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Integral Component (integral + component)
Selected AbstractsThe Drosophila nucleoporin gene nup154 is required for correct microfilament dynamics and cell death during oogenesisCYTOSKELETON, Issue 8 2007Maria Giovanna Riparbelli Abstract The Drosophila nucleoporin gene nup154 is required in both male and female germline for successful gametogenesis. Mutant flies lack differentiated sperm and lay abnormal eggs. We demonstrated that the egg phenotype was associated with specific alterations of the actin cytoskeleton at different stages of oogenesis. Actually, mutant egg chambers displayed an abnormal organization of both subcortical microfilaments and cytoplasmic actin bundles, that led to defective nurse cell dumping. TUNEL analysis also showed that the dumpless phenotype was associated with delayed apoptosis. The nup154 gene product was localized by conventional immunofluorescence microscopy to the nuclear envelope in a distinct punctuate pattern, characteristic of nuclear pore complex components. TEM analysis revealed that the protein was mainly distributed along filamentous structures that extended radially on the nuclear side of the pore, suggesting that Nup154 could be an integral component of the basket filaments associated with the nuclear pore complexes. We propose that Nup154 is necessary for correct nuclear pore complex functions and that the proper regulation of the actin cytoskeleton dynamics strongly relies upon nuclear pore integrity. Cell Motil. Cytoskeleton 2007. © 2007 Wiley-Liss, Inc. [source] A Pilot Study of the Clinical Impact of Hand-Carried Cardiac Ultrasound in the Medical ClinicECHOCARDIOGRAPHY, Issue 6 2006Lori B. Croft M.D. Background: Small, hand-carried ultrasound devices have become widely available, making point-of-care echocardiograms (echos) accessible to all medical personnel as a means to augment and improve the increasingly inefficient physical examination. This study was designed to determine the clinical utility of hand-carried echo by medical residents in clinical decision making. Methods: Nine residents underwent brief, practical echo training to perform and interpret a limited hand-carried echo as an integral component of their office examination. The residents' hand-carried echo consisting of four basic views to define left ventricular (LV) function and wall thickness, valvular disease, and any pericardial effusions was compared to one performed by a level III echocardiographer. Results: Seventy-two consecutive medical clinic patients were enrolled with an average image acquisition time of 4.45 minutes. Residents obtained diagnostic images in 94% of the cases and interpreted them correctly 93% of the time. They correctly identified 92% of the major echo findings and 78% of the minor findings. Their diagnosis of LV dysfunction, valvular disease, and LV hypertrophy improved by 19%, 39%, and 14% with hand-carried echo compared to history and physical alone. Management decisions were reinforced in 76% and changed in 40% of patients with the use of hand-carried echo. Conclusion: This study demonstrates that it is possible to train medical residents to perform an effective and reasonably accurate hand-carried echo during their physical examination, which can impact clinical management. [source] Intraoperative Transesophageal Echocardiography in Congenital Heart DiseaseECHOCARDIOGRAPHY, Issue 8 2002F.R.A.C.P., F.R.C.P.(C.)Article first published online: 24 JUL 200, Jeffrey F. Smallhorn M.B.B.S. Intraoperative transesophageal echocardiography has become an integral component of the repair of congenital heart defects. It currently has a direct impact on reducing morbidity and mortality in the pediatric cardiac population. To establish a successful program, it is important to follow guidelines for training as well as having a systematic approach to the evaluation of this patient population. This article addresses the specific indications in a patient population as practiced at the Hospital For Sick Children, Toronto. While there may be subtle differences between programs, the objectives are to provide excellent service to the pediatric cardiac patient in the operating room. [source] Both Fc,RIV and Fc,RIII are essential receptors mediating type II and type III autoimmune responses via FcR,-LAT-dependent generation of C5aEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2009Shahzad N. Syed Abstract Fc,RIV is a relatively new IgG Fc receptor (Fc,R) that is reported to contribute to the pathogenesis of autoimmune diseases, although its specific role in relation to Fc,RIII, complement and IgG2 subclasses remains uncertain. Here we define Fc,RIV on macrophages as a receptor for soluble IgG2a/b complexes but not for cellular bound IgG2a and show that simultaneous activation of Fc,RIV and Fc,RIII is critical to mediate certain type II/III autoimmune responses. Fc,RIII-deficient mice display compensatory enhanced Fc,RIV expression, are protected from lung inflammation after deposition of IgG complexes, and show reduced sensitivity to IgG2a/b-mediated hemolytic anemia, indicating that increased Fc,RIV alone is not sufficient to trigger these diseases in the absence of Fc,RIII. Importantly, however, blockade of Fc,RIV is also effective in inhibiting phagocytosis and cytokine production in IgG2b-induced anemia and acute lung injury, processes that display a further dependence on C5a anaphylatoxin receptor. Using gene deletion and functional inhibition studies, we found that Fc,RIII and Fc,RIV are each essential to trigger an FcR,-linker for activation of T-cell-dependent signal that drives C5a production in the Arthus reaction. Together, the results demonstrate a combined requirement for Fc,RIII and Fc,RIV in autoimmune injury, and identify the linker for activation of T cells adaptor as an integral component of linked Fc,R and C5a anaphylatoxin receptor activation to generate inflammation. [source] How