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Adequate Levels (adequate + level)
Selected AbstractsConformational analysis of arginine in gas phase,A strategy for scanning the potential energy surface effectivelyJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 3 2008Sebastian Schlund Abstract The determination of all possible low-lying energy conformers of flexible molecules is of fundamental interest for various applications. It necessitates a reliable conformational search that is able to detect all important minimum structures and calculates the energies on an adequate level of theory. This work presents a strategy to identify low-energy conformers using arginine as an example by means of a force-field based conformational search in combination with high-level geometry optimizations (RI-MP2/TZVPP+). The methods used for various stages in the conformational search strategy are shown and various pitfalls are discussed. We can show that electronic energies calculated on a DFT level of theory with standard exchange-correlation functionals strongly underestimate the intramolecular stabilization resulting from stacked orientations of the guanidine and carbonyl moiety of arginine due to the deficiency of DFT to describe dispersion effects. In this case by usage of electron correlation methods, low energy conformers comprising stacked arrangements that are counterintuitive become favorable. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] Inhibition of neural activity depletes orexin from rat hypothalamic slice cultureJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2010Shotaro Michinaga Abstract Orexins (hypocretins) are neuropeptides produced by a small population of hypothalamic neurons whose dysregulation may lead to narcolepsy, a neurological disorder characterized by disorganization of sleep and wakefulness. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors causes preferential loss of orexin neurons in the hypothalamus, whereas an adequate level of neuronal excitatory activities is generally known to be important for the maintenance of central neurons. By examining the effect of manipulation of neural activity, we found that 24,72 hr application of tetrodotoxin (TTX) caused a substantial decrease in the number of orexin-immunoreactive neurons, but not of melanin-concentrating hormone-immunoreactive neurons, in hypothalamic slice culture. Similar results were obtained when neural activity was arrested by added extracellular Mg2+. Reduction of orexin expression by TTX and Mg2+ was also observed at mRNA level. The decrease of orexin-immunoreactive neurons was attributable to depletion of orexin, because it was reversible after washout of TTX or elevated extracellular Mg2+ and was not associated with induction of cell death. Blockers of voltage-dependent Ca2+ channels as well as of NMDA receptors also induced a significant and selective decrease of orexin-immunoreactive neurons. Moreover, TTX-induced decrease of orexin immunoreactivity was largely abrogated by concurrent application of a moderate concentration of NMDA. These results suggest that Ca2+ entry associated with nontoxic levels of spontaneous activity of glutamatergic inputs plays an important role in the maintenance of orexin neurons in a tissue culture model. © 2009 Wiley-Liss, Inc. [source] Psychosocial Factors Affecting Adults With Intellectual Disabilities With Psychiatric Disorders in Cali, ColombiaJOURNAL OF POLICY AND PRACTICE IN INTELLECTUAL DISABILITIES, Issue 3 2009Miguel Ángel Verdugo Abstract Increases in life expectancy have heightened concerns for people with intellectual disability (ID) who are growing old and who have be designated as "dually diagnosed",that is, who have, apart from their ID, a psychiatric disorder, and who because of this conjoint condition, are subjected to social exclusion due to three factors: old age, cognitive limitation, and mental illness. The objective of this study was to describe the psychosocial factors associated with the comorbidity between ID and psychiatric disorder of adults in the city of Cali, Colombia. Subjects were 50 dyads consisting of a carer and a person with ID. The Caregivers Questionnaire and the Integral Quality of Life Scale were adapted for use in the study. The analysis of information was based on three factors: person, family, and society. In the case of the personal factor, an adequate level of physical well-being and a good level of self-care were found in more than 60% of the adults with dual diagnosis, good adherence to treatment