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More importantly generic sildenafil 25 mg without prescription, nuclear inclusions could also be detected with an N-terminal antibody in the brains of patients with the disease (DiFiglia et al buy 75 mg sildenafil visa. Furthermore order sildenafil 100 mg without prescription, 336 Chesselet and Levine their distribution does not clearly parallel the pattern of neurodegeneration in humans (Gutekunst et al effective sildenafil 50mg. In these mice, more than 50% of neurons in the cerebral cortex, hippocampus, cerebellum and amygdala and 10 50% of striatal neurons contained nuclear inclusions. Curiously, other mouse models did not show prominent nuclear inclu- sions despite the presence of behavioral anomalies and even cell death (Hodgson et al. Although large enough to be detected with light microscopy, these aggregates were much smaller than the nuclear inclusions described in other mouse models. Furthermore, in our hands, these macroaggregates could not be detected in tissue from animals perfused with the milder fixative paraformaldehyde, suggesting that they may be more labile than nuclear inclusions. It is not yet known whether such labile aggregates also stain for chaperone proteins and ubiquitin-like nuclear inclusions. Mutant huntingtin also forms aggregates in the cytoplasm, particularly of neuronal processes. The presence of neuropil aggregates has been reported in human brain, in R6/2 transgenic mice (Li et al. An important question that is not fully resolved is whether these precede nuclear aggregates. Therefore, the respec- tive role of nuclear localization of huntingtin and of neuropil aggregates in the early phases of the disease process remains unclear. Furthermore, in postmortem human brain, the distribution of nuclear inclusions does not parallel the pattern of neurodegeneration. However, abnormal location of huntingtin in the nucleus appears to be a common feature of most models. This abnormal nuclear staining is coupled to the presence of macroaggregates or microaggregates that can only be retained in tissue section with strong fixatives. A role for nuclear transport of truncated huntingtin is further suggested by evidence that preventing nuclear entry of mutated huntingtin protects tranfected primary neurons in culture, whereas preventing aggregation does not (Saudou et al. An impor- tant conclusion from these studies is that proteolytic processing of huntingtin appears to be critical for the disease process. This is further supported by the results of in vitro studies that show an increased toxicity of smaller compared to larger huntingtin fragments in transfected cells (see below). Transgenic mice expressing huntingtin 1 171 with 82 glutamine repeats do not show any increase in indices of oxidative stress (Schilling et al. It is possible, however, that the increased resistance to excitotoxicity observed in the R6/1 mice is the result of the development of compensatory mechanisms in vivo. The analysis of excitotoxicity and sensitivity to oxida- tive stress in mice is complicated by the fact that different strains show marked differences in sensitivity (Alexi et al. These changes clearly precede overt neuronal death and perhaps even the onset of neurological symptoms. Importantly, these effects are not the result of the massive loss of striatal or cortical neurons at this age, suggesting a selective neuronal dysfunction (Davies et al. Although this hypothesis has not yet been directly tested at the striato-pallidal synapse, it should be noted that huntingtin is associ- ated with synaptic vesicles and interacts with proteins involved in vesicle trafficking (DiFiglia et al. Normal huntingtin is thought to influence vesicle transport in the secretory and endocytic pathway through association with clathrin-coated vesicles (Velier et al. It is not known whether the polyglutamine expansion in huntingtin alters these functions. However, our recent data suggest that the mutation also causes marked anomalies in the functional properties of striatal and cortical neurons in these mice (Levine et 340 Chesselet and Levine al. In the striatum, this effect was accompanied by a depolarization of the resting membrane and an increase in membrane input resistance. Slices of 6-mo-old mice with 72 repeats showed hyperexcitability and displayed a greater short-term poten- tiation following tetanization. Although paired-pulse facilitation was not affected in 10-mo-old mutant mice, posttetanic potentiation was reduced in these mice. This suggests an impairment of presynaptic release in response to high frequency stimulation. Long-term potentiation was also reduced in one line of knock-in mice (Usdin et al. These cellular deficits could form the basis of the neuronal dysfunction, leading to behav- ioral symptoms at early stages of the disease. It is not possible to evaluate the level of expression of the transgene in these mice for technical reasons. However, other trangenics with a high level of the full-length mutated huntingtin have a milder phenotype. An explanation for this paradox may be