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PubMed1998

Physiological, biochemical and molecular aspects of mitochondrial complex I in plants

Respiratory complex I of plant mitochondria has to date been investigated with respect to physiological function, biochemical properties and molecular structure. In the respiratory chain complex I is the major entry gate for low potential electrons from matrix NADH, reducing ubiquinone and utilizing the released energy to pump protons across the inner membrane. Plant complex I is active against a background of several other NAD(P)H dehydrogenases, which do not contribute in proton pumping, but permit and establish several different routes of shuttling electrons from NAD(P)H to ubiquinone. Identification of the corresponding molecular structures, that is the proteins and genes of the different NADH dehydrogenases, will allow more detailed studies of this interactive regulatory network in plant mitochondria. Present knowledge of the structure of complex I and the respective mitochondrial and nuclear genes encoding various subunits of this complex in plants is summarized here. Copyright 1998 Elsevier Science B.V.

Journal Article↗
PubMed2002

Science writers' reactions to a medical "breakthrough" story.

In numerous incidences, the news coverage of medical research has incited unjustified optimism or fear. The medical literature provides an archive of the scientific community's condemnation of these misleading reports, but little is known about how they are judged by newsmakers. This study explored science writers' reactions to a controversial New York Times story that inflated the hopes of thousands of cancer patients. More than 60 science writers in the US, Canada, and Great Britain participated in a 12-day email discussion triggered by the Times article. We analyzed 255 of these email postings and coded (1) positive and negative critiques of the Times story, (2) references to the article's repercussions including the creation of false hope, (3) attributions of responsibility for the resulting public misunderstanding, and (4) suggestions to improve the public's comprehension of medical research news. The participating science writers generally responded negatively to the controversial article: 83% of the critiques were unfavorable. In addition, the science writers in the sample were cognizant and concerned about the impact of their work on the public, and accepted the largest share of the responsibility for the false hope created by the news coverage of medical research. Finally, the suggestions offered by respondents to improve the public's understanding of medical research news were similar to those proposed by the scientific community. Thus, some commonality exists between how scientists and science writers believe the news coverage of medical research could be improved.

Attitude to Health↗
PubMed1977

Toward a Biocommunications Network.

Development and implementation of the Biocommunications Network in the Memphis region have relied on sharing of resources among hospital libraries. Implied in this system is the recognition that all health care professionals have a right of access to health sciences libraries.

Costs and Cost Analysis↗
PubMed2002

Organisational and educational internal impediments of psychoanalysis: contemporary challenges.

Our psychoanalytic discipline originated, has evolved and is still located within a congregational network that blends and binds together, in an inextricable and contradictory way, the missionary mandates and commendations of a 'movement' and a 'cause' with the inherent prerogatives and functions of academic professions and sciences. In this paper the author explores the consequential past and present impedimenta of this organisational and educational syncretism, for six fundamental dimensions of action for psychoanalysis. Subsequently, the nature of a proposition is delineated, suggesting a reorganisation, local and international, to address what the author visualises as five of our most pressing contemporary challenges: a) an autonomous university educational model, freed from regressive societal-political inertias, enabling us to abandon our seclusive monasticism; b) the consolidation of an epistemological frame of reference, idiographic and nomothetically substantiated against our cumulative inductivism, which is the seedbed of our sectarianism, cross-sterilisation and pseudo-ecumenism; c) local and external educational and professional systems of accreditation and certification, independent from affiliation and membership privileges of our supraordinate ecclesia; d) social relevance and community presence, moving away from our meaningless organisational and educational cloistering; and e) a local and international functional and interdependent reorganisation, in the context of sovereignty and integrity, in contrast to our prevalently crusading and indoctrinating homogamous pathological co-dependency. The author concludes that only a harmonisation of objectives and administrative structure might loosen the talons of faith that keep us retrogressively tied to our past.

Humans↗
PubMed1991

Clinical immunology: past, present and future challenges and prospects.

