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Results for “New approach methodologies”

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PubMed1997

[New methodological approaches to the study and assessment of health status in occupational medicine].

The authors present materials on work conditions and workers' health state, that necessitate urgent measures to increase living standards, to meet sanitary and hygienic demands, to preserve health through alternative methods (time-related defence, early rehabilitation), to set strict economic penalties for employers' higher concern for better work conditions. The topics discussed include consideration of complex hazards (effects of chemicals coming from various media, influence of occupational and household physical factors) in setting an Allowable Daily Dose. Regional peculiarities should be taken into account in hygienic standardization.

Absenteeism↗

PubMed1993

[The stress test in nuclear cardiology--present status].

In nuclear cardiology the exercise test is used above all to assess the diagnosis when ischaemic heart disease is suspected and to assess the extent and site of ischaemic heart disease. The objective of the submitted paper is to present new possibilities in this area where more perfect technical equipment and new methodological approaches contribute new quality to clinical decision taking. Greatest attention is devoted to tomographic analyses of perfusion of the heart muscle during the exercise test.

Coronary Disease↗

PubMed2026

The maternal-to-zygotic transition is a critical window for PFOA-induced disruption of developmental programming.

Early embryogenesis is governed by precisely timed gene regulatory programs that coordinate cell fate specification, tissue patterning, and morphogenesis. The maternal-to-zygotic transition (MZT) represents a pivotal developmental milestone during which regulatory control shifts from maternally deposited transcripts to activation of the zygotic genome. Disruption of this transition has the potential to alter developmental trajectories with lasting consequences. Per- and polyfluoroalkyl substances (PFAS), environmentally persistent contaminants, have been linked to developmental abnormalities, yet their impact on core embryonic gene regulatory networks especially with exposure during MZT is not well understood. Using zebrafish (Danio rerio), a tractable vertebrate model and New Approach Methodology (NAM), we investigated how PFAS exposure during the MZT alters early developmental programming. Embryos were exposed starting at different times before and within the MZT time window and collected at 24 h post-fertilization (hpf) for transcriptomic analysis. Targeted qRT-PCR revealed dysregulation of genes controlling transcriptional activation, lineage specification, proliferation, and differentiation. Whole-transcriptome RNA sequencing (RNA-seq) further identified widespread perturbations in gene networks governing transcriptional regulation, cell signaling, and embryonic morphogenesis. Temporal analysis revealed that exposure beginning at 3.5 hpf, followed by 8 hpf, corresponding to early zygotic genome activation and near completion of zygotic activation, respectively, resulted in the greatest differential gene expression changes at 24 hpf. Consistent with these early gene regulatory perturbations, larvae exposed starting at 8 hpf also exhibited altered behavior at 5 days post-fertilization. Together, these findings demonstrate that PFAS exposure during MZT disrupts the establishment of embryonic gene regulatory networks, linking environmental toxicant exposure to altered developmental patterning and organismal outcomes. This work underscores the vulnerability of early developmental transitions to environmental perturbation and positions MZT as a critical window of susceptibility during development.

NAMs (new approach methodologies)↗

PubMed2003

Dual excitation multi- fluorescence flow cytometry for detailed analyses of viability and apoptotic cell transition.

The discrimination of live/dead cells as well as the detection of apoptosis is a frequent need in many areas of experimental biology. Cell proliferation is linked to apoptosis and controlled by several genes. During the cell life, specific events can stimulate proliferation while others may trigger the apoptotic pathway. Very few methods (i.e. TUNEL) are now available for studies aimed at correlation between apoptosis and proliferation. Therefore, there is interest in developing new methodological approaches that are able to correlate apoptosis to the cell cycle phases. Recently new approaches have been proposed to detect and enumerate apoptotic cells by flow cytometry. Among these, the most established and applied are those based on the cell membrane modifications induced in the early phases of the apoptotic process. The dye pair Hoechst 33342 (HO) and Propidium Iodide (PI), thanks to their peculiar characteristics to be respectively permeable and impermeable to the intact cell membrane, seems to be very useful. Unfortunately the spectral interaction of these dyes generates a consistent "energy transfer" from HO to PI. The co-presence of the dyes in a nucleus results in a modification in the intensity of both the emitted fluorescences. In order to designate the damaged cells (red fluorescence) to the specific cell cycle phases (blue fluorescence), we have tested different staining protocols aimed to minimize the interference of these dyes as much as possible. In cell culture models, we are able to detect serum-starved apoptotic cells as well as to designate their exact location in the cell cycle phases using a very low PI concentration. Using a Partec PAS flow cytometer equipped with HBO lamp and argon ion laser, a double UV/blue excitation has been performed. This analytical approach is able to discriminate live blue cells from the damaged (blue-red) ones even at 0.05 micro g/mL PI. The same instrumental setting allows performing other multi-colour analyses including AnnexinV-FITC as well as the possibility to make a correlated analysis to phenotype markers.