provided by in vitro studies that have clearly demonstrated that short huntingtin fragments with expanded polyglutamine repeats are more toxic to neurons than the full-length protein with an identical mutation (Cooper et al. This observation led to the hypothesis that cleavage of huntingtin by proteases is a critical step in the pathophysiology of the disease. Huntingtin can be cleaved by caspase 3, a protease involved in the apoptotic cascade (Wellington et al. Interestingly, the blockade of caspase 1 in transgenic mice delays the onset of motor symptoms, of neurochemical anomalies, and the death of the mice (Ona et al. Noncaspase proteases, however, also seem to be important for the processing of huntingtin. Whether this abnormal processing contributes to the pathophysiology and which proteases are involved, however, remains unknown. Furthermore, few studies have examined the same behavioral, cellular, or molecular effects across several mouse models. Nevertheless, several lines of consistent evidence are emerging from the available comparisons. The mutation seems to induces neuronal dysfunction long before it induces cell death and neuronal dysfunction appears sufficient to induce motor symptoms. Another emerging theme is the importance of protein aggregates, as opposed to nuclear inclusions, at early stages of the disease. Finally, the mouse models are beginning to provide the most sought after infor- mation: a rational approach to the design of new therapies and a way to test them preclinically. In that respect, a critical contribution of the mouse models will be to identify the link between parameters that can be measured in humans (in accessible peripheral tissues or by brain imaging) and the progressive brain pathology. Once validated, these accessible measures will permit great improve- ment in the design of clinical trials, an essential step in bringing the benefit of bench science to the patients. Huntington s Disease Collaborative Research Group (1993) A novel gene contain- ing a trinucleotide repeat that is expanded and unstable in Huntington s disease chromosomes.

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Besides lectins order sildenafil 100 mg without a prescription, defensins 25 mg sildenafil fast delivery, lysozyme and possibly other antimicrobial peptides are secreted into the hemolymph plasma to combat invasion by foreign organisms (Goodman et al discount sildenafil 50 mg line. More studies are necessary to understand the role of hemolymph contents in humoral immunity purchase sildenafil 100mg on-line. Diseases of Mites and Ticks 87 Many studies on the tick immune system are limited in identifying and quantifying hemocytes, or in characterizing antimicrobial peptides (Sonenshine 1991; Carneiro and Daemon 1996; Pereira et al. The expression of four forms of defensin was observed in the intestine, fat body and reproductive tract of Orni- thodorus moubata (Nakajima et al. It is not known, however, if expression of these peptides increases after infection. Greater understanding of the immune responses of ticks to infection by entomopatho- genic fungi would help elucidate the infection process, and this information might be useful in choosing appropriate entomopathogenic fungal isolates for biological control of ticks. Also, knowledge on the effects of formulation products may prove important in devising superior formulations for eld use. Biocontrol strategies Based on the results reviewed in this study and the ecological conditions in South America, the best use of entomopathogenic fungi to control ticks would probably be to apply formulated conidia directly onto tick-infested animals. Although the spraying of conidial suspensions on pasture plants has reduced the population of tick larvae (see Table 5), the concentration of fungal inoculum used to control ticks in the eld still remains high in comparison to those used for agriculture arthropod pests (Maniania et al. On the other hand, a system with pheromones and carbon dioxide delivery in the eld could possibly attract ticks to a localized fungus-treated spot in the vegetation; however, further investigation is needed to improve this system (Maranga et al. Combinations of chemical acaricides and entomopathogenic fungi also have been studied, aiming for compatibility and synergism between them. It is important to note that most of the studies evaluated the possible negative effects of chemical products on entomopathogenic fungi; however, Paiao et al. The results suggest that the combination of chemical acaricides with entomopathogenic fungi is potentially an important tool for integrated management of ticks. Conclusion Entomopathogenic fungi are the most promising of the currently available alternatives to chemical acaricides for tick control; especially since these organisms penetrate directly 88 J. In addition, fungi might initiate natural epizootic outbreaks (Alves 1998), and where environmental conditions (e. The genetic variability among fungal isolates is another advantage, in that simple assays may detect the most virulent isolates, level of host specicity, and