219 research outputs found
Medication risk communication with cancer patients in a Middle East cancer care setting
No full textKerry Wilbur,1 Maha Al-Okka,1 Ebaa Jumaat,1 Nesma Eissa,1 Merwa Elbashir,1 Sumaya M Al Saadi Al-Yafei21College of Pharmacy, Qatar University, 2Pharmacy Department, National Center for Cancer Care and Research, Doha, QatarPurpose: Cancer treatments are frequently associated with adverse effects, but there may be a cultural reluctance by care providers to be forthcoming with patients regarding these risks for fear of promoting nonadherence. Conversely, research in a number of countries indicates high levels of patient desire for this information. We sought to explore cancer patient experiences, satisfaction, and preferences for medication risk communication in a Middle East care setting.Methods: We developed and administered a ten-item questionnaire (Arabic and English) to a convenience sample of consenting adult patients receiving treatment at the National Center for Cancer Care and Research in Qatar.Results: One hundred and forty-three patients were interviewed. Most (88%) stated that the level of side effect information they received was sufficient, with physicians (86%) followed by pharmacists (39%) as the preferred sources. The majority (97%) agreed that knowing about possible side effects would help them recognize and manage the reaction, and 92% agreed that it would help them understand how to minimize or prevent the risks. Eighteen percent indicated that this information would make them not want to take treatment. Two-thirds (65%) had previously experienced intolerance to their cancer treatment regimen.Conclusion: Most patients surveyed expressed preference for the details of possible side effects they may encounter in their treatment. However, one in five considered such information a factor for nonadherence, indicating the need for patient-specific approaches when communicating medication risks.Keywords: risk communication, cancer treatment, Middle Eas
Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing
No full textWe report that combining a DNA analog (2?F-ANA) with rigid RNA analogs [2?F-RNA and/or locked nucleic acid (LNA)] in siRNA duplexes can produce gene silencing agents with enhanced potency. The favored conformations of these two analogs are different, and combining them in a 1–1 pattern led to reduced affinity, whereas alternating short continuous regions of individual modifications increased affinity relative to an RNA:RNA duplex. Thus, the binding affinity at key regions of the siRNA duplex could be tuned by changing the pattern of incorporation of DNA-like and RNA-like nucleotides. These heavily or fully modified duplexes are active against a range of mRNA targets. Effective patterns of modification were chosen based on screens using two sequences targeting firefly luciferase. We then applied the most effective duplex designs to the knockdown of the eIF4E binding proteins 4E-BP1 and 4E-BP2. We identified modified duplexes with potency comparable to native siRNA. Modified duplexes showed dramatically enhanced stability to serum nucleases, and were characterized by circular dichroism and thermal denaturation studies. Chemical modification significantly reduced the immunostimulatory properties of these siRNAs in human peripheral blood mononuclear cells. <br/
Assessment and reinforcement of existing dowel-type timber joints
No full textDissertação de mestrado em Structural Analysis of Monuments and Historical ConstructionsJoints in timber structures have an evident effect on the behaviour of the structure in general. The failure mechanism of timber joints with mechanical fasteners among other things depends on the geometry of the joint and the type of fastener. Substantially, under compressive stresses, timber as a material may be loaded far over its elastic limit. For the case of dowel-type joints with mechanical fasteners, the steel used is able to deform in a distinctly plastic manner. Even though, not in all cases timber connections deform plastically before failure resulting in brittle failure modes. Avoiding the causes for brittle failure modes, specifically high tensile perpendicular to the grain and shear stresses, leads to distinctly plastic failure modes of connections with mechanical fasteners. Joints with dowel-type fasteners are considered potentially ductile due to the interaction between the highly nonlinear behaviour of the wood under embedding stresses and the bending behaviour of the steel fasteners. The challenge is to avoid the brittle failure mechanisms by either avoiding perpendicular to the grain tensile stresses or by using reinforcement techniques. These stresses are caused by many reasons such as the wedge effect of the mechanical fasteners or as an amplification of restrained shrinkage. Both effects can be counteracted by reinforcing the connection area. Thus, the main aim of reinforcement is to increase the embedment strength of the timber elements so that it can resist these effects.