in 82%, and medium satisfaction in the individual-context relationship in 54%. With regard to the family factor, a high level of satisfaction of needs (84%) was found. Good family functioning was observed in 86%, while family participation in rehabilitation was reported to be between moderate and deficient in 60% of the cases. With respect to the social factor, cases of support between moderate and deficient were found in 68%, and a regular inclusion was observed in 48%. The authors conclude that the family functioning aspect appeared as the major protective factor, while the inclusion and social support were shown as the main risk factors. [source] Vitamin/mineral supplements: of questionable benefit for the general populationNUTRITION REVIEWS, Issue 4 2010Donald B McCormick In the United States today, there is a multibillion dollar industry in dietary supplements with at least a third sold as vitamin/mineral pills and drinks. Though everyone requires small amounts of these essential micronutrients, and supplements are of benefit to some within the population, the considerable majority of people can fulfill their needs with the intake of healthy diets of mixed foods. In addition, the fortification of some processed foods adds extra amounts of several micronutrients, especially those for which there is deemed to be a need in special segments of our population. In spite of this safe and adequate level of intake, there are many who have been led to believe that the frequent ingestion of supplements will be helpful in their efforts to maintain optimal health, live longer, and even prevent or cure non-deficiency diseases. It is the intent of this article to unravel the causes and misconceptions behind this practice and to emphasize that most of the money spent on unnecessary supplementation could be better used for other purposes. [source] China rose (Hibiscus rosasinensis) petals: a potent natural carotenoid source for goldfish (Carassius auratus L.)AQUACULTURE RESEARCH, Issue 11 2007Archana Sinha Abstract Goldfish (Carassius auratus) are in demand in world markets due to their attractive golden colour. Carotenoids are the primary source of colour in the skin of fish. To optimize the colour in captivity, fish must obtain an adequate level of carotenoids in their feed. With this objective, four natural colour enhancers were tested. A common batch of feed was divided into five equal portions and colour ingredients, spirulina (D-S), china rose petals (D-C), marigold petals (D-M) and Lactobacil, a commercial probiotic (D-L), were added at 5 mg kg,1 to four portions of feed; one portion (D-O) was kept as a control without any additive. A feeding trial was conducted for 8 weeks. Each 70 L aquarium was stocked with 10 fish (average weight 1.6 g) and feed was given at 5% of the body weight. Growth rate, survival, biochemical composition and pigmentation in the skin of fish were measured. Histological studies of gonads were also conducted. Growth of fish in different treatments was significantly different. There was no difference in the proximate composition of the fish at the start of the experiment but after 8 weeks of feeding, fish fed the diet supplemented with china rose petals had a lower moisture content (70.48%) and higher protein (17.7%) and lipid (5.25%) levels than the group fed the control diet. Pigmentation was the highest (4.01 ,g g,1) in D-C, followed by D-M (3.16 ,g g,1), D-S (2.92 ,g g,1) and D-L (2.84 ,g g,1) and the lowest (0.24 ,g g,1) in D-O. Gonad development of fish fed with the D-C diet was better compared with the gonads of control (D-O) fish, followed by D-M-, D-L- and D-S-fed fish. Gonads of fish, fed D-C, showed well-marked changes in the testis where a large number of seminiferous tubules bound together by means of a thin layer of connective tissue were observed. These tubules were highly convoluted and were separated from each other by thin connective tissue stroma. The intra space contained connective tissue, blood capillaries and interstitial cells. The spermatogonia could be seen as a large spherical cell containing a large central nucleus with a distinct nucleolus. The study shows that the china rose (Hibiscus rosasinensis) petal is a potent natural carotenoid source for goldfish to enhance its colour and also accelerate gonadal development. [source] LMI Approach to Guaranteed Cost Control for Networked Control SystemsASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 3-4 2005Shanbin Li This paper addresses the time-varying but bounded delay issue of networked