- and collective diffusivity. As seen earlier [V. N. Michailidou, G. Petekidis, J. W. Swan, and J. F. Brady, Phys. Rev. Lett. 102, 068302 (2009)] while the near wall dynamics in the dilute regime slow down compared to the free bulk diffusion, the reduction is negligible at higher volume fractions due to an interplay between the particle-wall and particle-particle hydrodynamic interactions. Here, we provide a comprehensive comparison between experiments and simulations and discuss the interplay of particle-wall and particle-particle hydrodynamics in the self- and cooperative dynamics determined at different scattering wave vectors and penetration depths. PMID- 24182078 TI - The escape of a charged dendrimer from an oppositely charged planar surface. AB - Many of the envisioned applications of dendrimers revolve around placing these molecules at and removing them from charged interfaces. Herein, we provide a prescription for the conditions needed to release a charged dendrimer from an oppositely charged flat substrate. Identifying an effective segment step length that reflects the intramolecular repulsions due to excluded volume and electrostatics, as well as the dendrimer's branching, provides the essential concept leading to an analytical prediction for the boundary between captured and free molecules. We find that this effective step length obeys trends similar to those predicted for linear chains, but is modified by the dendrimer's connectivity. Moreover, the boundary predicted for the capture of linear chains holds for dendrimers once this effective step length is employed. Monte Carlo computer simulations of coarse-grained model dendrimers escaping from charged surfaces validate these findings. The simulations consider generations 2 through 6 with a range of lengths between the branch points, as well as a range of solution ionic strengths and surface charge densities. PMID- 24182079 TI - Treadmilling and length distributions of active polar filaments. AB - The cytoskeleton is a network of filamentous proteins, notably, actin filaments and microtubules. These filaments are active as their assembly is driven by the hydrolysis of nucleotides bound to the constituting protomers. In addition, the assembly kinetics differs at the two respective ends, making them active polar filaments. Experimental evidence suggests, that, in vivo, actin filaments and microtubules can grow at one and shrink at the other end at the same rate, a state that is known as treadmilling. In this work, we use a generic discrete two state model for active polar filaments to analyze the conditions leading to treadmilling. We find that a single filament can self-organize into the treadmilling state for a broad range of monomer concentrations. In this regime the corresponding length distribution has a pronounced maximum at a finite value. We then extend our description to consider specifically the dynamics of actin filaments. We show that actin treadmilling should be observable in vitro in the presence of appropriate depolymerization promoting factors. PMID- 24182080 TI - Interfacial exciplex formation in bilayers of conjugated polymers. AB - The donor-acceptor interactions in sequential bilayer and blend films are investigated. Steady-state and time-resolved photoluminescence (PL) were measured to characterize the samples at different geometries of photoluminescence collection. At standard excitation, with the laser incidence at 45 degrees of the normal direction of the sample surface, a band related to the aggregate states of donor molecules appears for both blend and bilayer at around 540 nm. For the PL spectra acquired from the edge of the bilayer, with the laser incidence made at normal direction of the sample surface (90 degrees geometry), a new featureless band emission, red-shifted from donor and acceptor emission regions was observed and assigned as the emission from interfacial exciplex states. The conformational complexity coming from donor/acceptor interactions at the heterojunction interface of the bilayer is at the origin of this interfacial exciplex emission. PMID- 24182081 TI - Dipolar Poisson-Boltzmann approach to ionic solutions: a mean field and loop expansion analysis. AB - We study the variation of the dielectric response of ionic aqueous solutions as function of their ionic strength. The effect of salt on the dielectric constant appears through the coupling between ions and dipolar water molecules. On a mean field level, we account for any internal charge distribution of particles. The dipolar degrees of freedom are added to the ionic ones and result in a generalization of the Poisson-Boltzmann (PB) equation called the Dipolar PB (DPB). By looking at the DPB equation around a fixed point-like ion, a closed form formula for the dielectric constant is obtained. We express the dielectric constant using the "hydration length" that characterizes the hydration shell of dipoles around ions, and thus the strength of the dielectric decrement. The DPB equation is then examined for three additional cases: mixture of solvents, polarizable medium, and ions of finite size. Employing field-theoretical methods, we expand the Gibbs free-energy to first order in a loop expansion and calculate self-consistently the dielectric constant. For pure water, the dipolar fluctuations represent an important correction to the mean-field value and good agreement with the water dielectric constant is obtained. For ionic solutions we predict analytically the dielectric decrement that depends on the ionic strength in a nonlinear way. Our prediction fits rather well a large range of concentrations for different salts using only one fit parameter related to the size of ions and dipoles. A linear dependence of the dielectric constant on the salt concentration is observed at low salinity, and a noticeable deviation from linearity can be seen for ionic strength above 1 M, in agreement with experiments. PMID- 24182082 TI - Statistical mechanics of DNA rupture: theory and simulations. AB - We study the effects of the shear force on the rupture mechanism on a double stranded DNA. Motivated by recent experiments, we perform the atomistic simulations with explicit solvent to obtain the distributions of extension in hydrogen and covalent bonds below the rupture force. We obtain a significant difference between the atomistic simulations and the existing results in the literature based on the coarse-grained models (theory and simulations). We discuss the possible reasons and improve the coarse-grained model by incorporating the consequences of semi-microscopic details of the nucleotides in its description. The distributions obtained by the modified model (simulations and theoretical) are qualitatively similar to the one obtained using atomistic simulations. PMID- 24182083 TI - Motional heterogeneity in human acetylcholinesterase revealed by a non-Gaussian model for elastic incoherent neutron scattering. AB - We study the dynamical transition of human acetylcholinesterase by analyzing elastic neutron scattering data with a simulation gauged analytical model that goes beyond the standard Gaussian approximation for the elastic incoherent structure factor [G. R. Kneller and K. Hinsen, J. Chem. Phys. 131, 045104 (2009)]. The model exploits the whole available momentum transfer range in the experimental data and yields not only a neutron-weighted average of the atomic mean square position fluctuations, but also an estimation for their distribution. Applied to the neutron scattering data from human acetylcholinesterase, it reveals a strong increase of the motional heterogeneity at the two transition temperatures T = 150 K and T = 220 K, respectively, which can be located with less ambiguity than with the Gaussian model. We find that the first transition is essentially characterized by a change in the form of the elastic scattering profile and the second by a homogeneous increase of all motional amplitudes. These results are in agreement with previous combined experimental and simulation studies of protein dynamics, which attribute the first transition to an onset of methyl rotations and the second to more unspecific diffusion processes involving large amplitude motions. PMID- 24182084 TI - The universality of beta-hairpin misfolding indicated by molecular dynamics simulations. AB - Previous molecular dynamics simulations showed that besides the experimentally measured folded structures, several beta-structured polypeptides could also have misfolded "out-of-register" structures. Through the enhanced sampling molecular dynamics simulations on a series of polypeptides using either implicit or explicit solvent model, the present study systematically investigated the universality of beta-hairpin misfolding and its determinants. It was observed that the misfolding could take place for almost all polypeptides under study, especially in the presence of weak side chain hydrophobicity. Moreover, the observed misfolded structures for various polypeptides share the following common features: (1) the turn length in misfolded structure is one-residue shorter than that in folded structure; (2) the hydrophobic side chains on the two strands are pointed to the opposite directions instead of packing in the same direction to form hydrophobic core cluster in the folded structure; and (3) the misfolded structure is one-residue-shifted asymmetric beta-hairpin structure. The detailed analysis suggested that the misfolding of beta-hairpin is the result of the competition between the formation of the alterable turn configurations and the inter-strand hydrophobic interactions. These predictions are desired to be tested by experiments. PMID- 24182085 TI - Exploring chemical reaction mechanisms through harmonic Fourier beads path optimization. AB - Here, we apply the harmonic Fourier beads (HFB) path optimization method to study chemical reactions involving covalent bond breaking and forming on quantum mechanical (QM) and hybrid QM/molecular mechanical (QM/MM) potential energy surfaces. To improve efficiency of the path optimization on such computationally demanding potentials, we combined HFB with conjugate gradient (CG) optimization. The combined CG-HFB method was used to study two biologically relevant reactions, namely, L- to D-alanine amino acid inversion and alcohol acylation by amides. The optimized paths revealed several unexpected reaction steps in the gas phase. For example, on the B3LYP/6-31G(d,p) potential, we found that alanine inversion proceeded via previously unknown intermediates, 2-iminopropane-1,1-diol and 3 amino-3-methyloxiran-2-ol. The CG-HFB method accurately located transition states, aiding in the interpretation of complex reaction mechanisms. Thus, on the B3LYP/6-31G(d,p) potential, the gas phase activation barriers for the inversion and acylation reactions were 50.5 and 39.9 kcal/mol, respectively. These barriers determine the spontaneous loss of amino acid chirality and cleavage of peptide bonds in proteins. We conclude that the combined CG-HFB method further advances QM and QM/MM studies of reaction mechanisms. PMID- 24182086 TI - Myths and verities in protein folding theories: from Frank and Evans iceberg conjecture to explanation of the hydrophobic effect. AB - Starting from the seminal article by Frank and Evans where the "iceberg formation" idea was first expressed, we follow the evolution of this idea to the explanation of the hydrophobic effect. We show that the idea of iceberg formation can provide an explanation to the entropy, and enthalpy of solvation of non-polar solutes in water, provided one first explains why a simple non-polar solute would form icebergs in the first place. Having done that, the questions regarding the outstanding large hydrophobic solvation Gibbs energy remains unexplained. This conclusion follows from the exact entropy-enthalpy-compensation pertaining to any structural changes induced in the solvent. We also comment on some misinterpretation of the partial molar heat capacity of non-polar solutes in water. PMID- 24182087 TI - Mechanism of ion permeation through a model channel: roles of energetic and entropic contributions. AB - Mechanism of ion permeation through an anion-doped carbon nanotube (ANT), a model of ion channel, is investigated. Using this model system, many trajectory calculations are performed to obtain the potential energy profile, in addition to the free energy profile, that enables to separate the energy and the entropic contributions, along the ion permeation. It is found that the mechanism of the transport is governed by the interplay between the energetic and the entropic forces. The rate of the ion permeation can be controlled by changing the balance between these contributions with altering, for example, the charge and/or the length of ANT, which increases the rate of the ion permeation by nearly two orders of magnitude. The dominant free energy barrier at the entrance of ANT is found to be caused by the entropy bottleneck due to the narrow phase space for the exchange of a water molecule and an incoming ion. PMID- 24182088 TI - Note: Vibrationally mediated photodissociation of carbon dioxide cation. AB - The photodissociation dynamics of carbon dioxide cation, CO2(+), mediated by its different A(2)Piu,1/2(upsilon1,upsilon2,0) vibronic states has been investigated by means of time-sliced velocity map imaging. Through analysis of the recorded translational energy release spectra of photofragment CO(+), we found that the photodissociation of CO2(+) exhibits drastic change in a rather narrow energy region. A conformational barrier in the CO2(+)(A(2)A1) state is suggested to be ~5600 cm(-1) relative to the CO2(+)(A(2)Piu,1/2(0,0,0)) state, in reasonable agreement with previous prediction. PMID- 24182089 TI - Note: Parameter-independent bounding of the stochastic Michaelis-Menten steady state intrinsic noise variance. AB - Using the (slow-scale) linear noise approximation, we give parameter-independent bounds to the substrate and product intrinsic noise variance for the stochastic Michaelis-Menten approximation at steady state. PMID- 24182090 TI - Comment on "Ab initio analytical infrared intensities for periodic systems through a coupled perturbed Hartree-Fock/Kohn-Sham method" [J. Chem. Phys. 137, 204113 (2012)]. PMID- 24182094 TI - Invited Article: Indenter materials for high temperature nanoindentation. AB - As nanoindentation at high temperatures becomes increasingly popular, a review of indenter materials for usage at high temperatures is instructive for identifying appropriate indenter-sample materials combinations to prevent indenter loss or failure due to chemical reactions or wear during indentation. This is an important consideration for nanoindentation as extremely small volumes of reacted indenter material will have a significant effect on measurements. The high temperature hardness, elastic modulus, thermal properties, and chemical reactivities of diamond, boron carbide, silicon carbide, tungsten carbide, cubic boron nitride, and sapphire are discussed. Diamond and boron carbide show the best elevated temperature hardness, while tungsten carbide demonstrates the lowest chemical reactivity with the widest array of elements. PMID- 24182095 TI - Instrumentation for laser physics and spectroscopy using 32-bit microcontrollers with an Android tablet interface. AB - Several high-performance lab instruments suitable for manual assembly have been developed using low-pin-count 32-bit microcontrollers that communicate with an Android tablet via a USB interface. A single Android tablet app accommodates multiple interface needs by uploading parameter lists and graphical data from the microcontrollers, which are themselves programmed with easily modified C code. The hardware design of the instruments emphasizes low chip counts and is highly modular, relying on small "daughter boards" for special functions such as USB power management, waveform generation, and phase-sensitive signal detection. In one example, a daughter board provides a complete waveform generator and direct digital synthesizer that fits on a 1.5 in. * 0.8 in. circuit card. PMID- 24182096 TI - Monochromatizing and focussing femtosecond high-order harmonic radiation with one optical element. AB - A novel approach for monochromatizing and focussing the Vacuum-Ultraviolet and soft x-ray radiation from high-order harmonic generation of a femtosecond optical laser with only one optical element is presented. We demonstrate that off-axis reflection zone plates applied as focussing monochromators allow for efficiently optimizing the trade-off between energy resolution and temporal dispersion of the femtosecond pulses. In the current experimental realization, we show how the temporal dispersion can be varied between 2 fs and 16 fs with a correlating variation of the energy resolution E/DeltaE between 20 and 90 for an off-axis reflection zone plate optimized for harmonic 13 at 20.41 eV. We also show how the focal spot size varies correspondingly between 80 * 90 MUm(2) and 290 * 140 MUm(2) as determined with a computational fitting approach based on a 3D Gaussian model. The diffraction efficiency for the tested zone plates amounts to up to 10%. We furthermore evaluate the influence of pointing stability on the performance of the zone plates. Based on our results we propose an optimized realization of a dedicated beam line for femtosecond pulses from high-order harmonic generation with an off-axis reflection zone plate. PMID- 24182097 TI - Visibility oscillation in a multimode laser interferometer signal and its use in optimizing path lengths. AB - The interference signal visibility V (difference to sum ratio of intensities at maximum and minimum interference) of an interferometer that uses a multimode laser is here derived for a given laser gain profile and spectral mode separation as a function of the difference Z(S) between the probe and reference beam optical path lengths and the spectral separation k(S) between the center of the laser gain profile and the nearest laser mode of higher frequency. k(S) has a significant effect on V for a given Z(S). This parameter, in lasers where it sweeps freely across the gain profile, and other effects, such as various misalignments and optical coupling inefficiencies, render V alone an unreliable parameter for quantifying Z(S) (for the purpose of reducing it, say). However, the difference