Regarding dowel-type connections in general, the mechanical fasteners deform under load resulting in their embedment into the surrounding timber fibres. This deformation is assumed a rigid-plastic deformation according to Johansen K.W, 1949, which is developed based on the European Yield Model (YEM), both approaches are discussed thoroughly within the scope of this work. However, dowel-type joints reinforced with self-tapping screws are more protected against brittle failure modes, as they tend to increase the embedding strength, consequently increasing the load-carrying capacity with the possibility of reducing the end-distance. Since embedment is a nonlinear process, the stiffness of the connections then depends on the nature of the applied load. Thus, for this research project, the specimens will be tested under monotonic and cyclic loading in order to assess the behaviour of the joints in both cases.
This research addresses the assessment of timber-to-timber dowel-type joints in double shear, with reinforcement using FRP, specifically fiberglass (GFRP), and self-tapping screws (STS). For the reinforcement with GFRP, a previous study, (Matos, 2011), had addressed the failure of this type of joints, with and without reinforcement, under both monotonic and cyclic loading. Subsequently, the results obtained in this study, are analysed within the scope of this work for conducting a comparison of reinforcement techniques and discussed accordingly.
Regarding reinforcement with self-tapping screws, an experimental campaign was carried out for the same wood species used in the former study mentioned above, following the same testing procedures, monotonic (EN 26891) and cyclic (EN 12512), for the purpose of comparison and validation.As ligações estruturais de madeira têm um efeito óbvio no comportamento global da estrutura. O modo de rotura destas ligações que usam ligadores metálicos depende, entre outros parâmetros, da geometria da ligação e do tipo de ligador. Sob compressão, a madeira apresenta comportamento pós elástico. Também o ligador metálico é capaz de apresentar deformação plástica. No entanto, nem todas as ligações apresentam deformações plásticas ocorrendo roturas de natureza frágil, sem plasticidade. Deste modo, prevenir modos de rotura frágeis, que envolvam tensões de tração perpendicular às fibras e de corte, promove um comportamento plástico das ligações.
As ligações do tipo cavilha são consideradas potencialmente dúcteis dada a interação entre o comportamento não linear da madeira sob tensões de esmagamento localizado e a flexão do ligador metálico. É assim crucial evitar os mecanismos de rotura frágeis reduzindo as tensões de tração perpendiculares às fibras ou reforçando as ligações. As tensões de tração perpendicular ás fibras resultam de vários fatores, como são exemplos o efeito grupo dos ligadores e as tensões internas induzidas por variações do teor de água da madeira. Ambos estes efeitos podem ser reduzidos recorrendo a técnicas de reforço das ligações. Normalmente, o principal objetivo do reforço é o aumento da capacidade da ligação ao esmagamento localizado de forma a aumentar a sua resistência a estes dois efeitos.
No que se refere ás ligações tipo cavilha em geral, o ligador metálico deforma-se sob carregamento provocando o esmagamento das fibras da madeira. Esta deformação é assumida como rígido-plástica de acordo com Johansen 1949, teoria esta que está na base do European Yield Model (EYM) e que será analisada ao longo deste trabalho. Contudo, ligações tipo cavilha reforçadas com parafusos autoperfurantes apresentam uma maior resistência a modos de rotura fragéis, uma vez que tendem a aumentar a capacidade ao esmagamento localizado da madeira e assim aumentam a capacidade resistente da ligação, permitindo distâncias mínimas, entre ligadores e entre estes e os topos e lados dos elementos ligados, inferiores. Uma vez que o esmagamento localizado é um processo não-linear, a rigidez da ligação depende do tipo de carga aplicada. Deste modo, neste trabalho, as ligações estudadas foram submetidas a ensaios monotónicos e cíclicos.
Este trabalho visa análise de ligações de madeira do tipo cavilha em corte duplo, reforçadas com FRP, nomeadamente, fibras de vidro (GFRP), e parafusos autoperfurantes (STS). No caso do reforço com GFRP, uma dissertação anterior, Matos (2011), analisou os modos de rotura destas ligações com e sem reforço, sob carregamento monotónico e cíclico. Os resultados obtidos são alvo de uma nova análise servindo ainda como comparação entre as duas técnicas de reforço consideradas.