tolerance to eld conditions. Unfortunately, most eld trials performed to date have reported rather low efcacy of fungi for the control of tick populations in South America, with the exception of A. Only a few eld trials have been conducted in South America, and in most cases, a simple aqueous conidial suspension was used. In Brazil, an acaricide needs to achieve 95% efcacy to be commercialized (Ministerio da Agricultura, Pecuaria e Abas- tecimento 1997). Therefore, studies on formulation are required to improve conidial performance under environmental conditions. These programs may vary with tick species due to different biological behavior and geographic region. Tick biological control offers several advantages over currently available chemical acaricides, including lower costs; and therefore, there are increased efforts in South America to develop new biological products. Unfortunately, regulations for microbial pesticides in many South American countries are poorly developed and/or virtually not enforced, and thus have impeded the development of quality biological control products. However, while more research is necessary, entomopathogenic fungi have great promise as alternatives to current tick control methods, and they could alleviate many of the current environmental and health concerns that come with the present-day methods. Am J Trop Med 19:103 108 Dutra V, Nakazato L, Broetto L et al (2004) Application of representational difference analysis to identify sequence tags expressed by Metarhizium anisopliae during the infection process of the tick Boophi- lus microplus. Rev Bras Parasitol 15:157 162 Ministerio da Agricultura Pecuaria e Abastecimento (1997) Regulamento tecnico para licenciamento e/ou renovacao de licenca de produtos antiparasitarios de uso veterinario. Cienc Rural 35:855 861 Prior C, Jollands P, Le Patourel G et al (1988) Infectivity of oil and water formulation of Beauveria bas- siana (Deuteromycotina: Hyphomycetes) to the cocoa weevil pest Pantorhytes plutus (Coleoptera: Curculionidae). Academic, New York Samish M, Rehacek J (1999) Pathogens and predators of ticks and their potential in biological control. J Parasitol 87:1355 1359 Samish M, Ginsberg H, Glazer I (2004) Biological control of ticks. Losson Originally published in the journal Experimental and Applied Acarology, Volume 46, Nos 1 4, 95 104. Biological control is considered as a realistic alternative to chemotherapeutic control. Laboratory experiments were carried out to evaluate the pathogenicity and the thermotolerance of twelve isolates of entomopathogenic fungi from four genera (Beauveria Vuillemin, Metarhizium Sorokin, Paecilomyces Bainier and Verticillium Nees). At this concentration the entire mite population became infected with all isolates but B. The thermotolerance of each isolate was evaluated by measuring its growth on an articial medium kept between 25 and 37. These two isolates could be considered as good candidates for further use as biopesticide taking into account their virulence and thermotolerance. Other critical factors linked with the implementation of this type of biocontrol in P. Keywords Psoroptes ovis Biological control Entomopathogenic fungi Temperature Virulence M. Nevertheless treatment failures and environmental consid- erations have led to the development of alternative approaches, particularly the use of entomopathogenic fungi (Smith et al. Because infection by entomopathogenic fungi such as Beauveria and Metarhizium species results from direct penetration of the tegument without any requirement for ingestion, these organisms often display wide host ranges. There is a growing literature dealing with their virulence and use in insects, ticks and other members of the class Arachnida (Kaaya and Munyinyi 1995; Chandler et al. Additionally inter- and intraspecic differences in the pathogenicity were observed in different arthropod species (Ferron and Diomande 1969; Daoust and Roberts 1982; Barson et al. To abate the development of psoroptic mange, 50% of the mite population must be killed every 2 days (Wall et al. These two factors were unfortunately not achieved with the isolates 8 -1 evaluated by these authors at a concentration of 10 conidia ml. It seemed thus inter- esting to test various isolates belonging to different genera and species in order to identify a highly virulent one. Moreover the high temperature prevailing at the skin surface of the hosts could limit the use of these fungi for the control of P. Indeed the temperature at the skin level varies between 31 and 37 C in sheep, and between 30 and 35 C in cattle (Brooks et al. However, differences can be observed between isolates with respect to thermotolerance. The aim of the present study was thus to investigate in twelve entomopathogenic fungal isolates the in vitro pathogenicity against P. These isolates belonged to four genera and originated from temperate and tropical areas. Materials and methods Mites Psoroptes mites were isolated from the ears of chronically infested rabbits maintained at the laboratory of the Faculty of Veterinary Medicine, Liege,` Belgium.