to sum ratio of the maximum and minimum V due to variations in k(S) for a given Z(S) is an intrinsic property of the laser insensitive to configurational details. Parameter W so defined, therefore, proves very useful for balancing path lengths. This is of particular importance for systems where probe and/or reference beams are transmitted via long single mode optical fibers, so this application is detailed. Optical path lengths within such fibers often cannot be measured to sufficient accuracy by spatial path length measurements due to fiber nonuniformity resulting in variations in the mode's group velocity (needed to convert to optical path length). Two examples are provided using different makes and models of 0.633 MUm HeNe lasers with similar specifications. In the first case, the function W(Z(S)) is calculated directly from the laser's published gain profile and mode separation. In the second case, W is determined empirically for a range of Z(S)values for a laser with an unknown gain profile in a (heterodyned) interferometer whose interference signal oscillates between maximum and minimum intensity at 80 MHz due to the reference beam's optical frequency being acousto-optically upshifted by that amount, while k(S) spontaneously varies on an acoustic time scale. A single high-bandwidth waveform record for each Z(S), therefore, provides all the information needed to determine W. Despite the second laser's gain profile apparently differing in detail, qualitative agreement is achieved between the two methods sufficient to validate the technique. PMID- 24182099 TI - A study of pile-up in integrated time-correlated single photon counting systems. AB - Recent demonstration of highly integrated, solid-state, time-correlated single photon counting (TCSPC) systems in CMOS technology is set to provide significant increases in performance over existing bulky, expensive hardware. Arrays of single photon single photon avalanche diode (SPAD) detectors, timing channels, and signal processing can be integrated on a single silicon chip with a degree of parallelism and computational speed that is unattainable by discrete photomultiplier tube and photon counting card solutions. New multi-channel, multi detector TCSPC sensor architectures with greatly enhanced throughput due to minimal detector transit (dead) time or timing channel dead time are now feasible. In this paper, we study the potential for future integrated, solid state TCSPC sensors to exceed the photon pile-up limit through analytic formula and simulation. The results are validated using a 10% fill factor SPAD array and an 8-channel, 52 ps resolution time-to-digital conversion architecture with embedded lifetime estimation. It is demonstrated that pile-up insensitive acquisition is attainable at greater than 10 times the pulse repetition rate providing over 60 dB of extended dynamic range to the TCSPC technique. Our results predict future CMOS TCSPC sensors capable of live-cell transient observations in confocal scanning microscopy, improved resolution of near infrared optical tomography systems, and fluorescence lifetime activated cell sorting. PMID- 24182098 TI - Double momentum spectrometer for ion-electron vector correlations in dissociative photoionization. AB - We have developed a new momentum spectrometer dedicated to momentum vector correlations in the context of deep core photoionization of atomic and molecular species in the gas phase. In this article, we describe the design and operation of the experimental setup. The capabilities of the apparatus are illustrated with a set of measurements done on the sulphur core 1s photoionization of gas-phase CS2. PMID- 24182101 TI - A model of field and spherical aberration in soft/hard edge solenoid magnets. AB - A solenoid magnetic field model is presented that describes the on axis field by a parameter of its hard edginess and axial half-width at half-maximum field, which universally define its spherical aberration without solving the ray equation. The model shows an increase in spherical aberration from real soft edge fields to hard edge models, as used in beam tracking. It compares well with existing field models. It simply and accurately finds the spherical aberration in many types of solenoids. PMID- 24182100 TI - Diamond sensors and polycapillary lenses for X-ray absorption spectroscopy. AB - Diamond sensors are evaluated as incident beam monitors for X-ray absorption spectroscopy experiments. These single crystal devices pose a challenge for an energy-scanning experiment using hard X-rays due to the effect of diffraction from the crystalline sensor at energies which meet the Bragg condition. This problem is eliminated by combination with polycapillary lenses. The convergence angle of the beam exiting the lens is large compared to rocking curve widths of the diamond. A ray exiting one capillary from the lens meets the Bragg condition for any reflection at a different energy from the rays exiting adjacent capillaries. This serves to broaden each diffraction peak over a wide energy range, allowing linear measurement of incident intensity over the range of the energy scan. Extended X-ray absorption fine structure data are measured with a combination of a polycapillary lens and a diamond incident beam monitor. These data are of comparable quality to data measured without a lens and with an ionization chamber monitoring the incident beam intensity. PMID- 24182102 TI - Theoretical study of energy deposition in ionization chambers for tritium measurements. AB - Energy deposition in ionization chambers has been theoretically studied for tritium measurements in gaseous form. A one-dimension model is introduced to establish the quantitative relationship between energy deposition rate and many factors, including carrier gas, gas pressure, wall material, chamber size, and gas temperature. Energy deposition rate has been calculated at pressure varying from 5 kPa to 500 kPa based on some approximations. It is found that energy deposition rate varies greatly for different parameters, especially at low gas pressure. For the same chamber, energy deposition rate in argon is much higher than in deuterium, as much as 70.7% higher at 5 kPa. Gold plated chamber gives highest energy deposition rate in the calculations while aluminum chamber results in the lowest. As chamber size gets smaller, beta ray emitted by tritium will deposit less energy in the sensitive region of the chamber. For chambers flowing through with the same gas, energy deposition rate in a 10 L chamber is 23.9% higher than in a 0.05 L chamber at 5 kPa. Gas temperature also places slight influence on energy deposition rate, and 373 K will lead to 6.7% lower deposition rate than 233 K at 5 kPa. In addition, experiments have been performed to obtain energy deposition rate in a gold plated chamber, which show good accordance with theoretical calculations. PMID- 24182103 TI - Particle beam experiments for the analysis of reactive sputtering processes in metals and polymer surfaces. AB - A beam experiment is presented to study heterogeneous reactions relevant to plasma-surface interactions in reactive sputtering applications. Atom and ion sources are focused onto the sample to expose it to quantified beams of oxygen, nitrogen, hydrogen, noble gas ions, and metal vapor. The heterogeneous surface processes are monitored in situ by means of a quartz crystal microbalance and Fourier transform infrared spectroscopy. Two examples illustrate the capabilities of the particle beam setup: oxidation and nitriding of aluminum as a model of target poisoning during reactive magnetron sputtering, and plasma pre-treatment of polymers (PET, PP). PMID- 24182104 TI - Small plasma focus as neutron pulsed source for nuclides identification. AB - In this paper, we present preliminary results on the feasibility of employing a low energy (2 kJ, 31 kV) plasma focus device as a portable source of pulsed neutron beams (2.45 MeV) generated by nuclear fusion reactions D-D, for the "in situ" analysis of substances by nuclear activation. This source has the relevant advantage of being pulsed at requirement, transportable, not permanently radioactive, without radioactive waste, cheap, among others. We prove the feasibility of using this source showing several spectra of the characteristic emission line for manganese, gold, lead, and silver. PMID- 24182105 TI - Development of very small-diameter, inductively coupled magnetized plasma device. AB - In order to miniaturize a high-density, inductively coupled magnetized plasma or helicon plasma to be applied to, e.g., an industrial application and an electric propulsion field, small helicon device has been developed. The specifications of this device along with the experimental results are described. We have succeeded in generating high-density (~10(19) m(-3)) plasmas using quartz tubes with very small diameters of 10 and 20 mm, with a radio frequency power ~1200 and 700 W, respectively, in the presence of the magnetic field less than 1 kG. PMID- 24182106 TI - Chevron beam dump for ITER edge Thomson scattering system. AB - This paper contains the design of the beam dump for the ITER edge Thomson scattering system and mainly concerns its lifetime under the harsh thermal and electromagnetic loads as well as tight space allocation. The lifetime was estimated from the multi-pulse laser-induced damage threshold. In order to extend its lifetime, the structure of the beam dump was optimized. A number of bent sheets aligned parallel in the beam dump form a shape called a chevron which enables it to avoid the concentration of the incident laser pulse energy. The chevron beam dump is expected to withstand thermal loads due to nuclear heating, radiation from the plasma, and numerous incident laser pulses throughout the entire ITER project with a reasonable margin for the peak factor of the beam profile. Structural analysis was also carried out in case of electromagnetic loads during a disruption. Moreover, detailed issues for more accurate assessments of the beam dump's lifetime are clarified. Variation of the bi directional reflection distribution function (BRDF) due to erosion by or contamination of neutral particles derived from the plasma is one of the most critical issues that needs to be resolved. In this paper, the BRDF was assumed, and the total amount of stray light and the absorbed laser energy profile on the beam dump were evaluated. PMID- 24182107 TI - The coordinate transformation method for design of polarizers on HL-2A electron cyclotron resonance heating and current drive systems. AB - Polarizers are widely used to change the polarization of millimeter waves on the electron cyclotron resonance heating and current drive (ECRH and CD) systems. A new method based on the coordinate transformation and the Fourier expansion (the so-called C-method) has been developed for design of polarizers on the HL-2A ECRH and CD systems. This method transforms the grating problem to an eigenvalue problem, making it easy and clear to understand and solve. The comparison between the C-method, the integral method, and the low power test results is presented. It indicates that the C-method can be considered as a rigorous numerical method for the design of polarizers. Finally, two polarizers were designed based on the C-method which can be used together to achieve almost arbitrary polarization. PMID- 24182108 TI - Study of transmission line attenuation in broad band millimeter wave frequency range. AB - Broad band millimeter wave transmission lines are used in fusion plasma diagnostics such as electron cyclotron emission (ECE), electron cyclotron absorption, reflectometry and interferometry systems. In particular, the ECE diagnostic for ITER will require efficient transmission over an ultra wide band, 100 to 1000 GHz. A circular corrugated waveguide transmission line is a prospective candidate to transmit such wide band with low attenuation. To evaluate this system, experiments of transmission line attenuation were performed and compared with theoretical loss calculations. A millimeter wave Michelson interferometer and a liquid nitrogen black body source are used to perform all the experiments. Atmospheric water vapor lines and continuum absorption within this band are reported. Ohmic attenuation in corrugated waveguide is very low; however, there is Bragg scattering and higher order mode conversion that can cause significant attenuation in this transmission line. The attenuation due to miter bends, gaps, joints, and curvature are estimated. The measured attenuation of 15 m length with seven miter bends and eighteen joints is 1 dB at low frequency (300 GHz) and 10 dB at high frequency (900 GHz), respectively. PMID- 24182109 TI - Reduction of plasma density in the Helicity Injected Torus with Steady Inductance experiment by using a helicon pre-ionization source. AB - A helicon based pre-ionization source has been developed and installed on the Helicity Injected Torus with Steady Inductance (HIT-SI) spheromak. The source initiates plasma breakdown by injecting impurity-free, unmagnetized plasma into the HIT-SI confinement volume. Typical helium spheromaks have electron density reduced from (2-3) * 10(19) m(-3) to 1 * 10(19) m(-3). Deuterium spheromak formation is possible with density as low as 2 * 10(18) m(-3). The source also enables HIT-SI to be operated with only one helicity injector at injector frequencies above 14.5 kHz. A theory explaining the physical mechanism driving the reduction of breakdown density is presented. PMID- 24182110 TI - The enhanced ASDEX Upgrade pellet centrifuge launcher. AB - Pellets played an important role in the program of ASDEX Upgrade serving both for investigations on efficient particle fuelling and high density scenarios but also for pioneering work on Edge Localised Mode (ELM) pacing and mitigation. Initially designed for launching fuelling pellets from the magnetic low field side, the system was converted already some time ago to inject pellets from the magnetic high field side as much higher fuelling efficiency was found using this configuration. In operation for more than 20 years, the pellet launching system had to undergo a major revision and upgrading, in particular of its control system. Furthermore, the control system installed adjacent to the launcher had to be transferred to a more distant location enforcing a complete galvanic separation from torus potential and a fully remote control solution. Changing from a hybrid system consisting of PLC S5/S7 and some hard wired relay control to a state of the art PLC system allowed the introduction of several new operational options enabling more flexibility in the pellet experiments. This article describes the new system architecture of control hardware and software, the operating procedure, and the extended operational window. First successful applications for ELM pacing and triggering studies are presented as well as utilization for the development of high density scenarios. PMID- 24182111 TI - Response functions of imaging plates to photons, electrons and 4He particles. AB - Imaging plates from Fuji (BAS-SR, MS, and TR types) are phosphor films routinely used in ultra high intensity laser experiments. However, few data are available on the absolute IP response functions to ionizing particles. We have previously measured and modeled the IP response functions to protons. We focus here on the determination of the responses to photons, electrons, and (4)He particles. The response functions are obtained on an energy range going from a few tens of keV to a few tens of MeV and are compared to available data. The IP sensitivities to the different ionizing particles demonstrate a quenching effect depending on the particle stopping power. PMID- 24182112 TI - Microwave Doppler reflectometer system in the Experimental Advanced Superconducting Tokamak. AB - A Doppler reflectometer system has recently been installed in the Experimental Advanced Superconducting (EAST) Tokamak. It includes two separated systems, one for Q-band (33-50 GHz) and the other for V-band (50-75 GHz). The optical system consists of a flat mirror and a parabolic mirror which are optimized to improve the spectral resolution. A synthesizer is used as the source and a 20 MHz single band frequency modulator is used to get a differential frequency for heterodyne detection. Ray tracing simulations are used to calculate the scattering location and the perpendicular wave number. In EAST last experimental campaign, the Doppler shifted signals have been obtained and the radial profiles of the perpendicular propagation velocity during L-mode and H-mode are calculated. PMID- 24182113 TI - Diffracted X-ray tracking for monitoring intramolecular motion in individual protein molecules using broad band X-ray. AB - Diffracted X-ray tracking (DXT) enables the tilting and twisting motions of single protein molecules to be monitored with micro- to milliradian resolution using a highly brilliant X-ray source with a wide energy bandwidth. We have developed a technique to monitor single molecules using gold nanocrystals attached to individual protein molecules using the BL28B2 beamline at SPring-8. In this paper we present the installation of a single toroidal X-ray mirror at BL28B2 to focus X-rays in an energy range of 10-20 keV (DeltaE/E = 82% for an X ray with a wide energy bandwidth). With this beamline we tracked diffraction spots from gold nanocrystals over a wide angle range than that using quasi monochromatic X-rays. Application of the wide angle DXT technique to biological systems enabled us to observe the on-site motions of single protein molecules that have been functionalized in vivo. We further extend the capability of DXT by observing the fractional tilting and twisting motions of inner proteins under various conditions. As a proof of this methodology and to determine instrumental performance the intramolecular motions of a human serum albumin complex with 2 anthracenecarboxylic acid was investigated using the BL28B2 beamline. The random tilting and twisting intramolecular motions are shown to be directly linked to the movement of individual protein molecules in the buffer solution. PMID- 24182115 TI - Quantitative thermal microscopy using thermoelectric probe in passive mode. AB - A scanning thermal microscope working in passive mode using a micronic thermocouple probe is presented as a