apoptosis got the immune system in shapeEUROPEAN JOURNAL OF IMMUNOLOGY, Issue S1 2007Christine Feig Abstract The discovery that apoptosis is an integral component of normal development has facilitated the widespread recognition that cell death is not at all inimical to life. For much of our lifetime the body maintains a cellular homeostasis persisting until, ultimately, it is broken during the aging process. However, unlike the body as a whole, fluctuations at any age in this cellular balance are frequent in the immune system, which responds to infections via massive clonal expansions and elimination of reactive T and B cells. Moreover, cell death also plays a key, and essential, role in the education of immune cells in the thymus and the bone marrow, where autoreactive cells are eliminated, thereby establishing tolerance to self tissues. Furthermore, the mechanism by which cytotoxic T and NK cells kill virus infected or transformed target cells is by inducing apoptotic cell death. Thus, cell death, and in particular apoptosis, is an integral facet of almost all aspects of immune function. Failure to execute apoptosis appropriately has dire consequences leading to the development of autoimmune disease and malignant growth. This narration provides a historical overview of the impact that the discovery of apoptosis had on the understanding of the function of the immune system. [source] A review on the interactions between gut microbiota and innate immunity of fishFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2008Geovanny D. Gómez Abstract Although fish immunology has progressed in the last few years, the contribution of the normal endogenous microbiota to the overall health status has been so far underestimated. In this context, the establishment of a normal or protective microbiota constitutes a key component to maintain good health, through competitive exclusion mechanisms, and has implications for the development and maturation of the immune system. The normal microbiota influences the innate immune system, which is of vital importance for the disease resistance of fish and is divided into physical barriers, humoral and cellular components. Innate humoral parameters include antimicrobial peptides, lysozyme, complement components, transferrin, pentraxins, lectins, antiproteases and natural antibodies, whereas nonspecific cytotoxic cells and phagocytes (monocytes/macrophages and neutrophils) constitute innate cellular immune effectors. Cytokines are an integral component of the adaptive and innate immune response, particularly IL-1,, interferon, tumor necrosis factor-,, transforming growth factor-, and several chemokines regulate innate immunity. This review covers the innate immune mechanisms of protection against pathogens, in relation with the installation and composition of the normal endogenous microbiota in fish and its role on health. Knowledge of such interaction may offer novel and useful means designing adequate therapeutic strategies for disease prevention and treatment. [source] Similar Ends, Differing Means: Contractualism and Civil Service Reform in Denmark and New ZealandGOVERNANCE, Issue 1 2004Robert Gregory State sector reform was an integral component of the radical economic and social policy changes enacted by New Zealand governments between 1984 and 1991. This reform replaced the traditional tenured public service with a contractual regime. Through a comparison with Denmark, it is shown that New Zealand's reforms were not unique. Similar reforms were enacted in Denmark. But contrary to what occurred in New Zealand, the Danish reforms had already begun in the 1960s, and have since been gradually expanded. The parallel contractual regimes introduced in the two countries are accounted for by an increasing demand among politicians to secure a civil service that is responsive to political executive demands. However, because of institutional differences and diverging regulatory regimes, the strategic approaches in the two countries have been different. Whereas the New Zealand approach was dominated by an appeal to a coherent and sophisticated body of theoretical knowledge, combined with strict formalization, the Danish strategy has been based on political bargaining with the civil service unions. In both cases the reforms rest on critical assumptions regarding their positive and negative implications. [source] Local Electrochemical Functionality in Energy Storage Materials and Devices by Scanning Probe Microscopies: Status and PerspectivesADVANCED MATERIALS, Issue 35 2010Sergei V. Kalinin Abstract Energy storage and conversion systems are an integral component of emerging green technologies, including mobile electronic devices, automotive, and storage components of solar and wind energy economics. Despite the rapidly expanding manufacturing capabilities and wealth of phenomenological information on the macroscopic device behaviors, the microscopic mechanisms underpinning battery and fuel cell operations in the nanometer,micrometer range are virtually unknown. This lack of information is due to the dearth of experimental techniques capable of addressing elementary mechanisms involved in battery operation, including electronic and ion transport, vacancy injection, and interfacial reactions, on the nanometer scale. In this article, a brief overview of scanning probe microscopy (SPM) methods addressing nanoscale electrochemical functionalities is provided and compared with macroscopic electrochemical methods. Future applications of emergent SPM methods, including near field optical, electromechanical, microwave, and thermal probes and combined SPM-(S)TEM (scanning transmission electron microscopy) methods in energy storage and conversion materials are discussed. [source] The influence of framing on attitudes toward diversity trainingHUMAN RESOURCE DEVELOPMENT QUARTERLY, Issue 3 2003Courtney L. Holladay Although diversity training is becoming an integral