control systems (NCS) within the framework of a discrete-time linear state-delayed system with norm-bounded uncertainty. A delay-dependent sufficient condition for the existence of a guaranteed cost controller for NCS is presented by a new Lyapunov-Krasovskii functional. The condition is formulated as a set linear matrix inequalities (LMIs). The resulting controller can not only asymptotically stabilize the system but also guarantee an adequate level of performance. Theoretical analysis and simulation results show that the control strategy presented in this paper is effective and feasible. [source] Guaranteed Cost Sampled-Data Control for Refining ProcessASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 1-2 2001Yingquan Lu This paper presents a synthetic design procedure of guaranteed cost sampled-data control (GCSDC) for refining process. When a digital controller controls the refining process with appropriate sample and hold devices, the closed loop system is periodic time varying. Based on this sampled-data system, considering the uncertainties in the continuous-time plant, we define the guaranteed cost control and a controller that not only stabilizes the closed loop system but also guarantees an adequate level of the performance. Simulation results show that the control scheme is effective and practicable. [source] Protecting IPTV against packet loss: Techniques and trade-offsBELL LABS TECHNICAL JOURNAL, Issue 1 2008Natalie Degrande Packet loss ratios that are harmless to the quality of data and Voice over Internet Protocol (VoIP) services may still seriously jeopardize that of Internet Protocol television (IPTV) services. In digital subscriber line (DSL)-based access networks, the last mile in particular suffers from packet loss, but other parts of the network may do so too. While on the last mile link, the packet loss is due to bit errors, in other parts of the network it is caused by buffers overflowing or the network experiencing (short) outages due to link or node failures. To retrieve lost packets, the application layer (AL) can use either a forward error correction (FEC) or a retransmission scheme. These schemes, when properly tuned, increase the quality of an IPTV service to an adequate level, at the expense of some overhead bit rate, extra latency, and possibly an increase in channel change time. This paper compares the performance of FEC schemes based on Reed-Solomon (RS) codes with that of retransmission schemes, all tuned to conform to the same maximum overhead bit rate allowed on the last mile link and on the feeder link, and their possible impact on the channel change time. We take into account two kinds of loss processes that can occur: isolated packet losses and burst packet losses. In almost all scenarios, retransmission outperforms FEC. © 2008 Alcatel-Lucent. [source] Development of lentiviral vectors for gene therapy for Usher syndrome type 1BACTA OPHTHALMOLOGICA, Issue 2007T HASHIMOTO Purpose: Usher 1B, one of the major subtypes of a combined blindness and deafness disease, is caused by mutations in the MYO7A gene, which encodes a large unconventional myosin expressed in the retinal pigment epithelium (RPE) and photoreceptor (PR) cells. This study aims at developing viral vectors expressing the wild type human MYO7A at an adequate level in order to rescue cellular phenotypes of MYO7A mutation. Methods: The full-length (7 kb) human MYO7A cDNA was cloned into the third generation, self-inactivating lentiviral vector under different promoters and enhancers. Human genomic 4-kb DNA fragment including exon 1 through 2 was cloned by PCR. Activities of different promoters and enhancers were tested by reporter assays using ARPE-19 cells. Previously identified Myo7a-null phenotypes in shaker-1 mouse were used to test the efficacy of various lentiviruses. Results: Lentiviral vectors could successfully transduce large genes (up to 7.6 kb) in vitro and in vivo for the purpose of gene therapy. Reporter assay indicated that regions with a suppressor activity and an enhancer activity existed within intron 1. The CMV promoter drove excessive MYO7A expression in the RPE, and thus caused cell death. A chimeric promoter that consists of partial CMV promoter with 160-bp MYO7A enhancer could direct moderate levels of gene expression in RPE and PR in vivo, and rescued a number of phenotypes in the mutant mice. Conclusions: These results illustrate the importance of regulating transgene expression levels in achieving therapeutic outcomes. They demonstrate the efficacy of