quantitative technique. We show that actual surface temperature distributions of microsystems are measurable under conditions for which most of usual techniques cannot operate. The quantitative aspect relies on the necessity of an appropriate calibration procedure which takes into account of the probe-to-sample thermal interaction prior to any measurement. Besides this consideration that should be treated for any thermal contact probing system, the main advantages of our thermal microscope deal with the temperature available range, the insensitivity to the surface optical parameters, the possibility to image DC, and AC temperature components up to 1 kHz typically and a resolution limit related to near-field behavior. PMID- 24182114 TI - Integrated imaging instrument for self-calibrated fluorescence protein microarrays. AB - Protein microarrays, or multiplexed and high-throughput assays, monitor multiple protein binding events to facilitate the understanding of disease progression and cell physiology. Fluorescence imaging is a popular method to detect proteins captured by immobilized probes with high sensitivity and specificity. Reliability of fluorescence assays depends on achieving minimal inter- and intra-assay probe immobilization variation, an ongoing challenge for protein microarrays. Therefore, it is desirable to establish a label-free method to quantify the probe density prior to target incubation to calibrate the fluorescence readout. Previously, a silicon oxide on silicon chip design was introduced to enhance the fluorescence signal and enable interferometric imaging to self-calibrate the signal with the immobilized probe density. In this paper, an integrated interferometric reflectance imaging sensor and wide-field fluorescence instrument is introduced for sensitive and calibrated microarray measurements. This platform is able to analyze a 2.5 mm * 3.4 mm area, or 200 spots (100 MUm diameter with 200 MUm pitch), in a single field-of-view. PMID- 24182116 TI - Precision platform for convex lens-induced confinement microscopy. AB - We present the conception, fabrication, and demonstration of a versatile, computer-controlled microscopy device which transforms a standard inverted fluorescence microscope into a precision single-molecule imaging station. The device uses the principle of convex lens-induced confinement [S. R. Leslie, A. P. Fields, and A. E. Cohen, Anal. Chem. 82, 6224 (2010)], which employs a tunable imaging chamber to enhance background rejection and extend diffusion-limited observation periods. Using nanopositioning stages, this device achieves repeatable and dynamic control over the geometry of the sample chamber on scales as small as the size of individual molecules, enabling regulation of their configurations and dynamics. Using microfluidics, this device enables serial insertion as well as sample recovery, facilitating temporally controlled, high throughput measurements of multiple reagents. We report on the simulation and experimental characterization of this tunable chamber geometry, and its influence upon the diffusion and conformations of DNA molecules over extended observation periods. This new microscopy platform has the potential to capture, probe, and influence the configurations of single molecules, with dramatically improved imaging conditions in comparison to existing technologies. These capabilities are of immediate interest to a wide range of research and industry sectors in biotechnology, biophysics, materials, and chemistry. PMID- 24182117 TI - Active drift stabilization in three dimensions via image cross-correlation. AB - By monitoring stage drift via the normalized cross-correlation of an image of a stuck bead, obtained in real-time, with an out-of-focus "template" image of a similar immobile bead, stored in memory, we implement a simple approach to actively stabilize drift in all three dimensions for existing video microscopy setups. We demonstrate stability to 0.0062 nm along the Z-axis and 0.0031 nm along the X- and Y-axes for long (100 s) timescales. PMID- 24182118 TI - SIMS instrumentation and methodology for mapping of co-localized molecules. AB - We describe an innovative mode for localizing surface molecules. In this methodology, individual C60 impacts at 50 keV are localized using an electron emission microscope, EEM, synchronized with a time-of-flight mass spectrometer for the detection of the concurrently emitted secondary ions. The instrumentation and methodologies for generating ion maps are presented. The performance of the localization scheme depends on the characteristics of the electron emission, those of the EEM and of the software solutions for image analysis. Using 50 keV C60 projectiles, analyte specific maps and maps of co-emitted species have been obtained. The individual impact sites were localized within 1-2 MUm. A distinctive feature of recording individual impacts is the ability to identify co emitted ions which originate from molecules co-located within ~10 nm. PMID- 24182119 TI - Growth rate measurements of lysozyme crystals under microgravity conditions by laser interferometry. AB - The growth rate vs. supersaturation of a lysozyme crystal was successfully measured in situ together with the crystal surface observation and the concentration measurements onboard the International Space Station. A Michelson type interferometer and a Mach-Zehnder interferometer were, respectively, employed for real-time growth rate measurements and concentration field measurements. The hardware development, sample preparation, operation, and analysis methods are described. PMID- 24182120 TI - Compact, single-tube scanning tunneling microscope with thermoelectric cooling. AB - We have designed and built a scanning tunneling microscope with a compact inertial-approach mechanism that fits inside the piezoelectric scanner tube. Rigid construction allows the microscope to be operated without the use of external vibration isolators or acoustic enclosures. Thermoelectric cooling and a water-ice bath are used to increase temperature stability when scanning under ambient conditions. PMID- 24182121 TI - Operation of astigmatic-detection atomic force microscopy in liquid environments. AB - The astigmatic detection system (ADS) based on commercial optical pickup head was demonstrated to achieve a sub-nanometer sensitivity in detecting the vertical movement of an object surface in air. The detection laser spot of the ADS was sub MUm and the detection bandwidth was over 80 MHz. These advantages allow detection of high-frequency mechanical resonance of very small objects, which would have many important applications in nanotechnology. In this work, we optimized the operation conditions of ADS to achieve good sensitivity in aqueous solutions. We demonstrated good contrast and good spatial resolution of cancer cells in water with the optical profilometry mode. We also built an ADS-AFM (atomic force microscopy) for imaging in water. A novel cantilever holder was designed, and the spurious peaks were suppressed down to 26.0% of the real resonance peak. Most importantly, we demonstrated that the ADS-AFM could resolve single atomic steps on a graphite substrate and image soft DNA molecules on mica in water. PMID- 24182122 TI - Femtosecond photoelectron point projection microscope. AB - By utilizing a nanometer ultrafast electron source in a point projection microscope we demonstrate that images of nanoparticles with spatial resolutions of the order of 100 nanometers can be obtained. The duration of the emission process of the photoemitted electrons used to make images is shown to be of the order of 100 fs using an autocorrelation technique. The compact geometry of this photoelectron point projection microscope does not preclude its use as a simple ultrafast electron microscope, and we use simple analytic models to estimate temporal resolutions that can be expected when using it as a pump-probe ultrafast electron microscope. These models show a significant increase in temporal resolution when comparing to ultrafast electron microscopes based on conventional designs. We also model the microscopes spectroscopic abilities to capture ultrafast phenomena such as the photon induced near field effect. PMID- 24182123 TI - Low-energy inverse photoemission spectroscopy using a high-resolution grating spectrometer in the near ultraviolet range. AB - An inverse photoemission spectroscopy (IPES) apparatus using a Czerny-Turner grating spectrometer is demonstrated. Previous IPES instruments based on grating spectrometers used a concave grating and operated in the vacuum ultraviolet range. The reflectance of such gratings is lower than 20% and the aberration cannot be finely corrected leading to an energy resolution of up to 0.1 eV. In the present study, employing the low energy IPES regime [H. Yoshida, Chem. Phys. Lett. 539-540, 180 (2012)], incident electrons with a kinetic energy below 5 eV are used, while photon emission in the range of between 250 and 370 nm is analyzed with a 10-cm Czerny-Turner grating spectrometer. The signal intensity is at least 30 times higher than the previous apparatus. The resolution of photon detection is set at 0.07 eV though the ultimate resolution is one order of magnitude higher. The experiment is performed both by sweeping the electron energy (isochromat mode) and by simultaneously analyzing the photon of whole wavelength range (tunable photon energy mode). PMID- 24182124 TI - Critical role of the sample preparation in experiments using piezoelectric actuators inducing uniaxial or biaxial strains. AB - We report on a systematic study of the stress transferred from an electromechanical piezo-stack into GaAs wafers under a wide variety of experimental conditions. We show that the strains in the semiconductor lattice, which were monitored in situ by means of X-ray diffraction, are strongly dependent on both the wafer thickness and on the selection of the glue which is used to bond the wafer to the piezoelectric actuator. We have identified an optimal set of parameters that reproducibly transfers the largest distortions at room temperature. We have studied strains produced not only by the frequently used uniaxial piezostressors but also by the biaxial ones which replicate the routinely performed experiments using substrate-induced strains but with the advantage of a continuously tunable lattice distortion. The time evolution of the strain response and the sample tilting and/or bending are also analyzed and discussed. PMID- 24182125 TI - Design and performance of an ultra-high vacuum scanning tunneling microscope operating at dilution refrigerator temperatures and high magnetic fields. AB - We describe the construction and performance of a scanning tunneling microscope capable of taking maps of the tunneling density of states with sub-atomic spatial resolution at dilution refrigerator temperatures and high (14 T) magnetic fields. The fully ultra-high vacuum system features visual access to a two-sample microscope stage at the end of a bottom-loading dilution refrigerator, which facilitates the transfer of in situ prepared tips and samples. The two-sample stage enables location of the best area of the sample under study and extends the experiment lifetime. The successful thermal anchoring of the microscope, described in detail, is confirmed through a base temperature reading of 20 mK, along with a measured electron temperature of 250 mK. Atomically resolved images, along with complementary vibration measurements, are presented to confirm the effectiveness of the vibration isolation scheme in this instrument. Finally, we demonstrate that the microscope is capable of the same level of performance as typical machines with more modest refrigeration by measuring spectroscopic maps at base temperature both at zero field and in an applied magnetic field. PMID- 24182126 TI - Effect of laser annealing of pressure gradients in a diamond-anvil cell using common solid pressure media. AB - Pressure media are one of the most effective deterrents of pressure gradients in diamond-anvil cell (DAC) experiments. The media, however, become less effective with increasing pressure, particularly for solid pressure media. One of the most popular ways of alleviating the increase in pressure gradients in DAC samples is through laser annealing of the sample. We explore the effectiveness of this technique for six common solid pressure media that include: alkali metal halides LiF, NaCl, KCl, CsCl, KBr, as well as amorphous SiO2. Pressure gradients are determined through the analysis of the first-order diamond Raman band across the sample before and after annealing the sample with a near-infrared laser to temperatures between ~2000 and 3000 K. As expected, we find that in the absence of sample chamber geometrical changes and diamond anvil damage, laser annealing reduces pressure gradients, albeit to varying amounts. We find that under ideal conditions, NaCl provides the best deterrent to pressure gradients before and after laser annealing, at least up to pressures of 60 GPa and temperatures between ~2000 and 3000 K. Amorphous SiO2, on the other hand, transforms in to harder crystalline stishovite upon laser annealing at high pressures resulting in increased pressure gradients upon further compression without laser annealing. PMID- 24182127 TI - A compact rotating dilution refrigerator. AB - We describe the design and performance of a new rotating dilution refrigerator that will primarily be used for investigating the dynamics of quantized vortices in superfluid (4)He. All equipment required to operate the refrigerator and perform experimental measurements is mounted on two synchronously driven, but mechanically decoupled, rotating carousels. The design allows for relative simplicity of operation and maintenance and occupies a minimal amount of space in the laboratory. Only two connections between the laboratory and rotating frames are required for the transmission of electrical power and helium gas recovery. Measurements on the stability of rotation show that rotation is smooth to around 10(-3) rad s(-1) up to angular velocities in excess of 2.5 rad s(-1). The behavior of a high-Q mechanical resonator during rapid changes in rotation has also been investigated. PMID- 24182128 TI - Numerical study of the effect of normalised window size, sampling frequency, and noise level on short time Fourier transform analysis. AB - Photonic Doppler velocimetry, also known as heterodyne velocimetry, is a widely used optical technique that requires the analysis of frequency modulated signals. This paper describes an investigation into the errors of short time Fourier transform analysis. The number of variables requiring investigation was reduced by means of an equivalence principle. Error predictions, as the number of cycles, samples per cycle, noise level, and window type were varied, are presented. The results were found to be in good agreement with analytical models. PMID- 24182129 TI - Volumetric apparatus for hydrogen adsorption and diffusion measurements: sources of systematic error and impact of their experimental resolutions. AB - The development of a volumetric apparatus (also known as a Sieverts' apparatus) for accurate and reliable hydrogen adsorption measurement is shown. The instrument minimizes the sources of systematic errors which are mainly due to inner volume calibration, stability and uniformity of the temperatures, precise evaluation of the skeletal volume of the measured samples, and thermodynamical properties of the gas species. A series of hardware and software solutions were designed and introduced in the apparatus, which we will indicate as f-PcT, in order to deal with these aspects. The results are represented in terms of an accurate evaluation of the equilibrium and dynamical characteristics of the molecular hydrogen adsorption on two well-known porous media. The contribution of each experimental solution to the error propagation of the adsorbed moles is assessed. The developed volumetric apparatus for gas storage capacity measurements allows an accurate evaluation over a 4 order-of-magnitude pressure range (from 1 kPa to 8 MPa) and in temperatures ranging between 77 K and 470 K. The acquired results are in good agreement with the values reported in the literature. PMID- 24182130 TI - Measuring the three-photon self-annihilation fraction of positronium in and above thin films: a tool for determining film morphology. AB - A technique is described for evaluating the fraction of positrons F incident on thin film samples which form ortho-positronium and subsequently decay into three gamma photons. The method involves the measurement of two linked phenomena: the decrease in the number of annihilation events involving the emission of two gamma photons with approximately 511 keV in the germanium detector photopeak, and the increase in the number of decays into three gamma photons with energies in the range 395-505 keV. After the application of a number of systematic corrections to the raw data, these measurements allow the determination of the absolute value of F without the need for calibration on a sample with known F values, thereby avoiding problems with changing samples of different geometries measured under different conditions. PMID- 24182131 TI - Fabrication and application of high impedance graded density impactors in light gas gun experiments. AB - Recent advances in Graded Density Impactor fabrication technique have increased the maximum achievable pressure in gas gun quasi-isentropic experiments to 5 Mbars. In this report, we outline the latest methodologies and applications of Graded Density Impactors in experiments at extreme conditions. These new Graded Density Impactors are essentially metallic discs made of nearly one hundred layers of precisely mixed Mg, Cu, and W. The density gradients in these impactors are specifically designed to generate the desired thermodynamic path required for each experiment. We carried out a number of experiments at various pressures using these Graded Density Impactors. These experimental results and their simulations will be presented here. PMID- 24182132 TI - A transparent Pyrex MU-reactor for combined in situ optical characterization and photocatalytic reactivity measurements. AB - A new Pyrex-based MU-reactor for photocatalytic and optical characterization experiments is presented. The reactor chamber