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PubMedDate not supplied

An age-dependent sensitivity of the roll-induced vestibuloocular reflex to hypergravity exposure of several days in an amphibian (Xenopus laevis).

In tadpoles of the Southern Clawed Toad (Xenopus laevis), the effects of an exposure to hypergravity of several days duration on the development of the roll-induced static vestibuloocular reflex (rVOR) were investigated. Special attention was given to the onset of the 9 or 12 days lasting 3G-period during early life. First recordings of the rVOR characteristics for complete 360 degrees rolls of the tadpoles were performed 24 hrs after the end of the 3G-period. The rVOR peak-to-peak amplitudes as well as the VOR-gain for a roll angle of 15 degrees from 3G-and 1G-samples recorded at the 2nd and 3rd day after 3G-termination agreed for the youngest group, but were reduced by approx. 30% in the older tadpoles. Long-term observations lasting up to 8 weeks after termination of the 3G-period, demonstrated (i) an early retardation of the development, and (ii) a developmental acceleration in all groups so that after 2 weeks in the stage 6/9- and 33/36-samples and after 8 weeks in the stage 45-tadpoles, the rVOR-amplitude as well as the rVOR-gain for a 15 degrees roll were at the same level in both the 3G- and the 1G-samples. The results support the existence of a sensitive period for the rVOR development, and additionally demonstrate the importance of the period of the first appearance of the rVOR for the development of adaptive properties of the underlying neuronal network. They also demonstrate the dominant efficiency of genetic programs in the functional development of the vestibular system. Methodological approaches are discussed which will be useful in the further description of the critical period. They include studies on the neuronogenesis and synaptic maturation within the vestibular pathways as well as on the fundamentals of buoyancy control during swimming. A modular but closed mini-system for experimental use is described which allows survival periods lasting many weeks and multiple types of treatments of developing aquatic animals in orbit, controlled automatically.

Adaptation, Physiological↗
PubMedDate not supplied

Discrimination between epidemiological cycles of rabies in Mexico.

BACKGROUND: The design of efficient rabies control programs within a geographic area requires an appropriate knowledge of the local epidemiological cycles. In Latin America, there is a geographical overlap of the two main epidemiological cycles: (a) the terrestrial cycle, where the dog is the main terrestrial vector and the principal cause of human transmission; and (b) the aerial cycle, in which the vampire bat Desmodus rotundus is representative in Mexico. This bat is the major sylvatic rabies vector transmitting rabies to cattle. The purpose of this study was to distinguish between the epidemiological cycles of rabies virus (aerial and terrestrial) circulating in Mexico, using restriction fragment length polymorphism (RFLP). METHODS: Thirty positive rabies isolates were obtained from different species (including humans, domestic, and wildlife animals) and geographical regions. The methodology included the extraction of RNA, and synthesis of cDNA, PCR, and RFLP using four restriction endonucleases. To determine the aerial cycle, BsaW I and BsrG I were utilized, and for terrestrial cycle, BamH I and Stu I. Most of the samples belonged to the aerial and terrestrial cycles, except for two skunk isolates from Northwestern Mexico, which were not cut by any of the enzymes. RESULTS: Three different migration patterns were detected: (a) the first was observed in six amplicons, which were cut by BsaW I and BsrG I (aerial cycle); (b) 19 amplified samples were digested with BamH I and Stu I enzymes (terrestrial cycle); and (c) two skunk isolates from Northwest Mexico, were not cut by any of the enzymes utilized in the experiments (hypervariable cycle). CONCLUSIONS: This concludes that RFLP can be used for the classification of rabies field samples in epidemiological studies. Moreover, it has demonstrated its usefulness, not only for differentiating between the main epidemiological rabies cycles present in Mexico, but also to detect new cycles in wildlife species.

Animals↗
PubMedDate not supplied

Current issues in staff training.

