Factors Relevant (factor + relevant)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Generation and characterization of low-energy structures in atomic clusters

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2010
J. M. C. Marques
Abstract Factors relevant for controlling the structures determined in the local optimization of argon clusters are investigated. In particular, the role of volume and shape for the box where initial structures are generated is assessed. A thorough characterization of the optimization is also presented, based on a nearest-neighbor analysis, in clusters ranging from 30 to 55 atoms. This includes the assessment of the degree of preservation of aspects of the initial randomly generated structure in the final optimized counterpart, and the correlation between optimized energy and the number of nearest neighbors and average departure from the diatomic reference distance. The usefulness of this analysis to explore the energy landscape of atomic clusters is also highlighted. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]


Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease,

HUMAN MUTATION, Issue 6 2008
Veerle Bogaerts
Abstract In one genetic study, the high temperature requirement A2 (HTRA2) mitochondrial protein has been associated with increased risk for sporadic Parkinson disease (PD). One missense mutation, p.Gly399Ser, in its C-terminal PDZ domain (from the initial letters of the postsynaptic density 95, PSD-95; discs large; and zonula occludens-1, ZO-1 proteins [Kennedy, 1995]) resulted in defective protease activation, and induced mitochondrial dysfunction when overexpressed in stably transfected cells. Here we examined the contribution of genetic variability in HTRA2 to PD risk in an extended series of 266 Belgian PD patients and 273 control individuals. Mutation analysis identified a novel p.Arg404Trp mutation within the PDZ domain predicted to freeze HTRA2 in an inactive form. Moreover, we identified six patient-specific variants in 5, and 3, regulatory regions that might affect HTRA2 expression as supported by data of luciferase reporter gene analyses. Our study confirms a role of the HTRA2 mitochondrial protein in PD susceptibility through mutations in its functional PDZ domain. In addition, it extends the HTRA2 mutation spectrum to functional variants possibly affecting transcriptional activity. The latter underpins a previously unrecognized role for altered HTRA2 expression as a risk factor relevant to parkinsonian neurodegeneration. Hum Mutat 29(6), 832,840, 2008. © 2008 Wiley-Liss, Inc. [source]


Secretion of interferon-, by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18

IMMUNOLOGY, Issue 3 2009
Laila Darwich
Summary The interferon (IFN)-, component of the immune response plays an essential role in combating infectious and non-infectious diseases. Induction of IFN-, secretion by human T and natural killer (NK) cells through synergistic costimulation with interleukin (IL)-12 and IL-18 in the adaptive immune responses against pathogens is well established, but induction of similar activity in macrophages is still controversial, with doubts largely focusing on contamination of macrophages with NK or T cells in the relevant experiments. The possible contribution of macrophages to the IFN response is, however, an important factor relevant to the pathogenesis of many diseases. To resolve this issue, we analysed the production of IFN-, at the single-cell level by immunohistochemistry and by enzyme-linked immunosorbent spot (ELISPOT) analysis and unequivocally demonstrated that human macrophages derived from monocytes in vitro through stimulation with a combination of IL-12 and IL-18 or with macrophage colony-stimulating factor (M-CSF) were able to produce IFN-, when further stimulated with a combination of IL-12 and IL-18. In addition, naturally activated alveolar macrophages immediately secreted IFN-, upon treatment with IL-12 and IL-18. Therefore, human macrophages in addition to lymphoid cells contribute to the IFN-, response, providing another link between the innate and acquired immune responses. [source]


Deliberate self-harm (DSH) among older people: a retrospective study in Barnet, North London