component of organizations, little empirical research on the topic exists. The study examined here investigated how framing of diversity training (title, focus of content, assignment) and gender influenced participants' attitudes. In this study, 160 adults (72 men, 88 women; 124 white; 36 minority) read a diversity course description and answered questions assessing their attitudes about the course and the organization. Results revealed that (1) a frame with a traditional title and a broad focus was responded to most favorably by participants, (2) men reacted more negatively than women to the diversity training course, and (3) men reacted more negatively than women to a frame with a narrow focus and remedial assignment. Findings are discussed in terms of the effect that different frames can have on participants' pretraining attitudes toward diversity training. Implications for researchers and consultants are also discussed. [source] Toll-like receptors , sentries in the B-cell responseIMMUNOLOGY, Issue 3 2009Isabelle Bekeredjian-Ding Summary Toll-like receptors (TLR) play a central role in the initiation of the innate immune response to pathogens. Upon recognition of molecular motifs specific for microbial molecules TLR mediate pro-inflammatory cytokine secretion and enhance antigen presentation; in B cells they further promote expansion, class switch recombination and immunoglobulin secretion. As a result of their adjuvant properties, TLR ligands have become an integral component of antimicrobial vaccines. In spite of this, little is known of the direct effects of TLR engagement on B-lymphocyte function. The scope of this review is to outline the differences in TLR expression and reactivity in murine and human B-cell subsets and to provide an overview of the currently available literature. We will further discuss the possible roles of TLR in regulating B-cell effector functions and shaping antibody-mediated defence against microbial pathogens in vivo. [source] Termination as a therapeutic intervention when treating children who have experienced multiple lossesINFANT MENTAL HEALTH JOURNAL, Issue 1 2009Michele M. Many Children who have endured traumatizing events often have a history of prior disruptions and losses which also have been experienced as traumatic. Termination of therapy with these children, therefore, provides a unique opportunity for the clinician to provide the traumatized child and his or her caregiver with a new experience of loss; one that is controlled, predictable, and paced. Through this experience, the child and caregiver can develop a new model for loss, one that permits for losses that are a natural part of healthy growth and change. This article outlines one approach to utilizing termination as an integral component of the therapeutic process with infants, toddlers, and preschoolers and their caregivers. Using a psychodynamic model and working dyadically with the child and the caregiver, termination is approached as a primary intervention, pivotal to the successful treatment of this vulnerable population. [source] Toll-Like Receptors in Older AdultsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2007David Van Duin MD Toll-like receptors (TLRs) recognize a limited number of conserved elements in pathogens and, by activating antigen-presenting cells such as dendritic cells and monocytes and macrophages, play a crucial role in the immune response to infection and vaccination. Most data on TLR function in the context of human aging focus on responses to lipopolysaccharide, an integral component of gram-negative bacteria, which signals through TLR4. However, such studies have not led to a consensus conclusion and are limited by differences in epidemiological and laboratory methods. A recent comprehensive evaluation of TLR function in monocytes from older adults was conducted using a multivariable mixed statistical model to account for covariates. It was found that cytokine production after TLR1/2 engagement, which is essential for the recognition of triacylated lipopeptides found in a variety of bacteria, is substantially lower in monocytes from older adults. The upregulation of costimulatory proteins such as CD80, essential for optimal activation of T cells, on monocytes from older adults was less for all TLR ligands tested than for cells from young individuals, and the extent of CD80 upregulation predicted subsequent antibody response to influenza immunization. These and other consequences of aging on human TLR function may impair activation of the immune response and contribute to poorer vaccine responses and greater morbidity and mortality from infectious diseases in older adults. Such age-associated alterations have particular relevance in view of the interest in TLR agonists as therapeutic agents not only for infections, but also for allergic, autoimmune, and malignant disease. [source] An exploratory study of web-enhanced learning in undergraduate nurse educationJOURNAL OF CLINICAL NURSING, Issue 12 2007BSc (Hons), Elizabeth A Mitchell MSc, PG Dip Ed Aim.,The aim of the study was to explore undergraduate nursing students' views of web-enhanced learning and to examine issues relating to their pattern of access to a rehabilitation nursing module website. Background.,As information technology is an integral component of western health care, all nurses are expected to have the necessary knowledge, skills and attitudes to be competent in its use. Methods.,In phase 1, a focus group interview was conducted with students (n = 6) who had not logged onto a similar module website. In phase 2, a questionnaire was administered to students undertaking the web-enhanced module. In phase 3, each student's (n = 231) pattern of access to the module was identified and compared with the student's performance as evidenced by their module assignment mark. Results.,Students held favourable attitudes towards web-enhanced learning but some students experienced