Staff competence in the application of behavioral techniques is critical to improve quality of life for persons with a developmental disability. Development of efficient staff training programs is therefore of great importance. This paper describes some of the procedures most frequently used in staff training research. Research in this area is reviewed in relation to client outcomes as a function of staff training, maintenance of staff skills, and transfer of staff skills across settings, clients, and programs. Current concerns and further improvements in behavioural techniques, acquisitional strategies, and assessment are discussed.

Behavior Therapy↗
PubMedDate not supplied

[Conformal radiotherapy in cancer of the upper aerodigestive tract].

The outcome of head and neck malignancies is closely related to the achievement of local tumor control. The occurrence of severe late complications is the consequence of the anatomic vicinity between dose-limiting normal tissues and the tumor, thus reducing the curative potential of radiotherapy. Conformal radiotherapy is presently actively investigated as a way to improve the dose distribution in head and neck malignancies (especially when originating from the nasopharynx or the sinuses) while protecting healthy organs. Such an approach requires a chain of sophisticated procedures, including efficient quality assurance programs, in order to achieve the proper degree of safety. The relatively limited clinical studies published to-date have already confirmed the advantage of conformal radiotherapy in terms of dose delivery. The development of beam intensity modulation is likely to further contribute to the improvement of the therapeutic ratio.

Adult↗
PubMed2002

[Safety in radiotherapy: Control of software and informatics systems].

The development of computerized systems in radiotherapy opens new challenging possibilities. There is however a major risk of specific errors if the use of such systems is not properly controlled. On the other hand, the software sophistication, such as encountered in modern treatment planning systems (TPS), makes it very difficult to set up efficient quality assurance programs compatible with the workload of users in charge of daily routine. From the analysis of previous accidents involving TPS, we can conclude that the major risks are erroneous calculations of monitor units resulting from a poor understanding of the software capabilities combined to a lack of vigilance with respect to the data obtained from a computer. To reduce the risks, it is necessary to setup a comprehensive quality assurance program covering all steps of the process, including commissioning of a new system and systematic checks of individual treatment plans. Such a program offers the users the opportunity to acquire a deeper understanding of the system and avoid potential pitfalls. There is presently a lack of consensus for an international protocol related to quality assurance of computerized systems in radiotherapy. It is therefore important to define protocols at the national level, with special consideration of the aspects which are more likely to generate significant errors.

Computer Simulation↗
PubMedDate not supplied

Maximum symmetrical split of molecular graphs. Application to organic synthesis design.

Whereas the potential symmetry of a molecule may be a feature of importance in synthesis design, this one is often difficult to detect visually in the structural formula. In the present article, we describe an efficient algorithm for the perception of this molecular property. We have addressed this problem in terms of graph theory and defined it as the Maximum Symmetrical Split of a molecular graph. A solution is obtained by deleting in such a graph a minimum number of edges and vertices so that the resulting subgraph consists of exactly two isomorphic connected components that correspond to a pair of synthetically equivalent synthons. In view to reduce the search space of the problem, we have based our algorithm on CSP techniques. In this study, we have found that the maximum symmetrical split is an original kind of Constraint Satisfaction Problem. The algorithm has been implemented into the RESYN_Assistant system, and its performance has been tested on a set of varied molecules which were the targets of previously published synthetic studies. The results show that potential symmetry is perceived quickly and efficiently by the program. The graphical display of this perception information may help a chemist to design reflexive or highly convergent syntheses.

Journal Article↗
PubMed2001

A two-dimensional (magnetic field and concentration) electron paramagnetic resonance method for analysis of multispecies complex equilibrium systems. information content of EPR spectra.

A two-dimensional simulation method has been developed for the interpretation of electron paramagnetic resonance (EPR) spectra consisting of a multitude of strongly overlapping signal components. The set of EPR spectra for complex equilibrium systems is analyzed simultaneously as a function of metal and ligand concentrations and pH. The formation constants of the various species are adjusted together with the magnetic parameters of the component EPR spectra. At most 10 EPR-active and 5 EPR-silent species can be involved to simulate a maximum of 36 experimental spectra, while the number of adjusted parameters is at most 100. Statistical parameters are suggested to give the confidence intervals for parameter estimation and to distinguish alternative speciation models. The efficiency of the program is demonstrated for the copper(II)--L-asparagine system, in which 10 species, including 3 pairs of isomers, are characterized with magnetic parameters and formation constants. On the basis of the magnetic parameters, a structural assignment is made for the detected species. The two-dimensional approach can also supply the formation constant of the EPR-silent species, as demonstrated for the copper(II)--glycyl-L-serine system.