Over the past four decades, immunology has undergone a revolution changing from a largely phenomenological science into a deeply analytical and technical field. Questions concerning the primary cell involved in cell-mediated immunity, the mechanisms responsible for antibody diversity as well as the molecules used by the network of immunological cells to communicate with one another that could barely be asked in the 1950s, have been definitely answered. A major contributor to this revolution in immunological knowledge has been the scientist focussing on patient-oriented clinical immunology, a form of clinical research requiring the presence of the patient or materials freshly derived from the patient. This type of research has led to the discovery of new diseases, the definition of new infectious agents causing disease and the delineation of functional defects using applied variables on mononuclear cells removed from the patient. Moreover, this type of research is absolutely required to test hypotheses concerning the pathogenesis of disease in humans and to provide the scientific basis for the development of new approaches to therapy. As I look to the future, there are great threats to patient-oriented clinical research. The road ahead seems long and daunting. Nevertheless, I am encouraged that the patient-oriented clinical research scientist in the future will make major contributions to the use of the immune system in preventing human disease, in the development of immunological methods for diagnosis, and in the use of immune intervention to provide a new perspective for the prevention of allograft rejection, and for the treatment of neoplastic, immunodeficiency, and autoimmune disease.

Allergy and Immunology↗
PubMed1991

Digital chest radiography.

It is apparent that digital radiography holds considerable promise. Although there are some immediate advantages to be gained from using digital technology at present, such as more consistent image quality in portable radiography, most of the benefits have not been fully realized. To do so requires a completely integrated digital radiology department using high-resolution video displays throughout the hospital connected to a large digital image archiving system. This concept, referred to as picture archiving and communication systems (PACS), represents the logical culmination of the extensive research that is continuing in this area. Because of the great expense involved, it is likely that the transition from conventional to digital radiography will be evolutionary in most medical centers, with establishment of local PACS networks initially, such as between the intensive care units and the radiology department. At a more basic level, limited digital radiography systems can function in isolation and address specific needs successfully. Although the science of computer-aided diagnosis is at an early stage, it seems likely that the sensitivity and specificity of these programs will continue to improve. Their eventual utility will depend on their accuracy and ease of use. The ultimate goal would be a relatively "transparent" multifaceted program that would screen all radiographs prior to interpretation to provide the radiologist or clinician with diagnostic suggestions and quantitative data. Given the present rate of progress in this area, such a concept is not unrealistic. However, even the most ardent enthusiasts do not envision totally independent computer-based interpretation of radiographic images for some time. Although digital image processing has not greatly improved diagnostic accuracy merely by enhancing the appearance of the radiographs, there are other potential diagnostic advantages in using digital images, such as rapid retrieval of previous examinations and the ability to correlate chest radiographs with CT or MRI studies rapidly on a video display. Direct image correlation with registration and superimposition has been achieved in the case of positron-emission tomography and MRI studies of the brain. For chest radiograph examinations, superimposition and subtraction of earlier radiographs to enhance the detection of interval change is being studied. The question of when digital chest radiography will replace conventional imaging is controversial. In a recent multiauthored review of this subject, it was estimated that digital chest radiography will replace conventional film radiography in at least 50% of large teaching hospitals by the turn of the century.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnosis, Computer-Assisted↗
PubMed1972

Mechanization of library procedures in the medium-sized medical library. 8. Computer applications in hospital departmental libraries.

To test the hypothesis that a standard library system could be designed for hospital departmental libraries, a system was developed and partially tested for four departmental libraries in the Washington University School of Medicine and Associated Hospitals. The system from determination of needs through design and evaluation, is described. The system was limited by specific constraints to control of the monograph collection. Products of control include catalog cards, accessions list, new book list, location list, fund list, missing book list, and discard book list. Sample data form and pages from a procedure manual are given, and conversion from a manual to an automated system is outlined. The question of standardization of library records and procedures is discussed, with indications of the way in which modular design, as utilized in this system, could contribute to greater flexibility in design of future systems. Reference is made to anticipating needs for organizing departmental libraries in developing regional medical library programs and to exploring the role of the departmental library in a medical library network.

Computers↗
PubMed2005

Creating accessible science museums with user-activated environmental audio beacons (ping!).

In 2003, Touch Graphics Company carried out research on a new invention that promises to improve accessibility to science museums for visitors who are visually impaired. The system, nicknamed Ping!, allows users to navigate an exhibit area, listen to audio descriptions, and interact with exhibits using a cell phone-based interface. The system relies on computer telephony, and it incorporates a network of wireless environmental audio beacons that can be triggered by users wishing to travel to destinations they choose. User testing indicates that the system is effective, both as a way-finding tool and as a means of providing accessible information on museum content. Follow-up development projects will determine if this approach can be successfully implemented in other settings and for other user populations.