O reforço com parafusos autoperfurantes, foi estudado tendo por base uma vasta campanha experimental que foi conduzida adotando as mesmas condições, incluindo as duas espécies de madeira, geometria das ligações, setup, procedimentos de ensaio, monotónicos (EN 26891) e cíclicos (EN 12512) etc., da dissertação que analisou o reforço com GFRP, para efeitos de comparação
Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation
No full textThe study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA( siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficient uptake of siRNA by entire populations of cultured primary mammalian hippocampal and sympathetic neurons. This treatment leads to specific knock-down of targeted proteins within hours without the toxicity associated with transfection. In contrast to current methods, our technique permits study of protein function across entire populations with minimal disturbance of complex cellular networks. Using this technique, we found that protein knock-down ( evident after 6 hr) precedes any decrease in targeted message ( evident after 24 hr), suggesting an early, translational repression by perfectly targeted siRNAs.PT: J; CR: BARTEL DP, 2004, CELL, V116, P281 BERTRAND E, 2001, MOL CELL NEUROSCI, V18, P503 DEROSSI D, 1994, J BIOL CHEM, V269, P10444 DOENCH JG, 2003, GENE DEV, V17, P438 DOSTIE JE, 2003, RNA, V9, P180 ELBASHIR SM, 2001, EMBO J, V20, P6877 FINK CC, 2003, NEURON, V39, P283 FIRE A, 1998, NATURE, V391, P806 GAUDILLIERE B, 2002, J BIOL CHEM, V277, P46442 HANNON GJ, 2002, NATURE, V418, P244 HUTVAGNER G, 2002, SCIENCE, V297, P2056 JOHNSTON RJ, 2003, NATURE, V426, P845 JOLIOT A, 2004, NAT CELL BIOL, V6, P189 KHVOROVA A, 2003, CELL, V115, P209 KIM J, 2004, P NATL ACAD SCI USA, V101, P360 KRICHEVSKY AM, 2002, P NATL ACAD SCI USA, V99, P11926 KRICHEVSKY AM, 2003, RNA, V9, P1274 LAI EC, 2003, CURR BIOL, V13, R925 LLAVE C, 2002, SCIENCE, V297, P2053 MURATOVSKA A, 2004, FEBS LETT, V558, P63 OMI K, 2004, FEBS LETT, V558, P89 RABACCHI SA, 2004, NEUROBIOL AGING, V25, P1057 REYNOLDS A, 2004, NAT BIOTECHNOL, V22, P326 SAXENA S, 2003, J BIOL CHEM, V278, P44312 SCHERER LJ, 2003, NAT BIOTECHNOL, V21, P1457 SCHWARZ DS, 2003, CELL, V115, P199 THEODORE L, 1995, J NEUROSCI, V15, P7158 TOROCSIK B, 2002, J NEUROSCI, V22, P8971 TROY CM, 1994, P NATL ACAD SCI USA, V91, P6384 TROY CM, 1996, J NEUROSCI, V16, P253 TROY CM, 1996, P NATL ACAD SCI USA, V93, P5635 TROY CM, 2001, J NEUROSCI, V21, P5007 TROY CM, 2002, J BIOL CHEM, V277, P34295 VICKERS TA, 2003, J BIOL CHEM, V278, P7108 ZENG Y, 2003, P NATL ACAD SCI USA, V100, P9779; NR: 35; TC: 22; J9: J NEUROSCI; PG: 7; GA: 869ZASource type: Electronic(1
Global Call to Action: maximize the public health impact of intermittent preventive treatment of malaria in pregnancy in sub-Saharan Africa.
No full textIntermittent preventive treatment of malaria in pregnancy is a highly cost-effective intervention which significantly improves maternal and birth outcomes among mothers and their newborns who live in areas of moderate to high malaria transmission. However, coverage in sub-Saharan Africa remains unacceptably low, calling for urgent action to increase uptake dramatically and maximize its public health impact. The 'Global Call to Action' outlines priority actions that will pave the way to success in achieving national and international coverage targets. Immediate action is needed from national health institutions in malaria-endemic countries, the donor community, the research community, members of the pharmaceutical industry and private sector, along with technical partners at the global and local levels, to protect pregnant women and their babies from the preventable, adverse effects of malaria in pregnancy
The Role of Growth Factors and Nutrition in Cancer Cachexia.