Journal Article↗
PubMed2003

Syntheses and binding studies of new [(aryl)(aryloxy)methyl]piperidine derivatives and related compounds as potential antidepressant drugs with high affinity for serotonin (5-HT) and norepinephrine (NE) transporters.

In a wide search program toward new, efficient, and fast-acting antidepressant drugs, we have prepared series of new compounds having an (aryl)(aryloxy)methyl moiety linked directly or through a methylene chain to different substituted and unsubstituted cycles (isoquinoline, piperazine, piperidine, tetrahydropyran, or cyclopentane). These compounds have been evaluated for their affinities for serotonin (5-HT) transporter (SERT) and 5-HT(1A) and 5-HT(2A) receptors. Racemic mixtures of 4-[(aryl)(aryloxy)methyl]piperidine derivatives showed much higher affinity values for SERT than fluoxetine and resulted in lack of affinity for 5-HT(1A) and 5-HT(2A) receptors. Some of these racemic mixtures were resolved to their enantiomers and tested for binding to norepinephrine (NE) transporter (NET), dopamine (DA) transporter (DAT), and alpha(2) receptor. Several of these enantiomers [(-)-15b, (-)-15j, (-)-15t, (+)-15u] displayed a dual binding profile with affinities for SERT and NET with K(i) < 25 nM and a NET/SERT ratio <10. Compound (-)-15j (coded as F-98214-TA for development studies) showed a dual binding profile with very high affinity values for SERT and NET (K(i) = 1.9 and 13.5 nM, respectively), and further pharmacological characterization is in progress for its evaluation as a antidepressant.

Adrenergic Uptake Inhibitors↗
PubMed2002

Prospects for using genetic transformation for improved SIT and new biocontrol methods.

The genetic manipulation of non-drosophilid insect species is possible by the creation of recombinant DNA constructs that can be integrated into host genomes by several transposon-based vector systems. This technology will allow the development and testing of a variety of systems that can improve existing biological control methods, and the development of new highly efficient methods. For programs such as sterile insect technique (SIT), transgenic strains may include fluorescent protein marker genes for detection of released insects, and conditional gene expression systems that will result in male sterility and female lethality for genetic sexing. Conditional expression systems include the yeast GAL4 system and the bacterial Tet-off and Tet-on systems that can, respectively, negatively or positively regulate expression of genes for lethality or sterility depending on a dietary source of tetracycline. Importantly, strains for male sterility must also incorporate an effective system for genetic sexing, since typically, surviving females would remain fertile. Models for the use of these expression systems and associated genetic material come from studies in Drosophila and, while many of these systems should be transferable to other insects, continued research will be necessary in insects of interest to clone genes, optimize germ-line transformation, and perform vector stability studies and risk assessment for their release as transgenic strains.

Animal Identification Systems↗
PubMed2003

The prevalence of tongue lesions in 5150 Turkish dental outpatients.

OBJECTIVE: The aim of this study was to assess the prevalence of nine tongue conditions and relate to data obtained about oral hygiene or habits in Turkish dental outpatients. SUBJECTS: A total of 5150 subjects (2837 women, 2313 men) were included in this study. RESULTS: Of the 5150 subjects, 2690 subjects were detected as having tongue lesions with a prevalence of 44.2 and 62.0% for women and men, respectively. The difference was found to be statistically significant (P < 0.0001). There was a strong correlation between tongue lesions and increasing age. There was also a strong association between tongue lesions and smoking, black tea drinking, and fair or poor oral hygiene. Hairy and coated tongue was significantly higher in males. Contrary to this, papillary atrophy was more prominent in women. CONCLUSION: A strong correlation was found between tongue lesions and age, sex, oral hygiene and habits in Turkish dental outpatients. An efficient oral health program such as the elimination of risk habits and attention to cultural practices may improve tongue hygiene.