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Am Entomol 40:240 253 Skirvin D buy generic sildenafil 25 mg online, Fenlon J (2003a) Of mites and movement: the effect of plant connectedness and temperature on movement of Phytoseiulus persimilis buy sildenafil 25mg without a prescription. Biol Control 27:242 250 Skirvin D cheap 50 mg sildenafil fast delivery, Fenlon J (2003b) The effect of temperature on the functional response of Phytoseiulus persimilis (Acari: Phytoseiidae) sildenafil 25 mg low price. Nature 361:66 68 Sut akova G (1988) Electron microscopic study of developmental stages of Rickettsiella phytoseiuli in Phytoseiulus persimilis Athias-Henriot (Gamasoidea: Phytoseiidae) mites. Acta Virol 32:50 54 Sut akova G (1991) Rickettsiella phytoseiuli and its relation to mites and ticks. Academia, Praque, pp 45 48 Sut akova G (1994) Phenomenon of Rickettsiella phytoseiuli in Phytoseiulus persimilis mite. Acta Entomol Bohemoslov 87:431 434 Sut akova G, Rehacek J (1989) Experimental infection with Rickettsiella phytoseiuli in adult female Der- macentor reticulatus (Ixodidae): an electron microscopy study. Exp Appl Acarol 7:299 311 Sut akova G, Ruttgen F (1978) Rickettsiella phytoseiuli and virus-like particles in Phytoseiulus persimilis (Gamasoidea: Phytoseiidae) mites. Int J Syst Evol Microbiol 54:961 968 Zemek R, Nachman G (1999) Interaction in tritrophic acarine predator-prey metapopulation system: prey locationanddistancemovedbyPhytoseiuluspersimilis(Acari:Phytoseiidae). ExpApplAcarol23:21 40 Symbionts, including pathogens, of the predatory mite Metaseiulus occidentalis: current and future analysis methods Marjorie A. Jeyaprakash Originally published in the journal Experimental and Applied Acarology, Volume 46, Nos 1 4, 329 347. Until molecular tools became available, analysis meth- ods were limited primarily to microscopic observations; some viruses and rickettsia-like organisms were observed infecting diseased M. A new phylogenetic analysis of the Bacteroidetes-Flavobacterium group suggests the unnamed Bacteroidetes in M. However, much of our current information about the role these microorganisms play in the biology of M. We also currently lack any knowledge of the importance of these microorganisms under Weld conditions. Keywords Phytoseiidae Metaseiulus (= Typhlodromus or Galendromus) occidentalis Microbial symbionts Pathogens Assessment methods Metagenomics Bacteroidetes Wolbachia Cardinium Enterobacter Oligosporidium Viruses Serratia M. It has been imported and established in Australia and New Zealand in classical biological control programs for the control of mites in apple and peach orchards (Readshaw 1975; Field 1978). Between 1970 and early 1981, at least 470 papers were published on the Phytoseiidae (Tanigoshi 1982) and between 1960 and 1994, more than 420 papers were published on M. The number of chromosomes (3 and 6 in males and females, respectively) and the genetic system of M. Whether this unusual genetic system is inXuenced by the microbial associates (Wolbachia or Cardinium) of M. Whether pesticide-resistant microbial symbionts are associated with these resistances also remains unknown, but many soil microorganisms have been documented to degrade pesticides (Felsot 1989) and microbial gut symbionts of a tephritid have been implicated in the pesticide resistance of its host (Boush and Matsumura 1967). Because mitochondrial organelles are derived from endosymbiotic bacteria, these unusual features will be discussed brieXy below. Diseases of Mites and Ticks 331 Despite this extensive research conducted over the past 60 years, until recently we knew little about the microbial associates of M. We adhere to the term symbiosis in its original deWnition of organisms living together, usu- ally in