difficulties. There was a significant positive association between the students' assignment mark and the number of times logged onto the module website. Significant negative correlations were found between mark and week of first log on, and week of first log on and number of hits onto the module site. This suggests that students who logged onto the module in the first few weeks were more likely to achieve higher marks. Conclusions.,This study's findings suggest that students who accessed the module website early and often were more likely to produce more comprehensive nursing assessments and consequently achieve higher assignment marks than their colleagues. Relevance to clinical practice.,The findings have relevance to all nurses as lifelong learning is a mandatory requirement for maintaining clinical competence and electronic learning can provide students (regardless of registration status) with the flexibility to gain access to course content at a time and place convenient to them. The role of electronic learning in promoting a more holistic nursing assessment is also discussed. [source] Curing Dental Resins and Composites by PhotopolymerizationJOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 6 2000JEFFREY W. STANSBURY PHD ABSTRACT The development and continued evolution of photopolymerizable dental materials, particularly dental composite restoratives, represent a significant, practical advance for dentistry. The highly successful integration of the light-activated curing process for dental applications is described in this review. The basic mechanisms by which the photoinitiators efficiently convert monomers into polymers are discussed along with the variety of factors that influence the photopolymerization process. The conventional camphorquinone-amine visible light photoinitiator system used in most dental restorative materials is illustrated in addition to some alternative initiator systems that have been studied for dental materials applications. CLINICAL SIGNIFICANCE Photopolymerization has become an integral component of the practice of dentistry. A better appreciation of the photopolymerization process as well as its potential and limitations may aid the dentist in the delivery of both esthetic and restorative dental care. [source] Nutritional advice and treatment by dietitians to patients with amyotrophic lateral sclerosis/motor neurone disease: a survey of current practice in England, Wales, Northern Ireland and CanadaJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 1 2007A. Rio Abstract Background, The management of amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) has shifted from an attitude of nihilism to treatments that prolong survival and offer hope. Nutrition is an integral component of ALS/MND care requiring coordination among acute and community multi-disciplinary teams (MDT). Evidence-based nutrition guidelines exist for this patient group but their use among dietitians is unknown. The aim of this study was to survey the knowledge, practice and guideline use of dietitians working in ALS/MND centres/clinics across England, Wales, Northern Ireland (EWNI) and Canada. Method, Dietetic contact details were obtained from the Motor Neurone Disease Association (MNDA) and the ALS Society of Canada (ALSSC) websites. Telephone interviews were conducted with 23 dietitians using a standardized questionnaire. Results, Multi-disciplinary team membership was high (78%). Only 22% dietitians had >4-years experience in ALS/MND care. Dietitians reported using body weight, percentage weight loss (PWL) and body mass index (BMI) to assess nutritional status. Equations used to estimate energy and protein requirements differed. Most frequent dietary advice was high calorie, texture modification and prescription nutritional supplements. Artificial nutrition and hydration (ANH) was discussed when patients developed dysphagia, energy intake was inadequate, weight loss of 10% or forced vital capacity (FVC) was reduced. A percutaneous endoscopic gastrostomy (PEG) service was available at all clinics/centres. Conclusion, Nutritional assessment techniques and dietary advice should be standardized. Dietetic collaboration at national and international level is recommended to reduce professional isolation. Training and support in ALS/MND nutrition should be made available as part of post-dietetic registration. Further dietetic research is required to stimulate nutritional care. [source] Human brain aminopeptidase A: biochemical properties and distribution in brain nucleiJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Nadia De Mota Abstract Aminopeptidase A (APA) generated brain angiotensin III, one of the main effector peptides of the brain renin angiotensin system, exerting a tonic stimulatory effect on the control of blood pressure in hypertensive rats. The distribution of APA in human brain has not been yet studied. We first biochemically characterized human brain APA (apparent molecular mass of 165 and 130 kDa) and we showed that the human enzyme exhibited similar enzymatic characteristics to recombinant mouse APA. Both enzymes had similar sensitivity to Ca2+. Kinetic studies showed that the Km (190 ,mol/L) of the human enzyme for the synthetic substrate- l -glutamyl-,-naphthylamide was close from that of the mouse enzyme (256 ,mol/L). Moreover, various classes of inhibitors including the specific and selective APA inhibitor, (S)-3-amino-4-mercapto-butyl sulfonic acid, had similar inhibitory potencies toward both enzymes. Using (S)-3-amino-4-mercapto-butyl sulfonic acid, we then specifically measured the activity of APA in 40 microdissected areas of the adult human brain. Significant heterogeneity was found in the activity of APA in the various analyzed regions. The highest activity was measured in the choroids plexus and the pineal gland. High activity was also detected in the dorsomedial medulla oblongata, in the septum, the prefrontal cortex, the olfactory