and gas channels are microfabricated in a thin poly-silicon coated Pyrex chip that is sealed with a Pyrex lid by anodic bonding. The device is transparent to light in the UV-vis near infrared range of wavelengths (photon energies between ~0.4 and ~4.1 eV). The absorbance of a photocatalytic film obtained with a light transmission measurement during a photocatalytic reaction is presented as a proof of concept of a photocatalytic reactivity measurement combined with in situ optical characterization. Diffuse reflectance measurements of highly scattering photocatalytic nanopowders in a sealed Pyrex MU-reactor are also possible using an integrating sphere as shown in this work. These experiments prove that a photocatalyst can be characterized with optical techniques after a photocatalytic reaction without removing the material from the reactor. The catalyst deposited in the cylindrical reactor chamber can be illuminated from both top and bottom sides and an example of application of top and bottom illumination is presented. PMID- 24182133 TI - The electrically detected magnetic resonance microscope: combining conductive atomic force microscopy with electrically detected magnetic resonance. AB - We present the design and implementation of a scanning probe microscope, which combines electrically detected magnetic resonance (EDMR) and (photo-)conductive atomic force microscopy ((p)cAFM). The integration of a 3-loop 2-gap X-band microwave resonator into an AFM allows the use of conductive AFM tips as a movable contact for EDMR experiments. The optical readout of the AFM cantilever is based on an infrared laser to avoid disturbances of current measurements by absorption of straylight of the detection laser. Using amorphous silicon thin film samples with varying defect densities, the capability to detect a spatial EDMR contrast is demonstrated. Resonant current changes as low as 20 fA can be detected, allowing the method to realize a spin sensitivity of 8*10(6)spins/?Hz at room temperature. PMID- 24182134 TI - Novel recirculating loop reactor for studies on model catalysts: CO oxidation on Pt/TiO2(110). AB - A novel recirculating loop microreactor coupled to an ultrahigh vacuum (UHV) chamber has been constructed for the kinetic evaluation of model catalysts, which can be fully characterized by UHV surface science techniques. The challenge for this reactor design is to attain sufficient sensitivity to detect reactions on model single-crystal surfaces, which have a low number of active sites compared to conventional catalysts of equivalent mass. To this end, the total dead volume of the reactor system is minimized (32 cm(3)), and the system is operated in recirculation mode so that product concentrations build up to detectable levels over time. The injection of gas samples into the gas chromatography column and the refilling of the recirculation loop with fresh feed gas are achieved with computer-controlled, automated switching valves. In this manner, product concentrations can be followed over short time intervals (15 min) for extended periods of time (24 h). A proof of principle study in this reactor for CO oxidation at 145-165 degrees C on Pt clusters supported on a rutile TiO2(110) single crystal yields kinetic parameters that are comparable to those reported in the literature for CO oxidation on Pt clusters on powdered oxide supports, as well as on Pt(100). The calculated activation energy is 16.4 +/- 0.7 kcal/mol, the turnover frequency is 0.03-0.06 molecules/(site.s) over the entire temperature range, and the reaction orders in O2 and CO at 160 degrees C are 0.9 +/- 0.2 and -0.82 +/- 0.03, respectively. PMID- 24182135 TI - Evaluation of mechanical behavior of soft tissue by means of random laser emission. AB - We demonstrate the use of random laser emission for mechanical testing of bovine pericardium. An apparatus designed for tensile tests of soft and thin materials, incorporating optical and mechanical devices, allows for obtaining the mechanical behavior of the tissue samples. Using both, digital image correlation (DIC) and random laser emission analysis, the apparatus provides information regarding the response of the bovine pericardium under different stress levels. Our results show that changes in the spectral features of the random laser correlate well to the mechanical response obtained with conventional uniaxial tensile analysis coupled with DIC. Furthermore, parameters such as the shear and Young moduli are consistent with values reported previously and obtained with other techniques. Changes at the microstructural level of the tissue may thus be evaluated through spectral analysis of the random laser emission from biological samples. PMID- 24182136 TI - Data acquisition in a high-speed rotating frame for New Mexico Institute of Mining and Technology liquid sodium alphaomega dynamo experiment. AB - New Mexico Institute of Mining and Technology liquid sodium alphaomega-dynamo experiment models the magnetic field generation in the universe as discussed in detail by Colgate, Li, and Pariev [Phys. Plasmas 8, 2425 (2001)]. To obtain a quasi-laminar flow with magnetic Reynolds number R(m) ~ 120, the dynamo experiment consists of two co-axial cylinders of 30.5 cm and 61 cm in diameter spinning up to 70 Hz and 17.5 Hz, respectively. During the experiment, the temperature of the cylinders must be maintained to 110 degrees C to ensure that the sodium remains fluid. This presents a challenge to implement a data acquisition (DAQ) system in such high temperature, high-speed rotating frame, in which the sensors (including 18 Hall sensors, 5 pressure sensors, and 5 temperature sensors, etc.) are under the centrifugal acceleration up to 376g. In addition, the data must be transmitted and stored in a computer 100 ft away for safety. The analog signals are digitized, converted to serial signals by an analog-to-digital converter and a field-programmable gate array. Power is provided through brush/ring sets. The serial signals are sent through ring/shoe sets capacitively, then reshaped with cross-talk noises removed. A microcontroller-based interface circuit is used to decode the serial signals and communicate with the data acquisition computer. The DAQ accommodates pressure up to 1000 psi, temperature up to more than 130 degrees C, and magnetic field up to 1000 G. First physics results have been analyzed and published. The next stage of the alphaomega-dynamo experiment includes the DAQ system upgrade. PMID- 24182137 TI - A cylindrical electrical resistivity tomography array for three-dimensional monitoring of hydrate formation and dissociation. AB - The LArge Reservoir Simulator (LARS) was developed to investigate various processes during gas hydrate formation and dissociation under simulated in situ conditions of relatively high pressure and low temperature (close to natural conditions). To monitor the spatial hydrate distribution during hydrate formation and the mobility of the free gas phase generated during hydrate dissociation, a cylindrical Electrical Resistivity Tomography (ERT) array was implemented into LARS. The ERT contains 375 electrodes, arranged in 25 circular rings featuring 15 electrodes each. The electrodes were attached to a neoprene jacket surrounding the sediment sample. Circular (2D) dipole-dipole measurements are performed which can be extended with additional 3D cross measurements to provide supplemental data. The data quality is satisfactory, with the mean standard deviation due to permanent background noise and data scattering found to be in the order of 2.12%. The measured data are processed using the inversion software tool Boundless Electrical Resistivity Tomography to solve the inverse problem. Here, we use data recorded in LARS to demonstrate the data quality, sensitivity, and spatial resolution that can be obtained with this ERT array. PMID- 24182138 TI - Reproducing continuous radio blackout using glow discharge plasma. AB - A novel plasma generator is described that offers large-scale, continuous, non magnetized plasma with a 30-cm-diameter hollow structure, which provides a path for an electromagnetic wave. The plasma is excited by a low-pressure glow discharge, with varying electron densities ranging from 10(9) to 2.5 * 10(11) cm( 3). An electromagnetic wave propagation experiment reproduced a continuous radio blackout in UHF-, L-, and S-bands. The results are consistent with theoretical expectations. The proposed method is suitable in simulating a plasma sheath, and in researching communications, navigation, electromagnetic mitigations, and antenna compensation in plasma sheaths. PMID- 24182139 TI - Improvement of the accuracy of noise measurements by the two-amplifier correlation method. AB - We present a novel method for device noise measurement, based on a two-channel cross-correlation technique and a direct "in situ" measurement of the transimpedance of the device under test (DUT), which allows improved accuracy with respect to what is available in the literature, in particular when the DUT is a nonlinear device. Detailed analytical expressions for the total residual noise are derived, and an experimental investigation of the increased accuracy provided by the method is performed. PMID- 24182140 TI - Ultra-stable radio frequency dissemination in free space. AB - We demonstrate an ultra-stable radio frequency (RF) dissemination scheme over 80 m free space. The frequency dissemination stability is 3.2 * 10(-13)/s and 4.4 * 10(-17)/day, which can be applied to transfer frequency signal without compromising its stability in a global navigation satellite system (GNSS) or radio astronomy. PMID- 24182142 TI - Suppression of zero-crossing distortion for single-phase grid-connected photovoltaic inverters with unipolar modulation. AB - For single-phase grid-connected photovoltaic inverters, current-control with unipolar modulation can reduce the losses of power tubes and improve the efficiency compared with using the bipolar modulation. However, it suffers inherent zero-crossing distortion which is related to the grid current and voltage. In this paper, the reason for zero-crossing distortion is analyzed and simulated, also a novel current-control approach with commutating in advance is proposed to resolve this problem. This approach obtains a leading angle of the grid current by using the feedback of proportional-integral controller of the unipolar inverter, and then set the working mode of power tubes according to this angle through commutation. PMID- 24182141 TI - In-process measuring of the electrical shunt resistance of laser-scribed thin film stacks by nested circular scribes. AB - Laser scribing of functional thin-film stacks attracts increasing attention especially for applications of flexible electronics or photovoltaics. Laser can perform selective removal of the thin-film stacks that is essential for the isolation and interconnection of the solar cells. The optimization of the laser scribing process concerning the functional properties of the device requires customized characterization techniques minimizing side effects. The proposed and demonstrated nested circular laser scribing technique allows the in-process measurement of the electrical characteristics, e.g., the shunt formation due to laser scribing of the thin-film stack, minimizing secondary effects originating from aging, contacting, changing of sample characteristics, or alterations of the measurement conditions. This technique enables the identification of reliable and quick information on the changes of the solar cell characteristics by laser scribing as this is demonstrated in this work. PMID- 24182143 TI - Efficient continuous-duty Bitter-type electromagnets for cold atom experiments. AB - We present the design, construction, and characterization of Bitter-type electromagnets which can generate high magnetic fields under continuous operation with efficient heat removal for cold atom experiments. The electromagnets are constructed from a stack of alternating layers consisting of copper arcs and insulating polyester spacers. Efficient cooling of the copper is achieved via parallel rectangular water cooling channels between copper layers with low resistance to flow; a high ratio of the water-cooled surface area to the volume of copper ensures a short length scale (~1 mm) to extract dissipated heat. High copper fraction per layer ensures high magnetic field generated per unit energy dissipated. The ensemble is highly scalable and compressed to create a watertight seal without epoxy. From our measurements, a peak field of 770 G is generated 14 mm away from a single electromagnet with a current of 400 A and a total power dissipation of 1.6 kW. With cooling water flowing at 3.8 l/min, the coil temperature only increases by 7 degrees C under continuous operation. PMID- 24182144 TI - Modeling of stored charge in metallized biaxially oriented polypropylene film capacitors based on charging current measurement. AB - Metallized biaxially oriented polypropylene film (BOPP) capacitors are widely used in pulsed power systems. When the capacitor is used as the energy storage equipment under high electric field, more charges should be provided to maintain the voltage of the capacitor. This should be ascribed to the completion of the slow polarization which may take several hours or even longer. This paper focuses on the stored charge in metallized BOPP film capacitors. The modeling of the stored charge by the equivalent conversion of circuits is conducted to analyse the slow polarization in the BOPP film. The 3-RC network is proposed to represent the time-dependent charge stored in the capacitor. A charging current measurement system is established to investigate the charge storage property of the capacitor. The measurement system can measure the long time charging current with a sampling rate of 300 Hz. The total charge calculated by the charging current indicates that the stored charge in the capacitor under the electric field of 400 V/MUm is 13.5% larger than the product of the voltage and the capacitance measured by the AC bridge. The nonlinear effect of the electric field on the slow polarization charge is also demonstrated. And the simulation of charge storage based on the 3-RC network can match well with the trend of the stored charge increasing with the time. PMID- 24182145 TI - A comparative study of principal component analysis and independent component analysis in eddy current pulsed thermography data processing. AB - Eddy Current Pulsed Thermography (ECPT), an emerging Non-Destructive Testing and Evaluation technique, has been applied for a wide range of materials. The lateral heat diffusion leads to decreasing of temperature contrast between defect and defect-free area. To enhance the flaw contrast, different statistical methods, such as Principal Component Analysis and Independent Component Analysis, have been proposed for thermography image sequences processing in recent years. However, there is lack of direct and detailed independent comparisons in both algorithm implementations. The aim of this article is to compare the two methods and to determine the optimized technique for flaw contrast enhancement in ECPT data. Verification experiments are conducted on artificial and thermal fatigue nature crack detection. PMID- 24182146 TI - Determination of the spatial temperature distribution from combustion products: a diagnostic study. AB - Temperature measurements within the highly complex reaction field of energetic materials are complicated but existing technology enables point source measurements that identify a maximum temperature at a single location. This study presents a method to extend point source measurements to thermally map the spatial distribution of temperature over a large field of interest. The method couples point source temperature measurements from a multi-wavelength pyrometer with irradiance measurements from an infrared camera to produce a highly discretized thermal map that includes the reaction and surrounding field. This technique enables analysis of temperature gradients within the field of interest and an understanding of energy propagation beyond the point of reaction. Point source measurements of maximum temperature are within 10% of reported values. The method was illustrated for the aluminum and polytetrafluoroethylene reaction and the thermal distribution of temperature produced 30,720 temperature measurements over a field of interest corresponding to 3.5 cm * 8 cm. PMID- 24182147 TI - A method for thermal diffusivity measurement in fluids. AB - A technique is proposed for thermal diffusivity measurement in fluids. It is based on the Angstrom method, but with excitation of thermal waves by electromagnetic energy absorption and pyroelectric detection. The good agreement between measured thermal diffusivity of air and some test liquids with literature values shows the validity of the method. It is free of some limitations of conventional photopyroelectric technique with length scanning because it is free of moving parts inside the sample and because it avoids problems associated with the non-parallelism between thermal wave generator surface and sensor. It does not require any data normalization procedure or special sample preparation. PMID- 24182148 TI - Thermal property microscopy with frequency domain thermoreflectance. AB - A thermal property microscopy technique based on frequency domain thermoreflectance (FDTR) is presented. In FDTR, a periodically modulated laser locally heats a sample while a second probe beam monitors the surface reflectivity, which is related to the thermal properties of the sample with an analytical model. Here, we extend FDTR into an imaging technique capable of producing micrometer-scale maps of several thermophysical properties simultaneously. Thermal phase images are recorded at multiple frequencies chosen for maximum sensitivity to thermal properties of interest according to a thermal model of the sample. The phase versus frequency curves are then fit point-by point to obtain quantitative thermal property images of various combinations of thermal properties in multilayer samples, including the in-plane and cross-plane thermal conductivities, heat capacity, thermal interface conductance, and film thickness. An FDTR microscope based on two continuous-wave lasers is described, and a sensitivity analysis of the technique to different thermal properties is carried out. As a demonstration, we image ~3 nm of patterned titanium under 100 nm of gold on a silicon substrate, and simultaneously create maps of the thermal interface conductance and substrate thermal conductivity. Results confirm the potential of our technique for imaging and quantifying thermal properties of buried layers, indicating its utility for mapping thermal properties in integrated circuits. PMID- 24182149 TI - Optical absorptance measurement of an individual multiwall carbon nanotube using a T type thermal probe method. AB - Optical absorptance is an important property of carbon nanotubes for practical applications but has rarely been accurately measured. We developed a T type thermal probe method to measure the optical absorptance of an individual multiwall carbon nanotube. In this method, one end of the carbon nanotube (CNT) is attached to the center of a platinum nanofilm in a T shape and the Pt nanofilm acts as a thermometer. A laser beam irradiates at the CNT and the absorbed laser power can be determined by measuring the average temperature rise of the Pt nanofilm based on the temperature dependence of the electric resistance. Experimental results showed that a 100-nm-diameter multiwall CNT could absorb 13.2% of the 514-nm-wavelength laser power with the laser spot diameter being 1 MUm. This method is useful for determining the optical absorptance of CNTs and other one-dimensional nanostructures such as Si/Ge nanowires for various optical wavelengths in their photovoltaic, photoelectrolysis and other optical applications. PMID- 24182150 TI - High spatial resolution Raman thermometry analysis of TiO2 microparticles. AB - A new technique of high-resolution micro-Raman thermometry using anatase TiO2 microparticles (0.5-3 MUm) is presented. These very high spatial resolution measurements (280 nm) reveal temperature gradients even within individual microparticles. Potential applications of this technique are demonstrated by probing the temperature distribution of a micro-fabricated heater consisting of a thin silicon nitride (Si-N) membrane with a gold coil on top of the membrane. Using TiO2 microparticle micro-Raman thermometry, the temperature from the outer edge of the coil to the inner portion was measured to increase by ~40 degrees C. These high spatial resolution microscopic measurements were also used to measure the temperature gradient within the 20 MUm wide Si-N between the gold heating coils. 