Adolescent↗
PubMed1983

Training generative repertoires within agent-action-object miniature linguistic systems with children.

This study investigated processes responsible for generative language acquisition through the use of a miniature linguistic system. The miniature linguistic system consisted of nonsense syllables and concrete-enactive, agent-action referents. The purpose of Experiment 1 was to determine (a) whether children would recombine agent and action constituents to produce novel utterances and (b) whether children would generate further extensions of the linguistic system (e.g., agent-action-object sentences) following training of a novel syntactic construction. Four children (aged 8:8, 7:4, 4:9, and 4:5) produced novel utterances to describe untrained agent-action referents. They also progressed from agent-action learning to producing agent-action-object sentences after training on only one or two examples of this sentence type with the appropriate referents. Experiment 2 explored conditions more likely to facilitate recombinative generalization among preschoolers. In particular, how a history of lexical learning affects subsequent language learning was investigated with seven 4-year-olds. Results indicated that a history of lexical learning greatly enhanced generative production of untrained agent-action utterances. In addition, all seven children learned new syntactic rules to generate three-word utterances, regardless of the orderings of agent, action, and object words. Implications for developing efficient language remediation programs are discussed.

Child↗
PubMed2001

Global aspects of tuberculosis in children.

Tuberculosis (TB) in children reflects the prevalence of the disease in adults as well as current transmission rates. Africa and South-east Asia have the largest number of tuberculosis cases and the situation there has been worsened by the HIV epidemic. Children born to HIV-infected parents, whether infected or not, are at high risk of developing tuberculosis because of the increased risk of exposure to the disease. Tuberculosis is more common among the disadvantaged and vulnerable groups in each society and the impact of overcrowding, under-nutrition and poverty is particularly severe on children. Recent studies have documented the increase in the occurrence of tuberculosis in children, both in developed and developing countries. The peak age of notification of tuberculosis decreases as the incidence of the disease increases in the region. Tuberculosis infection can progress rapidly to disease, particularly in infancy and early childhood. Most of the morbidity occurs in the first few years after infection. Recently infected children and those with large tuberculin reaction (>18 mm) are at increased risk for progression and should be followed closely. Mortality from tuberculosis is also highest in early childhood, mainly due to disseminated forms like meningeal and miliary tuberculosis. Tuberculosis can be controlled either by preventing the infection from occurring or by treating early infection after it has occurred. An efficient tuberculosis control program with early detection of infectious adults and their cure is the best long-term approach to the reduction of TB disease in children. The DOTS strategy advocated by the WHO has the potential to have a significant impact on the epidemiology of tuberculosis by achieving high cure rates and thereby decreasing community transmission. BCG vaccination, through effective against disseminated forms of the disease in childhood, has very little impact on adult forms of the disease. Chemoprophylaxis or preventive therapy is effective, but difficult to implement on a mass scale and is only recommended for special high-risk groups in developing countries.

AIDS-Related Opportunistic Infections↗
PubMed2004

Extending the role of antithrombotic agents: an example based on the low-molecular-weight heparin, tinzaparin.