close association with one another, to the beneWt of at least one organism, with the partners referred to as symbionts. Infection by a particular bacterium may be beneWcial to a host under some circumstances but harmful in other hosts or environ- ments. At one extreme are the ancient symbionts that live in specialized bacteriomes (host organs or cells specialized for housing the symbionts) and are required by their hosts. Facultative symbionts may not reside exclusively in specialized organs and are not strictly necessary for host survival. Pathogenic symbionts may be pathogens at all times, or they may become pathogenic only when the host immune system allows the microorganism to increase in density. The goal of this review is to discuss what we know about the microbial associates (whether they are called endosymbionts, mutualists, pathogens, or have an unknown rela- tionship) of this important predator and provide a brief overview of what can be learned as new methods are applied to understanding these relationships. Then we will discuss what we know (and don t) about the microbial endosymbionts of M. In addition, we will discuss some of the methodological issues restricting our understanding of these relationships. One was located in epithelial cells, and was 47 nm in diameter with a 35-nm electron dense core. Some particles appeared hexagonal in cross section and were some- times associated with paracrystalline structures. Poinar and Poinar (1998) indicated these icosahedral particles were similar to those reported in Panonychus citri (McGregor), and also were similar to the icosahedral particles found in epithelial cells of infected and healthy T. These particles occurred in large numbers in the midgut nuclei, but free virions also were found in the cytoplasm of the gut cells and the lumen of the midgut. It is not clear if one or more of these viruses were the cause of symptoms observed in these laboratory colonies of M. Nor do we know whether the viruses occur in Weld populations because the specimens provided were all from crowded laboratory 332 J. Much more needs to be done to resolve the eVects, if any, of viruses on the biology of M. Microsporidia A new species of microsporidium, Oligosporidium occidentalis, was described by Becnel et al. Both ultrastructural and molecular data were used to describe the species, which is in the Nosema/Vairimorpha clade of microsporidia based on molecular data, although the morphological and molecular data are not congruent. Sporogony is disporoblastic and spores are formed in eggs, immatures, and adults of M. There are two types of spores, one with a short and one with a longer polar Wlament. Horizontal transmission occurs by cannibalism of eggs and other stages and perhaps involves the spores with the long polar Wlament. Spores with the short polar Wlament may play a role in autoinfection and vertical (transovarial) transmission, which is highly eYcient in transferring the microsporidium from adults of M. The sequence data were unique, but most closely related to sequences obtained from GenBank from Nosema apis (U26534), N. There are other recent examples where mor- phological and molecular data conXict and future molecular data on microsporidia from other mites and arachnids, as well as members of the Unikaryonidae, may establish better relationships. Infection status appeared to have no eVect on male longevity or progeny survival to larval and adult stages. Three diVerent heat treatments were tested to determine if it was possible to heat-cure the colonies (Olson and Hoy 2002). By contrast, Diseases of Mites and Ticks 333 when Go eggs were deposited within the growth chamber and they and their progeny (G1) were reared to adulthood at 33 C, all the G1 mites were disease free.