2D numerical simulations of the micro heater temperature distribution are in excellent agreement with the experimental measurements of the temperatures. These measurements illustrate the potential to extend applications of micro-Raman thermometry to obtain temperature details on a sub-micrometer spatial resolution by employing microparticles. PMID- 24182151 TI - Photoacoustic correlation signal-to-noise ratio enhancement by coherent averaging and optical waveform optimization. AB - Photoacoustic (PA) imaging of biological tissues using laser diodes instead of conventional Q-switched pulsed systems provides an attractive alternative for biomedical applications. However, the relatively low energy of laser diodes operating in the pulsed regime, results in generation of very weak acoustic waves, and low signal-to-noise ratio (SNR) of the detected signals. This problem can be addressed if optical excitation is modulated using custom waveforms and correlation processing is employed to increase SNR through signal compression. This work investigates the effect of the parameters of the modulation waveform on the resulting correlation signal and offers a practical means for optimizing PA signal detection. The advantage of coherent signal averaging is demonstrated using theoretical analysis and a numerical model of PA generation. It was shown that an additional 5-10 dB of SNR can be gained through waveform engineering by adjusting the parameters and profile of optical modulation waveforms. PMID- 24182152 TI - A two-axis in-plane motion measurement system based on optical beam deflection. AB - Measurement of in-plane motion with high resolution and large bandwidth enables model-identification and real-time control of motion-stages. This paper presents an optical beam deflection based system for measurement of in-plane motion of both macro- and micro-scale motion stages. A curved reflector is integrated with the motion stage to achieve sensitivity to in-plane translational motion along two axes. Under optimal settings, the measurement system is shown to theoretically achieve sub-angstrom measurement resolution over a bandwidth in excess of 1 kHz and negligible cross-sensitivity to linear motion. Subsequently, the proposed technique is experimentally demonstrated by measuring the in-plane motion of a piezo flexure stage and a scanning probe microcantilever. For the former case, reflective spherical balls of different radii are employed to measure the in-plane motion and the measured sensitivities are shown to agree with theoretical values, on average, to within 8.3%. For the latter case, a prototype polydimethylsiloxane micro-reflector is integrated with the microcantilever. The measured in-plane motion of the microcantilever probe is used to identify nonlinearities and the transient dynamics of the piezo-stage upon which the probe is mounted. These are subsequently compensated by means of feedback control. PMID- 24182153 TI - Measurement of optical coupling between adjacent bi-material microcantilevers. AB - Low thermal conductance bi-material microcantilevers are fabricated with a pad area near the free end to accommodate a focused laser spot. A pair of such cantilevers are proposed as a configuration for measuring thermal conductance of a nanostructure suspended between the two. We determine the resolution of such a device by measuring the stray conductance it would detect in the absence of any nanostructure. Stray conductance, primarily due to optical coupling, is measured for cantilevers with varying pad size and found to be as low as 0.05 nW K(-1), with cantilevers with larger pad size yielding the smallest stray conductance. PMID- 24182154 TI - Microfabricated suspended island platform for the measurement of in-plane thermal conductivity of thin films and nanostructured materials with consideration of contact resistance. AB - A technique based on suspended islands is described to measure the in-plane thermal conductivity of thin films and nano-structured materials, and is also employed for measurements of several samples with a single measurement platform. Using systematic steps for measurements, the characterization of the thermal resistances of a sample and its contacts are studied. The calibration of the contacts in this method is independent of the geometry, size, materials, and uniformity of contacts. To verify the technique, two different Si samples with different thicknesses and two samples of the same SiN(x) wafer are characterized on a single device. One of the Si samples is also characterized by another technique, which verifies the current results. Characterization of the two SiN(x) samples taken from the same wafer showed less than 1% difference in the measured thermal conductivities, indicating the precision of the method. Additionally, one of the SiN(x) samples is characterized and then demounted, remounted, and characterized for a second time. The comparison showed the change in the thermal resistance of the contact in multiple measurements could be as small as 0.2 K/MUW, if a similar sample is used. PMID- 24182155 TI - Energy harvesting from electric power lines employing the Halbach arrays. AB - This paper proposes non-invasive energy harvesters to scavenge alternating magnetic field energy from electric power lines. The core body of a non-invasive energy harvester is a linear Halbach array, which is mounted on the free end of a piezoelectric cantilever beam. The Halbach array augments the magnetic flux density on the side of the array where the power line is placed and significantly lowers the magnetic field on the other side. Consequently, the magnetic coupling strength is enhanced and more alternating magnetic field energy from the current carrying power line is converted into electrical energy. An analytical model is developed and the theoretical results verify the experimental results. A power of 566 MUW across a 196 kOmega resistor is generated from a single wire, and a power of 897 MUW across a 212 kOmega resistor is produced from a two-wire power cord carrying opposite currents at 10 A. The harvesters employing Halbach arrays for a single wire and a two-wire power cord, respectively, exhibit 3.9 and 3.2 times higher power densities than those of the harvesters employing conventional layouts of magnets. The proposed devices with strong response to the alternating currents are promising to be applied to electricity end-use environment in electric power systems. PMID- 24182156 TI - Graphene/polydimethylsiloxane nanocomposite strain sensor. AB - The objective of this research is to fabricate graphene nanopowder composites based on polydimethylsiloxane (PDMS) and to characterize the gauge factor of the graphene/PDMS composites for the use of strain sensors. The fabrication of graphene/PDMS composites can be accomplished by simple sonication and micro molding processes. We found that the measured gauge factors strongly depend on the concentration of graphene flakes in the composites. Obtained gauge factor of the graphene/PDMS composite strain sensor reached about 233 at a graphene concentration of 8.33 vol.%, which was measured within a strain range of 2%. PMID- 24182157 TI - Application of maximum likelihood methods to laser Thomson scattering measurements of low density plasmas. AB - Laser Thomson scattering (LTS) is an established plasma diagnostic technique that has seen recent application to low density plasmas. It is difficult to perform LTS measurements when the scattered signal is weak as a result of low electron number density, poor optical access to the plasma, or both. Photon counting methods are often implemented in order to perform measurements in these low signal conditions. However, photon counting measurements performed with photo multiplier tubes are time consuming and multi-photon arrivals are incorrectly recorded. In order to overcome these shortcomings a new data analysis method based on maximum likelihood estimation was developed. The key feature of this new data processing method is the inclusion of non-arrival events in determining the scattered Thomson signal. Maximum likelihood estimation and its application to Thomson scattering at low signal levels is presented and application of the new processing method to LTS measurements performed in the plume of a 2-kW Hall effect thruster is discussed. PMID- 24182158 TI - Cooling a low noise amplifier with a micromachined cryogenic cooler. AB - The sensitivity of antenna systems increases with increasing active area, but decreases at higher noise figure of the low-noise amplifier (LNA). Cooling the LNA locally results in significant improvement in the gain and in lowering the noise figure of the LNA. Micromachined Joule-Thomson (JT) coolers can provide a cryogenic environment to the LNA. They are attractive because they have no cold moving parts and can be scaled down to match the size and the power consumption of LNAs. The performance of a LNA mounted on a JT microcooler with dimensions of 60.0 * 9.5 * 0.72 mm(3) is reported in this paper. The microcooler is operated with nitrogen gas and the cold-end temperature is controlled at 115 K. The measured net cooling power of the microcooler is about 43 mW when the LNA is not operating. The power dissipation of the LNA is 26 mW, with a supply voltage of 2 V. At room temperature the noise figure of the LNA is 0.83 dB and the gain lies between 17.9 and 13.1 dB, in the frequency range of 0.65 and 1.05 GHz. Upon cooling to 115 K, the noise figure drops to 0.50 dB and the increase in gain varies in the range of 0.6-1.5 dB. PMID- 24182159 TI - Measurement system of the Seebeck coefficient or of the electrical resistivity at high temperature. AB - A high temperature Seebeck coefficient or electrical resistivity apparatus has been designed and fabricated to measure sample with typical size ~10 * 1 * 1 mm(3). It can measure both transport properties from 300 K to 1000 K in argon atmosphere. The sample lies transversely on top of two metallic half-cylinders, which contain heating cartridges and allow temperature and thermal gradient control and reversal. The temperature gradient is measured by two type N thermocouples pressed against the upper surface of the sample. The key feature of this apparatus is the disk-shaped junction of each type N thermocouple which strongly improves the thermal contact with the sample. The Seebeck coefficient is obtained by averaging over two measured values with opposite thermal gradient directions (~+/-2 K). For the resistivity measurements, the temperature is stabilized and the temperature gradient is actively reduced below 0.2 K to make negligible any spurious thermal voltage. Uncertainties of ~3% for the Seebeck coefficient and 1% for the resistivity were obtained on Ni samples. The Seebeck coefficient and resistivity have also been measured on a skutterudite sample as small as ~7 * 1.5 * 0.5 mm(3) with very good agreement with literature. PMID- 24182160 TI - Instrument performance study on the short and long pulse options of the second Spallation Neutron Source target station. AB - The Spallation Neutron Source (SNS) facility at the Oak Ridge National Laboratory is designed with an upgrade option for a future low repetition rate, long wavelength second target station. This second target station is intended to complement the scientific capabilities of the 1.4 MW, 60 Hz high power first target station. Two upgrade possibilities have been considered, the short and the long pulse options. In the short pulse mode, proton extraction occurs after the pulse compression in the accumulator ring. The proton pulse structure is thus the same as that for the first target station with a pulse width of ~0.7 MUs. In the long pulse mode, protons are extracted as they are produced by the linac, with no compression in the accumulator ring. The time width of the uncompressed proton pulse is ~1 ms. This difference in proton pulse structure means that neutron pulses will also be different. Neutron scattering instruments thus have to be designed and optimized very differently for these two source options which will directly impact the overall scientific capabilities of the SNS facility. In order to assess the merits of the short and long pulse target stations, we investigated a representative suit of neutron scattering instruments and evaluated their performance under each option. Our results indicate that the short pulse option will offer significantly better performance for the instruments and is the preferred choice for the SNS facility. PMID- 24182161 TI - Generating diffuse discharge via repetitive nanosecond pulses and line-line electrodes in atmospheric air. AB - Diffuse discharge in atmospheric air can generate extremely high power density and large-scale non-thermal plasma. An achievable method of generating diffuse discharge is reported in this paper. Based on the resonance theory, a compact high-voltage repetitive nanosecond pulse generator (HRNPG) has been developed as discharge excitation source. The HRNPG mainly consists of repetitive charging circuit, Tesla transformer and sharpening switch. With the voltage lower than 1.0 kV, the primary repetitive charging circuit comprises two fast thyristors as low voltage switches. A spiral Tesla transformer is designed to provide a peak transformation ratio of more than 100. The HRNPG prototype is capable of generating a pulse with over 100 kV peak voltage and ~30 ns rise-time at the repetition frequency of 500 Hz. Using the copper line electrodes with a diameter of 0.4 mm, the gaps with highly non-uniform electric field are structured. With the suitable gap spacing and applied pulse, the glow-like diffuse discharge has been generated in line-type and ring-type electrode pairs. Some typical images are presented. PMID- 24182162 TI - Continuous critical current measurement of high-temperature superconductor tapes with magnetic substrates using magnetic-circuit method. AB - The critical current (I(c)) of high-temperature superconductor (HTS) tapes has to be examined not only for short samples, but also for the entire tape, because local weak points can possibly lead to the quenching of the whole HTS device. Some methods were reported for continuous I(c) measurement along the length of a HTS tape, but few of them were applicable to tapes with magnetic substrates represented by YBa2Cu3O(7-delta)(YBCO)-coated conductors based on Ni5W alloy substrate by rolling assisted bi-axially textured substrate process. We previously presented a contact-free method using magnetic circuits to measure I(c) continuously of long HTS tapes, namely the magnetic-circuit (MC) method. This method has been previously applied with high speed and resolution to measure I(c) of HTS tapes with non-magnetic substrates, due to its resistance to noise aroused by mechanical vibration. In this work, its ability to measure HTS tapes with magnetic substrates is demonstrated both theoretically and experimentally. A 100 m long commercial YBCO tape based on Ni5W alloy substrate was measured and regular I(c) fluctuations were discovered. The MC method can be a powerful tool for quality control of HTS tapes, especially for tapes with magnetic substrates. PMID- 24182163 TI - Optical fiber-based force transducer for microscale samples. AB - We discuss the design, instrumentation, and calibration of a versatile force transducer with feedback control, called the Micro-Extensional Rheometer (MER). A force range of eight decades (1-10(8) pN) and a displacement range of four decades (10-10(5) nm) with a spatial resolution of the order of nanometers are accessible with the instrument. A feedback-loop algorithm is used to control the commanded force or the extensional strain on the sample and implement different rheometric protocols such as step-strain, step-force, exponential strain, among others. The device may also be used to measure the forces exerted by active suspensions, pulling neurons, etc. PMID- 