lentivirus-mediated expression of the large MYO7A cDNA as a gene therapy strategy for correcting the MYO7A deficiency underlying Usher 1B. [source] The Pharmacokinetics of Antiepileptic Drugs in Rats: Consequences for Maintaining Effective Drug Levels during Prolonged Drug Administration in Rat Models of EpilepsyEPILEPSIA, Issue 7 2007Wolfgang Löscher Summary:, Rodent models of chronic epilepsy with spontaneous recurrent seizures likely represent the closest parallel to the human condition. Such models may be best suited for therapy discovery for pharmacoresistant epilepsy and for antiepileptogenic or disease-modifying therapeutics. However, the use of such rodent models for therapy discovery creates problems with regard to maintaining effective drug levels throughout a prolonged testing period. This is particularly due to the fact that rodents such as rats and mice eliminate most drugs much more rapidly than humans. Thus, knowledge about elimination rate of a test drug in a laboratory species is essential for development of a treatment paradigm that allows maintaining adequate drug levels in the system over the period of treatment. Currently, the most popular models of epilepsy with spontaneous seizures are poststatus epilepticus models of temporal lobe epilepsy in rats. Such models are both used for studies on antiepileptogenesis and drug resistance. For validation of these models, current antiepileptic drugs (AEDs) have to be used. In this article, the elimination rates of these AEDs and their effective plasma levels in rats are reviewed as a guide for developing treatment protocols for chronic drug testing. The advantages and disadvantages of several technologies for drug delivery are discussed, and some examples for calculation of adequate treatment protocols are given. As shown in this review, because of the rapid elimination of most AEDs in rats, it is no trivial task to maintain effective steady-state AED levels in the plasma throughout the day over multiple days to ensure that there will be adequate levels in the system for the purpose of the experiment. However, the use of an adequate dosing regimen that is based on elimination rate is an absolute prerequisite when using rat models for discovery of new antiepileptogenic therapies or therapies for pharmacoresistant epilepsy, because otherwise such models may lead to erroneous conclusions about drug efficacy. [source] An evidence-based approach to equine parasite control: It ain't the 60s anymoreEQUINE VETERINARY EDUCATION, Issue 6 2010R. M. Kaplan Summary Most veterinarians continue to recommend anthelmintic treatment programmes for horses that derive from knowledge and concepts more than 40 years old. However, much has changed since these recommendations were first introduced and current approaches routinely fail to provide optimal or even adequate levels of parasite control. There are many reasons for this. Recent studies demonstrate that anthelmintic resistance in equine parasites is highly prevalent and multiple-drug resistance is common in some countries, but few veterinarians take this into account when making treatment decisions or when recommending rotation of anthelmintics. Furthermore, the current approach of treating all horses at frequent intervals was designed specifically to control the highly pathogenic large strongyle, Strongylus vulgaris. But this parasite is now quite uncommon in managed horses in most of the world. Presently, the cyathostomins (small strongyles) are the principal parasitic pathogens of mature horses. The biology and pathogenesis of cyathostomins and S. vulgaris are very different and therefore require an entirely different approach. Furthermore, it is known that parasites are highly over-dispersed in hosts, such that a small percentage of hosts harbour most of the parasites. The common practices of recommending the same treatment programme for all horses despite great differences in parasite burdens, recommending prophylactic treatment of all horses without indication of parasitic disease or knowing what species of parasites are infecting the horses, recommending use of drugs without knowledge of their efficacy and failing to perform diagnostic (faecal egg count) surveillance for estimating parasite burdens and determining treatment efficacy, are all incompatible with current standards of veterinary practice. Consequently, it is necessary that attitudes and approaches to parasite control in horses undergo a complete overhaul. This is best achieved by following an evidence-based approach that takes