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 2 2005
Florian Alexander Ruths
Abstract Background Rates of suicide remain high among older people and those who deliberately self harm are believed to be at an increased risk of killing themselves in the future. If older people who deliberately harm themselves are to be helped by developments in services we need to understand what currently happens to them in terms of service provision and outcome. Methods A retrospective paper and electronic case note survey was carried out on all older people living in the London Borough of Barnet who presented to Accident & Emergency Departments with DSH over a two-year period. Ensuing actions and events were then tracked. Results Forty-three older people with DSH were identified. 18/43 (42%) had previous contact with local psychiatric services. The main method of DSH was overdose of medication (36/43 or 84%). Compared to the general population there were more women and widows. There were similar levels of physical ill-health. Thirty-seven of 43 (86%) received documented psychiatric input outside of hospital following the DSH. The mean follow-up period was 789.0 days (SD 419.8) and during this time 8/43 (19%) had a further documented episode of DSH, and 18/43 (40%) died from natural causes. Conclusions This study confirms the need for improved documentation of DSH and its coding; this needs to be reviewed at local and national level. The vast majority of older people who attempt suicide do have subsequent contact with psychiatric services. There is a strong likelihood of repeat DSH and a higher risk of death by natural causes, emphasising the need to conceptualise DSH as a risk factor relevant to all medical specialities. Copyright © 2005 John Wiley & Sons, Ltd. [source]


Prevalence of foot diseases in outpatients attending the Institute of Dermatology, Bangkok, Thailand

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2004
R. Ungpakorn
Summary Two thousand patients who visited the outpatient department at the Institute of Dermatology, Bangkok, were assessed for the presence of foot diseases by questionnaire and physical examination. Abnormalities were detected in 741 individuals (37.1%). Nonfungal conditions were more prevalent (31.4%), mainly consisting of eczema (254 cases, 12.7%) and psoriasis (176 cases, 8.8%). Fungal disease was observed in 119 cases (6.0%). There were 76 cases (3.8%) with tinea pedis and 33 cases (1.7%) with onychomycosis. The identified organisms causing tinea pedis were 57.9% nondermatophyte moulds, 36.8% dermatophytes, and 2.6%Candida spp. The corresponding organisms causing onychomycosis were 51.6% nondermatophyte moulds, 36.3% dermatophytes, and 6.0%Candida spp. Among nondermatophytes, Scytalidium dimidiatum was the leading pathogen while Trichophyton rubrum and T. mentagrophytes were the predominant dermatophytes identified. Diabetes mellitus, peripheral vascular disease and activities related to foot trauma were noted to be predisposing factors for onychomycosis. Footwear, particularly sandals and cut shoes, was the only factor relevant to individuals with tinea pedis (P , 0.05). In contrast with other published data on fungal foot infections, this study disclosed a higher prevalence of nondermatophyte organisms, predominantly S. dimidiatum, as the major cause of tinea pedis and onychomycosis. An increase in awareness is necessary to identify such cases, prevent misdiagnosis and initiate appropriate treatment. [source]


Aetiology of molar,incisor hypomineralization: a critical review

INTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 2 2009
FELICITY CROMBIE
Objective., The objective of this study was to assess the strength of evidence for the aetiology of molar,incisor hypomineralization (MIH), often as approximated by demarcated defects. Method., A systematic search of online medical databases was conducted with assessment of titles, abstracts, and finally full articles for selection purposes. The level and quality of evidence were then assessed for each article according to Australian national guidelines. Results., Of 1123 articles identified by the database search, 53 were selected for review. These covered a variety of potential aetiological factors, some of which were grouped together for convenience. The level of evidence provided by the majority of papers was low and most did not specifically investigate MIH. There was moderate evidence that polychlorinated biphenyl/dioxin exposure is involved in the aetiology of MIH; weak evidence for the role of nutrition, birth and neonatal factors, and acute or chronic childhood illness/treatment; and very weak evidence to implicate fluoride or breastfeeding. Conclusion., There is currently insufficient evidence in the literature to establish aetiological factor/s relevant for MIH. Improvements in study design, as well as standardization of diagnostic and examination protocols, would improve the level and strength of evidence. [source]


The importance of exposure estimation in the assessment of skin sensitization risk