24182164 TI - Automated modular high energy evaluation system for experimental thyristor devices. AB - A high energy, modular, completely automated test bed with integrated data acquisition and characterization systems was successfully designed in order to perform both safe operating area as well as very high volume reliability testing on experimental silicon carbide Super Gate Turn Off (SGTO) thyristors. Although the system follows a modular design philosophy, with each functional block acting as a peripheral to a main control module and can be adapted to arbitrary power and pulse width levels, for the specific SGTO devices initially evaluated it was configured to have the device discharge variable current levels of up to 6 kA into a 0.5 Omega resistive load with a relatively square pulse fixed at 100 MUs full width at half maximum delivering energy levels up to 1.8 kJ to the load. PMID- 24182165 TI - Response in electrostatic analyzers due to backscattered electrons: case study analysis with the Juno Jovian Auroral Distribution Experiment-Electron instrument. AB - In this study, we introduce a model to characterize electron scattering in an electrostatic analyzer. We show that electrons between 0.5 and 30 keV scatter from internal surfaces to produce a response up to ~20% of the ideal, unscattered response. We compare our model results to laboratory data from the Jovian Auroral Distribution Experiment-Electron sensor onboard the NASA Juno mission. Our model reproduces the measured energy-angle response of the instrument well. Understanding and quantifying this scattering process is beneficial to the analysis of scientific data as well as future instrument optimization. PMID- 24182166 TI - Unsteady pressure-sensitive paint measurement based on the heterodyne method using low frame rate camera. AB - The pressure-sensitive paint technique based on the heterodyne method was proposed for the precise pressure measurement of unsteady flow fields. This measurement is realized by detecting the beat signal that results from interference between a modulating illumination light source and a pressure fluctuation. The beat signal is captured by a camera with a considerably lower frame rate than the frequency of the pressure fluctuation. By carefully adjusting the frequency of the light and the camera frame rate, the signal at the frequency of interest is detected, while the noise signals at other frequencies are eliminated. To demonstrate the proposed method, we measured the pressure fluctuations in a resonance tube at the fundamental, second, and third harmonics. The pressure fluctuation distributions were successfully obtained and were consistent with measurements from a pressure transducer. The proposed method is a useful technique for measuring unsteady phenomena. PMID- 24182167 TI - High performance rotational vibration isolator. AB - We present a new rotational vibration isolator with an extremely low resonant frequency of 0.055 +/- 0.002 Hz. The isolator consists of two concentric spheres separated by a layer of water and joined by very soft silicone springs. The isolator reduces rotation noise at all frequencies above its resonance which is very important for airborne mineral detection. We show that more than 40 dB of isolation is achieved in a helicopter survey for rotations at frequencies between 2 Hz and 20 Hz. Issues affecting performance such as translation to rotation coupling and temperature are discussed. The isolator contains almost no metal, making it particularly suitable for electromagnetic sensors. PMID- 24182168 TI - In situ gas analysis for high pressure applications using property measurements. AB - As the production, distribution, and storage of renewable energy based fuels usually are performed under high pressures and as there is a lack of in situ high pressure gas analysis instruments on the market, the aim of this work was to develop a method for in situ high pressure gas analysis of biogas and hydrogen containing gas mixtures. The analysis is based on in situ measurements of optical, thermo physical, and electromagnetic properties in gas mixtures with newly developed high pressure sensors. This article depicts the calculation of compositions from the measured properties, which is carried out iteratively by using highly accurate equations of state for gas mixtures. The validation of the method consisted of the generation and measurement of several mixtures, of which three are presented herein: a first mixture of 64.9 mol. % methane, 17.1 mol. % carbon dioxide, 9 mol. % helium, and 9 mol. % ethane at 323 K and 423 K in a pressure range from 2.5 MPa to 17 MPa; a second mixture of 93.0 mol. % methane, 4.0 mol. % propane, 2.0 mol. % carbon dioxide, and 1.0 mol. % nitrogen at 303 K, 313 K, and 323 K in a pressure range from 1.2 MPa to 3 MPa; and a third mixture of 64.9 mol. % methane, 30.1 mol. % carbon dioxide, and 5.0 mol. % nitrogen at 303 K, 313 K, and 323 K in a pressure range from 2.5 MPa to 4 MPa. The analysis of the tested gas mixtures showed that with measured density, velocity of sound, and relative permittivity the composition can be determined with deviations below 1.9 mol. %, in most cases even below 1 mol. %. Comparing the calculated compositions with the generated gas mixture, the deviations were in the range of the combined uncertainty of measurement and property models. PMID- 24182169 TI - Neutron spin evolution through broadband current sheet spin flippers. AB - Controlled manipulation of neutron spin is a critical tool for many neutron scattering techniques. We have constructed current-sheet, neutron spin flippers for use in Spin Echo Scattering Angle Measurement (SESAME) that comprise pairs of open-faced solenoids which introduce an abrupt field reversal at a shared boundary. The magnetic fields generated by the coils have been mapped and compared with both an analytical approximation and a numerical boundary integral calculation. The agreement is generally good, allowing the former method to be used for rapid calculations of the Larmor phase acquired by a neutron passing through the flipper. The evolution of the neutron spin through the current sheets inside the flipper is calculated for various geometries of the current-carrying conductors, including different wire shapes, arrangements, and common imperfections. The flipping efficiency is found to be sensitive to gaps between wires and between current sheets. SESAME requires flippers with high fields and flipping planes inclined to the neutron beam. To avoid substantial neutron depolarization, such flippers require an interdigitated arrangement of wires. PMID- 24182170 TI - A Tesla-type repetitive nanosecond pulse generator for solid dielectric breakdown research. AB - A Tesla-type repetitive nanosecond pulse generator including a pair of electrode and a matched absorption resistor is established for the application of solid dielectric breakdown research. As major components, a built-in Tesla transformer and a gas-gap switch are designed to boost and shape the output pulse, respectively; the electrode is to form the anticipated electric field; the resistor is parallel to the electrode to absorb the reflected energy from the test sample. The parameters of the generator are a pulse width of 10 ns, a rise and fall time of 3 ns, and a maximum amplitude of 300 kV. By modifying the primary circuit of the Tesla transformer, the generator can produce both positive and negative pulses at a repetition rate of 1-50 Hz. In addition, a real-time measurement and control system is established based on the solid dielectric breakdown requirements for this generator. With this system, experiments on test samples made of common insulation materials in pulsed power systems are conducted. The preliminary experimental results show that the constructed generator is capable to research the solid dielectric breakdown phenomenon on a nanosecond time scale. PMID- 24182171 TI - A portable hydro-thermo-mechanical loading cell for in situ small angle neutron scattering studies of proton exchange membranes. AB - A portable hydro-thermo-mechanical loading cell has been designed to enable in situ small angle neutron scattering (SANS) studies of proton exchange membranes (PEMs) under immersed tensile loadings at different temperatures. The cell consists of three main parts as follows: a letter-paper-size motor-driven mechanical load frame, a SANS friendly reservoir that provides stable immersed and thermal sample conditions, and a data acquisition and control system. The ex situ tensile tests of Nafion 212 membranes demonstrated a satisfactory thermo mechanical testing performance of the cell for either dry or immersed conditions at elevated temperatures. The in situ SANS tensile measurements on the Nafion 212 membranes immersed in D2O at 70 degrees C proved the feasibility and capability of the cell for small angle scattering study on deformation behaviors of PEM and other polymer materials under hydro-thermo-mechanical loading. PMID- 24182172 TI - Broad-band magnetic induction probe calibration using a frequency-corrected reference probe. AB - Finite impedances of magnetic induction probes attenuate and shift the field fluctuations measured by the probe so that they differ from the measured signal at the digitizer. These effects vary with frequency. Traditionally, impedance effects have been accounted for in the calibration process by sweeping the frequency of the magnetic field source through a range of frequencies. Situations arise where the conventional calibration method is not feasible due to probe geometry or hardware constraints. A new calibration technique is presented in this paper which calibrates the probe in situ at a single frequency and uses impedance measurements of the probe assembly across the desired frequency range to account for broad-band effects. The in situ calibration technique requires a reference probe with a known proportionality constant NA and known impedances. Impedance effects are corrected in the probe signal using broad-band impedance measurements included in a transfer function in frequency space. The in situ calibration technique is shown to be complicated by capacitive coupling between the probes and the high voltage source coil. Circuit modeling demonstrates that this coupling introduces negligible attenuation and a small phase-delay so that the relative phase-delay between the reference and target probe signals can be corrected by shifting the signals in time. In summary, this calibration method extends traditional single-frequency calibration techniques to broad-band applications, accounting for important non-ideal effects to improve the accuracy of the magnetic field measurement. PMID- 24182173 TI - An experimental UHV AFM-STM device for characterizing surface nanostructures under stress/strain at variable temperature. AB - A compression setup fully integrated in an ultra high vacuum chamber is presented. The system has been designed to combine in situ mechanical test together with near field microscopy at variable temperature, from 90 to 600 K. Compressive stress can be applied on the samples up to 500 MPa at different strain rates ranging from 10(-6) s(-1) to 10(-2) s(-1). The setup performances are highlighted through investigations on Au and Ni3(Al,Ta) single crystals. In particular, it is demonstrated that the high mechanical stability of the original apparatus allows us to follow in situ the evolution of the same area of interest over a large range of temperature and to keep the high spatial resolution offered by near field microscopy, even at high strain levels. PMID- 24182174 TI - Note: Accurate determination of thickness of multiple layers of thin film deposited on a piezoelectric quartz crystal. AB - Modern day piezoelectric quartz crystal microbalances for thin film deposition control are based on Z-match equation, which is mathematically valid for deposition of a single material on a given quartz crystal. When multiple layers are deposited, thickness and deposition rate errors accumulate due to mismatch of acoustic impedance of different materials. Here we present a novel method, based on the acoustic transfer matrix formalism, for accurate determination of thickness of an arbitrary number of layers of dissimilar materials deposited on a quartz crystal. Laboratory data show excellent accuracy of the method compared to conventional Z-match equation. PMID- 24182175 TI - Note: Radial-thrust combo metal mesh foil bearing for microturbomachinery. AB - This Note proposes a novel radial-thrust combo metal mesh foil bearing (MMFB). Although MMFBs have advantages such as higher stiffness and damping over conventional air foil bearings, studies related to MMFBs have been limited to radial MMFBs. The novel combo MMFB is composed of a radial top foil, thrust top foils, and a ring-shaped metal mesh damper--fabricated by compressing a copper wire mesh--with metal mesh thrust pads for the thrust bearing at both side faces. In this study, the combo MMFB was fabricated in half-split type to support the rotor for a micro gas turbine generator. The manufacture and assembly process for the half-split-type combo MMFB is presented. In addition, to verify the proposed combo MMFB, motoring test results up to 250,000 rpm and axial displacements as a function of rotational speed are presented. PMID- 24182176 TI - Note: Characterization of a high-photon-energy X-ray imager. AB - The Bragg angle, rocking curve, and reflection efficiency of a quartz crystal x ray imager (Miller indices 234) were measured at photon energy of 15.6909 keV, corresponding to the K(alpha2) line of Zr, using the X15A beamline at the National Synchrotron Light Source at Brookhaven National Laboratory. One flat and three spherically curved samples were tested. The peak reflectivity of the best performing crystal was determined to be (3.6 +/- 0.7) * 10(-4) with a rocking curve full width at half maximum of 0.09 degrees . The Zr K(alpha2) emission was imaged from a hot Zr plasma generated by a 10-J multiterawatt laser. PMID- 24182177 TI - Note: A 1-m Foucault pendulum rolling on a ball. AB - We have built a short Foucault pendulum of 1-m length. The aim of this work was to increase the sensitivity to elliptical trajectories from other longer pendula. The design was a semi-rigid pendulum that rolls over a small ball. The measurements of the movements (azimuth and elliptical trajectory) were done by an optical method. The resulting pendulum works in a medium satisfactory way due to problems of the correct choice of the mass of the bob together with the diameter of the supporting ball. It is also important to keep the rolling surface very clean. PMID- 24182178 TI - Note: Resistance spot welding using a microgripper. AB - Interest in thin-film nanostructures as building blocks for nanoelectronics and nanoelectromechanical systems (NEMS) is increasing. Resistance spot welding (RSW) on a nano or micro scale can play a significant role; similar to that of its macro counterpart for forming connections in device assembly processes. This Note presents a novel micron scale RSW technique using a microgripper as mobile spot welding electrodes to assemble ultra-thin film nanostructures. As an example, assembly of three-dimensional helical nanobelt (HNB) based device was successfully demonstrated using the proposed system. The spot-welding process was fully monitored by the built-in capacitive micro force sensor of the microgripper. Experiments show that RSW, using the microgripper, provides a stable electrical contact with sufficient mechanical strength for the construction of devices such as HNB based devices demonstrated here. PMID- 24182179 TI - Note: High resolution alternating current/direct current Harman technique. AB - This note describes the construction and engineering of a high precision Harman set-up for metrology of the thermoelectric figure of merit (ZT) of modules and materials based on steady state AC and DC measurements. The Harman technique presented in this article has a resolution of milli-ZT and it does not employ lock-in amplifiers or AC bridges; rather, the technique is developed to avoid typical complications experienced in AC Harman systems. By one-time reference measurements the best operation point for the system is chosen, minimizing the effects of capacitive loads due to AC signals. PMID- 24182180 TI - Note: Tunable overlapping half-ring resonator. AB - A unique tunable microwave resonator with a pair of half-rings is introduced and validated by experimental data. The capacitive gap between the overlapping areas can be controlled accurately using a magnetic actuator for tunability. The design geometry is scalable to cover different bands of electromagnetic spectrum. Transmission characteristics of the resonators have been modeled using finite element analysis and have been measured. The experimental results indicate the resonant frequency can be controlled with a resolution of a few MHz in a tuning range of 38%. The resonator exhibits sharp transmission dips within the tuning range with measured quality factors larger than 2500. PMID- 24182181 TI - Note: Compact optical fiber coupler for diamond anvil high pressure cells. AB - A compact optical fiber coupler has been developed to allow transmission of light through an optical fiber to and from the high pressure region of a diamond anvil high pressure cell. Despite its small size the coupler has focusing adjustments and optics, which allows the light to be focused precisely on the sample within the pressure cell. The coupler is suitable for a wide range of optical measurements and particularly for high pressure measurements at low temperatures in cryostats with no optical windows. The use of the coupler to determine the pressure in a diamond anvil cell at 1.2 K using the ruby fluorescence spectra of ruby is demonstrated. The small size of the coupler and its construction out of nonmagnetic beryllium copper makes it suitable for use in high magnetic fields and for magnetization experiments. PMID- 24182182 TI - Note: A passively cooled heat pipe for spectroscopy. AB - We have developed and characterized a heat pipe for lithium spectroscopy, which is cooled only by air-convection, although its operating temperature is 330 degrees C: its construction is simple, of moderate cost and it is very reliable. A thermal model proves that heat-pipes without water cooling