Architectural Accessibility↗
PubMed1999

Laureate ESCI award for excellence in clinical science 1999. Cytokines and the human immunodeficiency virus: from bench to bedside. European Society for Clinical Investigation.

Replication of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), is under the control of both viral and host factors. Among the latter, the regulatory network of cytokines has been shown to affect virtually every step of the virus life cycle, from cell entry to budding of new progeny virions. Proinflammatory cytokines, such as tumour necrosis factor alpha, can either trigger or potentiate HIV expression via activation of the cellular transcription factor NF-kappaB. Other molecules, including interleukin 6 (IL-6) and the interferons, can up-regulate HIV expression by acting predominantly at post-transcriptional and/or post-translational levels. Anti-inflammatory cytokines, including transforming growth factor beta, IL-4 and IL-10, counteract these effects but can also potentiate viral replication under different experimental conditions. Chemotactic cytokines (chemokines) have recently entered the arena of host factors controlling viral spreading as potent inhibitors competing with the virus for cell-surface 7-transmembrane domain receptors also acting, together with CD4, as entry co-receptors for HIV. The cytokine network is constitutively activated in most HIV-infected individuals, as demonstrated by recent analysis of intracellular signalling molecules such as the Janus kinase/signal transducer and activator of transcription pathway. Finally, cytokines have already shown their potential use as pharmacological agents able to restore at least some of the compromised immune functions in infected individuals, as exemplified by the potent enhancing effect of IL-2 on the number of circulating CD4+ T lymphocytes.

Awards and Prizes↗
PubMed2004

Identifying priority health conditions, environmental data, and infrastructure needs: a synopsis of the Pew Environmental Health tracking project.

In this article we describe the methodologic approaches of the Pew Environmental Health Commission at the Johns Hopkins Bloomberg School of Public Health used to identify priority environmental health conditions and develop recommendations to establish a national environmental public health tracking network. We present the results of a survey of public health and environmental practitioners to uncover state and local health tracking needs and priorities. We describe the steps that combined the findings from the state and local health tracking survey and a review of the state of the science on environmental impacts on health to identify priority health end points. Through an examination of national health and health care databases, we then describe trends and public health effects of those diseases that may be linked to the environment. Based on this analysis, respiratory diseases and neurologic diseases are recommended as priorities for tracking. Specific end points recommended for tracking include asthma and chronic respiratory diseases, and chronic neurodegenerative diseases such as multiple sclerosis. Based on trends in reported prevalence, consideration should also be given to developmental disabilities, reproductive disorders, and endocrine/metabolic disorders. Strengthening of current efforts to track cancer and birth defects should also be included as components of a nationwide health tracking network. Finally, we present the recommendations for environmental public health tracking. These recommendations provided the groundwork for the development of the Centers for Disease Control and Prevention's National Environmental Public Health Tracking Progam that now includes 21 states, three cities, and three academic centers throughout the nation.

Centers for Disease Control and Prevention, U.S.↗
PubMed2002

5.3 Global challenges in research and strategic planning.

Health sciences research is experiencing dramatic progress. How can dental schools throughout the world best make these research advances relevant for dental students, as well as providing them with the means to assess and utilize the research advances that will occur in the future? This complex question presents a critical challenge to the dental educational community. Research is clearly integral to the mission of dental education. By providing dental students with active learning strategies, dental educators can inculcate the ability for independent scientific thinking and thereby develop reflective as well as technically competent practitioners. However, there is a shortage of well-trained individuals to fill faculty and research positions in certain parts of the world. Global networks for mutual information exchange are imperative to overcome resource limitations in individual institutions, as is dedicated funding for research in the dental educational setting.

Computer Communication Networks↗
PubMed2006

Assessment of Internet-based tele-medicine in Africa (the RAFT project).