bulb, the nucleus accumbens, and the hypothalamus, especially in the paraventricular and supraoptic nuclei. Immunostaining of human brain sections at the level of the medulla oblongata strengthened these data, showing for the first time a high density of immunoreactive neuronal cell bodies and fibers in the motor hypoglossal nucleus, the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, the Roller nucleus, the ambiguus nucleus, the inferior olivary complex, and in the external cuneate nucleus. APA immunoreactivity was also visualized in vessels and capillaries in the dorsal motor nucleus of the vagus and the inferior olivary complex. The presence of APA in several human brain nuclei sensitive to angiotensins and involved in blood pressure regulation suggests that APA in humans is an integral component of the brain renin angiotensin system and strengthens the idea that APA inhibitors could be clinically tested as an additional therapy for the treatment of certain forms of hypertension. [source] NURSES' KNOWLEDGE AND PRACTICE OF VASCULAR ACCESS INFECTION CONTROL IN HAEMODIALYSIS PATIENTS IN THE REPUBLIC OF IRELANDJOURNAL OF RENAL CARE, Issue 2 2008DipNS, Margaret Higgins RN SUMMARY Vascular access hygiene is an integral component of haemodialysis care. Ensuring nurses possess sufficient knowledge and utilise recommended guidelines on infection control is essential for safe practice and patient safety. The study aimed to investigate nurses' knowledge and practice of vascular access infection control among adult haemodialysis patients in the Republic of Ireland. A confidential self-completion questionnaire was sent to all 190 qualified nurses employed in nine haemodialysis units in the Republic of Ireland, which assessed knowledge and behaviour in infection control. Although 92% of respondents reported that policies had been developed by their units and 47% had received infection control education in the previous year, knowledge and adherence to best practice demonstrated significant scope for improvement. The study recommended the development of standard guidelines and regular reviews and updates of policies. Systems should also be developed to ensure a high level of compliance. [source] Time-Resolved Small-Angle Neutron Scattering as a Tool for Studying Controlled Release from Liposomes using Polymer-Enzyme ConjugatesMACROMOLECULAR RAPID COMMUNICATIONS, Issue 19 2010Elaine L. Ferguson Abstract The action of phospholipase A2 (PLA2) on 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) liposomes (vesicles) , an integral component in the polymer enzyme liposome therapy (PELT) mechanism (R. Duncan et al., J. Controlled Release2001, 74, 135) for the controlled delivery of poorly soluble therapeutic molecules within liposomes , may be "masked" by conjugation to the biodegradable polymer dextrin and subsequently regenerated by the endogenous enzyme , -amylase that degrades the dextrin; that is, incorporating the so-called polymer-unmasked-masked protein therapy (PUMPT) approach (R. Duncan, et al. Biomacromolecules2008, 9, 1146). Small-angle neutron scattering (SANS) has been used to quantify the detailed structure of DPPC liposomes and any perturbation in that structure induced by the presence of PLA2 in native, "masked" (dextrin,PLA2 conjugate) and an in situ , -amylase-unmasked form. A time-dependent degradation of the vesicular structure was observed for the two active PLA2 cases, but not for the masked case. This study demonstrates that the PLA2 -induced hydrolysis of the DPPC , and the associated rupture of the liposome and the release of the enclosed material , may be controlled through masking with dextrin. Accordingly, the viability of using such a combinatorial nanomedicine approach as a general route for the controlled delivery of poorly soluble therapeutic molecules is shown. [source] Money matters: students' perceptions of the costs associated with placementsMEDICAL EDUCATION, Issue 10 2007Natalie Wray Context, Placements are an integral component of the medical, nursing and allied health curricula. However, apart from the relocation costs associated with placements, little research on students' understandings and experiences of the financial implications of placements has been carried out. Objectives, We report on students' financial concerns associated with placements, which emerged as a main theme in a broader study we conducted on the impact of undergraduate student placement experiences on graduate practice. Methods, We conducted a qualitative study which included focus group discussions (n = 17), individual interviews (n = 48) and written responses (n = 2) with undergraduate students (n = 103) and graduates (n = 27) from a tertiary institution in Victoria, Australia. Results, Students identified that income generation and the costs associated with transport and placement location contributed to the financial burden of placements. Students also spoke of the implications of high financial strain impacting on their accumulation of debt as well as on their health and wellbeing. Discussion, Our study advances our understanding of the implications of financial hardship experienced by medical, nursing and allied health students. In our study, students, regardless of their placement location, experienced increased demands and associated stress as a result of managing placements, paid employment and limited financial resources. We recommend that further quantitative research be conducted to measure the variables identified as emerging themes in this study. [source] The role of cell-specific circadian clocks in metabolism and diseaseOBESITY REVIEWS, Issue 2009M. S. Bray Summary Biological rhythms are an integral component of essentially all aspects of life. These rhythms are controlled in part by circadian clocks, transcriptionally based mechanisms that synchronize the organism to its changing environment. The central circadian clock is located within the