into account all of these issues and is based on science, not tradition. [source] Changes in subgingival microflora and humoral immune response following periodontal therapyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2001I. B. Darby Abstract Objectives: To investigate the effect of scaling and root planing (SRP) on the microflora and humoral immune response in adult periodontitis. Materials & Methods: Clinical measurements, subgingival plaque samples, gingival crevicular fluid and sera were taken from 4 sites in 28 adult periodontitis patients before and after SRP. Polymerase chain reaction was used to determine the presence of A. actinomycetemcomitans, P. gingivalis,B. forsythus, P. intermedia, and T. denticola. ELISA was used to investigate the systemic and local antibody titres to these organisms, and thiocyanate dissociation for the determination of serum antibody avidity. Results: SRP produced a good clinical improvement. On a subject basis there was little significant change in the microflora. However, on a site basis, there were significant reductions in P. intermedia, B. forsythus and T. denticola. There was little change in systemic and local antibody titres following SRP, although there was a significant reduction in antibody avidity to P. gingivalis and P. intermedia Conclusion: Post-therapy clinical improvement was associated with a reduction in bacterial prevalence, but statistical significance was only reached at a site level and this microbial reduction was not significant for all organisms. No significant post-therapy effects on the humoral immune response were noted other than a reduced antibody avidity to P. gingivalis and P. intermedia. The lack of a clear pattern in the humoral immune response may reflect a failure of the host response to produce adequate levels of biologically functional antibodies, and complex interactions between the subgingival flora and the host response. Zusammenfassung Ziele: Untersuchung des Effektes von Scaling und Wurzelglättung (SRP) auf die Mikroflora und menschliche Immunantwort bei der Erwachsenen-Parodontitis. Material und Methoden: Klinische Messungen, subgingivale Plaqueproben, gingivale Sulkusflüssigkeit und Serum wurden von 4 Flächen bei 28 Patienten mit Erwachsenen-Parodontitis vor und nach SRP aufgenommen. Die Polymerase-Ketten-Reaktion wurde genutzt, um die Präsenz von A. actinomycetemcomitans, P. gingivalis, B. forsythus, P. intermedia und T. denticola zu bestimmen. ELISA wurde für die Bestimmung der systemischen und lokalen Antikörpertiter gegen diese Organismen genutzt. Die Thiocyanat-Dissoziation wurde für die Bestimmung der Serumantikörperaktivitart genutzt. Ergebnisse: SRP erbrachte eine gute klinische Verbesserung. Auf der Basis der Person gab es eine geringe signifikante Veränderung der Mikroflora. Jedoch gab es auf der Basis der Fläche eine signifikante Reduktion von P. intermedia, B. forsythus und T. denticola. Geringe Veränderungen in den systemischen und lokalen Antikörpertitern in der Folge von SRP waren zu beobachten, obwohl eine signifkante Reduktion der Antikörperaktivität zu P. gingivalis und P. intermedia vorhanden war. Schlußfolgerung: Die posttherapeutischen klinischen Verbesserungen waren mit einer Reduktion der bakteriellen Prävalenz verbunden, die statistische Signifikanz wurde aber nur auf der Basis der Fläche erreicht, und diese mikrobielle Reduktion war nicht signifikant für alle Organismen. Keine signifikanten posttherapeutischen Effekte auf die menschliche Immunantwort wurden außer einer reduzierten Antikörperaktivität zu P. gingivalis und P. intermedia beobachtet. Der Mangel in einem klaren Muster in der menschlichen Immunantwort könnte einen Fehler in der Wirtsantwort zur Produktion adäquater Level von biologisch funktionellen Antikörpern und komplexen Interaktionen zwischen der subgingivalen Flora und der Wirtsantwort reflektieren. Résumé But: L'objectif de cette étude est de rechercher les effets du détartrage et du surfaçage radiculaire (SRP) sur la microflore et la réponse immunitaire humorale chez des patients atteints de parodontite de l'adulte. Méthodes: Les mesures cliniques, les échantillons de plaque sous-gingivale, le fluide gingivale et le serum ont été prélevés sur 4 sites chez 28 patients atteints de parodontite de l'adulte avant et après SRP. La réaction de polymérase en chaine a été utilisé pour déterminer la présence de Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus, Prevotella intermedia et Treponema denticola. Le test ELISA a été utilisé pour rechercher les titres