Chagas' disease afflicts more than 18 million people throughout South and Central America. Some areas of North America have also seen an increased incidence in recent years. The Trypanosoma cruzi (T. cruzi) parasite, which causes the disease, is most often transmitted by Triatomid bugs living in close proximity to humans. The T. cruzi parasite depends heavily on a small molecule called trypanothione to protect itself against damage from free radicals produced during normal metabolism. The concentration of trypanothione in the cell is carefully maintained by an enzyme called trypanothione reductase (TR). Drugs that inhibit TR should cause the parasite to die. Human cells have a similar enzyme-substrate pair: glutathione and glutathione reductase (GR). Fortunately, the enzyme GR differs electrostatically from TR, so there is hope of developing a drug that will be safe for human cells. The molecular structures of both TR and GR are known from ongoing X-ray crystallography studies. Both enzymes are dimers, that is, they consist of two equivalent domains, each having its own active site (the place where glutathione or trypanothione binds). One surprising feature of this system is a long tunnel passing through the center of the dimer and connecting the active sites of the two domains. While this is a naturally interesting feature to explore in a VR environment, the goal of the research is to evaluate the binding ability of particular drugs. For purposes of early testing, we chose chlorpromazine, an antidepressant drug. Large doses of the drug are known to kill the parasite, but are also toxic to the human host. It is possible that minor structural changes to this molecule would improve the selectivity and potency of the drug. For purposes of testing our VR environment, we present only a token calculation on chlorpromazine 相似文献
This article provides an introduction to the 5 instrument articles in this special section, each of which presents a psychometric evaluation of a self-administered questionnaire developed for use in addictions treatment research. An overview of measurement theory is presented, and social-psychological factors that affect reliability and validity are considered. The instruments evaluated in this issue are summarized, and the 2 common data sources for the 5 reports, the Project MATCH baseline data set and the Project MATCH Reliability Study, are described. The article concludes with a brief summary that offers recommendations regarding how psychometric investigation should be undertaken and applied to the development of self-report questionnaires in addictions research. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
Twenty-four ill or dead desert tortoises (Gopherus agassizii) were received between March 1992 and July 1995 for necropsies from the Mojave and Colorado deserts of California (USA). Diseases observed in these animals included cutaneous dyskeratosis (n = 7); shell necrosis (n = 2); respiratory diseases (n = 7); urolithiasis (n = 3); and trauma (n = 5). In tortoises with cutaneous dyskeratosis the horn layer of shell was disrupted by multiple crevices and fissures and, in the most severe lesions, dermal bone showed osteoclastic resorption, remodeling, and osteopenia. In tortoises with shell necrosis, multiple foci of necrotic cell debris and heterophilic inflammation within the epidermal horn layer were subtended by necrotic dermal bone colonized by bacteria and fungi. Of the seven tortoises with respiratory disease, five were diagnosed with mycoplasmosis. The diagnosis of mycoplasmosis was based on the presence of chronic proliferative rhinitis and positive serologic tests and/or isolation of Mycoplasma sp. Chronic fungal pneumonia was diagnosed in one tortoise with respiratory disease. In the three tortoises with urolithiasis, two were discovered dead, and the live tortoise had renal and articular gout. Traumatic injuries consisted of one tortoise entombed within its burrow, one tortoise burned in a brush fire, two tortoises struck by moving vehicles, and one tortoise attacked by a predator. While the primary cause of illness could be attributed to one or two major disease processes, lesions were often found in multiple organ systems, and a variety of etiologies were responsible for morbidity and mortality. 相似文献
An investigation was conducted in five companies in the distribution branch. These companies were divided into three different working systems, i.e., highly mechanized (HM), moderately mechanized (MM), and slightly mechanized (SM). The three systems differed in logistics and kind of appliances used. The purpose of this study was to compare the three working systems with different degrees of mechanization concerning the time spent on tasks, activities during the working day, postures that occurred, physiological work load, perceived exertion and recovery from work. To investigate the different tasks, activities and working postures, 50 warehouse workers, originating from the three working systems, were observed by means of a direct observation method, called: ‘TRAC’. To investigate the physiological work load the heart rate was recorded continuously during the working day and related to the individually determined relation between heart rate and oxygen uptake. This relation was constructed with the results of a cycle ergometer test done in the laboratory. During lunch and at the end of the working day the warehouse workers filled in a questionnaire concerning their perceived exertion and recovery from work.