The objectives of this paper on the Réseau Afrique Francophone de Télémédecine (RAFT) project are the evaluation of feasibility, potential, problems and risks of an Internet-based tele-medicine network in developing countries of Africa. The RAFT project was started in Western African countries 5 years ago and has now extended to other regions of Africa as well (i.e. Madagascar, Rwanda). A project for the development of a national tele-medicine network in Mali was initiated in 2001, extended to Mauritania in 2002 and to Morocco in 2003. By 2006, a total of nine countries are connected. The entire technical infrastructure is based on Internet technologies for medical distance learning and tele-consultations. The results are a tele-medicine network that has been in productive use for over 5 years and has enabled various collaboration channels, including North-to-South (from Europe to Africa), South-to-South (within Africa), and South-to-North (from Africa to Europe) distance learning and tele-consultations, plus many personal exchanges between the participating hospitals and Universities. It has also unveiled a set of potential problems: (a) the limited importance of North-to-South collaborations when there are major differences in the available resources or the socio-cultural contexts between the collaborating parties; (b) the risk of an induced digital divide if the periphery of the health system in developing countries is not involved in the development of the network; and (c) the need for the development of local medical content management skills. Particularly point (c) is improved through the collaboration between the various countries as professionals from the medical and the computer science field are sharing courses and resources. Personal exchanges between partners in the project are frequent, and several persons received an education at one of the partner Universities. As conclusion, we can say that the identified risks have to be taken into account when designing large-scale tele-medicine projects in developing countries. These problems can be mitigated by fostering South-South collaboration channels, by the use of satellite-based Internet connectivity in remote areas, the appreciation of local knowledge and its publication on-line. The availability of such an infrastructure also facilitates the development of other projects, courses, and local content creation.

Africa↗
PubMed2006

Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy.

Basic science studies of the human brain have supported the cortical representation of cardiovascular responses, including heart rate variability. Clinical observations of ictal bradyarrhythmia may be mechanistically explained by the influence of the central autonomic network, although the localization and lateralization issues need to be considered in the light of patterns of seizure spread, hand dominance, and presence of lesions. Ictal bradyarrhythmia also offers a mechanistic explanation of sudden unexpected death in epilepsy (SUDEP), though it may explain only some but not all cases of SUDEP. The missing links are (1) clinical evidence of common factors shared by patients with ictal bradyarrhythmia and patients who die from SUDEP, (2) evidence of arrhythmia as a risk factor for SUDEP from epidemiological studies, and, (3) determination of the importance of ictal bradyarrhythmia in SUDEP with respect to other proposed mechanisms including apnea and intrinsic cardiac abnormalities. There remains a need to review the seizure mechanisms in cases of SUDEP and to step up the amount of concurrent ECG/intracranial EEG analysis in both ictal bradyarrhythmia and SUDEP cases.

Autonomic Nervous System↗
PubMed1997

Non-indexed medical journals in the Web: new perspectives in the medical literature.

Many medical journals, publishing in national languages, meet serious financial problems and difficulties when they attempt to become indexed in the international indices. Obviously, this not only affects the scientific quality of non-indexed medical journals (NIMJs) but also affects the awareness of the scientific community of topics with apparently local but potentially broader scientific significance. This is a reality for over 100 Greek medical journals, none of which has a life longer than 30 years or more than 2000 subscribers. Among them, the 'Archives of Hellenic Medicine' (AHM) is published and sponsored by the Athens Medical Society (the oldest medical society in Greece founded in 1835). This peer-reviewed Journal is being published for 13 years, bimonthly, in Greek. Attempting to overcome the above mentioned problems and to be involved in the process of discovering the most effective way of scientific 'skywriting', 2 years ago, the AHM entered full-text in the Web and it was decided that up to 500% of its volume should be covered by English-language papers. As a result, the AHM are now included in the main Web lists of medical journals and their home page is linked in many academic pages having approximately 500 hits/month. Furthermore, 45 retrievals of AHM's English-language papers or English abstracts of Greek-language articles were reported by e-mail response from abroad. Considered apart from the paper-publishing, the expenses of the digital publishing of the AHM are about half of those of paper-publishing, as they were before the appearance of the Journal in the Web. Up to now, about 40% of the Journal's digital publishing cost is covered by advertisements included in its pages and by a modification of its paper-publishing policy. It is concluded that the international scientific community is not indifferent for information published in NIMJs. Medical national minorities working abroad express special interest for this type of information. The Web makes the NIMJs accessible to these potential readers, who would never have the chance to acquire them in their printed form.