No full textThe importance of growth factors and nutrition in cancer cachexia was investigated in a group of patients with advanced malignant disease, in mice bearing the Lewis lung tumour, and in cultures of the human hepatoma cell line HEP G2. In addition, the effect of treatment with medroxyprogesterone acetate was also studied. The patients studied show that, in addition to poor appetite and weight loss, cancer cachexia is associated with low levels of serum IGF-I, and high levels of TNF-aand ferritin. Levels of the mean growth hormone and serum cortisol were in the high normal range. Treatment with medroxyprogesterone acetate (MPA) for 4 weeks associated with an improvement in appetite in all patients. This was accompanied by an increase in fasting plasma insulin levels but no change in serum albumin, total proteins or mean levels of IGF-I. A weight gain of more than 3 kg was observed in 28% of patients. This degree of weight gain was associated with a decrease in fasting levels of growth hormone, tumour necrosis factor and cortisol, followed by a significant increase in the levels of IGF-I. Patients who failed to gain or who lost further weight showed an increase in plasma levels of ferritin, cortisol and tumour necrosis factor. While levels of both growth hormone and IGF-I remain low. In the study of tumour-bearing mice, it was found that overall plasma and liver levels of IGF-I were lower in tumour-bearing than normal animals, levels were also lower in muscle but showed evidence of recovery in the later stage of the study. Treatment with MPA had no effect on food intake and no significant effect on non-tumour weight but appear significantly to increase tumour weight. It also prevented the fall in plasma IGF-I levels seen in nontreated animals. Levels of tumour necrosis factor -a (TNF-a) were undetectable in plasma in all animals but were markedly increased in muscle of all tumour-bearing animals, particularly those treated with MPA. This was accompanied by a decrease in muscle glycogen contents and an apparent increase (possibly only relative) in muscle protein content. The low IGF-I and high TNF-a levels in the muscle of tumour-bearing animals may be important factors in the development of muscle wasting in these animals. In studies on the human hepatoma cell line in culture, the addition of insulin and human growth hormone (hGH) together resulted in an increase in the synthesis of IGF-I. While the addition of each separately was without effect. The addition of TNF-a along with insulin and hGH counteracted their ability to increase IGF-I synthesis. Reduction in the glutamine content of the medium resulted in a significant reduction in IGF-I release by the cultured cells. MPA had no direct effect on either cell growth or IGF-I production. In patients with cancer who are losing weight, a reduction in TNF-a levels appears to allow IGF-I levels to rise in response to the prevailing high levels of growth hormone, with restoration of the normal relationship between IGF-I and growth hormone. These changes probably predispose to weight gain. The increase in tumour growth seen in animals treated with MPA suggests that it may be preferable to give such treatment only after removal of the tumour or radiation therapy
The safety of artemisinins during pregnancy: a pressing question.
No full textBACKGROUND: An increasing number of countries in sub-Saharan Africa are changing to artemisinins combination therapy (ACT) as first or second line treatment for malaria. There is an urgent need to assess the safety of these drugs in pregnant women who may be inadvertently exposed to or actively treated with ACTs. OBJECTIVES: To examine existing published evidence on the relationship between artemisinin compounds and adverse pregnancy outcomes and consider the published evidence with regard to the safety of these compounds when administered during pregnancy. METHODS: Studies on ACT use in pregnancy were identified via searches of MEDLINE, EMBASE, Cochrane and Current Contents databases. Data on study characteristics, maternal adverse events, pregnancy outcomes and infant follow up were extracted. RESULTS: Fourteen relevant studies (nine descriptive/case reports and five controlled trials) were identified. Numbers of participants in these studies ranged from six to 461. Overall there were reports on 945 women exposed to an artemisinin during pregnancy, 123 in the 1st trimester and 822 in 2nd or 3rd trimesters. The primary end points for these studies were drug efficacy and parasite clearance. Secondary endpoints were birth outcomes including low birth weight, pre-term birth, pregnancy loss, congenital anomalies and developmental milestones. While none of the studies found evidence for an association between the use of artemisinin compounds and increased risk of adverse pregnancy outcomes, none were of sufficient size to detect small differences in event rates that could be of public health importance. Heterogeneity between studies in the artemisinin and comparator drugs used, and in definitions of adverse pregnancy outcomes, limited any pooled analysis. CONCLUSION: The limited data available suggest that artemisinins are effective and unlikely to be cause of foetal loss or abnormalities, when used in late pregnancy. However, none of these studies had adequate power to rule out rare serious adverse events, even in 2nd and 3rd trimesters and there is not enough evidence to effectively assess the risk-benefit profile of artemisinin compounds for pregnant women particularly for 1st trimester exposure. Methodologically rigorous, larger studies and post-marketing pharmacovigilance are urgently required
Systematic review: Impact of meningococcal vaccination on pharyngeal carriage of meningococci.