In the slightly mechanized system more time was spent with the trunk flexed more than 75° as compared with the other two systems. This posture was very common during lifting of objects, and lifting was done more often in this system than in the other systems. In the MM system the warehouse workers had the highest estimated oxygen uptake and reported the highest perceived exertion at the end of the working day. The workers in the HM system had a shorter working day and had less problems with recovery from work than the workers of the other two systems. Poor working postures like rotation and lateroflexion were commonly found in the HM working system. An important explanation was the difference in time spent driving an electric car. This activity was done mostly in the HM system. In conclusion, the HM system was considered most favourable when it concerned work load and recovery from work. The appliances used in the HM system, and especially the electric car, need to be designed according to ergonomic guidelines to avoid poor working postures. 相似文献
Recent advances in miniaturization have provided clinicians with hearing aids that can be comfortably inserted as far as the bony portion of the ear canal. It is possible to take advantage of these deeply inserted hearing aids in new ways. For example, the physical vibrations of microphone and receiver components may be used to improve hearing aid gain through bone conduction. Three cases are presented that will introduce this phenomenon for two transcranial CROS fittings and for one unilateral otosclerosis fitting. In each case, functional gain measurements under headphones were obtained with the hearing aid receivers acoustically plugged. Considerable gain was still present. Potential benefits, ramifications, and side effects are discussed. 相似文献
The ligament supporting the leading edge of birds' wings is a connective tissue structure with unusual morphologic and elastic features. Its center section is made of a highly extensible composite of elastin and collagen fibers and its two end sections of nearly inextensible pure collagen; these are joined end-to-end in short interdigitating junctions. Substantial forces are transmitted through the junctions showing that collagen and elastin are mechanically connected. The junctions and elastic segment are sufficiently strong that when the intact ligament is maximally strained, the point of failure is commonly in the collagenous segments or their attachments to the tissues of origin or insertion. Here we outline the morphology and describe static force-length properties of this ligament. 相似文献
This paper aims to explore the meaning of spirituality in relation to nursing care using concept synthesis. Walker and Avant give three ways in which concept synthesis can occur: discovering new dimensions to old concepts, searching for similarities and discrepancies among sets of related concepts, and observing previously undescribed phenomena. It is the first two of these methods which have been used here. The phenomena that emerged from a reading of the literature around spirituality were meaning, presencing, empathy/compassion, giving hope, love, religion/transcendence, touch and healing. These phenomena were studied in order to sort them into fewer categories. They all appeared to be products of a relationship, some physical (presencing, touch and healing), and others emotional (meaning, empathy/compassion, hope, love, and religion/transcendence). Some of the phenomena appeared to fit in both categories, especially healing, which could be of a physical or emotional/spiritual nature. Once the two main categories had been arranged, it was obvious that a split between psyche and soma was not appropriate for labelling the spiritual dimensions of nursing care, as the original definition of spirit was something which motivated the body. Spiritual care is inseparable from physical, social and psychological care because together they form the whole (Bradshaw 1994 p. 282). The two categories were then collapsed into one and given the label 'connection'. 相似文献
The authors report on clinical features and mortality rates in a group of 149 patients with apparent idiopathic parkinsonism starting before the age of 40 years. Ten had juvenile parkinsonism (JP; onset before age 21 years) and 139 had young-onset Parkinson's disease (YOPD; onset at age 21 to 40 years). Included were 60 patients originally reported 10 years ago. Fifty percent of the JP group had a positive family history of parkinsonism in a first-degree relative, and clinical presentation was heterogeneous. Mortality risk was threefold that of the normal population. In the YOPD group, the mortality risk was double that of the normal population. Poor initial response to L-dopa was a risk factor for early death. In two previously reported patients, the diagnosis had been changed to multiple system atrophy and Machado-Joseph disease. After a median disease duration of 18 years, cognitive impairment was found in only 19% of YOPD patients (13% of those younger than 60 years and 43% of those 60 years or older). Age was the most important factor for development of dementia, but female sex and positive family history of parkinsonism also had more modest predictive value. After a disease duration of 10 years or less, only 5% of patients were experiencing falls and 30% freezing, but all patients had developed L-dopa-related fluctuations and dyskinesias. The authors conclude that the mortality rate in parkinsonism starting before the age of 40 is increased in comparison to the normal population and is similar to the general Parkinson's disease population. Intellectual function and postural reflexes are usually well preserved for many years despite a long history of parkinsonism and the early and frequent occurrence of treatment complications, provided the patients remain biologically and chronologically young. 相似文献
Chromogenic hexapeptides Dnp-Ala-Ala/Ser-Phe-Phe-Ala-Arg-NH2 containing a Phe-Phe bond, which is sensitive to aspartic proteinases, were used as substrates for assaying the activity of pepsin, chymosin, and aspergillopepsin A. The assay was performed after the separation of hydrolyzates on SP-Sephadex by measuring at 360 nm the absorbance of the dinitrophenylpeptide lacking the cationic group, which was formed upon the cleavage of the substrate. The kinetic parameters of the hydrolysis of the substrates were evaluated. It is shown that replacing the Ala residue with Ser in the P2 position does not substantially change the kinetic parameters. The substrates were hydrolyzed by pepsin several times faster than by aspergillopepsin A or chymosin. The method is sensitive and enables the activity of aspartic proteinases to be determined easily. 相似文献