Abstracting and Indexing↗
PubMed2006

Minimal model of spiky oscillations in NF-kappaB signaling.

The NF-kappaB signaling system is involved in a variety of cellular processes including immune response, inflammation, and apoptosis. Recent experiments have found oscillations in the nuclear-cytoplasmic translocation of the NF-kappaB transcription factor [Hoffmann, A., et al. (2002) Science 298, ; Nelson, D. E., et al. (2004) Science 306, .] How the cell uses the oscillations to differentiate input conditions and send specific signals to downstream genes is an open problem. We shed light on this issue by examining the small core network driving the oscillations, which we show is designed to produce periodic spikes in nuclear NF-kappaB concentration. The presence of oscillations is extremely robust to variation of parameters, depending mainly on the saturation of the active degradation rate of IkappaB, an inhibitor of NF-kappaB. The oscillations can be used to regulate downstream genes in a variety of ways. In particular, we show that genes to whose operator sites NF-kappaB binds and dissociates fast can respond very sensitively to changes in the input signal, with effective Hill coefficients of >20.

Cytoplasm↗
PubMed2026

Current knowledge in pharmacogenomics and precision medicine: perspectives of the PGRN global PGx committee on improving drug therapies in underrepresented ethnic populations.

A precision medicine strategy is likely to be more impactful, when pharmacogenomics (PGx) guided selection of drugs and dosage wherever applicable is implemented across the globe. In regions where resources are disproportionately distributed, PGx implementation in routine clinical care can play a critical role in ensuring the optimal use of limited healthcare infrastructure. At present, PGx data from the majority of the distinct ethnic populations across Asia, Africa, and South America is limited. While international consortia, working groups, and scientific bodies have made significant contributions toward evaluating the evidence for PGx implementation, the majority of existing guidelines and recommendations are derived primarily from studies conducted in a limited number of ethnic groups. Precision Medicine Initiatives in countries like Korea, Taiwan, and Malaysia and PGx organizations like the African Institute of Biomedical Science and Technology (AiBST), Consortium for Genomics & Therapeutics in Africa (CGTA), implementation of pharmacogenetic testing for the effective care and treatment in Africa, Greater Middle East (GME) whole exome sequencing program, Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF), Latin American Society of Pharmacogenomics and Personalized Medicine (SOLFAGEM), Latin American Network for Validation and Implementation of Pharmacogenomic Clinical Guidelines (RELIVAF), IndiGen initiative, Southeast Asian Pharmacogenomics Research Network (SEAPharm), are working toward consolidating the PGx presence in these regions.

Precision Medicine↗
PubMed2002

Single-base-pair discrimination of terminal mismatches by using oligonucleotide microarrays and neural network analyses.

The effects of single-base-pair near-terminal and terminal mismatches on the dissociation temperature (T(d)) and signal intensity of short DNA duplexes were determined by using oligonucleotide microarrays and neural network (NN) analyses. Two perfect-match probes and 29 probes having a single-base-pair mismatch at positions 1 to 5 from the 5' terminus of the probe were designed to target one of two short sequences representing 16S rRNA. Nonequilibrium dissociation rates (i.e., melting profiles) of all probe-target duplexes were determined simultaneously. Analysis of variance revealed that position of the mismatch, type of mismatch, and formamide concentration significantly affected the T(d) and signal intensity. Increasing the concentration of formamide in the washing buffer decreased the T(d) and signal intensity, and it decreased the variability of the signal. Although T(d)s of probe-target duplexes with mismatches in the first or second position were not significantly different from one another, duplexes with mismatches in the third to fifth positions had significantly lower T(d)s than those with mismatches in the first or second position. The trained NNs predicted the T(d) with high accuracies (R(2) = 0.93). However, the NNs predicted the signal intensity only moderately accurately (R(2) = 0.67), presumably due to increased noise in the signal intensity at low formamide concentrations. Sensitivity analysis revealed that the concentration of formamide explained most (75%) of the variability in T(d)s, followed by position of the mismatch (19%) and type of mismatch (6%). The results suggest that position of the mismatch at or near the 5' terminus plays a greater role in determining the T(d) and signal intensity of duplexes than the type of mismatch.

Base Pair Mismatch↗