Apoptosis↗

PubMed2001

The pathophysiology of tremor.

Tremor is defined as rhythmic oscillatory activity of body parts. Four physiological basic mechanisms for such oscillatory activity have been described: mechanical oscillations; oscillations based on reflexes; oscillations due to central neuronal pacemakers; and oscillations because of disturbed feedforward or feedback loops. New methodological approaches with animal models, positron emission tomography, and mathematical analysis of electromyographic and electroencephalographic signals have provided new insights into the mechanisms underlying specific forms of tremor. Physiological tremor is due to mechanical and central components. Psychogenic tremor is considered to depend on a clonus mechanism and is thus believed to be mediated by reflex mechanisms. Symptomatic palatal tremor is most likely due to rhythmic activity of the inferior olive, and there is much evidence that essential tremor is also generated within the olivocerebellar circuits. Orthostatic tremor is likely to originate in hitherto unidentified brainstem nuclei. Rest tremor of Parkinson's disease is probably generated in the basal ganglia loop, and dystonic tremor may also originate within the basal ganglia. Cerebellar tremor is at least in part caused by a disturbance of the cerebellar feedforward control of voluntary movements, and Holmes' tremor is due to the combination of the mechanisms producing parkinsonian and cerebellar tremor. Neuropathic tremor is believed to be caused by abnormally functioning reflex pathways and a wide variety of causes underlies toxic and drug-induced tremors. The understanding of the pathophysiology of tremor has made significant progress but many hypotheses are not yet based on sufficient data. Modern neurology needs to develop and test such hypotheses, because this is the only way to develop rational medical and surgical therapies.

Animals↗

PubMed2001

Differential diagnosis in multiple sclerosis.

Multiple sclerosis can usually be diagnosed from a patient's history, clinical examination, cerebrospinal fluid (CSF) analysis, and observations from magnetic resonance imaging (MRI). However, sometimes, the classic clinical criteria, even when supported by MRI findings or by abnormalities of the CSF, may not be sufficiently specific. Many conditions can produce a multifocal central nervous system syndrome with a relapsing-remitting course in young adults. The rate of misdiagnosis is around 5%, indicating that 1 in 20 patients thought to have MS have instead a condition resembling MS. The need to reach diagnostic certainty is particularly important given the availability of treatments which may potentially prevent the progression of the disease. Therefore, the search for new methodological approaches which increase the sensitivity and specificity of the diagnosis is warranted. While waiting for the development of new techniques to facilitate an early and correct diagnosis, a correct approach to a suspect MS patient has to be underlined in order to reduce the risk of a misdiagnosis. In this paper, I illustrate the diagnostic work-up that the practicing physician should follow when first confronted by a patient suspected of having MS.

Diagnosis, Differential↗

PubMed1982

[Vigilance behavior in interaction of the serotonin-selective antidepressant zimelidine and parenterally administered ethanol].

A randomized, placebo-controlled double-blind crossover study was carried out in 8 healthy male subjects to evaluate the interaction of (Z)-3-(4-bromphenyl)-N,N-dimethyl-3-(3-pyridyl)-allylamine-dihydrochloride-monohydrate (zimelidine, Normud) -- a new antidepressive drug -- and alcohol. New methodological approaches to the problem consisted in a parenteral application of ethanol and the introduction of the computer-assisted Oculodynamic Test -- a new multi-dimensional psychophysiological research instrument -- monitoring saccadic eye movements, choice-reaction parameters and cardiorespiratory parameters. Classical disimprovement of these parameters after ethanol infusion (equivalent to 1 mg % BEC) could be seen up to 5 h after administration. Alcohol effects were not potentiated by the selective serotonin-reuptake inhibitor zimelidine -- in contrary even a significant vigilance-stabilizing effect and improvement against placebo/ethanol values could be demonstrated for most of the vigilance-related parameters.