d'anticorps locaux et systèmiques vis à vis de ces organismes, et la dissociation au thiocyanate a été utilisée pour la détermination de l'avidité des anticorps sériques. Résultats: SRP entrainait une bonne amélioration clinique. Individuellement par patient, il y avait peu de modifications de la microflore. Cependant, en ce qui concerne les sites, il y avait des réductions significatives de Prevotella intermedia, Bacteroides forsythus et Treponema denticola. Il y avait peu de changements pour les titres d'anticorps systèmiques et locaux suite au SRP, bien que l'on observait une réduction significative de l'avidité des anticorps envers Porphyromonas gingivalis et Prevotella intermedia. Conclusions: L'amélioration clinique consécutive au traitement était associée avec une réduction de la prévalence bactérienne, mais une signification statistique n'était obtenue que pour les sites, et cette réduction microbienne n'était pas significative pour tous les organismes. Suite au traitement, aucun effet significatif sur la réponse immunitaire humorale n'était mis en évidence, en dehors de la diminution de l'avidité des anticorps vis à vis de Porphyromonas gingivalis et Prevotella intermedia. L'absence de caractéristiques nettes de la réponse immunitaire humorale pourrait reflèter l'échec de la réponse de l'hôte à produire des niveaux suffisants d'anticorps biologiquement fonctionnels, et également les interactions complexes entre la flore sous-gingivale et cette réponse de l'hôte. [source] Identification of Cochliobolus sativus (Spot Blotch) Isolates Expressing Differential Virulence on Barley Genotypes in SyriaJOURNAL OF PHYTOPATHOLOGY, Issue 8-9 2004M. I. E. Arabi Abstract Spot blotch, caused by Cochliobolus sativus, is a common foliar disease of barley. Information on the variability of virulence in C. sativus is essential for the production of spot-resistant barley cultivars. The virulence variability of isolates of this pathogen collected from different regions of Syria was evaluated using 10 differential barley genotypes originating from widely dispersed areas. Genotypes showed a continuous range of response from very susceptible to moderately resistant but none was immune to the disease. A cluster analysis indicated that the isolates had distinct differential virulence patterns within the three groups. A mean disease rating of 3.71 was the separation point between avirulent and virulent reactions. The data demonstrated that variation occurred in the virulence of and the resistance level to isolates and among genotypes, respectively. Isolate C41 exhibited distinct differential virulence patterns, high frequency and low variance in all genotypes. To incorporate adequate levels of resistance into future barley genotypes, disease evaluations should be made with C. sativus isolates that express the full spectrum of virulence found in Syria. [source] Optimizing outcomes with incretin-based therapies: Practical information for nurse practitioners to share with patientsJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 2009BC-ADM, C-RNP, CDE Nurse Practitioner, Evelyne Fleury-Milfort MSN, Instructor in Clinical Medicine Abstract Purpose: To introduce the role of incretin therapies and suggest strategies for nurse practitioners to implement them in practice. Data sources: PubMed, Medline, summary of product characteristics/package inserts. Conclusions: Incretin-based therapies offer a new alternative to currently available agents. They provide adequate levels of glycemic control and are associated with low incidence of hypoglycemia and weight gain. Dipeptidyl peptidase-4 inhibitors, for example sitagliptin, have a modest effect on A1c levels (,0.7%) as monotherapy; however, they reduce A1c to a greater extent when combined with metformin (,2.0%). Typical starting dose of sitagliptin is 100 mg; dose adjustments are required in subjects with renal complications. Glucagon-like peptide-1 receptor agonists, exenatide and liraglutide, reduce A1c levels (often in excess of 1.5%) and body weight. Exenatide has a starting dose of 5 ,g and is not recommended for patients with hepatic impairment or severe/end-stage renal disease. Liraglutide has been found to benefit from a stepwise dose escalation (i.e., 0.6 mg weekly increments) until a 1.8-mg dose is reached. Unlike exenatide, dose adjustments in patients with renal and hepatic complications are not required. Implications for practice: Incretin-based therapies may help to overcome some of the drawbacks of current therapies used to treat type 2 