No full textOBJECTIVE: To investigate the effect of meningococcal vaccines on pharyngeal carriage of meningococci. METHODS: Systematic review. MEDLINE and EMBASE were searched for relevant studies. Controlled trials and observational studies which used comparison groups or compared carriage rates before and after vaccination were included in the review. RESULTS: Twenty-nine studies satisfied the inclusion criteria. Twenty-five studies reported the effect of a polysaccharide vaccine, one the effect of a serogroup C conjugate vaccine and three the impact of serogroup B outer-membrane vaccines on overall and/or serogroup-specific meningococcal carriage rates. Ten studies of meningococcal polysaccharide vaccines found reduced serogroup-specific carriage; seven of these focussed on high-risk groups and had a short follow-up period. Only one of five studies of civilian populations in Africa showed a significantly reduced carriage. Many studies had methodological shortcomings. The one study which assessed the effect of a meningococcal conjugate vaccine on carriage showed a significant impact. Three studies of serogroup B outer-membrane protein vaccines showed no effect on carriage. CONCLUSIONS: A few well-designed trials of the impact of meningococcal vaccines on carriage have been undertaken. Such studies should be an essential component of the evaluation of new meningococcal vaccines, particularly those introduced to control epidemic meningococcal disease in Africa
Occurrence, Effects, and Treatment of Endocrine-Disrupting Chemicals in Water
No full textWater is an essential commodity for human well-being. The World Health Organization (Howard and Bartram, 2003) has estimated that a person needs at least 7.5 L of water per day for drinking, food, and personal hygiene. A person requires 50 L of water per day to meet other needs. A poor water supply can affect health either directly or indirectly. Incidents of many water-connected diseases can be reduced noticeably by providing sufficient quantity of potable water (Fewtrell et al., 2005). Pathogens from human and animal excreta are transmitted through soil, surface and groundwater, and by hands, flies, and other vectors (Figure 3.1). Finally, humans get exposed to these pathogens either through consumption of contaminated water, food, or through unsanitary contact
Identifying transmission cycles at the human-animal interface: the role of animal reservoirs in maintaining gambiense human african trypanosomiasis.
No full textMany infections can be transmitted between animals and humans. The epidemiological roles of different species can vary from important reservoirs to dead-end hosts. Here, we present a method to identify transmission cycles in different combinations of species from field data. We used this method to synthesise epidemiological and ecological data from Bipindi, Cameroon, a historical focus of gambiense Human African Trypanosomiasis (HAT, sleeping sickness), a disease that has often been considered to be maintained mainly by humans. We estimated the basic reproduction number [Formula: see text] of gambiense HAT in Bipindi and evaluated the potential for transmission in the absence of human cases. We found that under the assumption of random mixing between vectors and hosts, gambiense HAT could not be maintained in this focus without the contribution of animals. This result remains robust under extensive sensitivity analysis. When using the distributions of species among habitats to estimate the amount of mixing between those species, we found indications for an independent transmission cycle in wild animals. Stochastic simulation of the system confirmed that unless vectors moved between species very rarely, reintroduction would usually occur shortly after elimination of the infection from human populations. This suggests that elimination strategies may have to be reconsidered as targeting human cases alone would be insufficient for control, and reintroduction from animal reservoirs would remain a threat. Our approach is broadly applicable and could reveal animal reservoirs critical to the control of other infectious diseases
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