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Folic acid-supplemented groups had significantly lower toxicity scores (duration of toxic events intensity clinical severity factor per 4 weeks in the protocol) buy sildenafil 50mg with mastercard. Among 28 patients in the placebo group order 25mg sildenafil with mastercard, dietary folate was negatively correlated with toxicity score safe sildenafil 25mg. Negligible toxic effects were observed when dietary folate intake exceeded 400 g per day cheap sildenafil 25 mg mastercard. Interaction of Glutamine With Methotrexate Glutamine is another nutrient that has been reported to have a significant inter- action with methotrexate (38 40). Animals on a 3% glutamine-supplemented diet for 35 days had a 25% lower mean methotrexate total serum clearance and 65% lower renal methotrexate elimination compared with animals on a control diet (3% glycine diet). An increased methotrexate concentration with glutamine supplementation may increase the risk for methotrexate toxicity if the methotrexate dose is not adjusted. Rheumatic diseases are chronic inflammatory conditions that put patients at higher risk of oxidative stress; therefore, antioxidant nutrient requirements may increase. Methotrexate treatment decreases folate levels and corticosteroid treatment can cause low calcium and zinc status. Symptoms of rheumatic diseases such as pain and joint problems may lower appetites or limit patients from getting access to a variety of fresh ingredients. Concomitant consumption of food with medication can greatly influence absorption and efficacy of drugs. Specific instruction for the timing of medication is important for timely action and maximal absorption of drugs. Folate deficiency is frequently observed in patients with rheumatic disease, especially those treated with methotrexate. Lower folate status can adversely impact toxic effects of methotrexate therapy, resulting in discontinuation of the therapy. Patients should be encouraged to consume a balanced diet to at least meet the recom- mended dietary allowance for folate (400 g per day for adults) to minimize side effects of methotrexate. When it is hard to achieve proper levels of folate from the diet, folate supplementation, at an individually adjusted level, should be considered to provide some protection from toxicity of methotrexate therapy. However, levels or ranges of n-3 fatty acids that provide consistent clinical effects are not well defined. Drug nutrient interactions of commonly used drugs in rheumatic diseases are listed in Table 1. Drug, meal and formulation interactions influencing drug absorption after oral administration. Influence of sulphasalazine, methotrexate, and the combi- nation of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption. Ibuprofen extrudate, a novel, rapidly dissolving ibuprofen formulation: relative bioavailability compared to ibuprofen lysinate and regular ibuprofen, and food effect on all formulations. The effect of food on the bioavailability of ibuprofen and flurbiprofen from sustained release formulations. Nabumetone a novel anti- inflammatory drug: the influence of food, milk, antacids, and analgesics on bioavailability of single oral doses. Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite. Long-term effect of omega-3 fatty acid supple- mentation in active rheumatoid arthritis. Reduction of cardiovascular risk factors with longterm fish oil treatment in early rheumatoid arthritis. Dietary fish oil impairs primary host resistance against Listeria monocytogenes more than the immunological memory response. Fish oil feeding delays influenza virus clearance and impairs production of interferon-gamma and virus-specific immunoglobulin A in the lungs of mice. Vitamin E supple- mentation suppresses prostaglandine E2 synthesis and enhances the immune response of aged mice. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Proinflammatory and Anti-inflammatory Cytokines in Rheumatoid Arthritis: A Primer for Clinicians, 2nd ed. How does infliximab work in rheumatoid arthritis Arthritis Res 2002;4(suppl 2):S22 S28. Risk and prevention of tuberculosis and other serious opportunistic infections associated with the inhibition of tumor necrosis factor. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. Immunologic effects of national cholesterol education panel Step-2 diets with and without fish-derived n-3 fatty acid enrichment. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Effect of a glutamine- supplemented enteral diet on methotrexate-induced enterocolitis. Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis. Hurley Summary Physical activity and exercise are safe and beneficial for the vast majority of people, including those with rheumatic disease. Therefore, an adequate level of habitual physical activity is vital for everyone, including people with arthritis. Physical activity is defined as any bodily movement produced by skeletal muscles and resulting in energy expenditure (1). It is planned, structured, and repetitive, and produces an improvement or maintenance of one or more facets of physical fitness (e. Historically, exercise science investigated healthy, active, young males or athletes. Consequently, much of the information about fitness testing and the recommenda- tions for exercise prescription to improve physical fitness indicated intensive exercise regimens were needed. However, studies are beginning to show that less fit, healthy people or people with musculoskeletal impairment and rheumatic disease do not need to participate in intense exercise programs to obtain health benefits (2,3). For people with rheumatic conditions, physical activity is as important as it is for the healthy population.

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