diabetes. [source] High Level of Immunity against Poliomyelitis in Albanian Refugees in Southern ItalyJOURNAL OF TRAVEL MEDICINE, Issue 3 2000P.L. Lopalco Background: The Apulia region (Southern Italy) may be considered a "border region" which, due to its position, has to face daily arrivals of refugees, especially from Albania. When the exodus of Albanians took place in 1991, a seroepidemiologic study revealed a low seroimmunity to poliomyelitis. In 1996, a large outbreak of paralytic poliomyelitis occurred in Albania. The aim of the study was to evaluate the poliomyelitis immunization level in a sample of Albanian refugees who arrived in the Apulia region between April and May 1997. Methods: Blood samples were obtained, after informed consent and on a voluntary basis, from 667 subjects housed in seven refugee camps in the Apulia region. Titration of neutralizing antibodies to the three polioviruses was carried out. Results: The findings showed that Albanian refugees had adequate levels of immunity to all polioviruses (95%for poliovirus type 1, 98.6%for poliovirus type 2 and 91.4%for poliovirus type 3). Moreover, a high immunization rate was found in all age groups irrespective of the areas of origin of the refugees and their socioeconomic conditions. Conclusions: Our findings show that Albanian refugees in Apulia region have adequate levels of immunity against polioviruses and confirm the effectiveness of mass vaccination campaigns with OPV conducted by WHO in Albania following an outbreak of poliomyelitis in 1996. [source] First-line therapy for chronic myeloid leukemia: Past, present, and future,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Carolina Pavlovsky The development of Bcr-Abl tyrosine kinase inhibitors has dramatically changed the prognosis of patients with newly diagnosed chronic myeloid leukemia (CML). Standard-dose imatinib (400 mg/day in chronic phase, 600 mg/day in advanced CML) now dominates the management of this disease, producing considerably higher hematologic, cytogenetic, and molecular response rates than seen with previous drug therapies. However, although many patients respond well to standard-dose imatinib initially, some patients do not achieve adequate levels of response or discontinue therapy because of resistance. One approach to improving treatment response with first-line imatinib may be to increase the imatinib dose (800 mg/day), although recent trial data indicate that overall increases in response rates may be modest. Newer Bcr-Abl tyrosine kinase inhibitors can induce responses in patients with all phases of imatinib-resistant CML, even those with imatinib-resistant mutations in the BCR-ABL gene. Furthermore, in initial studies, first-line dasatinib or nilotinib treatment has produced response rates that compare favorably with historical controls treated with imatinib, although confirmation is required from head-to-head clinical trials. Future clinical approaches may include drug combinations, which may allow quiescent leukemia stem cells to be eradicated. Further improvements in drug treatment for first-line CML are expected during the next few years. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Sources of protein in two semi-arid zone mistletoe specialists: Insights from stable isotopesAUSTRAL ECOLOGY, Issue 7 2009LAURENCE P. BAREA Abstract Obtaining adequate levels of dietary protein is essential for the physiology of consumers. This presents potential problems for frugivorous birds because fruit is generally low in protein rendering it nutritionally inadequate and potentially explaining the rarity of exclusive frugivory in birds. We addressed this issue by determining the isotope composition (15N/14N) in the whole blood of two mistletoe consumers, that is, painted honeyeater (Grantiella picta, Meliphagidae) and mistletoebird (Dicaeum hirundinaceum, Dicaeidae) during the grey mistletoe (Amyema quandang, Loranthaceae) fruiting peak in a semi-arid woodland, NSW, Australia. Grey mistletoe fruit pulp and arthropods were isotopically distinct (mean ,15N fruit 4.4,vs. arthropods 7.1,), thus readily discriminated using the stable isotope approach. Painted honeyeaters and mistletoebirds formed a single group based on their mean ,15N values and, on average, assimilated approximately half of their nitrogen from mistletoe fruit although individual variation was high. The importance of nitrogen derived from mistletoe fruit did not track its abundance in the environment, suggesting that at least during peak fruiting, this resource is not limiting at