suprachiasmatic nucleus of the brain, while peripheral clocks are located within virtually all cells outside of the suprachiasmatic nucleus. Although our understanding of central clock structure and function is well advanced, the role of peripheral clocks in whole body energy metabolism is just beginning to be elucidated. Both central and peripheral circadian clocks likely regulate many physiological functions, including insulin sensitivity, endocrine regulation, energy homeostasis, satiety signalling, cellular proliferation and cardiovascular function. Widely varying phenotypes have been reported following global genetic disruption of the clock mechanism in mice, with phenotype dependent on both the clock component targeted and genetic background. The inconsistency in phenotypes associated with clock disruption may be due, in part, to cell-specific effects of the circadian clocks. To address this question, many laboratories have begun generating animal models of cell type-specific clock disruption. In this review, we summarize the existing literature on tissue-specific models of circadian clock disruption and provide a focus for future research in this area. [source] Effective management of smoking in an oral dysplasia clinic in LondonORAL DISEASES, Issue 1 2006TWJ Poate Background:, Precancerous lesions precede the development of oral cancer; of several clinical types the most common is leukoplakia. The risk factors include tobacco and excess alcohol use and diets low in antioxidants. Studies concerning the management of risk factors related to oral precancer are meager. Objectives:, We investigated the effectiveness of smoking cessation at a dysplasia clinic among patients followed up for at least for 12 months. Methods:, Data from case notes relating to180 patients with white and red patches of oral mucosa (excluding other benign disorders confirmed by biopsy findings) attending a dysplasia clinic at a teaching hospital in London and seen by one consultant between 1993 and 2003 were transcribed. Effect of referring to a smoker's clinic to receive specialist help was evaluated against brief advice given at the dysplasia clinic ± medications. Results:, The mean age at the first visit was 48.5 years (±12.5), 65% were male, and 88% were white European. One hundred and sixty-two patients (90%) had used tobacco and 83% were current smokers. Of the smokers 95% had smoked over 10 years, the majority smoking over 10 cigarettes per day. Nine were alcohol misusers including two binge drinkers. One hundred and forty-six were diagnosed with oral leukoplakia, 16 with non-homogeneous types (speckled or nodular). Three patients were diagnosed with an erythroplakia. Nineteen per cent exhibited the presence of dysplasia and one subject had in situ carcinoma. Five patients in the sample quit smoking prior to arrival in the dysplasia clinic. Twenty-seven cases (20%) with oral leukoplakia quit smoking while registered as a patient at the dysplasia clinic: 17 of 100 subjects quit with brief advice ± medications and 10 of 30 following referral to the smoker's clinic. The difference between the two groups was significant for point prevalence abstinence at the last visit to the clinic (minimum 12 months follow up). Out of a total of 180 precancer cases managed in the dysplasia clinic (mean follow up 4.2 years) three patients subsequently developed invasive carcinoma during follow up. Conclusions:, Smoking cessation needs to be an integral component of management of cases attending a dysplasia clinic and referring to smoker's clinics could help to improve the effectiveness of managing patients with oral precancer to quit smoking. [source] Annotation: The use of psychotropic medications in children: an American viewTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 2 2003Mark L. Wolraich Background: Psychotropic medications have become an integral component in the treatment of children with mental illnesses. Methods: Selective reviews of the empirical evidence for the efficacy of psychotropic medications and studies of their use patterns were reviewed. Results: Very strong efficacy for at least the short-term benefits and safety of stimulant medications was found and some good efficacy and safety evidence for the treatment of anxiety and depressive disorders with seratonin reuptake inhibitors (SSRI) was also found. Efficacy for tricyclic antidepressants to treat attention deficit hyperactivity disorder was found but the presence of significant side effects makes them less the drugs of choice. Other medications are presented but with less rigorous evidence. Studies of use found that stimulant medications are extensively prescribed in the US by both psychiatrists and primary care physicians. SSRI are also prescribed extensively but not to the extent of stimulants and are more frequently prescribed by psychiatrists. Conclusions: There is now good evidence for the efficacy of some psychotropic agents and their use is an integral component in the management of childhood mental illnesses. [source] Use of Laboratory Evaluation and Radiologic Imaging in the Diagnostic Evaluation of Children With Sensorineural Hearing Loss,THE LARYNGOSCOPE, Issue 1 2002Derek D. Mafong BS Abstract Objective Laboratory testing and radiologic imaging are commonly used to delineate syndromic from nonsyndromic sensorineural HL (SNHL). The aim of this study was to examine the yield of laboratory tests and radiologic imaging commonly used in the diagnostic evaluation of SNHL in children. Study Design Retrospective analysis of 114 (54 female, 60 male) consecutively investigated children with SNHL between 1998 and 2000 at a tertiary-care university hospital. Methods Results of routine laboratory testing to assess autoimmunity, blood dyscrasias, endocrine abnormalities, renal function, infection, and cardiac testing were reviewed. Results of radiologic evaluation were also reviewed. In general, computed tomography (CT) was obtained in