CONTACT DERMATITIS, Issue 5 2000
Michael K. Robinson
The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) as a case study. [source]


The Influence of Gender and Sex Steroids on Craniofacial Nociception

HEADACHE, Issue 2 2007
Brian E. Cairns PhD
Several pain conditions localized to the craniofacial region show a remarkable sex-related difference in their prevalence. These conditions include temporomandibular disorders and burning mouth syndrome as well as tension-type, migraine, and cluster headaches. The mechanisms that underlie sex-related differences in the prevalence of these craniofacial pain conditions remain obscure and likely involve both physiological and psychosocial factors. In terms of physiological factors relevant to the development of headache, direct evidence of sex-related differences in the properties of dural afferent fibers or durally activated second-order trigeminal sensory neurons has yet to be provided. There is, however, evidence for sex-related differences in the response properties of afferent fibers and second-order trigeminal sensory neurons that convey nociceptive input from other craniofacial tissues associated with sex-related differences in chronic pain conditions, such as those that innervate the masseter muscle and temporomandibular joint. Further, modulation of craniofacial nociceptive input by opioidergic receptor mechanisms appears to be dependent on biological sex. Research into mechanisms that may contribute to sex-related differences in trigeminal nociceptive processing has primarily focused on effect of the female sex hormone estrogen, which appears to alter the excitability of trigeminal afferent fibers and sensory neurons to noxious stimulation of craniofacial tissues. This article discusses current knowledge of potential physiological mechanisms that could contribute to sex-related differences in certain craniofacial pain conditions. [source]


Temporal variability of phytoplankton in a salt wedge estuary, the Swan,Canning Estuary, Western Australia

HYDROLOGICAL PROCESSES, Issue 13 2001
Peter A. Thompson
Abstract The temporal cycles of variation in salinity, temperature and river flow in the Swan,Canning Estuary plus rainfall in the vicinity are examined. A ,normal' pattern is defined for rainfall and river flow based on long-term median monthly values from available historical data. Long-term monthly median rainfall and median monthly river flow were highly correlated. Deviations from the ,normal' patterns of rainfall and river flow are documented. Three years of detailed data on the temporal distribution of the algal biomass and phytoplankton community composition from the Swan,Canning Estuary are presented and discussed. Significant interannual variability in the phytoplankton biomass was observed with 1996 having a significantly lower median chlorophyll a concentration than 1995 or 1997. Different years also had pronounced differences in the timing, persistence and occurrence of algal blooms. Links with, and between, rainfall, river flow, nutrient concentrations and phytoplankton biomass are made by careful examination of the temporal patterns. Deviations from the proposed ,normal' temporal pattern of physical and chemical environmental factors relevant to the growth of phytoplankton biomass are assessed. Deviations from ,normal' rainfall and river flow, depending upon their timing and intensity, appear to be associated with occurrence of algal blooms. For example, the lack of a dinoflagellate bloom in December 1996 or January 1997 appears to be associated with a wetter than normal spring. Based upon the observed data, published reports and basic principles of algal ecology a set of predicted responses to variation in the major environmental variables (rainfall and river flow) are tabulated. The tabulated predictions are proposed as a useful tool for resource managers. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Trust, power and interorganizational information systems: the case of the electronic trading community TransLease