Adult↗

PubMed2004

Lipid raft proteins and their identification in T lymphocytes.

This review focuses on how membrane lipid rafts have been detected and isolated, mostly from lymphocytes, and their associated proteins identified. These proteins include transmembrane antigens/receptors, GPI-anchored proteins, cytoskeletal proteins, Src-family protein kinases, G-proteins, and other proteins involved in signal transduction. To further understand the biology of lipid rafts, new methodological approaches are needed to help characterize the raft protein component, and changes that occur in this component as a result of cell perturbation. We describe the application of new proteomic approaches to the identification and quantification of raft proteins in T-lymphocytes. Similar approaches, applied to other model cell systems, will provide valuable new insights into both cellular signal transduction and lipid raft biology.

Animals↗

PubMed2005

Hybrid and customized approach in telemedicine systems: an unavoidable destination.

Several important problems in the majority of industrialized countries have challenged the centralized and overburdened current model of healthcare. Telehealthcare systems are presented as a new paradigm, offering high expectations to provide effective solutions to this picture. With this paper we present a new methodological approach for telehealthcare systems that pursues the generation of clinical and physiological knowledge of the patient in a real time and personalized manner. This approach is based on a computational component, identified as patient physiological image (PPI), which is responsible for generating an image of the state of the patient and therapy devices. Three key issues of the proposed methodological approach are evaluated. With the objective to validate the capability of the PPI to determine the internal state of a patient, a digital simulation experiment over the mathematical model of a PPI is done. Numerical results are compared to those obtained by a validated mathematical model. Secondly, a laboratory prototype of a novel human physical activity monitor that follows the designed methodological approach will be tested, in order to evaluate the trade-off between processing capacity, portability, and cost-efficiency and power consumption, which are necessary to assure its compliance with the methodology. As a third key issue, the capability of our methodology to integrate physiological information belonging to different scales is analyzed. This is done by means of a case study related to the integration of the regulation of water function of AQP2 channels (genomic, proteomic and cellular levels) into a kidney collecting duct epithelium mathematical model of a PPI. The analysis and preliminary evaluation of the proposed telehealthcare methodological approach, featured by an advanced personalization of health assistance, have been satisfactory.

Delivery of Health Care↗

PubMed2006

Recommendations of the National Heart, Lung, and Blood Institute working group on cerebrovascular biology and disease.

The National Heart, Lung, and Blood Institute (NHLBI) convened a conference call working group, consisting of experts in stroke and cerebrovascular biology on January 28, 2005. The purpose of this working group was to develop a prioritized set of recommendations for NHLBI to establish a focused and comprehensive set of research activities in cerebrovascular biology and disease. Three thematic areas of research emerged: (1) molecular and cellular neurobiology of cerebral blood vessels, focusing on genomics and proteomics, neurovascular signaling and cerebrovascular embryogenesis, development and plasticity; (2) resource development, involving the development of new methodological approaches for normal and altered function of the neurovascular unit, collaborative research, and training in cerebrovascular pathobiology; and (3) cerebrovascular diseases and translational approaches, addressing vascular mechanisms of disease, the role of risk factors, importance of biomarkers with the ultimate goal of developing new treatments.

Animals↗

PubMed1993

Short-term forecasting of internal migration.

A new methodological approach to the forecasting of short-term trends in internal migration in the United States is introduced. "Panel-data (or longitudinal-data) models are used to represent the relationship between destination-specific out-migration and several explanatory variables. The introduction of this methodology into the migration literature is possible because of some new and improved databases developed by the U.S. Bureau of the Census.... Data from the Bureau of Economic Analysis are used to investigate the incorporation of exogenous factors as variables in the model." The exogenous factors considered include employment and unemployment, income, population size of state, and distance between states. The author concludes that "when one...includes additional parameters that are estimable in longitudinal-data models, it turns out that there is little additional information in the exogenous factors that is useful for forecasting."

Americas↗

PubMed2003

Linear and nonlinear parameters for the analysis of fetal heart rate signal from cardiotocographic recordings.