can be used up to considerably higher temperatures. PMID- 24182183 TI - Note: Four-port microfluidic flow-cell with instant sample switching. AB - A simple device for high-speed microfluidic delivery of liquid samples to a surface plasmon resonance sensor surface is presented. The delivery platform is comprised of a four-port microfluidic cell, two ports serve as inlets for buffer and sample solutions, respectively, and a high-speed selector valve to control the alternate opening and closing of the two outlet ports. The time scale of buffer/sample switching (or sample injection rise and fall time) is on the order of milliseconds, thereby minimizing the opportunity for sample plug dispersion. The high rates of mass transport to and from the central microfluidic sensing region allow for SPR-based kinetic analysis of binding events with dissociation rate constants (k(d)) up to 130 s(-1). The required sample volume is only 1 MUL, allowing for minimal sample consumption during high-speed kinetic binding measurement. PMID- 24182184 TI - Note: Complementary metal-oxide-semiconductor high voltage pulse generation circuits. AB - We present two types of on-chip pulse generation circuits. The first is based on CMOS pulse-forming-lines (PFLs). It includes a four-stage charge pump, a four stacked-MOSFET switch and a 5 mm long PFL. The circuit is implemented in a 0.13 MUm CMOS process. Pulses of ~1.8 V amplitude with ~135 ps duration on a 50 Omega load are obtained. The obtained voltage is higher than 1.6 V, the rated operating voltage of the process. The second is a high-voltage Marx generator which also uses stacked MOSFETs as high voltage switches. The output voltage is 11.68 V, which is higher than the highest breakdown voltage (~10 V) of the CMOS process. These results significantly extend high-voltage pulse generation capabilities of CMOS technologies. PMID- 24182185 TI - Note: Repetitive operation of the capacitor bank of the low-voltage miniature plasma focus at 50 Hz. AB - We have already reported the low-voltage operation of a plasma focus describing the operation of plasma focus at 4.2 kV which proposes possibility of making a repetitive system using compact driving source. Another recent article describes that the same capacitor-bank can drive the plasma focus for a measured ~5 * 10(4) neutrons per shot at 5 kV and 59 kA current. In the present work, repetitive operation of the capacitor-bank of plasma focus is done and that too is being reported at a very high repetition rate of 50 Hz using very simple scheme of charging and triggering the bank. The bank is continuously discharged to burst duration of 20 s in this configuration admeasuring a thousand shots. PMID- 24182186 TI - Note: Design principles of a linear array multi-channel effusive metal-vapor atom source. AB - Atomic beams can easily be produced by allowing atoms to effuse through a channel. In an earlier investigation [A. Majumder et al., Vacuum 83, 989 (2009)], we had designed, fabricated, and characterized an effusive metal-vapor source using collinear-array of multi-channel. In this note, we describe the theoretical basis of designing the source. Atom density in atomic beam has been estimated using a set of analytical expressions for long-channel operated in transparent mode. Parametric studies on aspect ratio of channel, inter-channel separation, beam width, and vertical distance from the source are carried out. They are useful in providing physical picture and optimizing design parameters. PMID- 24182190 TI - The purine metabolite allantoin enhances abiotic stress tolerance through synergistic activation of abscisic acid metabolism. AB - Purine catabolism is regarded as a housekeeping function that remobilizes nitrogen for plant growth and development. However, emerging evidence suggests that certain purine metabolites might contribute to stress protection of plants. Here, we show that in Arabidopsis, the intermediary metabolite allantoin plays a role in abiotic stress tolerance via activation of abscisic acid (ABA) metabolism. The aln loss-of-function of ALN, encoding allantoinase, results in increased allantoin accumulation, genome-wide up-regulation of stress-related genes and enhanced tolerance to drought-shock and osmotic stress in aln mutant seedlings. This phenotype is not caused by a general response to purine catabolism inhibition, but rather results from a specific effect of allantoin. Allantoin activates ABA production both through increased transcription of NCED3, encoding a key enzyme in ABA biosynthesis, and through post-translational activation via high-molecular-weight complex formation of BG1, a beta-glucosidase hydrolysing glucose-conjugated ABA. Exogenous application of allantoin to wild type plants also activates the two ABA-producing pathways that lead to ABA accumulation and stress-responsive gene expression, but this effect is abrogated in ABA-deficient and BG1-knockout mutants. We propose that purine catabolism functions not only in nitrogen metabolism, but also in stress tolerance by influencing ABA production, which is mediated by the possible regulatory action of allantoin. PMID- 24182193 TI - Redox regulation of transcription factors in plant stress acclimation and development. AB - SIGNIFICANCE: The redox regulatory signaling network of the plant cell controls and co-regulates transcriptional activities, thereby enabling adjustment of metabolism and development in response to environmental cues, including abiotic stress. RECENT ADVANCES: Our rapidly expanding knowledge on redox regulation of plant transcription is driven by methodological advancements such as sensitive redox proteomics and in silico predictions in combination with classical targeted genetic and molecular approaches, often in Arabidopsis thaliana. Thus, transcription factors (TFs) are both direct and indirect targets of redox dependent activity modulation. Redox control of TF activity involves conformational switching, nucleo-cytosolic partitioning, assembly with coregulators, metal-S-cluster regulation, redox control of upstream signaling elements, and proteolysis. CRITICAL ISSUES: While the significance of redox regulation of transcription is well established for prokaryotes and non-plant eukaryotes, the momentousness of redox-dependent control of transcription in plants still receives insufficient awareness and, therefore, is discussed in detail in this review. FUTURE DIRECTIONS: Improved proteome sensitivity will enable characterization of low abundant proteins and to simultaneously address the various post-translational modifications such as nitrosylation, hydroxylation, and glutathionylation. Combining such approaches by gradually increasing biotic and abiotic stress strength is expected to result in a systematic understanding of redox regulation. In the end, only the combination of in vivo, ex vivo, and in vitro results will provide conclusive pictures on the rather complex mechanism of redox regulation of transcription. PMID- 24182189 TI - Delivering nanoparticles to lungs while avoiding liver and spleen through adsorption on red blood cells. AB - Nanoparticulate drug delivery systems are one of the most widely investigated approaches for developing novel therapies for a variety of diseases. However, rapid clearance and poor targeting limit their clinical utility. Here, we describe an approach to harness the flexibility, circulation, and vascular mobility of red blood cells (RBCs) to simultaneously overcome these limitations (cellular hitchhiking). A noncovalent attachment of nanoparticles to RBCs simultaneously increases their level in blood over a 24 h period and allows transient accumulation in the lungs, while reducing their uptake by liver and spleen. RBC-adsorbed nanoparticles exhibited ~3-fold increase in blood persistence and ~7-fold higher accumulation in lungs. RBC-adsorbed nanoparticles improved lung/liver and lung/spleen nanoparticle accumulation by over 15-fold and 10-fold, respectively. Accumulation in lungs is attributed to mechanical transfer of particles from the RBC surface to lung endothelium. Independent tracing of both nanoparticles and RBCs in vivo confirmed that RBCs themselves do not accumulate in lungs. Attachment of anti-ICAM-1 antibody to the exposed surface of NPs that were attached to RBCs led to further increase in lung targeting and retention over 24 h. Cellular hitchhiking onto RBCs provides a new platform for improving the blood pharmacokinetics and vascular delivery of nanoparticles while simultaneously avoiding uptake by liver and spleen, thus opening the door for new applications. PMID- 24182194 TI - An azine-linked covalent organic framework. AB - Condensation of hydrazine with 1,3,6,8-tetrakis(4-formylphenyl)pyrene under solvothermal conditions yields highly crystalline two-dimensional covalent organic frameworks. The pyrene units occupy the vertices and the diazabutadiene ( C?N-N?C-) linkers locate the edges of rohmbic-shaped polygon sheets, which further stack in an AA-stacking mode to constitute periodically ordered pyrene columns and one-dimensional microporous channels. The azine-linked frameworks feature permanent porosity with high surface area and exhibit outstanding chemical stability. By virtue of the pyrene columnar ordering, the azine-linked frameworks are highly luminescent, whereas the azine units serve as open docking sites for hydrogen-bonding interactions. These synergestic functions of the vertices and edge units endow the azine-linked pyrene frameworks with extremely high sensitivity and selectivity in chemosensing, for example, the selective detection of 2,4,6-trinitrophenol explosive. We anticipate that the extension of the present azine-linked strategy would not only increase the structural diversity but also expand the scope of functions based on this highly stable class of covalent organic frameworks. PMID- 24182195 TI - Identification of direction in gene networks from expression and methylation. AB - BACKGROUND: Reverse-engineering gene regulatory networks from expression data is difficult, especially without temporal measurements or interventional experiments. In particular, the causal direction of an edge is generally not statistically identifiable, i.e., cannot be inferred as a statistical parameter, even from an unlimited amount of non-time series observational mRNA expression data. Some additional evidence is required and high-throughput methylation data can viewed as a natural multifactorial gene perturbation experiment. RESULTS: We introduce IDEM (Identifying Direction from Expression and Methylation), a method for identifying the causal direction of edges by combining DNA methylation and mRNA transcription data. We describe the circumstances under which edge directions become identifiable and experiments with both real and synthetic data demonstrate that the accuracy of IDEM for inferring both edge placement and edge direction in gene regulatory networks is significantly improved relative to other methods. CONCLUSION: Reverse-engineering directed gene regulatory networks from static observational data becomes feasible by exploiting the context provided by high-throughput DNA methylation data.An implementation of the algorithm described is available at http://code.google.com/p/idem/. PMID- 24182197 TI - Reply to high rates of uncontrolled blood pressure: pulse wave velocity and future opportunities. PMID- 24182198 TI - Classification of the pH-oscillatory hydrogen peroxide-thiosulfate-sulfite reaction. AB - The reaction of hydrogen peroxide with thiosulfate and sulfite in acidic solution is characterized by marked temporal pH variations suggesting autocatalytic nature of hydrogen ions. When carried out in a continuous-flow stirred tank reactor this reaction provides nonlinear dynamical regimes including periodic oscillations, chaotic behavior, and multiple steady states coexisting over a range of operating conditions. The aim of the presented experimental study is a classification of the role of species and the underlying mechanism in the periodic oscillatory mode by applying single pulse additions of chosen reaction species. The external perturbations at various phases of the periodically oscillating system may cause phase advance or phase delay of the oscillations. The resulting phase transition curves are obtained for hydrogen ions, hydroxide ions, thiosulfate ions, sulfite ions, and hydrogen sulfite ions. These curves are compared with the phase transition curves calculated using the prototype mechanisms representing categories of chemical oscillators established in previous work. We found our system to be compatible with the mechanism of the category 1CX. PMID- 24182196 TI - Long-term prognostic impact of cystatin C on acute coronary syndrome octogenarians with diabetes mellitus. AB - OBJECTIVE: Cystatin C (Cys C) is a marker of renal dysfunction. Prior studies have shown that blood Cys C is related to the prognosis of coronary heart disease. The aim of the present study was to evaluate the long-term prognostic impact of Cys C on acute coronary syndrome (ACS) octogenarians with diabetes mellitus (DM). METHODS: We enrolled 660 consecutive ACS octogenarians who underwent coronary angiography and were classified into two groups based on diabetes. The baseline characters and Cys C level were measured on admission. Survival curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of mortality and of major adverse cardiac events (MACE) rate. RESULTS: There were 223 and 398 patients in groups DM and non-DM who fulfilled the follow-up. The average follow-up period was 28 (IQR 16-38) months. Diastolic blood pressure (DBP) was lower, ratios of hypertension and chronic renal failure (CRF), fasting blood glucose, HbA1c and Cys C levels were higher in DM group than those in non-DM group (P<0.01). The cumulative survival of DM group was significantly lower than that of non-DM group in the long term (P = 0.018). All cause mortality and MACE of DM group were higher than those of non-DM group (P<0.05). The plasma Cys C concentration (OR = 3.32, 95% CI = 1.18-10.92, P = 0.023) was the uniqueness independent predictor for long-term all cause mortality. The plasma Cys C concentration (OR = 2.47, 95% CI = 1.07 7.86, P = 0.029) and Genesis score (OR = 1.01, 95% CI = 1.00-1.03, P = 0.043) were independent predictors for MACE in DM group. ROC curve analysis showed that the predictive cut-off value of Cys C for mortality of DM group was 1.605 (0.718, 0.704). CONCLUSIONS: Cys C is an independent predictor for long-term mortality and MACE of ACS octogenarians with DM. PMID- 24182200 TI - Association of personality with physical, social, and mental activities across the lifespan: Findings from US and French samples. AB - Despite evidence for its health-related benefits, little is known on the psychological predictors of the participation in leisure activities across the lifespan. Therefore, this study aimed to identify whether personality is associated with a variety of different types of activities, involving physical, cognitive, and social components. The samples included individuals from the second wave of the National Study of Midlife in the United States (N = 3,396) and community-dwelling French individuals (N = 2,917) aged between 30 and 84. Both samples completed measures of the five-factor model of personality. To create an activity index, we combined the physical, social, and cognitive (games and developmental) activities performed at least once a month. In both samples, individuals who scored higher on extraversion and openness were more likely to engage in a variety of activity types. The findings were consistent across two samples from different western societies and suggest that extraversion and openness contribute to social, cognitive, and physical functioning across the lifespan. PMID- 24182201 TI - Reversible effects of vitamins C and E combination on oxidative stress-induced apoptosis in melamine-treated PC12 cells. AB - Due to its high nitrogen content, melamine was deliberately added to raw milk for increasing the apparent protein content. Previous studies showed that melamine induced apoptosis and oxidative damage on PC12 cells and rats' hippocampus. Several evidences suggested that vitamin antioxidant reduced oxidative stress and improved organic function. Whether treatments with antioxidant vitamins C or E, otherwise combination of them can attenuate oxidative stress after melamine administration remains to be elucidated. In this study, the reversible effects of vitamin antioxidants was investigated on melamine-induced neurotoxicity in cultured PC12 cells, an in vitro model of neuronal cells. When comparing vitamin C and E, the combination of both statistically increased PC12 cells viability. The results further showed that vitamin complex has effectively reduced the formation of reaction oxygen species, decreased the level of malondialdehyde, and elevated the activities of antioxidative enzymes. Hoechst 33342 staining and flow cytometric analysis of apoptosis showed that vitamin combination treatment effectively prevented PC12 cells from this melamine-induced apoptosis. It revealed the apoptotic nuclear features of the melamine-induced cell death. Additionally, a combination treatment of vitamins effectively inhibited apoptosis via blocking the increased activation of caspase-3. In summary, the vitamin E and C combination treatment could rescue PC12 cells from the injury induced by melamine through the downregulation of oxidative stress and prevention of melamine-induced apoptosis. PMID- 24182202 TI - Homo- and hetero- p-n junctions formed on graphene steps. AB - p-n junction is a fundamental building block in modern electronic circuits. We report graphene p-n junctions formed by a one-step thickness-dependent surface treatment of mono-/bilayer graphene steps. The junction electronic properties are systemically studied by means of Kelvin probe force microscopy (KPFM) and transport measurements. Because of the dissimilar modifications to graphene electronic properties, the junctions behave distinctly, i.e., two-component resistance-like for organic charge transfer doping and Shottky-junction-like for covalent doping. By exploring the spatially potential distribution, we clarify the potential profiles as well as the transport attributes across the graphene p n junction interface under lateral bias and electrical gating. Our results not