INFORMATION SYSTEMS JOURNAL, Issue 1 2000
David K. Allen
Abstract. This paper focuses on Cap Gemini's electronic commerce system, TransLease. TransLease is an interorganizational information system (IOS), which facilitates electronic commerce between motor vehicle leasing and repair companies. During our investigation, the system was used by approximately 1000 repair agents working for seven of the UK's leading vehicle leasing and contract hire companies. This system was originally developed by AT&T and acquired by Cap Gemini in July 1998. At the time of acquisition, the system was seen as being of high strategic value, although it was also seen as underperforming. This paper reports the results of an action research project, which formed one element of the process by which Cap Gemini investigated the former problem. In the paper, TransLease is described as a complex electronic community, dependent upon the existence of symbiotic relationships. As such, the problems that the system users and developers experienced can be attributed to factors that impeded the mutual benefit accruing from participation in the system. The efficacy of the terms of exchange and the degree to which participants mutually benefit through electronic interaction is determined by the complex interplay of a number of relational and organizational factors. The research therefore illustrates the importance of the ,soft' organizational issues in IOS management and development, and suggests a conceptual model of the factors relevant in this case. At the time of this study, TransLease was still in the early stages of its life cycle, having only been available in the marketplace for approximately 18 months. During this time, through recognizing the complex problems and issues detailed in this paper, Cap Gemini accordingly redressed the way in which the system was managed and maintained. TransLease is now seen as having matured into a highly successful example of an IOS , a view reflected by its position as market leader in the industry. As this paper will show, the key to improving the existing service has been the emphasis Cap Gemini now places on managing the ,soft' aspects of the electronic community. [source]


Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts

MOLECULAR MICROBIOLOGY, Issue 5 2000
Shalina Mahajan-Miklos
Several strains of the human opportunistic pathogen Pseudomonas aeruginosa infect plants, nematodes and insects. Our laboratory has developed a multihost pathogenesis system based on the P. aeruginosa clinical isolate PA14, in which non-mammalian hosts are used to screen directly for virulence-attenuated mutants. The majority of PA14 mutants isolated using non-mammalian hosts also displayed reduced virulence in a burned mouse model. Surprisingly, only a few host-specific virulence factors were identified, and many of the P. aeruginosa mutants were attenuated in virulence in all the hosts. These studies illustrate the extensive conservation in the virulence mechanisms used by P. aeruginosa to infect evolutionarily diverged hosts, and validate the multihost method of screening for virulence factors relevant to mammalian pathogenesis. Through the use of genetically tractable hosts, the multihost pathogenesis model also provides tools for elucidating host responses and dissecting the fundamental molecular interactions that underlie bacterial pathogenesis. [source]


Future of cell and gene therapies for Parkinson's disease,

ANNALS OF NEUROLOGY, Issue S2 2008
Ole Isacson MD
The experimental field of restorative neurology continues to advance with implantation of cells or transfer of genes to treat patients with neurological disease. Both strategies have generated a consensus that demonstrates their capacity for structural and molecular brain modification in the adult brain. However, both approaches have yet to successfully address the complexities to make such novel therapeutic modalities work in the clinic. Prior experimental cell transplantation to patients with PD utilized dissected pieces of fetal midbrain tissue, containing mixtures of cells and neuronal types, as donor cells. Stem cell and progenitor cell biology provide new opportunities for selection and development of large batches of specific therapeutic cells. This may allow for cell composition analysis and dosing to optimize the benefit to an individual patient. The biotechnology used for cell and gene therapy for treatment of neurological disease may eventually be as advanced as today's pharmaceutical drug-related design processes. Current gene therapy phase 1 safety trials for PD include the delivery of a growth factor (neurturin via the glial cell line,derived neurotrophic factor receptor) and a transmitter enzyme (glutamic acid decarboxylase and aromatic acid decarboxylase). Many new insights from cell biological and molecular studies provide opportunities to selectively express or suppress factors relevant to neuroprotection and improved function of neurons involved in PD. Future gene and cell therapies are likely to coexist with classic pharmacological therapies because their use can be tailored to individual patients' underlying disease process and need for neuroprotective or restorative interventions. Ann Neurol 2008;64 (suppl):S122,S138 [source]


Drosophila melanogaster as a model for elucidating the pathogenicity of Francisella tularensis