Antepartum fetal monitoring based on the classical cardiotocography (CTG) is a noninvasive and simple tool for checking fetal status. Its introduction in the clinical routine limited the occurrence of fetal problems leading to a reduction of the precocious child mortality. Nevertheless, very poor indications on fetal pathologies can be inferred from the even automatic CTG analysis methods, which are actually employed. The feeling is that fetal heart rate (FHR) signals and uterine contractions carry much more information on fetal state than is usually extracted by classical analysis methods. In particular, FHR signal contains indications about the neural development of the fetus. However, the methods actually adopted for judging a CTG trace as "abnormal" give weak predictive indications about fetal dangers. We propose a new methodological approach for the CTG monitoring, based on a multiparametric FHR analysis, which includes spectral parameters from autoregressive models and nonlinear algorithms (approximate entropy). This preliminary study considers 14 normal fetuses, eight cases of gestational (maternal) diabetes, and 13 intrauterine growth retarded fetuses. A comparison with the traditional time domain analysis is also included. This paper shows that the proposed new parameters are able to separate normal from pathological fetuses. Results constitute the first step for realizing a new clinical classification system for the early diagnosis of most common fetal pathologies.

Algorithms↗

PubMed1993

Restenosis revisited: insights provided by quantitative coronary angiography.

In this editorial, the problem of restenosis after coronary balloon angioplasty and other transluminal interventions is reviewed from the perspective of quantitative coronary angiography. The review is largely based on the experience of the Thoraxcentre in the application of quantitative angiography to the study of restenosis over the past decade, with incorporation and discussion of relevant and significant contributions from other groups. Current discrepancies in the angiographic definition of restenosis are highlighted and the use of percent diameter stenosis or MLD as the measurement parameter of choice is objectively addressed. Perspectives on the pathologic paradigm of restenosis are briefly reviewed as a basis from which to evaluate quantitative angiographic information provided by various studies. Particular attention is then paid, in chronologic fashion, to discussion and elaboration of insights to the restenosis process provided by quantitative angiographic studies, which have led to the introduction of some new methodological approaches to the comparison of short- and long-term angiographic luminal changes after various interventions. A word of caution on the potential pitfalls of quantitative angiographic studies is provided and counterbalanced with a discussion of clinical correlations of quantitative angiographic measurements. Finally, a proposal is made for the application of quantitative angiographic measurements to randomized clinical trials for the purpose of comparing new interventional devices.

Angioplasty, Balloon, Coronary↗

PubMed1991

[New principles of ambulatory care of adult patients with pulmonary tuberculosis].

New methodologic approaches have been developed to the outpatient care of patients with respiratory tuberculosis, which accelerates their cure and shorten the terms of their follow-up in dispensary registry groups. These methods were tested in antituberculosis institutions of 26 regions and cities of the RSFSR during 10 years. At present they have been introduced into the antituberculosis establishments of some RSFSR administrative areas. The use of the new method of outpatient care of tuberculosis patients enables the number of the contingents requiring specialized phthisiatric care to be defined more accurately and specified. Introduction of the method requires no additional material and technical expenses and resources. On the contrary, it provides their more effective use in order to improve the quality of diagnostic and therapeutic care to tuberculosis patients.

Adult↗

PubMed2003

Toward the next quarter-century: conceptual and methodological challenges for attachment theory.

Attachment theory and research have offered fundamental insights into early sociopersonality development for the past quarter-century. As its scope expands throughout the life course with applications to developmental psychopathology, however, attachment work faces important conceptual and methodological challenges. These include (a) expanding Bowlby's theoretical formulations to address developmental changes in the nature of attachment organization beyond infancy, the converging influence of multiple attachment relationships, and the nature and development of internal working models: (b) systematically validating assessments of attachment security for older ages in the context of enhanced theoretical understanding of how attachment itself changes with age; (c) new methodological approaches to understanding the relations between attachment and later behavior in light of empirical evidence of stability and change in attachment security and the need for explicit theoretical predictions of the sequelae of attachment security; and (d) more complex conceptualizations of the associations among attachment, contextual risk, and later behavior. These are similar to the challenges facing the original pioneers of attachment theory and research, suggesting that familiar problems must now be reconsidered against the landscape of new applications of attachment work and the insights of contemporary developmental science.