We illustrate a strategy for developing an antithrombotic agent based on the low-molecular-weight heparin (LMWH) tinzaparin experience. After anti-factor Xa and IIa activity pharmacokinetic characterization in healthy volunteers, clinical studies first explored the doses and then confirmed thrombosis prevention effects in postoperative (general and hip or knee replacement surgery) settings as compared with placebo and active treatments. This experience and additional dose-finding assessments led to large clinical studies verifying the effectiveness of tinzaparin in the treatment of deep vein thrombosis and acute pulmonary embolism. Subgroup analyses from these studies and preclinical experiments suggested a role for tinzaparin in patients with malignancy who are at high risk for thromboembolic complications. Challenging patient populations and other thrombotic disorders spawned interest in tinzaparin studies in the obese, the hemodialysis, the stroke, peripheral angioplasty, and the pregnant patient as well as in children with thromboembolic disorders. New therapeutic challenges were addressed with a bridging study for patients requiring interruption of oral anticoagulant therapy, a study of patients undergoing cardioversion for atrial fibrillation, and outpatient venous thromboembolism treatment studies. Efficient antithrombotic development programs not only build on traditional indications but elaborate on new therapeutic hypotheses generated from clinical studies, new therapeutic areas, and on-going basic science research programs.

Fibrinolytic Agents↗
PubMed2004

The Vibrio cholerae chitin utilization program.

Chitin, an insoluble polymer of GlcNAc, is an abundant source of carbon, nitrogen, and energy for marine microorganisms. Microarray expression profiling and mutational studies of Vibrio cholerae growing on a natural chitin surface, or with the soluble chitin oligosaccharides (GlcNAc)(2-6), GlcNAc, or the glucosamine dimer (GlcN)2 identified three sets of differentially regulated genes. We show that (i) ChiS, a sensor histidine kinase, regulates expression of the (GlcNAc)(2-6) gene set, including a (GlcNAc)2 catabolic operon, two extracellular chitinases, a chitoporin, and a PilA-containing type IV pilus, designated ChiRP (chitin-regulated pilus) that confers a significant growth advantage to V. cholerae on a chitin surface; (ii) GlcNAc causes the coordinate expression of genes involved with chitin chemotaxis and adherence and with the transport and assimilation of GlcNAc; (iii) (GlcN)2 induces genes required for the transport and catabolism of nonacetylated chitin residues; and (iv) the constitutively expressed MSHA pilus facilitates adhesion to the chitin surface independent of surface chemistry. Collectively, these results provide a global portrait of a complex, multistage V. cholerae program for the efficient utilization of chitin.

Cell Adhesion↗
PubMed2003

Evidence for lasting sequence segmentation in the discrete sequence-production task.

It is well known that movement sequences are initiated and executed more slowly as they become longer. Those effects of sequence length, which have been found to lessen with practice, have been attributed to the development of a single motor chunk that represents the entire sequence. But an increasingly efficient distribution of programming can also explain the effects. To examine the mechanisms underlying skill in executing keying sequences, the authors examined the performance of participants (N = 18) who practiced a discrete sequence-production task involving fixed sequences of 3 and 6 key presses. Detailed examination of the effects of extensive practice, of regularities in key pressing order, and of a preceding choice RT task on the production of those sequences showed that most participants executed the 6-key sequence as 2 or more successive segments and continued to do so in the various conditions. The preceding choice RT task restored the sequence-length effect in latency that had disappeared with practice. The present results suggest that practice induces the development of motor chunks, each representing a short segment, and with longer sequences a control scheme for concatenating the motor chunks. Segmentation of longer sequences appeared to be concealed by individual segmentation differences unless there were regularities that imposed a common segmentation pattern.

Adult↗
PubMed2005

Reducing the digital divide for low-income women with breast cancer: a feasibility study of a population-based intervention.

A fundamental challenge to helping underserved women and their families cope with breast cancer is providing them with easily accessible, reliable health care information and support. This is especially true for low-income families living in rural areas where resources are few and frequently distant as well as low-income families in urban areas where access to information and support can be complex and overwhelming. The Internet is one mechanism that has tremendous potential to help these families cope with breast cancer. This article describes a feasibility test of the potential for the National Cancer Institute's (NCI's) Cancer Information Service (CIS) to provide access to an Internet-based system that has been shown to improve quality of life for underserved breast cancer patients. The test was conducted in rural Wisconsin (low socioeconomic status [SES] Caucasian women) and in Detroit, Michigan (low SES African American women), and compares the effectiveness of several different dissemination strategies. Using these results we propose a model for how CIS telephone and partnership program services could efficiently disseminate such information and support systems. In doing so we believe that important steps can be taken to close the digital divide that separates low-income families from the resources they need to effectively face cancer. This is the first of two articles coming from this study. A companion article reports on an evaluation of the use and impact of this system on the women who were given access to it.