patients with symmetric SNHL, whereas magnetic resonance imaging (MRI) with or without CT was obtained in asymmetric SNHL. Results Laboratory evaluation of the blood did not yield the etiology of SNHL in any patient. Blood tests for autoimmune disease were often positive but did not correlate with clinical disease. Nonspecific elevation of erythrocyte sedimentation rate (ESR) and antinuclear antibody (ANA) was present in 22% of cases. An abnormal electrocardiogram with a prolonged QT interval resulted in the diagnosis of Jervall and Lange-Nielsen syndrome. In the 97 patients who underwent radiologic studies, abnormalities were present in 38 of 97 studies (39%). Isolated inner ear malformations were twice as common as multiple abnormalities with large vestibular aqueducts as the most common isolated finding. Conclusion In the evaluation of children with unexplained SNHL, routine laboratory evaluation should be reconsidered given its low diagnostic yield. However, radiologic abnormalities of the inner ear are common. Identification of inner ear malformations has direct impact on management of these children, suggesting that all children should undergo radiologic imaging as an integral component of evaluation of SNHL. [source] Prohibitin regulates TGF-, induced apoptosis as a downstream effector of smad-dependent and -independent signalingTHE PROSTATE, Issue 1 2010Brian Zhu Abstract BACKGROUND Prohibitin (PHB), a protein located on the inner mitochondrial membrane and nuclei, is an intracellular effector of transforming growth factor-, (TGF-,) signaling in prostate cancer cells. This study investigated the involvement of PHB in the apoptosis and survival outcomes of human prostate cancer cell to TGF-,. shRNA PHB loss of function in prostate cancer cells led to enhanced apoptotic response to TGF-, via Smad-dependent mechanism. METHOD TGF-, activation of Raf-Erk intracellular signaling, led to PHB phosphorylation, decreased inner mitochondrial permeability, and increased cell survival. Calcein-based immunofluorescence studies revealed the functional involvement of PHB in maintaining inner mitochondrial membrane permeability as an integral component of TGF-, induced apoptosis in prostate cancer cells. RESULTS These finding indicates that induction of TGF-, apoptosis is mediated by Smad-dependent and Smad-independent signaling (MAPK) converging at PHB as a downstream effector regulating inner mitochondrial permeability. Putative PHB associated proteins were identified by subjecting TGF-, treated cells to immunoprecipitation with anti-PHB, and mass spectrometry. A screen for the kinase specific phosphorylation sites of PHB revealed three protein kinase (PKC) binding sites. CONCLUSION Our results demonstrate that TGF-, led to upregulation of the PKC inhibitor 14-3-3 protein and promoted its association with PHB, while PHB association with PKC-,, was inhibited by the MEK1 inhibitor, documenting a critical interdependence between the MEK-ERK signaling and prohibitin phosphorylation. These findings suggest a dual role for PHB as a downstream determinant of the cellular response to TGF-, via Smad-dependent pathway (apoptosis) and MAPK intracellular signaling (survival). Prostate 70: 17,26, 2010. © 2009 Wiley-Liss, Inc. [source] NK Cells Mediate Costimulation Blockade-Resistant Rejection of Allogeneic Stem Cells During Nonmyeloablative TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2006L. S. Kean Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism to promote immune tolerance during murine allotransplantation, it has not yet been successfully translated to clinical transplantation. We determined the impact of natural killer (NK) cells on costimulation blockade-resistant rejection of donor bone marrow. We found that NK cells represent a potent barrier to engraftment: host NK depletion led to increased donor stem cell survival, increased mixed hematopoietic chimerism and to engraftment of low doses of donor marrow (1 × 108/kg) that were otherwise rejected. To understand the mechanisms of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We found that an increased proportion of target cells were killed between days 2 and 8 after cell transfer, and that NK killing of parental targets was inducible: NK cells preprimed with allotargets were more efficient at their elimination upon reexposure. Finally, both transplant and in vivo NK-killing models were used to determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led to decreased NK-mediated killing, and increased alloengraftment. These results identify NK alloreactivity as an integral component to costimulation blockade-resistant rejection, and suggest that its inhibition may represent an important target in the clinical translation of tolerance-induction transplantation. [source] Cerebellar morphology in Tourette syndrome and obsessive-compulsive disorderANNALS OF NEUROLOGY, Issue 4 2010Russell H. Tobe MD Objective Neuroanatomical and functional imaging studies have identified the cerebellum as an integral component of motor and language control. Few studies, however, have investigated the role of the cerebellum in Tourette syndrome (TS), a condition defined by the presence of semi-involuntary movements and sounds. Methods Magnetic resonance imaging was conducted in 163 persons with TS and 147 control participants. Multivariate linear regression models were used to explore effects on cerebellar surface morphology and underlying volumes for the main diagnosis effects of TS as well as comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder. Additionally, the correlations of symptom severity with cerebellar morphology were also assessed. Results The TS group demonstrated reduced volumes of the cerebellar hemispheres bilaterally that derived primarily from reduced gray matter in crus I and lobules VI, VIIB, and VIIIA. These decreased regional volumes accompanied increasing tic symptom severity and motoric disinhibition as