Child↗

PubMed1976

[Results of 8 years' research on the toxicologic evaluation of animal food additives by the so-called relay toxicity method].

The authors report the underlying principles of the new methodological approach called "relay toxicity" which they proposed eight years ago for the toxicological evaluation of animal feed additives. They stress its value either as a possible criterion of rejection or as a criterion of acceptability. In the latter case, the limiting factor is the difficulty of applying an adequate safety factor when food products destined for human consumption and obtained from animals receiving the additives to be evaluated are administered to laboratory animals. Amongst the examples of the additives which have been subjected to toxicological evaluation using the authors' new method, the following are examined: as growth factor, carbadox, anabolising agents and, in particular, diethylstilboestrol, and steroids used as egglaying potentializers. The results obtained are discussed.

Anabolic Agents↗

PubMed2005

Primate spermatogenesis: new insights into comparative testicular organisation, spermatogenic efficiency and endocrine control.

Owing to the close phylogenetic relationship of Platyrrhini (New World monkeys) and Catarrhini (Old World monkeys) to man, nonhuman primates are often used as models for the study of male reproductive physiology and endocrinology. This review aims at providing new data and insights into comparative primate spermatogenesis, dealing specifically with quantitative aspects of germinal epithelial organisation and germ cell production, and with the roles of gonadotrophic hormones in this process. Typically, the seminiferous epithelium is composed of specific germ cell associations (spermatogenic stages). In rodents, prosimians and most Catarrhini, tubular cross sections contain a single spermatogenic stage whereas in Platyrrhini, great apes and man multi-stage tubules are present. Since Platyrrhini represent a more basal type of primate, this spermatogenic feature must have developed convergently. The primate multi-stage tubular arrangement was previously believed to be associated with low spermatogenic efficiency. However, recent studies using new methodological approaches and comparing primate species from all taxa have revealed that multistage organisation is compatible with highly efficient spermatogenesis. In fact, meta-analysis demonstrated that the efficiency of spermatogenesis in several nonhuman primate species is comparable to that of rodents which are considered as species with highly efficient germ cell production. The duration of the spermatogenic process was not related to organisation or efficiency of spermatogenesis. Sertoli cell work load was species-specific but had no impact on germ cell numbers and on the efficiency of spermatogenesis. The gonadotrophic hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH) are the primary regulators of primate testicular function. Recent studies revealed that in New World monkeys chorionic gonadotrophin (CG)--the primate pregnancy hormone--regulates testosterone production instead of LH. Receptor studies demonstrated a dual action of the closely related hormones LH and CG in primates. It is hypothesised that following the divergence of the Platyrrhini lineage from Catarrhini, the LH/CG system evolved independently with ancestral functions of the LH/CG system retained in the neotropical taxa. In summary, key spermatogenic features are preserved across all primate taxa whereas male reproductive endocrinology features appear substantially different in the neotropical primates compared to other primate lineages.

Animals↗

PubMed1990

[Tissue renin-angiotensin system. Physiology and physiopathological value of their inhibition by ramipril].

The existence of tissue renin angiotensin system (RAS) has been widely suggested in the recent literature by 2 main approaches: first, a dissociation between antihypertensive effects of angiotensin converting enzyme (ACE) inhibitors and the levels of stimulation of the circulating RAS; secondly, by the demonstration of the presence of the 3 key-proteins of the system (angiotensinogen, creatinine, and converting enzyme) within the 3 main target-organs of hypertension (i.e. kidney, heart and vessels). Those organs are capable to synthetize locally angiotensin II. Ramipril, a new ACE inhibitor (Triatec), which possesses a high affinity for tissue CE of those organs, according to previous publications by Unger, has been used as a tool for the investigations of the inhibition of those systems in human hypertension: a decrease of micro proteinuria has been without antihypertensive effects. In binephrectomized patients, ramipril has been shown to possess an antihypertensive effect. Finally, an important improvement of myocardial hypertrophy has been shown in hypertensive patients. Furthermore, this effect has been observed in animals (rats with aortic stenosis) even with low doses without antihypertensive effects. Further studies with new methodological approaches are still necessary.

Angiotensin-Converting Enzyme Inhibitors↗