this site. Researchers should account for intraspecific variation and take a cautious approach when reconstructing diets using stable isotopes by incorporating individual-based analyses rather than presenting mean values alone. This is the first study to use the isotope approach to investigate the dietary relationship of mistletoe frugivores and mistletoe fruit and has implications for our understanding of the nutritional ecology of frugivores and its functional relationship to ecosystem processes such as seed dispersal. [source] Overcoming barriers to physical activity among culturally and linguistically diverse older adults: A randomised controlled trialAUSTRALASIAN JOURNAL ON AGEING, Issue 2 2010Karen Borschmann Aim:, To investigate by randomised trial, health professional facilitated sessions aiming to overcome barriers to physical activity (PA), improve readiness to undertake PA, increase PA participation and improve fitness among older Australian adults from Macedonian and Polish backgrounds. Method:, One hundred and twenty-one participants (mean age 70 years, 63% female) were block randomised to the intervention group (three one-hour group education and goal setting sessions over 7 weeks) or control group (one-hour health promotion talk) following baseline assessment, with reassessment approximately 9 weeks later. Results:, No significant differences were found between experimental groups in primary (Stages of Change Questionnaire (SocQ), steps per day and Human Activity Profile) or secondary outcomes. Conclusion:, This study has highlighted methodological considerations for PA health promotion and research with older adults from culturally and linguistically diverse (CALD) backgrounds in a community setting. Investigation of older CALD adults' perceptions of what are ,adequate levels of PA' and methods of increasing PA is warranted. [source] MYST family histone acetyltransferases take center stage in stem cells and developmentBIOESSAYS, Issue 10 2009Anne K. Voss Abstract Acetylation of histones is an essential element regulating chromatin structure and transcription. MYST (Moz, Ybf2/Sas3, Sas2, Tip60) proteins form the largest family of histone acetyltransferases and are present in all eukaryotes. Surprisingly, until recently this protein family was poorly studied. However, in the last few years there has been a substantial increase in interest in the MYST proteins and a number of key studies have shown that these chromatin modifiers are required for a diverse range of cellular processes, both in health and disease. Translocations affecting MYST histone acetyltransferases can lead to leukemia and solid tumors. Some members of the MYST family are required for the development and self-renewal of stem cell populations; other members are essential for the prevention of inappropriate heterochromatin spreading and for the maintenance of adequate levels of gene expression. In this review we discuss the function of MYST proteins in vivo. [source] Encouraging results of a VEGF kinoid against experimental choroidal neovascularizationACTA OPHTHALMOLOGICA, Issue 2009B ABITBOL Purpose The goal of this preliminary study was to evaluate the preventive and curative antiangiogenic properties of a VEGF KINOID vaccine produced by NEOVACS againt experimentally laser induced murine choroidal neovessels Methods 3 groups of 12 adult mice (30g) were submitted to laser impacts breaking slightly the Bruch's membrane and initiating the development of subretinal choroidal neovessels. These laser impacts did not create immediately obvious choroidal lesions leading to blood hemorrhages.One Group of mice was submitted to repeated immunizations up to 5 immunizations by the VEGF Kinoid vaccine associated to a modified freund's adjuvant solution. One group of mice received only the mofified Freund's adjuvant and one group of mice sham injections of PBS in the same conditions. Results We were able to observe a decrease or even the disappearance of the abnormal choroidal neovessels even in animals that had been immunized but had not reached adequate levels of neutralizing antibodies against VEGF. Transient adverse effects were observed in some mice in all the groups of mice. Conclusion Obviously The modified freund's adjuvant solution utilized in this first set of experiments must be avoided or modified in order to avoid adverse effects. The chemistry for the production of the VEGF kinoid production must be improved in order to obtain a better immunizing vaccine. Commercial interest [source] | |||||||||||||||||||