Breast Neoplasms↗
PubMedDate not supplied

Socioeconomic development, status of women, family planning, and fertility in Bangladesh: a district level analysis.

In this paper we examine the effects of socioeconomic development, the status of women, and family planning on fertility and the extent to which these effects vary among the nineteen districts of Bangladesh. The 1983 and 1991 Bangladesh Contraceptive Prevalence Survey data are used to examine the effects of these factors on differences in contraceptive use among currently married women aged 15-49. The proportion of currently married women aged 15-49 using contraception was 46.3 per cent in 1991, a considerable increase from 26.5 per cent in 1983. Contraceptive use rates for all the districts increased substantially over the period between 1983 and 1991 and the gap between Dhaka's rate and those of other districts was narrower in 1991 than in 1983. An analytical model composed of socioeconomic development, status of women, and family planning variables is tested using logistic regression. The logit model is used to evaluate the effects of a selected group of variables on the probability of using contraceptive methods. The analysis demonstrates clearly that socioeconomic development and women's status significantly impact the use of contraceptive methods in Bangladesh. The results also suggest that better-educated, employed women are more likely to use contraception than those who have little or no formal education and who are not employed. In 1983, rural-urban differences in contraceptive use were significant, but in 1991 area of residence was not significant, which suggests that family planning programs may have played an important role in providing contraceptive information and technology to rural areas. Our analysis also suggests that family planning programs operated more efficiently in some districts than in others, and regional differences remained important in 1991 as they were in 1983. Decomposition analysis suggests that shifts in population structure favored increased contraceptive use in Bangladesh. This analysis also indicates that change in rate is also important, contributing about 21 per cent of the overall increase in contraceptive use.

Adolescent↗
PubMed1999

Relationships between the activity of MMP1/TIMP1 enzymes and the TH1/TH2 cytokine network.

The evaluation of the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) would appear to be important in cancer patients. Since the activity of these enzymes is regulated at the gene level by cytokines, we studied the serum relationships between MMP1/TIMP1 and the network of TH1/TH2 cytokines in healthy subjects to better understand how the physiological network of cytokines regulates MMP1/TIMP1 activity. Such a study could lead to suggestions for follow-up experiments to create prognostic and diagnostic indices for more efficient disease prevention programs and biotherapeutic treatments of patients. For this purpose, we determined serum levels of MMP1, TIMP1 and interleukin (IL)2, interferon (IFN) gamma, IL4 and IL10 in both healthy men and women (men and women were analyzed separately as hormones are one of the non-cytokine regulatory factors of TH1 or TH2 polarization). These cytokines make up our basic network. Cytokines within the physiological network function simultaneously so mathematical models of multivariate statistical methods were used to study MMP1/TIMP1 and TH1/TH2 network relationships. It has been suggested that mathematical modeling is the only effective way of studying the immune system as a whole. The influence of network activation, antigen presenting cells, antibody response and chemokines on MMP1/TIMP1 balance was also studied. Network activation was evaluated by measuring the levels of soluble IL2 receptors (sIL2R) and sIL6R; the influence of antigen presenting cells was evaluated by measuring serum levels of tumor necrosis factor alpha (TNF alpha) and IL1 beta; antibody response was evaluated by measuring IL5 and IL6 serum levels and the influence of chemokines was evaluated by measuring serum levels of IL8. Our overall results suggest that there are relationships between the activity of MMP1/TIMP1 and the TH1/TH2 network in physiological conditions. These data may be useful in gaining a clearer insight into how the two systems interact and hence regulate the physiological homeostasis. Therefore, this paper provides suggestions for experimental studies on MMP1/TIMp1 enzymes and TH1/TH2 cytokines to create clinical and prognostic markers for patient evaluation.

Adult↗