only unveil the detailed properties of graphene p-n junction interface, but also gain an insight into its practical applications in nanoelectronics. PMID- 24182203 TI - Distinct roles of NK cells in viral immunity during different phases of acute Friend retrovirus infection. AB - BACKGROUND: In many virus infections natural killer (NK) cells are critical for the rapid containment of virus replication. Polymorphisms in NK cell receptors as well as viral escape from NK cell responses are associated with pathogenesis and viral loads in HIV-infected individuals, emphasizing their importance in retroviral immunity. In contrast, NK cells of LCMV-infected mice dampened virus specific T cell responses resulting in impaired virus control. Thus, the exact role of NK cells during different phases of viral infections remains elusive. In this study we characterized the NK cell response at different time points of an acute retroviral infection by using the Friend retrovirus (FV) mouse model. FINDINGS: Depletion of NK1.1+ cells during the initial phase of FV infection (3 to 4 days post infection) resulted in increased viral loads, which correlated with enhanced target cell killing and elevated NK cell effector functions. At days 7 to 15 post infection, NK and NKT cells did not contribute to anti retroviral immunity. In the transition phase between acute and chronic infection (30 days post infection), NK and NKT cells exhibited an inhibitory role and their depletion resulted in reduced viral loads and significantly improved FV-specific CD8+ T cell responses. CONCLUSIONS: Our results demonstrate an opposed activity of NK cells during retroviral infection. They were protective in the initial phase of infection, when adaptive T cell responses were not yet detectable, but were dispensable for viral immunity after T cell expansion. At later time points they exhibited regulatory functions in inhibiting virus-specific CD8+ T cell responses. PMID- 24182204 TI - Impact of placement type on the development of clinical competency in speech language pathology students. AB - BACKGROUND: Speech-language pathology students gain experience and clinical competency through clinical education placements. However, currently little empirical information exists regarding how competency develops. Existing research about the effectiveness of placement types and models in developing competency is generally descriptive and based on opinions and perceptions. The changing nature of education of speech-language pathology students, diverse student cohorts, and the crisis in finding sufficient clinical education placements mean that establishing the most effective and efficient methods for developing clinical competency in students is needed. AIMS: To gather empirical information regarding the development of competence in speech-language pathology students; and to determine if growth of competency differs in groups of students completing placements that differ in terms of caseload, intensity and setting. METHODS & PROCEDURES: Participants were students in the third year of a four-year undergraduate speech-language pathology degree who completed three clinical placements across the year and were assessed with the COMPASS(r) competency assessment tool. Competency development for the whole group across the three placements is described. Growth of competency in groups of students completing different placement types is compared. Interval-level data generated from the students' COMPASS(r) results were subjected to parametric statistical analyses. OUTCOMES & RESULTS: The whole group of students increased significantly in competency from placement to placement across different placement settings, intensities and client age groups. Groups completing child placements achieved significantly higher growth in competency when compared with the competency growth of students completing adult placements. Growth of competency was not significantly different for students experiencing different intensity of placements, or different placement settings. CONCLUSIONS & IMPLICATIONS: These results confirm that the competency of speech-language pathology students develops across three clinical placements over a one-year period regardless of placement type or context, indicating that there may be a transfer of learning between placements types. Further research investigating patterns of competency development in speech-language pathology students is warranted to ensure that assumptions used to design clinical learning opportunities are based on valid evidence. PMID- 24182205 TI - Love in the time of cancer. PMID- 24182206 TI - It is time for clinical guidelines to enter the digital age. PMID- 24182207 TI - Time trends in cancer incidence and mortality. PMID- 24182210 TI - Building Queensland's human capital: the case for health advocacy. PMID- 24182211 TI - The Papua New Guinea cholera outbreak: implications for PNG, Australia and the Torres Strait. PMID- 24182212 TI - Assessment of medical students' learning outcomes in Australia: current practice, future possibilities. PMID- 24182213 TI - The dilemmas of prostate cancer screening. PMID- 24182214 TI - The dilemmas of prostate cancer screening. PMID- 24182215 TI - The dilemmas of prostate cancer screening. PMID- 24182216 TI - The dilemmas of prostate cancer screening. PMID- 24182217 TI - The dilemmas of prostate cancer screening. PMID- 24182218 TI - The dilemmas of prostate cancer screening. PMID- 24182219 TI - Prostate cancer screening. PMID- 24182220 TI - Should we screen for lung cancer in Australia? PMID- 24182221 TI - Should we screen for lung cancer in Australia? PMID- 24182222 TI - Should we screen for lung cancer in Australia? PMID- 24182223 TI - The principles of problem-based learning are more important than the method. PMID- 24182224 TI - Update on the management of atrial fibrillation. AB - Atrial fibrillation (AF) is a common arrhythmia, with a prevalence that increases markedly with increasing age. Presence of AF has implications for management of future stroke risk. If the patient's pulse is irregular, an electrocardiogram should be ordered. Key management decisions are whether to adopt a rhythm control or a rate control strategy and whether to initiate anticoagulation. The primary aim of a rhythm control strategy is improved symptom control. AF ablation may be considered in younger patients (aged < 65 years) with paroxysmal or early persistent AF. AF increases the risk of stroke, and anticoagulation should be considered on the basis of stroke risk - clearly indicated with a CHADS 2 score (congestive heart failure, hypertension, age >= 75 years, diabetes, 1 point each; previous stroke or transient ischaemic attack, 2 points) of >= 2 - independent of the type of AF. In most patients with AF, the benefit of stroke reduction with systemic anticoagulation will outweigh its bleeding risks. All anticoagulants and antiplatelet agents increase the risk of bleeding. However, the new oral anticoagulants tend to have an improved safety profile, particularly in regard to intracranial bleeding, and are at least as effective as warfarin for stroke prevention. PMID- 24182225 TI - Psychological distress and streamlined BreastScreen follow-up assessment versus standard assessment. AB - OBJECTIVES: To establish whether altered protocol characteristics of streamlined StepDown breast assessment clinics heightened or reduced the psychological distress of women in attendance compared with standard assessment. Willingness to attend future screening was also compared between the assessment groups. DESIGN: Observational, prospective study of women attending either a mammogram-only StepDown or a standard breast assessment clinic. Women completed questionnaires on the day of assessment and 1 month later. PARTICIPANTS AND SETTING: Women attending StepDown (136 women) or standard assessment clinics (148 women) at a BreastScreen centre between 10 November 2009 and 7 August 2010. MAIN OUTCOME MEASURES: Breast cancer worries; positive and negative psychological consequences of assessment (Psychological Consequences Questionnaire); breast cancer-related intrusion and avoidance (Impact of Event Scale); and willingness to attend, and uneasiness about, future screening. RESULTS: At 1-month follow-up, no group differences were evident between those attending standard and StepDown clinics on breast cancer worries (P= 0.44), positive (P= 0.88) and negative (P = 0.65) consequences, intrusion (P = 0.64), and avoidance (P = 0.87). Willingness to return for future mammograms was high, and did not differ between groups (P = 0.16), although higher levels of unease were associated with lessened willingness to rescreen (P = 0.04). CONCLUSIONS: There was no evidence that attending streamlined StepDown assessments had different outcomes in terms of distress than attending standard assessment clinics for women with a BreastScreen-detected abnormality. However, unease about attending future screening was generally associated with less willingness to do so in both groups; thus, there is a role for psycho-educational intervention to address these concerns. PMID- 24182226 TI - Australia is continuing to make progress against cancer, but the regional and remote disadvantage remains. AB - OBJECTIVE: To measure progress, over the past decade, in reducing the disadvantage in cancer death rates among people living in regional and remote areas of Australia. DESIGN: Analysis of routinely collected death certificate and corresponding population data from the Australian Bureau of Statistics. SETTING: Population-based, Australia-wide comparison of mortality rates in regional and remote areas compared with metropolitan areas from 1 January 2001 to 31 December 2010. MAIN OUTCOME MEASURES: Absolute and relative excess of cancer deaths in regional and remote areas. RESULTS: The number of excess cancer deaths in regional and remote areas from 2001 to 2010 was 8878 (95% CI, 8187-9572). For men, the age-standardised mortality ratios (comparing regional and remote areas with metropolitan areas) showed no evidence of improvement, from 1.08 in 1997 2000 to 1.11 in 2006-2010. For women, they increased from 1.01 in 1997-2000 to 1.07 in 2006-2010. The age-standardised cancer death rate in regional and remote areas (annual percentage change [APC], - 0.6%; 95% CI, - 0.8% to - 0.4%) is decreasing more slowly than in metropolitan areas (APC, - 1.1%; 95% CI, - 1.3% to - 1.0%). CONCLUSIONS: The regional and remote disadvantage for cancer deaths has been recognised as a problem for more than two decades, yet we have made little progress. This is not surprising - we have not invested in research into solutions. The benefits of laboratory and clinical research to identify innovative cancer treatments will not be fully realised across the entire Australian population unless we also invest in health systems and policy research. PMID- 24182227 TI - Nature and outcomes of the increased incidence of colorectal malignancy after liver transplantation in Australasia. AB - OBJECTIVES: To examine whether incidence of colorectal malignancy is increased in Australasian liver transplant recipients compared with the general population of Australia, and to assess the characteristics and outcomes of colorectal malignancy in this patient group. DESIGN, SETTING AND PATIENTS: Data on patients who underwent orthotopic liver transplantation (OLTx) and had a diagnosis of de novo colorectal malignancy after transplantation during the period 1985-2011 were obtained from the Australia and New Zealand Liver Transplant Registry, and these data were compared with colorectal malignancy data from the Australian Institute of Health and Welfare. MAIN OUTCOME MEASURES: Time from OLTx to diagnosis of colorectal malignancy, stage of colorectal malignancy at diagnosis, patient survival, and standardised incidence ratio (SIR) for colorectal malignancy. RESULTS: Forty-eight of 3735 recipients (1.3%) were diagnosed with colorectal malignancy at a median of 7.3 years after OLTx. More advanced colorectal malignancy (regional or metastatic disease) was evident at diagnosis in 20 of the 48 patients; these patients tended to be younger than patients with less advanced malignancy (P = 0.01) and diagnosed sooner after OLTx (P = 0.005). Despite treatment predominantly with surgery, 19 of the 48 patients died from the malignancy. The overall SIR for colorectal malignancy liver transplant recipients compared with the general population of Australia was 2.80 (95% CI, 2.06-3.71). CONCLUSIONS: The incidence of colorectal malignancy is increased in liver transplant recipients in comparison with the general population. Of concern is the tendency for advanced malignancy to be diagnosed in younger patients. These data highlight the importance of considering whether specific guidelines for colorectal malignancy screening in the Australasian adult liver transplant population are needed. PMID- 24182228 TI - Human papillomavirus vaccine coverage among female Australian adolescents: success of the school-based approach. AB - OBJECTIVE: To describe quadrivalent human papillomavirus (HPV) vaccination coverage achieved in the HPV vaccination catch-up program for girls aged 12-17 years. DESIGN: Analysis of data from the Australian National HPV Vaccination Program Register. PARTICIPANTS: Girls aged 12-17 years as at 30 June 2007. MAIN OUTCOME MEASURES: HPV vaccine coverage by dose (1, 2 and 3), age and state of residence, using Australian Bureau of Statistics estimates of resident populations as the denominator. RESULTS: Notified vaccination coverage for girls aged 12-17 years nationally was 83% for dose 1, 78% for dose 2 and 70% for dose 3. The Australian Capital Territory and Victoria recorded the highest three-dose coverage for the 12-17-year-old cohort overall at 75%. The highest national three dose coverage rate by age was achieved in 12-year-olds (74%). In Queensland, coverage among Indigenous girls compared with non-Indigenous girls was lower with each dose (lower by 4% for dose 1, 10% for dose 2 and 15% for dose 3). This pattern was not seen in the NT, where initial coverage was 17% lower among Indigenous girls, but the course completion rate among those who started vaccination was identical (84%). CONCLUSIONS: The catch-up HPV vaccination program delivered over 1.9 million doses of HPV vaccine to girls aged 12-17 years, resulting in 70% of girls in this age group being fully vaccinated. The range in coverage achieved and the lower uptake documented among Indigenous girls suggest that HPV vaccination programs can be further improved. PMID- 24182229 TI - Estimated impacts of alternative Australian alcohol taxation structures on consumption, public health and government revenues. AB - OBJECTIVE: To examine health and economic implications of modifying taxation of alcohol in Australia. DESIGN AND SETTING: Economic and epidemiological modelling of four scenarios for changing the current taxation of alcohol products, including: replacing the wine equalisation tax (WET) with a volumetric tax; applying an equal tax rate to all beverages equivalent to a 10% increase in the current excise applicable to spirits and ready-to-drink products; applying an excise tax rate that increases exponentially by 3% for every 1% increase in alcohol content above 3.2%; and applying a two-tiered volumetric tax. We used annual sales data and taxation rates for 2010 as the base case. MAIN OUTCOME MEASURES: Alcohol consumption, taxation revenue, disability-adjusted life-years (DALYs) averted and health care costs averted. RESULTS: In 2010, the Australian Government collected close to $8.6 billion from alcohol taxation. All four of the proposed variations to current rates of alcohol excise were shown to save money and more effectively reduce alcohol-related harm compared with the 2010 base case. Abolishing the WET and replacing it with a volumetric tax on wine would increase taxation revenue by $1.3 billion per year, reduce alcohol consumption by 1.3%, save $820 million in health care costs and avert 59 000 DALYs. The alternative scenarios would lead to even higher taxation receipts and greater reductions in alcohol use and harm. CONCLUSIONS: Our research findings suggest that any of the proposed variations to current rates of alcohol excise would be a cost-effective health care intervention; they thus reinforce the evidence that taxation is a cost-effective strategy. Of all the scenarios, perhaps the most politically feasible policy option at this point in time is to abolish the WET and replace it with a volumetric tax on wine. This analysis supports the recommendation of the National Preventative Health Taskforce and the Henry Review towards taxing alcohol according to alcohol content. PMID- 24182230 TI - Pregabalin-associated rhabdomyolysis. PMID- 24182231 TI - Social media and medical education: making an animated video for YouTube. PMID- 24182232 TI - Can you tell a siren from a tocsin? PMID- 24182233 TI - Reductions in log P improved protein binding and clearance predictions enabling the prospective design of cannabinoid receptor (CB1) antagonists with desired pharmacokinetic properties. AB - Several strategies have been employed to reduce the long in vivo half-life of our lead CB1 antagonist, triazolopyridazinone 3, to differentiate the pharmacokinetic profile versus the lead clinical compounds. An in vitro and in vivo clearance data set revealed a lack of correlation; however, when compounds with <5% free fraction were excluded, a more predictable correlation was observed. Compounds with log P between 3 and 4 were likely to have significant free fraction, so we designed compounds in this range to give more predictable clearance values. This strategy produced compounds with desirable in vivo half-lives, ultimately leading to the discovery of compound 46. The progression of compound 46 was halted due to the contemporaneous marketing and clinical withdrawal of other centrally acting CB1 antagonists; however, the design strategy successfully delivered a potent CB1 antagonist with the desired pharmacokinetic properties and a clean off-target profile. PMID- 24182235 TI - Past quantum states of a monitored system. AB - A density matrix rho(t) yields probabilistic information about the outcome of measurements on a quantum system. We introduce here the past quantum state, which, at time T, accounts for the state of a quantum system at earlier times t