CELLULAR MICROBIOLOGY, Issue 6 2008
Malin Vonkavaara
Summary Drosophila melanogaster is a widely used model organism for research on innate immunity and serves as an experimental model for infectious diseases. The aetiological agent of the zoonotic disease tularaemia, Francisella tularensis, can be transmitted by ticks and mosquitoes and Drosophila might be a useful, genetically amenable model host to elucidate the interactions between the bacterium and its arthropod vectors. We found that the live vaccine strain of F. tularensis was phagocytosed by Drosophila and multiplied in fly haemocytes in vitro and in vivo. Bacteria injected into flies resided both inside haemocytes and extracellularly in the open circulatory system. A continuous activation of the humoral immune response, i.e. production of antimicrobial peptides under control of the imd/Relish signalling pathway, was observed and it may have contributed to the relative resistance to F. tularensis as flies defective in the imd/Relish pathway died rapidly. Importantly, bacterial strains deficient for genes of the F. tularensis intracellular growth locus or the macrophage growth locus were attenuated in D. melanogaster. Our results demonstrate that D. melanogaster is a suitable model for the analysis of interactions between F. tularensis and its arthropod hosts and that it can also be used to identify F. tularensis virulence factors relevant for mammalian hosts. [source]


Solid-phase synthesis and characterization of N -methyl-rich peptides

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 2 2005
M. Teixidó
Abstract:, A library of peptides required for a project investigating the factors relevant for blood,brain barrier transport was synthesized on solid phase. As a result of the high N -methylamino acid content in the peptides, their syntheses were challenging and form the basis of the work presented here. The coupling of protected N -methylamino acids with N -methylamino acids generally occurs in low yield. (7-azabenzotriazol-1-yloxy)-tris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP) or PyBOP/1-hydroxy-7-azabenzotriazole (HOAt), are the most promising coupling reagents for these couplings. When a peptide contains an acetylated N -methylamino acid at the N-terminal position, loss of Ac- N -methylamino acid occurs during trifluoroacetic acid (TFA) cleavage of the peptide from the resin. Other side reactions resulting from acidic cleavage are described here, including fragmentation between consecutive N -methylamino acids and formation of diketopiperazines (DKPs). The time of cleavage is shown to greatly influence synthetic results. Finally, high-performance liquid chromatography (HPLC) profiles of N -methyl-rich peptides show multiple peaks because of slow conversion between conformers. [source]


Assessment of a Cross-Disciplinary Domestic Violence Training for Emergency Medicine Residents and Law Students

ACADEMIC EMERGENCY MEDICINE, Issue 2008
Cameron Crandall
Objectives:, Domestic violence (DV) patients often have complex medical, social and legal issues that challenge assessment, treatment and referral. We designed a brief cross-disciplinary training for emergency medicine residents and upper level law students to determine the baseline level of resident and law student competence in assessment and management of patients with a history of domestic violence. Methods:, The study included 23 emergency medicine residents and 28 upper level law students at an urban university. The design included pretest, intervention, and retest with 4 standardized patient assessments. The intervention included for each 2 hours of cross-disciplinary lectures on DV and one joint case-based 2 hour learning session with the medical and legal learners. Communication skills (CSs) were assessed using a validated criterion standard. History taking competence (HX) was assessed with a prespecified checklist of critical elements designed to elicit key medico-legal factors relevant to each case. Data were compared with t tests. Results:, 18 (78%) residents and 26 (93%) law students completed the study. Pre-intervention, residents scored 63% (8% standard deviation (SD)) on CS and gathered 71% (13%) of critical HX elements. Law students scored 62% (8%) on CS and gathered 66% (8%) of critical HX elements. Residents (64% (6%)) and law students (63% (6%) showed similar post-intervention CS scores. Both residents (77% (10%), improvement 6%, p = 0.13) and law students (71% (14%), improvement 8%, p = .15) showed modest but non-significant improvement in critical HX gathering. Conclusions:, A brief cross-disciplinary training between medical and legal learners demonstrated low baseline scores in DV assessment for both learning groups with modest, but non-significant improvements in gathering of critical HX elements following intervention. Longer didactic training or more focused skill building might improve skills. [source]