demonstrated by a finger tapping test. Males had reduced volumes of these same regions compared with females, irrespective of diagnosis. Comorbid OCD was associated with relative enlargement of these regions in proportion to the increasing severity of OCD symptoms. Interpretation The cerebellum is involved in the pathogenesis of TS and tic-related OCD. Baseline gender differences in cerebellar morphology may in part account for the more prevalent expression of TS in males. ANN NEUROL 2010;67:479,487 [source] Radiographs in periodontal disease diagnosis and managementAUSTRALIAN DENTAL JOURNAL, Issue 2009EF Corbet Abstract Radiographs are an integral component of a periodontal assessment for those with clinical evidence of periodontal destruction. A close consideration of the current approach to periodontal diagnosis compatible with the current classification of periodontal diseases reveals that radiographs only inform with respect to diagnosis for a small proportion of conditions. The area in periodontal assessment in which radiographs play a pivotal role is in treatment planning. A variety of radiographic exposure types assist in the development of periodontal treatment plans. This "therapeutic yield" can be achieved by panoramic oral radiographs supplemented by selective intra-oral views. Digital panoramic oral radiographs viewed on screen appear to offer advantages over printouts or films. Newer imaging approaches, such as cone-beam computed (digital volume) tomography, may come to show some usefulness but experience has shown that digital subtraction radiography will probably remain a research tool without much clinical application. [source] Routine administration of the Canadian Occupational Performance Measure: Effect on functional outcomeAUSTRALIAN OCCUPATIONAL THERAPY JOURNAL, Issue 2 2010Heather Colquhoun Background/aim:,Routinely using outcome measures as an integral component of practice has been encouraged for decades yet has not been widely adopted. There are many reasons to measure outcomes yet any positive effect of measurement on our programs or clients has not been substantiated. If the time-consuming nature of outcome measurement is to be encouraged, we need to begin addressing larger questions of the value of outcome measurement on care and outcomes. This cohort study evaluated the impact of routinely administering the Canadian Occupational Performance Measure on client outcomes on a geriatric rehabilitation unit. Methods:,Changes in Functional Independence MeasureÔ scores between an experimental group (n = 45) that received the routine use of the Canadian Occupational Performance Measure for evaluation/planning versus a historical comparison group (n = 58) that received ,usual' care were analysed using generalised linear modeling. Results:,Both groups had significant changes in Functional Independence MeasureÔ scores over time. Results for differences between groups were inconclusive with a significantly underpowered analysis; however, results suggest that a medium to large effect of this intervention cannot be expected. Conclusions:,Results are significant for the field of routine outcome measurement, suggesting that when adding the Canadian Occupational Performance Measure to routine assessment within an inpatient rehabilitation setting, substantially improved Functional Independence MeasureÔ score outcomes should not be expected. The value of routine outcome measurement on client outcomes remains largely unexplored. Routinely, using outcome measures requires additional research to determine the specific benefits to our programs and client outcomes. [source] Facets of psychopathy, Axis II traits, and behavioral dysregulation among jail detaineesBEHAVIORAL SCIENCES & THE LAW, Issue 4 2007Richard Rogers Ph.D. Forensic evaluations of offender populations often consider psychopathy as an integral component of these consultations. Vexing issues remain of whether psychopathic traits should be evaluated consistently irrespective of demographic characteristics (e.g. gender), comorbidity (e.g. other Axis II pathology), or setting (e.g. jail or community). The current study examined gender differences for psychopathy and Axis II traits in a nonreferred jail sample of predominantly nonviolent offenders. Participants with moderate to high levels of psychopathy evidenced substantial comorbidity, especially with Cluster B personality disorders. Facets of psychopathy and Axis II traits varied substantially across both genders. In addition, the research evaluated Lynam's Hyperactivity, Impulsivity, and Attention difficulties (HIA) model of psychopathy. These initial data found little support for the HIA model in this jail sample. In testing competing hypotheses, the HIA model was substantially better at predicting Cluster B traits than psychopathy per se. Copyright © 2007 John Wiley & Sons, Ltd. [source] Developing Technical Expertise in Emergency Medicine,The Role of Simulation in Procedural Skill AcquisitionACADEMIC EMERGENCY MEDICINE, Issue 11 2008Ernest E. Wang MD Abstract Developing technical expertise in medical procedures is an integral component of emergency medicine (EM) practice and training. This article is the work of an expert panel composed of members from the Society for Academic Emergency Medicine (SAEM) Interest Group, the SAEM Technology in Medical Education Committee, and opinions derived from the May 2008 Academic Emergency Medicine Consensus Conference, "The Science of Simulation in Healthcare." The writing group reviewed the simulation literature on procedures germane to EM training, virtual reality training, and instructional learning theory as it pertains to skill acquisition and procedural skills decay. The authors discuss the role of simulation in teaching technical expertise, identify training conditions that lead to effective learning, and provide recommendations for future foci of research. [source] | ||||||||||||||||||||||||||||||||||||||||